Molecular Characterization Analysis of Prevalent Infectious Bronchitis Virus and Pathogenicity Assessment of Recombination Strain in China.

Avian coronavirus infectious bronchitis virus (IBV) is a respiratory pathogen of chickens, resulting in severe economic losses in the poultry industry. This study aimed to monitor and isolate the molecular identity of IBV in broiler flocks with respiratory symptoms in eight provinces of China. In total, 910 samples (oropharyngeal and cloacal mixed swabs) from broiler flocks showed IBV positive rates of 17.6% (160/910) using PCR assay. Phylogenetic analysis of the complete S1 genes of 160 IBV isolates was performed and revealed that QX-type (GI-19), TW-type (GI-7), 4/91-type (GI-13), HN08-type (GI-22),TC07-2-type (GVI-1), and LDT3-type (GI-28) exhibited IBV positive rates of 58.15, 25, 8.12, 1.86, 5.62, and 1.25%. In addition, recombination analyses revealed that the four newly IBV isolates presented different recombination patterns. The CK/CH/JS/YC10-3 isolate likely originated from recombination events between strain YX10 (QX-type) and strain TW2575-98 (TW-type), the pathogenicity of which was assessed, comparing it with strain GZ14 (TW-type) and strain CK/CH/GD/JR07-7 (QX-type). The complete S1 gene data from these isolates indicate that IBV has consistently evolved through genetic recombination or mutation, more likely changing the viral pathogenicity and leading to larger outbreaks in chick populations, in China.

Bilobalide Enhances AMPK Activity to Improve Liver Injury and Metabolic Disorders in STZ-Induced Diabetes in Immature Rats via Regulating HMGB1/TLR4/NF-κB Signaling Pathway.

This study was aimed at examining the effect and underlying mechanisms of bilobalide (BB) on hepatic injury in streptozotocin- (STZ-) induced diabetes mellitus (DM) in immature rats. Immature rats (one day old) were randomly divided into five groups: group I, control nondiabetic rats; group II, STZ-induced, untreated diabetic rats; groups III/IV/V, STZ-induced and BB-treated diabetic rats, which were intraperitoneally injected with BB (2.5 mg/kg, 5 mg/kg, or 10 mg/kg) after 3 days followed by STZ treatment. We observed that BB improved the histopathological changes and maintained normal glucose metabolism, blood lipid, and liver function indicators, such as fasting blood glucose, obesity index, HbA1c, HOMA-IR, fast serum insulin, adiponectin, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), aspartate transaminase (AST), and alanine transaminase (ALT) in STZ-induced DM in immature rats by a biochemical analyzer or ELISA. Meanwhile, Western blot analysis showed that in STZ-induced DM immature rats, BB decreased the expression of apoptosis-related proteins Bax, cleaved caspase-3, and cleaved caspase-9 while enhancing the Bcl-2 expression; BB downregulated the expression of ACC related to fat anabolism, while upregulating the expression of CPT-1 related to fat catabolism. Strikingly, treatment with BB significantly increased the expression of AMPKα1 as well as inhibited HMGB1, TLR4, and p-P65 expression in hepatic tissues of immature DM rats. AMPK inhibitor (compound C, CC) cotreated with BB undermined the protective effect of BB on the liver injury. The results of the present study suggested BB may have a significant role in alleviating liver damage in the STZ-induced immature DM rats.

Transplantation of human matrix metalloproteinase-1 gene-modified bone marrow-derived mesenchymal stem cell attenuates CCL4-induced liver fibrosis in rats.

It has been reported that bone marrow-derived mesenchymal stem cells (BMSCs) alleviated liver fibrosis. We investigated whether BMSCs transfected with human matrix metalloproteinase 1 (BMSCs/MMP1) would improve their therapeutic effect in liver fibrosis induced by carbon tetrachloride (CCl4) in rats. BMSCs were transfected with an adenovirus carrying enhanced green fluorescence protein (GFP) and human MMP1 gene. BMSCs or BMSCs/MMP1 were directly injected into fibrotic rats via the tail vein. GFP-labeled cells appeared in the fibrotic liver after BMSC transplantation. The expression of BMSCs/MMP1 elevated levels of MMP1 in vitro. Although BMSC administration reduced liver fibrosis, transplantation of BMSCs/MMP1 enhanced the reduction of liver fibrosis to a higher level. Treatment with BMSCs/MMP1 not only decreased collagen content but also suppressed activation of hepatic stellate cells (HSCs) in fibrotic liver, which led to subsequent improvement of both liver injury and fibrosis. Treatment with BMSCs/MMP1 resulted in an improved therapeutic effect compared with BMSCs alone, which is probably because of the sustainably expressed MMP1 level in the liver. BMSCs/MMP1 transplantation not only improved biochemical parameters but also attenuated progression of liver fibrosis, suggesting that BMSCs may be a potential cell source in preventing liver fibrosis and MMP1 gene may enhance the anti-fibrotic effect of BMSCs.