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Carica papaya leaf and root extracts attenuate hyperglycemia-induced insulin resistance by modulating MAPK and PI3K/AKT signalling in hepatic and skeletal muscle cells 番木瓜叶和根提取物通过调节肝脏和骨骼肌细胞中的MAPK和PI3K/AKT信号通路减轻高血糖诱导的胰岛素抵抗
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-13 DOI: 10.1016/j.bbrep.2026.102497
Mthokozisi Bongani Nxumalo, Rene Bernadette Khan, Nosipho Ntanzi, Fave Yohanna Tata, Hezekiel Mathambo Kumalo
Type 2 diabetes mellitus (T2DM) is characterised by impaired glucose homeostasis arising from insulin resistance and inadequate insulin action in peripheral tissues. Carica papaya has been reported to exert antidiabetic effects; however, its molecular mechanisms in hepatic and skeletal muscle cells under hyperglycemic conditions remain incompletely understood. This study investigated the effects of C. papaya leaf and root extracts on glucose uptake and insulin-related signalling pathways in HepG2 hepatocytes and C2C12 myotubes. Enzyme inhibition assays were used to assess α-amylase and α-glucosidase activity, while protein and gene expression of key components of the MAPK and PI3K/AKT pathways were evaluated using Western blotting and qPCR. C. papaya extracts significantly inhibited α-amylase activity (p < 0.05), with a non-significant inhibitory trend observed for α-glucosidase, suggesting reduced glucose availability under hyperglycemic conditions. In both HepG2 and C2C12 cells, C. papaya attenuated MAPK signalling through suppression of Erk1/2 and p38 MAPK, while JNK inhibition was observed exclusively in HepG2 cells (p < 0.05). In HepG2 cells, AKT and GLUT2 gene expression remained unchanged; however, AMPKα and IRS-1 were significantly upregulated, indicating enhanced glucose uptake potential despite a concomitant reduction in glycogen synthase expression (p < 0.05). In contrast, C2C12 myotubes exhibited enhanced insulin signalling characterised by increased phosphorylated IRS-1, AKT activation, and elevated glycogen synthase expression, supporting improved glucose uptake and storage (p < 0.05). Collectively, these findings demonstrate that C. papaya extracts mitigate hyperglycemia-induced insulin resistance by suppressing MAPK signalling and enhancing glucose uptake through distinct, cell-specific mechanisms in hepatic and skeletal muscle cells.
2型糖尿病(T2DM)的特征是由胰岛素抵抗和外周组织胰岛素作用不足引起的葡萄糖稳态受损。据报道,番木瓜具有抗糖尿病作用;然而,其在高血糖条件下肝脏和骨骼肌细胞中的分子机制仍不完全清楚。本研究探讨木瓜叶和根提取物对HepG2肝细胞和C2C12肌管中葡萄糖摄取和胰岛素相关信号通路的影响。酶抑制法检测α-淀粉酶和α-葡萄糖苷酶活性,Western blotting和qPCR检测MAPK和PI3K/AKT通路关键组分的蛋白和基因表达。C.木瓜提取物显著抑制α-淀粉酶活性(p <; 0.05),对α-葡萄糖苷酶无显著抑制趋势,提示高血糖状态下葡萄糖利用率降低。在HepG2和C2C12 细胞中,番木瓜通过抑制Erk1/2和p38 MAPK来减弱MAPK信号,而JNK仅在HepG2细胞中被抑制(p <; 0.05)。在HepG2细胞中,AKT和GLUT2基因表达保持不变;然而,AMPKα和IRS-1显著上调,表明尽管糖原合成酶表达减少,但葡萄糖摄取电位增强(p <; 0.05)。相比之下,C2C12肌管表现出增强的胰岛素信号传导,其特征是磷酸化的IRS-1、AKT活化和糖原合成酶表达升高,支持改善葡萄糖摄取和储存(p <; 0.05)。总的来说,这些发现表明木瓜提取物通过抑制MAPK信号传导和增强肝脏和骨骼肌细胞中不同的细胞特异性机制来减轻高血糖诱导的胰岛素抵抗。
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引用次数: 0
The development of a methodology to measure primary ciliary length in neural progenitor cells with a target molecule knocked down 一种方法的发展,以测量初级纤毛长度的神经祖细胞与靶分子敲除
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-12 DOI: 10.1016/j.bbrep.2026.102489
Masaki Saito , Wataru Otsu , Kenichi Ishibashi , Gen-ichi Atsumi
The primary cilium is an immotile cellular antenna that extends from the basal body and protrudes from the cell surface during the G0/G1 phases. The cilium is resorbed when it receives growth factor stimuli, and the ciliary resorption triggers the cell cycle re-entry into the G1/S phases. The dysregulation of ciliary dynamics during embryonic development can lead to various hereditary organ dysplasias, including microcephaly. Neural progenitor cells display primary cilia on their apical surfaces during the embryonic stage. Ciliary resorption in the cells is responsible for cell proliferation and corticogenesis. However, the molecular mechanisms underlying ciliary resorption in the neural progenitor cells in vivo are poorly understood. Mapping cilia to knockdown cells on a one-to-one basis is technically challenging and represents the biggest barrier to solving these mechanisms. In this study, we developed a short hairpin RNA (shRNA)-based pCAGI-Arl13b-tdTomato plasmid to label cilia in knockdown cells. This plasmid contains a shRNA sequence and a cilium marker, Arl13b-tdTomato. Using in utero electroporation, we transfected the plasmid into embryonic neural progenitor cells and found that the primary cilia of the transfected cells specifically expressed Arl13b-tdTomato. We also found that Arl13b-tdTomato expression did not alter the ciliary length. Microtubule-associated serine/threonine kinase and t-complex testis expressed-1 are major regulators of ciliary resorption. Knocking down each of these molecules resulted in longer cilia. These results suggest that the pCAGI-Arl13b-tdTomato plasmid is useful for measuring ciliary length in the shRNA-transfected developing cortical neural progenitor cells in vivo.
初级纤毛是一种固定的细胞天线,在G0/G1期从基体长出,从细胞表面突出。纤毛在受到生长因子刺激时被吸收,纤毛的吸收触发细胞周期重新进入G1/S期。胚胎发育过程中纤毛动力学的失调可导致各种遗传性器官发育不良,包括小头畸形。在胚胎期,神经祖细胞在其顶端表面显示初级纤毛。细胞中的纤毛吸收是细胞增殖和皮质生成的主要原因。然而,体内神经祖细胞纤毛吸收的分子机制尚不清楚。在一对一的基础上绘制纤毛击倒细胞在技术上具有挑战性,并且代表了解决这些机制的最大障碍。在这项研究中,我们开发了一种基于短发夹RNA (shRNA)的pCAGI-Arl13b-tdTomato质粒来标记敲除细胞中的纤毛。该质粒包含一个shRNA序列和一个纤毛标记Arl13b-tdTomato。利用子宫内电穿孔法将质粒转染到胚胎神经祖细胞中,发现转染细胞的原代纤毛特异性表达Arl13b-tdTomato。我们还发现Arl13b-tdTomato的表达不改变纤毛长度。微管相关丝氨酸/苏氨酸激酶和t复合物睾丸表达-1是纤毛吸收的主要调节因子。敲除这些分子导致纤毛变长。这些结果表明pCAGI-Arl13b-tdTomato质粒可用于测量shrna转染的发育中的皮质神经祖细胞的纤毛长度。
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引用次数: 0
The research progress of ferroptosis in acute lung injury 急性肺损伤中铁下垂的研究进展
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-21 DOI: 10.1016/j.bbrep.2025.102434
Yixuan Bai , Yongming Ma , Xingfang Li
Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly recognized as a pivotal mechanism in the pathogenesis of acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS). Its core molecular machinery, including glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), and the cystine/glutamate antiporter system Xc-, becomes dysregulated across various ALI subtypes, such as sepsis, ischemia-reperfusion, and COVID-19.This review delineates how ferroptosis contributes to ALI through iron overload, uncontrolled lipid peroxidation, and failure of antioxidant defenses, ultimately leading to pulmonary endothelial and epithelial cell death. We further summarize subtype-specific mechanisms and evaluate emerging therapeutic strategies, including ferroptosis inhibitors (e.g., liproxstatin-1), Nrf2 activators, and iron chelators, highlighting their potential for targeted intervention in ALI/ARDS.
铁下沉是一种由脂质过氧化驱动的铁依赖性细胞死亡形式,越来越被认为是急性肺损伤(ALI)及其严重形式急性呼吸窘迫综合征(ARDS)发病机制的关键机制。其核心分子机制,包括谷胱甘肽过氧化物酶4 (GPX4)、酰基辅酶a合成酶长链家族成员4 (ACSL4)和胱氨酸/谷氨酸反转运系统Xc-,在脓毒症、缺血再灌注和COVID-19等各种ALI亚型中变得失调。这篇综述描述了铁下沉如何通过铁超载、不受控制的脂质过氧化和抗氧化防御失败导致ALI,最终导致肺内皮细胞和上皮细胞死亡。我们进一步总结了亚型特异性机制,并评估了新兴的治疗策略,包括铁下沉抑制剂(如利普司他汀-1),Nrf2激活剂和铁螯合剂,强调了它们在ALI/ARDS中的靶向干预潜力。
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引用次数: 0
Enhancement of prime editing by recruiting engineered or evolved components and implementing novel strategies 通过招募工程或进化的组件和实施新的策略来增强原始编辑。
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-18 DOI: 10.1016/j.bbrep.2026.102495
Mobina Arabi , Farzaneh Alizadeh , Yasamin Yousefi , Hamed Afarandeh , Sina Mozaffari Jovin , Atieh Eslahi , Majid Mojarrad
Prime editing has recently gained attention for its promising potential in treating genetic disorders caused by different types of mutations. This method, based on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), has led to the development of new strategies that offer improved editing efficiency. Additionally, the components of prime editing—namely, the prime editor (PE) and the prime editing guide RNA (PegRNA)—have been enhanced through rational design and direct evolution of structural modifications. These improvements have resulted in better performance and new capabilities, driven by novel mutations or components. In this review, we compare various studies that report enhanced versions of PE or PegRNA, which achieve more efficient results. These advancements hold the potential to accelerate and simplify the development of gene therapies for a range of genetic disorders.
启动编辑最近因其在治疗由不同类型突变引起的遗传疾病方面的巨大潜力而受到关注。这种基于聚类规则间隔短回文重复序列(CRISPR)的方法导致了新策略的发展,从而提高了编辑效率。此外,启动编辑的组成部分,即启动编辑器(PE)和启动编辑指南RNA (PegRNA),通过合理的设计和结构修饰的直接进化得到了增强。这些改进带来了更好的性能和新的功能,由新的突变或组件驱动。在这篇综述中,我们比较了报告PE或PegRNA增强版本的各种研究,它们获得了更有效的结果。这些进步有可能加速和简化针对一系列遗传疾病的基因疗法的开发。
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引用次数: 0
Analysis and characterization of a novel metallophosphoesterase from Akkermansia muciniphila involved in lipid degradation 一种新型金属磷酸酯酶的分析与表征
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-06 DOI: 10.1016/j.bbrep.2025.102437
Miao Guan , Lei Li , Yang Zheng , Shaoxing Dai , Runling Wei , Zhenglong Sun
Gut microbes play an important role in the regulation of host health. Multiple studies have shown that Akkermansia muciniphila, as a promising beneficial gut bacterium, is robustly associated with positive effects on host metabolism, immunological regulation, and its presence inversely correlates with body weight. But the precise function played by this bacterium underlying lipid degradation is still unknown. Here we identify a metallophosphoesterase from A. muciniphila. The metallophosphoesterase is composed of a binuclear metal center connected with tyrosine residues and a highly conserved calcineurin-like_PHP_ApaH domain. The enzyme activity has reached its peak in the conditions of pH 8.0, temperature of 37 °C. The enzyme is active for esters with short fatty-acid chains, and has high catalytic activity for hydrolysis of phospholipid sodium salts. In addition, five of predicted active sites of the metallophosphoesterase affecting its enzymatic activity are individually analyzed. Point mutation of H47 reduces the catalytic activity of the metallophosphoesterase for its most preferred substrate, while mutation of H181 has the opposite effect of increasing the enzymatic activity. Overall, we report the first characterization of AMUC-1901, a novel metallophosphoesterase from A. muciniphila with lipid degradation capabilities, which has potential for further exploration in developing novel food or pharma supplements for obesity therapies.
肠道微生物在调节宿主健康方面发挥着重要作用。多项研究表明,嗜粘Akkermansia muciniphila作为一种有前景的有益肠道细菌,与宿主代谢、免疫调节的积极作用密切相关,其存在与体重呈负相关。但是这种细菌在脂质降解中所起的确切作用仍然未知。我们从嗜粘杆菌中鉴定出一种金属磷酸酯酶。金属磷酸酯酶由连接酪氨酸残基的双核金属中心和高度保守的钙调磷酸酶样结构域组成。酶活性在pH 8.0、温度37 ℃条件下达到峰值。该酶对短脂肪酸链的酯类具有活性,对磷脂钠盐的水解具有较高的催化活性。此外,还分别分析了影响金属磷酸酯酶活性的5个预测活性位点。H47的点突变降低了金属磷酸酯酶对其首选底物的催化活性,而H181的点突变则相反,提高了酶的活性。总之,我们报道了AMUC-1901的首次鉴定,AMUC-1901是一种来自嗜粘杆菌的新型金属磷酸酯酶,具有脂质降解能力,具有进一步开发用于肥胖治疗的新型食品或药物补充剂的潜力。
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引用次数: 0
Electrochemical and optical biosensors for periodontitis detection 用于牙周炎检测的电化学和光学生物传感器
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2025-11-26 DOI: 10.1016/j.bbrep.2025.102378
Amir masoud zarasvandi , Mohammad Gerayeli , Mina Abasi , Mehdi Goodarzi , Shabnam Ganjehzadeh , Raheleh solhmirzaei , Asieh Mozaffari , Haniyeh Alavi Milani
Periodontitis is a common chronic inflammatory disease that frequently results in tooth loss and systemic complications. Traditional diagnostic methods have limited sensitivity and often fail to detect early disease activity. Biosensors have emerged as promising tools for the early and accurate detection of specific biomarkers in saliva and gingival crevicular fluid. This review highlights recent advancements in electrochemical, optical, lab-on-a-chip technologies, and nanosensors for periodontal diagnosis. These innovations provide rapid, non-invasive, point-of-care capabilities, enabling improved monitoring and personalized treatment. While challenges remain in clinical translation, biosensors have significant potential to transform periodontal diagnostics and enhance patient outcomes.

Clinical trial number

not applicable.
牙周炎是一种常见的慢性炎症性疾病,经常导致牙齿脱落和全身并发症。传统的诊断方法灵敏度有限,往往不能发现早期疾病活动。生物传感器已经成为早期和准确检测唾液和龈沟液中特定生物标志物的有前途的工具。本文综述了最近在电化学、光学、芯片实验室技术和牙周诊断纳米传感器方面的进展。这些创新提供了快速、无创、即时护理的能力,从而改善了监测和个性化治疗。虽然在临床转化方面仍存在挑战,但生物传感器在改变牙周诊断和提高患者预后方面具有巨大的潜力。临床试验编号不适用。
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引用次数: 0
Unlocking the potential of endophytes in enhancing plant secondary metabolite biosynthesis 释放内生菌在促进植物次生代谢物生物合成方面的潜力
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2025-11-26 DOI: 10.1016/j.bbrep.2025.102385
Esther Ugo Alum , Olisa Alfred Nwuruku , Daniel Ejim Uti , Darlington Arinze Echegu , Okechukwu Paul-Chima Ugwu , Simeon Ikechukwu Egba , Peter Chinedu Agu , Patrick Maduabuchi Aja
Plant secondary metabolites (PSMs) are vital bioactive compounds with wide pharmaceutical, agricultural, and industrial applications. However, their commercial production faces challenges due to low yields, environmental variability, and high extraction costs. Endophytes, microorganisms living within plant tissues, have emerged as key regulators of plant metabolism, enhancing PSM production through activation of biosynthetic gene clusters, secretion of precursor molecules, and modulation of plant stress responses. This narrative review explores recent advances in understanding endophyte-plant interactions, focusing on their mechanisms for stimulating metabolite production. It highlights biotechnological applications, including metabolic engineering, genome editing, and co-cultivation strategies, for optimizing endophyte-mediated biosynthesis. The review also identifies challenges in large-scale application and proposes recommendations for integrating endophytes into sustainable agriculture and pharmaceutical production. Harnessing endophytes offers an eco-friendly, cost-effective approach for scalable natural product biosynthesis, with significant potential for addressing global health, agricultural sustainability, and industrial needs.
植物次生代谢物(psm)是一种重要的生物活性化合物,具有广泛的制药、农业和工业应用。然而,由于产量低、环境变化和开采成本高,它们的商业生产面临着挑战。内生菌是指生活在植物组织内的微生物,它们是植物代谢的关键调节因子,通过激活生物合成基因簇、分泌前体分子和调节植物的胁迫反应来促进PSM的产生。这篇叙述性综述探讨了了解内生菌与植物相互作用的最新进展,重点是它们刺激代谢物产生的机制。它强调了生物技术的应用,包括代谢工程、基因组编辑和共同培养策略,以优化内生菌介导的生物合成。这篇综述还指出了大规模应用的挑战,并提出了将内生菌整合到可持续农业和药品生产中的建议。利用内生菌为可扩展的天然产物生物合成提供了一种生态友好、成本效益高的方法,在解决全球健康、农业可持续性和工业需求方面具有巨大潜力。
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引用次数: 0
Recognition of immunogenomic signature and prognostic value of the subtype of epithelial-mesenchymal transition in breast cancer 乳腺癌上皮-间质转化亚型的免疫基因组特征识别及其预后价值
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-19 DOI: 10.1016/j.bbrep.2026.102456
Wei Liang , Zi-ying Wang , Quan-feng Shao , Yuan-yuan Li , Bei Zhu , Xi-hu Qin , Wei-xian Chen

Background

Accumulating evidence has revealed that epithelial-mesenchymal transition (EMT) plays a crucial role in tumor progression and the immune microenvironment, which further results in a high rate of recurrence and metastasis. The EMT immune signaling pathway provides a great perspective for designing personalized therapies.

Methods

In this study, 1223 RNA-seq samples were obtained from the TCGA-BRCA dataset. A total of 381 EMT-related differentially expressed genes were analyzed and combined with clinical parameters, and the matrix was randomly divided into training and testing cohorts at a ratio of 7:3. The training cohort was used to develop an EMT signature, including GKN2, FZD2, NDRG2, SCUBE2, ALX4, CCL19, SDC1, EZR, CPEB1, and HRG genes, and the accuracy of this signature was validated by testing and GSE158309 cohorts.

Results

A risk score model and clinical parameters were used to establish a nomogram for predicting prognosis. The C-index (0.719), calibration curves, and model comparison with four previous studies demonstrated the reliability of the EMT signature, the biological phenotypes of which were tested for functional enrichment, immune infiltration, and tumor mutation. Additionally, patients' responses to immunotherapy and chemotherapy were assessed. Our results showed that the low-risk group had higher immune infiltration, tumor mutational burden, microsatellite instability levels, immune checkpoint inhibitor expression, tumor immune dysfunction and exclusion scores, and immunophenoscore, which could predict patient sensitivity to immunotherapy. Moreover, low-risk patients exhibit better sensitivity to chemotherapy.

Conclusion

This novel EMT signature offers excellent potential for predicting the prognosis, tumor immune heterogeneity, and therapeutic responses in breast cancer.
越来越多的证据表明,上皮间质转化(epithelial-mesenchymal transition, EMT)在肿瘤的进展和免疫微环境中起着至关重要的作用,这进一步导致了肿瘤的高复发和转移率。EMT免疫信号通路为设计个性化治疗提供了一个很好的视角。方法本研究从TCGA-BRCA数据集中获得1223个RNA-seq样本。共分析381个emt相关差异表达基因并结合临床参数,将基质按7:3的比例随机分为训练组和测试组。训练队列用于建立EMT签名,包括GKN2、FZD2、NDRG2、SCUBE2、ALX4、CCL19、SDC1、EZR、CPEB1和HRG基因,并通过测试和GSE158309队列验证该签名的准确性。结果采用风险评分模型和临床参数建立预测预后的nomogram。c -指数(0.719)、校准曲线以及与先前4项研究的模型比较证明了EMT特征的可靠性,并对其进行了功能富集、免疫浸润和肿瘤突变的生物学表型检测。此外,还评估了患者对免疫治疗和化疗的反应。我们的研究结果显示,低危组免疫浸润、肿瘤突变负担、微卫星不稳定性水平、免疫检查点抑制剂表达、肿瘤免疫功能障碍和排斥评分以及免疫表型评分较高,可以预测患者对免疫治疗的敏感性。此外,低风险患者对化疗的敏感性更好。结论这种新的EMT特征在预测乳腺癌的预后、肿瘤免疫异质性和治疗反应方面具有很好的潜力。
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引用次数: 0
Exploring potential biomarkers of NETosis-Related genes in spinal cord injury through machine learning and multi-omics analysis 通过机器学习和多组学分析探索脊髓损伤中netosis相关基因的潜在生物标志物
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-20 DOI: 10.1016/j.bbrep.2025.102439
Xinliao Sun , Yuchang Gui , Yuting Lu , Kewen Wang , Jingzhi Yao , Zi Li , Dandan Lu , Qian Guo , Ruixue Liu , Jianwen Xu
Spinal cord injury (SCI) is a serious condition typically caused by mechanical trauma, often resulting in significant motor, sensory, and autonomic dysfunction. It places a heavy burden on individuals, families, and society; however, effective treatment options are still limited because of the complex pathophysiology behind primary and secondary injury mechanisms. Neutrophil extracellular traps (NETs) created by neutrophils play a crucial role in exacerbating secondary injury following spinal cord injury by promoting inflammation and hindering neural repair. This study aims to clarify the molecular basis of neutrophil extracellular trap-related genes (NRGs) in SCI through an integrated bioinformatics approach. We utilized the GSE151371 dataset from the GEO database, which includes gene expression profiles from 38 SCI patients and 10 healthy controls, and we identified differentially expressed genes (DEGs) using the limma package in R. We identified 4878 DEGs, and we performed functional analysis of these genes using GO and KEGG. Immune cell infiltration analysis conducted with CIBERSORT showed significant differences in immune cell populations between the SCI group and the control group, with notable differences in the infiltration of Neutrophils, B cells memory and Macrophages M0. Weighted gene co-expression network analysis (WGCNA) identified a module highly associated with SCI, which resulted in the selection of 12 candidate genes. We built a predictive model using machine learning algorithms, identifying NLRP3, LRG1, and TLR8 as key genes with high diagnostic potential (AUC >0.9). Subsequently, through multi-omics analysis, including gene set enrichment analysis (GESA), protein interaction analysis, and correlation analysis between key genes and immune cells, we explored the relationship between key NRGs and the pathological processes in SCI patients. Finally, these findings were validated through molecular biology experiments in a rat SCI model and clinical samples, confirming the clinical relevance of our findings regarding these biomarkers. In summary, this study provides a comprehensive analysis of NRGs in SCI, highlighting their diagnostic and therapeutic potential. Future research could focus on developing interventions targeting NETs formation, providing new opportunities to enhance treatment outcomes for SCI.
脊髓损伤(SCI)是一种严重的疾病,通常由机械性创伤引起,通常导致明显的运动、感觉和自主神经功能障碍。它给个人、家庭和社会带来了沉重的负担;然而,由于原发性和继发性损伤机制背后的复杂病理生理,有效的治疗选择仍然有限。中性粒细胞产生的中性粒细胞胞外陷阱(NETs)通过促进炎症和阻碍神经修复,在加重脊髓损伤后的继发性损伤中起着至关重要的作用。本研究旨在通过综合生物信息学方法,阐明脊髓损伤中性粒细胞胞外陷阱相关基因(NRGs)的分子基础。我们利用GEO数据库中的GSE151371数据集,其中包括38名SCI患者和10名健康对照者的基因表达谱,我们使用r中的limma软件包鉴定了差异表达基因(DEGs)。我们鉴定了4878个DEGs,并使用GO和KEGG对这些基因进行了功能分析。免疫细胞浸润分析CIBERSORT显示脊髓损伤组与对照组免疫细胞群差异显著,中性粒细胞、B细胞记忆和巨噬细胞M0的浸润差异显著。加权基因共表达网络分析(Weighted gene co-expression network analysis, WGCNA)鉴定出一个与SCI高度相关的模块,并由此筛选出12个候选基因。我们利用机器学习算法建立了预测模型,确定了NLRP3、LRG1和TLR8为具有高诊断潜力的关键基因(AUC >0.9)。随后,我们通过多组学分析,包括基因集富集分析(GESA)、蛋白相互作用分析、关键基因与免疫细胞的相关性分析等,探讨了关键NRGs与SCI患者病理过程的关系。最后,通过大鼠脊髓损伤模型和临床样本的分子生物学实验验证了这些发现,证实了我们的研究结果与这些生物标志物的临床相关性。总之,本研究对脊髓损伤中的NRGs进行了全面分析,突出了其诊断和治疗潜力。未来的研究可以专注于开发针对神经网络形成的干预措施,为提高脊髓损伤的治疗效果提供新的机会。
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引用次数: 0
In silico exploration of the genomic repertoire of Iranian aquatic bacteria: Prophage carriage, bioactive compound potential, CRISPR-Cas immunity, and integrated defensive-metabolic islands 伊朗水生细菌基因组库的计算机探索:原噬菌体携带、生物活性化合物潜力、CRISPR-Cas免疫和综合防御代谢岛
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-28 DOI: 10.1016/j.bbrep.2026.102452
Mohammadreza Rahimian , Mohammad Aghazadeh-Soltan-Ahmadi , Bahman Panahi
The unique and underexplored aquatic ecosystems of Iran represent a significant reservoir of microbial diversity. This study presents the first comprehensive genomic survey of 38 native Iranian bacterial strains from hypersaline lakes and wetlands, integrating in silico analyses of their secondary metabolome, bacteriocin potential, resident prophages, and genomic architecture. Our genome mining revealed a prolific capacity for secondary metabolite production, identifying dozens of biosynthetic gene clusters (BGCs). Ectoine biosynthesis was ubiquitous, underscoring its role as a key osmoprotectant, while diverse BGCs for terpenes, polyketides, and hybrid metabolites were also prevalent. Concurrently, we identified a wide array of ribosomally synthesized and post-translationally modified peptides (RiPPs), including known bacteriocins. Furthermore, we characterized eight high-quality prophages integrated within these genomes, encoding auxiliary genes such as carbohydrate-active enzymes (CAZymes) and putative anti-CRISPR (ACR) proteins. The bacterial hosts themselves were equipped with robust defense systems, with CRISPR-Cas loci, predominantly Type I, detected in most strains. Crucially, we identified multi-functional genomic islands that physically link BGCs with defense systems (e.g., CRISPR-Cas, restriction-modification) and prophage regions. We propose the “Fortress Hypothesis” to explain this architecture, wherein the co-localization of metabolite production and defense machinery protects metabolic investment against phage predation and genetic loss. This integrative genomic arrangement highlights a sophisticated co-evolutionary strategy for survival in extreme environments. Our findings position these indigenous bacteria as a promising genetic repository for discovering novel bioactive compounds, enzymes, and biotechnological tools, with implications for antibiotic discovery, CRISPR modulation, and understanding adaptive microbial genomics in extreme niches.
伊朗独特的和未充分开发的水生生态系统代表了微生物多样性的重要水库。本研究首次对来自高盐湖泊和湿地的38种伊朗原生细菌菌株进行了全面的基因组调查,整合了它们的次级代谢组、细菌素潜力、常驻噬菌体和基因组结构的计算机分析。我们的基因组挖掘揭示了次生代谢物生产的丰富能力,确定了数十个生物合成基因簇(bgc)。外托因的生物合成是普遍存在的,强调了其作为关键渗透保护剂的作用,而各种萜类、聚酮类和杂交代谢物的bgc也很普遍。同时,我们鉴定了一系列核糖体合成和翻译后修饰的肽(RiPPs),包括已知的细菌素。此外,我们鉴定了整合在这些基因组中的8个高质量的噬菌体,它们编码辅助性基因,如碳水化合物活性酶(CAZymes)和抗crispr (ACR)蛋白。细菌宿主本身配备了强大的防御系统,在大多数菌株中检测到CRISPR-Cas位点,主要是I型。至关重要的是,我们确定了将bgc与防御系统(例如CRISPR-Cas,限制性修饰)和噬菌体区域物理连接起来的多功能基因组岛。我们提出“堡垒假说”来解释这种结构,其中代谢物生产和防御机制的共定位保护代谢投资免受噬菌体捕食和遗传损失。这种整合的基因组排列突出了在极端环境中生存的复杂的共同进化策略。我们的研究结果将这些本土细菌定位为一个有希望的遗传资源库,用于发现新的生物活性化合物、酶和生物技术工具,对抗生素的发现、CRISPR调节和极端生态位中适应性微生物基因组学的理解具有重要意义。
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