Moseswatts2570

Demethylenetetrahydroberberine (DMTHB) is a novel derivative of berberine and demethyleneberberine. This research explored the pharmacological effects and molecular mechanisms of DMTHB on nonalcoholic fatty liver disease (NAFLD).

C57BL/6 mice were induced by a methionine- and choline- deficient (MCD) diet and L02 cells were induced by palmitic acid to establish NAFLD animal and cell models. qPCR and western blotting were used to detect the expression of genes and proteins associated with pharmacological mechanism. A biotin-labeled DMTHB pulldown assay was used to further clarify the pharmacological targets.

Our results indicated that DMTHB significantly alleviates NAFLD in mice. Biochemical assays showed that serum alanine aminotransferase, aspartate aminotransferase and hepatic lipids were significantly decreased in MCD-induced NAFLD mice orally administered of DMTHB (50mg/kg or 150mg/kg body weight daily) for 30d. qPCR and ELISA analysis demonstrated that DMTHB reduced the expression of serum proinflammatory cytokines, such as TNF-α, IL-1β and IL-6. Moreover, pull-down assays and compound-centric chemical proteomics illustrated that DMTHB inhibited NOD-like receptor protein 3 (NLRP3) inflammasome signaling. In addition, DMTHB also attenuated oxidative stress and endoplasmic reticulum stress by downregulation CYP2E-1 and ATF-4 expression. Moreover, DMTHB treatment ameliorated the liver fibrosis in MCD-induced NAFLD mice by suppressing the expression of TGF-β1, α-SMA and collagen 1A1.

DMTHB targeted the NLRP3 inflammasome to suppress inflammation and inhibited CYP2E1 to reduce oxidative stress and ER stress. Consequently, DMTHB may have therapeutic benefits in the treatment of NAFLD in the clinic.

DMTHB targeted the NLRP3 inflammasome to suppress inflammation and inhibited CYP2E1 to reduce oxidative stress and ER stress. Selleck TGFbeta inhibitor Consequently, DMTHB may have therapeutic benefits in the treatment of NAFLD in the clinic.Treatment of cancer cells exemplifies a difficult test in the light of challenges associated with the nature of cancer cells and the severe side effects too. After making a large number of trials using both traditional and advanced therapies (immunotherapy and hormone therapy), approaches to design new therapies have reached a saturation level. However, nanotechnology-based approaches exhibit higher efficacy and great potential to bypass many of such therapeutic limitations. Because of their higher target specificity, the use of nanoparticles offers incredible potential in cancer therapeutics. Mitochondria, acting as a factory of energy production in cells, reveal an important role in the death as well as the survival of cells. Because of its significant involvement in the proliferation of cancer cells, it is being regarded as an important target for cancer therapeutics. Numerous studies reveal that nanotechnology-based approaches to directly target the mitochondria may help in improving the survival rate of cancer patients. In the current study, we have detailed the significance of mitochondria in the development of cancer phenotype, as well as indicated it as the potential targets for cancer therapy. Our study further highlights the importance of different nanoparticle-based approaches to target mitochondria of cancer cells and the associated outcomes of different studies. Though, nanotechnology-based approaches to target mitochondria of cancer cells demonstrate a potential and efficient way in cancer therapeutics. Yet, further study is needed to overcome the linked limitations.Postprandial lipemia consists of changes in concentrations and composition of plasma lipids after food intake, commonly presented as increased levels of triglyceride-rich lipoproteins. Postprandial hypertriglyceridemia may also affect high-density lipoprotein (HDL) structure and function, resulting in a net decrease in HDL concentrations. Elevated triglycerides (TG) and reduced HDL levels have been positively associated with risk of cardiovascular diseases development. Here, we investigated the plasma lipidome composition of 12 clinically healthy, nonobese and young women in response to an acute high-caloric (1135 kcal) and high-fat (64 g) breakfast meal. For this purpose, we employed a detailed untargeted mass spectrometry-based lipidomic approach and data was obtained at four sampling points fasting and 1, 3 and 5 h postprandial. Analysis of variance revealed 73 significantly altered lipid species between all sampling points. Nonetheless, two divergent subgroups have emerged at 5 h postprandial as a function of differential plasma lipidome responses, and were thereby designated slow and fast TG metabolizers. Late responses by slow TG metabolizers were associated with increased concentrations of several species of TG and phosphatidylinositol (PI). Lipidomic analysis of lipoprotein fractions at 5 h postprandial revealed higher TG and PI concentrations in HDL from slow relative to fast TG metabolizers, but not in apoB-containing fraction. These data indicate that modulations in HDL lipidome during prolonged postprandial lipemia may potentially impact HDL functions. A comprehensive characterization of plasma lipidome responses to acute metabolic challenges may contribute to a better understanding of diet/lifestyle regulation in the metabolism of lipid and glucose.Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and results in adverse outcomes for pregnant women and their offspring. Endoplasmic reticulum (ER) stress is associated with insulin resistance and implicates in the development of GDM. Zinc, selenium and chromium have been shown to maintain glucose homeostasis via multiple mechanisms, but how these trace elements affect the insulin resistance and ER stress in GDM are largely unknown. To address this, a GDM rat model was induced by feeding female Sprague-Dawley rats a high-fat (45%) and sucrose diet, while zinc (10 mg/kg.bw), selenium (20 ug/kg.bw), chromium (20 ug/kg.bw) were daily supplemented alone or in combination from 6 weeks before mating to the end of lactation period. Maternal metabolic parameters, hepatic ER stress and insulin signaling were analyzed. The results showed that zinc, selenium and chromium co-supplementation dramatically alleviated high-fat and sucrose-induced glucose intolerance and oxidative stress during entire experiment period.