Physiological Reports最新文献

The oral administrated thiazolidinediones (TZDs) have been widely reported to alleviate experimental pulmonary hypertension (PH). However, previous studies mainly focused on their beneficial effects on the cardiopulmonary vascular system but failed to determine their potential roles on gut microenvironment. This study aims to investigate the effects of pioglitazone, an oral TZD drug, on gut microbiome in classic PH rat models induced by hypoxia (HPH) or SU5416/hypoxia (SuHx-PH) and evaluate the therapeutic potential of supplementation of selective probiotics for experimental PH. Pioglitazone remarkably inhibited the PH pathogenesis in both models and reshaped the gut microbiome and plasma metabolome. Correlation analyses represented strong and unique association between the protective metabolites and bacteria genera (Roseburia, Lactobacillus, and Streptococcus) that were positively stimulated by pioglitazone. Supplementation of selective probiotics Roseburia intestinalis (R. intestinalis) partially attenuated SuHx-PH and rebuilt a novel gut microbiome and host metabolome. This study reports for the first time that oral administration of pioglitazone protects PH by regulating the gut microbiome and host metabolome, providing novel insights for the TZD drugs. The data also supports that modulation of gut microbiota by supplementation of selective probiotics could be a novel effective therapeutic strategy for the treatment of PH.

Contrary to cardiovascular risk reductions by aerobic exercise, arterial stiffness, as assessed by brachial-ankle pulse wave velocity (PWV), is higher in swimmers and controls than in other aerobically trained individuals. The main muscles actively recruited in swimming are in the upper limbs, so this study aimed to investigate heart-brachial PWV in swimmers and to compare arterial stiffness indices between modes and measurement localities. Subjects comprised 60 individuals (18-22 years), including 20 untrained controls (Con), 20 aerobically trained cyclists (Aero), and 20 swimmers (Swim). Characteristics and strength did not differ, but peak oxygen uptake was significantly higher in Aero and Swim than in Con. Brachial-ankle PWV was significantly lower in Aero than in Con and Swim and no significant difference was observed between Con and Swim (Con, 1070 ± 115; Aero, 916 ± 109; Swim, 1035 ± 91 cm/s). Nevertheless, heart-brachial PWV was significantly lower in Swim than in Con and tended to be lower in Swim than in Aero (Con, 344 ± 25; Aero, 330 ± 41; Swim, 308 ± 31 cm/s). Heart-ankle PWV was significantly lower in both Swim and Aero than in Con (Con, 618 ± 47; Aero, 580 ± 54; Swim, 576 ± 43 cm/s). Therefore, these findings indicate that swimmers can develop segment-specific reductions in heart-brachial arterial stiffness, unlike aerobically trained cyclists.

Inflammation and a metabolic shift from oxidative metabolism to glycolysis are common in the ischemic heart, the latter partly controlled by pyruvate kinase (muscle, PKM). We previously identified alternative splicing promoting the PKM2 isoform after myocardial infarction (MI). We examined the role of PKM2 physiological upregulation after MI, modeled by ligation of the left anterior descending coronary artery, using global PKM2 knockout (PKM2^-/-) mice. Echocardiography showed similar cardiac function between PKM2^-/- and control mice after MI. However, PKM2^-/- infarcted hearts had increased abundances of transcripts associated with oxidative stress and immune responses. Immunohistochemistry revealed greater abundance of macrophages in PKM2^-/- hearts prior to MI, with a small increase in CD86⁺ macrophages in PKM2^-/- infarcted hearts. Elevated baseline plasma IL-6, IL-1β, and C-reactive protein, and cardiac IL-6, 3 days post-MI, were observed in PKM2^-/- mice. Oxidative lipid products were also elevated in baseline PKM2^-/- hearts, while antioxidant glutathione peroxidase 4 was reduced. Greater fibrosis was seen in PKM2^-/- hearts 28 days after MI. These findings suggest Pkm2 ablation primes the heart for increased oxidative stress, inflammation, and fibrosis post-MI. The natural upregulation of PKM2 may mitigate fibrosis by reducing oxidative stress and inflammation, highlighting its protective role in the infarcted heart.

Given the growing concern over the impact of brain health in individuals with overweight, understanding how mental exertion (ME) during exercise affects substrate oxidation and cardiorespiratory outcomes is crucial. This study examines how ME impacts these outcomes during an incremental exercise test in adults with overweight. Seventeen adults who were overweight completed an incremental exercise test on a cycle ergometer two times, with and without the Stroop task. Energy expenditure (EE), carbohydrate and fat oxidation, maximum heart rate (HR_max), maximal oxygen uptake (VO2_max), maximum fat oxidation (MFO), and the intensity of exercise that elicited MFO (Fat_max) are measured by indirect calorimetry. ME did not change the EE, carbohydrate, and fat oxidation at any stages of the incremental test. However, ME resulted in significantly lower HR_max, VO2_max, and MFO (p < 0.01) and increased NASA-TLX scores but showed no change in Fat_max. These results show ME decreases the value of HR_max, VO2_max, and MFO during the incremental exercise test. Due to the increased mental workload demonstrated by the NASA-TLX test, adults with overweight are unable to complete the test to the same extent as they did in the test without ME according to maximal levels in this study.

While autonomic dysregulation and repolarization abnormalities are observed in subarachnoid hemorrhage (SAH), their relationship remains unclear. We aimed to measure skin sympathetic nerve activity (SKNA), a novel method to estimate stellate ganglion nerve activity, and investigate its association with electrocardiogram (ECG) alterations after SAH. We recorded a total of 179 SKNA data from SAH patients at three distinct phases and compared them with 20 data from controls. Compared with control data, in the acute phase data (days 1-3 of SAH), T peak-to-end (Tp-e) interval was significantly prolonged (81 [interquartile range {IQR}: 71-93] vs. 58 [IQR: 54-64] ms, p < 0.001), non-burst amplitude of SKNA was significantly increased (2.4 [IQR: 1.3-4.1] vs. 0.7 [IQR: 0.5-1.7] μV, p < 0.001), and the ratio of low frequency to high frequency (HF) was significantly decreased (0.8 [IQR: 0.5-1.1] vs. 1.1 [IQR: 0.7-1.3], p = 0.028). Linear mixed model revealed a relationship between Tp-e interval and SKNA. Although these abnormalities gradually normalized, delayed cerebral ischemia episodes were associated with increased HF oscillation. Transient sympathetic dysregulation contributes to repolarization impairment after SAH. SKNA may have the potential to monitor adverse outcomes.

MicroRNAs (miRNAs) are small, noncoding RNAs that play a critical role in regulating gene expression post-transcriptionally. They are involved in various developmental and physiological processes, and their dysregulation is linked to various diseases. Skeletal muscle-specific miRNAs, including miR-1, play a crucial role in the development and maintenance of skeletal muscle. It has been demonstrated that the expression of miR-1 decreases by approximately 50% in response to hypertrophic stimuli, suggesting its potential involvement in muscle hypertrophy. In our study, we hypothesize that reduction of miR-1 levels is necessary for skeletal muscle growth due to its interaction to essential pro-growth genes. Promoting a smaller reduction of miR-1 levels, we observed a blunted hypertrophic response in mice undergoing a murine model of muscle hypertrophy. In addition, our results suggest that miR-1 inhibits the expression of Itm2a, a membrane-related protein, as potential miR-1-related candidate for skeletal muscle hypertrophy. While the exact mechanism in muscle hypertrophy has not been identified, our results suggest that miR-1-regulated membrane proteins are important for skeletal muscle hypertrophy.

Police officers are exposed to high levels of stress. Serving on Special Weapons and Tactics (SWAT) teams is a highly demanding duty that may further increase levels of stress in police personnel. This stress may accumulate, thereby increasing allostatic load. As such, holistic stress measures may be valuable for quantifying multifactorial stress accumulation in SWAT personnel. Heart rate variability (HRV) is one field-deployable measure that may be suitable in this context. However, with logistical challenges present in this population, determining if 30 s; rather than more the typical 5-min ECG data collection, provides sufficient reliability may be beneficial for reducing the logistical barrier to adoption of HRV monitoring in SWAT personnel. This study compared 30-s to 5-min HRV analyses of ECG data obtained from 15 male SWAT personnel. Findings demonstrated good (ICC >0.8) reliability only in the VLF, HF, SD1, and SD2 HRV domains. The VLF and SD2 measures may be erroneous, as 5-min may still insufficiently characterize these measures. However, this study confirms the robust quality of nonlinear HRV analysis, as the SD1 value demonstrated the highest ICC reported here (0.902). Therefore, while 5-min ECGs may still preferable, the 30-s measure may still be viable for organizations considering HRV assessment.

Sepsis leads to an acute breakdown of muscle to support increased caloric and amino acid requirements. Little is known about the role of adipose and muscle tissue breakdown and intestinal metabolism in glucose substrate supply during the acute phase of sepsis. In a translational porcine model of sepsis, we explored the across organ net fluxes of gluconeogenic substrates. In 13 pigs, acute sepsis was induced by IV infusion of Pseudomonas aeruginosa, while in 9 pigs saline (control) was given for 18 h. Blood samples were collected between 12 and 18 h and analyzed with HPLC and LCMS. In sepsis, glucose plasma concentration was reduced (p = 0.0028). A concordant increase in splanchnic area net release of glucose (p = 0.0049), due to reduced uptake in the portal drained viscera (PDV) (p = 0.0032) with an unchanged liver production (p = 0.7861). The hindquarter showed a higher release of alanine (p = 0.0002), glutamine (p = 0.003), and lactate (p = 0.0007), but not for glycerol (p = 0.5718). Diminished PDV uptake of gluconeogenic amino acids, increased liver uptake of these substrates (p < 0.05), while no change in liver glycerol uptake (p = 0.3170), did not lead to an increased net liver glucose release. In the acute phase of sepsis, we hypothesize an important role of altered intestinal amino acid metabolism and breakdown of muscle proteins, but not of glycolysis to support gluconeogenesis.

Both resistance training (RT) and long-duration, high-intensity stretching induce muscular adaptations; however, it is unknown whether the modalities are complementary or redundant, particularly in well-trained individuals. A case-study was conducted on a competitive bodybuilder implementing long-duration, high-intensity stretching of the plantar flexors (60 min 6x/week for 12 weeks) in conjunction with their habitual RT. Ultrasound muscle architecture (muscle thickness [MT], fascicle length [FL], and pennation angle [PA]) measurements were collected at multiple sites at four weekly baseline sessions, six (mid) and 12 (post1) weeks following the commencement of the intervention, and a week after the intervention (post2) while isometric strength and range of motion (RoM) were obtained once at baseline, mid, post1, and post2. 2SD band plots were constructed to determine meaningful changes in MT, FL, and PA from the four baseline measures while percentage and absolute change across each timepoint were calculated for all variables. From baseline to post 1, RoM, strength, and MT increased 25.9%, 11.4%, and 7.4%-23.4%, respectively, while four MT and two PA sites exceeded the threshold for meaningful change. The combined stretching and RT protocols resulted in flexibility, strength, and MT adaptations; however, findings should be generalized with caution given the case-study nature of our investigation.

Melatonin is a multifunctional biomolecule with demonstrated stimulatory, inhibitory, and antioxidant effects, including both receptor-mediated and receptor-independent mechanisms of action. One of its more perplexing effects is the disruption of regeneration in planaria. Head regeneration in planaria is a remarkable phenomenon in which stem cells (neoblasts) migrate to the wound site, proliferate, then differentiate into all functional tissue types within days of injury. We investigated how both the timing and duration of melatonin exposure affect head regeneration in the planaria Phagocata gracilis (Haldeman). Our results demonstrate that P. gracilis is capable of recovery from the melatonin-induced delay of regeneration and reveal the time required to recover to control levels. Further, we found evidence of regenerative stage-specific responses to discontinuous melatonin exposure, including non-inhibitory effects. Further exploration of melatonin's effects on regeneration can be targeted to specific regenerative processes, and the possibility of multiple mechanisms of action should be recognized.