Oxyberberine suppressed the carbon tetrachloride-induced liver fibrosis by inhibiting liver inflammation in a sirtuin 3-dependent manner in mice.

Previous studies have shown that oxyberberine (OBB), a novel gut microbiota metabolite of berberine, exhibited prominent protective property against acute liver injury and non-alcoholic fatty liver diseases, however, the effect of OBB on liver fibrosis and its potential mechanisms remain largely unknown. This study was aimed to study the effects of OBB on carbon tetrachloride (CCl4)-induced liver fibrosis and tried to clarify the potential mechanisms by focusing on regulating of sirtuin 3 (SIRT3)-mediated liver inflammation. OBB significantly alleviated the liver injury and fibrosis in CCl4-treated C57/BL6 mouse livers. OBB evidently down-regulated the expression of inflammatory factors and reduced the levels of inflammatory factors in CCl4-treated mouse livers. Noteworthy, CCl4-treated decreased the mRNA and protein expression of SIRT3, and treatment with OBB notably increased the expression of SIRT3 both in transcriptional and translational levels in CCl4-treated mice livers. OBB also suppressed the cell viability of TGF-ß1-stimulated JS-1 cells and inhibited the protein expression of α-SMA but increased the expression of SIRT3 in stimulated JS-1 cells. Moreover, depletion of SIRT3 weakened the anti-inflammatory effects of OBB in stimulated JS-1 cells. Interestingly, the anti-liver injury and anti-fibrotic effects of OBB could be available in CCl4-treated WT (129S1/SvImJ) mice but were unavailable in CCl4-treated SIRT3 knockout (KO) mice. In addition, the anti-inflammatory effect of OBB was only found in CCl4-treated WT mice but was not in SIRT3 KO mice. Collectively, these findings suggested that OBB suppressed the liver injury and fibrosis through inhibition of liver inflammation in a SIRT3-dependent manner in CCl4-treated mice.

Increasing anhydrous chromium chloride concentration in AlCl3-EMIC ionic liquid: a step towards non-hydrogen-embrittlement chromium electroplating.

Non-hydrogen-embrittlement chromium electroplating has wide applications in industry. Using an ionic liquid (AlCl3-1-ethyl-3-methyl-imidazolium chloride, AlCl3-EMIC) as the electrolyte provides a viable way for metal electrodeposition. However, the low solubility of anhydrous chromium chloride salt in acidic AlCl3-EMIC IL makes the electrodeposition process essentially impractical. We propose a new method for dissolving CrCl3 or CrCl2, which effectively increases the concentration of anhydrous chromium salts in AlCl3-EMIC IL. Moreover, we demonstrate for the first time that the electroless deposition of BCC Cr can be realized on an Al substrate using this solution, which indicates that the reduction potential of chromium ions in AlCl3-EMIC IL is more positive than that of aluminum ions. This proves the thermodynamic possibility of electroplating metallic Cr. Therefore, our work paves the way for the engineering application of electroplating non-hydrogen-embrittlement chromium.

Alpinetin exerts anti-inflammatory, anti-oxidative and anti-angiogenic effects through activating the Nrf2 pathway and inhibiting NLRP3 pathway in carbon tetrachloride-induced liver fibrosis.

Alpinetin is the major active ingredient of Alpiniakatsumadai Hayata. As a kind of novel plant-derived flavonoid, alpinetin has shown potent hepatoprotective effect against many liver diseases such as non-alcoholic fatty liver and lipopolysaccharide/d-Galactosamine-induced liver injury. However, its roles in liver fibrosis remain to be determined. The aim of the current study was to investigate the effect of alpinetin in mice with carbon tetrachloride (CCl4)-induced liver fibrosis, and to elucidate the underlying mechanisms of action. Alpinetin ameliorated the CCl4-induced liver injury and fibrosis in mice, as shown by decreased collagen deposition and the decreased expression of liver fibrosis marker proteins. Alpinetin suppressed the inflammation and oxidative stress in fibrotic livers of mice, as evidenced by decreased levels of proinflammatory factors, the decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and the increased activities of antioxidant enzymes. In addition, alpinetin attenuated the angiogenesis in fibrotic livers of the test animals. Mechanistically, alpinetin inhibited the CCl4-induced expression of NLRP3, ASC, cleaved caspase-1, mature (cleaved-) IL-1ß, and IL-18 in livers of mice. Furthermore, alpinetin resulted in an increased in the nuclear expression and a decrease in the cytoplasmic expression of Nrf2, as well as increased protein expression of downstream target enzymes, GCLC, HO-1, NQO1, and GCLM, thus exerting the antioxidant effect. Overall, these findings suggested that the anti-fibrotic effect of alpinetin can be attributed to the inhibition of NLRP3-mediated anti-inflammatory activities and Nrf2-mediated anti-oxidative activities, in addition to the decrement of hepatic angiogenesis.

Nucleotide exchange factor SIL1 promotes the progress of breast cancer cells via regulating the cell cycle and apoptosis.

Breast cancer, as one of the most malignant tumors, poses a serious threat to the lives of females. Nucleotide exchange factor SIL1 is an important regulator of endoplasmic reticulum function that might have a specific role in tumor progression. In this study, we aimed to investigate the effect of SIL1 on the proliferation, apoptosis, and metastasis of human breast cancer. SIL1-specific small interfering RNA was transfected into two breast cancer cell lines, MCF7 and MDA-MB-231, to generate SIL1 knockdown cells. Clone formation and Cell Counting Kit-8 assays were performed to determine cell proliferation. Wound healing and transwell assays were used to detect the cell migration and invasion, respectively. Cell cycle and apoptosis were determined by flow cytometry. The messenger RNA and protein levels of target genes were analyzed using quantitative real-time PCR and western blot. According to the results of TCGA and GTEx database analysis, we determined that SIL1 was overexpressed in 1085 breast cancer samples compared with 291 normal samples. Knockdown of SIL1 inhibited the proliferation, migration, and invasion of MCF7 and MDA-MB-231 cells, accordingly. The cell cycle was blocked at the G1 phase following transfection of SIL1-specific small interfering RNA through the inhibition of Cyclin D1, CDK4, and CDK6. SIL1 knockdown induced apoptosis and also promoted the activity of Caspase9 and Bax. Furthermore, SIL1 was able to promote phosphorylation of ERK1/2. Based on these results, SIL1 might act as an oncogene and accelerate the progression of human breast cancer.