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Hijacking the epigenetic mechanisms of A. baumannii. 劫持鲍曼不动杆菌的表观遗传机制。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/MBRC.2024.48801.1899
S A Smiline Girija

Epigenetic mechanisms attribute to the resistance and virulence of Acinetobacter baumannii sparking a renewed area of research. Unveiling the targets pertained to the epigenetic modulation in the bacterium would aid in the curbing its complications in various recalcitrant infections. This review thus throws light on the various epigenetic mechanisms exhibited by A. bauamnnii, urging the need to implement epigenetic based novel strategies in precision medicine.

表观遗传学机制是鲍曼不动杆菌产生抗药性和毒性的原因之一,这引发了一个新的研究领域。揭示与鲍曼不动杆菌表观遗传调控有关的靶标将有助于遏制其在各种顽固感染中的并发症。因此,这篇综述揭示了鲍曼不动杆菌表现出的各种表观遗传学机制,敦促人们在精准医疗中实施基于表观遗传学的新策略。
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引用次数: 0
Genome-wide mining and characterization of MATE transporters in Coriandrum sativum L. 芫荽中 MATE 转运体的全基因组挖掘和特征描述
IF 1.5 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/mbrc.2024.49840.1954
Deepu Mathew, Ravisankar Valsalan, M Shijili

Multidrug and Toxic Compound Extrusion (MATE) proteins are responsible for the transport of a wide range of metabolites out of plant cells. This helps to protect the cells from toxins and other harmful compounds. MATE proteins also play a role in plant development, by regulating the transport of hormones and other signalling molecules. They transport a wide variety of substances, including organic acids, plant hormones, flavonoids, alkaloids, terpenes and other secondary metabolites. MATE proteins are thought to play similar roles in Coriander, in addition to stress responses. The MATE genes in the coriander genome have been identified and characterized. Detailed genome homology search and domain identification analysis have identified 91 MATE proteins in the genome assembly of coriander. A phylogenetic analysis of the identified proteins divided them into five major clades. The functions of the transporters in each cluster were predicted based on the clustering pattern of the functionally characterized proteins. The amino acid sequences, exon-intron structures and motif details of all the 91 proteins are identified and described. This is the first work on the MATE transporters in coriander and the results deliver clues for the molecular mechanisms behind the stress responses and secondary metabolite transport in coriander.

多药和有毒化合物挤压(MATE)蛋白负责将多种代谢物从植物细胞中运出。这有助于保护细胞免受毒素和其他有害化合物的侵害。MATE 蛋白还通过调节激素和其他信号分子的运输,在植物发育过程中发挥作用。它们运输的物质种类繁多,包括有机酸、植物激素、类黄酮、生物碱、萜烯和其他次生代谢物。除了应激反应外,MATE 蛋白被认为在芫荽中也起着类似的作用。芫荽基因组中的 MATE 基因已被鉴定和表征。通过详细的基因组同源性搜索和结构域鉴定分析,在芫荽基因组中发现了 91 个 MATE 蛋白。对已鉴定蛋白质的系统进化分析将其分为五大支系。根据功能表征蛋白的聚类模式,预测了每个聚类中转运体的功能。对所有 91 个蛋白质的氨基酸序列、外显子内含子结构和主题细节进行了鉴定和描述。这是首次对芫荽中的 MATE 转运体进行研究,研究结果为芫荽胁迫响应和次生代谢物转运背后的分子机制提供了线索。
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引用次数: 0
The effects of thymidylate synthase 3'UTR genotype on methylation of tumor-specific genes promoter in 22 colorectal cancer patients from southern Iran. 伊朗南部 22 名结直肠癌患者胸苷酸合成酶 3'UTR 基因型对肿瘤特异基因启动子甲基化的影响
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/mbrc.2023.48009.1850
Maryam Niknam, Fakhraddin Naghibalhossaini, Mozhdeh Zamani, Seyed Vahid Hosseini, Pooneh Mokarram

To investigate the effects of thymidylate synthase (TS) 3'UTR genotype on promotor methylation of tumor-related genes in 22 patients with sporadic colorectal cancer (CRC) from southern Iran. We evaluated the correlations of TS 3'UTR genotype with promoter methylation of hTERT, hMLH1, MSH2, MMP2, CDH1, p14, p16, and p21 genes in CRC patients. The polymorphism of TS 3'UTR was evaluated through mutagenically specific PCR. The genes promoter methylation was determined using methylation-specific PCR. For 10 patients, the gene expression profile of epigenetic regulating enzymes, histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), was also examined in both tumor and normal adjacent tissues by quantitative real time PCR. There was a significant association between the hMLH1 methylation and age of patients (P= 0.039) and also between MSH2 methylation and tumor site (P= 0.036). There was insignificant association between gene-specific methylation and TS 3'UTR genotype. However, all polymorphic genotypes of TS were associated with higher methylation of hMLH1 and CDH1 and lower methylation of MSH2. The -6bp/+6bp (heterozygous mutant) and [-6bp/+6bp, +6bp/+6bp] (homozygous mutant) genotypes resulted in higher methylation of p16, and -6bp/+6bp and [-6bp/+6bp, +6bp/+6bp] genotypes were correlated with lower methylation of MMP2. The overexpression of epigenetic enzymes, HDACs and DNMTs, was also demonstrated. There was no association between DNMTs transcript levels and gene-specific hypermethylation. The polymorphic TS genotypes, especially -6bp/+6bp, could affect methylation frequencies of studied genes. Moreover, promoter methylation status was not dependent on DNMTs gene expression. Large sample size studies may contribute to validate these findings.

研究伊朗南部 22 名散发性结直肠癌(CRC)患者胸苷酸合成酶(TS)3'UTR 基因型对肿瘤相关基因启动子甲基化的影响。我们评估了 TS 3'UTR 基因型与 CRC 患者中 hTERT、hMLH1、MSH2、MMP2、CDH1、p14、p16 和 p21 基因启动子甲基化的相关性。通过诱变特异性 PCR 评估了 TS 3'UTR 的多态性。使用甲基化特异性 PCR 测定基因启动子甲基化。还通过实时定量 PCR 检测了 10 例患者肿瘤和邻近正常组织中表观遗传调控酶、组蛋白去乙酰化酶(HDACs)和 DNA 甲基转移酶(DNMTs)的基因表达谱。hMLH1甲基化与患者年龄(P= 0.039)和MSH2甲基化与肿瘤部位(P= 0.036)之间有明显的相关性。基因特异性甲基化与 TS 3'UTR 基因型之间的关系不明显。然而,TS的所有多态基因型都与hMLH1和CDH1的较高甲基化和MSH2的较低甲基化相关。-6bp/+6bp(杂合子突变体)和[-6bp/+6bp, +6bp/+6bp](同源突变体)基因型导致p16的甲基化程度较高,而-6bp/+6bp和[-6bp/+6bp, +6bp/+6bp]基因型与MMP2的甲基化程度较低相关。表观遗传酶、HDACs 和 DNMTs 的过度表达也得到了证实。DNMTs 转录水平与基因特异性高甲基化之间没有关联。多态的TS基因型,尤其是-6bp/+6bp,会影响所研究基因的甲基化频率。此外,启动子甲基化状态与 DNMTs 基因表达无关。大样本量研究可能有助于验证这些发现。
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引用次数: 0
A survey of resistance mutations to reverse transcriptase inhibitors (RTIs) among HIV-1 patients in northeast of Iran. 伊朗东北部 HIV-1 患者对逆转录酶抑制剂 (RTI) 的耐药性突变调查。
IF 1.5 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/mbrc.2024.48729.1895
Zahra Mazaheri, Sahar Tahaghoghi-Hajghorbani, Kazem Baesi, Kiarash Ghazvini, Saeid Amel-Jamehdar, Masoud Youssefi

The use of a combination of three-drug regimen has improved HIV-1 infected patients' life span and quality; however the emergence of drug-resistant strains remains a main problem. Reverse transcriptase inhibitors (RTIs) consist of a main part of highly active anti-retroviral therapy (HAART) regimen. The present study aimed to investigate resistant mutations to RTI drugs in both treatment naïve and under treatment HIV patients in Mashhad city, north-eastern Iran. RNA was extracted from sera of 22 treatment naïve and 22 under treatment patients. The mean age of under treated and treatment naive groups were 38.5±6.7 and 40.8±7.9 respectively. cDNA was synthesized and amplified with Nested PCR assay targeting specific sequences of RT gene. The PCR products were sent for sequencing. Bidirectional sequencing results were analysed using HIV drug resistance database supplied by Stanford University (HIV Drug Resistance Database, https://hivdb.stanford.edu). Among under treatment patients 10 out of 22 (45%) had at least one high-level resistance mutation which was higher than high level resistance mutation rate among treatment naive cases (P<0.01). Detected resistance mutations were as follows: K101E, K103N, K103E, V106M, V108I, E138A, V179T, Y181C, M184V, Y188L, Y188H, Y188F, G190A, L210W, T215F, T215Y, K219Q, and P225H. A high level of resistance mutations to RT inhibitors was observed that causes drug resistance especially against lamivudine (3TC). Such mutations should be considered as probable responsible for therapeutic failure. Serial surveillance studies of circulating drug resistance mutations are recommended.

三药联合疗法的使用改善了 HIV-1 感染者的寿命和质量,但耐药菌株的出现仍是一个主要问题。逆转录酶抑制剂(RTI)是高效抗逆转录病毒疗法(HAART)的主要组成部分。本研究旨在调查伊朗东北部马什哈德市未接受治疗和正在接受治疗的艾滋病患者对 RTI 药物的耐药突变。研究人员从 22 名治疗无望和 22 名治疗不足患者的血清中提取了 RNA。针对 RT 基因的特定序列合成 cDNA 并用巢式 PCR 方法进行扩增。PCR 产物被送去测序。双向测序结果通过斯坦福大学提供的 HIV 耐药性数据库(HIV 耐药性数据库,https://hivdb.stanford.edu)进行分析。在接受治疗的患者中,22 人中有 10 人(45%)至少出现了一种高水平耐药性突变,高于未接受治疗病例的高水平耐药性突变率(P<0.05)。
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引用次数: 0
Using several pseudo amino acid composition types and different machine learning algorithms to classify and predict archaeal phospholipases. 利用几种伪氨基酸组成类型和不同的机器学习算法对古菌磷脂酶进行分类和预测。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.47756.1845
Nour Samman, Hassan Mohabatkar, Parisa Rabiei

Phospholipases, as important lipolytic enzymes, have diverse industrial applications. Regarding the stability of extremophilic archaea's proteins in harsh conditions, analyses of unusual features of their proteins are significantly important for their utilization. This research was accomplished to in silico study of archaeal phospholipases' properties and to develop a pioneering method for distinguishing these enzymes from other archaeal enzymes via machine learning algorithms and Chou's pseudo-amino acid composition concept. The non-redundant sequences of archaeal phospholipases were collected. BioSeq-Analysis sever was used with Support Vector Machine (SVM), Random Forests (RF), Covariance Discrimination (CD), and Optimized Evidence-Theoretic K-nearest Neighbor (OET-KNN) as powerful machine learnings algorithms. Also, different Chou's pseudo-amino acid composition modes were performed and then, 5-fold cross-validation was applied to the sequences. Based on our results, the OET-KNN predictor, with 96% accuracy, yields the best performance in SC-PseAAC mode by 5-fold cross-validation. This predictor also achieved very high values of specificity (95%), sensitivity (96%), Matthews's correlation coefficient (0.92), and accuracy (96%). The present investigation yielded a robust anticipatory model for the archaeal phospholipase prediction utilizing the tenets PseAAC and OET-KNN machine learning algorithm.

磷脂酶是重要的脂溶酶,具有广泛的工业应用。关于极端嗜酸性古菌蛋白质在恶劣条件下的稳定性,分析其蛋白质的异常特征对其利用具有重要意义。本研究完成了对古细菌磷脂酶性质的计算机研究,并通过机器学习算法和Chou的伪氨基酸组成概念开发了一种将这些酶与其他古细菌酶区分开来的开创性方法。收集了古细菌磷脂酶的非冗余序列。BioSeq-Analysis sever采用支持向量机(SVM)、随机森林(RF)、协方差判别(CD)和优化证据理论k近邻(OET-KNN)作为强大的机器学习算法。采用不同的Chou伪氨基酸组成模式,对序列进行5倍交叉验证。基于我们的结果,经5倍交叉验证,OET-KNN预测器在SC-PseAAC模式下表现最佳,准确率为96%。该预测器还具有很高的特异性(95%)、敏感性(96%)、马修斯相关系数(0.92)和准确性(96%)。本研究利用PseAAC和OET-KNN机器学习算法建立了古细菌磷脂酶预测的稳健预测模型。
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引用次数: 0
Comparison of five DNA extraction methods in three medicinal plants: Peganum harmala L., Tamarix ramosissima Ledeb., and Potentilla reptans L. 三种药用植物荆芥、柽柳五种DNA提取方法的比较。和Potentilla reptans L。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.45131.1798
Zahra Salehi, Atefe Amirahmadi, Arezou Rezaei, Parisa Farrokh, Javad Ghasemian

Extracting high-yield, high-quality DNA from plant samples is challenging due to the presence of the cell wall, pigments, and some secondary metabolites. The main CTAB method, two of its modified protocols (beta-mercaptoethanol or ammonium acetate were eliminated), the modified Murray and Thompson method, and the Gene All kit were statistically compared based on the quantity and quality of the total DNA (tDNA) extracted from fresh and dried leaves of three medicinal herbs P. harmala, T. ramosissima, and P. reptans. The suitability of the tDNAs for molecular studies was evaluated by polymerase chain reaction (PCR) of the fragments of the internal transcribed spacer (ITS) in nuclear DNA and the trnL-F region in chloroplast DNA. Some significant differences were found between the tDNAs extracted by five extraction methods. With the exception of P. harmala, where the PCR of both the ITS fragments and the trnL-F region worked successfully in all DNA samples, but only the ITS fragments, not the chloroplast trnL-F region, were amplified in the DNA samples of T. ramosissima and P. reptans. The chloroplast trnL-F region was amplified only in DNA samples extracted from fresh and dried leaves of the three studied herbs using the commercial kit. Gene All kit, the main CTAB method, and its modified protocols were the less time-consuming protocols that yielded DNA suitable for downstream PCR vis-a-vis the modified Murray and Thompson method.

由于细胞壁、色素和一些次生代谢物的存在,从植物样品中提取高产量、高质量的DNA具有挑战性。对主要的CTAB法及其两种改进方案(β -巯基乙醇或乙酸铵)、改进的Murray和Thompson法以及Gene All试剂盒从三种药材的鲜叶和干叶中提取的总DNA (tDNA)的数量和质量进行统计比较。利用核DNA内转录间隔段(ITS)片段和叶绿体DNA trl - f区片段的聚合酶链反应(PCR)对tdna进行分子研究的适宜性评价。五种提取方法提取的tdna存在显著差异。除甘蓝花(P. harmala)的ITS片段和trnL-F区域的PCR在所有DNA样品中都成功扩增外,但在毛毛田鼠(T. ramosissima)和爬行田鼠(P. reptans)的DNA样品中只能扩增ITS片段,而不能扩增叶绿体trnL-F区域。叶绿体trnL-F区域仅在使用商业试剂盒从三种研究草药的新鲜和干燥叶片中提取的DNA样本中扩增。与改进的Murray和Thompson方法相比,主要的CTAB方法Gene All kit及其改进方案是产生适合下游PCR的DNA所需时间较少的方案。
{"title":"Comparison of five DNA extraction methods in three medicinal plants: <i>Peganum harmala</i> L., <i>Tamarix ramosissima</i> Ledeb., and <i>Potentilla reptans</i> L.","authors":"Zahra Salehi,&nbsp;Atefe Amirahmadi,&nbsp;Arezou Rezaei,&nbsp;Parisa Farrokh,&nbsp;Javad Ghasemian","doi":"10.22099/mbrc.2023.45131.1798","DOIUrl":"https://doi.org/10.22099/mbrc.2023.45131.1798","url":null,"abstract":"<p><p>Extracting high-yield, high-quality DNA from plant samples is challenging due to the presence of the cell wall, pigments, and some secondary metabolites. The main CTAB method, two of its modified protocols (beta-mercaptoethanol or ammonium acetate were eliminated), the modified Murray and Thompson method, and the Gene All kit were statistically compared based on the quantity and quality of the total DNA (tDNA) extracted from fresh and dried leaves of three medicinal herbs <i>P. harmala</i>, <i>T. ramosissima</i>, and <i>P. reptans</i>. The suitability of the tDNAs for molecular studies was evaluated by polymerase chain reaction (PCR) of the fragments of the internal transcribed spacer (ITS) in nuclear DNA and the <i>trn</i>L-F region in chloroplast DNA. Some significant differences were found between the tDNAs extracted by five extraction methods. With the exception of <i>P. harmala</i>, where the PCR of both the ITS fragments and the <i>trn</i>L-F region worked successfully in all DNA samples, but only the ITS fragments, not the chloroplast <i>trn</i>L-F region, were amplified in the DNA samples of <i>T. ramosissima</i> and <i>P. reptans</i>. The chloroplast <i>trn</i>L-F region was amplified only in DNA samples extracted from fresh and dried leaves of the three studied herbs using the commercial kit. Gene All kit, the main CTAB method, and its modified protocols were the less time-consuming protocols that yielded DNA suitable for downstream PCR vis-a-vis the modified Murray and Thompson method.</p>","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":"12 1","pages":"1-16"},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10186858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9845450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
A comparison of phylogenetic and distance-based approaches for the distinction of genetically closed species, Draba rimarum (Rech.f.) A.R. Khosravi & A. Eslami-Farouji, and Draba aucheri Boiss. (Brassicaceae) as a case study. 遗传封闭物种Draba rimarum(Rech.f.)A.R.Khosravi和A.Eslami Farouji和Draba aucheri Boiss的系统发育和基于距离的方法的比较。(十字花科)为例研究。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.47706.1842
Atena Eslami-Farouji, Ahmad Reza Khosravi, Mahdi Gholami, Sasan Mohsenzadeh

Circumscribing species boundries is necessary in systematic plant biology. Even a mistake in delimiting taxa may lead to incorrect scientific interpretations. Draba rimarum (Rech.f.) A.R. Khosravi & A. Eslami-Farouji is an endemic Iranian species with a narrow geographic distribution, and is genetically close to D. aucheri. The present study provided a phylogenetic review, time divergence, and planar network of both species to unravel the distinct position of both species along with the prediction of any conflicting or ambiguous signals. Regarding this purpose, here we represent that phylogenetic trees may fail to show reliable results toward the distinct position of genetically close species.

在系统植物生物学中,环绕物种边界是必要的。即使在划分分类群时出现错误,也可能导致不正确的科学解释。Draba rimarum(Rech.f.)A.R.Khosravi和A.Eslami Farouji是一种地理分布狭窄的伊朗特有物种,在基因上与D.aucheri接近。本研究提供了两个物种的系统发育综述、时间差异和平面网络,以揭示两个物种不同的位置,并预测任何冲突或模糊的信号。关于这一目的,我们在这里表示,系统发育树可能无法显示出可靠的结果来确定基因相近物种的独特位置。
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引用次数: 0
Design and construction of a chimeric peptide, MeICT/IMe-AGAP, from two anti-cancer toxins of Iranian Mesobuthus eupeus scorpion. 伊朗Mesobuthus eupeus蝎两种抗癌毒素嵌合肽MeICT/IMe-AGAP的设计与构建
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.46450.1804
Razieh Seifi, Hoda Ayat, Ali Mohammad Ahadi

Scorpion venom contains various toxin peptides with pharmacological and biological properties. Scorpion toxins specifically interact with membrane ion channels which play key roles in progression of cancer. Therefore, scorpion toxins have received special attention for targeting cancer cells. Two new toxins MeICT and IMe-AGAP, isolated from Iranian yellow scorpion, Mesobuthus eupeus, interact specifically with chloride and sodium channels, respectively. Anti-cancer properties of MeICT and IMe-AGAP have been determined before, in addition they show 81 and 93% similarity with two well-known anti-cancer toxins, CTX and AGAP, respectively. The aim of this study was construction of a fusion peptide MeICT/IMe-AGAP to target different ion channels involved in cancer progression. Design and structure of the fusion peptide were investigated by bioinformatics studies. Two fragments encoding MeICT and IMe-AGAP were fused using overlapping primers by SOEing-PCR. MeICT/IMe-AGAP chimeric fragment was cloned into pET32Rh vector, expressed in Escherichia coli host and analyzed by SDS-PAGE. The in silico studies showed that chimeric peptide with GPSPG linker preserved the three-dimensional structure of both peptides and can be functional. Due to the high expression of chloride and sodium channels in various cancer cells, MeICT/IMe-AGAP fusion peptide can be used as an effective agent to target both channels in cancers, simultaneously.

蝎子毒液含有多种具有药理和生物学特性的毒素肽。蝎子毒素与在癌症进展中起关键作用的膜离子通道特异性相互作用。因此,蝎子毒素在靶向癌细胞方面受到了特别的关注。从伊朗黄蝎meobuthus eupeus中分离出两种新毒素MeICT和IMe-AGAP,分别与氯离子和钠离子通道特异性相互作用。MeICT和IMe-AGAP的抗癌特性此前已被确定,它们与两种著名的抗癌毒素CTX和AGAP的相似性分别为81%和93%。本研究的目的是构建MeICT/IMe-AGAP融合肽,以靶向参与癌症进展的不同离子通道。利用生物信息学方法对融合肽的设计和结构进行了研究。利用重叠引物将编码MeICT和time - agap的两个片段进行soing - pcr融合。将MeICT/IMe-AGAP嵌合片段克隆到pET32Rh载体中,在大肠杆菌宿主中表达,并进行SDS-PAGE分析。实验结果表明,含GPSPG连接体的嵌合肽保留了两种肽的三维结构,具有一定的功能性。由于氯离子通道和钠离子通道在多种癌细胞中的高表达,MeICT/IMe-AGAP融合肽可以作为一种有效的药物同时靶向两种通道。
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引用次数: 0
The genetic polymorphisms at the promoter region of HLA-DQB1 gene, creating responsive elements for NF1/CTF and converting the TFII-D binding site to GR-alpha. HLA-DQB1基因启动子区域的遗传多态性,产生NF1/CTF的应答元件,并将TFII-D结合位点转化为gr - α。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.46890.1813
Khyber Saify

Human leukocyte antigen-DQB1 (HLA-DQB1, OMIM: 604305) is the human major histocompatibility complex (MHC) system. HLA genes are classified into three classes (I, II, and III). The HLA-DQB1 belongs to class II, is mainly involved in the actions of the human immune system and plays a fundamental role in donor-recipient matching in transplantation and can be associated with most autoimmune diseases. In this study, the potential influence(s) of the G-71C (rs71542466) and T-80C (rs9274529) genetic polymorphisms were investigated. These polymorphisms, located in the HLA-DQB1 promoter region, have a significant frequency in the world population. The online software ALGGEN-PROMO.v8.3 was used in this work. The results indicate that the C allele at the -71 position actually creates a new potential binding site for NF1/CTF and the C allele at the -80 position changes the TFII-D binding site into a GR-alpha response element. The NF1/CTF plays the role of activator and the GR-alpha is the inhibitor; thus, according to the roles of these transcription factors, it is suggested that the above-mentioned polymorphisms alter the expression levels of HLA-DQB1. Therefore, this genetic variation is associated with autoimmune diseases; however, this cannot be generalized because this is the first report and more studies are needed in the future.

人白细胞抗原- dqb1 (HLA-DQB1, OMIM: 604305)是人主要组织相容性复合体(MHC)系统。HLA基因分为I、II、III三类,其中HLA- dqb1属于II类,主要参与人体免疫系统的活动,在移植供体-受体匹配中起基础作用,与大多数自身免疫性疾病有关。本研究探讨了G-71C (rs71542466)和T-80C (rs9274529)遗传多态性的潜在影响。这些多态性位于HLA-DQB1启动子区域,在世界人群中具有显著的频率。本工作使用在线软件ALGGEN-PROMO.v8.3。结果表明,位于-71位的C等位基因实际上为NF1/CTF创造了一个新的潜在结合位点,而位于-80位的C等位基因将TFII-D结合位点改变为gr - α响应元件。NF1/CTF为活化剂,gr - α为抑制剂;因此,根据这些转录因子的作用,我们认为上述多态性改变了HLA-DQB1的表达水平。因此,这种遗传变异与自身免疫性疾病有关;然而,这并不能一概而论,因为这是第一份报告,未来还需要更多的研究。
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引用次数: 0
Toxicity and autophagy effects of fluorinated cycloplatinated(II) complex bearing dppm ligand on cancer cells in in-vitro culture and in-silico prediction. 含dppm配体的氟化环铂(II)配合物对癌细胞的体外培养和计算机预测的毒性和自噬作用。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.44705.1781
Zahra Kamalzade, Elham Hoveizi, Masood Fereidoonnezhad

Toxicity and autophagy effects of a new complex of platinum II (CPC) were evaluated on HeLa cells cultured on a PCL/gelatin electrospinning scaffold. HeLa cells were treated with CPC on the first, third, and fifth days and the concentration of IC50 was determined. The autophagic and apoptotic effects of CPC were examined by MTT assay, Acridine Orange, Giemsa, DAPI, MDC, real-time PCR, Western blot testing, and molecular docking. The cell viability was obtained on days 1, 3, and 5 as much as 50, 7.28, and 19%, respectively with a concentration of IC50 (100μM) of CPC. The staining results indicated that the treatment of HeLa cells with CPC had antitumor and autophagic effects. Results of RT-PCR showed that the expression of BAX, BAD, P53, and LC3 genes was significantly increased in the sample treated with IC50 concentration compared to the control sample whereas the expression of BCL2, mTOR, and ACT genes in cells was significantly decreased compared to the control group. Also, these results were confirmed by Western blotting. The data indicated the induction of apoptotic death and autophagy in the studied cells. The new compound of CPC has antitumor effects.

研究了新型铂复合物(CPC)对PCL/明胶静电纺丝支架上培养的HeLa细胞的毒性和自噬作用。CPC分别于第1、3、5天作用于HeLa细胞,测定IC50浓度。采用MTT法、吖啶橙法、Giemsa法、DAPI法、MDC法、实时PCR法、Western blot法、分子对接法检测CPC的自噬和凋亡作用。CPC浓度为IC50 (100μM)时,第1天、第3天和第5天细胞存活率分别为50%、7.28%和19%。染色结果表明,CPC对HeLa细胞具有抗肿瘤和自噬作用。RT-PCR结果显示,与对照组相比,IC50浓度处理后的细胞中BAX、BAD、P53和LC3基因的表达量显著增加,而BCL2、mTOR和ACT基因的表达量显著降低。Western blotting也证实了这些结果。结果表明,该药物可诱导细胞凋亡和自噬。该新化合物具有抗肿瘤作用。
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引用次数: 0
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