Therapeutic effect of quinolone oxizime on fibrotic kidney diseases

Purpose: To investigate the anti-fibrotic effect and mechanism of action of quinolone oxizime in vitro and in vivo.Methods: Proliferation of renal fibroblasts was determined using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while laser confocal fluorescence microscope was used for immuno-cytochemical studies. Total TGF β1 was determined by enzyme linked immunosorbent assay (ELISA).Results: Quinolone oxizime decreased the proliferation of renal fibroblasts in a dose-dependent manner (p < 0.05) in vitro. Proliferation of renal fibroblasts was 39, 63, 82, 95, 97 and 99 % on treatment with quinolone oxizime at doses of 10, 8, 6, 4, 2 and 1 μM, respectively, after 48 h. The expression of TGF β1 in the peripheral blood lymphocytes was reduced significantly by quinolone oxizime treatment. In the animal model of renal fibrosis, quinolone oxizime treatment decreased development of lesions, prevented tubular dilation and expansion of interstitium. After 30 days of quinolone oxizime treatment, tubulo-interstitial lesions were completely absent in rats in the 5 mg/kg treatment group. Moreover, quinolone oxizime treatment for 30 days inhibited accumulation of extracellular matrix and prevented renal injury in rats.Conclusion: These results show that quinolone oxizime exhibits anti-fibrotic effects through targeting the expression of TGF β1. Therefore, quinolone can potentially be used for the treatment of fibrotic kidney diseases but further studies are required to ascertain this.Keywords: Quinolone oxizime, Anti-fibrosis, Tubulo-interstitium, Interstitium, Fibroblast

miR-202 suppresses cell proliferation in human hepatocellular carcinoma by downregulating LRP6 post-transcriptionally

AbstractMicroRNAs have emerged as important regulators of carcinogenesis. In the current study, we observed that microRNA-202 (miR-202) is downregulated in hepatocellular carcinoma (HCC) cells and tissues, indicating a significant correlation between miR-202 expression and HCC progression. Overexpression of miR-202 in HCC cells suppressed cell proliferation and tumorigenicity, while downregulation of miR-202 enhanced the cells’ proliferative capacity. Furthermore, we identified low-density lipoprotein receptor-related protein 6 (LRP6) as a direct target of miR-202. miR-202 suppresses the expression of LRP6 by binding to the 3′-untranslated region (UTR) of its mRNA. Finally, we found that silencing the expression of LRP6 is the essential biological function of miR-202 during HCC cell proliferation. Collectively, our findings reveal that miR-202 is a potential tumor suppressive miRNA that participates in carcinogenesis of human HCC by suppressing LRP6 expression

Pretreatment Donors after Circulatory Death with Simvastatin Alleviates Liver Ischemia Reperfusion Injury through a KLF2-Dependent Mechanism in Rat

Objective. Severe hepatic ischemia reperfusion injury (IRI) can result in poor short- and long-term graft outcome after transplantation. The way to improve the viability of livers from donors after circulatory death (DCD) is currently limited. The aim of the present study was to explore the protective effect of simvastatin on DCD livers and investigate the underlying mechanism. Methods. 24 male rats randomly received simvastatin or its vehicle. 30 min later, rat livers were exposed to warm ischemia in situ for 30 min. Livers were removed and cold-stored in UW solution for 24 h, subsequently reperfused for 60 min with an isolated perfused rat liver system. Liver injury was evaluated during and after warm reperfusion. Results. Pretreatment of DCD donors with simvastatin significantly decreased IRI liver enzyme release, increased bile output and ATP, and ameliorated hepatic pathological changes. Simvastatin maintained the expression of KLF2 and its protective target genes (eNOS, TM, and HO-1), reduced oxidative stress, inhibited innate immune responses and inflammation, and increased the expression of Bcl-2/Bax to suppress hepatocyte apoptosis compared to DCD control group. Conclusion. Pretreatment of DCD donors with simvastatin improves DCD livers’ functional recovery probably through a KLF2-dependent mechanism. These data suggest that simvastatin may provide a potential benefit for clinical DCD liver transplantation

Microarray expression profile of circular RNAs in lung tissues from rats with lipopolysaccharide-induced acute respiratory distress syndrome

The data presented in this article are related to the research article entitled âThe expression profiles of circRNAs in lung tissues from rats with lipopolysaccharide-induced acute respiratory distress syndrome (ARDS): A microarray study.â (Wan et al., 2017) [1]. ARDS remains a common and devastating syndrome. The development of circRNA microarray has facilitated the study of the role of circRNAs in regulating gene expression in ARDS. This research was designed to explore the expression profile of circRNAs in lung tissues from rats with lipopolysaccharide-induced ARDS. The field dataset is made publicly available to enable critical or extended analyzes. Keywords: Microarray, Circular RNAs, Lipopolysaccharide, Acute respiratory distress syndrom

Multiple Roles of 25-Hydroxycholesterol in Lipid Metabolism, Antivirus Process, Inflammatory Response, and Cell Survival

As an essential lipid, cholesterol is of great value in keeping cell homeostasis, being the precursor of bile acid and steroid hormones, and stabilizing membrane lipid rafts. As a kind of cholesterol metabolite produced by enzymatic or radical process, oxysterols have drawn much attention in the last decades. Among which, the role of 25-hydroxycholesterol (25-HC) in cholesterol and bile acid metabolism, antivirus process, and inflammatory response has been largely disclosed. This review is aimed at revealing these functions and underlying mechanisms of 25-HC

The Inhibition of P-Selectin Reduced Severe Acute Lung Injury in Immunocompromised Mice

In an immunocompetent host, excess infiltration of immune cells in the lung is a key factor in infection-induced severe acute lung injury. Kidney transplant patients are immunocompromised by the use of immunosuppressive drugs. Immune cell infiltration in the lung in a renal transplant recipient suffering from pulmonary infection is significantly less than that in an immunocompetent host; however, the extent of lung injury in renal transplant patients is more serious than that in immunocompetent hosts. Therefore, we explored the role of platelet activation in a Klebsiella pneumoniae-induced lung injury model with P-selectin gene knockout mice or wild-type mice. Our study suggested that the inhibition of platelets reduced severe acute lung injury and increased survival after acute lung infection in mice. In addition, P-selectin expression on the surface of platelets in mice increased after administration of immunosuppressive drugs, and the extent of lung injury induced by infection decreased in P-selectin gene knockout mice. In conclusion, p-selectin plays a key role in severe acute lung injury in immunocompromised mice by reducing platelet activation and inflammatory processes

LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression

Background Aberrant expression of long noncoding RNAs are implicated in the pathogenesis of human malignancies. LINC00844 expression is dramatically downregulated in prostate cancer, and functional studies have revealed the association between the aberrant expression of LINC00844 and prostate cancer cell invasion and metastasis. However, the function and mechanism of action of LINC00844 in the pathogenesis of hepatocellular carcinoma (HCC) are poorly understood. Methods LINC00844 and N-Myc downstream-regulated 1 (NDRG1) expression in HCC tissues and cell lines was detected with real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Correlations between LINC00844 expression level and clinicopathological features were investigated using the original data from The Cancer Genome Atlas (TCGA) database. HepG2 and HCCLM9 cell lines were transfected with Lv-LIN00844 virus to obtain LINC00844-overexpressing cell lines. Cell proliferation and cell invasion and migration were examined with the cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, the correlation between LINC00844 and NDRG1 expression was analysed using Pearson’s correlation analysis. Results LINC00844 expression was significantly downregulatedin HCC tissues and cell lines, and a statistical correlation was detected between low LINC00844 expression and sex (Female), advanced American Joint Committee on Cancer (AJCC) stage (III + IV), histological grade (G3 + G4), and vascular invasion (Micro and Macro). In vitro experiments showed that LINC00844 overexpression significantly repressed the proliferation, migration, and invasion of HCC cells. NDRG1 expression was higher in HCC tissues and LINC00844 could partly inhibit the expression of NDRG1