Activated hepatic stellate cells (HSCs) are the principal effectors during hepatic fibrosis, which is characterized by the accumulation of extracellular matrix. Therefore, present therapies and investigations into hepatic fibrosis mainly focus on the suppression of activated HSCs. Astragaloside IV (ASIV) is an effective constituent extracted from the plant Astragalus membranaceus and has exhibited anti-fibrotic properties in hepatic fibrosis. However, its protective mechanism against hepatic fibrosis is not fully understood. The present study aimed to investigate the mechanistic role of ASIV on rat HSC-T6 cells activated with platelet-derived growth factor (PDGF)-BB. HSC-T6 cells were activated using PDGF-BB and subsequently treated with ASIV (final concentrations of 20 and 40 µg/ml) for 48 h. ASIV treatment decreased the expression of α1 type I collagen, α-smooth muscle actin and fibronectin on mRNA and protein levels, suggesting that ASIV suppresses PDGF-BB-induced HSC-T6 activation. Senescence-associated β-galactosidase activity, p21, high-mobility group AT-hook 1 and p53, common biomarkers of senescence, were upregulated by ASIV treatment. In addition, the expression of telomerase reverse transcriptase was reduced. ASIV promoted apoptosis of PDGF-BB-activated HSC-T6 cells. The NF-κB signaling pathway, which controls cellular senescence and apoptosis, was demonstrated to be stimulated by ASIV by increasing p65, p52, p50 and inhibitor of NF-κB kinase α expression levels, and by suppressing the expression of NF-κB inhibitor α. Taken together, these results demonstrated that ASIV promoted cellular senescence and apoptosis by activating the NF-κB pathway to suppress PDGF-BB-induced HSC-T6 activation; with potential implications for the treatment of hepatic fibrosis.
9 Abstract Olfactory ensheathing cells (OECs) are a type of 10 glia from the mammalian olfactory system, with neuro-11 protective and regenerative properties. b-Amyloid peptides 12 are a major component of the senile plaques characteristic 13 of the Alzheimer brain. The amyloid beta (Ab) precursor 14 protein is cleaved to amyloid peptides, and Ab 25-35 is 15 regarded to be the functional domain of Ab, responsible for 16 its neurotoxic properties. It has been reported that Ab [25][26][27][28][29][30][31][32][33][34][35] 17 triggers reactive oxygen species (ROS)-mediated oxidative 18 damage, altering the structure and function of mitochon-19 dria, leading to the activation of the mitochondrial intrinsic 20 apoptotic pathway. Our goal is to investigate the effects of 21 OECs on the toxicity of aggregated Ab [25][26][27][28][29][30][31][32][33][34][35]
Background: The purpose of the present meta-analysis was to compare the efficacy of rifaximin and nonabsorbable disaccharides (NADs) in hepatic encephalopathy (HE). Methods: After the registration of the present meta-analysis on INPLASY, all procedures were performed according to PRISMA 2020. Relevant literature was retrieved on PubMed, Embase, and the Cochrane Library up to September 5, 2021. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the enrolled studies, and Review Manager software (version 5.3) was used to analyze the clinical efficacy, blood ammonia and adverse effects. Results: Six studies with 559 patients were included in the present meta-analysis. There were no significant differences in the basic characteristics of the included studies. Analysis of the complete resolution of HE showed that rifaximin was better than NADs (risk ratio [RR] = 1.87, 95% confidence interval [CI] = 1.03–3.39, P = .04). However, there were no significant differences in mental status (RR = 1.04, 95% CI = 0.92–1.18, P = .53), blood ammonia level (standard mean difference = −0.02, 95% CI = −0.40–0.02, P = .08), or drug adverse drug effects (OR = 0.43, 95% CI = 0.10–1.77, I 2 = 56%, P = .24) between the rifaximin and NADs treatment groups. Conclusion: Rifaximin is not superior to NADs in the treatment of HE.
Background. Rhein is the main extract of Rheum palmatum L., which has been proved to improve the renal function of chronic kidney disease, but its mechanism is not clear. Therefore, this experiment explored the potential pharmacological effect of rhein on renal interstitial fibrosis rats. Methods. This study explores the potential pharmacological action of rhein. In this work, we investigate the potential pharmacological action of rhein in unilateral urethral obstruction (UUO) rats. Thirty Sprague Dawley rats were randomly divided into three groups: sham, UUO, and rhein (rhein-treated UUO rats) groups. The left ureters of the UUO group rats were exposed and bluntly dissected. The rhein group rats were administered an intragastric gavage of rhein (2 mg·kg−1·d−1) for 14 d. Kidney function-related indicators were monitored in these rats, while indexes of pathologic aspects were determined histologically. The expression of α-SMA, TGF-β1, SHH, Gli1, and Snail was quantified using real-time polymerase chain reaction and western blotting. The NRK-49F cells were incubated with and without SHH (100 ng·ml−1) for 48 hours. The SHH-activated NRK-49F cells were incubated with cyclopamine (CNP, 20 umol L−1) or rhein (1 ng·ml−1). The Gli1 and Snail mRNA and protein level were detected. Results. In the in vivo experiment, the results exhibited that UUO caused renal pathological damages. However, these changes could be significantly reversed by the administration of rhein. Compared with the untreated UUO group, the rhein group showed reduced kidney tubular atrophy and necrosis, interstitial fibrosis, hyperplasia, and abnormal deposition of extracellular matrix. Rhein reduced the RNA and protein expression of SHH, Gli1, and Snail of the UUO rats. In the in vitro experiment, CNP or rhein treatment decreased the expression of Gli1 and Snail on mRNA and protein levels in SHH-induced NRK-49F cells, suggesting that CNP or rhein suppresses SHH-induced NRK-49F activation. Taken together, these results demonstrated that rhein suppresses SHH-Gli1-Snail signal pathway activation, with potential implications for the treatment of renal fibrosis. Conclusions. Treatment with rhein remarkably ameliorated renal interstitial fibrosis in UUO rats by regulating the SHH-Gli1-Snail signal pathway.
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