JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"GADD45A is Essential for Granulosa Cells Differentiation and Ovarian Reserve in Human and Mice","authors":"Juncen Guo,&nbsp;Yuanyuan Hu,&nbsp;Qi Cao,&nbsp;Ying Zhang,&nbsp;Yihe Jia,&nbsp;Lan Liu,&nbsp;Yanru Zeng,&nbsp;Xiao Wu,&nbsp;Yuelin Song,&nbsp;Maosen Yang,&nbsp;Wenming Xu,&nbsp;Yang Hu,&nbsp;Wei Huang,&nbsp;Tian Tang","doi":"10.1111/jcmm.70820","DOIUrl":"https://doi.org/10.1111/jcmm.70820","url":null,"abstract":"<p>Diminished ovarian reserve (DOR) poses significant challenges in reproductive health, with emerging evidence implicating DNA damage repair pathways. While GADD45A is a critical regulator of DNA repair, cell cycle and apoptosis, its role in DOR pathogenesis remains unexplored. We employed transcriptome sequencing, qPCR and Western Blot analyses to compare <i>GADD45A</i> expression in granulosa cells (GCs) between DOR patients and controls. Functional studies included <i>GADD45A</i> overexpression/knockdown in human granulosa cells (KGN line) and phenotypic characterisation of <i>Gadd45a</i> knockout (KO) mice. Ovarian reserve parameters (follicle counts, hormone levels, oestrus cyclicity) and in vitro fertilisation outcomes were systematically evaluated. DOR patients exhibited significant upregulation of GADD45A in GCs, concomitant with reduced FSHR and CYP19A1 expression. In vitro experiments revealed that <i>GADD45A</i> overexpression disrupted both proliferation (Cell cycle analysis and EdU staining) and differentiation (Reduced CYP19A1 and FSHR expression) in GCs, while knockdown specifically impaired differentiation (Elevated CYP19A1 and FSHR expression). <i>Gadd45a</i> KO mice displayed hallmark DOR features: irregular oestrus cycles (Shorter oestrus), ovarian volume reduction, ovarian hormones dysregulation and decreased ovarian reserve (reduced primordial follicles and antral follicles, and increased atretic follicles). We found GADD45A was robustly expressed in the ovarian stroma and GCs of atretic follicles. KO oocytes showed compromised developmental competence with decreased two-cell embryo rate in vitro fertilisation. Our findings establish <i>GADD45A</i> dysregulation as a mechanistic contributor to DOR through dual impacts on granulosa cell differentiation and follicle survival. The <i>Gadd45a</i> KO mouse recapitulates key clinical DOR phenotypes, providing a validated model for therapeutic discovery.</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.70820","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012039","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":"Berberine Sensitises Breast Cancer Cells to Radiation via the Attenuation of DNA Ligase III","authors":"Yuxin Sun,&nbsp;Cong Li,&nbsp;Hang Yin,&nbsp;Kunyan Li,&nbsp;Ying Wang,&nbsp;Shuailong Zhang,&nbsp;Yi Zhao,&nbsp;Jing Wang,&nbsp;Weifeng Mao","doi":"10.1111/jcmm.70836","DOIUrl":"https://doi.org/10.1111/jcmm.70836","url":null,"abstract":"<p>Berberine (BBR) is an isoquinoline alkaloid with a variety of biological activities, including anti-microbial and anti-tumoral activities. However, the cellular targets of BBR and the roles of BBR in the radiosensitivity of breast cancer cells are not well defined. In this study, we investigated the effects of BBR on the radiosensitivity of BT549 triple-negative breast cancer cells. Through RNA-seq results, we found that BBR significantly down-regulated the expression of DNA ligases. The results of western blot and comet assay confirmed that BBR attenuated DNA ligase III (LIGIII) expression and caused DNA damage in a dose-dependent manner. The results of electron microscopy showed that BBR decreased mitochondrial copies and induced mitochondrial autophagy. Clonal formation analysis showed that BBR sensitised breast cancer cells to irradiation. The genetic complementation and interference assays showed that the effect of BBR on the radiosensitivity of BT549 breast cancer cells is dependent on the expression of LIGIII. These results contribute to the understanding of the effects of BBR on cellular DNA repair and the clinical application of BBR in breast cancer therapy.</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.70836","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012159","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":"Regional Transcriptomic Architecture of Glioblastoma Reveals NUCB2 as a Key Orchestrator of Tumour Aggression and Immune Dysfunction","authors":"Xiaodong Huang,&nbsp;Xuemei Hu,&nbsp;Hang Xu,&nbsp;Bowen Yang,&nbsp;Lidong Yan,&nbsp;Junti Lu,&nbsp;Kuanming Huang,&nbsp;Huibin Chen,&nbsp;Shengli Hu","doi":"10.1111/jcmm.70814","DOIUrl":"https://doi.org/10.1111/jcmm.70814","url":null,"abstract":"<p>Glioblastoma (GBM) exhibits remarkable intra-tumoral heterogeneity, which contributes to therapeutic resistance and poor clinical outcomes. In this study, we employed integrative single-cell RNA sequencing analysis across two complementary public datasets encompassing diverse cellular populations from GBM centre and periphery regions to elucidate potential spatial molecular programmes driving tumour progression. Our analyses revealed substantial transcriptomic divergence between anatomically distinct tumour regions, with NUCB2 emerging as significantly upregulated in centre-residing neural progenitor cell-like (NPC-like) tumour cells. Functional characterisation demonstrated NUCB2's critical role in regulating GBM stem cell proliferation, with knockdown experiments resulting in significant reduction in tumour cell growth. Intriguingly, NUCB2 expression strongly associated with immunosuppressive molecular signatures and paradoxical immune cell infiltration patterns. Specifically, CD8+ T cells from GBM centre regions exhibited distinctive transcriptional programmes enriched for interferon response, complement activation, and inflammatory pathways, suggesting a state of functional impairment despite enhanced infiltration. Survival analyses confirmed that elevated NUCB2 expression significantly associated with poorer patient survival. Collectively, our findings establish NUCB2 as a multifaceted regulator that coordinates both intrinsic proliferative capacity and extrinsic immunomodulatory functions within the GBM microenvironment. This previously uncharacterised NUCB2-driven axis represents a promising therapeutic target, potentially enabling simultaneous targeting of tumour cell proliferation and immune evasion mechanisms in this aggressive malignancy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70814","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999054","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 EphrinB2–EphB4 Signalling Pathway in Regeneration of Inflammatory Bone Defect","authors":"Lili Shen,&nbsp;Ning Wei,&nbsp;Dong Wang,&nbsp;Rongjing Zhou","doi":"10.1111/jcmm.70840","DOIUrl":"https://doi.org/10.1111/jcmm.70840","url":null,"abstract":"<p>The important role of the EphrinB2–EphB4 signalling pathway in bone remodelling has been demonstrated, while its effect on inflammatory bone defect regeneration remains poorly understood. This study was to assess the effect of EphB4–EphrinB2 signalling on inflammation-mediated bone defect repair in murine models. The modelling method of inflammation-mediated bone defect in mice was established by intraperitoneally injecting different concentrations of TNF-α. Then, three randomly assigned groups were administered vehicle (PBS, control), EphrinB2 siRNA, and EphB4 siRNA into a 1.5-mm diameter mandibular bone defect with 5 μg/kg TNF-α intraperitoneally injected every 2 days. The gene expression of osteogenic differentiation markers Runx2, Osterix, ALP, OCN and BSP in healing tissue of the bone defect was examined by quantitative real-time polymerase chain reaction (PCR). Runx2 and BSP protein expressions were examined by western blot, and the decalcified tissues were subjected to histological examination. Compared with the control group, the EphB4 siRNA group mice exhibited lower levels of osteogenic differentiation markers and higher levels of the osteoclastogenic marker. H&amp;E staining, TRACP staining and bone histomorphometry showed that the bones were thinner and the number of giant osteoclasts in the EphB4 siRNA group was higher compared with the control group, whereas there were no significant differences in osteoblastic and osteoclastic differentiation between EphrinB2 siRNA mice and control mice. In conclusion, the EphrinB2–EphB4 signalling pathway plays a critical role in the inflammation-induced bone defect repair process; selective inhibition of EphB4 using siRNA results in decreased bone formation and increased bone resorption under high inflammatory circumstances in vivo.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997888","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 Hedgehog Pathway Promotes Monocytes Infiltration Through CCL20–CCR6 Axis in Hepatocellular Carcinoma","authors":"Pei-Han Chu,&nbsp;Yu-Fu Hsu,&nbsp;Chen-Yi Chang,&nbsp;Chuen-Miin Leu,&nbsp;Kuo-Hsin Chen,&nbsp;Chiung-Fang Chang,&nbsp;Ping-Hui Tseng","doi":"10.1111/jcmm.70824","DOIUrl":"https://doi.org/10.1111/jcmm.70824","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) is one of the leading cancers worldwide, and its development is strongly associated with the tumour microenvironment, particularly fibrosis and chronic inflammation. This study aims to investigate the role of the Hedgehog (Hh) pathway, a key signalling pathway in HCC progression, in the interaction between HCC cells and monocytes, which are central players in inflammation. Using a transwell migration assay, GLI1, the downstream transcriptional effector of the Hh pathway in HCC cells, was found to promote the migration of THP-1 monocyte cells. Among the cytokines regulated by the Hh pathway in HCC cells, CCL20 was identified as a crucial factor that interacts with CCR6 in THP-1 cells to facilitate migration. Next, using a luciferase reporter assay and chromatin immunoprecipitation, GLI1 binding sites within the <i>CCL20</i> promoter region were confirmed. In a xenograft tumour mouse model, tumour growth and monocyte infiltration were inhibited in <i>GLI1</i> or <i>CCL20</i> knockout PLC5 cells. Moreover, mRNA expressions of <i>GLI1</i> and <i>CCL20</i> were positively correlated in clinical samples, with patients exhibiting high CCL20 expression showing poorer overall survival. Overall, our findings highlight that the Hh pathway in HCC contributes to monocyte infiltration via the CCL20–CCR6 axis, providing potential insights for future therapeutic strategies.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70824","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997956","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":"Sweroside Inhibits Inflammation and Alleviates Endothelial Injury and Atherosclerosis in Mice","authors":"Minjiang Huang,&nbsp;Huiming Yin,&nbsp;Qiansheng Yang,&nbsp;Lingli Liu,&nbsp;Yuefu Chen,&nbsp;Ling Jin,&nbsp;Yang Yang,&nbsp;Ke Hu,&nbsp;Yan Ding","doi":"10.1111/jcmm.70837","DOIUrl":"https://doi.org/10.1111/jcmm.70837","url":null,"abstract":"<p>The underlying mechanisms in atherosclerotic vascular diseases are not entirely clear, posing a challenging hurdle to treatment. Inflammation is a root cause of atherosclerosis (AS); therefore, anti-inflammatory agents have potential for its management. Sweroside, possessing anti-inflammatory properties, emerges as a potential agent to impede AS progression. In this study, we investigated the effects of sweroside on AS mice and elucidated its molecular mechanisms. We conducted in vivo experiments using an apolipoprotein E mice model of AS to explore the effects of sweroside on vascular inflammation adhesion responses, endothelial injury and AS. In vitro experiments, mouse aorta endothelial cells were treated with palmitic acid (PA) and sweroside, and the protective effects of sweroside on endothelial injury were analysed. AS is a chronic inflammatory disease and activation of nuclear factor κB (NF-κB) signalling contributes to inflammatory reactions and AS. Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) has been identified as an upstream target of NF-κB signalling. We detected MAP4K4/NF-κB signalling pathways using gene siRNA silencing and knockdown assays and investigated the protective effects of sweroside in PA-mediated endothelial injury and western-diet-induced AS. The findings demonstrated that sweroside attenuated vascular inflammation, adhesion responses, and leukocyte homing and alleviated endothelial injury and atherosclerosis in vivo. Sweroside attenuated endothelial inflammation, apoptosis, permeability and adhesion responses induced by PA in vitro. Sweroside alleviated endothelial injury and atherosclerosis through MAP4K4/NF-κB signalling. Hence, sweroside is a promising candidate for treating AS, acting by targeting the MAP4K4/NF-κB pathway.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70837","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997958","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":"METTL3 Silencing Suppresses Cardiac Fibrosis Post Myocardial Infarction via m6A Modification of SMOC2","authors":"Yanru He,&nbsp;Xiaodong Pan,&nbsp;Zhuyuan Liu,&nbsp;Pengfei Zuo,&nbsp;Zulong Sheng,&nbsp;Chunshu Hao,&nbsp;Zaixiao Tao,&nbsp;Zhongpu Chen,&nbsp;Jiali Song,&nbsp;Genshan Ma,&nbsp;Sunkai Ling","doi":"10.1111/jcmm.70829","DOIUrl":"https://doi.org/10.1111/jcmm.70829","url":null,"abstract":"<p>Cardiac fibrosis, especially in the infarct border zone, leads to decreased cardiac compliance, impaired systolic and diastolic function, resulting in heart failure. M6A methylation plays a role in fibrosis development. However, its underlying mechanism remains poorly understood. This study explores the role and molecular mechanisms of m6A methylation in regulating cardiac fibrosis after myocardial infarction (MI). A mouse myocardial fibrosis model post-MI was established by ligating the left coronary artery. Corresponding gene knockdown was achieved in vitro or in vivo using short hairpin RNA or fibroblast-specific AAV9 virus. Echocardiography assessed cardiac function in mice, while Masson staining determined the degree of collagen deposition post-MI. The meRIP-Seq kit detected mRNA methylation levels in myocardial tissue and hypoxia-treated cardiac fibroblasts. Expression of RNA methylation-related enzymes, fibrosis-related proteins, and SMOC2 expression in the myocardial tissue or cardiac fibroblasts were detected using western blotting. Actinomycin D assessed SMOC2 mRNA stability. Results demonstrated increased levels of m6A methylation and METTL3 expression in myocardial fibrosis tissue post-MI and in hypoxia-treated cardiac fibroblasts. In vivo METTL3 downregulation reduced the fibrotic area and improved cardiac function, while METTL3 downregulation in vitro can alleviate cardiac fibroblast proliferation and differentiation after hypoxia. Mechanistically, METTL3 promoted SMOC2 mRNA stability by increasing its m6A methylation level, thereby regulating cardiac fibroblast proliferation and differentiation. Together, our work uncovers a critical link between METTL3 and SMOC2, providing insight into the functional importance of the mRNA m6A methylation and its modulators in cardiac fibrosis post MI.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70829","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997887","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":"Iron and Manganese Azooxime Complexes as Anti-Microbial Agents Against Antibiotics Resistant Wild Bacteria From Hospital Drainage","authors":"Aratrika Samajdar,&nbsp;Supriyo Halder,&nbsp;Sukanya Chatterjee,&nbsp;Debjeet Chakraborty,&nbsp;Arup Kumar Mitra,&nbsp;Anindita Banerjee,&nbsp;Kausikisankar Pramanik,&nbsp;Sanjib Ganguly,&nbsp;Ajoy Kumer,&nbsp;Bikram Dhara","doi":"10.1111/jcmm.70826","DOIUrl":"https://doi.org/10.1111/jcmm.70826","url":null,"abstract":"<p>Antibiotic resistance is the never-ending war among medical researchers and microbial life forms. The extensive evolving potential of the microorganisms, in combination with improper usage, storage and disposal of the marketed antibiotics generated from natural or artificial sources, always calls for the need for novel antimicrobial agents with different modes of action. In this project, azo-oxime complexes of iron and manganese (seven in total) have been applied to wild multidrug-resistant pathogenic bacterial strains (isolated from sewage water of hospital). All complexes were inhibitory to bacterial strains present in the sewage water sample, which have been authenticated by a significant reduction in colony count upon their application to the microbial population of the water sample. Four of the most abundant colonies were isolated for further investigation about the bacterial characteristics, as well as to comprehend the molecular mechanism of action of these complexes to inhibit bacterial growth. Biochemical experiments in the form of the Catalase test, Coagulase test and lipase assay point towards the pathogenicity of bacterial strains. The strains were treated with various broad-spectrum antibiotics, namely, Penicillin G, Oxacillin, Cephalothin, Clindamycin, Erythromycin, Amoxyclav, Cefotaxime, Levofloxacin, Aztreonam, Imipenem, Amikacin, Ceftazidime, and found to be resistant against many of them, viz., Clindamycin, Ceftazidime, Erythromycin, Amoxyclav, and some others, thereby signifying that the molecular mechanism of action of the aforesaid complexes is multidimensional. These complexes were producing ROS in sufficient amounts that can cause lipid peroxidation, and subsequent damage to the bacterial cell membrane and translation machinery was found to be inhibited by RNA. Bacterial genomic DNA was also affected by the chelates, and this has been authenticated by the decreased genomic DNA concentration and presence of DNA debris on agarose gel electrophoresis of the DNA of bacterial cultures treated with the complexes.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997959","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":"Differential Expression Patterns of SLCO Solute Carriers in Human Breast Cancer Cell Lines and Tumour Samples","authors":"Rachel Telfer-Sutherland,&nbsp;Louise Page,&nbsp;Annette Meeson,&nbsp;Simon Lowes","doi":"10.1111/jcmm.70838","DOIUrl":"https://doi.org/10.1111/jcmm.70838","url":null,"abstract":"<p>The cellular uptake of nutrients essential for cell growth and survival is facilitated by solute carrier (SLC) transporters. Members of the SLCO subfamily of SLCs mediate the uptake of substrates relevant to breast cancer (BC), including steroid hormones and anticancer drugs. Accumulating evidence suggests that altered expression of these transporters may affect BC pathogenesis by influencing cell proliferation and anticancer drug resistance. In this study, we investigated differential expression of 11 SLCO transporters using semi-quantitative and quantitative PCR in MCF-7 and MDA-MB-231 BC cell lines and in human BC tissue samples. Eight SLCO transporters were expressed in at least one cell line. Of these, SLCO1B1 and SLCO1B3 showed higher expression in MDA-MB-231 than MCF-7 cells. Conversely, SLCO2A1, SLCO4C1 and SLCO5A1 showed higher expression in MCF-7 than MDA-MB-231 cells. Quantitative PCR analysis of 18 patients' BC tissue samples revealed variable expression of a number of SLCO transporters, regardless of patients having been treated with or without endocrine therapy prior to tumour excision. Proliferation and gene expression studies were conducted on the cell lines following exposure to β-estradiol, which stimulated cell proliferation in MCF-7 cells, as well as causing a significant increase in SLCO4C1 gene expression.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70838","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935202","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":"Recent Advances in Deciphering Normal and Diseased Aortic Valve Biology Using Transcriptomic Technologies","authors":"Monica Madalina Tucureanu,&nbsp;Ileana Manduteanu","doi":"10.1111/jcmm.70835","DOIUrl":"https://doi.org/10.1111/jcmm.70835","url":null,"abstract":"<p>Calcific aortic valve disease (CAVD) is a growing global health burden, with no approved pharmacological treatments to date, indicating a substantial therapeutic gap and the need for deeper insight into its underlying mechanisms. Transcriptomic approaches, particularly RNA sequencing (RNAseq) and single-cell sequencing (scRNAseq), are emerging as powerful tools for unravelling the complex biology of the aortic valve (AV) in both normal and diseased states. This review summarises recent advances in our understanding of AV structure and function, with emphasis on valvular cell plasticity, heterogeneity and intercellular interactions—especially between valvular endothelial cells (VECs) and monocytes under physiological and pathological conditions. We further underscore the importance of characterising baseline molecular and cellular processes in the healthy AV to properly interpret disease-associated alterations. By integrating recent transcriptomic findings, this review identifies key molecular targets and prioritises them for validation through wet-lab experiments, with the ultimate goal of informing the development of effective therapies for CAVD.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70835","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935201","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}