diff --git a/indication_paths.json b/indication_paths.json
index f02c30587..0039ebf1a 100644
--- a/indication_paths.json
+++ b/indication_paths.json
@@ -74803,7 +74803,7 @@
     ]
   },
   {
-    "comments": "Heme (MESH:D006418) and hemin (MESH:D006427) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.",
+    "comment": "Heme (MESH:D006418) and hemin (MESH:D006427) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.",
     "directed": true,
     "graph": {
       "_id": "DB12975_MESH_D016780_1",
@@ -74869,7 +74869,7 @@
     ]
   },
   {
-    "comments": "Hemin (MESH:D006427) and heme (MESH:D006418) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.",
+    "comment": "Hemin (MESH:D006427) and heme (MESH:D006418) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.",
     "directed": true,
     "graph": {
       "_id": "DB12975_MESH_D016780_2",
@@ -74893,11 +74893,11 @@
       {
         "key": "location of",
         "source": "CL:0000232",
-        "target": "MESH:D012100"
+        "target": "GO:0019954"
       },
       {
         "key": "in taxon",
-        "source": "MESH:D012100",
+        "source": "GO:0019954",
         "target": "NCBITaxon:5855"
       },
       {
@@ -74924,9 +74924,9 @@
         "name": "erythrocyte"
       },
       {
-        "id": "MESH:D012100",
+        "id": "GO:0019954",
         "label": "BiologicalProcess",
-        "name": "Reproduction, Asexual"
+        "name": "asexual reproduction"
       },
       {
         "id": "NCBITaxon:5855",
@@ -74944,7 +74944,7 @@
     ]
   },
   {
-    "comments": "Heme (MESH:D006418) and hemin (MESH:D006427) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.",
+    "comment": "Heme (MESH:D006418) and hemin (MESH:D006427) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.",
     "directed": true,
     "graph": {
       "_id": "DB12975_MESH_D016778_1",
@@ -75010,7 +75010,7 @@
     ]
   },
   {
-    "comments": "Hemin (MESH:D006427) and heme (MESH:D006418) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.",
+    "comment": "Hemin (MESH:D006427) and heme (MESH:D006418) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.",
     "directed": true,
     "graph": {
       "_id": "DB12975_MESH_D016778_2",
@@ -75034,11 +75034,11 @@
       {
         "key": "location of",
         "source": "CL:0000232",
-        "target": "MESH:D012100"
+        "target": "GO:0019954"
       },
       {
         "key": "in taxon",
-        "source": "MESH:D012100",
+        "source": "GO:0019954",
         "target": "NCBITaxon:5833"
       },
       {
@@ -75065,9 +75065,9 @@
         "name": "erythrocyte"
       },
       {
-        "id": "MESH:D012100",
+        "id": "GO:0019954",
         "label": "BiologicalProcess",
-        "name": "Reproduction, Asexual"
+        "name": "asexual reproduction"
       },
       {
         "id": "NCBITaxon:5833",
@@ -75165,7 +75165,7 @@
     ]
   },
   {
-    "comments": "The disease is denoted as Acute necrotizing ulcerative gingivitis in the original file but the name used for the path is the one seen in the MESH website.",
+    "comment": "The disease is denoted as Acute necrotizing ulcerative gingivitis in the original file but the name used for the path is the one seen in the MESH website.",
     "directed": true,
     "graph": {
       "_id": "DB00257_MESH_D005892_1",
@@ -75261,7 +75261,7 @@
     ]
   },
   {
-    "comments": "Sulfur's usefulness as a topical remedy for acne dates back to at least the reign of Cleopatra i.e. 69\u201330 BCE (https://en.wikipedia.org/wiki/Acne#History).",
+    "comment": "Sulfur's usefulness as a topical remedy for acne dates back to at least the reign of Cleopatra i.e. 69\u201330 BCE (https://en.wikipedia.org/wiki/Acne#History).",
     "directed": true,
     "graph": {
       "_id": "DB00257_MESH_D000152_3",
@@ -75351,7 +75351,7 @@
     ]
   },
   {
-    "comments": "The disease is denoted as Aphthous ulcer of mouth in the original file but the name used for the path is the one seen in the MESH website. The causes for this disease are not well known (https://ada.com/conditions/aphthous-ulcers/#causes). It's important to prevent secondary infection of the ulcers (https://en.wikipedia.org/wiki/Aphthous_stomatitis#Medication); that's when anti-bacterial agents can be administered.",
+    "comment": "The disease is denoted as Aphthous ulcer of mouth in the original file but the name used for the path is the one seen in the MESH website. The causes for this disease are not well known (https://ada.com/conditions/aphthous-ulcers/#causes). It's important to prevent secondary infection of the ulcers (https://en.wikipedia.org/wiki/Aphthous_stomatitis#Medication); that's when anti-bacterial agents can be administered.",
     "directed": true,
     "graph": {
       "_id": "DB00257_MESH_D013281_1",
@@ -75996,7 +75996,7 @@
     ]
   },
   {
-    "comments": "This disease is denoted as Streptococcus pyogenes infection in the original file but it's named Streptococcal Infections by MESH.",
+    "comment": "This disease is denoted as Streptococcus pyogenes infection in the original file but it's named Streptococcal Infections by MESH.",
     "directed": true,
     "graph": {
       "_id": "DB01416_MESH_D013290_1",
@@ -76089,11 +76089,11 @@
     ]
   },
   {
-    "comments": "The disease is denoted Hot Flashes in MESH. The etiology of hot flashes has yet to be determined (https://pubmed.ncbi.nlm.nih.gov/15065632/).",
+    "comment": "The disease is denoted Menopausal flushing in the original file but Hot flashes in MESH. The etiology of hot flashes has yet to be determined (https://pubmed.ncbi.nlm.nih.gov/15065632/).",
     "directed": true,
     "graph": {
       "_id": "DB06710_MESH_D019584_1",
-      "disease": "Menopausal flushing",
+      "disease": "Menopausal Flushing",
       "disease_mesh": "MESH:D019584",
       "drug": "methyltestosterone",
       "drug_mesh": "MESH:D008777",
@@ -76201,7 +76201,7 @@
       {
         "id": "MESH:D019584",
         "label": "Disease",
-        "name": "Menopausal flushing"
+        "name": "Menopausal Flushing"
       }
     ],
     "reference": [
@@ -76213,7 +76213,7 @@
     ]
   },
   {
-    "comments": "MESH:D005058 is named male hypogonadism in the original file.",
+    "comment": "MESH:D005058 is named male hypogonadism in the original file.",
     "directed": true,
     "graph": {
       "_id": "DB06710_MESH_D005058_1",
@@ -76440,7 +76440,7 @@
     ]
   },
   {
-    "comments": "This drug may also affect GABA-mediated synaptic transmission (https://go.drugbank.com/drugs/DB00555#BE0000013). However this is rather contentious, so it has not been annotated as such in here. Besides if the drug does modulate gamma-aminobutyric acid receptor it's a rather weak inhibition seen in animal models (yet to be determined in humans). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, note that this disease is denoted as Tonic-clonic seizure in the original file but known as Seizures in MESH.",
+    "comment": "This drug may also affect GABA-mediated synaptic transmission (https://go.drugbank.com/drugs/DB00555#BE0000013). However this is rather contentious, so it has not been annotated as such in here. Besides if the drug does modulate gamma-aminobutyric acid receptor it's a rather weak inhibition seen in animal models (yet to be determined in humans). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, note that this disease is denoted as Tonic-clonic seizure in the original file but known as Seizures in MESH.",
     "directed": true,
     "graph": {
       "_id": "DB00555_MESH_D012640_1",
@@ -76476,16 +76476,6 @@
         "source": "GO:0061535",
         "target": "HP:0020219"
       },
-      {
-        "key": "negatively correlated with",
-        "source": "GO:0061535",
-        "target": "MESH:D000066829"
-      },
-      {
-        "key": "negatively correlated with",
-        "source": "MESH:D000066829",
-        "target": "MESH:D012640"
-      },
       {
         "key": "positively correlated with",
         "source": "HP:0020219",
@@ -76519,11 +76509,6 @@
         "label": "PhenotypicFeature",
         "name": "Motor seizure"
       },
-      {
-        "id": "MESH:D000066829",
-        "label": "PhenotypicFeature",
-        "name": "Neuroprotection"
-      },
       {
         "id": "MESH:D012640",
         "label": "Disease",
@@ -76537,7 +76522,7 @@
     ]
   },
   {
-    "comments": "This drug may also affect GABA-mediated synaptic transmission (https://go.drugbank.com/drugs/DB00555#BE0000013). However this is rather contentious, so it has not been annotated as such in here. Besides if the drug does inhibit gamma-aminobutyric acid receptor it's a rather weak inhibition seen in animal models (yet to be determined in humans). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, this disease is denoted as Tonic-clonic seizure in the original file but known as Seizures in MESH.",
+    "comment": "This drug may also affect GABA-mediated synaptic transmission (https://go.drugbank.com/drugs/DB00555#BE0000013). However this is rather contentious, so it has not been annotated as such in here. Besides if the drug does inhibit gamma-aminobutyric acid receptor it's a rather weak inhibition seen in animal models (yet to be determined in humans). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, this disease is denoted as Tonic-clonic seizure in the original file but known as Seizures in MESH.",
     "directed": true,
     "graph": {
       "_id": "DB00555_MESH_D012640_2",
@@ -76578,16 +76563,6 @@
         "source": "GO:0061535",
         "target": "HP:0020219"
       },
-      {
-        "key": "negatively correlated with",
-        "source": "GO:0061535",
-        "target": "MESH:D000066829"
-      },
-      {
-        "key": "negatively correlated with",
-        "source": "MESH:D000066829",
-        "target": "MESH:D012640"
-      },
       {
         "key": "positively correlated with",
         "source": "HP:0020219",
@@ -76626,11 +76601,6 @@
         "label": "PhenotypicFeature",
         "name": "Motor seizure"
       },
-      {
-        "id": "MESH:D000066829",
-        "label": "PhenotypicFeature",
-        "name": "Neuroprotection"
-      },
       {
         "id": "MESH:D012640",
         "label": "Disease",
@@ -76647,7 +76617,7 @@
     ]
   },
   {
-    "comments": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, this disease is denoted as Simple partial seizure in the original file but known as Epilepsies, Partial in MESH.",
+    "comment": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, this disease is denoted as Simple partial seizure in the original file but known as Epilepsies, Partial in MESH.",
     "directed": true,
     "graph": {
       "_id": "DB00555_MESH_D004828_1",
@@ -76683,16 +76653,6 @@
         "source": "GO:0061535",
         "target": "HP:0032843"
       },
-      {
-        "key": "negatively correlated with",
-        "source": "GO:0061535",
-        "target": "MESH:D000066829"
-      },
-      {
-        "key": "negatively correlated with",
-        "source": "MESH:D000066829",
-        "target": "MESH:D004828"
-      },
       {
         "key": "positively correlated with",
         "source": "HP:0032843",
@@ -76726,11 +76686,6 @@
         "label": "PhenotypicFeature",
         "name": "Focal-onset epileptic spasm"
       },
-      {
-        "id": "MESH:D000066829",
-        "label": "PhenotypicFeature",
-        "name": "Neuroprotection"
-      },
       {
         "id": "MESH:D004828",
         "label": "Disease",
@@ -76745,7 +76700,7 @@
     ]
   },
   {
-    "comments": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, this disease is denoted as Simple partial seizure in the original file but known as Epilepsies, Partial in MESH.",
+    "comment": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, this disease is denoted as Simple partial seizure in the original file but known as Epilepsies, Partial in MESH.",
     "directed": true,
     "graph": {
       "_id": "DB00555_MESH_D004828_2",
@@ -76786,16 +76741,6 @@
         "source": "GO:0061535",
         "target": "HP:0032843"
       },
-      {
-        "key": "negatively correlated with",
-        "source": "GO:0061535",
-        "target": "MESH:D000066829"
-      },
-      {
-        "key": "negatively correlated with",
-        "source": "MESH:D000066829",
-        "target": "MESH:D004828"
-      },
       {
         "key": "positively correlated with",
         "source": "HP:0032843",
@@ -76834,11 +76779,6 @@
         "label": "PhenotypicFeature",
         "name": "Focal-onset epileptic spasm"
       },
-      {
-        "id": "MESH:D000066829",
-        "label": "PhenotypicFeature",
-        "name": "Neuroprotection"
-      },
       {
         "id": "MESH:D004828",
         "label": "Disease",
@@ -76855,7 +76795,7 @@
     ]
   },
   {
-    "comments": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).",
+    "comment": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).",
     "directed": true,
     "graph": {
       "_id": "DB00555_MESH_D065768_1",
@@ -76891,16 +76831,6 @@
         "source": "GO:0061535",
         "target": "HP:0032792"
       },
-      {
-        "key": "negatively correlated with",
-        "source": "GO:0061535",
-        "target": "MESH:D000066829"
-      },
-      {
-        "key": "negatively correlated with",
-        "source": "MESH:D000066829",
-        "target": "MESH:D065768"
-      },
       {
         "key": "positively correlated with",
         "source": "HP:0032792",
@@ -76934,11 +76864,6 @@
         "label": "PhenotypicFeature",
         "name": "Tonic seizure"
       },
-      {
-        "id": "MESH:D000066829",
-        "label": "PhenotypicFeature",
-        "name": "Neuroprotection"
-      },
       {
         "id": "MESH:D065768",
         "label": "Disease",
@@ -76953,7 +76878,7 @@
     ]
   },
   {
-    "comments": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).",
+    "comment": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).",
     "directed": true,
     "graph": {
       "_id": "DB00555_MESH_D065768_2",
@@ -76994,16 +76919,6 @@
         "source": "GO:0061535",
         "target": "HP:0032792"
       },
-      {
-        "key": "negatively correlated with",
-        "source": "GO:0061535",
-        "target": "MESH:D000066829"
-      },
-      {
-        "key": "negatively correlated with",
-        "source": "MESH:D000066829",
-        "target": "MESH:D065768"
-      },
       {
         "key": "positively correlated with",
         "source": "HP:0032792",
@@ -77042,11 +76957,6 @@
         "label": "PhenotypicFeature",
         "name": "Tonic seizure"
       },
-      {
-        "id": "MESH:D000066829",
-        "label": "PhenotypicFeature",
-        "name": "Neuroprotection"
-      },
       {
         "id": "MESH:D065768",
         "label": "Disease",
@@ -77063,7 +76973,7 @@
     ]
   },
   {
-    "comments": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).",
+    "comment": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).",
     "directed": true,
     "graph": {
       "_id": "DB00555_MESH_D004827_1",
@@ -77099,16 +77009,6 @@
         "source": "GO:0061535",
         "target": "HP:0020219"
       },
-      {
-        "key": "negatively correlated with",
-        "source": "GO:0061535",
-        "target": "MESH:D000066829"
-      },
-      {
-        "key": "negatively correlated with",
-        "source": "MESH:D000066829",
-        "target": "MESH:D004827"
-      },
       {
         "key": "positively correlated with",
         "source": "HP:0020219",
@@ -77142,11 +77042,6 @@
         "label": "PhenotypicFeature",
         "name": "Motor seizure"
       },
-      {
-        "id": "MESH:D000066829",
-        "label": "PhenotypicFeature",
-        "name": "Neuroprotection"
-      },
       {
         "id": "MESH:D004827",
         "label": "Disease",
@@ -77161,7 +77056,7 @@
     ]
   },
   {
-    "comments": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).",
+    "comment": "This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).",
     "directed": true,
     "graph": {
       "_id": "DB00555_MESH_D004827_2",
@@ -77202,16 +77097,6 @@
         "source": "GO:0061535",
         "target": "HP:0020219"
       },
-      {
-        "key": "negatively correlated with",
-        "source": "GO:0061535",
-        "target": "MESH:D000066829"
-      },
-      {
-        "key": "negatively correlated with",
-        "source": "MESH:D000066829",
-        "target": "MESH:D004827"
-      },
       {
         "key": "positively correlated with",
         "source": "HP:0020219",
@@ -77250,11 +77135,6 @@
         "label": "PhenotypicFeature",
         "name": "Motor seizure"
       },
-      {
-        "id": "MESH:D000066829",
-        "label": "PhenotypicFeature",
-        "name": "Neuroprotection"
-      },
       {
         "id": "MESH:D004827",
         "label": "Disease",
@@ -77271,7 +77151,6 @@
     ]
   },
   {
-    "comments": "The dopamine neurons are located in the mesolimbic dopaminergic system (BTO:0005591), which is a component pathway of the medial forebrain bundle (UBERON:0001910). See https://en.wikipedia.org/wiki/Medial_forebrain_bundle#Anatomy for more details.",
     "directed": true,
     "graph": {
       "_id": "DB00850_MESH_D012559_2",
@@ -77297,14 +77176,9 @@
         "source": "GO:0014046",
         "target": "CHEBI:18243"
       },
-      {
-        "key": "located in",
-        "source": "CHEBI:18243",
-        "target": "UBERON:0001910"
-      },
       {
         "key": "positively correlated with",
-        "source": "UBERON:0001910",
+        "source": "CHEBI:18243",
         "target": "MESH:D012559"
       }
     ],
@@ -77330,11 +77204,6 @@
         "label": "ChemicalSubstance",
         "name": "dopamine"
       },
-      {
-        "id": "UBERON:0001910",
-        "label": "GrossAnatomicalStructure",
-        "name": "mesolimbic dopaminergic system"
-      },
       {
         "id": "MESH:D012559",
         "label": "Disease",
@@ -86114,7 +85983,7 @@
     ]
   },
   {
-    "comments": "Muscarinic receptor antagonists (also known as anticholinergics) seem to be used in patients with Schizophrenia to alleviate motor side effects caused by first-generation antipsychotics. However these antagonists do seem to lead to cognitive dysfunction in healthy controls. So whether these muscarinic receptors should be positively or negatively regulated in schizophrenia is a matter of debate (see https://www.nature.com/articles/4001924 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726271/). In addition, some suggest that schizophrenia involves an overactivation of cholinergic neurons, which could provide cholinergic input to dopaminergic neurons. The dopamine neurons are located in the mesolimbic dopaminergic system (BTO:0005591), which is a component pathway of the medial forebrain bundle (UBERON:0001910). See https://en.wikipedia.org/wiki/Medial_forebrain_bundle#Anatomy for more details.",
+    "comment": "Muscarinic receptor antagonists (also known as anticholinergics) seem to be used in patients with Schizophrenia to alleviate motor side effects caused by first-generation antipsychotics. However these antagonists do seem to lead to cognitive dysfunction in healthy controls. So whether these muscarinic receptors should be positively or negatively regulated in schizophrenia is a matter of debate (see https://www.nature.com/articles/4001924 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726271/). In addition, some suggest that that schizophrenia involves an overactivation of cholinergic neurons, which could provide cholinergic input to dopaminergic neurons. The dopamine neurons are located in the mesolimbic dopaminergic system (BTO:0005591), which is a component pathway of the medial forebrain bundle (UBERON:0001910). See https://en.wikipedia.org/wiki/Medial_forebrain_bundle#Anatomy for more details.",
     "directed": true,
     "graph": {
       "_id": "DB01239_MESH_D012559_1",
@@ -86151,13 +86020,8 @@
         "target": "HP:0011442"
       },
       {
-        "key": "caused by",
+        "key": "manifestation of",
         "source": "HP:0011442",
-        "target": "MESH:D014150"
-      },
-      {
-        "key": "treats",
-        "source": "MESH:D014150",
         "target": "MESH:D012559"
       },
       {
@@ -86173,11 +86037,6 @@
       {
         "key": "positively correlated with",
         "source": "GO:0007213",
-        "target": "MESH:D059290"
-      },
-      {
-        "key": "positively regulates",
-        "source": "MESH:D059290",
         "target": "GO:0014046"
       },
       {
@@ -86186,23 +86045,8 @@
         "target": "GO:0014046"
       },
       {
-        "key": "increases abundance of",
+        "key": "positively correlated with",
         "source": "GO:0014046",
-        "target": "CHEBI:18243"
-      },
-      {
-        "key": "located in",
-        "source": "CHEBI:18243",
-        "target": "UBERON:0001910"
-      },
-      {
-        "key": "correlated with",
-        "source": "UBERON:0001910",
-        "target": "HP:0000746"
-      },
-      {
-        "key": "manifestation of",
-        "source": "HP:0000746",
         "target": "MESH:D012559"
       }
     ],
@@ -86248,31 +86092,6 @@
         "label": "PhenotypicFeature",
         "name": "Abnormal central motor function"
       },
-      {
-        "id": "CHEBI:18243",
-        "label": "ChemicalSubstance",
-        "name": "dopamine"
-      },
-      {
-        "id": "UBERON:0001910",
-        "label": "GrossAnatomicalStructure",
-        "name": "medial forebrain bundle"
-      },
-      {
-        "id": "HP:0000746",
-        "label": "PhenotypicFeature",
-        "name": "Delusions"
-      },
-      {
-        "id": "MESH:D059290",
-        "label": "Cell",
-        "name": "Dopaminergic Neurons"
-      },
-      {
-        "id": "MESH:D014150",
-        "label": "Drug",
-        "name": "Antipsychotic Agents"
-      },
       {
         "id": "MESH:D012559",
         "label": "Disease",
@@ -86312,30 +86131,15 @@
       {
         "key": "produces",
         "source": "MESH:D005753",
-        "target": "MESH:D009093"
-      },
-      {
-        "key": "negatively correlated with",
-        "source": "MESH:D009093",
-        "target": "MESH:D010437"
-      },
-      {
-        "key": "positively correlated with",
-        "source": "MESH:C061681",
-        "target": "MESH:D010437"
-      },
-      {
-        "key": "negatively correlated with",
-        "source": "MESH:C061681",
-        "target": "GO:0070254"
+        "target": "UBERON:0000912"
       },
       {
         "key": "negatively correlated with",
-        "source": "GO:0070254",
+        "source": "UBERON:0000912",
         "target": "MESH:D010437"
       },
       {
-        "key": "molecularly interacts with",
+        "key": "disrupts",
         "source": "MESH:C061681",
         "target": "CHEBI:16412"
       },
@@ -86402,11 +86206,6 @@
         "label": "BiologicalProcess",
         "name": "inflammatory response"
       },
-      {
-        "id": "GO:0070254",
-        "label": "BiologicalProcess",
-        "name": "mucus secretion"
-      },
       {
         "id": "UBERON:0001276",
         "label": "GrossAnatomicalStructure",
@@ -86433,8 +86232,8 @@
         "name": "gastric mucus glycoproteins"
       },
       {
-        "id": "MESH:D009093",
-        "label": "MacromolecularComplex",
+        "id": "UBERON:0000912",
+        "label": "GrossAnatomicalStructure",
         "name": "Mucus"
       },
       {
@@ -86451,7 +86250,7 @@
     "reference": [
       "https://go.drugbank.com/drugs/DB05265#mechanism-of-action",
       "https://en.wikipedia.org/wiki/Peptic_ulcer_disease#H._pylori",
-      "https://drugs.ncats.io/drug/2K02669KWP"
+      "https://drugs.ncats.io/drug/2K02669KW"
     ]
   },
   {
@@ -86531,7 +86330,7 @@
     ]
   },
   {
-    "comments": "The antihypertensive mechanism of chlorothiazide is not very well understood. References at https://go.drugbank.com/drugs/DB00880#BE0000267 seem to suggest the \"mechanism of action is achieved by meaans of pH changes\". Also note that \"the reduction in blood pressure of thiazides is not due to decreased blood volume resulting from increased urine production, but occurs through other mechanisms and at lower doses than that required to produce diuresis\" (https://en.wikipedia.org/wiki/Diuretic#Medical_uses).",
+    "comment": "The hypotensive effects of chlorothiazide and other thiazides are not necessarily due to their diuretic activity (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904515/#S1title). The exact mechanism is yet not fully understood.",
     "directed": true,
     "graph": {
       "_id": "DB00880_MESH_D006973_1",
@@ -86542,6 +86341,31 @@
       "drugbank": "DB:DB00880"
     },
     "links": [
+      {
+        "key": "decreases activity of",
+        "source": "MESH:D002740",
+        "target": "UniProt:P55017"
+      },
+      {
+        "key": "positively regulates",
+        "source": "UniProt:P55017",
+        "target": "GO:0070294"
+      },
+      {
+        "key": "positively correlated with",
+        "source": "GO:0070294",
+        "target": "GO:0003092"
+      },
+      {
+        "key": "positively correlated with",
+        "source": "GO:0003092",
+        "target": "HP:0033533"
+      },
+      {
+        "key": "positively correlated with",
+        "source": "HP:0033533",
+        "target": "HP:0032263"
+      },
       {
         "key": "decreases activity of",
         "source": "MESH:D002740",
@@ -86558,12 +86382,27 @@
         "target": "GO:0042310"
       },
       {
-        "key": "contributes to",
+        "key": "positively correlated with",
         "source": "GO:0042310",
         "target": "HP:0032263"
       },
       {
-        "key": "positively correlated with",
+        "key": "positively regulates",
+        "source": "MESH:D002740",
+        "target": "UniProt:Q12791"
+      },
+      {
+        "key": "positively regulates",
+        "source": "UniProt:Q12791",
+        "target": "GO:0060087"
+      },
+      {
+        "key": "negatively correlated with",
+        "source": "GO:0060087",
+        "target": "HP:0032263"
+      },
+      {
+        "key": "manifestation of",
         "source": "HP:0032263",
         "target": "MESH:D006973"
       }
@@ -86575,11 +86414,41 @@
         "label": "Drug",
         "name": "chlorothiazide"
       },
+      {
+        "id": "UniProt:P55017",
+        "label": "Protein",
+        "name": "Solute carrier family 12 member 3"
+      },
+      {
+        "id": "GO:0070294",
+        "label": "BiologicalProcess",
+        "name": "renal sodium ion absorption"
+      },
+      {
+        "id": "GO:0003092",
+        "label": "BiologicalProcess",
+        "name": "renal water retention"
+      },
+      {
+        "id": "HP:0033533",
+        "label": "PhenotypicFeature",
+        "name": "Increased cardiac output"
+      },
+      {
+        "id": "UniProt:Q12791",
+        "label": "Protein",
+        "name": "Calcium-activated potassium channel subunit alpha-1"
+      },
       {
         "id": "UniProt:P00918",
         "label": "Protein",
         "name": "Carbonic anhydrase 2"
       },
+      {
+        "id": "GO:0060087",
+        "label": "BiologicalProcess",
+        "name": "relaxation of vascular associated smooth muscle"
+      },
       {
         "id": "GO:0038166",
         "label": "BiologicalProcess",
@@ -86603,14 +86472,13 @@
     ],
     "reference": [
       "https://go.drugbank.com/drugs/DB00880#BE0000322",
-      "https://en.wikipedia.org/wiki/Thiazide#Hypertension",
-      "https://en.wikipedia.org/wiki/Chlorothiazide#Indications",
-      "https://en.wikipedia.org/wiki/Hypertension#Treatment",
-      "https://en.wikipedia.org/wiki/Blood_pressure#Regulation_of_blood_pressure"
+      "https://go.drugbank.com/drugs/DB00880#BE0000419",
+      "https://en.wikipedia.org/wiki/Category:Carbonic_anhydrase_inhibitors",
+      "https://pubchem.ncbi.nlm.nih.gov/compound/2720#section=Mechanism-of-Action"
     ]
   },
   {
-    "comments": "This drug may be able to bind to UniProt:P08908 but its pharmacological activity (agonism vs. antagonism) is not known (https://go.drugbank.com/drugs/DB00422#BE0000291).",
+    "comment": "This drug may be able to bind to UniProt:P08908 but its pharmacological activity (agonism vs. antagonism) is not known (https://go.drugbank.com/drugs/DB00422#BE0000291).",
     "directed": true,
     "graph": {
       "_id": "DB00422_MESH_D001289_1",
@@ -86692,7 +86560,7 @@
     ]
   },
   {
-    "comments": "This drug may be able to bind to UniProt:P08908 but its pharmacological activity (agonism vs. antagonism) is not known (https://go.drugbank.com/drugs/DB00422#BE0000291).",
+    "comment": "This drug may be able to bind to UniProt:P08908 but its pharmacological activity (agonism vs. antagonism) is not known (https://go.drugbank.com/drugs/DB00422#BE0000291).",
     "directed": true,
     "graph": {
       "_id": "DB00422_MESH_D009290_1",
@@ -87139,7 +87007,7 @@
     ]
   },
   {
-    "comments": "This drug can also inhbit human proteins and affect with the mammalian cell division/replication, which make them an attractive antitumour agent (https://pubmed.ncbi.nlm.nih.gov/11102564/).",
+    "comment": "This drug can also inhbit human proteins and affect with the mammalian cell division/replication, which make them an attractive antitumour agent (https://pubmed.ncbi.nlm.nih.gov/11102564/).",
     "directed": true,
     "graph": {
       "_id": "DB01179_MESH_D003218_1",
@@ -87441,13 +87309,13 @@
         "target": "GO:0044557"
       },
       {
-        "key": "positively correlated with",
+        "key": "negatively correlated with",
         "source": "GO:0044557",
-        "target": "MESH:D010410"
+        "target": "HP:0100639"
       },
       {
-        "key": "negatively correlated with",
-        "source": "MESH:D010410",
+        "key": "manifestation of",
+        "source": "HP:0100639",
         "target": "MESH:D007172"
       }
     ],
@@ -87487,9 +87355,9 @@
         "name": "relaxation of smooth muscle"
       },
       {
-        "id": "MESH:D010410",
+        "id": "HP:0100639",
         "label": "PhenotypicFeature",
-        "name": "Penile Erection"
+        "name": "Erectile dysfunction"
       },
       {
         "id": "MESH:D007172",
@@ -87547,11 +87415,11 @@
       {
         "key": "positively correlated with",
         "source": "GO:0035623",
-        "target": "MESH:D001786"
+        "target": "HP:0003074"
       },
       {
-        "key": "positively correlated with",
-        "source": "MESH:D001786",
+        "key": "manifestation of",
+        "source": "HP:0003074",
         "target": "MESH:D003924"
       }
     ],
@@ -87588,9 +87456,9 @@
         "name": "renal glucose absorption"
       },
       {
-        "id": "MESH:D001786",
+        "id": "HP:0003074",
         "label": "PhenotypicFeature",
-        "name": "Blood Glucose"
+        "name": "Hyperglycemia"
       },
       {
         "id": "MESH:D003924",
@@ -87620,18 +87488,13 @@
         "target": "UniProt:P25815"
       },
       {
-        "key": "molecularly interacts with",
+        "key": "positively correlated with",
         "source": "UniProt:P25815",
-        "target": "MESH:D000067759"
-      },
-      {
-        "key": "positively regulates",
-        "source": "MESH:D000067759",
         "target": "GO:0043303"
       },
       {
-        "key": "positively regulates",
-        "source": "MESH:D000067759",
+        "key": "positively correlated with",
+        "source": "UniProt:P25815",
         "target": "GO:0043308"
       },
       {
@@ -87677,11 +87540,6 @@
         "label": "Protein",
         "name": "Protein S100-P"
       },
-      {
-        "id": "MESH:D000067759",
-        "label": "Protein",
-        "name": "Receptor for Advanced Glycation End Products"
-      },
       {
         "id": "GO:0043303",
         "label": "BiologicalProcess",
@@ -87724,7 +87582,7 @@
     ]
   },
   {
-    "comments": "This condition does not seem to be a true ocular allergic reaction, rather caused by repeated mechanical irritation of the conjunctiva (https://en.wikipedia.org/wiki/Allergic_conjunctivitis#Giant_papillary_conjunctivitis). So the treatment with cromoglicic acid may not be needed/useful at all but interruption of contact lens wearing.",
+    "comment": "This condition does not seem to be a true ocular allergic reaction, rather caused by repeated mechanical irritation of the conjunctiva (https://en.wikipedia.org/wiki/Allergic_conjunctivitis#Giant_papillary_conjunctivitis). So the treatment with cromoglicic acid may not be needed/useful at all but interruption of contact lens wearing.",
     "directed": true,
     "graph": {
       "_id": "DB01003_MESH_D003233_1",
@@ -87741,18 +87599,13 @@
         "target": "UniProt:P25815"
       },
       {
-        "key": "molecularly interacts with",
+        "key": "positively correlated with",
         "source": "UniProt:P25815",
-        "target": "MESH:D000067759"
-      },
-      {
-        "key": "positively regulates",
-        "source": "MESH:D000067759",
         "target": "GO:0043303"
       },
       {
-        "key": "positively regulates",
-        "source": "MESH:D000067759",
+        "key": "positively correlated with",
+        "source": "UniProt:P25815",
         "target": "GO:0043308"
       },
       {
@@ -87798,11 +87651,6 @@
         "label": "Protein",
         "name": "Protein S100-P"
       },
-      {
-        "id": "MESH:D000067759",
-        "label": "Protein",
-        "name": "Receptor for Advanced Glycation End Products"
-      },
       {
         "id": "GO:0043303",
         "label": "BiologicalProcess",
@@ -87861,13 +87709,8 @@
         "target": "UniProt:P25815"
       },
       {
-        "key": "molecularly interacts with",
+        "key": "positively correlated with",
         "source": "UniProt:P25815",
-        "target": "MESH:D000067759"
-      },
-      {
-        "key": "positively regulates",
-        "source": "MESH:D000067759",
         "target": "GO:0043303"
       },
       {
@@ -87908,11 +87751,6 @@
         "label": "Protein",
         "name": "Protein S100-P"
       },
-      {
-        "id": "MESH:D000067759",
-        "label": "Protein",
-        "name": "Receptor for Advanced Glycation End Products"
-      },
       {
         "id": "GO:0043303",
         "label": "BiologicalProcess",
@@ -87967,13 +87805,8 @@
         "target": "UniProt:P25815"
       },
       {
-        "key": "molecularly interacts with",
+        "key": "positively correlated with",
         "source": "UniProt:P25815",
-        "target": "MESH:D000067759"
-      },
-      {
-        "key": "positively regulates",
-        "source": "MESH:D000067759",
         "target": "GO:0043303"
       },
       {
@@ -88014,11 +87847,6 @@
         "label": "Protein",
         "name": "Protein S100-P"
       },
-      {
-        "id": "MESH:D000067759",
-        "label": "Protein",
-        "name": "Receptor for Advanced Glycation End Products"
-      },
       {
         "id": "GO:0043303",
         "label": "BiologicalProcess",
@@ -94152,7 +93980,7 @@
     ]
   },
   {
-    "comments": "Different bacterial species can cause pneumonia, the most frequent ones are Streptococcus pneumoniae,\u00a0Staphylococcus aureus, and\u00a0Bacillus anthracis, among the gram-positive types of bacteria. Gram-negative examples of bacteria causing pneumonia are Haemophilus influenzae, Klebsiella pneumoniae and Escherichia coli.",
+    "comment": "Different bacterial species can cause pneumonia, the most frequent ones are Streptococcus pneumoniae,\u00a0Staphylococcus aureus, and\u00a0Bacillus anthracis, among the gram-positive types of bacteria. Gram-negative examples of bacteria causing pneumonia are Haemophilus influenzae, Klebsiella pneumoniae and Escherichia coli.",
     "directed": true,
     "graph": {
       "_id": "DB01137_MESH_D018410_1",
@@ -94397,7 +94225,7 @@
     ]
   },
   {
-    "comments": "Different bacterial species can cause pneumonia, the most frequent ones are Streptococcus pneumoniae,\u00a0Staphylococcus aureus, and\u00a0Bacillus anthracis, among the gram-positive types of bacteria. Gram-negative examples of bacteria causing pneumonia are Haemophilus influenzae, Klebsiella pneumoniae and Escherichia coli.",
+    "comment": "Different bacterial species can cause pneumonia, the most frequent ones are Streptococcus pneumoniae,\u00a0Staphylococcus aureus, and\u00a0Bacillus anthracis, among the gram-positive types of bacteria. Gram-negative examples of bacteria causing pneumonia are Haemophilus influenzae, Klebsiella pneumoniae and Escherichia coli.",
     "directed": true,
     "graph": {
       "_id": "DB01137_MESH_D011023_1",
@@ -94968,7 +94796,7 @@
     ]
   },
   {
-    "comments": "This drug is used in combination with dalfopristin. Both interfere with the bacterial protein synthesis, at different stages of the translation. Quinupristin inhibits the late phase of protein synthesis, whereas dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome. In combination, both drugs are more effective than each used individually (https://go.drugbank.com/drugs/DB01369#description).",
+    "comment": "This drug is used in combination with dalfopristin. Both interfere with the bacterial protein synthesis, at different stages of the translation. Quinupristin inhibits the late phase of protein synthesis, whereas dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome. In combination, both drugs are more effective than each used individually (https://go.drugbank.com/drugs/DB01369#description).",
     "directed": true,
     "graph": {
       "_id": "DB01369_MESH_D013290_1",
@@ -95204,7 +95032,7 @@
     },
     "links": [
       {
-        "key": "has metabolite",
+        "key": "produces",
         "source": "MESH:D007660",
         "target": "CHEBI:35628"
       },
@@ -95278,7 +95106,7 @@
       },
       {
         "id": "REACT:R-HSA-2162123",
-        "label": "Pathway",
+        "label": "BiologicalProcess",
         "name": "Synthesis of Prostaglandins (PG) and Thromboxanes (TX)"
       },
       {
@@ -95308,7 +95136,7 @@
     ]
   },
   {
-    "comments": "The activation of Atrial natriuretic peptide receptor 1 has been observed in vitro (https://pubmed.ncbi.nlm.nih.gov/12890708/) and it's reported in DrugBank whereas ChEMBL favours the Soluble Guanylyl Cyclase route. Also note that when the drug is admnistered at low doses, it dilates veins and reduces the volume of blood in the heart after filling (this is supposedly the main mechanism of action). At higher doses, it dilates arteries as well.",
+    "comment": "The activation of Atrial natriuretic peptide receptor 1 has been observed in vitro (https://pubmed.ncbi.nlm.nih.gov/12890708/) and it's reported in DrugBank whereas ChEMBL favours the Soluble Guanylyl Cyclase route. Also note that when the drug is admnistered at low doses, it dilates veins and reduces the volume of blood in the heart after filling (this is supposedly the main mechanism of action). At higher doses, it dilates arteries as well.",
     "directed": true,
     "graph": {
       "_id": "DB00727_MESH_D000787_1",
@@ -95327,21 +95155,11 @@
       {
         "key": "positively regulates",
         "source": "CHEBI:16480",
-        "target": "MESH:D000071756"
-      },
-      {
-        "key": "positively regulates",
-        "source": "MESH:D000071756",
-        "target": "GO:0019934"
-      },
-      {
-        "key": "positively regulates",
-        "source": "MESH:D000071756",
-        "target": "GO:0019934"
+        "target": "GO:0038060"
       },
       {
         "key": "positively correlated with",
-        "source": "GO:0019934",
+        "source": "GO:0038060",
         "target": "GO:0042311"
       },
       {
@@ -95352,7 +95170,12 @@
       {
         "key": "positively regulates",
         "source": "UniProt:P16066",
-        "target": "GO:0019934"
+        "target": "GO:0007168"
+      },
+      {
+        "key": "positively correlated with",
+        "source": "GO:0007168",
+        "target": "GO:0042311"
       },
       {
         "key": "negatively correlated with",
@@ -95381,14 +95204,14 @@
         "name": "Atrial natriuretic peptide receptor 1"
       },
       {
-        "id": "MESH:D000071756",
-        "label": "Protein",
-        "name": "Soluble Guanylyl Cyclase"
+        "id": "GO:0038060",
+        "label": "BiologicalProcess",
+        "name": "nitric oxide-cGMP-mediated signaling pathway"
       },
       {
-        "id": "GO:0019934",
+        "id": "GO:0007168",
         "label": "BiologicalProcess",
-        "name": "cGMP-mediated signaling"
+        "name": "receptor guanylyl cyclase signaling pathway"
       },
       {
         "id": "GO:0042311",
@@ -95498,7 +95321,7 @@
     ]
   },
   {
-    "comments": "There appears to be no connection between Niacin deficiency and nicotine. Although niacin and nicotine are somehow related (nicotine can turn into nicotinic acid via oxidation), nicotine may not be able to replace niacin as treatment for Niacin deficiency. Actually nicotine could compete with niacin for binding sites in the enzymes necessary for vitamin B3 metabolism, and therefore would decrease the amount of B3 available for the cells.",
+    "comment": "There appears to be no connection between Niacin deficiency and nicotine. Although niacin and nicotine are somehow related (nicotine can turn into nicotinic acid via oxidation), nicotine may not be able to replace niacin as treatment for Niacin deficiency. Actually nicotine could compete with niacin for binding sites in the enzymes necessary for vitamin B3 metabolism, and therefore would decrease the amount of B3 available for the cells.",
     "directed": true,
     "graph": {
       "_id": "DB00184_MESH_D010383_1",
@@ -95539,7 +95362,7 @@
     ]
   },
   {
-    "comments": "Both DrugBank (https://go.drugbank.com/drugs/DB06718#mechanism-of-action) and ChEMBL (https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2079587/) have this drug modulating target AR (UniProt:P10275) but that's not the mechanism of action for this disease (MESH:D054179).",
+    "comment": "Both DrugBank (https://go.drugbank.com/drugs/DB06718#mechanism-of-action) and ChEMBL (https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2079587/) have this drug modulating target AR (UniProt:P10275) but that's not the mechanism of action for this indication (MESH:D054179).",
     "directed": true,
     "graph": {
       "_id": "DB06718_MESH_D054179_1",
@@ -95563,7 +95386,7 @@
       {
         "key": "positively correlated with",
         "source": "GO:0006956",
-        "target": "MESH:D001920"
+        "target": "Pfam:PF06753"
       },
       {
         "key": "negatively correlated with",
@@ -95573,16 +95396,16 @@
       {
         "key": "positively correlated with",
         "source": "MESH:D007610",
-        "target": "MESH:D001920"
+        "target": "Pfam:PF06753"
       },
       {
         "key": "positively correlated with",
-        "source": "MESH:D001920",
+        "source": "Pfam:PF06753",
         "target": "MESH:D002199"
       },
       {
         "key": "positively correlated with",
-        "source": "MESH:D001920",
+        "source": "Pfam:PF06753",
         "target": "GO:0042311"
       },
       {
@@ -95620,12 +95443,12 @@
       },
       {
         "id": "MESH:D007610",
-        "label": "Protein",
+        "label": "GeneFamily",
         "name": "Kallikreins"
       },
       {
-        "id": "MESH:D001920",
-        "label": "Protein",
+        "id": "Pfam:PF06753",
+        "label": "GeneFamily",
         "name": "Bradykinin"
       },
       {
@@ -95797,7 +95620,6 @@
     ]
   },
   {
-    "comments": "Phenoxybenzamine is an alpha blocker (https://en.wikipedia.org/wiki/Alpha_blocker#Pheochromocytoma https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL753/).",
     "directed": true,
     "graph": {
       "_id": "DB06718_MESH_D010673_1",
@@ -95811,11 +95633,61 @@
       {
         "key": "decreases activity of",
         "source": "MESH:D010643",
-        "target": "MESH:D011942"
+        "target": "UniProt:P35348"
+      },
+      {
+        "key": "decreases activity of",
+        "source": "MESH:D010643",
+        "target": "UniProt:P08913"
+      },
+      {
+        "key": "decreases activity of",
+        "source": "MESH:D010643",
+        "target": "UniProt:P18825"
+      },
+      {
+        "key": "decreases activity of",
+        "source": "MESH:D010643",
+        "target": "UniProt:P25100"
+      },
+      {
+        "key": "decreases activity of",
+        "source": "MESH:D010643",
+        "target": "UniProt:P35368"
+      },
+      {
+        "key": "decreases activity of",
+        "source": "MESH:D010643",
+        "target": "UniProt:P18089"
       },
       {
         "key": "positively regulates",
-        "source": "MESH:D011942",
+        "source": "UniProt:P35348",
+        "target": "GO:0042310"
+      },
+      {
+        "key": "regulates",
+        "source": "UniProt:P08913",
+        "target": "GO:0042310"
+      },
+      {
+        "key": "positively regulates",
+        "source": "UniProt:P18825",
+        "target": "GO:0042310"
+      },
+      {
+        "key": "positively regulates",
+        "source": "UniProt:P25100",
+        "target": "GO:0042310"
+      },
+      {
+        "key": "positively regulates",
+        "source": "UniProt:P35368",
+        "target": "GO:0042310"
+      },
+      {
+        "key": "positively regulates",
+        "source": "UniProt:P18089",
         "target": "GO:0042310"
       },
       {
@@ -95842,9 +95714,34 @@
         "name": "phenoxybenzamine"
       },
       {
-        "id": "MESH:D011942",
-        "label": "GeneFamily",
-        "name": "Receptors, Adrenergic, alpha"
+        "id": "UniProt:P35348",
+        "label": "Protein",
+        "name": "Alpha-1A adrenergic receptor"
+      },
+      {
+        "id": "UniProt:P08913",
+        "label": "Protein",
+        "name": "Alpha-2A adrenergic receptor"
+      },
+      {
+        "id": "UniProt:P18825",
+        "label": "Protein",
+        "name": "Alpha-2C adrenergic receptor"
+      },
+      {
+        "id": "UniProt:P25100",
+        "label": "Protein",
+        "name": "Alpha-1D adrenergic receptor"
+      },
+      {
+        "id": "UniProt:P18089",
+        "label": "Protein",
+        "name": "Alpha-2B adrenergic receptor"
+      },
+      {
+        "id": "UniProt:P35368",
+        "label": "Protein",
+        "name": "Alpha-1B adrenergic receptor"
       },
       {
         "id": "GO:0042310",
@@ -95869,6 +95766,7 @@
     ],
     "reference": [
       "https://go.drugbank.com/drugs/DB00925#mechanism-of-action",
+      "https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL753/",
       "https://en.wikipedia.org/wiki/Alpha_blocker#Hypertension",
       "https://en.wikipedia.org/wiki/Phenoxybenzamine#Pharmacology",
       "https://en.wikipedia.org/wiki/Pheochromocytoma#Alpha_blockade"
diff --git a/indication_paths.yaml b/indication_paths.yaml
index 43f300b04..6fc832400 100644
--- a/indication_paths.yaml
+++ b/indication_paths.yaml
@@ -46822,10 +46822,10 @@
     reference:
     - https://pubchem.ncbi.nlm.nih.gov/compound/3651
     - https://go.drugbank.com/drugs/DB09352
--   comments: Heme (MESH:D006418) and hemin (MESH:D006427) are related substances
-        resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas
-        hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also
-        known as hematin.
+-   comment: Heme (MESH:D006418) and hemin (MESH:D006427) are related substances resulting
+        from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin
+        is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known
+        as hematin.
     directed: true
     graph:
         _id: DB12975_MESH_D016780_1
@@ -46867,10 +46867,10 @@
     reference:
     - https://www.ema.europa.eu/en/documents/medicine-outside-eu/pyramax-product-information_en.pdf
     - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483207/
--   comments: Hemin (MESH:D006427) and heme (MESH:D006418) are related substances
-        resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas
-        hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also
-        known as hematin.
+-   comment: Hemin (MESH:D006427) and heme (MESH:D006418) are related substances resulting
+        from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin
+        is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known
+        as hematin.
     directed: true
     graph:
         _id: DB12975_MESH_D016780_2
@@ -46888,9 +46888,9 @@
         target: CL:0000232
     -   key: location of
         source: CL:0000232
-        target: MESH:D012100
+        target: GO:0019954
     -   key: in taxon
-        source: MESH:D012100
+        source: GO:0019954
         target: NCBITaxon:5855
     -   key: causes
         source: NCBITaxon:5855
@@ -46906,9 +46906,9 @@
     -   id: CL:0000232
         label: Cell
         name: erythrocyte
-    -   id: MESH:D012100
+    -   id: GO:0019954
         label: BiologicalProcess
-        name: Reproduction, Asexual
+        name: asexual reproduction
     -   id: NCBITaxon:5855
         label: OrganismTaxon
         name: Plasmodium vivax
@@ -46917,10 +46917,10 @@
         name: Malaria, Vivax
     reference:
     - https://www.ema.europa.eu/en/documents/medicine-outside-eu/pyramax-product-information_en.pdf
--   comments: Heme (MESH:D006418) and hemin (MESH:D006427) are related substances
-        resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas
-        hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also
-        known as hematin.
+-   comment: Heme (MESH:D006418) and hemin (MESH:D006427) are related substances resulting
+        from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin
+        is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known
+        as hematin.
     directed: true
     graph:
         _id: DB12975_MESH_D016778_1
@@ -46962,10 +46962,10 @@
     reference:
     - https://www.ema.europa.eu/en/documents/medicine-outside-eu/pyramax-product-information_en.pdf
     - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483207/
--   comments: Hemin (MESH:D006427) and heme (MESH:D006418) are related substances
-        resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas
-        hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also
-        known as hematin.
+-   comment: Hemin (MESH:D006427) and heme (MESH:D006418) are related substances resulting
+        from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin
+        is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known
+        as hematin.
     directed: true
     graph:
         _id: DB12975_MESH_D016778_2
@@ -46983,9 +46983,9 @@
         target: CL:0000232
     -   key: location of
         source: CL:0000232
-        target: MESH:D012100
+        target: GO:0019954
     -   key: in taxon
-        source: MESH:D012100
+        source: GO:0019954
         target: NCBITaxon:5833
     -   key: causes
         source: NCBITaxon:5833
@@ -47001,9 +47001,9 @@
     -   id: CL:0000232
         label: Cell
         name: erythrocyte
-    -   id: MESH:D012100
+    -   id: GO:0019954
         label: BiologicalProcess
-        name: Reproduction, Asexual
+        name: asexual reproduction
     -   id: NCBITaxon:5833
         label: OrganismTaxon
         name: Plasmodium falciparum
@@ -47062,7 +47062,7 @@
     reference:
     - https://go.drugbank.com/drugs/DB09353#mechanism-of-action
     - https://en.wikipedia.org/wiki/Seborrhoeic_dermatitis#Causes
--   comments: The disease is denoted as Acute necrotizing ulcerative gingivitis in
+-   comment: The disease is denoted as Acute necrotizing ulcerative gingivitis in
         the original file but the name used for the path is the one seen in the MESH
         website.
     directed: true
@@ -47124,7 +47124,7 @@
     reference:
     - https://go.drugbank.com/drugs/DB09353#mechanism-of-action
     - https://en.wikipedia.org/wiki/Acute_necrotizing_ulcerative_gingivitis#Causes
--   comments: "Sulfur's usefulness as a topical remedy for acne dates back to at least\
+-   comment: "Sulfur's usefulness as a topical remedy for acne dates back to at least\
         \ the reign of Cleopatra i.e. 69\u201330 BCE (https://en.wikipedia.org/wiki/Acne#History)."
     directed: true
     graph:
@@ -47181,7 +47181,7 @@
         name: Acne vulgaris
     reference:
     - https://go.drugbank.com/drugs/DB09353#mechanism-of-action
--   comments: The disease is denoted as Aphthous ulcer of mouth in the original file
+-   comment: The disease is denoted as Aphthous ulcer of mouth in the original file
         but the name used for the path is the one seen in the MESH website. The causes
         for this disease are not well known (https://ada.com/conditions/aphthous-ulcers/#causes).
         It's important to prevent secondary infection of the ulcers (https://en.wikipedia.org/wiki/Aphthous_stomatitis#Medication);
@@ -47590,7 +47590,7 @@
     reference:
     - https://go.drugbank.com/drugs/DB01416#mechanism-of-action
     - https://en.wikipedia.org/wiki/Gonorrhea#Cause
--   comments: This disease is denoted as Streptococcus pyogenes infection in the original
+-   comment: This disease is denoted as Streptococcus pyogenes infection in the original
         file but it's named Streptococcal Infections by MESH.
     directed: true
     graph:
@@ -47649,12 +47649,12 @@
         name: Streptococcal Infections
     reference:
     - https://go.drugbank.com/drugs/DB01416#mechanism-of-action
--   comments: The disease is denoted Hot Flashes in MESH. The etiology of hot flashes
-        has yet to be determined (https://pubmed.ncbi.nlm.nih.gov/15065632/).
+-   comment: The disease is denoted Menopausal flushing in the original file but Hot
+        flashes in MESH. The etiology of hot flashes has yet to be determined (https://pubmed.ncbi.nlm.nih.gov/15065632/).
     directed: true
     graph:
         _id: DB06710_MESH_D019584_1
-        disease: Menopausal flushing
+        disease: Menopausal Flushing
         disease_mesh: MESH:D019584
         drug: methyltestosterone
         drug_mesh: MESH:D008777
@@ -47721,14 +47721,14 @@
         name: Temperature instability
     -   id: MESH:D019584
         label: Disease
-        name: Menopausal flushing
+        name: Menopausal Flushing
     reference:
     - https://go.drugbank.com/drugs/DB06710#mechanism-of-action
     - https://en.wikipedia.org/wiki/Methyltestosterone#Pharmacodynamics
     - https://en.wikipedia.org/wiki/Methylestradiol#Pharmacodynamics
     - https://en.wikipedia.org/wiki/Hot_flash#Mechanism
     - https://academic.oup.com/jcem/article/100/11/3975/2836060
--   comments: MESH:D005058 is named male hypogonadism in the original file.
+-   comment: MESH:D005058 is named male hypogonadism in the original file.
     directed: true
     graph:
         _id: DB06710_MESH_D005058_1
@@ -47869,7 +47869,7 @@
     reference:
     - https://go.drugbank.com/drugs/DB06710#mechanism-of-action
     - https://en.wikipedia.org/wiki/Delayed_pubertydrugs/DB06710#mechanism-of-action
--   comments: This drug may also affect GABA-mediated synaptic transmission (https://go.drugbank.com/drugs/DB00555#BE0000013).
+-   comment: This drug may also affect GABA-mediated synaptic transmission (https://go.drugbank.com/drugs/DB00555#BE0000013).
         However this is rather contentious, so it has not been annotated as such in
         here. Besides if the drug does modulate gamma-aminobutyric acid receptor it's
         a rather weak inhibition seen in animal models (yet to be determined in humans).
@@ -47901,12 +47901,6 @@
     -   key: positively correlated with
         source: GO:0061535
         target: HP:0020219
-    -   key: negatively correlated with
-        source: GO:0061535
-        target: MESH:D000066829
-    -   key: negatively correlated with
-        source: MESH:D000066829
-        target: MESH:D012640
     -   key: positively correlated with
         source: HP:0020219
         target: MESH:D012640
@@ -47927,9 +47921,6 @@
     -   id: HP:0020219
         label: PhenotypicFeature
         name: Motor seizure
-    -   id: MESH:D000066829
-        label: PhenotypicFeature
-        name: Neuroprotection
     -   id: MESH:D012640
         label: Disease
         name: Seizures
@@ -47937,7 +47928,7 @@
     - https://go.drugbank.com/drugs/DB00555#mechanism-of-action
     - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
     - https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)#Disease,_disabilities,_and_pharmacology
--   comments: This drug may also affect GABA-mediated synaptic transmission (https://go.drugbank.com/drugs/DB00555#BE0000013).
+-   comment: This drug may also affect GABA-mediated synaptic transmission (https://go.drugbank.com/drugs/DB00555#BE0000013).
         However this is rather contentious, so it has not been annotated as such in
         here. Besides if the drug does inhibit gamma-aminobutyric acid receptor it's
         a rather weak inhibition seen in animal models (yet to be determined in humans).
@@ -47972,12 +47963,6 @@
     -   key: positively correlated with
         source: GO:0061535
         target: HP:0020219
-    -   key: negatively correlated with
-        source: GO:0061535
-        target: MESH:D000066829
-    -   key: negatively correlated with
-        source: MESH:D000066829
-        target: MESH:D012640
     -   key: positively correlated with
         source: HP:0020219
         target: MESH:D012640
@@ -48001,9 +47986,6 @@
     -   id: HP:0020219
         label: PhenotypicFeature
         name: Motor seizure
-    -   id: MESH:D000066829
-        label: PhenotypicFeature
-        name: Neuroprotection
     -   id: MESH:D012640
         label: Disease
         name: Seizures
@@ -48014,7 +47996,7 @@
     - https://pubmed.ncbi.nlm.nih.gov/9579933/
     - https://en.wikipedia.org/wiki/Anticonvulsant
     - https://en.wikipedia.org/wiki/Neuroprotection
--   comments: This drug may also affect GABA-mediated synaptic transmission as listed
+-   comment: This drug may also affect GABA-mediated synaptic transmission as listed
         by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this
         is contentious and if the drug does modulate GABA it's not known whether it
         is as agonist or antagonist due to conflicting data (at best it would be a
@@ -48047,12 +48029,6 @@
     -   key: positively correlated with
         source: GO:0061535
         target: HP:0032843
-    -   key: negatively correlated with
-        source: GO:0061535
-        target: MESH:D000066829
-    -   key: negatively correlated with
-        source: MESH:D000066829
-        target: MESH:D004828
     -   key: positively correlated with
         source: HP:0032843
         target: MESH:D004828
@@ -48073,9 +48049,6 @@
     -   id: HP:0032843
         label: PhenotypicFeature
         name: Focal-onset epileptic spasm
-    -   id: MESH:D000066829
-        label: PhenotypicFeature
-        name: Neuroprotection
     -   id: MESH:D004828
         label: Disease
         name: Epilepsies, Partial
@@ -48084,7 +48057,7 @@
     - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
     - https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)#Disease,_disabilities,_and_pharmacology
     - https://en.wikipedia.org/wiki/Focal_seizure
--   comments: This drug may also affect GABA-mediated synaptic transmission as listed
+-   comment: This drug may also affect GABA-mediated synaptic transmission as listed
         by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this
         is contentious and if the drug does modulate GABA it's not known whether it
         is as agonist or antagonist due to conflicting data (at best it would be a
@@ -48120,12 +48093,6 @@
     -   key: positively correlated with
         source: GO:0061535
         target: HP:0032843
-    -   key: negatively correlated with
-        source: GO:0061535
-        target: MESH:D000066829
-    -   key: negatively correlated with
-        source: MESH:D000066829
-        target: MESH:D004828
     -   key: positively correlated with
         source: HP:0032843
         target: MESH:D004828
@@ -48149,9 +48116,6 @@
     -   id: HP:0032843
         label: PhenotypicFeature
         name: Focal-onset epileptic spasm
-    -   id: MESH:D000066829
-        label: PhenotypicFeature
-        name: Neuroprotection
     -   id: MESH:D004828
         label: Disease
         name: Epilepsies, Partial
@@ -48162,7 +48126,7 @@
     - https://pubmed.ncbi.nlm.nih.gov/9579933/
     - https://en.wikipedia.org/wiki/Anticonvulsant
     - https://en.wikipedia.org/wiki/Neuroprotection
--   comments: This drug may also affect GABA-mediated synaptic transmission as listed
+-   comment: This drug may also affect GABA-mediated synaptic transmission as listed
         by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this
         is contentious and if the drug does modulate GABA it's not known whether it
         is as agonist or antagonist due to conflicting data (at best it would be a
@@ -48193,12 +48157,6 @@
     -   key: positively correlated with
         source: GO:0061535
         target: HP:0032792
-    -   key: negatively correlated with
-        source: GO:0061535
-        target: MESH:D000066829
-    -   key: negatively correlated with
-        source: MESH:D000066829
-        target: MESH:D065768
     -   key: positively correlated with
         source: HP:0032792
         target: MESH:D065768
@@ -48219,9 +48177,6 @@
     -   id: HP:0032792
         label: PhenotypicFeature
         name: Tonic seizure
-    -   id: MESH:D000066829
-        label: PhenotypicFeature
-        name: Neuroprotection
     -   id: MESH:D065768
         label: Disease
         name: Lennox-Gastaut syndrome
@@ -48230,7 +48185,7 @@
     - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
     - https://en.wikipedia.org/wiki/Lennox%E2%80%93Gastaut_syndrome#Signs_and_symptoms
     - https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)#Disease,_disabilities,_and_pharmacology
--   comments: This drug may also affect GABA-mediated synaptic transmission as listed
+-   comment: This drug may also affect GABA-mediated synaptic transmission as listed
         by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this
         is contentious and if the drug does modulate GABA it's not known whether it
         is as agonist or antagonist due to conflicting data (at best it would be a
@@ -48264,12 +48219,6 @@
     -   key: positively correlated with
         source: GO:0061535
         target: HP:0032792
-    -   key: negatively correlated with
-        source: GO:0061535
-        target: MESH:D000066829
-    -   key: negatively correlated with
-        source: MESH:D000066829
-        target: MESH:D065768
     -   key: positively correlated with
         source: HP:0032792
         target: MESH:D065768
@@ -48293,9 +48242,6 @@
     -   id: HP:0032792
         label: PhenotypicFeature
         name: Tonic seizure
-    -   id: MESH:D000066829
-        label: PhenotypicFeature
-        name: Neuroprotection
     -   id: MESH:D065768
         label: Disease
         name: Lennox-Gastaut syndrome
@@ -48306,7 +48252,7 @@
     - https://pubmed.ncbi.nlm.nih.gov/9579933/
     - https://en.wikipedia.org/wiki/Anticonvulsant
     - https://en.wikipedia.org/wiki/Neuroprotection
--   comments: This drug may also affect GABA-mediated synaptic transmission as listed
+-   comment: This drug may also affect GABA-mediated synaptic transmission as listed
         by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this
         is contentious and if the drug does modulate GABA it's not known whether it
         is as agonist or antagonist due to conflicting data (at best it would be a
@@ -48337,12 +48283,6 @@
     -   key: positively correlated with
         source: GO:0061535
         target: HP:0020219
-    -   key: negatively correlated with
-        source: GO:0061535
-        target: MESH:D000066829
-    -   key: negatively correlated with
-        source: MESH:D000066829
-        target: MESH:D004827
     -   key: positively correlated with
         source: HP:0020219
         target: MESH:D004827
@@ -48363,9 +48303,6 @@
     -   id: HP:0020219
         label: PhenotypicFeature
         name: Motor seizure
-    -   id: MESH:D000066829
-        label: PhenotypicFeature
-        name: Neuroprotection
     -   id: MESH:D004827
         label: Disease
         name: Epilepsy
@@ -48374,7 +48311,7 @@
     - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
     - https://en.wikipedia.org/wiki/Lennox%E2%80%93Gastaut_syndrome#Signs_and_symptoms
     - https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)#Disease,_disabilities,_and_pharmacology
--   comments: This drug may also affect GABA-mediated synaptic transmission as listed
+-   comment: This drug may also affect GABA-mediated synaptic transmission as listed
         by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this
         is contentious and if the drug does modulate GABA it's not known whether it
         is as agonist or antagonist due to conflicting data (at best it would be a
@@ -48408,12 +48345,6 @@
     -   key: positively correlated with
         source: GO:0061535
         target: HP:0020219
-    -   key: negatively correlated with
-        source: GO:0061535
-        target: MESH:D000066829
-    -   key: negatively correlated with
-        source: MESH:D000066829
-        target: MESH:D004827
     -   key: positively correlated with
         source: HP:0020219
         target: MESH:D004827
@@ -48437,9 +48368,6 @@
     -   id: HP:0020219
         label: PhenotypicFeature
         name: Motor seizure
-    -   id: MESH:D000066829
-        label: PhenotypicFeature
-        name: Neuroprotection
     -   id: MESH:D004827
         label: Disease
         name: Epilepsy
@@ -48450,11 +48378,7 @@
     - https://pubmed.ncbi.nlm.nih.gov/9579933/
     - https://en.wikipedia.org/wiki/Anticonvulsant
     - https://en.wikipedia.org/wiki/Neuroprotection
--   comments: The dopamine neurons are located in the mesolimbic dopaminergic system
-        (BTO:0005591), which is a component pathway of the medial forebrain bundle
-        (UBERON:0001910). See https://en.wikipedia.org/wiki/Medial_forebrain_bundle#Anatomy
-        for more details.
-    directed: true
+-   directed: true
     graph:
         _id: DB00850_MESH_D012559_2
         disease: Schizophrenia
@@ -48472,11 +48396,8 @@
     -   key: increases abundance of
         source: GO:0014046
         target: CHEBI:18243
-    -   key: located in
-        source: CHEBI:18243
-        target: UBERON:0001910
     -   key: positively correlated with
-        source: UBERON:0001910
+        source: CHEBI:18243
         target: MESH:D012559
     multigraph: true
     nodes:
@@ -48492,9 +48413,6 @@
     -   id: CHEBI:18243
         label: ChemicalSubstance
         name: dopamine
-    -   id: UBERON:0001910
-        label: GrossAnatomicalStructure
-        name: mesolimbic dopaminergic system
     -   id: MESH:D012559
         label: Disease
         name: Schizophrenia
@@ -54010,14 +53928,14 @@
         name: Acne vulgaris
     reference:
     - https://en.wikipedia.org/wiki/Nicotinamide#Acne
--   comments: Muscarinic receptor antagonists (also known as anticholinergics) seem
+-   comment: Muscarinic receptor antagonists (also known as anticholinergics) seem
         to be used in patients with Schizophrenia to alleviate motor side effects
         caused by first-generation antipsychotics. However these antagonists do seem
         to lead to cognitive dysfunction in healthy controls. So whether these muscarinic
         receptors should be positively or negatively regulated in schizophrenia is
         a matter of debate (see https://www.nature.com/articles/4001924 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726271/).
-        In addition, some suggest that schizophrenia involves an overactivation of
-        cholinergic neurons, which could provide cholinergic input to dopaminergic
+        In addition, some suggest that that schizophrenia involves an overactivation
+        of cholinergic neurons, which could provide cholinergic input to dopaminergic
         neurons. The dopamine neurons are located in the mesolimbic dopaminergic system
         (BTO:0005591), which is a component pathway of the medial forebrain bundle
         (UBERON:0001910). See https://en.wikipedia.org/wiki/Medial_forebrain_bundle#Anatomy
@@ -54046,11 +53964,8 @@
     -   key: positively correlated with
         source: GO:0007274
         target: HP:0011442
-    -   key: caused by
+    -   key: manifestation of
         source: HP:0011442
-        target: MESH:D014150
-    -   key: treats
-        source: MESH:D014150
         target: MESH:D012559
     -   key: positively regulates
         source: InterPro:IPR002231
@@ -54060,24 +53975,12 @@
         target: GO:0007213
     -   key: positively correlated with
         source: GO:0007213
-        target: MESH:D059290
-    -   key: positively regulates
-        source: MESH:D059290
         target: GO:0014046
     -   key: positively regulates
         source: InterPro:IPR000929
         target: GO:0014046
-    -   key: increases abundance of
+    -   key: positively correlated with
         source: GO:0014046
-        target: CHEBI:18243
-    -   key: located in
-        source: CHEBI:18243
-        target: UBERON:0001910
-    -   key: correlated with
-        source: UBERON:0001910
-        target: HP:0000746
-    -   key: manifestation of
-        source: HP:0000746
         target: MESH:D012559
     multigraph: true
     nodes:
@@ -54105,21 +54008,6 @@
     -   id: HP:0011442
         label: PhenotypicFeature
         name: Abnormal central motor function
-    -   id: CHEBI:18243
-        label: ChemicalSubstance
-        name: dopamine
-    -   id: UBERON:0001910
-        label: GrossAnatomicalStructure
-        name: medial forebrain bundle
-    -   id: HP:0000746
-        label: PhenotypicFeature
-        name: Delusions
-    -   id: MESH:D059290
-        label: Cell
-        name: Dopaminergic Neurons
-    -   id: MESH:D014150
-        label: Drug
-        name: Antipsychotic Agents
     -   id: MESH:D012559
         label: Disease
         name: Schizophrenia
@@ -54147,20 +54035,11 @@
         target: MESH:D005753
     -   key: produces
         source: MESH:D005753
-        target: MESH:D009093
-    -   key: negatively correlated with
-        source: MESH:D009093
-        target: MESH:D010437
-    -   key: positively correlated with
-        source: MESH:C061681
-        target: MESH:D010437
-    -   key: negatively correlated with
-        source: MESH:C061681
-        target: GO:0070254
+        target: UBERON:0000912
     -   key: negatively correlated with
-        source: GO:0070254
+        source: UBERON:0000912
         target: MESH:D010437
-    -   key: molecularly interacts with
+    -   key: disrupts
         source: MESH:C061681
         target: CHEBI:16412
     -   key: positively regulates
@@ -54201,9 +54080,6 @@
     -   id: GO:0006954
         label: BiologicalProcess
         name: inflammatory response
-    -   id: GO:0070254
-        label: BiologicalProcess
-        name: mucus secretion
     -   id: UBERON:0001276
         label: GrossAnatomicalStructure
         name: epithelium of stomach
@@ -54219,8 +54095,8 @@
     -   id: MESH:C047874
         label: GeneFamily
         name: gastric mucus glycoproteins
-    -   id: MESH:D009093
-        label: MacromolecularComplex
+    -   id: UBERON:0000912
+        label: GrossAnatomicalStructure
         name: Mucus
     -   id: MESH:D005753
         label: GrossAnatomicalStructure
@@ -54231,7 +54107,7 @@
     reference:
     - https://go.drugbank.com/drugs/DB05265#mechanism-of-action
     - https://en.wikipedia.org/wiki/Peptic_ulcer_disease#H._pylori
-    - https://drugs.ncats.io/drug/2K02669KWP
+    - https://drugs.ncats.io/drug/2K02669KW
 -   directed: true
     graph:
         _id: DB00880_MESH_D004487_1
@@ -54280,12 +54156,9 @@
     - https://go.drugbank.com/drugs/DB00880#BE0000419
     - https://en.wikipedia.org/wiki/Diuretic#Thiazides
     - https://en.wikipedia.org/wiki/Thiazide
--   comments: The antihypertensive mechanism of chlorothiazide is not very well understood.
-        References at https://go.drugbank.com/drugs/DB00880#BE0000267 seem to suggest
-        the "mechanism of action is achieved by meaans of pH changes". Also note that
-        "the reduction in blood pressure of thiazides is not due to decreased blood
-        volume resulting from increased urine production, but occurs through other
-        mechanisms and at lower doses than that required to produce diuresis" (https://en.wikipedia.org/wiki/Diuretic#Medical_uses).
+-   comment: The hypotensive effects of chlorothiazide and other thiazides are not
+        necessarily due to their diuretic activity (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904515/#S1title).
+        The exact mechanism is yet not fully understood.
     directed: true
     graph:
         _id: DB00880_MESH_D006973_1
@@ -54295,6 +54168,21 @@
         drug_mesh: MESH:D002740
         drugbank: DB:DB00880
     links:
+    -   key: decreases activity of
+        source: MESH:D002740
+        target: UniProt:P55017
+    -   key: positively regulates
+        source: UniProt:P55017
+        target: GO:0070294
+    -   key: positively correlated with
+        source: GO:0070294
+        target: GO:0003092
+    -   key: positively correlated with
+        source: GO:0003092
+        target: HP:0033533
+    -   key: positively correlated with
+        source: HP:0033533
+        target: HP:0032263
     -   key: decreases activity of
         source: MESH:D002740
         target: UniProt:P00918
@@ -54304,10 +54192,19 @@
     -   key: positively correlated with
         source: GO:0038166
         target: GO:0042310
-    -   key: contributes to
+    -   key: positively correlated with
         source: GO:0042310
         target: HP:0032263
-    -   key: positively correlated with
+    -   key: positively regulates
+        source: MESH:D002740
+        target: UniProt:Q12791
+    -   key: positively regulates
+        source: UniProt:Q12791
+        target: GO:0060087
+    -   key: negatively correlated with
+        source: GO:0060087
+        target: HP:0032263
+    -   key: manifestation of
         source: HP:0032263
         target: MESH:D006973
     multigraph: true
@@ -54315,9 +54212,27 @@
     -   id: MESH:D002740
         label: Drug
         name: chlorothiazide
+    -   id: UniProt:P55017
+        label: Protein
+        name: Solute carrier family 12 member 3
+    -   id: GO:0070294
+        label: BiologicalProcess
+        name: renal sodium ion absorption
+    -   id: GO:0003092
+        label: BiologicalProcess
+        name: renal water retention
+    -   id: HP:0033533
+        label: PhenotypicFeature
+        name: Increased cardiac output
+    -   id: UniProt:Q12791
+        label: Protein
+        name: Calcium-activated potassium channel subunit alpha-1
     -   id: UniProt:P00918
         label: Protein
         name: Carbonic anhydrase 2
+    -   id: GO:0060087
+        label: BiologicalProcess
+        name: relaxation of vascular associated smooth muscle
     -   id: GO:0038166
         label: BiologicalProcess
         name: angiotensin-activated signaling pathway
@@ -54332,11 +54247,10 @@
         name: Hypertensive disorder
     reference:
     - https://go.drugbank.com/drugs/DB00880#BE0000322
-    - https://en.wikipedia.org/wiki/Thiazide#Hypertension
-    - https://en.wikipedia.org/wiki/Chlorothiazide#Indications
-    - https://en.wikipedia.org/wiki/Hypertension#Treatment
-    - https://en.wikipedia.org/wiki/Blood_pressure#Regulation_of_blood_pressure
--   comments: This drug may be able to bind to UniProt:P08908 but its pharmacological
+    - https://go.drugbank.com/drugs/DB00880#BE0000419
+    - https://en.wikipedia.org/wiki/Category:Carbonic_anhydrase_inhibitors
+    - https://pubchem.ncbi.nlm.nih.gov/compound/2720#section=Mechanism-of-Action
+-   comment: This drug may be able to bind to UniProt:P08908 but its pharmacological
         activity (agonism vs. antagonism) is not known (https://go.drugbank.com/drugs/DB00422#BE0000291).
     directed: true
     graph:
@@ -54389,7 +54303,7 @@
     - https://go.drugbank.com/drugs/DB00422#mechanism-of-action
     - https://en.wikipedia.org/wiki/Methylphenidate#Pharmacodynamics
     - https://www.targetvalidation.org/summary?drug=CHEMBL796
--   comments: This drug may be able to bind to UniProt:P08908 but its pharmacological
+-   comment: This drug may be able to bind to UniProt:P08908 but its pharmacological
         activity (agonism vs. antagonism) is not known (https://go.drugbank.com/drugs/DB00422#BE0000291).
     directed: true
     graph:
@@ -54669,7 +54583,7 @@
     - https://en.wikipedia.org/wiki/Imiquimod#Mechanism_of_action
     - https://en.wikipedia.org/wiki/Actinic_keratosis#Other_risk_factors
     - https://en.wikipedia.org/wiki/Actinic_keratosis#Medication
--   comments: This drug can also inhbit human proteins and affect with the mammalian
+-   comment: This drug can also inhbit human proteins and affect with the mammalian
         cell division/replication, which make them an attractive antitumour agent
         (https://pubmed.ncbi.nlm.nih.gov/11102564/).
     directed: true
@@ -54866,11 +54780,11 @@
     -   key: positively correlated with
         source: GO:0007263
         target: GO:0044557
-    -   key: positively correlated with
-        source: GO:0044557
-        target: MESH:D010410
     -   key: negatively correlated with
-        source: MESH:D010410
+        source: GO:0044557
+        target: HP:0100639
+    -   key: manifestation of
+        source: HP:0100639
         target: MESH:D007172
     multigraph: true
     nodes:
@@ -54894,9 +54808,9 @@
     -   id: GO:0044557
         label: BiologicalProcess
         name: relaxation of smooth muscle
-    -   id: MESH:D010410
+    -   id: HP:0100639
         label: PhenotypicFeature
-        name: Penile Erection
+        name: Erectile dysfunction
     -   id: MESH:D007172
         label: Disease
         name: Impotence
@@ -54933,9 +54847,9 @@
         target: GO:0035623
     -   key: positively correlated with
         source: GO:0035623
-        target: MESH:D001786
-    -   key: positively correlated with
-        source: MESH:D001786
+        target: HP:0003074
+    -   key: manifestation of
+        source: HP:0003074
         target: MESH:D003924
     multigraph: true
     nodes:
@@ -54957,9 +54871,9 @@
     -   id: GO:0035623
         label: BiologicalProcess
         name: renal glucose absorption
-    -   id: MESH:D001786
+    -   id: HP:0003074
         label: PhenotypicFeature
-        name: Blood Glucose
+        name: Hyperglycemia
     -   id: MESH:D003924
         label: Disease
         name: Diabetes mellitus type 2
@@ -54978,14 +54892,11 @@
     -   key: decreases activity of
         source: MESH:D004205
         target: UniProt:P25815
-    -   key: molecularly interacts with
+    -   key: positively correlated with
         source: UniProt:P25815
-        target: MESH:D000067759
-    -   key: positively regulates
-        source: MESH:D000067759
         target: GO:0043303
-    -   key: positively regulates
-        source: MESH:D000067759
+    -   key: positively correlated with
+        source: UniProt:P25815
         target: GO:0043308
     -   key: caused by
         source: GO:0043303
@@ -55013,9 +54924,6 @@
     -   id: UniProt:P25815
         label: Protein
         name: Protein S100-P
-    -   id: MESH:D000067759
-        label: Protein
-        name: Receptor for Advanced Glycation End Products
     -   id: GO:0043303
         label: BiologicalProcess
         name: mast cell degranulation
@@ -55042,8 +54950,8 @@
     - https://pubmed.ncbi.nlm.nih.gov/12645002/
     - https://en.wikipedia.org/wiki/RAGE_(receptor)#RAGE_and_disease
     - https://en.wikipedia.org/wiki/S100P#Interactions
--   comments: This condition does not seem to be a true ocular allergic reaction,
-        rather caused by repeated mechanical irritation of the conjunctiva (https://en.wikipedia.org/wiki/Allergic_conjunctivitis#Giant_papillary_conjunctivitis).
+-   comment: This condition does not seem to be a true ocular allergic reaction, rather
+        caused by repeated mechanical irritation of the conjunctiva (https://en.wikipedia.org/wiki/Allergic_conjunctivitis#Giant_papillary_conjunctivitis).
         So the treatment with cromoglicic acid may not be needed/useful at all but
         interruption of contact lens wearing.
     directed: true
@@ -55058,14 +54966,11 @@
     -   key: decreases activity of
         source: MESH:D004205
         target: UniProt:P25815
-    -   key: molecularly interacts with
+    -   key: positively correlated with
         source: UniProt:P25815
-        target: MESH:D000067759
-    -   key: positively regulates
-        source: MESH:D000067759
         target: GO:0043303
-    -   key: positively regulates
-        source: MESH:D000067759
+    -   key: positively correlated with
+        source: UniProt:P25815
         target: GO:0043308
     -   key: caused by
         source: GO:0043303
@@ -55093,9 +54998,6 @@
     -   id: UniProt:P25815
         label: Protein
         name: Protein S100-P
-    -   id: MESH:D000067759
-        label: Protein
-        name: Receptor for Advanced Glycation End Products
     -   id: GO:0043303
         label: BiologicalProcess
         name: mast cell degranulation
@@ -55134,11 +55036,8 @@
     -   key: decreases activity of
         source: MESH:D004205
         target: UniProt:P25815
-    -   key: molecularly interacts with
+    -   key: positively correlated with
         source: UniProt:P25815
-        target: MESH:D000067759
-    -   key: positively regulates
-        source: MESH:D000067759
         target: GO:0043303
     -   key: caused by
         source: GO:0043303
@@ -55163,9 +55062,6 @@
     -   id: UniProt:P25815
         label: Protein
         name: Protein S100-P
-    -   id: MESH:D000067759
-        label: Protein
-        name: Receptor for Advanced Glycation End Products
     -   id: GO:0043303
         label: BiologicalProcess
         name: mast cell degranulation
@@ -55202,11 +55098,8 @@
     -   key: decreases activity of
         source: MESH:D004205
         target: UniProt:P25815
-    -   key: molecularly interacts with
+    -   key: positively correlated with
         source: UniProt:P25815
-        target: MESH:D000067759
-    -   key: positively regulates
-        source: MESH:D000067759
         target: GO:0043303
     -   key: caused by
         source: GO:0043303
@@ -55231,9 +55124,6 @@
     -   id: UniProt:P25815
         label: Protein
         name: Protein S100-P
-    -   id: MESH:D000067759
-        label: Protein
-        name: Receptor for Advanced Glycation End Products
     -   id: GO:0043303
         label: BiologicalProcess
         name: mast cell degranulation
@@ -59087,11 +58977,11 @@
     reference:
     - https://go.drugbank.com/drugs/DB08936
     - https://en.wikipedia.org/wiki/Antihistamine#H1-antihistamines
--   comments: "Different bacterial species can cause pneumonia, the most frequent\
-        \ ones are Streptococcus pneumoniae,\_Staphylococcus aureus, and\_Bacillus\
-        \ anthracis, among the gram-positive types of bacteria. Gram-negative examples\
-        \ of bacteria causing pneumonia are Haemophilus influenzae, Klebsiella pneumoniae\
-        \ and Escherichia coli."
+-   comment: "Different bacterial species can cause pneumonia, the most frequent ones\
+        \ are Streptococcus pneumoniae,\_Staphylococcus aureus, and\_Bacillus anthracis,\
+        \ among the gram-positive types of bacteria. Gram-negative examples of bacteria\
+        \ causing pneumonia are Haemophilus influenzae, Klebsiella pneumoniae and\
+        \ Escherichia coli."
     directed: true
     graph:
         _id: DB01137_MESH_D018410_1
@@ -59246,11 +59136,11 @@
     - https://go.drugbank.com/drugs/DB01137#mechanism-of-action
     - https://en.wikipedia.org/wiki/Anthrax#Bacteria
     - https://en.wikipedia.org/wiki/Levofloxacin#Mechanism_of_action
--   comments: "Different bacterial species can cause pneumonia, the most frequent\
-        \ ones are Streptococcus pneumoniae,\_Staphylococcus aureus, and\_Bacillus\
-        \ anthracis, among the gram-positive types of bacteria. Gram-negative examples\
-        \ of bacteria causing pneumonia are Haemophilus influenzae, Klebsiella pneumoniae\
-        \ and Escherichia coli."
+-   comment: "Different bacterial species can cause pneumonia, the most frequent ones\
+        \ are Streptococcus pneumoniae,\_Staphylococcus aureus, and\_Bacillus anthracis,\
+        \ among the gram-positive types of bacteria. Gram-negative examples of bacteria\
+        \ causing pneumonia are Haemophilus influenzae, Klebsiella pneumoniae and\
+        \ Escherichia coli."
     directed: true
     graph:
         _id: DB01137_MESH_D011023_1
@@ -59623,7 +59513,7 @@
     - https://go.drugbank.com/drugs/DB01137#mechanism-of-action
     - https://en.wikipedia.org/wiki/Levofloxacin#Mechanism_of_action
     - https://en.wikipedia.org/wiki/Conjunctivitis#Bacterial
--   comments: This drug is used in combination with dalfopristin. Both interfere with
+-   comment: This drug is used in combination with dalfopristin. Both interfere with
         the bacterial protein synthesis, at different stages of the translation. Quinupristin
         inhibits the late phase of protein synthesis, whereas dalfopristin inhibits
         the early phase of protein synthesis in the bacterial ribosome. In combination,
@@ -59781,7 +59671,7 @@
         drug_mesh: MESH:D007660
         drugbank: DB:DB00461
     links:
-    -   key: has metabolite
+    -   key: produces
         source: MESH:D007660
         target: CHEBI:35628
     -   key: decreases activity of
@@ -59826,7 +59716,7 @@
         label: Protein
         name: Prostaglandin G/H synthase 2
     -   id: REACT:R-HSA-2162123
-        label: Pathway
+        label: BiologicalProcess
         name: Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
     -   id: MESH:D011453
         label: ChemicalSubstance
@@ -59843,7 +59733,7 @@
     reference:
     - https://go.drugbank.com/drugs/DB00461#mechanism-of-action
     - https://en.wikipedia.org/wiki/Nabumetone
--   comments: The activation of Atrial natriuretic peptide receptor 1 has been observed
+-   comment: The activation of Atrial natriuretic peptide receptor 1 has been observed
         in vitro (https://pubmed.ncbi.nlm.nih.gov/12890708/) and it's reported in
         DrugBank whereas ChEMBL favours the Soluble Guanylyl Cyclase route. Also note
         that when the drug is admnistered at low doses, it dilates veins and reduces
@@ -59863,22 +59753,19 @@
         target: CHEBI:16480
     -   key: positively regulates
         source: CHEBI:16480
-        target: MESH:D000071756
-    -   key: positively regulates
-        source: MESH:D000071756
-        target: GO:0019934
-    -   key: positively regulates
-        source: MESH:D000071756
-        target: GO:0019934
+        target: GO:0038060
     -   key: positively correlated with
-        source: GO:0019934
+        source: GO:0038060
         target: GO:0042311
     -   key: positively regulates
         source: CHEBI:16480
         target: UniProt:P16066
     -   key: positively regulates
         source: UniProt:P16066
-        target: GO:0019934
+        target: GO:0007168
+    -   key: positively correlated with
+        source: GO:0007168
+        target: GO:0042311
     -   key: negatively correlated with
         source: GO:0042311
         target: MESH:D000787
@@ -59895,12 +59782,12 @@
     -   id: UniProt:P16066
         label: Protein
         name: Atrial natriuretic peptide receptor 1
-    -   id: MESH:D000071756
-        label: Protein
-        name: Soluble Guanylyl Cyclase
-    -   id: GO:0019934
+    -   id: GO:0038060
+        label: BiologicalProcess
+        name: nitric oxide-cGMP-mediated signaling pathway
+    -   id: GO:0007168
         label: BiologicalProcess
-        name: cGMP-mediated signaling
+        name: receptor guanylyl cyclase signaling pathway
     -   id: GO:0042311
         label: BiologicalProcess
         name: vasodilation
@@ -59967,7 +59854,7 @@
     reference:
     - https://go.drugbank.com/drugs/DB01280#mechanism-of-action
     - https://en.wikipedia.org/wiki/Nelarabine
--   comments: There appears to be no connection between Niacin deficiency and nicotine.
+-   comment: There appears to be no connection between Niacin deficiency and nicotine.
         Although niacin and nicotine are somehow related (nicotine can turn into nicotinic
         acid via oxidation), nicotine may not be able to replace niacin as treatment
         for Niacin deficiency. Actually nicotine could compete with niacin for binding
@@ -60000,10 +59887,10 @@
     - https://en.wikipedia.org/wiki/Nicotine#Biosynthesis
     - https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL3/
     - https://hopes.stanford.edu/nicotinamide/#relationship-between-nicotinamide-and-nicotine
--   comments: Both DrugBank (https://go.drugbank.com/drugs/DB06718#mechanism-of-action)
+-   comment: Both DrugBank (https://go.drugbank.com/drugs/DB06718#mechanism-of-action)
         and ChEMBL (https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2079587/)
         have this drug modulating target AR (UniProt:P10275) but that's not the mechanism
-        of action for this disease (MESH:D054179).
+        of action for this indication (MESH:D054179).
     directed: true
     graph:
         _id: DB06718_MESH_D054179_1
@@ -60021,18 +59908,18 @@
         target: GO:0006956
     -   key: positively correlated with
         source: GO:0006956
-        target: MESH:D001920
+        target: Pfam:PF06753
     -   key: negatively correlated with
         source: UniProt:P05155
         target: MESH:D007610
     -   key: positively correlated with
         source: MESH:D007610
-        target: MESH:D001920
+        target: Pfam:PF06753
     -   key: positively correlated with
-        source: MESH:D001920
+        source: Pfam:PF06753
         target: MESH:D002199
     -   key: positively correlated with
-        source: MESH:D001920
+        source: Pfam:PF06753
         target: GO:0042311
     -   key: positively correlated with
         source: MESH:D002199
@@ -60055,10 +59942,10 @@
         label: BiologicalProcess
         name: vasodilation
     -   id: MESH:D007610
-        label: Protein
+        label: GeneFamily
         name: Kallikreins
-    -   id: MESH:D001920
-        label: Protein
+    -   id: Pfam:PF06753
+        label: GeneFamily
         name: Bradykinin
     -   id: MESH:D002199
         label: BiologicalProcess
@@ -60166,9 +60053,7 @@
     - https://journals.sagepub.com/doi/abs/10.3181/00379727-37-9668P
     - https://www.medicalnewstoday.com/articles/165749#complications
     - https://en.wikipedia.org/wiki/Vitamin_K#History
--   comments: Phenoxybenzamine is an alpha blocker (https://en.wikipedia.org/wiki/Alpha_blocker#Pheochromocytoma
-        https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL753/).
-    directed: true
+-   directed: true
     graph:
         _id: DB06718_MESH_D010673_1
         disease: Pheochromocytoma
@@ -60179,9 +60064,39 @@
     links:
     -   key: decreases activity of
         source: MESH:D010643
-        target: MESH:D011942
+        target: UniProt:P35348
+    -   key: decreases activity of
+        source: MESH:D010643
+        target: UniProt:P08913
+    -   key: decreases activity of
+        source: MESH:D010643
+        target: UniProt:P18825
+    -   key: decreases activity of
+        source: MESH:D010643
+        target: UniProt:P25100
+    -   key: decreases activity of
+        source: MESH:D010643
+        target: UniProt:P35368
+    -   key: decreases activity of
+        source: MESH:D010643
+        target: UniProt:P18089
     -   key: positively regulates
-        source: MESH:D011942
+        source: UniProt:P35348
+        target: GO:0042310
+    -   key: regulates
+        source: UniProt:P08913
+        target: GO:0042310
+    -   key: positively regulates
+        source: UniProt:P18825
+        target: GO:0042310
+    -   key: positively regulates
+        source: UniProt:P25100
+        target: GO:0042310
+    -   key: positively regulates
+        source: UniProt:P35368
+        target: GO:0042310
+    -   key: positively regulates
+        source: UniProt:P18089
         target: GO:0042310
     -   key: positively correlated with
         source: GO:0042310
@@ -60197,9 +60112,24 @@
     -   id: MESH:D010643
         label: Drug
         name: phenoxybenzamine
-    -   id: MESH:D011942
-        label: GeneFamily
-        name: Receptors, Adrenergic, alpha
+    -   id: UniProt:P35348
+        label: Protein
+        name: Alpha-1A adrenergic receptor
+    -   id: UniProt:P08913
+        label: Protein
+        name: Alpha-2A adrenergic receptor
+    -   id: UniProt:P18825
+        label: Protein
+        name: Alpha-2C adrenergic receptor
+    -   id: UniProt:P25100
+        label: Protein
+        name: Alpha-1D adrenergic receptor
+    -   id: UniProt:P18089
+        label: Protein
+        name: Alpha-2B adrenergic receptor
+    -   id: UniProt:P35368
+        label: Protein
+        name: Alpha-1B adrenergic receptor
     -   id: GO:0042310
         label: BiologicalProcess
         name: vasoconstriction
@@ -60214,6 +60144,7 @@
         name: Pheochromocytoma
     reference:
     - https://go.drugbank.com/drugs/DB00925#mechanism-of-action
+    - https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL753/
     - https://en.wikipedia.org/wiki/Alpha_blocker#Hypertension
     - https://en.wikipedia.org/wiki/Phenoxybenzamine#Pharmacology
     - https://en.wikipedia.org/wiki/Pheochromocytoma#Alpha_blockade
diff --git a/submission.yaml b/submission.yaml
index c70ed0f08..8b1378917 100644
--- a/submission.yaml
+++ b/submission.yaml
@@ -1,2344 +1 @@
-- directed: true
-  graph:
-    _id: DB12975_MESH_D016780_1
-    disease: Malaria, Vivax
-    disease_mesh: MESH:D016780
-    drug: Pyronaridine
-    drug_mesh: MESH:C027871
-    drugbank: DB:DB12975
-  links:
-    - key: negatively regulates
-      source: MESH:C027871
-      target: GO:0042540
-    - key: increases abundance of
-      source: GO:0042540
-      target: MESH:D006418
-    - key: disrupts
-      source: MESH:D006418
-      target: NCBITaxon:5855
-    - key: causes
-      source: NCBITaxon:5855
-      target: MESH:D016780
-  multigraph: true
-  nodes:
-    - id: MESH:C027871
-      label: Drug
-      name: Pyronaridine
-    - id: GO:0042540
-      label: BiologicalProcess
-      name: hemoglobin catabolic process
-    - id: MESH:D006418
-      label: ChemicalSubstance
-      name: Heme
-    - id: NCBITaxon:5855
-      label: OrganismTaxon
-      name: Plasmodium vivax
-    - id: MESH:D016780
-      label: Disease
-      name: Malaria, Vivax
-  reference:
-    - https://www.ema.europa.eu/en/documents/medicine-outside-eu/pyramax-product-information_en.pdf
-    - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483207/
-  comment: Heme (MESH:D006418) and hemin (MESH:D006427) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.
-- directed: true
-  graph:
-    _id: DB12975_MESH_D016780_2
-    disease: Malaria, Vivax
-    disease_mesh: MESH:D016780
-    drug: Pyronaridine
-    drug_mesh: MESH:C027871
-    drugbank: DB:DB12975
-  links:
-    - key: molecularly interacts with
-      source: MESH:C027871
-      target: MESH:D006427
-    - key: disrupts
-      source: MESH:D006427
-      target: CL:0000232
-    - key: location of
-      source: CL:0000232
-      target: GO:0019954
-    - key: in taxon
-      source: GO:0019954
-      target: NCBITaxon:5855
-    - key: causes
-      source: NCBITaxon:5855
-      target: MESH:D016780
-  multigraph: true
-  nodes:
-    - id: MESH:C027871
-      label: Drug
-      name: Pyronaridine
-    - id: MESH:D006427
-      label: ChemicalSubstance
-      name: Hemin
-    - id: CL:0000232
-      label: Cell
-      name: erythrocyte
-    - id: GO:0019954
-      label: BiologicalProcess
-      name: asexual reproduction
-    - id: NCBITaxon:5855
-      label: OrganismTaxon
-      name: Plasmodium vivax
-    - id: MESH:D016780
-      label: Disease
-      name: Malaria, Vivax
-  reference: https://www.ema.europa.eu/en/documents/medicine-outside-eu/pyramax-product-information_en.pdf
-  comment: Hemin (MESH:D006427) and heme (MESH:D006418) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.
-- directed: true
-  graph:
-    _id: DB12975_MESH_D016778_1
-    disease: Malaria, Falciparum
-    disease_mesh: MESH:D016778
-    drug: Pyronaridine
-    drug_mesh: MESH:C027871
-    drugbank: DB:DB12975
-  links:
-    - key: negatively regulates
-      source: MESH:C027871
-      target: GO:0042540
-    - key: increases abundance of
-      source: GO:0042540
-      target: MESH:D006418
-    - key: disrupts
-      source: MESH:D006418
-      target: NCBITaxon:5833
-    - key: causes
-      source: NCBITaxon:5833
-      target: MESH:D016778
-  multigraph: true
-  nodes:
-    - id: MESH:C027871
-      label: Drug
-      name: Pyronaridine
-    - id: GO:0042540
-      label: BiologicalProcess
-      name: hemoglobin catabolic process
-    - id: MESH:D006418
-      label: ChemicalSubstance
-      name: Heme
-    - id: NCBITaxon:5833
-      label: OrganismTaxon
-      name: Plasmodium falciparum
-    - id: MESH:D016778
-      label: Disease
-      name: Malaria, Falciparum
-  reference:
-    - https://www.ema.europa.eu/en/documents/medicine-outside-eu/pyramax-product-information_en.pdf
-    - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483207/
-  comment: Heme (MESH:D006418) and hemin (MESH:D006427) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.
-- directed: true
-  graph:
-    _id: DB12975_MESH_D016778_2
-    disease: Malaria, Falciparum
-    disease_mesh: MESH:D016778
-    drug: Pyronaridine
-    drug_mesh: MESH:C027871
-    drugbank: DB:DB12975
-  links:
-    - key: molecularly interacts with
-      source: MESH:C027871
-      target: MESH:D006427
-    - key: disrupts
-      source: MESH:D006427
-      target: CL:0000232
-    - key: location of
-      source: CL:0000232
-      target: GO:0019954
-    - key: in taxon
-      source: GO:0019954
-      target: NCBITaxon:5833
-    - key: causes
-      source: NCBITaxon:5833
-      target: MESH:D016778
-  multigraph: true
-  nodes:
-    - id: MESH:C027871
-      label: Drug
-      name: Pyronaridine
-    - id: MESH:D006427
-      label: ChemicalSubstance
-      name: Hemin
-    - id: CL:0000232
-      label: Cell
-      name: erythrocyte
-    - id: GO:0019954
-      label: BiologicalProcess
-      name: asexual reproduction
-    - id: NCBITaxon:5833
-      label: OrganismTaxon
-      name: Plasmodium falciparum
-    - id: MESH:D016778
-      label: Disease
-      name: Malaria, Falciparum
-  reference: https://www.ema.europa.eu/en/documents/medicine-outside-eu/pyramax-product-information_en.pdf
-  comment: Hemin (MESH:D006427) and heme (MESH:D006418) are related substances resulting from the parasite hemoglobin catabolism. Heme is bound to iron whereas hemin is the hydroxide counterpart of heme. Both are cytotoxic. Hemin is also known as hematin.
-- directed: true
-  graph:
-    _id: DB00257_MESH_D005892_1
-    disease: Gingivitis, Necrotizing Ulcerative
-    disease_mesh: MESH:D005892
-    drug: sulfur
-    drug_mesh: MESH:D013455
-    drugbank: DB:DB00257
-  links:
-    - key: precedes
-      source: MESH:D013455
-      target: CHEBI:16136
-    - key: subclass of
-      source: CHEBI:16136
-      target: MESH:D000900
-    - key: disrupts
-      source: MESH:D000900
-      target: NCBITaxon:28131
-    - key: disrupts
-      source: MESH:D000900
-      target: NCBITaxon:848
-    - key: disrupts
-      source: MESH:D000900
-      target: NCBITaxon:157
-    - key: causes
-      source: NCBITaxon:157
-      target: MESH:D005892
-    - key: causes
-      source: NCBITaxon:848
-      target: MESH:D005892
-    - key: causes
-      source: NCBITaxon:28131
-      target: MESH:D005892
-  multigraph: true
-  nodes:
-    - id: MESH:D013455
-      label: Drug
-      name: sulfur
-    - id: CHEBI:16136
-      label: ChemicalSubstance
-      name: hydrogen sulfide
-    - id: MESH:D000900
-      label: Drug
-      name: Anti-Bacterial Agents
-    - id: NCBITaxon:157
-      label: OrganismTaxon
-      name: Treponema
-    - id: NCBITaxon:848
-      label: OrganismTaxon
-      name: Fusobacterium
-    - id: NCBITaxon:28131
-      label: OrganismTaxon
-      name: Prevotella intermedia
-    - id: MESH:D005892
-      label: Disease
-      name: Gingivitis, Necrotizing Ulcerative
-  reference:
-    - https://go.drugbank.com/drugs/DB09353#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Acute_necrotizing_ulcerative_gingivitis#Causes
-  comment: The disease is denoted as Acute necrotizing ulcerative gingivitis in the original file but the name used for the path is the one seen in the MESH website.
-- directed: true
-  graph:
-    _id: DB00257_MESH_D000152_3
-    disease: Acne vulgaris
-    disease_mesh: MESH:D000152
-    drug: sulfur
-    drug_mesh: MESH:D013455
-    drugbank: DB:DB00257
-  links:
-    - key: precedes
-      source: MESH:D013455
-      target: CHEBI:16136
-    - key: subclass of
-      source: CHEBI:16136
-      target: MESH:D007641
-    - key: subclass of
-      source: CHEBI:16136
-      target: MESH:D000900
-    - key: disrupts
-      source: MESH:D000900
-      target: NCBITaxon:1747
-    - key: decreases abundance of
-      source: MESH:D007641
-      target: HP:0025249
-    - key: causes
-      source: NCBITaxon:1747
-      target: MESH:D000152
-    - key: positively correlated with
-      source: HP:0025249
-      target: MESH:D000152
-  multigraph: true
-  nodes:
-    - id: MESH:D013455
-      label: Drug
-      name: sulfur
-    - id: CHEBI:16136
-      label: ChemicalSubstance
-      name: hydrogen sulfide
-    - id: MESH:D000900
-      label: Drug
-      name: Anti-Bacterial Agents
-    - id: MESH:D007641
-      label: Drug
-      name: Keratolytic Agents
-    - id: HP:0025249
-      label: PhenotypicFeature
-      name: Comedo
-    - id: NCBITaxon:1747
-      label: OrganismTaxon
-      name: Cutibacterium acnes
-    - id: MESH:D000152
-      label: Disease
-      name: Acne vulgaris
-  reference: https://go.drugbank.com/drugs/DB09353#mechanism-of-action
-  comment: Sulfur's usefulness as a topical remedy for acne dates back to at least the reign of Cleopatra i.e. 69–30 BCE (https://en.wikipedia.org/wiki/Acne#History).
-- directed: true
-  graph:
-    _id: DB00257_MESH_D013281_1
-    disease: Stomatitis, Aphthous
-    disease_mesh: MESH:D013281
-    drug: sulfur
-    drug_mesh: MESH:D013455
-    drugbank: DB:DB00257
-  links:
-    - key: precedes
-      source: MESH:D013455
-      target: CHEBI:16136
-    - key: subclass of
-      source: CHEBI:16136
-      target: MESH:D000900
-    - key: disrupts
-      source: MESH:D000900
-      target: NCBITaxon:210
-    - key: causes
-      source: NCBITaxon:210
-      target: MESH:D013281
-  multigraph: true
-  nodes:
-    - id: MESH:D013455
-      label: Drug
-      name: sulfur
-    - id: CHEBI:16136
-      label: ChemicalSubstance
-      name: hydrogen sulfide
-    - id: MESH:D000900
-      label: Drug
-      name: Anti-Bacterial Agents
-    - id: NCBITaxon:210
-      label: OrganismTaxon
-      name: Helicobacter pylori
-    - id: MESH:D013281
-      label: Disease
-      name: Stomatitis, Aphthous
-  reference:
-    - https://go.drugbank.com/drugs/DB09353#mechanism-of-action
-    - https://ada.com/conditions/aphthous-ulcers/#causes
-    - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441245/
-    - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002348/
-    - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227248/
-    - https://www.mayoclinic.org/diseases-conditions/canker-sore/symptoms-causes/syc-20370615
-  comment: The disease is denoted as Aphthous ulcer of mouth in the original file but the name used for the path is the one seen in the MESH website. The causes for this disease are not well known (https://ada.com/conditions/aphthous-ulcers/#causes). It's important to prevent secondary infection of the ulcers (https://en.wikipedia.org/wiki/Aphthous_stomatitis#Medication); that's when anti-bacterial agents can be administered.
-- directed: true
-  graph:
-    _id: DB01416_MESH_D013290_1
-    disease: Streptococcal Infections
-    disease_mesh: MESH:D013290
-    drug: cefpodoxime proxetil
-    drug_mesh: MESH:C053267
-    drugbank: DB:DB01416
-  links:
-    - key: decreases activity of
-      source: MESH:C053267
-      target: InterPro:IPR012338
-    - key: decreases activity of
-      source: MESH:C053267
-      target: InterPro:IPR037532
-    - key: positively regulates
-      source: InterPro:IPR012338
-      target: GO:0009252
-    - key: positively regulates
-      source: InterPro:IPR037532
-      target: GO:0009252
-    - key: positively correlated with
-      source: GO:0009252
-      target: GO:0071555
-    - key: in taxon
-      source: GO:0071555
-      target: NCBITaxon:1301
-    - key: causes
-      source: NCBITaxon:1301
-      target: MESH:D013290
-  multigraph: true
-  nodes:
-    - id: MESH:C053267
-      label: Drug
-      name: cefpodoxime proxetil
-      alt_ids:
-         - MESH:C053268
-    - id: InterPro:IPR012338
-      label: GeneFamily
-      name: Beta-lactamase/transpeptidase-like
-    - id: InterPro:IPR037532
-      label: GeneFamily
-      name: Peptidoglycan D,D-transpeptidase FtsI
-    - id: GO:0009252
-      label: BiologicalProcess
-      name: peptidoglycan biosynthetic process
-    - id: GO:0071555
-      label: BiologicalProcess
-      name: cell wall organization
-    - id: NCBITaxon:1301
-      label: OrganismTaxon
-      name: Streptococcus
-    - id: MESH:D013290
-      label: Disease
-      name: Streptococcal Infections
-  reference: https://go.drugbank.com/drugs/DB01416#mechanism-of-action
-  comment: This disease is denoted as Streptococcus pyogenes infection in the original file but it's named Streptococcal Infections by MESH.
-- directed: true
-  graph:
-    _id: DB06710_MESH_D019584_1
-    disease: Menopausal Flushing
-    disease_mesh: MESH:D019584
-    drug: methyltestosterone
-    drug_mesh: MESH:D008777
-    drugbank: DB:DB06710
-  links:
-    - key: increases activity of
-      source: MESH:D008777
-      target: UniProt:P10275
-    - key: precedes
-      source: MESH:D008777
-      target: CHEBI:34179
-    - key: increases activity of
-      source: CHEBI:34179
-      target: UniProt:P03372
-    - key: positively regulates
-      source: UniProt:P03372
-      target: GO:0006874
-    - key: correlated with
-      source: UniProt:P10275
-      target: GO:0097746
-    - key: correlated with
-      source: GO:0097746
-      target: MESH:D014666
-    - key: regulates
-      source: GO:0006874
-      target: MESH:D014666
-    - key: positively regulates
-      source: MESH:D014666
-      target: GO:0001659
-    - key: negatively correlated with
-      source: GO:0001659
-      target: HP:0005968
-    - key: positively correlated with
-      source: HP:0005968
-      target: MESH:D019584
-  multigraph: true
-  nodes:
-    - id: MESH:D008777
-      label: Drug
-      name: methyltestosterone
-    - id: UniProt:P10275
-      label: Protein
-      name: Androgen receptor
-    - id: CHEBI:34179
-      label: Drug
-      name: 17alpha-Methylestradiol
-    - id: UniProt:P03372
-      label: Protein
-      name: Estrogen receptor
-    - id: MESH:D014666
-      label: GrossAnatomicalStructure
-      name: Vasomotor System
-    - id: GO:0097746
-      label: BiologicalProcess
-      name: blood vessel diameter maintenance
-    - id: GO:0006874
-      label: BiologicalProcess
-      name: cellular calcium ion homeostasis
-    - id: GO:0001659
-      label: BiologicalProcess
-      name: temperature homeostasis
-    - id: HP:0005968
-      label: PhenotypicFeature
-      name: Temperature instability
-    - id: MESH:D019584
-      label: Disease
-      name: Menopausal Flushing
-  reference:
-    - https://go.drugbank.com/drugs/DB06710#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Methyltestosterone#Pharmacodynamics
-    - https://en.wikipedia.org/wiki/Methylestradiol#Pharmacodynamics
-    - https://en.wikipedia.org/wiki/Hot_flash#Mechanism
-    - https://academic.oup.com/jcem/article/100/11/3975/2836060
-  comment: The disease is denoted Menopausal flushing in the original file but Hot flashes in MESH. The etiology of hot flashes has yet to be determined (https://pubmed.ncbi.nlm.nih.gov/15065632/).
-- directed: true
-  graph:
-    _id: DB06710_MESH_D005058_1
-    disease: Eunuchism
-    disease_mesh: MESH:D005058
-    drug: methyltestosterone
-    drug_mesh: MESH:D008777
-    drugbank: DB:DB06710
-  links:
-    - key: increases activity of
-      source: MESH:D008777
-      target: UniProt:P10275
-    - key: positively regulates
-      source: UniProt:P10275
-      target: GO:0060742
-    - key: positively regulates
-      source: UniProt:P10275
-      target: GO:0048808
-    - key: positively regulates
-      source: UniProt:P10275
-      target: GO:0008584
-    - key: positively regulates
-      source: UniProt:P10275
-      target: GO:0019102
-    - key: positively regulates
-      source: UniProt:P10275
-      target: GO:0007283
-    - key: positively correlated with
-      source: GO:0060742
-      target: CHEBI:17347
-    - key: positively correlated with
-      source: GO:0048808
-      target: CHEBI:17347
-    - key: positively correlated with
-      source: GO:0008584
-      target: CHEBI:17347
-    - key: positively correlated with
-      source: GO:0019102
-      target: CHEBI:17347
-    - key: positively correlated with
-      source: GO:0007283
-      target: CHEBI:17347
-    - key: negatively correlated with
-      source: CHEBI:17347
-      target: MESH:D005058
-  multigraph: true
-  nodes:
-    - id: MESH:D008777
-      label: Drug
-      name: methyltestosterone
-    - id: UniProt:P10275
-      label: Protein
-      name: Androgen receptor
-    - id: GO:0060742
-      label: BiologicalProcess
-      name: epithelial cell differentiation involved in prostate gland development
-    - id: GO:0048808
-      label: BiologicalProcess
-      name: male genitalia morphogenesis
-    - id: GO:0008584
-      label: BiologicalProcess
-      name: male gonad development
-    - id: GO:0019102
-      label: BiologicalProcess
-      name: male somatic sex determination
-    - id: GO:0007283
-      label: BiologicalProcess
-      name: spermatogenesis
-    - id: CHEBI:17347
-      label: ChemicalSubstance
-      name: testosterone
-    - id: MESH:D005058
-      label: Disease
-      name: Eunuchism
-  reference:
-    - https://go.drugbank.com/drugs/DB06710#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Hypogonadism#Treatment
-    - https://en.wikipedia.org/wiki/Hypogonadism#Men
-  comment: MESH:D005058 is named male hypogonadism in the original file.
-- directed: true
-  graph:
-    _id: DB00555_MESH_D012640_1
-    disease: Seizures
-    disease_mesh: MESH:D012640
-    drug: lamotrigine
-    drug_mesh: MESH:C047781
-    drugbank: DB:DB00555
-  links:
-    - key: negatively regulates
-      source: MESH:C047781
-      target: InterPro:IPR001696
-    - key: positively regulates
-      source: InterPro:IPR001696
-      target: GO:0061530
-    - key: positively regulates
-      source: InterPro:IPR001696
-      target: GO:0061535
-    - key: positively correlated with
-      source: GO:0061530
-      target: HP:0020219
-    - key: positively correlated with
-      source: GO:0061535
-      target: HP:0020219
-    - key: positively correlated with
-      source: HP:0020219
-      target: MESH:D012640
-  multigraph: true
-  nodes:
-    - id: MESH:C047781
-      label: Drug
-      name: lamotrigine
-    - id: InterPro:IPR001696
-      label: GeneFamily
-      name: Voltage gated sodium channel, alpha subunit
-    - id: GO:0061530
-      label: BiologicalProcess
-      name: aspartate secretion, neurotransmission
-    - id: GO:0061535
-      label: BiologicalProcess
-      name: glutamate secretion, neurotransmission
-    - id: HP:0020219
-      label: PhenotypicFeature
-      name: Motor seizure
-    - id: MESH:D012640
-      label: Disease
-      name: Seizures
-  reference:
-    - https://go.drugbank.com/drugs/DB00555#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
-    - https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)#Disease,_disabilities,_and_pharmacology
-  comment: This drug may also affect GABA-mediated synaptic transmission (https://go.drugbank.com/drugs/DB00555#BE0000013). However this is rather contentious, so it has not been annotated as such in here. Besides if the drug does modulate gamma-aminobutyric acid receptor it's a rather weak inhibition seen in animal models (yet to be determined in humans). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, note that this disease is denoted as Tonic-clonic seizure in the original file but known as Seizures in MESH.
-- directed: true
-  graph:
-    _id: DB00555_MESH_D012640_2
-    disease: Seizures
-    disease_mesh: MESH:D012640
-    drug: lamotrigine
-    drug_mesh: MESH:C047781
-    drugbank: DB:DB00555
-  links:
-    - key: negatively regulates
-      source: MESH:C047781
-      target: UniProt:Q15878
-    - key: participates in
-      source: UniProt:Q15878
-      target: REACT:R-HSA-112308
-    - key: participates in
-      source: UniProt:Q15878
-      target: REACT:R-HSA-112308
-    - key: positively correlated with
-      source: REACT:R-HSA-112308
-      target: GO:0007268
-    - key: positively correlated with
-      source: GO:0007268
-      target: GO:0061535
-    - key: positively correlated with
-      source: GO:0061535
-      target: HP:0020219
-    - key: positively correlated with
-      source: HP:0020219
-      target: MESH:D012640
-  multigraph: true
-  nodes:
-    - id: MESH:C047781
-      label: Drug
-      name: lamotrigine
-    - id: UniProt:Q15878
-      label: Protein
-      name: Voltage-dependent R-type calcium channel subunit alpha-1E
-    - id: REACT:R-HSA-112308
-      label: Pathway
-      name: Presynaptic depolarization and calcium channel opening
-    - id: GO:0007268
-      label: BiologicalProcess
-      name: chemical synaptic transmission
-    - id: GO:0061535
-      label: BiologicalProcess
-      name: glutamate secretion, neurotransmission
-    - id: HP:0020219
-      label: PhenotypicFeature
-      name: Motor seizure
-    - id: MESH:D012640
-      label: Disease
-      name: Seizures
-  reference:
-    - https://go.drugbank.com/drugs/DB00555#BE0009609
-    - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
-    - https://pubmed.ncbi.nlm.nih.gov/10530688/
-    - https://pubmed.ncbi.nlm.nih.gov/9579933/
-    - https://en.wikipedia.org/wiki/Anticonvulsant
-    - https://en.wikipedia.org/wiki/Neuroprotection
-  comment: This drug may also affect GABA-mediated synaptic transmission (https://go.drugbank.com/drugs/DB00555#BE0000013). However this is rather contentious, so it has not been annotated as such in here. Besides if the drug does inhibit gamma-aminobutyric acid receptor it's a rather weak inhibition seen in animal models (yet to be determined in humans). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, this disease is denoted as Tonic-clonic seizure in the original file but known as Seizures in MESH.
-- directed: true
-  graph:
-    _id: DB00555_MESH_D004828_1
-    disease: Epilepsies, Partial
-    disease_mesh: MESH:D004828
-    drug: lamotrigine
-    drug_mesh: MESH:C047781
-    drugbank: DB:DB00555
-  links:
-    - key: negatively regulates
-      source: MESH:C047781
-      target: InterPro:IPR001696
-    - key: positively regulates
-      source: InterPro:IPR001696
-      target: GO:0061530
-    - key: positively regulates
-      source: InterPro:IPR001696
-      target: GO:0061535
-    - key: positively correlated with
-      source: GO:0061530
-      target: HP:0032843
-    - key: positively correlated with
-      source: GO:0061535
-      target: HP:0032843
-    - key: positively correlated with
-      source: HP:0032843
-      target: MESH:D004828
-  multigraph: true
-  nodes:
-    - id: MESH:C047781
-      label: Drug
-      name: lamotrigine
-    - id: InterPro:IPR001696
-      label: GeneFamily
-      name: Voltage gated sodium channel, alpha subunit
-    - id: GO:0061530
-      label: BiologicalProcess
-      name: aspartate secretion, neurotransmission
-    - id: GO:0061535
-      label: BiologicalProcess
-      name: glutamate secretion, neurotransmission
-    - id: HP:0032843
-      label: PhenotypicFeature
-      name: Focal-onset epileptic spasm
-    - id: MESH:D004828
-      label: Disease
-      name: Epilepsies, Partial
-  reference:
-    - https://go.drugbank.com/drugs/DB00555#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
-    - https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)#Disease,_disabilities,_and_pharmacology
-    - https://en.wikipedia.org/wiki/Focal_seizure
-  comment: This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, this disease is denoted as Simple partial seizure in the original file but known as Epilepsies, Partial in MESH.
-- directed: true
-  graph:
-    _id: DB00555_MESH_D004828_2
-    disease: Epilepsies, Partial
-    disease_mesh: MESH:D004828
-    drug: lamotrigine
-    drug_mesh: MESH:C047781
-    drugbank: DB:DB00555
-  links:
-    - key: negatively regulates
-      source: MESH:C047781
-      target: UniProt:Q15878
-    - key: participates in
-      source: UniProt:Q15878
-      target: REACT:R-HSA-112308
-    - key: participates in
-      source: UniProt:Q15878
-      target: REACT:R-HSA-112308
-    - key: positively correlated with
-      source: REACT:R-HSA-112308
-      target: GO:0007268
-    - key: positively correlated with
-      source: GO:0007268
-      target: GO:0061535
-    - key: positively correlated with
-      source: GO:0061535
-      target: HP:0032843
-    - key: positively correlated with
-      source: HP:0032843
-      target: MESH:D004828
-  multigraph: true
-  nodes:
-    - id: MESH:C047781
-      label: Drug
-      name: lamotrigine
-    - id: UniProt:Q15878
-      label: Protein
-      name: Voltage-dependent R-type calcium channel subunit alpha-1E
-    - id: REACT:R-HSA-112308
-      label: Pathway
-      name: Presynaptic depolarization and calcium channel opening
-    - id: GO:0007268
-      label: BiologicalProcess
-      name: chemical synaptic transmission
-    - id: GO:0061535
-      label: BiologicalProcess
-      name: glutamate secretion, neurotransmission
-    - id: HP:0032843
-      label: PhenotypicFeature
-      name: Focal-onset epileptic spasm
-    - id: MESH:D004828
-      label: Disease
-      name: Epilepsies, Partial
-  reference:
-    - https://go.drugbank.com/drugs/DB00555#BE0009609
-    - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
-    - https://pubmed.ncbi.nlm.nih.gov/10530688/
-    - https://pubmed.ncbi.nlm.nih.gov/9579933/
-    - https://en.wikipedia.org/wiki/Anticonvulsant
-    - https://en.wikipedia.org/wiki/Neuroprotection
-  comment: This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/). Finally, this disease is denoted as Simple partial seizure in the original file but known as Epilepsies, Partial in MESH.
-- directed: true
-  graph:
-    _id: DB00555_MESH_D065768_1
-    disease: Lennox-Gastaut syndrome
-    disease_mesh: MESH:D065768
-    drug: lamotrigine
-    drug_mesh: MESH:C047781
-    drugbank: DB:DB00555
-  links:
-    - key: negatively regulates
-      source: MESH:C047781
-      target: InterPro:IPR001696
-    - key: positively regulates
-      source: InterPro:IPR001696
-      target: GO:0061530
-    - key: positively regulates
-      source: InterPro:IPR001696
-      target: GO:0061535
-    - key: positively correlated with
-      source: GO:0061530
-      target: HP:0032792
-    - key: positively correlated with
-      source: GO:0061535
-      target: HP:0032792
-    - key: positively correlated with
-      source: HP:0032792
-      target: MESH:D065768
-  multigraph: true
-  nodes:
-    - id: MESH:C047781
-      label: Drug
-      name: lamotrigine
-    - id: InterPro:IPR001696
-      label: GeneFamily
-      name: Voltage gated sodium channel, alpha subunit
-    - id: GO:0061530
-      label: BiologicalProcess
-      name: aspartate secretion, neurotransmission
-    - id: GO:0061535
-      label: BiologicalProcess
-      name: glutamate secretion, neurotransmission
-    - id: HP:0032792
-      label: PhenotypicFeature
-      name: Tonic seizure
-    - id: MESH:D065768
-      label: Disease
-      name: Lennox-Gastaut syndrome
-  reference:
-    - https://go.drugbank.com/drugs/DB00555#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
-    - https://en.wikipedia.org/wiki/Lennox%E2%80%93Gastaut_syndrome#Signs_and_symptoms
-    - https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)#Disease,_disabilities,_and_pharmacology
-  comment: This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).
-- directed: true
-  graph:
-    _id: DB00555_MESH_D065768_2
-    disease: Lennox-Gastaut syndrome
-    disease_mesh: MESH:D065768
-    drug: lamotrigine
-    drug_mesh: MESH:C047781
-    drugbank: DB:DB00555
-  links:
-    - key: negatively regulates
-      source: MESH:C047781
-      target: UniProt:Q15878
-    - key: participates in
-      source: UniProt:Q15878
-      target: REACT:R-HSA-112308
-    - key: participates in
-      source: UniProt:Q15878
-      target: REACT:R-HSA-112308
-    - key: positively correlated with
-      source: REACT:R-HSA-112308
-      target: GO:0007268
-    - key: positively correlated with
-      source: GO:0007268
-      target: GO:0061535
-    - key: positively correlated with
-      source: GO:0061535
-      target: HP:0032792
-    - key: positively correlated with
-      source: HP:0032792
-      target: MESH:D065768
-  multigraph: true
-  nodes:
-    - id: MESH:C047781
-      label: Drug
-      name: lamotrigine
-    - id: UniProt:Q15878
-      label: Protein
-      name: Voltage-dependent R-type calcium channel subunit alpha-1E
-    - id: REACT:R-HSA-112308
-      label: Pathway
-      name: Presynaptic depolarization and calcium channel opening
-    - id: GO:0007268
-      label: BiologicalProcess
-      name: chemical synaptic transmission
-    - id: GO:0061535
-      label: BiologicalProcess
-      name: glutamate secretion, neurotransmission
-    - id: HP:0032792
-      label: PhenotypicFeature
-      name: Tonic seizure
-    - id: MESH:D065768
-      label: Disease
-      name: Lennox-Gastaut syndrome
-  reference:
-    - https://go.drugbank.com/drugs/DB00555#BE0009609
-    - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
-    - https://pubmed.ncbi.nlm.nih.gov/10530688/
-    - https://pubmed.ncbi.nlm.nih.gov/9579933/
-    - https://en.wikipedia.org/wiki/Anticonvulsant
-    - https://en.wikipedia.org/wiki/Neuroprotection
-  comment: This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).
-- directed: true
-  graph:
-    _id: DB00555_MESH_D004827_1
-    disease: Epilepsy
-    disease_mesh: MESH:D004827
-    drug: lamotrigine
-    drug_mesh: MESH:C047781
-    drugbank: DB:DB00555
-  links:
-    - key: negatively regulates
-      source: MESH:C047781
-      target: InterPro:IPR001696
-    - key: positively regulates
-      source: InterPro:IPR001696
-      target: GO:0061530
-    - key: positively regulates
-      source: InterPro:IPR001696
-      target: GO:0061535
-    - key: positively correlated with
-      source: GO:0061530
-      target: HP:0020219
-    - key: positively correlated with
-      source: GO:0061535
-      target: HP:0020219
-    - key: positively correlated with
-      source: HP:0020219
-      target: MESH:D004827
-  multigraph: true
-  nodes:
-    - id: MESH:C047781
-      label: Drug
-      name: lamotrigine
-    - id: InterPro:IPR001696
-      label: GeneFamily
-      name: Voltage gated sodium channel, alpha subunit
-    - id: GO:0061530
-      label: BiologicalProcess
-      name: aspartate secretion, neurotransmission
-    - id: GO:0061535
-      label: BiologicalProcess
-      name: glutamate secretion, neurotransmission
-    - id: HP:0020219
-      label: PhenotypicFeature
-      name: Motor seizure
-    - id: MESH:D004827
-      label: Disease
-      name: Epilepsy
-  reference:
-    - https://go.drugbank.com/drugs/DB00555#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
-    - https://en.wikipedia.org/wiki/Lennox%E2%80%93Gastaut_syndrome#Signs_and_symptoms
-    - https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)#Disease,_disabilities,_and_pharmacology
-  comment: This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).
-- directed: true
-  graph:
-    _id: DB00555_MESH_D004827_2
-    disease: Epilepsy
-    disease_mesh: MESH:D004827
-    drug: lamotrigine
-    drug_mesh: MESH:C047781
-    drugbank: DB:DB00555
-  links:
-    - key: negatively regulates
-      source: MESH:C047781
-      target: UniProt:Q15878
-    - key: participates in
-      source: UniProt:Q15878
-      target: REACT:R-HSA-112308
-    - key: participates in
-      source: UniProt:Q15878
-      target: REACT:R-HSA-112308
-    - key: positively correlated with
-      source: REACT:R-HSA-112308
-      target: GO:0007268
-    - key: positively correlated with
-      source: GO:0007268
-      target: GO:0061535
-    - key: positively correlated with
-      source: GO:0061535
-      target: HP:0020219
-    - key: positively correlated with
-      source: HP:0020219
-      target: MESH:D004827
-  multigraph: true
-  nodes:
-    - id: MESH:C047781
-      label: Drug
-      name: lamotrigine
-    - id: UniProt:Q15878
-      label: Protein
-      name: Voltage-dependent R-type calcium channel subunit alpha-1E
-    - id: REACT:R-HSA-112308
-      label: Pathway
-      name: Presynaptic depolarization and calcium channel opening
-    - id: GO:0007268
-      label: BiologicalProcess
-      name: chemical synaptic transmission
-    - id: GO:0061535
-      label: BiologicalProcess
-      name: glutamate secretion, neurotransmission
-    - id: HP:0020219
-      label: PhenotypicFeature
-      name: Motor seizure
-    - id: MESH:D004827
-      label: Disease
-      name: Epilepsy
-  reference:
-    - https://go.drugbank.com/drugs/DB00555#BE0009609
-    - https://en.wikipedia.org/wiki/Lamotrigine#Mechanism_of_action
-    - https://pubmed.ncbi.nlm.nih.gov/10530688/
-    - https://pubmed.ncbi.nlm.nih.gov/9579933/
-    - https://en.wikipedia.org/wiki/Anticonvulsant
-    - https://en.wikipedia.org/wiki/Neuroprotection
-  comment: This drug may also affect GABA-mediated synaptic transmission as listed by DrugBank (https://go.drugbank.com/drugs/DB00555#BE0000013). However, this is contentious and if the drug does modulate GABA it's not known whether it is as agonist or antagonist due to conflicting data (at best it would be a weak modulation seen in animal models only). Note that the drug could be contraindicated for treatment of seizures as it can exacerbate them, specially the myoclonic type (https://pubmed.ncbi.nlm.nih.gov/9596203/).
-- directed: true
-  graph:
-      _id: DB00850_MESH_D012559_2
-      disease: Schizophrenia
-      disease_mesh: MESH:D012559
-      drug: prochlorperazine
-      drug_mesh: MESH:D011346
-      drugbank: DB:DB00850
-  links:
-    -   key: decreases activity of
-        source: MESH:D011346
-        target: UniProt:P14416
-    -   key: positively regulates
-        source: UniProt:P14416
-        target: GO:0014046
-    -   key: increases abundance of
-        source: GO:0014046
-        target: CHEBI:18243
-    -   key: positively correlated with
-        source: CHEBI:18243
-        target: MESH:D012559
-  multigraph: true
-  nodes:
-    -   id: MESH:D011346
-        label: Drug
-        name: prochlorperazine
-    -   id: UniProt:P14416
-        label: Protein
-        name: D(2) dopamine receptor
-    -   id: GO:0014046
-        label: BiologicalProcess
-        name: dopamine secretion
-    -   id: CHEBI:18243
-        label: ChemicalSubstance
-        name: dopamine
-    -   id: MESH:D012559
-        label: Disease
-        name: Schizophrenia
-  reference:
-    - https://go.drugbank.com/drugs/DB00433#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Prochlorperazine#Pharmacology
-    - https://en.wikipedia.org/wiki/Antipsychotic#Mechanism_of_action
-    - https://en.wikipedia.org/wiki/Mesolimbic_pathway#Relation_to_neurological_and_psychological_disorders
-- directed: true
-  graph:
-      _id: DB01239_MESH_D012559_1
-      disease: Schizophrenia
-      disease_mesh: MESH:D012559
-      drug: chlorprothixene
-      drug_mesh: MESH:D002749
-      drugbank: DB:DB01239
-  links:
-    -   key: decreases activity of
-        source: MESH:D002749
-        target: InterPro:IPR000995
-    -   key: decreases activity of
-        source: MESH:D002749
-        target: InterPro:IPR000929
-    -   key: decreases activity of
-        source: MESH:D002749
-        target: InterPro:IPR002231
-    -   key: positively regulates
-        source: InterPro:IPR000995
-        target: GO:0007274
-    -   key: positively correlated with
-        source: GO:0007274
-        target: HP:0011442
-    -   key: manifestation of
-        source: HP:0011442
-        target: MESH:D012559
-    -   key: positively regulates
-        source: InterPro:IPR002231
-        target: GO:0014046
-    -   key: positively regulates
-        source: InterPro:IPR000995
-        target: GO:0007213
-    -   key: positively correlated with
-        source: GO:0007213
-        target: GO:0014046
-    -   key: positively regulates
-        source: InterPro:IPR000929
-        target: GO:0014046
-    -   key: positively correlated with
-        source: GO:0014046
-        target: MESH:D012559
-  multigraph: true
-  nodes:
-    -   id: MESH:D002749
-        label: Drug
-        name: chlorprothixene
-    -   id: InterPro:IPR000995
-        label: GeneFamily
-        name: Muscarinic acetylcholine receptor family
-    -   id: InterPro:IPR002231
-        label: GeneFamily
-        name: 5-hydroxytryptamine receptor family
-    -   id: InterPro:IPR000929
-        label: GeneFamily
-        name: Dopamine receptor family
-    -   id: GO:0014046
-        label: BiologicalProcess
-        name: dopamine secretion
-    -   id: GO:0007274
-        label: BiologicalProcess
-        name: neuromuscular synaptic transmission
-    -   id: GO:0007213
-        label: BiologicalProcess
-        name: G protein-coupled acetylcholine receptor signaling pathway
-    -   id: HP:0011442
-        label: PhenotypicFeature
-        name: Abnormal central motor function
-    -   id: MESH:D012559
-        label: Disease
-        name: Schizophrenia
-  reference:
-    - https://go.drugbank.com/drugs/DB01239#mechanism-of-action
-    - https://go.drugbank.com/drugs/DB01239#BE0000092
-    - https://www.targetvalidation.org/summary?drug=CHEMBL908
-    - https://en.wikipedia.org/wiki/Antipsychotic#Mechanism_of_action
-    - https://en.wikipedia.org/wiki/Mesolimbic_pathway#Relation_to_neurological_and_psychological_disorders
-    - https://en.wikipedia.org/wiki/Schizophrenia#Medication
-  comment: Muscarinic receptor antagonists (also known as anticholinergics) seem to be used in patients with Schizophrenia to alleviate motor side effects caused by first-generation antipsychotics. However these antagonists do seem to lead to cognitive dysfunction in healthy controls. So whether these muscarinic receptors should be positively or negatively regulated in schizophrenia is a matter of debate (see https://www.nature.com/articles/4001924 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726271/). In addition, some suggest that that schizophrenia involves an overactivation of cholinergic neurons, which could provide cholinergic input to dopaminergic neurons. The dopamine neurons are located in the mesolimbic dopaminergic system (BTO:0005591), which is a component pathway of the medial forebrain bundle (UBERON:0001910). See https://en.wikipedia.org/wiki/Medial_forebrain_bundle#Anatomy for more details.
-- directed: true
-  graph:
-    _id: DB02701_MESH_D010437_1
-    disease: Peptic ulcer
-    disease_mesh: MESH:D010437
-    drug: ecabet
-    drug_mesh: MESH:C061681
-    drugbank: DB:DB02701
-  links:
-    - key: molecularly interacts with
-      source: MESH:C061681
-      target: MESH:C047874
-    - key: located in
-      source: MESH:C047874
-      target: MESH:D005753
-    - key: produces
-      source: MESH:D005753
-      target: UBERON:0000912
-    - key: negatively correlated with
-      source: UBERON:0000912
-      target: MESH:D010437
-    - key: disrupts
-      source: MESH:C061681
-      target: CHEBI:16412
-    - key: positively regulates
-      source: CHEBI:16412
-      target: REACT:R-HSA-166016
-    - key: positively correlated with
-      source: REACT:R-HSA-166016
-      target: GO:0006954
-    - key: located in
-      source: GO:0006954
-      target: UBERON:0001276
-    - key: location of
-      source: UBERON:0001276
-      target: MESH:D010437
-    - key: negatively regulates
-      source: MESH:C061681
-      target: InterPro:IPR017950
-    - key: positively regulates
-      source: InterPro:IPR017950
-      target: GO:0009039
-    - key: in taxon
-      source: GO:0009039
-      target: NCBITaxon:210
-    - key: causes
-      source: NCBITaxon:210
-      target: MESH:D010437
-  multigraph: true
-  nodes:
-    - id: MESH:C061681
-      label: Drug
-      name: ecabet
-    - id: CHEBI:16412
-      label: ChemicalSubstance
-      name: lipopolysaccharide
-    - id: REACT:R-HSA-166016
-      label: Pathway
-      name: Toll Like Receptor 4 (TLR4) Cascade
-    - id: GO:0006954
-      label: BiologicalProcess
-      name: inflammatory response
-    - id: UBERON:0001276
-      label: GrossAnatomicalStructure
-      name: epithelium of stomach
-    - id: InterPro:IPR017950
-      label: GeneFamily
-      name: Urease active site
-    - id: GO:0009039
-      label: MolecularActivity
-      name: urease activity
-    - id: NCBITaxon:210
-      label: OrganismTaxon
-      name: Helicobacter pylori
-    - id: MESH:C047874
-      label: GeneFamily
-      name: gastric mucus glycoproteins
-    - id: UBERON:0000912
-      label: GrossAnatomicalStructure
-      name: Mucus
-    - id: MESH:D005753
-      label: GrossAnatomicalStructure
-      name: Gastric Mucosa
-    - id: MESH:D010437
-      label: Disease
-      name: Peptic ulcer
-  reference:
-    - https://go.drugbank.com/drugs/DB05265#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Peptic_ulcer_disease#H._pylori
-    - https://drugs.ncats.io/drug/2K02669KW
-- directed: true
-  graph:
-    _id: DB00422_MESH_D001289_1
-    disease: Attention deficit hyperactivity disorder
-    disease_mesh: MESH:D001289
-    drug: methylphenidate
-    drug_mesh: MESH:D008774
-    drugbank: DB:DB00422
-  links:
-    - key: decreases activity of
-      source: MESH:D008774
-      target: UniProt:Q01959
-    - key: decreases activity of
-      source: MESH:D008774
-      target: UniProt:P23975
-    - key: positively regulates
-      source: UniProt:Q01959
-      target: GO:0090494
-    - key: positively regulates
-      source: UniProt:P23975
-      target: GO:0051620
-    - key: positively correlated with
-      source: GO:0051620
-      target: MESH:D001289
-    - key: positively correlated with
-      source: GO:0090494
-      target: MESH:D001289
-  multigraph: true
-  nodes:
-    - id: MESH:D008774
-      label: Drug
-      name: methylphenidate
-    - id: UniProt:Q01959
-      label: Protein
-      name: Sodium-dependent dopamine transporter
-    - id: UniProt:P23975
-      label: Protein
-      name: Sodium-dependent noradrenaline transporter
-    - id: GO:0090494
-      label: BiologicalProcess
-      name: dopamine uptake
-    - id: GO:0051620
-      label: BiologicalProcess
-      name: norepinephrine uptake
-    - id: MESH:D001289
-      label: Disease
-      name: Attention deficit hyperactivity disorder
-  reference:
-    - https://go.drugbank.com/drugs/DB00422#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Methylphenidate#Pharmacodynamics
-    - https://www.targetvalidation.org/summary?drug=CHEMBL796
-  comment: This drug may be able to bind to UniProt:P08908 but its pharmacological activity (agonism vs. antagonism) is not known (https://go.drugbank.com/drugs/DB00422#BE0000291).
-- directed: true
-  graph:
-    _id: DB00422_MESH_D009290_1
-    disease: Narcolepsy
-    disease_mesh: MESH:D009290
-    drug: methylphenidate
-    drug_mesh: MESH:D008774
-    drugbank: DB:DB00422
-  links:
-    - key: decreases activity of
-      source: MESH:D008774
-      target: UniProt:Q01959
-    - key: decreases activity of
-      source: MESH:D008774
-      target: UniProt:P23975
-    - key: positively regulates
-      source: UniProt:Q01959
-      target: GO:0090494
-    - key: positively regulates
-      source: UniProt:P23975
-      target: GO:0051620
-    - key: positively correlated with
-      source: GO:0051620
-      target: MESH:D009290
-    - key: positively correlated with
-      source: GO:0090494
-      target: MESH:D009290
-  multigraph: true
-  nodes:
-    - id: MESH:D008774
-      label: Drug
-      name: methylphenidate
-    - id: UniProt:Q01959
-      label: Protein
-      name: Sodium-dependent dopamine transporter
-    - id: UniProt:P23975
-      label: Protein
-      name: Sodium-dependent noradrenaline transporter
-    - id: GO:0090494
-      label: BiologicalProcess
-      name: dopamine uptake
-    - id: GO:0051620
-      label: BiologicalProcess
-      name: norepinephrine uptake
-    - id: MESH:D009290
-      label: Disease
-      name: Narcolepsy
-  reference:
-    - https://go.drugbank.com/drugs/DB00422#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Methylphenidate#Pharmacodynamics
-    - https://www.targetvalidation.org/summary?drug=CHEMBL796
-    - https://en.wikipedia.org/wiki/Narcolepsy#Treatment
-  comment: This drug may be able to bind to UniProt:P08908 but its pharmacological activity (agonism vs. antagonism) is not known (https://go.drugbank.com/drugs/DB00422#BE0000291).
-- directed: true
-  graph:
-    _id: DB01179_MESH_D003218_1
-    disease: Condyloma acuminatum
-    disease_mesh: MESH:D003218
-    drug: podophyllotoxin
-    drug_mesh: MESH:D011034
-    drugbank: DB:DB01179
-  links:
-    - key: negatively regulates
-      source: MESH:D011034
-      target: UniProt:P03120
-    - key: positively regulates
-      source: UniProt:P03120
-      target: GO:0039693
-    - key: in taxon
-      source: GO:0039693
-      target: NCBITaxon:10566
-    - key: causes
-      source: NCBITaxon:10566
-      target: MESH:D003218
-  multigraph: true
-  nodes:
-    - id: MESH:D011034
-      label: Drug
-      name: podophyllotoxin
-    - id: UniProt:P03120
-      label: Protein
-      name: Regulatory protein E2
-    - id: GO:0039693
-      label: BiologicalProcess
-      name: viral DNA genome replication
-    - id: NCBITaxon:10566
-      label: OrganismTaxon
-      name: Human papillomavirus
-    - id: MESH:D003218
-      label: Disease
-      name: Condyloma acuminatum
-  reference: https://drugcentral.org/drugcard/3481?q=Podofilox
-  comment: This drug can also inhbit human proteins and affect with the mammalian cell division/replication, which make them an attractive antitumour agent (https://pubmed.ncbi.nlm.nih.gov/11102564/).
-- directed: true
-  graph:
-    _id: DB01003_MESH_D003233_1
-    disease: Giant papillary conjunctivitis
-    disease_mesh: MESH:D003233
-    drug: cromoglicic acid
-    drug_mesh: MESH:D004205
-    drugbank: DB:DB01003
-  links:
-    - key: decreases activity of
-      source: MESH:D004205
-      target: UniProt:P25815
-    - key: positively correlated with
-      source: UniProt:P25815
-      target: GO:0043303
-    - key: positively correlated with
-      source: UniProt:P25815
-      target: GO:0043308
-    - key: caused by
-      source: GO:0043303
-      target: REACT:R-HSA-2454202
-    - key: positively correlated with
-      source: REACT:R-HSA-2454202
-      target: GO:0002441
-    - key: positively correlated with
-      source: REACT:R-HSA-2454202
-      target: GO:0002540
-    - key: positively correlated with
-      source: GO:0043308
-      target: GO:0002540
-    - key: positively correlated with
-      source: GO:0002441
-      target: MESH:D003233
-    - key: positively correlated with
-      source: GO:0002540
-      target: MESH:D003233
-  multigraph: true
-  nodes:
-    - id: MESH:D004205
-      label: Drug
-      name: cromoglicic acid
-    - id: UniProt:P25815
-      label: Protein
-      name: Protein S100-P
-    - id: GO:0043303
-      label: BiologicalProcess
-      name: mast cell degranulation
-    - id: GO:0043308
-      label: BiologicalProcess
-      name: eosinophil degranulation
-    - id: GO:0002540
-      label: BiologicalProcess
-      name: leukotriene production involved in inflammatory response
-    - id: REACT:R-HSA-2454202
-      label: Pathway
-      name: Allergen dependent IgE bound FCERI aggregation
-    - id: GO:0002441
-      label: BiologicalProcess
-      name: histamine secretion involved in inflammatory response
-    - id: MESH:D003233
-      label: Disease
-      name: Giant papillary conjunctivitis
-  reference:
-    - https://go.drugbank.com/drugs/DB01003#mechanism-of-action
-    - https://pubmed.ncbi.nlm.nih.gov/25450399/
-    - https://pubchem.ncbi.nlm.nih.gov/compound/2882#section=Pharmacology-and-Biochemistry
-    - https://pubmed.ncbi.nlm.nih.gov/12645002/
-    - https://en.wikipedia.org/wiki/RAGE_(receptor)#RAGE_and_disease
-    - https://en.wikipedia.org/wiki/Mast_cell_stabilizer
-    - https://en.wikipedia.org/wiki/S100P#Interactions
-  comment: This condition does not seem to be a true ocular allergic reaction, rather caused by repeated mechanical irritation of the conjunctiva (https://en.wikipedia.org/wiki/Allergic_conjunctivitis#Giant_papillary_conjunctivitis). So the treatment with cromoglicic acid may not be needed/useful at all but interruption of contact lens wearing.
-- directed: true
-  graph:
-    _id: DB01003_MESH_D034721_1
-    disease: Systemic mast cell disease
-    disease_mesh: MESH:D034721
-    drug: cromoglicic acid
-    drug_mesh: MESH:D004205
-    drugbank: DB:DB01003
-  links:
-    - key: decreases activity of
-      source: MESH:D004205
-      target: UniProt:P25815
-    - key: positively correlated with
-      source: UniProt:P25815
-      target: GO:0043303
-    - key: caused by
-      source: GO:0043303
-      target: REACT:R-HSA-2454202
-    - key: positively correlated with
-      source: REACT:R-HSA-2454202
-      target: GO:0002441
-    - key: positively correlated with
-      source: REACT:R-HSA-2454202
-      target: GO:0002540
-    - key: positively correlated with
-      source: GO:0002441
-      target: MESH:D034721
-    - key: positively correlated with
-      source: GO:0002540
-      target: MESH:D034721
-  multigraph: true
-  nodes:
-    - id: MESH:D004205
-      label: Drug
-      name: cromoglicic acid
-    - id: UniProt:P25815
-      label: Protein
-      name: Protein S100-P
-    - id: GO:0043303
-      label: BiologicalProcess
-      name: mast cell degranulation
-    - id: REACT:R-HSA-2454202
-      label: Pathway
-      name: Allergen dependent IgE bound FCERI aggregation
-    - id: GO:0002540
-      label: BiologicalProcess
-      name: leukotriene production involved in inflammatory response
-    - id: GO:0002441
-      label: BiologicalProcess
-      name: histamine secretion involved in inflammatory response
-    - id: MESH:D034721
-      label: Disease
-      name: Systemic mast cell disease
-  reference:
-    - https://go.drugbank.com/drugs/DB01003#mechanism-of-action
-    - https://pubmed.ncbi.nlm.nih.gov/25450399/
-    - https://pubchem.ncbi.nlm.nih.gov/compound/2882#section=Pharmacology-and-Biochemistry
-    - https://pubmed.ncbi.nlm.nih.gov/12645002/
-    - https://en.wikipedia.org/wiki/RAGE_(receptor)#RAGE_and_disease
-    - https://en.wikipedia.org/wiki/S100P#Interactions
-    - https://en.wikipedia.org/wiki/Mastocytosis#Anti-mediator_therapy
-    - https://en.wikipedia.org/wiki/Mast_cell_stabilizer
-- directed: true
-  graph:
-    _id: DB01003_MESH_D001249_1
-    disease: Asthma
-    disease_mesh: MESH:D001249
-    drug: cromoglicic acid
-    drug_mesh: MESH:D004205
-    drugbank: DB:DB01003
-  links:
-    - key: decreases activity of
-      source: MESH:D004205
-      target: UniProt:P25815
-    - key: positively correlated with
-      source: UniProt:P25815
-      target: GO:0043303
-    - key: caused by
-      source: GO:0043303
-      target: REACT:R-HSA-2454202
-    - key: positively correlated with
-      source: REACT:R-HSA-2454202
-      target: GO:0002441
-    - key: positively correlated with
-      source: REACT:R-HSA-2454202
-      target: GO:0002540
-    - key: positively correlated with
-      source: GO:0002441
-      target: MESH:D001249
-    - key: positively correlated with
-      source: GO:0002540
-      target: MESH:D001249
-  multigraph: true
-  nodes:
-    - id: MESH:D004205
-      label: Drug
-      name: cromoglicic acid
-    - id: UniProt:P25815
-      label: Protein
-      name: Protein S100-P
-    - id: GO:0043303
-      label: BiologicalProcess
-      name: mast cell degranulation
-    - id: REACT:R-HSA-2454202
-      label: Pathway
-      name: Allergen dependent IgE bound FCERI aggregation
-    - id: GO:0002540
-      label: BiologicalProcess
-      name: leukotriene production involved in inflammatory response
-    - id: GO:0002441
-      label: BiologicalProcess
-      name: histamine secretion involved in inflammatory response
-    - id: MESH:D001249
-      label: Disease
-      name: Asthma
-  reference:
-    - https://go.drugbank.com/drugs/DB01003#mechanism-of-action
-    - https://pubmed.ncbi.nlm.nih.gov/25450399/
-    - https://pubchem.ncbi.nlm.nih.gov/compound/2882#section=Pharmacology-and-Biochemistry
-    - https://pubmed.ncbi.nlm.nih.gov/12645002/
-    - https://en.wikipedia.org/wiki/RAGE_(receptor)#RAGE_and_disease
-    - https://en.wikipedia.org/wiki/S100P#Interactions
-    - https://en.wikipedia.org/wiki/Mastocytosis#Anti-mediator_therapy
-    - https://en.wikipedia.org/wiki/Mast_cell_stabilizer
-    - https://en.wikipedia.org/wiki/Asthma#Management
-- directed: true
-  graph:
-    _id: DB01003_MESH_D065631_1
-    disease: Allergic rhinitis
-    disease_mesh: MESH:D065631
-    drug: cromoglicic acid
-    drug_mesh: MESH:D004205
-    drugbank: DB:DB01003
-  links:
-    - key: decreases activity of
-      source: MESH:D004205
-      target: UniProt:P25815
-    - key: positively correlated with
-      source: UniProt:P25815
-      target: GO:0043303
-    - key: positively correlated with
-      source: UniProt:P25815
-      target: GO:0043308
-    - key: caused by
-      source: GO:0043303
-      target: REACT:R-HSA-2454202
-    - key: positively correlated with
-      source: REACT:R-HSA-2454202
-      target: GO:0002441
-    - key: positively correlated with
-      source: REACT:R-HSA-2454202
-      target: GO:0002540
-    - key: positively correlated with
-      source: GO:0043308
-      target: GO:0002540
-    - key: positively correlated with
-      source: GO:0002441
-      target: MESH:D065631
-    - key: positively correlated with
-      source: GO:0002540
-      target: MESH:D065631
-  multigraph: true
-  nodes:
-    - id: MESH:D004205
-      label: Drug
-      name: cromoglicic acid
-    - id: UniProt:P25815
-      label: Protein
-      name: Protein S100-P
-    - id: GO:0043303
-      label: BiologicalProcess
-      name: mast cell degranulation
-    - id: GO:0043308
-      label: BiologicalProcess
-      name: eosinophil degranulation
-    - id: REACT:R-HSA-2454202
-      label: Pathway
-      name: Allergen dependent IgE bound FCERI aggregation
-    - id: GO:0002540
-      label: BiologicalProcess
-      name: leukotriene production involved in inflammatory response
-    - id: GO:0002441
-      label: BiologicalProcess
-      name: histamine secretion involved in inflammatory response
-    - id: MESH:D065631
-      label: Disease
-      name: Allergic rhinitis
-  reference:
-    - https://go.drugbank.com/drugs/DB01003#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Mast_cell_stabilizer
-    - https://pubmed.ncbi.nlm.nih.gov/25450399/
-    - https://pubchem.ncbi.nlm.nih.gov/compound/2882#section=Pharmacology-and-Biochemistry
-    - https://pubmed.ncbi.nlm.nih.gov/12645002/
-    - https://en.wikipedia.org/wiki/RAGE_(receptor)#RAGE_and_disease
-    - https://en.wikipedia.org/wiki/S100P#Interactions
-- directed: true
-  graph:
-    _id: DB01137_MESH_D018410_1
-    disease: Bacterial pneumonia
-    disease_mesh: MESH:D018410
-    drug: levofloxacin
-    drug_mesh: MESH:D064704
-    drugbank: DB:DB01137
-  links:
-    - key: negatively regulates
-      source: MESH:D064704
-      target: InterPro:IPR035516
-    - key: negatively regulates
-      source: MESH:D064704
-      target: InterPro:IPR013760
-    - key: positively regulates
-      source: InterPro:IPR035516
-      target: GO:0006260
-    - key: positively regulates
-      source: InterPro:IPR013760
-      target: GO:0006260
-    - key: in taxon
-      source: GO:0006260
-      target: NCBITaxon:1392
-    - key: causes
-      source: NCBITaxon:1392
-      target: MESH:D018410
-  multigraph: true
-  nodes:
-    - id: MESH:D064704
-      label: Drug
-      name: levofloxacin
-    - id: InterPro:IPR035516
-      label: GeneFamily
-      name: DNA gyrase/topoisomerase IV, subunit A, C-terminal
-    - id: InterPro:IPR013760
-      label: GeneFamily
-      name: DNA topoisomerase, type IIA-like domain superfamily
-    - id: GO:0006260
-      label: BiologicalProcess
-      name: Bacterial DNA replication
-    - id: NCBITaxon:1392
-      label: OrganismTaxon
-      name: Bacillus anthracis
-    - id: MESH:D018410
-      label: Disease
-      name: Bacterial pneumonia
-  reference:
-    - https://go.drugbank.com/drugs/DB01137#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Bacterial_pneumonia#Types
-    - https://en.wikipedia.org/wiki/Levofloxacin#Mechanism_of_action
-  comment: Different bacterial species can cause pneumonia, the most frequent ones are Streptococcus pneumoniae, Staphylococcus aureus, and Bacillus anthracis, among the gram-positive types of bacteria. Gram-negative examples of bacteria causing pneumonia are Haemophilus influenzae, Klebsiella pneumoniae and Escherichia coli.
-- directed: true
-  graph:
-    _id: DB01137_MESH_D011023_1
-    disease: Staphylococcal pneumonia
-    disease_mesh: MESH:D011023
-    drug: levofloxacin
-    drug_mesh: MESH:D064704
-    drugbank: DB:DB01137
-  links:
-    - key: negatively regulates
-      source: MESH:D064704
-      target: InterPro:IPR035516
-    - key: negatively regulates
-      source: MESH:D064704
-      target: InterPro:IPR013760
-    - key: positively regulates
-      source: InterPro:IPR035516
-      target: GO:0006260
-    - key: positively regulates
-      source: InterPro:IPR013760
-      target: GO:0006260
-    - key: in taxon
-      source: GO:0006260
-      target: NCBITaxon:1280
-    - key: causes
-      source: NCBITaxon:1280
-      target: MESH:D011023
-  multigraph: true
-  nodes:
-    - id: MESH:D064704
-      label: Drug
-      name: levofloxacin
-    - id: InterPro:IPR035516
-      label: GeneFamily
-      name: DNA gyrase/topoisomerase IV, subunit A, C-terminal
-    - id: InterPro:IPR013760
-      label: GeneFamily
-      name: DNA topoisomerase, type IIA-like domain superfamily
-    - id: GO:0006260
-      label: BiologicalProcess
-      name: Bacterial DNA replication
-    - id: NCBITaxon:1280
-      label: OrganismTaxon
-      name: Staphylococcus aureus
-    - id: MESH:D011023
-      label: Disease
-      name: Staphylococcal pneumonia
-  reference:
-    - https://go.drugbank.com/drugs/DB01137#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Bacterial_pneumonia#Gram-positive
-    - https://en.wikipedia.org/wiki/Staphylococcus_aureus#Role_in_disease
-    - https://en.wikipedia.org/wiki/Levofloxacin#Mechanism_of_action
-  comment: Different bacterial species can cause pneumonia, the most frequent ones are Streptococcus pneumoniae, Staphylococcus aureus, and Bacillus anthracis, among the gram-positive types of bacteria. Gram-negative examples of bacteria causing pneumonia are Haemophilus influenzae, Klebsiella pneumoniae and Escherichia coli.
-- directed: true
-  graph:
-    _id: DB01369_MESH_D013290_1
-    disease: Streptococcus pyogenes infection
-    disease_mesh: MESH:D013290
-    drug: quinupristin
-    drug_mesh: MESH:C113825
-    drugbank: DB:DB01369
-  links:
-    - key: decreases activity of
-      source: MESH:C113825
-      target: MESH:D054681
-    - key: negatively regulates
-      source: MESH:C113825
-      target: Pfam:PF00466
-    - key: negatively regulates
-      source: MESH:C113825
-      target: Pfam:PF00237
-    - key: positively regulates
-      source: Pfam:PF00466
-      target: GO:0006412
-    - key: positively regulates
-      source: Pfam:PF00237
-      target: GO:0006412
-    - key: location of
-      source: MESH:D054681
-      target: GO:0000048
-    - key: positively correlated with
-      source: GO:0000048
-      target: GO:0006412
-    - key: in taxon
-      source: GO:0006412
-      target: NCBITaxon:1314
-    - key: causes
-      source: NCBITaxon:1314
-      target: MESH:D013290
-  multigraph: true
-  nodes:
-    - id: MESH:C113825
-      label: Drug
-      name: quinupristin
-    - id: MESH:D054681
-      label: ChemicalSubstance
-      name: Ribosome Subunits, Large, Bacterial
-    - id: GO:0006412
-      label: BiologicalProcess
-      name: translation
-    - id: GO:0000048
-      label: MolecularActivity
-      name: peptidyltransferase activity
-    - id: Pfam:PF00237
-      label: GeneFamily
-      name: Ribosomal protein L22p/L17e
-    - id: Pfam:PF00466
-      label: GeneFamily
-      name: Ribosomal protein L10
-    - id: NCBITaxon:1314
-      label: OrganismTaxon
-      name: Streptococcus pyogenes
-    - id: MESH:D013290
-      label: Disease
-      name: Streptococcus pyogenes infection
-  reference:
-    - https://go.drugbank.com/drugs/DB01369#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Quinupristin
-    - https://www.tandfonline.com/doi/abs/10.1517/13543784.7.4.591
-    - https://en.wikipedia.org/wiki/Quinupristin/dalfopristin#Mechanism_of_action
-  comment: This drug is used in combination with dalfopristin. Both interfere with the bacterial protein synthesis, at different stages of the translation. Quinupristin inhibits the late phase of protein synthesis, whereas dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome. In combination, both drugs are more effective than each used individually (https://go.drugbank.com/drugs/DB01369#description).
-- directed: true
-  graph:
-    _id: DB11792_MESH_D007172_1
-    disease: Impotence
-    disease_mesh: MESH:D007172
-    drug: mirodenafil
-    drug_mesh: MESH:C528396
-    drugbank: DB:DB11792
-  links:
-    - key: negatively regulates
-      source: MESH:C528396
-      target: UniProt:O76074
-    - key: positively regulates
-      source: UniProt:O76074
-      target: GO:0046069
-    - key: decreases abundance of
-      source: GO:0046069
-      target: CHEBI:16356
-    - key: positively correlated with
-      source: CHEBI:16356
-      target: GO:0007263
-    - key: positively correlated with
-      source: GO:0007263
-      target: GO:0044557
-    - key: negatively correlated with
-      source: GO:0044557
-      target: HP:0100639
-    - key: manifestation of
-      source: HP:0100639
-      target: MESH:D007172
-  multigraph: true
-  nodes:
-    - id: MESH:C528396
-      label: Drug
-      name: mirodenafil
-      all_id:
-        - MESH:C518762
-    - id: UniProt:O76074
-      label: Protein
-      name: cGMP-specific 3',5'-cyclic phosphodiesterase
-    - id: GO:0046069
-      label: BiologicalProcess
-      name: cGMP catabolic process
-    - id: CHEBI:16356
-      label: ChemicalSubstance
-      name: 3',5'-cyclic GMP
-    - id: GO:0007263
-      label: BiologicalProcess
-      name: nitric oxide mediated signal transduction
-    - id: GO:0044557
-      label: BiologicalProcess
-      name: relaxation of smooth muscle
-    - id: HP:0100639
-      label: PhenotypicFeature
-      name: Erectile dysfunction
-    - id: MESH:D007172
-      label: Disease
-      name: Impotence
-  reference:
-    - https://en.wikipedia.org/wiki/Mirodenafil
-    - https://en.wikipedia.org/wiki/PDE5_inhibitor#Mechanism_of_action
-    - https://en.wikipedia.org/wiki/Nitric_oxide#Biological_functions
-- directed: true
-  graph:
-    _id: DB12214_MESH_D003924_1
-    disease: Diabetes mellitus type 2
-    disease_mesh: MESH:D003924
-    drug: luseogliflozin
-    drug_mesh: MESH:C549343
-    drugbank: DB:DB12214
-  links:
-    - key: negatively regulates
-      source: MESH:C549343
-      target: UniProt:P13866
-    - key: negatively regulates
-      source: MESH:C549343
-      target: UniProt:Q8WWX8
-    - key: positively regulates
-      source: UniProt:P13866
-      target: GO:0098708
-    - key: positively regulates
-      source: UniProt:Q8WWX8
-      target: GO:1904659
-    - key: positively correlated with
-      source: GO:0098708
-      target: GO:0035623
-    - key: positively correlated with
-      source: GO:1904659
-      target: GO:0035623
-    - key: positively correlated with
-      source: GO:0035623
-      target: HP:0003074
-    - key: manifestation of
-      source: HP:0003074
-      target: MESH:D003924
-  multigraph: true
-  nodes:
-    - id: MESH:C549343
-      label: Drug
-      name: luseogliflozin
-    - id: UniProt:P13866
-      label: Protein
-      name: Sodium/glucose cotransporter 1
-    - id: UniProt:Q8WWX8
-      label: Protein
-      name: Sodium/myo-inositol cotransporter 2
-    - id: GO:0098708
-      label: BiologicalProcess
-      name: glucose import across plasma membrane
-    - id: GO:1904659
-      label: BiologicalProcess
-      name: glucose transmembrane transport
-    - id: GO:0035623
-      label: BiologicalProcess
-      name: renal glucose absorption
-    - id: HP:0003074
-      label: PhenotypicFeature
-      name: Hyperglycemia
-    - id: MESH:D003924
-      label: Disease
-      name: Diabetes mellitus type 2
-  reference:
-    - https://en.wikipedia.org/wiki/Luseogliflozin
-    - https://en.wikipedia.org/wiki/SGLT2_inhibitor
-- directed: true
-  graph:
-    _id: DB00461_MESH_D001172_1
-    disease: Rheumatoid arthritis
-    disease_mesh: MESH:D001172
-    drug: Nabumetone
-    drug_mesh: MESH:D007660
-    drugbank: DB:DB00461
-  links:
-    - key: produces
-      source: MESH:D007660
-      target: CHEBI:35628
-    - key: decreases activity of
-      source: CHEBI:35628
-      target: UniProt:P23219
-    - key: decreases activity of
-      source: CHEBI:35628
-      target: UniProt:P35354
-    - key: participates in
-      source: UniProt:P23219
-      target: REACT:R-HSA-2162123
-    - key: participates in
-      source: UniProt:P35354
-      target: REACT:R-HSA-2162123
-    - key: increases abundance of
-      source: REACT:R-HSA-2162123
-      target: MESH:D011453
-    - key: positively correlated with
-      source: MESH:D011453
-      target: HP:0002829
-    - key: positively correlated with
-      source: MESH:D011453
-      target: HP:0001386
-    - key: positively correlated with
-      source: HP:0001386
-      target: MESH:D001172
-    - key: positively correlated with
-      source: HP:0002829
-      target: MESH:D001172
-  multigraph: true
-  nodes:
-    - id: MESH:D007660
-      label: Drug
-      name: Nabumetone
-    - id: CHEBI:35628
-      label: Drug
-      name: (6-methoxy-2-naphthyl)acetic acid
-    - id: UniProt:P23219
-      label: Protein
-      name: Prostaglandin G/H synthase 1
-    - id: UniProt:P35354
-      label: Protein
-      name: Prostaglandin G/H synthase 2
-    - id: REACT:R-HSA-2162123
-      label: BiologicalProcess
-      name: Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
-    - id: MESH:D011453
-      label: ChemicalSubstance
-      name: Prostaglandins
-    - id: HP:0002829
-      label: PhenotypicFeature
-      name: Joint pain
-    - id: HP:0001386
-      label: PhenotypicFeature
-      name: Joint swelling
-    - id: MESH:D001172
-      label: Disease
-      name: Rheumatoid arthritis
-  reference:
-    - https://go.drugbank.com/drugs/DB00461#mechanism-of-action
-    - https://en.wikipedia.org/wiki/Nabumetone
-  comment: Nabumetone is a prodrug, which is metabolised into the pharmacologically active drug (CHEBI:35628, 6-methoxy-2-naphthyl acetic acid). Note that the drug preferentially blocks COX-2 activity.
-- directed: true
-  graph:
-    _id: DB00727_MESH_D000787_1
-    disease: Angina pectoris
-    disease_mesh: MESH:D000787
-    drug: glyceryl trinitrate
-    drug_mesh: MESH:D005996
-    drugbank: DB:DB00727
-  links:
-    - key: produces
-      source: MESH:D005996
-      target: CHEBI:16480
-    - key: positively regulates
-      source: CHEBI:16480
-      target: GO:0038060
-    - key: positively correlated with
-      source: GO:0038060
-      target: GO:0042311
-    - key: positively regulates
-      source: CHEBI:16480
-      target: UniProt:P16066
-    - key: positively regulates
-      source: UniProt:P16066
-      target: GO:0007168
-    - key: positively correlated with
-      source: GO:0007168
-      target: GO:0042311
-    - key: negatively correlated with
-      source: GO:0042311
-      target: MESH:D000787
-  multigraph: true
-  nodes:
-    - id: MESH:D005996
-      label: Drug
-      name: glyceryl trinitrate
-      alt_names:
-         - Nitroglycerin
-    - id: CHEBI:16480
-      label: ChemicalSubstance
-      name: nitric oxide
-    - id: UniProt:P16066
-      label: Protein
-      name: Atrial natriuretic peptide receptor 1
-    - id: GO:0038060
-      label: BiologicalProcess
-      name: nitric oxide-cGMP-mediated signaling pathway
-    - id: GO:0007168
-      label: BiologicalProcess
-      name: receptor guanylyl cyclase signaling pathway
-    - id: GO:0042311
-      label: BiologicalProcess
-      name: vasodilation
-    - id: MESH:D000787
-      label: Disease
-      name: Angina pectoris
-  reference:
-    - https://go.drugbank.com/drugs/DB00727#mechanism-of-action
-    - https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL730/
-    - https://en.wikipedia.org/wiki/Nitroglycerin#Medical_use
-  comment: The activation of Atrial natriuretic peptide receptor 1 has been observed in vitro (https://pubmed.ncbi.nlm.nih.gov/12890708/) and it's reported in DrugBank whereas ChEMBL favours the Soluble Guanylyl Cyclase route. Also note that when the drug is admnistered at low doses, it dilates veins and reduces the volume of blood in the heart after filling (this is supposedly the main mechanism of action). At higher doses, it dilates arteries as well.
-- directed: true
-  graph:
-    _id: DB00184_MESH_D010383_1
-    disease: Niacin deficiency
-    disease_mesh: MESH:D010383
-    drug: nicotine
-    drug_mesh: MESH:D009538
-    drugbank: DB:DB00184
-  links:
-    - key: treats
-      source: MESH:D009538
-      target: MESH:D010383
-  multigraph: true
-  nodes:
-    - id: MESH:D009538
-      label: Drug
-      name: nicotine
-      alt_ids:
-         - MESH:D061485
-    - id: MESH:D010383
-      label: Disease
-      name: Niacin deficiency
-  reference:
-    - https://go.drugbank.com/drugs/DB00184#indication
-    - https://en.wikipedia.org/wiki/Nicotine#Biosynthesis
-    - https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL3/
-    - https://hopes.stanford.edu/nicotinamide/#relationship-between-nicotinamide-and-nicotine
-  comment: There appears to be no connection between Niacin deficiency and nicotine. Although niacin and nicotine are somehow related (nicotine can turn into nicotinic acid via oxidation), nicotine may not be able to replace niacin as treatment for Niacin deficiency. Actually nicotine could compete with niacin for binding sites in the enzymes necessary for vitamin B3 metabolism, and therefore would decrease the amount of B3 available for the cells.
-- directed: true
-  graph:
-    _id: DB06718_MESH_D010673_1
-    disease: Pheochromocytoma
-    disease_mesh: MESH:D010673
-    drug: phenoxybenzamine
-    drug_mesh: MESH:D010643
-    drugbank: DB:DB06718
-  links:
-  - key: decreases activity of
-    source: MESH:D010643
-    target: UniProt:P35348
-  - key: decreases activity of
-    source: MESH:D010643
-    target: UniProt:P08913
-  - key: decreases activity of
-    source: MESH:D010643
-    target: UniProt:P18825
-  - key: decreases activity of
-    source: MESH:D010643
-    target: UniProt:P25100
-  - key: decreases activity of
-    source: MESH:D010643
-    target: UniProt:P35368
-  - key: decreases activity of
-    source: MESH:D010643
-    target: UniProt:P18089
-  - key: positively regulates
-    source: UniProt:P35348
-    target: GO:0042310
-  - key: regulates
-    source: UniProt:P08913
-    target: GO:0042310
-  - key: positively regulates
-    source: UniProt:P18825
-    target: GO:0042310
-  - key: positively regulates
-    source: UniProt:P25100
-    target: GO:0042310
-  - key: positively regulates
-    source: UniProt:P35368
-    target: GO:0042310
-  - key: positively regulates
-    source: UniProt:P18089
-    target: GO:0042310
-  - key: positively correlated with
-    source: GO:0042310
-    target: MESH:D014655
-  - key: positively correlated with
-    source: MESH:D014655
-    target: HP:0002640
-  - key: manifestation of
-    source: HP:0002640
-    target: MESH:D010673
-  multigraph: true
-  nodes:
-  - id: MESH:D010643
-    label: Drug
-    name: phenoxybenzamine
-  - id: UniProt:P35348
-    label: Protein
-    name: Alpha-1A adrenergic receptor
-  - id: UniProt:P08913
-    label: Protein
-    name: Alpha-2A adrenergic receptor
-  - id: UniProt:P18825
-    label: Protein
-    name: Alpha-2C adrenergic receptor
-  - id: UniProt:P25100
-    label: Protein
-    name: Alpha-1D adrenergic receptor
-  - id: UniProt:P18089
-    label: Protein
-    name: Alpha-2B adrenergic receptor
-  - id: UniProt:P35368
-    label: Protein
-    name: Alpha-1B adrenergic receptor
-  - id: GO:0042310
-    label: BiologicalProcess
-    name: vasoconstriction
-  - id: MESH:D014655
-    label: BiologicalProcess
-    name: Vascular Resistance
-  - id: HP:0002640
-    label: PhenotypicFeature
-    name: Hypertension associated with pheochromocytoma
-  - id: MESH:D010673
-    label: Disease
-    name: Pheochromocytoma
-  reference:
-    - https://go.drugbank.com/drugs/DB00925#mechanism-of-action
-    - https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL753/
-    - https://en.wikipedia.org/wiki/Alpha_blocker#Hypertension
-    - https://en.wikipedia.org/wiki/Phenoxybenzamine#Pharmacology
-    - https://en.wikipedia.org/wiki/Pheochromocytoma#Alpha_blockade
-- directed: true
-  graph:
-    _id: DB06718_MESH_D054179_1
-    disease: Hereditary angioneurotic edema
-    disease_mesh: MESH:D054179
-    drug: stanozolol
-    drug_mesh: MESH:D013197
-    drugbank: DB:DB06718
-  links:
-    - key: positively regulates
-      source: MESH:D013197
-      target: UniProt:P05155
-    - key: negatively regulates
-      source: UniProt:P05155
-      target: GO:0006956
-    - key: positively correlated with
-      source: GO:0006956
-      target: Pfam:PF06753
-    - key: negatively correlated with
-      source: UniProt:P05155
-      target: MESH:D007610
-    - key: positively correlated with
-      source: MESH:D007610
-      target: Pfam:PF06753
-    - key: positively correlated with
-      source: Pfam:PF06753
-      target: MESH:D002199
-    - key: positively correlated with
-      source: Pfam:PF06753
-      target: GO:0042311
-    - key: positively correlated with
-      source: MESH:D002199
-      target: MESH:D054179
-    - key: positively correlated with
-      source: GO:0042311
-      target: MESH:D054179
-  multigraph: true
-  nodes:
-    - id: MESH:D013197
-      label: Drug
-      name: stanozolol
-    - id: UniProt:P05155
-      label: Protein
-      name: Plasma protease C1 inhibitor
-    - id: GO:0006956
-      label: BiologicalProcess
-      name: complement activation
-    - id: GO:0042311
-      label: BiologicalProcess
-      name: vasodilation
-    - id: MESH:D007610
-      label: GeneFamily
-      name: Kallikreins
-    - id: Pfam:PF06753
-      label: GeneFamily
-      name: Bradykinin
-    - id: MESH:D002199
-      label: BiologicalProcess
-      name: Capillary Permeability
-    - id: MESH:D054179
-      label: Disease
-      name: Hereditary angioneurotic edema
-  reference:
-    - https://en.wikipedia.org/wiki/C1-inhibitor
-    - https://en.wikipedia.org/wiki/Bradykinin
-    - https://en.wikipedia.org/wiki/Kallikrein
-    - https://en.wikipedia.org/wiki/Kinin%E2%80%93kallikrein_system#C1-INH_Involvement
-    - https://en.wikipedia.org/wiki/Hereditary_angioedema
-    - https://en.wikipedia.org/wiki/Complement_system#Regulation
-    - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666183/
-  comment: Both DrugBank (https://go.drugbank.com/drugs/DB06718#mechanism-of-action) and ChEMBL (https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2079587/) have this drug modulating target AR (UniProt:P10275) but that's not the mechanism of action for this indication (MESH:D054179).
-- directed: true
-  graph:
-    _id: DB00880_MESH_D006973_1
-    disease: Hypertensive disorder
-    disease_mesh: MESH:D006973
-    drug: chlorothiazide
-    drug_mesh: MESH:D002740
-    drugbank: DB:DB00880
-  links:
-    - key: decreases activity of
-      source: MESH:D002740
-      target: UniProt:P55017
-    - key: positively regulates
-      source: UniProt:P55017
-      target: GO:0070294
-    - key: positively correlated with
-      source: GO:0070294
-      target: GO:0003092
-    - key: positively correlated with
-      source: GO:0003092
-      target: HP:0033533
-    - key: positively correlated with
-      source: HP:0033533
-      target: HP:0032263
-    - key: decreases activity of
-      source: MESH:D002740
-      target: UniProt:P00918
-    - key: positively regulates
-      source: UniProt:P00918
-      target: GO:0038166
-    - key: positively correlated with
-      source: GO:0038166
-      target: GO:0042310
-    - key: positively correlated with
-      source: GO:0042310
-      target: HP:0032263
-    - key: positively regulates
-      source: MESH:D002740
-      target: UniProt:Q12791
-    - key: positively regulates
-      source: UniProt:Q12791
-      target: GO:0060087
-    - key: negatively correlated with
-      source: GO:0060087
-      target: HP:0032263
-    - key: manifestation of
-      source: HP:0032263
-      target: MESH:D006973
-  multigraph: true
-  nodes:
-    - id: MESH:D002740
-      label: Drug
-      name: chlorothiazide
-    - id: UniProt:P55017
-      label: Protein
-      name: Solute carrier family 12 member 3
-    - id: GO:0070294
-      label: BiologicalProcess
-      name: renal sodium ion absorption
-    - id: GO:0003092
-      label: BiologicalProcess
-      name: renal water retention
-    - id: HP:0033533
-      label: PhenotypicFeature
-      name: Increased cardiac output
-    - id: UniProt:Q12791
-      label: Protein
-      name: Calcium-activated potassium channel subunit alpha-1
-    - id: UniProt:P00918
-      label: Protein
-      name: Carbonic anhydrase 2
-    - id: GO:0060087
-      label: BiologicalProcess
-      name: relaxation of vascular associated smooth muscle
-    - id: GO:0038166
-      label: BiologicalProcess
-      name: angiotensin-activated signaling pathway
-    - id: GO:0042310
-      label: BiologicalProcess
-      name: vasoconstriction
-    - id: HP:0032263
-      label: PhenotypicFeature
-      name: Increased blood pressure
-    - id: MESH:D006973
-      label: Disease
-      name: Hypertensive disorder
-  reference:
-    - https://go.drugbank.com/drugs/DB00880#BE0000322
-    - https://go.drugbank.com/drugs/DB00880#BE0000419
-    - https://en.wikipedia.org/wiki/Category:Carbonic_anhydrase_inhibitors
-    - https://pubchem.ncbi.nlm.nih.gov/compound/2720#section=Mechanism-of-Action
-  comment: The hypotensive effects of chlorothiazide and other thiazides are not necessarily due to their diuretic activity (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904515/#S1title). The exact mechanism is yet not fully understood.
+