JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Resveratrol Upregulates miR-124-3p Expression to Target DAPK1, Regulating the NLRP3/Caspase-1/GSDMD Pathway to Inhibit Pyroptosis and Alleviate Spinal Cord Injury","authors":"Daohui Li,&nbsp;Yongwen Dai,&nbsp;Zhengtao Li,&nbsp;Hangchuan Bi,&nbsp;Haotian Li,&nbsp;Yongquan Wang,&nbsp;Yuan Liu,&nbsp;Xinpeng Tian,&nbsp;Lingqiang Chen","doi":"10.1111/jcmm.70338","DOIUrl":"10.1111/jcmm.70338","url":null,"abstract":"<p>Currently, an effective treatment for spinal cord injury (SCI) is not available. Due to the irreversible primary injury associated with SCI, the prevention and treatment of secondary injury are very important. In the secondary injury stage, pyroptosis exacerbates the deterioration of the spinal cord injury, and inhibiting pyroptosis is beneficial for recovery from SCI. The aim of this study was to clarify the role of resveratrol (RES) and the antipyroptotic mechanisms of RES and miR-124-3p in SCI to lay a theoretical foundation for the clinical treatment of SCI and provide new therapeutic approaches. Using cell staining and related molecular protein detection techniques to assess DAPK1, the effects of miR-124-3p and RES on pyroptosis were investigated, and the effects of RES on injured spinal cord repair in rats were evaluated using tissue staining and related functional recovery experiments. In vitro, DAPK1 interacts with NLRP3, exerting a pyroptotic effect through the NLRP3/Caspase-1/GSDMD pathway and DAPK1 knockdown inhibits pyroptosis. miR-124-3P negatively regulates the level of DAPK1 and reduced cell pyroptosis. RES increased miR-124-3p expression and reduces DAPK1 expression, affecting the NLRP3/Caspase-1/GSDMD pathway and inhibiting pyroptosis. In vivo, RES reduces GSDMD-N levels in rats with SCI, promotes functional recovery, and thus promotes recovery from SCI. Therefore, we concluded that RES increases the level of miR-124-3p, which targets DAPK1, regulates the NLRP3/Caspase-1/GSDMD pathway, inhibits pyroptosis and alleviates SCI.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059151","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":"NKD2 as a Mediator of IFIX Antioncogene-Induced Wnt Signalling and Epithelial–Mesenchymal Transition in Human OSCC","authors":"Shan Wang,&nbsp;Haixia Fan,&nbsp;Jie Bai","doi":"10.1111/jcmm.70342","DOIUrl":"10.1111/jcmm.70342","url":null,"abstract":"<p>The activation of the human interferon-inducible protein X (IFIX) isoform is associated with maintaining a stable cytoskeleton and inhibiting epithelial–mesenchymal transition (EMT). However, the mechanisms and pathways underlying IFIX-mediated oncogenesis are not well understood. In this study, we investigated the effects of IFIX overexpression and knockdown in CAL-27 and SCC-25 oral squamous cell carcinoma (OSCC) cells. We observed significant variations in the expression of E-cadherin, N-cadherin, vimentin and Snail, as well as changes in wingless/integrated (Wnt) signalling. Our results indicated a strong correlation between IFIX and EMT, as evidenced by quantitative reverse-transcription PCR and Western blotting, which revealed that Wnt3a and Wnt4 pathway components were regulated in IFIX-overexpressing or knockdown cells, with naked cuticle 2 (NKD2) showing the strongest positive correlation. Both IFIX overexpression and knockdown modulated NKD2 expression. NKD2 silencing mimicked the phenotypic effects of IFIX knockdown, inhibiting E-cadherin expression and increasing N-cadherin, Snail and vimentin expression. Additionally, silencing NKD2 restored the anticarcinogenic phenotype associated with IFIX overexpression, affecting cell proliferation, invasion and migration. These findings provide mechanistic insights into the antioncogenic effects of IFIX in OSCC, involving the inhibition of Wnt signalling through NKD2, which leads to cancer-inhibiting phenotypic effects, including restricted EMT.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006048","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":"Hypotonic Swelling Method for the Isolation of Pure Mitochondria From Primary Human Skeletal Myoblasts for Proteomic Studies","authors":"Evrim Aksu-Menges,&nbsp;Eray Taha Kumtepe,&nbsp;Gurler Akpinar,&nbsp;Burcu Balci-Hayta","doi":"10.1111/jcmm.70370","DOIUrl":"10.1111/jcmm.70370","url":null,"abstract":"<p>Mitochondria play a fundamental role in energy metabolism, particularly in high-energy-demand tissues such as skeletal muscle. Understanding the proteomic composition of mitochondria in these cells is crucial for elucidating the mechanisms underlying muscle physiology and pathology. However, effective isolation of mitochondria from primary human skeletal muscle cells has been challenging due to the complex cellular architecture and the propensity for contamination with other organelles. Here, we compared four different methods to isolate mitochondria from primary human skeletal myoblasts regarding total protein yield, mitochondrial enrichment capacity and purity of the isolated fraction. We presented a modified method that combines differential centrifugation with a hypotonic swelling step and a subsequent purification process to minimise cellular contamination. We validated our method by demonstrating its ability to obtain highly pure mitochondrial fractions, as confirmed by Western Blot with mitochondrial, cytosolic and nuclear markers. We demonstrated that proteomic analysis can be performed with isolated mitochondria. Our approach provides a valuable tool for investigating mitochondrial dynamics, biogenesis and function in the context of skeletal muscle biology in health and disease. This methodological advancement opens new avenues for mitochondrial research and its implications in myopathies, sarcopenia, cachexia and metabolic disorders.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006116","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":"Dual-Selection Strategy for Generating Knock-Out Lines of Human Embryonic Stem Cells","authors":"Ziyu Zhou,&nbsp;Lingling Tong,&nbsp;Yunbing Chen,&nbsp;Ruoming Wang,&nbsp;Yu Shen,&nbsp;Di Chen","doi":"10.1111/jcmm.70259","DOIUrl":"10.1111/jcmm.70259","url":null,"abstract":"&lt;p&gt;Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), possess the capacity to differentiate into all the cell types in the adults, forming the basis for generating functional cells in vitro for regenerative medicine [&lt;span&gt;1&lt;/span&gt;]. The purity and functionality of the hPSC-derived cells are the two key factors for clinical applications, which are largely determined by the differentiation protocols and conditions. The generation of knock-out lines of hPSCs is critical for dissecting the functions of the genes-of-interest and investigating the molecular mechanisms involved, essential for optimising differentiation protocols towards different lineages [&lt;span&gt;2, 3&lt;/span&gt;]. The development of the CRISPR/Cas9 technique has greatly improved the efficiency of gene targeting, bursting the functional analysis of genes-of-interest in hPSCs [&lt;span&gt;4, 5&lt;/span&gt;]. Moreover, the development of stem cells- and hPSCs-based organoid platforms further necessitated the genomic engineering for generating knock-out mutants and knock-in reporters [&lt;span&gt;6, 7&lt;/span&gt;]. However, the efficiency of gene editing in hPSCs is low and the whole process is tedious [&lt;span&gt;4, 8, 9&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;To reduce the workload and increase the efficiency of gene targeting for hPSCs, we designed a dual-selection strategy that incorporates antibiotic selection and fluorescent enrichment. Two donor vectors for homologous recombination were constructed, one with &lt;i&gt;GFP-2A-drug resistant gene&lt;/i&gt; (&lt;i&gt;DRG&lt;/i&gt;) and the other with &lt;i&gt;RFP-2A-DRG&lt;/i&gt;. A pair of guide RNAs (gRNAs) was designed to delete the whole region of the gene-of-interest. Two donor vectors served as templates for homologous recombination–based DNA repair. In a few cells, the genomic region of the gene-of-interest could be replaced with one allele of &lt;i&gt;GFP-2A-DRG&lt;/i&gt; and the other allele of &lt;i&gt;RFP-2A-DRG&lt;/i&gt;, forming the basis for antibiotic selection and fluorescent selection for a successful knock-out cell population. Furthermore, the cassettes &lt;i&gt;of GFP-2A-DRG&lt;/i&gt; and &lt;i&gt;RFP-2A-DRG&lt;/i&gt; are flanked by loxP. Both could be removed after the expression of Cre (Figure 1A). Thus, mutant hPSC lines could be easily selected by one round of antibiotic selection and another round of fluorescent enrichment.&lt;/p&gt;&lt;p&gt;One of the most time-consuming steps for generating knock-out lines in hPSCs is the screening of homozygous mutants. According to our experience, the efficiency for generating homozygous mutants of gene-of-interest in hESCs was usually less than 5% [&lt;span&gt;10, 11&lt;/span&gt;]. Therefore, more than 100 single colonies were required to be individually picked, expanded, passaged and genotyped by at least two rounds of polymerase chain reaction (PCR). With the dual-selection strategy, 800,000 single cells were nucleofected with two donor vectors and a pair of gRNAs deleting the genomic region of gene-of-interest. The nucleofected cells were recovered and expand","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006099","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":"Modulation of the Oxygenation State and Intracellular pH of Erythrocytes by Inositol-Trispyrophosphate Investigated by 31P NMR Study of 2,3-DPG","authors":"Sabina Koj,&nbsp;Tomasz Niedziela,&nbsp;Joanna Rossowska,&nbsp;Jean-Louis Schmitt,&nbsp;Jean-Marie Lehn,&nbsp;Claude Nicolau,&nbsp;Claudine Kieda","doi":"10.1111/jcmm.70343","DOIUrl":"10.1111/jcmm.70343","url":null,"abstract":"<p>The hypoxic microenvironment is crucial for tumour cell growth and invasiveness. Tumour tissue results from adaptation to reduced oxygen availability. Hypoxia first activates pro-angiogenic signals for alleviation. Pathologic, tumour angiogenesis maintains hypoxia, impairing treatment outcomes. Vessel normalisation requires physioxia. Oxygen delivery by red blood cell (RBC) carrying haemoglobin (Hb) is enhanced by <i>myo</i>-inositol trispyrophosphate (ITPP), an effector of oxygen transport by RBCs. Altering glycolytic activity, it lowers intracellular pH and increases oxygen release from Hb. ³¹P NMR tracking of 2,3-diphosphoglycerate (2,3-DPG), allosteric effector of Hb and non-penetrating anion in RBCs, reports on erythrocytes internal environment. ³¹P resonances of 2,3-DPG are pH-sensitive, their positions indicate the oxygenation state of RBCs and interactions with effectors such as ITPP. Here we show in vitro and in vivo, that modifying Hb activity through band-3 anion transporter, ITPP enhances oxygen release and controls RBC internal pH. Its blood availability validates applicability of ITPP-based strategies.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006130","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":"Comprehensive Analysis of m6A-Related Programmed Cell Death Genes Unveils a Novel Prognostic Model for Lung Adenocarcinoma","authors":"Xiao Zhang,&nbsp;Yaolin Cao,&nbsp;Jiatao Liu,&nbsp;Wei Wang,&nbsp;Qiuyue Yan,&nbsp;Zhibo Wang","doi":"10.1111/jcmm.70255","DOIUrl":"10.1111/jcmm.70255","url":null,"abstract":"<p>Lung adenocarcinoma (LUAD) involves complex dysregulated cellular processes, including programmed cell death (PCD), influenced by N6-methyladenosine (m6A) RNA modification. This study integrates bulk RNA and single-cell sequencing data to identify 43 prognostically valuable m6A-related PCD genes, forming the basis of a 13-gene risk model (m6A-related PCD signature [mPCDS]) developed using machine-learning algorithms, including CoxBoost and SuperPC. The mPCDS demonstrated significant predictive performance across multiple validation datasets. In addition to its prognostic accuracy, mPCDS revealed distinct genomic profiles, pathway activations, associations with the tumour microenvironment and potential for predicting drug sensitivity. Experimental validation identified RCN1 as a potential oncogene driving LUAD progression and a promising therapeutic target. The mPCDS offers a new approach for LUAD risk stratification and personalised treatment strategies.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006064","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":"Trajectory of Cardiogenic Dementia: A New Perspective","authors":"Nawaf AlRawili,&nbsp;Hayder M. Al-Kuraishy,&nbsp;Ali I. Al-Gareeb,&nbsp;Maha M. Abdel-Fattah,&nbsp;Nasser A. Al-Harchan,&nbsp;Mubarak Alruwaili,&nbsp;Marios Papadakis,&nbsp;Athanasios Alexiou,&nbsp;Gaber El-Saber Batiha","doi":"10.1111/jcmm.70345","DOIUrl":"10.1111/jcmm.70345","url":null,"abstract":"<p>The functions of the heart and brain are closely linked and essential to support human life by the heart-brain axis, which is a complex interconnection between the heart and brain. Also, cardiac function and cerebral blood flow regulate the brain's metabolism and function. Therefore, deterioration of cardiac function may affect cognitive function and may increase the risk of dementia. Cardiogenic dementia is defined as a cognitive deterioration due to heart diseases such as heart failure, myocardial infarction, and atrial fibrillation. The prevalence of cognitive impairment in patients with heart failure was 29%. In addition, coronary artery disease (CAD) is also associated with the development of cognitive impairment. CAD and reduction of myocardial contractility reduced cerebral blood flow and increased the risk of dementia in CAD patients. Furthermore, myocardial infarction and subsequent systemic haemodynamic instability promote the development and progression of cardiogenic dementia. These findings indicated that many cardiac diseases are implicated in the development and progression of cognitive impairment. Nevertheless, the underlying mechanism for the development of cardiogenic dementia was not fully elucidated. Consequently, this review aims to discuss the potential mechanisms involved in the pathogenesis of cardiogenic dementia.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006059","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":"Effective Reduction of Transgene-Specific Immune Response With rAAV Vectors Co-Expressing miRNA-UL112-5p or ERAP1 shRNA","authors":"Xiaoping Huang,&nbsp;Xiao Wang,&nbsp;Yaqi Sun,&nbsp;Xinrui Xie,&nbsp;Luming Xiao,&nbsp;Yihang Xu,&nbsp;Qiongshi Yan,&nbsp;Xianxiang Xu,&nbsp;Ling Li,&nbsp;Wentao Xu,&nbsp;Wenting Weng,&nbsp;Wenlin Wu,&nbsp;Xiaolan Xie,&nbsp;Congjie Dai,&nbsp;Yong Diao","doi":"10.1111/jcmm.70308","DOIUrl":"10.1111/jcmm.70308","url":null,"abstract":"<p>Recombinant adeno-associated virus (rAAV) has emerged as one of the best gene delivery vectors for human gene therapy in vivo. However, the clinical efficacy of rAAV gene therapy is often hindered by the host immune response against its transgene products. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is specialised to process peptides presented by class I molecules of major histocompatibility complex. Therefore, we hypothesise that modulation of the ERAP1 activity in rAAV transduced cells may be favoured to evade immune response against transgene products. In this study, we incorporated either miRNA-UL112-5p or ERAP1 shRNA into rAAV vectors expressing full-length ovalbumin (OVA) as a model antigen, and evaluated their effects for antigen presentation, cellular and humour immune response induced by OVA expression. The results indicated that silencing ERAP1 using miR-UL112-5p or ERAP1 shRNA did not affect the expression of OVA in cells, but inhibited the processing and presentation of OVA antigen peptide SIINFEKL in antigen presenting cells (APCs). Moreover, the rAAV vector co-expressing ERAP1 shRNA maintains stable and high expression of OVA in vivo, while simultaneously suppressing the humoral immunity of OVA. In addition, experimental results demonstrated that rAAV vectors incorporated ERAP1 shRNA efficiently repress costimulatory signals in dendritic cells (DCs), significantly attenuated the cytotoxic T-cell response, allowed for sustained transgene expression and reduced clearance of transduced muscle cells in mice. Moreover, our study suggested that the incorporation of miRNA-UL112-5p or ERAP1 shRNA into rAAV vectors effectively reduced transgene products induced immune response. The proposed method may potentially be applied in clinics to deliver therapeutic proteins safely and efficiently.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006112","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":"Aucubin Promotes BMSCs Proliferation and Differentiation of Postmenopausal Osteoporosis Patients by Regulating Ferroptosis and BMP2 Signalling","authors":"Yang Zheng,&nbsp;Rongtai Sun,&nbsp;Huan Yang,&nbsp;Tianyuan Gu,&nbsp;Meichun Han,&nbsp;Congcong Yu,&nbsp;Pengyu Chen,&nbsp;Jianhua Zhang,&nbsp;Ting Jiang,&nbsp;Yangyang Ding,&nbsp;Long Liang,&nbsp;Renfu Quan,&nbsp;Shasha Yao,&nbsp;Xing Zhao","doi":"10.1111/jcmm.70288","DOIUrl":"10.1111/jcmm.70288","url":null,"abstract":"<p>Postmenopausal osteoporosis (PMOP) is a chronic systemic bone metabolism disorder. Promotion in the patterns of human bone marrow mesenchymal stem cells (hBMSCs) differentiation towards osteoblasts contributes to alleviating osteoporosis. Aucubin, a natural compound isolated from the well-known herbal medicine Eucommia, was previously shown to possess various pharmacological effects. However, its effects on hBMSCs of PMOP patients are unknown. The aim of this present research was to investigate the impact and underlying process of aucubin on cell proliferation and osteogenic differentiation in hBMSCs isolated from PMOP patients. The ability of aucubin to inhibit the ferroptosis induced by erastin in hBMSCs was detected; ROS production, ferrous ion levels, SOD, MDA, and GPX activities were tested by using commercial kits. Next, ALP staining, ARS staining, RT-qPCR, RNA-sequencing, and Western blot were applied for determining the mRNA and protein expression levels associated with the osteogenesis of hBMSCs. The study also explored the involvement of BMP2/Smads signalling in aucubin promoting the osteogenesis of hBMSCs and evaluated the effects of aucubin intervention on osteoporosis using an ovariectomised rat model. The results indicated that aucubin significantly inhibited ROS generation and oxidative stress induced by erastin and protected against ferroptosis in hBMSCs. Additionally, aucubin facilitated osteogenic differentiation of hBMSCs by activating the BMP2/SMADs pathway and attenuated the progression of osteoporosis in OVX rats, suggesting a potential therapeutic benefit for postmenopausal osteoporosis (PMOP).</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006038","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":"Diagnostic Power of MicroRNAs in Melanoma: Integrating Machine Learning for Enhanced Accuracy and Pathway Analysis","authors":"Haniyeh Rafiepoor,&nbsp;Alireza Ghorbankhanloo,&nbsp;Soroush Soleimani Dorcheh,&nbsp;Elham Angouraj Taghavi,&nbsp;Alireza Ghanadan,&nbsp;Reza Shirkoohi,&nbsp;Zeinab Aryanian,&nbsp;Saeid Amanpour","doi":"10.1111/jcmm.70367","DOIUrl":"10.1111/jcmm.70367","url":null,"abstract":"<p>This study identifies microRNAs (miRNAs) with significant discriminatory power in distinguishing melanoma from nevus, notably hsa-miR-26a and hsa-miR-211, which have exhibited diagnostic potential with accuracy of 81% and 78% respectively. To enhance diagnostic accuracy, we integrated miRNAs into various machine-learning (ML) models. Incorporating miRNAs with AUC scores above 0.70 significantly improved diagnostic accuracy to 94%, with a sensitivity of 91%. These findings underscore the potential of ML models to leverage miRNA data for enhanced melanoma diagnosis. Additionally, using the miRNet tool, we constructed a network of miRNA–miRNA interactions, revealing 170 key genes in melanoma pathophysiology. Protein–protein interaction network analysis via Cytoscape identified hub genes including MYC, BRCA1, JUN, AURKB, CDKN2A, DDX5, MAPK14, DDX3X, DDX6, FOXM1 and GSK3B. The identification of hub genes and their interactions with miRNAs enhances our understanding of the molecular mechanisms driving melanoma. Pathway enrichment analyses highlighted key pathways associated with differentially expressed miRNAs, including the PI3K/AKT, TGF-beta signalling pathway and cell cycle regulation. These pathways are implicated in melanoma development and progression, reinforcing the significance of our findings. The functional enrichment of miRNAs suggests their critical role in modulating essential pathways in melanoma, suggesting their potential as therapeutic targets.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006087","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}