JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Single Cell RNA-Seq Identifies Cell Subpopulations Contributing to Idiopathic Pulmonary Fibrosis in Humans","authors":"Tangjuan Zhang,&nbsp;Zhichao Hou,&nbsp;Zheng Ding,&nbsp;Peng Wang,&nbsp;Xue Pan,&nbsp;Xiangnan Li","doi":"10.1111/jcmm.70402","DOIUrl":"https://doi.org/10.1111/jcmm.70402","url":null,"abstract":"<p>The cell populations, particularly subpopulations, involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) remain incompletely understood. This study employed single-cell RNA-seq to identify cell populations and subpopulations with significantly altered proportions in the lungs of patients with IPF. In IPF lungs, endothelial cell proportions were significantly increased, while alveolar epithelial cell proportions were markedly decreased. Among the three identified fibroblast subpopulations, the proportion of myofibroblasts was significantly increased, while the proportions of the other two fibroblast subtypes were reduced. Similarly, within the three macrophage subpopulations, the macrophage_SPP1 subpopulation, localised to fibroblastic foci, showed a significant increase in proportion, while the alveolar macrophage subpopulation was significantly reduced. Trajectory analysis revealed that fibroblasts in IPF lungs could differentiate into myofibroblasts, and alveolar macrophages could transition into the macrophage_SPP1 subpopulation. Among T-cell subpopulations, only the CD4 T_FOXP3 subpopulation exhibited a significant change, whereas all four B-cell subpopulations showed significant proportional shifts. These findings provide a comprehensive view of the cellular alterations contributing to IPF pathogenesis. Extensive interactions among various cell populations and subpopulations were identified. The proportions of various cell populations and subpopulations in IPF lungs, including endothelial cells, fibroblasts, macrophages and B cells, were significantly altered. Further in-depth investigation into the roles of cell subpopulations with significantly altered proportions in the onset and progression of IPF will provide valuable insights into the pathological mechanisms underlying the disease. This understanding could facilitate the development of novel therapeutic strategies and medications for IPF treatment.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380445","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":"Machine Learning Accurately Predicts Muscle Invasion of Bladder Cancer Based on Three miRNAs","authors":"Lea Eckhart,&nbsp;Sabrina Rau,&nbsp;Markus Eckstein,&nbsp;Phillip R. Stahl,&nbsp;Hiresh Ayoubian,&nbsp;Julia Heinzelbecker,&nbsp;Farzaneh Zohari,&nbsp;Arndt Hartmann,&nbsp;Michael Stöckle,&nbsp;Hans-Peter Lenhof,&nbsp;Kerstin Junker","doi":"10.1111/jcmm.70361","DOIUrl":"https://doi.org/10.1111/jcmm.70361","url":null,"abstract":"<p>The aim of this study was to validate the diagnostic potential of four previously identified miRNAs in two independent cohorts and to develop accurate classification models to predict invasiveness of bladder cancer. Furthermore, molecular subtypes were investigated. The miRNAs were isolated from pTa low-grade (lg) (<i>n</i> = 113), pT1 high-grade (hg) (<i>n</i> = 133) and muscle-invasive bladder cancer (MIBC) (<i>n</i> = 136) tumour tissue samples (FFPE) after either transurethral resection of a bladder tumour (TURB) or cystectomy (CYS). In both cohorts, the expression of miR-138-5p and miR-200a-3p was significantly lower, and the expression of miR-146b-5p and miR-155-5p was significantly higher in MIBC compared to pTa lg. A k-nearest neighbours (KNN) classifier trained to distinguish pTa lg from MIBC based on three miRNAs achieved an accuracy of 0.94. The accuracy remained at 0.91 when the classifier was applied exclusively to the TURB samples. To guarantee reliable predictions, a <i>conformal prediction</i> approach was applied to the KNN model, which eliminated all misclassifications on the test cohort. pT1 hg samples were classified as MIBC in 32% of cases using the KNN model. miR-146b-5p, miR-155-5p and miR-200a-3p expressions are significantly associated with particular molecular subtypes. In conclusion, we confirmed that the four miRNAs significantly distinguish MIBC from NMIBC. A classification model based on three miRNAs was able to accurately classify the phenotype of invasive tumors. This could potentially support the histopathological diagnosis in bladder cancer and therefore, the clinical decision between performing a radical cystectomy and pursuing bladder-conserving strategies, especially in pT1 hg tumors.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70361","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380379","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":"Targeting the Epigenetic Landscape for Lung Cancer Treatment","authors":"Kostas A. Papavassiliou,&nbsp;Amalia A. Sofianidi,&nbsp;Antonios N. Gargalionis,&nbsp;Athanasios G. Papavassiliou","doi":"10.1111/jcmm.70425","DOIUrl":"https://doi.org/10.1111/jcmm.70425","url":null,"abstract":"&lt;p&gt;The term ‘epigenetics’ was introduced in 1942 by embryologist Conrad Waddington [&lt;span&gt;1&lt;/span&gt;]. However, it was not until the early 21st century that the concept began to attract widespread attention. The field reached a pivotal moment in 2022 when Douglas Hanahan identified epigenetic alterations as a fundamental hallmark of cancer, emphasising their critical contribution to tumour development and progression [&lt;span&gt;2&lt;/span&gt;]. Notably, lung cancer is characterised by both intra- and intertumoral heterogeneity, driven by genetic changes alongside epigenetic modifications [&lt;span&gt;3&lt;/span&gt;]. Due to the extensive and multifaceted role of epigenetic regulation in lung cancer, targeting the reversible nature of the epigenome presents a promising therapeutic approach to address the complexity of tumour heterogeneity, which has long posed serious challenges in lung cancer treatment. Herein, we highlight recent advances in epigenome-targeting strategies in the highly demanding field of lung cancer therapeutics.&lt;/p&gt;&lt;p&gt;The antitumor potential of histone deacetylase (HDAC) inhibitors has been well recognised for almost 20 years [&lt;span&gt;4&lt;/span&gt;]. Suberoylanilide hydroxamic acid (SAHA; commonly known as vorinostat) is a leading pan-HDAC inhibitor of class I/II HDAC enzymes (HDAC1/2) with a demonstrated favourable safety profile in a phase I clinical trial involving patients with &lt;i&gt;Bcl-2-like protein 11&lt;/i&gt; (&lt;i&gt;BIM&lt;/i&gt;) deletion-containing non-small cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy [&lt;span&gt;5&lt;/span&gt;]. Hydroxamic acid-derived HDAC inhibitors, such as trichostatin A (TSA) and quinostat, have shown promising preclinical efficacy against NSCLC [&lt;span&gt;6&lt;/span&gt;]. These compounds induce alterations in tight junction proteins of human lung adenocarcinoma cells while preserving the integrity of the normal epithelial barrier in healthy cells [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Other compelling targets within the epigenome of lung cancer are DNA methyltransferases (DNMTs). In a phase I study, the DNMT inhibitor azacitidine (5-azacytidine) demonstrated a reduction in global DNA methylation of the bronchial epithelium following aerosolised treatment in NSCLC patients [&lt;span&gt;7&lt;/span&gt;]. The treatment was associated with negligible plasma concentrations of the DNMT inhibitor, which indicate minimal systemic absorption of the drug, and thus, exhibited excellent tolerability [&lt;span&gt;7&lt;/span&gt;]. Another DNMT inhibitor, decitabine (a deoxycycline and cytarabine nucleotide derivative), was recently found to preclinically abate NSCLC cell growth and metastatic potential when co-administered with aspirin by inhibiting the β-catenin/signal transducer and activator of transcription 3 (STAT3) signalling axis [&lt;span&gt;8&lt;/span&gt;]. An additional drug influenced by DNMTs is temozolomide, an oral alkylating agent that interferes with DNA through the ability of its metabolites to deposit methyl groups on DNA guanine bases","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380380","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":"Iloprost Concentration-Dependently Attenuates Platelet Function and Apoptosis by Elevating PKA Activity","authors":"Xuexiang Wang,&nbsp;Shuang Chen,&nbsp;Jun Wan,&nbsp;Chunliang Liu,&nbsp;Yan Yan,&nbsp;Muhammad Shoaib Khan,&nbsp;Ziyu Zhao,&nbsp;Kang Sun,&nbsp;Renping Hu,&nbsp;Mengnan Yang,&nbsp;Yue Xia,&nbsp;Kesheng Dai","doi":"10.1111/jcmm.70403","DOIUrl":"https://doi.org/10.1111/jcmm.70403","url":null,"abstract":"<p>Iloprost, a prostacyclin (PGI₂) analogue, stimulates the IP receptor (PTGIR) to interact with the Gsα β/γ complex, leading to the activation of adenylate cyclase, which enzyme produces the second messenger cAMP. Elevation in cAMP triggers intracellular signalling events and regulates a wide variety of cellular activities. Thus, we evaluated the effects of Iloprost on platelet function and apoptosis and in vivo haemostasis and thrombosis, as well as the underlying mechanisms. Firstly, we showed that Iloprost concentration-dependently inhibited agonist-induced P-selectin exposure, integrin αIIbβ3 activation, platelet aggregation, ATP release, platelet spreading, and clot retraction. Moreover, Iloprost dose-dependently inhibited FeCl₃-induced mouse mesenteric arteriole thrombosis and markedly prolonged the tail bleeding time. Iloprost also concentration-dependently inhibited mitochondrial membrane potential (ΔΨm) depolarisation and phosphatidylserine (PS) externalisation in platelets, thereby inhibiting platelet apoptosis, and Iloprost at concentrations lower than 2 nM inhibited only platelet apoptosis but not platelet function. Importantly, Iloprost at low doses markedly elevated peripheral platelet counts in GPIbα antibody-induced immune thrombocytopenia (ITP). Mechanistic studies showed that Iloprost concentration-dependently antagonised agonist-induced decline of protein kinase A (PKA) activity and elevation of cytoplasmic Ca²⁺ in platelets, thereby attenuating platelet activation and aggregation. Elevation in PKA activity inhibited dephosphorylation of proapoptotic protein BAD and reduced caspase-3 activity, thus retarding platelet apoptosis. These data demonstrate that Iloprost dose-dependently inhibits platelet function and apoptosis by elevating PKA activity. Moderate-dose Iloprost impairs haemostasis and thrombosis via suppression of platelet function, and low-dose Iloprost elevates peripheral platelet levels by inhibiting platelet apoptosis while having no effects on platelet function.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380446","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 Bioinformatics Analysis Reveals the Role of Shared Cuproptosis- and Ferroptosis-Related DEG DLD in Abdominal Aortic Aneurysm","authors":"Xingwei Hu,&nbsp;Lu Hu,&nbsp;Xiaoyun Si,&nbsp;Qian Feng,&nbsp;Yi Ma,&nbsp;Zhijiang Liu,&nbsp;Xiang He,&nbsp;Bei Shi","doi":"10.1111/jcmm.70399","DOIUrl":"https://doi.org/10.1111/jcmm.70399","url":null,"abstract":"<p>Ferroptosis plays a crucial role in the progression of abdominal aortic aneurysm (AAA). Cuproptosis, as a new mode of death, has some similarities with ferroptosis. The primary objective of this study was to develop the role of shared cuproptosis-related differentially expressed genes (CRDEGs) and ferroptosis-related differentially expressed genes (FRDEGs) in AAA. RNA sequencing and bioinformatic analyses of human AAA tissue were used to identify dihydrolipoamide dehydrogenase (DLD), which is involved in cuproptosis and ferroptosis. qRT-PCR and IHC assays further confirmed that the DLD level was substantially higher in the AAA group than in the control group. Finally, experimental verification was conducted to identify that DLD could promote the necrosis, apoptosis and mitophagy of SMCs. In summary, our research identified DLD, linked to cuproptosis and ferroptosis, as differentially expressed in AAA across human and murine samples. DLD's role in regulating SMC necrosis, apoptosis and mitophagy positions it as a potential AAA biomarker and therapeutic target, warranting further investigation for clinical applications.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248826","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":"Progranulin Protects Against Osteoporosis by Regulating Osteoclast and Osteoblast Balance via TNFR Pathway","authors":"Shaoyi Wang,&nbsp;Hengyan Zhang,&nbsp;Yanbin Zhu,&nbsp;Xiaocong Zhou,&nbsp;Haoxin Zhai,&nbsp;Qiting He,&nbsp;Xuetao Zhu,&nbsp;Yuanqiang Zhang","doi":"10.1111/jcmm.70385","DOIUrl":"https://doi.org/10.1111/jcmm.70385","url":null,"abstract":"<p>Osteoporosis is a disease of bone metabolism caused by an imbalance between osteoclast-mediated bone destruction and osteoblast-mediated bone formation. Tumour necrosis factor α (TNFα) has been reported to promote osteoclast generation and inhibit osteoblast generation. Progranulin (PGRN), which has a strong anti-inflammatory effect, interacts with tumour necrosis factor receptor (TNFR). Serum and bone tissues from patients with or without osteoporosis were collected to analyse the relationship between PGRN content and bone metabolic markers. The role of TNFα and PGRN in osteoclast differentiation was explored by using RAW 264.7 cells and BMMs. MC3T3-E1 cells and BMSCs were used to observe the role of TNFα and PGRN in osteoblast differentiation. The PGRN content in the serum and bone tissues of osteoporosis patients was lower than that in the serum and bone tissues of nonosteoporosis patients. TNFα promoted osteoclast differentiation, while PGRN inhibited this effect by interacting with TNFR1. PGRN inhibited TNFα-mediated attenuation of osteoblast differentiation by interacting with TNFR1. Moreover, PGRN alone promoted osteoblast differentiation by interacting with TNFR2. Our findings reveal that PGRN can effectively inhibit TNFα-induced osteoporosis and has a certain osteogenic effect. This discovery might provide a potential target for osteoporosis treatment.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248615","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":"Unlocking the Potential of Extracellular Vesicles in Cardiovascular Disease","authors":"Hanbin Li,&nbsp;Lu Wang,&nbsp;Hongxin Cheng,&nbsp;Qing Zhang,&nbsp;Shiqi Wang,&nbsp;Wen Zhong,&nbsp;Chengqi He,&nbsp;Quan Wei","doi":"10.1111/jcmm.70407","DOIUrl":"https://doi.org/10.1111/jcmm.70407","url":null,"abstract":"<p>Extracellular vesicles (EVs) are micro-nanoscale biological particles encapsulated by phospholipid bilayers, which regulate cell migration, angiogenesis and tumour cell growth by transmitting various biomolecules such as nucleic acids and proteins. EVs are composed of exosomes, microparticles and apoptotic bodies. Its benefits pass through biofilms and are not degraded by various enzymes, so it can be used as a biomarker in potential diseases and has attracted much attention from researchers. Current studies have found that EVs are involved in the development of various cardiovascular diseases (CVD), such as heart failure and myocardial ischemia–reperfusion injury. In addition, stem cell-derived EVs play an important role in the diagnosis and treatment of a variety of CVD. In this review, we present the biological features of EVs, the role of EVs in various CVD, and the challenges they encounter in the treatment of CVD.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70407","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248616","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":"Geniposide Protects Against Myocardial Infarction Injury via the Restoration in Gut Microbiota and Gut–Brain Axis","authors":"Jie Chen,&nbsp;Tong Zhu,&nbsp;Jinbao Yang,&nbsp;Mengqing Shen,&nbsp;Danmei Wang,&nbsp;Boyuan Gu,&nbsp;Jin Xu,&nbsp;Mingxia Zhang,&nbsp;Xiuli Hao,&nbsp;Zheng Tang,&nbsp;Jie Tong,&nbsp;Yan Du,&nbsp;Bao Zhang,&nbsp;Hongbao Li,&nbsp;MengLu Xu","doi":"10.1111/jcmm.70406","DOIUrl":"https://doi.org/10.1111/jcmm.70406","url":null,"abstract":"<p>Improving gut dysbiosis and impaired gut–brain axis has been a potent therapeutic strategy for treating myocardial infarction (MI). Geniposide (GEN), a traditional Chinese medicine extract, has demonstrated substantial cardioprotective properties post-MI. Nevertheless, the effect of GEN on gut microbial, gut–brain communication, and its potential mechanism remains unclear. In this study, we initially found that GEN significantly alleviated MI-induced cardiac dysfunction from echocardiographic data and decreased myocardial fibrosis, inflammation, apoptosis and hypertrophy post-MI. Additionally, we investigated the effects of GEN on gut pathology, and observed that GEN led to a remarkable change in gut microbiota as evidenced by altering β-diversity and short-chain fatty acids (SCFAs) levels, and alleviated intestinal damage indicated by reduced inflammation and barrier permeability post-MI. Finally, our investigation into brain pathology revealed that GEN induced a remarkable inhibition in PVN inflammation and sympathetic activity following MI. Collectively, these findings imply that the cardioprotective effects of GEN against MI were mediated possibly via an improvement in the impaired gut–brain axis. Mechanically, GEN-induced increase of microbiota-derived SCFAs might be the critical factor linking gut microbiota and reduced neuroinflammation with PVN, which leads to the suppression of sympathetic activation, therefore protecting the myocardium against MI-induced damage.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70406","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248618","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":"Prediction of Hepatocellular Carcinoma Prognosis and Immunotherapy Response Using Mitochondrial Dysregulation Features","authors":"Jia Yu,&nbsp;Shengli Wu,&nbsp;Jinglong Gong,&nbsp;Wenbing Deng,&nbsp;Zhongsheng Xiao,&nbsp;LiangLiang Wu,&nbsp;Hong Long","doi":"10.1111/jcmm.70389","DOIUrl":"https://doi.org/10.1111/jcmm.70389","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) is a major contributor to cancer-related deaths globally. Although there have been improvements in identifying treating the disease, patient outcomes are still unfavourable because of the significant variation in HCC. Mitochondrial-related genes (MRGs) are crucial in tumour metabolism, cell death and immune response, emerging as potential therapeutic targets. We analysed 2030 MRGs using TCGA, GEO and HCCDB18 databases. Differentially expressed genes were identified using edgeR and limma, and enrichment analysis was performed via the clusterProfiler package. A prognostic model was built using machine learning algorithms and evaluated using LOOCV. Immune infiltration was assessed with CIBERSORT, EPIC, MCPCounter and TIMER algorithms, and drug sensitivity was analysed using the CTRP and PRISM datasets. MRG expression levels are significantly associated with worse outcomes in HCC patients outperformed conventional clinical indicators in immune response revealed that individuals at high risk exhibited weaker immune responses, characterised by reduced immune scores, and elevated levels of CD8+ T cells and macrophages. Notably, high-risk patients also displayed heightened susceptibility to chemotherapy agents such as paclitaxel and irinotecan. Abnormal MRG expression serves as a significant biomarker for HCC prognosis. The developed model accurately predicts disease progression and can guide personalised treatment, especially for immune and chemotherapeutic therapies. Further validation with broader clinical samples is needed.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248750","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–GLI1 Pathway Regulates Osteogenic Differentiation of Human Cervical Posterior Longitudinal Ligament Cells by BMP Signalling Pathway","authors":"Wenbo Xu,&nbsp;Bingbing Ran,&nbsp;Toshimi Aizawa,&nbsp;Wanguo Liu,&nbsp;Jianhui Zhao,&nbsp;Renrui Niu,&nbsp;Zeping Liu,&nbsp;Rui Gu","doi":"10.1111/jcmm.70393","DOIUrl":"https://doi.org/10.1111/jcmm.70393","url":null,"abstract":"<p>Cervical ossification of the posterior longitudinal ligament (OPLL) is an ectopic ossification disorder characterised by endochondral ossification. Its aetiology remains to be fully elucidated. This study aimed to clarify its pathogenesis through RNA sequencing of primary cells cultured from patients without cervical OPLL (control, PLL) and patients with cervical OPLL (disease, OPLL). We revealed for the first time the role of GLI1 within OPLL cells. Functional experiments indicated that GLI1, acting as a pivotal mediator between the upstream Hedgehog pathway and downstream BMP pathway, influences the pathogenesis of OPLL. The positive/negative effects on osteogenic differentiation following activation/inhibition of the Hedgehog pathway can be rescued by manipulating GLI1 expression. Overexpression of GLI1 activates BMP signalling, enhancing osteogenic capacity in PLL cells, while GLI1 knockdown suppresses BMP signal transduction, attenuating osteogenic differentiation in OPLL cells. Our findings highlight the significant role of the canonical Hedgehog signalling pathway and its interaction with the BMP pathway in the pathogenesis of OPLL.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70393","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248617","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}