{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:28:39Z","timestamp":1793237319509,"version":"4.5.0"},"reference-count":190,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Throughout the history of melatonin research, almost exclusive focus has been on nocturnally-generated pineal melatonin production, which accounts for its circadian rhythm in the blood and cerebrospinal fluid; these light\/dark melatonin cycles drive the daily and seasonal photoperiodic alterations in organismal physiology. Because pineal melatonin is produced and secreted primarily at night, it is referred to as the chemical expression of darkness. The importance of the other sources of melatonin has almost been ignored. Based on current evidence, there are at least four sources of melatonin in vertebrates that contribute to the whole-body melatonin pool. These include melatonin produced by (1) the pineal gland; (2) extrapineal cells, tissues, and organs; (3) the microbiota of the skin, mouth, nose, digestive tract, and vagina as well as (4) melatonin present in the diet. These multiple sources of melatonin exhibit differentially regulated mechanisms for its synthesis. Visible light striking the retina or an intense physical stimulus can suppress nocturnal pineal melatonin levels; in contrast, there are examples where extrapineal melatonin levels are increased during heavy exercise in daylight, which contains the whole range of NIR radiation. The cumulative impact of all cells producing augmented extrapineal melatonin is sufficient to elevate sweat concentrations, and potentially, if the exposure is sustained, to also increasing the circulating values. The transient increases in sweat and plasma melatonin support the premise that extrapineal melatonin has a production capacity that exceeds by far what can be produced by the pineal gland, and is used to maintain intercellular homeostasis and responds to rapid changes in ROS density. The potential regulatory mechanisms of near infrared light (NIR) on melatonin synthesis are discussed in detail herein. Combined with the discovery of high levels of melanopsin in most fat cells and their response to light further calls into question pineal centric theories. While the regulatory processes related to microbiota-derived melatonin are currently unknown, there does seem to be crosstalk between melatonin derived from the host and that originating from microbiota.<\/jats:p>","DOI":"10.3390\/biology12010089","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T03:19:54Z","timestamp":1672975194000},"page":"89","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Melatonin: Both a Messenger of Darkness and a Participant in the Cellular Actions of Non-Visible Solar Radiation of Near Infrared Light"],"prefix":"10.3390","volume":"12","author":[{"given":"Dun-Xian","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Cell Systems and Anatomy, UT Health San Antonio, Long School of Medicine, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-4225","authenticated-orcid":false,"given":"Russel J.","family":"Reiter","sequence":"additional","affiliation":[{"name":"Department of Cell Systems and Anatomy, UT Health San Antonio, Long School of Medicine, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Silas, Inc., Basking Ridge, NJ 07920, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0178-6378","authenticated-orcid":false,"given":"Ruediger","family":"Hardeland","sequence":"additional","affiliation":[{"name":"Johann Friedric Blumenbach Institute of Zoology and Anthropology, University of G\u00f6ttingen, D-37073 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1021\/ja01543a060","article-title":"Isolation of melatonin, the pineal gland factor that lightens melanocytes","volume":"80","author":"Lerner","year":"1958","journal-title":"J. Am. Chem. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/j.1469-185X.2009.00118.x","article-title":"The changing biological roles of melatonin during evolution: From an antioxidant to signals of darkness, sexual selection and fitness","volume":"85","author":"Tan","year":"2010","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15858","DOI":"10.3390\/ijms150915858","article-title":"Fundamental issues related to the origin of melatonin and melatonin isomers during evolution: Relation to their biological functions","volume":"15","author":"Tan","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lee, K., Choi, G.-H., and Back, K. (2022). Functional characterization of serotonin n-acetyltransferase in archaeon Thermoplasma volcanium. Antioxidants, 11.","DOI":"10.3390\/antiox11030596"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/j.1600-079X.2006.00379.x","article-title":"Interactions of melatonin and its metabolites with the ABTS cation radical: Extension of the radical scavenger cascade and formation of a novel class of oxidation products, C2-substituted 3-indolinones","volume":"41","author":"Rosen","year":"2006","journal-title":"J. Pineal Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1600-079X.2006.00407.x","article-title":"One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species?","volume":"42","author":"Tan","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1076\/brhm.28.1.144.12978","article-title":"Dramatic rises of melatonin and 5-methoxytryptamine in gonyaulax exposed to decreased temperature","volume":"28","author":"Fuhrberg","year":"1997","journal-title":"Biol. Rhythm Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e12392","DOI":"10.1111\/jpi.12392","article-title":"Overexpression of rice serotonin N-acetyltransferase 1 in transgenic rice plants confers resistance to cadmium and senescence and increases grain yield","volume":"62","author":"Lee","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15963","DOI":"10.1038\/s41598-022-20164-0","article-title":"Melatonin ameliorates disease severity in a mouse model of multiple sclerosis by modulating the kynurenine pathway","volume":"12","author":"Jand","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12953","DOI":"10.1021\/acs.jafc.2c04337","article-title":"Melatonin prevents against ethanol-induced liver injury by mitigating ferroptosis via targeting brain and muscle ARNT-like 1 in mice liver and HepG2 cells","volume":"70","author":"Zhao","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"C153","DOI":"10.1016\/0303-7207(91)90087-9","article-title":"Melatonin: The chemical expression of darkness","volume":"79","author":"Reiter","year":"1991","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1095\/biolreprod.108.075655","article-title":"Melatonin and reproduction revisited","volume":"81","author":"Reiter","year":"2009","journal-title":"Biol. Reprod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1080\/07420528.2016.1197234","article-title":"The effect of cataract surgery on salivary melatonin and sleep quality in aging people","volume":"33","author":"Shenshen","year":"2016","journal-title":"Chronobiol. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/jmv.27312","article-title":"Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial","volume":"94","author":"Mousavi","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/jpi.12137","article-title":"Melatonin, energy metabolism, and obesity: A review","volume":"56","author":"Amaral","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.pneurobio.2015.02.001","article-title":"Melatonin and brain inflammaging","volume":"127\u2013128","author":"Hardeland","year":"2015","journal-title":"Prog. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.32794\/mr11250042","article-title":"Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1\u03b1 and energy metabolic pathway in the in vitro and in vivo models of breast cancer","volume":"2","author":"Mota","year":"2019","journal-title":"Melatonin Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1177\/1074248416660622","article-title":"Melatonin and human cardiovascular disease","volume":"22","author":"BaHammam","year":"2017","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1159\/000494889","article-title":"Neuroendocrine-metabolic dysfunction and sleep disturbances in neurodegenerative disorders: Focus on alzheimer\u2019s disease and melatonin","volume":"108","author":"Spinedi","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"736","DOI":"10.2174\/1871527320666210804155617","article-title":"Melatonin and sleep disturbances in Alzheimer\u2019s disease","volume":"20","author":"Prodhan","year":"2021","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101394","DOI":"10.1016\/j.arr.2021.101394","article-title":"The potential role of melatonin in retarding intervertebral disc ageing and degeneration: A systematic review","volume":"70","author":"Cheng","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hardeland, R. (2019). Aging, Melatonin, and the Pro- and Anti-Inflammatory. Int J Mol Sci., 20.","DOI":"10.3390\/ijms20051223"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/bs.vh.2020.12.004","article-title":"Melatonin and healthy aging","volume":"115","author":"Cardinali","year":"2021","journal-title":"Vitam. Horm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1210\/edrv-12-2-151","article-title":"Pineal melatonin: Cell biology of its synthesis and of its physiological interactions","volume":"12","author":"Reiter","year":"1991","journal-title":"Endocr. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3389\/fendo.2019.00249","article-title":"Melatonin synthesis and function: Evolutionary history in animals and plants","volume":"10","author":"Zhao","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1152\/physiol.00034.2019","article-title":"Melatonin in mitochondria: Mitigating clear and present dangers","volume":"35","author":"Reiter","year":"2020","journal-title":"Physiology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/0024-3205(92)90402-B","article-title":"Effect of tryptophan administration on circulating melatonin levels in chicks and rats: Evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract","volume":"51","author":"Huether","year":"1992","journal-title":"Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1055\/s-2007-1014427","article-title":"The influence of intravenous L-tryptophan on plasma melatonin and sleep in men","volume":"24","author":"Hajak","year":"1991","journal-title":"Pharmacopsychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1743-7075-2-22","article-title":"Melatonin, a potent agent in antioxidative defense: Actions as a natural food constituent, gastrointestinal factor, drug and prodrug","volume":"2","author":"Hardeland","year":"2005","journal-title":"Nutr. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1023\/A:1020107915919","article-title":"Gastrointestinal melatonin: Localization, function, and clinical relevance","volume":"47","author":"Bubenik","year":"2002","journal-title":"Dig. Dis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/exd.13208","article-title":"Metabolism of melatonin in the skin: Why is it important?","volume":"26","author":"Slominski","year":"2017","journal-title":"Exp. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jid.2017.10.025","article-title":"Melatonin: A cutaneous perspective on its production, metabolism, and functions","volume":"138","author":"Slominski","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1002\/biot.201500143","article-title":"Glucose-based microbial production of the hormone melatonin in yeast Saccharomyces cerevisiae","volume":"11","author":"Germann","year":"2016","journal-title":"Biotechnol. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"131742","DOI":"10.1016\/j.foodchem.2021.131742","article-title":"Isotopic labelling-based analysis elucidates biosynthesis pathways in Saccharomyces cerevisiae for Melatonin, Serotonin and Hydroxytyrosol formation","volume":"374","author":"Valero","year":"2022","journal-title":"Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1600-079X.2006.00367.x","article-title":"A melatonin-rich germplasm line of St John\u2019s wort (Hypericum perforatum L.)","volume":"41","author":"Murch","year":"2006","journal-title":"J. Pineal Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/jpi.12336","article-title":"On the significance of an alternate pathway of melatonin synthesis via 5-methoxytryptamine: Comparisons across species","volume":"61","author":"Tan","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4677","DOI":"10.1093\/jxb\/eraa235","article-title":"An evolutionary view of melatonin synthesis and metabolism related to its biological functions in plants","volume":"71","author":"Tan","year":"2020","journal-title":"J. Exp. Bot."},{"key":"ref_38","first-page":"13","article-title":"Localization of indoleamine and protein synthesis in the mammalian pineal gland","volume":"12","author":"Kappers","year":"1978","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF02463562","article-title":"Localizing acethyl-serotonin transferase by electron microscopy","volume":"46","author":"Somogyi","year":"1975","journal-title":"Histochemistry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/jpi.12026","article-title":"Mitochondria and chloroplasts as the original sites of melatonin synthesis: A hypothesis related to melatonin\u2019s primary function and evolution in eukaryotes","volume":"54","author":"Tan","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E7997","DOI":"10.1073\/pnas.1705768114","article-title":"Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release","volume":"114","author":"Suofu","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jns.2010.04.013","article-title":"Arylalkylamine N-acetyltransferase (AANAT) is expressed in astrocytes and melatonin treatment maintains AANAT in the gerbil hippocampus induced by transient cerebral ischemia","volume":"294","author":"Park","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0168-0102(02)00011-1","article-title":"Neuronal expression of arylalkylamine N-acetyltransferase (AANAT) mRNA in the rat brain","volume":"42","author":"Uz","year":"2002","journal-title":"Neurosci. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.exger.2009.02.002","article-title":"Age-related changes in melatonin synthesis in rat extrapineal tissues","volume":"44","author":"Naranjo","year":"2009","journal-title":"Exp. Gerontol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.intimp.2014.06.038","article-title":"MT1 receptor expression and AA-NAT activity in lymphatic tissue following melatonin administration in male golden hamster","volume":"22","author":"Vishwas","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1096\/fj.01-0952fje","article-title":"Serotoninergic and melatoninergic systems are fully expressed in human skin","volume":"16","author":"Slominski","year":"2002","journal-title":"FASEB J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"113693","DOI":"10.1016\/j.ygcen.2020.113693","article-title":"Gut melatonin: A potent candidate in the diversified journey of melatonin research","volume":"303","author":"Yasmin","year":"2021","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/andr.12117","article-title":"Evidence of melatonin synthesis in the ram reproductive tract","volume":"4","author":"Hamilton","year":"2016","journal-title":"Andrology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1600-079X.2007.00421.x","article-title":"Melatonin and its synthesizing enzymes (arylalkylamine N-acetyltransferase-like and hydroxyindole-O-methyltransferase) in avian eggs and early embryos","volume":"42","author":"Bozenna","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s10495-007-0756-2","article-title":"Mitochondria, oxidative stress and cell death","volume":"12","author":"Ott","year":"2007","journal-title":"Apoptosis"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Tan, D.X., and Hardeland, R. (2021). The Reserve\/Maximum Capacity of Melatonin\u2019s synthetic function for the potential dimorphism of melatonin production and its biological significance in mammals. Molecules, 26.","DOI":"10.3390\/molecules26237302"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"119597","DOI":"10.1016\/j.lfs.2021.119597","article-title":"Part-time cancers and role of melatonin in determining their metabolic phenotype","volume":"278","author":"Reiter","year":"2021","journal-title":"Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Fukushi, A., Do Kim, H., Chang, Y.C., and Kim, C.H. (2022). Revisited metabolic control and reprogramming cancers by means of the warburg effect in tumor Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231710037"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"34","DOI":"10.32794\/mr112500118","article-title":"Combination of melatonin with paclitaxel reduces the TLR4-mediated inflammatory pathway, PD-L1 levels, and survival of ovarian carcinoma cells","volume":"5","author":"Gaiotte","year":"2022","journal-title":"Melatonin Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Cucielo, M.S., Ces\u00e1rio, R.C., Silveira, H.S., Gaiotte, L.B., Dos Santos, S.A.A., de Campos Zuccari, D.A.P., Seiva, F.R.F., Reiter, R.J., and de Almeida Chuffa, L.G. (2022). Melatonin reverses the warburg-type metabolism and reduces mitochondrial membrane potential of ovarian cancer cells independent of mt1 receptor activation. Molecules, 27.","DOI":"10.3390\/molecules27144350"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5879090","DOI":"10.1186\/s40169-017-0144-7","article-title":"Thermodynamics in cancers: Opposing interactions between PPAR gamma and the canonical WNT\/beta-catenin pathway","volume":"6","author":"Lecarpentier","year":"2017","journal-title":"Clin. Transl. Med."},{"key":"ref_57","first-page":"557","article-title":"Melatonin in human breast cancer tissue: Association with nuclear grade and estrogen receptor status","volume":"75","author":"Maestroni","year":"1996","journal-title":"Lab. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.lfs.2006.11.048","article-title":"Altered expression profiles of clock genes hPer1 and hPer2 in peripheral blood mononuclear cells of cancer patients undergoing surgery","volume":"80","author":"Azama","year":"2007","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"625020","DOI":"10.3389\/fcell.2021.625020","article-title":"mtDNA heteroplasmy at the core of aging-associated heart failure. An integrative view of OXPHOS and mitochondrial life cycle in cardiac mitochondrial physiology","volume":"9","author":"Elorza","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_60","first-page":"55","article-title":"Mitochondrial DNA mutations and oxidative damage in aging and diseases: An emerging paradigm of gerontology and medicine","volume":"22","author":"Wei","year":"1998","journal-title":"Proc. Natl. Sci. Counc. Repub. China B"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.tree.2004.02.002","article-title":"Mother\u2019s curse: The effect of mtDNA on individual fitness and population viability","volume":"19","author":"Gemmell","year":"2004","journal-title":"Trends Ecol. Evol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1111\/j.1558-5646.2011.01465.x","article-title":"Reversing mother\u2019s curse revisited","volume":"66","author":"Hedrick","year":"2012","journal-title":"Evolution"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Wehbe, Z., Hammoud, S.H., Yassine, H.M., Fardoun, M., El-Yazbi, A.F., and Eid, A.H. (2021). Molecular and biological mechanisms underlying gender differences in COVID-19 severity and mortality. Front. Immunol., 1603.","DOI":"10.3389\/fimmu.2021.659339"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/13625187.2021.2000959","article-title":"COVID-19, gender and estroprogestins, what do we know?","volume":"27","author":"Fidecicchi","year":"2022","journal-title":"Eur. J. Contracept. Reprod. Health Care"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1089\/ars.2018.7555","article-title":"Aanat knockdown and melatonin supplementation in embryo development: Involvement of mitochondrial function and DNA methylation","volume":"30","author":"Yang","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e49799","DOI":"10.15252\/embr.201949799","article-title":"Mitochondrial DNA in inflammation and immunity","volume":"21","author":"Riley","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3124","DOI":"10.1172\/JCI135026","article-title":"Melatonin inhibits cytosolic mitochondrial DNA-induced neuroinflammatory signaling in accelerated aging and neurodegeneration","volume":"130","author":"Jauhari","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_68","first-page":"1648","article-title":"COVID-19 and cardiovascular diseases","volume":"141","author":"Mai","year":"2020","journal-title":"J. Cardiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.bbadis.2017.11.023","article-title":"Melatonin protects diabetic heart against ischemia-reperfusion injury, role of membrane receptor-dependent cGMP-PKG activation","volume":"1864","author":"Yu","year":"2018","journal-title":"Biochim. Biophys. Acta\u2014Mol. Basis Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3233\/JAD-150161","article-title":"Melatonin attenuates memory impairment, amyloid-\u03b2 accumulation, and neurodegeneration in a rat model of sporadic Alzheimer\u2019s disease","volume":"47","author":"Rudnitskaya","year":"2015","journal-title":"J. Alzheimers. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/j.1600-079X.1998.tb00396.x","article-title":"Monozygotic twins with Alzheimer\u2019s disease treated with melatonin: Case report","volume":"25","author":"Brusco","year":"1998","journal-title":"J. Pineal Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s10571-019-00720-5","article-title":"Melatonin and Parkinson disease: Current status and future perspectives for molecular mechanisms","volume":"40","author":"Tamtaji","year":"2020","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3999","DOI":"10.1007\/s00018-017-2614-x","article-title":"Melatonin as a mitochondrial protector in neurodegenerative diseases","volume":"74","author":"Wongprayoon","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"173329","DOI":"10.1016\/j.ejphar.2020.173329","article-title":"Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of Covid-19","volume":"882","author":"Othman","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1007\/s00018-019-03438-1","article-title":"Melatonin inhibits Warburg-dependent cancer by redirecting glucose oxidation to the mitochondria: A mechanistic hypothesis","volume":"77","author":"Reiter","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e12755","DOI":"10.1111\/jpi.12755","article-title":"Melatonin inhibits lung cancer development by reversing the Warburg effect via stimulating the SIRT3\/PDH axis","volume":"71","author":"Chen","year":"2021","journal-title":"J. Pineal Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"105","DOI":"10.32794\/mr11250033","article-title":"Inhibition of mitochondrial pyruvate dehydrogenase kinase: A proposed mechanism by which melatonin causes cancer cells to overcome cytosolic glycolysis, reduce tumor biomass and reverse insensitivity to chemotherapy","volume":"2","author":"Reiter","year":"2019","journal-title":"Melatonin Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1034\/j.1600-079X.2000.280407.x","article-title":"Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo","volume":"28","author":"Escames","year":"2000","journal-title":"J. Pineal Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1600-079X.2011.00868.x","article-title":"Melatonin improves mitochondrial respiratory chain activity and liver morphology in ob\/ob mice","volume":"51","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/jpi.12089","article-title":"Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats","volume":"55","author":"Campos","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Hu, L., Zhang, S., Wen, H., Liu, T., Cai, J., Du, D., Zhu, D., Chen, F., and Xia, C. (2019). Melatonin decreases M1 polarization via attenuating mitochondrial oxidative damage depending on UCP2 pathway in prorenin-treated microglia. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0212138"},{"key":"ref_82","first-page":"19","article-title":"Ischemic postconditioning reduced myocardial ischemia-reperfusion injury: The roles of melatonin and uncoupling protein 3","volume":"23","author":"Aslan","year":"2020","journal-title":"Anatol. J. Cardiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"566","DOI":"10.32794\/mr112500112","article-title":"Melatonin, tunneling nanotubes and anastasis: Cheating cell death","volume":"4","author":"Reiter","year":"2021","journal-title":"Melatonin Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"692022","DOI":"10.3389\/fimmu.2021.692022","article-title":"Exosomes and melatonin: Where their destinies intersect","volume":"12","author":"Novais","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.reprotox.2022.08.004","article-title":"Melatonin attenuates di-(2-ethylhexyl) phthalate-induced apoptosis of human granulosa cells by inhibiting mitochondrial fission","volume":"113","author":"Xue","year":"2022","journal-title":"Reprod. Toxicol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Agil, A., Chayah, M., Visiedo, L., Navarro-Alarcon, M., Ferrer, J.M.R., Tassi, M., Reiter, R.J., and Fern\u00e1ndez-V\u00e1zquez, G. (2020). Melatonin improves mitochondrial dynamics and function in the kidney of z\u00fccker diabetic fatty rats. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092916"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6043","DOI":"10.1111\/jcmm.15157","article-title":"Melatonin attenuates vascular calcification by inhibiting mitochondria fission via an AMPK\/Drp1 signalling pathway","volume":"24","author":"Chen","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"8463125","DOI":"10.1155\/2019\/8463125","article-title":"Melatonin affects mitochondrial fission\/fusion dynamics in the diabetic retina","volume":"2019","author":"Chang","year":"2019","journal-title":"J. Diabetes Res."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Guerra-Librero, A., Fernandez-Gil, B.I., Florido, J., Martinez-Ruiz, L., Rodr\u00edguez-Santana, C., Shen, Y.Q., Garc\u00eda-Verdugo, J.M., L\u00f3pez-Rodr\u00edguez, A., Rusanova, I., and Qui\u00f1ones-Hinojosa, A. (2021). Melatonin targets metabolism in head and neck cancer cells by regulating mitochondrial structure and function. Antioxidants, 10.","DOI":"10.3390\/antiox10040603"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1111\/rda.13771","article-title":"Melatonin improves cryopreservation of ram sperm by inhibiting mitochondrial permeability transition pore opening","volume":"55","author":"Fang","year":"2020","journal-title":"Reprod. Domest. Anim."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s13048-021-00912-y","article-title":"Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1\/Akt in granulosa cells of PCOS","volume":"14","author":"Zheng","year":"2021","journal-title":"J. Ovarian Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1093\/toxsci\/kfu164","article-title":"Melatonin Improves mitochondrial function by promoting MT1\/SIRT1\/PGC-1 alpha-dependent mitochondrial biogenesis in cadmium-induced hepatotoxicity in vitro","volume":"142","author":"Guo","year":"2014","journal-title":"Toxicol. Sci."},{"key":"ref_93","first-page":"457","article-title":"In vitro enzymatic formation of melatonin by human erythrocytes","volume":"4","author":"Rosengarten","year":"1972","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_94","first-page":"234","article-title":"Photoperiod influences endogenous indoleamines in cultured green alga Dunaliella bardawil","volume":"49","author":"Ramakrishna","year":"2011","journal-title":"Indian J. Exp. Biol."},{"key":"ref_95","first-page":"391","article-title":"Melatonin immunoreactivity in the photosynthetic prokaryote Rhodospirillum rubrum: Implications for an ancient antioxidant system","volume":"41","author":"Manchester","year":"1995","journal-title":"Cell. Mol. Biol. Res."},{"key":"ref_96","first-page":"113","article-title":"A hypothesis on the evolutionary origins of photoperiodism based on circadian rhythmicity of melatonin in phylogenetically distant organisms","volume":"1","author":"Hardeland","year":"1993","journal-title":"Chronobiol. Chronomedicine"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1590\/S0100-879X1997000300003","article-title":"Evolution of circadian organization in vertebrates","volume":"30","author":"Menaker","year":"1997","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/203087a0","article-title":"Flow of Blood to the Pineal Body of the Rat","volume":"203","author":"Goldman","year":"1964","journal-title":"Nature"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Tan, D.X., Xu, B., Zhou, X., and Reiter, R.J. (2018). Pineal calcification, melatonin production, aging, associated health consequences and rejuvenation of the pineal gland. Molecules, 23.","DOI":"10.3390\/molecules23020301"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1007\/s00429-014-0719-7","article-title":"Delivery of pineal melatonin to the brain and SCN: Role of canaliculi, cerebrospinal fluid, tanycytes and Virchow-Robin perivascular spaces","volume":"219","author":"Reiter","year":"2014","journal-title":"Brain Struct. Funct."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1034\/j.1600-079X.2002.2e001.x","article-title":"Role of CSF in the transport of melatonin","volume":"33","author":"Reiter","year":"2002","journal-title":"J. Pineal Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1042\/BST20140153","article-title":"Interaction of neurons and astrocytes underlies the mechanism of A\u03b2-induced neurotoxicity","volume":"42","author":"Angelova","year":"2014","journal-title":"Biochem. Soc. Trans."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1600-079X.2007.00466.x","article-title":"Cultured rat cortical astrocytes synthesize melatonin: Absence of a diurnal rhythm","volume":"43","author":"Liu","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Iba\u00f1ez Rodriguez, M.P., Noctor, S.C., and Mu\u00f1oz, E.M. (2016). Cellular basis of pineal gland development: Emerging role of microglia as phenotype regulator. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167063"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/ar.1091840306","article-title":"Quantitation of ultrastructural changes in the mouse pineal in response to continuous illumination","volume":"184","author":"Upson","year":"1976","journal-title":"Anat. Rec."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/0014-4827(56)90026-X","article-title":"The demonstration of a secretory material and cycle in the parenchymal cells of the mammalian pineal organ","volume":"10","author":"Quay","year":"1956","journal-title":"Exp. Cell Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.bbrc.2022.03.025","article-title":"Melatonin in ventricular and subarachnoid cerebrospinal fluid: Its function in the neural glymphatic network and biological significance for neurocognitive health","volume":"605","author":"Reiter","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1126\/science.841305","article-title":"Melatonin: Daily cycle in plasma and cerebrospinal fluid of calves","volume":"195","author":"Hedlund","year":"1977","journal-title":"Science"},{"key":"ref_109","first-page":"311","article-title":"Origin of cerebrospinal fluid melatonin and possible function in the integration of photoperiod","volume":"61","author":"Tricoire","year":"2003","journal-title":"Reprod. Suppl."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1210\/endo.143.1.8585","article-title":"Melatonin enters the cerebrospinal fluid through the pineal recess","volume":"143","author":"Tricoire","year":"2002","journal-title":"Endocrinology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1042\/bst0300365","article-title":"14-3-3 Proteins and photoneuroendocrine transduction: Role in controlling the daily rhythm in melatonin","volume":"30","author":"Klein","year":"2002","journal-title":"Biochem. Soc. Trans."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1196\/annals.1356.028","article-title":"Mechanisms regulating melatonin synthesis in the mammalian pineal organ","volume":"1057","author":"Schomerus","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1007\/s00018-008-8001-x","article-title":"Melatonin, hormone of darkness and more: Occurrence, control mechanisms, actions and bioactive metabolites","volume":"65","author":"Hardeland","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1016\/j.cub.2007.11.034","article-title":"Short-wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer retina","volume":"17","author":"Zaidi","year":"2007","journal-title":"Curr. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1177\/0748730418784041","article-title":"Spectral tuning of white light allows for strong reduction in melatonin suppression without changing illumination level or color temperature","volume":"33","author":"Souman","year":"2018","journal-title":"J. Biol. Rhythms"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1159\/000122222","article-title":"Influence of pinealectomy on the breeding capability of hamsters maintained under natural photoperiodic and temperature conditions","volume":"13","author":"Reiter","year":"1974","journal-title":"Neuroendocrinology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1111\/1749-4877.12409","article-title":"Bright artificial light at night is associated with increased body mass, poor reproductive success and compromised disease tolerance in Australian budgerigars (Melopsittacus undulatus)","volume":"14","author":"Malek","year":"2019","journal-title":"Integr. Zool."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"S213","DOI":"10.1016\/S0753-3322(05)80034-4","article-title":"Chronomics: Circadian lead of extrapineal vs. pineal melatonin rhythms with an infradian hypothalamic exploration","volume":"59","author":"Zeman","year":"2005","journal-title":"Biomed. Pharmacother."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"S220","DOI":"10.1016\/S0753-3322(05)80035-6","article-title":"Chronomics affirm extending scope of lead in phase of duodenal vs. pineal circadian melatonin rhythms","volume":"59","author":"Poeggeler","year":"2005","journal-title":"Biomed. Pharmacother."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"S209","DOI":"10.1016\/S0753-3322(05)80033-2","article-title":"Chronomics reveal and quantify circadian rhythmic melatonin in duodenum of rats","volume":"59","author":"Stebelova","year":"2005","journal-title":"Biomed. Pharmacother."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"16332","DOI":"10.1038\/s41598-017-16689-4","article-title":"Subcutaneous white adipocytes express a light sensitive signaling pathway mediated via a melanopsin\/TRPC channel axis","volume":"7","author":"Ondrusova","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"138","DOI":"10.32794\/mr11250016","article-title":"Melatonin and the optics of the human body","volume":"2","author":"Zimmerman","year":"2019","journal-title":"Melatonin Res."},{"key":"ref_123","first-page":"1345","article-title":"Biological effects of sunlight, ultraviolet radiation, visible light, infrared radiation and vitamin D for health","volume":"36","author":"Holick","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"E267","DOI":"10.1212\/WNL.0000000000013045","article-title":"Association between time spent outdoors and risk of multiple sclerosis","volume":"98","author":"Sebastian","year":"2022","journal-title":"Neurology"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Philipp, D., Vogel, M., Brandt, M., Rauscher, F.G., Hiemisch, A., Wahl, S., Kiess, W., and Poulain, T. (2022). The relationship between myopia and near work, time outdoors and socioeconomic status in children and adolescents. BMC Public Health, 22.","DOI":"10.1186\/s12889-022-14377-1"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1002\/lsm.22343","article-title":"Quantitative analysis of transcranial and intraparenchymal light penetration in human cadaver brain tissue","volume":"47","author":"Tedford","year":"2015","journal-title":"Lasers Surg. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"256","DOI":"10.5455\/OVJ.2022.v12.i2.14","article-title":"Transcranial photobiomodulation (laser) therapy for cognitive impairment: A review of molecular mechanisms and potential application to canine cognitive dysfunction (CCD)","volume":"12","author":"Dewey","year":"2022","journal-title":"Open Vet. J."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Stepanov, Y.V., Golovynska, I., Zhang, R., Golovynskyi, S., Stepanova, L.I., Gorbach, O., Dovbynchuk, T., Garmanchuk, L.V., Ohulchanskyy, T.Y., and Qu, J. (2022). Near-infrared light reduces \u03b2-amyloid-stimulated microglial toxicity and enhances survival of neurons: Mechanisms of light therapy for Alzheimer\u2019s disease. Alzheimers. Res. Ther., 14.","DOI":"10.1186\/s13195-022-01022-7"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/978-3-319-17121-0_58","article-title":"Near-infrared photobiomodulation in retinal injury and disease","volume":"854","author":"Eells","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.3233\/JAD-201600","article-title":"Photobiomodulation enhances memory processing in older adults with mild cognitive impairment: A functional near-infrared spectroscopy study","volume":"83","author":"Chan","year":"2021","journal-title":"J. Alzheimers. Dis."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/phpp.12715","article-title":"The review of the light parameters and mechanisms of photobiomodulation on melanoma cells","volume":"38","author":"Chen","year":"2022","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1089\/photob.2021.0145","article-title":"Photobiomodulation: Evolution and adaptation","volume":"40","author":"Lipko","year":"2022","journal-title":"Photobiomodulation Photomed. Laser Surg."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.mito.2017.05.002","article-title":"Photostimulation of mitochondria as a treatment for retinal neurodegeneration","volume":"36","author":"Beirne","year":"2017","journal-title":"Mitochondrion"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e201700282","DOI":"10.1002\/jbio.201700282","article-title":"Aging of lymphoid organs: Can photobiomodulation reverse age-associated thymic involution via stimulation of extrapineal melatonin synthesis and bone marrow stem cells?","volume":"11","author":"Odinokov","year":"2018","journal-title":"J. Biophotonics"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Agil, A., Navarro-Alarcon, M., Ali, F.A.Z., Albrakati, A., Salagre, D., Campoy, C., and Elmahallawy, E.K. (2021). Melatonin enhances the mitochondrial functionality of brown adipose tissue in obese-diabetic rats. Antioxidants, 10.","DOI":"10.3390\/antiox10091482"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"121835","DOI":"10.1016\/j.saa.2022.121835","article-title":"Effects of photobiomodulation on mitochondrial function in diabetic adipose-derived stem cells in vitro","volume":"285","author":"Fallahi","year":"2022","journal-title":"Spectrochim. Acta. A Mol. Biomol. Spectrosc."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"20382","DOI":"10.1038\/s41598-020-77290-w","article-title":"Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa","volume":"10","author":"Gopalakrishnan","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3934\/biophy.2017.3.337","article-title":"Mechanisms and applications of the anti-inflammatory effects of photobiomodulation","volume":"4","author":"Hamblin","year":"2017","journal-title":"AIMS Biophys."},{"key":"ref_139","first-page":"154","article-title":"Therapeutic photobiomodulation: Nitric oxide and a novel function of mitochondrial cytochrome c oxidase","volume":"11","author":"Poyton","year":"2011","journal-title":"Discov. Med."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Schirmer, I., Bualeong, T., Budde, H., Cimiotti, D., Appukuttan, A., Klein, N., Steinwascher, P., Reusch, P., M\u00fcgge, A., and Meyer, R. (2018). Soluble adenylyl cyclase: A novel player in cardiac hypertrophy induced by isoprenaline or pressure overload. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192322"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"jcs215178","DOI":"10.1242\/jcs.215178","article-title":"Mitochondrial cAMP exerts positive feedback on mitochondrial Ca2+ uptake via the recruitment of Epac1","volume":"131","author":"Szanda","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"20200034","DOI":"10.1098\/rsfs.2020.0034","article-title":"Bicarbonate, carbon dioxide and pH sensing via mammalian bicarbonate-regulated soluble adenylyl cyclase","volume":"11","author":"Rossetti","year":"2021","journal-title":"Interface Focus"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/nchembio.2151","article-title":"Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase","volume":"12","author":"Kleinboelting","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/j.1530-0277.2008.00875.x","article-title":"Alcohol stimulates ciliary motility of isolated airway axonemes through a nitric oxide, cyclase, and cyclic nucleotide-dependent kinase mechanism","volume":"33","author":"Sisson","year":"2009","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1152\/physiol.00004.2013","article-title":"cAMP and mitochondria","volume":"28","author":"Valsecchi","year":"2013","journal-title":"Physiology"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/jnr.24477","article-title":"Soluble adenylyl cyclase-mediated cAMP signaling and the putative role of PKA and EPAC in cerebral mitochondrial function","volume":"97","author":"Jakobsen","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1016\/j.bbadis.2014.05.035","article-title":"Role of soluble adenylyl cyclase in mitochondria","volume":"1842","author":"Valsecchi","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"83","DOI":"10.31083\/j.fbl2703083","article-title":"Arginine promotes the expression of aquaporin-3 and water transport in porcine trophectoderm cells through NO- and cAMP-dependent mechanisms","volume":"27","author":"Zhu","year":"2022","journal-title":"Front. Biosci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1385\/CBB:47:1:99","article-title":"Cyclic GMP modulates the expression of Gi protein and adenylyl cyclase signaling in vascular smooth muscle cells","volume":"47","author":"Bassil","year":"2007","journal-title":"Cell Biochem. Biophys."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.niox.2018.03.007","article-title":"Nitric oxide and cyclic GMP functions in bone","volume":"76","author":"Kalyanaraman","year":"2018","journal-title":"Nitric Oxide Biol. Chem."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1111\/bph.15345","article-title":"NO-sensitive guanylyl cyclase in the lung","volume":"179","author":"Friebe","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.bbrc.2003.12.136","article-title":"8Br-cGMP mediates relaxation of tracheal smooth muscle through PKA","volume":"314","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1038\/sj.jid.5700907","article-title":"Involvement of protein kinase A in nitric oxide stimulating effect on a BK(Ca) channel of human dermal fibroblasts","volume":"127","author":"Roh","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"4314","DOI":"10.1182\/blood.V94.12.4314","article-title":"Ontogeny of catecholamine and adenosine receptor-mediated cAMP signaling of embryonic red blood cells: Role of cGMP-inhibited phosphodiesterase 3 and hemoglobin","volume":"94","author":"Baumann","year":"1999","journal-title":"Blood"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1034\/j.1600-079X.2003.02937.x","article-title":"Protective effect of melatonin and its precursor L-tryptophan on acute pancreatitis induced by caerulein overstimulation or ischemia\/reperfusion","volume":"34","author":"Jaworek","year":"2003","journal-title":"J. Pineal Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"e12551","DOI":"10.1111\/jpi.12551","article-title":"Apple tree flowering is mediated by low level of melatonin under the regulation of seasonal light signal","volume":"66","author":"Zhang","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"100534","DOI":"10.1016\/j.animal.2022.100534","article-title":"Light from heat lamps affects sow behaviour and piglet salivary melatonin levels","volume":"16","author":"Liu","year":"2022","journal-title":"Animal"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"673","DOI":"10.4085\/1062-6050-47.6.08","article-title":"Red light and the sleep quality and endurance performance of Chinese female basketball players","volume":"47","author":"Zhao","year":"2012","journal-title":"J. Athl. Train."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"295","DOI":"10.32794\/mr112500133","article-title":"Transient responses of melatonin to stress","volume":"5","author":"Zimmerman","year":"2022","journal-title":"Melatonin Res."},{"key":"ref_160","first-page":"838","article-title":"Effect of physical exercise on plasma melatonin levels in normal volunteers","volume":"66","author":"Theron","year":"1984","journal-title":"Afr. Med. J."},{"key":"ref_161","unstructured":"Zhu, M., Anderson, K., and Gronowski, A. (2018). Investigating Eccrine Sweat as a Noninvasive Biomarker Resource. [Ph.D. Thesis, Arizona state university]."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.2741\/3589","article-title":"The gut microbiota ecology: A new opportunity for the treatment of metabolic diseases?","volume":"14","author":"Burcelin","year":"2009","journal-title":"Front. Biosci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1016\/j.biotechadv.2016.08.003","article-title":"The gut microbiota: A treasure for human health","volume":"34","author":"Li","year":"2016","journal-title":"Biotechnol. Adv."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Ju\u00e1rez-Fern\u00e1ndez, M., Porras, D., Garc\u00eda-Mediavilla, M.V., Rom\u00e1n-Sag\u00fcillo, S., Gonz\u00e1lez-Gallego, J., Nistal, E., and S\u00e1nchez-Campos, S. (2020). Aging, gut microbiota and metabolic diseases: Management through physical exercise and nutritional interventions. Nutrients, 13.","DOI":"10.3390\/nu13010016"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Wu, H., Chen, X., Zhang, S., and Li, J. (2022). Gut microbiota, the potential biological medicine for prevention, intervention and drug sensitization to fight diseases. Nutrients, 14.","DOI":"10.3390\/nu14204220"},{"key":"ref_166","first-page":"121","article-title":"Targeting microbiota-mitochondria inter-talk: Microbiota control mitochondria metabolism","volume":"61","author":"Attaf","year":"2015","journal-title":"Cell. Mol. Biol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"e12399","DOI":"10.1111\/jpi.12399","article-title":"Melatonin prevents obesity through modulation of gut microbiota in mice","volume":"62","author":"Xu","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"e12524","DOI":"10.1111\/jpi.12524","article-title":"Melatonin reprogramming of gut microbiota improves lipid dysmetabolism in high-fat diet-fed mice","volume":"65","author":"Yin","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1007\/s12275-020-0094-4","article-title":"Melatonin attenuates microbiota dysbiosis of jejunum in short-term sleep deprived mice","volume":"58","author":"Gao","year":"2020","journal-title":"J. Microbiol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/j.1600-079X.1997.tb00310.x","article-title":"Melatonin production in an aerobic photosynthetic bacterium: An evolutionarily early association with darkness","volume":"22","author":"Tilden","year":"1997","journal-title":"J. Pineal Res."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Vanden Driessche, T., Guisset, J.-L., and Petiau-de Vries, G.M. (2000). Occurrence and comparative physiology of melatoninin evolutionary diverse organisms. The Redox State and Circadian Rhythms, Kluver.","DOI":"10.1007\/978-94-015-9556-8"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.biocel.2005.08.020","article-title":"Melatonin","volume":"38","author":"Hardeland","year":"2006","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1051\/rnd:19990311","article-title":"Melatonin and 5-methoxytryptamine in non-metazoans","volume":"39","author":"Hardeland","year":"1999","journal-title":"Reprod. Nutr. Dev."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.3389\/fmicb.2019.02424","article-title":"Glycolytic proteins interact with intracellular melatonin in saccharomyces cerevisiae","volume":"10","author":"Valera","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"127192","DOI":"10.1016\/j.foodchem.2020.127192","article-title":"Occurrence of melatonin and indolic compounds derived from l-tryptophan yeast metabolism in fermented wort and commercial beers","volume":"331","author":"Valero","year":"2020","journal-title":"Food Chem."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Luo, H., He, C., and Han, L. (2018). Heterologous expression of ZjOMT from Zoysia japonica in Escherichia coli confers aluminum resistance through melatonin production. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196952"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1016\/S0024-3205(99)00519-6","article-title":"High physiological levels of melatonin in the bile of mammals","volume":"65","author":"Tan","year":"1999","journal-title":"Life Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"4788","DOI":"10.2174\/1381612819666131119105826","article-title":"Melatonin in the biliary tract and liver: Health implications","volume":"20","author":"Reiter","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1021\/acssynbio.0c00065","article-title":"Microbial synthesis of human-hormone melatonin at gram scales","volume":"9","author":"Luo","year":"2020","journal-title":"ACS Synth. Biol."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Ouyang, J., Wang, M., Bu, D., Ma, L., Liu, F., Xue, C., Du, C., Aboragah, A., and Loor, J.J. (2021). Ruminal microbes exhibit a robust circadian rhythm and are sensitive to melatonin. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.760578"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1007\/s12275-021-0305-7","article-title":"Role of melatonin in murine \u201crestraint stress\u201d-induced dysfunction of colonic microbiota","volume":"59","author":"Lin","year":"2021","journal-title":"J. Microbiol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"120612","DOI":"10.1016\/j.lfs.2022.120612","article-title":"Melatonin: A mitochondrial resident with a diverse skill set","volume":"301","author":"Reiter","year":"2022","journal-title":"Life Sci."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.nut.2005.02.005","article-title":"Melatonin in walnuts: Influence on levels of melatonin and total antioxidant capacity of blood","volume":"21","author":"Reiter","year":"2005","journal-title":"Nutrition"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/0006-8993(91)91270-B","article-title":"Food restriction retards aging of the pineal gland","volume":"545","author":"Stokkan","year":"1991","journal-title":"Brain Res."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0531-5565(02)00146-8","article-title":"Calorie restriction in rhesus monkeys","volume":"38","author":"Mattison","year":"2003","journal-title":"Exp. Gerontol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/S0929-6646(10)60113-1","article-title":"Detection of nighttime melatonin level in Chinese Original Quiet Sitting","volume":"109","author":"Liou","year":"2010","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1177\/13623613211062952","article-title":"Effects of exercise on sleep, melatonin level, and behavioral functioning in children with autism","volume":"26","author":"Tse","year":"2022","journal-title":"Autism"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2014.07.024","article-title":"Melatonin and its metabolites accumulate in the human epidermis in vivo and inhibit proliferation and tyrosinase activity in epidermal melanocytes in vitro","volume":"404","author":"Kim","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_189","first-page":"349","article-title":"Nutritional metabolic diseases of poultry and disorders of the biological antioxidant defence system","volume":"45","author":"Surai","year":"1997","journal-title":"Acta Vet. Hung."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Hardeland, R. (2021). Melatonin and microglia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158296"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/1\/89\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:00:56Z","timestamp":1760119256000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/1\/89"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,6]]},"references-count":190,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["biology12010089"],"URL":"https:\/\/doi.org\/10.3390\/biology12010089","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,6]]}}}