JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Correction to ‘Potential Inflammatory Mediators in Pericardial Fluids of Patients With Coronary Artery Diseases and Their Association With Plasma Biomarkers’","authors":"","doi":"10.1111/jcmm.71319","DOIUrl":"10.1111/jcmm.71319","url":null,"abstract":"<p>Dikme R, Aydın MS, Temiz E, Koyuncu İ, Işık M. “ Potential Inflammatory Mediators in Pericardial Fluids of Patients With Coronary Artery Diseases and Their Association With Plasma Biomarkers,” <i>Journal of Cellular and Molecular Medicine</i>, 2025; 29: e70625. https://doi.org/10.1111/jcmm.70625.</p><p>In the originally published version of this article, the Funding statement was incorrectly stated as follows:</p><p>‘The authors received no specific funding for this work’.</p><p>The correct Funding statement is:</p><p>‘This study was supported by Harran University Scientific Research Projects Coordination Unit (Project No. 17009)’.</p><p>The authors apologize for this error.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712285","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":"RETRACTION: LINC01614: A Potential Therapeutic Target in Astrocytoma Progression","authors":"","doi":"10.1111/jcmm.71311","DOIUrl":"10.1111/jcmm.71311","url":null,"abstract":"&lt;p&gt;&lt;b&gt;RETRACTION&lt;/b&gt;: F. Karimpour, M. H. Hooshiar, S. Abbasnejad, K. Abdi, A. Jalili, A. Khanmirzaei, S. Tutunchi, A.-R. Javanmard, M. Hajiesmaeili, S. M. H. Ghaderian, “LINC01614: A Potential Therapeutic Target in Astrocytoma Progression,” &lt;i&gt;Journal of Cellular and Molecular Medicine&lt;/i&gt; 29, no. 15 (2025): e70623. https://doi.org/10.1111/jcmm.70623.&lt;/p&gt;&lt;p&gt;The above article, published online on 30 July 2025 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stefan Constantinescu; and John Wiley &amp; Sons Ltd. A third party reported on PubPeer [1] that the ethics approval numbers listed in this article (IR.SBMU.RETECH.REC.1398.485 and IR.SBMU.RETECH.REC.1399.1330) do not correspond to the topic of the article. Further reports from another third party expressed concerns that the western blot experiments reported in Figure 3 did not specify target proteins, lacked controls, and did not contain sufficient methodological details. The editors reviewed these concerns and agreed that the Methods presented in the article contained insufficient information.&lt;/p&gt;&lt;p&gt;Additional investigation by the publisher found that the Mock+PBS data in Figure 6A and Knock down Linc01614 data in Figure 6B had also been published in another article by a different author group [Liu et al. 2025 (https://doi.org/10.1007/s12672-025-02748-0)]. Both articles were under review at their respective journals at the same time and both articles report these data as deriving from different experimental conditions. The investigation also found that Supplementary File S1 did not correlate to its in-text citation.&lt;/p&gt;&lt;p&gt;The authors responded to an inquiry by the publisher and stated that both ethical approval codes were supplied because the research in this article used samples collected from two other clinical projects involving patients with diagnosed glioma and astrocytoma cases. They further stated that the apoptosis assay data were generated by an external service provider and that similarity between the data was coincidental. Original data presented in Figure 6 were provided by the authors. Subsequently, a review by an independent expert found that the data and explanation were insufficient and that there were discrepancies between the data provided and the results presented in the article.&lt;/p&gt;&lt;p&gt;The publisher and journal editorial board agree that they cannot verify the concerns regarding ethical approval. However, while the authors provided some further information regarding the methods and the data issues, their response was not adequate to address these concerns. The retraction has been agreed to by the publisher and editorial board because the evidence of data re-use with another article, combined with concerns about the reliability of the methods and further concerns about the original data, fundamentally compromises the editors’ confidence in the results presented. The authors were informed of the retraction","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712315","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 Novel Mechanism of Tumour Communication: Malignant Extracellular Vesicles-Induced Aggressiveness in Benign Cells and Melatonin-Driven Reversal","authors":"Barbara Maria Frigieri,&nbsp;Guilherme Silva Bruno Barbosa,&nbsp;Adriana Alonso Novais,&nbsp;Caroline Patini de Rezende,&nbsp;Fausto Almeida,&nbsp;Vinicius Augusto Simão,&nbsp;Mari Cleide Sogayar,&nbsp;Luiz Gustavo de Almeida Chuffa,&nbsp;Russel J. Reiter,&nbsp;Debora Aparecida Pires de Campos Zuccari","doi":"10.1111/jcmm.71309","DOIUrl":"10.1111/jcmm.71309","url":null,"abstract":"<p>Extracellular vesicles (EVs/EV) are key mediators of intercellular communication and influence proliferation, migration, and metabolic reprogramming. In breast cancer, EVs released by malignant cells carry bioactive molecules capable of altering the behaviour of surrounding cells. However, it remains uncertain whether these vesicles can directly induce a more aggressive phenotype in benign mammary cells. Melatonin, known for its oncostatic properties, regulates proliferation, metabolism, and signalling pathways associated with tumour progression and may modulate EV-mediated intercellular communication. This study evaluated whether EVs derived from four breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-453 and HCC70), treated or not with melatonin, can modify the phenotype of benign MCF10A cells. EVs were isolated from conditioned media and co-cultured with benign cells. Assays of proliferation, viability, colony formation, migration, lactate production and immunofluorescence were performed to assess EV-mediated effects. EVs derived from malignant cells promoted a more aggressive phenotype in benign cells, as evidenced by increased proliferation, migration, and phenotypic remodelling. In contrast, EVs derived from melatonin-treated malignant cells were associated with reduced lactate production and attenuation of pro-tumoural features. Overall, these findings demonstrate that tumour-derived EVs can induce aggressive traits in benign mammary cells and suggest that melatonin exposure in donor cells modulates EV-mediated effects, attenuating their pro-tumoural influence.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712369","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":"miR-640 Enhances Abemaciclib Sensitivity by Suppressing CDK Inhibitor Resistance-Associated Genes in Breast Cancer Cells","authors":"Ismail Mert Alkac,&nbsp;Cigir Biray Avci","doi":"10.1111/jcmm.71298","DOIUrl":"10.1111/jcmm.71298","url":null,"abstract":"<p>We investigated the potential of miR-640 to downregulate CDK4/6 inhibitor resistance-associated genes and evaluated its apoptotic, anti-metastatic and anti-proliferative effects, both alone and in combination with abemaciclib in breast cancer cells. miR-640 was identified via GSE126125 dataset analysis. Targets were predicted using miRDB, TargetScan and TargetMiner, filtering for resistance-associated genes. MTT assays determined IC50 values for abemaciclib and combinations. Functional effects were evaluated in MCF7 and MDA-MB-231 cells through Annexin V, cell cycle and wound healing assays. Target gene expression was quantified by RT-qPCR. Successful transfection significantly upregulated miR-640 (~50-fold). The miR-640/abemaciclib combination strongly inhibited migration, induced apoptosis and triggered cell line-specific phase arrests (S and G2/M in MCF7; G0/G1 in MDA-MB-231). Gene expression analysis showed significant downregulation of a comprehensive resistance network (including <i>CDK4/6</i>, <i>CDKN2B</i>, <i>WNT7B</i>, <i>MAP3K1</i> and <i>AURKA</i>) in MCF7 cells. In MDA-MB-231 cells, <i>PDK1</i>, <i>CDK6</i>, <i>CDKN2B</i>, <i>SMAD2</i>, <i>ZFP91</i>, <i>MAP3K1</i> and <i>AURKA</i> were significantly suppressed. This study identifies miR-640 as a potent tumour suppressor that resensitises breast cancer cells to CDK4/6 inhibition. By post-transcriptionally downregulating key resistance genes, miR-640—alone or additively with abemaciclib—suppresses proliferation and migration while inducing apoptosis, emerging as a promising combinatorial therapeutic strategy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701323","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":"PRKCD Orchestrates Sevoflurane-Induced Cognitive Dysfunction in Aged Rats by Regulating PINK1/PRKN Mitophagy Pathway","authors":"Yang Yu,&nbsp;Wei Zhang,&nbsp;Yingying Zhao,&nbsp;Yue Zhang,&nbsp;Pingle Li,&nbsp;Zepeng He","doi":"10.1111/jcmm.71315","DOIUrl":"10.1111/jcmm.71315","url":null,"abstract":"<p>Post-operative cognitive dysfunction (POCD) is a cognitive disorder characterized by a decline in cognitive function following surgical procedures, with mitophagy identified as a significant underlying mechanism. Protein kinase C delta (PRKCD), localized within the mitochondria, is implicated in the regulation of PINK1/PRKN mitophagy pathway; however, the potential regulatory role of PRKCD in POCD through this pathway remains to be elucidated. Neurons and rats were exposed to sevoflurane (SEV) to illuminate the function and mechanism of PRKCD in POCD. Various methodologies were employed, including immunofluorescence, quantitative real-time PCR, CCK-8 assays, mitochondrial membrane potential (MMP) assessments, MitoSOX generation detection, Seahorse metabolic flux analysis, co-immunoprecipitation, western blotting and behavioural experiments like Morris water maze, novel object recognition and fear conditioning, along with haematoxylin and eosin and immunohistochemical staining. PRKCD was expressed in neurons and that SEV administration led to an upregulation of PRKCD expression. Furthermore, interference with PRKCD was found to restore cell viability in SEV-treated neurons. Additionally, inhibition of PRKCD resulted in the recovery of LC3 expression and the normalization of p62 levels in neurons subjected to SEV treatment. Suppressing PRKCD restored MMP and OCR, reduced MitoSOX in SEV-affected neurons and interacted with PRKN and PINK1, decreasing their expression. Overexpressing PRKN mitigated PRKCD inhibition's impact on mitochondrial damage. In vivo, SEV increased PRKCD, PINK1 and PRKN levels, but PRKCD knockdown improved behavioural and pathological outcomes, reversing changes in LC3-II, PINK1, PRKN and p62 expression. PRKCD enhanced SEV-induced POCD in aged rats via the regulation of PINK1/PRKN mitophagy pathway.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706668","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":"RAS Inhibitor RMC-7977 Blocks Vascular Overgrowth of NRASQ61R Mutant Endothelial Cells","authors":"Sara Alharbi,&nbsp;Svatava Merkle,&nbsp;Patricia Pastura,&nbsp;C. Griffin McDaniel,&nbsp;George S. Zaky,&nbsp;Andrew M. Waters,&nbsp;Timothy D. Le Cras","doi":"10.1111/jcmm.71316","DOIUrl":"10.1111/jcmm.71316","url":null,"abstract":"<p>RAS mutations occur in patients with several types of vascular anomalies, but effective treatments remain limited. To address this need, we evaluated the RAS (ON) multi-selective inhibitor RMC-7977 in human endothelial cells (ECs) expressing the NRAS^Q61R mutation found in kaposiform lymphangiomatosis (KLA). RMC-7977 was evaluated using in vitro and in vivo models. Doxycycline-inducible NRAS^WT and NRAS^Q61R human ECs were treated with RMC-7977 (3.12–100 nM) or vehicle. We assessed signalling pathways, proliferation, migration, morphology, and angiopoietin-2 (ANG-2) production. NRAS^Q61R ECs in a 3D angiogenesis assay were also treated with RMC-7977. For in vivo studies, NRAS^Q61R ECs were injected into flanks of nude mice on a doxycycline diet to generate xenografts. Mice received oral RMC-7977 or vehicle, and xenografts were collected after 11 days. RMC-7977 inhibited NRAS^Q61R-induced ERK phosphorylation and reduced proliferation, migration, spindle-like morphology, and ANG-2 production in a dose-dependent manner. RMC-7977 reduced vascular area in the angiogenesis assay. In vivo, RMC-7977 reduced xenograft weight, vascular area, and p-ERK staining. Overall, RMC-7977 suppressed NRAS^Q61R-mediated signalling, aberrant EC behaviour, and ANG-2 production in vitro and reduced vascular overgrowth in angiogenesis assays and mouse xenografts. Therefore, RMC-7977 may be a promising therapeutic candidate for RAS-driven vascular anomalies, including KLA.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71316","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706646","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 and Mechanism of Berberine as a Candidate Drug for the Treatment of Radiation-Induced Intestinal Injury","authors":"Xihao Liu,&nbsp;Li Guo,&nbsp;Lu Guo,&nbsp;Lei Zhu,&nbsp;Jianyu Wang,&nbsp;Fei Da,&nbsp;Wei Zhang,&nbsp;Qiaohui Gao,&nbsp;Juan Guo,&nbsp;Xia Miao,&nbsp;Junye Liu","doi":"10.1111/jcmm.71281","DOIUrl":"10.1111/jcmm.71281","url":null,"abstract":"<p>Radiation-induced intestinal injury (RIII) is among the most common complications of radiotherapy in patients with abdominaltumours. At present, there are no effective methods for reducing the occurrence or severity of RIII. Berberine (BBR) is a quaternary ammonium alkaloid extracted from <i>Coptis chinensis</i> that has antioxidant, anti-inflammatory, and protective effects on the intestine. A RIII model was established using 10 Gy of X-ray total abdominal irradiation (TAI). The effects of BBR on mice exposed to 10 Gy of X-ray TAI were determined by analysing pathological sections of the mouse intestine. TUNEL staining was used to detect apoptosis of intestinal epithelial cells in mice. Immunohistochemistry was applied to detect the expression of proliferation indicators PCNA and Ki-67, and immunofluorescence staining was used to quantify BrdU-positive proliferative cells. BBR stimulates crypt formation ex vivo after irradiation and upregulates the expression of FXR. The expression of goblet cell and intestinal stem cell markers was quantified by qRT-PCR. The expression of farnesoid X receptor (FXR) in RIII was detected via qRT-PCR and Western blot. Additionally, a Western blot was performed to detect the protein levels of NF-κB, p-p38, total p38, and β-catenin, and qRT-PCR was used to measure the mRNA expression levels of pro-inflammatory factors TNF-α, IL-1β, and IL-6. BBR alleviated RIII, mainly manifested as body weight loss, longer colons, greater numbers of villi, and greater numbers of crypts. BBR also maintained the regeneration ability and promoted the proliferation of crypt cells, reduced the apoptosis rate, and alleviated intestinal injury. Importantly, BBR rescued radiation-induced dysregulation of these key signalling proteins and pro-inflammatory factors. BBR failed to promote the repair of RIII when FXR was inhibited. BBR treatment increased the expression of FXR in crypts and was at least protective against radiation-induced intestinal damage in mice through the modulation of FXR. BBR may be a potential drug for the treatment of radiation-induced intestinal damage.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701320","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":"Single-Cell RNA Sequencing Revealed the Role of Interferon-Gamma Related Genes in Primary Sjögren's Syndrome","authors":"Lei Shi,&nbsp;Tian-chi Wei,&nbsp;Jing Zhang","doi":"10.1111/jcmm.71313","DOIUrl":"10.1111/jcmm.71313","url":null,"abstract":"<p>Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder. Dysregulated interferon-gamma (IFN-γ) signalling is implicated in pSS pathogenesis, yet the underlying mechanisms remain elusive. This study aimed to identify key IFN-γ-associated diagnostic genes and delineate their roles in immune dysregulation using peripheral blood transcriptomic and single-cell RNA sequencing (scRNA-seq) data. Publicly available Gene Expression Omnibus (GEO) datasets were used, and the bioinformatics findings were further supported by reverse transcription-quantitative PCR (RT-qPCR) validation. Peripheral blood transcriptomic data from training and validation cohorts were analysed, and key genes were screened using machine learning algorithms, receiver operating characteristic (ROC) curve analysis, and differential expression analysis. A diagnostic model and nomogram were subsequently constructed. Immune infiltration, pathway enrichment, and gene regulatory networks were also investigated, while scRNA-seq analysis was performed to characterize cellular heterogeneity, pseudotime trajectories, and cell–cell communication. Four key genes, HERC6, IL15, CD58 and PTGS2, were identified, and the resulting diagnostic model and nomogram demonstrated high diagnostic accuracy. Immune profiling revealed marked dysregulation of the immune microenvironment in pSS, accompanied by extensive alterations in metabolic and signalling pathways. Pathway enrichment analysis further demonstrated both distinct and shared functional roles of the four key genes. Single-cell analysis suggested that macrophages may act as central regulators in pSS pathogenesis, as evidenced by altered pseudotime trajectories, enrichment in early differentiation states, and intensified cell–cell communication networks. RT-qPCR further confirmed the significant upregulation of HERC6, IL15, and PTGS2 in patients with pSS. Collectively, this study established an IFN-γ-associated diagnostic model for pSS and implicated macrophages as potential key contributors to immune dysregulation through altered differentiation, enhanced intercellular communication, and IFN-γ-associated gene expression. These findings provide new insights into the pathogenesis of pSS and identify potential diagnostic biomarkers and therapeutic targets.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689272","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":"Multi-Omics Profiling Identifies Novel Therapeutic Targets and Pathobiological Mechanisms in Oral Cancer","authors":"Meishan Huang,&nbsp;Hongwei Wang,&nbsp;Xiaoqiang Mo,&nbsp;Xiong Huang,&nbsp;Tao Liang,&nbsp;Xiuwen Mo,&nbsp;Minsi Li,&nbsp;Rong Fu,&nbsp;Xidai Long,&nbsp;Xuanping Huang","doi":"10.1111/jcmm.71272","DOIUrl":"10.1111/jcmm.71272","url":null,"abstract":"&lt;p&gt;Oral cancer (OC) remains a therapeutic challenge due to limited validated targets. Cis-pQTLs from the deCODE cohort (&lt;i&gt;n&lt;/i&gt; = 35,559) were harmonized with OC-GWAS (3547 cases and 691,466 controls) meta-data through a two-sample Mendelian randomization (MR) framework. Robust Validation included replication in the UKB-PPP dataset, colocalization analysis, SMR (Summary-based MR), HEIDI (Heterogeneity in Dependent Instruments) tests, and eQTL evidence. Additional analyses encompassed protein–protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes annotation (KEGG)/Gene Ontology (GO) pathway enrichment, mediation, Druggability and side effects analysis. Oral cancer (OC) remains a therapeutic challenge due to limited validated targets. Cis-pQTLs from the deCODE cohort (&lt;i&gt;n&lt;/i&gt; = 35,559) were harmonized with OC-GWAS (3547 cases and 691,466 controls) meta-data through a two-sample Mendelian randomization (MR) framework. Robust Validation included replication in the UKB-PPP dataset, colocalization analysis, SMR (Summary-based MR), HEIDI (Heterogeneity in Dependent Instruments) tests, and eQTL evidence. Additional analyses encompassed protein–protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes annotation (KEGG)/Gene Ontology (GO) pathway enrichment, mediation, Druggability and side effects analysis. To experimentally corroborate the MR findings, the quantitative real-time PCR (qRT-PCR) was performed to examine the mRNA expression levels of selected genes in oral squamous cell carcinoma (OSCC) cell lines (SCC-9 and SCC-25) and normal human oral epithelial cells (HOEC). Multi-omics MR identified TNFSF8 (&lt;i&gt;p&lt;/i&gt; = 2.49 × 10&lt;sup&gt;−8&lt;/sup&gt;, OR = 1.24) as a Tier 1 target. XXYLT1 (&lt;i&gt;p&lt;/i&gt; = 1.41 × 10&lt;sup&gt;−4&lt;/sup&gt;, OR = 1.34) and HSD17B14 (&lt;i&gt;p&lt;/i&gt; = 0.04, OR = 2.00) achieved Tier 2. eQTLs-pQTLs Relationship revealed XXYLT1 expression explained 24.65% of risk through elevated plasma protein levels, TNFSF8 eQTLs mediated 72.80% via protein upregulation. Mediation analyses on CD4 on HLA DR+ CD4+ T cells (7.18%) contributed to the risk of OC by upregulating plasma HSD17B14, while daily cigarette consumption (20.63%) and CD8+ T cell percentage leukocytes (12.06%) contributed to the risk of OC by upregulating plasma TNFSF8. Drug safety assessments highlighted systemic TNFSF8 inhibition may elevate skin cancer risk. Multi-omics MR prioritizes TNFSF8 as a therapeutic target for oral cancer. Multi-omics MR identified TNFSF8 (&lt;i&gt;p&lt;/i&gt; = 2.49 × 10&lt;sup&gt;−8&lt;/sup&gt;, OR = 1.24) as a Tier 1 target. XXYLT1 (&lt;i&gt;p&lt;/i&gt; = 1.41 × 10&lt;sup&gt;−4&lt;/sup&gt;, OR = 1.34) and HSD17B14 (&lt;i&gt;p&lt;/i&gt; = 0.04, OR = 2.00) achieved Tier 2. eQTLs-pQTLs Relationship revealed XXYLT1 expression explained 24.65% of risk through elevated plasma protein levels, TNFSF8 eQTLs mediated 72.80% via protein upregulation. Mediation analyses on CD4 on HLA DR+ CD4+ T cells (7.18%) contributed to the risk of OC by upregulating plasma HSD17B14, while daily cigarette consumption ","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13434842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669621","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":"Inhibiting HIF-1α-Induced miR-663b Improves Pulmonary Arterial Hypertension by Reducing Dysfunctions of PASMCs Through Repressing Sirt1-ZBP1-Mediated PANoptosis","authors":"Le Shen,&nbsp;Honghong Ma,&nbsp;Yang Yu,&nbsp;Yan Xu,&nbsp;Qun Yuan,&nbsp;Xia Zhao,&nbsp;Bing Zhuan","doi":"10.1111/jcmm.71285","DOIUrl":"10.1111/jcmm.71285","url":null,"abstract":"<p>Pulmonary arterial hypertension (PAH) is a progressive disease characterised by vascular remodelling. Inflammatory responses and oxidative stress have been shown to contribute to its progression. This study investigated the effects of a novel HIF-1α-miR-663b axis on pulmonary arterial smooth muscle inflammation, oxidative stress and apoptosis in a monocrotaline (MCT)-induced PAH rat model. A PAH rat model was constructed via MCT injection; moreover, miR-663b inhibitors were administered to inhibit miR-663b. PASMCs were cultured under hypoxic conditions to establish an in vitro PAH model. The data revealed that miR-663b was highly expressed in PAH rats and hypoxia-induced PASMC models. Overexpression of miR-663b exacerbated hypoxia-induced proliferation, apoptosis, migration and inflammation in PASMCs. Conversely, miR-663b inhibition reversed hypoxia-induced dysfunction in PASMCs. ZBP1 downregulation dampened miR-663b upregulation-mediated dysfunctions in PASMCs. In vivo experiments revealed that miR-663b inhibitors mitigated pulmonary arterial remodelling, inflammation and PANoptosis in MCT-induced PAH rats. HIF-1α expression was upregulated in hypoxia-induced PASMCs. ChIP–qPCR and dual-luciferase reporter gene assays confirmed that HIF-1α transcriptionally regulated and promoted miR-663b expression. Upregulation of miR-663b inhibited AMPK/Sirt1 signalling pathway activation and promoted ZBP1-mediated PANoptosis. However, miR-663b inhibitors reversed hypoxia-induced PANoptosis in PASMCs. The protective effects of miR-663b inhibitors on PASMCs and their inhibitory effects on PANoptosis were significantly weakened by treatment with an AMPK inhibitor or a Sirt1 inhibitor. Collectively, these findings suggest that inhibiting HIF-1α-mediated miR-663b expression improves PAH by reducing PASMC dysfunction through the attenuation of inflammatory responses, oxidative stress and apoptosis in PASMCs and the activation of the AMPK/Sirt1 pathway.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669586","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}