Optimized QRT-PCR Approach for the Measurable Impact of Adjuvant Cholecalciferol Therapy in Ameliorating Cytokine Gene Expression



Abstract Views
693

Downloads
424

Citations

Share

##plugins.themes.bootstrap3.article.sidebar##

Submitted Oct 23, 2021
Published Nov 16, 2021
10.24018/ejmed.2021.3.6.1117

Abstract viewed = 693 times

Table of Contents

##plugins.themes.bootstrap3.article.main##

The endemic Vitamin D deficiency in Pakistan and the current COVID-19 epidemic have converged into a double whammy scenario in Pakistan [1]. Nutritional epigenomic studies have highlighted Vitamin D as a master Vitamin influencing various genomic expressions through its active metabolite 1α,25-dihydroxyvitamin D3 [2]. The objective of this study was to evaluate the measurable impact of adjuvant Cholecalciferol therapy in the Cytokine gene expression of COVID-19 patients by quantitative Real-Time Polymerase Chain Reaction analysis. The trial was a randomized control prospective open label interventional trial done on moderate to severe COVID-19 patients with deranged inflammatory and coagulation biomarkers. SunnyD STAT (Vitamin D3 200000 IU) softgels were given at Day 1, Day 3 and Day 5 of the treatment. Optimized quantitative Real-Time Polymerase Chain Reaction analysis showed decreased genetic expressions of Interleukin 6 (IL-6), Interleukin 2RA (IL-2RA) and Tumor Necrosis Factor (TNF-a) in the interventional group against the age and co-morbidities matched controls, providing molecular and genetic level evidence for the purported mechanism of amelioration of Cytokines induced pathogenic inflammation. However, inherent limitations of the design restrict the generalizability of the results and warrants caution for extrapolation. We recommend randomized placebo-controlled trials with larger sampling and genome wide profiling to infer more definite interpretations.

Keywords: Adjuvant therapy, Cholecalciferol, genetic expression, vitamin D3

Downloads

Download data is not yet available.

References

  1. Farooka, Waris M, Aslam SS, Tarar MA, Rafi M, Ahmad A, Rafique N, Bilal M. Vitamin D perspective in front line healthcare workers amid COVID-19. European Journal of Medical and Health Sciences. 2021; 3(4): 65-72.
    DOI  |   Google Scholar
  2. Carlberg C. Nutrigenomics of vitamin D. Nutrients. 2019; 11(3): 676.
    DOI  |   Google Scholar
  3. Ghareghomi S, Ahmadian S, Zarghami N, Kahroba H. Fundamental insights into the interaction between telomerase/TERT and intracellular signaling pathways. Biochimie. 2020.
    DOI  |   Google Scholar
  4. Bikle DD. Vitamin D biochemistry and physiology. In Extraskeletal Effects of Vitamin D. Humana Press, Cham. 2018; 1-40.
    DOI  |   Google Scholar
  5. Zhu M, Tan Z, Luo Z, Hu H, Wu T, Fang S, et al. Association of the vitamin D metabolism gene GC and CYP27B1 polymorphisms with cancer susceptibility: a meta-analysis and trial sequential analysis. Bioscience Reports. 2019; 39(9): BSR20190368.
    DOI  |   Google Scholar
  6. Staniszewski LJ, Shahani P, Heck M, Hasan DS, Wagner C, Jurutka PW. Assessment of novel vitamin d receptor antagonists that mediate suppression of vitamin D signaling. The FASEB Journal. 2018; 32: lb98.
    DOI  |   Google Scholar
  7. Dimitrov V, Barbier C, Ismailova A, Wang Y, Dmowski K, Salehi-Tabar R, et al. Vitamin D-regulated gene expression profiles: Species-specificity and cell-specific effects on metabolism and immunity. Endocrinology. 2021; 162(2): bqaa218.
    DOI  |   Google Scholar
  8. Al-Daghri NM, Torretta E, Capitanio D, Fania C, Guerini FR, Sabico SB, et al. Intermediate and low abundant protein analysis of vitamin D deficient obese and non-obese subjects by MALDI-profiling. Scientific Reports. 2017; 7(1): 1-10.
    DOI  |   Google Scholar
  9. Carlberg C. Vitamin D genomics: from in vitro to in vivo. Frontiers in endocrinology. 2018; 9: 250.
    DOI  |   Google Scholar
  10. Zenata O, Vrzal R. Fine tuning of vitamin D receptor (VDR) activity by post-transcriptional and post-translational modifications. Oncotarget. 2017; 8(21): 35390.
    DOI  |   Google Scholar
  11. Meza-Meza MR, Ruiz-Ballesteros AI, de la Cruz-Mosso U. Functional effects of vitamin D: From nutrient to immunomodulator. Critical Reviews in Food Science and Nutrition. 2020: 1-21.
    DOI  |   Google Scholar
  12. Carlberg C. Molecular endocrinology of vitamin D on the epigenome level. Molecular and Cellular Endocrinology. 2017; 453: 14-21.
    DOI  |   Google Scholar
  13. Perino M, Veenstra GJ. Chromatin control of developmental dynamics and plasticity. Developmental Cell. 2016; 38(6): 610-620.
    DOI  |   Google Scholar
  14. Mangelsdorf DJ, Evans RM. The RXR heterodimers and orphan receptors. Cell. 1995; 83(6): 841-50.
    DOI  |   Google Scholar
  15. Carlberg C, Bendik I, Wyss A, Meier E, Sturzenbecker LJ, Grippo JF, et al. Two nuclear signalling pathways for vitamin D. Nature. 1993; 361(6413): 657-660.
    DOI  |   Google Scholar
  16. Carlberg C. Genome-wide (over) view on the actions of vitamin D. Frontiers in Physiology. 2014; 5: 167.
    DOI  |   Google Scholar
  17. Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nature Reviews Cancer. 2007; 7(9): 684-700.
    DOI  |   Google Scholar
  18. Tuoresmäki P, Väisänen S, Neme A, Heikkinen S, Carlberg C. Patterns of genome-wide VDR locations. PloS One. 2014; 9(4): e96105.
    DOI  |   Google Scholar
  19. Seuter S, Neme A, Carlberg C. Epigenomic PU. 1-VDR crosstalk modulates vitamin D signaling. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2017; 1860(4): 405-415.
    DOI  |   Google Scholar
  20. Neme A, Seuter S, Carlberg C. Vitamin D-dependent chromatin association of CTCF in human monocytes. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2016; 1859(11): 1380-1388.
    DOI  |   Google Scholar
  21. Carlberg C, Neme A. Machine learning approaches infer vitamin D signaling: Critical impact of vitamin D receptor binding within topologically associated domains. The Journal of Steroid Biochemistry and Molecular Biology. 2019; 185: 103-109.
    DOI  |   Google Scholar
  22. Dunlop TW, Väisänen S, Frank C, Molnár F, Sinkkonen L, Carlberg C. The human peroxisome proliferator-activated receptor δ gene is a primary target of 1α, 25-dihydroxyvitamin D3 and its nuclear receptor. Journal of Molecular Biology. 2005; 349(2): 248-260.
    DOI  |   Google Scholar
  23. Barragan M, Good M, Kolls JK. Regulation of dendritic cell function by vitamin D. Nutrients. 2015; 7(9): 8127-8151.
    DOI  |   Google Scholar
  24. Limketkai BN, Mullin GE, Limsui D, Parian AM. Role of vitamin D in inflammatory bowel disease. Nutrition in Clinical Practice. 2017; 32(3): 337-345.
    DOI  |   Google Scholar
  25. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. Jama. 2006; 296(23): 2832-2838.
    DOI  |   Google Scholar
  26. Zeitelhofer M, Adzemovic MZ, Gomez-Cabrero D, Bergman P, Hochmeister S, N'diaye M, et al. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis‬. Proceedings of the National Academy of Sciences. 2017; 114(9): E1678-87.
    DOI  |   Google Scholar
  27. Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nature Medicine. 2020; 26(10): 1636-1643.
     Google Scholar
  28. Henry BM, De Oliveira MH, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clinical Chemistry and Laboratory Medicine (CCLM). 2020; 58(7): 1021-1028.
    DOI  |   Google Scholar
  29. Wright DJ. Prevention of the cytokine storm in COVID-19. The Lancet Infectious Diseases. 2021; 21(1): 25-26.
    DOI  |   Google Scholar
  30. Besnier E, Tuech JJ, Schwarz L. We asked the experts: Covid-19 outbreak: is there still a place for scheduled surgery?“Reflection from pathophysiological data”. World Journal of Surgery. 2020; 44(6): 1695-1698.
    DOI  |   Google Scholar
  31. Ulhaq ZS, Soraya GV. Interleukin-6 as a potential biomarker of COVID-19 progression. Medecine et Maladies Infectieuses. 2020; 50(4): 382.
    DOI  |   Google Scholar
  32. Scherger S, Henao-Martínez A, Franco-Paredes C, Shapiro L. Rethinking interleukin-6 blockade for treatment of COVID-19. Medical Hypotheses. 2020; 144: 110053.
    DOI  |   Google Scholar
  33. Coomes EA, Haghbayan H. Interleukin‐6 in COVID‐19: a systematic review and meta‐analysis. Reviews in Medical Virology. 2020; 30(6): 1-9.
    DOI  |   Google Scholar
  34. Leija-Martínez JJ, Huang F, Del-Río-Navarro BE, Sanchéz-Muñoz F, Muñoz-Hernández O, Giacoman-Martínez A, et al. IL-17A and TNF-α as potential biomarkers for acute respiratory distress syndrome and mortality in patients with obesity and COVID-19. Medical Hypotheses. 2020; 144: 109935.
    DOI  |   Google Scholar
  35. Perlin DS, Zafir-Lavie I, Roadcap L, Raines S, Ware CF, Neil GA. Levels of the TNF-related cytokine light increase in hospitalized COVID-19 patients with cytokine release syndrome and ARDS. MSphere. 2020; 5(4): e00699-e00720.
    DOI  |   Google Scholar
  36. Tjan LH, Furukawa K, Nagano T, Kiriu T, Nishimura M, Arii J, et al. Early Differences in Cytokine Production by Severity of Coronavirus Disease 2019. The Journal of Infectious Diseases. 2021; 223(7): 1145-1149.
    DOI  |   Google Scholar
  37. Huang CG, Dutta A, Huang CT, Chang PY, Hsiao MJ, Hsieh YC. Relative COVID-19 viral persistence and antibody kinetics. Pathogens. 2021; 10(6): 752.
    DOI  |   Google Scholar
  38. Guo J, Wang S, Xia H, Shi D, Chen Y, Zheng S, et al. Cytokine Signature Associated with Disease Severity in COVID-19. Frontiers in Immunology. 2021: 3276.
    DOI  |   Google Scholar
  39. Kalia V, Xiao H, Yuzefpolskiy Y, Sarkar S. IL-2 Signals Program the Fate of Exhausted CD8 T cells, 2019.
    DOI  |   Google Scholar
  40. Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nature Medicine. 2020; 26(10): 1636-1643.
    DOI  |   Google Scholar


Most read articles by the same author(s)