Baicalin attenuated metabolic dysfunction-associated fatty liver disease by suppressing oxidative stress and inflammation via the p62-Keap1-Nrf2 signalling pathway in db/db mice.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.

Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

A novel treatment strategy using indocyanine green for transarterial chemoembolization in BCLC stage C hepatocellular carcinoma.

PURPOSE: The aim of our study was to propose a strategy based on indocyanine green (ICG) (SBI) to provide better clinical guidelines for transarterial chemoembolization (TACE) treatments for Barcelona clinic liver cancer (BCLC) stage C hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From October 2005 to December 2012, 112 BCLC stage C HCC patients initially treated with TACE were investigated, randomly divided into a training cohort (n = 79) and validation cohort (n = 33). In training group, the patients were grouped based on their 15 minutes ICG retention rate (ICG R15), different chemo drugs and dose of lipidol in TACE. Overall survival (OS) and progression-free survival (PFS) were analyzed in subgroups. Strategy based on ICG was built and verified in validation group. RESULTS: For those patients with ICG R15 values >10%, the lipiodol ≤10 mL group showed better survival than the lipiodol >10 mL group. For those patients with ICG R15 values ≤10%, the group that received triple-drug chemotherapy treatments with lipiodol diameter ratio values between 1 and 3 showed better survival than the other group. Patients who conformed with the SBI had better survival times than those who did not conform with the SBI, in both the training cohort (median OS 10.3 vs 5.1 months; P < .001; median PFS, 3.3 vs 2.1 months; P = .006) and the validation cohort (median OS 8.9 vs 7.1 months; P = .087; median PFS, 6.6 vs 2.3 months; P < .001). CONCLUSIONS: The SBI is suitable and may provide survival benefits for TACE treatments in BCLC stage C HCC patients.

Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.

BACKGROUND: The effect of green tea catechins (GTCs) with or without caffeine on glycemic control is controversial. OBJECTIVE: We aimed to identify and quantify the effects of GTCs or GTC-caffeine mixtures on glucose metabolism in adults. DESIGN: A comprehensive literature search was conducted to identify relevant trials of GTCs with or without caffeine on markers of glycemic control [fasting blood glucose (FBG), fasting blood insulin (FBI), glycated hemoglobin (Hb A1c), and homeostatic model assessment of insulin resistance (HOMA-IR)]. Weighted mean differences were calculated for net changes by using fixed-effects models. Prespecified subgroup analyses were performed to explore the influence of covariates on net changes in FBG and FBI concentrations. RESULTS: Twenty-two eligible randomized controlled trials with 1584 subjects were identified. Pooled analyses showed that FBG (-1.48 mg/dL; 95% CI: -2.57, -0.40 mg/dL) decreased significantly with GTCs with or without caffeine, whereas FBI (0.04 µU/mL; 95% CI: -0.36, 0.45 µU/mL), Hb A1c (-0.04%; 95% CI: -0.15, 0.08%), and HOMA-IR (-0.05; 95% CI: -0.37, 0.26) did not. Subgroup analyses indicated that the glucose-lowering effect was apparent when the duration of follow-up was over a median of 12 wk. Overall, no significant heterogeneity was detected for FBG, FBI, Hb A1c, or HOMA-IR. CONCLUSIONS: The meta-analysis showed that the administration of GTCs with or without caffeine resulted in a significant reduction in FBG. The limited data available on GTCs did not support a positive effect on FBI, Hb A1c, or HOMA-IR. Thus, more large and well-designed trials are needed in the future. This trial was registered at http://www.crd.york.ac.uk/prospero as CRD42012002139.

Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials.

BACKGROUND: The effect of green tea beverage and green tea extract on lipid changes is controversial. OBJECTIVE: We aimed to identify and quantify the effect of green tea and its extract on total cholesterol (TC), LDL cholesterol, and HDL cholesterol. DESIGN: We performed a comprehensive literature search to identify relevant trials of green tea beverages and extracts on lipid profiles in adults. Weighted mean differences were calculated for net changes in lipid concentrations by using fixed-effects or random-effects models. Study quality was assessed by using the Jadad score, and a meta-analysis was conducted. RESULTS: Fourteen eligible randomized controlled trials with 1136 subjects were enrolled in our current meta-analysis. Green tea consumption significantly lowered the TC concentration by 7.20 mg/dL (95% CI: -8.19, -6.21 mg/dL; P < 0.001) and significantly lowered the LDL-cholesterol concentration by 2.19 mg/dL (95% CI: -3.16, -1.21 mg/dL; P < 0.001). The mean change in blood HDL-cholesterol concentration was not significant. Subgroup and sensitivity analyses showed that these changes were not influenced by the type of intervention, treatment dose of green tea catechins, study duration, individual health status, or quality of the study. Overall, no significant heterogeneity was detected for TC, LDL cholesterol, and HDL cholesterol; and results were reported on the basis of fixed-effects models. CONCLUSION: The analysis of eligible studies showed that the administration of green tea beverages or extracts resulted in significant reductions in serum TC and LDL-cholesterol concentrations, but no effect on HDL cholesterol was observed.

Effect of oral isoflavone supplementation on vascular endothelial function in postmenopausal women: a meta-analysis of randomized placebo-controlled trials.

BACKGROUND: The effect of isoflavone on endothelial function in postmenopausal women is controversial. OBJECTIVE: The objective of this study was to evaluate the effect of oral isoflavone supplementation on endothelial function, as measured by flow-mediated dilation (FMD), in postmenopausal women. DESIGN: A meta-analysis of randomized placebo-controlled trials was conducted to evaluate the effect of oral isoflavone supplementation on endothelial function in postmenopausal women. Trials were searched in PubMed, Embase, the Cochrane Library database, and reviews and reference lists of relevant articles. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. RESULTS: A total of 9 trials were reviewed in the present meta-analysis. Overall, the results of the 9 trials showed that isoflavone significantly increased FMD (WMD: 1.75%; 95% CI: 0.83%, 2.67%; P = 0.0002). Meta-regression analysis indicated that the age-adjusted baseline FMD was inversely related to effect size. Subgroup analysis showed that oral supplementation of isoflavone had no influence on FMD if the age-adjusted baseline FMD was > or = 5.2% (4 trials; WMD: 0.24%; 95% CI: -0.94%, 1.42%; P = 0.69). This improvement seemed to be significant when the age-adjusted baseline FMD levels were <5.2% (5 trials; WMD: 2.22%; 95% CI: 1.15%, 3.30%; P < 0.0001), although significant heterogeneity was still detected in this low-baseline-FMD subgroup. CONCLUSIONS: Oral isoflavone supplementation does not improve endothelial function in postmenopausal women with high baseline FMD levels but leads to significant improvement in women with low baseline FMD levels.

[Influence of Hovenia dulcis on alcohol concentration in blood and activity of alcohol dehydrogenase (ADH) of animals after drinking].

OBJECTIVE: To observe the effects of H. dulcis on relieving alcohol toxicity by animal experiments. METHOD: Male kunming mice were ovraiectomized and randomly divided into 5 groups: control group, model group, and aqueous extracts of H. dulcis group at 0.5, 0.25, 0.125 g x mL(-1). The acute alcohlism animals induced by gastral administration with "Er Guo Tou" and the alchol concentrations in serum were detected after treated with the extracts within 0.5-3 h by biochemical enzymes. RESULT: The alcohol concentration in blood was up to the maximum in 0.5-1.5 h. However, the alcohol concentrations in blood of aqueous extract from H. dulcis group were decreased in 0.5-3 h. The activity of ADH in the liver in aqueous extract of H. dulcis group was increased in 2-3 h, while it was significantly increased in 1-1.5 h (P <0.05). CONCLUSION: The aqueous extract of H. dulcis could reduce the alchol concentration in blood of animals and inrease the activity of ADH after given alcohol. It means the extract has the effect of relieving alcohol toxicity and preventing drunkenness through restraining the absorption of alcohol in the gastrointestinal tract and promoting the metabolism of alcohol in the liver.

[Expression of cellular repressor of E1A-stimulated genes in vascular smooth muscle cells of different phenotypes].

OBJECTIVES: The phenotypic modulation of vascular smooth muscle cells (VSMC) plays a central role in the pathogenesis of arteriosclerosis. The purpose of this study was to investigate the expression of the cellular repressor of E1A-activated genes (CREG) at the transcriptional and protein level in human internal thoracic artery smooth muscle cells (HITASY), which express different patterns of differentiation markers after serum withdrawal. METHODS: After cloning and recombining the CREG vector, the antiserum against the CREG protein was produced from the rabbits immunized by the purification CREG protein. The specificity of purified polyclonal antibody was detected by Western blot assay. The DNA synthesis of HITASY cultured in serum-free and serum-supplemented medium was measured by the [(3)H]-thymidine incorporation. Western blot analysis detected the expression of smooth muscle-specific markers (smooth muscle alpha-actin, calponin). The localization of CREG in cells was examined with immunohistochemistry staining and expression of CREG mRNA and protein were analyzed by RT-PCR and Western blot in HITASY after serum withdrawal. RESULTS: The high specificity of polyclonal antibody against CREG obtained from rabbits was confirmed by Western blot assay. In response to serum withdrawal, cultured HITASY cells exhibited phenotypic conversion from synthetic into contractile one as evidenced by the data of [(3)H]-thymidine incorporation and Western blot. The DNA synthesis of HITASY precipitously dropped to background levels after serum withdrawal and nearly restored after reintroduction of serum to culture medium 2 days later. Western blot revealed a reversible upregulation of smooth muscle alpha-actin and calponin in HITASY after serum deprivation. Moreover, serum withdrawal also induced a prominent increase of CREG mRNA and protein expression which reached a peak on 3 days and decreased gradually on 5 approximately 7 days after serum withdrawal. Immunohistochemistry stain indicated the CREG protein mainly localizes in a perinuclear pattern in HITASY cells. CONCLUSIONS: Those data provide evidence that the coordinated changes in CREG gene and protein expression as well as smooth muscle-specific markers may take place in connection with the process of phenotypic modulation of VSMC in vitro.

[Bone marrow stromal cells of adult mice differentiate into smooth muscle cells in vitro].

OBJECTIVE: To explore the potential of murine bone marrow stromal cells (MSCs) to differentiate into vascular smooth muscle cells so as to contribute to neointimal formation after vascular injury. METHODS: Murine MSCs were isolated from bone marrow and cultured in M199 with 10% FBS supplemented with medium conditioned from human smooth muscle cell culture to induce differentiation. Immunofluorescent technique was used to observe the morphology of cells to examine the smooth muscle characters. Vasoactive substance was added onto the cultured smooth muscle-like cells. Inverted microscopy was used to observe the contractile changes of the cells. RESULTS: After 6 passages of subculture in differentiation medium, MSCs demonstrated smooth muscle cell-like spindle-shaped morphology and assumed a hill-and-valley growth pattern. Immunofluorescent technique revealed positive signals for alpha-smooth muscle actin, calponin and smooth muscle myosin heavy chains. The smooth muscle cell-like cells displayed robust calcium transients. In response to stimulation of vasoactive substance the [Ca(2+)] of the cells instantaneously increased which was coupled by prominent cell contraction. CONCLUSION: MSCs can differentiate into vascular smooth muscle cells with contractile ability. This model may be useful in study of smooth muscle cell differentiation and the origin of neointimal cells after vascular injury.