Comprehensive Physiology最新文献

Aim: Intermittent fasting or exercise could be used as an adjunct to regulating abnormal glucose metabolism. However, the mechanism of action of intermittent fasting and exercise to regulate normal glucose metabolism is still unclear. We want to investigate the regulatory effect and mechanism of action of intermittent fasting combined with exercise on glucose metabolism in normal mice.

Methods: All mice were randomized into six groups of 12 animals each. The effects of 6-week alternate-day fasting (ADF) or time-restricted fasting (TRF) combined with running exercise on blood glucose regulation in normal C57BL/6 male mice were evaluated. The expressions of the proteins involved, AMPK, SIRT1, BDNF, MAPK, and Nrf2 signaling pathways, were detected by western blot.

Results: Running exercise could increase muscle glycogen content in mice, and both types of fasting combined with running exercise could decrease glycated serum protein and hepatic glycogen content. Furthermore, we found that fasting and exercise up-regulated the expressions of AMPK, PGC-1α, Glut-4, SIRT1, and PPAR-γ protein, and down-regulated the expression of FoxO1 protein, modulating the ability of the liver and skeletal muscle to uptake glucose and convert glucose-lipid metabolism. Meanwhile, fasting and running exercise increase hippocampal BDNF, activating the MAPK and Nrf2/HO-1 pathways to enhance antioxidant capacity. The regulatory effect of TRF on the above proteins was significantly greater than ADF.

Conclusion: TRF was more effective than ADF in regulating glucose metabolism. Taken together, the regulatory effect of fasting combined with exercise on glucose metabolism was better than the effect of mono-fasting.

Acute lung injury can be a devastating ailment leading to death in patients of all ages. In preterm neonates, lung injury is unique and unlike what is seen in pediatric and adult populations. The physiology behind the acute lung injury endured in developing lungs and the chronicity of harmful stimuli vastly distinguish how bronchopulmonary dysplasia (BPD), the most common complication of prematurity, settles in as a chronic lung disease with lifetime sequelae. Despite being recognized for over 50 years, BPD continues to puzzle the world of neonatology with a shifting phenotype that parallels improvement in neonatal care. The improved understanding of BPD's far-reaching and long-term consequences on the lung and other organs highlights the need to find effective interventions, making it a priority of neonatal research. In this review, we provide an overview of BPD and its associated consequences. Then, we examine the biological premises for mesenchymal stromal cells as a promising therapy, reviewing current translational efforts, challenges, and future directions toward bringing mesenchymal stromal cell therapy to BPD patients.

Placental dysfunction is implicated in the pathogenesis of multiple pregnancy complications. Mitochondria are the powerhouse of the cell and are critical for placental metabolism and function. Several pregnancy complications are associated with oxidative stress and mitochondrial alterations. Mitochondrial function is also essential for epigenetic modifications, which are pivotal in regulating gene expression during pregnancy. Extracellular vesicles (EVs) carry and transfer a variety of biological molecules, including intact mitochondria and mitochondrial components, and act as modifiers of epigenetics in recipient cells. Changes in the EV profile may serve as biomarkers for pregnancy complications. In the present review, we summarize the associations of mitochondrial dysfunction, epigenetic alterations, and changes in EVs that are associated with pregnancy complications. We also describe the link between mitochondria and epigenetics, mitochondria in EVs, and EVs in epigenetic modifications, which provide insight into the possible implications of crosstalk among mitochondria, epigenetics, and EVs in regulating placental function and adverse pregnancy outcomes.

Adipose tissue serves not only as a storage organ but also plays an active role in maintaining the body's homeostasis as an endocrine component. Mainly made up of adipocytes that store energy as triglyceride droplets, this tissue also contains fibroblasts, immune cells, neuronal cells, and endothelial cells. Collectively, these non-adipocyte cells are known as the stromal vascular fraction. Evidence suggests that both the quantity and quality of adipose tissue are crucial in regulating vascular physiology by influencing lipid metabolism and secreting important signaling molecules called adipokines. This review aims to systematically explore the complex effects of adipose tissue on vascular regulation with a particular focus on two well-characterized adipokines-leptin and adiponectin-whose receptors are abundantly expressed in the vasculature. We further aim to provide an overview of both classical and recent research to emphasize the significance of the interplay between adipose tissue and vascular biology.

Emerging evidence highlights the pivotal role of gut microbiota in regulating cardiovascular health and disease. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, interacts with its host through metabolites, immune modulation, and systemic signaling pathways, collectively shaping cardiovascular physiology. Dysbiosis, or an imbalance in gut microbial composition, has been linked to various cardiovascular diseases (CVDs), including hypertension, heart failure and atherosclerosis. Key microbial metabolites such as short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO) and lipopolysaccharides (LPS) have been implicated in mechanisms involving endothelial, cardiac fibroblast, cardiomyocyte dysfunction, systemic inflammation, and metabolic dysregulation. This review explores the dynamic interplay between the gut and the heart, focusing on: gut microbiota composition and its alterations in CVD; microbial-derived metabolites and their mechanistic roles in cardiovascular pathophysiology; pathways linking gut dysbiosis to endothelial, cardiac fibroblast and cardiomyocyte dysfunction, inflammation, and immune responses; and therapeutic opportunities targeting the gut-heart axis, including dietary interventions, prebiotics, probiotics and emerging microbiota-based strategies. By unraveling these intricate relationships, we aim to provide a comprehensive understanding of how gut microbiota shape CVD pathophysiology and discuss potential avenues for novel therapeutics in precision medicine.

The integrative influence of heat acclimation (HA) protocol characteristics and approach on adaptation kinetics and exercise capacity/performance in the heat remains unclear. Bayesian multilevel regression models were used to estimate adaptations with the number of exposures, exposure duration, ambient temperature, water vapor pressure, and HA approach (e.g., constant workrate) as predictors. Data from 211 papers were included in meta-analyses with results presented as posterior means and 90% credible intervals. Mean protocol characteristics were as follows: 8 ± 4 exposures, 90 ± 36 min/exposure, 39.1°C ± 4.8°C, and 2.78 ± 0.83 kPa. HA decreased resting (-5 beats·min^-1 [-7, -3]) and end-exercise heart rate (-17 beats·min^-1 [-19, -14]), resting (-0.19°C [-0.23, -0.14]) and end-exercise core temperature (-0.43°C [-0.48, -0.36]), and expanded plasma volume (5.6% [3.8, 7.0]). HA also lowered exercise metabolic rate (-87 mL·min^-1 [-126, -49]), increased whole-body sweat rate (WBSR) (163 mL·h^-1 [94, 226]), time to exhaustion (49% [35, 61]) and incremental exercise time (14% [7, 24]), and improved time trial performance (3.1% [1.8, 4.5]). An additional HA exposure increased hemoglobin mass (1.9 g [0.6, 3.2]) and WBSR (9 mL·h^-1 [1, 17]), and an additional 15 min/exposure further lowered end-exercise core temperature (-0.04°C [-0.05, -0.03]) and expanded plasma volume (0.4% [0.1, 0.7]). A 5°C increase in ambient temperature further lowered end-exercise HR (-2 beats·min^-1 [-3, -1]) and a 1 kPa increase enhanced WBSR (37 mL·h^-1 [4, 72]). End-exercise heart rate and core temperature decreased similarly following controlled hyperthermia (-16 beats·min^-1 [-18, -14]; -0.43°C [-0.48, -0.36]) and constant workrate HA (-17 beats·min^-1 [-18, -16]; -0.45°C [-0.49, -0.42]). HA protocol characteristics influence the adaptive response and may be manipulated to optimize adaptations. A predictor for estimating HA adaptations based on protocol characteristics is available at: https://www.canberra.edu.au/research/centres/uc-rise/research/environmental-physiology/exercise-heat-acclimation-predictor.

Leukotrienes are potent inflammatory lipid mediators produced primarily by immune cells. Inflammation, being the center stone of two major disease conditions, namely, asthma and inflammatory bowel disease (IBD), has led researchers to study the role of leukotrienes (LTs) in both these disease settings extensively. Several studies indicate a crucial role for LTs in the development and progression of IBD, whereas LTs, especially cysteinyl leukotrienes (cys-LTs), have been identified as the major contributors to asthma initiation and progression for over three decades. Additionally, the lungs and the gut share several common characteristics, including their exposure to the external environment, similar microbiome composition, and inflammatory responses. These similarities suggest a bidirectional relationship, supported by the increased risk of IBD in asthma patients and vice versa. However, the specific role of LTs in this lung-gut connection remains unclear. This review will examine how several common factors, such as physiology, microbiome, environment, and inflammatory mediators, especially LTs, modulate this crosstalk. The review also highlights in detail how altered leukotriene biosynthesis and signaling contribute to the pathogenesis of both asthma and IBD. Furthermore, we will consider the therapeutic implications of targeting leukotriene pathways for patients with concurrent asthma and IBD in the hope of developing more efficient treatment outcomes for these interconnected conditions. Finally, this review will very briefly explore the involvement of neuronal connections in mediating the lung-gut crosstalk.

Pulmonary fibrosis is a complex pathophysiological process characterized by local pulmonary inflammation and fibrosis, along with systemic inflammation and distal organ damage. The acidic environment of lysosomes, as intracellular degradation and recycling centers, is important for cellular homeostasis and function. This review summarizes the potential role of lysosomal acidification in pulmonary fibrosis pathogenesis and its implications for cross-organ effects. Various proteins and ion channels, such as V-ATPase, ClC-7, CFTR, TRPML1, and NHE, regulate lysosomal acidification. Lung fibrosis involves many cells, including lung epithelial cells, endothelial cells, macrophages, fibroblasts, and myofibroblasts. Studies have shown that abnormal lysosomal acidification significantly contributes to the onset and progression of pulmonary fibrosis. Damaged epithelial cells activate inflammatory and fibrotic signals through lysosomal dysfunction; abnormal lysosomal acidification in endothelial cells causes tissue edema and inflammatory responses; macrophages exacerbate inflammatory responses due to impaired lysosomal acidification; and fibroblasts hyperproliferate and transform into myofibroblasts due to deficient lysosomal acidification. Chronic pulmonary inflammation increases blood-gas barrier permeability, facilitating extravasation of inflammatory mediators (e.g., IL-6, TNF-α, and TGF-β) into the circulation, where they act as endocrine signals affecting distant organs. These findings provide a rationale for exploring novel therapeutic targets; future pharmacologic modulation of lysosomal acidification and inhibition of key inflammatory mediators may represent important strategies for preventing and treating pulmonary fibrosis and its systemic complications.

Long Covid is a post-viral syndrome characterized by persistent symptoms targeting multiple organ systems after initial SARS-CoV-2 infection. Current literature suggests that the mechanisms causing Long Covid involve viral persistence, immune dysregulation, systemic inflammation, endothelial dysfunction, and metabolic disturbances. By forming reservoirs in the tissues of various organs, SARS-CoV-2 may evade immunological clearances while triggering immune responses and contributing to chronic symptoms through cytokine imbalances, T-cell exhaustion, and systemic inflammation. These symptoms parallel other post-viral syndromes such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), suggesting similar mechanisms of pathology. The coronavirus has also been linked to neuroinflammation and endothelial dysfunction causing cognitive symptoms and cardiovascular complications. Furthermore, its ability to lower energy production links it to post-exertion malaise (PEM) and muscle pain. These symptoms may result from iron dysregulation and persistent oxidative stress due to Covid-impaired mitochondrial function. This review synthesizes current data on the mechanisms that drive Long Covid pathogenesis and explores potential therapeutic strategies to mitigate viral persistence, immune dysfunction, and metabolic disturbances. It is critical to understand these interactions to develop targeted interventions that address the long-term sequelae of SARS-CoV-2 infection and improve patient outcomes.