EBioMedicine最新文献

{"title":"Genome-wide analysis of genetic modifiers of Crohn's disease and ulcerative colitis risk in response to tobacco smoking.","authors":"Jingjing Bai, Ranko Gacesa, Johannes R Björk, Bernadien H Jansen, Klaas N Faber, Rinse K Weersma, Gerard Dijkstra, Kimberley W J van der Sloot, Eleonora A M Festen","doi":"10.1016/j.ebiom.2026.106486","DOIUrl":"10.1016/j.ebiom.2026.106486","url":null,"abstract":"<p><strong>Background: </strong>Gene-environment interactions (GxE) are fundamental for understanding the mechanisms of human diseases. Tobacco smoking is of particular interest for Inflammatory bowel disease (IBD), as it worsens Crohn's disease (CD) but protects against ulcerative colitis (UC). Here, we systematically examined the genome-wide genetic modifiers of tobacco smoking and analysed functional smoking-dependent expression quantitative trait loci (eQTL) in IBD intestinal tissues.</p><p><strong>Methods: </strong>Multiplicative interaction effects of genetic variants and tobacco smoking were estimated and meta-analysed from two independent cohorts (cohort A, N = 990; cohort B, N = 2540). Subsequent separate analyses were conducted for CD and UC to identify opposite interaction. The association between HLA classical alleles/amino acid residues and smoking status was tested. GxE eQTL analysis was performed by combining IBD genotype and mucosal transcriptome data. Colocalisation analysis was conducted to identify the shared loci across the results from genome-wide interaction meta-analysis and the GxE eQTL analysis.</p><p><strong>Findings: </strong>A total of 572 candidate independent lead genetic variants with multiplicative interactions with tobacco smoking regarding IBD risk were prioritised at a suggestive significance level (meta-analysis P < 5.0 × 10^-5). Thirty genetic loci exhibited noteworthy opposite interactions between CD and UC, implicated genes such as ANKS1B, C7, and PARD3B. HLA-DRβ1 harboured the greatest number of polymorphic residues associated with current smoking in IBD. Significant decrease of the frequency of Leu156 in HLA-A was only observed in UC former smokers but not in CD (FDR <0.05). 67 smoking-dependent cis-eQTL- eGene pairs were found in IBD affected intestinal tissues.</p><p><strong>Interpretation: </strong>This study deepens the understanding of complex interactions between tobacco smoking and genetic variants for IBD. As a result, it sheds new light on the genetic contribution to the divergent effects of tobacco smoking on CD and UC risk, which might illuminate the future development of genotype-guided primordial preventive strategies in genetically susceptible individuals.</p><p><strong>Funding: </strong>JB acknowledges funding from CSC and University Medical Center Groningen top-up Program. EAMF acknowledges funding from ZonMw.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106486"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105848","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":"Serum biomarkers for the diagnosis and management of adolescent polyendocrine metabolic ovarian syndrome: a systematic review and meta-analysis.","authors":"Yue Shi, Chi Chiu Wang, Elisabet Stener-Victorin, Pui Wah Chung, Yao Wang","doi":"10.1016/j.ebiom.2026.106471","DOIUrl":"10.1016/j.ebiom.2026.106471","url":null,"abstract":"<p><strong>Background: </strong>Adolescent polyendocrine metabolic ovarian syndrome (PMOS) poses immediate and lifelong risks to women's health. However, reliable biomarkers for adolescent PMOS remain elusive in current clinical practice.</p><p><strong>Methods: </strong>We systematically searched six databases from inception to April 2026, following PRISMA guidelines (PROSPERO No.: CRD420251033057). Eligible studies included adolescents with PMOS and healthy controls. Primary outcomes were effect sizes of serum reproductive hormones, insulin indices, and adipokines (Hedges' g in random-effects models), with diagnostic performance assessed by AUC, sensitivity, and specificity.</p><p><strong>Findings: </strong>Fifty-one moderate-to-high quality studies comprising 4892 adolescents were included. Large effect sizes were observed for total testosterone (TT, 1.10), free androgen index (FAI, 1.19), ratio of luteinising hormone to follicle-stimulating hormone (LH/FSH, 1.07), anti-Müllerian hormone (AMH, 0.98), and adiponectin (-1.12), all with moderate-to-low certainty. Insulin resistance indices (homoeostatic model assessment of insulin resistance [HOMA-IR], 0.64; quantitative insulin sensitivity check index [QUICKI], -0.47) and leptin (0.40) showed small effect sizes with low certainty. In adolescents with obesity, AMH (1.39) and adiponectin (-1.54) showed pronounced effects. For diagnostic performance, TT (cutoff = 55.96 ng/dL), FAI (cutoff = 6.78), and LH/FSH (cutoff = 1.59) each achieved an AUC of 0.74. AMH effectively identified PMOS in obese group (AUC = 0.85, cutoff = 4.47 ng/mL) and the <17-year-old group (AUC = 0.77, cufoff = 6.05 ng/mL). For metabolic stratification, HOMA-IR performed modestly overall AUC of 0.65 (cutoff = 4.35), while adiponectin (AUC = 0.78, cutoff = 10.92 μg/mL) and leptin (AUC = 0.67, cutoff = 36.17 ng/mL) emerged as BMI-dependent markers in obese and non-obese groups, respectively. Of note, LH/FSH and dehydroepiandrosterone sulphate (DHEAS) showed significant publication bias; thus, these results should be interpreted with caution.</p><p><strong>Interpretation: </strong>TT and FAI are primary diagnostic biomarkers in adolescent PMOS, with LH/FSH providing supportive value. AMH is discriminative in adolescents with obesity in early-mid adolescence. HOMA-IR is a primary biomarker for metabolic monitoring, while adiponectin and leptin are BMI-dependent markers for early metabolic risk stratification.</p><p><strong>Funding: </strong>This study was supported by HMRF, CUHK direct grant, CUHK-Chulalongkorn University Research Fund, 1 + 1 + 1 CUHK-CUHK(SZ)-GDST Joint Collaboration Fund, and PhD International Mobility for Partnerships and Collaboration Award.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106471"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036959","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":"Spatial membrane lipid remodelling encodes epithelial lineage and state in human colon cancer.","authors":"Ramon M Rodriguez, Karim Pérez-Romero, Albert Maimó-Barceló, Teresa Ximelis, Cristina Huergo-Baños, Marcos A Martínez, Juan José Segura-Sampedro, Rafael Morales-Soriano, Cristina Pineño-Flores, Álvaro García-Granero, Sebastián Jerí, Ana M Aransay, José A Fernández, Gwendolyn Barceló-Coblijn","doi":"10.1016/j.ebiom.2026.106473","DOIUrl":"10.1016/j.ebiom.2026.106473","url":null,"abstract":"<p><strong>Background: </strong>Cancer progression is driven by spatially organised intratumoural heterogeneity, yet the molecular basis of this organisation remains incompletely understood. While spatial transcriptomics has advanced rapidly, the spatial architecture and functional relevance of tumour lipid metabolism remain poorly characterised. We aimed to resolve whether membrane phospholipid remodelling is spatially organised across epithelial cell states in human colon cancer.</p><p><strong>Methods: </strong>We developed an integrative spatial multi-omic strategy linking mass spectrometry imaging to transcriptome-defined cellular states on consecutive tissue sections from primary and intraperitoneal metastatic human colon cancer specimens. Epithelial lipid phenotypes were characterised, validated in an independent cohort, and linked to transcriptional programmes.</p><p><strong>Findings: </strong>We identified four spatially organised epithelial lipid phenotypes defined by membrane phospholipid composition. These phenotypes aligned with transcriptional programmes reflecting epithelial lineage and differentiation state, and were organised along a differentiation axis marked by coordinated remodelling of arachidonic acid-, oleic acid-, and linoleic acid-containing phospholipids. Secretory-associated states, enriched in metastatic lesions, showed increased DHA-containing phospholipids and activation of peroxisomal pathways. Lipid phenotype assignments were reproducible across an independent cohort.</p><p><strong>Interpretation: </strong>Membrane phospholipid composition encodes biologically meaningful epithelial cell states within human tumours, establishing lipid remodelling as a structured and spatially organised dimension of tumour heterogeneity.</p><p><strong>Funding: </strong>This study was supported by the ISCIII (PI19/00002, PI24/00313), the Health Research Institute of the Balearic Islands (IMP22/04), the Government of the Balearic Islands (AP_2021_001), the Basque Government (IT1491-22), the European Regional Development Fund, and the Scientific Foundation, Spanish Association Against Cancer (INVES222995RODR).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106473"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929019","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":"Cancer genomic data systems in precision oncology: from integration to clinical implementation.","authors":"David Torrents, Oliver Hofmann, Karen Ann Cranston, Raffaella Casolino, Andrew V Biankin, Andrés F Cardona, Robert L Grossman, Amber Johns, Mark Lawler, Kjong-Van Lehmann, Raquel Manzano Garcia, Nicola Mulder, Travis Osterman, Timothy Rebbeck, Solomon Rotimi, Zbyslaw Sondka, Shawn Sweeney, Samuel Volchenboum, Alex Wagner, Jianmin Wu, Takayuki Yoshino, Mélanie Courtot, Lincoln Stein","doi":"10.1016/j.ebiom.2026.106480","DOIUrl":"10.1016/j.ebiom.2026.106480","url":null,"abstract":"<p><p>Cancer genomic data sharing is a core pillar of precision oncology, underpinning reproducibility, scalability, and equity. The ability to discover, access, integrate, interpret, and reuse cancer 'omics data is a key determinant of precision oncology's value and benefit at scale. This work has been conducted as part of The Lancet Oncology Commission on Cancer Genomics and Precision Oncology to examine the practical data architecture required to support cancer genomics in research, clinical care, and health-system learning. We conclude that without robust data stewardship, including effective data sharing and global integration, the potential of cancer genomics will remain fragmented across projects, platforms, and jurisdictions. This disaggregation limits reproducibility, equity, patient benefit, and societal value. Healthcare systems must prioritise implementing fully efficient data ecosystems as a central challenge for precision oncology.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"106480"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059180","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":"Integration of biological avatars and digital twins for \"ex vivo clinical trials\".","authors":"Charles L Howe","doi":"10.1016/j.ebiom.2026.106467","DOIUrl":"10.1016/j.ebiom.2026.106467","url":null,"abstract":"<p><p>Drug development is slow, costly, and prone to late-stage failure, in part because animal models poorly predict human responses. Two human-relevant technologies are maturing in parallel: biological avatars, defined as patient- or stem-cell-derived models such as organoids and organ-on-a-chip systems, and digital twins, defined as computational models that integrate a patient's molecular and clinical data to forecast treatment responses. We propose the ex vivo clinical trial concept, in which an avatar and a digital twin are coupled in an iterative loop so that laboratory measurements refine the computational prediction and the prediction guides the next experiment, allowing candidate therapies to be tested and prioritised before a patient is exposed. We review the platforms, their predictive performance in cancer, cystic fibrosis, and liver toxicity, the conditions under which they fail, and the qualification, turnaround, and standardisation requirements that must be met before such trials can inform drug development or clinical care.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106467"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873175","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":"Metabolomic profiling of ultra-processed food consumption and cardiovascular risk in Spanish preschool children: a cross-sectional study.","authors":"Josué A Pérez-Acosta, Jesús F García-Gavilán, Hernando J Margara-Escudero, Concepción M Aguilera, Rosaura Leis, Irina Gheorghita, María L Miguel-Berges, Santiago Navas-Carretero, José V Sorlí, Iolanda Lázaro, Belén Pastor-Villaescusa, Rocío Vázquez-Cobela, Lucía Iglesias-Vázquez, Pilar De Miguel-Etayo, Natalia Vazquez-Bolea, José Manuel Jurado-Castro, Rosaura Picáns-Leis, Joaquín Escribano, Luis A Moreno, MJosé de la Torre-Aguilar, Mercedes Gil-Campos, Jordi Salas-Salvadó, Nancy Babio","doi":"10.1016/j.ebiom.2026.106488","DOIUrl":"10.1016/j.ebiom.2026.106488","url":null,"abstract":"<p><strong>Background: </strong>Ultra-processed food (UPF) consumption has increased substantially among children worldwide and has been associated with early cardiovascular alterations. We aimed to identify plasma metabolomic profiles associated with UPF consumption in children aged 3-6 years and to assess their association with cardiovascular risk factors.</p><p><strong>Methods: </strong>This cross-sectional analysis used baseline data from the Childhood Obesity Risk Assessment Longitudinal Study (CORALS), with children recruited between March 2019 and June 2022 through primary schools and health-care centres in seven Spanish cities. 1148 children were included (mean age 5.0 years [SD 1.1]; 50.6% girls) after exclusions due to medical conditions and incomplete or implausible dietary or metabolomic data. Energy-adjusted UPF intake (g/d) was assessed using a validated food frequency questionnaire and categorised with NOVA classification. 249 metabolites were quantified by NMR-based metabolomics, and lipid-related and amino acid-related profiles/scores were derived. A composite cardiovascular risk score (CVRs) was constructed by summing sex-specific, age-adjusted z-scores for fat-mass index, HDL-and LDL-cholesterol, triglycerides, mean arterial pressure, and Homoeostatic Model Assessment for Insulin Resistance.</p><p><strong>Findings: </strong>19 metabolites were associated with UPF consumption after false discovery rate correction (FDR). A lipid-related score was positively associated with CVRs (β = 0.511; 95% CI: 0.413-0.610; FDR <0.001) and the amino acid-related score was associated with a lower CVRs (β = -0.494; 95% CI: -0.667 to -0.321; FDR <0.001). Discrimination of cardiovascular risk beyond covariates alone was higher after inclusion of metabolomic scores, particularly when both scores were considered jointly (ΔAUC 0.092, 95% CI: 0.013-0.172; p = 0.020).</p><p><strong>Interpretation: </strong>In Spanish pre-schoolers UPF-related metabolomic profiles were associated with different cardiovascular risk factors. These diet-related metabolomic scores capture biological correlates relevant to early cardiovascular health and align with early-life metabolic pattering, supporting future longitudinal studies and prevention strategies.</p><p><strong>Funding: </strong>CIBEROBN; Instituto de Salud Carlos III (ISCIII-FIS; EU ERDF/ESF); ISCIII PFIS.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106488"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030139","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":"Proteomic signatures during pregnancy: an exploratory cohort study of long-term health indicators.","authors":"Lucy A Bartho, Susan P Walker, Teresa MacDonald, Danica Idzes, Ping Cannon, Tuong-Vi Nguyen, Gordon Smith, D Stephen Charnock-Jones, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino","doi":"10.1016/j.ebiom.2026.106491","DOIUrl":"10.1016/j.ebiom.2026.106491","url":null,"abstract":"<p><strong>Background: </strong>Pregnancies complicated by fetal growth restriction (FGR) and preeclampsia are associated with increased long-term chronic disease risk. A blood test could possibly identify those at risk, opening the door to early interventions soon after delivery. Prior work in non-pregnant people have identified protein signatures associated with 18 different health parameters, called SomaSignal Tests.</p><p><strong>Methods: </strong>This study applied SomaSignal tests to plasma samples collected in pregnancy from two independent cohorts to assess the 18 health parameters in those who later developed FGR and preeclampsia. SomaScan Assay measured ∼7000 modified aptamers in plasma from two independent cohorts. Plasma samples (Melbourne, Australia) were collected at 36 weeks' gestation from women who later delivered an FGR infant (<3rd birthweight centile, n = 118), preeclampsia at term (n = 92) or did not develop either condition (n = 177). The second cohort (Cambridge, UK) were plasma samples collected at 36 weeks' gestation from women who later delivered an FGR infant (n = 80), and those who did not (n = 172).</p><p><strong>Findings: </strong>In the Australian cohort, women who later delivered growth-restricted infants had composite protein signatures associated with reduced cardiac function (p = 0.001), increased cardiovascular events (p = 7.6 × 10^-6), mid-life dementia (p = 1.5 × 10^-9), and higher visceral fat (p = 4.06 × 10^-6), compared to pregnancies without complications. Findings were largely consistent in both Australian and UK sample sets. Those who developed preeclampsia had protein signatures signifying cardiovascular (p = 5.54 × 10^-6), hepatic (p = 0.001), and renal (p = 0.0007) disease risks, compared to pregnancies without complications.</p><p><strong>Interpretation: </strong>Since signatures were more pronounced in pregnancies that were later diagnosed with FGR and preeclampsia, underlying physiological changes may have been present before diagnosis. These changes result in protein signatures concordant with those associated with poor long-term health outcomes in non-pregnant populations. These associations require validation in large, longitudinal cohorts investigating pregnancy, with long-term maternal follow-up.</p><p><strong>Funding: </strong>Stillbirth CRE, Mercy Hospital Foundation and National Health and Medical Research Council, Royal Australian and New Zealand College of Obstetricians and Gynaecologists, Taylor Hammond Scholarship, National Health and Medical Research Council Fellowships and Australian Research Council Future Fellowships.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106491"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059191","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":"Age-related molecular IgE sensitization to indoor and outdoor respiratory allergens: a two-step cross-sectional study in Algeria and Türkiye.","authors":"Lydia Lamara Mahammed, Susanne Vrtala, Oluwatoyin Akinfenwa, Maria-Roxana Buzan, Kuan-Wei Chen, Alp Kazancioglu, Raffaela Campana, Monica-Daniela Cotarcă, Mirela Curin, Yulia Dorofeeva, Nishelle Dsouza, Alexandra Dubovets, Margarete Focke-Tejkl, Pia Gattinger, Heinrich Grausgruber, Huey-Jy Huang, Alexander Karaulov, Evgenii Kozlov, Andrea Krisai, Lun Li, Birgit Linhart, Carmen Panaitescu, Eszter Sarzsinszky, Daria Trifonova, Mikhail Tulaev, Milena Weber, Brahim Belaid, Recep Sancak, Mehmet Halil Celiksoy, Lynda Sekfali, Nafissa Benhalla, Merzak Gharnaout, Bulent Enis Sekerel, Rudolf Valenta, Reda Djidjik","doi":"10.1016/j.ebiom.2026.106484","DOIUrl":"10.1016/j.ebiom.2026.106484","url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin E-mediated allergy is the most important hypersensitivity disease affecting more than 30% of the population worldwide. The analysis of molecular IgE sensitization profiles in defined populations and age groups is important for the development of allergen-specific preventive and therapeutic interventions. The present study was performed to examine if there are differences regarding molecular IgE reactivity profiles in children and adults from two regions with similar climate and exposome.</p><p><strong>Methods: </strong>This two-step cross-sectional study assessed molecular IgE reactivity profiles using an experimental allergen microarray comprising 105 allergen molecules. In the first step, an exploratory cross-sectional study, serum samples from 539 allergic patients (259 children, 280 adults) who were born and grew up in the Algiers region were analyzed. The second step was a prospective cross-sectional study performed in 272 Turkish allergic patients (133 children, 139 adults) from Istanbul and Samsun regions with a climate and allergen exposome similar to Algiers, with the goal of investigating the reproducibility of possible differences in molecular IgE sensitization profiles between children and adults.</p><p><strong>Findings: </strong>In both the exploratory Algiers study and the prospective Turkish study, significantly more children than adults with respiratory allergy were sensitized to major respiratory house dust mite allergens (Algiers: Der p 1, Der p 2: p < 0.001 and Der p 23: p = 0.001; Türkiye: Der p 1: p = 0.018 and Der p 2: p = 0.019) whereas significantly more adults than children were sensitized to regionally common respiratory outdoor allergens (Algiers: Ole e 1: p = 0.037; Phl p 1: p = 0.046; Türkiye: Ole e 1: p = 0.016; Amb a 1: p = 0.002; Amb a 8: p < 0.001). Asthma was significantly more common in children than in adult patients with respiratory allergy (Algiers: p < 0.001; Türkiye: p = 0.034).</p><p><strong>Interpretation: </strong>Our study demonstrates different molecular IgE sensitization profiles in two age groups (children and adults) on two different continents with a similar climate and allergen exposome which may be due to exogenous factors such as climate change, different lifestyles, pollution and changes in vegetation. Both major house dust mite sensitization and asthma were more common in children, suggesting sensitization profile may contribute to asthma risk.</p><p><strong>Funding: </strong>Danube Allergy Research Cluster, Country of Lower Austria, Medical University of Vienna and Russian Science Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"106484"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037053","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":"Multi-omic profiling and pathways related to changes in liver histology after Roux-en-Y gastric bypass: a longitudinal study.","authors":"Yasaman Ghorbani, Katherine J P Schwenger, Heather Maughan, Anastasia Teterina, Wendy Lou, Elena M Comelli, Sandra E Fischer, Timothy D Jackson, Allan Okrainec, Johane P Allard","doi":"10.1016/j.ebiom.2026.106498","DOIUrl":"10.1016/j.ebiom.2026.106498","url":null,"abstract":"<p><strong>Background: </strong>Roux-en-Y gastric bypass (RYGB) improves metabolic dysfunction-associated steatotic liver disease (MASLD). However, the impact of RYGB on hepatic transcriptome, faecal microbiome and serum/faecal metabolome remain understudied. Our objective was to investigate the change in these omics and their relationships with changes in liver histology.</p><p><strong>Methods: </strong>In this prospective cohort study, patients undergoing RYGB were recruited between 2013 and 2020 and followed for 12 months. Anthropometrics, biochemistry, hepatic transcriptome, faecal microbiome (shotgun metagenomics) and serum/faecal metabolomes were measured. Liver histology and NAFLD Score (NAS) were assessed.</p><p><strong>Findings: </strong>Thirty-eight patients completed the study. Anthropometrics, biochemical and histological parameters improved post-RYGB (p < 0.05). Hepatic transcriptome analysis revealed a co-expression module enriched in fatty acid metabolism which correlated with changes in NAS post-RYGB (ρ = 0.38, p = 0.019). The core enrichment genes in this pathway were involved in mitochondrial and peroxisomal β-oxidation (ACADVL, ACOX1, and EHHADH) and the tricarboxylic acid (TCA) cycle (SUCLG2, SDHC, and SERINC1). There was an increase in TCA cycle gene expression associated with the resolution of ballooning, while upregulation of β-oxidation genes correlated with less reduction in NAS, ballooning, and inflammation. Metabolomic changes related to the identified co-expression module and pathways reveal a significant increase in faecal acylcarnitines, likely due to malabsorption from RYGB, with a significant reduction in circulating acylcarnitines which correlated positively with SUCLG2 expression and resolution of ballooning. Additionally, the increase in faecal acylcarnitines positively correlated with the bacterial species utilising acylcarnitines. In network analysis, ballooning of hepatocytes was associated with faecal/serum acylcarnitines and TCA metabolites while SUCLG2 was the hub gene associated with these changes.</p><p><strong>Interpretation: </strong>These findings provide insight on how post-RYGB changes in the transcriptome, metabolome, and microbiome could be associated with improvement in liver histology and may inform the development of future strategies for MASLD management.</p><p><strong>Funding: </strong>Canadian Institutes of Health Research and American College of Gastroenterology.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106498"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080043","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":"Single-cell study of human ovarian response to phthalate exposure reveals glial cell susceptibility and disruption of adhesion and mitochondrial pathways.","authors":"Eleftheria Maria Panagiotou, Loren Méar, Ilmatar Rooda, Alesandro Haxhiu, Elisabeth Moussaud-Lamodière, Karolina Wasilewska, Tianyi Li, Catarina Arnelo, Karin Pettersson, Kiriaki Papaikonomou, Cecilia Lindskog, Pauliina Damdimopoulou","doi":"10.1016/j.ebiom.2026.106487","DOIUrl":"10.1016/j.ebiom.2026.106487","url":null,"abstract":"<p><strong>Background: </strong>Phthalates are known male endocrine disruptors and reproductive toxicants. Despite growing evidence of female effects, mechanistic knowledge in key reproductive organs remains limited, hindering regulations. Here, we conducted an experimental study to map the impact of mono(2-ethylhexyl) phthalate (MEHP), the primary metabolite of di(2-ethylhexyl) phthalate (DEHP), on adult human ovarian tissue at single-cell resolution.</p><p><strong>Methods: </strong>Ovarian tissue explants from seven donors (five gender-affirming surgery, two caesarean-section) were exposed to two MEHP concentrations: an epidemiologically relevant 20.51 nM and a 1000-fold higher 20.51 μM. After six days, single-cell RNA sequencing (one donor) and immunostainings (six donors) were used to characterise gene expression changes across cell types. Primary ovarian cells derived from three gender-affirming surgery patients and stem cell-derived Schwann cells were used for validation.</p><p><strong>Findings: </strong>Explants retained all major ovarian cell types, including rare glial cells and oocytes. MEHP altered transcriptomes across all cell types, disrupting pathways related to actin cytoskeleton, cell adhesion, and oxidative phosphorylation (OXPHOS). Protein analyses confirmed altered EIF5A, MT-ND3, MT-ND4L, and VCL expression, genes linked to mitochondrial translation, OXPHOS, adhesion, and cytoskeleton. MEHP also reduced cell-cell communication, particularly glial-stromal interactions. Mitochondrial stress assay in primary cells indicated increased proton leakage, and Schwann cell responses mirrored the scRNA-seq findings.</p><p><strong>Interpretation: </strong>Ovarian toxicity studies traditionally focus on follicles, but this study reveals the susceptibility of non-follicular cells. Importantly, the sensitivity of ovarian nervous system cells to MEHP offers new mechanistic insights into reported links between phthalates, altered ovarian sensitivity index, and polyendocrine metabolic ovarian syndrome. Our findings highlight the need for a holistic assessment of ovarian toxicity that considers all ovarian cell types, not only follicles.</p><p><strong>Funding: </strong>Swedish Research Council for Sustainable Development and the European Union.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"106487"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105817","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}