Cells最新文献

{"title":"Exosomal microRNAs in Bronchial Aspirate and Other Liquid Biopsy Specimens for Lung Cancer: Current Evidence and Future Perspectives-A Narrative Review.","authors":"Dragoș Huțanu, Mara Andreea Vultur, Corina Eugenia Budin, Dumitru Cătălin Sârbu, Maria Beatrice Ianoși, Edith Simona Ianoși, Hédi Katalin Sárközi, Gabriela Jimborean","doi":"10.3390/cells15080731","DOIUrl":"https://doi.org/10.3390/cells15080731","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer mortality worldwide, with most cases diagnosed at advanced stages. Conventional tissue biopsy is invasive, and low-dose CT (LDCT) screening-although effective-faces practical and logistical limitations. Liquid biopsy has emerged as a minimally invasive approach to capture tumor-derived material, including circulating tumor DNA (ctDNA), cells, and extracellular vesicles (EVs). Among EVs, exosomes and their microRNA (miRNA) cargo offer a stable, disease-specific signal. Airway-proximal fluids such as bronchial aspirate and bronchoalveolar lavage fluid (BALF) are in direct contact with the tumor microenvironment and may contain higher concentrations of tumor-derived exosomal miRNAs compared with blood. This review synthesizes the limited but promising evidence for exosomal miRNAs in bronchial aspirate and BALF as diagnostic and prognostic biomarkers in lung cancer, examines methodological and standardization challenges, and discusses potential integration into clinical workflows, with particular emphasis on Romania's lung cancer epidemiology and healthcare context. While only two primary studies in the last five years have explored BALF exosomal miRNAs, these data justify further multicenter investigations aligned with MISEV2023 guidelines. Integrating airway-proximal exosomal miRNA analysis into bronchoscopy procedures could enhance diagnostic precision in resource-limited health systems and support the transition towards personalized thoracic oncology.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Transcriptomics Reveals Immune Modulation by Telmisartan in Colorectal Cancer.","authors":"Jinxin Li, Decao Yang, Xiaoyue Wang, Runqing Ju, Shaomeng Chen, Jingyi Zhao, Jiaxing Xu, Jiaxin Chen, Jiayu Ye, Baohui Xu, Qianqian Yin, Yan Wang","doi":"10.3390/cells15080729","DOIUrl":"https://doi.org/10.3390/cells15080729","url":null,"abstract":"<p><p>Telmisartan, an angiotensin II type 1 receptor blocker with established anti-inflammatory and antihypertensive properties, has been reported to inhibit tumor cell proliferation, yet its impact on the tumor immune microenvironment remains poorly understood. In this study, we evaluated the immunomodulatory effects of telmisartan using a syngeneic MC38 colorectal cancer model in C57BL/6 mice. Daily intragastric administration of telmisartan significantly suppressed tumor growth and reduced endpoint tumor weight compared with controls. To elucidate the underlying mechanisms, we performed single-cell RNA sequencing on tumor-infiltrating CD45⁺ immune cells and revealed a macrophage-dominated immune landscape comprising multiple transcriptionally distinct subclusters. Telmisartan broadly downregulated pro-tumoral and M2-associated macrophage programs, including decreased expression of genes such as <i>Mrc1</i> and <i>Spp1</i>, while also suppressing cell proliferation-related pathways. In contrast to its overall suppressive impact on macrophages, telmisartan increased the proportion of cytotoxic CD8⁺ T cells, reduced regulatory T cell counts, and enhanced major histocompatibility complex class I antigen presentation, consistent with an immune-activating effect. These results indicate that telmisartan reshapes the colorectal tumor immune microenvironment by simultaneously attenuating tumor-promoting macrophage activity and augmenting cytotoxic T cell responses. Overall, this study provides a single-cell framework to understand how angiotensin receptor blockade reshapes tumor-infiltrating immune programs, highlighting the translational potential of repurposing telmisartan for novel cancer immunotherapy strategies.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Phase Serum Concentration Kinetics of FGF23 in a Clinical Model of Acute Myocardial Infarction.","authors":"Nora Strack, Praveen Gajawada, Christoph Liebetrau, Oliver Dörr, Till Keller, Yeong-Hoon Choi, Manfred Richter","doi":"10.3390/cells15080728","DOIUrl":"https://doi.org/10.3390/cells15080728","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Fibroblast growth factor-23 (FGF23) is a key regulator of phosphate homeostasis and an emerging biomarker in cardiovascular disease. Emerging data suggest that FGF23 may also contribute to the pathophysiology of myocardial infarction (MI), but existing studies have largely focused on non-acute stages. To address this gap, we investigated early FGF23 regulation by characterizing serum concentration kinetics over the first 24 h following MI, using both a clinical MI model (TASH) and a cohort of patients with ST-elevation myocardial infarction (STEMI).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Circulating FGF23 concentrations (cFGF23; RU/mL) were determined by C-terminal ELISA in patients with preserved renal function (eGFR &gt; 30 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;). TASH (transcoronary septal ablation) was carried out in patients with hypertrophic obstructive cardiomyopathy (&lt;i&gt;n&lt;/i&gt; = 38). Venous serum samples were taken at baseline (pre-TASH) and at 30', 60', 2 h, 4 h and 24 h post-TASH. For the STEMI cohort (&lt;i&gt;n&lt;/i&gt; = 18), serum was sampled immediately before and 3 h after coronary recanalization. All samples were processed using standardized procedures prior to analysis. Changes over time were assessed using the Friedman test with Bonferroni-corrected pairwise Wilcoxon comparisons.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;FGF23 concentrations changed significantly over time after TASH (Friedman test, &lt;i&gt;p&lt;/i&gt; &lt; 0.000001, Kendall's W = 0.518). Baseline FGF23 was 28.9 (19.4-71.0) RU/mL and increased significantly at 30' (68.2 (36.2-178.7) RU/mL, adjusted &lt;i&gt;p&lt;/i&gt; &lt; 0.0001 **) after TASH. Concentrations remained elevated at 60' (54.8 (31.6-118.3) RU/mL; adjusted &lt;i&gt;p&lt;/i&gt; = 0.0019 *), returned to baseline at 2 h (30.9 (20-71.2) RU/mL; adjusted &lt;i&gt;p&lt;/i&gt; = 1.0 vs. baseline) and decreased significantly below baseline at 4 h (24 (12.13-37.5) RU/mL, adjusted &lt;i&gt;p&lt;/i&gt; = 0.0215 *). By 24 h, FGF23 had returned to baseline levels (28.8 (12.8-57.3) RU/mL; adjusted &lt;i&gt;p&lt;/i&gt; = 1.0 vs. baseline). Although concentrations were numerically higher than at the 4 h nadir, this recovery did not reach statistical significance (adjusted &lt;i&gt;p&lt;/i&gt; = 0.136 vs. 4 h). In STEMI patients, a non-significant decrease was observed from baseline (27 (15.5-35.75) RU/mL) to 3 h after recanalization (15.5 (6.75-34.25) RU/mL; &lt;i&gt;p&lt;/i&gt; = 0.074, effect size r = 0.422). In an exploratory normalized analysis, the decline reached significance (&lt;i&gt;p&lt;/i&gt; = 0.0241).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The triphasic kinetics of circulating FGF23 in TASH patients-characterized by an early rise, transient undershoot, and a recovery toward baseline with a continuing upward trend-are consistent with a dynamic release-and-clearance pattern following myocardial injury. These findings are hypothesis-generating and warrant further investigation in larger cohorts with additional biomarkers to elucidate the source, regulation, and potential functional significance of FGF23 in the acute phase of myoca","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stemness and Survival: CD117⁺/CD133⁺ Subpopulations Sustain PI3K Signaling and Drive Imatinib Resistance in Head and Neck Mucosal Melanoma.","authors":"Sofie-Yasmin Hassan, Simeon Santourlidis, Thomas W Flanagan, Sarah-Lilly Hassan, He Zhou, Morna F Schmidt, Claudio Cacchi, Matthias Ferdinand Lammert, Mossad Megahed, Amir Sadegh Yazdi, Danny David Jonigk, Marcos J Araúzo-Bravo, Robert T Brodell, Sybille Facca, Youssef Haikel, Mohamed Hassan","doi":"10.3390/cells15080721","DOIUrl":"https://doi.org/10.3390/cells15080721","url":null,"abstract":"<p><p>Head and neck mucosal melanoma (HNMM) arises in the nasal and oral cavities and has the propensity to metastasize to local and distant body sites. HNMM is also notable for its resistance to available therapeutics. The rarity of this disease makes it difficult to conduct large-scale clinical studies to develop standard treatment protocols. In contrast to cutaneous melanoma, c-Kit-dependent pathways are well studied in HNNMM and provide a potential therapeutic target. We identified and isolated genetically distinct subpopulations with stem cell characteristics in HNMM samples bearing Kit wild-type and mutations. Functional analysis of these subpopulations reveals that, in addition to expressing the stem cell marker proteins CD20, CD117, CD133, and CD166, these subpopulations are characterized by self-renewal potential, migratory capacity, and resistance to Kit inhibitors such as Imatinib. Immunofluorescence staining and inhibition experiments demonstrate that the maintenance and resistance of HHMM subpopulations to Kit inhibitors is mediated by the Kit signal to the PI3K signaling pathway. The KIT signal to the PI3K signaling pathway does not result exclusively from a KIT mutation localized to Exon 17, but can also be triggered by mutations localized to Exons 11 and 13. In the present study, we identify and characterize an HNMM subpopulation with stemness properties in patients with c-Kit wild-type and mutation, and demonstrate for the first time the mechanisms by which the CD117⁺/CD133⁺ HNMM subpopulations survive and confer resistance to the specific inhibitor of c-Kit mutation.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Editing Strategies for Neurological and Mental Disorders: Advances in Delivery, Methodology, and Clinical Translation.","authors":"Amer Elias, Shani Stern","doi":"10.3390/cells15080720","DOIUrl":"https://doi.org/10.3390/cells15080720","url":null,"abstract":"<p><p>Neurological and mental disorders are among the main causes of disability worldwide, affecting over three billion people and increasing the socioeconomic burden. Advances in molecular genetics and genome engineering have led to gene-targeted therapies that address root causes rather than just symptoms. This review covers current genome-editing tools, including CRISPR/Cas, base editing, and prime editing. The focus is on the benefits of gene editing in the central nervous system, where post-mitotic neurons allow lasting effects after a single treatment. It also discusses emerging delivery platforms such as viral vectors, nanoparticles, and exosome systems, as well as methods to bypass the blood-brain barrier. Recent clinical progress in spinal muscular atrophy, Parkinson's disease, Huntington's disease, and Alzheimer's disease is highlighted, with promising preclinical results for autism, bipolar disorder, epilepsy, and other neurogenetic conditions. The review concludes with regulatory issues, market trends, and ongoing clinical trials, underscoring the potential of gene therapies to transform disease management and provide long-term solutions.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in Circulating Progenitor Cell Composition in Rheumatoid Arthritis.","authors":"Eva Camarillo-Retamosa, Jan Devan, Camino Calvo-Cebrián, Alexandra Khmelevskaya, Kristina Bürki, Raphael Micheroli, Adrian Ciurea, Stefan Dudli, Caroline Ospelt","doi":"10.3390/cells15080726","DOIUrl":"https://doi.org/10.3390/cells15080726","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by persistent joint inflammation and systemic immune dysregulation. While bone marrow activation has been linked to RA pathogenesis, direct access to bone marrow tissue for progenitor analysis remains limited by ethical and technical constraints. Analysis of progenitor cells in peripheral blood can serve as a surrogate reflecting bone marrow activation. In this study, we analysed peripheral blood cells from 12 RA patients and 9 healthy controls using high-dimensional spectral flow cytometry with a nine-marker panel (CD45, CD31, CD235, CD133, CD34, CD105, CD271, CD90, PDPN). Flow Self-Organizing Map (FlowSOM) clustering identified 20 distinct cell populations. Additionally, a complementary flow cytometry panel was used to assess CD31 expression on immune subsets in peripheral mononuclear cells (PBMCs) from 9 RA and 9 healthy donors of this cohort. RA patients showed increased CD45⁺CD31^- immune cells, but not their putative progenitors. Conversely, putative CD45⁺CD31^int progenitors and CD45⁺CD31^int mature cells were reduced, along with CD31 expression on T cells. Levels of CD235a⁺ putative erythroid precursors and CD45⁺CD31⁺ progenitors were significantly increased in RA patients. Three putative stromal cell populations were detected in circulation. Together, these findings reveal expanded erythroid precursor populations and reduced CD31 expression on T cells in RA. Our data underscore broad systemic alterations in cellular homeostasis in RA patients. In conclusion, our results suggest that the loss of CD31 expression on immune cell precursors plays a role in age-associated immune remodelling and immune activation in RA and provides the rationale for further studies on erythroblast differentiation and the functional role of erythroblasts in chronic inflammation.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating miR-22 Early Predicts TACE Non-Response and Targets WEE1 in Hepatocellular Carcinoma.","authors":"Laura Gramantieri, Clara Vianello, Ilaria Leoni, Giuseppe Galvani, Elisa Monti, Marco Bella, Giorgia Marisi, Irene Salamon, Manuela Ferracin, Gloria Ravegnini, Catia Giovannini, Claudio Stefanelli, Maria Laura Lazzari, Fabio Piscaglia, Camelia A Coada, Cristian Bassi, Massimo Negrini, Andrea Casadei-Gardini, Giuseppe Francesco Foschi, Davide Trerè, Francesca Fornari","doi":"10.3390/cells15080722","DOIUrl":"https://doi.org/10.3390/cells15080722","url":null,"abstract":"<p><p>Transarterial chemoembolization (TACE) is the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC), yet nearly half of treated patients fail to achieve durable benefit, and reliable biomarkers enabling early therapeutic stratification are still lacking. Treatment response is typically assessed by imaging one month after TACE and at three-month intervals, potentially delaying timely access to alternative therapies in non-responding patients. Circulating microRNAs (miRNAs) represent promising biomarkers due to their stability in body fluids and ease of detection. Here, we evaluated circulating miR-22 as an early predictor of TACE non-responder status and as a mechanistically relevant therapeutic target. Circulating miR-22 levels were measured by microarray and quantitative RT-PCR in three independent cohorts of early-to-intermediate-stage HCC patients undergoing TACE. Circulating miR-22 increased significantly in non-responders as early as 48 h after treatment, and fold changes consistently predicted treatment failure across two independent validation cohorts. Mechanistically, we identified the G2/M checkpoint kinase WEE1 as a direct functional target of miR-22. Modulation of the miR-22/WEE1 axis affected cell-cycle progression, proliferation, apoptosis, and DNA damage response in HCC cell lines and xenograft models. Under hypoxia-mimicking conditions combined with doxorubicin exposure, pharmacological inhibition of WEE1 induced mitotic catastrophe in highly proliferative miR-22-silenced cells. Collectively, these findings identify early post-TACE elevation of circulating miR-22 as a biomarker of non-response and highlight the miR-22/WEE1 axis as a potential target for precision treatment strategies in HCC.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Pigment Epithelium Ageing: Cellular and Molecular Mechanisms of Long-Term Homeostasis and Age-Related Dysfunction.","authors":"Yijing Yang, Pei Liu, Jiangwei Li, Ying Deng, Li Xiao, Qinghua Peng, Jun Peng","doi":"10.3390/cells15080725","DOIUrl":"https://doi.org/10.3390/cells15080725","url":null,"abstract":"<p><p>The retinal pigment epithelium (RPE) is a long-lived, highly polarised epithelial monolayer that performs essential functions in retinal homeostasis, including outer blood-retina barrier maintenance, visual cycle activity, metabolic exchange, phagocytic clearance of photoreceptor outer segments, and regulation of oxidative and immune balance. Because RPE cells persist for decades under conditions of sustained oxidative, metabolic, and phagocytic stress, this tissue provides a valuable model for examining how long-lived post-mitotic cells preserve function over time and how age-related dysfunction emerges when that balance weakens. Although much of the current literature on RPE ageing has been shaped by age-related macular degeneration (AMD), age-dependent change in the RPE should not be understood solely as a preclinical stage of disease. Rather, the ageing RPE offers a broader framework for studying cellular maintenance under chronic physiological load. In this review, we synthesise current evidence on RPE ageing across four interrelated domains: structural remodelling, mitochondrial and metabolic imbalance, proteostatic and lysosomal burden, and chronic inflammatory dysregulation. Across these processes, ageing in the RPE is expressed less as widespread cell loss than as progressive decline in cellular organisation, buffering capacity, and functional precision. Structural irregularity, altered mitochondrial regulation, incomplete degradative clearance, and persistent low-grade inflammatory signalling together reduce the ability of the RPE to maintain long-term homeostasis and increase vulnerability to age-related retinal dysfunction. We further argue that ageing in the RPE is best understood not as abrupt failure of isolated pathways, but as gradual loss of system coherence among interacting homeostatic systems that remain active while operating under increasing constraint. This view helps integrate diverse cellular and molecular findings and highlights the RPE as an informative model for understanding ageing in long-lived post-mitotic tissues.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid Dysfunction as a Component of an Immuno-Metabolic Depression-A Possible Role of Gut Microbiota and a Rationale for Future Studies.","authors":"Karolina Michno, Mateusz Kapela, Dominik Strzelecki, Oliwia Gawlik-Kotelnicka","doi":"10.3390/cells15080723","DOIUrl":"https://doi.org/10.3390/cells15080723","url":null,"abstract":"<p><p>Depression is one of the most prevalent psychiatric disorders worldwide, with a steadily increasing incidence and complex, multifactorial pathophysiology. Beyond classical neurochemical mechanisms, growing evidence points to the role of systemic low-grade inflammation and immuno-metabolic disturbances in its development. Gut microbiota dysbiosis has emerged as a key factor linking metabolic, immune, and neuroendocrine pathways, potentially exacerbating neuroinflammation and contributing to the onset and progression of depressive symptoms. Immune activation, which is a result of gut dysbiosis, may play a crucial role in the pathogenesis of immuno-metabolic depression. Thyroid dysfunction appears to be an important, yet insufficiently understood component of this network. Thyroid hormones play a crucial role in regulating metabolism, immune responses, and central nervous system function. Alterations in thyroid function, even within subclinical ranges, have been associated with mood disturbances and may share common inflammatory and metabolic pathways with depression. Furthermore, emerging data suggest that gut microbiota may influence thyroid hormone metabolism, including deiodinase activity, linking dysbiosis with thyroid axis dysregulation. Despite these insights, the integrated interactions between thyroid function, gut microbiota, metabolic syndrome, and inflammation in depression remain largely unexplored. This review explores current evidence to highlight gaps in existing research and synthesizes current knowledge, aiming to clarify mechanisms underlying immuno-metabolic depression. Understanding these relationships may provide a rationale for redefining depression as an immuno-metabolic disorder and support the development of more integrative therapeutic strategies targeting not only the brain, but also the gut-thyroid axis.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypomagnetic Field Enhances U2OS Cell Proliferation and Migration by Promoting β-Catenin Phosphorylation and Upregulating FN1 and LOX Expression.","authors":"Taotao Gao, Wenfeng Zhong, Mengli Tao, Yu Guo, Kun Yang, Yaohui He, Guosheng Hu, Long Li, Xiangyan Kong, Fulai Li, Yufen Zhao","doi":"10.3390/cells15080727","DOIUrl":"https://doi.org/10.3390/cells15080727","url":null,"abstract":"<p><p>Accumulating evidence indicates that a hypomagnetic field (HMF, <5 μT) has a significant impact on various organ systems in animals. However, the cellular and molecular mechanisms underlying these biological effects remain unclear. Understanding the molecular mechanisms underlying mammalian responses to a HMF is crucial for addressing health and safety concerns associated with HMF exposure. In this study, we investigated the changes in intracellular protein phosphorylation under HMF conditions and validated the functional mechanisms by which HMF-induced protein phosphorylation affects cell behavior. We found that U2OS cells can rapidly sense changes in magnetic fields, leading to alterations in protein phosphorylation levels within the cell. The quantitative phosphoproteomics results revealed that the exposure of U2OS cells to the HMF environment for 0.5 h and 3 days resulted in the alteration of 1101 and 1543 phosphosites, respectively. Notably, HMF exposure enhanced the phosphorylation of β-Catenin at Ser552, and this increased phosphorylation-promoted U2OS proliferation and migration. Furthermore, quantitative proteomics showed that exposure to a HMF for 3 days upregulated the expression of LOX and FN1, while the knockdown of LOX or FN1 suppressed the proliferation and migration of the U2OS cells. These results suggest that a HMF enhances U2OS cell proliferation and migration by promoting β-Catenin phosphorylation and upregulating FN1 and LOX expression.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}