Protective role of zinc in the pathogenesis of respiratory diseases

Clinical Trials & Research
  • Soriano JB, Kendrick PJ, Paulson KR, Gupta V, Abrams EM, Adedoyin RA, et al. Prevalence and attributable health burden of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respiratory Med. 2020;8:585–96.

    Article 

    Google Scholar
     

  • Lynch DA, Sverzellati N, Travis WD, Brown KK, Colby TV, Galvin JR, et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. The Lancet. Respiratory Med. 2018;6:138–53.


    Google Scholar
     

  • Blumenthal GM, Bunn PA Jr, Chaft JE, McCoach CE, Perez EA, Scagliotti GV, et al. Current status and future perspectives on neoadjuvant therapy in lung cancer. J Thorac Oncol: Off Publ Int Assoc Study Lung Cancer. 2018;13:1818–31.

    CAS 
    Article 

    Google Scholar
     

  • Ferguson GT, Rabe KF, Martinez FJ, Fabbri LM, Wang C, Ichinose M, et al. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial. Lancet Respiratory Med. 2018;6:747–58.

    CAS 
    Article 

    Google Scholar
     

  • Vettorazzi S, Bode C, Dejager L, Frappart L, Shelest E, Klaßen C, et al. Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1. Nat Commun. 2015;6:7796.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, et al. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials. Lancet Respiratory Med. 2013;1:210–23.

    CAS 
    Article 

    Google Scholar
     

  • Asher MI, García-Marcos L, Pearce NE, Strachan DP. Trends in worldwide asthma prevalence. Eur Respir J. 2020;56. https://doi.org/10.1183/13993003.02094-2020.

  • Wang C, Xu J, Yang L, Xu Y, Zhang X, Bai C, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet (Lond, Engl). 2018;391:1706–17.

    Article 

    Google Scholar
     

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer J clinicians 2021;71:209–49.


    Google Scholar
     

  • Ali MK, Kim RY, Karim R, Mayall JR, Martin KL, Shahandeh A, et al. Role of iron in the pathogenesis of respiratory disease. Int J Biochem cell Biol. 2017;88:181–95.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Prasad AS. Zinc: role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab care. 2009;12:646–52.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Yu Q, Liu H, Yang K, Tang X, Chen S, Ajuwon KM, et al. Effect of the level and source of supplementary dietary zinc on egg production, quality, and zinc content and on serum antioxidant parameters and zinc concentration in laying hens. Poult Sci. 2020;99:6233–8.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Signorell C, Zimmermann MB, Cakmak I, Wegmüller R, Zeder C, Hurrell R, et al. Zinc absorption from agronomically biofortified wheat is similar to post-harvest fortified wheat and is a substantial source of bioavailable zinc in humans. The. J Nutr. 2019;149:840–6.

    PubMed 
    Article 

    Google Scholar
     

  • Donangelo CM, Woodhouse LR, King SM, Toffolo G, Shames DM, Viteri FE, et al. Iron and zinc absorption from two bean (Phaseolus vulgaris L.) genotypes in young women. J Agric food Chem. 2003;51:5137–43.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Lafarga T, Hayes M. Bioactive peptides from meat muscle and by-products: generation, functionality and application as functional ingredients. Meat Sci. 2014;98:227–39.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Adams CL, Hambidge M, Raboy V, Dorsch JA, Sian L, Westcott JL, et al. Zinc absorption from a low-phytic acid maize. Am J Clin Nutr. 2002;76:556–9.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Ma G, Li Y, Jin Y, Zhai F, Kok FJ, Yang X. Phytate intake and molar ratios of phytate to zinc, iron and calcium in the diets of people in China. Eur J Clin Nutr. 2007;61:368–74.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Brnić M, Hurrell RF, Songré-Ouattara LT, Diawara B, Kalmogho-Zan A, Tapsoba C, et al. Effect of phytase on zinc absorption from a millet-based porridge fed to young Burkinabe children. Eur J Clin Nutr. 2017;71:137–41.

    PubMed 
    Article 
    CAS 

    Google Scholar
     

  • Saunders AV, Craig WJ, Baines SK. Zinc and vegetarian diets. Med J Aust. 2013;199:S17–21.

    PubMed 
    Article 

    Google Scholar
     

  • Hemalatha S, Platel K, Srinivasan K. Influence of germination and fermentation on bioaccessibility of zinc and iron from food grains. Eur J Clin Nutr. 2007;61:342–8.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Norouzi S, Adulcikas J, Sohal SS, Myers S. Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease. J Biomed Sci. 2017;24:87.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Gibson RS, Hess SY, Hotz C, Brown KH. Indicators of zinc status at the population level: a review of the evidence. Br J Nutr. 2008;99:S14–23.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Maret W, Sandstead HH. Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol: organ Soc Miner Trace Elem (GMS). 2006;20:3–18.

    CAS 
    Article 

    Google Scholar
     

  • Hotz C, Peerson JM, Brown KH. Suggested lower cutoffs of serum zinc concentrations for assessing zinc status: reanalysis of the second National Health and Nutrition Examination Survey data (1976-1980). Am J Clin Nutr. 2003;78:756–64.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Tran CD, Miller LV, Krebs NF, Lei S, Hambidge KM. Zinc absorption as a function of the dose of zinc sulfate in aqueous solution. Am J Clin Nutr. 2004;80:1570–3.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Prasad AS. Discovery of human zinc deficiency: its impact on human health and disease. Adv Nutr (Bethesda, Md) 2013;4:176–90.

    CAS 
    Article 

    Google Scholar
     

  • Mammadova-Bach E, Braun A. Zinc homeostasis in platelet-related diseases. Int J of Mol Sci. 2019;20. https://doi.org/10.3390/ijms20215258.

  • Maywald M, Wessels I, Rink L. Zinc signals and immunity. Int J of Mol Sci. 2017;18. https://doi.org/10.3390/ijms18102222.

  • Kimura T, Kambe T. The functions of metallothionein and ZIP and ZnT transporters: an overview and perspective. Int J Mol Sci. 2016;17:336.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Florea D, Molina-López J, Hogstrand C, Lengyel I, de la Cruz AP, Rodríguez-Elvira M, et al. Changes in zinc status and zinc transporters expression in whole blood of patients with Systemic Inflammatory Response Syndrome (SIRS). J Trace Elem Med Biol: organ Soc Miner Trace Elem (GMS). 2018;49:202–9.

    CAS 
    Article 

    Google Scholar
     

  • Kambe T, Tsuji T, Hashimoto A, Itsumura N. The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism. Physiological Rev. 2015;95:749–84.

    CAS 
    Article 

    Google Scholar
     

  • Wessels I, Cousins RJ. Zinc dyshomeostasis during polymicrobial sepsis in mice involves zinc transporter Zip14 and can be overcome by zinc supplementation. Am J Physiol Gastrointest liver Physiol. 2015;309:G768–78.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Hood MI, Skaar EP. Nutritional immunity: transition metals at the pathogen-host interface. Nat Rev Microbiol. 2012;10:525–37.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune function. Nutrients. 2017;9.

  • Wessels I, Haase H, Engelhardt G, Rink L, Uciechowski P. Zinc deficiency induces production of the proinflammatory cytokines IL-1β and TNFα in promyeloid cells via epigenetic and redox-dependent mechanisms. The. J nutritional Biochem. 2013;24:289–97.

    CAS 
    Article 

    Google Scholar
     

  • Kloubert V, Rink L. Zinc as a micronutrient and its preventive role of oxidative damage in cells. Food Funct. 2015;6:3195–204.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Arigliani M, Spinelli AM, Liguoro I, Cogo P. Nutrition and lung growth. Nutrients. 2018;10. https://doi.org/10.3390/nu10070919.

  • Napolitano JR, Liu MJ, Bao S, Crawford M, Nana-Sinkam P, Cormet-Boyaka E, et al. Cadmium-mediated toxicity of lung epithelia is enhanced through NF-κB-mediated transcriptional activation of the human zinc transporter ZIP8. Am J Physiol Lung Cell Mol Physiol. 2012;302:L909–18.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Hamon R, Homan CC, Tran HB, Mukaro VR, Lester SE, Roscioli E, et al. Zinc and zinc transporters in macrophages and their roles in efferocytosis in COPD. PloS one. 2014;9:e110056.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Krone A, Fu Y, Schreiber S, Kotrba J, Borde L, Nötzold A, et al. Ionic mitigation of CD4(+) T cell metabolic fitness, Th1 central nervous system autoimmunity and Th2 asthmatic airway inflammation by therapeutic zinc. Sci Rep. 2022;12:1943.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Knoell DL, Smith D, Bao S, Sapkota M, Wyatt TA, Zweier JL, et al. Imbalance in zinc homeostasis enhances lung Tissue Loss following cigarette smoke exposure. J Trace Elem Med Biol: organ Soc Miner Trace Elem (GMS). 2020;60:126483.

    CAS 
    Article 

    Google Scholar
     

  • Gao Y, Xu Y, Wu D, Yu F, Yang L, Yao Y, et al. Progressive silencing of the zinc transporter Zip8 (Slc39a8) in chronic cadmium-exposed lung epithelial cells. Acta biochimica et biophysica Sin. 2017;49:444–9.

    CAS 
    Article 

    Google Scholar
     

  • Fahy JV. Type 2 inflammation in asthma—present in most, absent in many. Nat Rev Immunol. 2015;15:57–65.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Voehringer D, Reese TA, Huang X, Shinkai K, Locksley RM. Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system. J Exp Med. 2006;203:1435–46.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Locksley RM. Asthma and allergic inflammation. Cell 2010;140:777–83.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Bao B, Prasad AS, Beck FW, Bao GW, Singh T, Ali S, et al. Intracellular free zinc up-regulates IFN-γ and T-bet essential for Th1 differentiation in Con-A stimulated HUT-78 cells. Biochemical biophysical Res Commun. 2011;407:703–7.

    CAS 
    Article 

    Google Scholar
     

  • Prasad AS. Lessons learned from experimental human model of zinc deficiency. J Immunol Res. 2020;2020:9207279.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Rosenkranz E, Hilgers RD, Uciechowski P, Petersen A, Plümäkers B, Rink L. Zinc enhances the number of regulatory T cells in allergen-stimulated cells from atopic subjects. Eur J Nutr. 2017;56:557–67.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Li H, Cao R, Wasserloos KJ, Bernal P, Liu ZQ, Pitt BR, et al. Nitric oxide and zinc homeostasis in pulmonary endothelium. Ann N. Y Acad Sci. 2010;1203:73–8.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Thambiayya K, Kaynar AM, St Croix CM, Pitt BR. Functional role of intracellular labile zinc in pulmonary endothelium. Pulm circulation. 2012;2:443–51.

    CAS 
    Article 

    Google Scholar
     

  • St Croix CM, Leelavaninchkul K, Watkins SC, Kagan VE, Pitt BR. Nitric oxide and zinc homeostasis in acute lung injury. Proc Am Thorac Soc 2005;2:236–42.

    Article 
    CAS 

    Google Scholar
     

  • Bernal PJ, Leelavanichkul K, Bauer E, Cao R, Wilson A, Wasserloos KJ, et al. Nitric-oxide-mediated zinc release contributes to hypoxic regulation of pulmonary vascular tone. Circulation Res. 2008;102:1575–83.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Ban Y, Liu Y, Li Y, Zhang Y, Xiao L, Gu Y, et al. S-nitrosation impairs KLF4 activity and instigates endothelial dysfunction in pulmonary arterial hypertension. Redox Biol. 2019;21:101099.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Li J, Zhang L, Zhang Y, Liu Y, Zhang H, Wei L, et al. A20 deficiency leads to angiogenesis of pulmonary artery endothelial cells through stronger NF-κB activation under hypoxia. J Cell Mol Med. 2016;20:1319–28.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Wessels I, Pupke JT, von Trotha KT, Gombert A, Himmelsbach A, Fischer HJ, et al. Zinc supplementation ameliorates lung injury by reducing neutrophil recruitment and activity. Thorax 2020;75:253–61.

    PubMed 
    Article 

    Google Scholar
     

  • Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel Coronavirus-infected pneumonia. The N Engl J Med. 2020;382:1199–207.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Morawska L, Cao J. Airborne transmission of SARS-CoV-2: the world should face the reality. Environ Int. 2020;139:105730.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Weiss P, Murdoch DR. Clinical course and mortality risk of severe COVID-19. Lancet (Lond, Engl). 2020;395:1014–5.

    CAS 
    Article 

    Google Scholar
     

  • Panchariya L, Khan WA, Kuila S, Sonkar K, Sahoo S, Ghoshal A, et al. Zinc(2+) ion inhibits SARS-CoV-2 main protease and viral replication in vitro. Chem Commun (Camb, Engl). 2021;57:10083–6.

    CAS 
    Article 

    Google Scholar
     

  • Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front Immunol. 2020;11:827.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, et al. 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 regulators Homeost agents. 2020;34:327–31.

    CAS 

    Google Scholar
     

  • Aziz M, Fatima R, Assaly R. Elevated interleukin-6 and severe COVID-19: a meta-analysis. J Med Virol. 2020;92:2283–5.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Martin AI, Rao G. COVID-19: a potential risk factor for acute pulmonary embolism. Methodist DeBakey cardiovascular J. 2020;16:155–7.

    Article 

    Google Scholar
     

  • Wessels I, Rolles B, Slusarenko AJ, Rink L. Zinc deficiency as a possible risk factor for increased susceptibility and severe progression of Corona Virus Disease 19. Br J Nutr. 2022;127:214–32.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Ghanei E, Baghani M, Moravvej H, Talebi A, Bahmanjahromi A, Abdollahimajd F. Low serum levels of zinc and 25-hydroxyvitmain D as potential risk factors for COVID-19 susceptibility: a pilot case-control study. European journal of clinical nutrition. 2022;1–6. https://doi.org/10.1038/s41430-022-01095-5.

  • Heller RA, Sun Q, Hackler J, Seelig J, Seibert L, Cherkezov A, et al. Prediction of survival odds in COVID-19 by zinc, age and selenoprotein P as composite biomarker. Redox Biol. 2021;38:101764.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Jothimani D, Kailasam E, Danielraj S, Nallathambi B, Ramachandran H, Sekar P, et al. COVID-19: Poor outcomes in patients with zinc deficiency. Int J Infect Dis: IJID: Off Publ Int Soc Infect Dis. 2020;100:343–9.

    CAS 

    Google Scholar
     

  • Finzi E. Treatment of SARS-CoV-2 with high dose oral zinc salts: a report on four patients. Int J Infect Dis: IJID: Off Publ Int Soc Infect Dis. 2020;99:307–9.

    CAS 

    Google Scholar
     

  • Sampath V, Rabinowitz G, Shah M, Jain S, Diamant Z, Jesenak M, et al. Vaccines and allergic reactions: the past, the current COVID-19 pandemic, and future perspectives. Allergy 2021;76:1640–60.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Srivastava V, Niu L, Phadke KS, Bellaire BH, Cho MW. Induction of potent and durable neutralizing antibodies against SARS-CoV-2 using a receptor binding domain-based immunogen. Front Immunol. 2021;12:637982.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J respiratory Crit care Med. 2017;195:557–82.

    CAS 
    Article 

    Google Scholar
     

  • Yao RQ, Ren C, Xia ZF, Yao YM. Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles. Autophagy 2021;17:385–401.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Tanwar VS, Zhang X, Jagannathan L, Jose CC, Cuddapah S. Cadmium exposure upregulates SNAIL through miR-30 repression in human lung epithelial cells. Toxicol Appl Pharmacol. 2019;373:1–9.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Jiang Y, Wang X, Hu D. Mitochondrial alterations during oxidative stress in chronic obstructive pulmonary disease. Int J chronic Obstr Pulm Dis. 2017;12:1153–62.

    CAS 
    Article 

    Google Scholar
     

  • Ito S, Araya J, Kurita Y, Kobayashi K, Takasaka N, Yoshida M, et al. PARK2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis. Autophagy 2015;11:547–59.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Wang J, Whiteman MW, Lian H, Wang G, Singh A, Huang D, et al. A non-canonical MEK/ERK signaling pathway regulates autophagy via regulating Beclin 1. J Biol Chem. 2009;284:21412–24.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Nuttall JR, Oteiza PI. Zinc and the ERK kinases in the developing brain. Neurotox Res. 2012;21:128–41.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Bian X, Teng T, Zhao H, Qin J, Qiao Z, Sun Y, et al. Zinc prevents mitochondrial superoxide generation by inducing mitophagy in the setting of hypoxia/reoxygenation in cardiac cells. Free Radic Res. 2018;52:80–91.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Morgan CI, Ledford JR, Zhou P, Page K. Zinc supplementation alters airway inflammation and airway hyperresponsiveness to a common allergen. J Inflamm (Lond, Engl). 2011;8:36.

    CAS 
    Article 

    Google Scholar
     

  • Hönscheid A, Rink L, Haase H. T-lymphocytes: a target for stimulatory and inhibitory effects of zinc ions. Endocr, Metab immune Disord drug targets. 2009;9:132–44.

    Article 

    Google Scholar
     

  • Lu H, Xin Y, Tang Y, Shao G. Zinc suppressed the airway inflammation in asthmatic rats: effects of zinc on generation of eotaxin, MCP-1, IL-8, IL-4, and IFN-γ. Biol trace Elem Res. 2012;150:314–21.

    PubMed 
    Article 
    CAS 

    Google Scholar
     

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer J clinicians. 2016;66:7–30.


    Google Scholar
     

  • Zaynagetdinov R, Stathopoulos GT, Sherrill TP, Cheng DS, McLoed AG, Ausborn JA, et al. Epithelial nuclear factor-κB signaling promotes lung carcinogenesis via recruitment of regulatory T lymphocytes. Oncogene 2012;31:3164–76.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Xiao L, Lan X, Shi X, Zhao K, Wang D, Wang X, et al. Cytoplasmic RAP1 mediates cisplatin resistance of non-small cell lung cancer. Cell death Dis. 2017;8:e2803.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Chen PM, Cheng YW, Wu TC, Chen CY, Lee H. MnSOD overexpression confers cisplatin resistance in lung adenocarcinoma via the NF-κB/Snail/Bcl-2 pathway. Free Radic Biol Med. 2015;79:127–37.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Scheffler M, Bos M, Gardizi M, König K, Michels S, Fassunke J, et al. PIK3CA mutations in non-small cell lung cancer (NSCLC): genetic heterogeneity, prognostic impact and incidence of prior malignancies. Oncotarget 2015;6:1315–26.

    PubMed 
    Article 

    Google Scholar
     

  • Heavey S, Godwin P, Baird AM, Barr MP, Umezawa K, Cuffe S, et al. Strategic targeting of the PI3K-NFκB axis in cisplatin-resistant NSCLC. Cancer Biol Ther. 2014;15:1367–77.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Xu H, Yuan R, Liu X, Li X, Qiao G, Li C, et al. Zn-doped CuO nanocomposites inhibit tumor growth by NF-κB pathway cross-linked autophagy and apoptosis. Nanomed (Lond, Engl). 2019;14:131–49.

    CAS 
    Article 

    Google Scholar
     

  • Jong MT, Gray TA, Ji Y, Glenn CC, Saitoh S, Driscoll DJ, et al. A novel imprinted gene, encoding a RING zinc-finger protein, and overlapping antisense transcript in the Prader-Willi syndrome critical region. Hum Mol Genet. 1999;8:783–93.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Shin C, Ito Y, Ichikawa S, Tokunaga M, Sakata-Sogawa K, Tanaka T. MKRN2 is a novel ubiquitin E3 ligase for the p65 subunit of NF-κB and negatively regulates inflammatory responses. Sci Rep. 2017;7:46097.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Jiang J, Xu Y, Ren H, Wudu M, Wang Q, Song X, et al. MKRN2 inhibits migration and invasion of non-small-cell lung cancer by negatively regulating the PI3K/Akt pathway. J Exp Clin cancer Res: CR. 2018;37:189.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Kocdor H, Ates H, Aydin S, Cehreli R, Soyarat F, Kemanli P, et al. Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer. Drug Des, Dev Ther. 2015;9:3899–909.

    CAS 
    Article 

    Google Scholar
     

  • Hanley C, Layne J, Punnoose A, Reddy KM, Coombs I, Coombs A, et al. Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles. Nanotechnology 2008;19:295103.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Anand SS, Islam S, Rosengren A, Franzosi MG, Steyn K, Yusufali AH, et al. Risk factors for myocardial infarction in women and men: insights from the INTERHEART study. Eur heart J. 2008;29:932–40.

    PubMed 
    Article 

    Google Scholar
     

  • Al-Sulaiti H, Diboun I, Agha MV, Mohamed FFS, Atkin S, Dömling AS, et al. Metabolic signature of obesity-associated insulin resistance and type 2 diabetes. J Transl Med. 2019;17:348.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Thais Fantozzi E, Rodrigues-Garbin S, Yamamoto Ricardo-da-Silva F, Oliveira-Filho RM, Spina D, Tavares-de-Lima W, et al. Acute lung injury induced by intestinal ischemia and reperfusion is altered in obese female mice. Pulm Pharmacol therapeutics. 2018;49:54–9.

    CAS 
    Article 

    Google Scholar
     

  • Manicone AM, Gong K, Johnston LK, Giannandrea M. Diet-induced obesity alters myeloid cell populations in naïve and injured lung. Respiratory Res. 2016;17:24.

    Article 
    CAS 

    Google Scholar
     

  • Lambert AA, Putcha N, Drummond MB, Boriek AM, Hanania NA, Kim V, et al. Obesity is associated with increased morbidity in moderate to severe COPD. Chest 2017;151:68–77.

    PubMed 
    Article 

    Google Scholar
     

  • Zhi G, Xin W, Ying W, Guohong X, Shuying L. “Obesity Paradox” in acute respiratory distress syndrome: asystematic review and meta-analysis. PloS one. 2016;11:e0163677.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Hsu PS, Wu CS, Chang JF, Lin WN. Leptin promotes cPLA2 gene expression through activation of the MAPK/NF-κB/p300 cascade. Int J Mol Sci. 2015;16:27640–58.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Hao W, Wang J, Zhang Y, Wang Y, Sun L, Han W. Leptin positively regulates MUC5AC production and secretion induced by interleukin-13 in human bronchial epithelial cells. Biochemical biophysical Res Commun. 2017;493:979–84.

    CAS 
    Article 

    Google Scholar
     

  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Investig. 2003;112:1796–808.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Suganami T, Tanimoto-Koyama K, Nishida J, Itoh M, Yuan X, Mizuarai S, et al. Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arteriosclerosis, thrombosis, Vasc Biol. 2007;27:84–91.

    CAS 
    Article 

    Google Scholar
     

  • Liu MJ, Bao S, Bolin ER, Burris DL, Xu X, Sun Q, et al. Zinc deficiency augments leptin production and exacerbates macrophage infiltration into adipose tissue in mice fed a high-fat diet. J Nutr. 2013;143:1036–45.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell 2014;156:20–44.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Tang X, Shay NF. Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and Akt in 3T3-L1 fibroblasts and adipocytes. J Nutr. 2001;131:1414–20.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Rios-Lugo MJ, Madrigal-Arellano C, Gaytán-Hernández D, Hernández-Mendoza H, Romero-Guzmán ET. Association of serum zinc levels in overweight and obesity. Biol trace Elem Res. 2020;198:51–7.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Khorsandi H, Nikpayam O, Yousefi R, Parandoosh M, Hosseinzadeh N, Saidpour A, et al. Zinc supplementation improves body weight management, inflammatory biomarkers and insulin resistance in individuals with obesity: a randomized, placebo-controlled, double-blind trial. Diabetol Metab Syndr. 2019;11:101.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Notz Q, Herrmann J, Schlesinger T, Helmer P, Sudowe S, Sun Q, et al. Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS. Nutrients. 2021;13. https://doi.org/10.3390/nu13062113.

  • Kamei S, Fujikawa H, Nohara H, Ueno-Shuto K, Maruta K, Nakashima R, et al. Zinc deficiency via a splice switch in zinc importer ZIP2/SLC39A2 causes cystic fibrosis-associated MUC5AC hypersecretion in airway epithelial cells. EBioMedicine 2018;27:304–16.

    PubMed 
    Article 

    Google Scholar
     

  • Mossad SB, Macknin ML, Medendorp SV, Mason P. Zinc gluconate lozenges for treating the common cold. A randomized, double-blind, placebo-controlled study. Ann Intern Med. 1996;125:81–8.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Ghaffari H, Tavakoli A, Moradi A, Tabarraei A, Bokharaei-Salim F, Zahmatkeshan M, et al. Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicine. J Biomed Sci. 2019;26:70.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Prasad AS, Fitzgerald JT, Bao B, Beck FW, Chandrasekar PH. Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000;133:245–52.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Kurugöl Z, Akilli M, Bayram N, Koturoglu G. The prophylactic and therapeutic effectiveness of zinc sulphate on common cold in children. Acta paediatrica (Oslo, Nor: 1992) 2006;95:1175–81.

    Article 

    Google Scholar
     

  • Fang L, Roth M, S’Ng CT, Tamm M, Han B, Hoang BX. Zinc salicylate reduces airway smooth muscle cells remodelling by blocking mTOR and activating p21((Waf1/Cip1)). J nutritional Biochem. 2021;89:108563.

    CAS 
    Article 

    Google Scholar
     

  • Derwand R, Scholz M. Does zinc supplementation enhance the clinical efficacy of chloroquine/hydroxychloroquine to win today’s battle against COVID-19? Med hypotheses. 2020;142:109815.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Abdulhamid I, Beck FW, Millard S, Chen X, Prasad A. Effect of zinc supplementation on respiratory tract infections in children with cystic fibrosis. Pediatr Pulmonol. 2008;43:281–7.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Roth DE, Richard SA, Black RE. Zinc supplementation for the prevention of acute lower respiratory infection in children in developing countries: meta-analysis and meta-regression of randomized trials. Int J Epidemiol. 2010;39:795–808.

    PubMed 
    Article 

    Google Scholar
     

  • Shah UH, Abu-Shaheen AK, Malik MA, Alam S, Riaz M, Al-Tannir MA. The efficacy of zinc supplementation in young children with acute lower respiratory infections: a randomized double-blind controlled trial. Clin Nutr (Edinb, Scotl). 2013;32:193–9.

    CAS 
    Article 

    Google Scholar
     

  • Martinez-Estevez NS, Alvarez-Guevara AN, Rodriguez-Martinez CE. Effects of zinc supplementation in the prevention of respiratory tract infections and diarrheal disease in Colombian children: A 12-month randomised controlled trial. Allergologia et immunopathologia. 2016;44:368–75.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Hsu HH, Tzao C, Chang WC, Wu CP, Tung HJ, Chen CY, et al. Zinc chloride (smoke bomb) inhalation lung injury: clinical presentations, high-resolution CT findings, and pulmonary function test results. Chest 2005;127:2064–71.

    PubMed 
    Article 

    Google Scholar
     

  • Malo JL, Cartier A, Dolovich J. Occupational asthma due to zinc. Eur respiratory J. 1993;6:447–50.

    CAS 

    Google Scholar
     

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