Function (Oxford, England)最新文献

{"title":"Machine learning integrated extracellular vesicle proteome analysis for early markers of bronchopulmonary dysplasia.","authors":"Shaili Amatya, Shawn Rice, Anne Stanley, Han Chen, Ann Donnelly, Heather Stephens, Roopa Siddaiah, Chandra P Belani, Zissis C Chroneos","doi":"10.1152/function.090.2025","DOIUrl":"10.1152/function.090.2025","url":null,"abstract":"<p><p>Bronchopulmonary dysplasia (BPD) is a serious and often lethal complication of preterm birth that typically manifests about 1 mo after preterm delivery. The lungs of premature infants are underdeveloped and vulnerable to mechanical damage, inflammation, and oxidative stress. Collectively, these stressors impair the normal alveolarization of the premature lungs after birth. The multifactorial pathophysiology of BPD necessitates the identification of the molecular factors that mediate cell-to-cell communication that discriminates normal lung development from progression to BPD. Extracellular vesicles (EVs) mediate intercellular cross talk by transporting functional molecules, including proteins and nucleic acids, to recipient cells through biological fluids. This feasibility study determined the utility of profiling the discarded plasma-derived EV proteome to predict BPD susceptibility risk in extremely preterm infants. Discarded plasma was obtained from routine laboratory draws from infants born at less than 32 wk of gestation and weighing less than 1,500 g. Plasma EVs were captured using a magnetic bead-based immunoaffinity method. Subsequently, mass spectrometry and differential protein content analysis workflow identified a novel nine-EV-protein signature [APOD, heterogenous nuclear ribonucleoprotein M (HNRNPM), high-mobility group nucleosome-binding domain-containing protein 2 (HMGN2), intelectin-1 (ITLN1), proteinase 3 (PRTN3), RNA-binding protein4 (RBM4), RNA-binding motif protein, X chromosome (RBMX), TATA-binding protein-associated factor 2 N (TAF15, transcription elongation regulator 1 (TCERG1)] that distinguished preterm infants who developed BPD from those who did not. Application of machine learning statistical modeling using Promor tool trained on the nine-protein signature template identified a high specificity and selectivity prognostic threshold for the development of BPD. HNRNPM emerged as the most consistent biological response component predicting development of BPD in our patient cohort. Our study suggests that circulating EVs derived from discarded plasma are a suitable \"liquid biopsy\" to help stratify the vulnerability risk for BPD in preterm infants.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0902025"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12934772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term time-restricted feeding improves metabolic rhythms and liver mitochondrial bioenergetic function in high-fat diet-fed mice.","authors":"Jennifer A Valcin, Telisha Millender-Swain, Jodi R Paul, Brandon K Collins, Fatme Ghandour, Sameer Al Diffalha, Jennifer S Pollock, David M Pollock, Scott W Ballinger, Karen L Gamble, Shannon M Bailey","doi":"10.1152/function.082.2025","DOIUrl":"10.1152/function.082.2025","url":null,"abstract":"<p><p>Time-restricted feeding (TRF), which confines food intake to specific time periods without altering nutrient content or reducing calories, has shown promise in improving cardiometabolic health. This study tested whether a 2-wk TRF intervention during the active (dark) period could reverse long-term effects of a high-fat diet (HFD) on liver mitochondrial function, steatosis, and metabolism in mice. Male C57BL/6J mice were fed either a normal-fat diet (NFD, 10% kcal fat) or an HFD (45% kcal fat) ad libitum for 18 wk, followed by 2 wk of active period TRF. Assessments included whole body metabolism, gene expression, histopathology, plasma lipid levels, and mitochondrial bioenergetic function. Chronic HFD feeding abolished the day-night difference in the respiratory exchange ratio (RER), altered 24-h expression rhythms of clock, lipid, and mitochondrial metabolism genes in the liver, and eliminated diurnal variation in liver mitochondrial bioenergetics. TRF partially restored RER rhythmicity without altering body composition or reducing caloric intake in HFD mice. TRF also reset 24-h expression rhythms in clock and several metabolic genes, normalized liver and plasma triglyceride oscillations, and reduced small droplet macrosteatosis in the livers of HFD mice. Importantly, TRF improved liver mitochondrial respiration and reduced circulating levels of mitochondrial transcription factor A, a mitochondrially-derived damage-associated molecule pattern, indicating reduced mitochondrial injury in HFD mice. These findings suggest that TRF can rapidly reverse HFD-induced disruptions in metabolic and mitochondrial function, offering a promising new nonpharmacologic strategy for improving liver health in obesity-related metabolic disease.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0822025"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146108890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic modifications of VEGF, cerebral hypoxia, and impaired cerebrovascular autoregulation as early indicators for preterm brain injury.","authors":"Celina L Brunsch, Daphne H Klerk, Dorian Blommaert, Richelle G Harbers-Middel, Bineta E Lahr, Annemiek M Roescher, Torsten Plösch, Elisabeth M W Kooi","doi":"10.1152/function.088.2025","DOIUrl":"10.1152/function.088.2025","url":null,"abstract":"<p><p>Neurodevelopmental impairments after preterm birth remain prevalent. Preterm brain injury, such as intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), occurs due to immature vascularization and impaired cerebral blood flow. We explored epigenetic changes in the vascular endothelial growth factor A (<i>VEGFA</i>) and cerebrovascular autoregulation as biomarkers for preterm brain injury. Preterm neonates <30 wk gestational age and/or <1,000 g were prospectively enrolled in a single-center observational cohort study. We compared cerebral hemodynamics and cerebrovascular autoregulation during the first 3 postnatal days and VEGFA methylation from buccal samples during the first 2 wk between neonates without brain injury and those with IVH, PVL, or with IVH and/or PVL. Of 73 neonates with a means ± SD gestational age and birth weight of 27.7 ± 1.6 wk and 1,017 ± 235 g, 33 (45.2%) had IVH and/or PVL. Upon multivariable regression, IVH was associated with sedation, cerebral hypoxia, and impaired cerebrovascular autoregulation on <i>day 3</i>. Neonates with PVL had more methylated <i>VEGFA</i> in both weeks (median_week1 3.12% vs. 2.50%, <i>P</i> = 0.022). Upon multivariable regression, PVL was associated with lower Apgar scores and <i>VEGFA</i> hypermethylation in <i>week 2</i>. Neonates with IVH and/or PVL had lower cerebral tissue oxygenation (<i>P_day1</i> = 0.005, <i>P_day3</i> = 0.001) and more impaired cerebrovascular autoregulation on <i>day 1</i> (<i>P</i> < 0.001) than those without cerebral injury. Our findings indicate associations between both hemodynamic and epigenetic biomarkers and preterm brain injury. IVH and PVL showed associations with impaired cerebrovascular autoregulation, whereas IVH was associated with cerebral hypoxia and PVL with epigenetic downregulation of <i>VEGFA</i>. Hemodynamic changes appeared early postnatally, underscoring their clinical relevance.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0882025"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dysfunction at the intersection of alcohol use disorder and chronic pain.","authors":"Xavier R Chapa-Dubocq, Scott Edwards","doi":"10.1152/function.091.2025","DOIUrl":"10.1152/function.091.2025","url":null,"abstract":"<p><p>Alcohol use for pain relief dates back centuries. This profound analgesic efficacy also represents a strong motivational force that drives excessive drinking, fostering the development and severity of alcohol use disorder (AUD) in vulnerable individuals. Paradoxically, excessive alcohol drinking contributes to a multifactorial neuropathy, increasing nociceptive sensitivity (termed hyperalgesia) and pain-related negative affect, which may promote further alcohol use to manage either preexisting or newly emerging pain symptoms via stress-related neural damage and potentiation of negative reinforcement behavioral systems. These close relationships reflect the urgent need for better research conceptualizations and translational successes for the treatment of both chronic pain and addiction-related disorders. Mitochondrial health is particularly important across critical networks of neurons and nociceptive fibers, where continuous bioenergetic supply is required for axonal transport, repair, and synaptic transmission. Specific bioenergetic mechanisms underlying peripheral nerve damage and subsequent central nervous system adaptations in functional association with pain and excessive alcohol drinking are starting to be discovered. This focused review proposes that mitochondrial damage may unify several convergent pathophysiological mechanisms known to manifest in the context of both chronic pain and AUD and to be particularly relevant for vulnerable patient populations such as persons living with human immunodeficiency virus (HIV). Future research directions aimed at developing and testing novel therapeutic avenues to support mitochondrial health may provide safer and more effective medications for the management of both chronic pain states and AUD.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0912025"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12934775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent suppression of phrenic motor plasticity after mild acute systemic inflammation in adult rats.","authors":"Kayla A Burrowes, Maria Nikodemova, Gordon S Mitchell","doi":"10.1152/function.074.2025","DOIUrl":"10.1152/function.074.2025","url":null,"abstract":"<p><p>Inflammation, which is commonly associated with lung and neurological disorders, undermines a form of spinal serotonin-dependent respiratory motor plasticity elicited by moderate acute intermittent hypoxia (mAIH), known as phrenic long-term facilitation (pLTF). In adult rats, pLTF suppression has been studied 24 h following exposure to low-dose lipopolysaccharide (LPS) or 8 h of intermittent hypoxia simulating sleep apnea. In this timeframe, pLTF is suppressed by an adenosine 2 A (A2a) receptor and p38 MAP kinase-dependent mechanism. However, the duration of plasticity suppression following acute inflammation is unknown. We hypothesized that pLTF recovers when neuroinflammatory molecules return to normal. Thus, in Sprague Dawley rats, we assessed pLTF, ventral spinal (C3-C6) adenosine, and proinflammatory molecules after LPS (100 µg/kg ip). LPS increased spinal adenosine and microglial inflammatory genes at 24 h, but not 1 wk after LPS. Regardless, mAIH-induced pLTF remained suppressed for 3 wk, and then slowly recovered between 3 and 5 wk after LPS. Thus, pLTF suppression outlasts active inflammation. Contrary to 24 hours, at 1 wk after LPS, spinal A2a receptor inhibition (MSX-3) failed to restore pLTF, whereas spinal p38 MAPK inhibition (SB202190) rescued pLTF at both 24 hours and 1 wk after LPS. These findings suggest that distinct mechanisms underlie pLTF suppression at 24 h versus 1 wk after LPS, although both mechanisms share downstream p38 MAPK signaling. Since mAIH is emerging as a therapeutic modality to improve respiratory and nonrespiratory motor function in people with neurological disorders, targeting p38 MAPK may prevent persistent plasticity suppression in individuals with a history of inflammation.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0742025"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tiny tools closing the gap: nanobodies in research and therapy.","authors":"Mustafa Abdellatif, Jyotirmoy Rajurkar, Heinrich Leonhardt","doi":"10.1152/function.107.2025","DOIUrl":"10.1152/function.107.2025","url":null,"abstract":"<p><p>Nanobodies, also known as single-domain antibodies, have become powerful tools in research, diagnosis, and therapy. Sourced from the heavy chain of camelid heavy chain-only antibodies, this domain retains many important characteristics of full-length antibodies while being ∼10 times smaller in molecular weight. Nanobody discovery has seen expansive development over the recent past, through both conventional antigen-exposed and completely synthetic repertoires. Along these lines, binding properties of candidates can be evolved by subsequent mutation and selection cycles to adjust their specificity and avidity. Due to their small size and compact structure, nanobodies can reach cryptic sites not accessible to conventional antibodies and also show superior tissue penetration. This penetrance, alongside their ease of handling, has made nanobodies ideal candidates for a myriad of immunotherapeutic and drug delivery applications. Furthermore, their small size imparts minimal linkage errors when conjugated to a fluorophore, making nanobodies ideal tools for high-resolution imaging techniques. Most importantly, nanobodies can be stably expressed in living cells to bind, block, or modify intracellular targets, enabling study of proteins in a native context at unprecedented detail. In this review, we present the latest developments in nanobody technology and discuss applications in bioimaging, therapy, and intracellular protein study.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e1072025"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12934779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146108925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelium-derived endothelin-1 mediates sickle cell nephropathy.","authors":"Malgorzata Kasztan, Patrick A Molina, Brandon M Fox, Elizabeth Saurage, Jackson C Colson, David M Pollock, Jennifer S Pollock","doi":"10.1152/function.001.2026","DOIUrl":"10.1152/function.001.2026","url":null,"abstract":"<p><p>Sickle cell nephropathy (SCN) significantly shortens the life expectancy of patients with sickle cell disease (SCD). We previously reported that endothelin-1 (ET-1) and endothelin A receptor (ET_A) are upregulated in SCN, and ET_A antagonism mitigates SCN early in the disease progression in a humanized mouse model of SCD. We hypothesized that endothelium-derived ET-1 mediates the progression of SCN and T cell inflammation in the kidney of SCD mice. To test this hypothesis, we first used allogenic bone marrow transplantation from humanized sickle cell mice (HbSS) into endothelial-derived ET-1 knockout (VEET KO) mice, revealing that endothelial-derived ET-1 mitigates SCN and regulates the renal inflammatory response and T cell infiltration. Second, using young (4-5 mo old) and middle-aged (10-15 mo old) HbSS mice lacking endothelial-specific ET-1 (HbSS-VEET KO), we found a temporal maintenance of glomerular filtration rate, reduced infiltration of T cells to the kidney, and reduced progression of SCN. Furthermore, 2-wk ET_A antagonism in middle-aged HbSS mice reduced infiltration of T cells. Finally, flow cytometric analyses revealed blunting of kidney T helper 17 (T_H17) cells without a change in kidney T regulatory cells in HbSS-VEET KO mice, suggesting T cell subset-specific regulation by endothelial-derived ET-1 signaling. In vitro studies showed that ET_A antagonism directly inhibits T_H17 polarization and IL-17A production, suggesting that in established sickle cell disease, the ET_A receptor-T_H17 cell axis may play a key role in maintenance of fibrosis in SCN. Taken together, these data indicate that endothelial-derived ET-1 mediates the progression of SCN and strengthens the rationale for targeting ET-1 signaling as a new therapeutic approach.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0012026"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary salt impairs circadian physiological metabolic adaptations in salt-sensitive hypertension.","authors":"Lashodya V Dissanayake, Adrian Zietara, Ratnakar Tiwari, Melissa Lowe, Olha Kravtsova, Vladislav Levchenko, Ruslan Bohovyk, Michelle L Gumz, Alexander Staruschenko","doi":"10.1152/function.106.2025","DOIUrl":"10.1152/function.106.2025","url":null,"abstract":"<p><p>The body's circadian rhythm is coordinated by core clock proteins [period (PER), cryptochrome circadian regulator (CRY), circadian locomotor output cycles kaput (CLOCK), and basic helix-loop-helix ARNT-like protein 1 (BMAL1)] that function in both the central hypothalamic and peripheral tissue molecular clocks. Our recent study demonstrated that deletion of <i>Per1</i> in Dahl salt-sensitive (SS) rats (SS^Per1-/-) exacerbated SS hypertension (HTN), kidney injury, and disrupted blood pressure rhythms. To define time-of-day-, genotype-, and diet-dependent alterations in the renal transcriptome and proteome associated with SS HTN, kidney cortex samples were collected from SS and SS^Per1-/- rats fed either a normal-salt (NS, 0.4% NaCl) or high-salt (HS, 4% NaCl) diet, during both the active (night) and inactive (day) periods. Dietary challenges were conducted for 3 wk in male rats. Bulk RNA-sequencing was performed on both NS- and HS-fed groups, and proteomic analyses were performed in HS-fed groups. In SS rats, HS intake blunted time-of-day-dependent transcriptional changes. Pathway analyses predicted significant stress and immune responses, as well as metabolic adaptations, induced by the HS diet. Specifically, the remodeling of the pyruvate dehydrogenase complex was identified as a key prediction in both transcriptomic and phosphoproteomic datasets. As expected, <i>Per1</i> deletion further exacerbated disruptions in immune regulation and metabolic adaptation. Collectively, these findings demonstrate that numerous renal genes exhibit diurnal oscillations under physiological conditions and are profoundly disrupted in SS HTN, likely contributing to impaired kidney function and circadian misalignment of blood pressure regulation.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e1062025"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellular calcium release activates carotid body afferents by fentanyl.","authors":"Ying-Jie Peng, Oren Kabil, Ning Wang, Zheng Xie, Aaron P Fox, Nanduri R Prabhakar","doi":"10.1152/function.078.2025","DOIUrl":"10.1152/function.078.2025","url":null,"abstract":"<p><p>We recently reported [Peng YJ, Nanduri J, Wang N, Xie Z, Fox AP, Prabhakar NR. <i>Function</i> (Oxf) 6: zqaf020, 2025] that fentanyl activates carotid body (CB) afferents via kappa opioid receptors (KORs), while CB denervation exacerbates, coadministration of fentanyl with a KOR agonist attenuates opioid-induced respiratory depression (OIRD). These findings indicated that CB chemoreflex activation by fentanyl may counteract OIRD. The present study investigated the cellular mechanisms underlying CB afferent activation by fentanyl. We hypothesized that Ca²⁺ signaling in glomus cells mediates CB activation by fentanyl. Using Fura-2 calcium imaging in rat glomus cells, we observed that fentanyl increased intracellular Ca²⁺ even in the absence of extracellular calcium. Pretreatment with thapsigargin, which depletes internal Ca²⁺ stores, abolished Ca²⁺ response, suggesting that fentanyl releases Ca²⁺ from intracellular stores. In human embryonic kidney cells expressing KOR and G protein alpha q subunit (Gαq), fentanyl promoted KOR-Gαq complex formation and stimulated phospholipase C (PLC), elevating inositol trisphosphate (IP₃) levels in the CB. Pharmacological blockade of KOR, Gαq, PLC, or IP₃ receptors prevented both the rise in [Ca²⁺]_i and CB afferent activation. Collectively, these results identify a previously uncharacterized KOR-Gαq-PLC-IP₃R-Ca²⁺ signaling pathway in glomus cells that mediates CB afferent activation by fentanyl, providing new mechanistic insight into how CB chemoreflex activation by fentanyl may mitigate OIRD.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0782025"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145769828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing matters: circadian rhythm disruption in alcohol-associated peripheral organ pathophysiology.","authors":"Shannon M Bailey","doi":"10.1152/function.099.2025","DOIUrl":"10.1152/function.099.2025","url":null,"abstract":"<p><p>Circadian rhythms influence the pathophysiological effects of alcohol. This review examines how alcohol disrupts circadian regulation in peripheral organs, particularly the liver, intestine, cardiovascular system, and skeletal muscle, and how circadian disruption exacerbates metabolic dysfunction and organ injury. Evidence from preclinical and human studies indicates that both genetic and environmental circadian disruption increases alcohol-induced gut permeability, systemic inflammation, and liver disease. This review also presents how other lifestyle and environmental factors such as diet, smoking, and shift work worsen circadian disruption and alcohol-related toxicity. Emerging circadian-based therapeutic strategies and key research priorities are discussed. Advancing understanding of alcohol-circadian interactions is essential for developing more effective, personalized treatments for alcohol-associated diseases.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0992025"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}