Physiological Reports最新文献

Doxorubicin treatment of mice represents a convenient model to study the effects of proteinuria on proteolytic processing of the epithelial Na⁺ channel (ENaC) and urinary Na⁺ and fluid handling. Prior studies have shown enhanced ENaC γ subunit proteolysis and Na⁺ and fluid retention in 129S1/SvImJ mice treated with doxorubicin. We examined whether 129S2/SvPas mice could be used to study doxorubicin-induced proteinuria. 129S2/SvPas mice treated with 18 μg/g doxorubicin exhibited significantly reduced urinary albumin/creatinine compared to that described for 129S1/SvImJ mice. Proteolytic processing of ENaC's γ subunit and sensitivity of urinary Na⁺ and K⁺ to the ENaC blocker, benzamil, were not enhanced by doxorubicin. Differences in the DNA repair enzyme, DNA-activated protein kinase (DNA-PKcs) may contribute to the difference in doxorubicin susceptibility of 129S2/SvPas and 129S1/SvImJ mice. Sequencing of the Prkdc, encoding DNA-PKcs, showed that 129S2/SvPas mice lack a polymorphism (Arg2140Cys) that has previously been implicated in doxorubicin sensitivity in 129S1/SvImJ mice. The status of this polymorphism in various experimental mouse strains, and therefore implications for studying doxorubicin-induced proteinuria, is discussed.

Early-life inflammation has a long-lasting impact on pain behaviors, with neonatal inflammation resulting in altered pain behaviors throughout life. Possible mechanisms underlying these changes lie within the first and second order neurons in the pain neuroaxis. We investigated neuroinflammatory markers in dorsal root ganglia (DRGs) and spinal cords (SC) of Wistar rats (both sexes) following neonatal injection with either LPS or saline (postnatal days (P) 3 and 5) and isolated tissues in early postnatal development. RT-qPCR revealed acute neuroinflammation in the DRGs, with expression levels of four inflammatory mediators elevated at P7, two at P13, and none at P21 in LPS-treated rats. In contrast, the SC showed no change in inflammatory mediators at P7, elevation of two at P13 and four at P21 in LPS-treated rats. These differences were greater in female SCs, indicating sex-specific modulation even at these early stages of postnatal development. The SCs of P21 LPS-treated rats also showed sex-specific modulation of astrocytes (GFAP), with females showing an increase and males a decrease in GFAP. Together, these data indicate that during early postnatal development DRG neurons are more susceptible to acute inflammation whereas inflammation is delayed in the SC, with sex-specific modulation occurring only in the SC.

The optimization of cerebral perfusion and sedation using autoregulation-derived physiologic targets such as optimal cerebral perfusion pressure (CPPopt), optimal mean arterial pressure (MAPopt), and optimal bispectral index (BISopt) has emerged as a promising strategy in neurocritical and perioperative care. However, the reliability and comparability of these optimal (Opt) parameters across different autoregulatory indices remain uncertain. This paper systematically reviews and synthesizes literature comparing CPPopt, MAPopt, and BISopt derived from invasive and noninvasive indices. Following PRISMA-ScR guidelines, studies directly comparing CPPopt, MAPopt, or BISopt from at least two indices were included. Ten studies compared CPPopt, mostly in traumatic brain injury, with mean values between 70 and 76 mmHg. Nine studies compared MAPopt, reporting strong correlations between transcranial doppler-, near-infrared spectroscopy-, and intracranial pressure-derived indices across populations, though limits of agreement were wide. One study compared BISopt across indices, showing internal consistency, while two cross-Opt studies found little correlation between BISopt and CPPopt or MAPopt. CPPopt and MAPopt appear physiologically robust across indices, supporting translational potential in both invasive and noninvasive settings. BISopt may represent a distinct optimization domain related to sedation rather than perfusion. Methodological heterogeneity and limited outcome validation remain barriers. Future work should emphasize standardization, multimodal integration, and outcome-driven trials.

Perivascular adipose tissue (PVAT) regulates vascular tone, and high-fat diets reportedly lead to the loss of its anti-contractile properties. Methionine restriction recapitulates many caloric restriction metabolic effects and increases liver expression of activating transcription factor 4 (ATF4) and downstream targets with anti-contractile properties such as cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). We hypothesized that dietary methionine restriction would prevent high-fat diet-induced PVAT dysfunction by increasing ATF4 expression. Male Wistar rats were fed control (C, 10% calories from fat) or high-fat diets (H, 60% calories from fat) (HFD) that were methionine replete (R, 0.86% methionine) or deplete (D, 0.12% methionine) for 12 weeks. Methionine restriction prevented body mass increases, independent of fat content, and had no effect on blood pressure or arterial contraction to norepinephrine (10 μM) or relaxation to acetylcholine (10 μM). In this feeding paradigm, HFD did not induce PVAT dysfunction. CR diet increased ATF4 transcript levels in multiple PVAT depots but did not consistently affect expression of downstream targets. Protein expression of ATF4 and its targets varied largely for all groups. In conclusion, 12 week methionine restriction profoundly affected body mass but not blood pressure or arterial reactivity in the presence or absence of PVAT.

To compile and statistically summarize quantitative evidence on the acute effects of resistance training sessions on muscle glycogen concentration, a systematic search was conducted on Pubmed, Web of Science, and Scopus databases up to 28th July 2024. Twenty studies including 168 male and 12 female participants were eligible. A multilevel, random-effects meta-analysis was used to calculate the overall mean difference (MD) with a 95% confidence interval (CI) and prediction interval (PI). The model (28 effect sizes across 20 clusters) revealed a significant glycogen decrease (MD = -104.3; 95% CI: -137.6 to -71.0; PI: -244.4 to 35.7; p < 0.001). Meta-regression showed greater depletion with more sets (Estimate = -11.2; 95% CI: -18.0 to -4.3; p = 0.001) and longer session duration (Estimate = -1.3; 95% CI: -2.3 to -0.3; p = 0.009), but less with higher intensity (Estimate = 2.88; 95% CI: 1.2 to 4.5; p = 0.0006). Subgroup analysis showed greater depletion with varied intensity (MD = -162.9) versus fixed (MD = -82.5), and in untrained (MD = -113.0) versus trained participants (MD = -101.3). A single resistance training session depletes glycogen in the vastus lateralis muscle, with depletion influenced by training intensity, session duration, number of sets within session and training status.

The effects of a 21-day live high-train low (LHTL) on hemoglobin mass (Hb_mass) and iron demand including the erythropoietin (EPO)-erythroferrone (ERFE)-hepcidin axis and routine iron markers were investigated. Fifteen female endurance athletes completed either 21-day LHTL in normobaric hypoxia (2500 m, ~18 h·day^-1) (INT, n = 8) or lived and trained in normoxia (CON, n = 7). Hb_mass and resting blood were collected before and after the intervention. An additional blood sample was collected on Day 6 for INT. 21-day LHTL increased Hb_mass 3.8% in INT (p < 0.001). EPO increased 35.6% from Day 0 to Day 6 in INT (p = 0.037) and then decreased 42.4% from Day 6 to Day 21 (p = 0.019). In INT, no changes were detected in ERFE or hepcidin, and from the routine iron markers only serum transferrin receptor increased from Day 0 to Day 21 (13.9%, p = 0.013). In CON, no changes were detected in Hb_mass or iron markers. In INT, Hb_mass and ferritin were positively associated (Day 0 to Day 6, p = 0.005). Thus, hepcidin and ERFE may not provide additional information regarding iron demand following 6- or 21-day LHTL compared to routine iron markers. The relationship between Hb_mass and ferritin indicates that adequate ferritin levels are needed during hypoxia to support hematological adaptations.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with increasing prevalence in Japan. While pharmacological therapies have advanced, the effect of dietary timing, particularly breakfast skipping, on disease course remains unclear. We conducted a retrospective cohort study using the JMDC database (2015-2023), which contains claims and annual health checkup data from about 8.17 million insured individuals. We identified 1645 UC patients who initiated corticosteroid therapy within 1 year after diagnosis and were followed for at least 3 years. Breakfast skipping was defined as skipping breakfast more than three times per week. The primary outcome was steroid withdrawal, defined as discontinuation of corticosteroid prescriptions. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for steroid withdrawal according to breakfast habits. Among 1645 patients, 303 (18.4%) reported skipping breakfast. Steroid withdrawal occurred in 543 patients (33.0%), including 108 (35.6%) in the breakfast skipping group and 435 (32.4%) in the breakfast consuming group. In fully adjusted models accounting for 5-aminosalicylic acid and immunosuppressant use, breakfast skipping was associated with higher odds of steroid withdrawal (OR 1.52, 95% CI 1.08-2.14). These findings suggest that meal timing may influence sustained remission in UC.

Obesity is linked to structural and functional cardiac changes. This study assessed the impact of body mass index (BMI) on left ventricular (LV) function. A cross-sectional study included 100 adults (50 obese and 50 nonobese), matched for age and sex. Echocardiographic parameters, end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), E/A, E/e ratios, Interventricular Septal thickness in Diastole (IVSd), stroke volume (SV), and cardiac output (CO), were measured by a blinded cardiologist using American Society of Echocardiography (guidelines. Spearman's correlation and multivariable regression evaluated associations between BMI and LV parameters. Obese participants had higher EDV (100.0 ± 23.3 vs. 84.6 ± 25.8 mL), ESV (35.6 ± 10.0 vs. 30.4 ± 12.5 mL), IVSd (9.33 ± 1.53 vs. 8.37 ± 0.91 mm), and SV (67.7 ± 15.2 vs. 57.8 ± 13.9 mL) than nonobese participants (all p < 0.05). EF and E/A ratio were similar. BMI correlated positively with EDV and ESV, negatively with E/A ratio, and independently predicted higher EDV and ESV. Obesity is associated with increased LV volumes, septal thickness, and diastolic dysfunction while preserving systolic function, highlighting the importance of early cardiac evaluation in obese adults.

Sex-related physiological differences influence health, disease, and responses to preventive interventions. We aimed to compare the effects of exercise training on cardiovascular autonomic modulation and oxidative stress in target organs, focusing on sex differences. Wistar rats were distributed into sedentary male (SM) and female (SF), and trained male (TM) and female (TF) groups. Arterial pressure was recorded intra-arterially, and autonomic modulation was assessed. Rats underwent treadmill training (5 days/week, 8 weeks). Oxidative stress was evaluated in cardiac and renal tissues. There were sex-related differences in anthropometric, functional, autonomic, and oxidative stress markers. In turn, aerobic exercise training led to significant enhancements in functional performance, cardiovascular autonomic control, and oxidative stress status. Notably, these benefits were more evident in females. Vascular sympathetic modulation correlated positively with renal lipid peroxidation (LPO). Cardiac LPO was lower in TM, SF, and TF (vs. SM). Only TF showed reduced renal LPO and improved cardiac redox balance. Trained females also demonstrated greater improvements in renal antioxidant capacity (TRAP: ~1.6 times), cardiac oxidized glutathione (~3.3 times) (vs. TM), and increased nitrite concentration (~2.1 times) (vs. SF). In conclusion, female rats exhibited greater improvements in cardiovascular autonomic modulation and oxidative profile in target organs in response to exercise training compared to male rats.

Portable near-infrared spectroscopy (NIRS) provides a noninvasive measure of local muscle metabolic demand through muscle oxygen saturation (SmO₂). This study aimed to evaluate acute SmO₂ responses in exercising and non-exercising muscles during an isometric test conducted before and after exercise. Twelve physically active men (25 ± 6 years; 1.75 ± 0.07 m) performed three maximal voluntary contractions (MVC) and a 45-s isometric contraction at 70% MVC (IC70%) before and after completing five sets of 30 concentric knee extensions at 180°·s^-1, with 60 s rest between sets, on an isokinetic dynamometer. SmO₂ was recorded in the vastus lateralis (exercised and non-exercised leg) and triceps brachii. Significant differences in SmO₂ were observed between exercised and non-exercised legs both pre- (p = 0.048) and post-exercise (p < 0.001), whereas no significant changes were found in the triceps brachii or non-exercising vastus lateralis. Acute responses to isometric exercise differed between SmO₂ and torque measures. While the torque of the IC70% did not change following the exercise protocol, SmO₂ showed a higher deoxygenation response during exercise. The isometric test did not indicate any redistribution of muscle oxygenation from non-exercising to exercising muscles. These results provide novel insights into the dissociation between mechanical and microvascular responses during isometric exercise and support the potential of this test as a practical tool for monitoring training loads.