Search Results (778)

Background/Objectives: Semen Ziziphi Spinosae (SZS), a medicinal and edible traditional Chinese herb, has been widely used to treat insomnia. As critical regulators of the central nervous system, astrocytes play a pivotal role in maintaining sleep homeostasis. However, the mechanisms by which SZS modulates astrocytic function to improve sleep remain unclear. Methods: In this study, we employed an integrated transcriptomics and metabolomics approach to investigate the protective effects of SZS extract against lipopolysaccharide (LPS)-induced inflammatory injury and metabolic dysfunction in astrocytes. Results: Transcriptomic analysis revealed that SZS ameliorates cellular damage (including apoptosis, autophagy, and cell cycle dysregulation) through a FOXO3-centric signaling network. Concurrently, SZS restored cellular energy metabolism by increasing ATP production and reducing Ca²⁺ overload, thereby activating the AMPK signaling pathway to support normal astrocytic function. Metabolomic profiling further demonstrated that SZS-mediated restoration of energy homeostasis sustains ABC transporter activity, which in turn modulates neurotransmitter (serotonin, L-glutamic acid, adenosine), metabolic mediators (leukotrienes, palmitoylethanolamide, succinic acid), and nucleotide (uridine 5′-diphosphate). These coordinated changes normalized GABAergic synapse activity and neuroactive ligand receptor interactions, ultimately resolving neural metabolic network disturbances. Conclusions: Our findings elucidate a novel FOXO3-energy metabolism-ABC transporter axis through which SZS extract attenuates neuroinflammation and metabolic dysfunction in astrocytes and exerts sleep-promoting and neuroprotective effects. This study provides a scientific foundation for understanding the modern pharmacological mechanisms of traditional Chinese medicine in insomnia treatment, highlighting astrocytic regulation as a potential therapeutic target. Full article

Memory consolidation is the process by which newly acquired experiences are stabilized into long-term memory, involving coordinated cellular and network-level activity across brain regions such as the hippocampus and prefrontal cortex. Dysregulation of this process has been implicated in psychiatric disorders including post-traumatic stress disorder (PTSD), which is characterized by the over-consolidation of traumatic memories. LIM kinase 1 (LIMK1), a key regulator of synaptic plasticity, is believed to play an important role in memory consolidation across hippocampal–cortical circuits. In this study, we investigated the function of LIMK1 using Limk1 knockout mice. Behavioral tests such as the novel object location memory task revealed significant memory impairments in knockout animals. In vivo recordings during sleep showed disrupted communication between the hippocampus and prefrontal cortex, suggesting impaired systems-level consolidation. Furthermore, in an underwater trauma exposure model, pharmacological inhibition of LIMK1 with LIMK-i3 alleviated trauma-induced behavioral abnormalities. These findings highlight LIMK1 as a critical mediator of hippocampal–cortical memory consolidation and provide experimental evidence that LIMK1 inhibition can modulate maladaptive memory processes associated with PTSD-like symptoms. Full article

Future Artemis-class missions to Mars will expose astronauts to prolonged space radiation (SR), sleep disruption, and operational demands requiring greater autonomy, placing decision making and executive function at heightened risk. Both SR and sleep fragmentation (SF) independently impair cognition, yet their combined effects remain poorly understood. Using the Associative Recognition Memory and Interference (ARMIT) task, we assessed cognitive performance in male rats exposed to 10 cGy of Galactic Cosmic Ray simulation (GCRsim), SF, or both. Under well-rested conditions, GCRsim-exposed rats exhibited overt deficits in the C.1.2 stage, performing at chance when reinforcement contingencies shifted, consistent with impaired cognitive flexibility. In contrast, high-performing GCRsim-exposed rats that initially performed comparably to Sham s revealed latent deficits following a single night of SF. Specifically, the SF-induced loss of C.1.3 performance was accompanied by perseverative errors (persistently selecting outdated cues despite negative feedback), reflecting impaired attentional control and decision updating. Sham s maintained stable performance after SF. These findings support a two-hit vulnerability model in which SR primes corticostriatal and frontoparietal networks for collapse under subsequent sleep disruption. Operationally, this suggests that astronauts may display either persistent or stress-induced deficits, with both modes threatening mission success. Identifying mechanisms of such vulnerabilities is essential for countermeasure development. Full article

Background/Objectives: The cerebellum is essential for motor coordination and has recently been implicated in sleep-related disorders. However, the neural mechanisms linking sleep disruption to motor dysfunction remain poorly understood. This study aimed to elucidate the roles of the deep cerebellar nuclei (DCN), particularly the lateral nucleus, in motor dysfunction induced by chronic sleep disruption (CSD). Methods: Using a validated mouse model of CSD with periodic sleep fragmentation induced by an orbital shaker during the light phase, we assessed neuronal activation via c-Fos immunostaining and performed chemogenetic manipulation of glutamatergic neurons within the lateral nucleus. Behavioral performance was evaluated using open-field and rotarod tests. Results: CSD selectively increased c-Fos expression in the lateral nucleus, with no significant changes observed in other DCN subregions. Chemogenetic activation or ablation of glutamatergic neurons in the lateral nucleus decreased locomotor activity in the open-field test and shortened latency to fall in the rotarod task. Conversely, chemogenetic inhibition of these neurons attenuated CSD-induced impairments, restoring locomotor performance toward control levels. Conclusions: Our findings provide direct experimental evidence that glutamatergic neurons in the lateral nucleus play a crucial role in mediating CSD-induced motor dysfunction. These results highlight the cerebellar contribution to the interplay between sleep and motor control and identify a potential target for therapeutic intervention in sleep-related motor disorders. Full article

Background/Objectives: Ingestion of galactooligosaccharides (GOSs) or GOS mixtures has been purported to improve exercise-induced gastrointestinal (GI) distress and post-exercise recovery. However, the effects have not been explored in recreationally trained endurance athletes. This triple-blind randomised controlled trial, therefore, investigated whether 12 weeks of B-GOS^® supplementation affects gastrointestinal comfort and psychological wellbeing in recreational athletes. Methods: Eighteen physically active individuals (12 males, 8 females, 44 ± 14 years, 1.7 ± 0.1 m and 73 ± 14 kg) volunteered for this study. Participants were assigned to independent groups in a placebo-controlled, triple-blind manner via stratified randomisation. A 20 min run at 80% VO_2max was completed, with measures for GI distress and Competitive State Anxiety Inventory-2 questionnaire (CSAI-2) pre- and post-exercise. A 12-week supplementation period then ensued, where participants ingested either 3.65 g of B-GOS or an appearance-matched maltodextrin placebo. During this time, physical activity levels (IPAQ-7), general stress (REST-Q), mental wellbeing (WEMWBS), and sleep (core consensus sleep diary) were measured at regular time points. Results: There were no significant differences in VO_2max (p = 0.437), GI discomfort (p = 0.227), or CSAI-2 (p = 0.739–0.954) from pre- to post-exercise at any time point or between conditions. Over the 12 weeks there were no significant differences between B-GOS and placebo in IPAQ-7 (p = 0.144–0.723), REST-Q (p = 0.282–0.954), WEMWBS (B-GOS pre = 51 ± 10, post = 53 ± 7; PLA pre = 51 ± 4, post 54; p = 0.862), or sleep (p = 0.065–0.992). The linear mixed model suggests that some may benefit on an individual level in terms of WEMWBS, general stress score, recovery-related scores, sleep, and sport-specific recovery score. Conclusions: There were no group benefits of B-GOS supplementation compared with placebo, although the individual variation may warrant further research in larger sample sizes and longer-duration studies. Full article

The bidirectional relationship between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM) represents a critical intersection in metabolic medicine. Therefore, the present review examines the most recent data regarding molecular mechanisms linking OSA and T2DM, analyzing key biomarkers including hypoxia-inducible factors (HIF 1α), inflammatory mediators, adipokines, microRNAs, hormones, and neuropeptides that serve as both diagnostic indicators and potential therapeutic targets. Key molecular findings from the scientific literature report elevated HIF-1α promoting insulin resistance, decreased SIRT1 levels, dysregulated microRNA-181a and microRNA-199a, increased inflammatory cytokines (TNF-α, IL-6, CRP), and altered adipokine profiles with reduced adiponectin and elevated leptin and resistin. Current clinical evidence reveals significant therapeutic potential for modern antidiabetic medications in the management of OSA. GLP-1 receptor agonists, particularly tirzepatide, received FDA approval as the first medication for moderate-to-severe OSA in obese adults, showing a 55–63% AHI reduction. SGLT2 inhibitors also demonstrate promising results through weight loss and cardiovascular protection mechanisms. This integrated approach represents the evolution toward comprehensive OSA management beyond traditional mechanical ventilation strategies. Future research should focus on developing personalized treatment algorithms based on individual molecular biomarker profiles, investigating combination therapies, and exploring novel targets, including chronotherapy agents. Full article

Obstructive sleep apnoea (OSA) is a complex health condition associated with significant health risks and diminished quality of life. Despite continuous positive airway pressure (CPAP) being the gold standard treatment for years, its poor adherence is well documented. With the emergence of drug-induced sleep endoscopy (DISE) and phenotypic approach to OSA, traditional surgical and non-surgical treatment pathways have been improved to allow personalised treatment and minimising suboptimal treatment to patients demonstrating various upper airway obstruction of OSA endotypes. Sedation protocol propofol, midazolam and dexmedetomidine have been suggested. The VOTE classification for documenting DISE findings have been proposed to unify results across studies. DISE plays an invaluable role in offering insights on treatment successes for positive airway pressure (PAP) therapy, mandibular advancement device (MAD) therapy, positional therapy, and surgical interventions including palatal surgeries, tongue base surgeries, upper airway stimulation (UAS) surgery and maxillomandibular advancement (MMA). This review aims at consolidating current evidence on DISE protocols, indications, and treatment implications to improve therapeutic success in OSA management. Full article

Background: Gallic acid (GA) is a dietary polyphenol widely found in walnuts, tea leaves, and grapes, and it is recognized for its potent antioxidant and anti-inflammatory properties. Chronic sleep deprivation (CSD) is known to disrupt redox balance, promote neuroinflammation, and impair cognition, while effective nutritional strategies to mitigate these effects remain scarce. This study was designed to evaluate the protective potential of GA against CSD-induced cognitive deficits in mice and to elucidate the underlying mechanisms. Methods: Seventy-two male ICR mice were randomly allocated to six groups, including control, CSD model, Ginkgo biloba extract, and GA at three doses (50, 100, and 200 mg/kg). After 28 days of treatment, cognitive performance was assessed using the open field test (OFT), novel object recognition (NOR), step-through passive avoidance (ST), and Morris water maze (MWM). Redox status and inflammatory mediators were determined by ELISA, while the hippocampal expression of proteins related to antioxidant defense and NF-κB signaling was analyzed by Western blotting. Results: GA supplementation improved exploratory activity, recognition memory, and spatial learning in the CSD mice. Biochemical evaluation revealed that total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were restored, while malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were reduced. These changes were accompanied by decreased circulating concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). At the molecular level, GA enhanced the expression of Nrf2, HO-1, and NQO1, while inhibiting p-p65, iNOS, and COX2 in the hippocampus. Conclusions: These findings demonstrate that GA alleviates CSD-induced cognitive deficits through the activation of the Nrf2/HO-1 antioxidant pathway and inhibition of NF-κB–mediated inflammatory responses. Thus, GA may represent a promising nutraceutical candidate for maintaining cognitive health under chronic sleep loss. Full article

Chronic sleep restriction (SR) impairs multiple organs. Although exogenous melatonin counteracts SR-induced gut microbiota disruption, its role in protecting renal function and the involvement of gut microbiota remain unclear. To this end, we subjected mice to a 28-day SR paradigm with exogenous melatonin treatment or antibiotic-induced microbiota depletion. SR mice demonstrated significant renal dysfunction evidenced by elevated serum creatinine, blood urea nitrogen, and uric acid levels compared to controls. Histopathological analysis revealed characteristic tubular abnormalities in SR mice, including epithelial degeneration and lumen dilation, with reduced expression of key renal filtration markers (Nephrin, Podocin, CD2-associated protein, and α-Actinin-4). All of these could be mitigated by melatonin treatment, and all changes were statistically significant (p < 0.05 or p < 0.01). Intriguingly, microbiota depletion significantly reversed the protective effect of exogenous melatonin on kidney injury in SR mice, while propionic acid supplementation mitigated SR-induced kidney injury. Furthermore, we found that gut microbiota and the metabolite propionic acid mediated the role of exogenous melatonin probably through attenuating SR-induced renal oxidative damage, including regulating renal superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) level. These findings collectively indicated that melatonin may ameliorate SR-associated kidney injury through gut microbiota-derived propionic acid. Our finding highlights a novel gut–kidney axis in SR-related pathophysiology. Full article

Autosomal-dominant sleep-related hypermotor epilepsy (ADSHE) was the first distinct genetic epilepsy proven to be caused by mutation of the CHRNA4 gene, originally reported in 1994. In the past three decades, pathomechanisms of ADSHE associated with mutant nicotinic acetylcholine receptors (nAChRs) have been explored via various studies, including in vitro experiments and genetic rodent models. However, findings emphasize that functional abnormalities of ADSHE-mutant nAChRs alone cannot generate ictogenesis; rather, development of abnormalities in various other transmission systems induced by ADSHE-mutant nAChRs during the neurodevelopmental process before the ADSHE onset is involved in development of epileptogenesis/ictogenesis. Intra-thalamic GABAergic disinhibition induced by loss-of-function of S284L-mutant nAChRs (S286L-mutant nAChRs in rat ADSHE models) contributes to enhancing propagation of physiological ripple-burst high-frequency oscillation (HFO) and Erk signaling during sleep, leading to enhancement of the trafficking of pannexin1, connexin43, and P2X7 purinergic receptor to the astroglial plasma membrane. The combination of activation of physiological ripple-HFO and upregulation of astroglial hemichannels under the GABAergic disinhibition plays an important role in generation of epileptogenic fast-ripple-HFO during sleep. Therefore, loss-of-function of the S284L-mutation alone cannot drive ictogenesis but contributes to the development of epileptogenesis as an initial abnormality. Based on these recent findings using genetic rat ADSHE models, harboring the rat S286L-mutant Chrna4 corresponding to the human S284L-mutant CHRNA4, this report proposes hypothetical pathomechanisms of ADSHE. Full article

Background/Objectives: In the age of digitalization, nomophobia has emerged as a relevant issue, especially among university students who utilize smartphones heavily for academic and social purposes. The Stressor–Strain–Outcome (SSO) framework explains the relationship between stressors, strain, and outcomes. Stressors such as nomophobia induce psychological strain. This strain subsequently influences outcomes like mindfulness. Nomophobia has been linked to higher distress, including depression, anxiety, and stress, that can negatively impact students’ focus. However, the mechanisms by which nomophobia impacts mindfulness remain less explored. Hence, this study aims to analyze the mediating effect of distress on the relation between student’s nomophobia and mindfulness. Methods: In this quantitative study, the researcher employed a structured close-ended survey to collect data from 723 students at the University of Ha’il in Saudi Arabia. Nomophobia was measured using the Nomophobia Questionnaire (NMP-Q). The level of distress was measured using the Depression, Anxiety, and Stress scale (DASS-21) Furthermore, the assessment of mindfulness was conducted using the Mindful Attention Awareness Scale (MAAS). Structural equation modeling was utilized to test the hypotheses of this study. Results: The results from PLS-SEM indicate that nomophobia did not directly reduce mindfulness, as its effect was statistically non-significant (β_1 = −0.052, p-value = 0.168). This suggests that nomophobia alone may not weaken focus. However, it significantly increased distress, particularly depression (β_2a = 0.327, p-value < 0.001), anxiety (β_2b = 0.294, p-value < 0.001) and stress (β_2c = 0.259, p-value < 0.001). In plain terms, students with higher nomophobia reported more depression and stress, which in turn reduced mindfulness. Anxiety, however, did not significantly affect mindfulness (β_3b = 0.006, p-value < 0.933), indicating its influence may be negligible or context-specific. Mediation analysis confirmed indirect effects of nomophobia on mindfulness through depression (β_4a = −0.096, p-value < 0.001) and stress (β_4c = −0.045, p-value < 0.020). Together, these mediators explained a substantial portion of the variance in mindfulness. Conclusions: The findings align with the SSO model, indicating that nomophobia acts as a stressor, exacerbating distress, which in turn reduces mindfulness. From a practical perspective, the results highlight the need for comprehensive student support. Universities should integrate digital wellness programs, stress-management resources, and mindfulness training into their services. Limitations and Future Research: The cross-sectional design and convenience sampling restrict causal inference and generalizability. Future studies should employ longitudinal research designs. They should also examine diverse cultural contexts. In addition, researchers should investigate potential mediators such as social support and sleep quality. Full article

(1) Background: The Iowa Oral Performance Instrument (IOPI) is the well-established device for assessing tongue strength. The current study aimed to assess the effectiveness of the HEAL device in patients with obstructive sleep apnea (OSA) exhibiting varying degrees of tongue base obstruction, as determined by drug-induced sleep endoscopy (DISE). All participants had undergone modified uvulopalatopharyngoplasty (UPPP), and tongue strength was measured using the IOPI. (2) Methods: This retrospective observational study utilized DISE to assess patterns of upper airway collapse in patients with OSA who were candidates for surgical intervention. Based on DISE findings, patients were divided into two groups: the M group (no or partial tongue base obstruction) and the S group (severe obstruction). The first tongue strength assessment using the IOPI was conducted one month after modified UPPP, prior to initiating HEAL training. Patients then underwent tongue muscle training with the HEAL device, starting one-month post-surgery. A second IOPI assessment was performed after at least one month of training. (3) Results: Forty-nine OSA patients with varying degrees of tongue base obstruction (assessed via DISE) received modified UPPP and were included in the analysis. The mean age was 38.3 ± 7.4 years, and mean BMI was 27.8 ± 3.9 kg/m². After training with the HEAL, average tongue strength increased by 20.6 ± 11.5 kPa. The M group showed significantly greater improvement than the S group (22.45 ± 11.77 vs. 13.33 ± 6.93 kPa, p = 0.024). Linear regression confirmed this difference remained significant (p = 0.024). (4) Conclusions: In this study, participants who received modified UPPP exhibited improvements in tongue base strength following a minimum of one month of training with the HEAL device. Those with no or mild tongue base obstruction, as determined by DISE prior to surgery, experienced greater improvements in tongue strength compared to those with severe tongue base obstruction. Full article

The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the “endocrine lung”. This narrative review summarizes current evidence on the endocrine–pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing’s syndrome, hypoventilation in hypothyroidism, restrictive “diabetic lung”, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic–pituitary–adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions. Full article

Spaceflight imposes unique physiological stressors that profoundly disrupt immune regulation, including impaired lymphocyte activation, latent viral reactivation, and chronic low-grade inflammation. While structured exercise is the cornerstone countermeasure for musculoskeletal and cardiovascular health, current protocols rarely integrate immune endpoints into their design. This review aims to synthesize current evidence on the immunological effects of exercise in spaceflight and propose a novel framework for immune-focused physical activity guidelines tailored to long-duration missions. Evidence indicates that exercise intensity and modality critically determine immune outcomes. Acute strenuous exercise may transiently suppress immunity via cortisol and reactive oxygen species pathways, whereas chronic moderate-to-vigorous training enhances immune surveillance, reduces systemic inflammation, and supports T-cell and NK-cell function. Exerkines such as IL-15, IL-7, and irisin emerge as central mediators of exercise-induced immunomodulation, with potential applications for spaceflight countermeasures. Incorporating immune health into exercise guidelines represents a necessary paradigm shift for astronaut care. A structured framework—emphasizing aerobic, resistance, and HIIT modalities; moderate-to-vigorous intensity; daily training; immune biomarker monitoring; and integration with nutrition and sleep—can enhance resilience against infection, viral reactivation, and cancer risk. Immune-focused countermeasures will be essential to safeguard astronaut health and ensure mission success on future deep-space expeditions. Full article

Background/Objectives: The 24 h activity cycle highlights the need to consider sedentary behavior (SED), non-exercise physical activity (NEPA), and sleep when introducing aerobic exercise. This study assessed changes in these components among breast cancer survivors (BCS) and non-oncologic menopausal women after a 3-month walking (W) or Nordic walking (NW) program. Methods: A total of 324 menopausal women participated: 156 non-oncologic (Meno), 102 BCS with natural menopause (BCS_Meno), and 66 BCS with medically induced menopause (BCS_Ind_Meno). Linear Mixed Effects (LME) modeling was applied. Age, BMI, hormonal therapy, cancer treatments, hypertension, sleep, and METs were included as covariates. Results: BCS_Meno and BCS_Ind_Meno had longer sleep durations at baseline (adj. diff.: +26.5 min/day, 95% CI 10.1 to 43.0; p = 0.002 and +25.7, 95% CI 6.7 to 44.6; p = 0.008). Sleep improved across all groups post-intervention (overall adj. effect = +17.4 min/day, 95% CI 4.8 to 30.0; p = 0.007). Higher sleep and METs were associated with reduced SED (sleep: β = −43.7 min/day per unit increase, −52.6 to −34.8; METs: β = −115.4, −126.4 to −104.4; both p < 0.001). A significant group × time interaction showed a decrease in SED in the BCS_Ind_Meno group (adj. diff. = −65.1 min/day, −102.8 to −27.4; p = 0.001). NEPA was negatively influenced by sleep (β = −8.7 min/day, −16.2 to −1.1, p = 0.024) and positively by METs (β = +121.1, 111.8 to 130.3; p < 0.001). NEPA increased only in BCS_Ind_Meno (adj. diff.: +70.6 min/day, 38.4 to 102.7; p < 0.001), not in BCS_Meno (+9.87, −18.7 to 38.4; p = 0.497). Conclusions: BCS_Ind_Meno showed the greatest benefits, with reduced SED, increased NEPA, and improved sleep. Sleep improved across all groups following aerobic interventions. Full article