JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"LncRNA SNHG14 Regulated by ZNF460 Promotes Gastric Cancer Progression and Metastasis by Targeting the miR-206/FNDC3A Axis","authors":"Bin Liu,&nbsp;Tingting Lu,&nbsp;Guangming Zhang,&nbsp;Xiaohua Dong,&nbsp;Miao Yu,&nbsp;Hui Cai","doi":"10.1111/jcmm.70652","DOIUrl":"https://doi.org/10.1111/jcmm.70652","url":null,"abstract":"<p>The current study investigated the functional role of long non-coding RNA SNHG14 (lncRNA SNHG14) in gastric cancer (GC) progression and its underlying mechanisms. Compared with para-carcinoma tissues, SNHG14 was upregulated in GC tissues, correlating with a poor prognosis in GC patients. SNHG14 knockdown significantly weakened the proliferation, migration and invasion capabilities of GC cell lines while enhancing the apoptosis ability of GC cells. Simultaneously, SNHG14 overexpression reversed these effects. RNA fluorescence in situ hybridization (FISH) and nucleocytoplasmic separation assays revealed that SNHG14 was primarily located in the cytoplasm of GC cells. Combined sequencing of the miRNAome and transcriptome depicted that miR-206 could be a potential target for SNHG14. Mechanistically, assays such as luciferase reporter, RNA immunoprecipitation (RIP) and RNA pulldown established that lncRNA SNHG14 acted as a sponge for miR-206. This prevented the degradation of its target gene, FNDC3A, playing a tumour-suppressive role in GC. In addition, FNDC3A directly interacted with the SNHG14 promoter and induced transcription, thus facilitating GC progression. Therefore, our research findings suggested a novel pathway to promote GC progression through the FNDC3A/lncRNA SNHG14/miR-206/FNDC3A axis. Moreover, the findings indicated that SNHG14 could become a potential biomarker and therapeutic target for GC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291875","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":"A Model of Butyrate Activity and Resistance in CRC","authors":"Michael Bordonaro","doi":"10.1111/jcmm.70656","DOIUrl":"https://doi.org/10.1111/jcmm.70656","url":null,"abstract":"<p>Butyrate, a breakdown product of dietary fibre, may in part mediate the ability of a high-fibre diet to reduce the risk of colorectal cancer (CRC). However, CRC can still develop despite a high-fibre diet; hence, butyrate resistance may influence colonic tumorigenesis. To model butyrate resistance in vitro, butyrate-resistant cells were developed and mechanisms identified by which these cells evade the effects of butyrate. These mechanisms can be interpreted in light of the existing literature to further our understanding of butyrate resistance. The current review integrates findings from various studies from my laboratory on butyrate-resistant cells, in addition to other work in the literature, to present a model of how butyrate-resistant CRC cells balance different signalling outputs to generate the resistant phenotype. Loss of p300 expression in butyrate resistance allows increased noncanonical Wnt signalling to occur without activating differentiation pathways, AKT/PKB survival signalling is activated, and CBP-Wnt activity is maintained in the pro-proliferative range. Further, overexpression of Tcf3 suppresses butyrate-induced Wnt hyperactivation. Other factors, signalling pathways and modifying influences also affect butyrate sensitivity vs. resistance. Understanding the possible role of butyrate resistance will assist in improving chemopreventive strategies for this disease.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70656","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273392","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":"LncRNA Dleu2 Serve as a Novel Biomarker for Ablation Recurrence and Promote Atrial Remodelling by Targeting Nr4a1 in Atrial Fibrillation","authors":"Feiyu Wei,&nbsp;Yazhe Ma,&nbsp;Hong Xiang,&nbsp;Xi Zhang,&nbsp;Jie Fan","doi":"10.1111/jcmm.70618","DOIUrl":"https://doi.org/10.1111/jcmm.70618","url":null,"abstract":"<p>Atrial remodelling is the principal pathological mechanism for atrial fibrillation (AF) development and progression. Long noncoding RNAs (LncRNAs) exhibit important effects on cardiovascular diseases. However, the role of LncRNAs in AF development requires further investigation. This study aimed to explore the function and mechanism of LncRNAs in AF. The differentially expressed LncRNAs of atrial tissue in a mouse AF model, which was established via continuous infusion of Ang II for 3 weeks, were screened with RNA sequencing. Experiments included an electrophysiological study; Masson, H&amp;E and TUNEL staining; flow cytometry; and RNA pull-down; FISH and RNA immunoprecipitation assays were performed to define the function and underlying mechanisms of LncRNAs in AF susceptibility and atrial remodelling. The Kaplan–Meier method was used to plot the curve of freedom from atrial tachyarrhythmia. LncRNA Dleu2 expression was increased in atrial tissue and peripheral blood and was positively associated with left atrial fibrosis in persistent AF. Furthermore, elevated expression of LncRNA Dleu2 was correlated with a higher AF recurrence rate after ablation at the 24-month follow-up (65.0% vs. 85.0%, <i>p</i> = 0.03). Accordingly, upregulation and downregulation of LncRNA Dleu2 expression could regulate atrial remodelling and AF susceptibility, and we also demonstrated that LncRNA Dleu2 directly bound to Nr4a1. Subsequently, inhibition of Nr4a1 expression could also regulate AF susceptibility and atrial remodelling and reverse the effects of LncRNA Dleu2 on AF occurrence. This study demonstrated that LncRNA Dleu2 was independently associated with atrial fibrosis and AF recurrence after ablation, and contributed to AF susceptibility by directly targeting Nr4a1.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70618","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273391","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":"Monoclonal Antibodies to Thyrotropin Receptor With Thyroid-Stimulating Activity Activate the NF-κB Pathway to Induce Chemokine Expression","authors":"Yang Yang,&nbsp;Chen Hui","doi":"10.1111/jcmm.70647","DOIUrl":"https://doi.org/10.1111/jcmm.70647","url":null,"abstract":"<p>The A subunit of thyrotropin receptor (TSHR) is thought to be the crucial gene mediating stimulatory autoantibodies in Graves' diease (GD), but it remains unclear what the molecular basis of this pathological antibody response is. Stimulatory TSHR autoantibodies may induce activation of multiple signalling pathways in GD, modulate chemokine exposure and further stimulate immune imbalance. In this study, we prepared TSHR 289 protein by using insect baculovirus expression, adenovirus-expressed TSHR289 immunised mice, and obtained three mouse anti-TSHR monoclonal antibodies (mAbs), 1A4, 7C3 and 22B1, by the hybridoma technique. Flow assay and ELISA tests tested the activity and competitive binding of the mAbs. After mAbs stimulation of human thyrocytes, RT-qPCR and ELISA were used to detect the expression of chemokine; Western blotting detected the expression of CCL19 and the level of phosphorylation of NF-κB. Nanogram concentrations of the IgG mAbs 1A4, 7C3 and 22B1 and their Fab induce TSHR stimulation. TRAb in the serum of GD patients competitively inhibits the binding of HRP-conjugated mAbs to TSHR on the coated plate. Injection of micrograms of 7C3 resulted in elevated serum thyroxine and columnar and papillary hyperplasia of thyroid follicular epithelial cells. All three mAbs induced distinct expression of CCL2, CCL19 and CCL5 by activating canonical and non-canonical NF-κB signalling pathways in human thyrocytes. Collectively, we obtained three mouse anti-TSHR mAbs which provide an improved approach to characterise the molecular basis of this pathological response, and confirmed that stimulating antibodies activate NF-κB, inducing chemokines involved in the autoimmune response.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70647","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264529","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":"From Growth Factors to Structure: PDGF and TGF-β in Granulation Tissue Formation. A Literature Review","authors":"Josiah Irma,&nbsp;Arief S. Kartasasmita,&nbsp;Angga Kartiwa,&nbsp;Irawati Irfani,&nbsp;Saraswati Anindita Rizki,&nbsp;Serena Onasis","doi":"10.1111/jcmm.70374","DOIUrl":"https://doi.org/10.1111/jcmm.70374","url":null,"abstract":"<p>Platelet-Derived Growth Factors (PDGFs) and Transforming Growth Factor β (TGFβ) are pivotal in orchestrating the complex wound healing process, particularly in granulation tissue formation. This review aims to comprehensively examine the roles of PDGF alongisde TGFβ in granulation tissue formation and their implications for abnormal wound healing. PDGFs, as homodimeric or heterodimeric combinations, such that PDGF-AA, PDGF-AB and PDGF-BB stimulate fibroblast proliferation and extracellular matrix synthesis, which is crucial for tissue repair. TGFβ, with its three isoforms, influences granulation tissue through diverse functions, with TGFβ-1 pivotal in fibrosis formation. Understanding their signalling pathways, notably PDGF's engagement with PDGF receptors and subsequent activation of cellular pathways, illuminates their roles in wound healing cascades. Excessive granulation, a complication of abnormal wound healing, involves dysregulated PDGF and TGFβ activity, leading to hypertrophic scar formation. Clinical management, particularly in ophthalmology, addresses excessive granulation's impact on procedures like endo-dacryocystorhinostomy. Strategies employing steroid agents and Mitomycin-C aim to mitigate ostium granulation. The potential use of PDGF receptor blockers, such as olaratumab, warrants further investigation for managing excessive granulation. In conclusion, PDGF and TGFβ emerge as critical regulators in granulation tissue formation, underscoring their significance in wound healing processes and offering avenues for therapeutic intervention.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255930","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":"Impact of SPP1 and HMOX1 Genes in Glioma: Correlations With Oncolytic Virus Infection, Adverse Prognosis and Increased Cell Proliferation","authors":"Chunze Cui,&nbsp;Chunyan Wu,&nbsp;Shaoqi Zhang,&nbsp;Xiaofeng Yin","doi":"10.1111/jcmm.70651","DOIUrl":"https://doi.org/10.1111/jcmm.70651","url":null,"abstract":"<p>A high death rate among glioma patients is primarily due to poor prognostic outcomes and tumour metastasis. Oncolytic viruses have gained attention as a potential therapeutic strategy as eliminating tumour cells and modifying tumour microenvironment. This research highlights the urgent necessity to investigate novel therapeutic targets and clarify molecular mechanisms in glioma. The GSE166914 dataset was analysed to examine the SPP1 and HMOX1 expression after VSV-M51 infection in glioma. By utilising the CancerSEA database, we assessed the potential function of SPP1/HMOX1 among pan-cancer. Analysis of gene/protein expression levels and clinical significance was performed to identify the roles of SPP1/HMOX1 using TCGA-glioma data. A correlation analysis was performed to screen co-expressed genes, followed by GSEA analysis. qPCR and HPA analysis were utilised to assess the mRNA/protein levels of SPP1 and HMOX1 in glioma tissues. The anti-apoptotic activity of SPP1 and HMOX1 was confirmed utilising the CCK-8 assay and flow cytometry. VSV-M51 infection resulted in SPP1/HMOX1 downregulation in T98 cells. The expression levels of SPP1/HMOX1 were significantly increased in glioma and associated with histological classifications and WHO grades. Elevated levels of SPP1/HMOX1 were related to poor prognosis in glioma. SPP1/HMOX1 was involved in influencing glioma cell motility through the PI3K/AKT, JAK–STAT and syndecan 1 signalling pathways. In vitro experiments showed higher expression levels of SPP1/HMOX1 in glioma tissues. Silencing SPP1/HMOX1 suppressed glioma cell proliferation and promoted apoptosis. In conclusion, dysregulated SPP1/HMOX1 expression was strongly related to glioma WHO grades and worse outcomes, providing deeper insights into glioma therapeutic targets and oncolytic virus-based treatments.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255933","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":"Inhibitors of p53 Apoptosis-Stimulating Protein Mitigate Acute Kidney Injury by Modulating the HIF-1α/SLC7A11 Pathway to Suppress Ferroptosis","authors":"Peng Kang,&nbsp;Xiangjun Zhou,&nbsp;Sheng Zhao,&nbsp;Weimin Yu,&nbsp;Zehua Ye,&nbsp;Fan Cheng","doi":"10.1111/jcmm.70580","DOIUrl":"https://doi.org/10.1111/jcmm.70580","url":null,"abstract":"<p>Acute kidney injury (AKI) is a complex disease caused by different causes, especially ischaemia–reperfusion (I/R) injury. Ferroptosis is the main form of I/R-induced organ injury, and blocking ferroptosis has demonstrated therapeutic potential in ameliorating organ injury. We investigated the roles of apoptosis-stimulating protein of p53 (iASPP) and hypoxia-inducible factor-1α (HIF-1α) in ferroptosis during renal I/R injury. HIF-1α gene was knocked out in a hypoxia/reoxygenation model of renal tubular epithelial cells, and iASPP overexpression and knockdown plasmids were transfected. In I/R mouse models, conditional knockout of HIF-1α mice and injection of overexpressed iASPP adeno-associated viruses were used to validate downstream ferroptosis-related changes. The results showed that the ferroptosis level of mice in the I/R group was increased, and the addition of Ferrostatin-1 (Fer-1) and FG-4592 could alleviate the ferroptosis. HIF-1α conditional knockout mice showed exacerbated ferroptosis. HIF-1α can directly interact with SLC7A11, a key ferroptosis regulator, modulating ferroptosis progression. Similar to HIF-1α, iASPP expression was significantly increased in the I/R group, and overexpression of iASPP upregulated HIF-1α and SLC7A11 expression, consequently mitigating ferroptosis-mediated damage. In summary, our study suggests that iASPP exerts renal protection during I/R injury by regulating the HIF-1α/SLC7A11 axis to suppress ferroptosis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244723","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":"Downregulation of Alox5 Inhibits Ferroptosis to Improve Doxorubicin-Induced Cardiotoxicity via the P53/SLC7A11 Pathway","authors":"Wenxi Fang,&nbsp;Zhefu Hu,&nbsp;Bo Shen,&nbsp;Xiaofeng Zeng,&nbsp;Si Chen,&nbsp;Shasha Wang,&nbsp;Saiyang Xie,&nbsp;Wei Deng","doi":"10.1111/jcmm.70641","DOIUrl":"https://doi.org/10.1111/jcmm.70641","url":null,"abstract":"<p>Doxorubicin (DOX) is an anthracycline chemotherapeutic drug used for tumour treatment. Due to DOX-induced cardiotoxicity (DIC), its clinical application has been widely limited. Multiple studies have shown that ferroptosis is involved in the pathogenesis of DIC and that arachidonate 5-lipoxygenase (Alox5) plays an important role in the occurrence and development of ferroptosis. The aim of this study was to provide evidence that silencing Alox5 alleviated DIC by affecting ferroptosis and identify mechanisms. Acute models of DIC were established in wild-type (WT) C57BL/6 and Alox5-deficient (Alox5 KO) mice and neonatal rat ventricular myocytes (NRVMs). Alox5 was upregulated in vivo and in vitro during DIC. Subsequently, we overexpressed the Alox5 gene in adult mice using a recombinant adenovirus expression vector (rAAV9). Compared with that in WT mice, overexpressing Alox5 accelerated DOX-induced myocardial injury and cardiac dysfunction. This finding was also confirmed in vitro. In contrast, silencing the Alox5 gene protected against myocardial injury in the DIC model and reduced ferroptosis and inflammation, and this effect was confirmed in vitro. In addition, transcriptomics and GO enrichment analysis of adult mouse cardiomyocytes showed that Alox5 could ameliorate DIC by inhibiting ferroptosis and inflammation. Moreover, P53 was identified as a target of Alox5. Subsequently, in vivo and in vitro experiments showed that silencing Alox5 could alleviate ferroptosis and inflammation. Further in vivo and in vitro experiments demonstrated that dexrazoxane (DXZ) could ameliorate DIC caused by Alox5 overexpression by alleviating ferroptosis. Mechanistically, silencing Alox5 could reduce reactive oxygen species (ROS) production through the P53/SLC7A11 pathway. Furthermore, P53 inhibitors significantly inhibited the adverse effects of Alox5 overexpression on DIC. The final experiment showed that pharmacological inhibition of Alox5 could prevent DIC in vivo and in vitro. Our study showed that the downregulation of Alox5 alleviated myocardial damage associated with DIC via the P53/SLC7A11 pathway. Therefore, inhibiting Alox5 might be a potential strategy for the treatment of DIC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244526","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":"Succinate Accumulation Accelerates Oxidative Stress to Promote Pulmonary Epithelial Cell Apoptosis During Lung Ischemia–Reperfusion Injury","authors":"Wenhao Wang,&nbsp;Nana Feng,&nbsp;Qi Shi,&nbsp;Jichun Yang,&nbsp;Yulong Tan,&nbsp;Wenyong Zhou,&nbsp;Meng Shi","doi":"10.1111/jcmm.70645","DOIUrl":"https://doi.org/10.1111/jcmm.70645","url":null,"abstract":"<p>During ischemia, succinate accumulates and leads to significant damage to the tissues. The specific role of succinate in lung ischemia–reperfusion injury (LIRI) remains unresolved. Differential metabolites in LIRI were identified through untargeted metabolomics using gas chromatography–mass spectrometry (GC–MS). Type II alveolar epithelial cells (AECs) were cultured and subjected to hypoxia/reoxygenation (H/R) in vitro, while an in vivo LIRI model was developed using C57BL/6 mice. Cytokine levels, lung oedema, histopathological alterations and lung functionality were evaluated. Protein levels were analysed through Western blotting. The mitochondrial membrane potential (Δψm) was measured using the JC-1 fluorescent dye, and mitochondrial morphology in Type II AECs following H/R damage was observed with a transmission electron microscope (TEM). Oxidative stress and apoptosis markers were detected in lung tissues and Type II AECs. Succinate was increased in the peripheral serum of LIRI patients and the C57BL/6 mices model. Succinate pre-treatment promotes Type II AEC cell apoptosis and oxidative stress, inhibits mitochondrial membrane potential and damages the alveolar epithelial cells' mitochondrial activity after H/R. Meanwhile, succinate may considerably reduce the amounts of acyl-CoA oxidase 1 (ACOX1) and isocitrate dehydrogenase 2 (IDH2) protein expression. Importantly, N-acetyl-L-cysteine (NAC) was observed to dramatically retard succinate-induced cell apoptosis, mitochondrial dysfunction and ROS levels in alveolar epithelial cells following H/R in vivo, with succinate-neutralising antibodies protecting LIRI in vitro. In conclusion, during ischemia, the build-up of succinate contributes to the advancement of LIRI by enhancing mitochondrial oxidative stress and promoting cell apoptosis, and blocking succinate may be a potential target for LIRI treatment.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70645","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244527","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":"Effects of Adalimumab on Mitochondria of Psoriatic Mesenchymal Stem Cells","authors":"Mariangela Di Vincenzo,&nbsp;Anna Campanati,&nbsp;Giulia Cannelonga,&nbsp;Federico Diotallevi,&nbsp;Giorgia Cerqueni,&nbsp;Andrea Marani,&nbsp;Saverio Marchi,&nbsp;Monia Orciani","doi":"10.1111/jcmm.70642","DOIUrl":"https://doi.org/10.1111/jcmm.70642","url":null,"abstract":"<p>Psoriasis is a systemic immune-mediated disorder involving multiple signalling pathways. Recent attempts to treat psoriasis involve monoclonal antibodies that block different inflammatory pathways. The monoclonal antibody Adalimumab (ADM) is one of the biologics that block the inflammatory cascade of TNF-alpha. We previously demonstrated the involvement of mesenchymal stem cells (MSCs) in psoriasis pathogenesis and showed their responsiveness to ADM, highlighting their dual role as contributors and therapeutic targets. Mitochondrial dysfunction is increasingly recognised in psoriasis, contributing to oxidative stress, altered metabolism, and immune dysregulation. These mitochondrial changes drive chronic inflammation, keratinocyte hyperproliferation, and immune activation—hallmarks of psoriasis—making mitochondria a key focus for therapeutic strategies. In this study, we further investigated ADM's impact on mitochondrial morphology and function in MSCs. MSCs were isolated from the skin of psoriatic patients (PSO-MSCs) and healthy controls (C-MSCs), then exposed to H₂O₂ or LPS to mimic the oxidative and inflammatory environment of psoriasis. PSO-MSCs were also treated with ADM for 72 h before mitochondrial analysis. Compared to C-MSCs, PSO-MSCs showed marked mitochondrial abnormalities. ADM treatment partially reversed these alterations, restoring mitochondrial parameters toward control levels under basal conditions. However, ADM failed to prevent mitochondrial dysfunction when additional stress (H₂O₂ or LPS) was introduced. In conclusion, ADM exerts a protective effect on mitochondrial health in MSCs from psoriatic patients, suggesting mitochondria are among its therapeutic targets. Nonetheless, ADM alone cannot counteract further environmental or inflammatory stressors, which may explain symptom relapse observed in clinical settings.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220368","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}