Physiological Reports最新文献

Arterionephrosclerosis is characterized by focal global glomerulosclerosis (FGGS), which is a constant feature of aging and hypertension. FGGS begins as normal-appearing glomeruli that undergo tuft contraction (TC) and progress to global glomerulosclerosis (GGS). Kidney tissue from 26 hypertensive and 25 age-matched non-hypertensive patients was analyzed for glomerular volume and for podocyte number using a WT1 antibody. Immunohistochemistry (IHC) was employed to detect the senescence-related biomarkers p16, p21, β-galactosidase (GLB1), and 5-nucleotidase (CD73). Antibodies against annexin 3 (ANXA3), cytokeratin 7, and CD44 were used to evaluate parietal epithelial cell (PEC) activation. The relationships between biomarkers, hypertension, TC, and GGS were quantitatively analyzed. With TC, podocyte numbers decreased in association with increased glomerular p16, p21, GLB1, and CD73 expression. With TC, WT1, CK7, and CD44-expressing PEC increased. TC and GGS expressed senescent markers in hypertensive and non-hypertensive kidneys; however, the frequency of TC (p < 0.01) and GGS (p < 0.001) was greater in hypertensive kidneys, and glomerular expression of senescence markers was correspondingly higher. Additionally, greater p16 and p21 expression was observed in the tubular atrophy of hypertension. As FGGS developed, podocyte depletion, cellular senescence markers, and PEC activation were associated with TC and increased with hypertension.

Prenatal exercise decreases offspring adiposity, but it is uncertain whether this relationship is present in offspring exposed to obesity in utero. We aimed to determine whether exercise during pregnancy reduces infant cellular and whole-body adiposity in offspring born to women with obesity. This is a sub-analysis of a randomized controlled trial, where women were randomized to supervised exercise or control for ~24 weeks during pregnancy. Exercise FITT-V metrics (frequency, intensity, time, type, and volume) were collected. Infant mesenchymal stem cells (MSCs) (healthy weight [n = 16], obesity [n = 21]) were adipogenically differentiated and stained for lipid content. Infant body composition was measured at 1 month of age via skinfold. Among women randomized to control, maternal BMI influenced infant adiposity; infants exposed to obesity had higher body fat percentage (p = 0.02). Birthweight was negatively correlated with infant body fat; offspring with lower birthweight had higher body fat (R² = 0.38, p = 0.03). Maternal weekly exercise volume trended toward negative association with infant body fat (R² = 0.33, p = 0.06) and lipid content (R² = 0.21, p = 0.06). For infants born to women with obesity, exercise during pregnancy helps reduce adiposity.

Asthma diagnosis can be challenging in children. Spirometry is highly effort-dependent and often normal in early disease. Forced oscillation technique (FOT) is an alternative to spirometry and is performed during tidal breathing. We investigated the feasibility of FOT with fewer acquisitions than suggested by technical standards in a pediatric outpatient care setting. We also studied the influence of tidal breathing patterns on FOT indices. Finally, the clinical utility of FOT was compared with spirometry. Ninety-five children aged 3-12 years performed FOT with single-frequency mode of 8 Hz (Resmon Pro, ResTech, Italy) during initial asthma assessment or follow-up. School-aged children (n = 61) also performed spirometry. In preschool age (<6 years), 94% managed one and 74% managed two approved FOT acquisitions, whereas in school-age 100% and 92% managed correspondingly. Reasonable agreement between two device-approved FOT measurements was found. No difference in FOT values was found with spontaneous higher respiratory rates or tidal volumes. Bronchodilation responses measured with FOT, but not spirometry, were associated with ongoing anti-inflammatory asthma medication. FOT with an integrated quality control was highly feasible in children 3-12 years. Reasonable agreement between two device-approved acquisitions was found suggesting one measurement might suffice. Deviations from normal tidal breathing had little influence on FOT results.

Slower oxidative fibers are more resistant to eccentric contraction (ECC)-induced muscle damage than fast-twitch glycolytic fibers, but the mechanisms remain unclear. This study investigated the roles of the exercise-inducible PGC-1α isoform PGC-1α-b and utrophin in protecting against ECC-induced damage. ECCs were induced by supramaximal electrical stimulation of the left triceps surae in C57BL/6N wild-type (WT), PGC-1α-b transgenic (Tg), utrophin knockout (Utrn KO), and PGC-1α-b Tg/Utrn KO mice. Although the proportion of fast-type myosin heavy chain (MyHC) IIb in the gastrocnemius muscle was modestly lower in PGC-1α-b Tg and PGC-1α-b Tg/Utrn KO mice than in WT and Utrn KO mice, MyHC IIb remained the predominant isoform. At 3 days post injury (dpi), WT and Utrn KO mice exhibited reduced maximum isometric torque (MIT), Evans blue dye (EBD) staining in MyHC IIb-positive fibers, and calpain-1 activation. In contrast, PGC-1α-b Tg and PGC-1α-b Tg/Utrn KO mice showed substantial MIT recovery at 1 dpi and minimal EBD uptake and calpain-1 activation at 3 dpi. PGC-1α-b Tg muscles also preserved excitation-contraction coupling proteins and displayed increased mitochondrial markers and integrin α7B expression. Together, our findings suggest that PGC-1α-b confers resistance to ECC-induced muscle damage through a Utrn-independent mechanism.

High-fat diet (HFD) is a cardiovascular risk factor that may disproportionately affect women compared to men. HFD alters perivascular adipose tissue (PVAT), which surrounds arteries and regulates vascular function. This study investigated the sex-specific effects of HFD on PVAT-mediated vascular dysfunction. Male and female Sprague-Dawley rats were fed a normal chow diet (NCD) or HFD for 16 weeks. Thoracic aortic PVAT was isolated, and PVAT adipokine expression and inflammatory markers were measured. We then assessed PVAT-conditioned media effects on vasodilation, endothelial oxidative stress, and endothelial nitric oxide (NO) synthase. PVAT-conditioned media from HFD female but not male rats impaired acetylcholine-induced vasodilation in mesenteric arteries; however, it did not increase oxidative stress or decrease endothelial NO synthase activation in rat endothelial cells in vitro. PVAT from HFD female rats had higher CD68 expression and acetyl-NF-κB/NF-κB ratio than PVAT from NCD female rats. Overall, HFD caused a greater PVAT-induced impairment in vasodilation in female as compared to male rats, which aligns with the heightened cardiovascular risk in women consuming a HFD.

The prevalence and incidence of Crohn's disease (CD) in pediatric populations have been steadily increasing. Growing evidence suggests that gut microbiomal community differences play a critical role in the pathogenesis of CD. Additionally, the clinical course of patients with CD is unpredictable, making treatment decisions challenging. We investigated the fecal microbiome of newly diagnosed, treatment-naïve pediatric CD patients (n = 43) compared to age- and sex-matched controls with other functional gastrointestinal disorders (n = 139). We also correlated microbial changes with CD disease activity, measured by the Pediatric Crohn's Disease Activity Index (PCDAI). Our results showed that microbial richness and diversity were significantly lower in CD patients. Furthermore, taxonomic analysis revealed an enrichment in pro-inflammatory bacteria (Fusobacteria and Proteobacteria) and depletion in favorable bacteria (Firmicutes and Verrucomicrobia). Higher PCDAI scores were linked to the enrichment of genera harboring pro-inflammatory taxa (Hungatella and Veillonella) and decreased abundance of genera harboring protective taxa (Lachnospiraceae). Our study underscores the potential of fecal microbiome profiling as an effective tool for understanding CD pathogenesis, identifying microbial biomarkers, and predicting disease activity for treatment response. This, in turn, can help to improve personalized treatment and management strategies in pediatric CD.

Siberian huskies (SH) and Alaskan huskies (AH), sharing ancestry with ancient sled dogs, were hypothesized to achieve similar skeletal muscle (SM) mitochondrial respiration capacities and densities through endurance training. High-resolution respirometry of SM biopsies from SH and AH during off-season (5 SH, 4 AH) and racing-season (5 SH, 7 AH) revealed a striking increase in mass-specific succinate-linked mitochondrial complex II (CII) activity during racing-season, in both SH (+75%) and AH (+129%). These increases were accompanied by increased protein content in SM for both SH (+37%) and AH (+56%). Elevated CII respiratory capacity can potentially reflect increased fatty acid utilization. NADH-linked complex I (CI) respiration increased significantly only in AH (+35%), which also, unlike SH, exhibited significantly elevated citrate synthase activity (+270%). Both groups showed reduced protein-specific residual oxygen consumption during racing-season (SH: -45%, AH: -48%) and increased reactive oxygen species production. Together, these changes point to more efficient mitochondria with minimized energy loss in raced dogs. A minimally invasive sampling approach was validated, using NSAIDs, local anesthesia, light oral sedation, a micro biopsy gun, and individualized environments to minimize distress. This secured good animal welfare and provided a practical method for field-based or repeated SM biopsies without general anesthesia.

Mathematical models are essential for understanding oxygen transport and utilization during metabolic transitions. An electrical analogy concept proposed that exponential PO₂ transients arise from interaction between oxygen storage capacitance and transport conductances, but lacked explicit circuit representation limiting quantitative predictions and experimental testing. We developed an explicit electrical circuit model with discrete resistive and capacitive components in physiologically defined topology to generate testable predictions for interstitial PO₂ transition dynamics during rest-work transitions in skeletal muscle. Circuit topology was constructed based on established physiological relationships in rat spinotrapezius muscle. The model equated oxygen partial pressure to voltage, oxygen flux to current, delivery and metabolic barriers to resistances, and tissue oxygen storage to capacitance. The model predicted that transition time constants should equal the product of capacitance and equivalent circuit resistance. Predictions were validated using interstitial PO₂ measurements during rest-work-rest transitions. The model successfully predicted asymmetric transition kinetics, with time constant ratios matching steady-state PO₂ ratios. Application to young (3-month) and old (23-month) rats quantified age-related changes: 2.5-fold higher delivery resistance in old muscle with compensatory 5.4-fold metabolic resistance reduction during exercise versus 3.1-fold in young muscle. An explicit, validated electrical circuit model confirmed that PO₂ transition kinetics are governed by capacitance-resistance interactions and quantitatively separated delivery versus metabolic limitations in aging muscle.

Cardiac fibrosis represents a consequence of hypertensive heart disease and is associated with ventricular dysfunction, arrhythmias, and mortality. Arginine vasopressin (AVP) promotes myofibroblast proliferation and collagen synthesis through V1a receptors. While hepatic studies suggest that AVP deficiency attenuates fibrosis, its cardiac impact remains unclear. This study evaluated the effects of AVP deficiency induced by neurointermediate pituitary lobectomy (NIL) and pharmacological V1a/V2 blockade with conivaptan (CV) in rats with fibrosis from abdominal aortic stenosis (AAC). Wistar rats were divided into seven groups with 10 animals each. Clinical variables and histopathology (H&E, Masson's trichrome, picrosirius red) were assessed. ANOVA, Fisher and Mantel-Cox tests were applied. The Fibrosis (F) group developed hypertrophy, hypertension, higher arrhythmia risk and increased fibrosis. In contrast, F+NIL and F+CV showed blood pressure and cardiac morphology comparable to controls, reduced arrhythmia risk and significantly less fibrosis. Histologically, F+NIL achieved partial regression, whereas F+CV nearly normalized tissue architecture. In conclusion, AVP deficiency or receptor blockade decreases and reverses AAC-induced fibrosis, improving hemodynamic, electrical, and structural outcomes. V1a/V2 blockade emerges as a potential therapeutic strategy.

High-altitude (HA) exposure induces cardiovascular, respiratory, and metabolic adjustments that often impair exercise performance. These physiological responses depend on hypoxic severity, exposure duration, and individual susceptibility. Although full acclimatization generally requires about 7 days, early adaptations can emerge within the first 72 h. This study aimed to characterize these early responses and to evaluate the potential of mathematical modeling to predict HA-related exercise performance decline. Nine healthy volunteers (age: 24.4 ± 3.3; weight: 63.7 ± 11.8; height: 169.4 ± 8.4; female: 44%) completed maximal cardiopulmonary exercise tests under three conditions: at sea level (SL), and at 3015 m after 12 h (HA12h) and 60 h (HA60h) of exposure. Although 60 h at HA was insufficient for full acclimatization, significant differences were observed between HA12h and HA60h, indicating partial physiological adaptation. Maximal power output declined at both HA time points. Notably, HA-induced performance deterioration was accurately predicted (R² = 0.81) using SL-derived parameters, particularly maximal oxygen pulse (VO₂/HR_max) and the ventilatory equivalent for carbon dioxide (VE/VCO₂). These findings provide novel insights into early physiological responses to HA and support the development of individualized, model-based tools to anticipate performance loss and optimize training and acclimatization strategies.