Physiological Reports最新文献

Parenchymal distribution of nebulized drug in healthy and diseased lungs has not, as evident from a literature review, been well characterized. We use a vibrating mesh nebulizer to deliver fluorescein solution in vivo to healthy or intratracheal-lipopolysaccharide (LPS)-instilled anesthetized rats in dorsal recumbency, or ex vivo to the lungs of LPS-instilled rats. Following in vivo nebulization (healthy/LPS-instilled), we quantify fluorescein intensity distribution by confocal microscopy in standard locations on the surface of freshly isolated lungs. Following LPS instillation (in vivo/ex vivo nebulization), we quantify fluorescein intensity in visibly injured locations. In standard locations, there is uniform, low-intensity basal fluorescein deposition. Focal regions receive high deposition that is, in upper (cranial), middle, and lower (caudal) locations, 6.4 ± 4.9, 3.3 ± 3.0, and 2.3 ± 2.8 times greater, respectively, than average basal intensity. Following LPS instillation, deposition in moderately injured regions can be high or low; deposition in severely injured regions is low. Further, actively phagocytic cells are observed in healthy and LPS-instilled lungs. And LPS particularly impairs mechanics and activates phagocytic cells in the male sex. We conclude that a low level of nebulized drug can be distributed across the parenchyma excepting to severely injured regions.

Correlation between echocardiographic and pathoanatomic variables and their prognostic value in murine cardiomyopathy models remain unknown. Using echocardiography, morphometrics, and survival monitoring, we characterized transgenic (TG) mice with dilated cardiomyopathy due to cardiac overexpression of β₂-adrenoceptors focusing on predicting heart failure (HF) risk and HF mortality. In 12-month-old non-TG and TG mice, echocardiography was performed to determine left ventricular (LV) dimensions (d), wall thickness (h), and fractional shortening (FS). Animals were monitored for 3 months for survival. Organ weights and pathological events indicating left HF were determined. TG mice (n = 76) had reduced FS and enlarged LV, and 79% died of HF or likely arrhythmias during the follow-up period while all non-TG mice (n = 26) survived. These mice with left HF also had pulmonary congestion and hypertrophy/dilatation of the right ventricle (RV). Weights of lungs, RV, and atria were intercorrelated (r = 0.79-0.83) and also negatively correlated with FS × (h/d) index (r = -0.502 to -0.609). By FS × (h/d) tertiles, TG mice of low tertiles were identified with the highest mortality (96%) largely due to HF (76%). In conclusion, in aged cardiomyopathy mice a good correlation existed between echocardiographic and pathoanatomic variables. Echocardiography-derived LV function and remodeling were useful in identifying a subgroup of TG mice with a high risk of HF and HF fatality.

A role for metabolically active adipose tissue in pulmonary hypertension (PH) pathogenesis is emerging. Alterations in cellular metabolism in metabolic syndrome are triggers of PH-related vascular dysfunction. Metabolic reprogramming in proliferative pulmonary vascular cells causes a metabolic switch from oxidative phosphorylation to glycolysis. PDE3A and PDE3B subtypes in the regulation of metabolism in pulmonary artery smooth muscle cells (PASMC) are poorly understood. We previously found that PDE3A modulates the cellular energy sensor, AMPK, in human PASMC. We demonstrate that global Pde3a knockout mice have right ventricular (RV) hypertrophy, elevated RV systolic pressures, and metabolic dysfunction with elevated serum free fatty acids (FFA). Therefore, we sought to delineate Pde3a/Pde3b regulation of metabolic pathways in PASMC. We found that PASMC Pde3a deficiency, and to a lesser extent Pde3b deficiency, downregulates AMPK, CREB and PPARγ, and upregulates pyruvate kinase dehydrogenase expression, suggesting decreased oxidative phosphorylation. Interestingly, siRNA Pde3a knockdown in adipocytes led to elevated FFA secretion. Furthermore, PASMC exposed to siPDE3A-transfected adipocyte media led to decreased α-SMA, AMPK and CREB phosphorylation, and greater viable cell numbers compared to controls under the same conditions. These data demonstrate that deficiencies of Pde3a and Pde3b alter pathways that affect cell growth and metabolism in PASMC.

In the present scenario, obesity is a challenging health problem and its prevalence along with comorbidities are on the rise around the world. Ingestion of fish becomes trendy in daily meals. Recent research has shown that marine fish oil (FO) (found in tuna, sardines, and mackerel) may offer an alternative method for reducing obesity and problems associated with it. Marine FO rich in long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) and long-chain omega-6 polyunsaturated fatty acids (LC n-6 PUFA) plays an important role in reducing abnormalities associated with the metabolic syndrome and has a variety of disease-fighting properties, including cardioprotective activity, anti-atherosclerotic, anti-obesity, anti-cancer, anti-inflammatory activity. Studies in rodents and humans have indicated that LC n-3 PUFA potentially elicit a number of effects which might be useful for reducing obesity, including suppression of appetite, improvements in circulation, enhanced fat oxidation, energy expenditure, and reduced fat deposition. This review discusses the interplay between inflammation and obesity, and their subsequent regulation via the beneficial role of marine FO, suggesting an alternative dietary strategy to ameliorate obesity and obesity-associated chronic diseases.

Anodal transcranial direct current stimulation (tDCS) promotes neuromodulation and neuroplasticity in the brain. The aim of this study was to determine the long-term effects of the anodal tDCS on postural and trunk stability, physical performance, anticipatory postural adjustment and quality of life in sub-acute stroke patients. Thirty-six participants with sub-acute stroke were divided into experimental and control groups using sealed envelope randomization. Outcome measures comprised the Postural Assessment Scale for Stroke, Trunk Impairment Scale, Time Up and Go Test, Functional Reach Test, and Stroke-Specific Quality of Life Scale. Assessments were conducted at 0, 3, 6, 9, and 12 weeks. Within-group analysis revealed significant improvement in both the experimental (p-value < 0.05) and control groups (p-value < 0.005). Notably, significant effects were observed in postural stability after intervention, and during one of the detraining assessments, the experimental group showed superior results compared to the control group in subacute stroke. Anodal tDCS yield significant short- and long-term effects on postural stability, while short term effects on trunk stability. Additionally, long term effects were observed on the physical performance and anticipatory postural adjustments while no effects at quality of life either short or long term basis among the subacute stroke patients.

In persons with a spinal cord injury (SCI), resistance training using neuromuscular electrical stimulation (NMES-RT) increases lean mass in the lower limbs. However, whether protein supplementation in conjunction with NMES-RT further enhances this training effect is unknown. In this randomized controlled pilot trial, 15 individuals with chronic SCI engaged in 3 times/week NMES-RT, with (NMES+PRO, n = 8) or without protein supplementation (NMES, n = 7), for 12 weeks. Before and after the intervention, whole body and regional body composition (DXA) and fasting glucose and insulin concentrations were assessed in plasma. Adherence to the intervention components was ≥96%. Thigh lean mass was increased to a greater extent after NMES+PRO compared to NMES (0.3 (0.2, 0.4) kg; p < 0.001). Furthermore, fasting insulin concentration and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were decreased similarly in both groups (fasting insulin: 1 [-9, 11] pmol∙L^-1; HOMA-IR: 0.1 [-0.3, 0.5] AU; both p ≥ 0.617). Twelve weeks of home-based NMES-RT increased thigh lean mass, an effect that was potentiated by protein supplementation. In combination with the excellent adherence and apparent improvement in cardiometabolic health outcomes, these findings support further investigation through a full-scale randomized controlled trial.

Menopause is associated with reduced endothelial-dependent vasodilation and increased cardiovascular disease (CVD) risk. Dietary nitrate, a non-pharmacological approach, may increase vasodilatory capacity consequentially reducing CVD risk. We investigated macro- and microvascular function after acute nitrate supplementation in postmenopausal females (PMF). Vascular function was studied with flow-mediated vasodilation (FMD) and near-infrared post occlusive reactive hyperemia (PORH). Incremental handgrip exercise was performed to investigate blood flow and tissue oxygenation. We hypothesized acute dietary nitrate would not impact resting endothelial measures but would increase post ischemic vasodilation and incremental exercise blood flow. Late-phase PMF (n = 12) participated in a randomized crossover design with 140 mL of nitrate-rich (NR) beetroot juice or nitrate-poor black currant juice. Testing included a 5-min FMD, a 3-min ischemic exercise FMD, and incremental exercise at 10%, 15%, and 20% maximal voluntary contraction to measure blood flow and pressure responses. A p ≤ 0.05 was considered significant. One-way ANOVA indicated lower resting pressures, but no change to FMD, or PORH in either protocol. Two-way repeated measures ANOVA indicated NR supplementation significantly reduced mean arterial pressure at rest and during incremental exercise at all intensities without changes to blood flow. Acute nitrate is effective for resting and exercising blood pressure management in PMF.

Interstitial lung diseases (ILDs) include a variety of inflammatory and fibrotic pulmonary conditions. This study employs high-resolution metabolomics (HRM) to explore plasma metabolites and pathways across ILD phenotypes, including non-fibrotic ILD, idiopathic pulmonary fibrosis (IPF), and non-IPF fibrotic ILD. The study used 80 plasma samples for HRM, and involved linear trend and group-wise analyses of metabolites altered in ILD phenotypes. We utilized limma one-way ANOVA and mummichog algorithms to identify differences in metabolites and pathways across ILD groups. Then, we focused on metabolites within critical pathways, indicated by high pathway overlap sizes and low p-values, for further analysis. Targeted HRM identified putrescine, hydroxyproline, prolyl-hydroxyproline, aspartate, and glutamate with significant linear increases in more fibrotic ILD phenotypes, suggesting their role in ILD fibrogenesis. Untargeted HRM highlighted pathway alterations in lysine, vitamin D3, tyrosine, and urea cycle metabolism, all associated with pulmonary fibrosis. In addition, methylparaben level had a significantly increasing linear trend and was higher in the IPF than fibrotic and non-ILD groups. This study highlights the importance of specific amino acids, metabolic pathways, and xenobiotics in the progression of pulmonary fibrosis.

Vaping use has skyrocketed especially among young adults, however there is no consensus on how vaping impacts the lungs. We aimed to determine whether there were changes in lung function acutely after a standard vaping session or if there were differences in lung function metrics between a healthy never-vaping cohort (N = 6; 27.3 ± 3.0 years) and a young asymptomatic vaping cohort (N = 14; 26.4 ± 8.0 years) indicating chronic changes. Pulmonary function measurements and impulse oscillometry were obtained on all participants. Oxygen-enhanced and Arterial Spin Labelling MRI were used to measure specific ventilation and perfusion, respectively, before and after vaping, and in the control cohort at baseline. MRI metrics did not show any significant differences in specific ventilation or perfusion after vaping. Heart rate increased post-vaping (68.1 ± 10.5 to 71.3 ± 8.7, p = 0.020); however, this and other metrics did not show a nicotine dose-dependent effect. There was a significant negative correlation between BMI and change in mean perfusion post-vaping (p = 0.003); those with normal/low BMI showing an increase in perfusion and vice versa for high BMI. This may be due to subjects lying supine during vaping inhalation. Pulmonary function metrics indicative of airways resistance showed significant differences between the vaping and control cohorts indicating early airway changes.

Skeletal muscle has a high regenerative ability and maintains homeostasis by rapidly regenerating from frequent damage caused by intense exercise or trauma. In sports, skeletal muscle damage occurs frequently due to intense exercise, so practical methods to promote skeletal muscle regeneration are required. Recent studies have shown that it may be possible to promote skeletal muscle regeneration through new pathways, such as promoting autophagy and improving mitochondrial function. Spermidine is a type of polyamine, and oral intake of spermidine promotes autophagy and improves mitochondrial function without inhibiting mTOR. Therefore, we evaluate the effects of spermidine intake on skeletal muscle regeneration after injury using a mouse model of cardiotoxin-induced muscle injury. Our results showed no significant change in skeletal muscle wet weight with spermidine intake at all time points. In addition, although spermidine intake significantly increased the mean fiber cross-sectional area 14 days after injury, these effects were not observed at other time points. In addition, we analyzed stem cells, autophagy, mTOR signaling, inflammation, and mitochondria, but no significant effects of spermidine intake were observed at almost all time points and protein expression levels. Therefore, spermidine intake does not affect skeletal muscle regeneration after chemical injury, and if there is any, it is very limited.