Human Gene最新文献_第10页

Influence of metformin on the expression of SESTRIN2, Nrf2, and TUG1 genes in the liver tissue of diabetic rats 二甲双胍对糖尿病大鼠肝组织中SESTRIN2、Nrf2、TUG1基因表达的影响

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-01 Epub Date: 2025-06-26 DOI: 10.1016/j.humgen.2025.201434

Roya Zanganeh , Hamed Fanaei , Anis saadatmand , Ali dashtkar , Mohsen Saravani

Background

This study, focusing on the role of metformin in reducing oxidative stress, examined the effects of this drug on the expression of stress-related genes SESTRIN2, Nrf2, and TUG1 in the liver of diabetic rats.

Methods

Animals (n = 30) were divided into four groups: a control group (C), a control group treated with metformin (400 mg/kg/day) (C + M), a diabetic group (D), and a diabetic group treated with metformin (D + M) (400 mg/kg/day). Streptozotocin (STZ) was injected to induce diabetes. Serum levels of fasting blood glucose (FBG), triglycerides (TG), LDL-cholesterol (LDL-C), HDL-cholesterol (HDLC), total cholesterol (TC), and insulin were measured. Gene expression was assessed using the RT-PCR technique.

Results

The expression levels of Nrf2 and SESTRIN2 were decreased in group D compared to groups C and C + M but were not statistically significant (p > 0.05). However, the expression of Nrf2 and SESTRIN2 was increased in group D + M compared to group D, but only for Nrf2 was it significant (p = 0.0164). In addition, the expression of Nrf2 was significantly increased in group D + M compared to group C (p = 0.0299). The expression of TUG1 was increased in group D compared to group C, while the D + M group (1.36 ± 0.43) showed a decrease in TUG1 expression compared to group D (3 ± 1.64), which was not statistically significant. In addition, MET reduced the insulin resistance index, FBG, and lipid profile in the D + M group compared to the D group.

Discussion

Metformin suppresses oxidative stress by activating antioxidant pathways through increasing NRF2 gene expression, thereby improving diabetes and playing a protective role in the liver.

本研究以二甲双胍为研究对象，研究了二甲双胍对糖尿病大鼠肝脏应激相关基因SESTRIN2、Nrf2和TUG1表达的影响。方法30只动物分为4组：对照组(C)、二甲双胍（400 mg/kg/ D）治疗组（C + M）、糖尿病组(D)和糖尿病组（D + M）治疗组（400 mg/kg/ D）。注射链脲佐菌素（STZ）诱导糖尿病。测定空腹血糖（FBG）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDLC）、总胆固醇（TC）、胰岛素水平。采用RT-PCR技术检测基因表达。结果D组Nrf2、SESTRIN2表达水平较C、C + M组降低，但差异无统计学意义(p >；0.05)。D + M组Nrf2和SESTRIN2的表达较D组增加，但只有Nrf2表达显著（p = 0.0164）。与C组相比，D + M组Nrf2的表达显著升高（p = 0.0299）。D组TUG1表达较C组升高，D + M组TUG1表达（1.36±0.43）较D组（3±1.64）降低，差异无统计学意义。此外，与D组相比，MET降低了D + M组的胰岛素抵抗指数、FBG和血脂。讨论二甲双胍通过增加NRF2基因表达激活抗氧化途径抑制氧化应激，从而改善糖尿病，对肝脏起到保护作用。

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引用次数: 0

Investigating molecular aspects of SARS-CoV-2 neurological manifestations, a systems biology approach 从系统生物学角度研究SARS-CoV-2神经学表现的分子方面

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-01 Epub Date: 2025-06-02 DOI: 10.1016/j.humgen.2025.201430

Maryam Mozafar , Seyed Amir Mirmotalebisohi , Ahmad Reza Shahverdi , Hakimeh Zali

Objectives

Amid the COVID-19 pandemic, reported neurological symptoms and potential syndromes such as ischemic stroke, seizure, and encephalitis highlight the neurological impact of SARS-CoV-2. We employed a systems biology approach to analyze omics transcriptional data, exploring the molecular mechanisms underlying neurological complications in COVID-19.

Methods

We retrieved post-mortem brain data of COVID-19 patients from the gene expression omnibus (GEO) dataset and constructed protein-protein interaction (PPI) networks for differentially expressed genes (DEGs) in the brain cortex and choroid plexus. Topologically crucial genes were identified, and MCODE clusters were analyzed for functional enrichment using the STRING database. Genes related to neurological symptoms (headache, seizure, stroke, meningitis, encephalitis) were extracted from the Comparative Toxicogenomics Database (CTD), and their associations with MCODE clusters were assessed via Fisher's exact test. Crucial gene interactions with FDA-approved drugs were also investigated.

Results

We identified a cluster of heat shock protein (HSP) genes (HSP90AA1, HSPA1A, HSPA1B, HSPB1, HSPH1, HSPA5, DNAJB1, FKBP5) significantly correlated with all neurological manifestations. KEGG pathway enrichment showed associations with immune processes, neurodegenerative diseases (Parkinson's, Alzheimer's, Huntington's), virus-related pathways (Influenza A, Epstein-Barr, Measles), and pathways activated in viral infections. FKBP5, a key Hsp90 co-chaperone, interacts most with drugs that affect the nervous system in our drug-gene network.

Conclusions

Shedding light on the molecular mechanisms behind COVID-19 neurological manifestations and possible drugs could pave the way for better managing future neurotrophic viruses.

在COVID-19大流行期间，报告的神经系统症状和潜在综合征，如缺血性卒中、癫痫发作和脑炎，突出了SARS-CoV-2对神经系统的影响。我们采用系统生物学方法分析组学转录数据，探索COVID-19神经系统并发症的分子机制。方法从基因表达综合（GEO）数据集中检索COVID-19患者死后脑数据，构建脑皮层和脉络膜丛差异表达基因（DEGs）的蛋白-蛋白相互作用（PPI）网络。在拓扑结构上鉴定了关键基因，并利用STRING数据库分析了MCODE簇的功能富集。从比较毒物基因组学数据库（CTD）中提取与神经系统症状（头痛、癫痫、中风、脑膜炎、脑炎）相关的基因，并通过Fisher精确检验评估它们与MCODE簇的相关性。关键基因与fda批准的药物的相互作用也进行了调查。结果热休克蛋白（HSP）基因簇（HSP90AA1、HSPA1A、HSPA1B、HSPB1、HSPH1、HSPA5、DNAJB1、FKBP5）与所有神经系统表现均有显著相关性。KEGG通路富集显示与免疫过程、神经退行性疾病（帕金森病、阿尔茨海默病、亨廷顿病）、病毒相关通路（甲型流感、爱普斯坦-巴尔病、麻疹）和病毒感染激活的通路相关。FKBP5是一个关键的Hsp90共同伴侣，在我们的药物基因网络中与影响神经系统的药物相互作用最多。结论揭示COVID-19神经学表现背后的分子机制和可能的药物为更好地管理未来的神经营养病毒铺平了道路。

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引用次数: 0

High-throughput genomic profiling in chronic myelogenous leukemia: How far have we come, and what lies ahead? 慢性骨髓性白血病的高通量基因组分析：我们已经走了多远，未来是什么？

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-01 Epub Date: 2025-05-21 DOI: 10.1016/j.humgen.2025.201425

Laras Pratiwi , Galih Januar Adytia , Henry Sutanto

Chronic Myelogenous Leukemia (CML) is a hematological malignancy characterized by the BCR::ABL1 fusion gene, a hallmark of its pathogenesis. Advances in molecular biology and genomic technologies have significantly enhanced our understanding of CML, with Next-Generation Sequencing (NGS) emerging as a potential transformative tool in the field. This review explores the expanding role of NGS in the diagnosis, prognostic stratification, and treatment monitoring of CML. By enabling comprehensive genomic profiling, NGS facilitates the identification of genetic mutations and clonal evolution, offering insights beyond traditional diagnostic methods. Additionally, the application of NGS in detecting treatment-resistant mutations and monitoring minimal residual disease (MRD) underscores its utility in tailoring precision therapies. However, challenges such as technical complexities, integration into clinical workflows, and cost constraints remain barriers to widespread adoption. This review highlights the clinical implications of NGS in CML management and discusses future directions, including emerging sequencing technologies and potential synergies with advanced analytics. As NGS continues to evolve, its role in shaping personalized medicine and improving patient outcomes in CML is becoming increasingly evident. This review provides a comprehensive overview of these developments while addressing the current limitations and opportunities for future research.

慢性髓性白血病（CML）是一种以BCR::ABL1融合基因为特征的血液系统恶性肿瘤，是其发病机制的一个标志。分子生物学和基因组技术的进步极大地增强了我们对CML的理解，下一代测序（NGS）正在成为该领域潜在的变革工具。这篇综述探讨了NGS在慢性粒细胞白血病的诊断、预后分层和治疗监测中的作用。通过实现全面的基因组分析，NGS促进了基因突变和克隆进化的识别，提供了超越传统诊断方法的见解。此外，NGS在检测耐药突变和监测最小残留病（MRD）方面的应用强调了其在定制精确治疗方面的实用性。然而，诸如技术复杂性、融入临床工作流程和成本限制等挑战仍然是广泛采用的障碍。这篇综述强调了NGS在CML治疗中的临床意义，并讨论了未来的发展方向，包括新兴的测序技术和与高级分析的潜在协同作用。随着NGS的不断发展，它在塑造个性化医疗和改善CML患者预后方面的作用越来越明显。这篇综述提供了这些发展的全面概述，同时解决了当前的局限性和未来研究的机会。

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引用次数: 0

Unravelling colorectal cancer mechanisms: Insights from a regulatory network of ncRNAs, TFs, and mutated genes 解开结直肠癌的机制：从ncrna， tf和突变基因的调控网络的见解

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-01 Epub Date: 2025-06-30 DOI: 10.1016/j.humgen.2025.201447

Pankaj Kumar Tripathi, Chakresh Kumar Jain

Colorectal cancer (CRC) presents a significant challenge due to its complexity and high mortality rates, yet the precise molecular drivers remain elusive. Non-coding RNAs (ncRNAs), known for their roles in various cancers including CRC, are implicated in these intricate mechanisms. This study aimed to elucidate key regulators by constructing a regulatory network integrating CRC patient-mutated genes with transcription factors (TFs) and ncRNAs. Utilizing Onco-DB and COSMIC, we detected overexpressed genes and analyzed their mutational profiles, constructing a curated interactome network. Topological analysis identified the top ten hub genes, with five (CDK1, MYC, TOP2A, CCNA2, BRCA1) implicated in the gene regulatory network (GRN). These genes, characterized by high mutation rates, play pivotal roles in CRC tumour formation via mechanisms like gene amplification, cancer progression, proliferation, and migration. Additionally, potential TFs (SP1, E2F1, ESR1, MYC, E2F3) and miRNAs (hsa-miR-16-5p, hsa-miR-186-5p, hsa-miR-29b-3p) were identified, as a regulatory element. Additionally, the construction of the ceRNA network revealed that the 7 circRNA and 3 lncRNA collectively sponged the same miRNA “hsa-miR-16-5p”, ultimately affecting the expression of targeted mRNA BRCA1 and CDK1. This comprehensive approach sheds light on the molecular mechanisms of regulatory elements underlying CRC development, offering insights for clinical diagnosis and innovative treatment strategies.

结直肠癌（CRC）由于其复杂性和高死亡率而面临重大挑战，但精确的分子驱动因素仍然难以捉摸。非编码rna （ncRNAs）因其在包括CRC在内的各种癌症中的作用而闻名，与这些复杂的机制有关。本研究旨在通过构建整合CRC患者突变基因与转录因子（tf）和ncRNAs的调控网络来阐明关键调控因子。利用Onco-DB和COSMIC，我们检测了过表达基因并分析了它们的突变谱，构建了一个精心策划的相互作用组网络。拓扑分析确定了前10个枢纽基因，其中5个（CDK1、MYC、TOP2A、CCNA2、BRCA1）与基因调控网络（GRN）有关。这些基因以高突变率为特征，通过基因扩增、癌症进展、增殖和迁移等机制在结直肠癌肿瘤形成中发挥关键作用。此外，潜在的tf （SP1, E2F1, ESR1， MYC, E2F3）和mirna （hsa-miR-16-5p, hsa-miR-186-5p, hsa-miR-29b-3p）被鉴定为调控元件。此外，ceRNA网络的构建表明，7个circRNA和3个lncRNA共同海绵相同的miRNA“hsa-miR-16-5p”，最终影响靶向mRNA BRCA1和CDK1的表达。这种全面的方法揭示了CRC发展的分子调控机制，为临床诊断和创新治疗策略提供了见解。

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引用次数: 0

Relationship between the rs1799752 polymorphism of angiotensin-converting enzyme gene and susceptibility to sepsis in Egyptian patients: A single-center prospective study 血管紧张素转换酶基因rs1799752多态性与埃及患者脓毒症易感性的关系：一项单中心前瞻性研究

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-01 Epub Date: 2025-07-11 DOI: 10.1016/j.humgen.2025.201450

Eman Mohamed Abdellatif , Emad Hamdy Hamouda Mohammed , Sally Wassfi Zaki Hammad

Background

Early diagnosis of sepsis is a crucial component in improving disease prognosis and reducing mortality. The interindividual variations in susceptibility to sepsis, and in disease outcome, can be affected by several interacting elements including genetic factors. We aimed to investigate the relation of the angiotensin converting enzyme 1 (ACE1) gene polymorphism rs1799752 with the risk of sepsis in adult patients, and its relation with disease severity and prognosis.

Methods

In this case-control prospective study, we included 65 adult sepsis patients and 65 control subjects. For all study subjects, blood samples were collected for DNA extraction, followed by polymerase chain reaction for ACE1 rs1799752 genotyping. Clinical, laboratory data, and severity scores were recorded. Patients were followed up, and were divided into survivors (n = 40) and non-survivors (n = 25).

Results

DD genotype and D allele were significantly more frequent in sepsis patients than in control group, (p = 0.011, p = 0.022, respectively). Although DD genotype was associated with an increased risk of sepsis in univariate analysis, it was an insignificant risk factor in multivariate analysis (OR 1.455, 95 %CI 0.609–3.476, p = 0.399). SOFA scores and APACHEII scores were significantly higher in patients with DD genotype than other genotypes (p < 0.001). Multivariate regression analysis showed that DD genotype was a significant independent predictor of mortality in the included patients.

Conclusion

The current observations revealed a potential prognostic role of the ACE1 insertion/deletion polymorphism in sepsis, where the DD genotype was significantly associated with greater disease severity and higher mortality rates, in comparison with other genotypes.

背景败血症的早期诊断是改善疾病预后和降低死亡率的重要组成部分。对败血症的易感性和疾病结局的个体间差异可能受到包括遗传因素在内的几个相互作用因素的影响。我们旨在探讨血管紧张素转换酶1 （ACE1）基因多态性rs1799752与成人患者脓毒症风险的关系，以及与疾病严重程度和预后的关系。方法在本病例-对照前瞻性研究中，我们纳入65例成人脓毒症患者和65例对照组。对所有研究对象采集血样进行DNA提取，然后进行聚合酶链反应进行ACE1 rs1799752基因分型。记录临床、实验室数据和严重程度评分。对患者进行随访，将患者分为幸存者（n = 40）和非幸存者（n = 25）。结果脓毒症患者中dd基因型和D等位基因的发生率明显高于对照组（p = 0.011, p = 0.022）。虽然DD基因型在单因素分析中与脓毒症风险增加相关，但在多因素分析中，它是一个不显著的危险因素（OR 1.4555, 95% CI 0.609-3.476, p = 0.399）。DD基因型患者的SOFA评分和APACHEII评分均显著高于其他基因型患者(p <；0.001)。多因素回归分析显示，DD基因型是入选患者死亡率的重要独立预测因子。目前的观察结果揭示了ACE1插入/缺失多态性在脓毒症中的潜在预后作用，与其他基因型相比，DD基因型与更大的疾病严重程度和更高的死亡率显著相关。

{"title":"Relationship between the rs1799752 polymorphism of angiotensin-converting enzyme gene and susceptibility to sepsis in Egyptian patients: A single-center prospective study","authors":"Eman Mohamed Abdellatif , Emad Hamdy Hamouda Mohammed , Sally Wassfi Zaki Hammad","doi":"10.1016/j.humgen.2025.201450","DOIUrl":"10.1016/j.humgen.2025.201450","url":null,"abstract":"<div><h3>Background</h3><div>Early diagnosis of sepsis is a crucial component in improving disease prognosis and reducing mortality. The interindividual variations in susceptibility to sepsis, and in disease outcome, can be affected by several interacting elements including genetic factors. We aimed to investigate the relation of the angiotensin converting enzyme 1 (ACE1) gene polymorphism rs1799752 with the risk of sepsis in adult patients, and its relation with disease severity and prognosis.</div></div><div><h3>Methods</h3><div>In this case-control prospective study, we included 65 adult sepsis patients and 65 control subjects. For all study subjects, blood samples were collected for DNA extraction, followed by polymerase chain reaction for ACE1 rs1799752 genotyping. Clinical, laboratory data, and severity scores were recorded. Patients were followed up, and were divided into survivors (<em>n</em> = 40) and non-survivors (<em>n</em> = 25).</div></div><div><h3>Results</h3><div>DD genotype and D allele were significantly more frequent in sepsis patients than in control group, (<em>p</em> = 0.011, <em>p</em> = 0.022, respectively). Although DD genotype was associated with an increased risk of sepsis in univariate analysis, it was an insignificant risk factor in multivariate analysis (OR 1.455, 95 %CI 0.609–3.476, <em>p</em> = 0.399). SOFA scores and APACHEII scores were significantly higher in patients with DD genotype than other genotypes (<em>p</em> < 0.001). Multivariate regression analysis showed that DD genotype was a significant independent predictor of mortality in the included patients.</div></div><div><h3>Conclusion</h3><div>The current observations revealed a potential prognostic role of the ACE1 insertion/deletion polymorphism in sepsis, where the DD genotype was significantly associated with greater disease severity and higher mortality rates, in comparison with other genotypes.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201450"},"PeriodicalIF":0.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632122","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

Association of mir196a2 and mir146a polymorphisms and colorectal cancer risk: A meta-analysis mir196a2和mir146a多态性与结直肠癌风险的关联：一项荟萃分析

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-01 Epub Date: 2025-07-10 DOI: 10.1016/j.humgen.2025.201448

Zahraa isam jameel , Hanan Ali Kareem , Zahraa Mohammed Yahya , Ahmed Ali Hussein , zahraa abdel Kareem

Non-coding RNAs known as microRNAs (miRNAs) play a role as oncogenes or tumor suppressors. One form of genetic variation in the human genome is single nucleotide polymorphism (SNP) in miRNA regions. The relationships between miRNA SNPs and different types of cancer have been the subject of numerous investigations. This article looks into the link between colorectal cancer (CRC) and specific variations known as mir-196a2 and mir-146a. It does this by reviewing related research studies. To find all the papers that were relevant, we searched the literature in PubMed, Web of Science, and Science Direct. We evaluated the associations using three genetic models, which included a pooled ratio and a 95 % confidence range. In the groups from China, Italy, and Greece, we found a strong connection between the mir-196a2 genetic variation and colorectal cancer (CRC). The odds ratios (OR) for the different models were: for the additive model, it was 1.99, which means there was a significant link; for the dominant model, it was 1.24, which also meant there was a significant link; and for the recessive model, it was 1.09, which also meant there was a significant link. We found that the mir-146a variant greatly lowered the risk of cancer in allele (OR 0.32, 95 % CI 0.30–0.34, p = 0.0001, G vs. C), dominant (OR 0.72, 95 % CI 0.68–0.77), and heterozygous codominant (OR 0.51, 95 % CI 0.49–0.54, p = 0.000, GC vs. CC) genetic models. Stratified studies found that the mir-146a variation significantly reduced the risk of colon cancer. This meta-analysis adds to the growing body of evidence linking the mir-196a2 gene variant to colorectal cancer, particularly in the populations of Greece, Italy, and China. Our results indicate that the C/G polymorphism of miR-146a does not seem to be associated with CRC susceptibility. We need additional case-control studies to back up our findings in the future.

被称为microRNAs （miRNAs）的非编码rna扮演癌基因或肿瘤抑制因子的角色。人类基因组遗传变异的一种形式是miRNA区域的单核苷酸多态性（SNP）。miRNA snp与不同类型癌症之间的关系已经成为许多研究的主题。本文探讨了结直肠癌（CRC）与mir-196a2和mir-146a特异性变异之间的联系。它通过回顾相关研究来做到这一点。为了找到所有相关的论文，我们搜索了PubMed、Web of Science和Science Direct的文献。我们使用三种遗传模型来评估相关性，其中包括合并比率和95%的置信范围。在来自中国、意大利和希腊的人群中，我们发现mir-196a2遗传变异与结直肠癌（CRC）之间存在很强的联系。不同模型的比值比（OR）为：加性模型的比值比为1.99，表明存在显著关联；对于主导模型，它是1.24，这也意味着有显著的联系；对于隐性模型，它是1.09，这也意味着有显著的联系。我们发现mir-146a变体大大降低了等位基因（OR 0.32, 95% CI 0.30-0.34, p = 0.0001, G vs C）、显性（OR 0.72, 95% CI 0.68-0.77）和杂合共显性（OR 0.51, 95% CI 0.49-0.54, p = 0.000, GC vs CC）遗传模型的癌症风险。分层研究发现，mir-146a变异显著降低结肠癌的风险。这项荟萃分析增加了越来越多的证据将mir-196a2基因变异与结直肠癌联系起来，特别是在希腊、意大利和中国的人群中。我们的研究结果表明，miR-146a的C/G多态性似乎与CRC易感性无关。我们需要更多的病例对照研究来支持我们未来的发现。

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引用次数: 0

A study conducted in breast cancer cells found that (valproic acid) inhibits CIP2A/c-MYC/PI3K/Akt/mTOR signaling molecules and PD-L1 一项对乳腺癌细胞的研究发现，丙戊酸可抑制CIP2A/c-MYC/PI3K/Akt/mTOR信号分子和PD-L1

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-01 Epub Date: 2025-06-15 DOI: 10.1016/j.humgen.2025.201437

Elahe Zeinali , Vahid Bagheri , Esmaeil Rostami , Gholamreza Anani Sarab

Resistant cells significantly undermine the efficacy of breast cancer treatment. CIP2A and PD-L1 are among the major therapeutic challenges in breast cancer, as they are key drivers of drug resistance and immune evasion, respectively. Hence, identifying agents—particularly epigenetic drugs—that can suppress these factors by altering gene expression is of great interest. This study aimed to evaluate the molecular mechanisms and effects of valproic acid (VPA), a histone deacetylase inhibitor, on CIP2A and PD-L1 expression in the MCF-7 breast cancer cell line. VPA inhibited MCF-7 cell proliferation in a dose- and time-dependent manner. Treatment with VPA resulted in downregulation of CIP2A and its downstream signaling molecules c-MYC, PI3K, AKT, and mTOR. Moreover, VPA treatment reduced PD-L1 expression in MCF-7 cells. These findings suggest that VPA may offer a novel approach to addressing challenges associated with CIP2A and PD-L1. Therefore, either as a monotherapy or in combination with existing treatments, VPA could represent a promising strategy for enhancing the efficacy of breast cancer therapy.

耐药细胞显著地破坏了乳腺癌治疗的效果。CIP2A和PD-L1是乳腺癌的主要治疗挑战之一，因为它们分别是耐药和免疫逃避的关键驱动因素。因此，寻找能够通过改变基因表达来抑制这些因素的药物，尤其是表观遗传药物，是人们非常感兴趣的。本研究旨在探讨组蛋白去乙酰化酶抑制剂丙戊酸（VPA）对MCF-7乳腺癌细胞系CIP2A和PD-L1表达的影响及其分子机制。VPA抑制MCF-7细胞增殖呈剂量和时间依赖性。VPA处理导致CIP2A及其下游信号分子c-MYC、PI3K、AKT和mTOR下调。此外，VPA处理降低了MCF-7细胞中PD-L1的表达。这些发现表明，VPA可能为解决CIP2A和PD-L1相关的挑战提供了一种新的方法。因此，无论是作为单一疗法还是与现有疗法联合使用，VPA都可能是一种很有前景的提高乳腺癌治疗效果的策略。

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引用次数: 0

Investigation the role of ADRB2 rs1042713 and rs1042714 polymorphisms among COPD patients of West Bengal population, India ADRB2 rs1042713和rs1042714多态性在印度西孟加拉邦COPD患者中的作用研究

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-01 Epub Date: 2025-06-30 DOI: 10.1016/j.humgen.2025.201446

Nasima Sultana , Indranil Ganai , Saheen Sultana , Himani Adhikari , Arghya Laha , Himani Biswas , Saibal Moitra , Sanjoy Podder

Background

Chronic obstructive pulmonary disease (COPD) is a complex lung disease characterized by restricted airflow and breathing problems. β2-adrenergic receptor (β2AR) encoded by β2-adrenergic receptor gene (ADRB2) is a transmembrane receptor protein expressed in the airway smooth muscle cells and found to be associated with COPD in various populations. However, no studies were performed in any Indian population so far.

Objectives

The present study aims to investigate the association between ADRB2 polymorphisms rs1042713 and ras1042714 and COPD focusing on their expression analysis on RNA level in West Bengal population, India.

Methods

Epidemiological details including smoking status of 523 patients and 428 controls between 40 and 80 years of age was recorded in self-prepared questionnaire. Spirometry was performed to assess forced expiratory volume in 1 s/forced vital capacity (FEV₁/FVC), FEV₁ and peak expiratory flow rate. Genotyping was done by Polymerase chain reaction-Restriction fragment length polymorphism. qRT-PCR results were calculated using 2-ΔΔCq method.

Results

Genotype frequencies of rs1042713AA and rs1042714CC genotypes were significantly higher in COPD patients than controls (P = 0.02 and 0.01 respectively). Smoker patients with rs1042713AA and rs1042714CC genotypes had significantly lower FEV₁ (P < 0.0001). A linear inverse relationship was found between smoking duration and both FEV₁ and FEV₁/FVC in smoker patients (P < 0.00001). The ADRB2 mRNA expression was significantly decreased in the 46AA/79CC haplotype (P = 0.04) than 46AA/79GG, 46GG/79CC as compared with wild-type haplotype 46GG/79GG.

Conclusion

The present study is the first to report that ADRB2 polymorphisms (rs1042713 and rs1042714) are associated with COPD susceptibility through mRNA expression analysis among West Bengal population, India.

慢性阻塞性肺疾病（COPD）是一种以气流受限和呼吸问题为特征的复杂肺部疾病。由β2-肾上腺素能受体基因（ADRB2）编码的β2-肾上腺素能受体（β2AR）是一种在气道平滑肌细胞中表达的跨膜受体蛋白，在多种人群中被发现与COPD相关。然而，到目前为止，还没有在任何印度人群中进行过研究。目的探讨ADRB2基因多态性rs1042713和ras1042714与慢性阻塞性肺病的关系，重点分析其在印度西孟加拉邦人群中的RNA水平表达。方法对523例40 ~ 80岁的患者和428例对照者的吸烟状况等流行病学资料进行问卷调查。采用肺活量测定法评估1 s用力呼气量/用力肺活量（FEV1/FVC）、FEV1和呼气峰值流速。采用聚合酶链反应-限制性片段长度多态性进行基因分型。采用2-ΔΔCq方法计算qRT-PCR结果。结果COPD患者rs1042713AA和rs1042714CC基因型频率显著高于对照组（P值分别为0.02和0.01）。rs1042713AA和rs1042714CC基因型吸烟者的FEV1显著降低(P <；0.0001)。吸烟时间与吸烟者FEV1及FEV1/FVC呈线性反比关系(P <；0.00001)。46AA/79CC单倍型与野生型46GG/79GG相比，ADRB2 mRNA的表达量显著降低（P = 0.04）； 46GG/79CC单倍型与野生型46GG/79GG相比显著降低（P = 0.04）。本研究首次通过对印度西孟加拉邦人群的mRNA表达分析报道了ADRB2多态性（rs1042713和rs1042714）与COPD易感性相关。

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引用次数: 0

Genetic and epidemiological features of fibrodysplasia ossificans progressiva in Venezuela 委内瑞拉进行性骨化性纤维发育不良的遗传和流行病学特征

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-01 Epub Date: 2025-04-29 DOI: 10.1016/j.humgen.2025.201412

Irene Paradisi, Gilberto Gómez, Sergio Arias

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disease of connective tissue caused by mutations in the ACVR1 gene, producing the formation of heterotopic bone in soft tissues. The hallmark sign of the disease is the congenital malformations of the great toes in the affected individuals. Heterotopic ossification is triggered by mild physical trauma, leading to progressive disability. Its incidence is approximately 1 patient per 1.4 million people worldwide, without gender, ethnic, or geographic localization predisposition. To date, around 25 different mutations have been described, but the substitution of adenine by guanine at nucleotide c.617 replacing an arginine by histidine at residue 206 (p.R206H) accounts for 97 % of cases with classical FOP. Identification of the pathological alterations in ACVR1 has significant diagnostic and therapeutic implications in the clinical management of FOP. Through molecular analysis of the ACVR1 gene in four unrelated Venezuelan patients, the study aimed to confirm the diagnosis, determine whether in-phase haplotypes differentiated between a de novo event or a common remote gene origin in the country, and aid in the nosography of this rare disease. The findings supported a de novo recurring phenomena by demonstrating that all the patients had the p.R206H mutation but did not share an in-phase haplotype.

进行性骨化纤维发育不良（FOP）是一种罕见的常染色体显性结缔组织疾病，由ACVR1基因突变引起，在软组织中产生异位骨。该疾病的标志是先天性畸形的大脚趾在受影响的个人。异位骨化是由轻微的身体创伤引发的，导致进行性残疾。在世界范围内，其发病率约为每140万人中有1例患者，没有性别、种族或地理定位易感性。到目前为止，已经描述了大约25种不同的突变，但是在核苷酸c.617上腺嘌呤被鸟嘌呤取代，在残基206上精氨酸被组氨酸取代（p.R206H）占经典FOP病例的97%。识别ACVR1的病理改变对FOP的临床治疗具有重要的诊断和治疗意义。通过对4名委内瑞拉无血缘关系患者的ACVR1基因进行分子分析，该研究旨在确认诊断，确定同期单倍型是否区分了该国的新生事件或共同的远程基因起源，并有助于这种罕见疾病的医院诊断。通过证明所有患者都有p.R206H突变，但没有共享同期单倍型，研究结果支持了一种重新出现的现象。

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引用次数: 0

Comprehensive analysis of Slc15a3 and Myo1f gene expression in renal carcinoma: Insights from RNA-seq data and validation via qRT-PCR Slc15a3和Myo1f基因在肾癌中表达的综合分析：来自RNA-seq数据和qRT-PCR验证的见解

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-01 Epub Date: 2025-05-24 DOI: 10.1016/j.humgen.2025.201422

Mahya Nazari , Seyed Abdolhamid Angaji , Behnaz Beikzadeh , Behzad Narouie , Mahdi Mohammadi

Background

Early detection of renal cell carcinoma (RCC) remains a challenge. Identification of novel biomarkers may improve the diagnosis, prognosis, and treatment of RCC. This study aimed to identify potential novel biomarkers for RCC by analyzing gene expression profiles by RNA sequencing (RNA-seq) and validating the results by laboratory tests.

Materials and methods

Data were retrieved from NCBI GEO datasets. After data processing and analysis, two genes with differential expression in RCC were selected: Slc15a3 and Myo1f. Blood samples were then collected from 26 RCC patients and 24 healthy controls. Following the extraction of RNA and the synthesis of cDNA, real-time polymerase chain reaction (PCR) was conducted. The expression of genes was evaluated and analyzed using GraphPad Prism, with a statistical significance threshold of P < 0.05.

Results

In silico analysis and RNA-seq data revealed that Slc15a3 and Myo1f were differentially expressed in RCC. Real-time PCR results showed a significant increase in Myo1f expression in RCC patients (P < 0.05), suggesting its potential as a novel biomarker. However, Slc15a3 did not show significant expression differences between RCC patients and controls (P > 0.05), indicating a limited biomarker potential.

Conclusion

This study suggests that Myo1f maybe a promising biomarker for RCC.

背景肾细胞癌（RCC）的检测仍然是一个挑战。鉴定新的生物标志物可以改善肾细胞癌的诊断、预后和治疗。本研究旨在通过RNA测序（RNA-seq）分析基因表达谱，并通过实验室测试验证结果，寻找潜在的RCC新生物标志物。资料和方法数据来源于NCBI GEO数据集。经过数据处理和分析，我们选择了两个在RCC中有差异表达的基因：Slc15a3和Myo1f。然后收集了26名RCC患者和24名健康对照者的血液样本。提取RNA合成cDNA后，进行实时聚合酶链反应（PCR）。使用GraphPad Prism对基因表达进行评估和分析，P <；0.05.结果硅分析和RNA-seq数据显示，Slc15a3和Myo1f在RCC中存在差异表达。Real-time PCR结果显示，Myo1f在RCC患者中的表达显著升高(P <；0.05)，提示其作为新型生物标志物的潜力。然而，Slc15a3在RCC患者和对照组中表达差异不显著(P >；0.05)，表明生物标志物潜力有限。结论Myo1f可能是一种有前景的RCC生物标志物。

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引用次数: 0