Pathology, research and practice最新文献

{"title":"CSB6B attenuates renal inflammation and fibrosis by inhibiting the activation of NLRP3 inflammasome through the NLRP3/Caspase-1/GSDMD/IL-1β signaling pathway","authors":"Shuo Chen ,&nbsp;Yonghong Zhu ,&nbsp;Tong Chen ,&nbsp;Yanyan Xu ,&nbsp;Qiuling Fan","doi":"10.1016/j.prp.2025.156286","DOIUrl":"10.1016/j.prp.2025.156286","url":null,"abstract":"<div><h3>Context</h3><div>Diabetic Kidney Disease (DKD) is a significant complication and leading cause of death in both type 1 and type 2 diabetes, as well as the primary cause of chronic kidney disease. Macrophage migration inhibitory factor (MIF) activates the NLRP3 inflammasome. Chicago sky blue 6B (CSB6B) is a MIF inhibitor with therapeutic potential in various inflammatory diseases, but its effect on DKD remains unexplored.</div></div><div><h3>Materials and methods</h3><div>HK-2 cell was used as the in vitro cell model. For the in vivo animal model, The db/db mice were randomly divided into three subgroups: the diabetic nephropathy model group, the low-dose CSB6B intervention group (2 mg/kg), and the high-dose CSB6B intervention group (8 mg/kg), with drug administration via intraperitoneal injection twice weekly for 12 weeks. CCK-8 assessed CSB6B toxicity, while qPCR measured MIF mRNA expression. Western blot, immunohistochemistry and ELISA detected protein expression level, and LDH release assessed membrane integrity. Histological analysis evaluated renal pathological changes.</div></div><div><h3>Results</h3><div>CSB6B significantly inhibited the secretion of inflammatory cytokines interleukin-1β (IL-1β) and TGF-β1 from high-glucose-stimulated HK-2 cells without affecting their viability. CSB6B effectively inhibited the expression and secretion of MIF in high-glucose-stimulated HK-2 cells, down-regulated the expression of NLRP3, suppressed the activation of NLRP3 inflammasomes, reduced the production of cell pyroptosis-related proteins, and significantly decreased collagen I and FN expression. CSB6B treatment significantly reduced the body weight, blood glucose, blood creatinine, urine ACR, and NGAL of db/db mice, and improved the pathological damage of diabetic nephropathy. CSB6B effectively reduced the expression level of MIF protein in diabetic nephropathy mice, down-regulated the expression of NLRP3, Caspase-1, GSDMD, IL-1β, Collagen I and FN in the renal cortex of diabetic nephropathy mice.</div></div><div><h3>Conclusions</h3><div>CSB6B mitigated DKD by inhibiting the NLRP3/Caspase-1/GSDMD pyroptosis signaling pathway, suppressed cell pyroptosis, reduced cytokine secretion, and decreasd extracellular matrix accumulation. CSB6B showed promise as a potential therapeutic for DKD.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156286"},"PeriodicalIF":3.2,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518577","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":"Therapeutic potential of natural compounds in the management of chronic diseases: Targeting PINK1–Parkin pathway","authors":"Naglaa F. Khedr ,&nbsp;Hend M. Selim ,&nbsp;Gamal A. Abourayya","doi":"10.1016/j.prp.2025.156284","DOIUrl":"10.1016/j.prp.2025.156284","url":null,"abstract":"<div><div>Chronic diseases like neurodegenerative disorders, musculoskeletal issues, metabolic diseases, cancer, liver and kidney disorders are increasingly linked to mitochondrial dysfunction. PINK1-Parkin-mediated mitophagy, a vital autophagic process, plays a central role in maintaining cellular homeostasis by selectively eliminating damaged mitochondria, which is crucial for preserving mitochondrial integrity and preventing reactive oxygen species accumulation. Activation of the PINK1-Parkin signaling pathway has emerged as a promising therapeutic strategy to restore mitochondrial function and attenuate disease progression. Recent studies have demonstrated that natural PINK1-Parkin activators offer significant therapeutic potential for treating a wide range of chronic diseases by modulating mitochondrial dynamics, alleviating cellular inflammation, and preventing mitochondrial damage. This review provides an in-depth analysis of the molecular mechanisms underlying PINK1-Parkin signaling, discusses the therapeutic benefits of natural activators, and presents them as a compelling strategy for addressing mitochondrial dysfunction and mitigating the progression of chronic diseases.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156284"},"PeriodicalIF":3.2,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145506307","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":"Oxidative stress and neuronal alteration: Mitochondrial dysfunction as a key player in intractable epilepsy - a narrative review","authors":"Muhammad Liaquat Raza ,&nbsp;Mustafa Hussain Imam ,&nbsp;Warisha Zehra ,&nbsp;Insa Binte Anwar ,&nbsp;Rukhsar Mehdi","doi":"10.1016/j.prp.2025.156285","DOIUrl":"10.1016/j.prp.2025.156285","url":null,"abstract":"<div><div>Drug-resistant epilepsy (DRE) still poses one of the greatest therapeutic challenges, afflicting about one-third of all patients with epilepsy in the world. Despite spectacular advances in the fields of anti-seizure medications and neurostimulation techniques, treatment outcomes in DRE have reached plateau levels, signifying an urgent need for better mechanistic understanding and therapeutic strategies. New evidence increasingly elucidates mitochondrial dysfunction as a lens through which to understand seizure generation, pharmacoresistance, and disease progression. Mitochondria are regulators of ATP production, calcium buffering, and redox homeostasis; disruption of any such pathway will result in neuronal hyperexcitability, oxidative injury, and cell death. Moreover, mitochondrial DNA mutations and heteroplasmy threshold can correlate with seizure onset, seizure severity, and <strong>Response</strong> to treatment, thus being potential biomarkers for risk stratification. This narrative review surveys both preclinical and clinical evidence for mitochondrial dysfunction in epilepsy, examining oxidative stress pathways, mitophagy, and mitochondrial permeability transition pore opening as key mechanisms of neuronal vulnerability. We subsequently analyze various preclinical models of mitochondrial dysfunction, pointing out their respective strengths and weaknesses. Emerging therapeutic strategies, encompassing pharmacological agents, gene therapy, diet, and natural compounds, are then reviewed, which aim to resolve issues surrounding mitochondrial health on a molecular basis. By straddling the mechanistic and clinical narratives, this work foregrounds mitochondrial-centered approaches as promises for both the diagnostic and therapeutic arsenal in the management of DRE.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156285"},"PeriodicalIF":3.2,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518578","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":"PTEN mutation status in uterine carcinosarcomas: A comprehensive overview and a new diagnostic approach","authors":"Maccio Livia ,&nbsp;Bragantini Emma ,&nbsp;Piermattei Alessia ,&nbsp;Santoro Angela ,&nbsp;Zannoni Gian Franco","doi":"10.1016/j.prp.2025.156278","DOIUrl":"10.1016/j.prp.2025.156278","url":null,"abstract":"<div><div>Uterine carcinosarcomas (UCS), also known as malignant mixed Müllerian tumors, are rare and aggressive neoplasms characterized by the coexistence of carcinomatous (epithelial) and sarcomatous (mesenchymal) components. PTEN (Phosphatase and Tensin Homolog) mutations, a hallmark of endometrioid-type carcinomas, play a significant role in the pathogenesis and histological presentation of a subset of uterine carcinosarcomas, contributing to their aggressive behavior and poor prognosis. This overview synthesizes the current understanding of PTEN mutations in carcinosarcomas and their implications for clinical management and therapy. A new approach based on morphological, immunohistochemical, and molecular characteristics is proposed.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156278"},"PeriodicalIF":3.2,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467116","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":"Epigenetic regulation of circulating tumor cells in precision oncology","authors":"Husni Farah ,&nbsp;Munthar Kadhim Abosaoda ,&nbsp;Hayjaa Mohaisen Mousa ,&nbsp;S. Renuka Jyothi ,&nbsp;Priya Priyadarshini Nayak ,&nbsp;J. Bethanney Janney ,&nbsp;Gurjant Singh ,&nbsp;Ashish Singh Chauhan","doi":"10.1016/j.prp.2025.156282","DOIUrl":"10.1016/j.prp.2025.156282","url":null,"abstract":"<div><div>Cancer metastasis causes the majority of cancer-related deaths. During metastasis, invasive tumor cells enter the bloodstream and become circulating tumor cells. These cells eventually populate the secondary organs. In addition to genetic mutations, epigenetic changes (such as DNA methylation, histone modifications, and noncoding RNA-associated changes) are important for regulating gene expression and preserving chromatin integrity in tumor cells. Dysregulation of these epigenetic patterns is critical for carcinogenesis, tumor growth, and metastatic spread. We presented an overview of CTC biology, including essential mechanisms such as epithelial-mesenchymal transition (EMT) and immune evasion. We discussed how epigenetic reprogramming of CTCs also occurs post-transcriptionally via non coding RNAs, The subject then moves to how epigenetic changes in CTCs affect these processes throughout migration, survival in circulation, and metastatic seeding. The following sections discuss the clinical implications of addressing CTC epigenetics, proposing CTC epigenetic changes as prospective biomarkers for early cancer detection, prognosis, and targeted therapy intervention to improve patient outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156282"},"PeriodicalIF":3.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467117","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":"Staphylococcal enterotoxins in cancer immunotherapy: An overview of translational advances and targeting strategies","authors":"Abbas Ali Imani Fooladi ,&nbsp;William C. Cho ,&nbsp;Russel J. Reiter ,&nbsp;Mina Alimohammadi ,&nbsp;Najma Farahani ,&nbsp;Kiavash Hushmandi","doi":"10.1016/j.prp.2025.156283","DOIUrl":"10.1016/j.prp.2025.156283","url":null,"abstract":"<div><div>Staphylococcal enterotoxins (SEs) are superantigens that polyclonally activate T cells by cross-linking MHC class II on antigen-presenting cells with T cell receptor (TCR) Vβ regions, generating potent IL-2/IFN-γ/TNF responses distinct from conventional peptide–MHC–restricted activation. This review synthesizes mechanistic and translational evidence for SEs in oncology, emphasizing disease-relevant contexts and advanced engineering strategies that improve therapeutic index. Preclinical studies demonstrate antitumor activity across melanoma, glioblastoma, renal cell carcinoma, bladder cancer, hepatocellular carcinoma, colorectal cancer, breast cancer, squamous cell carcinoma, and hematologic malignancies (e.g., acute myeloid leukemia, lymphoma). Tumor-targeted superantigen platforms, such as antibody or ligand–SE fusion proteins and oncolytic vectors encoding Ses, concentrate activity intratumorally, increase intratumoral IFN-γ/TNF, reduce proliferation and angiogenesis, and enhance necrosis while limiting systemic exposure. Engineered SE variants (for example, SEB with attenuated pyrogenicity) and localized delivery further mitigate risks associated with cytokine release. Early clinical experiences with SE-based constructs and SE-modified tumor vaccines report feasibility and signals of activity in head and neck cancer, glioma, renal cell carcinoma, and myeloma, but small, heterogeneous studies limit definitive conclusions. Although SEs can trigger cytokine storm and off-target activation via MHC II on healthy tissues, risk can be reduced through intratumoral/regional dosing, tumor-targeted fusions, dose–schedule optimization, and indication selection informed by MHC II biology; paradoxical, disease-specific effects (e.g., in cutaneous T-cell lymphoma) highlight the importance of microbiome-aware protocols. Priorities for translation include disease-focused development in MHC II–II-permissive tumors, combinations with immune checkpoint inhibitors, and biomarker-anchored trials integrating multi-omics and patient selection. With targeted engineering and controlled delivery, SEs can evolve from broadly inflammatory agents into precise immuno-oncology tools with meaningful clinical impact. This review underscores that, with targeted engineering, controlled delivery, and biomarker-guided patient selection, SEs can be advanced from broadly inflammatory agents to precise immuno-oncology platforms ready for rigorous clinical evaluation.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156283"},"PeriodicalIF":3.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445625","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":"Circulating biomarkers in osteoarthritis: a systematic review unveiling key trends and future prospects","authors":"Francesca Veronesi,&nbsp;Francesca Salamanna,&nbsp;Giulia Sacchi,&nbsp;Veronica Borsari,&nbsp;Gianluca Giavaresi","doi":"10.1016/j.prp.2025.156281","DOIUrl":"10.1016/j.prp.2025.156281","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a progressive and chronic joint disorder characterized by cartilage degradation, joint inflammation, and pain, leading to reduced mobility and quality of life. One of the major challenges in OA management is the early diagnosis and effective monitoring of disease progression, due to the lack of specific and sensitive biomarkers. This systematic review aimed to evaluate circulating biomarkers, including serum proteins and microRNAs (miRNAs), for their potential diagnostic and prognostic value in OA. A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus for studies published from March 18, 2015, to March 18, 2025, resulting in 471 studies. After applying inclusion and exclusion criteria, 18 clinical studies and among them, 12 investigated circulating proteins and 6 focused on miRNAs. Several serum proteins such as interleukins (IL-6, IL-1β, IL-38), complement 3 (C3), autotaxin (ATX), pentraxin 3 (PTX3), hyaluronic acid (HA), and clusterin (CLU) showed significant elevation in OA patients and were linked to disease severity. Regarding miRNAs, some (e.g., let-7e, miR-33b-3p) were downregulated, while others (e.g., miR-146a-5p, miR-92a-3p) were upregulated in OA. Functional analyses using STRING and miRNet tools revealed that these biomarkers are not only diagnostic indicators but may actively contribute to OA pathogenesis, particularly through inflammation and cartilage-related pathways. In conclusion, circulating proteins and miRNAs hold promise as non-invasive biomarkers for knee OA. By integrating evidence from 18 clinical studies with network analyses, we identify two predominant molecular phenotypes: an inflammatory–metabolic axis and a cartilage-turnover axis. However, further large-scale, standardized studies are necessary to confirm their clinical applicability and integration into routine practice</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156281"},"PeriodicalIF":3.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418290","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":"Next generation DNA sequencing data analysis and its application in clinical genomics","authors":"Abhijit Beura ,&nbsp;Gowrang Kasaba Manjunath ,&nbsp;Shweta Mahalingam ,&nbsp;Mangesh Sudhakar Rajguru ,&nbsp;Tikam Chand Dakal ,&nbsp;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":"2025-10-30","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}

{"title":"An MRI radiomics approach to predict the efficacy of chemotherapy for osteosarcoma","authors":"Danna Liu ,&nbsp;Xue Zhou ,&nbsp;Yixiong Liu ,&nbsp;Hong Wang ,&nbsp;Jixin Liu ,&nbsp;Zhengyuan Li ,&nbsp;Yanfei Liu ,&nbsp;Xin Hou ,&nbsp;Yuewen Hao","doi":"10.1016/j.prp.2025.156279","DOIUrl":"10.1016/j.prp.2025.156279","url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156279"},"PeriodicalIF":3.2,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476270","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":"Mechanistic insights into plant-derived natural compounds for the treatment of skin cancer: Targeting molecular signaling for therapeutic intervention","authors":"Ashutosh Pathak ,&nbsp;G. Surendra ,&nbsp;Sathvik Belagodu Sridhar ,&nbsp;Patibandla Jahnavi ,&nbsp;Jeetendra Kumar Gupta ,&nbsp;P. Balaji ,&nbsp;N. Juniorsundresh ,&nbsp;Konatham Teja Kumar Reddy ,&nbsp;Abdul Ajeed Mohathasim Billah ,&nbsp;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":"2025-10-22","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}