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An overview on microbial α-amylase and recent biotechnological developments 微生物α-淀粉酶研究进展及生物技术进展
Pub Date : 2022-03-28 DOI: 10.2174/2211550111666220328141044
Rajendra Singh, S. Kim, Anila Kumari, P. Mehta
The α-amylase is one of the most promising commercial enzymes that has tremendous applications in various industries. Microbial α-amylase share almost 25-30% in enzymes market due to its catalytic function in several industries, including sugar, detergent, paper, textile, pharmaceutical industries, etc. The α-amylase hydrolyze glycosidic linkages of structural components of starch result in maltose, glucose, and high fructose syrups. Starch, the second most abundant organic substance on the Earth, is a readily available, low-cost renewable substrate mainly in biorefinery and food industries. Amylases are ubiquitous in nature due to its involvement in carbohydrate metabolism. The α-amylases of microbial origin have technical advantage as compared to animal and plant origin. Considering physicochemical properties, bacterial α-amylases are most diverse. However, for industrial purpose, these properties of the biocatalyst, either individually or in a combination, are required to modify through genetic and protein engineering according to the targeted process. The review presents an overview on the current findings of microbial sourced α-amylases, commercial applications, market trends on relevant industries and achieved improvements in thermostability, catalytic function, pH tolerance, Substrate and product specificities through recombinant DNA technology and protein engineering.
α-淀粉酶是一种具有广泛应用前景的工业酶。微生物α-淀粉酶在制糖、洗涤剂、造纸、纺织、制药等行业具有催化作用,在酶类市场中占有近25-30%的份额。α-淀粉酶水解淀粉结构组分的糖苷键,生成麦芽糖、葡萄糖和高果糖糖浆。淀粉是地球上第二丰富的有机物质,是一种容易获得的低成本可再生基质,主要用于生物炼制和食品工业。淀粉酶因其参与碳水化合物代谢而在自然界中无处不在。微生物源α-淀粉酶相对于动植物源α-淀粉酶具有技术优势。考虑到理化性质,细菌α-淀粉酶是最多样化的。然而,对于工业用途,生物催化剂的这些特性,无论是单独的还是组合的,都需要根据目标过程通过基因和蛋白质工程进行修饰。本文综述了微生物源α-淀粉酶的研究现状、商业应用、相关行业的市场趋势,以及通过重组DNA技术和蛋白质工程技术在热稳定性、催化功能、pH耐受性、底物和产品特异性等方面取得的进展。
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引用次数: 5
Detection of phage and prophage expression in multidrug-resistant Salmonella serovars isolated from retail meats using mRNA-Seq mRNA-Seq法检测零售肉类中多重耐药沙门氏菌血清型噬菌体和前噬菌体的表达
Pub Date : 2022-03-04 DOI: 10.2174/2211550111666220304102952
Thuy Thi Bich Vo, V. T. Nguyen, Cuong Hoang, Duc Hieu Nguyen, Duc Minh Nguyen, T. B. Nguyễn, M. Nghiem
Salmonella serovars contamination of food items shows a negative effect for the food industry and causes a great hazard for the consumers. Although developed hygiene methods, Salmonella serovars still a high risk to human health, and new methods for the identify of Salmonella spp. are needed.Bacteriophages have considered as a good method for detecting bacteria since of its high target cell specificity, simple and cheap. Bacteriophages can be used for biocontrol of Salmonella spp. without the cultures methods. Moreover, phages or phage-derived proteins can also be used to detect quickly and specifically bacteria in food.This study provides bacteriophage expression in six multidrug-resistant Salmonella isolated from retail meats in Hanoi, Vietnam using mRNA sequencing.Our results showed that diverse bacteriophages are naturally present in retail meats (chicken, beef, and pork meat), and phage Salmon_118970_sal3_NC_031940 is the most common phage in Salmonella on the retail meats.These results provide useful information for developing a new method to detect Salmonella serovars effectively. Further surveillance programs and research are a necessity to limit the spread of multidrug-resistant Salmonella spp.
食品中沙门氏菌的污染对食品工业产生了负面影响,对消费者造成了极大的危害。虽然卫生方法已发展完善,但沙门氏菌血清型对人类健康的危害仍然很大,需要新的检测方法。噬菌体以其靶细胞特异性高、简单、廉价等优点被认为是检测细菌的良好方法。噬菌体可用于沙门氏菌的生物防治,无需培养法。此外,噬菌体或噬菌体衍生蛋白也可用于快速、特异地检测食物中的细菌。本研究利用mRNA测序技术对从越南河内零售肉类中分离的6种耐多药沙门氏菌进行噬菌体表达。结果表明,零售肉类(鸡肉、牛肉和猪肉)中天然存在多种噬菌体,其中噬菌体Salmon_118970_sal3_NC_031940是零售肉类中沙门氏菌中最常见的噬菌体。这些结果为开发有效检测沙门氏菌血清型的新方法提供了有益的信息。为了限制耐多药沙门氏菌的传播,进一步的监测项目和研究是必要的。
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引用次数: 0
Meet the Associate Editorial Board Member 认识编辑委员会副成员
Pub Date : 2022-03-01 DOI: 10.2174/221155011101220722143715
P. T. Campana
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引用次数: 0
Combination of biocatalysis and sonochemistry in the ethyl oleate production 生物催化与声化学在油酸乙酯生产中的结合
Pub Date : 2022-02-24 DOI: 10.2174/2211550111666220224110106
Natália Alves de Almeida, I. G. Rosset
Fatty acid alkyl esters (FAAEs) are a family of natural neutral lipids and can be produced cleanly and sustainably by esterification of free fatty acids (FFAs) with short chain alcohols using enzymatic catalysts. In this study, it was evaluated the use of lipases in enzymatic esterification of oleic acid with ethanol using the combination of biocatalysis and sonochemistry (ultrasound) in the absence of co-solvents.Reaction parameters, such as type of lipase, amount of enzyme, reaction time, alcohol hydration level and enzyme turnover were evaluated for the enzymatic synthesis of ethyl oleate.C. antarctica lipase provided yields above 95% in less than 10 h with 10% (w/w) of lipase. The use of hydrous ethanol (5% of water) showed a slight drop in yield but remained above 90% of ethyl oleate production. C. antarctica lipase showed no loss of efficiency even after 10 reaction cycles.The combination of biocatalysis and ultrasound radiation provided a high yield, showing that the combination of these tools may be a good choice for the enzymatic synthesis of ethyl oleate.
脂肪酸烷基酯(faae)是一类天然中性脂类,可由游离脂肪酸(FFAs)与短链醇在酶催化下酯化而产生。在这项研究中,评估了脂肪酶在没有共溶剂的情况下,利用生物催化和超声(超声)相结合的方法,在油酸与乙醇的酶促酯化反应中的应用。考察了脂肪酶类型、酶用量、反应时间、乙醇水合水平和酶周转等因素对酶促合成油酸乙酯的影响。在10% (w/w)的条件下,南极脂肪酶在不到10 h的时间内提供95%以上的产率。使用含水乙醇(5%的水)的产量略有下降,但仍保持在90%以上的油酸乙酯产量。C. antarctica脂肪酶在经过10个反应循环后仍未表现出效率损失。生物催化与超声辐射相结合可获得较高的产率,表明这两种手段的结合可能是酶促合成油酸乙酯的良好选择。
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引用次数: 0
Oral toxicity studies of Ethyl Acetate Polyherbal Extract Gel Formulation Obtained from Berries and Flaxseed (EAPEG-BF) in Wistar Rats 浆果亚麻籽乙酸乙酯提取物凝胶制剂对Wistar大鼠的口服毒性研究
Pub Date : 2022-02-15 DOI: 10.2174/2211550111666220215142143
A. Wal, U. Pandey, P. Wal, Tamsheel F. Roohi
Berries family and flaxseed have been used in ethnomedicinal practice for the treatment of various disorders and different ailments. Despite its beneficial uses, no studies on its polyherbal formulated gel combination toxicity potential have been reported. The present research study was designed to evaluate the acute oral toxicity (14 days) and sub-acute oral toxicity (repeated dose) study (28 days) of ethyl acetate polyherbal extract gel formulation obtained from berries and flaxseed according to OECD TG No. 423 and 407.Male Wistar Rats were taken for toxicological screening of acute and sub-acute oral toxicity as per OECD guidelines of ethyl acetate polyherbal extract gel formulation obtained from berries (Rubus idaeus, Vaccinium macrocarpon, Vaccinium angustifolium, Fragaria x ananassa) and flaxseed (Linum usitatissimum) at doses of 500 mg/kg, 1000 mg/kg, 2000 mg/kg and 5000 mg/kg b.w. p.o.The rats were orally treated and screened for various behavioural patterns and the clinical signs of toxicity after administration. In sub-acute oral toxicity screening, the highest dose of 5000 mg/kg was selected for repeated dose toxicity for 28 days. The data of the results showed that no toxic symptoms were observed up to the dose of 2000 mg/kg body weight. When testing is required a dose of 5000mg/kg, only one step. There was no toxic symptoms and mortality were observed up to the dose of 2000 mg/kg body weight during the 14 days of the observation. There is no visible change in the food intake and body weight when compared to control.The toxicological study revealed that LD50 of the extract formulation gel was greater than 5000 mg/kg body weight p.o.In comparison to the control group, there were no significant changes in levels of biochemical parameters and haematological parameters. It was concluded from the data obtained in this research study that though LD50 is greater than 5000 mg/kg body weight; but there was no occurrence of observed adverse effects levels appeared in the liver, kidney, lipid profile and blood parameters.
浆果家族和亚麻籽已经在民族医学实践中用于治疗各种疾病和不同的疾病。尽管其有益用途,但尚未有关于其多草药配方凝胶联合毒性潜在的研究报道。本研究旨在根据OECD TG No. 423和407评估从浆果和亚麻籽中提取的乙酸乙酯多草药提取物凝胶制剂的急性口服毒性(14天)和亚急性口服毒性(重复剂量)研究(28天)。以雄性Wistar大鼠为实验对象,按照OECD指南,对从浆果(Rubus idaeus, Vaccinium macrocaron, Vaccinium angustifolium, Fragaria x ananassa)和亚麻籽(Linum usitatissimum)中提取的乙酸乙酯多草药提取物凝胶配方进行急性和亚急性口服毒性毒理学筛选,剂量分别为500 mg/kg, 1000 mg/kg,每日口服2000 mg/kg和5000 mg/kg,观察大鼠给药后的各种行为模式和临床毒性症状。在亚急性口服毒性筛选中,选取最高剂量5000 mg/kg进行28天的重复剂量毒性试验。结果数据显示,直到2000 mg/kg体重的剂量,未观察到毒性症状。当测试需要5000mg/kg的剂量时,只需一步。在14天的观察中,没有出现中毒症状,直至2000 mg/kg体重的剂量,均未观察到死亡。与对照组相比,食物摄入量和体重没有明显变化。毒理学研究表明,提取物配方凝胶的LD50大于5000mg /kg体重p.与对照组相比,生物化学参数和血液学参数水平无显著变化。从本研究获得的数据可以得出结论:虽然LD50大于5000mg /kg体重;但在肝、肾、血脂和血液参数中未出现观察到的不良反应水平。
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引用次数: 0
Statistical Approach to Enhance α-Amylase Production from Bacillus licheniformis and Purification of the Enzyme 提高地衣芽孢杆菌α-淀粉酶产量的统计方法及酶的纯化
Pub Date : 2022-02-04 DOI: 10.2174/2211550111666220204125406
Kalpana Hiteshi, Reena Gupta
The most widely used thermostable enzymes are the amylases in the starch industry. These are among the most important enzymes and are of great significance in present day biotechnology.The main objective of the present study was to enhance α-amylase production from Bacillus licheniformis using Response Surface Methodology (RSM) and the purification of the enzyme to homogeneity.Bacterial culture producing α-amylase and isolated from hot spring (Himachal Pradesh) was identified as Bacillus licheniformis using 16S rDNA gene sequencing (NCBI Accession No.: KR340466). Medium components and pysical culture parameters viz. pH, temperature, inoculum size, peptone concentration and starch concentration were optimized using RSM. Among these five factors, three factors (starch concentration, peptone concentration and inoculum size) had positive effect on amylase production. A 4.09-fold increase in production of α-amylase from B. licheniformis was achieved using RSM as compared to One Factor At a Time. The enzyme was purified by using Diethylaminoethyl Cellulose column chromatography and subsequently by Sephadex G-75 gel filtration chromatography.A purification fold of 23.39 and a yield of 12.12% was observed. A single band of 33 kDa was obtained using Sodium Dodecyl Sulphate (SDS) and native-Poly Acrylamide Gel Electrophoresis (PAGE) which indicated that the enzyme was purified to homogeneity and was a monomer. The enzyme showed stability at 50 and 65°C temperatures and at alkaline pH.The stability of purified enzyme at high temperatures and alkaline pH suggested its wide application in textile, detergent and paper industries.Keywords: Amylase; Bacillus licheniformis; RSM; SDS-PAGE; alkaliphilic; thermostable enzymes
应用最广泛的耐热酶是淀粉工业中的淀粉酶。它们是最重要的酶之一,在当今的生物技术中具有重要意义。本研究的主要目的是利用响应面法(RSM)提高地衣芽孢杆菌α-淀粉酶的产量,并对酶进行纯化以达到均匀性。产α-淀粉酶的细菌培养物分离自喜马偕尔邦温泉,经16S rDNA基因测序鉴定为地衣芽孢杆菌(Bacillus licheniformis)。: KR340466)。采用RSM法对培养基组成和物理培养参数pH、温度、接种量、蛋白胨浓度和淀粉浓度进行了优化。其中淀粉浓度、蛋白胨浓度和接种量3个因素对淀粉酶产量有正向影响。与单因子法相比,采用RSM法,地衣芽孢杆菌α-淀粉酶的产量增加了4.09倍。采用二乙基氨基乙基纤维素柱层析和Sephadex G-75凝胶过滤层析对酶进行纯化。纯化倍数为23.39倍,产率为12.12%。利用十二烷基硫酸钠(SDS)和天然聚丙烯酰胺凝胶电泳(PAGE)获得了一个33 kDa的单条带,表明该酶被纯化到均匀性,是一个单体。该酶在50℃和65℃及碱性条件下均表现出稳定性,纯化后的酶在高温和碱性条件下的稳定性表明其在纺织、洗涤剂和造纸等工业中具有广泛的应用前景。关键词:淀粉酶;地衣芽孢杆菌;RSM;sds - page;alkaliphilic;耐热性的酶
{"title":"Statistical Approach to Enhance α-Amylase Production from Bacillus licheniformis and Purification of the Enzyme","authors":"Kalpana Hiteshi, Reena Gupta","doi":"10.2174/2211550111666220204125406","DOIUrl":"https://doi.org/10.2174/2211550111666220204125406","url":null,"abstract":"\u0000\u0000The most widely used thermostable enzymes are the amylases in the starch industry. These are among the most important enzymes and are of great significance in present day biotechnology.\u0000\u0000\u0000\u0000The main objective of the present study was to enhance α-amylase production from Bacillus licheniformis using Response Surface Methodology (RSM) and the purification of the enzyme to homogeneity.\u0000\u0000\u0000\u0000Bacterial culture producing α-amylase and isolated from hot spring (Himachal Pradesh) was identified as Bacillus licheniformis using 16S rDNA gene sequencing (NCBI Accession No.: KR340466). Medium components and pysical culture parameters viz. pH, temperature, inoculum size, peptone concentration and starch concentration were optimized using RSM. Among these five factors, three factors (starch concentration, peptone concentration and inoculum size) had positive effect on amylase production. A 4.09-fold increase in production of α-amylase from B. licheniformis was achieved using RSM as compared to One Factor At a Time. The enzyme was purified by using Diethylaminoethyl Cellulose column chromatography and subsequently by Sephadex G-75 gel filtration chromatography.\u0000\u0000\u0000\u0000A purification fold of 23.39 and a yield of 12.12% was observed. A single band of 33 kDa was obtained using Sodium Dodecyl Sulphate (SDS) and native-Poly Acrylamide Gel Electrophoresis (PAGE) which indicated that the enzyme was purified to homogeneity and was a monomer. The enzyme showed stability at 50 and 65°C temperatures and at alkaline pH.\u0000\u0000\u0000\u0000The stability of purified enzyme at high temperatures and alkaline pH suggested its wide application in textile, detergent and paper industries.\u0000Keywords: Amylase; Bacillus licheniformis; RSM; SDS-PAGE; alkaliphilic; thermostable enzymes\u0000","PeriodicalId":10850,"journal":{"name":"Current Biotechnology","volume":"194 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79748923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prediction of Secondary And Tertiary Structure And Docking of Rb1WT And Rb1R661W Proteins Rb1WT和Rb1R661W蛋白的二级和三级结构预测及对接
Pub Date : 2022-01-27 DOI: 10.2174/2211550111666220127100203
Aimen Sajid, Muhammad Shaoor Saeed, Rabbiah M anzoor Malik, S. Fazal, S. Malik, M. Kamal
Retinoblastoma, a malignancy occurring in the juvenile cells of retina, responsible for the light detection. It is one of the most emerging and rare childhood and infant cancer. It is initiated by the mutation in Rb1 a first tumor suppressor gene located on chromosome 13q14. Rb1 protein is responsible for cell cycle regulation.In our study, secondary and 3D-Structural prediction of Rb1WT and Rb1R661W were done by comparative or homology modeling for finding any structural change leading to the disruption in its further interactions. Quality assurance of the structures was done by Ramachandran Plot for a stable structure. Both the proteins were then applied by docking process with proteins of interest.Secondary Structure showed number of mutations in helixes, β-Hairpins of Rb1R661W. The major change was lost of β-Hairpin loop, extension and shortening of helixes. 3D comparison structure showed change in the groove of Rb1R661W. Docking results unlike to RB1WT were having different and also no interactions with some of the proteins of interest. This mutation in Rb1 protein was having a deleterious effect on the protein functionality.This study will help in designing the appropriate therapy and also understanding of mechanism of disease of retinoblastoma, for researchers and pharmaceuticals.
视网膜母细胞瘤,一种发生在视网膜幼细胞中的恶性肿瘤,负责光检测。它是儿童和婴儿最罕见的新发癌症之一。它是由位于染色体13q14上的第一个肿瘤抑制基因Rb1突变引发的。Rb1蛋白负责细胞周期调节。在我们的研究中,Rb1WT和Rb1R661W的二级和三维结构预测是通过比较或同源建模来进行的,以发现任何导致其进一步相互作用中断的结构变化。结构的质量保证由Ramachandran Plot完成,以确保结构稳定。然后通过对接过程将这两种蛋白质与感兴趣的蛋白质结合。二级结构显示Rb1R661W的螺旋、β-发夹突变数。主要变化是β-发夹环,螺旋的延长和缩短。三维对比结构显示Rb1R661W的凹槽发生了变化。与RB1WT不同的是,对接结果与一些感兴趣的蛋白质有不同的相互作用,也没有相互作用。Rb1蛋白的这种突变对蛋白质的功能有有害的影响。本研究将有助于视网膜母细胞瘤研究人员设计合适的治疗方法,并进一步了解其发病机制。
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引用次数: 0
The Impact of Microplastic on Human Health 微塑料对人体健康的影响
Pub Date : 2021-12-21 DOI: 10.2174/2211550111666211221120852
A. S. R. Almeida, C. B. de Souza
Microplastics are considered an emerging contaminant due to their wide distribution and production in the environment, representing constant exposure to humans. However, little is known about the effects it can trigger in the body. To establish a concrete relationship between microplastics and the human body, their means of production, exposure, systemic responses, and diseases caused by their presence In this context, a review article of foreign and national literature was developed, through the PubMed and Scielo Indexers, where studies were found that address the production of plastic, the paths that lead to the production of microplastics and the exposure and damage that it represents to human health, being possible to exclude the literary sums with a publication date before 2017hey showed that translocation of the residues occurs to the circulatory and lymphatic system via the respiratory and gastrointestinal tracts. Once in the body, microplastic can stimulate a chronic inflammatory response that functions as a precursor to neoplasia and fibrosis, or carry toxic compounds such as heavy metals, endogenous disruptors, biofilms, and persistent organic pollutants. In addition, lung biopsies have shown plastic fibers in patients with respiratory diseases, highlighting a potentially dangerous accumulation.The present moment demonstrates that experimental research to prove the effect of microplastics is extremely necessary, since the controversy among authors and the repetition of information already described affirm that the research done so far is not sufficient.
微塑料被认为是一种新兴污染物,因为它们在环境中的广泛分布和生产,代表着人类不断接触。然而,人们对它在体内引发的影响知之甚少。为了确立微塑料与人体、其生产手段、接触、系统反应以及因其存在而引起的疾病之间的具体关系,在此背景下,通过PubMed和Scielo Indexers编写了一篇对外国和国内文献的综述文章,其中发现了涉及塑料生产、导致微塑料生产的途径及其对人类健康的接触和损害的研究。可以排除出版日期在2017年之前的文献总数,他们表明残留物的易位通过呼吸道和胃肠道发生在循环和淋巴系统。一旦进入体内,微塑料就会刺激慢性炎症反应,作为肿瘤和纤维化的前兆,或者携带有毒化合物,如重金属、内源性干扰物、生物膜和持久性有机污染物。此外,肺部活组织检查显示,呼吸系统疾病患者体内存在塑料纤维,这凸显了一种潜在的危险积聚。目前的情况表明,实验研究证明微塑料的影响是非常必要的,因为作者之间的争议和已经描述的信息的重复证实了迄今为止所做的研究是不够的。
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引用次数: 0
Molecular Modeling, Interacting Residues and other Structural Analyses for Human SOCS3, Gp130 and JAK Proteins: A Detailed Computational Approach for Proteins Involved in Feedback Inhibition 人类SOCS3, Gp130和JAK蛋白的分子建模,相互作用残基和其他结构分析:参与反馈抑制的蛋白质的详细计算方法
Pub Date : 2021-12-21 DOI: 10.2174/2211550111666211221122707
A. Banerjee, R. Dasgupta
When STAT3 is activated only by the IL6 family of proteins, then gp130 (having a phosphopeptide motif) interacts with human SOCS3 which further binds to JAK and inhibits its protein kinase activity. Interaction of gp130 with SOCS3 targets only the IL-6 signaling cascade. The interaction occurs when SOCS3 binds to a particular motif on gp130 (centered upon pTyr759) after its phosphorylation. Previously, wet laboratory studies were done but computational exploration for the participating residues remained unexplored.The 3D structure of human SOCS3 protein was modeled and its stereo-chemical parameters were satisfied. Crystallographic structures of gp130-phosphopeptide and JAK were studied. After protein docking, the complex underwent minimization and molecular dynamics simulation. Different stability parameters and binding patterns with residues were evaluated The best modeled structure of SOCS3 protein was selected and found that it had three helices and seven sheets interspersed with coils. Arg133, Tyr137 and Tyr98 from SOCS3 formed manifold binding patterns with gp130 (mainly with pTyr759 and Glu758). Lys62, Lys63 and Arg65 from SOCS3 were also found to interact with Val762 of gp130. Interactions with JAK were also studied. Residue 53, 62-65, 98, 133, 136 and 137 formed the predominant binding pockets in SOCS3. They can serve as important target sites as well. Altogether, it created elctrostatically charged pockets to accommodate the partner proteins for each other. Gp130 phosphopeptide was observed to be tightly accommodated in the electrostatically positive zones on SOCS3 surface. Net area for solvent accessibility was also found to get drastically reduced implying high participation of residues. Earlier studies documented that the interaction of these three proteins occurs with affinity and have satisfactory association with each other. Here in this study, free energy of binding for the triple protein interaction through the ΔG values helped to infer that SOCS3 interacted spontaneously (in thermodynamic sense). Many helical conformations formed coiled-coils providing high flexibility to interact spontaneously. Most of the interactions were through the responsible SH2 domain (46-127 residue length) of SOCS3. Residues 53, 62-64 and 98 formed coils while the residue number 137adopted sheet conformation from coils.This study shall instigate to block the gp130-binding sites of SOCS3 through targeting of drugs, thereby preventing SOCS3-gp130 interaction. This would allow JAK-STAT signaling cascade which is paramount for several biological functions
当STAT3仅被IL6家族蛋白激活时,gp130(具有磷酸肽基序)与人类SOCS3相互作用,后者进一步结合JAK并抑制其蛋白激酶活性。gp130与SOCS3的相互作用仅针对IL-6信号级联。这种相互作用发生在SOCS3磷酸化gp130(以pTyr759为中心)后与gp130上的一个特定基序结合时。以前,湿实验室研究已完成,但计算探索参与残基仍未探索。建立了人SOCS3蛋白的三维结构模型,满足其立体化学参数。研究了gp130-磷酸肽和JAK的晶体结构。蛋白对接后,对复合物进行最小化和分子动力学模拟。分析了不同的稳定性参数和与残基的结合模式,选择了SOCS3蛋白的最佳模型结构,发现其具有3个螺旋和7个螺旋状结构。来自SOCS3的Arg133、Tyr137和Tyr98与gp130形成多种结合模式(主要与pTyr759和Glu758结合)。来自SOCS3的Lys62、Lys63和Arg65也发现与gp130的Val762相互作用。还研究了与JAK的相互作用。残基53、62-65、98、133、136和137是SOCS3中主要的结合口袋。它们也可以作为重要的靶点。总的来说,它创造了带电的口袋来容纳彼此的伴侣蛋白质。观察到Gp130磷酸肽在SOCS3表面的静电正区被紧密调节。溶剂可及性的净面积也大大减少,这意味着残留物的高参与。早期的研究证明,这三种蛋白质的相互作用发生亲和力和令人满意的相互关联。在本研究中,通过ΔG值,三蛋白相互作用的自由结合能有助于推断SOCS3自发相互作用(在热力学意义上)。许多螺旋构象形成了线圈,为自发相互作用提供了很高的灵活性。大部分相互作用通过SOCS3的SH2结构域(46-127残基长度)进行。残基53,62 -64和98形成线圈,残基137采用卷状构象。本研究将通过药物靶向阻断SOCS3的gp130结合位点,从而阻止SOCS3-gp130相互作用。这将允许JAK-STAT信号级联,这对几种生物功能至关重要
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引用次数: 0
Oral Toxicity Studies, Histopathology and Anti-Diabetic activity of Polyherbal Extract in STZ induced diabetes in Rats 中药提取物对STZ诱导的糖尿病大鼠的口服毒性、组织病理学及抗糖尿病活性研究
Pub Date : 2021-12-20 DOI: 10.2174/2211550111666211220165802
P. Wal, Nikita Saraswat, A. Wal, R. Pal, D. Maurya
Diabetes mellitus is a disease and endocrine disorder and it's a growing health problem in various countries. The prevalence of diabetes rises worldwide including South Africa 5.4% in 2025 increases as expected. The World Health Organization (WHO) estimated the diabetes mellitus problem in adults 173 million in developing counties. In this research observation of glucose levels indicated the diabetic state in Wistar rats by resulting from Streptozotocin administration and using a Metformin as a standard dose. This study demonstrated the acute oral toxicity and subacute oral toxicity of ethanolic extract of Saraca asoca leaves and Asparagus racemosus roots and showed the antidiabetic activity. To perform acute toxicity studies and sub-acute toxicity of the polyherbal ethanolic extract on the vital organ and isolated organ and record and noticed the visible changes on organs of each group of Wistar rats. Explore the hypoglycaemic action of the polyherbal extract of Saraca asoca and Asparagus racemosus. Wistar rats were divided into required groups for toxicity study first is acute oral toxicity 5,50, 300,2000 mg/kg body weight. Subacute oral toxicity studies were performed by administering a 250, 500, 1000mg/kg body weight. For demonstrating the antidiabetic activity the animals divided into 5 groups 1 normal control given saline group 2 standard dose Metformin compulsory dose groups 3 Streptozotocin-Induced diabetic 150mg/kg body weight body weight, groups 4 ethanolic extracts at a 100mg/kg groups 5 ethanolic extract 200mg/kg. On the last day of all the dosing period examined the Blood glucose levels and body weights of rat and histopathology studied were done by animal sacrifice and cut organs such as tissue pancreas, spleen, heart, lungs, liver, and kidney, placed on the slide and done a microscopic examination. Data selection has been complete by research papers from many databases such as NCBI, Web of science and Science direct and PubMed from year 1989 to 2020 by utilize research. skeywords such as “Antidiabetic”, “Saraca indica”, “Asparagus racemosus”, “ethanolic polyherbal extract”, “oral toxicity study”, “histopathology”, “Streptozotocin.The polyherbal ethanolic extract of Saraca asoca and Asparagus racemosus at a dose of 100mg/kg and 200mg/kg was showed better effects against Streptozotocin-Induced diabetic 150mg/kg body weight body weight. All the extracts showed significantly (P <0.05) and it is safe and non-toxic nature by performed a toxicity study acute and subacute oral toxicity and the bodyweight are also improved, no inflammation and erosion are seen on any organs of Wistar rat by demonstrated a histopathology analysis.The polyherbal ethanolic extract of Saraca asoca and Asparagus racemosus showed hypoglycaemic activity against STZ-induced diabetes in experimental Wistar rats in Wistar rats. The results are shown beneficial effects of these ethanolic extract it helps in improving the changes in lipid metabo
糖尿病是一种疾病和内分泌紊乱,是各国日益严重的健康问题。包括南非在内的全球糖尿病患病率在2025年如预期增长5.4%。世界卫生组织(WHO)估计,发展中国家有1.73亿成年人患有糖尿病。本研究以二甲双胍为标准剂量,通过观察链脲佐菌素对Wistar大鼠糖尿病状态的影响。本研究证实了荆芥叶和芦笋根乙醇提取物的急性和亚急性口服毒性,并显示出抗糖尿病活性。对各组Wistar大鼠进行重要脏器和离体脏器的急性毒性和亚急性毒性研究,记录并观察各组脏器的可见变化。探讨芦笋和刺尾草提取物的降糖作用。将Wistar大鼠分为急性口服毒性5、50、300、2000 mg/kg体重组进行毒性研究。亚急性口服毒性研究通过给予250、500、1000mg/kg体重进行。为了证明动物的抗糖尿病活性,将动物分为5组:1正常对照组给予生理盐水组2标准剂量二甲双胍强制剂量组3链脲霉素致糖尿病150mg/kg体重组4乙醇提取物100mg/kg组5乙醇提取物200mg/kg。在给药期的最后一天检查大鼠的血糖水平和体重,并采用动物祭祀法,将胰腺、脾脏、心、肺、肝、肾等组织切片置于载玻片上进行显微检查。数据选取利用1989 - 2020年NCBI、Web of science和science direct、PubMed等多个数据库的研究论文完成。关键词:“抗糖尿病”、“印度菝葜”、“总状芦笋”、“乙醇多药提取物”、“口服毒性研究”、“组织病理学”、“链脲佐菌素”。百合藤和总状芦笋乙醇提取物剂量分别为100mg/kg和200mg/kg时,对链脲佐菌素诱导的糖尿病有较好的抑制作用。经毒理研究,各提取物均有显著性差异(P <0.05),具有安全无毒的性质。经组织病理学分析,大鼠的急性和亚急性口服毒性及体重均有所改善,各脏器未见炎症和糜烂。菝葜和总状芦笋乙醇提取物对实验性Wistar大鼠stz诱导的糖尿病有降血糖作用。结果表明,乙醇提取物具有改善脂质代谢变化,保护Wistar大鼠肝、肾、脾、胰、肺、心等器官免受血糖和体重损害的作用。各脏器称重,切取脏器组织,用伊红染色,镜检照片观察变化。没有炎症和腐蚀的迹象。
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Current Biotechnology
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