The results suggested that ZnO nanoparticles can efficiently inhibit HTFs proliferation, disrupt the mitochondrial function, attenuate the adenosine triphosphate (ATP) generation, and damage the nuclear morphology of HTFs. Exposure of HTFs to ZnO nanoparticles can also induce the shifted peak, elevate the expression of Atg5, Atg12 and Becn1, enhance the autophagosome formation, and promote the LC3 expression, and thus activate autophagy signaling. Overall, ZnO nanoparticles can apparently trigger oxidative stress and activate autophagy signaling in HTFs, and thus inhibit HTFs proliferation and mediate HTFs apoptosis.Numerous studies indicate neuroprotective activity of statins, commonly used cholesterol lowering drugs in epilepsy and several other neurological diseases. Promising anti-convulsant and neuroprotective effects of statins, attributed to their anti-excitotoxic and anti-inflammatory action were reported in several animals' seizure models. To determine the effects of acute (single) and chronic (once daily for 7 consecutive days) administration of lovastatin on the protective activity of four classical antiepileptic drugs such as carbamazepine, phenobarbital, phenytoin and valproate in the mouse maximal electroshock seizure model. Seizure activity (maximal electroconvulsions) in mice were generated by alternating current delivered via ear-clip electrodes. Adverse-effect profile of lovastatin combinations with the tested antiepileptic drugs was assessed in the chimney test (motor performance). Total brain concentrations of antiepileptic drugs were evaluated with the fluorescence polarization immunoassay technique as a measure of the pharmacokinetic interaction between drugs.  https://www.selleckchem.com/products/bms-986165.html  Lovastatin administered acutely or chronically (5-20 mg/kg) did not significantly affect the threshold for electroconvulsions in mice. Acute lovastatin (10 mg/kg) significantly enhanced the anticonvulsant effect of valproate, which was accompanied with a 34% significant increase in total brain concentration of valproate. Acute lovastatin in combination with phenytoin impaired motor performance by notably decreasing the TD50 value of phenytoin. Chronic lovastatin (10 mg/kg) markedly enhanced the anticonvulsant potential of phenytoin. Acute lovastatin increased anticonvulsant action of valproate but also significantly raised level of valproate in brain after combined administration suggesting pharmacokinetic nature of interaction. The combinations of chronic lovastatin combined with phenytoin can potentially enhance the anticonvulsant potency of phenytoin.Atorvastatin (ATO) can improve the transplantation efficacy of mesenchymal stem cells (MSCs) after acute myocardial infarction. The present study aimed at ATO effects on the angiogenesis-signaling pathways from MSCs' differentiation to tissue angiogenesis. MSCs were first prepared from BALB/c mouse bone marrow. MTT assay was then done for the biodegradability of MSCs with the extracellular matrix. After that, the differentiation of cells into the bone and fat tissues was confirmed by Alizarin and Oil Red O staining. The extracellular matrix was then combined with the cells to the implant. Animals were intraperitoneally treated with ATO (2 and 40 mg/kg, daily) three days before cell transplantation to one week after. Finally, the assays were carried out by electron microscopy, immunocytochemistry, ELISA, Western blot, and RT-qPCR techniques. A phase-contrast microscope confirmed the morphology of cells. The cell differentiation into bone and fat tissues was confirmed by Alizarin red staining and flow cytometry, and the cell proliferation was confirmed by MTT assay. Unlike ATO 40 mg/kg group, ATO 2 mg/kg was significantly increased the CD31, eNOS, podocalyxin, von Willibrand factor, and alpha-smooth muscle actin proteins levels compared to the control group in vitro experiment. The expression of CD31 and VEGF proteins, as angiogenesis markers, and Ki-67 protein, as a proliferation marker, was significantly higher in a low dose of ATO (2 mg/kg) than that of the control group in vivo experiment. Unlike ATO 40 mg/kg, the expression levels of ERK, AKT, NF-ҝB, Rho, STAT3, Ets-1, HIF-1α, and VEGF proteins and genes were significantly increased in ATO 2 mg/kg compared to the control. A low dose of ATO can be a beneficial tool in the function of MSCs and their differentiation to tissue angiogenesis.Several lines of studies have indicated that the p53 pathway may have important anti-fibrotic functions. Previously we found that the novel selective RNA polymerase I inhibitor CX-5461 induced a robust response of p53 phosphorylation and activation in vascular smooth muscle cells. In the present study, we characterized the anti-fibrotic effects of CX-5461 in primary cardiac fibroblasts. We showed that CX-5461 suppressed spontaneous and mitogen-stimulated activation, proliferation, and myofibroblast differentiation, at a concentration (1 μM) with no cytotoxicity. The inhibitory effects of CX-5461 were primarily mediated by activation of the p53 pathway rather than limiting the rate of ribosome biogenesis. It was also shown that CX-5461 triggered a non-canonical DNA damage response in cardiac fibroblasts, which acted as the upstream signal leading to p53 activation. Taking these together, we suggest that p53 activation by pharmacological inhibition of Pol I may represent a viable approach to repress the development of cardiac fibrosis.Extensive investigations have revealed that iso-suillin, a secondary metabolite isolated from Suillus flavus, could induce cell cycle arrest and apoptosis in human chronic myeloid leukemia K562 cells, human hepatocellular carcinoma SMMC-7721 cell line, and human small cell lung cancer H446 cell line in vitro. In the present study, human lung cancer A549 cells were used to reveal the mechanism of iso-suillin's effects on lung adenocarcinoma, which were detected both in vitro and in vivo. Results showed that iso-suillin potently inhibited A549 cell proliferation through an early G1 arrest. Iso-suillin also induced A549 cell apoptosis in vitro. Phosphorylation of p53 at serines 15 and 20 may be one of the pivotal factors for cell cycle arrest and apoptosis after treatment of iso-suillin in A549 cells. Moreover, in an A549 xenograft model, tumor growth and progression could be inhibited by iso-suillin. Body weight change and some vital organs toxicity was also roughly examined, no significant toxic effects of iso-suillin were shown (at a dose of 5 mg/kg for each administration).