Physiological Reports最新文献

The E-cigarette or Vaping product-Associated Lung Injury (EVALI) causes severe acute respiratory failure and, in some cases, death. Most cases are linked to tetrahydrocannabinol-containing e-cigarette products adulterated with vitamin E acetate. Despite regulation and awareness efforts, VEA persists in biological samples from EVALI patients and remains a public health concern, particularly among adolescent males. The mechanisms driving VEA-induced lung injury, and how they may be differentiated by sex, remain poorly understood. To address this, age- and size-matched adolescent male and female mice were exposed to aerosolized VEA for 3 or 10 days. By Day 10, VEA exposure caused histopathologic lung injury and systemic inflammation, with alveolar barrier dysfunction evident on Day 3. Male mice developed more severe injury and immune dysregulation, with elevated lung interleukin-1β, interleukin-6, and keratinocyte chemoattractant and reduced expression of club cell secretory protein along the airway epithelium. Female mice showed higher serum levels of soluble receptor for advanced glycation end products, a biomarker of alveolar injury and inflammation that also functions as an immune modulator. This is the first study to identify sex-specific differences in pulmonary responses to VEA exposure. These findings offer insight into EVALI immunopathogenesis and may explain population-level sex disparities in disease severity.

Sensory processing disorder (SPD) is a neurodevelopmental condition characterized by impaired sensory discrimination and responsivity. Although the causes and neural correlates of SPD remain poorly understood, prenatal influences should be considered, as the prenatal environment is strongly implicated in the progression of neurodevelopmental disorders. One factor hypothesized to promote SPD is perinatal Western-style diet (WSD) exposure. This study explored the effects of perinatal WSD exposure on the proposed neural correlates of SPD in Japanese macaques. Functional connectivity between sensory and emotional processing areas was assessed at 4 months of age using resting-state functional magnetic resonance imaging (rs-fMRI). A machine learning model successfully predicted perinatal diet group based on functional connectivity strengths, indicating that differences in sensory connectivity exist between diet groups. Intra-somatomotor, visual-auditory, somatomotor-auditory, somatomotor-visual, and intra-visual network connections demonstrated the greatest differences between groups, with primary motor cortex connectivity being the most impacted. Connections to the amygdala were not major contributors to accurate model performance, but amygdala connectivity, especially to the somatomotor network, may still be a weak driver of model performance. These findings suggest that a proposed predictor of SPD, perinatal WSD exposure, impacts the functional connectivity of sensory processing areas relevant in SPD during early infancy.

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.

The molecular mechanisms underlying the salutary effects of exercise remain incompletely understood. Exerkines are signaling molecules with autocrine, paracrine, or endocrine effects released in response to exercise. Specific eicosanoids, small bioactive lipids, act as exerkines. Using a mass spectrometry-based platform, we assayed eicosanoids and related metabolites at rest and peak exercise in individuals undergoing cardiopulmonary exercise testing (CPET). We examined changes in metabolites with exercise and associations with cardiorespiratory fitness measured by peak VO₂ using multivariable linear regression. We studied 491 individuals (61% women, mean age 57 ± 15). We found 523 (59%) metabolites that dynamically changed with acute exercise (FDR q < 0.05). Of these, 278 (53%) including linoleic acid and arachidonic acid derivatives increased, and 245 (47%) decreased, including trihydroxyoctadecenoic acids (triHOMEs) and omega-3 fatty acids. For 39 metabolites, the magnitude of exercise-induced change correlated with peak VO₂, including omega-3 and omega-6 fatty acids and linoleic, palmitic, stearic, and arachidonic acid derivatives. We identified lipid metabolites underlying metabolomic responses to acute exercise that relate directly to cardiorespiratory fitness. Anti-inflammatory linoleic and arachidonic acid derivatives increased with exercise, while pro-inflammatory and pro-atherogenic triHOMEs decreased. Future studies may fully delineate metabolomic contributions to the effects of exercise including chronic exercise training.

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.