Experimental Physiology最新文献

Cathelicidins are evolutionarily conserved host defence peptides known for their dual antimicrobial and immunomodulatory functions. Among them, LL-37 in humans and CRAMP in rodents have emerged as crucial regulators of both mucosal immunity and CNS inflammation. This review explores the emerging evidence that positions cathelicidins as key modulators of the gut-brain axis, a bidirectional communication network increasingly implicated in neuroinflammatory and neurodegenerative disorders. Drawing on a diverse body of animal and human research, we examine the multifaceted roles of cathelicidin in maintaining intestinal barrier integrity, shaping microbiota composition and regulating innate immune signalling. Particular attention is paid to how gut-derived metabolites, such as short-chain fatty acids and vitamin D, influence cathelicidin expression, with downstream consequences for both gastrointestinal and neural health. In the CNS, cathelicidin exhibits context-dependent effects, acting as a neuroprotective modulator when derived from neurons, but exacerbating glial-mediated inflammation when sourced from peripheral immune cells. This functional dichotomy underscores the importance of cellular origin, concentration and microenvironmental cues. Furthermore, we delineate how cathelicidin facilitates crosstalk between peripheral and central compartments, serving as both a local effector and a systemic messenger. Collectively, these insights support a reconceptualization of cathelicidin not merely as a passive antimicrobial peptide, but as an active molecular bridge between mucosal immunity and neuroinflammation, with promising implications for diagnostics and therapeutics targeting dysfunction of the gut-brain axis.

Obesity (BMI ≥ 30 kg/m²) reduces skeletal muscle quality and impairs the myogenic response to muscle damage. The present study investigated if differences exist in myotubes from individuals with (OB) or without (LN) obesity incubated in control (bovine serum albumin [BSA]) or obesogenic (Ob) medium, at baseline or in response to cardiotoxin (CTX)-induced damage and recovery. Differentiated, primary human myotubes from LN and OB donors were cultured in control (BSA-DM) or (Ob-DM) (250 µM palmitate, 250 µM oleate, 100 nM insulin, and 2.5 ng/mL tumour necrosis factor) differentiation medium (DM) for 48 h and treated with 1.0 µM CTX or vehicle control for 1 h (immediately post [IP]). Myotubes recovered in Ob (Ob-GM) or BSA (BSA-GM) growth medium (GM) for 3 days (3D). At baseline, myotubes (LN and OB) incubated in Ob-DM had 5% lower fusion index (FI) and nuclei/tube than BSA-DM. At IP post-CTX, there were no differences in FI or membrane integrity (lactate dehydrogenase), but the reduction in cell viability was greater in OB than LN myotubes and greater in myotubes (LN and OB) incubated in Ob-DM than BSA-DM. At 3D post-CTX, total nuclei, FI, and nuclei/tube were ∼15% lower in myotubes (LN and OB) incubated in Ob-GM than BSA-GM. Expressed as recovery (3D-IP) post-CTX, Ob-GM lowered total nuclei and FI in myotubes without differences between LN and OB. In human myotubes, impaired formation and recovery following damage in obesity appear primarily due to the obesogenic environment rather than inherent, individual differences.

Current literature on the metabolic effects of long-distance hiking is limited to case studies with discrepant findings, and no prior studies have examined the role of diet in shaping these outcomes. In this study, we investigated changes in lipid profiles and dietary factors among 12 participants who completed the Colorado Trail. Blood lipid measures [low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, total cholesterol and triglycerides] were obtained pre- and post-trail after a 12 h fast using the Lysun Blood Lipid Analyzer. Dietary intake was assessed pre- and on-trail using a validated multiple-pass 24 h recall. Student's paired t-tests evaluated metabolic changes, and regression analyses assessed associations between lipid changes and dietary factors. No lipid exhibited a statistically significant change at the α = 0.05 threshold. However, LDL-C decreased by 17 mg/dL (P = 0.066), suggestive of a biologically meaningful reduction, given the small sample size. Among 81 dietary variables, LDL-C reduction was significantly associated with decreased intake of added sugars (P = 0.030) and ultra-processed foods (P = 0.039) and with increased intake of minimally processed foods (P = 0.044), vitamin C (P = 0.048) and vitamin K (P = 0.047) during hiking. These findings suggest that long-distance hiking might be associated with lower LDL-C and that diet quality, particularly food processing level, might be correlated with this trend. This study is the first to link dietary shifts systematically to metabolic outcomes in thru-hiking, providing hypothesis-generating insights into the physiological adaptations to prolonged physical exertion and the potential for dietary modulation of lipid metabolism.

Exercise influences gut microbiota composition and intestinal permeability, but the optimal intensity for maintaining gut health remains unclear. This study investigates the effects of different exercise intensities on abundance of some gut microbiota, epithelial barrier integrity and inflammatory markers. Male Wistar rats were randomly assigned to control (n = 5), low-intensity (10 m/min, n = 5), moderate-intensity (20 m/min, n = 5) and high-intensity (30 m/min, n = 5) exercise groups, exercising five times per week for 8 weeks. The relative abundance of Akkermansia muciniphila, Faecalibacterium prausnitzii and Escherichia coli was quantified using qPCR, whilst mRNA levels of zonula occludens-1 (ZO-1) and interleukin-6 (IL-6) were assessed as markers of barrier function and inflammation. A. muciniphila and F. prausnitzii abundance increased at moderate exercise intensity (P < 0.005), but decreased at high intensity (P = 0.0019), whereas E. coli rose sharply at high intensity (P < 0.001). ZO-1 expression was higher at moderate (β = 0.30, 95% CI 0.195-0.405, P < 0.001) and high intensity (β = 0.60, 0.495-0.705, P < 0.001), but not at low intensity (β = 0.10, -0.005-0.205, P > 0.05). IL-6 increases similarly (moderate β = 0.50, 0.247-0.753, high β = 1.10, 0.847-1.353, both P < 0.001). In conclusion, moderate-intensity exercise enhanced beneficial microbiota and epithelial barrier integrity, whereas high-intensity exercise promoted E. coli proliferation and IL-6-mediated inflammation, underscoring a dose-dependent, bidirectional regulation of the gut epithelial interface.

We investigated integrative physiological responses to eupnoeic exercise (EX), rebreathing exercise (RB), dynamic apnoea (DA) and dynamic apnoea with cold-water face immersion (DAFI) in 20 healthy participants. Trials involved non-steady-state cycle exercise at 60 W for an average duration of 66 s. With increases in heart rate and stroke volume, EX and RB increased cardiac output compared with baseline (mean [SD] EX +47 [13]%, RB +43 [15]%). During DA and DAFI, the increase in cardiac output was attenuated (DA +26 [23]%, DAFI +14 [21]%). EX and RB elicited reductions in total peripheral resistance (EX -37 [7]%, RB -23 [15]%). This reduction was absent during apnoeas (DA +3 [31]%, DAFI +15 [40]%). Pulmonary oxygen uptake was the lowest during DAFI. At the end of hypoxic trials, end-tidal partial pressures of O₂ were RB 50.3 [11.9], DA 57.9 [14.0] and DAFI 61.4 [13.6] mmHg, indicating a preservation of the central oxygen store during DA and DAFI. At the same time, peripheral tissue oxygen saturation, measured in the working rectus femoris muscle, declined the most during DA and DAFI (RB -1.4 [3.5]%, DA -4.7 [3.3]%, DAFI -5.6 [4.4]%). Splenic volume increased during EX (+8.4 [5.8]%) but decreased during RB (-10.5 [10.2]%), DA (-6.4 [10.8]) and DAFI (-13.3 [11.1]%) when compared with EX, suggesting erythrocyte mobilization in the threat of hypoxia. The non-steady-state apnoea interventions of the present study evoke a progressive shift from exercise-induced cardiovascular responses towards a diving response, including cardiac, vascular and splenic responses. These responses are amplified to some extent by cold-water face immersion. Apnoea-induced responses lead to central oxygen preservation and a decrease in peripheral oxygen stores.

Popular wearable devices that record a variety of health metrics, such as real-time blood pressure (BP), could play a role in detecting hypertension in the population. The objective of this study was to compare the validity of the Huawei D device with that of the Omron M3 Intellisense device used by health workers. Sampling was used to obtain patients with normal and abnormal BP. Measurements were taken on the wrist via the Huawei Watch D, while measurements were made using the Omron M3 Intellisense (prevalidated) device used by experienced healthcare personnel at the health centre. A total of 100 normotensive and 100 hypertensive patients were analysed. The concordance statistics were calculated, and linear regression analysis was performed. The intraclass correlation coefficient was calculated to assess the concordance between the instruments used in the measurement and among the observers who made the measurements under a two-factor mixed-effects model, with calculation of the degree of absolute concordance in mean measurements. We found moderate results (systolic blood pressure (SBP) at 30 and 60 min and heart rate at 30 min) and nil for the rest [0.63 (0.36-0.78) < 0.001]; in addition, the comparison of the two groups was verified by a Bland-Altamn graph, in which the disparity of the results was observed. The Huawei D BP measuring device was shown to be relatively effective for measuring BP in hypertensive patients. However, the specificity of BP measurement in normotensive patients was not as reliable as in hypertensive patients.

Reductions in brain insulin sensitivity and cerebral blood flow (CBF) have emerged as potential factors contributing to Alzheimer's disease and related dementia. However, no work has tested whether a single bout of exercise can raise brain insulin sensitivity in at-risk adults. The aim of the study was to test whether a single bout of exercise raises brain insulin sensitivity in middle-aged to older adults with cardiometabolic risk. In a counterbalanced pilot study design, 15 cognitively unimpaired (Montreal Cognitive Assessment, 28.2 ± 1.3 a.u.) adults [56.7 ± 2.1 years old; maximal oxygen consumption ( ${\dot{V}}_{O_2\max }$ ), 23.9 ± 0.9 mL/kg/min] with excess body weight (body mass index, 31.8 ± 1.3 kg/m²) and impaired glucose tolerance (haemoglobin A1c, 5.8% ± 0.30%) were randomized to a rest (time-matched control) or acute treadmill exercise bout (70% ${\dot{V}}_{O_2\max }$ for 60 min) in the evening. The next morning, participants arrived fasted to determine brain insulin sensitivity. Plasma glucose and insulin, in addition to CBF, were assessed by pseudo-continuous arterial spin labelling before and after intranasal insulin (40 IU). Cognition (NIH toolbox), aerobic fitness ( ${\dot{V}}_{O_2\max }$ ) and body composition (dual-energy X-ray absorptiometry) were also analysed. There was no difference in plasma glucose or insulin following intranasal with or without exercise. Although cognition was also not improved, exercise increased CBF in the hippocampus, putamen and pallidum (condition effect, P < 0.05). Exercise-induced increases in fasting hippocampus, caudate, pallidum and putamen CBF were correlated with a lowering of CBF responses to insulin. In middle-aged to older adults with cardiometabolic risk, a single bout of exercise increased fasting CBF, and this related to decreased CBF insulin responses in regions related to memory and motor control.

Central arterial stiffening, particularly of the proximal aorta, is increasingly recognised as a pivotal contributor to cardiovascular disease, dementia, and mild cognitive impairment. Loss of Windkessel function amplifies pulsatile pressure, reduces diastolic perfusion and accelerates microvascular damage in the brain. Evidence from epidemiological studies, magnetic resonance imaging investigations and longitudinal data demonstrates disproportionate age-related stiffening of the proximal aorta and its strong association with cognitive decline. Importantly, this process is modifiable: aerobic exercise and unique environmental adaptations, such as those observed in Japanese Ama divers, preserve proximal aortic elasticity. Targeting central arterial stiffness may represent a promising strategy for preventing both vascular disease and brain dysfunction.