Real-World Risk and Outcome of Liver Cirrhosis in Patients with Hyperlipidemia Treated with Red Yeast Rice: A Retrospective Cohort Study

Chuen-Chau Chang,1– 3,&ast; Chun-Chieh Yeh,4,5 Cheng Tiong,6,7 Mao-Feng Sun,8 Jaung-Geng Lin,8 Yih-Giun Cherng,3,9 Ta-Liang Chen,2,3,10,&ast; Chien-Chang Liao1– 3,8,11 1Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan; 2Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 3Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 5Department of Surgery, University of Illinois, Chicago, IL, USA; 6Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 7Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 9Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; 10Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 11Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chien-Chang Liao, Department of Anesthesiology, Taipei Medical University Hospital, 252 Wuxing St, Taipei, 110, Taiwan, Email [email protected]; [email protected]: Sustained hyperlipidemia contributes to fatty liver and liver cirrhosis. Red yeast rice (RYR) effectively improved the lipid profile; however, the effects of RYR on the risk of incident liver cirrhosis remain to be elucidated. We aimed to evaluate the beneficial effects of RYR use on the risk and outcome of liver cirrhosis.Patients and methods: We identified 156,587 adults who had newly diagnosed hyperlipidemia in 2010– 2016 from health insurance data in this retrospective cohort study. Using propensity score matching, we selected 34,367 patients who used RYR and 34,367 patients who used lovastatin. Events of incident liver cirrhosis that occurred in the two cohorts during the follow-up period of 2010– 2019 were identified. We calculated adjusted hazard ratios (HRs) and 95% confidence intervals (Cis) for liver cirrhosis risk associated with RYR use in the multiple Cox proportional hazard model.Results: Compared with patients who used lovastatin, patients who used RYR had a decreased risk of liver cirrhosis (HR 0.60, 95% CI 0.57– 0.63), and this association was significant in various subgroups. A biological gradient relationship between the frequency of RYR use and decreased liver cirrhosis was observed (p for trend < 0.0001). Reduced postcirrhosis jaundice (HR 0.56, 95% CI 0.43– 0.72), ascites (HR 0.37, 95% CI 0.28– 0.50), hepatic coma (HR 0.36, 95% CI 0.26– 0.50), and mortality (HR 0.48, 95% CI 0.38– 0.61) were also associated with RYR use.Conclusion: We demonstrated the beneficial effects of RYR use on the risk and outcome of liver cirrhosis; however, the lack of compliance data should be considered. However, our study did not infer causality or claim the superiority of RYR over lovastatin.Keywords: hyperlipidemia, liver cirrhosis, lovastatin, outcome, red yeast rice, ris

Effect of nitric oxide on mitochondrial activity of human synovial cells

<p>Abstract</p> <p>Background</p> <p>Nitric oxide (NO) is a messenger implicated in the destruction and inflammation of joint tissues. Cartilage and synovial membrane from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) have high levels of NO. NO is known to modulate various cellular pathways and, thus, inhibit the activity of the mitochondrial respiratory chain (MRC) of chondrocytes and induce the generation of reactive oxygen species (ROS) and cell death in multiple cell types. For these reasons, and because of the importance of the synovial membrane in development of OA pathology, we investigated the effects of NO on survival, mitochondrial function, and activity of fibroblastic human OA synovial cells.</p> <p>Methods</p> <p>Human OA synovia were obtained from eight patients undergoing hip joint replacement. Sodium nitroprusside (SNP) was used as a NO donor compound and cell viability was evaluated by MTT assays. Mitochondrial function was evaluated by analyzing the mitochondrial membrane potential (Δψm) with flow cytometry using the fluorofore DePsipher. ATP levels were measured by luminescence assays, and the activities of the respiratory chain complexes (complex I: NADH CoQ₁reductase, complex II: succinate dehydrogenase, complex III: ubiquinol-cytochrome c reductase, complex IV: cytochrome c oxidase) and citrate synthase (CS) were measured by enzymatic assay. Protein expression analyses were performed by western blot.</p> <p>Results</p> <p>SNP at a concentration of 0.5 mM induced cell death, shown by the MTT method at different time points. The percentages of viable cells at 24, 48 and 72 hours were 86.11 ± 4.9%, 74.31 ± 3.35%, and 43.88 ± 1.43%, respectively, compared to the basal level of 100% (*<it>p </it>< 0.05). SNP at 0.5 mM induced depolarization of the mitochondrial membrane at 12 hours with a decrease in the ratio of polarized cells (basal = 2.48 ± 0.28; SNP 0.5 mM = 1.57 ± 0.11; *<it>p </it>< 0.01). The time course analyses of treatment with SNP at 0.5 mM demonstrated that treatment reliably and significantly reduced intracellular ATP production (68.34 ± 14.3% vs. basal = 100% at 6 hours; *<it>p </it>< 0.05). The analysis of the MRC at 48 hours showed that SNP at 0.5 mM increased the activity of complexes I (basal = 36.47 ± 3.92 mol/min/mg protein, SNP 0.5 mM = 58.08 ± 6.46 mol/min/mg protein; *<it>p </it>< 0.05) and III (basal = 63.87 ± 6.93 mol/min/mg protein, SNP 0.5 mM = 109.15 ± 30.37 mol/min/mg protein; *<it>p </it>< 0.05) but reduced CS activity (basal = 105.06 ± 10.72 mol/min/mg protein, SNP at 0.5 mM = 66.88 ± 6.08 mol/min/mg protein.; *<it>p </it>< 0.05), indicating a decrease in mitochondrial mass. Finally, SNP regulated the expression of proteins related to the cellular cycle; the NO donor decreased bcl-2, mcl-1 and procaspase-3 protein expression.</p> <p>Conclusions</p> <p>This study suggests that NO reduces the survival of OA synoviocytes by regulating mitochondrial functionality, as well as the proteins controlling the cell cycle.</p