scholarly journals Jieduan-Niwan Formula Reduces Liver Apoptosis in a Rat Model of Acute-on-Chronic Liver Failure by Regulating the E2F1-Mediated Intrinsic Apoptosis Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Wenlong Yang ◽  
Yulin Hao ◽  
Weixin Hou ◽  
Xian Fang ◽  
Peng Fang ◽  
...  
Keyword(s):  
Liver Failure ◽  
Rat Model ◽  
Pathological Condition ◽  
Survival Rates ◽  
Chronic Liver ◽  
Group Model ◽  
Chronic Liver Failure ◽  
Apoptotic Pathway ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway

Acute-on-chronic liver failure (ACLF) is a serious and complicated disease that threatens human health because its pathogenesis is unclear, and the outcome of the current therapies has been less than satisfactory. A national famous doctor of traditional Chinese medicine, Qian Ying, created the Jieduan-Niwan Formula (JDNW), based on his long-term clinical experience. However, despite the good clinical outcome, the biological mechanism by which it works is unknown. In the current study, we established an ACLF rat model by administering human serum albumin (HSA) combined with D-galactosamine (D-GalN) and lipopolysaccharide (LPS) to explore the potential mechanism of JDNW in treating ACLF. The rats were treated with JDNW by administration of the model substances and sacrificed after 4, 8, and 12 h. Then we divided the rats into normal group, model at 4 h, model at 8 h, model at 12 h, JDNW at 4 h, JDNW at 8 h, and JDNW at 12 h. Biochemical and histopathological examinations were performed to compare the rats in different groups. Compared with the ACLF model group, expression levels of alanine transaminase, aspartate aminotransferase, total bilirubin, and TNF-α and IL-6 proteins were reduced in the JDNW group at the corresponding time points, the survival rates of rats were increased, and the pathological condition of the liver was improved. In addition, JDNW treatment improved the ultrastructure of hepatocytes and mitochondria and decreased the hepatocyte apoptosis index. E2F1, P53, P73, Apaf-1, p14ARF, caspase-3, caspase-6, and caspase-7 levels in the JDNW group were distinctly lower than those in the untreated rats. Moreover, Bcl-2 and Mcl-1 levels increased. Thus, JDNW decreases ACLF-induced mortality in rats by modulating the E2F1-mediated intrinsic apoptotic pathway.

scholarly journals The effect of fractal-like mechanical ventilation on vital signs in a rat model of acute-on-chronic liver failure

2018 ◽  
Vol 39 (11) ◽  
pp. 114008
Author(s):  
Arman Nataj ◽  
Golnar Eftekhari ◽  
Mohammad R Raoufy ◽  
Ali R Mani
Keyword(s):  
Mechanical Ventilation ◽  
Liver Failure ◽  
Rat Model ◽  
Vital Signs ◽  
Chronic Liver ◽  
Chronic Liver Failure

Regulation of IL-22 in a rat model for acute-on-chronic liver failure (ACLF)

2020 ◽  
Vol 73 ◽  
pp. S498
Author(s):  
Katharina Maria Schwarzkopf ◽  
Frank Uschner ◽  
Robert Schierwagen ◽  
Sabine Klein ◽  
Marcus Maximilian Muecke ◽  
...  
Keyword(s):  
Liver Failure ◽  
Rat Model ◽  
Chronic Liver ◽  
Chronic Liver Failure

scholarly journals Effectiveness of granulocyte colony-stimulating factor for patients with acute-on-chronic liver failure: a meta-analysis

2021 ◽  
Vol 41 (6) ◽  
pp. 383-391
Author(s):  
Wei Huang ◽  
Yuanji Ma ◽  
Lingyao Du ◽  
Shuang Kang ◽  
Chang-Hai Liu ◽  
...  
Keyword(s):  
Liver Failure ◽  
Sample Size ◽  
Meta Analysis ◽  
Survival Rates ◽  
Chronic Liver ◽  
Cochrane Library ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Chronic Liver Failure ◽  
Stimulating Factor

BACKGROUND: The safety and efficacy of granulocyte colony-stimulating factor (G-CSF) for the treatment of acute-on-chronic liver failure (ACLF) remain uncertain. Therefore, we conducted a meta-analysis to draw a firmer conclusion. METHODS: We searched the Cochrane library, PubMed, Embase, and China Biology Medicine disc to identify relevant RCTs performed before January 2020. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were calculated using a random effects model. MAIN OUTCOME MEASURES: RRs (95% CI) for 1-, 2-, and 3-month survival rates. SAMPLE SIZE: Six RCTs, including three open-label studies. RESULTS: The six studies included 246 subjects (121 in a G-CSF group and 125 in a control group). G-CSF administration significantly improved the 1-, 2-, and 3-month survival rates in patients with ACLF. The pooled RRs (95% CI, P) were 0.43 (0.27–0.69, P =.0004), 0.44 (0.32–0.62, P <.00001), and 0.39 (0.22–0.68, P =.0009), respectively. CONCLUSION: G-CSF may be beneficial and effective in the treatment of ACLF, but further studies are needed to verify this conclusion. LIMITATIONS: The sample size was small, and studies were restricted to countries in Asia. PROSPERO REGISTRATION NUMBER: CRD42021225681 CONFLICT OF INTEREST: None.

scholarly journals Hepatoprotective Effect of Yiqijianpi Formula (YQJPF) on Liver Failure Through Modulation of Hypoxic and Apoptosis Pathways

2020 ◽  
Author(s):  
Li Tang ◽  
Feixia Wang ◽  
Lingyan Xiao ◽  
Min Shen ◽  
Siwei Xia ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Signaling Pathways ◽  
Tunel Assay ◽  
Chronic Liver ◽  
Active Components ◽  
Chronic Liver Failure ◽  
Apoptosis Pathway ◽  
L02 Cells

Abstract BackgroundAcute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis, which seriously endanger human life and health. Yiqijianpi decoction (YQJPF) is a Traditional Chinese Medicine (TCM) formula that has been widely used in the treatment of liver failure with significant effect. The purpose of this study was to investigate the active components and mechanism to ameliorate acute on chronic liver failure(ACLF).MethodsLPS combined with D-Gal was used to establish the rat model of ACLF, pathological examination was detected by H&E staining, liver function test was assayed by ELISA. LPS was used to induce hepatocytes injury in vitro. Cell proliferation assay, TUNEL assay were used in human hepatic L02 cells. The active components and putative targets of YQJPF were predicted by network pharmacology approach and GEO analysis. Functional and pathway enrichment analysis were presented by using String, Cytoscape and Metascape. Further, experimental validation was done to verify the effect of YQJPF on PI3K/AKT-HIF-1ɑ and apoptosis-related signaling pathways by using Immunohistochemistry and Western blotting.ResultsAfter being treated with YQJPF, the rat liver injury and fibrosis were alleviated, and Cell Counting Kit-8 assay, TUNEL assay indicated YQJPF also inhibited the apoptosis in hepatic L02 cells. Through network pharmacologic analysis, 135 active components in YQJPF decoction, 573 known therapeutic targets and 2940 liver failure-related human genes were identified. 163 gene symbols maybe the key for liver failure treatment by YQJPF decoction. VEGF-A was hub gene in PPI network. The KEGG pathway and GO enrichment analyses indicated that the PI3K/AKT, HIF-1 signaling pathways were the prominently enriched signaling pathways. In vivo, YQJPF upregulated the expression of PI3K/AKT-HIF1-ɑ and VEGF-A. Moreover apoptosis pathway were verified by up-regulating Bcl2 expression and down-regulating Bax expression in vivo and in vitro.ConclusionYQJPF is beneficial for alleviating liver failure, may regulate hypoxic liver injury through PI3K/AKT-HIF1α dependent apoptosis pathway.

scholarly journals The Comparative Efficacy and Safety of Entecavir and Lamivudine in Patients with HBV-Associated Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-11
Author(s):  
Jiao Yang ◽  
Hang Sun ◽  
Qi Liu
Keyword(s):  
Survival Rate ◽  
Liver Failure ◽  
Meta Analysis ◽  
Survival Rates ◽  
Term Treatment ◽  
Chronic Liver ◽  
Efficacy And Safety ◽  
Chronic Liver Failure ◽  
Long Term Treatment

Background.Currently, both of entecavir and lamivudine are effective for patients with HBV-associated acute-on-chronic liver failure (ACLF). However, there is no consensus on the efficacy of entecavir versus lamivudine for patients with HBV-associated ACLF. The aim of the study was to compare the efficacy and safety of entecavir with that of lamivudine for HBV-associated ACLF patients.Methods.Publications on entecavir versus lamivudine in HBV-associated ACLF patients were comprehensively identified. Odds ratio and mean difference were used to measure the effect.Results.Ten studies, totaling 1254 patients, were eligible. No significant differences between the two drugs presented in the 1-, 2-, 3-, or 6-month survival rates. However, after 12 months of treatment, patients prescribed entecavir had a statistically higher survival rate (p=0.008) and lower total bilirubin (p<0.0001) and alanine aminotransferase (p=0.04) levels compared to patients prescribed lamivudine. More patients achieved HBV negative levels when taking entecavir as measured at 1-, 3-, and 12-month time points and had a lower rate of HBV recurrence.Conclusion.While entecavir and lamivudine are both relatively safe and well tolerated, entecavir was more efficacious in terms of survival rate and clinical improvement in long-term treatment. Further prospective randomized controlled trials are needed to validate these results.

scholarly journals Bacopa monnieriExtract (CDRI-08) Modulates the NMDA Receptor Subunits and nNOS-Apoptosis Axis in Cerebellum of Hepatic Encephalopathy Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Papia Mondal ◽  
Surendra Kumar Trigun
Keyword(s):  
Nitric Oxide ◽  
Hepatic Encephalopathy ◽  
Liver Failure ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Apoptosis Pathway ◽  
Nitric Oxide Level ◽  
Nmdar Activation ◽  
Oxide Synthase ◽  
The Brain

Hepatic encephalopathy (HE), characterized by impaired cerebellar functions during chronic liver failure (CLF), involves N-methyl-D-aspartate receptor (NMDAR) overactivation in the brain cells.Bacopa monnieri(BM) extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B) and its downstream mediators in cerebellum of rats with chronic liver failure (CLF), induced by administration of 50 mg/kg bw thioacetamide (TAA) i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS-) apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE.

scholarly journals Deregulation of Regulatory T Cells in Acute-on-Chronic Liver Failure: A Rat Model

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Shunlan Ni ◽  
Shanshan Li ◽  
Naibin Yang ◽  
Xinyue Tang ◽  
Shengguo Zhang ◽  
...  
Keyword(s):  
Liver Failure ◽  
Rat Model ◽  
Th17 Cell ◽  
Interleukin 10 ◽  
Treg Cells ◽  
Chronic Liver ◽  
Control Group ◽  
Chronic Liver Failure ◽  
T Helper 17 ◽  
Cell Proportion

Aims. Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are similar in many respects during their acute exacerbation; however, ACLF generally has a poorer prognosis. We aimed to investigate the role and dynamic changes of regulatory T cell (Treg) and T helper 17 (Th17) cell proportions during ACLF progress. Methods. All rats were classified into two groups randomly: ACLF group and ALF group (control group). The rat model of ACLF was preestablished by intraperitoneal injection of carbon tetrachloride for 2 months. Then acute liver injury was induced by combined D-galactosamine and lipopolysaccharide. Six time points were examined before or after acute induction. Liver samples were performed with hematoxylin-eosin and Masson staining; circulatory Treg and Th17 cell frequencies were determined using flow cytometry assays; serum levels of alanine aminotransferase, aspartate aminotransferase, interleukin-10 (IL-10), and interferon-γ (IFN-γ) were examined. Results. In group ACLF, both Th17 cell proportion and IFN-γ level presented upgrade firstly and then descend latter tendency; the trends of Treg cell proportion and IL-10 level were observed to gradually decrease and became stable. Conclusion. The Treg cells played an important role in the immunologic mechanism during the process of ACLF. And the function of Treg cells in ACLF was defective.

scholarly journals The Effect of Modified Sini Decoction on Survival Rates of Patients with Hepatitis B Virus Related Acute-on-Chronic Liver Failure

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Jian-Xing Luo ◽  
Yang Zhang ◽  
Xiao-Yu Hu ◽  
Chang Yu
Keyword(s):  
Internal Medicine ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Liver Failure ◽  
Survival Rates ◽  
Chronic Liver ◽  
Control Group ◽  
Observation Group ◽  
Chronic Liver Failure ◽  
B Virus

Aim of the Study.To verify the effect of modified sini decoction on patients with hepatitis B virus related acute-on-chronic liver failure.Materials and Methods.A retrospective cohort study was conducted. Patients who had been treated with modified sini decoction and standard comprehensive internal medicine were assigned to an observation group, and patients who had been treated with standard comprehensive internal medicine were selected as a control group. The total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), prothrombin activity (PTA), CTP, and MELD scores were analyzed at weeks 4, 8, and 12 after treatment, respectively. Meanwhile, the 12-week survival rate was analyzed.Results.The levels of TBIL and ALT were remarkably decreased, while the levels of ALB and PTA were remarkably increased in both groups at weeks 4, 8, and 12 after treatment, respectively, but the effects in the observation group were greater (P < 0.05). The CTP and MELD scores at 8-week and 12-week were lower in the observation group than in the control group (P < 0.05). At 12 weeks, the mean survival times of the observation group and the control group were 66.7 and 45.5 d, respectively. Significant improvement of 12-week survival rate [39/62 (62.9%) versus 18/50 (36.0%), P = 0.001] was observed in the observation group after treatment.Conclusions.Modified sini decoction could protect the liver function and improve the survival rates of patients with hepatitis B virus related acute-on-chronic liver failure.

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