Diagnostic value of methylated branched chain amino acid transaminase 1/IKAROS family zinc finger 1 for colorectal cancer

BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,several related studies have published their results and showed its diagnostic efficacy.AIM To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC.METHODS The candidate studies were identified by searching the PubMed,Embase,Cochrane Library,CNKI,and Wanfang databases from May 31,2003 to June 1,2023.Sensitivity,specificity,and diagnostic accuracy were calculated by merging ratios or means.RESULTS Twelve eligible studies were included in the analysis,involving 6561 participants.The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60%[95%confidence interval(CI)53-67]and specificity was 92%(95%CI:90-94).The positive and negative likelihood ratios were 8.0(95%CI:5.8-11.0)and 0.43(95%CI:0.36-0.52),respectively.Diagnostic odds ratio was 19(95%CI:11-30)and area under the curve was 0.88(95%CI:0.85-0.91).The sensitivity and specificity for CRC screening were 64%(95%CI:59-69)and 92%(95%CI:91-93),respectively.The sensitivity and specificity for recurrence detection during follow-up were 54%CONCLUSION The detection of methylated BCAT1/IKZF1 in plasma,as a non-invasive detection method of circulating tumor DNA,has potential CRC diagnosis,but the clinical application prospect needs to be further explored.

Branched-chain amino acids in liver diseases

Branched chain amino acids(BCAAs)have been shown to affect gene expression,protein metabolism,apoptosis and regeneration of hepatocytes,and insulin resistance.They have also been shown to inhibit the proliferation of liver cancer cells in vitro,and are essential for lymphocyte proliferation and dendritic cell maturation.In patients with advanced chronic liver disease,BCAA concentrations are low,whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high,conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients.Based on these basic observations,patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines,with positive effects.

Branched-chain amino acids to tyrosine ratio value as a potential prognostic factor for hepatocellular carcinoma

The prognosis of hepatocellular carcinoma(HCC) depends on tumor extension as well as hepatic function.Hepatic functional reserve is recognized as a factor affecting survival in the treatment of HCC;the ChildPugh classif ication system is the most extensively used method for assessing hepatic functional reserve in patients with chronic liver disease,using serum albumin level to achieve accurate assessment of the status of protein metabolism.However,insuff icient attention has been given to the status of amino acid(AA) metabolism in chronic liver disease and HCC.Fischer's ratio is the molar ratio of branched-chain AAs(BCAAs:leucine,valine,isoleucine) to aromatic AAs(phenylalanine,tyrosine) and is important for assessing liver metabolism,hepatic functional reserve and the severity of liver dysfunction.Although this ratio is diff icult to determine in clinical situations,BCAAs/tyrosine molar concentration ratio(BTR) has been proposed as a simpler substitute.BTR correlates with various liver function examinations,including markers of hepatic f ibrosis,hepatic blood flow and hepatocyte function,and can thus be considered as reflecting the degree of hepatic impairment.This manuscript examines the literature to clarify whether BTR can serve as a prognostic factor for treatment of HCC.

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

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.

Early administration of branched-chain amino acid granules

The effect of malnutrition on survival in patients with decompensated liver cirrhosis has not been well defined. Nutritional intervention with branched-chain amino acid (BCAA) can increase serum albumin concentration in patients with decompensated cirrhosis but its effects on survival are unclear. The BCAA to tyrosine ratio (BTR) is a surrogate marker (the normal range of BTR is between 4.41 and 10.05, and a Fischer's ratio of 1.8 corresponds to a BTR of 3.5) in patients with decompensated liver cirrhosis, and BCAA inhibits hepatic carcinogenesis in patients with compensated cirrhosis. This review discusses data regarding the effect of early administration of BCAA granules based on the ratio of BCAA to BTR on prognosis in patients with cirrhosis.

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

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.

Synergistic renoprotective effect of a compiled branched-chain amino acids and Cymbopogon schoenanthus extract against experimentally induced oxido-nitrosative renal insult

Objective: To better investigate the protective role of branched-chain amino acids(BCAAs)and Cymbopogon schoenanthus(CS) extract against the potassium dichromate(PDC)-induced oxido-nitrosative nephrotoxic insult in the experimental rat model. Methods: Thirty male rats were randomly divided into five equal groups: The 1 st group served as control; the 2^(nd)was injected with a single dose of PDC(15 mg/kg b.w i.p.);the 3^(rd), 4^(th), and 5^(th) groups were respectively treated with BCAAs, CS, and their combination for 15 d prior to induction of renal insult via PDC single dose(15 mg/kg b.w s.c.). The experimental period was terminated in all groups 2 d after induction of renal insult. The harvested kdney samples were divided for biochemical assays and histological examination. Results: The PDC-induced nephrotoxic effect caused a depletion of renal oxidative scavengers glutathione, superoxide dismutase with consequent lipo-oxidative cellular membrane deterioration manifested by a rise in malonaldehyde, oxidized glutathione, myeloperoxidase and the concomitant increase in inflammatory response elements tumor necrosis factor α, nitric oxide, and interleukin 1 β.Moreover, the comet assay and increased 8-hydroxy-2-deoxyguanosine proved an accelerated apoptotic DNA fragmentation. These local renal changes were met with global altered blood biochemistry. The BCAAs and CS or their compiled administration showed an ameliorative effect against PDC-induced nephrotoxic in a synergistic pattern. Conclusions: Both BCAAs and CS or their combined administration afford potential competitors against renal insult induced by polyvalent anion pollutants in experimentally studied animals model. As a route for novel drug discovery, further investigation should be attempted to optimize their augmenting reno-protecting potential.

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

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.

Functional microbiomics reveals branched-chain amino acids depletion for alleviation of insulin resistance by berberine

Increased circulating branched-chain amino acids(BCAAs)have been involved in the pathogenesis of obesity and insulin resistance.However,evidence relating berberine(BBR),gut microbiota,BCAAs,and insulin resis⁃tance is limited.Here,we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet(HFD)-fed mice.BBR reorganized gut microbiota populations under both the normal chow diet(NCD)and HFD.Particu⁃larly,BBR noticeably decreased the relative abundance of BCAA-producing bacteria,including order Clostridiales;fami⁃lies Streptococcaceae,Clostridiaceae,and Prevotellaceae;and genera Streptococcus and Prevotella.Compared with the HFD group,predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment.Accordingly,the elevated serum BCAAs of HFD group were significantly decreased by BBR.Furthermore,the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by acti⁃vation of the multienzyme branched-chain α-ketoacid dehydrogenase complex,whereas by inhibition of the phosphoryla⁃tion state of BCKDHA(E1α subunit)and branched-chain α-ketoacid dehydrogenase kinase.The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes.Finally,data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs.Besides,functional microbiomics integrated high-throughput microbial genomics,metabolomics and molecular biotechnology has also been successfully applied to reveal the anti-obesity mechanism of hydroxysafflor yellow A.

Plasma Levels of Amino Acids in Japanese Men and Their Changes after the Administration of Glucose and Sucrose

Background: It is not known whether plasma amino acids levels are different between young and old men in Japan. No research has been reported about changes in plasma levels of amino acids after the administration of glucose or sucrose to young and aged men. Objective: We want to know whether there are age differences in plasma levels of amino acids and if the administration of glucose or sucrose influences their levels. Results: Old people had lower plasma levels of most of amino acids, especially essential and branched-chain amino acids than young men. Plasma levels of amino acids were measured after the administration of 50 grams of glucose or sucrose to young (18 - 22 years old) and aged (≥50 years old) male adults. Plasma levels of total amino acids decreased after the administration of glucose. Decrease in the total amino acid levels was significant in aged men after the administration of sucrose. A significant decrease in plasma levels of total non-essential amino acids was observed at 120 min after the administration of glucose but not sucrose in both aged and young men. Both glucose and sucrose administrations resulted in a significant decrease in the plasma levels of the total essential amino acid levels and branched amino acids in young and aged men. Conclusion: These results suggest that there are age differences in plasma levels of amino acids. Upon the administration of glucose or sucrose amino acids, particularly essential amino acids, decreased in plasma. These amino acids may be transported from the blood soon after the administration of sugar (glucose or sucrose) to the tissues, such as muscles, possibly due to an increase in the insulin levels.

支链氨基酸代谢与2型糖尿病关系的研究进展

支链氨基酸(BCAAs)是一类因存在脂肪烃链而得名的必需氨基酸,包括亮氨酸、异亮氨酸以及缬氨酸。BCAAs同胰岛素抵抗的关系于1964年被提出,该类氨基酸在膳食中常见,其循环水平通过对糖脂代谢和胰岛素分泌的调控对2型糖尿病(T2DM)病程发展起着重要的作用。作为一种发病率高、并发症严重的慢性代谢性疾病,糖尿病已经对全球人民生活生产造成了极大的困扰。其中T2DM作为糖尿病中占比最高的类型,正大幅度降低患者的生活质量。本文通过糖脂代谢以及其他相关机制,将BCAAs代谢分解过程与T2DM发生发展联系起来,从而为临床T2DM的治疗诊断提供更多思路。

支链氨基酸的生理功能及其在反刍动物生产中的应用研究进展

支链氨基酸是维持动物机体生长发育、生命活动和生理功能的必需氨基酸。支链氨基酸由于其特殊的分子结构而具有特殊生理功能。近年来研究发现,支链氨基酸具有氧化供能、调节蛋白质代谢、调节脂肪代谢、调节激素分泌、调节免疫、缓解氧化应激等多种功能。本文综述了支链氨基酸的生理功能及其在反刍动物生产中的应用,旨在为支链氨基酸在反刍动物生产中的合理应用提供理论依据和参考。

支链氨基酸转氨酶1在食管鳞癌中的表达及其临床意义

目的探讨食管鳞癌(ESCC)患者癌组织中支链氨基酸转氨酶1(BCAT1)的表达及临床意义。方法采用qRT-PCR和Western blot技术检测食管鳞癌细胞系中BCAT1基因的表达水平,筛选出合适的食管癌细胞,作为后续研究。敲低和过表达BCAT1,采用Western blot检测ESCC细胞中BCAT1的蛋白表达水平。CCK-8活力测定、克隆形成实验、划痕实验、Transwell检测ESCC细胞增殖、迁移和侵袭等细胞表型的变化。结果qRT-PCR和Western blot结果显示,与正常细胞相比,BCAT1在ESCC中的相对表达量降低,尤其是KYSE150和Eca109细胞更为明显,因此选择这两株细胞进行研究。CCK-8细胞增殖实验结果显示,细胞在转染BCAT1 siRNA 48 h后,其增殖率明显高于对照组;而过表达BCAT1之后,效果则相反。克隆形成实验结果表明,BCAT1的敲低显著促进ESCC细胞的克隆形成,而BCAT1的过表达显著抑制ESCC细胞的克隆形成。细胞划痕实验和Transwell实验结果表明,与Control siRNA组相比,BCAT1 siRNA组ESCC细胞的迁移和侵袭明显升高;而过表达组中ESCC细胞的迁移和侵袭明显受到抑制。结论BCAT1在ESCC中低表达,BCAT1低表达显著促进ESCC细胞增殖、迁移和侵袭。

家禽支链氨基酸营养需要研究进展

支链氨基酸(branched-chain amino acids,BCAA)在家禽生长、生产性能、免疫功能和肠道健康等方面发挥着重要作用,涉及器官发育、免疫反应、肌肉蛋白周转和基因调控等关键过程。然而,单一BCAA的过量、缺乏或比例失衡均会影响家禽蛋白质合成和肠道健康,因此保持BCAA比例的平衡对于家禽的生产性能至关重要。尽管NRC(1994)提供了肉鸡、蛋鸡和种鸡的BCAA推荐量,但不同日粮蛋白质水平以及不同品种和生长阶段的家禽对BCAA的需求存在差异。同时,鉴于抗生素生长促进剂的禁用及养殖端所面临的多种疾病的挑战,也需要重新评估家禽对BCAA的推荐摄取水平。另外,BCAA在维持肠道完整性、调控肠道微生物组成以及提高机体蛋白周转效率的作用机理研究仍有待进一步探究。本综述在阐述BCAA在家禽中的营养生理作用以及其对生产和健康的基础上,推荐了不同饲养条件下不同肉鸡品种(肉鸡、蛋鸡和种鸡)BCAA需要量,以期为家禽低蛋白日粮BCAA推荐量提供理论参考。

支链氨基酸干预视域下军事作业性疲劳的防治机制研究进展

军事训练是我国培养军人强健体格与顽强意志的重要一环,有助于全面提升部队的备战与作战能力。战士由于长时间、高强度的军事训练作业产生运动性疲劳,从而影响训练效果。近年来,多项临床试验和基础研究均证明了支链氨基酸有助于缓解运动性疲劳,在军事预防医学领域具有良好前景。为进一步了解应用支链氨基酸缓解军事运动性疲劳的可行性与科学性,文章就运动性疲劳的发生机制与补充支链氨基酸缓解该类疲劳的机理进行综述。

Supplementation of branched-chain amino acids in protein-restricted diets modulates the expression levels of amino acid transporters and energy metabolism associated regulators in the adipose tissue of growing pigs

This experiment was conducted to investigate the effects of branched-chain amino acids(BCAA)supplemented in protein-restricted diets on the growth performance and the expression profile of amino acid transporters and energy metabolism related regulators in the white adipose tissue(WAT)of different regional depots including dorsal subcutaneous adipose(DSA) and abdominal subcutaneous adipose(ASA), A total of 24 crossbred barrows(7.40 ± 0.70 kg) were randomly divided into 4 groups and were fed the following isocaloric diets for 33 days: 1) a recommended adequate protein diet(AP, 20% CP, as a positive control); 2) a low protein diet(LP, 17% CP); 3) the LP diet supplemented with BCAA(LP + B, 17% CP) to reach the same level of the AP diet group; 4) the LP diet supplemented with 2 times the amount of BCAA(LP + 2B, 17% CP). The daily gain and daily feed intake of the LP diet group were the lowest among all the treatments(P < 0.01). The feed conversion was improved markedly in the group of LP + B compared with the LP diet group(P < 0.05). No significant difference was noted for the serum biochemical parameter concentrations of glucose, triglyceride, nonesterified fatty acid and insulin among the groups(P > 0.05). Moreover, BCAA supplementation down-regulated the expression levels of amino acid transporters including L-type amino acid transporter 1 and sodium-coupled neutral amino acid transporter 2 in DSA, but up-regulated the expression level of Ltype amino acid transporter 4 in ASA(P < 0.05), Meanwhile, the energy sensor AMP-activated protein kinase α was activated in the DSA of pigs fed LP diet and in the ASA of the pigs fed AP or LP + 2B diets(P < 0.05). The mRNA expression profile of the selected mitochondrial component and mitochondrial biogenesis associated regulators in DSA and ASA also responded differently to dietary BCAA supplementation. These results suggested that the growth performance of growing pigs fed protein restricted diets supplemented with BCAA could catch up to that of the pigs fed AP diets. The results also partly demonstrated that the regulation mechanisms of BCAA are different in the adipose tissues of different depots.

Enhancement of precursor amino acid supplies for improving bacitracin production by activation of branched chain amino acid transporter BrnQ and deletion of its regulator gene lrp in Bacillus licheniformis

Bacitracin,a new type of cyclic peptide antibiotic,is widely used as the feed additive in feed industry.Branched chain amino acids(BCAAs)are the key precursors for bacitracin synthesis.In this research,soybean meal was served as the raw material to supply precursor amino acids for bacitracin synthesis,and enhanced production of bacitracin was attempted by engineering BCAA transporter BrnQ and its regulator Lrp in the bacitracin industrial production strain Bacillus licheniformis DW2.Firstly,our results confirmed that Lrp negatively affected bacitracin synthesis in DW2,and deletion of lrp improved intracellular BCAA accumulations,as well as the expression level of BCAA transporter BrnQ,which further led to a 14.71%increase of bacitracin yield,compared with that of DW2.On the contrary,overexpression of Lrp decreased bacitracin yield by 12.28%.Secondly,it was suggested that BrnQ acted as a BCAA importer in DW2,and overexpression of BrnQ enhanced the intracellular BCAA accumulations and 10.43%of bacitracin yield.While,the bacitracin yield decreased by 18.27%in the brnQ deletion strain DW2△brnQ.Finally,BrnQ was further overexpressed in lrp deletion strain DW2△lrp,and bacitracin yield produced by the final strain DW2△lrp::BrnQ was 965.34 U/mL,increased by 22.42%compared with that of DW2(788.48 U/mL).Collectively,this research confirmed that Lrp affected bacitracin synthesis via regulating the expression of BCAA transporter BrnQ and BCAA distributions,and provided a promising strain for industrial production of bacitracin.

Branched chain amino acids and metabolic regulation

Amino acids are fundamental nutrients required for protein synthesis. The branched chain amino acids (BCAAs) leucine, isoleucine, and valine are the most abundant of the essential amino acids. BCAAs have recently been recognized as having functions in processes other than simple nutrition. For example, metabolic diseases are characterized by higher levels of circulating BCAAs. Moreover, supplementation with or deficiency in BCAAs is closely related to the regulation of metabolic homeostasis. Indeed, leucine deprivation induces increased lipolysis and thermogenesis, which result in fat loss, as well as suppressed lipogenesis and enhanced insulin sensitivity in the liver. Accumulating evidence has indicated that several amino acid sensors, including GCN2, ATF4, mTOR, and AMPK, play pivotal roles in the regulation of lipid metabolism, glucose metabolism, and energy homeostasis. Furthermore, the hypothalamus is critical for sensing amino acid levels and mediates the metabolic adaptation of the body upon limitation of essential amino acids (EAAs) through regulating expression of the S6K1, MC4R, and CRH. In this review, we highlight recent studies investigating the cellular mechanisms linking amino acids, amino acid sensors, metabolic regulation, and metabolic diseases. Amino acid sensing and metabolic regulation have become research hotspots in the metabolic field.

支链氨基酸对多囊卵巢综合征代谢与生殖的影响

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是育龄期女性常见的生殖内分泌疾病,患者常伴有胰岛素抵抗、肥胖、不孕及不良妊娠结局等临床表现,严重影响女性身心健康。近年研究表明,支链氨基酸(branched-chain amino acid,BCAA)在PCOS患者体内存在代谢异常,并且可能作为标志物预测PCOS相关并发症的发生风险。BCAA作为人体的必需氨基酸,通过多种途径参与胰岛素的调节、调控脂肪的生成与分化,对维持机体稳态具有重要作用,同时其水平变化可能会影响女性的生殖功能。PCOS患者循环中BCAA过高可导致糖脂代谢紊乱,促进胰岛素抵抗和肥胖的发生,也可对育龄期患者排卵及妊娠造成不利影响。综述BCAA在PCOS糖脂代谢和生殖方面的作用及研究进展,以期为PCOS代谢与生殖方面疾病的诊治提供新思路。