JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Robust Increase in IQCK Protein Expression in Mouse Models of Alzheimer's Disease and iPSC-Derived Neurons","authors":"Juliet Akkaoui,&nbsp;Dinesh Devadoss,&nbsp;Hongjie Wang,&nbsp;Alexandru Movila,&nbsp;Madepalli K. Lakshmana","doi":"10.1111/jcmm.70686","DOIUrl":"https://doi.org/10.1111/jcmm.70686","url":null,"abstract":"<p>Emerging studies indicate that the IQ-motif-containing protein K (IQCK) is a novel risk factor for Alzheimer's disease (AD), an age-associated disease. The expression patterns of IQCK in healthy and AD brains, within the context of age and sex are largely unknown. Therefore, we compared the age-dependent expression patterns of IQCK in males and females of wild-type (WT) mice with AD-like 3xTg and APΔE9 mice. Additionally, we measured IQCK protein expression in AD-derived human iPSC neurons. In WT mice, we found no IQCK expression at day 1 (1D) in the cortex (CX), hippocampus (HP), brainstem (BS) and cerebellum (CB). Overall, IQCK protein expression in different brain regions was first detected in 1-month-old wild-type (WT) mice, reaching its maximum in 1-year-old mice (1Y), and then gradually decreased in 2-year-old mice. In the APΔE9 mice, IQCK protein levels significantly increased by 1246% in the CX, 682% in the HP and 169% in the BS relative to WT controls. In the 3xTg mice, only HP showed an increase of IQCK protein by 277%. In addition, we also detected elevated tendencies in BS and CB regions but not in the CX. Finally, IQCK expression was also significantly increased by 68% in the AD-derived iPSC neurons relative to the NC-derived iPSC neurons. Thus, increased IQCK protein levels in the brain of AD-like 3xTg and APΔE9 mouse models suggest a possible role in AD pathogenesis, a finding that requires further clarification.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70686","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536794","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":"Kupffer Cells Regulate iNKT Cells Through Il-12 to Mitigate the Extent of APAP-Induced Damage in the Liver","authors":"Yinling Li,&nbsp;Shuang Wen,&nbsp;Jie Liu,&nbsp;Shuwei Li,&nbsp;Junping Shi,&nbsp;Haitao Wang","doi":"10.1111/jcmm.70549","DOIUrl":"https://doi.org/10.1111/jcmm.70549","url":null,"abstract":"<p>To explore the innate immune response in the occurrence and development of APAP-induced drug-induced liver injury and the biological effect caused by the interaction between immune cells through real-time, in vivo analysis. We used conventional molecular biology technology and multi-photon confocal live imaging to explore the effect of the interactive dialogue between iNKT and Kupffer cells on neutrophil recruitment in the occurrence and development of APAP-induced liver injury. iNKT cell deficient mice were more prone to liver injury induced by excessive APAP, and the degree of liver injury was more severe. After injury, iNKT cells were recruited into the liver and showed IL-4 high expression activation mode. Furthermore, we also found that Kupffer cells in APAP induced liver injury produce M1 polarisation and highly expressed IL-12, that Kupffer cells regulate the activation of iNKT cells through IL-12; and that IL-4 produced by iNKT cells in the liver can also inhibit inflammatory damage caused by neutrophil recruitment. Our study shows that Kupffer cells produce IL-12 and promote activated iNKT cells to produce more IL-4, and inhibit the recruitment of neutrophils, thereby reducing the degree of liver inflammatory injury induced by APAP.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70549","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524727","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 Mechanism Exploration of Traditional Chinese Medicine's “Different Treatments for Same Disease” Concept in Osteoporosis Therapy: A Serum Metabolomics Study","authors":"Jingyuan Wen,&nbsp;Xuefeng Li,&nbsp;Zhen Wu,&nbsp;Liu Jiangyuan,&nbsp;Guanyin Wang,&nbsp;Xu Wang,&nbsp;Zhengsheng Bao,&nbsp;Yang Yu,&nbsp;Pinger Wang,&nbsp;Zhenyu Shi,&nbsp;Bing Xu,&nbsp;Yunhuo Cai,&nbsp;Hongting Jin,&nbsp;Jiali Chen","doi":"10.1111/jcmm.70662","DOIUrl":"https://doi.org/10.1111/jcmm.70662","url":null,"abstract":"<p>The “different treatments for same disease” is an important concept of traditional Chinese medicine (TCM) therapy. In TCM, osteoporosis (OP) treatment is aimed at invigorating blood, strengthening spleen, and tonifying kidneys, and their typical herbs are <i>Angelica sinensis</i> (<i>Oliv.</i>) <i>Diels</i> (Danggui, DG), <i>Poria cocos</i> (<i>Schw.</i>) <i>Wolf</i> (Fuling, FL), and <i>Achyranthes bidentata Blume</i> (Niuxi, NX). Nevertheless, molecular mechanisms of these different therapies of OP under the concept of “different treatments for same disease” are still unclear. The objective of this study was to identify the related metabolites and biological processes in these three distinct therapeutic approaches for osteoporosis, by using serum metabolomics analysis. A model of postmenopausal OP (PMOP) was created using bilateral ovariectomized rats and then administered with DG, FL, or NX for 12 weeks. To assess the efficacy of the three treatments, we performed gross pathology evaluation, micro-computed tomography (micro-CT) scan, bone-strength test, and histopathologic examination. The results demonstrated that the treatment groups improved weight, rectal temperature, and 24-h urine output when compared to the model group. Furthermore, the PMOP models exhibited significant increases in bone strength, bone mass, and physical bone parameters after three distinct treatments. Serum metabolomics analysis subsequently showed that DG was predominantly associated with glycerophospholipids, prenol lipids, and steroid lipid metabolism. FL was primarily linked to glycerophospholipid and amino acid metabolism. The primary metabolisms associated with NX include sphingolipid, glycerophospholipid, amino acid, and purine metabolisms. In conclusion, the DG, FL, and NX herbs effectively alleviate PMOP by regulating lipid metabolism, while FL is also involved in amino acid metabolism and NX in amino acid and purine metabolisms. Our results provide biological evidence for the TCM principle of “different treatments for same disease”.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70662","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524729","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":"CD81 Aggravates Ovarian Cancer Progression via p-Cresyl Sulfate-Mediated Mitophagy in Tim4+ Tumour-Associated Macrophages","authors":"Jiali Ni,&nbsp;Xiaoying Li,&nbsp;Yue Wu,&nbsp;Xiaodi Tu,&nbsp;Xinxin Zhang,&nbsp;Lu Wang,&nbsp;Hao Xie,&nbsp;Yayi Hou,&nbsp;Huan Dou,&nbsp;Shuli Zhao","doi":"10.1111/jcmm.70701","DOIUrl":"https://doi.org/10.1111/jcmm.70701","url":null,"abstract":"<p>Ovarian cancer (OC) is characterised by widespread peritoneal metastasis. Tetraspanin CD81 is predominantly located at the cellular membrane and exhibits inconsistent roles in tumour progression. However, its precise function in OC remains unclear. We found that CD81 expression was significantly elevated in tumour tissues from OC patients with poor prognosis, and it directly promoted proliferation, and migration of OC cells. Stable knock-down of CD81 expression ameliorated disease progression in a murine model of OC and induced metabolic responses in OC cells. Metabolomics and mass spectrometry identified the protein-bound toxin p-cresyl sulfate (PCS) as a key metabolite regulated by the CD81-FAK signalling axis. One aspect is that PCS promoted the growth of OC cells. Furthermore, tumour-derived PCS combined with Cdh1 to enhance Bnip3-dependent mitophagy activity of Tim4 positive tumour-associated macrophages (TAMs). Intraperitoneal injection of PCS reversed the therapeutic effects observed following CD81 knock-down; the mitophagy of reprogrammed Tim4⁺ TAMs was also promoted, accompanied by alterations in antitumor immunity. In summary, we elucidated CD81 prompted Tim4⁺ TAMs mitophagy to induce OC progression via FAK/PCS/Cdh1 pathway, deepen our understanding of OC pathogenesis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536795","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":"Brazilin Inhibits the Proliferation of Non-Small Cell Lung Cancer by Regulating the STING/TBK1/IRF3 Pathway","authors":"Li-Ping Kang,&nbsp;Cong Xu,&nbsp;Pan Xu,&nbsp;Dong-Hui Huang,&nbsp;Ze-Bo Jiang","doi":"10.1111/jcmm.70688","DOIUrl":"https://doi.org/10.1111/jcmm.70688","url":null,"abstract":"<p>Non-small cell lung cancer (NSCLC) stands as a predominant cause of cancer-related mortality worldwide. Brazilin, an active isoflavonoid compound derived from Chinese herbs, has displayed anti-cancer properties across various cancer cell lines. However, the precise anti-tumour mechanism of Brazilin in NSCLC remains incompletely understood. In this paper, we demonstrated that Brazilin treatment significantly reduced the proliferation of NSCLC cells and induced apoptosis. Additionally, Brazilin caused G2 cell cycle arrest in NSCLC cells, characterised by decreased expression of Cyclin B1 and increased expression of P21. Brazilin also induced mitochondrial dysfunction and ROS production in NSCLC cells. Mechanistically, Brazilin treatment significantly activated the STING pathway and upregulated the expression of CXCL10, CXCL9, and CCL5 in NSCLC cell lines. Notably, the inhibition of the STING pathway with H-151 enhances cell viability, suggesting STING is involved in Brazilin-induced apoptosis. These findings underscore Brazilin as a promising anti-cancer agent for NSCLC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70688","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524802","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 Key Role of COA6 in Pancreatic Ductal Adenocarcinoma: Metabolic Reprogramming and Regulation of the Immune Microenvironment","authors":"Lai Jiang,&nbsp;Yuxuan Jiang,&nbsp;Xuancheng Zhou,&nbsp;Lexin Wang,&nbsp;Shengke Zhang,&nbsp;Chenglu Jiang,&nbsp;Hui Meng,&nbsp;Qingwen Hu,&nbsp;Yuheng Gu,&nbsp;Yipin Fu,&nbsp;Ke Xu,&nbsp;Hao Chi,&nbsp;Xiaolin Zhong","doi":"10.1111/jcmm.70685","DOIUrl":"https://doi.org/10.1111/jcmm.70685","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) is characterised by immune hypo-responsiveness due to its complex, immunosuppressive tumour microenvironment (TME). Mitochondrial metabolic reprogramming allows PDAC cells to shift between glycolysis and oxidative phosphorylation (OXPHOS), supporting energy production and cellular viability, thus promoting tumour progression and therapeutic resistance. Mitochondrial genes associated with PDAC were identified using SMR/HEIDI analysis combined with MRC IEU OpenGWAS and GTEx V8 pancreatic eQTL databases. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics were used to explore cellular interactions and construct spatial interaction networks. Potential small-molecule compounds targeting the TME were identified through drug prediction and molecular docking. COA6 expression was silenced in SW1990 and PANC-1 cells to assess effects on cell proliferation, migration, invasion and apoptosis. COA6, a key gene in the OXPHOS pathway, was upregulated in PDAC tumours compared to normal tissues. Functional assays showed that COA6 overexpression enhanced proliferation, migration and chemoresistance of PDAC cells. COA6 modulates OXPHOS, influences the TME and promotes drug resistance in PDAC. It is a promising therapeutic target for improving clinical outcomes in PDAC patients. Further research is needed to develop COA6-targeted therapies.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70685","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524801","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":"Global Thyroid Cancer Patterns and Predictive Analytics: Integrating Machine Learning for Advanced Diagnostic Modelling","authors":"Yao Sun,&nbsp;Yongsheng Jia,&nbsp;Kuan Fu,&nbsp;Xiaoyong Yang,&nbsp;Peiguo Wang,&nbsp;Zhiyong Yuan","doi":"10.1111/jcmm.70676","DOIUrl":"https://doi.org/10.1111/jcmm.70676","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The global increase in thyroid cancer prevalence, particularly among female populations, underscores critical gaps in our understanding of molecular pathogenesis and diagnostic capabilities. Our investigation addresses these knowledge deficits by examining molecular signatures and validating diagnostic markers using clinical specimens to facilitate earlier detection and targeted therapeutic development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted comprehensive analyses of thyroid cancer specimens through multiple methodologies. Quantitative PCR and ELISA techniques were employed to quantify gene expression profiles and cytokine concentrations. High-resolution single-cell transcriptomics illuminated cellular communications within the tumour ecosystem, with particular emphasis on myeloid cell interactions mediated by MIF and GALECTIN signalling networks. Rigorous statistical frameworks were implemented to evaluate differential expression patterns and cytokine alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our analyses demonstrated pronounced elevation of both pro-inflammatory mediators (TNF-α, IL-6, IL-8, VEGF) and immunoregulatory cytokines (TGF-β, IL-10) in neoplastic tissues relative to non-malignant adjacent regions, with magnitude changes of 2.5–4.0 fold (<i>p</i> &lt; 0.05). Network analysis revealed distinctive gene modules, notably MEblue and MEmagenta, exhibiting strong positive correlations with disease progression. Computational diagnostic algorithms, particularly penalised regression models (Ridge, Lasso), exhibited exceptional discriminatory capacity, achieving 0.963 AUC in external validation (GSE27155 dataset). Single-cell profiling uncovered extensive communication networks centred on myeloid cell populations, with MIF and GALECTIN pathways emerging as critical mediators of tumour development and immune suppression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings expand the molecular understanding of thyroid carcinogenesis, highlighting the significance of myeloid-centered communication networks. The molecular signatures and gene modules identified represent promising candidates for diagnostic applications and personalised therapeutic targeting. Prospective validation in expanded and heterogeneous patient populations remains essential to confirm clinical utility and optimise implementation strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70676","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524796","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":"Modified Qianghuo Shengshi Decoction Ameliorates Osteoarthritis via Inhibiting PI3K/Akt Pathway-Related Ferroptosis","authors":"Chen Zhuang,&nbsp;Enli Li,&nbsp;Wen-kai Li,&nbsp;Xiaojuan Geng,&nbsp;Chenxuan Hong,&nbsp;Yu Pan,&nbsp;Lei Yang","doi":"10.1111/jcmm.70691","DOIUrl":"https://doi.org/10.1111/jcmm.70691","url":null,"abstract":"<p>Modified Qianghuo Shengshi decoction (MQSD), a TCM formula, is clinically used for osteoarthritis (OA) symptom relief. Its exact molecular actions, however, are not fully understood. This investigation seeks to elucidate the molecular mechanisms by which MQSD impedes OA progression. High performance liquid chromatography (HPLC) was employed to delineate MQSD's chemical profile. The CCK-8 assay determined MQSD's impact on chondrocyte viability in the presence or absence of IL-1β. EDU and Annexin V-FITC assays evaluated chondrocyte proliferation and apoptosis, respectively. Alcian Blue staining probed extracellular matrix (ECM) secretion by chondrocytes. Network pharmacology was utilised to pinpoint disease targets, while various assays assessed ferroptosis-related chondrocyte phenotypes under Erastin or Ferrostatin-1 treatments. IHC, qRT-PCR and western blot analyses were conducted to ascertain MQSD's cellular effects. Micro-CT and Safranin O Fast Green staining provided insights into knee joint morphology and cartilage integrity. Molecular docking assessed the binding affinity of MQSD's active compounds to PI3K/Akt/GPX4. MQSD promotes chondrocyte proliferation, prevents apoptosis, and enhances viability. It further modulates the ECM output and the anabolic-to-catabolic ratio within chondrocytes. Through network pharmacology, ferroptosis linked to the PI3K/Akt pathway is identified as crucial. Pre-application of MQSD elevates the GSH/GSSG ratio and mitochondrial density, while it reduces Fe²⁺ levels, ROS, and lipid droplet accumulation in chondrocytes. Moreover, MQSD activates GPX4 and inhibits p-AKT levels. Molecular docking studies affirm the strong interaction between MQSD's key ingredients and the PI3K/Akt/GPX4 pathway components. Through modulation of ferroptosis via the PI3K/Akt pathway, MQSD retards OA progression.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70691","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514518","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":"Assessing Auranofin for Second-Line Use in Chemoresistant Ovarian Cancer: Effects on Tumour Spheroid and Primary Cell Growth","authors":"Militello Rosamaria,&nbsp;Becatti Matteo,&nbsp;Gamberi Tania,&nbsp;Fiaschi Tania,&nbsp;Alessandra Modesti,&nbsp;Paffetti Caterina,&nbsp;Sorbi Flavia,&nbsp;Fambrini Massimiliano,&nbsp;Magherini Francesca","doi":"10.1111/jcmm.70681","DOIUrl":"https://doi.org/10.1111/jcmm.70681","url":null,"abstract":"<p>Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women and the most lethal gynaecological malignancy. The high mortality rate is primarily due to late diagnosis and the lack of targeted therapies. The gold standard treatment consists of debulking surgery followed by platinum/taxane-based chemotherapy, which is initially effective in approximately 75% of patients. However, most women experience relapse and develop chemoresistance. To date, no therapy has proven to be decisive, underscoring the need for research into second-line or alternative treatments to overcome chemoresistance and prevent relapses. Auranofin (AF) is a promising repositioned anticancer agent with a multifaceted mode of action both cancer cell type- and dose-dependent. The current study evaluated AF's cytotoxicity on multicellular tumour spheroids derived from three ovarian cancer cell lines (SKOV3, A2780, and A2780 cisplatin-resistant). Results demonstrated that AF inhibited spheroid formation and growth by inducing apoptosis. Furthermore, we showed that AF's mode of action involves the PI3K/Akt and NF-κB pathways, and we highlighted differences in drug responses between cisplatin-sensitive, resistant, and primary ovarian cancer cells. Finally, by examining the efficacy of AF and cisplatin in combination, we identified differential sensitivities among the cell lines and primary ovarian cancer cells.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70681","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514519","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":"Thyroid Hormone Dynamics and DIO2 Variants in Schizophrenia: Exploring Genetic Links to Neuroendocrine Imbalance","authors":"Gokce Akan,&nbsp;Ismael Chatita Adolf,&nbsp;Adil Colak,&nbsp;Seda Acar,&nbsp;Fatih Oncu,&nbsp;Dogan Yesilbursa,&nbsp;Solmaz Turkcan,&nbsp;Fatmahan Atalar,&nbsp;Sema Bilgic Gazioglu","doi":"10.1111/jcmm.70694","DOIUrl":"https://doi.org/10.1111/jcmm.70694","url":null,"abstract":"<p>Thyroid hormone modulates multiple neurotransmitter systems, including dopaminergic, serotonergic, glutamatergic and GABAergic pathways, which are implicated in schizophrenia (SCH) pathophysiology. The Type II deiodinase (DIO2) enzyme plays a critical role in thyroid metabolism, converting thyroxine (T4) into the biologically active triiodothyronine (T3). This study aimed to investigate the potential association between DIO2 gene polymorphisms, Thr92Ala and ORFa-Gly3Asp, with serum levels of free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) in SCH susceptibility and symptomatology. The cohort included 582 unrelated patients diagnosed with SCH and 603 healthy controls. Genotyping of Thr92Ala and ORFa-Gly3Asp single nucleotide polymorphisms (SNPs) of the DIO2 gene was conducted along with serum measurements of TSH, fT4 and fT3 levels. The genotype distribution of Thr92Ala and ORFa-Gly3Asp genotypes differed significantly between SCH group and the controls (<i>p</i> &lt; 0.001). Furthermore, patients with SCH exhibited significantly lower levels of fT3 (<i>p</i> &lt; 0.001) and TSH (<i>p</i> &lt; 0.001) compared with controls. Notably, the Thr92Ala genotypes displayed a significant association with altered fT3 and TSH levels in SCH patients (<i>p</i> &lt; 0.05, respectively). This study identified a significant association between DIO2 polymorphisms and decreased levels of fT3 and TSH in Turkish patients with SCH. Given the impact of thyroid hormones on neurotransmitter systems involved in SCH, these results highlight the potential for thyroid hormone modulation as a therapeutic avenue. Further research could lead to more personalised treatment strategies, particularly for patients with genetic predispositions to altered thyroid hormone metabolism, improving clinical outcomes and offering new approaches to managing symptoms in schizophrenia.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514520","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}