JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"CXCL Gene Clusters Regulated by Enhancer-Mediated DNA Looping Alteration in Pancreatic Cancer Cells","authors":"Yifen Shen,&nbsp;Yanping Hu,&nbsp;Hua Li,&nbsp;Genhai Shen,&nbsp;Yihang Shen,&nbsp;Zheng Wang","doi":"10.1111/jcmm.70538","DOIUrl":"https://doi.org/10.1111/jcmm.70538","url":null,"abstract":"<p>Pancreatic cancer is one of the deadliest cancers. Chemokines affect the progression of pancreatic cancer through various mechanisms. Most of the CXC chemokine genes, CC chemokine genes and CX3C chemokine genes are clustered together within a very short region of chromatin. Transcription activity of gene clusters is usually influenced by the chromatin architecture and spatial organisation. Nevertheless, the chromatin-mediated regulatory mechanism on transcription of chemokine gene clusters has never been studied in pancreatic cancer. Herein, we determined that the expression of C-X-C motif chemokine ligand 8 (<i>CXCL8</i>), <i>CXCL6</i>, <i>CXCL4L1</i>, <i>CXCL1</i>, <i>CXCL4</i>, <i>CXCL7</i>, <i>CXCL5</i>, <i>CXCL3</i> and <i>CXCL2</i> was up-regulated, whereas <i>CXCL9</i>, <i>CXCL10</i> and <i>CXCL11</i> were down-regulated in pancreatic cancer cells compared with normal duct epithelial cells and further uncovered that four enhancer elements showed robust interaction to form DNA looping containing the up-regulated eight <i>CXCL</i> genes, whereas the other enhancer controlled <i>CXCL9</i>, <i>CXCL10</i> and <i>CXCL11</i> to form another DNA loop. Furthermore, after these enhancers were respectively destroyed by CRISPR-Cas9, we observed that the interaction with other enhancers was weakened as well as the expression of <i>CXCL</i> gene clusters and the tumour malignancy of pancreatic cancer cells was significantly changed. Taken together, our research exhibits the regulatory mechanism on transcription of <i>CXCL</i> gene clusters via enhance-dependent DNA looping alteration in pancreatic cancer cells.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793673","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":"Associations Between APOC3 and ANGPTL8 Gene Polymorphisms With MASLD Risk and the Mediation Effect of Triglyceride on MASLD in the Chinese Population","authors":"Jia Pan,&nbsp;Xue Wang,&nbsp;Youjin Zhang,&nbsp;Ting Wang,&nbsp;Saiqun Lv,&nbsp;Xiaoli Zhang,&nbsp;Yuanyuan Zhou,&nbsp;Tao Peng,&nbsp;Yongyan Song","doi":"10.1111/jcmm.70542","DOIUrl":"https://doi.org/10.1111/jcmm.70542","url":null,"abstract":"<p>Apolipoprotein C3 (<i>APOC3</i>) and angiopoietin-like protein 8 (<i>ANGPTL</i>8) genes are related to lipid metabolism. The relationships between single nucleotide polymorphisms (SNPs) in the <i>APOC3</i> and <i>ANGPTL</i>8 genes with metabolic dysfunction-associated steatotic liver disease (MASLD) remain controversial. This study aimed to investigate the associations between specific SNPs in the <i>APOC3</i> and <i>ANGPTL</i>8 genes and MASLD risk, with a particular focus on the mediating role of triglycerides (TG). A total of 440 participants were enrolled and categorised into MASLD and control groups. Genotyping of <i>APOC3</i> SNPs (rs5128, rs2854116 and rs2854117) and <i>ANGPTL</i>8 SNP (rs2278426) was conducted using polymerase chain reaction–restriction fragment length polymorphism or Sanger sequencing methods. Multivariate logistic regression was employed to estimate the associations between these SNPs and MASLD risk, and mediation analysis was performed to assess the potential mediating effect of TG. We found that <i>APOC3</i> SNPs were associated with MASLD risk, with increased odds ratios (ORs) indicating a higher risk of MASLD: rs5128 CG + GG genotype (OR = 1.8, 95% CI = 1.1–2.8), rs2854116 TC + CC genotype (OR = 1.9, 95% CI = 1.1–3.1) and rs2854117 CT + TT genotype (OR = 1.9, 95% CI = 1.2–3.2). No association was found between <i>ANGPTL</i>8 rs2278426 and MASLD (<i>p</i> &gt; 0.05). Mediation analysis revealed that TG significantly mediated these relationships, accounting for 80.25% of the effect for rs5128, 64.61% for rs2854116 and 62.59% for rs2854117. In summary, polymorphisms in <i>APOC3</i> (rs5128, rs2854116 and rs2854117) were associated with MASLD risk, with TG serving as a potential mediating factor. In contrast, <i>ANGPTL</i>8 rs2278426 polymorphism did not show any association with MASLD.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787176","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":"Identification of Safety Biomarkers for Autologous Blood Transfusion in Hepatocellular Carcinoma Patients","authors":"Yong Cheng,&nbsp;Yue Wang,&nbsp;Xiao-fang Zhou,&nbsp;Lai-wei You,&nbsp;Xiao-yi Xie,&nbsp;Hao Li,&nbsp;Mandi Wu,&nbsp;Jianrong Guo","doi":"10.1111/jcmm.70504","DOIUrl":"https://doi.org/10.1111/jcmm.70504","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) represents the predominant form of primary liver cancer, constituting 75%–85% of all liver cancer cases. Despite advances in understanding HCC mechanisms and treatment options, challenges remain and further research is needed to uncover new therapeutic targets and improve patient outcomes. intraoperative cell salvage (IOCS) is an important surgical method that minimises the necessity for transfusions of donor blood, improves haemodynamic stability and may enhance recovery. This study aims to identify safety biomarkers for autologous blood transfusion in HCC patients. We conducted a prospective case–control study on 80 HCC patients undergoing radical surgery. Blood and tumour tissues were collected for analysis. The control group provided blood directly from the surgical site without IOCS processing, while the experimental group used blood collected through the IOCS system. Dual-Luciferase reporter gene assays, immunofluorescence, Western blot and qRT-PCR techniques were employed to assess the expression of key proteins and microRNAs. Comparable demographic and baseline clinical characteristics were observed between groups. The experimental group showed significantly improved pathological features, with an increase in PTEN-positive cells and upregulated protein expression of PTEN, mTOR, c-Met and IGF1R. Additionally, miRNA levels (miRNA-21, miRNA-122, miRNA-223, miRNA-199a and miRNA-375) were significantly reduced in the experimental group (<i>p</i> &lt; 0.05), while mRNA levels for PTEN, mTOR, c-Met, YAP1 and IGF1R were significantly upregulated (<i>p</i> &lt; 0.05). IOCS has a positive impact on liver tissue pathology in HCC patients by reducing apoptosis and modulating key molecular pathways. These findings suggest that IOCS could be a valuable therapeutic strategy for HCC, potentially guiding future treatment approaches and improving patient outcomes.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70504","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793671","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":"Acute Sleep Loss Increases Circulating Morning Levels of Two MicroRNAs Implicated in Neurodegenerative Disease in Healthy Young Men","authors":"Lei Zhang,&nbsp;Anastasia Grip,&nbsp;Daisy Hjelmqvist,&nbsp;Christian Benedict,&nbsp;Luiz Eduardo Mateus Brandão,&nbsp;Jonathan Cedernaes","doi":"10.1111/jcmm.70523","DOIUrl":"https://doi.org/10.1111/jcmm.70523","url":null,"abstract":"<p>Chronic sleep disruption and shift work elevate the risk of neurodegeneration and Alzheimer's disease (AD). While disrupted sleep affects canonical AD biomarkers, its impact on other mechanisms, such as circulating microRNAs (miRNAs), remains less understood. Therefore, we here examined the effects of overnight wakefulness on plasma levels of several miRNAs implicated in neurodegeneration and AD, as well as in sleep and circadian regulation—namely miR-127-3p, miR-132-3p, and miR-142-3p. Following a baseline period in each highly controlled in-lab session, in total 15 healthy normal-weight young men underwent two conditions on separate occasions, in randomised order: a night of normal sleep, and a night of sustained wakefulness. After overnight wakefulness, morning plasma levels of miR-127-3p and miR-142-3p were significantly elevated compared with post-sleep levels. These changes were not associated with the significant increase in self-reported morning stress levels observed after wakefulness compared with sleep. This study is the first to demonstrate that a single night of wakefulness—mimicking overnight shift work—significantly elevates circulating levels of miR-127-3p and miR-142-3p in humans. These findings, though based on a limited sample size, suggest a potential molecular link between sleep loss and neurodegeneration, warranting further investigation.</p><p><b>Trial Registration:</b> Clinical Trial number: NCT01800253; www.clinicaltrials.gov</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793659","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 IGF Signalling Axis in Lung Cancer: Clinical Significance and Therapeutic Challenges","authors":"Kostas A. Papavassiliou,&nbsp;Amalia A. Sofianidi,&nbsp;Kyriaki Cholidou,&nbsp;Athanasios G. Papavassiliou","doi":"10.1111/jcmm.70540","DOIUrl":"https://doi.org/10.1111/jcmm.70540","url":null,"abstract":"&lt;p&gt;Lung cancer ranks as the leading cause of cancer-related mortality worldwide, with an estimated 1.8 million deaths in 2022 [&lt;span&gt;1&lt;/span&gt;]. The medical community has not managed to tame this deadly malignancy so far, which is mainly attributed to its high aggressiveness and our deficient understanding of its distinct biological features. Recently, metabolic reprogramming has emerged as an important cancer hallmark [&lt;span&gt;2&lt;/span&gt;], helping us better understand the profile of the tumour. In this vein, the insulin-like growth factor (IGF) axis, comprising IGF-1/IGF-2, related receptors (IGF-1R/-2R), and high-affinity binding proteins (IGFBP 1-6), has become apparent as a central player in lung cancer growth, invasion and metastasis [&lt;span&gt;3&lt;/span&gt;]. Herein, we provide an update on the clinical significance of the IGF signalling axis in lung cancer, highlighting the latest advancements that have developed in the past few years.&lt;/p&gt;&lt;p&gt;IGFs are polypeptides that serve as growth factors, tethering to IGF receptors and initiating signalling cascades. The IGF axis consists of two main ligands, IGF-1 and IGF-2, the associated cellular receptors IGF-1R and IGF-2R, and their binding soluble plasma proteins (IGFBPs). The interaction of the ligands with their receptors leads to the activation of the phosphoinositide-3-kinase (PI3K)–protein kinase B (PKB)/AKT and mitogen-activated protein kinase (MAPK) signalling pathways. On the other hand, IGFBPs bind IGFs and hinder them from tethering to their receptors and activating downstream signalling cascades [&lt;span&gt;4&lt;/span&gt;]. Structurally similar to insulin, IGFs control the development, differentiation, and proliferation of normal cells across the lifespan [&lt;span&gt;4&lt;/span&gt;]. Numerous studies have lately revealed that the IGF axis is intimately implicated in lung carcinogenesis [&lt;span&gt;3&lt;/span&gt;]. This observation is not a new one; the hypothesis that the IGF axis is involved in the tumorigenesis of several malignancies roots more than 20 years ago (e.g., [&lt;span&gt;5&lt;/span&gt;]).&lt;/p&gt;&lt;p&gt;It is nowadays well established that the IGF signalling cascade is upregulated in lung cancer [&lt;span&gt;3, 6, 7&lt;/span&gt;]. Studies have demonstrated that IGF-1R boosts the metastatic potential of lung cancer cells by enabling epithelial-to-mesenchymal transition (EMT) and promoting DNA damage processes [&lt;span&gt;8&lt;/span&gt;]. A novel study also showed that a tobacco smoke-specific carcinogen, namely nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (nicotine-derived nitrosamine ketone, NNK), activates IGF signalling, inducing lung tumorigenesis. NNK fosters Src-mediated signal transducer and activator of transcription 3 (STAT3) potentiation and increased release of calcium through the angiotensin II (AngII) receptor type 1 (AGTR1, AT1 receptor)−phospholipase C (PLC) axis, leading to transcriptional upregulation of IGF-2 and lung tumorigenesis in tobacco smokers [&lt;span&gt;9&lt;/span&gt;]. Remarkably, it was also found that IGF-1R acts in the lung tumo","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778241","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":"Systematic Characterisation and Analysis of Lysyl Oxidase Family Members as Drivers of Tumour Progression and Multiple Drug Resistance","authors":"Hongjin Liu,&nbsp;Xiaojiao Sun,&nbsp;Bingqi Dong,&nbsp;Jixin Zhang,&nbsp;Junling Zhang,&nbsp;Yanlun Gu,&nbsp;Lin Chen,&nbsp;Xiaocong Pang,&nbsp;Jingming Ye,&nbsp;Xin Wang,&nbsp;Zhuona Rong","doi":"10.1111/jcmm.70536","DOIUrl":"https://doi.org/10.1111/jcmm.70536","url":null,"abstract":"<p>The intricacies of tumour microenvironment, particularly the extracellular matrix (ECM), underscore its pivotal function in modulating tumour progression and drug resistance. Among the key regulators of ECM remodelling and homeostasis, the lysyl oxidases (LOXs) emerge as promising therapeutic targets of tumour treatment. Despite their significance, a holistic evaluation of the LOX family's genomics and clinical implications across diverse cancer types remains elusive. Herein, this study aimed to investigate the correlation between LOX family expression and patient outcomes, drug responsiveness and tumour microenvironment (TME) characteristics in a cohort of 33 tumours based on The Cancer Genome Atlas (TCGA) database. Notably, patients exhibiting elevated LOX family expression suffer from worse prognosis and resistance to a spectrum of antitumor therapies, encompassing chemotherapy, endocrine therapy, targeted therapy and immunotherapy, in contrast to counterparts with subdued LOX family expression levels. Furthermore, enrichment analysis indicated that the LOX family fosters tumour progression and drug resistance. These findings were further validated by multiplex immunofluorescence staining in breast, gastric and rectal cancer, as well as breast cancer organoids. Altogether, this study unravels the intricate association between the LOX family and tumour progression, alongside multidrug resistance. We have gained further insights into the roles of LOX family genes in various tumour types, offering a novel avenue for future research into the relationship between LOX family genes and tumorigenesis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70536","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770169","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":"Counteracting Skin Aging In Vitro by Phytochemicals","authors":"Sara Cruciani,&nbsp;Giuseppe Garroni,&nbsp;Diletta Serra,&nbsp;Fikriye Fulya Kavak,&nbsp;Rosanna Satta,&nbsp;Fernanda Martini,&nbsp;Mauro Tognon,&nbsp;Carlo Ventura,&nbsp;Margherita Maioli","doi":"10.1111/jcmm.70530","DOIUrl":"https://doi.org/10.1111/jcmm.70530","url":null,"abstract":"<p>The skin is the most extensive organ in the human body. Photo exposure to ultraviolet (UV) rays causes several damages to skin cells, including premature skin aging, the onset of possible DNA mutations, and the risk of developing cancers, including melanoma. Protecting skin from the damaging effects of sun exposure through the application of creams and filters is important to prevent irreversible damages. Several natural extracts and biomolecules with antioxidant activity are widely used in the production of dietary supplements or topical products, for the prevention and treatment of skin affections. Within this context, we pre-treated human skin fibroblasts (HFF1), skin-isolated stem cells (SSCs) and keratinocytes (HaCaT) with two creams containing a specific solar protection factor (SPF) for 72 h and then exposed the cells to UV light. Gene expression analysis was performed for the key cell cycle regulators (p16, p19, p21, p53 and TERT). Cell senescence was assessed by colorimetric assays of beta-galactosidase and antioxidant potential, revealing the ability of treated cells to counteract free radical production as a result of oxidative stress. Finally, possible mutations in DNA induced by photo exposure were studied. The results obtained demonstrated that the tested products elicit positive effects on all skin cell populations, preserving them from photo exposure damages and premature senescence, being also able to increase the DNA repairing mechanisms and inducing a youngest phenotype.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70530","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770079","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":"Systemic Lupus Erythematosus Exacerbates Hip Arthritis by Promoting Chondrocyte Pyroptosis in the Femoral Head via Activating the NF-κB Pathway","authors":"Xuliang Fang,&nbsp;Helou Zhang,&nbsp;Huiqing Zhou,&nbsp;Shuchao Shen,&nbsp;Zhaobai Lao,&nbsp;Zhiguo Zhang,&nbsp;Yishan Bian,&nbsp;Chengcong Zhou,&nbsp;Hongting Jin,&nbsp;Peijian Tong,&nbsp;Yanqun Huang,&nbsp;Hong Zhou,&nbsp;Hanbing Zeng,&nbsp;Fangda Fu,&nbsp;Chengliang Wu,&nbsp;Wenbiao Zheng,&nbsp;Hongfeng Ruan","doi":"10.1111/jcmm.70531","DOIUrl":"https://doi.org/10.1111/jcmm.70531","url":null,"abstract":"<p>Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by chronic inflammation and immune dysregulation, significantly impacting multiple organ systems, including the joints. While SLE is known to contribute to musculoskeletal complications, its role in hip arthritis development and the underlying mechanisms remain poorly understood. This study aims to investigate the relationship between SLE and hip arthritis progression using MRL/<i>lpr</i> mice, which exhibit early-onset SLE, compared with MRL/<i>MpJ</i> control mice at 14 weeks of age. Through comprehensive histological, immunohistochemical and molecular analyses, we evaluated articular cartilage (AC) degeneration, extracellular matrix (ECM) metabolism, inflammatory responses, and chondrocyte pyroptosis. Our results demonstrated that MRL/<i>lpr</i> mice developed an accelerated hip arthritis-like phenotype, manifesting as enhanced AC degeneration, impaired chondrocyte proliferation, heightened apoptosis and promoted inflammatory cytokine production. Notably, SLE markedly stimulated chondrocyte pyroptosis by increasing pyroptosis-related proteins, including NLRP3, ASC, CASPASE-1 and GSDMD, via activating the NF-κB pathway. These findings establish a novel mechanistic link between SLE and hip arthritis progression, demonstrating that SLE promotes chondrocyte pyroptosis to exacerbate AC degeneration via NF-κB activation, highlighting chondrocyte pyroptosis as a key driver of SLE-associated hip arthritis and a potential therapeutic target for mitigating SLE-induced joint manifestations.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770085","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":"NUPR1 Promotes Radioresistance in Colorectal Cancer Cells by Inhibiting Ferroptosis","authors":"Yimin Fang,&nbsp;Haiyan Chen,&nbsp;Yunhua Liu,&nbsp;Kai Jiang,&nbsp;Yucheng Qian,&nbsp;Jingsun Wei,&nbsp;Dongliang Fu,&nbsp;Hang Yang,&nbsp;Siqi Dai,&nbsp;Tian Jin,&nbsp;Tongtong Bu,&nbsp;Kefeng Ding","doi":"10.1111/jcmm.70519","DOIUrl":"https://doi.org/10.1111/jcmm.70519","url":null,"abstract":"<p>Radioresistance is a major clinical challenge and the underlying mechanism has not been thoroughly elucidated. In this study, a radioresistant (RR) cell line is established to explore the transcriptomic signatures of radioresistance in colorectal cancer (CRC). KEGG enriched pathway analysis demonstrated that ferroptosis is inactivated in RR cells. Further detection confirmed that radiotherapy can promote ferroptosis, and ferroptosis inactivation is one of the hallmarks of radioresistance in CRC. What's more, induction of ferroptosis can restore the radiosensitivity of CRC cells. Then, we performed RNA sequencing to compare gene expression between parental and RR cells, and cells pretreated with or without RSL3. Via high-throughput screening, NUPR1 was identified as a potential candidate for ferroptosis-mediated radioresistance in CRC. CRC cells can acquire radiation resistance by NUPR1-mediated ferroptosis suppression in the NUPR1-overexpressing cell line. More importantly, ZZW-115, an NUPR1 inhibitor, can sensitise RR cells to radiotherapy. Overall, our findings identify ferroptosis inactivation linked with resistance to radiotherapy. Besides, NUPR1 can promote radiation resistance by inhibiting ferroptosis, and targeting NUPR1 may be a potential strategy to relieve radioresistance associated with ferroptosis in CRC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762277","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":"Microbial Influences on Calcium-Phosphorus Homeostasis and Metabolic Bone Diseases: A Bidirectional Mendelian Randomisation Study on the Gut–Bone Axis","authors":"Yanling Zhou,&nbsp;Yao Yang,&nbsp;Wanbo Zhu,&nbsp;Nikolaos Kourkoumelis,&nbsp;Yingjie Wang,&nbsp;Yuan Chen,&nbsp;Lingxiang Hong,&nbsp;Junjie Wang,&nbsp;Junchen Zhu,&nbsp;Chen Zhu,&nbsp;Xianzuo Zhang","doi":"10.1111/jcmm.70491","DOIUrl":"https://doi.org/10.1111/jcmm.70491","url":null,"abstract":"<p>Observational studies have shown that the gut microbiota (GM) is associated with bone diseases, particularly calcium-phosphorus metabolic bone diseases, demonstrating the existence of a gut–bone axis. However, whether these associations are causal effects remains to be determined. This study employed bidirectional two-sample Mendelian randomisation (MR) using summary data from Genome-Wide Association Studies (GWAS) of 211 gut microbial taxa and six metabolic bone diseases (osteoporosis, Osteopenia, osteonecrosis, osteomyelitis, hypoparathyroidism and hyperparathyroidism) to explore causal relationships and their directionality. Comprehensive sensitivity analyses were conducted to ensure the robustness of the results, and a false discovery rate-corrected <i>p</i>_FDR of &lt; 0.05 was used as a threshold to support strong associations. Additionally, co-localisation analysis was conducted to consolidate the findings. We identified 35 causal relationships between GM and metabolic bone diseases, with 17 exhibiting positive and 18 negative correlations. Furthermore, reverse MR analysis indicated that osteomyelitis was associated with elevated abundance of two GMs (<i>p</i>_FDR &lt; 0.05, PP.H4 &lt; 75%). No evidence of horizontal pleiotropy or heterogeneity was observed, and co-localisation analysis further strengthened the evidence for these causal relationships. The study underscores the critical role of GM in influencing bone health through the gut–bone axis, paving the way for future therapeutic interventions targeting the gut–bone axis and offering new directions for research in bone metabolism and diseases.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70491","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741420","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}