Autologous bone marrow stem cell transplantation via the hepatic artery for the treatment of hepatitis B virus-related cirrhosis: a PRISMA-compliant meta-analysis based on the Chinese population.

OBJECTIVE: Autologous bone marrow stem cell (ABMSC) transplantation has been considered a promising option for hepatitis B virus-related cirrhosis (HBV-C). Although an analysis of the published literature has been performed, the exact effects and safety have yet to be systematically investigated. METHODS: We conducted a wide-ranging online search of electronic databases (Web of Science, PubMed, Cochrane Library, Embase, CNKI, VIP, and Wanfang database) to reach systematic conclusions. Outcome measurements, including therapeutic efficacy, clinical symptoms, and adverse events, were extracted and analyzed statistically. RESULTS: Ultimately, a total of 10 articles including 662 HBV-C patients were included in this analysis, which indicated that ABMSC therapy could significantly improve liver function in patients with HBV-C in terms of the MELD and Child-Pugh scores, total bilirubin, serum albumin, alanine aminotransferase, aspartate aminotransferase, and coagulation function. Compared with patients receiving routine therapy (RT), those treated with ABMSC and RT combined therapy showed improved clinical symptoms, as represented by increased appetite and reduced fatigue and ascitic fluid and abdominal distension. Moreover, the fibrosis indexes indicated a reduction in liver fibrosis in patients treated with combined therapy according to the improved levels of hyaluronic acid (MD = - 70.47, CI = - 103.72-37.21, P <  0.0001), laminin (MD = - 25.11, CI = - 37.73-12.49, P <  0.0001), type III procollagen (MD = - 22.42, CI = - 34.49-10.34, P = 0.0003), and type IV collagen (MD = - 22.50, CI = - 39.92-5.08, P = 0.01). No obvious adverse events occurred during ABMSC treatment. CONCLUSION: ABMSC transplantation via the hepatic artery was safe and effective in treating HBV-C without causing severe adverse events.

Zafirlukast, a Cysteinyl Leukotriene Receptor 1 Antagonist, Reduces the Effect of Advanced Glycation End-Products in Rat Renal Mesangial Cells In Vitro.

BACKGROUND Zafirlukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1). Advanced glycation end-products (AGEs) are formed by the glycation of lipids and proteins in hyperglycemia, including diabetes mellitus. Zafirlukast has not previously been studied in diabetic nephropathy. This study aimed to investigate the effects of zafirlukast on rat renal mesangial cells cultured with AGEs in vitro. MATERIAL AND METHODS Mesangial cells were cultured in AGEs (0, 20, 50, 100 µg/ml), and with AGEs (100 µg/ml) and zafirlukast (2.5 µm, 5 µm, and 100 µm). An enzyme-linked immunoassay (ELISA) was used to measure the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1ß (IL-1ß), IL-6, and monocyte chemoattractant protein-1 (MCP-1). Reactive oxygen species (ROS) were assessed by intracellular fluorescence measurement of 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and detection kits were used to measure malondialdehyde (MDA), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD). Cell apoptosis was assessed by flow cytometry, and Western blot was used to measure protein levels. RESULTS In mesangial cells cultured with AGEs, markers of inflammation, oxidative stress, and apoptosis and levels of CysLTR1 increased, and these effects were reduced by zafirlukast in a dose-dependent manner. The effects of zafirlukast as a CysLTR1 antagonist protected mesangial cells from the effects of AGE in vitro. CONCLUSIONS Zafirlukast, a CysLTR1 antagonist, reduced the levels of inflammatory cytokines, markers of oxidative stress, and cell apoptosis induced by AGE in mesangial cells in a dose-dependent way. Future in vivo studies are needed to investigate the potential role for zafirlukast in models of diabetic nephropathy.