Physiological Reports最新文献

Pulmonary congestion is a common complication in critically ill patients, but its quantification remains challenging. The wet-to-dry (W/D) lung weight ratio, widely used in experimental models, is a terminal and semi-quantitative method. Lung ultrasonography (LU) may offer a non-invasive and reproducible alternative for assessing pulmonary edema. To evaluate the accuracy and reproducibility of LU compared with the W/D ratio in a rat model of oleic acid-induced lung injury. Thirty Wistar-Kyoto rats were randomized into injury (oleic acid, n = 15) and control (saline, n = 15) groups. Echocardiography and LU were performed at baseline and 1 h after infusion. B-line scoring was independently analyzed by two echocardiographers, with reproducibility assessed by Bland-Altman plots. Evans blue dye evaluated vascular permeability. Oleic acid-treated rats showed significantly higher LU scores, B-line counts, W/D ratios, and Evans blue levels than controls. LU demonstrated good diagnostic performance in detecting lung edema in this experimental model, with excellent inter- and intraobserver agreement confirming strong reproducibility. LU proved accurate, reproducible, and non-terminal for detecting pulmonary congestion in rats, showing good agreement with traditional gravimetric measures and supporting its use for longitudinal assessment of pulmonary edema in experimental research.

This project studied the effects of regional body composition on the core temperature responses to water immersion. Forty-six volunteers participated in the study, with subgroups of eighteen immersed from the neck down in 18, 22, and 26°C water for up to 10 h, respectively. Regional body composition was measured by Dual-energy X-ray Absorptiometry. Rectal temperature (Tc), and 10-site mean skin temperatures (Tsk) were measured every minute. Immersion durations ranged from 0.83 to 10 h, and Tc ranged from 35.2 to 38.0°C at the end of immersion. Tc cooling rates were calculated over the first 0.83 h of immersion. Tc cooling rates varied widely, ranging from -0.37 to 0.93°C/h, -0.39 to 1.87°C/h, and -0.13 to 1.13°C/h at 18, 22 and 26°C water, respectively. The trunk fat mass was negatively and significantly correlated to Tc cooling rates (-0.58, -0.76, 0.60, -0.64, p ≤ 0.01) at 18, 22, 26°C water and across all temperatures combined. The arm fat mass, fat percentage and surface-to-mass ratio were negatively and significantly correlated with Tc cooling rates at most conditions, but not all. Individuals with high cooling rates (≥0.6°C/h) had on average half the trunk fat mass of those with low cooling rates (≤0.25°C/h), and those with low trunk fat mass are least capable of defending core body temperature.

Inhibitory control of external urethral sphincter motor neurons (EUS-MNs) in the spinal dorsolateral nucleus (DLN), which corresponds to a portion of Onuf's nucleus in humans, is essential for normal micturition by inducing EUS relaxation during voiding; yet synaptic mechanisms remain poorly characterized. Using neonatal mice P8-P12, we developed a slicing technique-cutting spinal cords at 150° from the coronal plane (30° from the horizontal plane in the agarose block), for maximizing EUS-MNs captured per slice. Using transgenic mice co-expressing channelrhodopsin-2 in inhibitory interneurons (VGAT-ChR2) and GFP in cholinergic neurons (ChAT-GFP), we investigated inhibitory synaptic transmission onto EUS-MNs. Optogenetic activation evoked robust inhibitory postsynaptic potentials (IPSPs), classified as sustained or transient based on temporal profiles. Pharmacology revealed that sustained IPSPs contained both glycinergic and GABAergic components, while GABAA receptors predominantly mediated transient IPSPs. Strychnine (1 μM) selectively blocked glycinergic transmission, while bicuculline (10 μM) eliminated GABAergic components. Insensitivity to glutamatergic antagonists (CNQX and AP5) confirmed purely inhibitory responses. Our findings demonstrate segregation of inhibitory inputs onto EUS-MNs, with glycinergic and GABAergic transmission contributing to sustained and transient inhibition, respectively, establishing the methodological foundation for investigating inhibitory circuit dynamics in pathological conditions such as spinal cord injury with deficient inhibitory control.

The growing prevalence of cardiorenal syndrome (CRS) worldwide underscores the need for specific clinical management, diagnosis, and identification of CRS-specific novel biomarkers. Acute-CRS is highly prevalent in Acute Heart Failure (AHF) patients, clinically driving adverse outcomes. However, there is a paucity of clinical data on the overlap between CRS, HF, and acute kidney injury (AKI). Pathophysiologically, acute-CRS begins with an acute myocardial injury, which subsequently leads to renal insufficiency. Clinically, reduced ejection fraction (EF), increased creatinine(sCr), and reduced eGFR are the standard parameters for diagnosis and treatment of acute-CRS. To understand the clinical need, this study compares the clinical characteristics of the acute-CRS patients with CHF, AKI, and healthy. Recruited participants were of Indian origin, diagnosed with any one of CRS-I, HF, or AKI, or healthy individuals. Baseline demographics were compared across groups and further subjected to clustering analyses. EF, eGFR, and sCr varied significantly across all groups in the cohort. Clustering analysis shows a distinct pathological grouping of Acute-CRS. Intriguing differences in eGFR and EF exhibit sex bias in clinical Acute-CRS cases. Acute-CRS is also clinically distinct in terms of clinical biomarkers of AKI. Hence, this cross-sectional cohort study establishes acute-CRS as a distinct pathological condition requiring comprehensive studies.

Patients after an acute coronary syndrome (ACS) with preserved left ventricle ejection fraction (LVEF) (n = 45, 10 female) were guided by exercise training for 6 months after percutaneous coronary intervention. Exercise capacity, LVEF, standard resting ECG, and 24-h Holter recording were measured at baseline. Time and frequency domain heart rate variability were analyzed over 24 h. Sokolow-Lyon index, as a marker of left ventricular hypertrophy and P wave Terminal Force in lead V₁ (PTF), a marker of left atrial dilatation, along with the standard parameters were analyzed from ECG. A training load of over 6 months (TRIMP) was calculated. Subjects were categorized according to training responses in exercise capacity as low (-3 ± 4%), average (6 ± 2%), and high (15 ± 6%) responders. PTF and P wave duration at baseline differed between the groups: 0.051 ± 0.018, 0.028 ± 0.023, and 0.016 ± 0.015 ms (p < 0.0001) and 120 ± 11, 113 ± 12 and 104 ± 13 ms (p = 0.002) for low, average, and high groups, respectively. Other ECG variables, or any clinical parameters (e.g., sex, age, baseline fitness, LVEF) at baseline or TRIMP were not associated with the training response. Left atrial dilatation, as indicated by PTF on surface ECG, is associated with a low training response in exercise capacity in patients after ACS.

Pulmonary microvascular endothelial cell (PMVEC) intercellular junctions are critical for maintaining barrier function and mitigating pulmonary edema. Previously, we demonstrated that aging exacerbated pulmonary microvascular permeability in a model of lung injury. Based on this, we hypothesized that aging was associated with increased PMVEC barrier dysfunction due to impaired cell-cell junction integrity. PMVEC were isolated from young and aged mice and cultured to confluence in vitro. Barrier function, junctional integrity, alterations in the proteome, markers of inflammation, and actin cytoskeleton organization were all assessed. To model injurious conditions, PMVEC were stimulated with inflammatory cytokines. PMVEC from aged mice exhibited increased permeability, both under basal and inflammatory conditions, which was associated with disrupted cell-surface localization of the adherens junction protein, vascular endothelial (VE)-cadherin. Protein abundance of VE-cadherin was increased with age, while levels of the adapter protein, $\gamma$ -catenin, and the tight junction protein, claudin-5, were decreased. Measures of inflammation, including cytokine expression and cell surface abundance of adhesion molecules, did not differ with age. Augmented presence of actin stress fibers was observed in aged PMVEC. We conclude that aging predisposes PMVEC to elevated injury, due to inherent deficiencies in cell-cell junctions and barrier function, potentially mediated through altered actin cytoskeleton organization.

Archaeological and anthropological evidence suggests that human ancestors' diets were rich in fiber, potassium, and complex carbohydrates, while low in sodium, refined sugars, and energy density. Over time, agroindustrialization led to diets poorer in fiber and micronutrients but higher in sodium, simple sugars, and calorie-dense foods. This shift contributed to the rise of noncommunicable diseases (NCDs) such as obesity, type 2 diabetes, and cardiovascular diseases, which now account for 70% of global premature deaths. Maternal nutrition affects fetal development and long-term health. High sucrose or fructose intake during pregnancy can alter placental function, impacting fetal growth and metabolism. Placentae from male and female fetuses may respond differently to maternal diet. However, the effects of excessive maternal fructose intake on the placenta and offspring remain underexplored. In this study, rat dams consuming fructose-sweetened beverages ate less food but drank more, significantly impacting placental volume and vascular structure. Long-term effects on offspring were sex-specific: females showed greater water retention and liver fat accumulation. High maternal fructose intake altered placental anatomy and had sex-specific effects on kidney and liver function in adult offspring, even without further fructose exposure. These findings highlight the importance of maternal diet in preventing future metabolic diseases.

Acetaminophen (APAP) overdose is associated with increased transforming growth factor beta 1 (TGFβ1) signaling and elevated oxidative stress, which exacerbate DNA damage. TGFβ1 has been shown to regulate ataxia-telangiectasia mutated (ATM) signaling and DNA repair in other cell types. This study investigates the DNA damage response (DDR) during APAP-induced liver injury, focusing on ATM-mediated regulation of TGFβ1 signaling. APAP administration in vitro and in vivo resulted in DNA damage, increased ATM signaling, accumulation of γH2AX, and activation of phosphorylated ataxia telangiectasia mutated (pATM) and phosphorylated checkpoint kinase 2 (pChk2). Pretreatment with an ATM inhibitor, KU55933, attenuated APAP-induced hepatocyte damage and resulted in attenuated mothers against decapentaplegic homolog 2/3 (SMAD2/3) signaling with no changes in activated TGFβ1 levels, suggesting that ATM activation modulates TGFβ1 signaling via post-translational mechanisms. APAP was found to promote transforming growth factor beta receptor 2 (TGFβRII) stabilization through activation of phosphorylated casitas B-lineage lymphoma (p-c-cbl) and subsequent neddylation of TGFβRII, which was attenuated by inhibitors of ATM signaling or neddylation machinery. In conclusion, APAP-induced hepatic DNA damage activates an ATM-mediated response that enhances TGFβ1 signaling through stabilization of TGFβRII, and inhibition of ATM consequently reduces APAP-induced hepatic injury.