Journal of Molecular Medicine-Jmm最新文献

{"title":"A bioactive soluble recombinant mouse LIGHT promotes effective tumor immune cell infiltration delaying tumor growth.","authors":"Maria-Luisa Del Rio, Oscar-Mariano Nuero-Garcia, Giovanna Roncador, Raquel Garcimartín-Bailon, Juan-Carlos Cubria, Pascal Schneider, Jose-Ignacio Rodriguez-Barbosa","doi":"10.1007/s00109-025-02552-x","DOIUrl":"https://doi.org/10.1007/s00109-025-02552-x","url":null,"abstract":"<p><p>The TNF family member LIGHT (TNFSF14) binds to two receptors, HVEM (TNFSFR14) and LTβR (TNFSFR3). HVEM functions as a costimulatory molecule, whereas LTβR is involved in the development of lymph nodes and ectopic tertiary lymphoid structures at chronic inflammation sites. The classical approach of fusing soluble recombinant proteins to the Fc fragment of IgG resulted in a functionally inactive Ig.mouse (m) LIGHT protein. However, in line with the fact that TNF family members cluster receptors as trimers, addition of a small homotrimeric domain (foldon) N-terminal of mLIGHT produced an Ig.Foldon-mLIGHT protein able to bind and engage HVEM and LTβR in a cell-based reporter bioassay. In the tumor model of B16.F10 melanoma cells implanted into syngeneic recipients, cells transduced with membrane-bound mLIGHT grew as aggressively as mock-transduced cells, but growth of tumors of B16.F10 cells expressing Ig.Foldon-mLIGHT was delayed and characterized by significant immune infiltration of dendritic cells and cytotoxic cells. This work unveils the potential of active soluble LIGHT, as a single agent, to recruit cytotoxic cells and dendritic cells at the tumor site to inhibit tumor growth. This effect may be further enhanced with immune checkpoint blockade therapies. KEY MESSAGES: The classical approach of fusing soluble recombinant proteins to the Fc fragment of IgG resulted in a functionally inactive Ig.mouse (m) LIGHT (TNFSF14) protein. The addition of a small homotrimeric domain (foldon) N-terminal of mouse LIGHT produces a proper folded bioactive mouse LIGHT recombinant protein. Constitutive intratumor expression of secreted Ig-Foldon-LIGHT, but not membrane LIGHT, delays tumor growth. Tumors secreting LIGHT, as a single agent, promote beneficial anti-tumor responses through the recruitment and infiltration of cytotoxic cells and dendritic cells.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flotillin- 1 ameliorates experimental diabetic retinopathy by inhibiting ferroptosis in blood-retinal barrier.","authors":"Jie Zhang, Ke Chang, Yanyu Shangguan, Ruoning Luo, Yanlong Bi, Zicheng Yu, Bing Li","doi":"10.1007/s00109-025-02544-x","DOIUrl":"10.1007/s00109-025-02544-x","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is a chronic disease that severely impairs the vision of working individuals and is closely linked to blood-retinal barrier (BRB) dysfunction. Flotillin- 1 (FLOT1), a protein located in membrane lipid rafts, is essential for various intracellular biological processes. However, its role in the pathogenesis of DR remains unclear. Ferroptosis in high-glucose was assessed using Cell counting kit- 8 (CCK- 8), Malondialdehyde (MDA), Glutathione (GSH), Fe²⁺ assays, and transferrin expression. BRB disruption was evaluated with Evans blue staining. The interaction between FLOT1 and NF-E2-related factor 2 (Nrf2) was confirmed by immunoprecipitation and ferroptosis mechanisms were explored by inhibiting Nrf2 with ML385. In db/db mice (a type 2 diabetes model) was intravitreal injection of an adeno-associated virus (AAV) overexpressing FLOT1. Expression levels of Nrf2, solute carrier family 7 member 11 (SLC7 A11), and glutathione peroxidase 4 (GPX4) were evaluated in retina. Our study indicated that FLOT1 significantly alleviated BRB damage in DR, reversing high-glucose induced reductions in GPX4 and GSH, and inhibited the elevation of MDA and Fe²⁺. FLOT1 also suppressed ROS accumulation. Mechanistically, FLOT1 activates the Nrf2 pathway by enhancing its expression and promoting its nuclear translocation, thereby stimulating the SLC7 A11/GPX4 pathway to inhibiting lipid peroxidation and ferroptosis. We have identified ferroptosis is a key mechanism driving BRB damage in DR.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"671-685"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD24, NFIL3, FN1, and KLRK1 signature predicts melanoma immunotherapy response and survival.","authors":"Bruna Pereira Sorroche, Renan de Jesus Teixeira, Vinicius Gonçalves de Souza, Isabela Cristiane Tosi, Katiane Tostes, Ana Carolina Laus, Iara Viana Vidigal Santana, Vinicius de Lima Vazquez, Lidia Maria Rebolho Batista Arantes","doi":"10.1007/s00109-025-02550-z","DOIUrl":"10.1007/s00109-025-02550-z","url":null,"abstract":"<p><p>Melanoma poses a significant health concern due to its propensity to metastasize and its high mortality rate. Immunotherapy has emerged as a promising treatment strategy for harnessing the patient's immune system to fight tumor cells. However, not all patients respond equally to immunotherapy, highlighting the need for predictive biomarkers to identify potential responders and optimize treatment strategies. Using data from 579 immunology-related genes evaluated by the NanoString nCounter Human Immunology v2 Panel, we integrated transcriptomic data with the clinical characteristics of 35 individuals to develop a predictive signature for immunotherapy response in melanoma patients. Through comprehensive analysis, we identified 18 genes upregulated in non-responder patients and three upregulated in responder patients. In multivariate analysis, CD24, NFIL3, FN1, and KLRK1 were identified as key predictors with significant potential for forecasting treatment outcomes. We then calculated a score incorporating the expression levels of these genes. The score achieved high accuracy in discriminating responders from non-responders, with an area under the curve of 0.935 (p < 0.001). The signature was also significantly associated with progression-free survival, overall survival, and survival following immunotherapy (p < 0.001). The validation of the signature in two independent cohorts confirmed its robustness and applicability, with areas under the curve of 0.758 (p = 0.036) and 0.833 (p = 0.004), respectively. This study represents a significant advance in precision medicine for melanoma. By identifying patients unlikely to benefit from immunotherapy, our approach could help optimize treatment allocation and improve patient outcomes. KEY MESSAGES: Novel 4-gene signature predicts immunotherapy failure in melanoma. High accuracy for personalized treatment decisions. Signature associated with decreased survival for non-responders. Signature validated in independent cohorts, enhancing generalizability. Potential to tailor treatment strategies and avoid unnecessary burden to patients.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"725-737"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of aberrant activated fibro/adipogenic progenitors and suppressed ferroptosis in disused skeletal muscle atrophy and fatty infiltration.","authors":"Jiale Tan, Yuqi Li, Jie Zhang, Beijie Qi, Jiwu Chen, Yaying Sun","doi":"10.1007/s00109-025-02548-7","DOIUrl":"10.1007/s00109-025-02548-7","url":null,"abstract":"<p><p>Muscle fatty infiltration (MFI) was characterized by the pathological accumulation of fat within skeletal muscle tissue. Previous studies have found that the progress of this pathological phenomenon in aging, acute muscle injury, and other conditions was triggered by the activation and adipogenic differentiation of the key cell population, fibro/adipogenic progenitors (FAPs), but there were few studies on the fat infiltration caused by disused skeletal muscle atrophy, and the regulatory role of FAPs in this situation has not been deeply explored, leaving the related molecular mechanisms still unknown. In this study, we conducted single-cell RNA sequencing on the disused skeletal muscle. The aberrant proliferation of FAPs in this state was found by subsequent analysis, along with the high expression of the ferroptosis inhibitory gene in the activated FAPs. By immunofluorescence staining, we verified the proliferation and adipogenic differentiation of FAPs, which proved the role of FAPs in fat infiltration of disused skeletal muscle. In order to further verify the relationship between ferroptosis inhibition and FAPs activation/adipogenic differentiation, we used ferrostatin-1, a commonly used ferroptosis inhibitor, to treat skeletal muscle fibroblasts and FAPs in vitro, and verified the enhancement of ferroptosis inhibition on their adipogenic/fibrogenic ability. Our study pinpointed the effect of aberrant activation of FAPs on MFI in disused skeletal muscle, and preliminarily recognized the potential effect of ferroptosis on the adipogenic differentiation of FAPs. KEY MESSAGES: • Muscle fatty infiltration (MFI) was characterized by the pathological accumulation of fat within skeletal muscle. Fibro/adipogenic progenitors (FAPs) were thought to be crucial regulators of MFI, but their correlations in disused skeletal muscle were unspecified. • In this study, we conducted single-cell RNA sequencing on the disused skeletal muscle and recognized the aberrant proliferation of FAPs along with the upregulated ferroptosis inhibition genes in this status. • Subsequently, we used ferrostatin-1 (ferroptosis inhibitor) to treat skeletal muscle fibroblasts in vitro, and verified the enhancement of ferroptosis inhibition on their adipogenic/fibrogenic ability. • Our study pinpointed the effect of aberrant activation of FAPs on MFI in disused skeletal muscle, and preliminarily recognized the potential effect of ferroptosis on the adipogenic differentiation of FAPs.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"713-724"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New mesenchymal stem/stromal cell-based strategies for osteoarthritis treatment: targeting macrophage-mediated inflammation to restore joint homeostasis.","authors":"María Jesús Araya-Sapag, Eliana Lara-Barba, Cynthia García-Guerrero, Yeimi Herrera-Luna, Yesenia Flores-Elías, Felipe A Bustamante-Barrientos, Guillermo G Albornoz, Consuelo Contreras-Fuentes, Liliana Yantén-Fuentes, Noymar Luque-Campos, Ana María Vega-Letter, Jorge Toledo, Patricia Luz-Crawford","doi":"10.1007/s00109-025-02547-8","DOIUrl":"10.1007/s00109-025-02547-8","url":null,"abstract":"<p><p>Macrophages are pivotal in osteoarthritis (OA) pathogenesis, as their dysregulated polarization can contribute to chronic inflammatory processes. This review explores the molecular and metabolic mechanisms that influence macrophage polarization and identifies potential strategies for OA treatment. Currently, non-surgical treatments for OA focus only on symptom management, and their efficacy is limited; thus, mesenchymal stem/stromal cells (MSCs) have gained attention for their anti-inflammatory and immunomodulatory capabilities. Emerging evidence suggests that small extracellular vesicles (sEVs) derived from MSCs can modulate macrophage function, thus offering potential therapeutic benefits in OA. Additionally, the transfer of mitochondria from MSCs to macrophages has shown promise in enhancing mitochondrial functionality and steering macrophages toward an anti-inflammatory M2-like phenotype. While further research is needed to confirm these findings, MSC-based strategies, including the use of sEVs and mitochondrial transfer, hold great promise for the treatment of OA and other chronic inflammatory diseases.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"651-669"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of disease and species differences on the intestinal CLCA4 gene expression.","authors":"K Teske, N A Erickson, A Huck, M Dzamukova, M Fulde, T Heinbokel, D Horst, N Klymiuk, E Pastille, A Mekes-Adamczyk, M Löhning, A D Gruber, R Glauben, L Mundhenk","doi":"10.1007/s00109-025-02538-9","DOIUrl":"10.1007/s00109-025-02538-9","url":null,"abstract":"<p><p>The human chloride channel regulator, calcium-activated (CLCA) 4 is discussed as a driver of epithelial-to-mesenchymal transition as well as a biomarker for colorectal cancer (CRC) and ulcerative colitis. In contrast to humans, the Clca4 gene is duplicated in the mouse, a common model species to study gene functions. However, the relevance of the functional murine Clca4 variants in healthy and diseased intestine is largely unknown. Here, we characterized the spatiotemporal expression patterns of the murine Clca4a and Clca4b genes in the healthy intestinal tract as well as in dextran sulfate sodium (DSS)-induced colitis and colitis-associated colon cancer (CAC) mouse model using RT-qPCR and in situ-hybridization. Similarly, we analyzed expression of the human CLCA4 in healthy, inflamed and cancerous intestinal tracts at single cell level. Murine Clca4a and -4b but not the human CLCA4 were detected in small intestine enterocytes of the respective species. Conversely, healthy colonocytes expressed the human CLCA4 and its murine ortholog Clca4a but not the murine Clca4b. Under inflammatory conditions, de novo expression of Clca4b was observed with both murine homologs abundantly expressed in enterocytes adjacent to ulcerations. Neoplastic colonocytes expressed none or only minimal amounts of the CLCA4 homologs both in humans and mice, whereas adjacent non-neoplastic colonocytes strongly up-regulated the human or both murine homologs, respectively. Our results suggest marked species- and homolog-specific differences in the expression patterns of the three CLCA4 homologs. Moreover, all three seem to play a role in reactive, non-neoplastic colonocytes adjacent to ulcerated and neoplastic lesions. KEY MESSAGES: Human CLCA4 and murine Clca4a, but not Clca4b, are expressed in healthy colonocytes. Inflammation leads to a de novo expression of the murine Clca4b in colonocytes. Human and murine CLCA4 homologs are absent from neoplastic enterocytes. Human and murine CLCA4s are highly expressed in tumor-adjacent, reactive colonocytes.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"687-697"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review of m6 A methylation in coronary heart disease.","authors":"Mei-Ning Diao, Yi-Jv Lv, Hui Xin, Yin-Feng Zhang, Rui Zhang","doi":"10.1007/s00109-025-02540-1","DOIUrl":"10.1007/s00109-025-02540-1","url":null,"abstract":"<p><p>The morbidity and mortality rates of coronary heart disease (CHD) are high worldwide. The primary pathological changes in CHD involve stenosis and ischemia caused by coronary atherosclerosis (AS). Extensive research on the pathogenesis of AS has revealed chronic immunoinflammatory processes and cell proliferation in all layers of coronary vessels, including endothelial cells (ECs), vascular smooth muscle cells, and macrophages. m6 A methylation is a common posttranscriptional modification of RNA that is coordinated by a variety of regulators (writers, readers, erasers) to maintain the functional stability of modified mRNAs and ncRNAs. In recent years, there has been increasing focus on the involvement of m6 A methylation in the incidence and progression of CHD, which starts with atherosclerotic plaque formation, leads to myocardial ischemia, and ultimately results in the occurrence of myocardial infarction (MI). m6 A regulators modulate relevant signaling pathways to participate in the inflammatory response, programmed death of cardiomyocytes, and fibrosis. Therefore, diagnostic models based on m6 A profiling are helpful for the early detection of CHD, and m6 A methylation shows promise as a sensitive target for new drugs to treat CHD in the future.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"619-633"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring endothelial dysfunction in major rheumatic diseases: current trends and future directions.","authors":"Arshiya S Anwar Husaini, Aseela Fathima, Dunia Halawa, Nada Aakel, Gian Luca Erre, Roberta Giordo, Hatem Zayed, Gianfranco Pintus","doi":"10.1007/s00109-025-02539-8","DOIUrl":"10.1007/s00109-025-02539-8","url":null,"abstract":"<p><p>The relationship between rheumatic diseases (RDs) and endothelial dysfunction (ED) is intricate and multifaceted, with chronic inflammation and immune system dysregulation playing key roles. RDs, including Osteoarthritis (OA), Rheumatoid arthritis (RA), Systemic Lupus erythematosus (SLE), Ankylosing spondylitis (AS), Psoriatic arthritis (PsA), Sjogren's syndrome (SS), Systemic sclerosis (SSc), Polymyalgia rheumatica (PMR) are characterized by chronic inflammation and immune dysregulation, leading to ED. ED is marked by reduced nitric oxide (NO) production, increased oxidative stress, and heightened pro-inflammatory and prothrombotic activities, which are crucial in the development of cardiovascular disease (CVD) and systemic inflammation. This association persists even in RD patients without conventional cardiovascular risk factors, suggesting a direct impact of RD-related inflammation on endothelial function. Studies also show that ED significantly contributes to atherosclerosis, thereby elevating cardiovascular risk in RD patients. This review synthesizes the molecular mechanisms connecting major RDs and ED, highlighting potential biomarkers and therapeutic targets. Ultimately, the review aims to enhance understanding of the complex interactions leading to ED in rheumatic patients and inform strategies to mitigate cardiovascular risks and improve patient outcomes.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"635-649"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased IL- 36γ in visceral adipose tissue as a key mediator of obesity-driven inflammation in colon cancer.","authors":"Gema Frühbeck, Sofía Criado, Javier Gómez-Ambrosi, Beatriz Ramírez, Sara Becerril, Amaia Rodríguez, Gabriela Neira, Laura Salmón-Gómez, Víctor Valentí, Rafael Moncada, Jorge Baixauli, Camilo Silva, Victoria Catalán","doi":"10.1007/s00109-025-02546-9","DOIUrl":"10.1007/s00109-025-02546-9","url":null,"abstract":"<p><p>Dysfunctional adipose tissue (AT) in the context of obesity promotes a chronic inflammatory state, associated with worse cancer progression and prognosis. Interleukin (IL)-36γ is a proinflammatory factor increased in obesity. The aim was to analyse the role of IL-36γ in colon cancer (CC) development in patients with obesity. Samples obtained from 74 volunteers (27 with normal weight (NW) and 47 with obesity (OB)) were used in a case-control study. Participants were also subclassified according to the presence of CC (45 without and 29 with CC). HT-29 cells were treated with pro-inflammatory factors, adipocyte conditioned media (ACM) and IL-36γ to evaluate the expression levels of inflammation- and extracellular matrix (ECM) remodelling-related molecules. Increased gene expression levels of IL36G and IL36R in visceral AT from patients with OB and CC were found. Moreover, mRNA levels of IL36G were significantly associated with the gene expression levels of its receptor and relevant genes involved in AT inflammation (ASC, IL1B and NLRP6). Consistently, IL36G expression was upregulated by hypoxia, inflammation-related factors (LPS, TNF-α and leptin) and by the adipocyte secretome from patients with obesity in HT-29 cancer cells. Furthermore, we revealed that IL-36γ increased the gene expression levels of inflammation-related genes (IL36G, IL1 A, IL1B, IL6, IL8 and NGAL) as well as ECM markers (MMP9, SPP1 and TNC) in HT-29 cells. Increased gene expression levels of IL36G in VAT from patients with OB and CC may promote a pro-inflammatory microenvironment favourable for tumour progression and migration. KEY MESSAGES: Obesity and colon cancer increase gene expression levels of IL36G and IL36R in visceral adipose tissue. Hypoxia, inflammation-related factors and the adipocyte secretome from patients with obesity upregulate mRNA levels of IL36G in HT-29 cancer cells. IL-36γ increase the gene expression levels of inflammation-related genes (IL36G, IL1A, IL1B, IL6, IL8 and NGAL) as well as ECM markers (MMP9, SPP1 and TNC) in HT-29 cells.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"699-711"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerium oxide nanoparticles as potent inhibitors of ferroptosis: role of antioxidant activity and protein regulation.","authors":"Chenran Feng, Tong Yang, Jie Zhou, Chen Wang, Zheng Chu, Ying Zhang, Junzhe Zhang, Yin Kwan Wong, Cui Liu, Peng Gao, Ang Ma, Huan Tang, Jigang Wang","doi":"10.1007/s00109-025-02554-9","DOIUrl":"https://doi.org/10.1007/s00109-025-02554-9","url":null,"abstract":"<p><p>Ferroptosis has been closely linked to the pathological processes of various diseases, making it a promising target for therapeutic intervention. Understanding the regulatory mechanisms underlying ferroptosis and developing effective pharmacological strategies is essential. Nanomedicine, particularly the use of nanozymes, offers a potential approach for regulating ferroptosis. In this study, we investigated the inhibitory activity of ultra-small, biocompatible cerium oxide nanoparticles (CeO₂ NPs) on ferroptosis and explored the underlying molecular mechanisms. CeO₂ NPs exhibited potent superoxide dismutase (SOD) and catalase (CAT) activities, efficiently scavenging multiple free radicals and lipid peroxidation products both intracellularly and extracellularly. These activities effectively prevented or alleviated ferroptosis in RSL3-induced cells. Proteomic analysis revealed that CeO₂ NPs significantly altered the expression of numerous proteins, including a reduction in pro-inflammatory cytokines. Mechanistically, CeO₂ NPs specifically regulated the expression of key proteins involved in ferroptosis-related metabolic processes, reducing iron accumulation and lipid peroxidation, and thereby decreasing cellular susceptibility to ferroptosis. Our findings demonstrate that CeO₂ NPs synergistically inhibit ferroptosis by both scavenging reactive oxygen species (ROS) and modulating the expression of ferroptosis-regulating proteins. In conclusion, this study highlights the potential of CeO₂ NPs as a promising nanozymes for ferroptosis inhibition, offering novel insights into the design of CeO₂ NPs-based therapies for ferroptosis-related diseases.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}