Impacts of the development of acute-on-chronic liver failure and bacterial infections on ß-cell function and glucose homeostasis in patients with liver cirrhosis.

BACKGROUND: The pathogenesis involved in glucose metabolism disorders (GMDs) in patients with liver cirrhosis remains unclear. AIMS: We investigated the effects of acute-on-chronic liver failure (ACLF) development and bacterial infections (BIs) on pancreatic ß-cell function and glucose homeostasis in individuals with liver cirrhosis. METHODS: A retrospective analysis was conducted on 327 patients experiencing acute deterioration of liver cirrhosis. Oral glucose tolerance tests (OGTTs) and OGTT-based ß-cell function indices were employed to assess ß-cell function and glucose homeostasis. Univariate and multivariate logistic regression analyses were employed to identify GMD-associated risk factors. RESULTS: Both the development of ACLF and BIs significantly increased the prevalence of GMDs. Both ACLF and BIs markedly elevated the homeostasis model of assessment 2-insulin resistance (HOMA2-IR). ACLF significantly impaired glucose-stimulated insulin secretion, as evidenced by reduced insulinogenic index (IGI). Patients with GMDs exhibited significantly lower IGI levels than those without GMDs. Independent risk factors associated with GMDs were prothrombin activity (odds ratio [OR]=0.981, 95% confidence interval [CI]: 0.960-0.995), HOMA2-IR (OR=1.749, 95% CI: 1.130-2.707), and IGI (OR=0.963, 95% CI: 0.947-0.978). CONCLUSIONS: In liver cirrhosis, the onset of ACLF impairs glucose-stimulated insulin secretion from ß-cells. Both liver impairment and BIs contribute to increased insulin resistance, ultimately disturbing glucose homeostasis.

AnnexinA5 Might Suppress the Phenotype of Human Gastric Cancer Cells via ERK Pathway.

Gastric cancer is one of the most fatal diseases around the world. However, the mechanism of the development of gastric cancer is still not clarified. In addition, the anticancer drugs have cytotoxicity with different degrees. AnnexinA5, a member of the annexin family, has a great binding ability with the membrane phospholipid in a calcium dependent manner and is involved in the development of various cancers. This study aims to explore the influence of annexinA5 on human gastric cancer cells and whether it has the potential to be an auxiliary treatment to gastric cancer. In this study, the role of annexinA5 was detected from both the endogenous and the exogenous aspects on the gastric cancer cell lines MGC-803 and MKN-45. The cells were divided into a knockdown group in which RNA interference technique was used to suppress annexinA5 expression and a protein-supplementing group in which annexinA5 protein was added in the culture supernatant. After the suppression ratio of RNA interference was determined and the IC50 of annexinA5 protein was decided respectively, the cells' proliferation was detected by MTT assay, colony formation assay, and the expression of PCNA. FCM assay and PI staining methods were applied to test cell apoptosis and necrosis. To investigate whether ANXA5 influence cell metastasis, wound healing assay and transwell assay were employed. To further detect the mechanism of annexinA5 action, the signal pathway was examined with Western Blot method. When ANXA5 gene was knocked down, cell proliferation and metastasis were promoted, while cell apoptosis was suppressed. On the other hand, after the annexinA5 protein was applied to the gastric cancer cells, cell proliferation and metastasis were inhibited, while cell apoptosis and necrosis were promoted. AnnexinA5 played its role via ERK signal pathway. ANXA5 acted as tumor suppressor gene in the gastric cancer by suppressing ERK signal pathway and has the potentiality to be an auxiliary anticancer agent.

Enantiomeric separation of indoxacarb on an amylose-based chiral stationary phase and its application in study of indoxacarb degradation in water.

Direct semipreparative enantioseparation of indoxacarb was performed on a semipreparative Chiralpak IA column using normal-phase high-performance liquid chromatography (HPLC) with n-hexane-isopropanol-ethyl acetate (70:20:10) mixture as mobile phase. Degradation of indoxacarb (2.33S + 1R) and its two enantiopure isoforms in three aqueous buffer solutions and four water samples collected from natural water sources was then elucidated by HPLC analysis on Chiralpak IA column. Degradation of all three indoxacarbs complied with first-order kinetics and demonstrated linearity with regression coefficients R(2) > n0.88. Indoxacarb (2.33S + 1R) underwent enantioselective degradation in river water, rain water, and buffer solution of pH 7.0. Enantiopure S-(+)-indoxacarb and R-(-)-indoxacarb were both found to be configurationally stable in water.

Cinchona alkaloid derivative-catalyzed enantioselective synthesis via a Mannich-type reaction and antifungal activity of ß-amino esters bearing benzoheterocycle moieties.

An efficient synthesis of highly functionalized chiral ß-amino ester derivatives containing benzothiophene and benzothiazole moieties is developed by a Mannich-type reaction using a cinchona alkaloid-derived thiourea catalyst. The desired products were obtained in good yields and high enantioselectivities (~86% yield, >99% ee) using to the optimized reaction conditions. The synthesized compounds were characterized by 1H-NMR, 13C-NMR, IR, and HREI-MS analyses. The bioassays identified that compound 5dr has excellent antifungal activity, with a 60.53% inhibition rate against F. oxysporum, higher than that of the commercial agricultural fungicide hymexazol, whose inhibition rate was 56.12%.

Synthesis and anti-TMV activity of dialkyl/dibenzyl 2-((6-substituted-benzo[d]thiazol-2-ylamino)(benzofuran-2-yl)methyl) malonates.

Starting from benzofuran-2-methanal, 6-substituted benzothiazole-2-amines and malonic esters, sixteen title compounds were designed and synthesized seeking to introduce anti-TMV activity. The structures of the newly synthesized compounds were confirmed by 1H-NMR, 13C-NMR, IR spectra, and MS (HREI) analysis. The bioassays identified some of these new compounds as having moderate to good anti-TMV activity. The compounds 5i and 5m have good antiviral activity against TMV with a curative rate of 52.23% and 54.41%, respectively, at a concentration of 0.5 mg/mL.