The activation of hepatic stellate cells (HSCs) plays a central role in liver fibrosis, however non-alcoholic fatty liver disease (NAFLD) associated liver fibrogenesis have been poorly understood. We aimed to determine the significance of mineralocorticoid receptor (MR)/osteopontin (OPN)/high-mobility group box-1 (HMGB1) axis in this setting.
 
  Liver specimens were collected from NAFLD patients and murine NAFLD models established with 12-week high fat diet (HFD) for analysis of both upstream signals of MR and intrahepatic MR/OPN/HMGB1 axis.  https://www.selleckchem.com/products/hada-hydrochloride.html  The in vitro cell model of NAFLD-associated liver fibrogenesis was established by treating LX-2 (a cell line of human HSCs) with free fatty acids (FFA). The effects of MR signaling were evaluated using with ALD (MR activator) or eplerenone (Ep, MR antagonist). Moreover, the in vitro loss- and gain- of function approaches were applied to confirm the upstream and downstream relationships of mediators contained in the intracellular MR/OPN/HMGB1 axis of LX-2.
 
  In NAFLD condition, both human and mouse liver tissue samples demonstrated a significant up-regulation of MR/OPN/HMGB1 axis simultaneously with enhanced expression of pro-fibrogenic markers, including ACTA2, TIMP1, TGFB1 and COL1A1. Besides, enhanced production of serum aldosterone (ALD) was also observed in mouse NAFLD models. Moreover, the in vitro data demonstrated MR play an essential role in FFA-induced HSCs fibrogenesis. Meanwhile, MR acts as the upstream effector mediator of OPN and shares downstream HMGB1 with OPN.
 
  The MR/OPN/HMGB1 axis could be therapeutically targeted to treat NAFLD associated hepatic fibrogenesis.
 The MR/OPN/HMGB1 axis could be therapeutically targeted to treat NAFLD associated hepatic fibrogenesis.Glucose metabolism enzymes and transporters play major role in cancer development and metastasis. In this study, we discuss glucose metabolism, transporters, receptors, hormones, oncogenes and tumor suppressors which interact with glucose metabolism and we try to discuss their major role in cancer development and cancer metabolism. We try to highlight the. Metabolic changes in cancer and metastasis upregulation of glycolysis is observed in many primary and metastatic cancers and aerobic glycolysis is the most favorable mechanism for glucose metabolism in cancer cells, and it is a kind of evolutionary change. The question that is posed at this juncture is Can we use aerobic glycolysis phenotype and enzymes beyond this mechanism in estimating cancer prognosis and metastasis? Lactate is a metabolite of glucose metabolism and it is a key player in cancer and metastasis in both normoxic and hypoxic condition so lactate dehydrogenase can be a good prognostic biomarker. Furthermore, monocarboxylic transporter which is the main lactate transporter can be good target in therapeutic studies. Glycolysis enzymes are valuable enzymes in cancer and metastasis diagnosis and can be used as therapeutic targets in cancer treatment. Designing a diagnostic and prognostic profile for cancer metastasis seems to be possible base on glycolysis enzymes and glucose transporters. Also, glucose metabolism enzymes and agents can give us a clear vision in estimating cancer metastasis. We can promote a panel of genes that detect genetic changes in glucose metabolism agents to diagnose cancer metastasis.The increase in intracellular reactive oxygen and nitrogen species plays a key role in ultraviolet B (UV-B)-induced inflammatory responses in the human skin. Piperine exhibits many pharmacological benefits. In the present study, the photoprotective effects and the possible underlying mechanisms of the anti-inflammatory effects of piperine on UV-B-irradiated keratinocytes were investigated. Piperine exerted strong, direct scavenging effects on DPPH radicals and exhibited free radical scavenging capabilities as demonstrated by the DCFH-DA and Griess assays. Consistent with these results, 10, 20, and 40 μM piperine pretreatments attenuated UV-B irradiation-induced keratinocyte cytotoxicity as reported by the resazurin assay. The highest concentration of piperine inhibited UV-B irradiation-induced cell apoptosis, as revealed by Hoechst 33342 staining. Moreover, we demonstrated the anti-inflammatory effects of piperine using western blot analysis, real-time PCR, and ELISA. Pretreatment with piperine suppressed the activation of phosphorylated p38, JNK, and AP-1 as well as the levels of COX-2/PGE2 and iNOS synthesis, while UV-B-irradiated cells triggered the induction of these signaling molecules. These results indicated that the inhibition of these inflammatory signaling pathways might play a key role in the regulation of the anti-inflammatory effects of piperine. In addition, piperine showed stronger anti-inflammatory effects than celecoxib which served as a positive control at the same concentration. All these results suggested that the anti-inflammatory properties of piperine protected keratinocytes from UV-B-induced damage, which might be due to its antioxidant properties. Therefore, piperine may be an effective therapeutic candidate compound for the treatment of UV irradiation-induced skin inflammation.
  Sepsis is a severe endothelial dysfunction syndrome. The role of endothelial nitric oxide synthase (eNOS) in endothelial dysfunction induced by sepsis is controversial. To explore the role of eNOS in vascular dysfunction.
 
  The effect of sepsis on vasodilation and eNOS levels was examined in septic mouse arteries and in cell models.
 
  In early sepsis mouse arteries, endothelium-dependent relaxation decreased and phosphorylation of the inhibitory Thr495 site in endothelial nitric oxide synthase increased. Mechanically, the phosphorylation of endothelial nitric oxide synthase at Thr497 in bovine aortic endothelial cells occurred in a protein kinase C-α dependent manner. In late sepsis, both nitric oxide-dependent relaxation responses and endothelial nitric oxide synthase levels were decreased in septic mice arteries. Endothelial nitric oxide synthase levels expression levels decreased in tumor necrosis factor-α-treated human umbilical vein endothelial cells and this could be prevented by the ubiquitin proteasome inhibitor (MG-132).