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Journal of Sleep Research Dec 2023Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and... (Review)
Review
Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).
Topics: Adult; Humans; Sleep Initiation and Maintenance Disorders; Melatonin; Sleep; Benzodiazepines; Antidepressive Agents
PubMed: 38016484
DOI: 10.1111/jsr.14035 -
Advanced Science (Weinheim,... Sep 2023Periodontitis is a chronic infectious disease caused by bacterial irritation. As an essential component of the host immunity, macrophages are highly plastic and play a...
Periodontitis is a chronic infectious disease caused by bacterial irritation. As an essential component of the host immunity, macrophages are highly plastic and play a crucial role in inflammatory response. An appropriate and timely transition from proinflammatory (M1) to anti-inflammatory (M2) macrophages is indispensable for treating periodontitis. As M2 macrophage-derived exosomes (M2-exos) can actively target inflammatory sites and modulate immune microenvironments, M2-exos can effectively treat periodontitis. Excessive endoplasmic reticulum stress (ER stress) and unfolded protein response (UPR) are highly destructive pathological characteristics during inflammatory periodontal bone loss. Although melatonin has antioxidant and anti-inflammatory effects, studies focusing on melatonin ER stress modulation remain limited. This study fabricates engineered M2-exos loading with melatonin (Mel@M2-exos) for treating periodontitis. As a result, M2-exos drive an appropriate and timely macrophage reprogramming from M1 to M2 type, which resolves chronic inflammation and accelerated periodontal healing. Melatonin released from Mel@M2-exos rescues the osteogenic and cementogenic differentiation capacity in inflammatory human periodontal ligament cells (hPDLCs) by reducing excessive ER stress and UPR. Injectable gelatin methacryloyl (GelMA) hydrogels with sustained-release Mel@M2-exos accelerate periodontal bone regeneration in rats with ligation-induced periodontitis. Taken together, melatonin engineering M2 macrophage-derived exosomes are promising candidates for inflammatory periodontal tissue regeneration.
Topics: Rats; Humans; Animals; Melatonin; Exosomes; Periodontitis; Endoplasmic Reticulum Stress; Inflammation; Macrophages
PubMed: 37452425
DOI: 10.1002/advs.202302029 -
Journal of Pineal Research Aug 2023It is widely known that lack of sleep damages the skin. Therefore, it is necessary to explore the relationship between sleep deprivation and skin damage and to find...
It is widely known that lack of sleep damages the skin. Therefore, it is necessary to explore the relationship between sleep deprivation and skin damage and to find effective treatments. We established a 28-day sleep restriction (SR) mice model simulating continuous long-term sleep loss. We found that SR would damage the barrier function of mice's skin, cause oxidative stress damage to the skin, weaken the oscillations of the skin's biological clock, and make the circadian rhythm of Bacteroides disappear. The circadian rhythm of short-chain fatty acids (SCFA) receptors in the skin was disordered. After melatonin supplementation, the skin damage caused by SR was improved, the oscillations of the biological clock were enhanced, the circadian rhythm of Bacteroides was restored, and the rhythm of the receptor GPR43 of propionic acid was restored. We speculated that the improving effect of melatonin may be mediated by propionic acid produced by the gut microbiota. We verified in vitro that propionic acid could improve the keratinocytes barrier function of oxidative damage. We then consumed the gut microbiota of mice through antibiotics and found that oral melatonin could not improve skin damage. Moreover, supplementing mice with propionic acid could improve skin damage. Our research showed that lack of sleep impaired skin barrier function. Oral melatonin could improve skin damage by restoring the circadian rhythm of Bacteroides and its propionic acid metabolite.
Topics: Animals; Mice; Melatonin; Propionates; Gastrointestinal Microbiome; Sleep; Circadian Rhythm
PubMed: 37057339
DOI: 10.1111/jpi.12874 -
Biochemical Pharmacology Dec 2023Ferroptosis, a regulated form of cell death, is characterized by iron-dependent lipid peroxidation leading to oxidative damage to cell membranes. Cell sensitivity to... (Review)
Review
Ferroptosis, a regulated form of cell death, is characterized by iron-dependent lipid peroxidation leading to oxidative damage to cell membranes. Cell sensitivity to ferroptosis is influenced by factors such as iron overload, lipid metabolism, and the regulation of the antioxidant system. Melatonin, with its demonstrated capacity to chelate iron, modulate iron metabolism proteins, regulate lipid peroxidation, and regulate antioxidant systems, has promise as a potential therapeutic agent in mediating ferroptosis. The availability of approved drugs targeting ferroptosis is limited; therefore, melatonin is a candidate for broad application due to its safety and efficacy in attenuating ferroptosis in noncancerous diseases. Melatonin has been demonstrated to attenuate ferroptosis in cellular and animal models of noncancerous diseases, showcasing effectiveness in organs such as the heart, brain, lung, liver, kidney, and bone. This review outlines the molecular mechanisms of ferroptosis, investigates melatonin's potential effects on ferroptosis, and discusses melatonin's therapeutic potential as a promising intervention against diseases associated with ferroptosis. Through this discourse, we aim to lay a strong foundation for developing melatonin as a therapeutic strategy to modulate ferroptosis in a variety of disease contexts.
Topics: Animals; Ferroptosis; Melatonin; Antioxidants; Iron; Cell Death; Lipid Peroxidation
PubMed: 37931663
DOI: 10.1016/j.bcp.2023.115909 -
The Lancet. Neurology Nov 2023
Topics: Humans; Melatonin; Cardiovascular Diseases; Sleep; Circadian Rhythm; Sleep Wake Disorders
PubMed: 37863599
DOI: 10.1016/S1474-4422(23)00363-0 -
Journal of Psychosomatic Research Jul 2023To assess the efficacy of melatonin and melatonergic agonist for the treatment of delirium in hospitalized patients. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the efficacy of melatonin and melatonergic agonist for the treatment of delirium in hospitalized patients.
METHODS
Embase, MEDLINE, PsycINFO, PubMed, CENTRAL, Cochrane Database of Systematic Reviews, TRIP Medical Database, ClinicalTrials.gov and Google were searched from inception to October 2022. Randomized controlled trials (RCT) and observational studies with any type of comparator evaluating melatonin or melatonergic agonist (ramelteon) enrolling any populations (ICU, surgery, geriatric) were included. Two reviewers independently selected and extracted data using the Cochrane risk of bias tools (RoB2 and ROBINSI).
RESULTS
Out of the 650 screened publications, three RCTs and six observational studies were included (n = 1211). All three RCTs compared melatonin to placebo, as the majority of observational studies compared melatonin or ramelteon to antipsychotics. Two RCTs reported the duration of delirium and a meta-analysis provided a statistical difference between melatonin and placebo (-1.72 days, 95% CI -2.66 to -0.77, p = 0.0004). Five observational studies reported the duration of delirium but only one reported a statistical reduction in the duration of delirium.
CONCLUSION
Although melatonin and ramelteon may be effective treatments for delirium, particularly to shorten the duration of delirium and to limit the use of rescue medication, current data is limited in number and in its quality. Clinicians should wait until higher quality data from ongoing RCTs are available before prescribing melatonin to delirious patients.
Topics: Humans; Aged; Melatonin; Delirium; Indenes; Antipsychotic Agents
PubMed: 37150157
DOI: 10.1016/j.jpsychores.2023.111345 -
Frontiers in Immunology 2024Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone with many physiological and biological roles. Melatonin is an antioxidant, anti-inflammatory, free... (Review)
Review
Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone with many physiological and biological roles. Melatonin is an antioxidant, anti-inflammatory, free radical scavenger, circadian rhythm regulator, and sleep hormone. However, its most popular role is the ability to regulate sleep through the circadian rhythm. Interestingly, recent studies have shown that melatonin is an important and essential hormone during pregnancy, specifically in the placenta. This is primarily due to the placenta's ability to synthesize its own melatonin rather than depending on the pineal gland. During pregnancy, melatonin acts as an antioxidant and anti-inflammatory, which is necessary to ensure a stable environment for both the mother and the fetus. It is an essential antioxidant in the placenta because it reduces oxidative stress by constantly scavenging for free radicals, i.e., maintain the placenta's integrity. In a healthy pregnancy, the maternal immune system is constantly altered to accommodate the needs of the growing fetus, and melatonin acts as a key anti-inflammatory by regulating immune homeostasis during early and late gestation. This literature review aims to identify and summarize melatonin's role as a powerful antioxidant and anti-inflammatory that reduces oxidative stress and inflammation to maintain a favorable homeostatic environment in the placenta throughout gestation.
Topics: Pregnancy; Female; Humans; Melatonin; Antioxidants; Placenta; Free Radical Scavengers; Anti-Inflammatory Agents
PubMed: 38361952
DOI: 10.3389/fimmu.2024.1339304 -
Expert Review of Endocrinology &... 2023Melatonin, originally isolated from the mammalian pineal gland, was subsequently identified in many animal cell types and in plants. While melatonin was discovered to... (Review)
Review
INTRODUCTION
Melatonin, originally isolated from the mammalian pineal gland, was subsequently identified in many animal cell types and in plants. While melatonin was discovered to inhibit cancer more than 5 decades ago, its anti-cancer potential has not been fully exploited despite its lack of serious toxicity over a very wide dose range, high safety margin, and its efficacy.
AREAS COVERED
This review elucidates the potential mechanisms by which melatonin interferes with tumor growth and metastasis, including its ability to alter tumor cell metabolism, inhibit epithelial-mesenchymal transition, reverse cancer chemoresistance, function synergistically with conventional cancer-inhibiting drugs while limiting many of their side effects. In contrast to its function as a potent antioxidant in normal cells, it may induce oxidative stress in cancer cells, contributing to its oncostatic actions.
EXPERT OPINION
Considering the large amount of experimental data supporting melatonin's multiple and varied inhibitory effects on numerous cancer types, coupled with the virtual lack of toxicity of this molecule, it has not been thoroughly tested as an anti-cancer agent in clinical trials. There seems to be significant resistance to such investigations, possibly because melatonin is inexpensive and non-patentable, and as a result there would be limited financial gain for its use.
Topics: Animals; Humans; Melatonin; Neoplasms; Antioxidants; Mammals
PubMed: 37466337
DOI: 10.1080/17446651.2023.2237103 -
Translational Psychiatry Oct 2023Depression is a common chronic psychiatric illness, which is resistant to medical treatments. While melatonin may alleviate certain depression symptoms, evidence for its...
Depression is a common chronic psychiatric illness, which is resistant to medical treatments. While melatonin may alleviate certain depression symptoms, evidence for its efficacy against core symptoms is lacking. Here, we tested a mechanism whereby melatonin rescues the behavioral outcomes of the chronic unpredictable mild stress (CUMS) mouse model of depression. CUMS mice showed depressive behaviors to tail suspension, open field behavior, and sucrose preference test, and cognitive dysfunction in the Morris water maze. Impairments in these measures were relieved by melatonin treatment. Moreover, CUMS mice had impaired glymphatic function across the sleep-wake cycle due to the astrocytic loss and disturbance of circadian regulation of the polarized expression of aquaporin-4 (AQP4) water channels in perivascular astrocytes. EEG results in CUMS mice showed a reduced total sleep time and non-rapid eye movement (NREM) sleep, due to sleep fragmentation in the light phase. CUMS mice lost the normal rhythmic expressions of circadian proteins Per2, Cry2, Bmal1, Clock, and Per1. However, the melatonin treatment restored glymphatic system function and the polarization of AQP4, while improving sleep structure, and rectifying the abnormal expression of Per2, Bmal1, Clock, and Per1 in CUMS mice. Interestingly, Per2 expression correlated negatively with the polarization of AQP4. Further studies demonstrated that Per2 directed the location of AQP4 expression via interactions with the α-dystrobrevin (Dtna) subunit of AQP4 in primary cultured astrocytes. In conclusion, we report a new mechanism whereby melatonin improves depression outcomes by regulating the expression of the circadian protein Per2, maintaining the circadian rhythm of astrocytic AQP4 polarization, and restoring glymphatic function.
Topics: Mice; Animals; Melatonin; Depression; ARNTL Transcription Factors; Circadian Rhythm; Cognitive Dysfunction
PubMed: 37802998
DOI: 10.1038/s41398-023-02614-z -
Rejuvenation Research Dec 2023Circadian rhythms (CRs) are 24-hour periodic oscillations governed by an endogenous circadian pacemaker located in the suprachiasmatic nucleus (SCN), which organizes the... (Review)
Review
Circadian rhythms (CRs) are 24-hour periodic oscillations governed by an endogenous circadian pacemaker located in the suprachiasmatic nucleus (SCN), which organizes the physiology and behavior of organisms. Circadian rhythm disruption (CRD) is also indicative of the aging process. In mammals, melatonin is primarily synthesized in the pineal gland and participates in a variety of multifaceted intracellular signaling networks and has been shown to synchronize CRs. Endogenous melatonin synthesis and its release tend to decrease progressively with advancing age. Older individuals experience frequent CR disruption, which hastens the process of aging. A profound understanding of the relationship between CRs and aging has the potential to improve existing treatments and facilitate development of novel chronotherapies that target age-related disorders. This review article aims to examine the circadian regulatory mechanisms in which melatonin plays a key role in signaling. We describe the basic architecture of the molecular circadian clock and its functional decline with age in detail. Furthermore, we discuss the role of melatonin in regulation of the circadian pacemaker and redox homeostasis during aging. Moreover, we also discuss the protective effect of exogenous melatonin supplementation in age-dependent CR disruption, which sheds light on this pleiotropic molecule and how it can be used as an effective chronotherapeutic medicine.
Topics: Humans; Animals; Melatonin; Circadian Rhythm; Circadian Clocks; Suprachiasmatic Nucleus; Aging; Mammals
PubMed: 37847148
DOI: 10.1089/rej.2023.0047