Physiology international最新文献

Breast cancer is characterized by oncobiosis, the abnormal composition of the microbiome in neoplastic diseases. The biosynthetic capacity of the oncobiotic flora in breast cancer is suppressed, as suggested by metagenomic studies. The microbiome synthesizes a set of cytostatic and antimetastatic metabolites that are downregulated in breast cancer, including cadaverine, a microbiome metabolite with cytostatic properties. We set out to assess how the protein expression of constitutive lysine decarboxylase (LdcC), a key enzyme for cadaverine production, changes in the feces of human breast cancer patients (n = 35). We found that the fecal expression of Escherichia coli LdcC is downregulated in lobular cases as compared to invasive carcinoma of no special type (NST) cases. Lobular breast carcinoma is characterized by low or absent expression of E-cadherin. Fecal E. coli LdcC protein expression is downregulated in E-cadherin negative breast cancer cases as compared to positive ones. Receiver operating characteristic (ROC) analysis of LdcC expression in lobular and NST cases revealed that fecal E. coli LdcC protein expression might have predictive values. These data suggest that the oncobiotic transformation of the microbiome indeed leads to the downregulation of the production of cytostatic and antimetastatic metabolites. In E-cadherin negative lobular carcinoma that has a higher potential for metastasis formation, the protein levels of enzymes producing antimetastatic metabolites are downregulated. This finding represents a new route that renders lobular cases permissive for metastasis formation. Furthermore, our findings underline the role of oncobiosis in regulating metastasis formation in breast cancer.

Sodium induced volume loading may alter pressor responses to physical stress, an early symptom of cardiovascular disease.

Purpose: Study 1: Determine the time point where total blood volume and serum sodium were elevated following saline consumption. Study 2: Examine the BP response to isometric handgrip (HG) and the cold pressor test (CPT) following saline consumption.

Methods: Study 1: Eight participants drank 423 mL of normal saline (sodium 154 mmol/L) and had blood draws every 30 min for 3 h. Study 2: Sixteen participants underwent two randomized data collection visits; a control and experimental visit 90 min following saline consumption. Participants underwent 2 min of isometric HG, post exercise ischemia (PEI), and CPT.

Results: Study 1: Total blood volume (3.8 ± 3.0 Δ%) and serum sodium (3.5 ± 3.6 Δ%) were elevated (P < 0.05) by the 90 min time point. Study 2: There were no differences in mean arterial pressure (MAP) during HG (EXP: 17.4 ± 8.2 ΔmmHg; CON: 19.1 ± 6.0 ΔmmHg), PEI (EXP: 16.9 ± 11.7 ΔmmHg; CON: 16.9 ± 7.8 ΔmmHg), or the CPT (EXP: 20.3 ± 10.8 ΔmmHg; CON: 20.9 ± 11.7 ΔmmHg) between conditions (P > 0.05). MAP recovery from the CPT was slower following saline consumption (1 min recovery: EXP; 15.7 ± 7.9 ΔmmHg, CON; 12.3 ± 8.9 ΔmmHg, P < 0.05).

Conclusion: Data showed no difference in cardiovascular responses during HG or the CPT between conditions. BP recovery was delayed by saline consumption following the CPT.

Introduction: Atherosclerosis is an inflammatory disease causing a vast array of cardiovascular diseases. Adipophilin has been reported to be highly expressed in atherosclerotic lesions. This study investigated the possible existence of auto-reactive T cells against an HLA-A02-restricted adipophilin-derived peptide as well as peptides from Epstein-barr virus (EBV), Cytomegalovirus (CMV) and influenza (Flu) virus in patients with atherosclerosis.

Methods: HLA-A02 expression on peripheral blood mononuclear cells (PBMCs) was examined by flow cytometry. PBMCs from HLA-A02 individuals were stimulated with adipophilin, CMV, EBV, and Flu peptides at a concentration of 10 µM. Interferon (IFN)-γ production was evaluated in the culture supernatant using a commercial ELISA test.

Results: The levels of IFN-γ production against an HLA-A02-restricted adipophilin peptide and peptides from CMV, EBV, and Flu revealed no statistically significant differences between patients and healthy controls. However, we found a positive correlation between IFN-γ production against adipophilin and Body mass index (BMI) of patients (R = 0.8, P = 0.003), whereas no significant correlation was found in healthy controls (R = -0.267, P = 0.378). No correlation between BMI and IFN-γ production against CMV, EBV, or Flu peptides was found.

Discussion: Atherosclerotic patients with higher BMIs might have greater numbers of T cells against adipophilin that is highly expressed in atherosclerotic plaques. Therefore, autoimmune reactions may have a greater role in the development of atherosclerosis in individuals with higher BMI.

Objective: It has been shown that high-intensity interval training (HIIT) leads to skeletal muscle hypertrophy; however, its mechanisms of cellular and molecular regulation are still unclear. The purpose of this study was to investigate the effect of HIIT on muscle hypertrophy and major signal transduction pathways.

Design: 12 male rats were randomly divided into two groups: control and HIIT. The exercise group performed 30-min HIIT in each session (5 × 4-min intervals running at 85-95% VO2max separated by 2-min active rest at 55-60% VO2max), 3 days/week for 8 weeks. Muscle fiber cross-sectional area (CSA) and the expression of signal transduction pathway proteins were determined in the gastrocnemius muscle.

Results: In the HIIT group, the expression of IGF-I, IGF-IR Akt, p-Akt, AMPKα, p-AMPKα and follistatin increased significantly, whereas a significant decrease was observed in the expression of FoxO1, p-FoxO1, myostatin, ActRIIB, Smad2/3 and p-Smad2/3 (P < 0.05). However, there were no significant differences between the HIIT and control groups in the expression of mTOR, p-mTOR, P70S6K, and p-P70S6K (P > 0.05). In addition, CSA and gastrocnemius muscle weight increased significantly in the HIIT group (P < 0.05).

Conclusions: HIIT induced muscle hypertrophy by improving IGF-I/Akt/FoxO and myostatin/Smad signal transduction pathways.

No previous studies have evaluated the potential combined effects of acute exercise and acute hypoxia exposure on memory function, which was the purpose of this study. Twenty-five participants (Mage = 21.2 years) completed two laboratory visits in a counterbalanced order, involving 1) acute exercise (a 20-min bout of moderate-intensity exercise) and then 30 min of exposure to hypoxia (FIO2 = 0.12), and 2) exposure to hypoxia alone (FIO2 = 0.12) for 30 min. Following this, participants completed a cued-recall and memory interference task (AB/AC paradigm), assessing cued-recall memory (recall 1 and recall 2) and memory interference (proactive and retroactive interference). For cued-recall memory, we observed a significant main effect for condition, with Exercise + Hypoxia condition having significantly greater cued-recall performance than Hypoxia alone. Memory interference did not differ as a function of the experimental condition. This experiment demonstrates that engaging in an acute bout of exercise prior to acute hypoxia exposure had an additive effect in enhancing cued-recall memory performance.

Introduction: During mammalian brain development, neural activity leads to maturation of glutamatergic innervations to locus coeruleus. In this study, fast excitatory postsynaptic currents mediated by N-methyl-d-aspartate (NMDA) receptors were evaluated to investigate the maturation of excitatory postsynaptic currents in locus coeruleus (LC) neurons.

Methods: NMDA receptor-mediated synaptic currents in LC neurons were evaluated using whole-cell voltage-clamp recording during the primary postnatal weeks. This technique was used to calculate the optimum holding potential for NMDA receptor-mediated currents and the best frequency for detecting spontaneous excitatory postsynaptic currents (sEPSC).

Results: The optimum holding potential for detecting NMDA receptor-mediated currents was + 40 to + 50 mV in LC neurons. The frequency, amplitude, rise time, and decay time constant of synaptic responses depended on the age of the animal and increased during postnatal maturation.

Conclusion: These findings suggest that most nascent glutamatergic synapses express functional NMDA receptors in the postnatal coerulear neurons, and that the activities of the neurons in this region demonstrate an age-dependent variation.

Introduction: Left ventricular (LV) twist is considered an essential part of LV function due to oppositely directed LV basal and apical rotations. Several factors could play a role in determining LV rotational mechanics in normal circumstances. This study aimed to investigate the relationship between LV rotational mechanics and mitral annular (MA) size and function in healthy subjects.

Methods: The study comprised 118 healthy adult volunteers (mean age: 31.5 ± 11.8 years, 50 males). All subjects had undergone complete two-dimensional (2D) Doppler echocardiography and three-dimensional speckle-tracking echocardiography (3DSTE) at the same time by the same echocardiography equipment.

Results: The normal mean LV apical and basal rotations proved to be 9.57 ± 3.33 and -3.75 ± 1.98°, respectively. LV apical rotation correlated with end-systolic MA diameter, area, perimeter, fractional area change, and fractional shortening, but did not correlate with any end-diastolic mitral annular morphologic parameters. The logistic regression model identified MA fractional area change as an independent predictor of ≤6° left ventricular apical rotation (P < 0.003).

Conclusions: Correlations could be detected between apical LV rotation and end-systolic MA size and function, suggesting relationships between MA dimensions and function and LV rotational mechanics.

Purpose: High central blood pressure is more predictive of cardiovascular disease (CVD) versus high peripheral blood pressure. Measures of central pressures (CPs) include, central systolic blood pressure (CSBP) and central diastolic blood pressure. Measures of central pressures augmentation (CPsA) include augmentation pressure (AP) and the augmentation index @ 75 beats·min-1 (AIx@75). Increased sympathetic tone (ST) is also associated with CVD. The low to high frequency ratio (LF/HF) is often used to determine sympatho-vagal balance. Given the association between ST, CPs, CPsA and CVD there is a need to understand the association between these predictors of CVD. The aims of this study were to examine the association between the LF/HF ratio, CPs, and CPsA in men and women collectively and based on gender.

Methods: We measured the LF/HF ratio, CSBP, AP, and AIx@75 in 102 participants (41F/61M). The LF/HF ratio was determined via power spectral density analysis. CSBP, AP, and AIx@75 were determined via applanation tonometry.

Results: The LF/HF ratio was inversely associated with AP (r = -0.26) and AIx @75 (r = -0.29) in the combined group of men and women. The LF/HF ratio was inversely associated with CSBP (r = -0.27), AP (r = -0.28), and AIx@75 (r = -0.32) in men, but not in women.

Conclusion: There is an inverse association between the LF/HF ratio, AP, and AIx@75 in men and women combined. The association between the LF/HF ratio, CSBP, AP, and AIx@75, differs based on gender.

Numerous studies indicate that smoking during pregnancy exerts harmful effects on fetal brain development. The aim of this study was to determine the influence of maternal smoking during pregnancy on the early physical and neurobehavioral development of newborn rats. Wistar rats were subjected to whole-body smoke exposure for 2 × 40 min daily from the day of mating until day of delivery. For this treatment, a manual closed-chamber smoking system and 4 research cigarettes per occasion were used. After delivery the offspring were tested daily for somatic growth, maturation of facial characteristics and neurobehavioral development until three weeks of age. Motor coordination tests were performed at 3 and 4 weeks of age. We found that prenatal cigarette smoke exposure did not alter weight gain or motor coordination. Critical physical reflexes indicative of neurobehavioral development (eyelid reflex, ear unfolding) appeared significantly later in pups prenatally exposed to smoke as compared to the control group. Prenatal smoke exposure also resulted in a delayed appearance of reflexes indicating neural maturity, including hind limb grasping and forelimb placing reflexes. In conclusion, clinically relevant prenatal exposure to cigarette smoke results in slightly altered neurobehavioral development in rat pups. These findings suggest that chronic exposure of pregnant mothers to cigarette smoke (including passive smoking) results in persisting alterations in the developing brain, which may have long-lasting consequences supporting the concept of developmental origins of health and disease (DoHAD).