Physiological genomics最新文献

{"title":"The transcriptomes of hypothalamic micropunches reveal sex differences in regulatory processes across hibernation in the Arctic ground squirrel.","authors":"Cole K Deal, M Hoshi Sugiura, Kelly L Drew, Cory T Williams","doi":"10.1152/physiolgenomics.00073.2025","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00073.2025","url":null,"abstract":"<p><p>Seasonal life-history events, such as migration, hibernation, and reproduction, depend on coordinated physiological changes. In vertebrates, a conserved thyroid hormone-signaling pathway in the hypothalamus is known to trigger many of these seasonal transitions. However, the broader processes and regulators modulating seasonal physiology are poorly defined. Recent research in Arctic ground squirrels (AGS, <i>Urocitellus parryii</i>) revealed hypothalamic thyroid hormone signaling is activated and markers of tanycytic remodeling are expressed in late hibernation in anticipation of springtime reproduction. We conducted RNA-seq on hypothalamic micropunches encompassing the arcuate nucleus, median eminence, pars tuberalis, and third ventricle in male and female AGS at early and late hibernation. We found substantial sex differences in the hypothalamic transcriptome across hibernation. Functional enrichment analysis of gene expression data revealed an upregulation of processes and pathways related to hormone transport and neurogenesis in females, whereas this was less apparent in males. Transcription factor binding site analysis of differentially expressed genes identified upstream regulators involved in glial cell differentiation, neuronal development, survival, and plasticity. Notably, many of the intersecting genes from these analyses were localized to specialized glial cells (tanycytes) lining the floor and walls of the third ventricle. Our findings support a model in which annual changes in gene expression rely on a progressive remodeling of tanycytes across hibernation. This remodeling may contribute to seasonal changes in neuronal plasticity and function of the hypothalamus, priming the brain in anticipation of shifting physiological demands upon hibernation termination.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic profiling of extracellular vesicles reveals enhanced oxidative stress and energy metabolism during intense military training; an exploratory study.","authors":"Meaghan E Beckner, J Philip Karl, Nicholes J Armstrong, Christopher T Carrigan, Marques A Wilson, Hoangha D Pirnstill, Anthony J Karis, Stefan M Pasiakos, James P McClung, Nicholas D Barringer, Lee M Margolis","doi":"10.1152/physiolgenomics.00155.2025","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00155.2025","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are small, membrane-bound vesicles that transfer biological content through the extracellular environment. The role of EVs in energy metabolism have primarily focused on EV proteins and microRNAs, with less attention on the metabolic content of EVs. <b>Purpose:</b> This exploratory study assessed changes in the EV metabolome in response to an arduous, 16-day military training exercise. <b>Methods:</b> Forty male Soldiers (21±2 years, 24.8±2.7 kg/m²) provided blood from which circulating EVs were isolated, and completed assessments of body composition, and lower body power on days 1 (PRE) and 16 (POST) of a mountain training exercise (MTX). <b>Results:</b> Total daily energy expenditure (TDEE) during the MTX was 4,187±519 kcal·d^-1. Fat mass (POST-PRE [95%CI]; -0.9[-1.3,-0.6] kg), lean body mass (-1.6[-2.0,-1.2] kg), body fat percentage (-0.7[-1.1,-0.3]%), and lower body power (-133[-204,-63] Watts) decreased from PRE to POST (<i>p</i><0.05). Global metabolite profiling identified 81 metabolites from lipid (81%), energy (5%), cofactor and vitamin (5%), xenobiotic (4%), carbohydrate (2%), amino acid (1%) and nucleotide (1%) pathways in serum-derived EVs. After adjusting for EV concentration, 11 metabolites were different PRE to POST (<i>p</i><0.05, <i>Q</i><0.20), with the largest increases in the oxidative stress-associated metabolites 5-oxoproline and benzoate. Changes in lean body mass were positively associated with changes the energy metabolites citrate (ρ=0.361, <i>p</i>=0.022) and phosphate (ρ=0.369, <i>p</i>=0.019). <b>Conclusion:</b> Findings suggest that EV metabolites change in response to physiological stress and reflect increased oxidative stress, energy metabolism, and fatty acid metabolism, which may provide early indicators of stress adaptations relevant for optimizing training and sustaining military performance.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysbiosis in PCOS: A Systematic Review of Microbiome Alterations Across Body Sites with GRADE Assessment of Evidence Quality.","authors":"Navjot Kaur, Nisha Yadav, Sarika Sachan, Priya Sharma, Preeti Khetarpal","doi":"10.1152/physiolgenomics.00072.2025","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00072.2025","url":null,"abstract":"<p><p>Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine-metabolic disorder that adversely affects reproductive, metabolic, and cardiovascular health in females, leading to menstrual irregularities and an increased risk of endometrial malignancies. Emerging research evidence suggests that the gut and extra gastrointestinal microbiome dysbiosis may play a significant role in the pathophysiology of PCOS. This systematic review aims to elucidate the microbiome dysbiosis patterns in PCOS patients compared to healthy controls. A systematic search was conducted across PubMed, Scopus, and Web of Science from inception until February 28^th, 2025, encompassing all original cross-sectional, cohort, or case-control studies that examined the gut, oral, blood, and lower genital tract (LGT) microbiomes of PCOS patients (cases) against healthy females (controls). Of the 4,377 studies identified, 64 were assessed for eligibility through full-text screening, and ultimately, 29 studies met inclusion criteria and were included into the systematic review. The results revealed inconsistent patterns in alpha and beta diversity, with reports of increased, decreased, or unchanged microbial diversity across studies. Key alterations were observed at different taxonomic levels, such as phylum, family, genus, and species. The most significant bacterial alterations include changes in the relative abundance of various bacterial taxa such as <i>Bacteroidetes</i>, <i>Firmicutes</i>, <i>Actinobacteria</i>, <i>Proteobacteria</i>, <i>Verrucomicrobia</i>, <i>Gammaproteobacteria</i>, <i>Fusobacteria</i>, <i>Eubacterium</i>, <i>Streptococcus</i>, <i>Paraprevotella</i>, <i>Tucibacter</i>, and <i>Tenericutes</i>. These findings indicate that complex dysbiotic microbial shifts may be involved in the pathogenesis of PCOS. As per the GRADE assessment, the quality of evidence is low for most of the studies. This systematic review supports the role of microbial dysbiosis in PCOS pathogenesis, however, additional research is required to elucidate these interactions to guide the development of therapeutic strategies in the future.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel locus and HbA1c: tracing pathophysiological links beyond diabetes.","authors":"Prasanth Puthanveetil","doi":"10.1152/physiolgenomics.00059.2025","DOIUrl":"10.1152/physiolgenomics.00059.2025","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"594-595"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic rewiring of microRNA networks in the brainstem autonomic control circuits during hypertension development in the female spontaneously hypertensive rat.","authors":"Alison Moss, Ankita Srivastava, Lakshmi Kuttippurathu, James S Schwaber, Rajanikanth Vadigepalli","doi":"10.1152/physiolgenomics.00136.2024","DOIUrl":"10.1152/physiolgenomics.00136.2024","url":null,"abstract":"<p><p>We describe global microRNA (miRNA) changes in the central autonomic control circuits during the development of neurogenic hypertension. Using the female spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto (WKY), we analyzed the dynamic miRNA expression changes in three brainstem regions-the nucleus of the solitary tract, caudal ventrolateral medulla, and rostral ventrolateral medulla-as a time series beginning at 8 wk of age before hypertension onset through to extended chronic hypertension. Our analysis yielded nine miRNAs that were significantly differentially regulated in all three regions between SHR and WKY over time. We collated computationally predicted gene targets of these nine miRNAs in pathways related to neuronal plasticity and autonomic regulation to construct a putative miRNA-target gene network involved in the development of neurogenic hypertension. We analyzed the dynamic correlations between the miRNAs and their putative targets to identify the regulatory interactions shifting between WKY and SHR. Comparing the results with previously published data in male SHR and WKY identified miRNA network dynamics specific to female SHR during hypertension development. Collectively, our results point to distinct rewiring of the miRNA regulatory networks governing angiotensin signaling and homeostasis, neuronal plasticity, and inflammatory processes contributing to the development of hypertension in female SHR.<b>NEW & NOTEWORTHY</b> Hypertension is the primary risk factor for cardiovascular complications and stroke. The microRNA expression changes in the central nervous system circuits driving hypertension development are understudied. Here, we show that microRNA-mediated regulatory networks are dynamically rewired during the development of high blood pressure phenotype by targeting key signaling pathways, neuronal plasticity, and inflammatory processes in a female rat model of human essential hypertension.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"575-593"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The skeletal muscle of aged male mice exhibits sustained growth regulatory transcriptional profile following glucocorticoid exposure compared with young males.","authors":"Grant R Laskin, Cynthia Vied, David S Waddell, Bradley S Gordon","doi":"10.1152/physiolgenomics.00083.2025","DOIUrl":"10.1152/physiolgenomics.00083.2025","url":null,"abstract":"<p><p>Excess glucocorticoids induce skeletal muscle myopathy by changing gene expression. Advanced age augments glucocorticoid-mediated muscle phenotypes, yet the transcriptional responses underlying those augmented phenotypes are unclear. The purpose of this study was to define the glucocorticoid-responsive transcriptome in young and aged muscle following both acute and more prolonged glucocorticoid treatment. Young (4-mo-old) or aged (24-mo-old) male mice were administered either an acute injection of dexamethasone (DEX) or vehicle or daily DEX or vehicle injections for 7 days. Muscles were harvested 6.5 h after the final or only injection. The tibialis anterior (TA) was selected for RNA sequencing analysis as DEX treatment lowered TA mass specifically in aged males. In silico analyses identified enriched pathways and transcription factors predicted to regulate DEX-sensitive genes. Acute DEX altered similar numbers of genes in young (950) versus aged males (913), although aged males had greater magnitudes of fold change. After 7 days of DEX treatment, aged muscle exhibited more DEGs compared with acute exposure (1,196 vs. 913), whereas young muscle exhibited fewer DEGs than after acute exposure (599 vs. 950). In aged males, glucocorticoid-sensitive genes were consistently enriched for growth regulatory processes across both time points, a pattern that was not evident in young males. Despite those age-associated transcriptional differences, the transcription factors predicted to regulate the glucocorticoid-sensitive genes were similar in young and aged males. These data expand our understanding into how aging modifies the transcriptional response to excess glucocorticoids in skeletal muscle.<b>NEW & NOTEWORTHY</b> Glucocorticoids promote mass loss in certain muscles with advanced age but not at younger ages. In a muscle whose mass is lost in response to elevated glucocorticoids only in advanced age in males, we show that glucocorticoids initiate a unique and exaggerated transcriptional profile after both acute exposure to the hormone and after prolonged treatment that is consistent with muscle atrophy. These findings expand our understanding of the effect primary aging has on glucocorticoid-induced atrophy in males.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"603-614"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144965050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping cardiac electrical abnormalities in rodents.","authors":"Ashish Kapoor, Peter A Doris","doi":"10.1152/physiolgenomics.00114.2025","DOIUrl":"10.1152/physiolgenomics.00114.2025","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"596-597"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144965074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological sex: why we should listen to genetics and lessons from race to guide precision medicine.","authors":"Jeremy W Prokop","doi":"10.1152/physiolgenomics.00065.2025","DOIUrl":"10.1152/physiolgenomics.00065.2025","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"598-602"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144965052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localization and quantification of <i>HDAC9</i> and <i>RGS2</i> expression in placenta during preeclampsia.","authors":"Megan A Opichka, M Christine Livergood, Kirthikaa Balapattabi, McKenzie L Ritter, Curt D Sigmund, Anne E Kwitek, Justin L Grobe, Jennifer J McIntosh","doi":"10.1152/physiolgenomics.00156.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00156.2024","url":null,"abstract":"<p><p>Preeclampsia is a multifaceted pregnancy-associated hypertensive disorder that poses a major threat to maternal and fetal health. Though the etiology is not fully understood, syncytiotrophoblast stress is postulated to be a major driver of maternal symptomology. We previously demonstrated that Regulator of G protein Signaling-2 (<i>RGS2</i>) expression is decreased in human preeclamptic placenta and has a transcriptional dependence on histone deacetylase 9 (<i>HDAC9</i>) in trophoblast cells. Further, experimental reductions of <i>Rgs2</i> expression in the mouse fetoplacental unit are sufficient to induce preeclampsia-like features, including placental stress, in C57BL/6J dams. Here we examined the hypotheses that <i>HDAC9</i> and <i>RGS2</i> are both expressed within syncytiotrophoblasts, that <i>HDAC9</i> and <i>RGS2</i> expression are positively correlated within these cells, and that expression of each is reduced within syncytiotrophoblasts during preeclampsia. <i>HDAC9</i> and <i>RGS2</i> mRNA were localized and quantified in syncytiotrophoblast cells of human placental samples from pregnancies with and without preeclampsia, using laser-capture microdissection and <i>in situ</i> hybridization methods. Expression of <i>Hdac9</i> and <i>Rgs2</i> were similarly localized in the syncytiotrophoblast of mouse placenta. Throughout, <i>HDAC9/Hdac9</i> and <i>RGS2/Rgs2</i> were detected and positively correlated in syncytiotrophoblasts, but expression of each was substantially reduced during preeclampsia. These results document reduced <i>HDAC9</i> and <i>RGS2</i> expression specifically in syncytiotrophoblast cells during preeclampsia and provide additional correlative support of HDAC9-mediated control of <i>RGS2</i> expression within this population of trophoblasts. This work provides rationale to further explore cell-specific disruptions in <i>HDAC9</i> and <i>RGS2</i> control and function as a cause of syncytiotrophoblast stress and ultimately preeclampsia.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Microbiome Shaping Cancer Development, Progression, and Therapeutic Response.","authors":"Rana Salihoglu","doi":"10.1152/physiolgenomics.00091.2025","DOIUrl":"10.1152/physiolgenomics.00091.2025","url":null,"abstract":"<p><p>The human microbiome is emerging as a key regulator of cancer biology, modulating tumor development, immune dynamics, and therapeutic responses across diverse malignancies. In this review, recent insights are synthesized regarding how microbial communities (bacterial, fungal, and viral) shape oncogenic signaling, immune checkpoint blockade (ICB) efficacy, and metabolic reprogramming in lung, pancreatic, colorectal, breast, cervical, melanoma, and gastric cancers. Mechanistic links between microbial metabolites, intratumoral colonization, and host immune phenotypes are highlighted proposing that the microbiome constitutes a programmable axis within the tumor immune-metabolic ecosystem. Drawing on multi-omics integration and translational studies, a shift from associative profiling toward causal, spatially resolved, and intervention-ready frameworks is proposed. This perspective positions the microbiome not as a passive bystander, but as a co-evolving participant in tumor progression and treatment response, with the potential to reshape diagnostics, prognostics, and therapeutic strategies in precision oncology.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144965131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}