Wiley最新文献

{"title":"Integrated assessment of rifampicin-mediated induction of transporters and drug-metabolizing enzymes in a long-term human liver tissue chip system.","authors":"Mattie E Hartauer, Raeanne M Lanphier, Shivam Ohri, Jessica Snyder, Jacqueline B Tiley, John K Fallon, Henry Ho, Murat Cirit, Shiny Amala Priya Rajan, Kim L R Brouwer","doi":"10.1002/cpt.70418","DOIUrl":"10.1002/cpt.70418","url":null,"abstract":"<p><p>Rifampicin is a prototypical clinical inducer used in drug-drug interaction (DDI) studies. However, the clinical relevance and predictability of rifampicin-mediated hepatic transporter induction remain poorly defined. Conventional hepatocyte culture models fail to capture clinically relevant regulation of transporters and drug-metabolizing enzymes (DMEs), particularly at the protein level. In this study, we characterized a liver tissue chip (LTC) as a new approach methodology (NAM) for long-term transporter- and DME-mediated induction risk assessment. Transporter-certified® cryopreserved primary human hepatocytes from three donors were cultured in the LTC under recirculating flow with or without 10 μM rifampicin for 7 days. The LTC facilitated simultaneous mRNA-protein quantification for transporters and mRNA-protein-activity profiling for cytochrome P450s (CYPs) within individual chips across treatment and control conditions. In addition, extracellular bile acid profiling and intracellular rifampicin concentrations were measured by LC-MS/MS. Rifampicin induced multiple transporters and enzymes at the protein level, including organic anion transporting polypeptide (OATP)2B1, P-glycoprotein, CYP3A4, CYP2C19, and uridine 5'-diphospho-glucuronosyltransferase (UGT)1A4. Induction patterns differed between transporter mRNA and protein in many cases, suggesting regulatory mechanisms beyond PXR-mediated activation. Matched mRNA-protein-activity measurements of five CYP enzymes also revealed discrepancies in rifampicin-mediated induction magnitude. Rifampicin altered bile acid composition, increasing taurine-conjugated bile acids and inducing bile acid-related genes. Measured intracellular rifampicin concentrations differed substantially from experimentally employed media concentrations. Overall, these findings demonstrate that the LTC enables integrated assessment of mRNA, protein, and activity measurements in addition to bile acid profiles and intracellular drug exposure, which may improve mechanistic understanding of induction processes.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":"1368-1378"},"PeriodicalIF":4.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium-Dependent Protein Kinase Regulatory Module Centred on TaCDPK5-2A Rewires Distinct Osmotic Stress-Associated Physiology and Enhances Wheat Yield.","authors":"Jiale Wang, Jiaqi Zhang, Xiaoyang Hou, Ziyi Wang, Hongning Zhang, Jinzhi Liu, Xiaoxin Fu, Haiyang Wang, Chengjin Guo, Kai Xiao","doi":"10.1111/pce.70753","DOIUrl":"10.1111/pce.70753","url":null,"abstract":"","PeriodicalId":222,"journal":{"name":"Plant, Cell & Environment","volume":" ","pages":"8302-8305"},"PeriodicalIF":6.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in GLP-1 Receptor Agonist Prescribing Without Documented Indications.","authors":"Chungsoo Kim, Kyungseon Choi, Harlan M Krumholz, Yuan Lu","doi":"10.1111/dom.71153","DOIUrl":"10.1111/dom.71153","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"10853-10856"},"PeriodicalIF":6.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667784","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":"Epigenetic Stress Memory and Adaptive Responses in Plants: Metabolic Reprogramming, Organelle Signalling and Systemic Acclimation.","authors":"Sajid Ali, Yong-Sun Moon","doi":"10.1111/pce.70764","DOIUrl":"10.1111/pce.70764","url":null,"abstract":"<p><p>Plants frequently encounter recurring, sequential and combined environmental stresses, yet their adaptive capacity cannot be explained solely by immediate signalling and short-term acclimation. Increasing evidence indicates that prior stress exposure can leave molecular, metabolic and physiological imprints that alter the magnitude, speed and quality of later responses, thereby giving rise to stress memory and adaptive plasticity. In plants, these persistent states are increasingly linked to epigenetic regulation, including changes in chromatin accessibility, histone modifications, DNA methylation, RNA-directed DNA methylation and non-coding RNA-mediated control. However, stress memory is not determined by chromatin regulation alone. It is also shaped by metabolic and cellular reprogramming involving osmolyte accumulation, redox buffering, energy redistribution, protein quality control, autophagy, selective protein turnover and membrane remodelling, all of which help sustain cellular homeostasis during stress and recovery. In parallel, chloroplasts, mitochondria and the endoplasmic reticulum act as stress-sensitive organelles that relay their functional state to the nucleus through retrograde signalling, while long-distance systemic communication mediated by reactive oxygen species, calcium waves, electrical and hydraulic signals, hormones and peptides coordinates whole-plant acclimation. This review synthesizes these layers into a unified framework and argues that plant resilience under fluctuating environments depends on the interaction between stress memory, metabolic plasticity, organelle-derived signalling and systemic acquired acclimation. Particular attention is given to the distinction between transient acclimation and true memory, the balance between maintenance and resetting of stress-induced states and the developmental and fitness trade-offs associated with persistent preparedness. This review also highlights major gaps that continue to limit the field, including the lack of standardized criteria for defining stress memory, insufficient causal validation of epigenetic marks, weak integration of chromatin and metabolic states with whole-plant phenotypes, and the limited translation of memory-associated mechanisms into crop performance under realistic field conditions. Overall, this review provides a comprehensive framework for understanding how plants not only respond to stress, but also encode, retain and deploy information from prior exposure to optimize subsequent adaptation.</p>","PeriodicalId":222,"journal":{"name":"Plant, Cell & Environment","volume":" ","pages":"8582-8603"},"PeriodicalIF":6.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Worldwide Survey Reveals Four Distinct Patterns of Photochemical Dehydration Tolerance Across Land Plant Phylogeny.","authors":"Jorge Gago, Beatriz Fernández-Marín, Roke Rojas, Miquel Nadal, Alicia V Perera-Castro, Melanie Morales, Miren I Arzac, Marina López-Pozo, Rafael Coopman, Meru Vivas, Leticia Poblete, Patricia L Sáez, Lohengrin A Cavieres, León A Bravo, Encarnación Núñez-Olivera, Javier Martínez-Abaigar, Marc Carriquí, María J Clemente-Moreno, Alisdair R Fernie, Agueda González-Rodríguez, Jose I García-Plazaola, Javier Gulías, Jaume Flexas","doi":"10.1111/pce.70761","DOIUrl":"10.1111/pce.70761","url":null,"abstract":"<p><p>The dehydration tolerance of photosynthetic tissues varies greatly along land plant's phylogeny. We investigated the photochemical response to severe dehydration and subsequent rehydration in 318 species representing the major terrestrial biomes and photosynthetic lineages: lichens, bryophytes, pteridophytes and spermatophytes. Using a standardized portable dehydration test with the maximum photochemical efficiency of PSII (F_v/F_m) as indicator, data meeting two key criteria were analyzed: (1) optimal physiological conditions before dehydration and (2) achieving relative water contents (RWC) below 25% at the dehydration stage (with approximately half dropping further to 5%-15%). Lichens and mosses displayed the highest overall Fv/Fm recovery after dehydration, whereas lower tolerance was observed in the other plant groups. Four distinct photochemical responses to dehydration emerged: dehydration-sensitive (61.2%), rehydration-sensitive (18.6%), dehydration-tolerant (13.6%), and dehydration-resistant (6.5%). Pteridophytes and spermatophytes predominantly exhibited dehydration- or rehydration-sensitive responses, whereas dehydration-tolerant dynamics were mainly observed in mosses and resurrection plants. Dehydration-resistant patterns were rare and occurred particularly in polar and high-altitude angiosperms such as Colobanthus quitensis, Deschampsia antarctica and Pozoa coriacea. These findings highlight the evolutionary divergence of dehydration tolerance strategies across the land plant phylogeny and provide insights into the underlying photochemical mechanisms.</p>","PeriodicalId":222,"journal":{"name":"Plant, Cell & Environment","volume":" ","pages":"8815-8827"},"PeriodicalIF":6.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to 'Association of Cardiovascular-Kidney-Syndrome and Brain Macrostructure and Microstructure Injury: A Prospective Cohort Study'.","authors":"","doi":"10.1111/dom.71081","DOIUrl":"10.1111/dom.71081","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"10917-10920"},"PeriodicalIF":6.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786138","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":"Synthetic Versus Reference Semaglutide for Weight Management: Reporting Gaps and Clinical Claims.","authors":"Awadhesh Kumar Singh, Akriti Singh, Ritu Singh","doi":"10.1111/dom.71283","DOIUrl":"10.1111/dom.71283","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"10899-10901"},"PeriodicalIF":6.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811472","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":"Cardiovascular Risk in Type 2 Diabetes With Substance Use Disorders: Questions of Exposure and Effect Modification.","authors":"Laurent Fauchier, Mickael Guglieri, Thibaud Genet","doi":"10.1111/dom.71288","DOIUrl":"10.1111/dom.71288","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"10905-10906"},"PeriodicalIF":6.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838695","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":"Correction to 'Glucose Tolerance and Mortality Across 24 Cancer Types and Stages: A K-CURE Nationwide Registry Study'.","authors":"","doi":"10.1111/dom.71276","DOIUrl":"10.1111/dom.71276","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"10923"},"PeriodicalIF":6.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987344","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":"Serum Lipidomics Profiling Identify Novel Biomarkers of Distal Symmetrical Polyneuropathy in Type 1 Diabetes.","authors":"Tik Muk, Tina Okdahl, Marietta Kokla, Tommi Suvitaival, Gurjeet Kaur, Ismo M Mattila, Simon M Kienle, Christian Buhl, Knud Yderstræde, Troels S Jensen, Peter Rossing, Flemming Pociot, Birgitte Brock, Cristina Legido-Quigley, Páll Karlsson, Christian S Hansen, Christina Brock, Joachim Størling, Karolina Sulek","doi":"10.1111/dom.71257","DOIUrl":"10.1111/dom.71257","url":null,"abstract":"<p><strong>Background: </strong>Distal symmetrical polyneuropathy (DSPN) is a common complication of type 1 diabetes (T1D), yet validated biomarkers for early detection or prognosis are lacking. Metabolic disturbances driven by chronic hyperglycemia and dyslipidemia contribute to DSPN development and progression.</p><p><strong>Methods: </strong>We used untargeted serum liquid chromatography-mass spectrometry lipidomics to identify DSPN biomarkers. The discovery cohort included 153 individuals with T1D (109 with and 44 without DSPN) and 50 non-diabetic controls. The independent validation cohort included 99 individuals with T1D with established DSPN status. Key lipids were identified using multivariate modelling, followed by ANCOVA and adjusted post hoc tests.</p><p><strong>Results: </strong>A total of 543 lipid species were identified in the discovery cohort. Among these, 14 lipids were associated with DSPN. Of which, 6 lipids, namely Cer(d42:1), PC(36:4), LPC(16:0), LPE(18:1), PE(36:2), and PE(O-40:5) or PE(P-40:4), showed a clear pattern among non-diabetic individuals, people affected by T1D with and without DSPN. In the validation cohort, 3 of the 6 initially identified lipids showed the same directional changes as in the discovery cohort. A logistic regression model combining the six lipid biomarkers with HbA1c, diastolic blood pressure, and age achieved AUCs of 0.83 (95% CI, 0.76-0.91) in the discovery cohort and 0.81 (95% CI, 0.73-0.90) in the validation cohort for detecting DSPN in T1D. AUC improvement was not significant by DeLong's test in either cohort (p = 0.086 and 0.089) but was significant when combined using Fisher's method (χ² = 9.7, p = 0.045). Additionally, 22 lipid species differed significantly between painful and painless DSPN.</p><p><strong>Conclusions: </strong>We identified a reproducible lipidomic signature discriminating DSPN in type 1 diabetes. Painful DSPN was characterized by reduced unsaturated PC/PE and increased sphingolipids, offering new insight into disease pathophysiology.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"10670-10682"},"PeriodicalIF":6.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}