Abstract Pristimerin (Pri) was a kind of extraction from natural plant, and it has anti- inflammation effects in previous studies, however, it has been unclear that Pri’s effect in renal fibrosis treatment. The purpose of this research was to evaluate pristimerin (Pri) treatment effects in renal fibrosis and relative mechanisms in vivo study. Using UUO and TGF-β1 to make renal fibrosis rats and HK-2 cell fibrosis model. Evaluating renal tissues pathological and fibrosis by HE and Masson staining; measuring Scr and BUN concentrations of serum, IL-1β, TNF-α, SOD and MDA concentrations by ELISA assay in serum and supernatant. Relative gene expressions were measured by RT-qPCR assay in renal tissues and cells and relative proteins expression by WB assay. Using Double luciferase assay to analysis correlation between miRNA-145-5p and TLR4. NF-κB(p65) nuclear volume were evaluated by cellular immunofluorescence. Scr, BUN, IL-1β, TNF-α and MDA concentrations were significantly increased and SOD concentration was significantly down-regulation (P < 0.001) in Model rats group; miRNA-145-5p gene expression was significantly depressed, TLR4, MyD88 and NF-κB(p65) gene expressions were significantly increased (P < 0.001, respectively); with Pri supplement, the renal pathological, masson region, Scr, BUN, IL-1β, TNF-α, SOD and MDA were significantly improved. In cell experiment, miRNA-145-5p play important role in Pri treatment of renal fibrosis by targeting TLR4. Pri could improve renal fibrosis by via regulation miRNA-145-5p to target TLR4.

Caspase recruitment domain-containing protein 9 (Card9) is located upstream of the nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) inflammatory pathways. This study investigated the therapeutic effect and potential mechanism of pioglitazone in rats with severe acute pancreatitis (SAP). SAP was induced by a retrograde infusion of 5.0% sodium taurocholate into the biliopancreatic duct of Sprague Dawley rats (n=54), which were then treated with pioglitazone. Blood and pancreatic tissues were harvested at 3, 6, and 12 h after SAP induction. Pancreatic pathological damage was evaluated by hematoxylin and eosin staining. Serum amylase, serum pro-inflammatory cytokines, and pancreatic myeloperoxidase (MPO) activities were determined by enzyme-linked immunosorbent assay. The expression of Card9 mRNA and protein in pancreatic tissues was detected by real-time polymerase chain reaction and western blotting. Pioglitazone had a therapeutic effect in treating rats with SAP by decreasing the level of amylase activity, ameliorating pancreatic histological damage, decreasing serum pro-inflammatory cytokine levels and tissue MPO activity, and downregulating the expression of NF-κB, p38MAPK, and Card9 mRNAs and proteins (P<0.05). The present study demonstrated that the inhibition of Card9 expression could reduce the severity of SAP. Card9 has a role in the pathogenic mechanism of SAP.

Protein degradation in bovine milk affects the quality of dairy products. Alpha 1-antitrypsin (AAT) can protect vulnerable elastic tissues from degradation by neutrophil elastase. The aim of this study was to assess the association of polymorphisms in bovine AAT gene with milk yield and milk composition in Chinese Holstein. Traits analyzed were fat percentage, protein percentage, 305-day milk yield and somatic cell score (SCS). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), created restriction site-polymerase chain reaction (CRS-PCR) and allele specific-polymerase chain reaction (AS-PCR) methods were used to genotype five loci in coding regions of the sequence, including position 5504, 5609, 5624, 5747 and 8178 in Chinese Holstein. The five mutations were all silent mutation that caused no alteration in the amino acid sequence. In order to determine the relationship between the polymorphisms of the AAT gene and milk production traits and SCS, the General Linear Model (GLM) procedure from the Statistical Analysis Software was used. SNP5504 affected milk fat percentage, SNP8178 affected milk protein percentage and SNP5609 and SNP5624 affected 305-day milk yield. These results suggest that AAT is a candidate gene that influences milk production traits and it could be implemented in breeding programmes to improve the production performance of Chinese Holstein cattle.