Search Results (261)

Obesity and overweight conditions, frequently accompanied by hypercholesterolemia, are major risk factors for cardiovascular disease. Lifestyle interventions remain the cornerstone of non-pharmacological treatment; however, their effectiveness in improving lipid profiles is limited. Intermittent hypoxic training (IHT) has recently emerged as a potential strategy to enhance metabolic outcomes. This study aimed to evaluate the effects of a 4-week intensive IHT program combined with a calorie-restricted diet on lipid profile and body composition in men with overweight or obesity and secondary hypercholesterolemia. Twenty physically inactive men (35.3 ± 5.4 years) were randomly assigned to either a hypoxic group (H, n = 10) or a normoxic control group (C, n = 10). Both groups followed the same training protocol and diet, differing only in environmental training conditions. Body composition, resting metabolic rate, and blood lipid parameters (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; non-high-density lipoprotein cholesterol, non-HDL-C; Triglycerides, TG) were assessed before and after the intervention. Compared with the C group, participants in the H group achieved significantly greater reductions in body mass (−5.4% vs. −2.6%, p < 0.05) and fat mass (−14.7% vs. −7%, p < 0.01). IHT also induced marked decreases in TC (−22.6%, p < 0.001), LDL-C (−25.8%, p < 0.001), non-HDL-C (−26.5%, p < 0.001), and TG (−31.4%, p < 0.01), along with a significant improvement in the atherogenic index of plasma (AIP, −24.4%, p < 0.05). In contrast, the C group showed only non-significant downward trends. No significant changes in HDL-C were observed in either group. These findings suggest that IHT combined with dietary restriction produces more favorable changes in lipid profile and body composition than normoxic training. IHT may therefore represent a promising adjunct to conventional lifestyle-based interventions in the management of obesity-related hypercholesterolemia. Full article

Obstructive sleep apnea is a common but underdiagnosed sleep-related breathing disorder characterized by recurrent episodes of upper airway obstruction during sleep, leading to intermittent episodes of hypoxia and systemic consequences. Anatomical and ventilatory control factors are well-established contributors, but less is known about how mitochondria influence upper airway muscle function in this condition. As central regulators of muscle performance and cellular adaptation to hypoxia, mitochondria are particularly vulnerable to dysfunction under chronic intermittent hypoxia. Mitochondrial dysfunction increases production of reactive oxygen species, predisposing to oxidative stress, that further impairs mitochondrial function. This review focuses on the mitochondrial involvement in obstructive sleep apnea, specifically synthesizing findings on the impact on upper airway muscles. The role of mitochondrial alterations in muscle dysfunction in this context is not well understood. A better understanding of oxidative damage in these muscles may also contribute to the development of therapeutic approaches, including antioxidant strategies, to mitigate the effects of chronic intermittent hypoxia in the upper airway muscles. Full article

Background/Objectives: Type 2 Diabetes Mellitus (T2DM) is a chronic disease with persistent hyperglycemia as the main clinical manifestation. Chronic Intermittent Hypobaric Hypoxia (CIHH) is a clinical intervention with intermittent low-pressure hypoxic environmental stimulation. The aim of this study was to evaluate the therapeutic effect and anti-inflammatory effect of CIHH in db/db mice. Methods: A simulated 5000 m altitude environment was used to intervene db/db mice. db/db mice were divided into an intervention group (6 h/d) (n = 10) and a control group (n = 10); meanwhile, healthy mice were divided into two groups, the intervention group (6 h/d) (n = 10) and the control group (n = 10). The intervention lasted for 6 weeks. Biochemical analyses and pathological tests were performed to evaluate the therapeutic effects, and for the evaluation of mitochondrial respiration, changes in the respiratory capacity of liver mitochondria at various stages of respiration were examined using Oxygraph-2 k. Changes in inflammatory factors in the liver of mice were analyzed using ELISA. Results: Following CIHH intervention, db/db mice exhibited significant reductions in body weight, food intake, FBG, TC, TG, and LDL, along with increased HDL levels. Liver indices, PEPCK, G-6-phosphate dehydrogenase, and GLUT2 decreased, while GLUT4 and p-AMPK increased. Hepatic HE staining revealed reduced lipid droplets in the liver. HOMA-IR decreased while HOMA-IS increased. Hepatocyte mitochondrial respiration-related indicators CI + CII stage RCR, CII stage RCR, and CI stage SCR increased, while CI stage SCR decreased. Inflammation-related factors NLRP3, TNF-α, IL-1β, and IL-6 decreased in liver tissue. Conclusions: CIHH effectively improves gluconeogenesis and insulin resistance in db/db mice, a result potentially linked to enhanced mitochondrial respiratory capacity and anti-inflammatory effects. Therefore, CIHH offers a potential therapeutic approach for type 2 diabetes. Full article

Background: Obstructive sleep apnea (OSA) is prevalent and often underdiagnosed in cardiology. Worldwide, approximately 936 million adults aged 30–69 are affected by OSA, with the highest numbers in the USA, China, Brazil, and India. In cardiovascular clinics, OSA is found in about 40–80% of patients with hypertension, heart failure, coronary artery disease, atrial fibrillation, or stroke. Meta-analyses link OSA to nearly twice the risk of cardiovascular disease, stroke, and all-cause mortality. Continuous positive airway pressure (CPAP) therapy addresses the underlying mechanisms of OSA and enhances intermediate cardiovascular indicators. Materials and Methods: We conducted a narrative review using major medical search engines (PubMed, Embase, Cochrane) to examine recent statements, meta-analyses, large cohorts, and key trials. The review focused on the cardiovascular burden of sleep apnea and its pathophysiology—including arrhythmic, hemodynamic, vascular, and coagulation aspects—as well as the effects of CPAP on intermediate cardiovascular outcomes. We aimed to provide a synthesised overview of current cardiovascular evidence related to the burden and mechanisms of OSA, and to summarise the effects of continuous positive airway pressure (CPAP) on intermediate and clinical cardiovascular outcomes. Results: Intermittent hypoxia, sleep fragmentation, and major negative fluctuations in intrathoracic pressure create a clear pathway leading to adverse cardiovascular outcomes. This occurs through mechanisms like sympathetic activation, RAAS activation, endothelial dysfunction, oxidative stress, and inflammation, linking OSA to these health issues. Studies show that greater severity of OSA correlates with higher cardiovascular risk, including increased incidence and recurrence of AF, resistant hypertension, and new cases of heart failure. CPAP effectively lowers AHI and enhances nocturnal oxygen levels, as well as intermediate cardiovascular indicators such as blood pressure, sympathetic activity, and certain aspects of ventricular function, with clinical benefits most evident in adherent patients. Conclusions: OSA is a significant, modifiable risk factor for cardiovascular disease. Routine cardiovascular care should include targeted screening for OSA, especially in cases of resistant hypertension, atrial fibrillation, and heart failure, along with timely sleep testing and adherence-focused CPAP therapy, in addition to traditional risk-reduction methods. Full article

Obstructive sleep apnea (OSA) is a chronic respiratory disorder characterized by intermittent hypoxia and is strongly associated with the development of type 2 diabetes mellitus (T2DM). Despite this link, the molecular mechanisms underlying OSA-related metabolic dysregulation remain incompletely understood. The aim of the study was to investigate the role of hypoxia-sensitive microRNAs, sirtuin 1 (SIRT1), and adiponectin in the metabolic profile of OSA patients, with and without T2DM. A total of 87 participants were stratified into three groups: OSA, OSA + T2DM, and healthy controls. Blood samples were collected in the evening and morning, and after continuous positive airway pressure (CPAP) therapy. Expression levels of miRNAs and SIRT1 were measured via RT-qPCR; adiponectin was quantified by ELISA. Significantly reduced expression of miRNA-181a and miRNA-199a was observed in the OSA + T2DM group compared to OSA (p = 0.035 and p = 0.042, respectively). In contrast, SIRT1 expression was highest in the OSA + T2DM group (p < 0.01), while adiponectin concentrations was lowest in this group and the highest among healthy controls (p = 0.001). Despite increased SIRT1 in OSA + T2DM patients, the parallel increase in adiponectin was not observed. Additionally, expression of SIRT1 was significantly increased in OSA patients who were taking metformin (n = 23) vs. patients without metformin (n = 32) 77.315 vs. 437.08 (p = 0.037). CPAP therapy had significant influence only on miRNA-181a—expression was increased after long-term treatment (p = 0.047). Increased miRNA-181a expression in patients with OSA is related to decreased SIRT1 expression, which may lead to T2DM development. Surprisingly, the expression of SIRT1 is significantly higher and expression of hypoxia-sensitive miRNAs is significantly lower in patients with already developed T2DM, which might be explained by metformin intake. Full article

While intermittent desaturations are a common occurrence in near-term and term infants, these may not be benign events with fluctuations in oxygen saturation associated with later neurodevelopmental impairment. Further, intermittent desaturation events do not necessarily result in intermittent hypoxia (IH). Polysomnography is the gold standard to diagnose intermittent desaturations in infants; however, it remains an expensive, inaccessible test. Therefore, overnight oximetry; an economical and more readily available test, is routinely used in this population. Overnight oximetry employs measurement of peripheral cutaneous arterial oxygen saturation (SpO₂) alone to inform clinical management of intermittent desaturations. Management strategies include discharging near-term and term infants on low-flow long-term oxygen therapy (LTOT), typically for upwards of six months. Oxygen saturation targets for neonates have been widely studied. However, interpretation of overnight oximetry is problematic due to a lack of established reference ranges with current approaches still based on limited evidence. This raises questions of the clinical relevancy of overnight oximetry in infants for diagnosing IH and the resultant need for LTOT. Given the association between IH and later neurodevelopmental impairment, concurrent measurement of cerebral tissue oxygen saturation by near-infrared spectroscopy (NIRS) may better identify those near-term and term infants in need of LTOT. Here we review the emerging evidence for the clinical use of cerebral NIRS and the relevance of overnight oximetry in identifying IH in near-term and term newborns and its potential role in identifying those requiring LTOT. Full article

Reduced oxygen availability, or hypoxia, is an environmental stress factor that modulates cellular and systemic functions. It plays a significant role in both physiological and pathological conditions, including tissue regeneration, where it influences angiogenesis, metabolic adaptation, inflammation, and stem cell activity. Hypoxia-inducible factors (HIFs) orchestrate these responses by activating genes that promote survival and repair, although HIF-independent mechanisms, particularly those related to mitochondrial function, are also involved. Depending on its duration and severity, hypoxia may exert either beneficial or harmful effects, ranging from enhanced regeneration to fibrosis or maladaptive remodeling. This review explores the systemic and cellular effects of acute, chronic, intermittent, and preconditioning hypoxia in the context of tissue regeneration. Hypoxia-driven responses are examined across tissues, organs, and complex structures, including the heart, muscle, bone, vascular structures, nervous tissue, and appendages such as tails. We analyze findings from animal models and in vitro studies, followed by biomedical and pharmacological strategies designed to modulate hypoxia and their initial exploration in clinical settings. These strategies involve regulatory molecules, signaling pathways, and microRNA activity, which are investigated across species with diverse regenerative capacities to identify mechanisms that may be conserved or divergent among taxa. Lastly, we emphasize the need to standardize hypoxic conditions to improve reproducibility and highlight their therapeutic potential when precisely controlled. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is a common disorder characterized by intermittent hypoxia and sleep fragmentation, assessed using the Apnea–Hypopnea Index (AHI). Systemic inflammation is central to OSA progression, and the systemic inflammatory response index (SIRI) has emerged as a potential biomarker for inflammatory diseases. This study investigates the relationship between SIRI and OSA severity while comparing other inflammatory markers. Methods: A retrospective study was conducted among 150 OSA patients at a tertiary care hospital. Based on AHI, patients were categorized into mild, moderate, and severe OSA groups. Blood parameters, including neutrophil, monocyte, and lymphocyte counts, were analyzed, and inflammatory indices (SIRI, NLR, PLR) were calculated. Correlation, ROCs, and regression analyses assessed associations between inflammatory markers and OSA severity. Results: SIRI demonstrated an excellent predictive ability for severe OSA with an AUC of 0.960 (cut-off: 1.105; sensitivity: 92.2%; specificity: 91.4%). The STOP-BANG score alone had lower discriminatory power (AUC: 0.737), but combining it with SIRI improved accuracy (AUC: 0.983). The best performance was observed when SIRI, STOP-BANG, PLR, and CRP were combined, yielding an AUC of 1.00, indicating perfect discrimination. Conclusions: SIRI shows strong predictive value for identifying severe OSA, underscoring its utility as a simple, cost-effective biomarker to aid early recognition and referral, particularly in primary care and resource-limited settings. Full article

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a potential risk factor for glaucoma due to its association with intermittent hypoxia and vascular dysregulation. The aim of this study was to investigate early glaucomatous changes in the eyes of patients with OSA. Methods: This case–control study included 25 patients with OSA and 25 age- and sex-matched healthy controls. According to the STOP-Bang Questionnaire, patients with an intermediate or severe risk of OSA underwent polysomnography. Based on the apnea-hypopnea index, only patients with severe OSA were included in the study group. All participants underwent a full ophthalmological examination, with measurements of the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness performed using optical coherence tomography (OCT). Results: Statistical comparisons revealed that intraocular pressure (IOP) was slightly elevated, while central corneal thickness (CCT) was slightly reduced in patients with OSA compared to healthy controls. OCT measurements showed an overall reduction in both RNFL and GCL thicknesses in the OSA group. Among these findings, only the differences in average and minimum GCL thickness in the left eye reached statistical significance. Conclusions: The results of our study indicate significant thinning of the GCL in patients with OSA, suggesting possible early glaucomatous changes and a potential link between OSA and glaucoma. Given the increasing prevalence of OSA, further large-scale, long-term studies are needed to better understand this relationship and its clinical implications. Full article

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. Full article

Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, in particular, is associated with a two- to three-fold increased risk of incident stroke, primarily through mechanisms involving intermittent hypoxia, systemic inflammation, endothelial dysfunction, and autonomic dysregulation. Conversely, stroke can disrupt sleep architecture and trigger or exacerbate sleep disorders, including insomnia, hypersomnia, circadian rhythm disturbances, and breathing-related sleep disorders. These post-stroke sleep disturbances are common and significantly impair rehabilitation, cognitive recovery, and quality of life, yet they remain underdiagnosed and undertreated. Early identification and management of sleep disorders in stroke patients are essential to optimize recovery and reduce the risk of recurrence. Therapeutic strategies include lifestyle modifications, pharmacological treatments, medical devices such as continuous positive airway pressure (CPAP), and emerging alternatives for CPAP-intolerant individuals. Despite growing awareness, significant knowledge gaps persist, particularly regarding non-OSA sleep disorders and their impact on stroke outcomes. Improved diagnostic tools, broader screening protocols, and greater integration of sleep assessments into stroke care are urgently needed. This narrative review synthesizes current evidence on the interplay between sleep and stroke, emphasizing the importance of personalized, multidisciplinary approaches to diagnosis and treatment. Advancing research in this field holds promise for reducing the global burden of stroke and improving long-term outcomes through targeted sleep interventions. Full article

Obstructive sleep apnea syndrome (OSAS) is characterized by cycles of decreased blood oxygen saturation followed by reoxygenation due to transient apnea. Cognitive dysfunction is a complication of OSAS, but its mechanisms remain unclear. Eight-week-old C57BL/6J mice were exposed to intermittent hypoxia (IH) to model OSAS, and cognitive function and hippocampal gene expression were analyzed. Three groups were maintained for 28 days: an IH group (oxygen alternating between 10 and 21% in 2 min cycles, 8 h/day), sustained hypoxia group (SH) (10% oxygen, 8 h/day), and control group (21% oxygen). Behavioral tests and RNA sequencing (RNA-seq) analysis were performed. While Y-maze test results showed no differences, the IH group demonstrated impaired memory and learning in passive avoidance tests compared to control and SH groups. RNA-seq revealed coordinated suppression of mitochondrial function genes and oxidative stress response pathways, specifically in the IH group. RT-qPCR showed decreased Lars2, Hmcn1, and Vstm2l expression in the IH group. Pathway analysis showed the suppression of the KEAP1-NFE2L2 antioxidant pathway in the IH group vs. the SH group. Our findings demonstrate that IH induces cognitive dysfunction through suppression of the KEAP1-NFE2L2 antioxidant pathway and downregulation of mitochondrial genes (Lars2, Vstm2l), leading to oxidative stress and mitochondrial dysfunction. These findings advance our understanding of the molecular basis underlying OSAS-related cognitive impairment. Full article

Obstructive sleep apnea (OSA) is a prevalent disorder linked to metabolic complications such as diabetes and cardiovascular disease. By fragmenting normal sleep architecture, OSA perturbs the growth hormone/insulin-like growth factor (GH/IGF) axis and alters circulating levels of IGF-binding proteins (IGFBPs). A prior clinical observation of elevated IGFBP4 in OSA patients motivated the present investigation in a controlled animal model. Building on the previously reported protocol, OSA was induced in male C57BL/6 mice (9–12 weeks old) through intralingual injection of polytetrafluoroethylene (PTFE), producing tongue hypertrophy, intermittent airway obstruction, and hypoxemia. After 8–10 weeks, the study assessed (1) hypoxia biomarkers—including HIF-1α and VEGF expression—and (2) neurobehavioral outcomes in anxiety and cognition using the open-field and novel object recognition tests. PTFE-treated mice exhibited a significant increase in circulating IGFBP4 versus both baseline and control groups. Hepatic Igfbp4 mRNA was also upregulated. Behaviorally, PTFE mice displayed heightened anxiety-like behavior and impaired novel object recognition, paralleling cognitive deficits reported in human OSA. These findings validate the PTFE-induced model as a tool for studying OSA-related hypoxia and neurocognitive dysfunction, and they underscore IGFBP4 as a promising biomarker and potential mediator of OSA’s systemic effects. Full article

Obstructive sleep apnea (OSA) is a common condition associated with intermittent hypoxia, systemic inflammation, and vascular dysfunction; mechanisms implicated in retinal disease pathogenesis. This real-world retrospective cohort study used data from the TriNetX Research Network to assess whether continuous positive airway pressure (CPAP) therapy reduces retinal disease incidence among adults with OSA and BMI between 25.0 and 30.0 kg/m². After 1:1 propensity score matching, 101,754 patients were included in the analysis. Retinal outcomes included diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), and central serous chorioretinopathy (CSC). CPAP use was associated with a modest but statistically significant reduction in DR (3.2% vs. 3.4%, RR: 0.922, p = 0.016) and AMD (2.1% vs. 2.3%, RR: 0.906, p = 0.018), while no significant differences were found for RVO or CSC. These findings support prior evidence linking CPAP to improved retinal microvascular health and suggest a protective effect against specific retinal complications. Limitations include a lack of data on CPAP adherence, OSA severity, and imaging confirmation. Still, this study highlights the importance of interdisciplinary care between sleep and eye health, and the need for further prospective studies to validate CPAP’s role in preventing retinal disease progression in OSA patients. Full article

Hypoxia can adversely affect multiple organ systems. This study investigated the impact of intermittent hypoxia on serotonin levels and depression-like behaviors across distinct neuroanatomical regions. Sixteen adult female Wistar albino rats were divided into two groups: control (n = 8) and hypoxia (n = 8). The hypoxia group was exposed to a simulated altitude of 3000 for 5 h daily over 14 days. Behavioral assessments included locomotor activity (open field test) and depression-like behaviors (forced swimming test). Serotonin levels were quantified via ELISA in the prefrontal cortex, striatum, thalamus, hypothalamus, hippocampus, and serum. Intermittent hypoxia did not alter locomotor activity (p > 0.05) but significantly increased depression-like behavior (p < 0.05), accompanied by a pronounced reduction in swimming behavior (p < 0.0001), a marker associated with serotonergic function. Serotonin levels were significantly reduced in the prefrontal cortex (p < 0.005) and striatum (p < 0.05), while no changes were observed in other regions or serum (p > 0.05). These findings demonstrate that intermittent hypoxia induces depression-like behaviors and region-specific serotonin depletion, particularly in the prefrontal cortex and striatum. This underscores the need to evaluate hypoxia-related brain health implications in conditions such as sleep apnea and acute mountain sickness. Full article