JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Standard Protocols for Characterising Primary and In Vitro-Generated Human Hepatocytes","authors":"Zahra Heydari,&nbsp;Roberto Gramignoli,&nbsp;Abbas Piryaei,&nbsp;Ensieh Zahmatkesh,&nbsp;Paria Pooyan,&nbsp;Homeyra Seydi,&nbsp;Andreas Nussler,&nbsp;Dagmara Szkolnicka,&nbsp;Hassan Rashidi,&nbsp;Mustapha Najimi,&nbsp;David C. Hay,&nbsp;Massoud Vosough","doi":"10.1111/jcmm.70390","DOIUrl":"https://doi.org/10.1111/jcmm.70390","url":null,"abstract":"<p>Hepatocyte-like cells (HLCs) derived from pluripotent stem cells (PSCs) or direct reprogramming are an unlimited source of human hepatocytes for biomedical applications. HLCs are used to model human diseases, develop precise drugs and establish groundbreaking regenerative cell-based therapies. Primary human hepatocytes are the gold standard for studying human liver biology and pathology. However, their widespread use is limited by their rapid dedifferentiation in vitro, reliance on transplant-rejected donor organs, poor scalability and significant batch-to-batch variations. Therefore, high-quality ‘off-the-shelf’ HLCs are needed to overcome those limitations. Basic stepwise differentiation protocols have been developed to generate HLCs from PSCs. To evaluate the quality of the in vitro generated products, HLCs have been phenotyped using various methods. This review discusses various biological assays and methods available for the robust evaluation of HLC quality, emphasising the importance of using 24-h cultured primary human hepatocytes (PHHs) as a reference standard for comparison.</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.70390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248809","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 Sequencing Reveals Heterogeneity and Interactions Between Epithelial Cells and Fibroblasts in Post-ESD Oesophageal Stricture","authors":"Lulong Tao,&nbsp;Junjun Xia,&nbsp;Die Hu,&nbsp;Guoxin Zhang,&nbsp;Yaoyao Gong,&nbsp;Jin Yan","doi":"10.1111/jcmm.70411","DOIUrl":"https://doi.org/10.1111/jcmm.70411","url":null,"abstract":"<p>Oesophageal stricture, especially circumferential lesions, is a common complication of endoscopic submucosal dissection (ESD). However, the exact mechanisms underlying its development remain unclear. Consequently, understanding tissue microenvironment changes is crucial for identifying therapeutic targets. To address this, single-cell RNA sequencing (scRNA-seq) was performed on oesophageal stricture samples and normal controls. Alterations in cellular composition were observed, particularly in epithelial, endothelial, fibroblast and immune cells. A notable increase was observed in the number of differentiating suprabasal cell_2 (DFSC_2), which displayed pro-keratinizing traits. Detailed investigations revealed augmentation in a subset of these cells, characterised by elevated FTH1 and ECM1 expression, indicating their role in epithelial remodelling. Furthermore, fibroblast heterogeneity was demonstrated, with significant activation of myofibroblasts within stricture tissues. MDK–NCL, CXCL5/6-CXCR2, and TGFA–EGFR ligand–receptor pairs were enhanced in stricture tissues, mediating epithelial–stromal interactions. This study dissected the transcriptional landscape of postoperative oesophageal stricture tissues, providing valuable insights into stricture mechanisms and potential preventive strategies.</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.70411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248751","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":"EZH2-Mediated PHF10 Suppression Amplifies HMGB1/NF-κB Axis That Confers Chemotherapy Resistance in Cholangiocarcinoma","authors":"Qiushi Yin,&nbsp;Daning Lin,&nbsp;Weiqian Zeng,&nbsp;Shijing Gu,&nbsp;Chuangshi Zhu,&nbsp;Changfu Liang,&nbsp;Yan Yang","doi":"10.1111/jcmm.70363","DOIUrl":"https://doi.org/10.1111/jcmm.70363","url":null,"abstract":"<p>Chemoresistance represents a major threat to the treatment of human cancers, including cholangiocarcinoma (CHOL). Aberrant epigenetic events contribute most to the progression of CHOL and chemotherapy efficacy. PHF10, one subunit of SWI/SNF complex, expressed highly in tumours that correlated with tumorigenesis. However, the roles of PHF10 in CHOL remains unclear. Here, we utilised the bioinformatic analysis to reveal that PHF10 expressed lowly in CHOL samples relative to normal tissues. Functionally, we demonstrated that PHF10 deficiency enhanced cell proliferation, migration and self-renewal capacities of CHOL cells. PHF10 ablation further enhanced the chemoresistance of CHOL cells. The transcriptome analysis revealed that PHF10-KO could notably alter several oncogenic crosstalk, including the NF-kB signalling. As the top hit, HMGB1 mRNA expressions had the sharpest increase upon PHF10 deficiency. PHF10 coordinated with Setdb1 to mediate the H3K9me3 modifications on the HMGB1 promoter to suppress its expressions. Low PHF10 relied on HMGB1 to promote the progression of CHOL cells in vitro and in vivo. Furthermore, EZH2 mediated the H3K27me3 enrichment on the PHF10 promoter region that contributes to its low expressions. Lastly, the HMGB1 inhibitor (Glycyrrhizin) decreased proliferation rate of PHF10-deleted cells in vitro and in vivo. Targeting HMGB1 rendered PHF10^low CHOL re-sensitive to chemotherapy. Collectively, this study demonstrated that PHF10 functions as a tumour suppressor in CHOL, and is a novel target to predict and overcome chemoresistance.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70363","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111533","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":"GPX3 Overexpression Ameliorates Cardiac Injury Post Myocardial Infarction Through Activating LSD1/Hif1α Axis","authors":"Qi-Qi Jiang,&nbsp;Chong Du,&nbsp;Ling-Ling Qian,&nbsp;Tian-Kai Shan,&nbsp;Yu-Lin Bao,&nbsp;Ling-Feng Gu,&nbsp;Si-Bo Wang,&nbsp;Tong-Tong Yang,&nbsp;Liu-Hua Zhou,&nbsp;Ze-Mu Wang,&nbsp;Ye He,&nbsp;Qi-Ming Wang,&nbsp;Hao Wang,&nbsp;Ru-Xing Wang,&nbsp;Lian-Sheng Wang","doi":"10.1111/jcmm.70398","DOIUrl":"https://doi.org/10.1111/jcmm.70398","url":null,"abstract":"<p>Myocardial infarction (MI) often results in significant loss of cardiomyocytes (CMs), contributing to adverse ventricular remodelling and heart failure. Therefore, promoting CM survival during the acute stage of MI is crucial. This study aimed to investigate the potential role of GPX3 in cardiac repair following MI. First, plasma GPX3 levels were measured in patients with acute MI (AMI), and myocardial GPX3 expression was assessed in a mouse MI model. Furthermore, the effects of GPX3 on MI were investigated through CM-specific overexpression or knockdown in vitro and in vivo models. RNA sequencing and subsequent experiments were performed to uncover the molecular mechanisms underlying GPX3-related effects. Multi-omics database analysis and experimental verification revealed a significant upregulation of GPX3 expression in ischemic myocardium following MI and in CMs exposed to oxygen–glucose deprivation (OGD). Immunofluorescence results further confirmed elevated cytoplasmic GPX3 expression in CMs under hypoxic conditions. In vitro, GPX3 overexpression mitigated reactive oxygen species (ROS) production and enhanced CM survival during hypoxia, while GPX3 knockdown inhibited these processes. In vivo, CM-specific GPX3 overexpression in the infarct border zone significantly attenuated CM apoptosis and alleviated myocardial injury, promoting cardiac repair and long-term functional recovery. Mechanistically, GPX3 overexpression upregulated LSD1 and Hif1α protein expression, and rescue experiments confirmed the involvement of the LSD1/Hif1α pathway in mediating the protective effects of GPX3. Overall, our findings suggest that GPX3 exerts a protective role in ischemic myocardium post-MI, at least partially through the LSD1/Hif1α axis, highlighting its potential as a therapeutic target for MI treatment.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70398","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111081","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 Transcriptomic Reveals the Involvement of Cell–Cell Junctions in the Early Development of Hypertrophic Cardiomyopathy","authors":"Dingchen Wang,&nbsp;Miao Lin,&nbsp;Ruobing Wang,&nbsp;Xiaoran Huang,&nbsp;Yaowen Liang,&nbsp;Xiran Wang,&nbsp;Yuge Chen,&nbsp;Yunfei Gao,&nbsp;Huiming Guo,&nbsp;Huiying Liang,&nbsp;Xin Li","doi":"10.1111/jcmm.70366","DOIUrl":"https://doi.org/10.1111/jcmm.70366","url":null,"abstract":"<p>The relationship between the changes in endothelial cell–cell junctions and microvascular abnormalities in the progression of hypertrophic cardiomyopathy (HCM), as well as their potential as early biomarkers, remains unclear. Here, we analysed single-nucleus RNA-sequencing data from the left ventricles of 44 health donors and HCM patients. First, we observed that endothelial cell–cell junctions were significantly altered in HCM vascular endothelial cells (ECs), including tight junctions, gap junctions and adherens junctions, especially in capillary ECs. The proposed pseudo-timing analysis predicted that endothelial cell–cell junctions abnormalities occurred in the early stages of HCM. Second, we verified that endothelial cell–cell junctions disorders occur at early stages of HCM disease progression in two time-series single-nucleus datasets of mice. The expression of eight cell–cell junction genes showed an initial increase in the early stage, followed by a slight decrease in the middle stage, and a sharp increase in the later stage. Subsequently, cell communication and transcription factor analysis were used to explore the underlying mechanisms. Furthermore, an early HCM prediction model was developed and independently validated using three mRNA datasets comprising 204 health individuals and HCM patients for the eight genes panel, the accuracy was 0.81 [0.63–0.98]. Finally, we validated this panel in HCM tissues. This study demonstrated in humans and mice that eight cell–cell junction genes were significantly elevated in the early stages of HCM and may be potential biomarkers for the early diagnosis of HCM.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70366","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111082","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 Oncopromoting Gene RBM6 Inhibits Prostate Tumour Cell Migration During Epithelial-to-Mesenchymal Transition","authors":"Ruoyang Liu,&nbsp;Yu Liu,&nbsp;Long Zhang,&nbsp;Xiang Li,&nbsp;Ningyang Li,&nbsp;Fubo Lu,&nbsp;Wansheng Gao,&nbsp;Zhankui Jia,&nbsp;Zhenlin Huang,&nbsp;Jinjian Yang","doi":"10.1111/jcmm.70397","DOIUrl":"https://doi.org/10.1111/jcmm.70397","url":null,"abstract":"<p>RBM6, implicated in the progression of multiple tumour types but unexplored in prostate tumours, was found to indicate potential therapeutic implications due to its elevated expression in prostate tumours. To elucidate its molecular function, scratch tests, transwell migration and invasion assays were conducted, with PCR and western blot analyses verifying molecular regulatory relationships. RNA pulldown and RNA immunoprecipitation tests were also employed to investigate underlying mechanisms. Results indicate that RBM6 enhances prostate cell migration by suppressing CDH1, yet ZEB1 overexpression alleviates this suppression. Notably, under these conditions, RBM6's inhibitory effect on MMP16 becomes more pronounced, reducing cell migration ability. Thus, under normal conditions, RBM6 promotes prostate tumour cell migration, but in the context of high ZEB1 expression, it inhibits migration. This shift in RBM6's regulatory capacity towards downstream genes underscores the importance of considering objective conditions in studying RBM6 molecules.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111441","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":"Anti-Inflammatory Resveratrol Protects Mice From Early Mortality After Haematopoietic Stem Cell Transplantation","authors":"Xiao Zhang,&nbsp;Wei Yu,&nbsp;Yimeng Sun,&nbsp;Xinyu Ye,&nbsp;Yu He,&nbsp;Xin Huang,&nbsp;Fuhao Wang,&nbsp;Yi Lu,&nbsp;Jian Zhang","doi":"10.1111/jcmm.70395","DOIUrl":"https://doi.org/10.1111/jcmm.70395","url":null,"abstract":"<p>The occurrence of inflammation subsequent to haematopoietic stem cell transplantation is associated with an elevated risk of transplant-related mortality (TRM). However, the duration of inflammation and the potential efficacy of anti-inflammatory agents in reducing TRM remain uncertain. We performed a comprehensive investigation to examine the post-transplantation alterations of inflammatory mediators and to ascertain the correlation between inflammation level and TRM through the neutrophil–lymphocyte ratio, ELISAs and cytometric bead array. The findings revealed that the 30-day interval following transplantation is characterised by the most pronounced inflammatory response in both human and murine subjects, thereby elevating the risk of TRM. The inflammation is primarily caused by myeloid bias during haematopoietic reconstitution, which is a commonly overlooked aspect in clinical transplantation, additionally, a lesser extent of irradiation-induced injury. The administration of the anti-inflammatory agent resveratrol has the potential to reduce systemic inflammation and TRM by suppressing the NOD-like receptor signalling pathway and slowing down granulocyte implantation in HSCT mice. This approach did not impair the differentiation potential of haematopoietic stem cells. These findings demonstrate that the 30-day post-transplant period represents an opportunity to facilitate HSCT colonisation, mitigate transplant-related adverse effects, and potentially reap the benefits of anti-inflammatory treatments.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111442","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":"CTSL Promotes Autophagy in Laryngeal Cancer Through the IL6-JAK-STAT3 Signalling Pathway","authors":"Xueying Wang,&nbsp;Junrong Wang,&nbsp;Lei Wang,&nbsp;Ming Song,&nbsp;Hongxue Meng,&nbsp;Erliang Guo,&nbsp;Susheng Miao","doi":"10.1111/jcmm.70364","DOIUrl":"10.1111/jcmm.70364","url":null,"abstract":"<p>Cathepsin L (CTSL) is an important oncogene. However, its mechanism of action in laryngeal cancer is still unclear. This study aims to explore the role of CTSL in laryngeal cancer and its clinical significance. Conducting bioinformatics analysis utilising the Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. Performing CCK8 analysis, Western blotting, qRT-PCR, wound healing assay and transwell invasion assay. Additionally, conducting immunoprecipitation experiments and immunohistochemical staining to investigate the impact of CTSL on cell proliferation, autophagy and related signalling pathways. We observed a significant upregulation of CTSL in laryngeal cancer tissues, and its elevated levels are indicative of poor prognosis in laryngeal cancer patients. The proliferation of laryngeal cancer cells relies on the expression of CTSL, with overexpression of this gene enhancing the proliferative capacity of these cells. Concurrently, CTSL is closely associated with the autophagic levels in laryngeal cancer cells. During the autophagic process mediated by CTSL, the IL6-JAK-STAT3 signalling pathway is activated, suggesting that CTSL promotes autophagy through the IL6-JAK-STAT3 pathway. Considering the correlation between CTSL and autophagy, we developed and validated a multi-gene signature. The risk score derived from this signature demonstrates significant potential in predicting various aspects. We found that CTSL upregulates autophagy in laryngeal cancer cells by activating the IL6-JAK-STAT3 signalling pathway. By taking into account the autophagy-regulating role of CTSL, the clinical predictive ability of CTSL in HNSC can be enhanced.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70364","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080076","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":"Unveiling Molecular Dynamics of MeCp2, CDKL5 and BDNF in the Hippocampus of Individuals With Intractable Mesial Temporal Lobe Epilepsy","authors":"NoorMohammad Meshkinkhood,&nbsp;Parastoo Barati Dowom,&nbsp;Farshid Noorbakhsh,&nbsp;Masoud Ghadipasha,&nbsp;Jaber Gharehdaghi,&nbsp;Christoph Kellinghaus,&nbsp;Erwin-Joseph Speckmann,&nbsp;Maryam Khaleghi Ghadiri,&nbsp;Walter Stummer,&nbsp;Ali Gorji","doi":"10.1111/jcmm.70373","DOIUrl":"10.1111/jcmm.70373","url":null,"abstract":"<p>Mutations occurring in the MeCp2, CDKL5 and BDNF genes have been linked to epileptogenesis in various epilepsy syndromes. This study employed bioinformatics analysis of transcriptomic data to examine the interrelationship among these genes in both epileptic and healthy individuals. Moreover, we assessed the expression of MeCp2, CDKL5 and BDNF at both mRNA and protein levels in human hippocampal tissues obtained from 22 patients undergoing epilepsy surgery for mesial temporal lobe epilepsy (MTLE) as well as from 25 autopsied specimens. Bioinformatics findings suggest that MeCp2, CDKL5 and BDNF genes play a role in regulating genes associated with epilepsy and disruptions in these genes may contribute to epilepsy development. Furthermore, the study reveals significantly lower MeCp2 and CDKL5 protein levels in the epileptic hippocampus compared to controls. Positive correlations are observed between MeCp2 and CDKL5 mRNA expression in autopsied samples and between CDKL5 and BDNF mRNA expression in epileptic hippocampal tissues. Differences in mRNA expression correlation patterns of MeCp2 and CDKL5 with BDNF are found between epileptic and control hippocampal tissues. Moreover, a significant positive correlation between MeCp2 and CDKL5 protein expression is noted in control hippocampal tissues. Our data suggest that altered expression of MeCp2, CDKL5 and BDNF within the hippocampus may contribute to epileptogenic processes in MTLE, impacting seizure characteristics, surgical outcomes and responses to antiepileptic drugs. Alterations in the expression of MeCp2, CDKL5 and BDNF within the hippocampus might contribute to the epileptogenic processes in MTLE. These changes could be linked to distinct functional consequences in epilepsy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065852","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":"OPG and BAFF as predictive biomarkers of the severity of SARS-CoV-2 infection","authors":"Andy Ruiz,&nbsp;Carlos Peña-Bates,&nbsp;Lucero A. Ramon-Luing,&nbsp;Daniel Baca-Nuñez,&nbsp;Marco Antonio Vargas,&nbsp;Karen Medina-Quero,&nbsp;Neptali Gutierrez,&nbsp;Joel A. Vázquez-Pérez,&nbsp;Ramcés Falfán-Valencia,&nbsp;Gloria Pérez-Rubio,&nbsp;Carolina Di Benedetto,&nbsp;Ivette Buendia-Roldan,&nbsp;Moisés Selman,&nbsp;Paola Betancur,&nbsp;Leslie Chavez-Galan","doi":"10.1111/jcmm.70189","DOIUrl":"10.1111/jcmm.70189","url":null,"abstract":"<p>Molecules of the tumour necrosis factor superfamily (TNFSF) are key players in immune regulation; an increase in some TNFSF molecules has been reported during severe COVID-19. In this study, we profiled and evaluated TNFSF members in the serum of COVID-19 vaccine-naïve patients to identify potential biomarkers associated with disease severity. Our data show that TRAIL serum levels are lower in severely affected patients than those mildly affected by COVID-19 (AUC 0.8, <i>p</i> = 0.0003). On the contrary, OPG and BAFF serum levels are higher in severe COVID-19 compared to mild COVID-19 cases (AUC 0.8, <i>p</i> = 0.0001; AUC 0.7, <i>p</i> = 0.0012; respectively) and moderate COVID-19 cases (OPG <i>p</i> &lt; 0.01), BAFF (<i>p</i> &lt; 0.05). At the transcriptional level, TRAIL, OPG and BAFF are elevated in severe compared to mild COVID-19 cases, with OPG and BAFF also higher in moderate compared to mild COVID-19 patients. Additionally, we found that APRIL, LIGHT, CD30L and CD40L protein-levels are higher in COVID-19 patients compared to healthy donors but not significantly different between various COVID-19 clinical statuses. Finally, we found that TNF-α, TNF-β, RANKL and TWEAK protein levels were not affected during COVID-19. Our work identifies OPG and BAFF as potential biomarkers and therapeutic targets for preventing severe COVID-19. Due to the opposite contradictory levels of TRAIL (protein/transcriptional level), its role during COVID-19 should be elucidated and clarified with more in-depth studies.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065865","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}