Gene Reports最新文献_第9页

Exome sequencing reveals a novel de novo ARHGAP31 frameshift variant in a neurodevelopmental disorder: Structural and functional insights into RhoGAP domain loss 外显子组测序揭示了神经发育障碍中新的ARHGAP31移码变体：RhoGAP结构域丢失的结构和功能见解

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-09-29 DOI: 10.1016/j.genrep.2025.102345

Jalal Gharesouran , Mohammad Reza Asadi , Samira Behroozi , Maryam Rezazadeh , Soudeh Ghafouri-Fard

ARHGAP31 is a GTPase activating protein that inactivates Rac1 and Cdc42 by promoting their conversion from the GTP to GDP bound state. Pathologic variants in ARHGAP31 are primarily associated with Adams-Oliver syndrome (AOS), a congenital disorder characterized by aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLDs), attributed to disrupted Rho GTPase signaling. In this study, exome sequencing and bioinformatic analysis were employed to investigate a 6-year-old male presenting with craniofacial anomalies (high palate, dental malalignment), developmental delay (motor and speech), and gastrointestinal dysmotility (feeding difficulties, constipation) notably without ACC or TTLDs. Trio exome sequencing revealed a heterozygous de novo frameshift variant in ARHGAP31 (NM_020754.4:c.732del, p.(Met245Ter)), absent from population databases (gnomAD, dbSNP) and both parental genomes. In silico predictions (MutationTaster, SWISS-MODEL) suggested a pathogenic effect (probability: 0.99), with nonsense-mediated decay (NMD) and truncation of the RhoGAP domain critical for cytoskeletal regulation. The variant's proximal truncation site likely disrupts autoinhibitory regulation, enhancing RhoGAP activity and impairing Cdc42/Rac1 signaling. Despite parental consanguinity, the de novo variant highlights the diagnostic value of trio sequencing in consanguineous families. Moreover, until now only gain-of-function mutation of ARHGAP31 was found to be associated with AOS, while this article reports a brand-new loss-of-function mutation. Overall, these findings support the existence of a novel ARHGAP31-related neurodevelopmental disorder distinct from AOS, expanding the allelic and phenotypic spectrum associated with this gene.

ARHGAP31是一种GTPase激活蛋白，通过促进Rac1和Cdc42从GTP转化为GDP结合状态来灭活它们。ARHGAP31的病理变异主要与亚当斯-奥利弗综合征（AOS）有关，这是一种先天性疾病，其特征是先天性皮肤发育不全（ACC）和终末横肢缺陷（ttld），归因于Rho GTPase信号传导中断。在这项研究中，外显子组测序和生物信息学分析研究了一名6岁的男性，其表现为颅面异常（高腭，牙齿错位），发育迟缓（运动和语言）和胃肠运动障碍（进食困难，便秘），特别是没有ACC或ttld。三外显子组测序结果显示，ARHGAP31 （NM_020754.4:c）中存在一个杂合的从头移码变异。732del, p.(Met245Ter)))，在种群数据库（gnomAD, dbSNP）和亲本基因组中缺失。计算机预测（MutationTaster, SWISS-MODEL）显示了致病作用（概率：0.99），无义介导的衰变（NMD）和RhoGAP结构域的截断对细胞骨架调节至关重要。该变体的近端截断位点可能会破坏自身抑制调节，增强RhoGAP活性并损害Cdc42/Rac1信号。尽管父母有血缘关系，但新生变异突出了三组测序在近亲家庭中的诊断价值。此外，迄今为止只发现了ARHGAP31的功能获得突变与AOS相关，而本文报道了一个全新的功能丧失突变。总的来说，这些发现支持存在一种不同于AOS的新型arhgap31相关神经发育障碍，扩大了与该基因相关的等位基因和表型谱。

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引用次数: 0

Prevalence and molecular characterization of carbapenem-resistant Pseudomonas aeruginosa and emergence of blaNDM gene 耐碳青霉烯铜绿假单胞菌的流行、分子特征及blaNDM基因的出现

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-09-26 DOI: 10.1016/j.genrep.2025.102346

Samira Ahmadi Asli , Shabnam Golbouy Daghdari , Farzin Asghari-Sana , Mohammad Sarkheili

Pseudomonas aeruginosa is a major cause of hospital-acquired infections, with increasing multidrug resistance. This study aimed to evaluate antimicrobial resistance patterns, assess phenotypic metallo-β-lactamase (MBL) detection, and investigate key resistance genes (bla_NDM, bla_IMP, bla_VIM, and bla_OXA-10) in clinical isolates. A total of 472 clinical samples were collected from three major hospitals in Urmia, Iran, resulting in the identification of 81 confirmed P. aeruginosa isolates. Antimicrobial susceptibility was tested using the disk diffusion method, and MBL production was assessed through four phenotypic tests (CDT-IPM, DDST-IPM, CDT-CAZ, and DDST-CAZ). Resistance genes were confirmed using both uniplex and multiplex PCR. The highest resistance was observed against cefoxitin (93.8 %) and meropenem (60.0 %), while colistin and amikacin remained the most effective agents. Among the phenotypic tests, DDST-IPM demonstrated the highest sensitivity (100 %), but showed limited specificity (57 %). CDT-IPM showed comparable specificity. In contrast, CDT-CAZ and DDST-CAZ exhibited lower specificity and variable sensitivity. PCR results showed that bla_OXA-10 was present in 85.7 % of carbapenem-resistant isolates, followed by bla_VIM (73.5 %), bla_IMP (53.0 %), and bla_NDM (38.8 %). The detection of colistin-resistant strains and the co-occurrence of multiple MBL genes raise concerns about treatment limitations and highlight the need for better diagnostics and resistance monitoring.

铜绿假单胞菌是医院获得性感染的主要原因，具有越来越多的耐多药性。本研究旨在评估临床分离菌株的耐药模式，评估表型金属β-内酰胺酶（MBL）检测，并研究关键耐药基因（blaNDM、blaIMP、blaVIM和blaOXA-10）。从伊朗乌尔米娅的三家大医院共收集了472份临床样本，鉴定出81株铜绿假单胞菌确诊菌株。采用纸片扩散法检测抗菌药物敏感性，通过CDT-IPM、DDST-IPM、CDT-CAZ和DDST-CAZ四种表型试验评估MBL的产生。采用单链和多重PCR鉴定耐药基因。头孢西丁（93.8%）和美罗培南（60.0%）的耐药率最高，粘菌素和阿米卡星的耐药率最高。在表型试验中，DDST-IPM表现出最高的敏感性（100%），但特异性有限（57%）。CDT-IPM表现出可比的特异性。相比之下，CDT-CAZ和DDST-CAZ表现出较低的特异性和可变敏感性。PCR结果显示，85.7%的碳青霉烯类耐药菌株中存在blaOXA-10，其次是blaVIM（73.5%）、blaIMP（53.0%）和blaNDM（38.8%）。对粘菌素耐药菌株的检测和多个MBL基因的共存引起了对治疗局限性的关注，并突出了更好的诊断和耐药性监测的必要性。

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引用次数: 0

A hypothetical link between FAHD1 and mitochondrial resilience? FAHD1和线粒体弹性之间的假设联系？

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-09-24 DOI: 10.1016/j.genrep.2025.102343

Konstantin A. Wilhelmy , Yana Rytchenko , Alexander K.H. Weiss

The mitochondrial enzyme FAHD1 may influence acetyl-CoA metabolism under certain conditions, although physiological relevance remains to be determined. This study explores the potential association between a naturally occurring FAHD1 variant with altered catalytic properties, that is statistically expressed in some long-lived species. Through comparative gene expression and metabolic pathway analyses in kidney, liver, and brain tissues, we examine whether this FAHD1 variant is associated with mitochondrial gene expression patterns indicative of metabolic adaptation. However, our conclusions remain exploratory and hypothesis-generating rather than definitive. The variant's altered catalytic properties might affect acetyl-CoA-related pathways, potentially influencing mitochondrial energy balance and biosynthesis, though in vivo physiological consequences remain unconfirmed. Given the exclusively transcriptomic nature of the data, no causal inferences can be drawn; the findings are exploratory and intended to generate hypotheses for future validation.

线粒体酶FAHD1可能在某些条件下影响乙酰辅酶a代谢，尽管生理相关性仍有待确定。本研究探讨了自然发生的FAHD1变异与催化特性改变之间的潜在关联，这在一些长寿物种中有统计学表达。通过比较肾脏、肝脏和脑组织的基因表达和代谢途径分析，我们研究了FAHD1变异是否与指示代谢适应的线粒体基因表达模式相关。然而，我们的结论仍然是探索性的和假设生成的，而不是决定性的。该变体催化特性的改变可能会影响乙酰辅酶a相关途径，潜在地影响线粒体能量平衡和生物合成，尽管体内生理后果尚未得到证实。考虑到数据的转录组学性质，无法得出因果推论；这些发现是探索性的，旨在为未来的验证产生假设。

引用次数: 0

Association of CDH1 gene variant C > A (rs16260) with expression and treatment outcomes in cervical cancer patients receiving chemoradiotherapy CDH1基因变异C > A （rs16260）与宫颈癌放化疗患者的表达和治疗结果的关系

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-09-19 DOI: 10.1016/j.genrep.2025.102344

Shireen Masood , Atar Singh Kushwah , Kirti Srivastava , Monisha Banerjee

Background

The CDH1 gene promoter variant C > A (rs16260) is associated with downregulation of E-cadherin, which compromises epithelial integrity and has been linked to poor prognosis in various cancers. This study investigates the association of the CDH1 C > A variant with gene expression and its potential as a prognostic biomarker for cervical cancer in an Indian population.

Methods

This case-control study involved 107 cervical cancer patients and 96 age-matched healthy controls. Genotyping of the CDH1 C > A (rs16260) variant was performed using PCR-RFLP, and gene expression was analyzed through qPCR. Kaplan-Meier and Cox regression analyses were used to correlate genotypes and gene expression with treatment response and survival outcomes. Statistical analysis was conducted using QUANTO (v.1.2), GraphPad Prism (v. 10), SPSS (v. 25).

Results

The CA and CA + AA genotypes of the CDH1 variant were significantly associated with cervical cancer risk (P = 0.011 and P = 0.004, respectively). CDH1 gene expression was significantly downregulated in cervical cancer patients compared to controls (P = 0.023). While the CA genotype was protective against recurrence and treatment toxicity (P < 0.001 and P = 0.050, respectively), the CC genotype was linked to increased toxicity and recurrence. CA genotype shows a trend toward better overall survival (median 27 vs. 19 months; HR < 1), though not statistically significant (P = 0.079).

Conclusion

The CDH1 C > A (rs16260) variant may be a prognostic biomarker to predict toxicity and recurrence of cervical cancer, with implications for personalized treatment strategies. However, further studies in larger, more diverse cohorts are necessary to validate these findings.

CDH1基因启动子变异C >； A （rs16260）与e -钙粘蛋白下调有关，e -钙粘蛋白会损害上皮完整性，并与各种癌症的不良预后有关。本研究探讨了印度人群中cdh1c >； A变异与基因表达的关系及其作为宫颈癌预后生物标志物的潜力。方法对107例宫颈癌患者和96例年龄匹配的健康对照者进行病例对照研究。采用PCR-RFLP对CDH1 C >； A （rs16260）变异进行基因分型，并通过qPCR分析基因表达。Kaplan-Meier和Cox回归分析将基因型和基因表达与治疗反应和生存结果相关联。采用QUANTO （v.1.2）、GraphPad Prism （v. 10）、SPSS （v. 25）进行统计分析。结果CDH1变异的CA和CA + AA基因型与宫颈癌发病风险有显著相关性（P = 0.011和P = 0.004）。宫颈癌患者与对照组相比，CDH1基因表达明显下调（P = 0.023）。虽然CA基因型对复发和治疗毒性具有保护作用（P <； 0.001和P = 0.050分别），但CC基因型与毒性和复发增加有关。CA基因型患者的总生存期有提高的趋势（中位27个月vs. 19个月；HR < 1），但无统计学意义（P = 0.079）。结论cdh1c >； A （rs16260）变异可能是预测宫颈癌毒性和复发的预后生物标志物，对个性化治疗策略具有指导意义。然而，需要在更大、更多样化的人群中进行进一步的研究来验证这些发现。

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引用次数: 0

Phylogenetic structure and paternal migration history of Sichuan Bouyei people revealed by Y-chromosomal STRs 四川布依族y染色体STRs揭示的系统发育结构与父系迁移史

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-09-18 DOI: 10.1016/j.genrep.2025.102342

Guang-Yao Fan , En-Na Wang , Jia-Xin Han , Xin-Ying Yu , An-Ying Zheng , Ying Zhu

This study investigates the phylogenetic structure and demographic history of the Sichuan Bouyei people. Genetic profiles of 37 Y-chromosomal short tandem repeat (STR) loci among 425 Bouyei males from eight regions in Sichuan Province were analyzed. Along with published datasets, multidimensional scaling plots, principal component analysis, and phylogenetic reconstruction were conducted on both an Asia-wide and national scale. Genetic stratification in the studied populations was influenced by linguistic and geographic distribution patterns. Significant genetic differentiation was observed between two predominant Bouyei groups from the counties of Ningnan and Muli. Machine learning-based category prediction was performed among contemporary Bouyei and non-Bouyei individuals using the Linear Discriminant Analysis (LDA) method. The results of the LDA indicated a deep fusion between Tai-Kadai-speaking and Hmong-Mien-speaking populations. The timing of population differentiations was estimated using BATWING. Furthermore, the migration rate between the Sichuan Bouyei and other populations was inferred using coalescence theory in the Migrate-n program. The migration models and directions were evaluated, revealing gene flow of Bouyei people from the Sichuan Muli to Vietnam. The data presented here for the Sichuan Bouyei people will be useful in establishing a more comprehensive Y-STR database, and enrich our understanding of the patrilineal history of Tai-Kadai-speaking peoples in China.

研究了四川布依族的系统发育结构和人口历史。对四川8个地区425名布依族男性的37个y染色体短串联重复序列（STR）位点进行了遗传分析。利用已发表的数据集，在亚洲和全国范围内进行了多维标度图、主成分分析和系统发育重建。研究群体的遗传分层受语言和地理分布模式的影响。来自宁南县和木里县的布依族两个优势类群之间存在显著的遗传分化。使用线性判别分析（LDA）方法对当代布依族和非布依族个体进行基于机器学习的类别预测。LDA的结果表明，台加泰语和苗语人口之间存在深度融合。利用BATWING估计种群分化的时间。此外，利用迁移-n程序中的聚结理论推断四川布依族与其他种群之间的迁移速率。对布依族的迁移模式和迁移方向进行了评价，揭示了布依族从四川木里向越南的基因流动。本文所提供的四川布依族的数据将有助于建立一个更全面的Y-STR数据库，并丰富我们对中国台加泰族父系历史的认识。

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引用次数: 0

Antimicrobial resistance and bioactive metabolites of Serratia marcescens CAB03 from a Palk Bay coral reef 柏克湾珊瑚礁粘质沙雷菌CAB03的耐药性和生物活性代谢物

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-09-18 DOI: 10.1016/j.genrep.2025.102339

S. Hari Krishna Kumar , Ragothaman Prathiviraj , Muregesan Sobanaa , George Seghal Kiran , Joseph Selvin

Antimicrobial-resistant pathogens are poorly understood and pose emerging threats to coral reef ecosystems. Coral-associated microbial diversity is crucial for reef resilience; however, there is a limited understanding of opportunistic pathogens from Indian reefs. Here, we report the identification of Serratia marcescens CAB03, which may be associated with coral disease, isolated from Acropora cythera of Palk Bay coral reef, India. Whole genome sequencing of S. marcescens CAB03 produced 24 contigs (total G + C 59.7 %) and 4713 predicted genes. Identification of functional annotation revealed 17 antimicrobial resistance (AMR) genes, including three copies of the adeF gene, which encapsulates a resistance-nodulation-division (RND) efflux system that provides resistance to tetracyclines and fluoroquinolones. At the same time, related genes were also associated with resistance to β-lactams, aminoglycosides, macrolides, glycopeptides, and disinfectants, suggesting that this strain may have multidrug resistance potential. Further secondary metabolite prediction revealed biosynthetic gene clusters for ririwpeptide, a cyclic lipopetide with membrane-disrupting antibacterial and anticancer activity, and prodigiosin, which has gained notoriety for its antimicrobial, anticancer, and immunosuppressant activities as a red-colored pigment. Genome-based evidence clearly indicates that S. marcescens CAB03 is a contributor to coral health degradation through the proliferation of AMR bacteria and also a potential repository of bioactive compounds for pharmaceutical purposes. We used whole-genome sequencing here to address a long-standing knowledge gap regarding AMR bacteria associated with coral from Indian reefs. This study illustrates the need for genomic surveillance and conservation for AMR bacteria, ideally and more generally advances the study of microbial metabolites for drug discovery. Linking pathogen genomic profiles to reef health and advances in applied biotechnology reveal new reasons for coral reef conservation and provide new sources of data for potential drug development.

人们对耐抗生素病原体了解甚少，并对珊瑚礁生态系统构成新威胁。与珊瑚相关的微生物多样性对珊瑚礁的恢复力至关重要；然而，人们对来自印度珊瑚礁的机会性病原体的了解有限。本文报道了从印度Palk Bay珊瑚礁的Acropora cythera中分离到的可能与珊瑚病有关的粘质沙雷氏菌CAB03。S. marcescens CAB03全基因组测序得到24个contigs（总G + C 59.7%）和4713个预测基因。功能注释鉴定揭示了17个抗微生物药物耐药性（AMR）基因，其中包括3个拷贝的adeF基因，该基因封装了一个耐药-结核-分裂（RND）外排系统，提供对四环素和氟喹诺酮类药物的耐药性。同时，相关基因还与β-内酰胺类、氨基糖苷类、大环内酯类、糖肽类和消毒剂耐药有关，提示该菌株可能具有多药耐药潜力。进一步的次生代谢物预测揭示了ririwpeptide（一种具有破坏膜的抗菌和抗癌活性的环状脂肽）和prodigiosin（作为一种红色色素，因其抗菌、抗癌和免疫抑制活性而闻名）的生物合成基因簇。基于基因组的证据清楚地表明，S. marcescens CAB03是通过AMR细菌的增殖导致珊瑚健康退化的一个贡献者，也是用于制药目的的生物活性化合物的潜在储存库。我们在这里使用全基因组测序来解决长期以来关于与印度珊瑚礁珊瑚相关的AMR细菌的知识差距。这项研究说明了AMR细菌基因组监测和保护的必要性，理想地和更广泛地推进了药物发现的微生物代谢物研究。将病原体基因组图谱与珊瑚礁健康和应用生物技术的进展联系起来，揭示了保护珊瑚礁的新理由，并为潜在的药物开发提供了新的数据来源。

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引用次数: 0

Comparative temporal transcriptome analysis identifies genes involved in gonadal differentiation and development in Pacific abalone 比较时间转录组分析确定了太平洋鲍鱼性腺分化和发育相关的基因

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-09-13 DOI: 10.1016/j.genrep.2025.102334

Yuanyuan Huang , Xiaobin Ye , Chaonan Tang , Xuan Luo , Weiwei You , Caihuan Ke , Mingyi Cai

The mechanisms governing sex determination and gonadal differentiation in mollusks remain largely unresolved. To characterize transcriptional regulation during early gonadal development in Haliotis discus hannai, a temporal transcriptomic analysis was conducted across six developmental stages. The results revealed a two-phase differentiation model. In Phase I (240–270 days post-fertilization), male and female gonads exhibited highly similar expression profiles, with few sex-biased genes. In Phase II (284 dpf to 24-month-old), a marked increase in sex-biased gene expression was observed, coinciding with functional divergence of gonads. Across all stages, 75 consistently sex-biased genes were identified, including evolutionarily conserved regulators such as Dmrt1, Foxl2, and Sohlh2, supporting their central roles in testicular and ovarian development. Co-expression network analysis uncovered distinct sex-associated gene modules: female-enriched modules featured Foxl2 and oocyte-related genes, while male-associated modules included Dmrt1 and spermatogenesis regulators. Additionally, sex-biased expression of genes involved in circadian rhythm and phototransduction suggests environmental cues may influence gonadal development. Together, these findings establish a dynamic regulatory framework for sex differentiation in abalone, integrating conserved genetic factors with environmentally responsive pathways. This work provides important insights into molluscan reproductive biology and lays a foundation for future applications in sex control and aquaculture breeding.

软体动物性别决定和性腺分化的机制仍未完全阐明。为了描述在早期生殖腺发育中的转录调控，在六个发育阶段进行了时间转录组学分析。结果揭示了一个两相分化模型。在第一阶段（受精后240-270天），雄性和雌性性腺表现出高度相似的表达谱，很少有性别偏向基因。在II期（284 dpf至24月龄），观察到性别偏倚基因表达显著增加，与性腺功能分化相一致。在所有阶段，鉴定出75个持续的性别偏向基因，包括进化上保守的调节因子，如Dmrt1、Foxl2和Sohlh2，支持它们在睾丸和卵巢发育中的核心作用。共表达网络分析揭示了不同的性别相关基因模块：女性富集模块包括Foxl2和卵母细胞相关基因，而男性相关模块包括Dmrt1和精子发生调节因子。此外，参与昼夜节律和光转导的基因的性别偏倚表达表明，环境因素可能影响性腺发育。总之，这些发现建立了鲍鱼性别分化的动态调控框架，将保守的遗传因素与环境响应途径相结合。本研究为软体动物生殖生物学的研究提供了重要的见解，为今后软体动物在性别控制和水产养殖中的应用奠定了基础。

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引用次数: 0

Exploring the influences on rheumatoid arthritis progression: A comprehensive review of autoimmunity and cellular mechanisms 探索对类风湿关节炎进展的影响：自身免疫和细胞机制的综合综述

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-09-12 DOI: 10.1016/j.genrep.2025.102337

Prachi Agnihotri , Mohd Saquib , Niyati Pal , Lovely Joshi , Sagarika Biswas

This review revealed the complex relationship between autoimmunity and Rheumatoid Arthritis (RA), emphasizing the importance of understanding various intrinsic and extrinsic factors contributing to disease progression. RA, affecting 1 % of the world's population, predominantly impacts females and presents clinical symptoms such as joint swelling and morning stiffness. Biomarkers like RF and ACPA are used for disease prognosis. Autoimmunity, characterized by the immune system's attack on self-cells, leads to the production of autoantibodies against self-biomolecules, initiating cellular impairment and disease onset. Our review aims to comprehensively synthesize the myriad risk factors involved in RA progression, encompassing genetic, epigenetic, cellular, and environmental determinants. These factors contribute to the production of autoantibodies and shape the autoimmune milieu within RA. The autoimmune nature of RA, demonstrated by the presence of ACPA and other autoantibodies, triggers immune responses and proinflammatory cytokine release, stimulating synovial fibroblast activity and joint destruction. Furthermore, aggressive epigenetically modified synovial fibroblasts play a role in disease pathology. In this article, we highlighted the significance of understanding immune tolerance alterations related to autoimmune diseases like RA and advocated for studying similar factors in other diseases to enhance our understanding of RA pathophysiology. Advances in clinical investigations, such as using RA-specific peptides or proteins and cell-based therapies, showed promise in improving RA patient outcomes. Overall, our review aims to provide valuable insights into the intricate mechanisms driving RA progression, offering potential avenues for therapeutic intervention and disease management.

这篇综述揭示了自身免疫与类风湿关节炎（RA）之间的复杂关系，强调了了解促进疾病进展的各种内在和外在因素的重要性。类风湿性关节炎影响着世界上1%的人口，主要影响女性，并表现出关节肿胀和晨僵等临床症状。RF和ACPA等生物标志物用于疾病预后。自身免疫以免疫系统对自身细胞的攻击为特征，导致产生针对自身生物分子的自身抗体，引发细胞损伤和疾病发作。我们的综述旨在全面综合涉及RA进展的无数危险因素，包括遗传、表观遗传、细胞和环境决定因素。这些因素有助于自身抗体的产生并形成RA内的自身免疫环境。通过ACPA和其他自身抗体的存在证明，RA的自身免疫特性引发免疫反应和促炎细胞因子释放，刺激滑膜成纤维细胞活性和关节破坏。此外，侵袭性表观遗传修饰的滑膜成纤维细胞在疾病病理中发挥作用。在本文中，我们强调了了解与RA等自身免疫性疾病相关的免疫耐受改变的重要性，并主张研究其他疾病的类似因素，以增强我们对RA病理生理学的理解。临床研究的进展，如使用RA特异性肽或蛋白质和基于细胞的治疗，显示出改善RA患者预后的希望。总的来说，我们的综述旨在为推动RA进展的复杂机制提供有价值的见解，为治疗干预和疾病管理提供潜在的途径。

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引用次数: 0

Comparative gonadal transcriptome analysis reveals sex-biased genes in Siniperca scherzeri 比较性腺转录组分析揭示了雪氏鳜的性别偏倚基因

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-09-12 DOI: 10.1016/j.genrep.2025.102340

Shengyue Lin , Dingxian Chen , Weiqian Liang , Weijian Chen , Weibin Li , Ziyan Deng , Guojun Cai , Sixun Li , Binhua Deng , Kaifeng Wang , Chong Han , Qiang Li

Siniperca scherzeri is a valuable freshwater fish in China. The economic value of female S. scherzeri far exceeds that of males. Nevertheless, the lack of sex-related research has significantly impeded the development of single-sex breeding programs for this species.

In this investigation, Illumina Novaseq technology was employed to perform a comparative analysis of the gonadal transcriptomes of S. scherzeri in the first time. Assembly yielded 33,690 unigenes, of which 31,395 were successfully annotated. A comparative analysis identified 15,146 differentially expressed genes between the ovary and testis. Specifically, 9514 genes were downregulated and 5632 genes were upregulated in the ovaries. Moreover, multiple genes participating in gonadal differentiation and development, steroid synthetic pathway, and gametogenesis were screened out. Among these genes, sox 1, sox3, cyp26a1, gdf9, bmp15, zp3, foxh1, and nr0b1 showed ovary-biased expression; Amh, dmrt1b, sox 4, and nanos 2 showed testis-bias expression. Our real-time PCR also confirmed the RNA-seq results of these genes. These results are of great significance for elucidating the molecular mechanisms of sex differentiation and development in S. scherzeri.

雪氏鳜是中国一种珍贵的淡水鱼。雌雪氏蜱的经济价值远远超过雄雪氏蜱。然而，性别相关研究的缺乏严重阻碍了该物种单性繁殖计划的发展。本研究首次采用Illumina Novaseq技术对舍氏弧菌的性腺转录组进行比较分析。组装得到33,690个unigenes，其中31,395个被成功注释。一项比较分析发现，卵巢和睾丸之间存在15,146个差异表达基因。具体来说，卵巢中9514个基因下调，5632个基因上调。此外，还筛选出了参与性腺分化发育、类固醇合成途径和配子体发生的多个基因。其中，sox1、sox3、cyp26a1、gdf9、bmp15、zp3、foxh1、nr0b1呈卵巢偏向性表达；Amh、dmrt1b、sox 4和nanos 2表现出睾丸偏倚表达。我们的real-time PCR也证实了这些基因的RNA-seq结果。这些结果对阐明沙蚕性别分化和发育的分子机制具有重要意义。

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引用次数: 0

Manool modulates Keap1/Nrf2/ARE pathway to protect against CCl₄-induced hepatotoxicity in mice Manool调节Keap1/Nrf2/ARE通路对CCl - 4诱导的小鼠肝毒性的保护作用

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-09-12 DOI: 10.1016/j.genrep.2025.102341

Hafiza Adeena Saleem Khan , Imtiaz Mustafa , Nimra Aziz , Khalil Ahmad , Syed Ali Raza Shah , Jaweria Nisar , Mirza Muhammad Suleman

Background

Liver diseases are a major health concern, with oxidative stress being a key contributor to hepatocellular injury. Manool, a diterpene from Salvia species, has reported antioxidant activity, but its hepatoprotective role remains underexplored.

Objective

To evaluate the protective effects of Manool against CCl4-induced hepatotoxicity in mice, focusing on the Keap1/Nrf2/ARE pathway.

Methods

Forty albino mice (n = 10 per group) were divided into negative control (NC; healthy mice), positive control (PC; CCl4 induced mice without treatment), standard control (SC; CCl4 induced mice treated with silymarin at dose 100 mg/kg body weight), and two treatment groups (Mn-1 and Mn-2; CCl4 induced mice treated with manool at dose of 1 and 2 mg/kg body weight respectively). Treatments were administered for 21 days. Serum liver function markers, oxidative stress indices, apoptotic proteins (Bcl-2, Bax, Caspase-3, Caspase-9), inflammatory mediators (NF-κB, TNF-α, IL-1β, IL-6, COX-2), and gene expression (Keap1, Nrf2, HO-1, NQO1) were assessed. Histopathological examination was performed to confirm liver protection.

Results

Manool restored ALT, AST, and protein profiles in a dose-dependent manner. It increased TAC and GST, while reducing TOS. Gene expression analysis showed downregulation of Keap1 and upregulation of Nrf2, HO-1, and NQO1. Manool also reduced pro-apoptotic (Bax, Caspase-3, Caspase-9) and inflammatory markers (NF-κB, TNF-α, IL-1β, IL-6, COX-2), while enhancing anti-apoptotic Bcl-2. Histological analysis confirmed attenuation of CCl₄-induced hepatic damage.

Conclusion

Manool exerts hepatoprotective effects by modulating oxidative stress, apoptosis, inflammation, and the Keap1/Nrf2/ARE pathway. These findings support its potential as a natural candidate for managing oxidative liver injury, though further mechanistic and translational studies are warranted.

肝脏疾病是一个主要的健康问题，氧化应激是肝细胞损伤的关键因素。甘露醇是一种来自鼠尾草的二萜，据报道具有抗氧化活性，但其保护肝脏的作用仍未得到充分研究。目的探讨甘露醇对ccl4诱导小鼠肝毒性的保护作用，重点探讨其对Keap1/Nrf2/ARE通路的保护作用。方法40只白化病小鼠（每组10只）分为阴性对照组（NC，健康小鼠）、阳性对照组（PC，未处理CCl4诱导小鼠）、标准对照组（SC，水飞蓟素诱导CCl4小鼠，剂量为100 mg/kg体重）和两个治疗组（Mn-1和Mn-2，剂量分别为1和2 mg/kg体重的CCl4诱导小鼠）。治疗21天。检测血清肝功能指标、氧化应激指标、凋亡蛋白（Bcl-2、Bax、Caspase-3、Caspase-9）、炎症介质（NF-κB、TNF-α、IL-1β、IL-6、COX-2）和基因表达（Keap1、Nrf2、HO-1、NQO1）。组织病理学检查证实肝保护。结果manool恢复ALT、AST和蛋白谱呈剂量依赖性。它增加了营业税和商品及服务税，同时降低了服务价格。基因表达分析显示Keap1下调，Nrf2、HO-1、NQO1上调。manol还能降低促凋亡（Bax、Caspase-3、Caspase-9）和炎症标志物（NF-κB、TNF-α、IL-1β、IL-6、COX-2），增强抗凋亡Bcl-2。组织学分析证实ccl4引起的肝损伤减弱。结论甘醇通过调节氧化应激、细胞凋亡、炎症及Keap1/Nrf2/ARE通路发挥肝保护作用。这些发现支持其作为氧化性肝损伤的天然候选物的潜力，尽管进一步的机制和转化研究是必要的。

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