Artificial lighting at night (ALAN) leads to pervasive light pollution, affecting ecosystems and human health globally. Satellite assessments reveal widespread nocturnal illumination worldwide and research indicates adverse health effects. Environmental light pollution disrupts natural cycles, affecting the behavior and reproduction of various organisms.

In this narrative review we aimed to present research on the effects of ALAN on glucose metabolism and diabetes and hone on its recently reported association with gestational diabetes (GDM).

Conflicting data exist on the effects of melatonin's administration vis-à-vis glycemia, with some studies suggesting beneficial outcomes for patients with type 2 diabetes mellitus and insomnia. Ambient light influences plasma glucose, with bright light increasing both fasting and postprandial glucose levels. Perinatal light exposure is linked to later-life health risks and prenatal exposure to ALAN is linked to fetal macrosomia. Analyzing European ALAN data in conjunction with epidemiological records for GDM reveals a notable probable association. Additionally, recent research from China (one case-control and two cohort studies) has shown that exposure to ALAN during pregnancy significantly increases the risk of GDM.

Despite progress, interdisciplinary research is needed to understand the impact of light pollution on health, especially regarding disrupted light-dark cycles and physiological functions relevant to conditions like GDM. At present, the simplest advice for all people and particularly for women who anticipate pregnancy, or for pregnant women, is to ensure a totally dark environment during sleep time.

Circadian rhythms and sleep processes are essential in human and their disruption affect health in many ways. They share anatomical-functional pathways with the vestibular system making vestibular stimulation an interesting tool that has yet to prove its efficacy at reducing such disruptions. This review aims at evaluating the effects of different types of vestibular stimulations on circadian rhythms and sleep.

It followed PRISMA recommendations and was registered to PROSPERO (CRD42024492913). The databases PubMed and ScienceDirect were searched until January 2024 for articles published between 1950 and 2023 to collect articles fitting the scope of the review.

Among the ninety-six screened studies, a total of twelve studies were included. A significant beneficial effect of vestibular stimulation was shown on a circadian rhythm and in eight out of eleven studies evaluating sleep. Among the twelve studies, three showed a high risk of bias, two induced some concerns and the seven left showed a low risk of bias.

Vestibular stimulation appears as a promising technique to improve both circadian rhythms and sleep.

Recent evidence highlights the potential impact of outdoor artificial light at night (ALAN) on sleep, and later sleep timing may be a risk factor for executive dysfunction. Depression is commonly associated with executive dysfunction, which significantly compromise prognosis. However, it remains unclear whether sleep-wake phase mediate the effects of outdoor ALAN on executive function. We assessed whether sleep timing mediated the association between outdoor ALAN and executive function among depressed patients. Between 2017 and 2023, 798 inpatients with depression were enrolled from the Fourth People's Hospital of Hefei. The outdoor ALAN exposure of patients was estimated using satellite images. All participants were assessed for sleep conditions using the Pittsburgh Sleep Quality Index (PSQI) and for executive function using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). We employed multifactor linear regression models to investigate the association between outdoor ALAN exposure and executive function, adjusted for potential confounders. Additionally, mediation models were utilized to explore the mediating role of sleep timing in this association. Our study found that greater ALAN exposure was significantly associated with higher executive function scores. The exposure of participants at 12 months prior to enrollment had the greatest effect, for each interquartile range (IQR 29.93 nW/cm2/sr) increase in outdoor ALAN exposure, the Global Executive Composite (GEC) scores increased by 6.12 (95 % confidence interval [CI]: 2.49, 9.74). Mediation analysis indicated that sleep midpoint significantly mediated the relationship between outdoor ALAN and executive function, with a mediated proportion of 22.39 %. The study suggested that outdoor ALAN exposure has adverse effects on executive function in depressed patients, and sleep-wake phase may mediate the association between outdoor ALAN exposure and executive function.

This special issue of the Biomedical Journal centers on circadian rhythms, examining the molecular mechanisms of the circadian clock, the consequences of circadian disruption, and their implications for health and disease. Featured topics include blue light therapy for sleep disorders in myocardial infarction patients; sex-specific links between clock genes and colorectal cancer; the impact of social jetlag on blood pressure; and how irregular light-dark cycles and misaligned eating patterns affect circadian stability. A study on Stenabolic (SR9009) in mice investigates its potential to mitigate weight gain, insulin resistance, and white fat accumulation under constant light exposure. Additional reviews address the role of purinoreceptors in extracellular vesicle-mediated communication, the evolving understanding of pseudogenes and their functional derivatives, and future prospects for hyperpolarized magnetic resonance imaging. Original research highlights the influence of corticosterone on white adipose tissue expansion in mice and challenges the assumed protective role of pentoxifylline against diabetic retinopathy in patients with chronic kidney disease and diabetes. A novel application of peripheral magnetic stimulation as a treatment for overactive bladder is also explored. Two studies on hidradenitis suppurativa are included: one linking the condition to an increased risk of migraine in women, and another examining its association with alopecia areata. The issue concludes with two letters to the editor on the effects of the SARS-CoV-2 spike protein on erythrocyte biology, along with a request for further clarification, which is addressed in detail.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among reproductive women, characterized by hyperandrogenism, oligo-ovulation and polycystic ovarian morphology. Incorporating complementary medicine alongside traditional lifestyle therapies for PCOS may offer additional benefits for affected women. Melatonin (MT), a hormone secreted by the pineal gland, has emerged as a potential treatment for regulating ovarian function in PCOS. However, the specific effects and underlying mechanisms of MT on PCOS need to be elucidated.

This review consolidates evidence from randomized controlled trials, original research articles, systematic reviews, and meta-analyses regarding MT supplementation in PCOS, with a particular focus on its interaction with the Hippo pathway, to provide a comprehensive overview of current knowledge.

Current evidence suggests that MT plays a role in modulating PCOS through various mechanisms and is associated with the Hippo pathway. However, several uncertainties and key limitations in the existing literature must be addressed before these treatments can be integrated into standard clinical practice.

Not applicable.

The increased prevalence of sleep disturbances in modern society is frequently linked to various metabolic disorders, including insulin resistance, obesity, hypertension, fatty liver disease, and cardiometabolic complications. Melatonin, a pineal gland-secreted neurohormone, plays a pivotal role in maintaining the circadian rhythm. It is involved in regulating adipose tissue development, lipid accumulation, browning of white adipose tissue, and activation of brown adipose tissue. The adipose tissue is a dynamic endocrine organ that secretes hormones and cytokines. Recent research has highlighted the significant role of melatonin in the modulation of lipid metabolism, adipogenesis, and thermogenesis in adipose tissues. Circadian rhythms are important in synchronizing metabolic functions with environmental cues, such as light and dark, feeding-fasting states, etc. Irregular sleep patterns, shift work, and exposure to artificial light at night disrupt these rhythms, affecting circadian regulation and compromising metabolic health. Melatonin imbalance due to sleep disturbances results in metabolic dysfunction, increased fat storage, and adipose tissue inflammation. As circadian rhythm and melatonin are both related, a change in circadian rhythm affects the physiology of adipose tissues thereby precipitating metabolic complications through melatonin signaling. This study attempted to understand the mechanisms by which melatonin influences adipose tissue activity, highlighting the role of circadian rhythms in this process. This will enable the development of melatonin-based therapies to mitigate the adverse effects of chronobiological disturbances on the physiology of adipose tissue. Understanding these interactions will provide novel insights for combating obesity and related metabolic conditions.

To evaluate the effectiveness of various nutritional supplements as interventions for patients with Chronic Obstructive Pulmonary Disease (COPD) using network meta-analysis.

We searched PubMed, Embase, Cochrane Library, and Web of Science databases for randomized controlled trials on nutritional supplements for COPD patients, with the search updated to March 24, 2025. The risk of bias for each included study was assessed using appropriate tools, and the certainty of evidence was evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Data synthesis was performed using R software, employing network meta-analysis methods to compare the relative efficacy of different nutritional interventions.

Thirty-seven studies involving 1975 COPD patients and 21 different nutritional supplements were analyzed. Butyrate [MD = 2.7, 95% CrI (1.0, 4.4)], Nanocurcumin [MD = 13, 95% CrI (5.4, 21)], and probiotics [MD = 7.1, 95% CrI (5.2, 9.1)] significantly improved Forced Expiratory Volume in One Second (FEV1). Nanocurcumin also slowed the decline in the ratio of Forced Expiratory Volume in One Second to Forced Vital Capacity (FEV1/FVC) [MD = 12, 95% CrI (5.5, 18)]. For exercise endurance, coenzyme Q10 combined with creatine [MD = 63, 95% CrI (36, 90)], Melatonin (MLT) [MD = 46, 95% CrI (1.3, 92)], Nitrate [MD = 30, 95% CrI (19, 41)], and whey proteins [MD = 11, 95% CrI (9.2, 13)] significantly improved 6-minute walk distance (6MWD). Regarding dyspnea reduction, MLT [MD = -0.90, 95% CrI (-1.6, -0.21)] and Yam-Epimedium [MD = -1.3, 95% CrI (-1.9, -0.67)] significantly lowered modified Medical Research Council (mMRC) scores. In terms of quality of life, MLT [MD = -8, 95% CrI (-12, -4.2)], Vitamin D (VD) [MD = -2.5, 95% CrI (-3.1, -1.9)], and whey proteins [MD = -0.70, 95% CrI (-0.99, -0.41)] reduced COPD Assessment Test (CAT) scores. Additionally, AKL1 [MD = -9.2, 95% CrI (-18, -0.41)], creatine [MD = -9.6, 95% CrI (-17, -2.8)], and Yam-Epimedium [MD = -24, 95% CrI (-34, -13)] lowered St. George's Respiratory Questionnaire (SGRQ) scores. The Surface Under the Cumulative Ranking Curve (SUCRA) analysis showed Nanocurcumin ranked highest for improving FEV1/FVC, coenzyme Q10 combined with creatine for 6MWD, Yam-Epimedium for reducing dyspnea and SGRQ, and MLT for lowering CAT scores.

This analysis indicates that various nutritional supplements, including Nanocurcumin, butyrate, probiotics, coenzyme Q10 combined with creatine, MLT, nitrate, whey proteins, VD, AKL1, creatine, and Yam-Epimedium, can potentially benefit COPD patients, demonstrating differing levels of effectiveness. Specifically, Nanocurcumin may be the best choice for improving lung function; coenzyme Q10 combined with creatine may be the most effective for enhancing exercise endurance; Additionally, Yam-Epimedium is the most likely supplement to reduce the symptoms of dyspnea in COPD patients. Yam-Epimedium and MLT may be the most effective for improving quality of life and overall health status.

This study aimed to examine the levels of microRNA-107 (miR-107) and its correlation with neurotransmitters (glutamate, serotonin, melatonin) and adiponectin in patients with obstructive sleep apnea (OSA) compared to healthy controls. The results showed that serum levels of miR107, melatonin, and adiponectin were significantly lower in OSA patients compared to controls, while serotonin and glutamate levels were significantly higher. Spearman correlation analysis revealed that in the control group, miR-107 levels were moderately correlated with glutamate (negative) and adiponectin (positive), but these associations were disrupted in the OSA group. Receiver operating characteristic (ROC) curve analysis demonstrated that miR-107 had excellent diagnostic performance, with 100% sensitivity and 89.3% specificity at a cut-off of 3.0 ng/mL. Adiponectin also showed strong diagnostic potential, with 78% sensitivity and 89% specificity. In contrast, serotonin, melatonin, and glutamate exhibited more moderate diagnostic accuracy. These findings suggest that miR-107 and adiponectin could serve as promising biomarkers for diagnosing OSA, and targeting miR-107 to modulate metabolic factors may offer novel therapeutic approaches for improving OSA management.

Melatonin is evaluated as a potential molecular therapy to counteract mitochondrial dysfunction caused by hypoxia/reoxygenation (H/R) in aortic endothelial cells (pAECs). The mitochondrial permeability transition pore (mPTP) opening undergoes a desensitizing action coupled with a reduction of superoxide anion production in mitochondria treated with melatonin. The effect on mPTP has been attributed to the direct interaction of melatonin with the hydrophilic F1 domain of Ca2+-activated F1FO-ATPase. Mutual exclusion analysis highlights an overlapping binding site between melatonin and the specific F1 inhibitor NBD-Cl. The results are corroborated by melatonin inhibition of ATPase activity of the purified F1 domain in the presence of Ca2+, but not in the presence of natural cofactor Mg2+. Moreover, the impairment of bioenergetics parameters in pAECs metabolism and the increase of oxidative stress arising by H/R injury have been rescued in cells protected by melatonin treatment.

Circadian rhythm disruption (CRD) affects the expression levels of a range of biological clock genes, such as brain and muscle ARNT-Like-1 (BMAL1), which is considered to be an important factor in triggering or exacerbating inflammatory response. However, the underlying effect of CRD on the pathogenesis of apical periodontitis, a common oral inflammatory disease, currently remains unknown. Exploring the effects and pathogenic mechanisms of CRD on apical periodontitis will be beneficial in providing new ideas for the prevention and treatment of apical periodontitis.

The cross-sectional study was conducted among patients with apical periodontitis visiting to hospital. Rat models combining CRD and apical periodontitis were constructed, and the destruction of periapical alveolar bone was assessed by Micro-CT, H&E, and TRAP staining assay. Rat periapical alveolar bone tissues were collected for RT-qPCR and immunohistochemistry to further detect the expression of periapical biological clock genes. A model of apical periodontitis was constructed using Bmal1-/- and WT rats to further verify the key role played by Bmal1. Finally, rats raised in CRD environment were intraperitoneally injected with melatonin to restore the circadian rhythm, and the periapical alveolar bone repair was observed by Masson's staining and staining of osteogenic markers (ALP, RUNX2).

A close association between CRD and acute exacerbation of chronic apical periodontitis (CAP) in patients was first found in an epidemiological survey. By constructing animal models of CRD and apical periodontitis, it was found that CRD could aggravate the inflammatory stress of apical periodontitis and even drive the acute exacerbation of CAP. Further investigations suggested that the expression of crucial clock genes, especially Bmal1, were significantly disrupted in the periapical tissue of apical periodontitis. In addition, the periapical tissue from Bmal1 knockout rat displayed stronger inflammatory response and more severe alveolar bone destruction in apical periodontitis. Restoring circadian rhythm by melatonin supplementation could effectively alleviate both the inflammatory response and alveolar bone loss in apical periodontitis.

CRD is a novel trigger in aggravating the inflammatory response and alveolar bone loss of apical periodontitis. Melatonin is expected to be used in the dental clinic as an important adjunctive therapy strategy for the healing of periapical tissue in apical periodontitis.

The circadian clock is a critical regulator of physiological rhythms, orchestrating metabolic processes to adapt to daily environmental changes. This review focuses on the intricate relationship between circadian regulation and glycolipid metabolism, with implications for metabolic diseases. Central and peripheral clocks coordinate the rhythmic expression of key enzymes and transporters, ensuring glycolipid homeostasis. Disruptions to these rhythms can result in metabolic disorders characterized by altered glucose utilization, insulin sensitivity, and lipid storage. The molecular mechanisms underlying these processes include transcriptional-translational feedback loops involving clock factors that regulate glycolipid metabolism. Emerging therapeutic strategies, such as pharmacological and dietary interventions, highlight the translational potential of circadian biology. This review underscores the importance of circadian rhythm maintenance for glycolipid metabolism and its role in preventing metabolic disorders. Further elucidation of the molecular mechanisms linking circadian regulation to glycolipid metabolism could pave the way for precision medicine approaches tailored to individual circadian profiles.

Angiogenesis facilitates the reinstatement of blood supply to cerebral tissues after stroke by reconstructing the vascular network, thereby rescuing the penumbra region and restoring neural functions. Melatonin can modulate angiogenesis under a variety of biological and disease-related states, and bone morphogenetic protein 6 (BMP6) targets regulators associated with angiogenesis. The specific functions of melatonin and BMP6 in angiogenesis following cerebral infarction, along with the potential intrinsic regulatory interactions between them, are currently unclear and need further investigation. Melatonin was given to the mice from the 1st day through the 28th day post permanent distal middle cerebral artery occlusion (dMCAO). Our research revealed that melatonin enhanced neurological performance and decreased the size of the brain infarction. Additionally, it boosted blood circulation and fostered angiogenesis in the penumbra area. Meanwhile, melatonin facilitated endothelial cells migration and tube formation after oxygen-glucose deprivation (OGD). Melatonin promoted the expression of BMP6 and its downstream targets, Smad1/5/9, as well as factors associated with angiogenesis Vascular Endothelial Growth Factor (VEGF) and Angiopoietin-1 (Ang1) in vivo and in vitro, which was counteracted or partially inhibited by suppression of BMP6 expression. Our research provides strong evidence that melatonin promotes angiogenesis after cerebral infarction through BMP6/Smad1/5/9 signaling pathway, supporting the restoration of neural function.

Insomnia, a prevalent sleep disorder, significantly impacts global health. While Western medications provide temporary relief, their risks of dependency and cognitive impairment have spurred the search for safer alternatives. Traditional Chinese Medicine (TCM) offers a promising approach to treating insomnia by focusing on harmonizing the balance of Yin and Yang and the functions of internal organs. This review explores recent research advances in TCM for insomnia treatment, integrating classical theories with modern scientific understanding of key pathological mechanisms, including neurotransmitter regulation (GABA, monoamines), immune-inflammatory responses, the HPA axis, and interactions with the gut microbiota. Growing clinical evidence supports the effectiveness of classical TCM prescriptions and treatments like acupuncture in improving sleep quality, particularly when combined with Western medications to enhance efficacy and reduce dependency. However, TCM also has its limitations. Future research directions should focus on modernizing TCM applications, addressing comorbidities associated with insomnia, exploring the role of gut microbiota, and optimizing medicinal and edible homologous products. By integrating traditional knowledge with cutting-edge technologies, TCM holds great potential for advancing personalized and effective insomnia treatments globally.

In this study, we aim to investigate whether therapeutic ultrasound can modulate the release of melatonin from the pineal gland-either increasing or decreasing its levels-and to assess the safety of this technique. This research could address a significant clinical need by providing a noninvasive method to potentially regulate sleep and circadian rhythms through the targeted modulation of melatonin.

Rat pineal glands were placed in a well with a Krebs Ringer Buffer solution. Ultrasound was applied to the glands using unfocused transducers set at an average intensity of 1 W/cm2 and three different frequencies (400, 600, and 800 kHz) with continuous exposure for 5 min. Fluid samples were collected from the well before (t = 0 min), immediately after (t = 5 min), and 30 min post-ultrasound treatment (t = 30 min). Melatonin release was subsequently measured using an ELISA kit and analyzed statistically. In addition, histological analysis was completed to determine any structural abnormalities due to ultrasound application.

In the 600 kHz group there was a statistically significant decrease from t = 0 min to t = 5 min. No other statistically significant differences were observed. In addition, no histological changes were observed in the pineal glands due to ultrasound application.

This study indicated that ultrasound may be able to modulate melatonin release, however follow-up studies are necessary to determine optimal ultrasound parameters for this application.

Delayed sleep-wake phase disorder(DSWPD)is a serious threat to the physical and mental health. There are some problems with current clinical treatment methods, and exercise is an alternative to chronotherapy. Therefore, we aimed to study the effects of two different exercise methods, aerobic and resistance, on sleep, melatonin, inflammatory factors and mood in college students with DSWPD.

Male college students aged 18-28 years with DSWPD and no regular exercise habits were recruited to participate in a randomized crossover trial. Three-day moderate-intensity aerobic and resistance exercises were conducted. Sleep quality, urine melatonin concentration, blood inflammatory factors, and mood changes were evaluated.

Resistance exercise (RE) improved five sleep indicators (P < 0.05),including sleep onset time, sleep onset latency, total sleep time, wake after sleep onset and sleep efficiency, whereas aerobic exercise (AE) only improved sleep onset time and sleep efficiency (P < 0.05). In addition, RE and AE increased urine aMT6s, IL-10 and decreased IL-6. But RE was more effective in improving sleep onset time, sleep efficiency and urine aMT6s, IL-6. In terms of mood indicators, aerobic and resistance reduced self-rating anxiety scale, but AE also had an improvement effect on self-rating depression scale.

Aerobic and resistance exercises can cause male college students with DSWPD to fall asleep earlier, improve sleep quality, increase melatonin concentration, reduce body inflammation, promote the synthesis of anti-inflammatory cytokines, and improve mood. Of the two exercise intervention methods, the effect of RE was more significant.

Melatonin, a hormone synthesized by the pineal gland, is renowned for its pivotal role in governing circadian rhythms and its promising therapeutic attributes encompassing anti-inflammatory, anti-aging, and cancer-preventative properties. Nevertheless, the improper utilization of melatonin may lead to health hazards, highlighting the critical necessity for accurate detection of melatonin in pharmaceutical or biological samples. Furthermore, melatonin metabolites exhibit analogous chemical structures yet divergent pathophysiological functions, emphasizing the significance of distinguishing between these analogs. In this study, we report a supramolecular sensor that combines amide naphthotube and toluidine blue O in an indicator displacement assay for the quantitative detection of melatonin and differentiation of its analogs. The sensor demonstrated remarkable sensitivity, with a low detection limit of approximately 0.70 μM, and a broad dynamic range of 0.70-98.8 μM, along with excellent selectivity and stability. Notably, the sensor enables the determination of melatonin levels in various sample matrices, including milk, artificial urine, and pharmaceutical preparations. Through optimization of the host-guest complex ratio, our newly designed sensor effectively distinguishes melatonin from its six analogs. This approach addresses a current research gap, as existing macrocycles have limited capability to differentiate between melatonin analogs, with only a few achieving precise melatonin quantification.

Colorectal cancer (CRC) poses a significant threat to human life and health. Global cancer prevalence data in 2022 indicated that the number of new cases of CRC was about 1.92 million and the deaths were around 900,000. A variety of risk factors, including genes and environment, can induce the occurrence of CRC. Previous studies have focused on the impact of dietary patterns on the development of CRC and have ignored sleep factors. Sleep deprivation is a common problem as people's work pressure increases. Sleep disorders can lead to metabolic and immune system dysregulation in people, contributing to the development and progression of many tumors. At present, there are few reports on the relationship between sleep disorders and tumors. Therefore, the purpose of this paper is to summarize and interpret the relationship between various sleep disorders and the onset and progression of CRC. This review is the first to investigate the possible mechanisms of sleep leading to CRC from the perspectives of metabolic reprogramming, intestinal microbiota disorders, and the release of inflammatory factors. In conclusion, this study highlights the rational sleep pattern and duration, which can help inhibit the occurrence of CRC.

Melatonin is mainly synthesized and secreted by pineal gland, and plays multiple functions, including its regulating effects on reproductive processes. Sperm capacitation is necessary for fertilization, but the effect of melatonin on mouse sperm capacitation remains to be elucidated. We thus investigated the roles of melatonin on capacitation by culturing the sperms from mouse cauda epididymis in the medium with different doses of melatonin. The results showed that 10-7 mol/L melatonin significantly enhanced the sperm capacitation by increasing the sperm tyrosine phosphorylation level, percentage of the capacitated sperms and intracellular calcium concentration. In addition, our in vitro and in vivo results showed that melatonin enhanced the fertilizing capacity by increasing the percentage of oocyte cleavage and the number of the fetuses from receptive females which were mated with melatonin-treated males. Mechanically, melatonin activated cyclic adenosine monophosphate (cAMP)/p-Protein kinase A (p-PKA) pathway. Furthermore, the melatonin-induced tyrosine phosphorylation of sperms was decreased by treatment of MT1 or PKA inhibitor. And the same result was found in the sperms cultured in non-capacitating medium (without bicarbonate and bovine serum albumin). Therefore, all those results indicate that MT1/cAMP/PKA pathway is one of key regulatory factors in melatonin-mediated sperm capacitation. The results here are crucial for understanding the molecular mechanisms by which melatonin regulates sperm capacitation, and providing theoretical support for controlling sperm capacitation during artificial insemination procedures.

Central nervous system (CNS) diseases pose a serious threat to human health, but the regulatory mechanisms and therapeutic strategies of CNS diseases need to be further explored. It has been demonstrated that the gut microbiota (GM) is closely related to CNS disease. GM structure disorders, abnormal microbial metabolites, intestinal barrier destruction and elevated inflammation exist in patients with CNS diseases and promote the development of CNS diseases. More importantly, GM remodeling alleviates CNS pathology to some extent.

Here, we have summarized the regulatory mechanism of the GM in CNS diseases and the potential treatment strategies for CNS repair based on GM regulation, aiming to provide safer and more effective strategies for CNS repair from the perspective of GM regulation.

The abundance and composition of GM is closely associated with the CNS diseases. On the basis of in-depth analysis of GM changes in mice with CNS disease, as well as the changes in its metabolites, therapeutic strategies, such as probiotics, prebiotics, and FMT, may be used to regulate GM balance and affect its microbial metabolites, thereby promoting the recovery of CNS diseases.

Microglia, the brain's resident macrophages, are key mediators of neuroinflammation, responding to immune pathogens and toxins. They play a crucial role in clearing cellular debris, regulating synaptic plasticity, and phagocytosing amyloid-β (Aβ) plaques in Alzheimer's disease (AD). Recent studies indicate that microglia not only exhibit intrinsic circadian rhythms but are also regulated by circadian clock genes, influencing specific functions such as phagocytosis and the modulation of neuroinflammation. Disruption of the circadian rhythm is closely associated with AD pathology. In this review, we will provide an overview of how circadian rhythms regulate microglia-mediated neuroinflammation in the progression of AD, focusing on the pathway from the central nervous system (CNS) and the peripheral immune system. We also discuss potential therapeutic targets, including hormone modulation, lifestyle interventions, and anti-inflammatory therapies, aimed at maintaining brain health in AD. This will shed light on the involvement of circadian rhythm in AD and explore new avenues for AD treatment.

Cavernous nerve injury-induced erectile dysfunction (CNI-ED) is a common complication after radical prostatectomy. Conventional treatment approaches have had little success in treating the severe cavernous fibrosis which is a consequence of CNI-ED.

Pre-treatment of adipose-derived stem cells with melatonin allows for the extraction of active exosomes (MT-hASC-EVs) from the conditioned medium. The therapeutic effects of MT-hASC-EVs were assessed in a rat model of CNI-ED, and the anti-fibrotic properties were evaluated. MicroRNA sequencing was used to identify specific microRNAs highly expressed in MT-hASC-EVs, and differential microRNAs were screened for regulatory pathways through target gene enrichment analysis. Finally, the conclusions from bioinformatics analysis were validated through in vitro experiments.

Intracavernous injection of MT-hASC-EVs significantly restored erectile function and reduced the extent of corpus cavernosum fibrosis in the CNI-ED rat model. MT-hASC-EVs promoted the proliferation and anti-apoptotic effects of corpus cavernosum smooth muscle cells (CCSMCs) in vitro. Mechanistically, MT-hASC-EVs inhibit fibrosis by delivering miR-145-5p, which targets TGF-β2/Smad3 axis.

MT-hASCs-EVs can inhibit cavernous fibrosis and improve erectile function in a rat model of CNI-ED by targeting the miR-145-5p/TGF-β/Smad axis.

Globally, diabetic retinopathy (DR) and diabetic macular edema (DME) are the leading causes of visual loss in working people. Current treatment approaches mostly target proliferative DR and DME, such as intravitreal injections of antivascular endothelial growth factor agents and laser photocoagulation. Before DR progresses into the more severe, sight-threatening proliferative stage, patients with early stages of the disease must get early and appropriate care. It has been suggested that nutraceuticals, which are natural functional foods with minimal adverse effects, may help diabetic patients with DR and DME. Several in vitro and in vivo studies were carried out over the last years, showing the potential benefits of several nutraceuticals in DR due to their neuroprotective, vasoprotective, anti-inflammatory, and antioxidant properties. Although most of the research is restricted to animal models and many nutraceuticals have low bioavailability, these compounds may adjuvate and implement conventional DR therapies. The purpose of this review is (i) to summarize the complex pathophysiology underlying DR and DME and (ii) to examine the main natural-derived molecules and dietary habits that can assist conventional therapies for the clinical management of DR and DME.

The ever-expanding use of a large number of electrical appliances and mobile communication systems, which outnumber the global population, emit electromagnetic radiation through mobile telephones, power stations, transmission lines, radar, microwave ovens, televisions, refrigerators, therapeutic and other electronic devices. Electromagnetic radiation has been classified by the International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (Group 2B). A large number of research results show that short-term and long-term exposure to electromagnetic radiation can lead to anxiety, depression, decreased learning ability, memory loss, sleep rhythm disorders and other adverse effects. Sleep rhythm disorders affect many people worldwide and may be associated with psychiatric disorders such as anxiety and depression. In this review, we summarise key experiments related to the effects of electric field exposure on mood and rhythms in animal and cellular studies over the past decade, describe the effects of electromagnetic radiation on emotional behaviors and circadian rhythms in humans and mammals, and explore the relationship between electromagnetic radiation，mood and rhythms as well as its underlying mechanisms of action. Most animal studies suggest that electromagnetic radiation may affect the physiological organization and functioning of the brain, influence neurotransmitters and receptors, interfere with neuronal formation and structure, or alter associated endocrine hormones and free radicals, which may lead to the unfavorable development of psychiatric disorders and sleep rhythm disorders. This summary may provide researchers with better clues and ideas to develop therapeutic solutions with sleep disorders and depressive psychiatric disorders.

This paper explores the progressive era of sleep monitoring, focusing on wearable and remote devices contributing to advances in the concept of home polysomnography. We begin by exploring the basic physiology of sleep, establishing a theoretical basis for understanding sleep stages and associated changes in physiological variables. The review then moves on to an analysis of specific cutting-edge devices and technologies, with an emphasis on their practical applications, user comfort, and accuracy. Attention is also given to the ability of these devices to predict neurological disorders, particularly Alzheimer's and Parkinson's disease. The paper highlights the integration of hardware innovations, targeted sleep parameters, and partially advanced algorithms, illustrating how these elements converge to provide reliable sleep health information. By bridging the gap between clinical diagnosis and real-world applicability, this review aims to elucidate the role of modern sleep monitoring tools in improving personalised healthcare and proactive disease management.

Circadian rhythms, driven by biological clocks, help organisms align their physiological functions with environmental changes, promoting homeostasis. The central clock in the suprachiasmatic nucleus coordinates peripheral clocks via neurohumoral feedback involving proteins like CLOCK, BMAL1, CRY 1/2, and PER 1-3. In the ICU, these circadian processes often face disruptions from constant lighting, noise, and irregular sleep-wake cycles, impairing sleep quality and worsening stress responses. These disruptions can lead to adverse clinical effects, including higher cardiovascular complication rates. This study examines how ICU stays affect circadian rhythm regulators and their association with cardiovascular outcomes.

Significant differences were identified in melatonin levels and the expression of BMAL1, PER1, RORA, and NR1D1 between ICU stays of ≤7 days and >7 days. The APACHE-II severity scale influenced melatonin and the expression of CLOCK, PER2, CRY2, and RORA. Nonlinear relationships were observed between melatonin, clock genes, heart rate, and blood pressure (systolic and diastolic). In certain groups, molecular and physiological data showed correlations exceeding 90%.

These findings highlight a robust association between circadian disruption, as measured by melatonin and clock genes, and cardiovascular physiological rhythms in ICU patients.

Osteoporosis (OP) is a prevalent bone disease characterized by reduced bone density and quality, increasing fragility and fracture risk. Osteoclast (OC) activity and circadian rhythm play a role in the pathogenesis of OP. Melatonin is a circadian regulator that affects bone metabolism, but its molecular mechanism has not been studied in detail. This study aimed to identify the relationship between melatonin-related genes and OP through bioinformatics methods and to verify it experimentally.We analysed microarray data from the GSE35959 dataset, identifying differentially expressed genes in OP patients. Circadian rhythm-related genes and melatonin-related genes intersect with these differentially expressed genes, highlighting that CSNK1D is a central gene. Functional enrichment, correlation and protein-protein interaction analyses were conducted. Experimental validation involved in vitro differentiation assays using RAW264.7 cells and in vivo studies with an ovariectomy-induced rat model of OP to evaluate the role of CSNK1D in osteoclastogenesis to verify its effect on OP. Differential expression analysis revealed 272 significant genes, with CSNK1D identified as central to the circadian rhythm and to melatonin and OP interplay. Functional analyses showed involvement of CSNK1D in OC differentiation and inflammatory pathways. in vitro experiments confirmed CSNK1D upregulation during OC differentiation, and small interfering RNA-mediated knockdown reduced OC marker expression and TRAP+ cell formation. in vivo, CSNK1D expression is associated with bone loss in OP rats. Melatonin-related CSNK1D promotes OC differentiation and promotes the development of OP. These findings suggest CSNK1D as a potential therapeutic target for OP, offering insights into new treatment strategies integrating circadian rhythm regulation.

Given its antioxidant, anti-inflammatory, and antiapoptotic properties, melatonin (MEL), a health-caring food to improve sleep disorders, is hypothesized to protect against nanomaterial exposure-induced toxicity. However, the conclusion derived from different studies seemed inconsistent. A meta-analysis of all available preclinical studies was performed to examine the effects of MEL on nanomaterial-induced damages. Eighteen relevant studies were retrieved through searching five electronic databases up to December 2023. The meta-analysis showed that relative to control, MEL treatment significantly increased cell viability (standardized mean difference [SMD = 1.27]) and alleviated liver function (lowered AST [SMD = -3.89] and ALT [SMD = -5.89]), bone formation (enhanced BV/TV [SMD = 4.13] and lessened eroded bone surface [SMD = -5.40]), and brain nerve (inhibition of AChE activity [SMD = -3.60]) damages in animals. The protective mechanisms of MEL against damages caused by nanomaterial exposure were associated with its antiapoptotic (decreased Bax/Bcl-2 ratio [SMD = -4.50] and caspase-3 levels [dose <100 μM: SMD = -3.66]), antioxidant (decreased MDA [in vitro: SMD = -2.84; in vivo: SMD = -4.27]), and anti-inflammatory (downregulated TNF-α [in vitro: SMD = -5.41; in vivo: SMD = -3.21] and IL-6 [in vitro: SMD = -5.90; in vivo: SMD = -2.81]) capabilities. In conclusion, our study suggests that MEL should be supplemented to prevent damages in populations exposed to nanomaterials.

Sleep disorders are among the common comorbidities of autism spectrum disorder (ASD), which not only affect the daily life and learning ability of children but may also exacerbate other symptoms of ASD, seriously impacting the quality of life of children and their families. Given this, understanding the neurobiological mechanisms of sleep disorders in children with ASD has significant research value for developing effective intervention strategies. Melatonin, 5-hydroxytryptamine (5-HT), and orexin are key neurotransmitters that regulate the sleep-wake cycle. Through in-depth analysis of the biological functions and regulatory pathways of these neurotransmitters, new perspectives may be provided for personalized treatment of sleep disorders in children with ASD. This article reviews the research progress on melatonin, 5-HT, and orexin in sleep disorders among children with ASD, focusing on exploring the mechanisms of these key neurotransmitters in sleep disorders of children with ASD and how they affect the sleep-wake cycle, providing a theoretical basis for improving the sleep quality of children with ASD.

Melatonin is indispensable for the homeostasis of plants and animals. In humans, it can help prevent or be an adjuvant treatment for several diseases mainly related to the immune system, inflammation, and oxidative stress. Moreover, a melatonin-rich diet is linked to several health benefits, such as regulation of circadian rhythm, regulation of the immunological system, epilepsy control, delaying the aging process, and diminishing hormones related to cancer. This review aimed to show the effects of melatonin in diseases beyond its traditional use. The results showed it can present scavenging of free radicals, reducing inflammatory cytokines, and modulating the immune system. Moreover, it can improve insulin resistance, blood pressure, LDL-c, adipose tissue mass, adhesion molecules, endothelial impairment, and plaque formation. These effects result in neuro- and cardioprotection, improvement of liver diseases, rheumatoid arthritis, dermatitis, COVID-19, polycystic ovaries, and sepsis. We conclude that plant melatonin can benefit patients with many diseases besides sleep problems and neurodegeneration. Plant melatonin may be more cost-effective and present fewer adverse events than synthetic. However, more clinical trials should be performed to show adequate doses, formulation, and treatment time.

Circadian rhythm is ubiquitous in nature. Circadian clock genes such as Bmal1 and Clock form a multi-level transcription-translation feedback network, and regulate a variety of physiological and pathological processes, including bone and cartilage metabolism. Deletion of the core clock gene Bmal1 leads to pathological bone alterations, while the phenotypes are not consistent. Studies have shown that multiple signaling pathways are involved in the process of Bmal1 regulating bone and cartilage metabolism, but the exact regulatory mechanisms remain unclear. This paper reviews the signaling pathways by which Bmal1 regulates bone/cartilage metabolism, the upstream regulatory factors that control Bmal1, and the current Bmal1 knockout mouse models for research. We hope to provide new insights for the prevention and treatment of bone/cartilage diseases related to circadian rhythms.

Melatonin is a hormone released by the pineal gland that regulates the sleep-wake cycle. It has been widely studied for its therapeutic effects on Alzheimer's disease (AD), particularly through the amyloidosis, oxidative stress, and neuroinflammation pathways. Nevertheless, the mechanisms through which it exerts its neuroprotective effects in AD are still largely unknown. Data mining was used to identify potential gene targets that link melatonin's effects to AD pathways, yielding a comprehensive view of the underlying molecular mechanisms. We identified 3397 genes related to AD from DisGeNet and 329 melatonin gene targets from ChEMBL, which revealed 223 overlapping genes and the potential shared pathways. These genes were used to construct a protein-protein interaction (PPI) network comprising 143 nodes and 823 edges, which demonstrated significant PPI enrichment. A cluster analysis highlighted two key clusters centered on MMP2 and NR3C1, with both genes playing crucial roles in steroid hormone signaling, apoptosis, and monoamine neurotransmission. Gene Ontology (GO) enrichment and KEGG pathway analyses further elucidated their involvement in critical pathways, for instance, steroid hormone signaling and apoptosis regulation, significantly influencing AD pathology through mechanisms such as extracellular matrix remodeling, epigenetic modifications, and neuroinflammation. Our findings emphasize MMP2 and NR3C1 as important gene targets for future research on melatonin treatment in AD, paving the way for further investigations into their roles in AD pathophysiology.

Cataracts are primarily caused by aging or gene mutations and are the leading cause of blindness globally. As the older population increases, the number of patients with a cataract is expected to grow rapidly. At present, cataract surgery to replace the lens with an artificial intraocular lens is the principal treatment method. However, surgery has several drawbacks, including economic burdens and complications such as inflammation, xerophthalmia, macular edema and posterior capsular opacification. Thus, developing an effective non‑surgical treatment strategy is beneficial to both patients and public health. Mechanistically, cataract formation may be due to various reasons but is primarily initiated and promoted by oxidative stress and is closely associated with crystallin aggregation. In the present review, the current research progress on anti‑cataract drugs, including antioxidants and protein aggregation inhibitors is examined. It summarizes strategies for preventing and treating cataract through cell apoptosis and protein aggregation inhibition while discussing their limitations and further prospects.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multisystemic disease with a multifactorial pathogenesis involving dietary, environmental, and genetic factors. Previous mouse models suggested that circadian misalignment may additionally influence its development as it influences metabolism in diverse organs including the liver. Further, data from sleep questionnaires proved sleep-wake disruption in patients with MASLD. We objectively assessed sleep-wake rhythms in patients with biopsy-proven MASLD (n = 35) and healthy controls (HC, n = 16) using actigraphy 24/7 for 4 weeks. With the aim to re-align sleep rhythms a single standardized sleep hygiene education session was performed after 2 weeks. Actigraphy data revealed that MASLD patients had more awakenings per night (MASLD vs. HC 8.5 vs. 5.5, p = 0.0036), longer wakefulness after sleep onset (MASLD vs. HC 45.4 min vs. 21.3 min, p = 0.0004), and decreased sleep efficiency (MASLD vs. HC 86.5% vs. 92.8%, p = 0.0008) compared with HC despite comparable sleep duration. Patients with MASLD self-reported shorter sleep duration (MASLD vs. HC 6 h vs. 6 h 45 min, p = 0.01) and prolonged sleep latency contributing to poorer sleep quality. Standardized sleep hygiene education did not produce significant changes in sleep parameters. Our findings indicate fragmented nocturnal sleep in patients with MASLD, characterized by increased wakefulness and reduced sleep efficiency, perceived subjectively as shortened sleep duration and delayed onset. A single sleep hygiene education session did not improve sleep parameters.

Postoperative delirium (POD) is a common complication that has important implications for surgical patients, often leading to both short- and long-term cognitive deficits, worse outcomes, and increased healthcare costs. Given these implications, there may be a benefit in reducing the incidence of POD. Pharmacologic interventions may have the potential to reduce the risk of a patient developing POD.

Recently studied therapies include dexmedetomidine, propofol, haloperidol, ketamine, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, acetaminophen, melatonin/ramelteon, corticosteroids, midazolam, physostigmine, and neostigmine. In addition, the implementation of regional anesthesia and reduction of overall anesthetic depth have been examined. Of these therapies, dexmedetomidine has been studied the most and has the most supporting evidence for prevention of POD, but current studies lack clarity on optimal dosing and timing of dexmedetomidine administration. Acetaminophen, corticosteroids, and melatonin/ramelteon are other plausible medications that have potential for reducing POD incidence, but they all require further investigation. Reduction of anesthetic depth and regional anesthetics are options for anesthetic management that show promise but still lack enough supporting evidence in recent literature to receive a strong recommendation. Future research should focus on identifying optimal strategies for the implementation of the pharmacological options listed, including doses and timing of administration. Attention should be given to dexmedetomidine given its promise demonstrated by recent literature.

The lack of current Canadian practice guidelines for the management of insomnia poses a challenge for healthcare providers (HCP) in selecting the appropriate treatment options. This study aimed to establish expert consensus recommendations for the management of chronic insomnia in Canada.

Sixteen multidisciplinary experts in sleep medicine and insomnia across Canada developed consensus recommendations based on their knowledge of the literature and their practical experience.

The consensus recommendations were developed through a Delphi method. Consensus was reached if at least 75 % of the voting participants "agreed" or "strongly agreed" with the corresponding statements. The quality of supporting evidence was rated using a GRADE rating system.

Among 37 recommendations that reached consensus for the management of chronic insomnia, the experts recommend and agree that.

These consensus recommendations highlight the need to increase awareness, capacity for, and access to CBT-I; integrate newly approved pharmacotherapy; reduce both self-medication and medications with limited evidence or low risk/benefit ratio.

Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.

Sleep disturbances are a hallmark feature of various autoimmune neurological diseases (AINDs). However, limited awareness of these sleep manifestations exists among clinicians. We provide a comprehensive overview of assessment methods, characteristic sleep disturbances, the impact of specific antibodies on sleep patterns, and treatment strategies for sleep disturbances in AINDs.

Research advancements in sleep disturbances in autoimmune neurological disease focus primarily on four areas: mechanisms, clinical characteristics, assessment, and treatment. Regarding mechanisms, animal models for AINDs, particularly those involving specific antibodies like anti-NMDAR, anti-LGI1, and anti-IgLON5, have become more comprehensive. Recent advancements in animal models have led to the establishment of numerous models for AINDs; these models include a wide range of antibodies, including anti-NMDAR, anti-LGI1, and anti-IgLON5. Several studies using these models have revealed common mechanisms underlying sleep disturbances in these diseases. In terms of clinical characteristics, the identification of antibodies associated with recently discovered AINDs has expanded the spectrum of sleep disturbance symptoms observed compared to prior findings. A comprehensive evaluation system for the assessment of sleep disturbances has been established, including questionnaires, polysomnography, functional magnetic resonance imaging, and 18F-FDG PET/CT. Additionally, cardiopulmonary coupling shows promise as a novel assessment tool. Currently, no universally effective treatment exists for sleep disturbances in autoimmune neurological diseases, either through symptomatic treatment or immunosuppressive therapy. Further studies are needed to confirm the efficacy of new therapies and validate the benefits of existing treatments. Sleep disturbances are a hallmark feature of AINDs. Recent advancements have significantly expanded our understanding of their assessment and treatment. However, further studies are needed to address the remaining uncertainties in sleep disturbance management.

The food-borne 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a potential human carcinogen abundant in cooked meat. While circadian rhythms are crucial biological oscillations, the negative impact of PhIP on circadian systems and the potential of mitigation remain underexplored. We investigated the effects of PhIP on circadian rhythms and the mitigating effects of the phytochemical antioxidant pterostilbene (PSB) in Caenorhabditis elegans. We show that exposure to 10 μM PhIP disrupts the 24-h circadian rhythms of C. elegans, an effect mitigated by co-exposure to 100 μM PSB. In addition, PhIP-induced circadian disruption can be linked to defective oxidative stress resistance, which is associated with the DAF-16/FOXO pathway and is modulated by PSB. Molecular docking suggested that PhIP and PSB bind similarly to DAF-16. Moreover, 10 μM PhIP abolished the rhythmic expression of the core clock gene prdx-2, which is restored by 100 μM PSB. Findings from this study provide novel insight of how food-borne contaminant like PhIP may contribute to the disruption of circadian rhythms and suggest potential for PSB to mitigate these effects in higher organisms.

In mammals, the melatonin (Mel) concentration in the gastrointestinal tract is 400 times greater than in the pineal gland. However, the origin of Mel in the gastrointestinal tract and its role in reproductive regulation remains unclear. Therefore, we analyzed three potential Mel sources (feed, microorganisms, and the rumen wall) for their contribution to high Mel levels in the rumen and their biological effects. The feed contained high Mel concentrations, and Mel in rumen fluid and blood peaked two hours after feeding. Rumen microbial analysis showed a strong positive correlation between Mel and specific microbes, including Megasphaera, Butyrivibrio, Acetobacter, and Olsenella. In vitro experiments indicated that rumen microorganisms synthesized Mel from tryptophan. The rumen wall also contains key enzymes, AANAT and HIOMT, which catalyze Mel synthesis and membrane receptors MT1 and MT2 that mediate the function of Mel, suggesting that the rumen wall synthesizes Mel. Mel peaked in both rumen fluid and blood two hours after feeding. Feeding also altered blood levels of Mel, Gonadotropin-releasing hormone (GnRH), Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), progesterone (P4), and Estradiol (E2), with a correlation between Mel and fluctuations in GnRH, LH, P4, and E2 levels. Our findings suggest that feed is the primary source of high Mel levels in the rumen and impacts reproductive hormone fluctuations. This study elucidates the origin of high rumen Mel concentrations and reveals that food intake affects the natural secretion of various hormones, offering a new perspective on food sources for regulating reproductive physiology.