Physiological Reports最新文献

Diving marine mammals are a diverse group of semi- to completely aquatic species. Some species are targets of conservation and rehabilitation efforts; other populations are permanently housed under human care and may contribute to clinical and biomedical investigations. Veterinary medical care for species under human care, at times, may necessitate the use of general anesthesia for diagnostic and surgical indications. However, the unique physiologic and anatomic adaptations of one representative diving marine mammal, the bottlenose dolphin, present several challenges in providing ventilatory and cardiovascular support to maintain adequate organ perfusion under general anesthesia. The goal of this review is to highlight the unique cardiopulmonary adaptations of the completely aquatic bottlenose dolphin (Tursiops truncatus), and to identify knowledge gaps in our understanding of how those adaptations influence their physiology and pose potential challenges for sedation and anesthesia of these mammals.

Prior studies have documented the role of the striatum and its dopaminergic input in time processing, but the contribution of local striatal cholinergic innervation has not been specifically investigated. To address this issue, we recorded the activity of tonically active neurons (TANs), thought to be cholinergic interneurons in the striatum, in two male macaques performing self-initiated movements after specified intervals in the seconds range have elapsed. The behavioral data showed that movement timing was adjusted according to the temporal requirements. About one-third of all recorded TANs displayed brief depressions in firing in response to the cue that indicates the interval duration, and the strength of these modulations was, in some instances, related to the timing of movement. The rewarding outcome of actions also impacted TAN activity, as reflected by stronger responses to the cue paralleled by weaker responses to reward when monkeys performed correctly timed movements over consecutive trials. It therefore appears that TAN responses may act as a start signal for keeping track of time and reward prediction could be incorporated in this signaling function. We conclude that the role of the striatal cholinergic TAN system in time processing is embedded in predicting rewarding outcomes during timing behavior.

The transplantation of collagen hydrogels encapsulating human dental pulp stem cell (DPSC)-derived chondrogenic cells is potentially a novel approach for the regeneration of degenerated nucleus pulposus (NP) and cartilage. Grafted cell migration allows cells to disperse in the hydrogels and the treated tissue from the grafted location. We previously reported the cell migration in type I and type II hydrogels. It is important to explore further how cell culture time affect the cell motility. In this study, we observed the decreased motility of DPSC-derived chondrogenic cells after culturing for 2 weeks compared with cells cultured for 2 days in these gels. The Alamarblue assay showed the cell proliferation during the two-week cell culture period. The findings suggest that the transitions of cell motility and proliferation during the longer culture time. The result indicates that the early culture stage is an optimal time for cell transplantation. In a degenerated disc, the expression of IL-1β and TNFα increased significantly compared with healthy tissue and therefore may affect grafted cell migration. The incorporation of IL-1β and TNFα into the collagen hydrogels decreased cell motility. The study indicates that the control of IL-1β and TNFα production may help to maintain cell motility after transplantation.

In cirrhotic patients, compromised hepatocyte function combined with disturbed hepatic blood flow could affect hepato-splanchnic substrate and metabolite fluxes and exacerbate fatigue during exercise. Eight cirrhotic patients performed incremental cycling trials (3 × 10 min; at light (28 [19-37] W; median with range), moderate (55 [41-69] W), and vigorous (76 [50-102] W) intensity). Heart rate increased from 68 (62-74) at rest to 95 (90-100), 114 (108-120), and 140 (134-146) beats/min (P < 0.05), respectively. The hepatic blood flow, as determined by constant infusion of indocyanine green with arterial and hepatic venous sampling, declined from 1.01 (0.75-1.27) to 0.69 (0.47-0.91) L/min (P < 0.05). Hepatic glucose output increased from 0.6 (0.5-0.7) to 1.5 (1.3-1.7) mmol/min, while arterial lactate increased from 0.8 (0.7-0.9) to 9.0 (8.1-9.9) mmol/L (P < 0.05) despite a rise in hepatic lactate uptake. Arterial ammonia increased in parallel to lactate from 47.3 (40.1-54.5) to 144.4 (120.5-168.3) μmol/L (P < 0.05), although hepatic ammonia uptake increased from 19.5 (12.4-26.6) to 69.5 (46.5-92.5) μmol/min (P < 0.05). Among the 14 amino acids measured, glutamate was released in the liver, while the uptake of free fatty acids decreased. During exercise at relatively low workloads, arterial lactate and ammonia levels were comparable to those seen in healthy subjects at higher workloads, while euglycemia was maintained due to sufficient hepatic glucose production. The accumulation of lactate and ammonia may contribute to exercise intolerance in patients with cirrhosis.

Standard cardiopulmonary exercise testing (CPET) produces a rich dataset but its current analysis is often limited to a few derived variables such as maximal or peak oxygen uptake (V̇O₂). We tested whether breath-by-breath CPET data could be used to determine sample entropy (SampEn) in 81 healthy children and adolescents (age 7-18 years old, equal sex distribution). To overcome challenges of the relatively small time-series CPET data size and its nonstationarity, we developed a Python algorithm for short-duration physiological signals. Comparing pre- and post-ventilatory threshold (VT₁) CPET phases, we found: (1) SampEn decreased by 9.46% for V̇O₂ and 5.01% for V̇CO₂ (p < 0.05), in the younger, early-pubertal participants; and (2) HR SampEn fell substantially by 70.8% in the younger and 77.5% in the older participants (p < 0.001). Across all ages, females exhibited greater HR SampEn than males during both pre- and post VT₁ CPET phases by 14.10% and 23.79%, respectively, p < 0.01. In females, late-pubertal had 17.6% lower HR SampEn compared to early-pubertal participants (p < 0.05). Breath-by-breath gas exchange and HR data from CPET are amenable to SampEn analysis that leads to novel insight into physiological responses to work intensity, and sex and maturational effects.

Cancer cachexia manifests as whole body wasting, however, the precise mechanisms governing the alterations in skeletal muscle and cardiac anabolism have yet to be fully elucidated. In this study, we explored changes in anabolic processes in both skeletal and cardiac muscles in the Yoshida AH-130 ascites hepatoma model of cancer cachexia. AH-130 tumor-bearing rats experienced significant losses in body weight, skeletal muscle, and heart mass. Skeletal and cardiac muscle loss was associated with decreased ribosomal (r)RNA, and hypophosphorylation of the eukaryotic factor 4E binding protein 1. Endoplasmic reticulum stress was evident by higher activating transcription factor mRNA in skeletal muscle and growth arrest and DNA damage-inducible protein (GADD)34 mRNA in both skeletal and cardiac muscles. Tumors provoked an increase in tissue expression of interferon-γ in the heart, while an increase in interleukin-1β mRNA was apparent in both skeletal and cardiac muscles. We conclude that compromised skeletal muscle and heart mass in the Yoshida AH-130 ascites hepatoma model involves a marked reduction translational capacity and efficiency. Furthermore, our observations suggest that endoplasmic reticulum stress and tissue production of pro-inflammatory factors may play a role in the development of skeletal and cardiac muscle wasting.

Kidney response to acute and mechanically induced variation in ventilation associated with different levels of PEEP has not been investigated. We aimed to quantify the effect of ventilatory settings on renal acid-base compensation. Forty-one pigs undergoing hypo- (<0.2 Lkg^-1 min^-1, PEEP 25 cmH₂O), intermediate (0.2-0.4 Lkg^-1 min^-1 with either PEEP 5 or 25 cmH₂O), or hyper-ventilation (>0.4 Lkg^-1 min^-1, PEEP 5 cmH₂O) for 48 h were retrospectively included. The decrease in pH paralleled the decrease in plasma strong ion difference (SID) in hyper- and intermediately ventilated groups with lower PEEP. In contrast, the plasma SID remained nearly constant in hypo- and intermediately ventilated groups with higher PEEP. Changes in plasma chloride concentration accounted for the changes in plasma SID (conditional R² = 0.86). The plasma SID changes were paralleled by mirror changes in urinary SID. Higher PEEP (25 cmH₂O), compared to lower PEEP (5 cmH₂O) dampened or abolished the renal compensation through its effect on hemodynamics (higher central venous and mean pulmonary pressures), irrespective of minute ventilation. During mechanical ventilation, the compensatory renal response to respiratory derangement is immediate and progressive but can be dampened by high PEEP levels.

The carotid body (CB) senses changes in arterial O₂ partial pressure (pO₂) and glucose levels; therefore, it is key for the detection of hypoxia and hypoglycemia. The CB has been suggested to detect pO₂ through an increase in reactive oxygen species (ROS) in the mitochondria. However, the mechanism protecting the chemoreceptor cells and their mitochondria from ROS and hyperglycemia is poorly understood. Here we measured glutathione levels in CB mitochondria of control and in streptozotocin (STZ)-induced type 1 diabetic male Wistar rats. We found a dramatic reduction in total glutathione from 11.45 ± 1.30 μmol/mg protein in control rats to 1.45 ± 0.31 μmol/mg protein in diabetic rats. However, the ratio of reduced to oxidized glutathione, a measure of the redox index, was increased in diabetic rats compared to controls. We conclude that the mitochondria of CB chemoreceptor cells in type 1 diabetic male Wistar rats were likely under glutathione-reducing stress.

Major histocompatibility complex class I (MHC I) molecules present peptides to CD8+ T-cells for immunosurveillance of infection and cancer. Recent studies indicate lineage-specific heterogeneity in MHC I expression. While respiratory diseases rank among the leading causes of mortality, studies in mice have shown that lung epithelial cells (LECs) express the lowest levels of MHC I in the lung. This study aims to answer three questions: (i) Do human LECs express low levels of MHC I? (ii) Is LEC MHC I expression modulated in chronic respiratory diseases? (iii) Which factors regulate MHC I levels in human LECs? We analyzed human LECs from parenchymal explants using single-cell RNA sequencing and immunostaining. We confirmed low constitutive MHC I expression in human LECs, with significant upregulation in chronic respiratory diseases. We observed a sexual dimorphism, with males having higher MHC I levels under steady-state conditions, likely due to differential redox balance. Our study unveils the complex interplay between MHC I expression, sex, and respiratory disease. Since MHC I upregulation contributes to the development of immunopathologies in other models, we propose that it may have a similar impact on chronic lung disease.

Insulin-like growth factor-1-induced activation of ATP citrate lyase (ACLY) improves muscle mitochondrial function through an Akt-dependent mechanism. In this study, we examined whether Akt1 deficiency alters skeletal muscle fiber type and mitochondrial function by regulating ACLY-dependent signaling in male Akt1 knockout (KO) mice (12-16 weeks old). Akt1 KO mice exhibited decreased body weight and muscle wet weight, with reduced cross-sectional areas of slow- and fast-type muscle fibers. Loss of Akt1 did not affect the phosphorylation status of ACLY in skeletal muscle. The skeletal muscle fiber type and expression of mitochondrial oxidative phosphorylation complex proteins were unchanged in Akt1 KO mice compared with the wild-type control. These observations indicate that Akt1 is important for the regulation of skeletal muscle fiber size, whereas the regulation of muscle fiber type and muscle mitochondrial content occurs independently of Akt1 activity.