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Effect of branched-chain amino acids in patients receiving intervention for hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第10期20卷 2673-2680页

作者： Tomoaki Ishihara Motoh Iwasa Hideaki Tanaka Masahiko Kaito Jiro Ikoma Toshiya Shibata Yoshiyuki Takei Department of Gastroenterology and Hepatology Yokkaichi Digestive Disease Center Komono Mie 510-1232 Japan Department of Gastroenterology and Hepatology Mie University Graduate School of Medicine Tsu Mie 514-8507 Japan Department of Gastroenterology and Hepatology Mie Shokakinaika Tsu Mie 514-0062 Japan Department of Diagnostic Imaging and Nuclear Medicine Kyoto University Graduate School of MedicineKyoto 606-8507 Japan

AIM:To investigate the usefulness of branched-chain amino acids(BCAA)before transarterial chemoembolization(TACE)or radiofrequency ablation(RFA).METHODS:We investigated the usefulness of preintervention with BCAAs by comparing patients treated with BCAAs at 12.45 g/d orally for at least 2 wk before TACE or RFA and those not receiving such pretreatment.A total of 270 patients with hepatocellular carcinoma complicated by cirrhosis were included in the study.Mean changes from baseline(Δ)in serum albumin(Alb),C-reactive protein(CRP),and transaminase levels,as well as peak body temperature were also determined and compared at days 2,5,and 10 after the start of TACE or RFA.RESULTS:In patients who underwent TACE or RFA,BCAA pre-intervention significantly suppressed the development of post-intervention hypoalbuminemia and reduced inflammatory reactions during the subsequent clinical course.After TACE,theΔAlb peaked on day 2,remained constantly lower in BCAA-treated patients,compared to the control group,and was-0.13±0.42g/dL in BCAA-treated patients and-0.33±0.51 g/dL in untreated patients on day 10.TheΔCRP was also significantly lower in BCAA-treated patients on days2,5 and 10 after TACE.Like the trends noted after TACE,a similar tendency was noted as to theΔAlb andΔCRP after RFA.The changes in serum Alb level were inversely correlated with CRP changes;therefore,a possible involvement of the anti-inflammatory effect of BCAAs was inferred as a factor contributory to the suppression of decrease in serum Alb level.CONCLUSION:Pre-intervention with BCAAs may hasten the recovery of serum Alb level and mitigate postoperative complications in patients undergoing TACE or RFA.

关键词： branched-chain amino acids Cirrhosis Hepatocellula

Impairment of innate immune responses in cirrhotic patients and treatment by branched-chain amino acids

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World Journal of Gastroenterology 2014年第23期20卷 7298-7305页

作者： Ikuo Nakamura Department of Gastroenterology Tokyo Medical UniversityTokyo 160-0023Japan Department of Gastroenterology Saitama Medical CenterJichi Medical UniversitySaitama 330-8503Japan

It has been reported that host defense responses,such as phagocytic function of neutrophils and natural killer(NK)cell activity of lymphocytes,are impaired in cirrhotic patients.This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids(BCAA)on innate immune responses.We already reported that phagocytic function of neutrophils was significantly improved by3-mo BCAA supplementation.In addition,the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation.Also,Fisher’s ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation.Therefore,administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host.In addition,it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients.The mechanisms of the effects will also be discussed in this review article.

关键词： branched-chain amino acids Liver cirrhosis Innate

branched-chain/aromatic amino acids as integrated biomarker of type 2 diabetes mellitus: a systematic review and meta-analysis

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Medical Data Mining 2020年第1期3卷 10-21页

作者： Jiang-Lan Long Zhi-Rui Yang Long Wang Yu-Mei Han Can Yan Dan Yan Beijing Key Laboratory and Joint Laboratory for International Cooperation of Bio-characteristic Profiling for Evaluation of Rational Drug Use Beijing Shijitan HospitalCapital Medical UniversityBeijing100038China Chengdu University of Traditional Chinese Medicine Chengdu611130China Department of Applied Mathematics and Statistics Johns Hopkins UniversityBaltimoreMD 21218USA Beijing Physical Examination Center Beijing100077China Guangzhou University of Chinese Medicine Guangzhou510006China

Background:As type 2 diabetes mellitus(T2DM)biomarkers,branched-chain amino acids(BCAAs:valine,leucine and isoleucine)and aromatic amino acids(AAAs:phenylalanine,tryptophan and tyrosine)may be correlated with the occurrence and development of T2DM.However,there is still no consensus on the disperse and isolated biomarkers of T2DM.Purpose:To explore the correlation between amino acids and T2DM based on integrated biomarker approach revealed.Methods:PubMed,Web of Science and CNKI were selected to search the literature published until August 31,2019.The included studies described the association between BCAAs,AAAs and T2DM.Random effect model and fixed effect model were adopted in pooled analysis to determine mean difference and 95 percent confidence interval of metabolites.Integrated biomarker was constructed in form of concentration change ratios or risk ratio(RR),relative risk(HR)and odds ratio(OR)of BCAAs and AAAs to reflect the integrated change information of amino acids.Results:The selected 20 studies contained 14942 healthy individuals and 3615 T2DM patients.The levels of BCAAs,phenylalanine and tyrosine both in plasma and serum samples were increased among all T2DM patients compared with those of the healthy control subjects(P<0.00001).However,the mean difference of tryptophan concentration was not statistically significant(P=0.60).The concentration change ratios or HR/RR/OR of BCAAs and AAAs were connected to form integrated biomarker.Conclusion:The integrated biomarker including BCAAs and AAAs could reflect the basic characteristics of T2DM,which has the potential clinical value on comprehensive diagnosis of T2DM.

关键词： branched-chain amino acids Aromatic amino acids Type 2 diabetes mellitus Integrated biomarker Meta-analysis

Effects of L-carnitine and branched-chain Amino Acids on Energy Metabolism,Body Composition,and Delayed-Onset Muscle Soreness after Exercise in Healthy Subjects

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Journal of Nutritional Oncology 2018年第1期3卷 25-33页

作者： Yoichi Sakurai Yumi Hasegawa Yuka Kurosaka Hideyuki Nanba Satoshi Odo Department of Ecology Wayo Women’s University Graduate SchoolChibaJapan Department of Surgery Chiba-ken Saiseikai Narashino HospitalChibaJapan Department of Clinical Nutrition Matsudo Municipal HospitalChibaJapan College of Science and Technology Nihon University Lonza Japan Ltd TokyoJapan

Background Specific nutrients combined with exercise may prevent a loss of lean body mass and consequently prevent sarcopenia.We examined the effects of 2 weeks of supplementation with L-carnitine and a single dose of branched-chain amino acids(BCAAs)on energy metabolism and body composition before and after exercise and on post-exercise muscle soreness in healthy subjects.Methods A total of 12 young,untrained,healthy women were randomly assigned to two groups who received either 2 weeks of supplementation with L-carnitine(1000 mg/day)and a single dose of BCAAs plus 200 kcal energy(LCAR+BCAA group,n=6)or 200 kcal energy alone(control group,n=6)before 60 min of exercise.Energy substrate metabolism and body composition by bio-impedance were examined before and after exercise.Delayed-onset muscle soreness(DOMS)was evaluated by using a visual analogue scale for 3 days after exercise.Results Serum concentrations of free and acyl-L-carnitine in the LCAR+BCAA group were not significantly different from those in the control group.There were no significant differences in body composition before or after exercise between the two groups.Although serum free fatty acid levels 120 min after the oral ingestion of BCAAs were significantly lower in the LCAR+BCAA group than in the control group,there were no significant differences in serum free fatty acid levels immediately after and 60 min after exercise.DOMS for 3 days after exercise was lower in the LCAR+BCAA group than in the control group,but this difference was not significant.Conclusion Continuous supplementation with L-carnitine combined with a dose of BCAAs in young,untrained,healthy subjects caused a blunted response of stimulated lipolysis after exercise.

关键词： Sarcopenia L-carnitine branched-chain amino acids Exercise Oxidative stress Delayed-onset muscle soreness

Herbicide-Resistant Mutations in Acetolactate Synthase Can Reduce Feedback Inhibition and Lead to Accumulation of branched-chain Amino Acids

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Food and Nutrition Sciences 2013年第5期4卷 522-528页

作者： Masaki Endo Tsutomu Shimizu Tamaki Fujimori Shuichi Yanagisawa Seiichi Toki Department of Applied Biological Chemistry Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo Japan Life Science Research Institute Kumiai Chemical Industry Co. Ltd. Shizuoka Japan Plant Genome Engineering Research Unit Agrogenomics Research Center National Institute of Agrobiological Sciences Tsukuba Japan

The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that are critical for animal growth and development. Animals need to obtain BCAAs from their diet because they cannot synthesize them. Plants are the ultimate source of these amino acids. Acetolactate synthase (ALS) is the first common enzyme in the biosynthesis of BCAAs. The metabolic control of BCAA biosynthesis involves allosteric regulation of ALS by the end-products of the pathway, i.e., valine, leucine and isoleucine. ALS holoenzyme seems to consist of two large catalytic subunits and two small regulatory subunits. In a previous study, using homologous recombination dependent gene targeting we created rice plants in which W548Land S627I mutations were induced into the endogenous gene encoding the ALS catalytic subunit. These two amino acid substitutions conferred hypertolerance to the ALS-inhibiting herbicide bispyripac-sodium. In this study, we revealed that feedback regulation by valine and leucine was reduced by these two amino acid substitutions. Furthermore, in leaves and seeds of ALS mutants with W548Land/or S627I substitution, a 2- to 3-fold increase in BCAAs was detected. Our results suggest that the ALS catalytic subunit is also involved in feedback regulation of ALS, and that judicious modification of the regulatory and catalytic subunits of ALS-coding genes by gene targeting can lead to the efficient accumulation of BCAA in plants.

关键词： Rice Acetolactate Synthase Herbicide-Resistance branched-chain Amino Acids

Chemoprevention of obesity-related liver carcinogenesis by using pharmaceutical and nutraceutical agents

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World Journal of Gastroenterology 2016年第1期22卷 394-406页

作者： Hiroyasu Sakai Yohei Shirakami Masahito Shimizu Department of Gastroenterology/Internal Medicine Gifu University Graduate School of Medicine

Obesity and its related metabolic disorders are serious health problems worldwide,and lead to various healthrelated complications,including cancer.Among human cancers,hepatocellular carcinoma(HCC)is one of the most common malignancies affected by obesity.Therefore,obesity and its related disorders might be a key target for the prevention of HCC.Recently,new research indicates that the molecular abnormalities associated with obesity,including insulin resistance/hyperinsulinemia,chronic inflammation,adipokine imbalance,and oxidative stress,are possible molecular mechanisms underlying the pathogenesis of obesityrelated hepatocarcinogenesis.Green tea catechins and branched-chain amino acids,both of which are classified as nutraceutical agents,have been reported to prevent obesity-related HCC development by improving metabolic abnormalities.The administration of acyclic retinoid,a pharmaceutical agent,reduced the incidence of HCC in obese and diabetic mice,and was also associated with improvements in insulin resistance and chronic inflammation.In this article,we review the detailed molecular mechanisms that link obesity to the development of HCC in obese individuals.We also summarize recent evidence from experimental and clinical studies using either nutraceutical or pharmaceutical agents,and suggest that nutraceutical and pharmaceutical approaches targeting metabolic abnormalities might be a promising strategy to prevent the development of obesity-related HCC.

关键词： Hepatocellular carcinoma Obesity Greentea catechins branched-chain amino acids Acyclicretinoid

Explosive limits and its container factors of polybasic explosive mixture gas containing H_2,CH_4 and CO

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Science China Chemistry 2002年第1期45卷 30-36页

作者：胡耀元李勇朱凯汉周邦智杨元法 Physical Chemistry Research Institute Zhejiang Normal University Jinhua China Department of Chemistry Qinghai Normal University Xining China

Explosive characteristics of polybasic explosive mixture gas are systematically researched. Over 28000 experimental data have been obtained from 1278 effective experiments. The paper probes into the concentration explosive limits and the container factors of polybasic explosive mixture gas which contains H2, CH4 and CO. It has worked out the sufficient and necessary condition for branch-chain explosion and the unified expression of the probability of the heterogeneous chain termination. Experiments indicate that the concentration explosive limits of polybasic explosive mixture gas (H2, CH4, CO) relate to many factors. They enlarge with the augmentability of the container (linear size, geometric shape, and flame spread direction). This will be of great significance to guiding the revision of related industrial safety targets, reclaiming and reusing related industrial tail gas and waste gas, taking precautions against the explosion hazard of mixture gas in correlated industry and mines, and applying the

关键词： branched-chain explosion heterogeneous chain termination concentration explosive limit container factor.

Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function

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World Journal of Gastroenterology 2016年第32期22卷 7252-7263页

作者： Taro Takami Takahiro Yamasaki Issei Saeki Toshihiko Matsumoto Yutaka Suehiro Isao Sakaida Department of Gastroenterology and Hepatology Yamaguchi University Graduate School of Medicine Department of Oncology and Laboratory Medicine Yamaguchi University Graduate School of Medicine

Hepatocellular carcinoma(HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids(BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis.

关键词： Hepatocellular carcinoma Liver cirrhosis branched-chain amino acids Late evening snack Iron chelators Bone marrow cells