These results demonstrate that in microglial cells, extracellular ATP induces activation of the ASK1-p38 MAP kinase pathway and ultimately apoptosis downstream of P2X7 receptor and ROS generation, and that EA promotes ATP-induced apoptosis through CaMKII-dependent hyperactivation of the ASK1-p38 pathway, in the same manner as in macrophages. Our study may provide an insight into the pathogenesis of NDs associated with TFAs.Renal insufficiency secondary to contrast administration remains a prevalent and debilitating complication of angiographic procedures. Contrast-induced nephropathy (CIN) is a common clinical problem for which there is no effective medical treatment. However, agmatine has been shown to be effective against ischemia/reperfusion-induced acute kidney injury in rats, a similar condition to CIN. Our aim was to examine the protective effects of agmatine in a rat model of CIN and, based on those results, in a rabbit model of CIN. CIN in the rat model was induced by intravenous administration of indomethacin (10 mg/kg), Nω-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg) and iopamidol (OYPALOMIN, 7.4 g iodine/kg) at 2 weeks after a unilateral nephrectomy. CIN in the rabbit model was induced by intrarenal arterial injection of only iopamidol (BYSTAGE, 4.8 g iodine/kg). Intravenous injection of agmatine (0.1 and 0.3 mmol/kg) did not attenuate the CIN-induced renal insufficiency in the rat model. Intravenous injection of agmatine (0.3 mmol/kg) attenuated the CIN-induced renal insufficiency in the rabbit model such as increases in blood urea nitrogen and plasma creatinine levels. Renal histological damage was also improved by the agmatine administration. The difference in effects of agmatine injection between CIN rats and CIN rabbits was caused by indomethacin and L-NAME administrations. These results indicate that agmatine prevents the development of CIN-induced renal insufficiency in rabbits, and the effect is accompanied by activation of nitric oxide synthase and subsequent increase of blood flow.miR-144-5p exhibits anti-tumor activities in various cancers. Although treatment for glioblastoma has progressed rapidly, novel targets for glioblastoma are insufficient, particularly those used in precision medicine. In the current study, we found that ginsenoside Rd reduced the proliferation and migration of glioblastoma cells. Ginsenoside Rd up-regulated the tumor-suppressive miR-144-5p in glioblastoma cells. TGF-beta inhibitor Moreover, Toll-like receptor 2, which is a target of miR-144-5p, was down-regulated. After inhibition of miR-144-5p, the effect of Ginsenoside Rd on proliferation inhibition and down-regulation of Toll-like receptor 2 was reduced. These data demonstrated the ginsenoside Rd/miR-144-5p/Toll-like receptor 2 regulatory nexus that controls the glioblastoma pathogenesis of glioblastoma. Our work provided novel targets for glioblastoma diagnosis and treatment.Imatinib-resistance is a significant concern for Bcr-Abl-positive chronic myelogenous leukemia (CML) treatment. Emodin, the predominant compound of traditional medicine rhubarb, was reported to inhibit the multidrug resistance by downregulating P-glycoprotein of K562/ADM cells with overexpression of P-glycoprotein in our previous studies. In the present study, we found that emodin can be a potential inhibitor for the imatinib-resistance in K562/G01 cells which are the imatinib-resistant subcellular line of human chronic myelogenous leukemia cells with overexpression of breakpoint cluster region-abelson (Bcr-Abl) oncoprotein. Emodin greatly enhanced cell sensitivity to imatinib, suppressed resistant cell proliferation and increased potentiated apoptosis induced by imatinib in K562/G01 cells. After treatment of emodin and imatinib together, the levels of p-Bcr-Abl and Bcr-Abl were significantly downregulated. Moreover, Bcr-Abl important downstream target, STAT5 and its phosphorylation were affected. Furthermore, the expression of Bcr-Abl and signal transducers and activators of transcription 5 (STAT5) related molecules, including c-MYC, MCL-1, poly(ADP-ribose)polymerase (PARP), Bcl-2 and caspase-3, were changed. Emodin also decreased Src expression and its phosphorylation. More importantly, emodin simultaneously targeted both the ATP-binding and allosteric sites on Bcr-Abl by molecular docking, with higher affinity with the myristoyl-binding site for enhanced Bcr-Abl kinase inhibition. Overall, these data indicated emodin might be an effective therapeutic agent for inhibiting resistance to imatinib in CML treatment.The anti-inflammatory agent colchicine may cause toxic effects such as rhabdomyolysis, pancytopenia, and acute respiratory distress syndrome in cases of overdose and when patients have renal or liver impairment. As colchicine is a substrate for CYP3A4 and P-glycoprotein (P-gp), drug-drug interactions are important factors that cause fatal colchicine-related side effects. Thus, we conducted a nation-wide survey to determine the status of inappropriate colchicine prescriptions in Japan. Patients prescribed the regular use of colchicine from April 2014 to March 2017 were identified using the Japanese large health insurance claims database. As the primary endpoint, we evaluated the concomitant prescription proportions of strong CYP3A4 and/or P-gp inhibitors classified as "contraindications for co-administration" with colchicine in patients with renal or liver impairment. We defined these cases as "inappropriate colchicine prescriptions." Additionally, factors affecting inappropriate colchicine prescriptions were analyzed. Among the 3302 enrolled patients, 43 (1.30%) were inappropriately prescribed colchicine. Of these 43 patients, 11 had baseline renal and/or liver impairment. By multiple regression analysis, the primary diseases "gout" and "Behçet's disease" were extracted as independent factors for inappropriate colchicine prescriptions with odds ratios of 0.40 (95% confidence interval 0.19-0.84) and 4.93 (95% confidence interval 2.12-11.5), respectively. We found that approximately 1% of patients had important colchicine interactions. Particularly, Behçet's disease was a risk factor for inappropriate prescriptions, with approximately 25% of patients showing renal and/or liver impairment (classified as "contraindications for co-administration"). These findings may be useful for medical professionals who prescribe colchicine therapy.