iScience最新文献_第4页

Divergent ectopic fat distribution and adipokine/hepatokine levels characterize the metabolically healthy overweight/obesity phenotype. 不同的异位脂肪分布和脂肪因子/肝因子水平表征了代谢健康的超重/肥胖表型。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117672

Antonio Clavero-Jimeno, Juan J Martin-Olmedo, Alessandro Gatti, Adrián Cortés-Martín, Alba Camacho-Cardenosa, Lucas Jurado-Fasoli, Manuel Dote-Montero, Marcos Molina-Fernandez, Alejandro López-Vázquez, Amaya Lopez-Pascual, Matías A Ávila, Estrella Petrina, Ana Zugasti, Iñigo Urdiain, Mara Concepción, Rafael Cabeza, José L Martín-Rodríguez, Idoia Labayen, Jonatan R Ruiz

{"title":"Divergent ectopic fat distribution and adipokine/hepatokine levels characterize the metabolically healthy overweight/obesity phenotype.","authors":"Antonio Clavero-Jimeno, Juan J Martin-Olmedo, Alessandro Gatti, Adrián Cortés-Martín, Alba Camacho-Cardenosa, Lucas Jurado-Fasoli, Manuel Dote-Montero, Marcos Molina-Fernandez, Alejandro López-Vázquez, Amaya Lopez-Pascual, Matías A Ávila, Estrella Petrina, Ana Zugasti, Iñigo Urdiain, Mara Concepción, Rafael Cabeza, José L Martín-Rodríguez, Idoia Labayen, Jonatan R Ruiz","doi":"10.1016/j.isci.2026.117672","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117672","url":null,"abstract":"The metabolically healthy overweight/obesity (MHOO) phenotype combines excess adiposity with preserved cardiometabolic health. We compared specific fat depots, circulating adipokine and hepatokine levels, and fecal microbiota composition between 384 adults classified as MHOO (n = 99) or metabolically unhealthy overweight/obesity (MUOO; n = 285). Magnetic resonance imaging was used to quantify visceral adipose tissue (VAT) volume, hepatic and pancreatic fat fractions, abdominal and mid-thigh intermuscular adipose tissue (IMAT), and subcutaneous adipose tissue (SAT). Despite similar whole-body fat mass, MHOO showed lower VAT volume, hepatic and pancreatic fat fractions, abdominal IMAT volume, abdominal VAT-to-SAT ratio, and mid-thigh IMAT area, together with higher mid-thigh SAT area. MHOO also had higher adiponectin and sex hormone-binding globulin (SHBG) and lower retinol-binding protein 4 (RBP4) levels. Fecal microbiota composition was similar between groups. VAT volume and hepatic fat fraction were the strongest discriminative features, supporting fat distribution rather than total adiposity as a key feature of preserved metabolic health.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117672"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HDAC inhibitor treatment restores transcriptome, chromatin accessibility, and memory deficits in a mouse model for Down syndrome. HDAC抑制剂治疗可恢复唐氏综合症小鼠模型的转录组、染色质可及性和记忆缺陷。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117670

Cesar Sierra, René A J Crans, Mara Dierssen

{"title":"HDAC inhibitor treatment restores transcriptome, chromatin accessibility, and memory deficits in a mouse model for Down syndrome.","authors":"Cesar Sierra, René A J Crans, Mara Dierssen","doi":"10.1016/j.isci.2026.117670","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117670","url":null,"abstract":"Down syndrome (DS) is associated with widespread molecular alterations, including aberrant gene expression, which not only affects chromosome 21 genes but perturbs the whole transcriptome. The genome-wide nature of this alteration suggests that it might be epigenetically mediated, which may also offer therapeutic opportunities given the reversibility of epigenetic modifications. Here, we show that decreased global acetylation level in the hippocampus of the trisomic mouse model Ts65Dn is associated with decreased chromatin accessibility at gene promoters in hippocampal neurons. Strikingly, pharmacological restoration of histone acetylation using the clinically approved histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) normalized transcriptomic, epigenetic, and cortico-hippocampal memory deficits in trisomic mice. This rescue was mediated by an unexpected heterochromatization of the supernumerary chromosome. Altogether, our results identify an unanticipated epigenetic mechanism linking histone acetylation dynamics to chromosomal dosage homeostasis.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117670"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Physiological elasticity and topography modulate in vitro prostate cancer cell behavior. 生理弹性和地形对体外前列腺癌细胞行为的调节。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117623

Marco Hoffmann, Richard Paul, Anna Herrmann, Sven Gerlach, Paul Bacmeister, Thomas Frank Ermler, Marie Book, Radu Alexa, Axel Honné, Julian Peter Müller, Julia Kristin Brach, Petra Fischer, Jennifer Kranz, Matthias Wessling, Matthias Saar

{"title":"Physiological elasticity and topography modulate in vitro prostate cancer cell behavior.","authors":"Marco Hoffmann, Richard Paul, Anna Herrmann, Sven Gerlach, Paul Bacmeister, Thomas Frank Ermler, Marie Book, Radu Alexa, Axel Honné, Julian Peter Müller, Julia Kristin Brach, Petra Fischer, Jennifer Kranz, Matthias Wessling, Matthias Saar","doi":"10.1016/j.isci.2026.117623","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117623","url":null,"abstract":"Tissue elasticity and microenvironment are a hallmark of cancer, particularly in prostate cancer. Here, we investigate, how physiologically relevant mechanical properties affect prostate cancer cells using 2D-poly(dimethylsiloxane) (PDMS) and topographic 2.5D-poly(ethylene glycol) diacrylate-glycidyl methacrylate hydrogel surfaces. Substrates reproducing the stiffness of tumor cell niches, altered cell morphology, metabolic activity, migration, cytokine expression, and therapeutic response. Elasticity-dependent effects included up to a 1.5-fold increase in LDH activity with concurrent cell proliferation, reduced migration rates with increased paxillin expression, and enhanced chemokine-mediated invasion. Adaptation to physiological elasticities was also associated with up to 90 % reduction in responsiveness to docetaxel and enzalutamide. Importantly, elasticity-adapted substrates supported primary prostate cancer cell growth while preserving characteristic expression profiles. These findings demonstrated that mechanical microenvironmental cues substantially shape prostate cancer cell phenotypes and highlight their importance for developing more physiologically relevant and translationally informative in vitro models.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117623"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thermoregulated photothermal therapy for bone defects using graphene oxide hydrogel with mesoporous silica-derived phase-change nanocapsules. 使用氧化石墨烯水凝胶和介孔二氧化硅衍生相变纳米胶囊进行骨缺损的热调节光热治疗。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117650

Qian Zhang, Shuang Zhao, Chenxi Shang, Yanan Jiang, Weiwei Zhang, Shuang Pan

{"title":"Thermoregulated photothermal therapy for bone defects using graphene oxide hydrogel with mesoporous silica-derived phase-change nanocapsules.","authors":"Qian Zhang, Shuang Zhao, Chenxi Shang, Yanan Jiang, Weiwei Zhang, Shuang Pan","doi":"10.1016/j.isci.2026.117650","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117650","url":null,"abstract":"The clinical translation of photothermal therapy for bone repair is hindered by the risk of thermal damage to surrounding healthy tissues due to uncontrolled high temperatures. We addressed this by integrating phase change materials (PCMs) into a photothermal platform, developing a hydrogel scaffold with temperature regulation. Polyethylene glycol (PEG) was encapsulated in mesoporous nanosilica (MSNs) to form nanocapsules, achieving 82.5% efficiency. This encapsulation prevents PEG leakage and enhances thermal regulation and bioactivity. Graphene oxide (GO) was integrated into an alginate-chitosan matrix, yielding a GO/chitosan scaffold containing PEG@MSNs nanocapsules. The scaffold exhibits a phase transition at 41.2°C and latent heat of 95.5 J/g. Characterization confirms its physicochemical properties, biocompatibility, and cell affinity meet bone repair requirements. In vitro mineralization assays, osteogenesis studies, and in vivo bone defect models demonstrated its efficacy in temperature-controlled photothermal bone regeneration. This integration of photothermal control and biological activity represents an advance in scaffold design.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117650"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Frequency-dependent cerebellar circuits independently gate social vocalizations and movement. 频率相关的小脑回路独立地控制社会发声和运动。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117706

Cheryl Brandenburg, Snigdha Srivastava, Alejandro G Rey Hipolito, Tao Lin, Benjamin R Arenkiel, Roy V Sillitoe

{"title":"Frequency-dependent cerebellar circuits independently gate social vocalizations and movement.","authors":"Cheryl Brandenburg, Snigdha Srivastava, Alejandro G Rey Hipolito, Tao Lin, Benjamin R Arenkiel, Roy V Sillitoe","doi":"10.1016/j.isci.2026.117706","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117706","url":null,"abstract":"Communication depends on precise coordination between motor execution and cognition. Here we reveal that the cerebellum exerts real-time control over social vocalizations in adult mice. Optogenetic activation of excitatory cerebellar output in the superior cerebellar peduncle suppressed ultrasonic vocalizations with frequency-dependent potency while inducing distinct motor phenotypes. Systematic functional mapping across cerebellar regions and cell types revealed that vocal suppression can occur in the absence of overt motor impairment, suggesting selective control of vocal output beyond gross movement disruption. We identified the periaqueductal gray (PAG), a conserved midbrain vocal control center, as a key downstream mediator of this effect. Deep brain stimulation of the PAG rescued vocal deficits in a model of cerebellar dysfunction without rescuing motor incoordination. These findings define a cerebellar-midbrain pathway that gates vocal behavior and demonstrate that targeted therapeutic neuromodulation can selectively restore communication-related output even in the presence of persistent cerebellar-driven motor deficits.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117706"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A method for expressing two proteins at a tunable ratio allows for studying the kinetics of creatine transport by MCT12. 一种以可调比例表达两种蛋白的方法允许研究MCT12的肌酸运输动力学。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117719

Danila Boytsov, Julia Bicher, Oliver Kudlacek, Klaus Schicker, Rodion Tsurikov, Sonja Sucic, Michael Freissmuth, Harald H Sitte, Walter Sandtner, Marko Roblek

{"title":"A method for expressing two proteins at a tunable ratio allows for studying the kinetics of creatine transport by MCT12.","authors":"Danila Boytsov, Julia Bicher, Oliver Kudlacek, Klaus Schicker, Rodion Tsurikov, Sonja Sucic, Michael Freissmuth, Harald H Sitte, Walter Sandtner, Marko Roblek","doi":"10.1016/j.isci.2026.117719","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117719","url":null,"abstract":"Interactions between physically or functionally coupled proteins are often studied by co-expression from the same or separate plasmids, but protein ratios can vary widely between individual cells. To overcome this limitation, we developed a strategy to generate tunable and constant expression ratios using a single vector encoding two proteins separated by a P2A site followed by short AAA codon repeats that progressively reduce ribosomal readthrough. After validating this approach with the fluorescent proteins eGFP and mCherry, we applied it to characterize the transport cycle of the electroneutral monocarboxylate transporter MCT12, a task that is otherwise difficult to achieve experimentally. By co-expressing MCT12 with the concentrative creatine transporter CRT1 at defined ratios, we were able to determine the substrate turnover rate of MCT12 and its substrate KM. This approach enables precise control of protein stoichiometry, facilitating quantitative mechanistic studies of interacting proteins in cells.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117719"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Ca²⁺ level-independent component of recovery from sensory adaptation supports continuous vesicle supply at cochlear hair cell ribbon synapses. 一种不依赖于水平的感觉适应恢复组分支持耳蜗毛细胞带状突触连续的囊泡供应。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117694

Walen L Gribaudo, Camila Catalano Di Meo, Lucía Agüero, Daniela Chequer Charan, Mark A Rutherford, Juan D Goutman

{"title":"A Ca²⁺ level-independent component of recovery from sensory adaptation supports continuous vesicle supply at cochlear hair cell ribbon synapses.","authors":"Walen L Gribaudo, Camila Catalano Di Meo, Lucía Agüero, Daniela Chequer Charan, Mark A Rutherford, Juan D Goutman","doi":"10.1016/j.isci.2026.117694","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117694","url":null,"abstract":"Maintenance of synaptic transmission can be accelerated by mechanisms dependent on intracellular Ca2+ signaling. However, at the first auditory synapse between sensory inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea, the process of synaptic vesicle recovery following strong, prolonged stimulation is unclear. To address this, we examined the Ca2+-dependence of presynaptic recovery in IHCs with measurements of postsynaptic activity in SGNs while depolarizing the IHC. Following vesicle-depleting stimulation of 1 second duration, SGN postsynaptic responses recovered completely within a few seconds. This process was unperturbed when reducing the intracellular Ca2+concentration by changing from 1 to 5 mM EGTA. Thus, synaptic recovery following depleting stimulation at IHC-SGN synapses may differ from the Ca2+-dependent process described during and after stimulation over shorter timescales. We propose a Ca2+ level-insensitive mechanism of recovery at this continuously active sensory synapse to support vesicle release rates of hundreds per second indefatigably.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117694"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chaperone protein DnaK-mediated regulation of spore coat assembly in Bacillus subtilis. 伴侣蛋白dna介导的枯草芽孢杆菌孢子外壳组装调控。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117681

Kangyi Mu, Chunrong Ling, Tianlin Cui, Zequn Zhang, Chen Fang, Li Dong, Xiaosong Hu

{"title":"Chaperone protein DnaK-mediated regulation of spore coat assembly in Bacillus subtilis.","authors":"Kangyi Mu, Chunrong Ling, Tianlin Cui, Zequn Zhang, Chen Fang, Li Dong, Xiaosong Hu","doi":"10.1016/j.isci.2026.117681","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117681","url":null,"abstract":"Bacterial spores pose a significant challenge to the food industry due to their ability to germinate from dormancy and their extreme resistance. Spores are encased by a multilayered proteinaceous structure termed the spore coat. Previous studies on spore coat assembly have predominantly focused on the interactions among coat proteins, while the involvement of broader protein quality control systems remains poorly understood. Here, we demonstrate that the molecular chaperone DnaK is essential for the proper assembly of the inner spore coat in Bacillus subtilis. Deletion of dnaK leads to mislocalization of key morphogenetic protein SafA, reduced accumulation of full-length SafA, altered transcriptional dynamics of spoIIID and sigK, and ultimately impaired coat integrity and function. Our findings reveal that DnaK facilitates spore coat assembly through both transcriptional and post-translational mechanisms, uncovering a previously unrecognized regulatory layer in spore coat morphogenesis.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117681"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteomic and functional profiling of suspended jejunal enteroids reveals pharmacokinetic fidelity to native intestine. 蛋白质组学和功能分析的暂停空肠肠状的揭示了药代动力学富达本机肠。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117654

Foteini Tzioufa, Merve Ceylan, Maria Letizia Di Martino, Dinh Son Vo, Ana C C Lopes, Rebekkah Hammar, Magnus Sundbom, Martin Skogar, Per M Hellström, Dominic-Luc Webb, Maria Karlgren, Iain Gardner, Patrik Lundquist, Jens Eriksson, Daisy Hjelmqvist, Mikael E Sellin, Madlen Hubert, Per Artursson

{"title":"Proteomic and functional profiling of suspended jejunal enteroids reveals pharmacokinetic fidelity to native intestine.","authors":"Foteini Tzioufa, Merve Ceylan, Maria Letizia Di Martino, Dinh Son Vo, Ana C C Lopes, Rebekkah Hammar, Magnus Sundbom, Martin Skogar, Per M Hellström, Dominic-Luc Webb, Maria Karlgren, Iain Gardner, Patrik Lundquist, Jens Eriksson, Daisy Hjelmqvist, Mikael E Sellin, Madlen Hubert, Per Artursson","doi":"10.1016/j.isci.2026.117654","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117654","url":null,"abstract":"Intestinal enteroids are \"mini-guts\" that recapitulate essential features of the intestinal epithelium in vitro. We developed and characterized native basal-out (BO) and morphogenically everted apical-out (AO) jejunal enteroids cultured in suspension. Using quantitative proteomics and a range of advanced microscopy techniques, we show that these enteroids progressively adopt protein profiles closely resembling those of freshly isolated villus enterocytes and human jejunal tissue. Optimally differentiated enteroids exhibit mature epithelial morphology, intact barrier function, nutrient absorption, and clinically relevant transporter activity (P-glycoprotein; Pgp/ABCB1, breast cancer resistance protein; BCRP/ABCG2), reflecting in vivo physiology. Metabolic assessment of orally administered cytochrome P450 3A4 (CYP3A4) probe drugs, terfenadine and midazolam, accurately predicted first-pass metabolism and clinical pharmacokinetics via physiologically based pharmacokinetic (PBPK) modeling. These findings establish suspension-grown 3D jejunal enteroids as a translationally relevant, human-derived platform that is advantageous over conventional cell line and animal models for studying drug disposition, nutrient transport, and intestinal barrier function.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117654"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Topical application of urolithin A activates mitophagy and enhances mitochondrial function to promote skin longevity. 局部应用尿素A激活线粒体自噬，增强线粒体功能，促进皮肤长寿。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117646

Davide D'Amico, Julie Faitg, Frédéric Amaral, Carine Ballihaut, Andréane M Fouassier, Charlotte Tissot, Isha Rana, Julien Laboureau, Natascha Hennighausen, Marianne Brandt, Nicholas Kron, Xavier Marat, Chantal Jouy, Annie F Black, Gayané Azadiguian, Delphine Guillon, Jean-Thierry Simonnet, Chris Rinsch, Anurag Singh

{"title":"Topical application of urolithin A activates mitophagy and enhances mitochondrial function to promote skin longevity.","authors":"Davide D'Amico, Julie Faitg, Frédéric Amaral, Carine Ballihaut, Andréane M Fouassier, Charlotte Tissot, Isha Rana, Julien Laboureau, Natascha Hennighausen, Marianne Brandt, Nicholas Kron, Xavier Marat, Chantal Jouy, Annie F Black, Gayané Azadiguian, Delphine Guillon, Jean-Thierry Simonnet, Chris Rinsch, Anurag Singh","doi":"10.1016/j.isci.2026.117646","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117646","url":null,"abstract":"Urolithin A (UA, Mitopure), a postbiotic that promotes mitophagy and mitochondrial function following oral administration, was evaluated for its effects on skin health in human skin models and when applied topically to healthy subjects in randomized clinical studies. UA tested in 2D and 3D reconstructed human skin and ex vivo human skin explants showed enhanced mitochondrial respiration, activated mitophagy markers, reduced inflammatory mediators and senescence-associated markers, and increased proteins involved in extracellular matrix structure and epidermal differentiation. Safety was confirmed in a human repeat-insult patch test. In randomized, placebo-controlled clinical studies, UA reduced periorbital wrinkle depth after 8 weeks and attenuated UVB-induced erythema. Skin transcriptomics supported increased extracellular matrix and epidermal development programs together with decreased inflammatory and senescence-associated signaling. These findings indicate that topical UA engages cellular pathways associated with skin resilience to promote skin health and longevity.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117646"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0