Experimental Physiology最新文献

Human skin wetness perception relies on the multisensory integration of thermal and mechanical cues during contact with moisture. Yet, it is unknown whether children and adolescents perceive skin wetness similarly to younger and older adults. We investigated skin wetness perceptions across the forehead, neck, forearm, and foot dorsum in 12 children/adolescents (4F/8M; 12 ± 3 years), 41 younger (21F/20M; 25 ± 3 years), and 21 older adults (11F/10M; 56 ± 6 years), during two established quantitative sensory tests. Our results indicated that, given the same moisture content (0.8 mL of water), very cold-wet stimuli applied to the forearm were perceived by all groups as wetter than neutral-wet (mean difference: 35.5 mm on a 100-mm visual analogue scale for wetness [95% CI: 22.3, 38.7]; P < 0.0001; ∼35% difference) and very hot-wet stimuli (mean difference: 22.7 mm [95% CI: 14.5, 40.9]; P < 0.0001; ∼23% difference). Children/adolescents also reported greater wetness perceptions than older adults during cold-wet stimulation of the forehead, neck and foot dorsum (mean difference: 20.6 mm; 95% CI: 1.5, 39.7; P = 0.031; ∼21% difference). In all age groups, the foot dorsum presented higher cold-wet sensitivity (mean difference: 11.1mm [95%CI 2.2, 20.0] p = 0.010; ~11% difference) and lower warm-wet sensitivity than the neck (mean difference: 12.9mm [95%CI 2.8, 23.0] p = 0.008; ~13% difference). We conclude that wetness perceptions in children/adolescents (age range: 7-16 years) are similar to those of adults in that both present (1) a characteristic U-shaped relationship between stimulus temperature and perceived wetness magnitude and (2) similar body regional patterns. These findings provide novel evidence on age-dependent variations in wetness perception which could inform user-centred innovation in thermal protection and garment design.

The gastrointestinal (GI) microbiota and GI barrier integrity are hypothesised to contribute to exertional heat illness (EHI) aetiology. We compared the faecal microbiome, GI barrier integrity, inflammation and thermoregulation of 29 recent (∼4 months) EHI patients (a group with elevated EHI risk) and 29 control individuals without prior EHI history, matched for variables influencing thermoregulation and GI microbiota. Participants completed an exercise heat tolerance assessment (HTA), with faecal microbiome assessed by 16S rRNA gene amplicon sequencing of stool samples and blood biomarkers of GI barrier integrity and inflammation measured pre- and post-HTA. With the exception of the Simpson index (patient = 0.97 ± 0.01 vs. control = 0.98 ± 0.00, P = 0.030), there were no between-groups differences in faecal microbiome composition (α-diversity, β-diversity, relative abundance, differential abundance), GI barrier integrity, inflammation or terminal thermoregulatory indices. Individuals were subsequently classified as heat tolerant (n = 46) or intolerant (n = 12) on the basis of the HTA. Heat intolerant individuals demonstrated lower sudomotor response (intolerant = 0.53 (0.17) vs. tolerant = 0.62 (0.20) L m^-2 h^-1, P = 0.011) despite greater thermoregulatory strain (e.g., terminal T_rec: intolerant = 39.20 ± 0.31 vs. tolerant = 38.80 ± 0.31°C, P < 0.001), lower Firmicutes:Bacteroidota ratio (intolerant = 3.7 (0.6) vs. tolerant = 4.5 (2.0), P = 0.019) and higher plasma [sCD14] (P = 0.014), but other aspects of faecal microbiome, GI integrity or inflammation did not differ from heat tolerant individuals. In conclusion, the faecal microbiome composition and the GI barrier integrity and inflammatory responses to exercise heat-stress showed limited differences between recent EHI patients and matched controls, or between individuals classified as heat intolerant or heat tolerant and are unlikely to explain elevated EHI risk in recent EHI patients, or heat intolerance.

The magnitude of changes in middle cerebral artery mean blood velocity (MCAv) is attenuated when mean arterial pressure (MAP) increases compared with when MAP decreases. This directional sensitivity has been characterized using a time-corrected ratio calculated on MCAv and MAP changes induced by repeated squat-stands (RSS) at 0.05 and 0.10 Hz for 300 s (∆MCAv_T/∆MAP_T). Herein, we examined the reliability of the metric within reduced RSS durations. Ninety-nine (25 females) healthy human participants (26 ± 5 years) performed 300 s RSS at 0.05 Hz (20 s cycles) and 0.10 Hz (10 s cycles) while MCAv and MAP were measured continuously. The ∆MCAv_T/∆MAP_T was calculated for each transition [increase (INC); decrease (DEC)] of MAP for 60, 120, 180, 240 and 300 s. A two-way ANOVA was completed, and the absolute (Bland-Altman plot) and relative (coefficient of variation and intraclass correlation coefficient) reliability were calculated to compare shorter-duration recordings with 300 s (reference standard). At 0.05 Hz, ∆MCAv_T/∆MAP_T was similar between INC and DEC and comparable to the 300 s reference from 120 s onwards. At 0.10 Hz, ∆MCAv_T/∆MAP_T was lower during INC (p < 0.0001). Bland-Altman plots indicated that differences trended towards zero (greater agreement) with increasing duration. Averaged coefficients of variation were <10% from 120 s (0.05 Hz) and 60 s (0.10 Hz) onwards. All intraclass correlation coefficients were >0.90 for recordings of ≥180 s in both frequencies. Although the 300 s reference is optimal, RSS duration could be shortened to 180 s, if needed, to identify this hysteresis-like pattern reliably using ∆MCAv_T/∆MAP_T.

Type 2 diabetes mellitus (T2DM) significantly increases the risk and severity of cerebral ischaemia-reperfusion (IR) injury, yet effective neuroprotective treatments for diabetic stroke remain limited. This study explored whether a combination of sinomenine and metformin could offer enhanced neuroprotection in diabetic rats subjected to cerebral IR injury, and investigated the molecular pathways involved. Male rats were rendered diabetic using a high-fat diet and low-dose streptozotocin. After establishing diabetes, rats underwent transient middle cerebral artery occlusion followed by 24 h of reperfusion. Animals received sinomenine, metformin, or their combination for 7 days prior to IR induction. Neurological function was assessed using standardized behavioural tests. Molecular analyses measured markers of pyroptosis (NLRP3, cleaved caspase-1, gasdermin D N-terminal fragment), mitophagy (PTEN-induced kinase 1 (PINK-1), Parkin), inflammation (interleukin (IL)-1β, IL-18) and oxidative stress (malondialdehyde, superoxide dismutase, glutathione peroxidase). To determine the role of mitophagy, a subset of animals was pretreated with the mitophagy inhibitor mitochondrial division inhibitor 1 (Mdv-1). Combination therapy led to significant improvements in neurological performance, accompanied by downregulation of pyroptosis-associated proteins and pro-inflammatory cytokines, as well as enhanced activation of the PINK-1/Parkin mitophagy pathway and improved antioxidant status. The neuroprotective effects of the combined treatment were abolished by Mdv-1, indicating a critical role for mitophagy in mediating these benefits. The combination of sinomenine and metformin confers additive neuroprotection against cerebral IR injury in diabetic rats, primarily through inhibition of NLRP3-mediated pyroptosis and activation of the PINK-1/Parkin mitophagy pathway. These findings highlight a promising therapeutic strategy for diabetic stroke and warrant further preclinical and clinical investigation.

Menopause increases the risk of hypertension in women, yet the factors contributing to this important change remain unclear. Because early life stress has persistent and sex-specific consequences on health, we hypothesized that ageing reveals the latent effects of neonatal maternal separation (NMS) on cardiovascular homeostasis in female rats. Following birth, rats were either subjected to NMS (3 h/day from postnatal days 3 to 12) or raised under standard conditions (CTRL). Cardiovascular and neuroendocrine functions were evaluated at three distinct ages: young adult (12 weeks), middle-age (35 weeks) and old (64 weeks). Measurements included hormonal profile (multiplex assay), mean arterial blood pressure (MAP; tail cuff method), activity of the plasma angiotensin-converting enzymes (ACE and ACE2), and activation of the paraventricular nucleus of the hypothalamus (PVN; FosB immunolabelling). Age-related decline in 17β-oestradiol (E₂) was greater in NMS rats than CTRL. Age-related rise in MAP was observed only in NMS; MAP was inversely correlated with E₂ levels in NMS rats but not CTRL. In old females, ACE2 activity was 35% less in NMS than CTRL. ACE2 activity was inversely correlated with MAP in old but not young females, regardless of treatment. In the PVN, the number of FosB expressing cells decreased with age; this effect was greater in NMS females. Experiencing stress during early life is an important determinant of the ageing trajectory of females and reproductive senescence marks a turning point in regulation of cardiovascular function. Disruption of estrogen signaling and/or the renin-angiotensin system are plausible mechanisms by which NMS stress compromises cardiovascular health.

While exercise induces physiological cardiac growth, the underlying cellular mechanisms remain incompletely understood. This study investigated the role of cardiac telocytes (TCs) and the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in mediating exercise intensity-dependent cardiac adaptation. Twenty-four male Wistar rats were assigned to control (CTRL), high-intensity interval training (HIIT) or low-intensity interval training (LIIT) groups for 8 weeks. Physiological hypertrophy was assessed via heart weight/body weight ratio, left ventricular wall thickness, cardiomyocyte size and number. Cardiac TCs were quantified by immunofluorescence (CD34-platelet-derived growth factor receptor (PDGFR)-α/β). Gene expression of IL-6, cardiotrophin-1 (CTF1), GP130, JAK2, STAT3 and GATA4 was analysed by qPCR, and interleukin (IL)-6 protein levels were measured by ELISA. Both HIIT and LIIT robustly induced physiological cardiac hypertrophy and cardiomyogenesis, with HIIT producing a significantly greater response. This was accompanied by a significant, intensity-dependent expansion of the cardiac TC population in both HIIT and LIIT groups compared to CTRL, with HIIT inducing a greater increase than LIIT (P < 0.001). Furthermore, GATA4 expression, a marker of cardiac stem cell activation, was significantly upregulated in both trained groups. While cardiac IL-6 gene expression and protein levels were elevated, particularly after HIIT (P = 0.003), the core components of the JAK/STAT pathway (GP130, JAK2, STAT3) remained transcriptionally unaltered. Our findings establish cardiac TCs as novel, intensity-sensing cellular mediators of exercise-induced physiological growth. The adaptive process, linked to stem cell activation, occurs without concomitant transcriptional upregulation of the core JAK/STAT signalling pathway components, suggesting the involvement of alternative, potentially non-canonical, mechanistic pathways. This highlights the TC-cardiac stem cell axis as a potential target for optimizing exercise regimens for cardiac repair.

A lack of consensus remains on whether normobaric hypoxia (NH) and hypobaric hypoxia (HH) may differentially impact physiological factors affecting cerebrovascular regulation, particularly with an additional strenuous exercise component. We sought to compare the acute effects of NH and HH on global cerebral blood flow (gCBF) at an altitude corresponding to 4000 m. In this randomised, single-blind crossover study, eight lowlanders (3 females) completed three identical trials inside a hypobaric chamber: the first in normobaric normoxia, for familiarisation, followed in random order by one in NH and one in HH. In each trial, gCBF was measured at two time points via duplex ultrasound, first after 25 min of rest, and second, directly after a graded exercise test (GXT) to volitional exhaustion. Cardiorespiratory responses and cerebral oxygenation ( $r{S}_{c{O}_2}$ ) were assessed during all gCBF measurements. At rest, gCBF was higher in HH than in NH (944 ± 230 vs. 883 ± 226 mL min^-1; P = 0.027, respectively), whereas $r{S}_{c{O}_2}$ remained unchanged. Cardiorespiratory parameters did not differ, except for a reduction in the ratio of dead space to tidal volume in HH compared to NH (P = 0.028). Post-GXT, no differential response between the two hypoxic conditions was found. In comparison to NH, at rest gCBF is increased in HH for a given partial pressure of inspired oxygen, a response that is subsequently abolished post maximal cycling exercise. Although subtle, this response indicates that cerebrovascular regulation is affected differently in NH and HH, despite negligible changes in ventilation, and thus, alternative explanations are explored for future investigation.

Acute myocardial infarction (MI) accelerates cardiomyocyte apoptosis, which underpins ventricular remodelling and dysfunction. The hormone ghrelin mitigates this remodelling, but the mechanisms remain unclear. Specific microRNAs (miRs) are key modulators and reliable biomarkers of early-stage apoptosis. We hypothesized that ghrelin targets anti-apoptotic miR-499 and miR-133 following MI to suppress cardiac apoptosis and thus mitigate cardiac dysfunction. C57/B6 mice received an injection of ghrelin (150 µg/kg, s.c.) or saline following left anterior descending coronary artery ligation (MI). Plasma levels of miR-499 and miR-133 at 3 or 24 h post-MI were measured using real-time PCR. Echocardiography and TUNEL staining were used to assess progressive cardiac function/structure and cardiomyocyte apoptosis, respectively. Myocardial ischaemia adversely decreased the levels of anti-apoptotic miR-499 by 3 h post-MI and increased the proportion of TUNEL-positive apoptotic cardiomyocytes by 24 h post-MI, contributing to cardiac remodelling and dysfunction by 2 weeks post-MI. Ghrelin prevented this MI-induced decrease in miR-499 by 3 h post-MI, then further increased the levels of miR-499 and miR-133 by 24 h. These ghrelin-mediated changes in microRNA were associated with a significant decrease in cardiomyocyte apoptosis and, consequently, significantly improved cardiac function and structure by 2 weeks post-MI. These results highlight miRs as effective biomarkers for the early detection of ischaemia-induced apoptotic signalling. Moreover, ghrelin appears to mitigate ischaemia-induced apoptosis by increasing the levels of anti-apoptotic miR-499 and miR-133, further solidifying ghrelin as a new therapeutic strategy for the clinical treatment of heart failure.