Physiological Reports最新文献

Exercise counters many adverse health effects of consuming a high-fat diet (HFD). However, complex molecular changes that occur in skeletal muscle in response to exercising while consuming a HFD are not yet known. We investigated the interplay between diverse exercise regimes and HFD consumption on the adaptation of skeletal muscle transcriptome. C57BL/6 male mice were randomized into five groups-one sedentary control group and four exercise groups. The exercise groups consisted of an unrestricted running group (8.3 km/day) and three groups that were restricted to 75%, 50%, or 25% of unrestricted running (6.3, 4.2, and 2.1 km/day, respectively). Total RNA was extracted from frozen gastrocnemius muscle for transcriptome analyses. DEG counts were 1347, 1823, 1103, and 1107 and there were 107, 169, 67, and 89 unique genes present in the HFD-25%, HFD-50%, HFD-75%, and HFD-U, respectively. Comparing exercise groups, we found that exercising at 50% resulted in the most differentially expressed transcripts with the MAPK and PPAR signaling pathways enriched in down- and up-regulated genes, respectively. These results demonstrate that running distance impacts the adaptation of the skeletal muscle transcriptome to exercise and suggest that middle-distance running may provide the greatest protection against high-fat diet-induced stress coupled with exercise.

Available evidence suggests that various medical/rehabilitation treatments evoke multiple effects on blood hemostasis. It was therefore the aim of our study to examine whether fascial manipulation, vibration exercise, motor imagery, or neuro-muscular electrical stimulation can activate the coagulation system, and, thereby, expose patients to thrombotic risk. Ten healthy young subject were enrolled in the study. Blood samples were obtained pre and posttreatment. Besides standard laboratory methods, calibrated automated thrombography (CAT) and thrombelastometry (TEM) were used allowing sensitive detection of hyper- and hypocoagulable states. Application of fascial manipulation, motor imagery, or neuro-muscular electrical stimulation had vitually no effect whereas a single bout of vibration exercise caused significant coagulation activation. For example, TEM-derived coagulation times were significantly shortened (209 ± 34 vs. 187 ± 41 s, p = 0.0098) and CAT-derived thrombin peaks were significantly higher (235 ± 88 vs. 268 ± 82 nM, p = 0.0020) in post compared with preexercise samples. Moreover, vibration exercise, motor imagery, and neuro-muscular electrical stimulation caused significant plasma expansion (6.15%, 7.53%, and 3.88% plasma volume changes, respectively). We conclude that vibrational exercise apparently represents a potential procoagulant stimulus, and ongoing studies have to clarify whether VE should be applied particularly to patients with an elevated risk for thrombosis.

To assess the impact of thoracic load carriage on the physiological response to exercise in hypoxia. Healthy males (n = 12) completed 3 trials consisting of 45 min walking in the following conditions: (1) unloaded normoxia (UN; F_IO₂:20.93%); (2) unloaded hypoxia (UH; F_IO₂:~13.0%); and (3) loaded hypoxia (LH; 29.5 kg; F_IO₂:~13.0%). Intensity was matched for absolute VO₂ (2.0 ± 0.2 L·min^-1) across conditions and relative VO₂ (64.0 ± 2.6 %VO_2max) across hypoxic conditions. With LH versus UH, there were increases in breathing frequency (5-11 breaths·min^-1; p < 0.05) and decreases in tidal volume (10%-18%; p < 0.05) throughout exercise due to reductions in end inspiratory lung volumes (p < 0.05). Consequently, deadspace (11%-23%; p < 0.05) and minute ventilation (7%-11%; p < 0.05) were increased starting at 20 and 30 min, respectively. In addition, LH increased perceived exertion/dyspnea and induced inspiratory (~12%; p < 0.05 vs. UN) and expiratory (~10%; p < 0.05 vs. pre-exercise) respiratory muscle fatigue. Expiratory flow limitation was present in 50% of subjects during LH. Cardiac output and muscle oxygenation were maintained during LH despite reduced stroke volume (6%-8%; p < 0.05). Finally, cerebral oxygenated/total hemoglobin were elevated in the LH condition versus UH starting at 15 min (p < 0.05). Thoracic load carriage increases physiological strain and interferes with the compensatory response to hypoxic exposure.

Sympathoexcitation is a hallmark of heart failure, with sustained β-adrenergic receptor (βAR)-G protein signaling activation. βAR signaling is modulated by regulator of G protein signaling (RGS) proteins. Previously, we reported that Gα_i/o regulation by RGS2 or RGS5 is key to ventricular rhythm regulation, while the dual loss of both RGS proteins results in left ventricular (LV) dilatation and dysfunction. Here, we tested whether sustained βAR stimulation with isoproterenol (ISO, 30 mg/kg/day, 3 days) exacerbates LV remodeling in male mice with germline deletion of Rgs2 and/or Rgs5. Rgs2 KO and Rgs2/5 dbKO mice showed LV dilatation at baseline, which was unchanged by ISO. Rgs2 or Rgs5 deletion decreased Rgs1 expression, whereas Rgs5 deletion increased Rgs4 expression. ISO induced cardiac hypertrophy and interstitial fibrosis in Rgs2/5 dbKO mice without increasing cardiomyocyte size or LV dilation but increased expression of cardiac fetal gene Nppa, α-actinin, and Ca²⁺-/calmodulin-dependent kinase II. Single Rgs2 and Rgs5 KO mice had markedly increased CD45⁺ cells, whereas tissue from Rgs5 KO mice showed increased CD68⁺ cells, as revealed by immunohistochemistry. The results together indicate that ventricular remodeling due to Rgs2 and/or Rgs5 deletion is associated with augmented myocardial immune cell presence but is not exacerbated by sustained βAR stimulation.

The effects of social isolation (SI) during middle age remain unclear, so we tested the hypothesis that SI would lead to an increase in impulsive choice (IC), anxiety-like behavior, and metabolic dysfunction in middle-aged rats. Male and female rats were housed individually or in groups of four with same-sex housing mates at 11 months of age. Two months later, IC behavior was assessed using a delay-discounting task and anxiety-like behavior through a novelty-suppressed feeding (NSF) task. Lastly, glucose tolerance and insulin sensitivity following exposure to a high-fat diet were assessed using an oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT). The results showed that socially isolated rats displayed more IC behavior than did group-housed rats of both sexes. However, no significant effect of housing was evident in the NSF task, OGTT, or ITT. Male rats had a higher plasma insulin concentration and insulin resistance index compared to females. Our findings demonstrate that SI in middle age is sufficient to increase IC behavior and highlight inherent sex-specific differences in metabolic profiles. These findings underscore the importance of investigating mechanisms that underlie the effects of social isolation during different stages of life.

The effect of acetazolamide on regional brain tissue oxygenation in patients with acute brain injury (ABI) is unknown. We studied adult patients with ABI who received acetazolamide as per the treating physician's decision and had ICP and brain oxygen pressure (PbtO₂) monitoring. Baseline measurements of ICP, cerebral perfusion pressure (CPP), and PbtO₂ were taken before administering acetazolamide; subsequent measurements were recorded every 5 min for a total of 20 min. Mean cerebral blood velocities (FVm) and pulsatility index (PI) were measured using transcranial color-coded duplex (TCCD) sonography at baseline and after 20 min. Fourteen patients with subarachnoid hemorrhage (n = 6), traumatic brain injury (n = 7), and intracranial hemorrhage (n = 1) were included. Following administration of acetazolamide, ICP showed a significant increase within 20 min (p < 0.001), with no significant change in CPP (p = 0.08). PbtO₂ demonstrated a significant increase (p < 0.001), with a noticeable change observed at 10 min after acetazolamide administration (15 [14-17] vs. 28 [26-30] mmHg). Additionally, FVm exhibited a significant increase (p < 0.001), and PI showed a reduction (p < 0.001). Administration of acetazolamide in ABI patients resulted in a significant increase in brain oxygenation, associated with a rise in ICP and FVm, suggesting increased cerebral volume and vasodilation.

Transient receptor potential (TRP) channels with temperature sensitivities (thermo-TRPs) are involved in various physiological processes. Thermo-TRPs that detect temperature changes in peripheral sensory neurons possess indispensable functions in thermosensation, eliciting defensive behavior against noxious temperatures and driving autonomic/behavioral thermoregulatory responses to maintain body temperature in mammals. Moreover, most thermo-TRPs are functionally expressed in cells and tissues where the temperature is maintained at a constant core body temperature. To perform physiological functions, the activity of each thermo-TRP channel must be regulated by endogenous mechanisms at body temperature. Dysregulation of this process can lead to various diseases. This review highlights the endogenous factors regulating thermo-TRP activity and physiological functions at constant core body temperature.

"I see, I forget, I read aloud, I remember, and when I do read purposefully by writing it, I do not forget it." This phenomenon is known as "interoception" and refers to the sensing and interpretation of internal body signals, allowing the brain to communicate with various body systems. Dysfunction in interoception is associated with cardiovascular disorders. We delve into the concept of interoception and its impact on heart failure (HF) by reviewing and exploring neural mechanisms underlying interoceptive processing. Furthermore, we review the potential of artificial intelligence (AI) in diagnosis, biomarker development, and HF treatment. In the context of HF, AI algorithms can analyze and interpret complex interoceptive data, providing valuable insights for diagnosis and treatment. These algorithms can identify patterns of disease markers that can contribute to early detection and diagnosis, enabling timely intervention and improved outcomes. These biomarkers hold significant potential in improving the precision/efficacy of HF. Additionally, AI-powered technologies offer promising avenues for treatment. By leveraging patient data, AI can personalize therapeutic interventions. AI-driven technologies such as remote monitoring devices and wearable sensors enable the monitoring of patients' health. By harnessing the power of AI, we should aim to advance the diagnosis and treatment strategies for HF. This review explores the potential of AI in diagnosing, developing biomarkers, and managing HF.

While total RNA concentrations putatively represent ribosome content, there is a need to homologize various quantification approaches. Thus, total RNA concentrations ([RNA]) provided through UV-Vis spectroscopy (UV), fluorometry-only (Fluor), and fluorometry-based microfluidic chip electrophoresis (MFGE) were examined in C2C12 myotubes and mouse skeletal muscle to determine if values aligned with [18S + 28S rRNA] (i.e., criterion ribosome metric). A novel antibody cocktail (termed RiboAb) was also tested and compared to [18S + 28S rRNA] in these models. In myotubes, 24-h IGF-1 treatments increased [18S + 28S rRNA] (~2.0-fold) and [RNA] based on UV (~1.9-fold), Fluor (~2.3 fold), and MFGE (~2.1-fold). In C57BL/6 mice, 10 days of mechanical overload (MOV) elevated plantaris [18S + 28S rRNA] (~1.7-fold) and [RNA] according to UV (~1.5-fold), Fluor (~1.6-fold), and MFGE (~1.8-fold). Myotube and mouse plantaris RiboAb levels were significantly higher with IGF-1 treatments and MOV, respectively, versus controls (1.3-fold and 1.7-fold, respectively), and values correlated with [18S + 28S rRNA] (r = 0.637 and r = 0.853, respectively, p ≤ 0.005). UV, Fluor, and MFGE [RNA] are seemingly valid surrogates of cell/tissue ribosome content, although each method has advantages (e.g., ease of use) and disadvantages (e.g., magnitudes of bias) discussed herein. Finally, the RiboAb cocktail may also represent ribosome content, although this should be further explored in other models.