JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Tumour Single-Cell Bioinformatics: From Immune Profiling to Molecular Dynamics","authors":"Jane Siu-fan Li,&nbsp;Zoey Zeyuan Ji,&nbsp;Aaron Qi Zhang,&nbsp;Calvin Sze-Hang Ng,&nbsp;Guibin Qiao,&nbsp;Dongmei Zhang,&nbsp;Chunjie Li,&nbsp;Qing Zhang,&nbsp;Ka-Fai To,&nbsp;Patrick Ming-Kuen Tang","doi":"10.1111/jcmm.70783","DOIUrl":"10.1111/jcmm.70783","url":null,"abstract":"<p>Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of tumours by enabling high-resolution profiling of their cellular composition. Traditionally perceived as masses of homogeneous cancer cells, tumours are now recognised as complex ecosystems shaped by the tumour microenvironment (TME), which includes diverse immune cells, cancer-associated fibroblasts and extracellular matrix components. scRNA-seq has revealed remarkable heterogeneity within the TME, identifying novel or rare immune cell subsets and delineating their dynamic functional states. In particular, it has illuminated intercellular signalling networks and temporal cell-state transitions that drive tumour progression and immune evasion. Moreover, the integration of scRNA-seq data with clinical information has highlighted its potential in improving patient stratification, biomarker discovery and therapeutic target identification. Here, we systematically summarise recent advances in applying scRNA-seq to dissect the TME, discuss the implications of these findings for immunotherapy resistance and precision oncology, and outline future opportunities for integrating scRNA-seq with emerging technologies to develop more effective and personalised cancer treatment strategies.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D-Chiro-Inositol and LPS Induce a PCOS-Like Hyperandrogenic Response in Human KGN Granulosa Cells","authors":"Cristiano Giuliani,&nbsp;Giovanni Casoli,&nbsp;Giovanna Di Emidio,&nbsp;Carla Tatone,&nbsp;Arturo Bevilacqua","doi":"10.1111/jcmm.70779","DOIUrl":"10.1111/jcmm.70779","url":null,"abstract":"<p>Hyperandrogenism is a key hallmark of polycystic ovary syndrome, a prevalent endocrine disorder affecting women of reproductive age and often leading to infertility. We previously observed that high doses of D-chiro-inositol in mice reduce ovarian aromatase expression, contributing to a hyperandrogenic state. Given that similar effects have been reported in tumour-derived human KGN granulosa cells treated with bacterial lipopolysaccharide, we investigated whether D-chiro-inositol could elicit a comparable hyperandrogenic response in these cells, thereby shedding light on aberrant mechanisms potentially involved in polycystic ovary syndrome. Using lipopolysaccharide and myo-inositol as controls, we assessed KGN cells for proliferation, viability, inflammatory response, cellular and mitochondrial reactive oxygen species, expression of antioxidant enzyme genes, aromatase expression, and estradiol secretion. None of the treatments affected cell proliferation or viability. Both D-chiro-inositol and myo-inositol showed anti-inflammatory and antioxidant effects, whereas lipopolysaccharide induced inflammation and acted as a pro-oxidant. Notably, D-chiro-inositol and lipopolysaccharide downregulated aromatase gene and protein expression, resulting in reduced estradiol secretion. In contrast, myo-inositol had no significant impact on aromatase expression or oestrogen production. These findings suggest that D-chiro-inositol and lipopolysaccharide may serve as useful tools for probing the dysregulated molecular and cellular pathways associated with polycystic ovary syndrome, particularly those contributing to hyperandrogenism.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70779","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered T Lymphocytes Mitochondrial Function and Inflammatory Factors of Peripheral Blood in HIV Patients With Mycobacterial Infection","authors":"Mengyan Wang,&nbsp;Xiaotian Dong,&nbsp;Hu Wan,&nbsp;Jinchuan Shi,&nbsp;Lu Hui,&nbsp;Wei Chen,&nbsp;Shourong Liu,&nbsp;Jun Yan","doi":"10.1111/jcmm.70832","DOIUrl":"https://doi.org/10.1111/jcmm.70832","url":null,"abstract":"<p>To characterise T-cell immunity and inflammatory profiles in HIV patients with mycobacterial co-infections. This study enrolled 41 HIV patients co-infected with <i>Mycobacterium tuberculosis</i> (HIV-TB, <i>n</i> = 27) or non-tuberculous mycobacteria (HIV-NTM, <i>n</i> = 14), along with 30 controls (20 HIV-monoinfected, 10 post-treatment) from a single centre. Flow cytometry quantified T-cell subsets (CD3 + CD4+, CD3 + CD8+, CD28+ subsets), mitochondrial parameters (mass [MM], low membrane potential [MMP-low%]) and cytokines (IFN-γ, IL-2/4/6/10/17A, TNF-α). Co-infected groups showed reduced T-cell counts versus HIV-monoinfected controls (<i>p</i> &lt; 0.05). Elevated MMP-low% in CD3 + CD4+/CD28+ T cells indicated mitochondrial dysfunction in co-infected patients (<i>p</i> &lt; 0.05). HIV-TB patients exhibited higher CD3 + CD4+/CD28+/CD8+ T-cell MM than HIV-NTM (<i>p</i> &lt; 0.05), while HIV-NTM demonstrated greater MMP-low% (<i>p</i> &lt; 0.05). Proinflammatory cytokines (IFN-γ, IL-6, IL-17A) inversely correlated with CD4+ counts and MM, but positively with CD8 + CD28+ MMP-low%. MMP-low% in CD3 + CD4 + CD28+ T cells and IL-2 differentiated IRIS/non-IRIS cases (<i>p</i> &lt; 0.05), with combined AUC = 0.834 for IRIS prediction (<i>p</i> = 0.001). HIV/mycobacterial co-infection exacerbates T-cell depletion and mitochondrial dysfunction, with HIV-NTM showing more severe impairment. MMP-low% and IL-2 may serve as biomarkers for IRIS risk stratification.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70832","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The miR-192-EGR1/HOXB9 Loop Regulates Glioma Cell Stemness and Malignant Phenotypes by Promoting Their Mesenchymal Transition","authors":"Guo-Wei Li,&nbsp;Yan-Ping Jin,&nbsp;Min-Feng Sheng","doi":"10.1111/jcmm.70842","DOIUrl":"https://doi.org/10.1111/jcmm.70842","url":null,"abstract":"<p>To clarify the regulatory effects of miR-192 on the malignant phenotypes of glioma cells. We used PCR, WB and immunofluorescence to detect regulatory factors in glioma samples. Then, we chose lentiviral plasmid transfection to construct cell models. We used CCK-8 and colony formation to evaluate the proliferation ability of these cells and used Transwell/scratch tests to evaluate their invasion ability. CD133-expressing GSCs were observed under a microscope, and their stemness properties were evaluated. We constructed a tumour-bearing model via subcutaneous inoculation. Tumour growth curves and tumour weights were determined subsequently. The proteins involved in the miR-192-EGR1/HOXB9 loop were evaluated via IHC staining. MiR-192 was significantly reduced in glioma samples, and this factor downregulated EGR1 and HOXB9 via targeted binding, thus forming a semi-open loop. Moreover, the proliferation, invasion and migration of glioma cells overexpressing miR-192 were significantly decreased. These malignant phenotypes were abrogated completely with EGR1 or HOXB9 overexpression. Similarly, these changes were essentially consistent with MT marker expression and the stem-like properties in glioma cells. Meanwhile, miR-192 inhibits the tumorigenesis of glioma cells via the EGR1-HOXB9 loop. MiR-192 could inhibit MT in glioma cells through the EGR1-HOXB9 loop. Thus, it reduces their stemness and abrogates their malignant phenotypes.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70842","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Prognostic Significance of IL10 Variants and Their Mechanistic Regulation in Diabetic Nephropathy","authors":"Neha Shukla,&nbsp;Shivani Kumari,&nbsp;Poornima Verma,&nbsp;Amisha Srivastava,&nbsp;Neelam Singh,&nbsp;Gyan Manjary Rao,&nbsp;Narayan Prasad,&nbsp;Sushil Gupta,&nbsp;Anshika Srivastava,&nbsp;M. S. Ansari,&nbsp;Soorya Janakiraman,&nbsp;Marey Baden,&nbsp;Olaf Wolkenhauer,&nbsp;Shailendra K. Gupta,&nbsp;Naveen Kumar Gautam","doi":"10.1111/jcmm.70819","DOIUrl":"https://doi.org/10.1111/jcmm.70819","url":null,"abstract":"<p><i>IL10</i> is a very effective anti-inflammatory cytokine. <i>IL10</i> imbalance is linked to type 2 diabetes mellitus (T2DM) and also to renal hypertrophy, glomerular membrane thickening, and onset of diabetic nephropathy (DN). We aimed to investigate the association of <i>IL10</i> gene polymorphism (rs1800871T/C, rs1800896A/G) with DN and determine the influence of variants on its expression level and interaction with transcription factors. We genotyped 301 study subjects, comprising 75 DN, 126 T2DM patients, and 100 controls. All were analysed for biochemical assays and genotypic analysis by PCR-RFLP and confirmed by Sanger sequencing. The haplotype analysis was calculated by Chi-square test. mRNA expression and its correlation with variants were assessed by using RT-PCR. Statistical analyses were done by using SPSS and GraphPad software. Screening of transcription factors with <i>IL10</i> gene variants was performed using the TRANSFAC database, and the variants impact on <i>IL10</i> molecular interactions was analysed. This study revealed that <i>IL10</i> gene polymorphism rs1800896 was significantly associated with DN. ‘CG’ and ‘TG’ haplotypes were significantly associated with DN. Expression levels of <i>IL10</i> were upregulated in DN patients. The genetic correlation study shows that <i>IL10</i> gene expression was downregulated in the rs1800871 alternate variant genotype (CC) while upregulated in the rs1800896 alternate variant genotype (GG). <i>In silico</i> analyses suggest that the binding affinity of transcription factor CEBPA decreases due to the rs1800871 alternate variant, while the affinity of KLF4 increases in the case of the rs1800896 alternate variant. Our <i>in silico</i> results correlated with <i>IL10</i> expression analysis in respective patient groups. Overall, our findings highlight the role of <i>IL10</i> gene polymorphism in DN progression in the North Indian population.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70819","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Mediation Role of Immune Cells in Gut Microbiota–Pneumonia Associations: A Mendelian Randomisation Study","authors":"Nianzong Hou,&nbsp;Zhenhong Zhang,&nbsp;Weiwei Song,&nbsp;Lin Wang,&nbsp;Guoxiang Xu,&nbsp;Rumin Zhang,&nbsp;Yulong Yang,&nbsp;Kai Wang","doi":"10.1111/jcmm.70839","DOIUrl":"https://doi.org/10.1111/jcmm.70839","url":null,"abstract":"<p>The gut–lung axis plays a pivotal role in pneumonia pathogenesis, with immune regulation serving as a key mechanistic link between gut microbiota and disease progression. Despite established associations among gut microbiota, immune cell traits and pneumonia, their causal interplay and underlying mechanisms remain poorly elucidated. To investigate the causal relationships between gut microbiota and pneumonia and quantify the mediating effects of immune cell traits using Mendelian randomisation (MR), we performed a two-sample MR and multivariable MR (MVMR) analysis employing inverse-variance weighted (IVW) as the primary method. Genetic instruments for 211 gut microbiota taxa and 731 immune cell traits were derived from genome-wide association studies (GWAS). Mediation analysis was conducted to estimate immune cell-mediated effects on microbiota-pneumonia associations. Genetically predicted abundance of the <i>Oxalobacteraceae</i> family was positively associated with pneumonia risk (OR: 1.090; 95% CI: 1.010–1.175; <i>p</i> = 0.026). Mediation analysis revealed that CD16⁺ monocytes significantly mediated this relationship (Mediated Effect: 0.025, proportion mediated: 29.1%). This study provides genetic evidence supporting <i>Oxalobacteraceae</i> as a causal risk factor for pneumonia, partially mediated through CD16⁺ monocyte regulation. These findings offer novel insights into microbiome-directed immunomodulatory strategies for pneumonia prevention.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70839","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis in Haematological Malignancies: From Regulatory Networks to Novel Therapeutic Opportunities","authors":"Maryam Shayanmanesh,&nbsp;Seyed Esmaeil Ahmadi,&nbsp;Ali Amini","doi":"10.1111/jcmm.70790","DOIUrl":"https://doi.org/10.1111/jcmm.70790","url":null,"abstract":"<p>Haematological malignancies encompass a wide spectrum of blood cell disorders with diverse prognoses. Despite recent advances in therapy, many of these disorders remain incurable or exhibit relapse and drug resistance. Ferroptosis, an iron-dependent form of cell death caused by lipid peroxidation, holds promise as a strategy to overcome the resistance seen with conventional therapies. This review aims to succinctly outline current research concerning the regulatory function of ferroptosis-related genes (FRGs) and various types of non-coding RNAs (ncRNAs), as well as various types of ferroptosis inducers (FINs), encompassing small molecule compounds, natural derivatives, synthetic agents and nanoparticles. The exploration delves into the mechanisms by which FINs operate, including inhibiting the system Xc⁻, deactivating the enzyme glutathione peroxidase 4 (GPX4), disrupting glutathione (GSH) production and interfering with iron or lipid metabolism. The investigation emphasises the functioning of these agents and the underlying molecular processes driving the initiation of ferroptosis. A comprehensive assessment reveals the potential utility of FINs as innovative treatments for haematological neoplasms, offering insights into a novel therapeutic approach.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CHDH Promotes Breast Cancer Metastasis Relying on IL17RB/CREB1 Signalling Activation","authors":"Yifei Li,&nbsp;Yipeng Liu,&nbsp;Xiaowen Yang,&nbsp;Xinzhuang Shen,&nbsp;Zongjun Liu,&nbsp;Yuqiu Ma,&nbsp;Yiting Zhan,&nbsp;Xinyu Jiang,&nbsp;Chengjin Liang,&nbsp;Xiaoyuan Zhang,&nbsp;Huan Liu,&nbsp;Wenzhi Shen","doi":"10.1111/jcmm.70792","DOIUrl":"https://doi.org/10.1111/jcmm.70792","url":null,"abstract":"<p>The involvement of Choline Dehydrogenase (CHDH) in metabolic disorders and tumour progression has garnered significant scholarly interest. However, the specific role of CHDH in the metastasis and progression of breast cancer (BC) has been less thoroughly investigated. Our research indicates that CHDH protein expression is markedly elevated in breast cancer tissues compared to normal tissues, and this expression is positively correlated with the tumour node metastasis (TNM) stage of breast cancer. Furthermore, CHDH levels were found to be significantly higher in breast cancer cell lines relative to normal breast cells. The silencing of CHDH expression resulted in a reduction of breast cancer cell migration, while the overexpression of CHDH facilitated increased migration and tumour metastasis in vivo. Investigations into the underlying mechanisms revealed that CHDH influences the expression of IL17RB and activates Cyclic-AMP Response Element-Binding Protein (CREB), thereby mediating breast cancer metastasis. The application of an IL17RB antibody and the CREB inhibitor 666-15 effectively abolished CHDH-mediated migration of breast cancer cells in vitro. These findings suggest that CHDH plays a critical role in promoting breast cancer metastasis, potentially offering new targets and strategies for the treatment of metastatic breast cancer.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70792","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Endometriosis in Intestinal Inflammation: A Combined Mendelian Randomization and Cellular Study","authors":"Zhigang Li,&nbsp;Fang Wang,&nbsp;Ernv Kang,&nbsp;Xiaoguang Zhen,&nbsp;Jianli Liu,&nbsp;Wenhao Wang","doi":"10.1111/jcmm.70799","DOIUrl":"https://doi.org/10.1111/jcmm.70799","url":null,"abstract":"<p>This study aims to assess whether endometriosis causally increases the risk of IBD through Mendelian randomisation (MR) analysis and to elucidate potential mechanisms using in vitro experiments. A two-sample Mendelian randomisation (MR) analysis was conducted using genome-wide association study datasets for endometriosis and IBD, including ulcerative colitis and Crohn's disease. Causal inference was assessed using inverse variance weighting, MR-Egger, and weighted median methods, with MR-PRESSO used to detect horizontal pleiotropy. Additionally, peritoneal fluid from endometriosis patients (EM-PF) and healthy controls (CN-PF) was used to treat Caco-2 cells. Cell viability, apoptosis, barrier function, and inflammatory cytokine expression were analysed using MTT, TUNEL, transepithelial electrical resistance (TEER), Western blot, and qRT-PCR assays. MR analysis identified a significant causal association between endometriosis and IBD risk (IVW: <i>β</i> = 0.15–0.47, <i>p</i> &lt; 0.05). Sensitivity analyses confirmed result robustness with minimal pleiotropy and heterogeneity. Experimental results showed that EM-PF significantly reduced Caco-2 cell viability and TEER values while increasing apoptosis and epithelial permeability (<i>p</i> &lt; 0.01). Western blot and immunofluorescence staining revealed a marked decrease in tight junction proteins (ZO-1, Occludin) and an upregulation of inflammatory cytokines (IL-6, IL-8, IL-1β) in the EM-PF group (<i>p</i> &lt; 0.01). Our findings provide genetic and experimental evidence supporting a causal role of endometriosis in increasing IBD risk. Endometriosis-associated peritoneal fluid may contribute to gut inflammation and epithelial dysfunction, offering new insights into the pathophysiological connection between these conditions.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70799","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Agents Modulating Ferroptosis in Cancer: Molecular Pathways and Therapeutic Perspectives","authors":"Md. Al Amin,&nbsp;Mehrukh Zehravi,&nbsp;Sherouk Hussein Sweilam,&nbsp;Patibandla Jahnavi,&nbsp;Jeetendra Kumar Gupta,&nbsp;Varikalla Rajashakar,&nbsp;Rajeshwar Vodeti,&nbsp;Abdul Ajeed Mohathasim Billah,&nbsp;G. Dharmamoorthy,&nbsp;Uppuluri Varuna Naga Venkata Arjun,&nbsp;Voleti Vijaya Kumar,&nbsp;Muath Suliman,&nbsp;Talha Bin Emran","doi":"10.1111/jcmm.70834","DOIUrl":"https://doi.org/10.1111/jcmm.70834","url":null,"abstract":"<p>Ferroptosis, a controlled cell death influenced by iron-dependent lipid peroxidation, presents potential therapeutic targets for cancer treatment due to its unique molecular pathways and potential drug resistance. Natural compounds, such as polyphenols, flavonoids, terpenoids and alkaloids, can influence ferroptosis via important signalling pathways, such as Nrf2/Keap1, p53, and GPX4. These are promising for combinational therapy due to their ability to cause ferroptotic death in cancer cells, exhibit tumour-specific selectivity and reduce systemic toxicity. Furthermore, these compounds, when combined with traditional chemotherapy or radiation therapy, can enhance therapeutic efficacy and overcome resistance. Natural compounds targeting ferroptosis offer innovative cancer treatment, particularly for resistant malignancies, due to their ability to interact with signalling pathways and produce specific cytotoxic effects. This review explores natural compounds' molecular mechanisms controlling ferroptosis in cancer, their interactions with traditional chemotherapeutics, translational hurdles, and clinical application directions, potentially leading to novel nature-inspired anticancer treatments. Further research and clinical trials are needed to confirm the safety, bioavailability, and effectiveness of ferroptosis medicines, focusing on improved formulation and transport methods.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70834","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}