Implications for Systemic Approaches to COVID-19: Effect Sizes of Remdesivir, Tocilizumab, Melatonin, Vitamin D3, and Meditation
Ryan D Castle, Michelle A Williams, William C Bushell, J Adam Rindfleisch, Christine Tara Peterson, James Marzolf, Kimberly Brouwer, Paul J Mills
Journal of Inflammation Research, doi:10.2147/jir.s323356
Introduction: COVID-19 poses a chronic threat to inflammatory systems, reinforcing the need for efficient anti-inflammatory strategies. The purpose of this review and analysis was to determine the efficacy of various interventions upon the inflammatory markers most affected by COVID-19. The focus was on the markers associated with COVID-19, not the etiology of the virus itself. Methods: Based on 27 reviewed papers, information was extracted on the effects of COVID-19 upon inflammatory markers, then the effects of standard treatments (Remdesivir, Tocilizumab) and adjunctive interventions (vitamin D 3 , melatonin, and meditation) were extracted for those markers. These data were used to approximate effect sizes for the disease or interventions via standardized mean differences (SMD). Results: The data that were available indicated that adjunctive interventions affected 68.4% of the inflammatory markers impacted by COVID-19, while standard pharmaceutical medication affected 26.3%. Discussion: Nonstandard adjunctive care appeared to have comparable or superior effects in comparison to Remdesivir and Tocilizumab on the inflammatory markers most impacted by COVID-19. Alongside standards of care, melatonin, vitamin D 3 , and meditation should be considered for treatment of SARS-COV-2 infection and COVID-19 disease.
Disclosure The authors report no conflicts of interest for this work.
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Journal of Inflammation Research
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References
Aiswarya, Arumugam, Dineshkumar, Use of remdesivir in patients with COVID-19 on hemodialysis: a Study of Safety and Tolerance, Kidney Int Rep,
doi:10.1016/j.ekir.2020.12.003Akbari, Tabrizi, Lankarani, The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis, Life Sci,
doi:10.1016/j.lfs.2020.118167Alamdari, Mahdavi, Roshanravan, Placebo-controlled trial related to the effects of melatonin on oxidative stress and inflammatory parameters of obese women, Horm Metab Res,
doi:10.1055/s-0034-1384587Amiri-Dashatan, Koushki, Ghorbani, Naderi, Increased inflammatory markers correlate with liver damage and predict severe COVID-19: a systematic review and meta-analysis, Gastroenterol Hepatol Bed Bench
Bartels, Jørgensen, Bendix, 25-hydroxy vitamin D3 modulates dendritic cell phenotype and function in crohn's disease, Inflammopharmacology,
doi:10.1007/s10787-012-0168-yBower, Crosswell, Stanton, Mindfulness meditation for younger breast cancer survivors: a randomized controlled trial, Cancer,
doi:10.1002/cncr.29194Bushell, Castle, Williams, Meditation and yoga practices as potential adjunctive treatment of SARS-CoV-2 infection and COVID-19: a brief overview of key subjects, Journal of Inflammation Research,
doi:10.1089/acm.2020.0177Bushell, Theise, Toward a unified field of study: longevity, regeneration, and protection of health through meditation and related practices, Ann N Y Acad Sci,
doi:10.1111/j.1749-6632.2009.04959.xCa, Kip, Post-White, Lymphocyte recovery after breast cancer treatment and mindfulness-based stress reduction (MBSR) therapy, Biol Res Nurs,
doi:10.1177/1099800411419245Cahn, Goodman, Peterson, Maturi, Mills, Yoga, meditation and mind-body health: increased BDNF, cortisol awakening response, and altered inflammatory marker expression after a 3-month yoga and meditation retreat, Front Hum Neurosci,
doi:10.3389/fnhum.2017.00315Carlson, Speca, Faris, Patel, One year pre-post intervention follow-up of psychological, immune, endocrine and blood pressure outcomes of mindfulness-based stress reduction (MBSR) in breast and prostate cancer outpatients, Brain Behav Immun,
doi:10.1016/j.bbi.2007.04.002Carlson, Speca, Patel, Goodey, Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate cancer outpatients, Psychoneuroendocrinology,
doi:10.1016/s0306-4530(03)00054-4Carlson, Speca, Patel, Goodey, Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress, and immune parameters in breast and prostate cancer outpatients, Psychosom Med,
doi:10.1097/01.psy.0000074003.35911.41Castillo, Costa, Barrios, Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: a pilot randomized clinical study, J Steroid Biochem Mol Biol,
doi:10.1016/j.jsbmb.2020.105751Celinski, Konturek, Slomka, Effects of treatment with melatonin and tryptophan on liver enzymes, parameters of fat metabolism and plasma levels of cytokines in patients with non-alcoholic fatty liver disease-14 months follow up, J Physiol Pharmacol
Chen, Wu, Guo, Clinical and immunological features of severe and moderate coronavirus disease 2019, J Clin Invest,
doi:10.1172/JCI137244Chen, Zheng, Yu, Blood molecular markers associated with COVID-19 immunopathology and multi-organ damage, EMBO J,
doi:10.15252/embj.2020105896Choudhary, Sharma, Silakari, The interplay between inflammatory pathways and COVID-19: a critical review on pathogenesis and therapeutic options, Microb Pathog,
doi:10.1016/j.micpath.2020.104673Cichoz-Lach, Celinski, Konturek, Konturek, Slomka, The effects of L-tryptophan and melatonin on selected biochemical parameters in patients with steatohepatitis, J Physiol Pharmacol
Conti, Ronconi, Caraffa, Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies, J Biol Regul Homeost Agents,
doi:10.23812/CONTI-EEpel, Puterman, Lin, Meditation and vacation effects have an impact on disease-associated molecular phenotypes, Transl Psychiatry,
doi:10.1038/tp.2016.164Faraone, Interpreting estimates of treatment effects, P T
Feitosa, Júnior, Neto, COVID-19: rational discovery of the therapeutic potential of melatonin as a SARS-CoV-2 main protease inhibitor, Int J Med Sci,
doi:10.7150/ijms.48053Gonzalez-Garcia, Ferrer, Borras, Effectiveness of mindfulness-based cognitive therapy on the quality of life, emotional status, and CD4 cell count of patients aging with HIV infection, AIDS Behav,
doi:10.1007/s10461-013-0612-zGrant, Lahore, Mcdonnell, Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths, Nutrients,
doi:10.3390/nu12040988Hu, Huang, Alleviation of inflammatory response of pulmonary fibrosis in acute respiratory distress syndrome by puerarin via Transforming Growth Factor (TGF-beta1), Med Sci Monit,
doi:10.12659/MSM.915570Hunter, The inflammation theory of disease. The growing realization that chronic inflammation is crucial in many diseases opens new avenues for treatment, EMBO Rep,
doi:10.1038/embor.2012.142Isik, Ozuguz, Tutuncu, Serum transforming growth factor-beta levels in patients with vitamin D deficiency, Eur J Intern Med,
doi:10.1016/j.ejim.2011.09.017Javanmard, Heshmat-Ghahdarijani, Mirmohammad-Sadeghi, Sonbolestan, Ziayi, The effect of melatonin on endothelial dysfunction in patient undergoing coronary artery bypass grafting surgery, Adv Biomed Res,
doi:10.4103/2277-9175.194801Jolliffe, Camargo, Sluyter, Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(21)00051-6Kapepula, Kabengele, Kingombe, Artemisia Spp. derivatives for COVID-19 treatment: anecdotal use, political hype, treatment potential, challenges, and road map to randomized clinical trials, Am J Trop Med Hyg,
doi:10.4269/ajtmh.20-0820Leijte, Wagemaker, Van Kraaij, Mortality and re-admission after hospitalization with COVID-19, Ned Tijdschr Geneeskd
Li, Wang, Jou, SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-beta1 via ROS/p38 MAPK/STAT3 pathway, Sci Rep,
doi:10.1038/srep25754Li, Zhang, Guan, SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation, Signal Transduct Target Ther,
doi:10.1038/s41392-020-00334-0Ling, Broad, Murphy, High-dose cholecalciferol booster therapy is associated with a reduced risk of mortality in patients with COVID-19: a Cross-Sectional Multi-Centre Observational Study, Nutrients,
doi:10.3390/nu12123799Magro, SARS-CoV-2 and COVID-19: is interleukin-6 (IL-6) the 'culprit lesion' of ARDS onset? What is there besides tocilizumab? SGP130Fc, Cytokine X,
doi:10.1016/j.cytox.2020.100029Meng, Xiao, Zhang, Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension, Emerg Microbes Infect,
doi:10.1080/22221751.2020.1746200Mihara M 1, Kasutani, Okazaki, Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family, Int Immunopharmacol,
doi:10.1016/j.intimp.2005.05.010Mu, Ding, Li, Chen, Ma, Heparin attenuates lipopolysaccharide-induced acute lung injury by inhibiting nitric oxide synthase and TGF-beta/Smad signaling pathway, Thromb Res,
doi:10.1016/j.thromres.2011.10.003Panigrahy, Gilligan, Huang, Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19?, Cancer Metastasis Rev,
doi:10.1007/s10555-020-09889-4Pittet, Griffiths, Geiser, TGF-beta is a critical mediator of acute lung injury, J Clin Invest,
doi:10.1172/JCI11963Pum, Ennemoser, Adage, Kungl, Cytokines and chemokines in SARS-CoV-2 infections-therapeutic strategies targeting cytokine storm, Biomolecules,
doi:10.3390/biom11010091Qin, Zhou, Hu, Dysregulation of immune response in patients with COVID-19 in Wuhan, China, Clin Infect Dis,
doi:10.1093/cid/ciaa248Ramezani, Simani, Karimialavijeh, Rezaei, Hajiesmaeili et al., The role of anxiety and cortisol in outcomes of patients with covid-19, Basic Clin Neurosci,
doi:10.32598/bcn.11.covid19.1168.2Rausch-Fan, Leutmezer, Willheim, Regulation of cytokine production in human peripheral blood mononuclear cells and allergen-specific th cell clones by 1alpha,25-dihydroxyvitamin D3, Int Arch Allergy Immunol,
doi:10.1159/000058001Raygan, Ostadmohammadi, Bahmani, Reiter, Asemi, Melatonin administration lowers biomarkers of oxidative stress and cardio-metabolic risk in type 2 diabetic patients with coronary heart disease: a randomized, double-blind, placebo-controlled trial, Clin Nutr,
doi:10.1016/j.clnu.2017.12.004Rea, Gibson, Mcgilligan, Mcnerlan, Alexander et al., Age and age-related diseases: role of inflammation triggers and cytokines, Front Immunol,
doi:10.3389/fimmu.2018.00586Renu, Prasanna, Valsala Gopalakrishnan, Coronaviruses pathogenesis, comorbidities and multi-organ damage -A review, Life Sci,
doi:10.1016/j.lfs.2020.117839Rosenkranz, Lutz, Perlman, Reduced stress and inflammatory responsiveness in experienced meditators compared to a matched healthy control group, Psychoneuroendocrinology,
doi:10.1016/j.psyneuen.2016.02.013Shakoor, Feehan, Dhaheri, Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: could they help against COVID-19?, Maturitas,
doi:10.1016/j.maturitas.2020.08.003Shete, Verma, Kulkarni, Bhogal, Effect of yoga training on inflammatory cytokines and C-reactive protein in employees of small-scale industries, J Educ Health Promot,
doi:10.4103/jehp.jehp_65_17Singh, Gillies, Singh, Prevalence of co-morbidities and their association with mortality in patients with COVID-19: a systematic review and meta-analysis, Diabetes Obes Metab,
doi:10.1111/dom.14124Smolen, Beaulieu, Rubbert-Roth, Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial, Lancet,
doi:10.1016/S0140-6736(08)60453-5Uckun, Saund, Windlass, Trieu, Repurposing anti-malaria phytomedicine artemisinin as a COVID-19 drug, Front Pharmacol,
doi:10.3389/fphar.2021.649532Verkhratsky, Li, Melino, Melino, Shi, Can COVID-19 pandemic boost the epidemic of neurodegenerative diseases?, Biol Direct,
doi:10.1186/s13062-020-00282-3Wang, Kream, Stefano, Long-term respiratory and neurological sequelae of COVID-19, Med Sci Monit,
doi:10.12659/MSM.928996Wang, Lu, Li, SARS coronavirus papain-like protease up-regulates the collagen expression through non-Samd TGF-beta1 signaling, Virus Res,
doi:10.1016/j.virusres.2017.04.008Wang, Nie, Wang, Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia, J Infect Dis,
doi:10.1093/infdis/jiaa150Wang, Zhang, Du, Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Lancet,
doi:10.1016/S0140-6736(20)31022-9Witek-Janusek, Albuquerque, Chroniak, Chroniak, Durazo-Arvizu et al., Effect of mindfulness based stress reduction on immune function, quality of life and coping in women newly diagnosed with early stage breast cancer, Brain Behav Immun,
doi:10.1016/j.bbi.2008.01.012Woods, Tazi, Chesarino, Amer, Davis, TGF-betainduced IL-6 prevents development of acute lung injury in influenza A virus-infected F508del CFTR-heterozygous mice, Am J Physiol Lung Cell Mol Physiol,
doi:10.1152/ajplung.00078.2015Xiong, Liu, Cao, Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients, Emerg Microbes Infect,
doi:10.1080/22221751.2020.1747363Zabetakis, Lordan, Norton, Tsoupras, COVID-19: the inflammation link and the role of nutrition in potential mitigation, Nutrients,
doi:10.3390/nu12051466{ 'indexed': {'date-parts': [[2023, 4, 21]], 'date-time': '2023-04-21T22:49:54Z', 'timestamp': 1682117394412},
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'DOI': '10.1111/dom.14124',
'volume': '22',
'author': 'Singh',
'year': '2020',
'journal-title': 'Diabetes Obes Metab'},
{ 'key': 'ref3',
'doi-asserted-by': 'publisher',
'first-page': '4',
'DOI': '10.1016/j.ajpath.2020.08.009',
'volume': '191',
'author': 'Gustine',
'year': '2021',
'journal-title': 'Am J Pathol'},
{ 'key': 'ref4',
'doi-asserted-by': 'publisher',
'first-page': '337',
'DOI': '10.1007/s10555-020-09889-4',
'volume': '39',
'author': 'Panigrahy',
'year': '2020',
'journal-title': 'Cancer Metastasis Rev'},
{ 'key': 'ref5',
'doi-asserted-by': 'publisher',
'first-page': '5',
'DOI': '10.3390/nu12051466',
'volume': '12',
'author': 'Zabetakis',
'year': '2020',
'journal-title': 'Nutrients'},
{ 'key': 'ref6',
'doi-asserted-by': 'publisher',
'first-page': '1',
'DOI': '10.1016/j.maturitas.2020.08.003',
'volume': '143',
'author': 'Shakoor',
'year': '2021',
'journal-title': 'Maturitas'},
{ 'key': 'ref7',
'doi-asserted-by': 'publisher',
'first-page': '968',
'DOI': '10.1038/embor.2012.142',
'volume': '13',
'author': 'Hunter',
'year': '2012',
'journal-title': 'EMBO Rep'},
{ 'key': 'ref8',
'doi-asserted-by': 'publisher',
'first-page': '586',
'DOI': '10.3389/fimmu.2018.00586',
'volume': '9',
'author': 'Rea',
'year': '2018',
'journal-title': 'Front Immunol'},
{ 'key': 'ref9',
'doi-asserted-by': 'publisher',
'first-page': 'S140',
'DOI': '10.1111/j.1753-4887.2007.tb00352.x',
'volume': '65',
'author': 'Libby',
'year': '2007',
'journal-title': 'Nutr Rev'},
{ 'key': 'ref10',
'doi-asserted-by': 'publisher',
'first-page': '2',
'DOI': '10.23812/CONTI-E',
'volume': '34',
'author': 'Conti',
'year': '2020',
'journal-title': 'J Biol Regul Homeost Agents'},
{ 'key': 'ref11',
'first-page': '282',
'volume': '13',
'author': 'Amiri-Dashatan',
'year': '2020',
'journal-title': 'Gastroenterol Hepatol Bed Bench'},
{ 'key': 'ref12',
'doi-asserted-by': 'publisher',
'first-page': '117839',
'DOI': '10.1016/j.lfs.2020.117839',
'volume': '255',
'author': 'Renu',
'year': '2020',
'journal-title': 'Life Sci'},
{ 'key': 'ref13',
'doi-asserted-by': 'publisher',
'first-page': '622',
'DOI': '10.1016/s0889-1591(02)00021-1',
'volume': '16',
'author': 'Black',
'year': '2002',
'journal-title': 'Brain Behav Immun'},
{ 'key': 'ref14',
'unstructured': 'Coronavirus Disease (COVID-19) situation reports. Avaiable from: '
'https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. '
'Accessed January 28, 2021.'},
{ 'key': 'ref15',
'doi-asserted-by': 'publisher',
'first-page': 'e928996',
'DOI': '10.12659/MSM.928996',
'volume': '26',
'author': 'Wang',
'year': '2020',
'journal-title': 'Med Sci Monit'},
{ 'key': 'ref16',
'doi-asserted-by': 'publisher',
'first-page': '28',
'DOI': '10.1186/s13062-020-00282-3',
'volume': '15',
'author': 'Verkhratsky',
'year': '2020',
'journal-title': 'Biol Direct'},
{ 'key': 'ref17',
'doi-asserted-by': 'publisher',
'first-page': 'L257',
'DOI': '10.1152/ajplung.00238.2020',
'volume': '320',
'author': 'McDonald',
'year': '2021',
'journal-title': 'Am J Physiol Lung Cell Mol Physiol'},
{ 'key': 'ref18',
'doi-asserted-by': 'publisher',
'first-page': 'e68',
'DOI': '10.7861/clinmed.2020-0204',
'volume': '21',
'author': 'O’Sullivan',
'year': '2021',
'journal-title': 'Clin Med'},
{ 'key': 'ref19',
'doi-asserted-by': 'publisher',
'first-page': '2',
'DOI': '10.1007/s11906-018-0812-z',
'volume': '20',
'author': 'Saklayen',
'year': '2018',
'journal-title': 'Curr Hypertens Rep'},
{ 'key': 'ref20',
'first-page': 'D5423',
'volume': '164',
'author': 'Leijte',
'year': '2020',
'journal-title': 'Ned Tijdschr Geneeskd'},
{ 'key': 'ref21',
'unstructured': 'NIH launches new initiative to study. “Long COVID.” National Institutes '
'of Health (NIH); February 23, 2021. Available from: '
'https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-launches-new-initiative-study-long-covid. '
'Accessed March 30, 2021.'},
{ 'key': 'ref22',
'doi-asserted-by': 'publisher',
'first-page': '235',
'DOI': '10.1038/s41392-020-00334-0',
'volume': '5',
'author': 'Li',
'year': '2020',
'journal-title': 'Signal Transduct Target Ther'},
{ 'key': 'ref23',
'doi-asserted-by': 'publisher',
'first-page': '1',
'DOI': '10.3390/biom11010091',
'volume': '11',
'author': 'Pum',
'year': '2021',
'journal-title': 'Biomolecules'},
{ 'key': 'ref24',
'doi-asserted-by': 'publisher',
'first-page': '104673',
'DOI': '10.1016/j.micpath.2020.104673',
'volume': '150',
'author': 'Choudhary',
'year': '2021',
'journal-title': 'Microb Pathog'},
{ 'key': 'ref25',
'doi-asserted-by': 'publisher',
'first-page': 'e105896',
'DOI': '10.15252/embj.2020105896',
'volume': '39',
'author': 'Chen',
'year': '2020',
'journal-title': 'EMBO J'},
{ 'key': 'ref26',
'doi-asserted-by': 'publisher',
'first-page': '1083',
'DOI': '10.1016/j.rmed.2009.01.005',
'volume': '103',
'author': 'Mak',
'year': '2009',
'journal-title': 'Respir Med'},
{ 'key': 'ref27',
'doi-asserted-by': 'publisher',
'first-page': '761',
'DOI': '10.1080/22221751.2020.1747363',
'volume': '9',
'author': 'Xiong',
'year': '2020',
'journal-title': 'Emerg Microbes Infect'},
{ 'key': 'ref28',
'doi-asserted-by': 'publisher',
'first-page': 'L1136',
'DOI': '10.1152/ajplung.00078.2015',
'volume': '308',
'author': 'Woods',
'year': '2015',
'journal-title': 'Am J Physiol Lung Cell Mol Physiol'},
{ 'key': 'ref29',
'doi-asserted-by': 'publisher',
'first-page': '479',
'DOI': '10.1016/j.thromres.2011.10.003',
'volume': '129',
'author': 'Mu',
'year': '2012',
'journal-title': 'Thromb Res'},
{ 'key': 'ref30',
'doi-asserted-by': 'publisher',
'first-page': '1537',
'DOI': '10.1172/JCI11963',
'volume': '107',
'author': 'Pittet',
'year': '2001',
'journal-title': 'J Clin Invest'},
{ 'key': 'ref31',
'doi-asserted-by': 'publisher',
'first-page': '1954',
'DOI': '10.7150/ijbs.46891',
'volume': '16',
'author': 'Chen',
'year': '2020',
'journal-title': 'Int J Biol Sci'},
{ 'key': 'ref32',
'doi-asserted-by': 'publisher',
'first-page': '6523',
'DOI': '10.12659/MSM.915570',
'volume': '25',
'author': 'Hu',
'year': '2019',
'journal-title': 'Med Sci Monit'},
{ 'key': 'ref33',
'doi-asserted-by': 'publisher',
'first-page': '25754',
'DOI': '10.1038/srep25754',
'volume': '6',
'author': 'Li',
'year': '2016',
'journal-title': 'Sci Rep'},
{ 'key': 'ref34',
'doi-asserted-by': 'publisher',
'first-page': '58',
'DOI': '10.1016/j.virusres.2017.04.008',
'volume': '235',
'author': 'Wang',
'year': '2017',
'journal-title': 'Virus Res'},
{ 'key': 'ref35',
'doi-asserted-by': 'publisher',
'first-page': '10',
'DOI': '10.7196/SAMJ.2020.v111i11.15433',
'volume': '111',
'author': 'Mendelson',
'year': '2020',
'journal-title': 'S Afr Med J'},
{ 'key': 'ref36',
'doi-asserted-by': 'publisher',
'first-page': 'S230',
'DOI': '10.1016/j.amepre.2015.07.019',
'volume': '49',
'author': 'Ali',
'year': '2015',
'journal-title': 'Am J Prev Med'},
{ 'key': 'ref37',
'doi-asserted-by': 'publisher',
'first-page': 'e100903',
'DOI': '10.1371/journal.pone.0100903',
'volume': '9',
'author': 'Morgan',
'year': '2014',
'journal-title': 'PLoS One'},
{ 'key': 'ref38',
'doi-asserted-by': 'publisher',
'first-page': '276',
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'DOI': '10.1016/j.lfs.2020.117583',
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'author': 'Zhang',
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'DOI': '10.1136/annrheumdis-2013-204378',
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'author': 'Zerr',
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'first-page': '93',
'DOI': '10.1016/j.ejim.2011.09.017',
'volume': '23',
'author': 'Isik',
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'doi-asserted-by': 'publisher',
'first-page': '960',
'DOI': '10.4269/ajtmh.20-0820',
'volume': '103',
'author': 'Kapepula',
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{ 'key': 'ref43',
'doi-asserted-by': 'publisher',
'first-page': '649532',
'DOI': '10.3389/fphar.2021.649532',
'volume': '12',
'author': 'Uckun',
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'first-page': '105751',
'DOI': '10.1016/j.jsbmb.2020.105751',
'volume': '203',
'author': 'Entrenas Castillo',
'year': '2020',
'journal-title': 'J Steroid Biochem Mol Biol'},
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'first-page': '12',
'DOI': '10.3390/nu12123799',
'volume': '12',
'author': 'Ling',
'year': '2020',
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'doi-asserted-by': 'publisher',
'DOI': '10.3390/nu12040988',
'volume': '12',
'author': 'Grant',
'year': '2020',
'journal-title': 'Nutrients'},
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'doi-asserted-by': 'publisher',
'first-page': '2133',
'DOI': '10.7150/ijms.48053',
'volume': '17',
'author': 'Feitosa',
'year': '2020',
'journal-title': 'Int J Med Sci'},
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'doi-asserted-by': 'publisher',
'first-page': '315',
'DOI': '10.3389/fnhum.2017.00315',
'volume': '11',
'author': 'Cahn',
'year': '2017',
'journal-title': 'Front Hum Neurosci'},
{ 'key': 'ref49',
'doi-asserted-by': 'publisher',
'first-page': '5',
'DOI': '10.1111/j.1749-6632.2009.04959.x',
'volume': '1172',
'author': 'Bushell',
'year': '2009',
'journal-title': 'Ann N Y Acad Sci'},
{ 'key': 'ref50',
'doi-asserted-by': 'publisher',
'first-page': '1569',
'DOI': '10.1016/S0140-6736(20)31022-9',
'volume': '395',
'author': 'Wang',
'year': '2020',
'journal-title': 'Lancet'},
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'doi-asserted-by': 'publisher',
'first-page': '1972',
'DOI': '10.1080/21645515.2017.1316909',
'volume': '13',
'author': 'Sheppard',
'year': '2017',
'journal-title': 'Hum Vaccin Immunother'},
{ 'key': 'ref52',
'doi-asserted-by': 'publisher',
'first-page': '547',
'DOI': '10.1089/acm.2020.0177',
'volume': '26',
'author': 'Bushell',
'year': '2020',
'journal-title': 'J Altern Complement Med'},
{ 'key': 'ref53',
'doi-asserted-by': 'publisher',
'first-page': '586',
'DOI': '10.1016/j.ekir.2020.12.003',
'volume': '6',
'author': 'Aiswarya',
'year': '2021',
'journal-title': 'Kidney Int Rep'},
{ 'key': 'ref54',
'doi-asserted-by': 'publisher',
'first-page': '118167',
'DOI': '10.1016/j.lfs.2020.118167',
'volume': '258',
'author': 'Akbari',
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'journal-title': 'Life Sci'},
{ 'key': 'ref55',
'doi-asserted-by': 'publisher',
'first-page': '504',
'DOI': '10.1055/s-0034-1384587',
'volume': '47',
'author': 'Alamdari',
'year': '2015',
'journal-title': 'Horm Metab Res'},
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'doi-asserted-by': 'publisher',
'first-page': '177',
'DOI': '10.1007/s10787-012-0168-y',
'volume': '21',
'author': 'Bartels',
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'doi-asserted-by': 'publisher',
'first-page': '1231',
'DOI': '10.1002/cncr.29194',
'volume': '121',
'author': 'Bower',
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'doi-asserted-by': 'publisher',
'first-page': '571',
'DOI': '10.1097/01.psy.0000074003.35911.41',
'volume': '65',
'author': 'Carlson',
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'doi-asserted-by': 'publisher',
'first-page': '448',
'DOI': '10.1016/s0306-4530(03)00054-4',
'volume': '29',
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'first-page': '1038',
'DOI': '10.1016/j.bbi.2007.04.002',
'volume': '21',
'author': 'Carlson',
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'journal-title': 'Brain Behav Immun'},
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'first-page': '75',
'volume': '65',
'author': 'Celinski',
'year': '2014',
'journal-title': 'J Physiol Pharmacol'},
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'doi-asserted-by': 'publisher',
'first-page': '2620',
'DOI': '10.1172/JCI137244',
'volume': '130',
'author': 'Chen',
'year': '2020',
'journal-title': 'J Clin Invest'},
{ 'key': 'ref63',
'doi-asserted-by': 'publisher',
'first-page': 'E005',
'DOI': '10.3760/cma.j.issn.1001-0939.2020.0005',
'volume': '43',
'author': 'Chen',
'year': '2020',
'journal-title': 'Zhonghua Jie He He Hu Xi Za Zhi'},
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'first-page': '577',
'volume': '61',
'author': 'Cichoz-Lach',
'year': '2010',
'journal-title': 'J Physiol Pharmacol'},
{ 'key': 'ref65',
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'first-page': 'e880',
'DOI': '10.1038/tp.2016.164',
'volume': '6',
'author': 'Epel',
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'first-page': '676',
'DOI': '10.1007/s10461-013-0612-z',
'volume': '18',
'author': 'Gonzalez-Garcia',
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'journal-title': 'AIDS Behav'},
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'first-page': '174',
'DOI': '10.4103/2277-9175.194801',
'volume': '5',
'author': 'Javanmard',
'year': '2016',
'journal-title': 'Adv Biomed Res'},
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'doi-asserted-by': 'publisher',
'first-page': '37',
'DOI': '10.1177/1099800411419245',
'volume': '15',
'author': 'Lengacher',
'year': '2013',
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'doi-asserted-by': 'publisher',
'author': 'Qin',
'year': '2020',
'journal-title': 'Clin Infect Dis',
'DOI': '10.1093/cid/ciaa248'},
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'first-page': '33',
'DOI': '10.1159/000058001',
'volume': '128',
'author': 'Rausch-Fan',
'year': '2002',
'journal-title': 'Int Arch Allergy Immunol'},
{ 'key': 'ref71',
'doi-asserted-by': 'publisher',
'first-page': '191',
'DOI': '10.1016/j.clnu.2017.12.004',
'volume': '38',
'author': 'Raygan',
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'journal-title': 'Clin Nutr'},
{ 'key': 'ref72',
'doi-asserted-by': 'publisher',
'first-page': '117',
'DOI': '10.1016/j.psyneuen.2016.02.013',
'volume': '68',
'author': 'Rosenkranz',
'year': '2016',
'journal-title': 'Psychoneuroendocrinology'},
{ 'key': 'ref73',
'doi-asserted-by': 'publisher',
'first-page': '76',
'DOI': '10.4103/jehp.jehp_65_17',
'volume': '6',
'author': 'Shete',
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'journal-title': 'J Educ Health Promot'},
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'doi-asserted-by': 'publisher',
'first-page': '987',
'DOI': '10.1016/S0140-6736(08)60453-5',
'volume': '371',
'author': 'Smolen',
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'first-page': '1762',
'DOI': '10.1093/infdis/jiaa150',
'volume': '221',
'author': 'Wang',
'year': '2020',
'journal-title': 'J Infect Dis'},
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'first-page': '969',
'DOI': '10.1016/j.bbi.2008.01.012',
'volume': '22',
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'first-page': '757',
'DOI': '10.1080/22221751.2020.1746200',
'volume': '9',
'author': 'Meng',
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'first-page': '179',
'DOI': '10.32598/bcn.11.covid19.1168.2',
'volume': '11',
'author': 'Ramezani',
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'first-page': '100029',
'DOI': '10.1016/j.cytox.2020.100029',
'volume': '2',
'author': 'Magro',
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'first-page': '2129',
'DOI': '10.1080/00031305.2016.1154108',
'volume': '70',
'author': 'Wasserstein',
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'journal-title': 'Am Stat'},
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'first-page': '700',
'volume': '33',
'author': 'Faraone',
'year': '2008',
'journal-title': 'P T'},
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'DOI': '10.1016/j.intimp.2005.05.010',
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'DOI': '10.3760/cma.j.cn121430-20200312-00412',
'volume': '32',
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'journal-title': 'Zhonghua Wei Zhong Bing Ji Jiu Yi Xue'}],
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