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Dapagliflozin (DAPA), a kind of sodium-glucose cotransporter 2(SGLT2) inhibitor is used to treat diabetes mellitus by inhibiting urine glucose reuptake. Recent clinical outcomes indicate that SGLT2 inhibitors may exert pharmacological activities against non-alcoholic fatty liver diseases. Nonetheless, the underlying molecular mechanisms are still poorly elucidated. TGF-beta inhibitor In this study, we investigated the potential anti-fatty liver effects of DAPA in vivo and in vitro and assayed their underlying mechanisms. Male NIH (National Institutes of Health) mice were fed with a high-fat diet (HFD) and then treated with DAPA by gavage for 4 weeks. In the following experiments, L02 cells were treated with oleic acid (OA) and different concentrations of DAPA to assess lipid metabolism. Our results revealed that DAPA administration could remarkably suppress excessive fat accumulation in the liver tissues of HFD-fed mice and OA-treated L02 cells. Importantly, DAPA could downregulate the expression levels of proteins related to lipid synthesis and upregulate the expression levels of genes associated with fatty acid oxidation in vitro and in vivo. We also found that DAPA intervention could activate adenosine monophosphate-activated protein kinase (AMPK) phosphorylation but inhibit mammalian target of rapamycin (mTOR) phosphorylation in vitro and in vivo. AMPK activation might be mediated by increasing liver kinase B1 activity and decreasing ATP level. Furthermore, these ameliorative effects were completely eliminated by an AMPK inhibitor, compound C. This study suggested that DAPA might remarkably ameliorate hepatic steatosis mediated through the AMPK/mTOR pathway and thus could be a potential drug candidate for the treatment of fatty liver diseases.Gastric cancer (G.C) is one of the most lethal cancer types worldwide. Current treatment requires surgery along with chemotherapy, which causes obstacles for speedy recovery. The discovery of novel drugs is needed for better treatment of G.C with minimum side effects. Latcripin-7A (LP-7A) is a newly discovered peptide extracted from Lentinula edodes. It is recently studied for its anti-cancer activity. In this study, LP-7A was modeled using a phyre2 server. Anti-proliferation effects of LP-7A on G.C cells were examined via CCK-8, colony formation, and morphology assay. Apoptosis of LP-7A treated G.C cells was evaluated via Hoechst Stain, western blot and flow cytometry. Autophagy was assessed via acridine orange staining and western blot. The cell cycle was assessed via flow cytometry assay and western blot. Pathway was studied via western blot and STRING database. Anti-migratory effects of LP-7A treated G.C cells were analyzed via wound healing, western blot, and migration and invasion assay. LP-7A effectively inhibited the growth of G.C cells by inhibiting the PI3K/Akt/mTOR pathway. G.C cells treated with LP-7A arrested the cell cycle at the G1 phase, contributing to the inhibition of migration and invasion. Furthermore, LP-7A induced apoptosis and autophagy in gastric cancer cells. These results indicated that LP-7A is a promising anti-cancer agent. It affected the proliferation and growth of G.C cells (SGC-7901 and BGC-823) by inducing apoptosis, autophagy, and inhibiting cell cycle at the G1 phase in G.C cells.The effects and underlying mechanisms of mibefradil on gluconeogenesis and glycogenesis were investigated using insulin-resistant HepG2 human hepatocellular carcinoma cells and a mouse model of type 2 diabetes mellitus (T2DM). HepG2 cells were divided into one of four groups control, palmitate (PA)-induced insulin-resistance (0.25 mM), low-concentration mibefradil (0.025 μM), or high-concentration mibefradil (0.05 μM). Glycogen synthesis and glucose consumption were evaluated in these HepG2 cells, and quantitative polymerase chain reaction (qPCR) and western blotting techniques were used to detect expression of forkhead box O1 (FoxO1), phosphoenolpyruvate carboxykinase (PEPCK), and glucose 6-phosphatase (G6Pase). Intracellular calcium concentrations were determined using Fluo-4 AM, and phosphorylation levels of calmodulin-dependent protein kinase II (CaMKII), protein kinase B (Akt) and FoxO1were detected by western blotting. Immunofluorescence was used for the localization and quantification of FoxO1.In vitro results were verified using a mouse model of T2DM. In HepG2 cells and mouse liver tissues, mibefradil decreased PA-induced cytoplasmic calcium levels and CaMKII phosphorylation, but increased the phosphorylation of Akt and FoxO1, thereby contributing to the cytoplasmic localization of FoxO1. Additionally, mibefradil alleviated PA-induced glucose output and insulin resistance through increased glucose consumption and glycogen synthesis, while decreasing the expression of key gluconeogenesis enzymes, including PEPCK and G6Pase. Mibefradil may help to control blood sugar levels by reducing glucose output and insulin resistance, and the mechanism of action may involve the Ca2+-CaMKII-dependent Akt/FoxO1 signaling pathway.In contrast to non-small cell lung cancer, there has been no significant progress in the development of therapies for the small cell lung cancer (SCLC) in recent decades. Although various targeted agents, including immunotherapies, have recently been developed for testing in clinical trials, novel therapeutic agents are still needed for SCLC. We developed a potent inhibitor of cyclin-dependent kinase 7 (CDK7), designated YPN-005, and sought to determine whether it showed any anticancer effects in SCLC cells, cisplatin or etoposide-resistant cells, or organoids derived from SCLC patients. In a panel of kinases assay, YPN-005 was highly selective for CDK7 and showed antiproliferative effects in SCLC and cells with acquired resistance to conventional anticancer drugs. Similar to other CDK7 inhibitors, YPN-005 treatment significantly decreased the phosphorylation of the carboxyl-terminal domain of RNA polymerase II. Consistent with the in vitro results, YPN-005 treatment showed a significant inhibition of tumor growth through the suppression of RNA polymerase II phosphorylation. Finally, YPN-005 showed potent anticancer effects in organoids derived from SCLC patients compared to another CDK7 inhibitor, THZ1. Therapeutic targeting of CDK7 in SCLC might be suitable for clinical investigation, and YPN-005 may be a promising therapeutic option for primary SCLC and SCLC with acquired resistance to conventional therapy.