Pub Date : 2025-12-01Epub Date: 2025-10-09DOI: 10.1016/j.prp.2025.156255
Xiaoyuan Ma , Zhihua Shao , Junyu Deng , Guangze Chen , Junchi Ma , Zeren Chen , Yu Zhang , Peng Han , Junsong Liu , Shan Gao , Yuan Shao , Fang Sui
Emerging evidence highlights the role of Endoplasmic Reticulum Membrane Protein Complex (EMC) subunits in tumorigenesis, yet the function of EMC8 (Endoplasmic Reticulum Membrane Protein Complex Subunit 8) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains elusive. In this study, we found EMC8 is significantly upregulated in HNSCC tissues compared to adjacent normal tissues, at both mRNA and protein levels. Kaplan-Meier survival analyses demonstrated that high EMC8 expression is associated with poorer overall survival, disease-specific survival, and progression-free interval in HNSCC patients. Further exploration into the tumor microenvironment showed that EMC8 expression negatively correlates with the infiltration of multiple immune cells, particularly CD8 + T cells, which was validated in clinical samples where high EMC8 expression corresponded to reduced CD8 + T cell infiltration. Additionally, single-cell RNA sequencing data indicated that EMC8 expression is positively associated with dedifferentiation, hypoxia, and stemness properties of HNSCC cells. Collectively, EMC8 upregulation in HNSCC correlates with poor prognosis, reduced CD8 + T cell infiltration, and aggressive phenotypes, positioning it as a potential prognostic marker with mechanistic links to immune evasion and malignancy warranting deeper exploration.
{"title":"EMC8 expression in head and neck squamous cell carcinoma: Implications for poor prognosis and deficient CD8+ T cell infiltration","authors":"Xiaoyuan Ma , Zhihua Shao , Junyu Deng , Guangze Chen , Junchi Ma , Zeren Chen , Yu Zhang , Peng Han , Junsong Liu , Shan Gao , Yuan Shao , Fang Sui","doi":"10.1016/j.prp.2025.156255","DOIUrl":"10.1016/j.prp.2025.156255","url":null,"abstract":"<div><div>Emerging evidence highlights the role of Endoplasmic Reticulum Membrane Protein Complex (EMC) subunits in tumorigenesis, yet the function of EMC8 (Endoplasmic Reticulum Membrane Protein Complex Subunit 8) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains elusive. In this study, we found EMC8 is significantly upregulated in HNSCC tissues compared to adjacent normal tissues, at both mRNA and protein levels. Kaplan-Meier survival analyses demonstrated that high EMC8 expression is associated with poorer overall survival, disease-specific survival, and progression-free interval in HNSCC patients. Further exploration into the tumor microenvironment showed that EMC8 expression negatively correlates with the infiltration of multiple immune cells, particularly CD8 + T cells, which was validated in clinical samples where high EMC8 expression corresponded to reduced CD8 + T cell infiltration. Additionally, single-cell RNA sequencing data indicated that EMC8 expression is positively associated with dedifferentiation, hypoxia, and stemness properties of HNSCC cells. Collectively, EMC8 upregulation in HNSCC correlates with poor prognosis, reduced CD8 + T cell infiltration, and aggressive phenotypes, positioning it as a potential prognostic marker with mechanistic links to immune evasion and malignancy warranting deeper exploration.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156255"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242391","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}
Pub Date : 2025-12-01Epub Date: 2025-10-15DOI: 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.
{"title":"Sperm DNA fragmentation and yoga: A narrative review on enhancing male reproductive health","authors":"Prabhakar Tiwari, Anjali Yadav, Deepika Kumari, Richa Mishra, Rima Dada","doi":"10.1016/j.prp.2025.156269","DOIUrl":"10.1016/j.prp.2025.156269","url":null,"abstract":"<div><div>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<strong>.</strong> 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.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156269"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318500","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}
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.
{"title":"Hypoxia-driven metabolic and molecular reprogramming: From tumor microenvironment to therapeutic interventions","authors":"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","doi":"10.1016/j.prp.2025.156271","DOIUrl":"10.1016/j.prp.2025.156271","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156271"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313433","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}
Pub Date : 2025-12-01Epub Date: 2025-10-20DOI: 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.
{"title":"CD47/HIF-1α circuit promotes cell proliferation in hepatocellular carcinoma","authors":"Cuicui Xu , Yuhui Pei , Xiaoman Zhang , Cuicui Wang , Min He , Zhicheng Wan , Ganyu Miao , Jun Hou , Lianghai Wang","doi":"10.1016/j.prp.2025.156275","DOIUrl":"10.1016/j.prp.2025.156275","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156275"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364454","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}
Pub Date : 2025-12-01Epub Date: 2025-10-20DOI: 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.
{"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":"2025-12-01","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}
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。
{"title":"Next generation DNA sequencing data analysis and its application in clinical genomics","authors":"Abhijit Beura , Gowrang Kasaba Manjunath , Shweta Mahalingam , Mangesh Sudhakar Rajguru , Tikam Chand Dakal , Abhishek Kumar","doi":"10.1016/j.prp.2025.156280","DOIUrl":"10.1016/j.prp.2025.156280","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156280"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417765","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}
Pub Date : 2025-12-01Epub Date: 2025-10-17DOI: 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。
{"title":"Chuanxing Qingfei Syrup ameliorates acute lung injury by suppressing BCL10 expression and blocking the IKK/IκBα/NF-κB pathway","authors":"Yuanyuan Song , Heng Li , Yanyun Zhao , Chen Cheng , Weiwei Zhang , Yingying Sun , Taiyu Jin","doi":"10.1016/j.prp.2025.156273","DOIUrl":"10.1016/j.prp.2025.156273","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>in vitro</em> 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>CQS inhibits ALI progression by targeting BCL10 and suppressing the IKK/IκBα/NF-κB pathway.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156273"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364456","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}
<div><h3>Background</h3><div>Gastric cancer (GC) is one of the leading causes of cancer-related mortality worldwide. Despite advances in treatment, the prognosis for advanced GC remains poor, highlighting the need for new therapeutic targets. Ferroptosis, a form of programmed cell death characterized by iron-dependent lipid peroxidation, has emerged as a potential pathway for cancer therapy. This study aims to identify ferroptosis-related genes in GC using transcriptomics and machine learning, and to validate the role of one key gene, Glutamic-Oxaloacetic Transaminase 1 (GOT1), in GC progression.</div></div><div><h3>Methods</h3><div>The Sangerbox platform was employed to analyze differentially expressed genes between GC tissues and adjacent non-cancerous tissues in the GSE184336 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify co-expressed gene modules from the GSE184336 dataset and their associations with phenotypes. Support Vector Machine (SVM) and Random Forest (RF) regression algorithms were applied to screen for core target genes. Quantitative Real-Time PCR (qRT-PCR) was used to analyze mRNA expression, while western blotting and immunohistochemistry (IHC) assays were used to determine protein expression. Cell proliferation was assessed using a 5-Ethynyl-2’-deoxyuridine assay, and cell migration was analyzed using a Transwell assay. Flow cytometry was used to quantify cell death. Fluorometric and colorimetric assays were performed to analyze Reactive Oxygen Species (ROS) and Fe<sup>2 +</sup> levels, respectively. A xenograft mouse model was used to evaluate the impact of GOT1 overexpression on tumor formation <em>in vivo</em>. Haematoxylin and eosin (HE) staining was used to analyze the pathological conditions of tumors.</div></div><div><h3>Results</h3><div>The analysis of the GSE184336 dataset identified 2297 dysregulated genes in GC tissues compared to adjacent non-cancerous tissues. WGCNA revealed strong correlations between gene significance and module membership in the “green,” “ivory,” and “lightsteelblue1” modules, encompassing 350 genes. Subsequent analysis identified 14 intersection genes among the 2297 dysregulated genes in GC tissues, the 350 genes from WGCNA, and the 1467 genes related to ferroptosis. Machine learning algorithms and protein-protein interaction analysis identified IDH2, BGN, IGFBP7, and GOT1 as key genes. GOT1 expression was downregulated in GC tissues with the lowest error value. Overexpression of GOT1 inhibited GC cell proliferation, migration, and induced ferroptosis, whereas these effects were reversed by treatment with Fer-1. Further, GOT1 overexpression suppressed the malignant phenotype of GC cells in vivo.</div></div><div><h3>Conclusion</h3><div>This study identified several ferroptosis-related genes in GC, with GOT1 being a critical regulator. Overexpression of GOT1 significantly inhibited GC cell proliferation and migration, and induced ferroptosis. These findings sugges
{"title":"Integrating transcriptomics and machine learning to predict ferroptosis-related genes and analyzing the role of GOT1 in gastric cancer progression","authors":"Xiao-Ling Wu , Li-Ping Lei , Shu-Rui Wu, Mei-Yan Chen, Yu-Qin Zhang, Yu-Ka Fu, Qiong-Dan Kang, Shan-Ti Lin, Pei Li, Zhang-Xing Chen","doi":"10.1016/j.prp.2025.156252","DOIUrl":"10.1016/j.prp.2025.156252","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) is one of the leading causes of cancer-related mortality worldwide. Despite advances in treatment, the prognosis for advanced GC remains poor, highlighting the need for new therapeutic targets. Ferroptosis, a form of programmed cell death characterized by iron-dependent lipid peroxidation, has emerged as a potential pathway for cancer therapy. This study aims to identify ferroptosis-related genes in GC using transcriptomics and machine learning, and to validate the role of one key gene, Glutamic-Oxaloacetic Transaminase 1 (GOT1), in GC progression.</div></div><div><h3>Methods</h3><div>The Sangerbox platform was employed to analyze differentially expressed genes between GC tissues and adjacent non-cancerous tissues in the GSE184336 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify co-expressed gene modules from the GSE184336 dataset and their associations with phenotypes. Support Vector Machine (SVM) and Random Forest (RF) regression algorithms were applied to screen for core target genes. Quantitative Real-Time PCR (qRT-PCR) was used to analyze mRNA expression, while western blotting and immunohistochemistry (IHC) assays were used to determine protein expression. Cell proliferation was assessed using a 5-Ethynyl-2’-deoxyuridine assay, and cell migration was analyzed using a Transwell assay. Flow cytometry was used to quantify cell death. Fluorometric and colorimetric assays were performed to analyze Reactive Oxygen Species (ROS) and Fe<sup>2 +</sup> levels, respectively. A xenograft mouse model was used to evaluate the impact of GOT1 overexpression on tumor formation <em>in vivo</em>. Haematoxylin and eosin (HE) staining was used to analyze the pathological conditions of tumors.</div></div><div><h3>Results</h3><div>The analysis of the GSE184336 dataset identified 2297 dysregulated genes in GC tissues compared to adjacent non-cancerous tissues. WGCNA revealed strong correlations between gene significance and module membership in the “green,” “ivory,” and “lightsteelblue1” modules, encompassing 350 genes. Subsequent analysis identified 14 intersection genes among the 2297 dysregulated genes in GC tissues, the 350 genes from WGCNA, and the 1467 genes related to ferroptosis. Machine learning algorithms and protein-protein interaction analysis identified IDH2, BGN, IGFBP7, and GOT1 as key genes. GOT1 expression was downregulated in GC tissues with the lowest error value. Overexpression of GOT1 inhibited GC cell proliferation, migration, and induced ferroptosis, whereas these effects were reversed by treatment with Fer-1. Further, GOT1 overexpression suppressed the malignant phenotype of GC cells in vivo.</div></div><div><h3>Conclusion</h3><div>This study identified several ferroptosis-related genes in GC, with GOT1 being a critical regulator. Overexpression of GOT1 significantly inhibited GC cell proliferation and migration, and induced ferroptosis. These findings sugges","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156252"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313444","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}
Pub Date : 2025-12-01Epub Date: 2025-10-15DOI: 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.
{"title":"U2AF2 drives malignant progression and chemo-resistance in hepatocellular carcinoma through cooperating with SRSF1 to modulate CCND1 splice-variant expression","authors":"Peng Luo , Shijie Dai , Xingyuan Xu , Gaoyu Liu, Fulong Wang, Jialun Li, Qin Xiong, Yang Wang, Chunmeng Shi","doi":"10.1016/j.prp.2025.156272","DOIUrl":"10.1016/j.prp.2025.156272","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156272"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364457","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}
Pub Date : 2025-12-01Epub Date: 2025-10-22DOI: 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.
{"title":"Mechanistic insights into plant-derived natural compounds for the treatment of skin cancer: Targeting molecular signaling for therapeutic intervention","authors":"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","doi":"10.1016/j.prp.2025.156277","DOIUrl":"10.1016/j.prp.2025.156277","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156277"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145392056","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}
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