Pathology, research and practice最新文献_第10页

Next generation DNA sequencing data analysis and its application in clinical genomics 下一代DNA测序数据分析及其在临床基因组学中的应用

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-10-30 DOI: 10.1016/j.prp.2025.156280

Abhijit Beura , Gowrang Kasaba Manjunath , Shweta Mahalingam , Mangesh Sudhakar Rajguru , Tikam Chand Dakal , Abhishek Kumar

Next-generation sequencing (NGS) has transformed genomics by enabling rapid, high-throughput analysis of DNA and RNA, driving significant progress across multiple fields, such as cancer research, rare disease diagnosis, and personalized medicine. This review discusses the wide-ranging applications of NGS, particularly in identifying genetic variants that guide the development of targeted therapies, improving patient outcomes. The NGS workflow involves crucial steps including data quality control, sequence alignment, and variant calling, supported by both open-source and commercial tools. Cloud-based platforms have further streamlined the storage, management, and processing of the vast datasets generated by NGS technologies. As NGS continues to evolve, ethical challenges, especially concerning genomic data privacy and informed consent, remain critical considerations. Looking ahead, the integration of multi-omics data and the advent of single-cell sequencing hold the potential to deepen our understanding of complex biological processes. Essential databases like dbSNP, COSMIC, and The Cancer Genome Atlas are key resources for interpreting NGS findings and their clinical significance. By effectively utilizing these tools and datasets, researchers can generate new genetic insights with far-reaching implications for advancing human health and understanding disease mechanisms.

下一代测序（NGS）通过实现DNA和RNA的快速、高通量分析，改变了基因组学，推动了癌症研究、罕见疾病诊断和个性化医疗等多个领域的重大进展。这篇综述讨论了NGS的广泛应用，特别是在识别遗传变异，指导靶向治疗的发展，改善患者预后方面。NGS工作流程包括关键步骤，包括数据质量控制、序列比对和变体调用，这些都得到了开源和商业工具的支持。基于云的平台进一步简化了NGS技术产生的大量数据集的存储、管理和处理。随着NGS的不断发展，伦理挑战，特别是关于基因组数据隐私和知情同意，仍然是关键的考虑因素。展望未来，多组学数据的整合和单细胞测序的出现有可能加深我们对复杂生物过程的理解。基本数据库如dbSNP、COSMIC和The Cancer Genome Atlas是解释NGS发现及其临床意义的关键资源。通过有效地利用这些工具和数据集，研究人员可以产生新的遗传见解，对促进人类健康和理解疾病机制具有深远的意义。

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引用次数: 0

An MRI radiomics approach to predict the efficacy of chemotherapy for osteosarcoma MRI放射组学方法预测骨肉瘤化疗疗效

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-10-27 DOI: 10.1016/j.prp.2025.156279

Danna Liu , Xue Zhou , Yixiong Liu , Hong Wang , Jixin Liu , Zhengyuan Li , Yanfei Liu , Xin Hou , Yuewen Hao

Objectives

Magnetic resonance imaging (MRI) and dynamic contrast enhancement MRI(DCE-MRI) data of osteosarcoma patients prior to neoadjuvant chemotherapy (NAC) were compared in order to investigate the value of imaging histological features in predicting the rate of tumor necrosis in osteosarcoma and patients' postoperative survival.

Methods

We enrolled 28 osteosarcoma patients who received three courses of NAC followed by tumor resection. Prior to chemotherapy both conventional MRI and DCE-MRI scans were performed Quantitative analysis of histological features within the tumor region was conducted using T1-weighted, T2-weighted, and DCE-MRI images. Recursive feature elimination guided the selection of relevant features, and a prediction model was constructed using five machine learning algorithms (Random Forest, Logistic Regression, Decision Tree, Gradient Boosting, and Bagging Decision Tree). Model performance was assessed using receiver operating characteristic (ROC) curves, area under the curve (AUC), and accuracy. The five imaging features with the strongest predictive capability were identified, and their association with postoperative survival was explored using Kaplan-Meier survival analysis.

Results

Among the five prediction models, the decision tree, gradient boosting and bagging decision tree models showed high prediction performance, with AUC values of 0.850, 0.856 and 0.872, respectively, and an accuracy of 0.857. Notably, Kaplan-Meier survival analysis highlighted the significance of two features extracted from DCE-MRI images -"Small Dependence Low Gray Level Emphasis" (based on the Gray Level Cooccurrence Matrix, GLCM）and "Run Length Non-Uniformity" (based on the Gray Level Run Length Matrix, GLRLM), were significantly predictive of postoperative survival (P < 0.05).

Conclusion

DCE-MRI-based imaging histology models of osteosarcoma patients prior to NAC can be a useful tool for predicting tumour necrosis rates and patient survival after surgery.

目的比较骨肉瘤患者在新辅助化疗（NAC）前的磁共振成像（MRI）和动态对比增强MRI（DCE-MRI）资料，探讨影像学组织学特征在预测骨肉瘤肿瘤坏死率和患者术后生存期中的价值。方法28例骨肉瘤患者接受3个疗程的NAC治疗并行肿瘤切除术。化疗前进行常规MRI和DCE-MRI扫描，采用t1加权、t2加权和DCE-MRI图像定量分析肿瘤区域的组织学特征。递归特征消除指导相关特征的选择，并使用随机森林、逻辑回归、决策树、梯度增强和Bagging决策树五种机器学习算法构建预测模型。采用受试者工作特征（ROC）曲线、曲线下面积（AUC）和准确性评估模型的性能。确定预测能力最强的五个影像学特征，并利用Kaplan-Meier生存分析探讨其与术后生存的关系。结果5种预测模型中，决策树、梯度增强和套袋决策树模型的AUC值分别为0.850、0.856和0.872，预测精度为0.857。值得注意的是，Kaplan-Meier生存分析强调了从DCE-MRI图像中提取的两个特征的重要性-“小依赖性低灰度强调”（基于灰度协同矩阵，GLCM）和“跑长非均匀性”（基于灰度跑长矩阵，GLRLM），可以显著预测术后生存（P <； 0.05）。结论基于dce - mri的骨肉瘤NAC术前影像学组织学模型可作为预测肿瘤坏死率和术后患者生存率的有效工具。

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引用次数: 0

Mechanistic insights into plant-derived natural compounds for the treatment of skin cancer: Targeting molecular signaling for therapeutic intervention 植物来源的天然化合物治疗皮肤癌的机制：靶向分子信号治疗干预。

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-10-22 DOI: 10.1016/j.prp.2025.156277

Ashutosh Pathak , G. Surendra , Sathvik Belagodu Sridhar , Patibandla Jahnavi , Jeetendra Kumar Gupta , P. Balaji , N. Juniorsundresh , Konatham Teja Kumar Reddy , Abdul Ajeed Mohathasim Billah , Karthickeyan Krishnan

Skin cancer, a prevalent global cancer, is primarily caused by chronic environmental exposures and cellular signaling pathway deregulation. Traditional therapies like radiation, chemotherapy, and surgery face toxicity, resistance, and recurrence issues. Natural compounds, with their diverse biological activity and minimal side effects, are increasingly recognized as potential therapeutic agents. This review explores the potential of natural compounds in treating skin cancer by modifying key molecular signaling pathways, including MAPK/ERK, PI3K/Akt, NF-κB, STAT3, and Wnt/β-catenin. Curcumin, resveratrol, quercetin, epigallocatechin gallate, and genistein are natural substances known to have potent anticancer effects by inhibiting cell proliferation, promoting apoptosis, and preventing metastasis. These substances regulate inflammation, prevent angiogenesis, enhance drug effectiveness, combat multidrug resistance, and have low toxicity to healthy skin cells, indicating potential therapeutic use. Additionally, their compatibility with current chemotherapeutic drugs underscores their significant role in combating drug resistance. The review underscores the importance of understanding the molecular mechanisms underlying phytochemicals' anticancer properties to facilitate their integration into modern treatment methods. Future initiatives should focus on clinical validation, increasing bioavailability, and targeting administration schemes to maximize the therapeutic potential of natural chemicals against skin cancer.

皮肤癌是一种全球普遍存在的癌症，主要是由慢性环境暴露和细胞信号通路失调引起的。传统的治疗方法，如放疗、化疗和手术，面临着毒性、耐药性和复发问题。天然化合物由于其多样的生物活性和最小的副作用，越来越被认为是潜在的治疗药物。本文通过对MAPK/ERK、PI3K/Akt、NF-κB、STAT3和Wnt/β-catenin等关键分子信号通路的调控，探讨了天然化合物治疗皮肤癌的潜力。姜黄素、白藜芦醇、槲皮素、没食子儿茶素没食子酸酯和染料木素是已知的天然物质，通过抑制细胞增殖、促进细胞凋亡和防止转移而具有有效的抗癌作用。这些物质调节炎症，防止血管生成，增强药物有效性，对抗多药耐药，并且对健康皮肤细胞毒性低，表明潜在的治疗用途。此外，它们与当前化疗药物的相容性强调了它们在对抗耐药性方面的重要作用。该综述强调了了解植物化学物质抗癌特性的分子机制的重要性，以促进它们与现代治疗方法的结合。未来的举措应侧重于临床验证、提高生物利用度和靶向给药方案，以最大限度地发挥天然化学物质对皮肤癌的治疗潜力。

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引用次数: 0

CD47/HIF-1α circuit promotes cell proliferation in hepatocellular carcinoma CD47/HIF-1α通路促进肝癌细胞增殖

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-10-20 DOI: 10.1016/j.prp.2025.156275

Cuicui Xu , Yuhui Pei , Xiaoman Zhang , Cuicui Wang , Min He , Zhicheng Wan , Ganyu Miao , Jun Hou , Lianghai Wang

Objective

Hepatocellular carcinoma (HCC) is a prevalent digestive system malignancy with a poor prognosis. Previous studies suggested that elevated CD47 expression, a member of the immunoglobulin superfamily, is correlated with poor outcomes in various cancers. However, the precise mechanisms through which CD47 influences HCC progression remain unclear.

Methods

CD47 expression in tumor and adjacent tissues was assessed using online databases and immunohistochemical staining. The effects of CD47 on tumor cell proliferation were evaluated through cell counting kit-8 and colony formation assays. Bioinformatics analyses, qRT-PCR, and western blotting were employed to investigate the underlying mechanisms by which CD47 regulates tumor progression.

Results

CD47 expression was significantly elevated in HCC tissues compared to normal counterparts, and its level was closely associated with tumor stage. Overexpression of CD47 enhanced HCC cell growth, whereas silencing CD47 inhibited proliferation. Mechanistically, HIF-1α directly binds to the CD47 promoter, regulating its transcription. Additionally, CD47 stabilizes HIF-1α protein by inhibiting autophagy-lysosome-mediated degradation, establishing a positive feedback loop that promotes HCC cell proliferation.

Conclusion

CD47 is upregulated in HCC tissues, and its interaction with HIF-1α accelerates tumor growth through a positive feedback loop. Targeting both CD47 and HIF-1α may offer a promising therapeutic strategy for patients with HCC.

目的肝细胞癌是一种常见的消化系统恶性肿瘤，预后较差。先前的研究表明，免疫球蛋白超家族成员CD47的表达升高与各种癌症的不良预后相关。然而，CD47影响HCC进展的确切机制尚不清楚。方法采用在线数据库和免疫组化染色检测scd47在肿瘤及癌旁组织中的表达。通过细胞计数试剂盒-8和集落形成实验评估CD47对肿瘤细胞增殖的影响。采用生物信息学分析、qRT-PCR和western blotting来研究CD47调节肿瘤进展的潜在机制。结果scd47在HCC组织中的表达水平明显高于正常组织，且与肿瘤分期密切相关。过表达CD47促进HCC细胞生长，而沉默CD47抑制增殖。在机制上，HIF-1α直接结合CD47启动子，调节其转录。此外，CD47通过抑制自噬溶酶体介导的降解来稳定HIF-1α蛋白，建立一个促进HCC细胞增殖的正反馈循环。结论cd47在HCC组织中表达上调，其与HIF-1α的相互作用通过正反馈回路加速肿瘤生长。同时靶向CD47和HIF-1α可能为HCC患者提供一种有希望的治疗策略。

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引用次数: 0

USP5 influences immune infiltration and prognosis in non-small-cell lung cancer USP5影响非小细胞肺癌的免疫浸润和预后

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-10-20 DOI: 10.1016/j.prp.2025.156276

Yonghong Xu , Yifei Xie , Jian Zhao , Jiansheng Zhang , Jie Zhao , Yongliang Du , Jianjie Zhu , Yuanyuan Zeng , Jian-an Huang , Zeyi Liu

Background

USP5, a deubiquitinating enzyme, is linked to various cancers. However, its relationship with immune infiltration and its prognostic significance in non–small-cell lung cancer (NSCLC) remains to be determined.

Methods

USP5 expression patterns in NSCLC were analyzed using data sourced from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Functional enrichment analyses were performed to predict the role of USP5 in NSCLC development, and Hub genes were identified through a protein–protein interaction (PPI) network. Immune cell infiltration was assessed via single-sample gene set enrichment analysis, while the prognostic significance of USP5 was evaluated using the Kaplan–Meier method and Cox regression analysis. To facilitate survival rate predictions at different time points, a prognostic model was developed. Previous findings were validated using real-time PCR and in vitro functional assays in NSCLC cell lines.

Results

USP5 expression was found to be markedly elevated in NSCLC tissues when compared to normal tissues. Functional enrichment analysis revealed the involvement of USP5 in regulating key pathways linked to lung adenocarcinoma development. PPI network analysis revealed several potential interactions contributing to NSCLC progression. A correlation was observed between higher USP5 levels and the reduced presence of immune cells (e.g., macrophages, CD8 +T cells, NK cells, and iDCs) within the tumor microenvironment. ROC curves confirmed the prognostic value of USP5 for NSCLC. Functional studies in NSCLC cell lines confirmed the molecular effects of USP5 on NSCLC development.

Conclusions

USP5 appears to be a reliable marker for diagnosing NSCLC and predicting its prognosis. Further investigation into the role of USP5 in immune responses may aid in the development of immunotherapies for NSCLC.

usp5是一种去泛素化酶，与多种癌症有关。然而，其与免疫浸润的关系及其在非小细胞肺癌（NSCLC）中的预后意义尚不明确。方法利用基因表达图谱（Gene expression Omnibus）和癌症基因组图谱（Cancer Genome Atlas）数据库的数据，分析NSCLC中sus5的表达模式。通过功能富集分析预测USP5在NSCLC发展中的作用，并通过蛋白-蛋白相互作用（PPI）网络鉴定Hub基因。通过单样本基因集富集分析评估免疫细胞浸润，采用Kaplan-Meier法和Cox回归分析评估USP5对预后的意义。为了便于预测不同时间点的生存率，我们建立了一个预后模型。之前的发现通过实时PCR和非小细胞肺癌细胞系的体外功能测定得到了验证。结果与正常组织相比，非小细胞肺癌组织中sus5的表达明显升高。功能富集分析揭示了USP5参与调节与肺腺癌发展相关的关键通路。PPI网络分析揭示了几种促进NSCLC进展的潜在相互作用。观察到USP5水平升高与肿瘤微环境中免疫细胞（如巨噬细胞、CD8 +T细胞、NK细胞和idc）的减少之间存在相关性。ROC曲线证实了USP5对NSCLC的预后价值。NSCLC细胞系的功能研究证实了USP5在NSCLC发展中的分子作用。结论sus5是诊断非小细胞肺癌和预测其预后的可靠标志物。进一步研究USP5在免疫应答中的作用可能有助于开发针对非小细胞肺癌的免疫疗法。

{"title":"USP5 influences immune infiltration and prognosis in non-small-cell lung cancer","authors":"Yonghong Xu , Yifei Xie , Jian Zhao , Jiansheng Zhang , Jie Zhao , Yongliang Du , Jianjie Zhu , Yuanyuan Zeng , Jian-an Huang , Zeyi Liu","doi":"10.1016/j.prp.2025.156276","DOIUrl":"10.1016/j.prp.2025.156276","url":null,"abstract":"<div><h3>Background</h3><div>USP5, a deubiquitinating enzyme, is linked to various cancers. However, its relationship with immune infiltration and its prognostic significance in non–small-cell lung cancer (NSCLC) remains to be determined.</div></div><div><h3>Methods</h3><div>USP5 expression patterns in NSCLC were analyzed using data sourced from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Functional enrichment analyses were performed to predict the role of USP5 in NSCLC development, and Hub genes were identified through a protein–protein interaction (PPI) network. Immune cell infiltration was assessed via single-sample gene set enrichment analysis, while the prognostic significance of USP5 was evaluated using the Kaplan–Meier method and Cox regression analysis. To facilitate survival rate predictions at different time points, a prognostic model was developed. Previous findings were validated using real-time PCR and <em>in vitro</em> functional assays in NSCLC cell lines.</div></div><div><h3>Results</h3><div>USP5 expression was found to be markedly elevated in NSCLC tissues when compared to normal tissues. Functional enrichment analysis revealed the involvement of USP5 in regulating key pathways linked to lung adenocarcinoma development. PPI network analysis revealed several potential interactions contributing to NSCLC progression. A correlation was observed between higher USP5 levels and the reduced presence of immune cells (e.g., macrophages, CD8 +T cells, NK cells, and iDCs) within the tumor microenvironment. ROC curves confirmed the prognostic value of USP5 for NSCLC. Functional studies in NSCLC cell lines confirmed the molecular effects of USP5 on NSCLC development.</div></div><div><h3>Conclusions</h3><div>USP5 appears to be a reliable marker for diagnosing NSCLC and predicting its prognosis. Further investigation into the role of USP5 in immune responses may aid in the development of immunotherapies for NSCLC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156276"},"PeriodicalIF":3.2,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of C-reactive protein in cervical intraepithelial neoplasia/cancer c反应蛋白在宫颈上皮内瘤变/癌中的作用

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-10-19 DOI: 10.1016/j.prp.2025.156274

Adriana Pedreañez , Yenddy Carrero , Renata Vargas , Juan P.Hernández Fonseca , Jesús Mosquera

Cervical cancer is one of the most common malignancies in women. This pathology originates from the progression of cervical intraepithelial neoplasia (CIN), induced by high-risk human papillomavirus (HPV) infection. During CIN, an inflammatory process characterized by immune system activation and increased levels of C-reactive protein (CRP) occurs. This protein, generally an indicator of inflammatory processes, also has functions that can influence the pathogenesis of several diseases. This review summarizes the current published literature (searched on Pubmed, EMBASE and Web of Science) regarding the factors that affect pathogenesis of cervical intraepithelial neoplasia/cancer mediated by CRP searched up to 2025. This review highlights the events present in CIN/cancer where CRP may be involved. CRP may induce progression of CIN to cervical cancer through its action on its lectin-like receptor oxidized low-density lipoprotein receptor-1 (LOX-1) and influence events involving complement activation, immune system activation, apoptosis induction, oxidative stress, and modulation of HPV biology.

子宫颈癌是女性最常见的恶性肿瘤之一。这种病理起源于宫颈上皮内瘤变（CIN）的进展，由高危人乳头瘤病毒（HPV）感染引起。在CIN期间，以免疫系统激活和c反应蛋白（CRP）水平升高为特征的炎症过程发生。这种蛋白质通常是炎症过程的指示器，也具有影响几种疾病发病机制的功能。本综述总结了目前已发表的文献（检索Pubmed、EMBASE和Web of Science），关于CRP介导的宫颈上皮内瘤变/癌发病机制的影响因素，检索至2025年。这篇综述强调了在CIN/癌症中CRP可能参与的事件。CRP可能通过其对凝集素样受体氧化低密度脂蛋白受体-1 （LOX-1）的作用诱导CIN进展为宫颈癌，并影响补体激活、免疫系统激活、细胞凋亡诱导、氧化应激和HPV生物学调节等事件。

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引用次数: 0

Chuanxing Qingfei Syrup ameliorates acute lung injury by suppressing BCL10 expression and blocking the IKK/IκBα/NF-κB pathway 川星清肺糖浆通过抑制BCL10表达和阻断IKK/ i -κB α/NF-κB通路改善急性肺损伤

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-10-17 DOI: 10.1016/j.prp.2025.156273

Yuanyuan Song , Heng Li , Yanyun Zhao , Chen Cheng , Weiwei Zhang , Yingying Sun , Taiyu Jin

Background

Acute lung injury (ALI) is a potentially lethal condition with a considerable mortality rate. This study aims to determine the protective effect of Chuanxing Qingfei Syrup (CQS) against ALI.

Methods

An ALI model was constructed by dropping lipopolysaccharide (LPS) into the trachea of mice, and mice were treated with low, medium, and high doses of CQS to evaluate the therapeutic effect of CQS. LPS-treated A549 cells were used to construct an in vitro ALI model, and low, medium, and high doses of CQS were used to treat A549 cells. The cytotoxicity and therapeutic efficacy of CQS were verified. Bioinformatic analysis was employed to predict the downstream targets of CQS. BCL10 expression in mouse lung tissues and A549 cells was detected. The phosphorylation level of IKKβ, IκBα, and NF-κB p65, and the nuclear translocation of NF-κB p65 were measured. BCL10 overexpression and treatment with the NF-κB pathway inhibitor PDTC were performed to explore their effects on A549 cell injury. Intranasal instillation of overexpressed BCL10 adeno-associated virus was performed to observe its effect on ALI mice.

Results

CQS effectively alleviated the infiltration of inflammatory cells, reduced levels of inflammatory factors, inhibited apoptosis, and alleviated lung edema in mice. CQS inhibited apoptosis in A549 cells. CQS inhibited BCL10, and BCL10 activated the IKK/IκBα/NF-κB pathway. Overexpression of BCL10 aggravated A549 cell injury and pathological changes in ALI mice. PDTC treatment mitigated LPS-induced injury in A549 cells overexpressing BCL10.

Conclusion

CQS inhibits ALI progression by targeting BCL10 and suppressing the IKK/IκBα/NF-κB pathway.

背景：急性肺损伤（ALI）是一种具有潜在致命性的疾病，死亡率相当高。本研究旨在探讨川兴清肺糖浆（CQS）对ALI的保护作用。方法将脂多糖（LPS）滴入小鼠气管，建立小鼠三ALI模型，并分别给予小鼠低、中、高剂量CQS，评价CQS对小鼠的治疗作用。采用lps处理的A549细胞构建体外ALI模型，并采用低、中、高剂量CQS处理A549细胞。验证了CQS的细胞毒性和治疗效果。采用生物信息学方法预测CQS的下游靶点。检测BCL10在小鼠肺组织和A549细胞中的表达。检测IKKβ、i -κB α、NF-κB p65磷酸化水平及NF-κB p65核易位。通过对BCL10过表达和NF-κB通路抑制剂PDTC的处理，探讨其对A549细胞损伤的影响。通过鼻内注射过表达的BCL10腺相关病毒，观察其对ALI小鼠的影响。结果scqs能有效减轻小鼠炎性细胞浸润，降低炎性因子水平，抑制细胞凋亡，减轻肺水肿。CQS抑制A549细胞凋亡。CQS抑制BCL10， BCL10激活IKK/ i -κB α/NF-κB通路。BCL10过表达加重了ALI小鼠A549细胞损伤及病理改变。PDTC处理可减轻lps诱导的过表达BCL10的A549细胞损伤。结论cqs通过靶向BCL10、抑制IKK/ i -κB α/NF-κB通路抑制ALI进展。

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引用次数: 0

Hypoxia-driven metabolic and molecular reprogramming: From tumor microenvironment to therapeutic interventions 缺氧驱动的代谢和分子重编程：从肿瘤微环境到治疗干预。

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-10-15 DOI: 10.1016/j.prp.2025.156271

Diksha Devi , Kanchan Sharma , Tabish Khan , Hema Rani , Rekha Rana , Heena Sharma , Parjinder Kaur , Lokesh Prajapati , Adil Rizwan , Moses Allieu , Sampita Pal , Vishal Kumar , Sunny Kumar

Hypoxia, characterized by reduced oxygen availability, significantly contributes to cancer development by affecting tumor growth and spread. In fast-growing tumors, the scarcity of oxygen forces cancer cells to modify their molecular structure and metabolism to survive and multiply. These alterations are predominantly governed by hypoxia-inducible factors (HIFs), with HIF-1α and HIF-2α serving crucial roles in the activation of genes related to invasion, angiogenesis, metabolic reprogramming, and metastasis. Such changes promote tumor development in low-oxygen environments and enhance resistance to conventional therapies. Hypoxia influences various aspects of cancer progression, heightening the risk of malignancy and worsening prognosis. This study investigates the fundamental mechanisms by which hypoxia influences tumor biology, including the facilitation of the epithelial-to-mesenchymal transition (EMT), the enhancement of angiogenesis through vascular endothelial growth factor (VEGF), and the metabolic shift from oxidative phosphorylation to glycolysis. In this review, we aim to elucidate the complex interaction of metabolic and molecular mechanisms within the cancer microenvironment under hypoxic conditions, which not only fosters tumor growth but also contributes to therapeutic resistance, making hypoxia a critical factor in cancer treatment strategies.

缺氧，以氧气供应减少为特征，通过影响肿瘤的生长和扩散，显著促进了癌症的发展。在快速生长的肿瘤中，氧气的缺乏迫使癌细胞改变其分子结构和新陈代谢以生存和繁殖。这些改变主要由缺氧诱导因子（hif）控制，HIF-1α和HIF-2α在侵袭、血管生成、代谢重编程和转移相关基因的激活中起着至关重要的作用。这些变化促进了肿瘤在低氧环境中的发展，并增强了对常规治疗的抵抗力。缺氧影响癌症进展的各个方面，增加恶性肿瘤的风险和恶化预后。本研究探讨了缺氧影响肿瘤生物学的基本机制，包括促进上皮细胞向间质转化（EMT），通过血管内皮生长因子（VEGF）促进血管生成，以及从氧化磷酸化到糖酵解的代谢转变。在这篇综述中，我们旨在阐明缺氧条件下癌症微环境中代谢和分子机制的复杂相互作用，这种相互作用不仅促进肿瘤生长，而且有助于治疗抵抗，使缺氧成为癌症治疗策略的关键因素。

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引用次数: 0

Sperm DNA fragmentation and yoga: A narrative review on enhancing male reproductive health 精子DNA碎片化与瑜伽：促进男性生殖健康的综述。

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-10-15 DOI: 10.1016/j.prp.2025.156269

Prabhakar Tiwari, Anjali Yadav, Deepika Kumari, Richa Mishra, Rima Dada

Infertility remains a significant global health issue, with oxidative stress and sperm DNA fragmentation (SDF) recognized as critical contributors to unexplained male infertility. SDF adversely impacts fertilization, embryo development, and assisted reproductive technology (ART) outcomes. Despite advances in diagnostics and clinical management, a large proportion of cases remain idiopathic, implicating complex genetic underpinnings involving over 2000 genes. This review synthesizes current knowledge on the mechanisms, types, and implications of DNA damage in sperm, emphasizing the need for robust diagnostic tools and targeted therapeutic strategies. Oxidative stress, driven by a combination of endogenous and environmental factors, is identified as the primary cause of SDF. While antioxidant therapy has shown mixed outcomes in clinical studies, emerging evidence supports the efficacy of non-invasive lifestyle interventions, notably yoga, in improving sperm DNA integrity. Yoga enhances mitochondrial function and antioxidant capacity, leading to reduced oxidative DNA adducts such as 8-hydroxy-2-deoxyguanosine (8OHDG) and promote the DNA repair pathways. By integrating insights from molecular biology, reproductive medicine, and holistic health practices, this review highlights the urgent need for personalized, mechanism-based approaches to male infertility and presents yoga as a promising adjunct therapy to improve sperm quality, mitigate genetic risks, and enhance ART success.

不育仍然是一个重要的全球健康问题，氧化应激和精子DNA断裂（SDF）被认为是导致不明原因男性不育的关键因素。SDF对受精、胚胎发育和辅助生殖技术（ART）结果有不利影响。尽管在诊断和临床管理方面取得了进展，但很大一部分病例仍然是特发性的，这意味着涉及2000多个基因的复杂遗传基础。这篇综述综合了目前关于精子DNA损伤的机制、类型和影响的知识，强调了对强大的诊断工具和靶向治疗策略的需求。氧化应激是SDF发生的主要原因，是内源性和环境因素共同作用的结果。虽然抗氧化疗法在临床研究中显示出好坏参半的结果，但新出现的证据支持非侵入性生活方式干预，特别是瑜伽，在改善精子DNA完整性方面的功效。瑜伽增强线粒体功能和抗氧化能力，减少氧化DNA加合物，如8-羟基-2-脱氧鸟苷（8OHDG），促进DNA修复途径。通过整合分子生物学、生殖医学和整体健康实践的见解，本综述强调了个性化、基于机制的男性不育症治疗方法的迫切需要，并提出瑜伽是一种有希望的辅助疗法，可以提高精子质量、减轻遗传风险和提高ART成功率。

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引用次数: 0

U2AF2 drives malignant progression and chemo-resistance in hepatocellular carcinoma through cooperating with SRSF1 to modulate CCND1 splice-variant expression U2AF2通过与SRSF1合作调节CCND1剪接变异体的表达，驱动肝癌的恶性进展和化疗耐药

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-10-15 DOI: 10.1016/j.prp.2025.156272

Peng Luo , Shijie Dai , Xingyuan Xu , Gaoyu Liu, Fulong Wang, Jialun Li, Qin Xiong, Yang Wang, Chunmeng Shi

Hepatocellular carcinoma (HCC) is a common malignancy with high risk of recurrence and metastasis. Growing evidences reveal that aberrant mRNA splicing represents a crucial molecular characteristic of cancer, which produces numerous and complex transcript variants to drive cancer development and progression. Here, we identified the splicing factor U2AF2 as a promising oncogenic biomarker in HCC, and subsequently explored its biological role and mechanism. Through bioinformatics analysis and clinical verification, U2AF2 was found to be significantly elevated in HCC, showing a strong correlation with the pathological grade and patient outcomes. Subsequent investigations demonstrated that U2AF2 promoted HCC growth and metastasis both in vitro and in vivo. Mechanically, U2AF2 exerted its oncogenic functions by cooperating with SRSF1 to bind to the pre-mRNA of CCND1(Cyclin D1) and facilitate the generation of CCND1b isoform. Moreover, U2AF2 could potentially be utilized for the prediction of chemo-responsiveness. Its depletion sensitized HCC cells to Doxorubicin, a first-line chemotherapy agent for advanced HCC patients. Altogether, this study deepens our understanding of U2AF2 in mRNA splicing and provides a potential therapeutic target for HCC.

肝细胞癌（HCC）是一种常见的恶性肿瘤，具有较高的复发和转移风险。越来越多的证据表明，异常的mRNA剪接是癌症的一个重要分子特征，它产生了大量复杂的转录变体，驱动癌症的发生和进展。本研究中，我们确定了剪接因子U2AF2作为HCC中一个有前景的致癌生物标志物，并随后探讨了其生物学作用和机制。通过生物信息学分析和临床验证，发现U2AF2在HCC中显著升高，与病理分级和患者预后有很强的相关性。随后的研究表明，U2AF2在体外和体内都促进了HCC的生长和转移。机械上，U2AF2通过与SRSF1合作，结合CCND1的前mrna (Cyclin D1)，促进CCND1b亚型的产生，发挥其致癌功能。此外，U2AF2可以潜在地用于预测化学反应性。它的耗竭使HCC细胞对阿霉素敏感，阿霉素是晚期HCC患者的一线化疗药物。总之，本研究加深了我们对U2AF2在mRNA剪接中的理解，并为HCC提供了一个潜在的治疗靶点。

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