EBioMedicine最新文献

{"title":"Microplastic abundance in placental chorionic villi detected by pyrolysis-gas chromatography/mass spectrometry in cases of spontaneous miscarriage during early pregnancy.","authors":"Peixin Wang, Guangxiao Li, Huafeng Shou, Xiaona Huang, Hubin Xu, Songying Zhang, Haiyan Zhu","doi":"10.1016/j.ebiom.2025.105918","DOIUrl":"10.1016/j.ebiom.2025.105918","url":null,"abstract":"<p><strong>Background: </strong>There is widespread concern regarding the effect of microplastics (MPs) on human reproductive health. The accumulation of MPs and their potential effect on adverse pregnancy outcomes must be determined, particularly from the perspective of the maternal-foetal interface during early gestation, because abnormal composition and metabolism of chorionic villi are closely related to early embryonic development. This study aimed to identify and quantify the mean mass concentrations and polymer types of MPs in human chorionic villi, and investigate the potential association between the abundance of MPs and spontaneous miscarriage.</p><p><strong>Methods: </strong>Chorionic villi were collected from 31 participants in their first trimester, including normal carriage terminated for social factors (NC, n = 13) and unexplained spontaneous miscarriage (SM, n = 18). Qualitative and quantitative detection of 11 types of MPs was performed by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). Differences in the abundance of specific MPs between the two groups were analysed by t-tests. Individual clinical characteristics and lifestyle information were collected to identify the primary sources and factors that may impact MPs in chorionic villi. Statistical analyses, including a correlation analysis and the binary logistic regression model, were used to assess the effect of MP accumulation on early pregnancy outcomes.</p><p><strong>Findings: </strong>MPs were detected in all samples and four main types were identified, namely polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS), and polypropylene (PP). PVC was the most abundant. The total abundance of MPs in patients with SM was significantly higher than that in controls (273.08 ± 50.89 μg/g vs 226.37 ± 42.35 μg/g, p = 0.011). The accumulation of total MPs (r = 0.5947, p < 0.01) and PVC (r = 0.5649, p < 0.05) in patients with SM was positively correlated with age but not body mass index. Participants who regularly consumed bottled water generally showed significantly elevated levels of PE and total MPs in their villi, while frequent seafood consumption had a significant effect on PE, PVC, PS, and PP concentrations.</p><p><strong>Interpretation: </strong>We identified the presence of MPs in chorionic villi during the first trimester and established an association between the abundance of MPs and unexplained SM. These findings suggest that accumulation of MPs at the maternal-foetal interface during the first trimester are related to an increased risk of miscarriage and that these cross-generational effects during early gestation represent potential reproductive toxicity of MPs. Further research is warranted to elucidate the underlying mechanisms, and larger sample sizes are required to validate the observed trends.</p><p><strong>Funding: </strong>This study was supported by grants from the \"Pioneer\" and \"Leading Goose\" R&D Program of Zhejiang (2024C03242) and the Medical","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105918"},"PeriodicalIF":10.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive cerebrospinal fluid in the 2024 McDonald criteria for multiple sclerosis.","authors":"Florian Deisenhammer, Harald Hegen, Georgina Arrambide, Brenda L Banwell, Tim Coetzee, Sharmilee Gnanapavan, Xavier Montalban, Hayrettin Tumani, Maria A Willrich, Mark S Freedman","doi":"10.1016/j.ebiom.2025.105905","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105905","url":null,"abstract":"<p><p>The 2024 McDonald diagnostic criteria for Multiple Sclerosis (MS) introduce kappa free light chains (κ-FLC) detection in cerebrospinal fluid (CSF) which can be used interchangeably with oligoclonal IgG bands (OCB) to demonstrate intrathecal immunoglobulin synthesis. Diagnostic sensitivity and specificity of κ-FLC is equal to OCB on a 95% confidence level. In rare cases determination of both, κ-FLC and OCB should be considered as the concordance rate is around 90%. We recommend calculating the κ-FLC index with values of ≥6.1 performing best for diagnosing MS. Validated turbidimetric or nephelometric assays should be applied for which proficiency testing programs are available. There is some prognostic use of the κ-FLC index with higher values predicting higher disease activity. Neurofilament light (NfL) should not be used for diagnostic purposes although it might be useful for prognosis and disease monitoring. All recommendations apply to paediatric and adult relapsing as well as progressive onset MS.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"105905"},"PeriodicalIF":10.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The type 1 diabetes candidate genes PTPN2 and BACH2 regulate the IFN-α-induced crosstalk between JAK/STAT and MAPKs pathways in human beta cells.","authors":"Arturo Roca-Rivada, Junior Garcia Oliveira, Eugenia Martin-Vazquez, Alexandra Coomans de Brachène, Xiaoyan Yi, Jose Maria Costa-Júnior, Priscila L Zimath, Flore Van Goethem, François Pattou, Julie Kerr-Conte, Antoine Buemi, Nizar I Mourad, Decio L Eizirik","doi":"10.1016/j.ebiom.2025.105932","DOIUrl":"10.1016/j.ebiom.2025.105932","url":null,"abstract":"<p><strong>Background: </strong>Type 1 diabetes (T1D) is a chronic autoimmune disease that leads to the progressive loss of pancreatic beta cells. Interferons (IFNs) contribute to the initiation and amplification of beta cell autoimmunity. STAT1 is the main mediator of IFN signalling but little is known about its complex activation processes and role in the progression of beta cell failure.</p><p><strong>Methods: </strong>We investigated the IFN-α-stimulated STAT1 pathway from three human beta cell models: EndoC-βH1 cells, iPSC-derived islet-like cells and human islets by directly targeting two T1D candidate genes, namely PTPN2 and BACH2.</p><p><strong>Findings: </strong>We presently show that PTPN2 and BACH2 modulate STAT1 activation via two different pathways, namely the JAK/STAT, involved in the phosphorylation of its tyrosine residue (Y701), and the MAPKs pathway, involved in the phosphorylation of its serine residue (S727). Each STAT1 phosphorylation type can independently induce expression of CXCL10, but both residues are necessary for the expression of MHC class I molecules. IFN-α-induced STAT1 activation is dynamic and residue-dependent, being STAT1-Y701 fast but transitory, while STAT1-S727 increases slowly and is associated with the long-term effects of IFN-α exposure.</p><p><strong>Interpretation: </strong>The present findings provide a better understanding of the dynamics of STAT1 activation in human beta cells and will be useful to develop new and targeted (i.e. favouring individuals with particular polymorphisms) therapies for T1D and other autoimmune diseases.</p><p><strong>Funding: </strong>EFSD and Sanofi European Diabetes Research Programme on autoimmunity in type 1 diabetes; Breakthrough T1D, HIRN-CBDS, NIDDK, Fondation Saint-Luc, Programme d'Investissement d'Avenir' to European Genomic Institute for Diabetes, and Fondation de la Recherche Médicale.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105932"},"PeriodicalIF":10.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of potential therapeutic targets for problematic alcohol use using multi-omics data.","authors":"Dong June Lee, Minku Song, Soohyun Lim, Sanghyeon Park, Hyejin Kim, Yeeun Ahn, Faith Choi, Woojae Myung, Hong-Hee Won","doi":"10.1016/j.ebiom.2025.105939","DOIUrl":"10.1016/j.ebiom.2025.105939","url":null,"abstract":"<p><strong>Background: </strong>Problematic alcohol use (PAU) is a serious global health issue with limited treatment options. Although genetic studies have identified genomic regions associated with PAU, the specific causal genes and proteins remain unclear. This study aimed to identify these causal genes by integrating diverse genetic and molecular data to inform better treatment strategies.</p><p><strong>Methods: </strong>We used Mendelian randomisation (MR) to identify genes and proteins that may cause PAU by combining genetic data with gene activity in brain and blood tissues. Multiple statistical tests confirmed shared genetic signals between expression and PAU. We also examined their effects on other traits and potential interactions with existing drugs.</p><p><strong>Findings: </strong>We identified 97 genes and 13 proteins that are likely to play a causal role in PAU through MR, with strong enrichment in brain tissues. These associations remained significant after Bonferroni correction and were further supported by colocalisation analyses (posterior probability of hypothesis 4 > 0.75) and consistency across multiple datasets. Some targets also showed concordant effects with PAU on other health outcomes, supported by Bonferroni-significant associations in phenome-wide analyses, suggesting potential for drug repurposing.</p><p><strong>Interpretation: </strong>This study highlights molecular signatures in both brain and blood tissues that may contribute to the development of PAU. Integrative multi-omics analyses revealed shared biological pathways across neural and peripheral systems, suggesting the potential for developing multi-systemic interventions with favourable safety profiles.</p><p><strong>Funding: </strong>This study was supported by Samsung Research Fund, Sungkyunkwan University, 2023.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105939"},"PeriodicalIF":10.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Transcription factor 7 promotes the progression of perihilar cholangiocarcinoma by inducing the transcription of c-Myc and FOS-like antigen 1.","authors":"Zengli Liu, Rongqi Sun, Xiaoming Zhang, Bo Qiu, Tianli Chen, Zhipeng Li, Yunfei Xu, Zongli Zhang","doi":"10.1016/j.ebiom.2025.105913","DOIUrl":"10.1016/j.ebiom.2025.105913","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105913"},"PeriodicalIF":10.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Directed-complement killing of Pseudomonas aeruginosa protects against lethal pneumonia.","authors":"Aubin Pitiot, Bianca Brandus, Gilles Iserentant, Camille Rolin, Jean-Yves Servais, Delphine Fouquenet, Adélaïde Chesnay, Ludovic Richert, Benoit Briard, Mustapha Si-Tahar, Yves Mely, Patrice Rassam, Jacques Zimmer, Guillaume Desoubeaux, Xavier Dervillez, Carole Seguin-Devaux","doi":"10.1016/j.ebiom.2025.105926","DOIUrl":"10.1016/j.ebiom.2025.105926","url":null,"abstract":"<p><strong>Background: </strong>Multidrug-resistant Pseudomonas aeruginosa raises major clinical concerns due to its capacity to cause a wide-array of infections in individuals with compromised immune defences and to withstand standard-of-care therapeutic treatments. Antibody-based approaches have proven to be efficient in the treatment of diverse infections. Here we propose an innovative approach harnessing the complement at the surface of bacteria for further killing.</p><p><strong>Methods: </strong>We developed two Complement-activating Multimeric immunotherapeutic compleXes (CoMiX) targeting the bacterium through a single-chain variable fragment directed against the exopolysaccharide Psl, and carrying one of two different effector functions, Factor H Related protein 1 (FHR1) or a Fc dimer. Each CoMiX was assessed in vitro for their antibacterial activity, and further evaluated in a mouse model of acute pneumonia.</p><p><strong>Findings: </strong>Both CoMiX-FHR1 and CoMiX-Fc effectively deposit C1q (for CoMiX-Fc), C3b, and C5b9 at the surface of multidrug-resistant clinical isolates, promoting their direct killing and/or opsonisation and subsequent phagocytosis for CoMiX-Fc (p < 0.001). Both CoMiX synergise with amikacin and protect epithelial cells against P. aeruginosa-induced cytotoxicity. Importantly, CoMiX administered intranasal to acutely infected mice significantly improve their survival (p < 0.001) by reducing local bacterial burden through the higher induction of C3b (opsonisation) and C5a (neutrophils recruitment and activation) and by decreasing lung inflammation.</p><p><strong>Interpretation: </strong>Our proof-of-concept demonstrates the efficient, direct and indirect killing of P. aeruginosa by the complement, highlighting the therapeutic potential of CoMiX to combat multidrug-resistant bacteria.</p><p><strong>Funding: </strong>Luxembourg National Research Fund, Ministry of Higher Education and Research of Luxembourg, COST action CA21145 EURESTOP, Institut National de la Santé et de la Recherche Médicale, and Tours University.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105926"},"PeriodicalIF":10.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of systemic SARS-CoV-2 vaccination on mucosal IgA responses to subsequent breakthrough infection.","authors":"Ulrika Marking, Oscar Bladh, Katherina Aguilera, Tamas Pongracz, Sebastian Havervall, Nina Greilert-Norin, Kim Blom, Jonas Klingström, Yunzhang Wang, Mikael Åberg, Charlotte Thålin","doi":"10.1016/j.ebiom.2025.105912","DOIUrl":"10.1016/j.ebiom.2025.105912","url":null,"abstract":"<p><strong>Background: </strong>Mucosal IgA responses are central to protection against SARS-CoV-2 infection and viral transmission. While systemic immunity following SARS-CoV-2 infection and vaccination is thoroughly investigated, we have limited understanding of factors affecting the generation and boosting of mucosal IgA.</p><p><strong>Methods: </strong>In this cohort study, we investigated factors influencing mucosal SARS-CoV-2 IgA responses among 879 healthcare workers enrolled in the longitudinal COMMUNITY study. Blood samples and clinical data were collected from all participants every four months since April 2020. SARS-CoV-2 immune histories are well characterized through national vaccine and infection registries along with regular monitoring of seroconversion of spike and/or nucleocapsid antigen. Regression models were developed to assess the influence of vaccinations and prior infections on the magnitude of SARS-CoV-2 spike-specific IgA in nasal secretions collected from the cohort in October 2022.</p><p><strong>Findings: </strong>Mucosal SARS-CoV-2 spike-specific IgA was detected in 81% of participants, with a positive association with number of prior infections, indicating a booster effect by reinfection. The increased odds ratio of detectable mucosal IgA remained for at least 22 months post infection. There was a strong association between repeated systemic vaccinations and a lower magnitude of mucosal IgA responses. Moreover, the temporal sequence of infection and vaccination influenced mucosal IgA responses, with higher levels among participants with infection prior to systemic vaccination as compared to those with breakthrough infection as the first viral encounter.</p><p><strong>Interpretation: </strong>The observation that repeated mucosal exposures elicit enhanced and long-lasting mucosal IgA responses strengthens the rationale for developing effective mucosal vaccines. While systemic vaccination remains essential for preventing severe disease, our findings suggest that it may influence subsequent generation of mucosal IgA trough a reduction of viral load and inflammation in the mucosa. This is highly relevant for both understanding the development of population immunity and for optimizing the timing of a sequential systemic and mucosal vaccination approach.</p><p><strong>Funding: </strong>This study was supported by grants from Region Stockholm, and SciLifeLab and the Knut and Alice Wallenberg Foundation, SSMF and European Research Council. We thank the Public Health Agency of Sweden for support.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105912"},"PeriodicalIF":10.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PNPLA3 polymorphism worsens chemotherapy associated liver injury and affects overall survival in colorectal cancer patients with liver metastasis undergoing hepatic resection.","authors":"Benedikt Rumpf, Jonas Santol, Anna E Kern, Markus Ammann, Joel Probst, Ruth Baumgartner, Anna S Jankoschek, Vanja Podrascanin, Florian Lehner, Felix X Huber, David Pereyra, Gregor Ortmayr, Yawen Dong, Sophia Petschnak, Brigitte Wolf, Alice Assinger, Hubert Hackl, Stefan Gilg, Thomas Gruenberger, Patrick Starlinger","doi":"10.1016/j.ebiom.2025.105928","DOIUrl":"10.1016/j.ebiom.2025.105928","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant chemotherapy (NAC) has been controversial for patients with colorecal cancer liver metastasis (CRLM) with resectable disease. Chemotherapy associated liver injury (CALI) may explain the lack of overall survival (OS) benefit in some studies. It remains unclear why CALI severity varies between patients despite receiving the same duration and type of NAC. Single nucleotide polymorphisms (SNPs) have been associated with liver disease and could account for these interindividual differences. Within this study we used the APRI + ALBI score, a non-invasive liver function marker that increases in response to CALI development during NAC, to assess whether preoperative liver function affects OS in CRLM patients undergoing hepatectomy and explore the impact of SNPs on CALI development.</p><p><strong>Methods: </strong>551 patients with CRLM undergoing liver surgery after NAC were included. In 149 patients, DNA from histological specimens was genotyped and the presence of SNPs associated with liver disease was assessed.</p><p><strong>Findings: </strong>Patients with APRI + ALBI scores (≥-2.46), associated with the development of CALI, showed decreased OS after hepatectomy (median OS APRI + ALBI < -2.46 = 46.1 months; median OS APRI + ALBI ≥ -2.46 = 34.3, p = 0.027). The mutated rs738409 variant on the patatin-like phospholipase domain-containing protein 3 (PNPLA3) displayed a close association with chemotherapy-associated steatohepatitis (p = 0.007) as well as intrahepatic fat (p = 0.004). Additionally, all PNPLA3 homozygotes shifted into the high-risk APRI + ALBI group during NAC.</p><p><strong>Interpretation: </strong>CALI and its effects on liver function not only impact immediate postoperative outcomes but also significantly affect OS in CRLM patients undergoing liver resection. PNPLA3 polymorphism was associated with CALI development. Considering that PNPLA3 polymorphisms are significantly higher in Asian populations, these results could partly explain the heterogeneity in reported effects of NAC in CRLM patients and might improve patient selection.</p><p><strong>Funding: </strong>None of the authors received funding related to the writing of this manuscript.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105928"},"PeriodicalIF":10.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic assessment of a novel mitochondrial complex I inhibitor in in vitro and in vivo models of Alzheimer's disease.","authors":"Sergey Trushin, Thi Kim Oanh Nguyen, Andrea Stojakovic, Mark Ostroot, J Trey Deason, Su-Youne Chang, Liang Zhang, Slobodan I Macura, Toshihiko Nambara, Wenyan Lu, Takahisa Kanekiyo, Eugenia Trushina","doi":"10.1016/j.ebiom.2025.105924","DOIUrl":"10.1016/j.ebiom.2025.105924","url":null,"abstract":"<p><strong>Background: </strong>Despite recent approval of monoclonal antibodies that reduce amyloid (Aβ) accumulation, the development of disease-modifying strategies targeting the underlying mechanisms of Alzheimer's disease (AD) is urgently needed.</p><p><strong>Methods: </strong>We demonstrate that mitochondrial complex I (mtCI) represents a druggable target, where its weak inhibition activates neuroprotective signalling, benefiting AD mouse models with Aβ and p-Tau pathologies. Rational design and structure‒activity relationship studies yielded mtCI inhibitors profiled in a drug discovery funnel designed to address safety, selectivity, and efficacy.</p><p><strong>Findings: </strong>The lead compound C458 is highly protective against Aβ toxicity, has favourable pharmacokinetics, and minimal off-target effects. C458 exhibited excellent brain penetrance, activating neuroprotective pathways with a single dose. Preclinical studies in APP/PS1 mice were conducted using functional tests, metabolic assessment, in vivo³¹P-NMR spectroscopy, blood cytokine panels, ex vivo electrophysiology, and Western blotting. Chronic oral administration improved long-term potentiation, reduced oxidative stress and inflammation, and enhanced mitochondrial biogenesis, antioxidant signalling, and cellular energetics. Efficacy against Aβ and p-Tau was confirmed in human organoids.</p><p><strong>Interpretation: </strong>These studies provide further evidence that the restoration of mitochondrial function in response to mild energetic stress represents a promising disease-modifying strategy for AD.</p><p><strong>Funding: </strong>This research was supported by grants from NIH AG 5549-06, NS1 07265, AG 062135, UG3/UH3 NS 113776, and ADDF 291204 (all to ET); U19 AG069701 (to TK); the Alzheimer's Association Research Fellowship grant 23AARF-1027342 (to TKON).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105924"},"PeriodicalIF":10.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron-sepsis associations in population health revealed by epidemiology.","authors":"Randi Marie Mohus, Lise T Gustad, Jan Kristian Damås, Hal Drakesmith","doi":"10.1016/j.ebiom.2025.105927","DOIUrl":"10.1016/j.ebiom.2025.105927","url":null,"abstract":"<p><p>Sepsis is a leading cause of death and disability worldwide, so identifying preventable risk factors is important. Iron is essential for immune function and microbial growth, and iron status varies substantially between individuals, across demographics, and is therapeutically modifiable. Here, we review the current understanding of iron status and associated risks of bloodstream infection, sepsis and severe COVID-19 highlighting relevant population-based studies and Mendelian randomisation studies. Both low and high iron status are associated with increased risk of sepsis. Low iron status is associated with sepsis, bloodstream infections and pneumonia. High iron status and mutations affecting hepcidin regulation are linked to increased risk of bloodstream infections, sepsis and COVID-19. Both iron status pathologies and sepsis are global health issues, and the epidemiological studies described indicate they may be linked. More population-scale investigations on iron status, infection and immunity, especially in areas of high iron deficiency and infectious burden are warranted.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105927"},"PeriodicalIF":10.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}