Untargeted metabolomics analysis of rat hippocampus subjected to sleep fragmentation

Sleep fragmentation (SF) commonly occurs in several pathologic conditions and is especially associated with impairments of hippocampus-dependent neurocognitive functions. Although the effects of SF on hippocampus in terms of protein or gene levels were examined in several studies, the impact of SF at the metabolite level has not been investigated. Thus, in this study, the differentially expressed large-scale metabolite profiles of hippocampus in a rat model of SF were investigated using untargeted metabolomics approaches. Forty-eight rats were divided into the following 4 groups: 4-day SF group, 4-day exercise control (EC) group, 15-day SF group, and 15-day EC group (n = 12, each). SF was accomplished by forced exercise using a walking wheel system with 30-s on/90-s off cycles, and EC condition was set at 10-min on/30-min off. The metabolite profiles of rat hippocampi in the SF and EC groups were analyzed using liquid chromatography/mass spectrometry. Multivariate analysis revealed distinctive metabolic profiles and marker signals between the SF and corresponding EC groups. Metabolic changes were significant only in the 15-day SF group. In the 15-day SF group, L-tryptophan, myristoylcarnitine, and palmitoylcarnitine were significantly increased, while adenosine monophosphate, hypoxanthine, L-glutamate, L-aspartate, L-methionine, and glycerophosphocholine were decreased compared to the EC group. The alanine, aspartate, and glutamate metabolism pathway was observed as the common key pathway in the 15-day SF groups. The results from this untargeted metabolomics study provide a perspective on metabolic impact of SF on the hippocampus.Peer reviewe

Coexistence of Moderate-to-Severe Obstructive Sleep Apnea and Inflammation Accelerates the Risk of Progression of Arterial Stiffness: A Prospective 6-Year Study

Both obstructive sleep apnea (OSA) and inflammation have now been recognized as imposing substantial cardiometabolic risk. However, no prospective study has reported whether the coexistence of OSA and inflammation exacerbates the progressive arterial stiffening. Thus, the purpose of this study is to examine whether these conditions increase the risk of the progression of arterial stiffening. A total of 1945 participants were randomly selected for the study. Subjects with elevated inflammation were divided by high-sensitivity C-reactive protein (hsCRP) levels. A polysomnography and brachial–ankle pulse wave velocity (baPWV) were performed. The elevation of the baPWV was defined as the levels in the highest quartile of the baPWV. The percentage of the elevated baPWV and the change in the baPWV (ΔbaPWV) were higher in individuals with OSA and higher hsCRP levels. After adjusting for confounders, the participants with OSA and inflammation in the groups not treated with antihypertensive medication had a higher risk of an elevated ΔbaPWV in contrast to those with neither variable. Particularly, the alteration in the baPWV differed significantly based on the existence of moderate-to-severe OSA and inflammation at the 6-year follow-up. In combination, these conditions are associated with an accelerated risk of a future burden of the progression of the arterial stiffness, suggesting a potential important role in the increased risk of CVD

Exosome and Melatonin Additively Attenuates Inflammation by Transferring miR-34a, miR-124, and miR-135b

The positive effects of mesenchymal stem cells (MSCs) are primarily activated through molecular secretions known as paracrine activity, which regulates the function of various cell types including immune cells. Accumulating evidence shows that exosomes of soluble factors released from MSCs are potential alternative agents for stem cell-based therapy, although the exact underlying mechanism has not been elucidated. The purpose of this study was to evaluate the potential effects of exosomes produced by adipose-derived MSCs and to examine the changes in anti-inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex vivo. Isolated exosomes were used to investigate the inflammatory modulation in pro-inflammatory cytokine-treated fibroblasts and THP-1 cells. The anti-inflammatory mRNA expression associated with M2 macrophages was significantly upregulated after exosome treatment in an interferon gamma and tumor necrosis factor alpha-treated inflammatory environment. Furthermore, melatonin-stimulated exosomes exerted superior anti-inflammatory modulation via exosomal miRNAs miR-34a, miR-124, and miR-135b, compared with exosomes. Our results indicate that melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and efficient tools for regenerative medicine to treat inflammatory diseases

A Case of Frequent Arousal Following Nocturnal Dyspnea Caused by Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common disorder that is associated with many esophageal syndromes and complications. Most cases of reflux event occur during the day, but reflux during sleep can cause not only esophageal problems, but also sleep problems, such as arousal and poor sleep quality. We report the case of a 17-year-old man who had been referred to us with frequent arousal following sudden dyspnea. On polysomnography, no respiratory disturbances and periodic limb movements were found during the sleep study, but frequent events of arousal were reported (arousal index: 12.3/h). On a 24-hr esophageal pH monitoring test, his DeMeester score was 176.43 and the total reflux time was 1120.9 min (76.9%), indicating the presence of significant acid reflux. After treatment with a proton-pump inhibitor, the arousals following nocturnal dyspnea and fatigue in the morning disappeared in the patient. GERD should be considered as a cause of spontaneous arousal or awakening not accompanying respiratory disturbances

Validation of a Walking Wheel Method to Fragment Sleep in Rats

Background and Objective Many attempts have sought to devise an animal model of sleep fragmentation (SF) to understand the clinical effects of sleep loss, but no study has investigated the usefulness of the walking wheel method to interrupt sleep in rats. Methods Seven-week-old male Wistar rats were divided into a SF group and an exercise control (EC) group, with five rats in each. SF was achieved with a walking wheel using a 30 s on, 90 s off interval (total walking time 6 h/day). The EC group walked the same distance. Rat multiple sleep latency test was performed to measure sleepiness in rats. Sleep data were collected at baseline, and 4, 12, and 18 days after treatment. Percent (%) time spent awake and in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, NREM and wake bout number, NREM bout length, and mean sleep latency were analyzed. Results Numbers of NREM and wake bout were higher in the SF group, whereas the NREM bout length was smaller than in the baseline group. Unlike NREM, REM sleep (%) in the SF group was significantly lower than in the baseline and EC groups. Mean sleep latency was shortened in the SF group compared to the baseline and EC groups. EC did not differ significantly with respect to the amount of sleep time (%), bout number of NREM and wakefulness, NREM bout length, and mean sleep latency, compared to its own baseline. Conclusions Use of a walking wheel is an effective means of interrupting sleep in rats during a long-term period

Tae-Eum Type as an Independent Risk Factor for Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is prevalent and associated with several kinds of chronic diseases. There has been evidence that a specific type of Sasang constitution is a risk factor for metabolic and cardiovascular diseases that can be found in patients with OSA, but there are no studies that address the association between the Sasang constitution type (SCT) and OSA. The purpose of this study was to investigate the association between the SCT and OSA. A total of 652 participants were included. All participants were examined for demographic information, medical history, and completed an interviewer-administered questionnaire on life style and sleep-related variables. Biochemical analyses were performed to determine the glucose and lipid profiles. An objective recording of OSA was done with an unattended home PSG using an Embla portable device. The apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were significantly higher in the Tae-eum (TE) type as compared to the So-eum (SE) and the So-yang (SY) types. Even after adjusting for confounding variables, the TE type still had a 2.34-fold (95% CI, 1.11–4.94; P=0.0262) increased risk for OSA. This population-based cohort study found that the TE constitutional type is an independent risk factor for the development of OSA

Tae-Eum type as an independent risk factor for obstructive sleep apnea,” Evidence-Based Complementary and Alternative Medicine,

Obstructive sleep apnea (OSA) is prevalent and associated with several kinds of chronic diseases. There has been evidence that a specific type of Sasang constitution is a risk factor for metabolic and cardiovascular diseases that can be found in patients with OSA, but there are no studies that address the association between the Sasang constitution type (SCT) and OSA. The purpose of this study was to investigate the association between the SCT and OSA. A total of 652 participants were included. All participants were examined for demographic information, medical history, and completed an interviewer-administered questionnaire on life style and sleep-related variables. Biochemical analyses were performed to determine the glucose and lipid profiles. An objective recording of OSA was done with an unattended home PSG using an Embla portable device. The apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were significantly higher in the Tae-eum (TE) type as compared to the So-eum (SE) and the So-yang (SY) types. Even after adjusting for confounding variables, the TE type still had a 2.34-fold (95% CI, 1.11-4.94; = 0.0262) increased risk for OSA. This population-based cohort study found that the TE constitutional type is an independent risk factor for the development of OSA