Analgesics
Antiandrogens
Antihistamines
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
PPIs
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
 
next
study
previous
study
c19early.org COVID-19 treatment researchMelatoninMelatonin (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta PPIs Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis       

Antiviral Effect of Melatonin on Caco-2 Cell Organoid Culture: Trick or Treat?

Šeškutė et al., International Journal of Molecular Sciences, doi:10.3390/ijms252211872
Nov 2024  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
Melatonin for COVID-19
11th treatment shown to reduce risk in December 2020, now with p = 0.0000002 from 18 studies.
Lower risk for mortality, ventilation, and recovery.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
In Vitro study showing that melatonin exhibits antiviral properties in gastrointestinal epithelial cells through modulation of type III interferon responses and cellular protection. Authors found that melatonin's effects varied based on timing of administration, with pretreatment (1-10 μM) enhancing cell proliferation and reducing apoptosis, while post-infection treatment preserved tissue structure and reduced inflammatory cytokine production. Using a Caco-2 cell organoid model, melatonin treatment after viral simulation increased IFNLR1 expression while reducing IFNλ1 and STAT1-3 protein levels, suggesting potential benefits for controlling excessive inflammatory responses. Authors stimulated viral inflammation using a TLR3 receptor agonist rather than live virus infection. While not specifically analyzing SARS-CoV-2, the findings support previous research showing melatonin's potential therapeutic value in COVID-19 through its immunomodulatory and tissue-protective properties.
6 preclinical studies support the efficacy of melatonin for COVID-19:
Melatonin may restore altered redox homeostasis in COVID-196, modulates type III interferon responses and reduces inflammatory cytokine production in TLR3 receptor agonist stimulated viral inflammation while preserving tissue integrity3, and negatively regulates genes critical for viral entry in lung tissue, including reduced expression of FURIN and components of the CD147 complex, while potentially disrupting TMPRSS2/ACE2-mediated entry mechanisms2. Melatonin reduces oxidative stress, inhibits NET formation, and protects tissues through anti-inflammatory and antioxidant actions7.
Šeškutė et al., 5 Nov 2024, peer-reviewed, 6 authors. Contact: lina.jankauskaite@lsmu.lt (corresponding author), milda.seskute@lsmu.lt, goda.laucaityte@lsmu.lt, mantas.malinauskas@lsmu.lt, dominyka.zukaite@stud.lsmu.lt, ruta.inciuraite@lsmu.lt.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperMelatoninAll
Antiviral Effect of Melatonin on Caco-2 Cell Organoid Culture: Trick or Treat?
Milda Šeškutė, Dominyka Žukaitė, Goda Laucaitytė, Rūta Inčiūraitė, Mantas Malinauskas, Lina Jankauskaitė
International Journal of Molecular Sciences, doi:10.3390/ijms252211872
Melatonin is a hormone naturally produced by the body that has recently been found to have antiviral properties. However, its antiviral mechanisms are not entirely understood. Using Caco-2 cells, we developed a gastrointestinal organoid model to investigate the impact of melatonin on cellular organoid culture response to Poly I:C-induced viral inflammation in the gastrointestinal tract. Melatonin was found to have different effect when applied as a pretreatment before the induction of viral inflammation or as a treatment after it. Melatonin pretreatment after Poly I:C stimulation did not protect organoids from size reduction but enhanced cell proliferation, especially when lower (1 and 10 µM) melatonin concentrations were used. On the other hand, treatment with melatonin after the induction of viral inflammation helped to maintain the size of the organoids while reducing cell proliferation. In pretreated cells, reduced IFNLR1 expression was found, while melatonin treatment increased IFNLR1 expression and reduced the production of viral cytokines, such as IFNλ1 and STAT1-3, but did not prevent from apoptosis. The findings of this study emphasize the importance of type III IFNs in antiviral defense in epithelial gastrointestinal cells and shed more light on the antiviral properties of melatonin as a potential therapeutic substance.
Author Contributions: Investigations, M.Š., D.Ž., G.L., R.I., M.M. and L.J.; data analysis, M.Š., D.Ž. and L.J., writing-original draft preparation, M.Š. and D.Ž.; writing-review and editing, L.J.; supervision, L.J.; funding acquisition, L.J. All authors have read and agreed to the published version of the manuscript. Conflicts of Interest: The authors declare no conflicts of interest.
References
Andersen, Gögenur, Rosenberg, Reiter, The Safety of Melatonin in Humans, Clin. Drug Investig, doi:10.1007/s40261-015-0368-5
Brzezinski, Rai, Purohit, Pandi-Perumal, Melatonin, clock genes, and mammalian reproduction: What is the link?, Int. J. Mol. Sci, doi:10.3390/ijms222413240
Bubenik, Gastrointestinal Melatonin: Localization, Function, and Clinical Relevance, Dig. Dis. Sci, doi:10.1023/A:1020107915919
Choi, Jin, Lee, Choi, Choi et al., Melatonin inhibits Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-6 in murine macrophages by suppressing NF-κB and STAT1 activity, J. Pineal Res, doi:10.1111/j.1600-079X.2010.00829.x
Dumoutier, Tounsi, Michiels, Sommereyns, Kotenko et al., Role of the interleukin (IL)-28 receptor tyrosine residues for antiviral and antiproliferative activity of IL-29/interferon-λ1. Similarities with type 1 interferon signaling, J. Biol. Chem, doi:10.1074/jbc.M404789200
Fang, Huang, Sun, Zhao, Sun et al., Melatonin attenuates cellular senescence and apoptosis in diabetic nephropathy by regulating STAT3 phosphorylation, Life Sci, doi:10.1016/j.lfs.2023.122108
Frias, Jones, Fifadara, Vijay-Kumar, Gewirtz, Rotavirus-induced IFN-β promotes anti-viral signaling and apoptosis that modulate viral replication in intestinal epithelial cells, J. Endotoxin Res, doi:10.1177/1753425911401930
Gebert, Scribano, Engevik, Perry, Hyser, Gastrointestinal organoids in the study of viral infections, Am. J. Physiol. Liver Physiol, doi:10.1152/ajpgi.00152.2022
Ghorbani-Anarkooli, Dabirian, Zendedel, Moladoust, Bahadori, Effects of melatonin on the toxicity and proliferation of human anaplastic thyroid cancer cell line, Acta Histochem, doi:10.1016/j.acthis.2021.151700
Giménez, Heras, Lahera, Tresguerres, Reiter et al., Melatonin as an Anti-Aging Therapy for Age-Related Cardiovascular and Neurodegenerative Diseases, Front. Aging Neurosci, doi:10.3389/fnagi.2022.888292
Juybari, Pourhanifeh, Hosseinzadeh, Hemati, Mehrzadi, Melatonin potentials against viral infections including COVID-19: Current evidence and new findings, Virus Res, doi:10.1016/j.virusres.2020.198108
Kitidee, Samutpong, Pakpian, Wisitponchai, Govitrapong et al., Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells, Sci. Rep, doi:10.1038/s41598-023-33254-4
Li, Liu, Wang, Xia, Huang et al., Melatonin ameliorates Parkinson's disease via regulating microglia polarization in a RORα-dependent pathway, Npj Park. Dis, doi:10.1038/s41531-022-00352-5
Liu, Xu, Reiter, Melatonin inhibits the proliferation of human osteosarcoma cell line MG-63, Bone, doi:10.1016/j.bone.2013.02.021
Maestroni, Conti, Pierpaoli, Pineal Melatonin, Its Fundamental Immunoregulatory Role in Aging and Cancer, Ann. N. Y. Acad. Sci, doi:10.1111/j.1749-6632.1988.tb35272.x
Maestroni, Role of Melatonin in Viral, Bacterial and Parasitic Infections, Biomolecules, doi:10.3390/biom14030356
Mannino, Caradonna, Cruciata, Lauria, Perrone et al., Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin-1β, J. Pineal Res, doi:10.1111/jpi.12598
Pan, Li, Wang, Li, Zhang et al., Effects of duodenal 5-hydroxytryptophan perfusion on melatonin synthesis in gi tract of sheep, Molecules, doi:10.3390/molecules26175275
Pérez-Martínez, Boga, Potes, Melón, Coto-Montes, Effect of Melatonin on Herpesvirus Type 1 Replication, Int. J. Mol. Sci, doi:10.3390/ijms25074037
Qin, Chen, Li, Wang, Ma et al., Role of IFNLR1 gene in PRRSV infection of PAM cells, J. Veter. Sci, doi:10.4142/jvs.2021.22.e39
Reiter, Sharma, Simko, Dominguez-Rodriguez, Tesarik et al., Melatonin: Highlighting its use as a potential treatment for SARS-CoV-2 infection, Cell Mol. Life Sci, doi:10.1007/s00018-021-04102-3
Samy, Levy, Phong, Demaree, Abate et al., Human intestinal spheroids cultured using Sacrificial Micromolding as a model system for studying drug transport, Sci. Rep, doi:10.1038/s41598-019-46408-0
Santos-Ferreira, Van Dycke, Neyts, Rocha-Pereira, Current and future antiviral strategies to tackle gastrointestinal viral infections, Microorganisms, doi:10.3390/microorganisms9081599
Schrire, Phillips, Chapman, Duffy, Wong et al., Safety of higher doses of melatonin in adults: A systematic review and meta-analysis, J. Pineal Res, doi:10.1111/jpi.12782
Stanifer, Guo, Doldan, Boulant, Importance of Type I and III Interferons at Respiratory and Intestinal Barrier Surfaces, Front. Immunol, doi:10.3389/fimmu.2020.608645
Steen, Gamero, The role of signal transducer and activator of transcription-2 in the interferon response, J. Interf. Cytokine Res, doi:10.1089/jir.2011.0099
Tan, Manchester, Esteban-Zubero, Zhou, Reiter, Melatonin as a potent and inducible endogenous antioxidant: Synthesis and metabolism, Molecules, doi:10.3390/molecules201018886
Van Winkle, Peterson, Kennedy, Wheadon, Ingle et al., Homeostatic interferon-lambda response to bacterial microbiota stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium, eLife, doi:10.7554/eLife.74072
Wongchitrat, Yasawong, Jumpathong, Chanmanee, Samutpong et al., Melatonin inhibits Zika virus replication in Vero epithelial cells and SK-N-SH human neuroblastoma cells, Melatonin Res, doi:10.32794/mr112500127
Zhang, Yuan, Zhang, Melatonin reduces inflammation in intestinal cells, organoids and intestinal explants, Inflammopharmacology, doi:10.1007/s10787-021-00869-w
Zheng, Zhou, Zhang, Ma, Gong et al., Intestinal melatonin levels and gut microbiota homeostasis are independent of the pineal gland in pigs, Front. Microbiol, doi:10.3389/fmicb.2024.1352586
{ 'indexed': { 'date-parts': [[2024, 11, 6]], 'date-time': '2024-11-06T05:24:19Z', 'timestamp': 1730870659820, 'version': '3.28.0'}, 'reference-count': 31, 'publisher': 'MDPI AG', 'issue': '22', 'license': [ { 'start': { 'date-parts': [[2024, 11, 5]], 'date-time': '2024-11-05T00:00:00Z', 'timestamp': 1730764800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [ {'name': 'Research Council of Lithuania', 'award': ['P-MIP-23-116', 'S-MIP-23-110']}, {'name': 'Research Fund of the Lithuanian University of Health Sciences'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>Melatonin is a hormone naturally produced by the body that has recently been found to ' 'have antiviral properties. However, its antiviral mechanisms are not entirely understood. ' 'Using Caco-2 cells, we developed a gastrointestinal organoid model to investigate the impact ' 'of melatonin on cellular organoid culture response to Poly I:C-induced viral inflammation in ' 'the gastrointestinal tract. Melatonin was found to have different effect when applied as a ' 'pretreatment before the induction of viral inflammation or as a treatment after it. Melatonin ' 'pretreatment after Poly I:C stimulation did not protect organoids from size reduction but ' 'enhanced cell proliferation, especially when lower (1 and 10 µM) melatonin concentrations ' 'were used. On the other hand, treatment with melatonin after the induction of viral ' 'inflammation helped to maintain the size of the organoids while reducing cell proliferation. ' 'In pretreated cells, reduced IFNLR1 expression was found, while melatonin treatment increased ' 'IFNLR1 expression and reduced the production of viral cytokines, such as IFNλ1 and STAT1-3, ' 'but did not prevent from apoptosis. The findings of this study emphasize the importance of ' 'type III IFNs in antiviral defense in epithelial gastrointestinal cells and shed more light ' 'on the antiviral properties of melatonin as a potential therapeutic substance.</jats:p>', 'DOI': '10.3390/ijms252211872', 'type': 'journal-article', 'created': {'date-parts': [[2024, 11, 5]], 'date-time': '2024-11-05T10:30:53Z', 'timestamp': 1730802653000}, 'page': '11872', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Antiviral Effect of Melatonin on Caco-2 Cell Organoid Culture: Trick or Treat?', 'prefix': '10.3390', 'volume': '25', 'author': [ { 'given': 'Milda', 'family': 'Šeškutė', 'sequence': 'first', 'affiliation': [ { 'name': 'Department of Pediatrics, Lithuanian University of Health ' 'Sciences, 44307 Kaunas, Lithuania'}, { 'name': 'Institute of Physiology and Pharmacology, Lithuanian University ' 'of Health Sciences, 44307 Kaunas, Lithuania'}]}, { 'given': 'Dominyka', 'family': 'Žukaitė', 'sequence': 'additional', 'affiliation': [ { 'name': 'Faculty of Medicine, Lithuanian University of Health Sciences, ' '44307 Kaunas, Lithuania'}]}, { 'ORCID': 'http://orcid.org/0000-0003-3182-9754', 'authenticated-orcid': False, 'given': 'Goda', 'family': 'Laucaitytė', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Pediatrics, Lithuanian University of Health ' 'Sciences, 44307 Kaunas, Lithuania'}, { 'name': 'Institute of Physiology and Pharmacology, Lithuanian University ' 'of Health Sciences, 44307 Kaunas, Lithuania'}]}, { 'ORCID': 'http://orcid.org/0000-0002-5806-6155', 'authenticated-orcid': False, 'given': 'Rūta', 'family': 'Inčiūraitė', 'sequence': 'additional', 'affiliation': [ { 'name': 'Institute for Digestive Research, Lithuanian University of ' 'Health Sciences, 44307 Kaunas, Lithuania'}]}, { 'given': 'Mantas', 'family': 'Malinauskas', 'sequence': 'additional', 'affiliation': [ { 'name': 'Institute of Physiology and Pharmacology, Lithuanian University ' 'of Health Sciences, 44307 Kaunas, Lithuania'}]}, { 'ORCID': 'http://orcid.org/0000-0002-6997-4917', 'authenticated-orcid': False, 'given': 'Lina', 'family': 'Jankauskaitė', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Pediatrics, Lithuanian University of Health ' 'Sciences, 44307 Kaunas, Lithuania'}, { 'name': 'Institute of Physiology and Pharmacology, Lithuanian University ' 'of Health Sciences, 44307 Kaunas, Lithuania'}]}], 'member': '1968', 'published-online': {'date-parts': [[2024, 11, 5]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'unstructured': 'Santos-Ferreira, N., Van Dycke, J., Neyts, J., and Rocha-Pereira, J. ' '(2021). Current and future antiviral strategies to tackle ' 'gastrointestinal viral infections. Microorganisms, 9.', 'DOI': '10.3390/microorganisms9081599'}, { 'key': 'ref_2', 'doi-asserted-by': 'crossref', 'first-page': '1555', 'DOI': '10.1007/s10787-021-00869-w', 'article-title': 'Melatonin reduces inflammation in intestinal cells, organoids and ' 'intestinal explants', 'volume': '29', 'author': 'Zhang', 'year': '2021', 'journal-title': 'Inflammopharmacology'}, { 'key': 'ref_3', 'doi-asserted-by': 'crossref', 'first-page': 'e12598', 'DOI': '10.1111/jpi.12598', 'article-title': 'Melatonin reduces inflammatory response in human intestinal epithelial ' 'cells stimulated by interleukin-1β', 'volume': '67', 'author': 'Mannino', 'year': '2019', 'journal-title': 'J. Pineal Res.'}, { 'key': 'ref_4', 'doi-asserted-by': 'crossref', 'first-page': '198108', 'DOI': '10.1016/j.virusres.2020.198108', 'article-title': 'Melatonin potentials against viral infections including COVID-19: ' 'Current evidence and new findings', 'volume': '287', 'author': 'Juybari', 'year': '2020', 'journal-title': 'Virus Res.'}, { 'key': 'ref_5', 'doi-asserted-by': 'crossref', 'first-page': '18886', 'DOI': '10.3390/molecules201018886', 'article-title': 'Melatonin as a potent and inducible endogenous antioxidant: Synthesis ' 'and metabolism', 'volume': '20', 'author': 'Tan', 'year': '2015', 'journal-title': 'Molecules'}, { 'key': 'ref_6', 'doi-asserted-by': 'crossref', 'first-page': '143', 'DOI': '10.1007/s00018-021-04102-3', 'article-title': 'Melatonin: Highlighting its use as a potential treatment for SARS-CoV-2 ' 'infection', 'volume': '79', 'author': 'Reiter', 'year': '2022', 'journal-title': 'Cell Mol. Life Sci.'}, { 'key': 'ref_7', 'doi-asserted-by': 'crossref', 'unstructured': 'Giménez, V.M.M., Heras, N.d.L., Lahera, V., Tresguerres, J.A.F., Reiter, ' 'R.J., and Manucha, W. (2022). Melatonin as an Anti-Aging Therapy for ' 'Age-Related Cardiovascular and Neurodegenerative Diseases. Front. Aging ' 'Neurosci., 14.', 'DOI': '10.3389/fnagi.2022.888292'}, { 'key': 'ref_8', 'doi-asserted-by': 'crossref', 'unstructured': 'Maestroni, G.J.M. (2024). Role of Melatonin in Viral, Bacterial and ' 'Parasitic Infections. Biomolecules, 14.', 'DOI': '10.20944/preprints202402.1454.v2'}, { 'key': 'ref_9', 'doi-asserted-by': 'crossref', 'first-page': '140', 'DOI': '10.1111/j.1749-6632.1988.tb35272.x', 'article-title': 'Pineal Melatonin, Its Fundamental Immunoregulatory Role in Aging and ' 'Cancer', 'volume': '521', 'author': 'Maestroni', 'year': '1988', 'journal-title': 'Ann. N. Y. Acad. Sci.'}, { 'key': 'ref_10', 'doi-asserted-by': 'crossref', 'first-page': '171', 'DOI': '10.32794/mr112500127', 'article-title': 'Melatonin inhibits Zika virus replication in Vero epithelial cells and ' 'SK-N-SH human neuroblastoma cells', 'volume': '5', 'author': 'Wongchitrat', 'year': '2022', 'journal-title': 'Melatonin Res.'}, { 'key': 'ref_11', 'doi-asserted-by': 'crossref', 'unstructured': 'Kitidee, K., Samutpong, A., Pakpian, N., Wisitponchai, T., Govitrapong, ' 'P., Reiter, R.J., and Wongchitrat, P. (2023). Antiviral effect of ' 'melatonin on Japanese encephalitis virus infection involves inhibition ' 'of neuronal apoptosis and neuroinflammation in SH-SY5Y cells. Sci. Rep., ' '13.', 'DOI': '10.1038/s41598-023-33254-4'}, { 'key': 'ref_12', 'doi-asserted-by': 'crossref', 'unstructured': 'Pérez-Martínez, Z., Boga, J.A., Potes, Y., Melón, S., and Coto-Montes, ' 'A. (2024). Effect of Melatonin on Herpesvirus Type 1 Replication. Int. ' 'J. Mol. Sci., 25.', 'DOI': '10.20944/preprints202402.1750.v1'}, { 'key': 'ref_13', 'doi-asserted-by': 'crossref', 'unstructured': 'Zheng, J., Zhou, Y., Zhang, D., Ma, K., Gong, Y., Luo, X., Liu, J., and ' 'Cui, S. (2024). Intestinal melatonin levels and gut microbiota ' 'homeostasis are independent of the pineal gland in pigs. Front. ' 'Microbiol., 15.', 'DOI': '10.3389/fmicb.2024.1352586'}, { 'key': 'ref_14', 'doi-asserted-by': 'crossref', 'unstructured': 'Pan, J., Li, F., Wang, C., Li, X., Zhang, S., Zhang, W., Zhao, G., Ma, ' 'C., Liu, G., and Yang, K. (2021). Effects of duodenal ' '5-hydroxytryptophan perfusion on melatonin synthesis in gi tract of ' 'sheep. Molecules, 26.', 'DOI': '10.3390/molecules26175275'}, { 'key': 'ref_15', '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_16', 'first-page': 'G51', 'article-title': 'Gastrointestinal organoids in the study of viral infections', 'volume': '324', 'author': 'Gebert', 'year': '2023', 'journal-title': 'Am. J. Physiol. Liver Physiol.'}, { 'key': 'ref_17', 'doi-asserted-by': 'crossref', 'unstructured': 'Samy, K.E., Levy, E.S., Phong, K., Demaree, B., Abate, A.R., and Desai, ' 'T.A. (2019). Human intestinal spheroids cultured using Sacrificial ' 'Micromolding as a model system for studying drug transport. Sci. Rep., ' '9.', 'DOI': '10.1038/s41598-019-46408-0'}, { 'key': 'ref_18', 'doi-asserted-by': 'crossref', 'first-page': 'e74072', 'DOI': '10.7554/eLife.74072', 'article-title': 'Homeostatic interferon-lambda response to bacterial microbiota ' 'stimulates preemptive antiviral defense within discrete pockets of ' 'intestinal epithelium', 'volume': '11', 'author': 'Peterson', 'year': '2022', 'journal-title': 'eLife'}, { 'key': 'ref_19', 'doi-asserted-by': 'crossref', 'unstructured': 'Stanifer, M.L., Guo, C., Doldan, P., and Boulant, S. (2020). Importance ' 'of Type I and III Interferons at Respiratory and Intestinal Barrier ' 'Surfaces. Front. Immunol., 11.', 'DOI': '10.3389/fimmu.2020.608645'}, { 'key': 'ref_20', 'first-page': '294', 'article-title': 'Rotavirus-induced IFN-β promotes anti-viral signaling and apoptosis ' 'that modulate viral replication in intestinal epithelial cells', 'volume': '18', 'author': 'Frias', 'year': '2012', 'journal-title': 'J. Endotoxin Res.'}, { 'key': 'ref_21', 'doi-asserted-by': 'crossref', 'first-page': 'e39', 'DOI': '10.4142/jvs.2021.22.e39', 'article-title': 'Role of IFNLR1 gene in PRRSV infection of PAM cells', 'volume': '22', 'author': 'Qin', 'year': '2021', 'journal-title': 'J. Veter. Sci.'}, { 'key': 'ref_22', 'doi-asserted-by': 'crossref', 'first-page': '32269', 'DOI': '10.1074/jbc.M404789200', 'article-title': 'Role of the interleukin (IL)-28 receptor tyrosine residues for ' 'antiviral and antiproliferative activity of IL-29/interferon-λ1. ' 'Similarities with type 1 interferon signaling', 'volume': '279', 'author': 'Dumoutier', 'year': '2004', 'journal-title': 'J. Biol. Chem.'}, { 'key': 'ref_23', 'doi-asserted-by': 'crossref', 'first-page': '197', 'DOI': '10.1111/j.1600-079X.2010.00829.x', 'article-title': 'Melatonin inhibits Prevotella intermedia lipopolysaccharide-induced ' 'production of nitric oxide and interleukin-6 in murine macrophages by ' 'suppressing NF-κB and STAT1 activity', 'volume': '50', 'author': 'Choi', 'year': '2011', 'journal-title': 'J. Pineal Res.'}, { 'key': 'ref_24', 'doi-asserted-by': 'crossref', 'first-page': '90', 'DOI': '10.1038/s41531-022-00352-5', 'article-title': 'Melatonin ameliorates Parkinson’s disease via regulating microglia ' 'polarization in a RORα-dependent pathway', 'volume': '8', 'author': 'Li', 'year': '2022', 'journal-title': 'Npj Park. Dis.'}, { 'key': 'ref_25', 'doi-asserted-by': 'crossref', 'first-page': '122108', 'DOI': '10.1016/j.lfs.2023.122108', 'article-title': 'Melatonin attenuates cellular senescence and apoptosis in diabetic ' 'nephropathy by regulating STAT3 phosphorylation', 'volume': '332', 'author': 'Fang', 'year': '2023', 'journal-title': 'Life Sci.'}, { 'key': 'ref_26', 'doi-asserted-by': 'crossref', 'first-page': '103', 'DOI': '10.1089/jir.2011.0099', 'article-title': 'The role of signal transducer and activator of transcription-2 in the ' 'interferon response', 'volume': '32', 'author': 'Steen', 'year': '2012', 'journal-title': 'J. Interf. Cytokine Res.'}, { 'key': 'ref_27', 'doi-asserted-by': 'crossref', 'first-page': 'e12782', 'DOI': '10.1111/jpi.12782', 'article-title': 'Safety of higher doses of melatonin in adults: A systematic review and ' 'meta-analysis', 'volume': '72', 'author': 'Schrire', 'year': '2022', 'journal-title': 'J. Pineal Res.'}, { 'key': 'ref_28', 'doi-asserted-by': 'crossref', 'first-page': '169', 'DOI': '10.1007/s40261-015-0368-5', 'article-title': 'The Safety of Melatonin in Humans', 'volume': '36', 'author': 'Andersen', 'year': '2016', 'journal-title': 'Clin. Drug Investig.'}, { 'key': 'ref_29', 'doi-asserted-by': 'crossref', 'unstructured': 'Brzezinski, A., Rai, S., Purohit, A., and Pandi-Perumal, S.R. (2021). ' 'Melatonin, clock genes, and mammalian reproduction: What is the link?. ' 'Int. J. Mol. Sci., 22.', 'DOI': '10.3390/ijms222413240'}, { 'key': 'ref_30', 'doi-asserted-by': 'crossref', 'first-page': '151700', 'DOI': '10.1016/j.acthis.2021.151700', 'article-title': 'Effects of melatonin on the toxicity and proliferation of human ' 'anaplastic thyroid cancer cell line', 'volume': '123', 'author': 'Dabirian', 'year': '2021', 'journal-title': 'Acta Histochem.'}, { 'key': 'ref_31', 'doi-asserted-by': 'crossref', 'first-page': '432', 'DOI': '10.1016/j.bone.2013.02.021', 'article-title': 'Melatonin inhibits the proliferation of human osteosarcoma cell line ' 'MG-63', 'volume': '55', 'author': 'Liu', 'year': '2013', 'journal-title': 'Bone'}], 'container-title': 'International Journal of Molecular Sciences', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.mdpi.com/1422-0067/25/22/11872/pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 11, 5]], 'date-time': '2024-11-05T10:43:17Z', 'timestamp': 1730803397000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.mdpi.com/1422-0067/25/22/11872'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 11, 5]]}, 'references-count': 31, 'journal-issue': {'issue': '22', 'published-online': {'date-parts': [[2024, 11]]}}, 'alternative-id': ['ijms252211872'], 'URL': 'http://dx.doi.org/10.3390/ijms252211872', 'relation': {}, 'ISSN': ['1422-0067'], 'subject': [], 'container-title-short': 'IJMS', 'published': {'date-parts': [[2024, 11, 5]]}}
Loading..
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop   
Submit