JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Clinical Significance of JAM-2 Expression in the Vaginal Wall Tissues of Patients With Pelvic Organ Prolapse","authors":"Yuan Liu,&nbsp;Yajing Mao,&nbsp;Yuelin Wu,&nbsp;Sheng Wan,&nbsp;Shengyi Gu,&nbsp;Jing Peng,&nbsp;Bo Jiao,&nbsp;Xiaolin Hua","doi":"10.1111/jcmm.70512","DOIUrl":"https://doi.org/10.1111/jcmm.70512","url":null,"abstract":"<p>This study aimed to elucidate the roles of junctional adhesion molecule 2 (JAM-2), collagen I and matrix metalloproteinase 2 (MMP-2) in the pathogenesis of pelvic organ prolapse (POP) and explore their potential as diagnostic markers. We examined 82 POP patients and 64 controls using enzyme-linked immunosorbent assay (ELISA) and quantitative Polymerase Chain Reaction (qPCR) to analyse protein and gene expression levels of JAM-2, Collagen I and MMP-2. Receiver operating characteristic (ROC) analysis evaluated their diagnostic efficacy, with correlation analyses linking molecular markers to POP severity based on POP-Q grades. Our study found no significant differences in age, BMI and vaginal parity between POP patients and controls. Molecular analyses revealed significant alterations in the expression levels of JAM-2, Collagen I and MMP-2 in POP patients. Specifically, there was a marked decrease in JAM-2 and collagen I levels, accompanied by an increase in MMP-2 expression, indicating a disruption in the balance between tissue synthesis and degradation. ROC analysis demonstrated the significant discriminative power of these markers, with substantial area under the curve (AUC) values for diagnosing POP. Correlation analysis further showed a significant association between the expression of JAM-2, Collagen I and MMP-2 and the clinical severity of POP, as indicated by POP-Q grades. Our findings revealed the significant changes in the expression of JAM-2, Collagen I and MMP-2 that may contribute to the POP pathogenesis. The diagnostic potential of these markers was substantiated, suggesting their utility in developing noninvasive diagnostic tools for POP.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70512","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741418","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":"Migration Dynamics of Human NK Cell Preparations in Microchannels and Their Invasion Into Patient-Derived Tissue","authors":"Alina Moter,&nbsp;Sonja Scharf,&nbsp;Hendrik Schäfer,&nbsp;Tobias Bexte,&nbsp;Philipp Wendel,&nbsp;Emmanuel Donnadieu,&nbsp;Martin-Leo Hansmann,&nbsp;Sylvia Hartmann,&nbsp;Evelyn Ullrich","doi":"10.1111/jcmm.70481","DOIUrl":"https://doi.org/10.1111/jcmm.70481","url":null,"abstract":"<p>Natural killer (NK) cells are characterised by their ability to attack cancer cells without prior antigen stimulation. Additionally, clinical trials revealed great potential of NK cells expressing chimeric antigen receptors (CARs). Successful anti-tumour efficacy remains limited by migration and infiltration to the tumour site by NK cell preparations, which is linked to the scarcity in the knowledge of migration dynamics and invasion potential. Here, we applied a recently reported innovative microfluidic microchannel technology to gain insight into the intrinsic motility of NK cells. We assessed the baseline activated and proliferating NK cells in direct comparison with T cells and investigated their motility patterns in the presence of tumour cells. Additionally, we performed high-resolution 4D confocal imaging in patient-derived hyperplastic lymphatic tissues to assess their invasive capacity. Our data revealed that the invasion potential of NK cells was greater than that of T cells, despite their similar velocities. The flexibility of the NK cell nucleus may have contributed to the higher invasion potential. The motility of CD19-CAR-NK cell preparations was similar to that of non-transduced NK cells in hyperplastic lymphoid tissue, with improved targeted migration in tumour tissue, suggesting the suitability of genetically engineered NK cells for difficult-to-reach tumour tissues.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741675","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":"Uncovering the Role of Tertiary Lymphoid Organs in the Inflammatory Landscape: A Novel Immunophenotype of Diabetic Foot Ulcers","authors":"Deboshmita Banerjee,&nbsp;Shouvik Paul,&nbsp;Chitra Selvan,&nbsp;Sreekar Pai,&nbsp;B. S. Nandakumar,&nbsp;Souvik Mukherjee,&nbsp;Pongali B. Raghavendra","doi":"10.1111/jcmm.70479","DOIUrl":"https://doi.org/10.1111/jcmm.70479","url":null,"abstract":"<p>Diabetes foot ulcers (DFU) are the most common foot injuries leading to lower extremity amputation. Our study aimed to provide the first representative analysis highlighting the vital role of Tertiary Lymphoid Organs (TLO) inflammatory landscape in diabetic foot ulcers. The study explores mechanisms of TLO formation and the disease-specific roles of TLOs in regulating peripheral inflammatory and immune responses. Additionally, comprehensive analysis of clinical data from DFU cases, focused on TLO pathophysiology and systemic immune-inflammation landscape, is documented, aiming to identify the risk factors contributing to the development of DFUs. Our experimental results showed very significant differences were observed among the IL-17 and IFN-γ cytokine levels between the DFU vs. Control and DFU vs. NIDFU (Non-Infectious Diabetic Foot Ulcers) groups, while minimal differences were observed in IL-6 and TNF-α cytokine levels. Immunohistochemistry staining or Immunophenotyping of DFU patient-derived wound samples for TLO inflammatory stratification showed remarkable differences between DFU, NIDFU, and control groups both in CD3⁺ T Cells and CD20⁺ B cells. Overall, our study findings highlight the perspective role of TLO in DFU mechanisms and its prudent role in regulating peripheral inflammatory-immune responses. TLO study-related significant findings might be one of the important mechanisms, and its effective unveil might be a valuable treatment modality for DFU-complications.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741417","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 Infarct Border Zone Remodelling in Ventricular Arrhythmias: Bridging Basic Research and Clinical Applications","authors":"Jin Ma,&nbsp;Qiuxiong Chen,&nbsp;Dongqun Lin,&nbsp;Shiyu Ma","doi":"10.1111/jcmm.70526","DOIUrl":"https://doi.org/10.1111/jcmm.70526","url":null,"abstract":"<p>Patients who experience post-myocardial infarction (MI) and present with a left ventricular ejection fraction of less than 35% are classified as being at high risk for sudden cardiac death due to ventricular arrhythmias (VAs). The expansion of scar tissue and the extension of the infarct border zone (IBZ) following MI play critical roles in the progression of heart failure and the onset of VAs. Various aspects of structural remodelling, including cardiac fibrosis, along with electrophysiological changes such as alterations in gap junctions, ion channels, and autonomic nervous system function within the IBZ may contribute to abnormal impulse generation and conduction, thereby increasing susceptibility to arrhythmias. Currently, management strategies for VAs primarily encompass pharmacologic interventions (e.g., β-blockers, amiodarone), device-based approaches (e.g., ICD implantation), or catheter ablation techniques as outlined by ESC Guidelines. In this review, we systematically summarise both structural characteristics inherent in ischaemic myocardial substrates and clinical treatment strategies regarding VAs. We propose that early prevention strategies aimed at mitigating arrhythmogenic substrate formation represent an innovative approach to treating VAs following MI.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741674","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":"Boric Acid Suppresses Glioblastoma Cellular Survival by Regulating Ferroptosis via SOX10/GPx4/ACSL4 Signalling and Iron Metabolism","authors":"Guven Kilic,&nbsp;Ceyhan Hacioglu,&nbsp;Cengiz Tuncer,&nbsp;Ezgi Kar,&nbsp;Fatih Kar,&nbsp;Ahmet Taskesen,&nbsp;Adem Kurtulus,&nbsp;Onder Ipek,&nbsp;Oben Devin Cetiner,&nbsp;Cigdem Erdin","doi":"10.1111/jcmm.70529","DOIUrl":"https://doi.org/10.1111/jcmm.70529","url":null,"abstract":"<p>Ferroptosis, a distinct form of regulated cell death, plays a role in glioma pathogenesis. SRY-box (SOX) transcription factors are key regulators of cancer progression. In this study, we investigated the role of SOX10 in ferroptosis induction in U87 cells following boric acid treatment. First, the cytotoxic effects of boric acid on HMC3 and U87 cells were assessed using CCK8 and BrdU incorporation assays. Subsequently, SOX10, GPX4, ACSL4, GSH, MDA, total ROS, Fe²⁺, and TFR levels were analysed using ELISA, Western blot, and RT-PCR techniques. Additionally, DAPI staining was performed to evaluate nuclear abnormalities. According to the CCK8 analysis, the IC50 value for boric acid was determined to be 3.12 mM for HMC3 cells and 532 μM for U87 cells, a finding further supported by BrdU incorporation analysis, which indicated that U87 cells were more sensitive to boric acid. Western blot and RT-PCR analyses revealed that SOX10 expression was significantly higher in U87 cells compared to HMC3 cells. Boric acid treatment led to a reduction in GSH, GPX4, and SOX10 levels in U87 cells, while inducing an increase in MDA, total ROS, ACSL4, Fe²⁺, and TFR levels. Moreover, microscopic analysis demonstrated that boric acid treatment induced both morphological and nuclear abnormalities in U87 cells. In conclusion, our findings demonstrate that SOX10 is involved in the ferroptosis signalling pathway and that boric acid effectively suppresses U87 cell viability by targeting the SOX10/GPX4/ACSL4 axis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70529","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741439","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":"Monocytes Expressing IL-36G Play a Crucial Role in Atopic Dermatitis","authors":"Yitao Yang,&nbsp;Lei Wang,&nbsp;Longmei Yu,&nbsp;Chenxi Chang,&nbsp;Honglei Zhang,&nbsp;Linhan Hu,&nbsp;Juntong Liu,&nbsp;Yihang Zhang,&nbsp;Hui Han,&nbsp;Haiyun Zhang,&nbsp;Yumei Zhou,&nbsp;Ji Wang","doi":"10.1111/jcmm.70503","DOIUrl":"https://doi.org/10.1111/jcmm.70503","url":null,"abstract":"<p>Atopic dermatitis (<span>ad</span>) is a chronic inflammatory skin disease, with recent studies indicating that immune cells, such as monocytes and inflammatory cytokines, play a crucial role. By retrieving datasets from public databases and analysing immune cell infiltration in lesional skin using CIBERSORT, we found that monocytes and M2 macrophages were significantly upregulated in atopic dermatitis. Differentially expressed gene (DEG) functional enrichment analysis revealed that cytokine-cytokine receptor interaction was the most significantly enriched pathway. Further analysis of cytokines and their receptors, along with their correlation with infiltrating immune cells, identified IL36G-expressing monocytes as a key target in atopic dermatitis. We compared immune cell infiltration and cytokine-related targets in similar inflammatory skin diseases, such as psoriasis and urticaria, to evaluate similarities and differences among these three skin conditions. The analysis revealed that IL36G-expressing monocytes were also highly expressed in psoriasis but did not play a pivotal role in urticaria. Finally, we used molecular docking to predict and validate drugs targeting IL36G. Our study highlights IL36G-expressing monocytes as a common key target in atopic dermatitis and psoriasis, offering novel insights and therapeutic strategies for these related diseases.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70503","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741438","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":"Unveiling the Angiogenic Potential and Functional Decline of Valve Interstitial Cells During Calcific Aortic Valve Stenosis Progression","authors":"Adeline Blandinières,&nbsp;Elisa Rossi,&nbsp;Nicolas Gendron,&nbsp;Jeanne Rancic,&nbsp;Mickael Rosa,&nbsp;Annabelle Dupont,&nbsp;Salim Idelcadi,&nbsp;Aurélien Philippe,&nbsp;Bastien Poitier,&nbsp;Ivan Bièche,&nbsp;Sophie Vacher,&nbsp;Bernard Cholley,&nbsp;Pascale Gaussem,&nbsp;Sophie Susen,&nbsp;David M. Smadja","doi":"10.1111/jcmm.70511","DOIUrl":"https://doi.org/10.1111/jcmm.70511","url":null,"abstract":"<p>Valve interstitial cells (VICs) play a critical role in aortic valve calcification and angiogenic processes associated with calcific aortic valve stenosis (CAVS). Within the same valve, VICs from differently calcified regions can exhibit diverse phenotypic and functional properties. We hypothesised that VICs isolated from noncalcified (NC-VICs) and calcified (C-VICs) areas of human aortic valves possess distinct angiogenic characteristics. In this study, we isolated C-VICs and NC-VICs from 23 valves obtained after aortic valve replacement due to CAVS. Both VIC types exhibited similar phenotypes in culture, characterised by morphology, expression of mesenchymal/fibroblastic markers, proliferation and osteogenic differentiation. No significant differences were observed in the secretion of angiogenic factors, including VEGF-A, Ang-1, Ang-2, PlGF, bFGF between NC-VICs and C-VICs. However, when co-injected with endothelial colony-forming cells (ECFCs) into Matrigel implants in vivo in mice, implants containing NC-VICs showed significantly higher microvessel density compared to those with C-VICs (<i>p</i> &lt; 0.001). Additionally, NC-VICs co-cultured with ECFCs expressed significantly higher levels of the perivascular markers αSMA and calponin compared to C-VICs (<i>p</i> &lt; 0.001 and <i>p</i> &lt; 0.05, respectively). In conclusion, our study reveals the heterogeneity in VIC plasticity within the aortic valve during CAVS. The diminished capacity of VICs from calcified areas to differentiate into perivascular cells suggests a loss of function as valve disease progresses. Furthermore, the ability of VICs to undergo perivascular differentiation may provide insights into valve homeostasis, angiogenesis and the exacerbation of calcification.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741440","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":"Sodium Hyaluronate-PDGF Repairs Cartilage and Subchondral Bone Microenvironment via HIF-1α-VEGF-Notch and SDF-1-CXCR4 Inhibition in Osteoarthritis","authors":"Zhengchao Wang,&nbsp;Pengfei Zhu,&nbsp;Hongmei Li,&nbsp;Bo Ye,&nbsp;Qiong Luo,&nbsp;Jiangxia Cheng,&nbsp;Yu Cai","doi":"10.1111/jcmm.70515","DOIUrl":"https://doi.org/10.1111/jcmm.70515","url":null,"abstract":"<p>Chronic degenerative changes in cartilage and subchondral bone that lead to instability of the cartilage microenvironment are essential for the development of osteoarthritis (OA) in the old. Synchronous repair of cartilage and subchondral bone may be a key strategy for OA treatment. PDGF-BB effectively promoted chondrocyte regeneration and angiogenesis. However, the mechanisms by which PDGF-BB affects subchondral bone and the delivery of PDGF-BB to the joint cavity need to be further explored. In this study, we used sodium hyaluronate to deliver PDGF-BB (SH-PDGF) to the joint space and aimed to determine the mechanisms of SH-PDGF in repairing cartilage and subchondral bone and stabilising the cartilage microenvironment. In this research, we determined the pharmacokinetics of PDGF-BB and SH-PDGF in cartilage. Moreover, we investigated the effects of PDGF-BB and SH-PDGF on cartilage and the subchondral bone microenvironment by identifying changes in the HIF-VEGF-Notch axis and SDF-1-CXCR4 axis in an OA rat model. The results showed that PDGF-BB increased cell viability, decreased HIF-1α levels, inhibited inflammation and improved matrix metabolism in osteoarthritic chondrocytes under hyperoxic or hypoxic conditions. We also found that PDGF-BB and SH-PDGF showed similar effects on repairing cartilage and subchondral bone simultaneously. However, SH-PDGF had some advantages over PDGF-BB in prolonging the injection interval and decreasing the injection time. These protective effects were mediated by the inhibition of both the HIF-1α-VEGF-Notch axis and the SDF-1-CXCR4 axis. The underlying mechanisms include the inhibition of HIF-1α-VEGF-Notch-mediated vessel invasion and SDF-1-CXCR4 axis-mediated crosstalk between cartilage and subchondral tissue.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741392","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":"Unravelling Cancer Immunity: Coagulation.Sig and BIRC2 as Predictive Immunotherapeutic Architects","authors":"Ziang Yao,&nbsp;Jun Fan,&nbsp;Yucheng Bai,&nbsp;Jiakai He,&nbsp;Xiang Zhang,&nbsp;Renquan Zhang,&nbsp;Lei Xue","doi":"10.1111/jcmm.70525","DOIUrl":"https://doi.org/10.1111/jcmm.70525","url":null,"abstract":"<p>Immune checkpoint inhibitors (ICIs) represent a groundbreaking advancement in cancer therapy, substantially improving patient survival rates. Our comprehensive research reveals a significant positive correlation between coagulation scores and immune-related gene expression across 30 diverse cancer types. Notably, tumours exhibiting high coagulation scores demonstrated enhanced infiltration of cytotoxic immune cells, including CD8⁺ T cells, natural killer (NK) cells, and macrophages. Leveraging the TCGA pan-cancer database, we developed the Coagulation.Sig model, a sophisticated predictive framework utilising a coagulation-related genes (CRGs) to forecast immunotherapy outcomes. Through rigorous analysis of ten ICI-treated cohorts, we identified and validated seven critical CRGs: BIRC2, HMGB1, STAT2, IFNAR1, BID, SPATA2, IL33 and IFNG, which form the foundation of our predictive model. Functional analyses revealed that low-risk tumours characterised by higher immune cell populations, particularly CD8⁺ T cells, demonstrated superior ICI responses. These tumours also exhibited increased mutation rates, elevated neoantigen loads, and greater TCR/BCR diversity. Conversely, high-risk tumours displayed pronounced intratumor heterogeneity (ITH) and elevated NRF2 pathway activity, mechanisms strongly associated with immune evasion. Experimental validation highlighted BIRC2 as a promising therapeutic target. Targeted BIRC2 knockdown, when combined with anti-PD-1 therapy, significantly suppressed tumour growth, enhanced CD8⁺ T cell infiltration, and amplified IFN-γ and TNF-α secretion in tumour models. Our findings position the Coagulation.Sig model as a novel, comprehensive approach to personalised cancer treatment, with BIRC2 emerging as both a predictive biomarker and a potential therapeutic intervention point.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741222","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":"Kaempferol Targets Global Epigenetic Modifiers to Impedes Growth and Migratory Ability of HeLa Cells","authors":"Nazia Afroze,&nbsp;Shafiul Haque,&nbsp;Arif Hussain","doi":"10.1111/jcmm.70498","DOIUrl":"https://doi.org/10.1111/jcmm.70498","url":null,"abstract":"<p>Dietary bioactive agents can curb tumour progression through chromatin alterations. Thus, this study attempts to evaluate the influence of kaempferol on epigenome modification in HeLa cells. Biochemical analysis for global DNA methylation-LINE 1, DNMTs (DNA methyltransferases), HAT (histone acetyl transferase), HDACs (histone deacetylases) and HMTs (histone methyltransferases) were examined with their transcript level expression through qPCR. Also, H3 and H4 histone modification marks were quantitated by an ELISA-based assay. Moreover, qPCR and protein profiler were performed to analyse the expression of migratory genes at both mRNA and protein levels, respectively, that was further substantiated through colony formation, invasion, and scratch wound assays. Finally, DNA methyl-sequencing was performed to analyse the promoter methylation of TSGs (tumour suppressor genes) and corroborated by analysing selected TSGs' expression. Kaempferol treatment did not alter the global DNA methylation-LINE 1 compared to untreated control, however, it reduced the expression and biochemical activities of DNMT and HDAC, which can be linked to their hypermethylation by kaempferol exposure. Concordant with the reduced expression of HMTs, HATs and other epi-enzymes, various histone H3 and H4 marks were also observed to be modulated. Kaempferol exposure led to promoter hypomethylation of various TSGs (such as <i>WIF1, RUNX1, RARβ, SOX1</i>), which subsequently led to enhanced expression at the mRNA level, which corresponds to their reactivation. Molecular studies were consistent with cell-based studies, which demonstrated a strong growth inhibitory and anti-migratory effect of kaempferol. This research helps to understand the probable mechanism used by kaempferol as a potential epigenetic modifier.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70498","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741441","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}