Tissue hypoxia caused by upper airway collapse is a main cause of excessive oxidative stress and systemic inflammation in obstructive sleep apnea (OSA) patients. Increased reactive oxygen species (ROS) and inflammatory responses affect cell survival and ultimately contribute to tissue injury. In the present study, we proposed that the induction of ROS by hypoxia, as an intrinsic stress, activates myoblast pyroptosis in OSA. We found increased cell death and abnormal expression of pyroptosis markers in the skeletal muscle of OSA mice. In vitro studies showed hypoxia-induced pyroptotic death of C2C12 myoblasts, as evidenced by the activation of caspase-1 and gasdermin D (GSDMD). Hypoxia induced ROS overproduction and accumulation in myoblasts. More importantly, applying N-acetylcysteine (NAC), an ROS scavenger, rescued cell swelling, downregulated the inflammatory response, and prevented pyroptotic death in hypoxia-cultured myoblasts. Hypoxia stimulation promoted NF-κB P65 phosphorylation and HIF-1α nuclear translocation. Moreover, hypoxia increased the nuclear level of cleaved caspase-1 and GSDMD. NAC inhibited hypoxia-induced variations in the HIF-1α and NF-κB signaling pathway. Taken together, our results determined that hypoxia-induced ROS contribute to myoblast pyroptosis. Therefore, our findings suggest that ROS may be a potential therapeutic target for ameliorating hypoxia-induced cell death and tissue injury, especially in OSA and hypoxia-related diseases.

Purpose: Obesity is a worldwide metabolic disease and a critical risk factor for several chronic conditions. Obstructive sleep apnea (OSA) is an important complication of obesity. With the soaring morbidity of obesity, the prevalence of OSA has markedly increased. However, the underlying mechanism of the high relevance between obesity and OSA has not been elucidated. This study investigated the effects of obesity on the structure and function of the genioglossus to explore the possible mechanisms involved in OSA combined with obesity. Methods: Six-week-old male C57BL/6J mice were fed high-fat diet (HFD, 60% energy) or normal diet (Control, 10% energy) for 16 weeks. The muscle fibre structure and electromyography (EMG) activity of genioglossus were measured. The ultrastructure and function of mitochondrial, oxidative damage and apoptosis in genioglossus were detected by transmission electron microscopy (TEM), qPCR, Western blotting, immunohistochemistry and TUNEL staining. We further studied the influence of palmitic acid (PA) on the proliferation and myogenic differentiation of C2C12 myoblasts, as well as mitochondrial function, oxidative stress, and apoptosis in C2C12 myotubes. Results: Compared with the control, the number of muscle fibres was decreased, the fibre type was remarkably changed, and the EMG activity had declined in genioglossus. In addition, a HFD also reduced mitochondria quantity and function, induced excessive oxidative stress and increased apoptosis in genioglossus. In vitro, PA treatment significantly inhibited the proliferation and myogenic differentiation of C2C12 myoblasts. Moreover, PA decreased the mitochondrial membrane potential, upregulated mitochondrial reactive oxygen species (ROS) levels, and activated the mitochondrial-related apoptotic pathway in myotubes. Conclusion: Our findings suggest that a HFD caused genioglossus injury in obese mice. The mitochondrial dysfunction and the accompanying oxidative stress were involved in the genioglossus injury, which may provide potential therapeutic targets for OSA with obesity.

Obstructive sleep apnea (OSA) is a common syndrome that features a complex etiology and set of mechanisms. Here we summarized the molecular pathogenesis of OSA, especially the prospective mechanism of upper? airway dilator fatigue and the current breakthroughs. Additionally, we also introduced the molecular mechanism of OSA in terms of related studies on the main signaling pathways and epigenetics alterations, such as microRNA, long non-coding RNA, and DNA methylation. We also reviewed small molecular compounds, which are potential targets for gene regulations in the future, that are involved in the regulation of OSA. This review will be beneficial to point the way for OSA research within the next decade.

The mammalian central nervous system (CNS) has a limited ability to renew the damaged cells after a brain or spinal cord injury whether it is nonhuman primates like monkeys or humans. Transplantation of neural stem cells (NSCs) is a potential therapy for CNS injuries due to their pluripotency and differentiation abilities. Cytokines play an important role in CNS development and repair of CNS injuries. However, the detailed cytokine signaling response in monkey neural stem cells is rarely studied. In our previous research, we isolated NSCs from the adult monkey brain and found the effects of cytokines on monkey NSCs. Now, we further analyzed the regulation mechanisms of cytokines to the proliferation of monkey NSCs such as bone morphogenic protein 4 (BMP4), BMP4/leukaemia inhibitory factor (LIF), or retinoic acid (RA)/Forskolin. The data showed that BMP4 inhibited cell proliferation to arrest, but it did not affect the stemness of NSCs. BMP4/LIF promoted the astrocyte‐like differentiation of monkey NSCs, and RA/forskolin induced the neuronal differentiation of monkey NSCs. BMP4/LIF and RA/forskolin induced monkey NSC differentiation by regulating Notch signaling. These results provide some theoretical evidence for NSC therapy to brain or spinal cord injury in regenerative medicine.

Background: Pediatric obstructive sleep apnea/hypopnea syndrome (OSAHS) is a multifactorial syndrome caused by many risk factors, such as craniofacial anomalies, adenotonsillar hypertrophy, obesity, and airway inflammation. Although new treatment patterns have recently been proposed, treatment methods for children remain particularly challenging and controversial. This randomized controlled trial was designed to investigate the efficacy of adenotonsillectomy and/or orthodontic treatment for children who have mild OSAHS with mandibular retrognathia. Methods: A sample of 352 children with mild OSAHS and mandibular retrognathia, who are aged between 7 and 10 years, will be enrolled in the study. They will be randomized into four groups: the drug treatment group, the surgical treatment group, the orthodontic treatment group, or the surgery and postoperative orthodontic group. After randomization the children will receive treatments within 4 weeks. Outcome assessment will take place at the following points: (1) baseline, (2) 7 months after the treatment starting point, (3) 12 months after the treatment starting point, and (4) 24 months after the treatment starting point. The primary endpoint of the trial is the mean change in obstructive apnea/hypopnea index. Other endpoints will consist of the lowest oxygen saturation, apnea index, and hypopnea index assessed by polysomnography, subjective symptoms (assessed by the OSA-20 questionnaire), cephalometric measurements, and morphologic analysis of the upper airway. Discussion: The results of this study will provide valuable evidence for the merits and long-term efficacy of different treatment approaches and contribute to facilitating the multidisciplinary treatment of pediatric OSAHS. Trial registration: ClinicalTrials.gov: NCT03451318. Registered on 2 March 2018 (last update posted 19 April 2018).

Aging of population brings related social problems, such as muscle attenuation and regeneration barriers with increased aging. Muscle repair and regeneration depend on muscle stem cells (MuSCs). Obstructive sleep apnea (OSA) rises in the aging population. OSA leads to hypoxia and upper airway muscle injury. However, little is known about the effect of increasing age and hypoxia to the upper airway muscle. The genioglossus (GG) is the major dilator muscle to keep the upper airway open. Here, we reported that muscle fiber and MuSC function declined with aging in GG. Increasing age also decreased the migration and proliferation of GG MuSCs. p53 and p21 were high expressions both in muscle tissue and in GG MuSCs. We further found that hypoxia inhibited GG MuSC proliferation and decreased myogenic differentiation. Then, hypoxia enhanced the inhibition effect of aging to proliferation and differentiation. Finally, we investigated that hypoxia and aging interact to form a vicious circle with upregulation of p53 and p21. This vicious hypoxia plus aging damage accelerated upper airway muscle injury. Aging and hypoxia are the major damage elements in OSA patients, and we propose that the damage mechanism of hypoxia and aging in GG MuSCs will help to improve upper airway muscle regeneration.