American journal of physiology. Regulatory, integrative and comparative physiology最新文献

{"title":"Microglia mediate sex-dependent memory deficits in pelvic pain.","authors":"Afrida Rahman-Enyart, Habib Jmii, Shivesh Ghura, Ryan E Yaggie, Anthony J Schaeffer, David J Klumpp","doi":"10.1152/ajpregu.00080.2026","DOIUrl":"10.1152/ajpregu.00080.2026","url":null,"abstract":"<p><p>Chronic pain is associated with memory deficits clinically and in animal models. Similarly, interstitial cystitis/bladder pain syndrome (IC/BPS) afflicts patients with severe chronic pelvic pain and urinary dysfunction as well as cognitive effects, including anxiety/depression and patient-reported memory deficits. In a genetic model of IC/BPS, mice deficient for the lipase acyloxyacyl hydrolase (AOAH) mimic key symptoms, including rodent correlates of chronic pelvic pain and anxiety/depression. Recently, we observed that pelvic pain of female AOAH-deficient mice is associated with microglial activation in the prefrontal cortex and paraventricular nucleus, and pain is dependent upon microglia. Because chronic pain is associated with memory deficits and microglia support learning and memory, we hypothesized that chronic pelvic pain is associated with memory deficits in IC/BPS models. In the hippocampus, we observed microglia in the dentate gyrus of AOAH-deficient females that exhibited a hyper-ramified morphology with increased branching, number of endpoints, and process length. In contrast, dentate gyrus microglia of AOAH-deficient males had an amoeboid morphology. Using specific memory tests, female AOAH-deficient mice exhibited deficits in both spatial and recognition memory relative to wild-type controls, whereas males had a modest phenotype. Depleting microglia pharmacologically with an antagonist of colony-stimulating factor-1 receptor resolved the deficit in recognition memory but did not improve spatial memory in females and had no significant effect in males. Overall, these data suggest a role for microglial modulation of cognitive function in pelvic pain that is sex-specific and thus identify a potential target for treating cognitive symptoms in female patients.<b>NEW & NOTEWORTHY</b> Interstitial cystitis/bladder pain syndrome (IC/BPS) afflicts patients with debilitating pelvic pain, voiding dysfunction, and cognitive deficits, but effective therapies are lacking. Using acyloxyacyl hydrolase-deficient mice as a genetic model of IC/BPS, we previously showed that microglia mediate pelvic pain and now show that microglia mediate sex-specific memory deficits. These findings identify microglia as potential therapeutic targets for pain and cognitive dysfunction in IC/BPS.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R65-R74"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific cytokine and signaling responses to acute high-intensity interval exercise in recreationally active young adults.","authors":"Kayleigh M Beaudry, Julian C Surdi, Jessica L Dowling, Vito A Pipitone, Michaela C Devries","doi":"10.1152/ajpregu.00285.2025","DOIUrl":"10.1152/ajpregu.00285.2025","url":null,"abstract":"<p><p>High-intensity interval exercise (HIIE) induces transient increases in reactive oxygen species (ROS) and inflammatory mediators that drive skeletal muscle adaptations. Sex influences oxidative stress and inflammation, yet the interplay between sex and exercise-induced signaling remains incompletely understood. The purpose of this study was to investigate sex differences in markers of inflammation, oxidative stress, and antioxidant status at rest and following acute HIIE in young, healthy males and females matched for aerobic fitness. Twenty-four participants (12/sex) underwent muscle biopsies and blood sampling at rest and immediately postexercise (10 × 1 min at 90% HRmax). Skeletal muscle was analyzed for oxidative stress [NADPH oxidase 2 (NOX2), 4-hydroxynonenal (4HNE), total protein carbonylation via oxyblot, p38 MAPK], antioxidant enzymes [thioredoxin 1 (TRX1), glutathione reductase (GR), and glutathione peroxidase 1 (GPX1)], and cytokine content (array), and plasma was analyzed for inflammatory markers (IL-6 and TNFα) and antioxidant status. Acute HIIE increased plasma IL-6 and TNFα and decreased total antioxidant status with no differences between sexes. Basally, females had higher phosphorylation of p38 MAPK and elevated growth- and repair-associated cytokines [insulin-like growth factor binding protein 1 and 3 (IGFBP-1/3), tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1/2), transforming growth factor- β2/3 (TGF-β2/3), FGF-7/9, macrophage colony-stimulating factor (M-CSF), and stromal cell derived factor (SDF)-1], whereas males had higher basal proinflammatory cytokines (IL-1α, IL-13, IP-10, and oncostatin M). Following exercise, males showed a greater upregulation of growth and repair mediators, whereas females had broader suppression of inflammatory and chemotactic factors. No sex differences were observed in muscle oxidative stress markers or antioxidant content. These findings indicate that although acute HIIE elicits comparable plasma inflammatory responses in males and females, underlying skeletal muscle cytokine signaling and adaptive potential are sex-specific, emphasizing the need to consider sex in exercise physiology studies. <b>NEW & NOTEWORTHY</b> We investigated whether sex influenced the inflammatory or oxidative stress response to acute exercise. Although no differences were observed in plasma markers, in skeletal muscle, females had elevated growth- and repair-associated cytokines, whereas males had higher proinflammatory cytokines at rest. Following exercise, males had greater upregulation of growth and repair mediators, whereas inflammatory and chemotactic factors were suppressed in females. The sex divergence in skeletal muscle cytokines may have implications postexercise signaling and chronic adaptations.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R102-R112"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impacts of common chronic disease on autophagy and cellular stress during exertional heat stress in peripheral blood mononuclear cells of older males.","authors":"James J McCormick, Kelli E McCormick, Nicholas Goulet, Kate P Hutchins, Glen P Kenny","doi":"10.1152/ajpregu.00115.2026","DOIUrl":"10.1152/ajpregu.00115.2026","url":null,"abstract":"<p><p>Autophagy plays a key role in maintaining cellular function during acute physiological stress, including exercise and heat stress. Although autophagic function declines with increasing age, the extent to which age-related chronic disease (e.g., hypertension and type 2 diabetes) influences autophagic responses during exertional heat stress remains unknown. Older males (means [SD]: aged 70 [5] yr) without (<i>n</i> = 10) and with hypertension (<i>n</i> = 10) or type 2 diabetes (<i>n</i> = 10) performed high-intensity semirecumbent cycling (70% of maximal oxygen consumption) in temperate (25°C, 15% relative humidity) or hot (40°C, 15% relative humidity) ambient conditions. Mean body temperature (rectal and skin) was measured throughout, whereas proteins associated with autophagy and cellular stress were assessed in peripheral blood mononuclear cells before and after exercise and following 6 h of seated recovery via Western blot. Mean body temperature increased similarly across all groups at the end of exercise in temperate (+0.40°C) and hot (+0.84°C) conditions. Indices of autophagy, including LC3-II, were greater in the healthy compared with both chronic disease groups at end-exercise and throughout the 6 h recovery in temperate conditions. However, between-group differences in LC3-II levels were less pronounced following heated exercise (<i>P</i> = 0.03), and p62 content was lower in individuals with hypertension and type 2 diabetes. Although apoptotic responses were similar across groups, disease-associated blunting of IL-6 responses may contribute to the observed differential levels in autophagic regulation in older males. Therefore, our findings reveal altered autophagic responses to exertional heat stress in older males with chronic health conditions, which may have implications for altered cellular vulnerability during exertional heat stress.<b>NEW & NOTEWORTHY</b> We show that age-related impairments in exercise-induced autophagic regulation are more pronounced in older adults with hypertension and type 2 diabetes. Performing the same high-intensity exercise in the heat led to additional reductions in autophagic regulation in these individuals. Taken together, our findings provide new insights into cellular mechanisms that may underlie increased vulnerability to exertional heat stress in older adults, both with and without common chronic diseases.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R75-R85"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148209806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intersectional expression of <i>Foxp2</i> and <i>Grp</i> identifies cold-activated parabrachial neurons.","authors":"Fillan S Grady, Mya L Leuang, Silvia Gasparini, Haidong Zhu, Joel C Geerling","doi":"10.1152/ajpregu.00133.2026","DOIUrl":"10.1152/ajpregu.00133.2026","url":null,"abstract":"<p><p>The parabrachial nucleus (PB) contains many neuronal subpopulations, including a cold-activated subset that relays thermosensory information to the forebrain. Although these neurons are part of the <i>Atoh1</i>-derived PB macropopulation, their precise genetic identity has remained unclear, limiting cell-type-specific investigation of cold-defense circuitry. In this study, we show that this subpopulation is selectively identified by coexpression of <i>Foxp2</i> and <i>Grp</i>. This intersectional molecular identity suggests a practical strategy for selectively targeting cold-activated PB neurons, enabling cell-type-specific dissection of the circuit mechanisms underlying autonomic and behavioral cold-defense responses.<b>NEW & NOTEWORTHY</b> Cold-activated neurons in the PB relay thermosensory signals that drive autonomic and behavioral cold-defense responses, but their molecular identity has remained unclear. Here, we show that these neurons are selectively identified by coexpression of <i>Foxp2</i> and <i>Grp</i>, a combination that distinguishes them from surrounding PB neurons. This intersectional genetic identity provides a practical strategy for selectively targeting this population, enabling future mechanistic studies of thermoregulatory circuits.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R44-R51"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13467074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired microvascular reactivity in post-COVID-19 syndrome is independent of cardiorespiratory fitness.","authors":"Franca Thiel, Rogerio N Soares, Raphael S Peter, Siri Göpel, Alexandra Nieters, Dietrich Rothenbacher, Winfried V Kern, Andreas M Nieß, Felipe Mattioni Maturana","doi":"10.1152/ajpregu.00050.2026","DOIUrl":"10.1152/ajpregu.00050.2026","url":null,"abstract":"<p><p>Current evidence demonstrates that patients who suffer from long-term SARS-CoV-2 symptoms [i.e., post-COVID-19 syndrome (PCS)] often present muscle fatigue and dyspnea. This is discussed to be a result of vascular dysfunction and oxidative stress triggered by the infection. However, its effects on the microvasculature remain unknown. Sixty-two participants (61.3% women) were recruited [50.0 ± 11.8 yr, body mass index (BMI) 27.6 ± 5.3 kg·m^-2, maximal oxygen uptake (V̇o_2max) 26.2 ± 9.4 mL·kg^-1·min^-1] from the epidemiology and clinical characteristics of PCS (EPILOC) phase 2 study. Participants were divided into either a case group (patients with new or prolonged symptoms and impaired general health or work ability compatible with persistent PCS) or a control group (symptom-free age-sex-matched patients with uneventful recovery after COVID-19). The brachial-ankle pulse wave velocity (baPWV) was assessed via the BOSO-ABI system 100. To evaluate the microvascular function, a tissue oxygen saturation reperfusion rate assessment using near-infrared spectroscopy was performed on the <i>flexor digitorum superficialis</i> muscle. No significant statistical differences were observed between the case and control groups in age, BMI, and baPWV (<i>P</i> > 0.05). The control group achieved a greater V̇o_2max than the case group (<i>P</i> = 0.02). After adjusting for V̇o_2max, a significant effect of group [<i>F</i>(1,52) = 5.28, <i>P</i> = 0.026] in microvascular function was observed, with the case group presenting lower values than the control group (β = -0.53, <i>P</i> = 0.02). No a priori power calculation was performed-post hoc sensitivity analysis indicated a minimum detectable effect of Cohen's <i>d</i> = 0.72, and secondary outcomes should be interpreted cautiously. Our results indicate a reduced microvascular function in patients with PCS, as compared with the control group. Such impairment may be linked to the prolonged symptoms experienced by patients, causing capillary flow disturbances and, subsequently, limiting muscle oxygen uptake.<b>NEW & NOTEWORTHY</b> We provide objective evidence that skeletal muscle microvascular reactivity is significantly impaired in patients with post-COVID-19 syndrome (PCS) compared with recovered controls. Using near-infrared spectroscopy, we demonstrate that this blunted microvascular reperfusion persists even after adjusting for maximal oxygen uptake (V̇o_2max). These findings suggest that microvascular dysfunction is a distinct pathophysiological feature of PCS that may contribute to exercise intolerance and fatigue, independent of physical deconditioning.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R664-R672"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential branched-chain amino acid metabolism in tissues of tumor-bearing male mice.","authors":"Miriam Zerrouk, Luca J Delfinis, Christopher G R Perry, Olasunkanmi A J Adegoke","doi":"10.1152/ajpregu.00320.2025","DOIUrl":"10.1152/ajpregu.00320.2025","url":null,"abstract":"<p><p>Cancer cachexia is a multifactorial syndrome characterized by involuntary loss of skeletal muscle and adipose tissue that is often resistant to nutritional support. The branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) stimulate protein synthesis, yet BCAA-targeted therapies have yielded limited clinical benefit and inconsistent results. This might be related to the altered metabolism of BCAA in cachexia. In this study, a C26 tumor allograft mouse model was used to examine how tumor burden alters BCAA metabolism across tumor tissue, liver, kidney, adipose tissue, and skeletal muscle. Tumor tissue at 4 wk exhibited higher BCAA levels and elevated branched-chain α-keto acid dehydrogenase (BCKD) activity compared to samples collected at 2 wk. At 4 wk, skeletal muscles from tumor-bearing mice showed reduced BCAA concentrations relative to controls. In contrast, liver and adipose tissue did not demonstrate uniform reductions in BCAA content, indicating tissue-specific metabolic responses. Multiple peripheral tissues also displayed lower expression of the L-type amino acid transporter 1 (LAT1) and alterations in downstream mechanistic target of rapamycin complex 1 (mTORC1) signaling. Notably, the soleus muscle maintained elevated phosphorylated S6 (P-S6) levels despite reduced BCAA availability, suggesting muscle-specific adaptations. These findings demonstrate distinct tumor and peripheral tissue alterations in BCAA handling in C26 tumor-bearing mice. The observed changes in BCAA metabolism may underlie the limited success of BCAA-based interventions in cachexia and highlight the need for therapies that address both tumor and host metabolism.<b>NEW & NOTEWORTHY</b> This is the first study to profile branched-chain α-keto acid (BCKA) levels together with branched-chain amino acid (BCAA) metabolism across multiple tissues in a cancer cachexia model. Tumor progression was associated with higher BCAA levels. Some peripheral tissues showed BCAA depletion, and all peripheral sites exhibited reduced expression of the L-type amino acid transporter 1 (LAT1). These tissue-specific adaptations reveal systemic metabolic reprogramming and may explain the limited efficacy of BCAA-based therapies.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R694-R714"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expiratory loading modulates the quadriceps muscle pump-induced venous return during rhythmic isometric exercise.","authors":"Kana Shiozawa, Haruna Kondo, Natsuki Seo, Koji Ishida, Shigehiko Ogoh, Keisho Katayama","doi":"10.1152/ajpregu.00052.2026","DOIUrl":"10.1152/ajpregu.00052.2026","url":null,"abstract":"<p><p>During exercise, venous return is enhanced by the skeletal muscle pump. Expiratory loading increases intra-abdominal pressure, which may impede venous return from the lower limbs. However, its effect on venous return mediated by the quadriceps muscle pump remains unclear. The purpose of this study was to elucidate the effect of expiratory loading on venous return facilitated by the quadriceps muscle pump. Healthy young participants performed rhythmic unilateral isometric knee-extension exercise of the right quadriceps (10% maximal isometric voluntary contraction; 2 s contraction/2 s relaxation), and data were successfully obtained from 12 participants. Controlled breathing (breathing frequency: 15 breaths/min; inspiratory-to-expiratory ratio: 1:1; tidal volume: twice the resting tidal volume) was performed with and without expiratory load. The expiratory phase was synchronized with the contraction phases. Expiratory load was adjusted to produce a mouth pressure of +20 cmH₂O during expiration. Quantity of blood flow in the right femoral vein ([Formula: see text]fv) was continuously measured using Doppler ultrasound. No significant differences were observed in the increases in force and electromyography during expiration between the nonloading and loading conditions. Quadriceps muscle contraction increased [Formula: see text]fv; however, the contraction-induced increase was smaller (<i>P</i> = 0.005) with expiratory loading (497.6 ± 350.5 mL/min, means ± standard deviation) than without expiratory loading (694.8 ± 358.9 mL/min). These findings suggest that increased expiratory loading may partly reduce the effectiveness of the quadriceps muscle pump in facilitating venous return during light-intensity exercise.<b>NEW & NOTEWORTHY</b> This study examined whether expiratory loading affects venous return generated by the quadriceps muscle pump during light-intensity exercise. Young adults performed rhythmic unilateral isometric knee extension under controlled breathing with or without expiratory load. Femoral venous blood flow increased during muscle contraction; however, the increase was significantly attenuated with expiratory load. These findings indicate that increased expiratory loading may reduce the effectiveness of the quadriceps muscle pump in enhancing venous return.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R639-R651"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac autonomic regulation across the menstrual cycle is highly individual: evidence from phase-aligned cyclic generalized additive mixed models.","authors":"Marcelle Schaffarczyk, Lucie Rückemann, Billy Sperlich, Thomas Gronwald","doi":"10.1152/ajpregu.00028.2026","DOIUrl":"10.1152/ajpregu.00028.2026","url":null,"abstract":"<p><p>Cardiac autonomic regulation, indexed by heart rate variability (HRV), is hypothesized to fluctuate across the menstrual cycle. Empirical findings remain inconsistent, likely due to sparse phase-based sampling and limited consideration of interindividual variability. This study examined cyclic HRV trajectories using longitudinal monitoring and phase-aligned cycle time scaling (PACTS) to distinguish population-level from individual-specific patterns and to evaluate associations with well-being. Daily HRV (smartphone photoplethysmography) and well-being were collected in 21 naturally cycling women. Cycle time was aligned using PACTS, with ovulation set to 0 and follicular and luteal phases rescaled to a common -1 to +1 interval. Vagally mediated HRV was indexed using log-transformed root mean square of successive differences [ln(RMSSD)] and the coefficient of variation (CV) of ln(RMSSD), calculated from a centered rolling window. Cyclic generalized additive mixed models separated population-level smooths from participant-specific cyclic deviations. Associations between well-being (sleep quality, stress, fatigue, and muscle soreness) and HRV were examined using mixed-effects models distinguishing within- and between-person effects. For ln(RMSSD), the population-level cyclic trajectory was flat and nonsignificant, whereas participant-specific cyclic deviations were significant, indicating pronounced interindividual heterogeneity despite a stable average pattern. Similar results were observed for CV ln(RMSSD). Within-person analyses showed that poorer sleep quality, higher stress, and greater fatigue were associated with lower ln(RMSSD), whereas between-person differences were unrelated to mean HRV. Increases in stress and muscle soreness were associated with modest increases in HRV fluctuations. When menstrual cycle timing is precisely aligned to ovulation, vagally mediated HRV shows no consistent population-level rhythm but marked individual-specific dynamics, strongly modulated by day-to-day well-being.<b>NEW & NOTEWORTHY</b> Using dense longitudinal monitoring and ovulation-aligned cycle scaling, this study shows that vagally mediated heart rate variability does not follow a consistent population-level rhythm across the menstrual cycle. Instead, cardiac autonomic regulation exhibits pronounced individual-specific cyclic patterns and is strongly influenced by day-to-day fluctuations in subjective well-being. These findings help explain previously inconsistent menstrual cycle effects on heart rate variability.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R623-R630"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human body surface area scales linearly with height and mass and is largely independent of body composition: a 3-D laser scanning and body composition study.","authors":"David J Jörg, Samantha Kennedy, Peter Kotanko, Steven B Heymsfield","doi":"10.1152/ajpregu.00065.2026","DOIUrl":"10.1152/ajpregu.00065.2026","url":null,"abstract":"<p><p>Body surface area is fundamental to clinical medicine, underpinning drug dosing in oncology and pediatrics and normalizing physiological variables such as cardiac output and glomerular filtration rate. Despite over a century of use, most body surface area equations adopt power-law forms derived empirically with little explicit biological justification, and whether body composition data improve prediction has remained unclear. Here, we used high-resolution three-dimensional laser scanning to measure body surface area and dual-energy X-ray absorptiometry to measure body composition in 106 healthy adults spanning a wide range of ages, body sizes, and demographic features. Notably, simple linear models predicted body surface area as accurately as complex power-law or body composition-aware formulations: according to sex-specific linear regression, body surface area changes by about 100-115 cm² per kilogram of body mass and about 70-80 cm² per centimeter of body height, with no substantial improvement from including lean, fat, or bone mineral mass as separate predictors within the anthropometric range studied. These findings suggest that the long-standing reliance on allometric power-law equations reflects historical convention rather than biological necessity, and that simple linear formulas may suffice for clinical body surface area estimation within the range of body sizes studied here.<b>NEW & NOTEWORTHY</b> Using three-dimensional body scanning and body composition measurements, we show that body surface area scales linearly with height and body mass and is largely independent of how mass is distributed between lean, fat, and bone tissue. Simple linear formulas perform as well as the traditional power-law equations used in clinical practice.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R565-R570"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose simulated galactic cosmic radiation exposure after hindlimb unloading has long-term impact on skeletal muscle metabolic proteins in female mice.","authors":"Matthew Martone, Brian A Irving, Guillaume Spielmann, Neil M Johannsen, Matthew M Robinson, Jeffery C Chancellor, Heather C M Allaway","doi":"10.1152/ajpregu.00014.2026","DOIUrl":"10.1152/ajpregu.00014.2026","url":null,"abstract":"<p><p>Spaceflight stressors, including microgravity-induced unloading and galactic cosmic radiation (GCR), acutely disrupt mitochondrial function and contribute to skeletal muscle atrophy. The long-term remodeling of skeletal muscle following combined unloading and radiation exposure remains poorly understood. We investigated protein abundance changes 9-mo postexposure to combined unloading and radiation exposure. Female, 6-mo-old, C57Bl/6J mice underwent 5 days of hindlimb unloading (HU) or weight-bearing (WB) conditions, followed by 0, 0.5, or 1.5 Gy of simulated GCR exposure using the simplified 5-ion beam exposure (simGCRsim) (<i>n</i> = 5/group). The gastrocnemius muscle was collected after 9 mo of WB and analyzed by data-independent acquisition mass spectrometry. Differentially abundant proteins were identified and evaluated using pathway enrichment analyses. WB mice exposed to 0.5 Gy exhibited increased abundance of electron transport system proteins and mitochondrial transport proteins, suggesting increased mitochondrial activity relative to control mice. HU mice exposed to 0.5 Gy displayed decreased glycolytic proteins, increased reliance on oxidative pathways, and reduced antioxidant proteins (glutaredoxins and peroxiredoxin) compared with WB0.5. In HU mice, a higher radiation dose (HU1.5 vs. HU0.5) led to the downregulation of 26S proteasome subunits and the upregulation of peroxisomal antioxidant, tricarboxylic acid cycle, and β-oxidation proteins, indicating dose-dependent mitochondrial adaptations. Long-term muscular remodeling after simGCRsim exposure is influenced by both muscle-loading status and radiation dose, with prolonged shifts toward oxidative metabolism and altered protein quality control persisting months after exposure. These findings provide new insights into skeletal muscle adaptation to spaceflight stressors and have important implications for astronaut health during and after long-duration missions.<b>NEW & NOTEWORTHY</b> Acute simGCRsim exposure causes changes in metabolic and mitochondrial protein abundance that are observable after 9 mo. Weight-bearing and unloaded muscle show unique metabolic protein profiles, with unloaded muscle experiencing reduced expression of glycolytic proteins relative to weight-bearing muscle after 9 mo. Significant dose-dependent response to acute simGCRsim exposure, with higher doses having more profound effects on metabolic and antioxidant protein abundance.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R582-R589"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}