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In-silico structural analysis of Heterocephalus glaber amyloid beta: an anti-Alzheimer's peptide. 褐藻淀粉样蛋白 beta:一种抗老年痴呆症肽的分子内结构分析。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/mbrc.2023.48223.1862
Ali Javanmard, Maryam Azimzadeh-Irani, Ghazal Tafazzoli, Ayla Esmaeilzadeh, Mohammad Shirinpoor-Kharf, Seyyed Mohammad Hasan Haghayeghi

Heterocephalus glaber, known as the Naked mole-rat, has an extraordinary immunity to Alzheimer's disease. The pathological hallmark of Alzheimer's disease is cerebral accumulations of plaques, consisting of self-aggregated amyloid beta peptides. Homo sapiens and H. glaber amyloid beta peptides are different in only one amino acid. Herein, computational structural analyses were carried out to determine whether plaque development in H. glaber is prevented by the replacement of His13 with Arg13 in the amyloid beta peptide. AlphaFold2 was used to predict the structure of the H. glaber amyloid beta peptide. HADDOCK and Hex were used to self-dock the peptides and dock ions on peptides, respectively. Illustrations were made by PyMol and ChimeraX. Using VMD, we calculated the radius of gyration. The phylogenetic analysis was conducted by Mega. The results showed an accurate structure with two alpha helices separated by a short coil for H. glaber. Self-docking of the two amyloid beta peptides demonstrated a globular conformation in the H. glaber dimer, implying the unlikeliness of amyloid beta peptides' self-aggregation to form fibrillar structures. This conformational state resulted in lower electrostatic energy compared to H. sapiens, contributing to H. glaber's lower tendency for fibril and, ultimately, plaque formation. Phylogenetic analysis confirmed that amyloid precursor protein is highly conserved in each taxon of rodentia and primata. This study provides insight into the connection between the structure of H. glaber amyloid beta and its plaque formation properties, showing that the Arg13 in H. glaber leads to fibril instability, and might prevent senile plaque accumulation.

被称为 "裸鼹鼠 "的 Heterocephalus glaber 对阿尔茨海默病具有超乎寻常的免疫力。阿尔茨海默氏症的病理特征是大脑积聚斑块,由自我聚集的淀粉样 beta 肽组成。智人和格拉伯人的β淀粉样肽只有一个氨基酸不同。在此,我们进行了计算结构分析,以确定用 Arg13 取代淀粉样 beta 肽中的 His13 是否能阻止 H. glaber 中斑块的形成。使用 AlphaFold2 预测了草履虫淀粉样 beta 肽的结构。HADDOCK 和 Hex 分别用于肽的自对接和肽上离子的对接。插图由 PyMol 和 ChimeraX 绘制。我们使用 VMD 计算了回旋半径。系统进化分析由 Mega 进行。结果表明,H. glaber 的结构准确,两个α螺旋之间有一个短线圈隔开。两种淀粉样β肽的自我对接表明,H. glaber二聚体中的淀粉样β肽呈球状构象,这意味着淀粉样β肽不可能自我聚集形成纤维状结构。与 H. sapiens 相比,这种构象状态产生的静电能量更低,从而使 H. glaber 更倾向于形成纤维,并最终形成斑块。系统发育分析证实,淀粉样前体蛋白在啮齿类动物和灵长类动物的各个类群中高度保守。这项研究深入探讨了草履虫淀粉样蛋白 beta 的结构与其斑块形成特性之间的联系,表明草履虫中的 Arg13 会导致纤维的不稳定性,并可能阻止老年斑块的积累。
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引用次数: 0
Down-regulation of key regulatory factors in sphingosine-1-phosphate (S1P) pathway in human lung fibroblasts transfected with selected microRNAs. 转染特定 microRNAs 的人肺成纤维细胞中鞘磷脂-1-磷酸(S1P)通路关键调控因子的下调。
IF 1.5 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/mbrc.2024.49810.1951
Abdolamir Allameh, Mostafa Atashbasteh, Esmaeil Mortaz, Bahareh Naeeni, Majid Jafari-Khorchani

Sphingosine 1 phosphate (S1P) is involved in the pathogenesis of asthma by stimulation of the alpha-smooth muscle actin (SMA) expression and remodeling of fibroblasts. This study was designed to determine the effects of selected micro RNAs in regulation of S1P and related metabolic pathways in a human lung fibroblast cell line. The fibroblast cell line (CIRC-HLF, C580) was cultured and transfected with individual viral vectors carrying miR124, mi125b, mi133b or mi130a. After 48 hours, expression level of miRNAs and their target genes, sphingosine kinase 1(SPHK1), sphingosine 1-phosphate lyase 1 (SGPL1), sphingosine 1- phosphate receptor 1 (S1PR1) and sphingosine 1- phosphate receptor 2 (S1PR2) were determined. Expression of miRNA and mRNA determined by reverse transcriptionquantitative polymerase chain reaction (qPCR) showed that the expression level of the miRNAs was significantly higher in human lung fibroblasts following transfection compared to controls (vector backbone without miRNA). The expressions of miRNAs-targeted genes were significantly downregulated in transfected fibroblasts compared to control cells (p<0.05). Data show that miR 124, miR 125b, miR 133b and miR130a by targeting regulatory genes in S1P-pathway can down-regulate key factors such as SPHK1, SGPL1, S1PR1 and S1PR2 genes in lung fibroblasts. The results showed that S1P pathway and key factors are suppressed in lung fibroblasts expressing miR124, miR125b, miR130a or miR133b. It appears that suppression of any of the intermediate factors in S1P by miRNA can affect the regulation of the entire S1P pathway.

磷酸鞘氨醇 1(S1P)通过刺激α-平滑肌肌动蛋白(SMA)的表达和成纤维细胞的重塑参与了哮喘的发病机制。本研究旨在确定所选微 RNA 在调节 S1P 及相关代谢途径方面对人肺成纤维细胞系的影响。培养成纤维细胞系(CIRC-HLF,C580)并用携带 miR124、mi125b、mi133b 或 mi130a 的病毒载体转染。48 小时后,测定 miRNA 及其靶基因鞘磷脂激酶 1(SPHK1)、1-磷酸鞘磷脂裂解酶 1(SGPL1)、1-磷酸鞘磷脂受体 1(S1PR1)和 1-磷酸鞘磷脂受体 2(S1PR2)的表达水平。反转录定量聚合酶链反应(qPCR)测定的 miRNA 和 mRNA 的表达表明,与对照组(不含 miRNA 的载体骨架)相比,转染后 miRNA 在人肺成纤维细胞中的表达水平显著升高。与对照组(不含 miRNA 的载体骨架)相比,转染成纤维细胞中 miRNAs 靶向基因的表达明显下调(p
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引用次数: 0
Examining the expression of low-density lipoprotein receptor (LDLR) and low-density lipoprotein receptor-related protein 6 (LRP6) genes in breast cancer cell lines. 研究乳腺癌细胞系中低密度脂蛋白受体(LDLR)和低密度脂蛋白受体相关蛋白 6(LRP6)基因的表达。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/MBRC.2024.48583.1882
Hamid Behrouj, Mehran Erfani, Pooneh Mokarram

Cholesterol and the Wnt/β-catenin pathway have an effective role in the proliferation, survival, drug resistance, immune exhaustion, and metastasis of all types of cancer cells. Considering the role of LDLR and LRP6 proteins in cholesterol uptake by cells and activation of Wnt/β-catenin pathway, this study aims to examine the gene expression of LDLR and LRP6 in cell lines of breast cancer. Human breast cancer cell lines MCF7, MD468 and SKBR3 were cultured in suitable conditions and after extracting total RNA from them, real-Time PCR was used to measure the levels of gene expression for LDLR and LRP6. Our results showed that the expression of LDLR and LRP6 genes is significantly increased in MCF7 and MD468 cells compared to SKBR3 cells. These results suggest that LRP6 and LDLR can be considered as a therapeutic target in tumors that have a genetic profile similar to MCF7 and MD468 cells.

胆固醇和Wnt/β-catenin通路在各类癌细胞的增殖、存活、耐药、免疫衰竭和转移中发挥着重要作用。考虑到 LDLR 和 LRP6 蛋白在细胞吸收胆固醇和激活 Wnt/β-catenin 通路中的作用,本研究旨在检测 LDLR 和 LRP6 在乳腺癌细胞系中的基因表达。在合适的条件下培养人乳腺癌细胞株 MCF7、MD468 和 SKBR3,提取它们的总 RNA 后,使用 real-Time PCR 检测 LDLR 和 LRP6 的基因表达水平。结果表明,与 SKBR3 细胞相比,MCF7 和 MD468 细胞中 LDLR 和 LRP6 基因的表达量明显增加。这些结果表明,LRP6 和 LDLR 可被视为与 MCF7 和 MD468 细胞遗传特征相似的肿瘤的治疗靶点。
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引用次数: 0
Comparison of Mir122 expression in children with biliary atresia and healthy group. 胆道闭锁儿童与健康组 Mir122 表达的比较
IF 1.5 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/mbrc.2024.49649.1950
Nasrin Motazedian, Negar Azarpira, Kimia Falamarzi, Seyed Mohsen Dehghani, Maryam Ataollahi, Elaheh Esfandiari, Mahintaj Dara, Razieh Toobafard, Mehrab Sayadi, Seyed Ali Shekarforoush, Seyed Hossein Owji, Seyed Ali Malekhosseini

Biliary atresia (BA) is the primary cause of neonatal jaundice with various pathological mechanisms. Many BA patients may experience progressive liver dysfunction and eventually need a liver transplant. Therefore, identifying potential non-invasive biomarkers for BA is crucial. miR-122, the most abundant microRNA in the liver, plays significant roles in different liver diseases. This study aimed to assess miR-122 levels in BA patients. Eighteen patients with biliary atresia were selected at random from the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), along with 18 healthy controls. Blood samples were collected, and biochemical parameters (such as liver function tests) were measured. Quantitative reverse-transcription PCR (RT-PCR) was conducted on serum samples from both the case and control groups to analyze miR-122 levels. The study results indicated that serum miR-122 expression in BA patients was elevated compared to the control group, although it did not reach statistical significance. Additionally, no correlation was found between miR-122 expression and serum levels of liver enzymes or other laboratory findings in BA cases. miR-122 could be a potential target for diagnosing BA; however, further research with a larger population is necessary to determine if miR-122 could serve as a useful biomarker for diagnosing BA.

胆道闭锁(BA)是导致新生儿黄疸的主要原因,其病理机制多种多样。许多胆道闭锁患者会出现进行性肝功能障碍,最终需要进行肝移植。miR-122是肝脏中含量最高的微RNA,在不同的肝脏疾病中发挥着重要作用。本研究旨在评估 BA 患者体内的 miR-122 水平。研究人员从设拉子小儿肝硬化队列研究(SPLCCS)中随机抽取了18名胆道闭锁患者和18名健康对照者。采集血样并测量生化指标(如肝功能检测)。研究人员对病例组和对照组的血清样本进行了定量反转录 PCR(RT-PCR),以分析 miR-122 的水平。研究结果表明,与对照组相比,BA 患者血清中的 miR-122 表达升高,但未达到统计学意义。然而,要确定 miR-122 能否作为诊断 BA 的有用生物标志物,还需要对更多人群进行进一步研究。
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引用次数: 0
In-silico comparison of fungal and bacterial asparaginase enzymes. 真菌和细菌天冬酰胺酶的分子内比较。
IF 1.5 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/mbrc.2024.50123.1981
Negar Tafvizi, Mandana Behbahani, Hassan Mohabatkar

L-asparaginase is a commercial enzyme with a wide variety of applications. Asparaginase is known as an anti-cancer agent that is effective for the treatment of certain lymphomas and leukemias by growth inhibition of human cancer cells. Additionally, asparaginase is used in the food industry in a pretreatment process to decrease the accumulation of carcinogenic acrylamide. In this paper, different aspects of bacterial and fungal asparaginases such as mass, hydrophobicity and hydrophilicity of pseudo amino acid composition (PseAAC), physicochem-ical properties, and structural motifs were studied, and ROC curve statistical analysis was used for the comparison. The results showed that none of the physicochemical properties of fungal and bacterial asparaginase could not be differed, except molecular weight and sequence length. MEME Suite analysis demonstrated that there was a motif that was specific for bacterial asparaginases. However, analysis based on the concept of PseACC indicated a differentiation line between fungal and bacterial asparaginases. In conclusion, although there was not any specific demonstration to separate the bacterial and fungal asparaginases in the case of physicochemical properties, PseAAC analysis can be an appropriate and usable method to differentiate between them.

L- 天冬酰胺酶是一种用途广泛的商用酶。众所周知,天冬酰胺酶是一种抗癌剂,通过抑制人类癌细胞的生长,可有效治疗某些淋巴瘤和白血病。此外,天冬酰胺酶还被用于食品工业的预处理过程,以减少致癌物质丙烯酰胺的积累。本文研究了细菌和真菌天冬酰胺酶的不同方面,如质量、假氨基酸组成(PseAAC)的疏水性和亲水性、理化性质和结构基团,并采用 ROC 曲线统计分析进行比较。结果表明,除分子量和序列长度外,真菌和细菌天冬酰胺酶的理化性质均无差异。MEME Suite 分析表明,细菌天冬酰胺酶有一个特异的主题。不过,基于 PseACC 概念的分析表明,真菌和细菌天冬酰胺酶之间存在着一条分界线。总之,虽然在理化性质方面没有任何具体的证据可以区分细菌和真菌天冬酰胺酶,但 PseAAC 分析可以作为区分它们的一种适当和可用的方法。
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引用次数: 0
Phylogenetic position inferred on SSU rDNA sequence gene and description of a new parasitic cnidarian (Endocnidozoa: Myxobolidae) infecting Markiana nigripinnis (Teleostei: Stevardiinae) from a small marginal lake floodplain, Brazil. 根据 SSU rDNA 序列基因推断其系统发育位置,并描述巴西一个小型边缘湖泊洪泛区感染 Markiana nigripinnis(Teleostei: Stevardiinae)的一种新寄生刺胞动物(Endocnidozoa: Myxobolidae)。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/MBRC.2024.48723.1894
Maria E B P Mota, Patrik D Mathews, Tiago Milanin, Omar Mertins, Fernando Paiva, Carina E Oliveira, Luiz E R Tavares

Herein, a detailed molecular phylogeny analysis was developed to determine the phylogenetic position of a new freshwater histozoic myxosporean cnidarian, Henneguya markiana sp. nov. from the world's largest tropical wetland area, Pantanal, Brazil. The new species is described using an integrative taxonomy approach including morphology, biological traits and molecular data. Phylogenetic analysis inferred by Maximum Likehood method showed the new Henneguya species in a well-supported clade of myxosporean gill parasites of South American characids fishes. In this same clade, the new Henneguya described appeared in a sub-clade clustering with H. lacustris and H. chydadea. Nevertheless, the sequences of the new species and H. lacustris and H. chydadea have a large genetic divergence of 10.4% (148 nucleotides-nt) and 10.5% (147 nt) respectively. To the best of our knowledge, this is the first report of a cnidarian myxosporean species parasitizing a fish from Stevardiinae from South America. In the light of the differences observed from the integrative taxonomy, we are confident that this isolate is a new species of Henneguya, increasing the knowledge of diversity of this enigmatic group of cnidarians.

本文通过详细的分子系统发育分析,确定了来自世界上最大的热带湿地--巴西潘塔纳尔--的一种新的淡水组织胞器动物 Henneguya markiana sp.该新物种的描述采用了综合分类方法,包括形态学、生物学特征和分子数据。通过最大似然法推断的系统进化分析表明,Henneguya 新种属于南美洲颊鱼类肌孢子虫鳃寄生虫中一个支持良好的支系。在同一支系中,新描述的 Henneguya 与 H. lacustris 和 H. chydadea 一起出现在一个亚支系中。然而,新种与 H. lacustris 和 H. chydadea 的序列在遗传学上存在较大差异,分别为 10.4%(148 个核苷酸-nt)和 10.5%(147 个 nt)。据我们所知,这是首次报道南美洲的一种刺胞动物肌孢子虫物种寄生在 Stevardiinae 的鱼类上。根据综合分类法观察到的差异,我们确信该分离物是 Henneguya 的一个新物种,从而增加了对这一神秘的刺胞动物群多样性的了解。
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引用次数: 0
Arginine to glutamine mutation in the substrate binding region impaired the isopentenyl activity of Mycobacterium tuberculosis MiaA. 底物结合区精氨酸到谷氨酰胺的突变损害了结核分枝杆菌 MiaA 的异戊烯基活性。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/mbrc.2023.47247.1825
Smitha Soman, Siya Ram

tRNAs act as adaptors during protein synthesis and are chemically modified post-transcriptionally for their structural stability as well as accuracy of the translation. Hypomodifications of tRNAs are known to cause various human diseases, including cancer. Studies in bacteria and yeasts showed that levels of tRNA modifications vary under different stress conditions, enabling the organism to modulate gene expression for survival. Isopentelylation of the base 37 (i6A37) in the anticodon stem-loop by tRNA isopentenyltransferase (MiaA) is well-conserved modification present in prokaryotes and eukaryotes. i6A37 modification increases both the speed and fidelity of translation. A homozygous p.Arg323Gln mutation in the tRNA binding region of tRNA isopentenyltransferase reduced i6A37 levels in humans, affecting mitochondrial translation and thereby causing neurodevelopmental disorder. In this study, we mutated the Arg residue at the conserved position to Gln in Mycobacterium tuberculosis (M. tb) MiaA and analyzed the i6A modification activity of the enzyme on its target tRNAs. We found that p.Arg274Gln mutant MiaA could not modify the target tRNAs, tRNALeuCAA, tRNAPheGAA, and tRNASerCGA from M. tb, confirming the role of Arg residue in tRNA binding.

tRNA 在蛋白质合成过程中充当适配体,并在转录后进行化学修饰,以保证其结构的稳定性和翻译的准确性。众所周知,tRNA 的过度修饰会导致包括癌症在内的多种人类疾病。对细菌和酵母菌的研究表明,在不同的压力条件下,tRNA 的修饰水平会发生变化,从而使生物体能够调节基因表达以获得生存。通过 tRNA 异戊烯基转移酶(MiaA)对反密码子茎环中的 37 号碱基(i6A37)进行异戊烯化是原核生物和真核生物中保存完好的修饰。在人类中,tRNA 异戊烯基转移酶的 tRNA 结合区的同源 p.Arg323Gln 突变会降低 i6A37 的水平,影响线粒体翻译,从而导致神经发育障碍。在本研究中,我们将结核分枝杆菌(M. tb)MiaA中保守位置的Arg残基突变为Gln,并分析了该酶对其靶tRNA的i6A修饰活性。我们发现,p.Arg274Gln 突变体 MiaA 不能修饰 M. tb 的靶 tRNA tRNALeuCAA、tRNAPheGAA 和 tRNASerCGA,证实了 Arg 残基在 tRNA 结合中的作用。
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引用次数: 0
Evaluation of Beclin1 and mTOR genes and p62 protein expression in breast tumor tissues of Iranian patients. 伊朗患者乳腺肿瘤组织中 Beclin1 和 mTOR 基因及 p62 蛋白表达的评估。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/mbrc.2023.47597.1837
Maryam Adelipour, Mahshid Naghashpour, Mohammad Reza Roshanazadeh, Hadi Chenaneh, Asma Mohammadi, Pegah Pourangi, Seyed Rouhollah Miri, Atefeh Zahedi, Mahmood Haghighatnezhad, Sahar Golabi

Autophagy is a cellular process that plays a major role in the fate of tumor cells. Understanding the role of autophagy in cancer therapy is a major challenge, particularly for breast cancer as the sole top cause of mortality among women. In this study, we evaluated the gene expression of mTOR and Beclin1 and the levels of p62 protein, in breast tumors and compared them to a control condition. To explore the role of autophagy in breast cancer, we acquired tumor biopsies from 41 new cases of breast cancer patients. We extracted total RNA from each biopsy and used real-time PCR to quantify Beclin1 and mTOR-specific RNA expression. In addition, we evaluated the expression of the p62 protein in paraffin-embedded tumor tissue using the immunohistochemistry technique. The data revealed an upregulation of Beclin1 and a downregulation of mTOR in tumor tissues compared to the control condition. The correlation between p62 expression and Beclin1/mTOR showed a negative and positive correlation, respectively, confirming autophagy activation in the tumor tissues. However, there was no correlation between autophagy markers and tumor size, grade and stage. The findings revealed that autophagy activation was found in breast tumor tissues, suggesting that autophagy can be a target for breast cancer therapy.

自噬是一种细胞过程,对肿瘤细胞的命运起着重要作用。了解自噬在癌症治疗中的作用是一项重大挑战,尤其是对于作为女性唯一致死原因的乳腺癌而言。在这项研究中,我们评估了乳腺肿瘤中 mTOR 和 Beclin1 的基因表达以及 p62 蛋白的水平,并与对照组进行了比较。为了探索自噬在乳腺癌中的作用,我们从 41 例新的乳腺癌患者身上获取了肿瘤活检样本。我们从每个活检组织中提取了总 RNA,并使用实时 PCR 对 Beclin1 和 mTOR 特异性 RNA 的表达进行了量化。此外,我们还使用免疫组化技术评估了石蜡包埋肿瘤组织中 p62 蛋白的表达。数据显示,与对照组相比,肿瘤组织中的 Beclin1 上调,而 mTOR 下调。p62的表达与Beclin1/mTOR的表达分别呈负相关和正相关,证实了肿瘤组织中自噬的激活。然而,自噬标记物与肿瘤大小、分级和分期没有相关性。研究结果表明,乳腺肿瘤组织中存在自噬激活现象,这表明自噬可作为乳腺癌治疗的靶点。
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引用次数: 0
The importance of examining the Hardy-Weinberg Equilibrium in genetic association studies. 在遗传关联研究中检查哈代-温伯格平衡的重要性。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/mbrc.2023.48386.1872
Mostafa Saadat
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引用次数: 0
A comprehensive in silico analysis of mutation spectrum of maple syrup urine disease (MSUD) genes in Iranian population. 伊朗人群中枫糖尿病(MSUD)基因突变谱的全面硅学分析。
IF 1.5 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.22099/mbrc.2024.49847.1958
Nahid Rezaie, Saeedeh Sadat Ghazanfari, Teymoor Khosravi, Fatemeh Vaghefi, Morteza Oladnabi

Maple syrup urine disease (MSUD) represents an infrequent metabolic disease precipitated by an insufficiency of the enzymatic complex known as branched-chain alpha-keto acid dehydrogenase. MSUD can be classified as classic (severe), intermediate, or intermittent based on the severity of the condition. The disease is associated with mutations in several genes, including BCKDHA, BCKDHB, DBT, and DLD. This study aimed to investigate the genetic landscape of MSUD in Iranian patients and explore the clinical implications of identified gene variants. A comprehensive analysis was conducted using various molecular techniques and bioinformatics tools to predict protein stability, pathogenicity, amino acid conservation, and secondary/tertiary structure. The in silico analysis highlighted high-risk pathogenic variants and provided insights into their potential impact on protein structure and function. Furthermore, the predicted 3D structures of wild-type and mutant proteins elucidated structural differences. Protein-protein interaction analysis shed light on the network of interactions involving MSUD-related proteins. The Iranome database uncovered a potential pathogenic variant (c.554C>T) in the Persian population. This research contributes to a better understanding of MSUD genetics in the Iranian population and outlines potential avenues for further clinical investigations. The findings have implications for genetic testing, prognosis, and genetic counseling in affected families.

枫糖浆尿病(MSUD)是一种不常见的代谢性疾病,由支链α-酮酸脱氢酶不足引起。根据病情的严重程度,枫糖尿症可分为典型(重度)、中度和间歇性三种。该病与多个基因的突变有关,包括 BCKDHA、BCKDHB、DBT 和 DLD。本研究旨在调查伊朗患者 MSUD 的遗传情况,并探讨已识别基因变异的临床意义。研究人员利用各种分子技术和生物信息学工具进行了全面分析,以预测蛋白质的稳定性、致病性、氨基酸保存和二级/三级结构。硅学分析突出了高风险致病变体,并深入了解了它们对蛋白质结构和功能的潜在影响。此外,野生型和突变型蛋白质的预测三维结构阐明了结构上的差异。蛋白-蛋白相互作用分析揭示了涉及 MSUD 相关蛋白的相互作用网络。伊朗基因组数据库发现了波斯人群中一个潜在的致病变体(c.554C>T)。这项研究有助于更好地了解伊朗人群中的 MSUD 遗传学,并为进一步的临床研究勾勒出潜在的途径。研究结果对受影响家庭的基因检测、预后和遗传咨询具有重要意义。
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引用次数: 0
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