Rabia Faizan , Muhammad Naveed , Inmaculada Bellido Estevez , Nimra Hanif , Arooj Arshad , Tariq Aziz , Abdulhakeem S. Alamri , Walaa F. Alsanie , Majid Alhomrani
{"title":"Computational exploration of natural inhibitors against toxin-associated proteins in Naegleria fowleri Karachi strain","authors":"Rabia Faizan , Muhammad Naveed , Inmaculada Bellido Estevez , Nimra Hanif , Arooj Arshad , Tariq Aziz , Abdulhakeem S. Alamri , Walaa F. Alsanie , Majid Alhomrani","doi":"10.1016/j.prp.2025.156184","DOIUrl":"10.1016/j.prp.2025.156184","url":null,"abstract":"<div><div><em>Naegleria fowleri</em>, a thermophilic, free-living amoeba, is the causative agent of Primary Amoebic Meningoencephalitis (PAM), a rare but nearly always fatal brain infection. The rising number of PAM cases in Karachi, Pakistan, particularly linked to a unique local strain, underscores the urgent need for effective therapeutic interventions. In this study, a computational approach was employed to identify potential natural inhibitors targeting toxin-producing proteins from the <em>N. fowleri</em> Karachi strain. Eight exons encoding toxin proteins were retrieved from the Soft Berry Fgenesh 2.6 database, annotated using Gene Ontology tools, and subjected to physicochemical characterization. Hypothetical protein 4 was prioritized for molecular docking in the NF001 Karachi strain of <em>Naegleria fowleri</em> because it was identified through comparative mapping with previously known strains. Its function was predicted based on sequence alignment, suggesting that it may serve as a promising target for drug docking studies. Protein structures were predicted via AlphaFold2 and validated using MolProbity and Ramachandran plot analysis. Virtual screening of phytochemicals was conducted using PyRx, identifying himbacine as the most promising ligand with a binding affinity of –8.7 kcal/mol against hypothetical protein 4. Binding interactions were further confirmed using CB-Dock2, which revealed key binding residues involved in hydrogen bonding and hydrophobic interactions. ADMET profiling indicated that himbacine possesses favorable pharmacokinetics, non-toxicity, and high gastrointestinal absorption. Density Functional Theory (DFT) analysis showed a small HOMO-LUMO energy gap, indicating high reactivity and binding potential. Molecular dynamics simulations confirmed the structural stability of the protein-ligand complex over time. These findings suggest that himbacine, a plant-derived compound, holds promise as a safe and effective inhibitor against <em>N. fowleri</em> infections. However, further in vitro and in vivo studies are essential to validate its therapeutic potential.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156184"},"PeriodicalIF":3.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894757","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}
Ting-Ting Yang , Xin-Xin Ma , Xuan Zhang , Zhen-Qing Han , Shuang Zhang , Qi Wang , Hong-Wei Dong , Jia-Ren Liu
{"title":"β-Ionone promotes ferroptosis of human gastric cancer cells by inhibiting the Wnt/β-catenin pathway in vitro and in vivo","authors":"Ting-Ting Yang , Xin-Xin Ma , Xuan Zhang , Zhen-Qing Han , Shuang Zhang , Qi Wang , Hong-Wei Dong , Jia-Ren Liu","doi":"10.1016/j.prp.2025.156180","DOIUrl":"10.1016/j.prp.2025.156180","url":null,"abstract":"<div><div>β-Ionone (BI) has shown the potent inhibitory malignant progression of multiple tumors including gastric cancer in vitro and in vivo. However, the mechanism by which BI inhibits gastric cancer remains to be clarified, especially in ferroptosis, which is a new form of programmed cell death. The aim of this study was to investigate whether BI could induce ferroptosis in gastric cancer and the underlying mechanisms. The results manifested that BI obviously inhibited cell viability and increased the Fe<sup>2 +</sup> level, total reactive oxygen species (ROS) and lipid ROS levels and the malondialdehyde (MDA) concentrations, but reduced the mitochondrial membrane potential (MMP) and the expression of SLC7A11 and GPX4 in MKN45 cells and AGS cells (<em>P</em> < 0.05 or <em>P</em> < 0.01). Besides, BI also arrested cell cycle and decreased the expression of Cyclin D1 and CDK4 (<em>P</em> < 0.05 or <em>P</em> < 0.01). Mechanistically, BI reduced the levels of β-catenin and pGSK-3β/GSK-3β in MKN45 cells and AGS cells (<em>P</em> < 0.05 or <em>P</em> < 0.01). Nevertheless, pretreatment with lithium chloride (LiCl), an inhibitor of GSK-3β, reversed BI-induced ferroptosis and cell cycle arrested in MKN45 cells (<em>P</em> < 0.05). In addition, BI effectively inhibited the growth of gastric cancer xenografts and downregulated the levels of GPX4, SLC7A11, PCNA, β-catenin and pGSK-3β/GSK-3β (<em>P</em> < 0.05 or <em>P</em> < 0.01). Collectively, our study reveals that BI inhibits proliferation of gastric cancer cells by induction ferroptosis via the Wnt/β-catenin signaling pathway and provides a novel therapy for gastric cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156180"},"PeriodicalIF":3.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863894","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}
Jianwei Shi , Linchuan Liang , Xiangzhi Meng , Jiacong Wei , Weijian Song , Boxuan Zhou , Mei Liang , Minjun Du , Yushun Gao
{"title":"Pathomics predict CD40LG expression and clinical prognosis in lung adenocarcinoma based on haematoxylin–eosin-stained images","authors":"Jianwei Shi , Linchuan Liang , Xiangzhi Meng , Jiacong Wei , Weijian Song , Boxuan Zhou , Mei Liang , Minjun Du , Yushun Gao","doi":"10.1016/j.prp.2025.156181","DOIUrl":"10.1016/j.prp.2025.156181","url":null,"abstract":"<div><h3>Aim</h3><div>To develop and validate a pathomics model that non-invasively predicts CD40LG expression from routine haematoxylin–eosin (HE) slides and clarifies its prognostic value in lung adenocarcinoma (LUAD).</div></div><div><h3>Methods</h3><div>HE whole-slide images from 327 TCGA-LUAD cases were randomly split into training (70 %) and internal-validation (30 %) sets; an external cohort of 89 patients from the Cancer Hospital Chinese Academy of Medical Sciences provided independent validation. From 1488 quantitative pathomic features, maximum-relevance minimum-redundancy and recursive feature elimination identified the most informative variables. A gradient-boosting machine (GBM) classified tumours as CD40LG-high or -low. Model performance was assessed with ROC curves, area under the curve (AUC), calibration plots and decision-curve analysis. Propensity-score matching (PSM) balanced baseline clinicopathologic factors in the TCGA cohort. Immune-cell deconvolution (CIBERSORTx) and gene-set variation analysis explored biological correlates of the pathomics score (PS).</div></div><div><h3>Results</h3><div>After PSM, high CD40LG expression remained an independent protective factor for overall survival (OS) in the TCGA cohort (HR = 0.601, <em>p</em> = 0.006) and in the external cohort. The GBM model achieved AUCs of 0.809 (training), 0.736 (internal validation) and 0.725 (external validation). The derived PS independently predicted improved OS and correlated with greater infiltration of naïve B cells and CD8⁺ T cells. Genes linked to epithelial-to-mesenchymal transition—including IL32 and TGM2—were up-regulated in tumours with high PS.</div></div><div><h3>Conclusions</h3><div>This pathomics model accurately infers CD40LG expression from standard histology and stratifies LUAD patients by prognosis, offering a practical, low-cost tool for precision oncology while providing insight into immune-mediated disease mechanisms.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156181"},"PeriodicalIF":3.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863947","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}
{"title":"Pathological extranodal extension in head and neck cancer: A prognostic biomarker with therapeutic ramifications and diagnostic pitfalls","authors":"Shikhar Chohan, Sufian Zaheer","doi":"10.1016/j.prp.2025.156183","DOIUrl":"10.1016/j.prp.2025.156183","url":null,"abstract":"<div><div>Extranodal extension (ENE), defined as the pathological spread of metastatic tumor cells beyond the lymph node capsule into adjacent soft tissues, represents a critical prognostic biomarker in head and neck squamous cell carcinoma (HNSCC). Its presence correlates with aggressive tumor biology, increased risk of locoregional recurrence, distant metastasis, and reduced survival, thereby influencing staging systems and therapeutic strategies. The 8th edition of the AJCC Cancer Staging Manual has formally incorporated ENE into nodal classification for select HNSCC subsites, with the 9th edition of UICC (2025) extending this to HPV-positive oropharyngeal carcinomas. Despite its prognostic significance, diagnostic evaluation of ENE—particularly microscopic ENE—remains challenging due to interobserver variability, ambiguous histological thresholds, and limitations of imaging modalities. The emergence of artificial intelligence and radiomics offers promising tools for improving ENE detection. Moreover, recent studies underscore the importance of quantifying ENE extent, with macroscopic ENE (>2 mm) portending a worse prognosis and guiding the need for adjuvant chemoradiotherapy. However, controversies persist, especially regarding its role in HPV-positive tumors and the utility of traditional cutoffs. This review synthesizes current evidence on the biological underpinnings, diagnostic complexities, therapeutic implications, and future research directions related to ENE in HNSCC, advocating for standardized assessment protocols to optimize patient management and outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156183"},"PeriodicalIF":3.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863892","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}
Jingjing Xu , Jiayan Feng , Feng Tian , Di Ding , Jing Zhao , Yangyang Ma
{"title":"Desmoplastic small round cell tumor in children: Report of six cases","authors":"Jingjing Xu , Jiayan Feng , Feng Tian , Di Ding , Jing Zhao , Yangyang Ma","doi":"10.1016/j.prp.2025.156182","DOIUrl":"10.1016/j.prp.2025.156182","url":null,"abstract":"<div><h3>Purpose</h3><div>To study the clinical, pathological, and prognostic features of desmoplastic small round cell tumor (DSRCT).</div></div><div><h3>Methods</h3><div>Six DSRCTs were retrieved from the archives of the Department of Pathology at Children’s Hospital of Fudan University. Clinical manifestations, radiologic characteristics, pathological features, and treatment methods were analyzed, and the postoperative status was evaluated at follow-up.</div></div><div><h3>Results</h3><div>All patients were males, aged 7–13 years (mean, 10; median, 10) at diagnosis. Primary tumor sites were the abdominal cavity (2/6), pleura, mediastinum, pelvic cavity, and pancreas (1/6 each). Presenting symptoms were abdominal distension and pain (3/6), coughing (2/6), and neck mass (1/6). Tumor diameters ranged from 3.3–21.7 cm (mean, 8.8; median, 7.5). Histologically, all tumors showed irregularly shaped nests of small round cells in abundant desmoplastic stroma. Cells had scant eosinophilic cytoplasm and small hyperchromatic nuclei with inconspicuous nucleoli. One case showed obvious epithelioid differentiation post-chemotherapy. Immunohistochemically, tumors were positive for CK (AE1/AE3) (5/6), desmin (6/6), Synaptophysin (Syn) (4/6), and CD99 (2/6). Ki-67 proliferation indices ranged from 20–70 %. Fluorescence in situ hybridization demonstrated EWSR1::WT1 gene fusion in all cases. Gene sequencing revealed EWSR1exon8-WT1exon8 fusion in DNA and RNA sequencing and WT1 exon7-EWSR1exon9 fusion in DNA sequencing in one case. Two cases underwent partial resection, one gross total resection, and three biopsy only. All received chemotherapy; some received concurrent radiotherapy or immunotherapy. Follow-up intervals were 7–26 months. Median overall survival was 24 months; four patients died, and two remain alive. The estimated 2-year overall survival ratio was 31.2 %.</div></div><div><h3>Conclusions</h3><div>DSRCT is rare and may exhibit typical clinicopathological and distinct genetic features in rare locations. This should be considered when encountering small round blue cell tumors at unusual sites to avoid misdiagnosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156182"},"PeriodicalIF":3.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863909","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}
Jianfeng Wu , Mingyang Li , Danhui Zhao , Yixiong Liu, Wanni Xu, Lu Wang, Zhenyu Ke, Zhe Wang
{"title":"Primary pulmonary spindle cell sarcoma with novel MBNL2::NUTM1 fusion and associated langerhans cell hyperplasia","authors":"Jianfeng Wu , Mingyang Li , Danhui Zhao , Yixiong Liu, Wanni Xu, Lu Wang, Zhenyu Ke, Zhe Wang","doi":"10.1016/j.prp.2025.156179","DOIUrl":"10.1016/j.prp.2025.156179","url":null,"abstract":"<div><div><em>NUTM1</em>-rearranged sarcomas are rare, genetically diverse tumors with variable histologic features and fusion partners. Their diagnosis remains challenging, especially in low-grade or unusual presentations. We describe the first reported case of a pulmonary spindle cell sarcoma with <em>MBNL2::NUTM1</em> fusion in a 67-year-old man. The patient presented with multiple lung masses and respiratory symptoms. Histology showed spindle cell proliferation with mild atypia and areas rich in eosinophils, lymphocytes, and Langerhans cells. Immunohistochemistry revealed NUT, CD31, SMA, and Cyclin D1 positivity in tumor cells; CD1a and Langerin were positive in Langerhans cells. RNA-based sequencing confirmed an in-frame fusion between <em>MBNL2</em> (exon 7) and <em>NUTM1</em> (exon 3). PET-CT(Positron emission tomography–computed tomography) revealed widespread metastasis despite the tumor’s low-grade morphology. This case expands the spectrum of NUTM1-rearranged sarcomas and highlights the potential for misdiagnosis in low-grade cases. NUT immunostaining and molecular testing are essential for accurate classification of undifferentiated or spindle cell tumors.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156179"},"PeriodicalIF":3.2,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858392","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}
Qinhan Fang , Yuetong Li , Yishi Wang , Nan Mu , Heng Ma , Lu Yu
{"title":"Parthanatos: A redox-dependent cell death pathway in cardiovascular disease and myocardial aging","authors":"Qinhan Fang , Yuetong Li , Yishi Wang , Nan Mu , Heng Ma , Lu Yu","doi":"10.1016/j.prp.2025.156178","DOIUrl":"10.1016/j.prp.2025.156178","url":null,"abstract":"<div><div>Parthanatos, a form of programmed cell death that is heavily dependent on redox imbalance, is gaining attention for its important role in cardiovascular disease (CVD) and myocardial aging. Its core mechanism involves hyperactivation of poly (ADP-ribose) polymerase-1 (PARP1), triggered primarily by oxidative stress-induced DNA damage. This hyperactivation initiates a detrimental cascade: excessive consumption of NAD+ and ATP leads to cellular energy crisis, while the resultant accumulation of poly (ADP-ribose) (PAR) polymers facilitates the nuclear translocation of apoptosis-inducing factor (AIF), culminating in large-scale DNA fragmentation and cell demise. Crucially, this pathway intertwines with oxidative stress, forming a vicious cycle that amplifies cellular damage. Within CVD, parthanatos is implicated in the pathogenesis of myocardial ischemia/reperfusion (MI/R) injury, atherosclerosis, and heart failure. Furthermore, in myocardial aging, the age-related accumulation of oxidative stress and DNA damage promotes parthanatos activation, contributing to cardiomyocyte loss, fibrosis, and functional decline. Understanding this redox-dependent death pathway reveals novel therapeutic targets, including PARP1 inhibitors, strategies to block AIF translocation, NAD+ precursors to restore redox and energy balance, and exercise interventions that enhance antioxidant defenses. Elucidating the intricate interplay between parthanatos and redox signaling offers significant potential for developing interventions to combat CVD and age-related cardiac dysfunction.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156178"},"PeriodicalIF":3.2,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863891","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}
{"title":"CDKN2A alternations in non-small cell lung cancer: An evaluation using next-generation sequencing","authors":"Xu Feng , Heng Chang , Yuyin Xu , Chengli Yu , Qianlan Yao , Liqin Jia , Xiaoli Zhu , Xiaoyan Zhou , Qianming Bai","doi":"10.1016/j.prp.2025.156177","DOIUrl":"10.1016/j.prp.2025.156177","url":null,"abstract":"<div><h3>Background</h3><div>Next-generation sequencing (NGS) is widely used for assessing CDKN2A status in cancers due to its high throughput and efficiency. However, discrepancies between NGS and fluorescence in situ hybridization (FISH)—the gold standard for detecting copy number variations (CNVs)—are occasionally observed. This study aimed to evaluate the accuracy of NGS in detecting CDKN2A deletions by comparing it with FISH.</div></div><div><h3>Methods</h3><div>A total of 1118 non-small cell lung cancer (NSCLC) patients who underwent NGS at Fudan University Shanghai Cancer Center (FUSCC) were retrospectively analyzed. Among them, 56 patients were identified with CDKN2A copy number deletions by NGS, and 51 cases with sufficient tissue were further validated by FISH.</div></div><div><h3>Results</h3><div>FISH confirmed CDKN2A deletion in 88.2 % (45/51) of cases identified by NGS. Among these, 93.3 % (42/45) showed homozygous deletions and 6.7 % (3/45) showed heterozygous deletions. The remaining 11.8 % (6/51) had normal CDKN2A copy number by FISH, with CDKN2A/CEP9 ratios ranging from 0.71 to 1.09. These discordant cases had intermediate CN values by NGS (average: 1.02), unstable CNV baselines, and in most cases (>30 %) evidence of haploidy, which may have contributed to misclassification.</div></div><div><h3>Conclusions</h3><div>While NGS demonstrates high concordance with FISH in detecting CDKN2A deletions, false positives may occur, particularly in samples with intermediate CN values, low tumor purity, or unstable CNV baselines. These factors should be carefully evaluated when interpreting NGS-based CDKN2A CNV results in clinical practice.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156177"},"PeriodicalIF":3.2,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863908","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}
{"title":"Evaluation of the LAMP-IDE-AI platform for the detection of the HLA-B*15:02 allele in clinical application","authors":"Ting Wu , Yaoyao Jia , Jing Wu , Lina Liao , Qiongzhi Yin , Cheng Jin , Jianxiong Wang , Qiaoling Chen","doi":"10.1016/j.prp.2025.156176","DOIUrl":"10.1016/j.prp.2025.156176","url":null,"abstract":"<div><div>The <em>HLA-B*15:02</em> allele is strongly associated with adverse drug reactions induced by aromatic antiseizure medications such as carbamazepine and oxcarbazepine. Consequently, it is strongly recommended to test for the presence of the <em>HLA-B*15:02</em> allele before prescribing these medications. Traditional HLA genotyping methods (e.g. polymerase chain reaction or Sanger sequencing) require laboratory environments and expert personnel, resulting in a typical report turnaround time of 1–2 weeks. In this study, we developed a rapid point-of-care test (POCT) using the LAMP-IDE-AI platform for the automatic detection of the <em>HLA-B*15:02</em> allele within one hour. We evaluated the platform's performance using blood samples collected from 537 children presented with a convulsion, comparing the results obtained with the LAMP-IDE-AI platform to those from PCR tests and further verifying them with Sanger Sequencing. The LAMP-IDE-AI platform exhibited 100 % sensitivity, correctly detecting all 25 positive samples. Meanwhile it demonstrated a specificity of 99.8 %, with only one sample yielding a \"False Positive\" result. These findings suggest that the LAMP-IDE-AI platform could potentially serve as a rapid, automated, simple, and accurate POCT for detecting the <em>HLA-B*15:02</em> allele in clinical application.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156176"},"PeriodicalIF":3.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863893","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}
Tonghan Li , Dongfang Wang , Ligang Xu , Zhikai Xu , Zhanfei Li , Xiangjun Bai , Hong Zhao , Jian Yang , Yukun Liu , Yuchang Wang
{"title":"The role of Heme oxygenase-1 (HO-1) in sepsis-associated organ damage: A systematic review","authors":"Tonghan Li , Dongfang Wang , Ligang Xu , Zhikai Xu , Zhanfei Li , Xiangjun Bai , Hong Zhao , Jian Yang , Yukun Liu , Yuchang Wang","doi":"10.1016/j.prp.2025.156175","DOIUrl":"10.1016/j.prp.2025.156175","url":null,"abstract":"<div><div>Sepsis-induced myopathy is a significant cause of intensive care unit-acquired weakness (ICUAW) and a leading cause of mortality in ICU patients. ICUAW primarily affects the respiratory muscles and limb skeletal muscles, leading to prolonged mechanical ventilation and bedridden periods. This condition increases the risk of complications such as pneumonia, atelectasis, and lower extremity venous thrombosis, thereby impacting patients' quality of life and, in severe cases, jeopardizing their lives. The pathogenesis of sepsis-induced myopathy is complex, and currently, there are no effective preventive or therapeutic measures available. Heme oxygenase-1 (HO-1) catalyzes the metabolism of heme, resulting in the production of carbon monoxide (CO), biliverdin, and ferritin. It possesses anti-inflammatory, antioxidant stress response, anti-apoptotic, and tissue perfusion improvement functions. Studies have demonstrated a correlation between HO-1 and the occurrence and progression of multiple organ dysfunction syndrome in sepsis, as well as its ability to ameliorate skeletal muscle dysfunction caused by various diseases. Based on the existing literature on HO-1, sepsis, and skeletal muscle myopathy, this review aims to explore the potential mechanisms and therapeutic potential of HO-1 in the treatment of sepsis-induced myopathy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156175"},"PeriodicalIF":3.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880079","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}