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Book ; Online: SIRT Family in Endocrinology

Yang, Yang / Reiter, Russel J.

2019

Keywords	Medicine ; Endocrinology ; Diabetes ; Cardiovascular medicine ; Silent information regulator ; Metabolism
Size	1 electronic resource (212 pages)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT021231402
ISBN	9782889630219 ; 2889630218
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia.

Loh, Doris / Reiter, Russel J

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: The swift rise in acceptance of molecular principles defining phase separation by a broad array of scientific disciplines is shadowed by increasing discoveries linking phase separation to pathological aggregations associated with numerous ... ...

Abstract	The swift rise in acceptance of molecular principles defining phase separation by a broad array of scientific disciplines is shadowed by increasing discoveries linking phase separation to pathological aggregations associated with numerous neurodegenerative disorders, including Alzheimer's disease, that contribute to dementia. Phase separation is powered by multivalent macromolecular interactions. Importantly, the release of water molecules from protein hydration shells into bulk creates entropic gains that promote phase separation and the subsequent generation of insoluble cytotoxic aggregates that drive healthy brain cells into diseased states. Higher viscosity in interfacial waters and limited hydration in interiors of biomolecular condensates facilitate phase separation. Light, water, and melatonin constitute an ancient synergy that ensures adequate protein hydration to prevent aberrant phase separation. The 670 nm visible red wavelength found in sunlight and employed in photobiomodulation reduces interfacial and mitochondrial matrix viscosity to enhance ATP production via increasing ATP synthase motor efficiency. Melatonin is a potent antioxidant that lowers viscosity to increase ATP by scavenging excess reactive oxygen species and free radicals. Reduced viscosity by light and melatonin elevates the availability of free water molecules that allow melatonin to adopt favorable conformations that enhance intrinsic features, including binding interactions with adenosine that reinforces the adenosine moiety effect of ATP responsible for preventing water removal that causes hydrophobic collapse and aggregation in phase separation. Precise recalibration of interspecies melatonin dosages that account for differences in metabolic rates and bioavailability will ensure the efficacious reinstatement of the once-powerful ancient synergy between light, water, and melatonin in a modern world.
MeSH term(s)	Humans ; Melatonin/metabolism ; Water ; Alzheimer Disease/metabolism ; Adenosine Triphosphate/metabolism ; Adenosine
Chemical Substances	Melatonin (JL5DK93RCL) ; Water (059QF0KO0R) ; Adenosine Triphosphate (8L70Q75FXE) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2023-03-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065835
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Melatonin in health and diseases.

Yousefi, Bahman / Reiter, Russel J

Biochimie

2022 Volume 202, Page(s) 1

MeSH term(s)	Melatonin/therapeutic use ; Antioxidants ; Oxidative Stress
Chemical Substances	Melatonin (JL5DK93RCL) ; Antioxidants
Language	English
Publishing date	2022-11-20
Publishing country	France
Document type	Editorial
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2022.10.003
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Article ; Online: Light, Water, and Melatonin

Doris Loh / Russel J. Reiter

International Journal of Molecular Sciences, Vol 24, Iss 5835, p

The Synergistic Regulation of Phase Separation in Dementia

2023 Volume 5835

Abstract	The swift rise in acceptance of molecular principles defining phase separation by a broad array of scientific disciplines is shadowed by increasing discoveries linking phase separation to pathological aggregations associated with numerous neurodegenerative disorders, including Alzheimer’s disease, that contribute to dementia. Phase separation is powered by multivalent macromolecular interactions. Importantly, the release of water molecules from protein hydration shells into bulk creates entropic gains that promote phase separation and the subsequent generation of insoluble cytotoxic aggregates that drive healthy brain cells into diseased states. Higher viscosity in interfacial waters and limited hydration in interiors of biomolecular condensates facilitate phase separation. Light, water, and melatonin constitute an ancient synergy that ensures adequate protein hydration to prevent aberrant phase separation. The 670 nm visible red wavelength found in sunlight and employed in photobiomodulation reduces interfacial and mitochondrial matrix viscosity to enhance ATP production via increasing ATP synthase motor efficiency. Melatonin is a potent antioxidant that lowers viscosity to increase ATP by scavenging excess reactive oxygen species and free radicals. Reduced viscosity by light and melatonin elevates the availability of free water molecules that allow melatonin to adopt favorable conformations that enhance intrinsic features, including binding interactions with adenosine that reinforces the adenosine moiety effect of ATP responsible for preventing water removal that causes hydrophobic collapse and aggregation in phase separation. Precise recalibration of interspecies melatonin dosages that account for differences in metabolic rates and bioavailability will ensure the efficacious reinstatement of the once-powerful ancient synergy between light, water, and melatonin in a modern world.
Keywords	melatonin ; dementia ; amyloid-β ; ATP ; adenosine ; phase separation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	612
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Multidrug nanoformulations of vitamin D, anandamide and melatonin as a synergistic treatment for vascular inflammation.

Martín Giménez, Virna Margarita / Reiter, Russel J / Manucha, Walter

Drug discovery today

2023 Volume 28, Issue 6, Page(s) 103539

MeSH term(s)	Humans ; Vitamin D/therapeutic use ; Melatonin/pharmacology ; Melatonin/therapeutic use ; Arachidonic Acids ; Inflammation/drug therapy ; Antioxidants
Chemical Substances	Vitamin D (1406-16-2) ; Melatonin (JL5DK93RCL) ; anandamide (UR5G69TJKH) ; Arachidonic Acids ; Antioxidants
Language	English
Publishing date	2023-02-23
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	1324988-5
ISSN	1878-5832 ; 1359-6446
ISSN (online)	1878-5832
ISSN	1359-6446
DOI	10.1016/j.drudis.2023.103539
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Zs.A 4725: Show issues

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Article: The Multiple Functions of Melatonin: Applications in the Military Setting.

Gancitano, Giuseppe / Reiter, Russel J

Biomedicines

2022 Volume 11, Issue 1

Abstract: The aim of this review is to provide the reader with a general overview on the rationale for the use of melatonin by military personnel. This is a technique that is being increasingly employed to manage growing psycho-physical loads. In this context, ... ...

Abstract	The aim of this review is to provide the reader with a general overview on the rationale for the use of melatonin by military personnel. This is a technique that is being increasingly employed to manage growing psycho-physical loads. In this context, melatonin, a pleotropic and regulatory molecule, has a potential preventive and therapeutic role in maintaining the operational efficiency of military personnel. In battlefield conditions in particular, the time to treatment after an injury is often a major issue since the injured may not have immediate access to medical care. Any drug that would help to stabilize a wounded individual, especially if it can be immediately administered (e.g., per os) and has a very high safety profile over a large range of doses (as melatonin does) would be an important asset to reduce morbidity and mortality. Melatonin may also play a role in the oscillatory synchronization of the neuro-cardio-respiratory systems and, through its epigenetic action, poses the possibility of restoring the main oscillatory waves of the cardiovascular system, such as the Mayer wave and RSA (respiratory sinus arrhythmia), which, in physiological conditions, result in the oscillation of the heartbeat in synchrony with the breath. In the future, this could be a very promising field of investigation.
Language	English
Publishing date	2022-12-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11010005
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Article ; Online: Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19.

Loh, Doris / Reiter, Russel J

International journal of molecular sciences

2022 Volume 23, Issue 15

Abstract: The relentless, protracted evolution of the SARS-CoV-2 virus imposes tremendous pressure on herd immunity and demands versatile adaptations by the human host genome to counter transcriptomic and epitranscriptomic alterations associated with a wide range ... ...

Abstract	The relentless, protracted evolution of the SARS-CoV-2 virus imposes tremendous pressure on herd immunity and demands versatile adaptations by the human host genome to counter transcriptomic and epitranscriptomic alterations associated with a wide range of short- and long-term manifestations during acute infection and post-acute recovery, respectively. To promote viral replication during active infection and viral persistence, the SARS-CoV-2 envelope protein regulates host cell microenvironment including pH and ion concentrations to maintain a high oxidative environment that supports template switching, causing extensive mitochondrial damage and activation of pro-inflammatory cytokine signaling cascades. Oxidative stress and mitochondrial distress induce dynamic changes to both the host and viral RNA m
MeSH term(s)	COVID-19 ; Host-Pathogen Interactions ; Humans ; Melatonin ; RNA, Viral ; SARS-CoV-2 ; Virus Replication
Chemical Substances	RNA, Viral ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-07-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23158122
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Article ; Online: A mid‑pandemic night's dream: Melatonin, from harbinger of anti‑inflammation to mitochondrial savior in acute and long COVID‑19 (Review).

Lempesis, Ioannis G / Georgakopoulou, Vasiliki Epameinondas / Reiter, Russel J / Spandidos, Demetrios A

International journal of molecular medicine

2024 Volume 53, Issue 3

Abstract: Coronavirus disease 2019 (COVID‑19), a systemic illness caused by severe acute respiratory distress syndrome 2 (SARS‑CoV‑2), has triggered a worldwide pandemic with symptoms ranging from asymptomatic to chronic, affecting practically every organ. ... ...

Abstract	Coronavirus disease 2019 (COVID‑19), a systemic illness caused by severe acute respiratory distress syndrome 2 (SARS‑CoV‑2), has triggered a worldwide pandemic with symptoms ranging from asymptomatic to chronic, affecting practically every organ. Melatonin, an ancient antioxidant found in all living organisms, has been suggested as a safe and effective therapeutic option for the treatment of SARS‑CoV‑2 infection due to its good safety characteristics and broad‑spectrum antiviral medication properties. Melatonin is essential in various metabolic pathways and governs physiological processes, such as the sleep‑wake cycle and circadian rhythms. It exhibits oncostatic, anti‑inflammatory, antioxidant and anti‑aging properties, exhibiting promise for use in the treatment of numerous disorders, including COVID‑19. The preventive and therapeutic effects of melatonin have been widely explored in a number of conditions and have been well‑established in experimental ischemia/reperfusion investigations, particularly in coronary heart disease and stroke. Clinical research evaluating the use of melatonin in COVID‑19 has shown various improved outcomes, including reduced hospitalization durations; however, the trials are small. Melatonin can alleviate mitochondrial dysfunction in COVID‑19, improve immune cell function and provide antioxidant properties. However, its therapeutic potential remains underexplored due to funding limitations and thus further investigations are required.
MeSH term(s)	Humans ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Antioxidants/metabolism ; COVID-19 ; Melatonin/pharmacology ; Melatonin/therapeutic use ; Melatonin/metabolism ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/metabolism
Chemical Substances	Antioxidants ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2024-02-01
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	1444428-8
ISSN	1791-244X ; 1107-3756
ISSN (online)	1791-244X
ISSN	1107-3756
DOI	10.3892/ijmm.2024.5352
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 4942: Show issues

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Article ; Online: Melatonin: Regulation of Prion Protein Phase Separation in Cancer Multidrug Resistance.

Loh, Doris / Reiter, Russel J

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 3

Abstract: The unique ability to adapt and thrive in inhospitable, stressful tumor microenvironments (TME) also renders cancer cells resistant to traditional chemotherapeutic treatments and/or novel pharmaceuticals. Cancer cells exhibit extensive metabolic ... ...

Abstract	The unique ability to adapt and thrive in inhospitable, stressful tumor microenvironments (TME) also renders cancer cells resistant to traditional chemotherapeutic treatments and/or novel pharmaceuticals. Cancer cells exhibit extensive metabolic alterations involving hypoxia, accelerated glycolysis, oxidative stress, and increased extracellular ATP that may activate ancient, conserved prion adaptive response strategies that exacerbate multidrug resistance (MDR) by exploiting cellular stress to increase cancer metastatic potential and stemness, balance proliferation and differentiation, and amplify resistance to apoptosis. The regulation of prions in MDR is further complicated by important, putative physiological functions of ligand-binding and signal transduction. Melatonin is capable of both enhancing physiological functions and inhibiting oncogenic properties of prion proteins. Through regulation of phase separation of the prion N-terminal domain which targets and interacts with lipid rafts, melatonin may prevent conformational changes that can result in aggregation and/or conversion to pathological, infectious isoforms. As a cancer therapy adjuvant, melatonin could modulate TME oxidative stress levels and hypoxia, reverse pH gradient changes, reduce lipid peroxidation, and protect lipid raft compositions to suppress prion-mediated, non-Mendelian, heritable, but often reversible epigenetic adaptations that facilitate cancer heterogeneity, stemness, metastasis, and drug resistance. This review examines some of the mechanisms that may balance physiological and pathological effects of prions and prion-like proteins achieved through the synergistic use of melatonin to ameliorate MDR, which remains a challenge in cancer treatment.
MeSH term(s)	Animals ; Drug Resistance, Multiple/genetics ; Drug Resistance, Multiple/physiology ; Humans ; Lipid Peroxidation ; Melatonin/metabolism ; Melatonin/pharmacology ; Melatonin/physiology ; Membrane Microdomains/metabolism ; Neoplasms/metabolism ; Prion Proteins/metabolism ; Prions/chemistry ; Prions/genetics ; Prions/metabolism ; Signal Transduction ; Tumor Microenvironment/physiology
Chemical Substances	Prion Proteins ; Prions ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-01-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27030705
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.MO 81: Show issues

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Article ; Online: Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality.

Tan, Dun-Xian / Reiter, Russel J

Life sciences

2022 Volume 294, Page(s) 120368

Abstract: The fear of SARS-CoV-2 infection is due to its high mortality related to seasonal flu. To date, few medicines have been developed to significantly reduce the mortality of the severe COVID-19 patients, especially those requiring tracheal intubation. The ... ...

Abstract	The fear of SARS-CoV-2 infection is due to its high mortality related to seasonal flu. To date, few medicines have been developed to significantly reduce the mortality of the severe COVID-19 patients, especially those requiring tracheal intubation. The severity and mortality of SARS-CoV-2 infection not only depend on the viral virulence, but are primarily determined by the cytokine storm and the destructive inflammation driven by the host immune reaction. Thus, to target the host immune response might be a better strategy to combat this pandemic. Melatonin is a molecule with multiple activities on a virus infection. These include that it downregulates the overreaction of innate immune response to suppress inflammation, promotes the adaptive immune reaction to enhance antibody formation, inhibits the entrance of the virus into the cell as well as limits its replication. These render it a potentially excellent candidate for treatment of the severe COVID-19 cases. Several clinical trials have confirmed that melatonin when added to the conventional therapy significantly reduces the mortality of the severe COVID-19 patients. The cost of melatonin is a small fraction of those medications approved by FDA for emergency use to treat COVID-19. Because of its self-administered, low cost and high safety margin, melatonin could be made available to every country in the world at an affordable cost. We recommend melatonin be used to treat severe COVID-19 patients with the intent of reducing mortality. If successful, it would make the SARS-CoV-2 pandemic less fearful and help to return life back to normalcy.
MeSH term(s)	Anti-Inflammatory Agents ; Antioxidants ; COVID-19/immunology ; COVID-19/mortality ; Cytokine Release Syndrome/drug therapy ; Humans ; Immunity, Innate/drug effects ; Melatonin/therapeutic use ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Virus Replication/drug effects ; COVID-19 Drug Treatment
Chemical Substances	Anti-Inflammatory Agents ; Antioxidants ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-01-30
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.120368
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