Life sciences最新文献

{"title":"CXCL10 modulates airway inflammation in asthma via Sirt3-dependent macrophage homeostasis","authors":"Wenqian Ding ,&nbsp;Pingping Wang ,&nbsp;Zhenyu Ding ,&nbsp;Beibei Yang ,&nbsp;Shaohu Huo ,&nbsp;Paiyu Lin ,&nbsp;Jiaying Zhao ,&nbsp;Yuanhong Xu ,&nbsp;Shenggang Ding","doi":"10.1016/j.lfs.2025.123849","DOIUrl":"10.1016/j.lfs.2025.123849","url":null,"abstract":"<div><h3>Background</h3><div>In recent years, it has been found that Th1 inflammation characterized by elevated levels of IFN-γ can be observed in the airways of patients with severe asthma, accompanied by polarization of M1 macrophages. However, the specific pathogenic role of M1 macrophages and their intrinsic regulatory factors in the development of asthma is still unclear.</div></div><div><h3>Objective</h3><div>We sought to investigate whether CXCL10 regulates M1 macrophage polarization through Sirt3.</div></div><div><h3>Methods</h3><div>Collecting peripheral blood samples from asthmatic children, ELISA was used to detect the levels of CXCL9, CXCL10, and CXCL11, and Western blot analyses was used to detect of the levels of Sirt3. We constructed an asthma mouse model and observed changes in macrophage polarization and Sirt3 by neutralizing CXCL10 or injecting CXCR antagonist AMG487. In addition, the effect of CXCL10 on Sirt3 mediated macrophage polarization was elucidated through in vitro experiments. The effect of M1 macrophage polarization on airway epithelial cells was investigated by co-culturing with conditioned medium.</div></div><div><h3>Results</h3><div>Clinical investigations showed that CXCL10 was highly expressed in peripheral blood of children with asthma, and was associated with impaired lung function (FEV1/FVC). Sirt3 expression in peripheral blood mononuclear cell was decreased. CXCL10 was found to the development of disease by promoting the M1 polarization of macrophages. Mechanistically, Sirt3 overexpression improved CXCL10-induced macrophage polarization.</div></div><div><h3>Conclusions</h3><div>CXCL10 promotes M1 macrophage polarization by inhibiting Sirt3, which plays an important role in the development of asthma.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"379 ","pages":"Article 123849"},"PeriodicalIF":5.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untargeted metabolomics profiling of 24-h ultramarathon runners: new insights into the biochemical alterations and the identification of performance biomarkers","authors":"Serena Benedetti ,&nbsp;Federica Biancucci ,&nbsp;Michele Menotta,&nbsp;Maria Gemma Nasoni,&nbsp;Francesca Luchetti","doi":"10.1016/j.lfs.2025.123853","DOIUrl":"10.1016/j.lfs.2025.123853","url":null,"abstract":"<div><h3>Aims</h3><div>Following our previous research experiences on the 24-h ultramarathon (UM) race - a highly demanding competition characterized by acute cardiorespiratory and metabolic responses - we herein explored for the first time the metabolic profile of UM runners (<em>n</em> = 17) participating in a 24-h race via an untargeted metabolomic approach to gain further insights into the biochemical changes induced by the ultra-endurance performance.</div></div><div><h3>Materials and methods</h3><div>Metabolomics analysis was conducted on pre- and post-race plasma samples by high-resolution mass spectrometry in combination with reversed-phase chromatography.</div></div><div><h3>Key findings</h3><div>The major metabolic changes induced by the 24-h running concerned lipid metabolism, with an increase in medium- and long-chain fatty acids as energy sources for muscle contraction during the prolonged physical activity. A significant accumulation of oxidized metabolites from linoleic and arachidonic acids was also detected, which are potent mediators of cellular responses associated with oxidative/inflammatory processes that could be of clinical relevance for athletes' health. Notably, some metabolites presented positive correlations with athletic performance. Higher pre-race levels of 5-methyltetrahydrofolic acid (5-MTHF), as well as higher post-race levels of 5-MTHF, β-alanine, and creatine, were associated with a greater distance covered in 24 h. This evidence may suggest that nutritional supplementation can play an important role before and during the race to sustain athletes' capacity and exercise efficiency throughout such challenging sporting events.</div></div><div><h3>Significance</h3><div>Overall, this study confirms that the metabolomic approach could be a helpful tool to the sport and health management of athletes, and to the identification of possible biomarkers of performance.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123853"},"PeriodicalIF":5.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic changes of peripheral blood mononuclear cells are related to the high cytokine levels in patients with pulmonary arterial hypertension","authors":"Rodrigo López-Velázquez MSc ,&nbsp;Silvia López-Morán MSc ,&nbsp;Alicia Ramírez-Rivera MD ,&nbsp;Nestor Rubio-Infante PhD ,&nbsp;Eduardo Vázquez-Garza PhD ,&nbsp;Elena C. Gónzalez PhD ,&nbsp;Mónica M. Velásquez-Esparza MSc ,&nbsp;María G. López-Treviño MD ,&nbsp;Perla Pérez-Treviño PhD ,&nbsp;Gerardo García-Rivas PhD ,&nbsp;Carlos Jerjes-Sánchez PhD ,&nbsp;Noemí García MSc","doi":"10.1016/j.lfs.2025.123852","DOIUrl":"10.1016/j.lfs.2025.123852","url":null,"abstract":"<div><div>Recently, innate immune activation has been reported to be associated with the development of Pulmonary Arterial Hypertension (PAH); nevertheless, the relationship between metabolic changes and the activation of inflammatory processes is poorly understood. In this retrospective study, we analyzed the relationship of hypoxia-inducible factor 1α (HIF-1α) with changes in proteins related to oxidative and non-oxidative metabolism in peripheral blood mononuclear cells (PBMCs), as well as cytokines in patients with PAH. The mRNA was extracted from PBMCs to analyze the gene expression of AMPKα2, HIF-1α, GLUT1, PFK2, PDHp, MTCO1, CO4, and MTATP6 by RT-PCR. Levels of HIF-1α, AMPK, and subunits from OXPHOS complexes proteins were analyzed by western blots. In addition, the mitochondrial DNA (mtDNA) levels from PBMCs were quantified by qPCR. Finally, plasmatic inflammatory cytokines were quantified. Results show an increased gene expression of MTCO1 (<em>p</em> &lt; 0.05) in patients with PAH. Furthermore, those patients showed significantly elevated protein levels of HIF-1α (<em>p</em> &lt; 0.005), p-AMPK (<em>p</em> &lt; 0.001), and subunits of OXPHOS complexes: CIII (p &lt; 0.005), CIV (<em>p</em> &lt; 0.05), and CV (p &lt; 0.05). Correlation analysis of cytokine levels with those proteins showed a positive, moderate, or strong correlation with protein levels. Interestingly, HIF-1α and AMPK protein levels positively correlated with levels of OXPHOS complexes. Conclusion: a significant elevation of protein levels of HIF-1α, and OXPHOS complexes, as well as a high activity in AMPK in patients with PAH, indicates an adaptive response mechanism in mononuclear cells that, in turn, modifies the systemic inflammatory response.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123852"},"PeriodicalIF":5.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erythropoietin-isosorbide dinitrate-loaded nanocomplex cryogel scaffold: a multifunctional smart dressing for diabetic wound healing","authors":"Toaa A. Abdelrahman ,&nbsp;Amira Motawea ,&nbsp;Marwa S. El-Dahhan ,&nbsp;Galal M. Abdelghani","doi":"10.1016/j.lfs.2025.123850","DOIUrl":"10.1016/j.lfs.2025.123850","url":null,"abstract":"<div><h3>Aims</h3><div>Multifunctional scaffolds hold significant promise for enhancing tissue regeneration, delivering therapeutics, and responding dynamically to physiological cues, particularly in chronic wounds like diabetic ulcers. In the current work, chitosan (CS)/unfractionated heparin (UFH) nanocomplex dispersions loaded with Erythropoietin (EPO) and isosorbide dinitrate (ISDN) was used to prepare a multifunctional cryogel.</div></div><div><h3>Materials and methods</h3><div>CS/UFH mass ratios of 0.5:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 8:1, and 10:1 were used to prepare nanocomplex dispersions. The prepared dispersions were characterized using physicochemical (DLS, zeta potential, FT-IR spectroscopy) and morphological (TEM and SEM) analyses. The effect of CS/UFH mass ratio as well as pH on the release was also studied. Finally, a stability study was conducted to identify the effect of long-term storage in refrigerated conditions on the formulation.</div></div><div><h3>Key findings</h3><div>The optimal formulation at a CS/UFH ratio of 5:1 exhibited favourable characteristics (size: 247 nm, PDI: 0.223, zeta potential: +43.3 mV, EE%: 59.4). TEM imaging consolidated the particle size detected. FT-IR analysis confirmed the electrostatic interaction between CS amino groups, and sulphate and carboxylate groups of EPO and UFH, respectively. Morphological analysis of the cryogel revealed a highly porous structure with large voids. Release experiments indicated a fast ISDN release over 6–8 h with a sustained release of EPO over 4 days. The stability study did not detect any deleterious effect on the physical form or active content over six months.</div></div><div><h3>Significance</h3><div>Our findings demonstrate that the developed cryogel may enhance diabetic wound healing through the sustained delivery of EPO and ISDN.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"379 ","pages":"Article 123850"},"PeriodicalIF":5.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human osteosarcoma cell secretome impairs neonatal mouse calvarial osteogenic cells functions and modifies the nanoparticles-derived protein profile","authors":"Argia Ucci ,&nbsp;Luca Giacchi ,&nbsp;Maria Concetta Cufaro ,&nbsp;Chiara Puri ,&nbsp;Michela Ciocca ,&nbsp;Fabio Di Ferdinando ,&nbsp;Piero Del Boccio ,&nbsp;Alfredo Cappariello ,&nbsp;Nadia Rucci","doi":"10.1016/j.lfs.2025.123837","DOIUrl":"10.1016/j.lfs.2025.123837","url":null,"abstract":"<div><div>Osteosarcoma is the most common pediatric primary bone tumor, whose growth strictly relies on a complex interplay among tumor cells, resident cells, and the bone matrix. We investigated the effects of secretome collected from the human osteosarcoma cell line MNNG/HOS on mouse primary osteogenic cells, finding that prolonged exposure alters osteoblast phenotype and activity. MNNG/HOS secretome also reduces the production and release of collagen type I, the most abundant constituent of the bone matrix, and hinders osteoblast ability to form nodule of mineralization, compared to osteogenic cells treated with their own secretome. Given the crucial role exerted by secretome on tumor growth, we aimed also to determine whether osteosarcoma cells secretome can influence the osteoblast release of extracellular nanoparticles (NPs) as well as NPs protein cargo. Intriguingly, we found that MNNG/HOS secretome exerts a direct effect on osteoblast-NPs, reprogramming their protein cargo and subsequently influencing extracellular matrix composition and collagen formation, in favor of tumor progression. Overall, our findings indicate the ability of MNNG/HOS cells to fuel their own malignancy by deranging bone matrix composition and stimulating osteoblast-nanoparticles shuttling of osteosarcoma promoting factors.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"379 ","pages":"Article 123837"},"PeriodicalIF":5.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Exercise improves cardiac function and attenuates myocardial inflammation and apoptosis by regulating APJ/STAT3 in mice with stroke” [Life Sci. 332 (2023) 122041]","authors":"Li Wang ,&nbsp;Wenzhan Tu ,&nbsp;Xuqing Li ,&nbsp;Caiyan Li ,&nbsp;Junhong Lu ,&nbsp;Peng Dai ,&nbsp;Yuewei Chen ,&nbsp;Meilin Gu ,&nbsp;Ming Li ,&nbsp;Songhe Jiang ,&nbsp;Guanhu Yang ,&nbsp;Shengcun Li","doi":"10.1016/j.lfs.2025.123841","DOIUrl":"10.1016/j.lfs.2025.123841","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123841"},"PeriodicalIF":5.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidivarin mitigates motor and cognitive impairments in a female mouse model of Rett syndrome","authors":"Diogo M. Lourenço ,&nbsp;Svitlana Zavalko ,&nbsp;Ana Laura Duarte ,&nbsp;Sónia Sá-Santos ,&nbsp;Joana M. Mateus ,&nbsp;Rui S. Rodrigues ,&nbsp;Catarina Miranda-Lourenço ,&nbsp;Francisco M. Mouro ,&nbsp;Ricardo Viais ,&nbsp;Ana M. Sebastião ,&nbsp;Susana Solá ,&nbsp;Maria José Diógenes ,&nbsp;Sara Xapelli","doi":"10.1016/j.lfs.2025.123846","DOIUrl":"10.1016/j.lfs.2025.123846","url":null,"abstract":"<div><div>Rett Syndrome (RTT, #312750 – OMIM) is a rare, progressive neurodevelopmental X-linked disorder, caused mostly by mutations in the gene for the methyl CpG binding protein 2 (<em>MECP2</em>). MECP2 is a transcriptional and epigenetic regulator that has been proposed to modulate neuronal development and adult neurogenesis, processes disrupted in both RTT patients and mouse models. Cannabidivarin (CBDV), a non-psychotropic cannabinoid, has recently been shown to promote adult neurogenesis through a mechanism mediated by transient receptor potential cation channel subfamily V member 1 (TRPV1). This study aimed to investigate the effects of chronic CBDV administration in a female RTT mouse model. Pre-symptomatic <em>Mecp2</em>^tm1.1Bird/J female mice underwent a chronic CBDV treatment (3 mg/kg/day), followed by behavioral tests to assess potential therapeutic effects. While CBDV did not prevent deficits in locomotor activity, it mitigated motor coordination impairments in RTT mice. Furthermore, the novel object recognition test suggested that CBDV treatment contributed to the preservation of cognitive function in these animals. Moreover, CBDV administration induced genotype-dependent differences in neural stem cell proliferation, indicating a potential vulnerability in adult hippocampal neurogenesis in <em>Mecp2</em>-deficient contexts. Taken together, these findings provide new insights into the role of CBDV in RTT and support for future research, highlighting its potential as a repurposed therapeutic agent.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123846"},"PeriodicalIF":5.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal PAC1 deletion impairs structural plasticity","authors":"Margo I. Jansen ,&nbsp;Haley Hrncir ,&nbsp;Allan MacKenzie-Graham ,&nbsp;James A. Waschek ,&nbsp;Judith Brinkman ,&nbsp;Laura A. Bradfield ,&nbsp;Minduli Withana ,&nbsp;Giuseppe Musumeci ,&nbsp;Velia D'Agata ,&nbsp;Alessandro Castorina","doi":"10.1016/j.lfs.2025.123843","DOIUrl":"10.1016/j.lfs.2025.123843","url":null,"abstract":"<div><h3>Aims</h3><div><u>P</u>ituitary <u>A</u>denylate <u>C</u>yclase-<u>A</u>ctivating <u>P</u>olypeptide (PACAP) is an endogenous neuropeptide of the central nervous system (CNS), whose biological activities are mediated via three G protein-coupled receptors PAC1, VPAC1, and VPAC2. While its neuroprotective functions are well-characterised, the role of PAC1 receptor-specific signalling in neuronal plasticity remains insufficiently understood. This study aimed to define the contribution of PAC1 signalling in excitatory pyramidal neurons across brain regions critical for cognitive and motor functions.</div></div><div><h3>Materials and methods</h3><div>We employed a tamoxifen-inducible, conditional knockout mouse model to delete the PAC1 receptor gene (<em>Adcyap1r1</em>) specifically in Camk2a-expressing excitatory neurons. The model was crossed with <em>Thy1-YFP</em> and <em>Thy1-mitoCFP</em> reporter lines to enable high-resolution imaging of neuronal structures and mitochondria in the cortex and hippocampus. Behavioural assessments, molecular analyses, and confocal imaging were conducted to evaluate structural, functional, and biochemical consequences of PAC1 deletion.</div></div><div><h3>Key findings</h3><div>Loss of PAC1 in Camk2a⁺ neurons resulted in spatial memory deficits and locomotor impairments. These were associated with elevated expression of neuronal nitric oxide synthase (nNOS) and GAD65/67, reduced CREB phosphorylation at Ser133, diminished dendritic spine density, and decreased mitochondrial content. The most pronounced effects were observed in the CA1 region of the hippocampus.</div></div><div><h3>Significance</h3><div>Our findings establish PAC1 as a key modulator of synaptic integrity, neuronal plasticity, and energy homeostasis in excitatory neurons. These insights underscore PAC1's potential as a therapeutic target in neurological disorders characterised by cognitive decline and synaptic dysfunction.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123843"},"PeriodicalIF":5.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From AKI to CKD: Role of miRNAs in disease progression","authors":"Marcela Sorelli Carneiro-Ramos ,&nbsp;Raquel Silva Neres-Santos ,&nbsp;Jéssica Verônica da Silva ,&nbsp;Beatriz Favero Bedin ,&nbsp;Aline Cristina Parletta ,&nbsp;Lara Mei Honda ,&nbsp;Carolina Victoria Cruz Junho","doi":"10.1016/j.lfs.2025.123836","DOIUrl":"10.1016/j.lfs.2025.123836","url":null,"abstract":"<div><div>Acute kidney injury (AKI) and chronic kidney disease (CKD) are closely linked, with AKI often accelerating CKD development through sustained inflammation, fibrosis, and tubular damage. Identifying biomarkers that track this transition is essential for early diagnosis and intervention. Recent research highlights microRNAs (miRNAs) as key regulators of AKI-to-CKD progression, with distinct expression patterns across experimental models and clinical samples. Given this context, this review consolidates recent advances in miRNA research related to the AKI-to-CKD transition. Animal studies demonstrate that miRNAs such as miR-101, miR-196a-5p, miR-874-3p, and miR-486-5p contribute to fibrosis, inflammatory signaling, and tubular cell injury-hallmarks of CKD progression. In vitro models further reveal that miRNAs drive pathological processes like epithelial-mesenchymal transition (EMT) and apoptosis, underscoring their role in kidney dysfunction at the cellular level. Clinically, miR-21 has emerged as a particularly promising biomarker, with elevated levels in urine and blood correlating with AKI severity and CKD advancement, suggesting its potential for early detection and disease monitoring. Despite growing evidence of miRNA involvement in AKI-to-CKD progression, research remains limited, particularly in translating findings into predictive diagnostic tools. Future studies should focus on validating miRNA signatures in large patient cohorts and uncovering their precise molecular mechanisms to refine therapeutic strategies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123836"},"PeriodicalIF":5.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon monoxide poisoning triggers intestinal injury, inflammation, and microbiota dysbiosis that drive metabolic perturbations","authors":"Tzu-Hao Chen ,&nbsp;Chien-Chin Hsu ,&nbsp;Hung-Jung Lin ,&nbsp;Chung-Han Ho ,&nbsp;Ching-Ping Chang ,&nbsp;Chien-Cheng Huang ,&nbsp;Ying-Jan Wang","doi":"10.1016/j.lfs.2025.123839","DOIUrl":"10.1016/j.lfs.2025.123839","url":null,"abstract":"<div><h3>Aims</h3><div>To determine whether carbon monoxide poisoning (COP) increases the long-term risk of intestinal diseases and to elucidate the underlying mechanisms through translational investigation using both population data and animal experiments.</div></div><div><h3>Materials and methods</h3><div>An epidemiological study using the Taiwan National Health Insurance Research Database identified 11,025 COP patients and matched controls to assess long-term intestinal disease risk. A rat COP model was used to evaluate intestinal injury, permeability, and tight junction integrity. Systemic inflammation and immune cell populations were assessed. Gastrointestinal and stress/metabolic hormones and metabolic markers were measured. Gut microbiota was analyzed by 16S rRNA sequencing, with functional prediction using Tax4Fun and KEGG.</div></div><div><h3>Key findings</h3><div>COP increased long-term intestinal disease risk in humans. Rats showed duodenal and jejunal injury with elevated permeability and barrier disruption. Systemic inflammation (increased CX3CL1, CXCL7, IL1-α/β, CXCL5, CCL20, TIMP-1, CD54) and immune activation (increased CD86⁺ macrophages, neutrophils, CD4⁺ T cells) were observed. Hormones (decreased cholecystokinin and insulin; increased glucagon-like peptide-1, ghrelin, glucose-dependent insulinotropic polypeptide, cortisol) and metabolism were altered (increased glucose and lipids). Microbiota alterations, including increased <em>Mycoplasma</em>, <em>Streptococcus</em>, and <em>Desulfovibrio</em>, were associated not only with proinflammatory cytokine responses but also with metabolic dysregulation, including lipid imbalance and pathways linked to type II diabetes mellitus.</div></div><div><h3>Significance</h3><div>This study provides the first integrated clinical and experimental evidence linking COP to intestinal and metabolic dysfunction. A pathogenic axis involving gut barrier disruption, microbiota dysbiosis, and metabolic-immune imbalance may underlie COP-related chronic diseases. These findings suggest targets for early monitoring and intervention.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123839"},"PeriodicalIF":5.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}