Calcitriol prevents SARS-CoV spike-induced inflammation in human trophoblasts through downregulating ACE2 and TMPRSS2 expression

Vargas-Castro et al., The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2024.106625 (date from preprint)

Nov 2023

Post
Facebook

Source PDF All Studies Meta AnalysisMeta

Vitamin D for COVID-19

8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.

Lower risk for mortality, ICU admission, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine treatments.

5,100+ studies for 109 treatments. c19early.org

In Vitro study showing that calcitriol prevents SARS-CoV-2 spike-induced inflammation in human trophoblasts through downregulation of ACE2 and TMPRSS2. Authors demonstrated that calcitriol significantly reduced expression of ACE2, TMPRSS2, and other renin-angiotensin system (RAS) components in both primary syncytiotrophoblasts and HTR-8/SVneo first-trimester trophoblast cells. Calcitriol treatment prevented spike protein-induced increases in inflammatory cytokines (TNFα, IL-1β, IL-6, IL-8, MCP-1) and reduced ACE1/ACE2 ratio. Effects were observed at concentrations as low as 0.1 nM calcitriol. The study suggests vitamin D may help prevent placental SARS-CoV-2 infection through multiple mechanisms: reducing viral entry receptor expression, decreasing inflammation, and modulating RAS components. Immunofluorescence confirmed reduced ACE2 protein levels and IL-6 expression with calcitriol treatment.

21 preclinical studies support the efficacy of vitamin D for COVID-19:

7 In Silico studies1-7

11 In Vitro studies8-18

3 In Vivo animal studies10,14,19

Vitamin D has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function20-23. Vitamin D inhibits SARS-CoV-2 replication in vitro10,17, mitigates lung inflammation, damage, and lethality in mice with an MHV-3 model for β-CoV respiratory infections10,17, reduces SARS-CoV-2 replication in nasal epithelial cells via increased type I interferon expression13, downregulates proinflammatory cytokines IL-1β and TNF-α in SARS-CoV-2 spike protein-stimulated cells9, attenuates nucleocapsid protein-induced hyperinflammation by inactivating the NLRP3 inflammasome through the VDR-BRCC3 signaling pathway14, may be neuroprotective by protecting the blood-brain barrier, reducing neuroinflammation, and via immunomodulatory effects24, downregulates ACE2 and TMPRSS2 in human trophoblasts and minimizes spike protein-induced inflammation12, minimizes platelet aggregation mediated by SARS-CoV-2 spike protein via inhibiting integrin αIIbβ3 outside-in signaling8, and improves regulatory immune cell levels and control of proinflammatory cytokines in severe COVID-1925. Symptomatic COVID-19 is associated with a lower frequency of natural killer (NK) cells and vitamin D has been shown to improve NK cell activity26,27.

Important missing comments or errors? Let us know.

1. Morales-Bayuelo et al., New findings on ligand series used as SARS-CoV-2 virus inhibitors within the frameworks of molecular docking, molecular quantum similarity and chemical reactivity indices, F1000Research, doi:10.12688/f1000research.123550.3.f1000research.com, doi.org.

2. Chellasamy et al., Docking and molecular dynamics studies of human ezrin protein with a modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors, Journal of King Saud University - Science, doi:10.1016/j.jksus.2022.102277.sciencedirect.com, doi.org.

3. Pandya et al., Unravelling Vitamin B12 as a potential inhibitor against SARS-CoV-2: A computational approach, Informatics in Medicine Unlocked, doi:10.1016/j.imu.2022.100951.sciencedirect.com, doi.org.

4. Mansouri et al., The impact of calcitriol and estradiol on the SARS-CoV-2 biological activity: a molecular modeling approach, Scientific Reports, doi:10.1038/s41598-022-04778-y.nature.com, doi.org.

5. Song et al., Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1964601.tandfonline.com, doi.org.

6. Qayyum et al., Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 replication machinery enzymes, Endocrinology and Metabolism, doi:10.1152/ajpendo.00174.2021.physiology.org, doi.org.

7. Al-Mazaideh et al., Vitamin D is a New Promising Inhibitor to the Main Protease (Mpro) of COVID-19 by Molecular Docking, Journal of Pharmaceutical Research International, doi:10.9734/jpri/2021/v33i29B31603.journaljpri.com, doi.org.

8. Wang et al., 1,25‐Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS‐CoV‐2 spike protein via inhibiting integrin αIIbβ3 outside‐in signaling, Cell Biochemistry and Function, doi:10.1002/cbf.4039.wiley.com, doi.org.

9. Alcalá-Santiago et al., Disentangling the Immunomodulatory Effects of Vitamin D on the SARS-CoV-2 Virus by In Vitro Approaches, The 14th European Nutrition Conference FENS 2023, doi:10.3390/proceedings2023091415.mdpi.com, doi.org.

10. Campolina-Silva et al., Dietary Vitamin D Mitigates Coronavirus-Induced Lung Inflammation and Damage in Mice, Viruses, doi:10.3390/v15122434.mdpi.com, doi.org.

11. Moatasim et al., Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E, Microorganisms, doi:10.3390/microorganisms11112777.mdpi.com, doi.org.

12. Vargas-Castro et al., Calcitriol prevents SARS-CoV spike-induced inflammation in human trophoblasts through downregulating ACE2 and TMPRSS2 expression, The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2024.106625.sciencedirect.com, doi.org.

13. Sposito et al., Age differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - effects of vitamin D, Mucosal Immunology, doi:10.1016/j.mucimm.2023.08.002.nih.gov, doi.org.

14. Chen et al., Vitamin D3 attenuates SARS‐CoV‐2 nucleocapsid protein‐caused hyperinflammation by inactivating the NLRP3 inflammasome through the VDR‐BRCC3 signaling pathway in vitro and in vivo, MedComm, doi:10.1002/mco2.318.wiley.com, doi.org.

15. Rybakovsky et al., Calcitriol modifies tight junctions, improves barrier function, and reduces TNF‐α‐induced barrier leak in the human lung‐derived epithelial cell culture model, 16HBE 14o‐, Physiological Reports, doi:10.14814/phy2.15592.wiley.com, doi.org.

16. DiGuilio et al., The multiphasic TNF-α-induced compromise of Calu-3 airway epithelial barrier function, Experimental Lung Research, doi:10.1080/01902148.2023.2193637.tandfonline.com, doi.org.

17. Pickard et al., Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells, PLOS Pathogens, doi:10.1371/journal.ppat.1009840.plos.org, doi.org.

18. Mok et al., Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis, bioRxiv, doi:10.1101/2020.06.21.162396.biorxiv.org, doi.org.

19. Fernandes de Souza et al., Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D, Cells, doi:10.3390/cells12071092.mdpi.com, doi.org.

20. Galmés et al., Suboptimal Consumption of Relevant Immune System Micronutrients Is Associated with a Worse Impact of COVID-19 in Spanish Populations, Nutrients, doi:10.3390/nu14112254.mdpi.com, doi.org.

21. Galmés (B) et al., Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework, Nutrients, doi:10.3390/nu12092738.mdpi.com, doi.org.

22. EFSA, Scientific Opinion on the substantiation of a health claim related to vitamin D and contribution to the normal function of the immune system pursuant to Article 14 of Regulation (EC) No 1924/2006, EFSA Journal, doi:10.2903/j.efsa.2015.4096.europa.eu, doi.org.

23. EFSA (B), Scientific Opinion on the substantiation of health claims related to vitamin D and normal function of the immune system and inflammatory response (ID 154, 159), maintenance of normal muscle function (ID 155) and maintenance of normal cardiovascular function (ID 159) pursuant to Article 13(1) of Regulation (E, EFSA Journal, doi:10.2903/j.efsa.2010.1468.wiley.com, doi.org.

24. Gotelli et al., Understanding the immune-endocrine effects of vitamin D in SARS-CoV-2 infection: a role in protecting against neurodamage?, Neuroimmunomodulation, doi:10.1159/000533286.karger.com, doi.org.

25. Saheb Sharif-Askari et al., Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons, Scientific Reports, doi:10.1038/s41598-023-43675-w.nature.com, doi.org.

26. Graydon et al., High baseline frequencies of natural killer cells are associated with asymptomatic SARS-CoV-2 infection, Current Research in Immunology, doi:10.1016/j.crimmu.2023.100064.sciencedirect.com, doi.org.

27. Oh et al., Vitamin D and Exercise Are Major Determinants of Natural Killer Cell Activity, Which Is Age- and Gender-Specific, Frontiers in Immunology, doi:10.3389/fimmu.2021.594356.frontiersin.org, doi.org.

Vargas-Castro et al., 7 Nov 2023, peer-reviewed, 6 authors. Contact: lorenza.diazn@incmnsz.mx (corresponding author), lorenza.diazn@incmnsz.mx (corresponding author), rrvvcc14@gmail.com, janice.garciaq@incmnsz.mx, euclides.avilac@incmnsz.mx, fernando.larreag@incmnsz.mx, nut.aolmos@gmail.com.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Vitamin D All

Calcitriol Downregulates ACE1/ACE2, Renin and TMPRSS2 Gene Expression in the Human Placenta

Rafael Vargas-Castro, Andrea Olmos-Ortiz, Janice García-Quiroz, Euclides Avila, Fernando Larrea, Lorenza Díaz

doi:10.20944/preprints202311.0402.v1

Angiotensin-converting enzyme (ACE)1, ACE2, and renin are components of the renin-angiotensin system (RAS), which regulates blood pressure. ACE2 also serves as a receptor for SARS-CoV-2 and together with the transmembrane serine protease 2 (TMPRSS-2), mediates viral cell-endocytosis. As the placenta expresses all these factors, it acts as a target for SARS-CoV-2 and also as a source of blood pressure modulators. An ACE1/ACE2 ratio imbalance can lead to RAS dysregulation and a bad prognosis in COVID-19 patients. Calcitriol, the vitamin D active metabolite, negatively regulates RAS, reduces inflammation, and enhances antiviral immunity, thereby playing a protective role against COVID-19 severity. Placental calcitriol has been inversely correlated with maternal blood pressure; however, its regulatory role in RAS components and SARS-CoV-2 receptors within the fetomaternal unit has been barely explored. Therefore, we investigated the effects of calcitriol on placental RAS components. Calcitriol downregulated ACE1, ACE2, TMPRSS-2, and renin gene expression in cultured syncytiotrophoblasts and the extravillous trophoblast cell line HTR-8/SVneo. The ACE1/ACE2 ratio was also downregulated by calcitriol. Similar results were obtained in syncytiotrophoblasts treated with calcidiol, the precursor of calcitriol. Altogether, these results support that vitamin D is essential in restricting SARS-CoV-2 placental infection while helping to regulate maternal blood pressure during pregnancy.

Funding: This study was supported by the Annual Acquisition Program from the Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, REF 2221 to L.D. The funders had no role in the study design, analysis and interpretation of the data, writing of the manuscript or the decision to submit the article for publication. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable Conflicts of Interest: The authors declare no conflict of interest.

References

Abate, Kassie, Kassaw, Aragie, Masresha, Sex difference in coronavirus disease (COVID-19): a systematic review and meta-analysis, BMJ Open, doi:10.1136/bmjopen-2020-040129

Alexander, Cockrell, Massey, Bennett, Granger, Tumor necrosis factor-alphainduced hypertension in pregnant rats results in decreased renal neuronal nitric oxide synthase expression, Am J Hypertens, doi:10.1016/s0895-7061(01)02255-5

Aranow, Vitamin D and the immune system, J Investig Med, doi:10.2310/JIM.0b013e31821b8755

Arboleda, Urcuqui-Inchima, Vitamin D Supplementation: A Potential Approach for Coronavirus/COVID-19 Therapeutics?, Front Immunol, doi:10.3389/fimmu.2020.01523

Ashique, Gupta, Gupta, Mishra, Singh et al., Vitamin D-A prominent immunomodulator to prevent COVID-19 infection, Int J Rheum Dis, doi:10.1111/1756-185X.14477

Barrera, Avila, Hernandez, Halhali, Biruete et al., Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol, J Steroid Biochem Mol Biol, doi:10.1016/j.jsbmb.2006.12.097

Barrera, Avila, Hernandez, Mendez, Gonzalez et al., Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts, Reprod Biol Endocrinol, doi:10.1186/1477-7827-6-3

Bloise, Zhang, Nakpu, Hamada, Dunk et al., Expression of severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensinconverting enzyme 2 and transmembrane protease serine 2, in the placenta across gestation and at the maternal-fetal interface in pregnancies complicated by preterm birth or preeclampsia, Am J Obstet Gynecol, doi:10.1016/j.ajog.2020.08.055

Botto, Lonati, Russo, Cazzaniga, Bulbarelli et al., Effects of PM2.5 Exposure on the ACE/ACE2 Pathway: Possible Implication in COVID-19 Pandemic, Int J Environ Res Public Health, doi:10.3390/ijerph20054393

Chen, Neil, Tan, Rudraraju, Mohenska et al., A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts, Nat Cell Biol, doi:10.1038/s41556-023-01182-0

Chen, Zheng, Wang, Li, Zhang et al., Regulatory Effect of Vitamin D on Renin Expression at Maternal-Fetal Interface, Sichuan Da Xue Xue Bao Yi Xue Ban, doi:10.12182/20220860107

Colotta, Jansson, Bonelli, Modulation of inflammatory and immune responses by vitamin D, J Autoimmun, doi:10.1016/j.jaut.2017.07.007

Diaz, Noyola-Martinez, Barrera, Hernandez, Avila et al., Calcitriol inhibits TNF-alpha-induced inflammatory cytokines in human trophoblasts, J Reprod Immunol, doi:10.1016/j.jri.2009.02.005

Diaz, Sanchez, Avila, Halhali, Vilchis et al., Identification of a 25-hydroxyvitamin D3 1alpha-hydroxylase gene transcription product in cultures of human syncytiotrophoblast cells, J Clin Endocrinol Metab, doi:10.1210/jcem.85.7.6693

Forman, Scott, Ng, Drake, Suarez et al., Effect of vitamin D supplementation on blood pressure in blacks, Hypertension, doi:10.1161/HYPERTENSIONAHA.111.00659

Gilani, Bin-Jumah, Nadeem, Kazmi, Vitamin D attenuates COVID-19 complications via modulation of proinflammatory cytokines, antiviral proteins, and autophagy, Expert Rev Anti Infect Ther, doi:10.1080/14787210.2021.1941871

Glinsky, Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells, Biomedicines, doi:10.3390/biomedicines8050129

Gomez, Albaiceta, Garcia-Clemente, Lopez-Larrea, Amado-Rodriguez et al., Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome, Gene, doi:10.1016/j.gene.2020.145102

Granger, Alexander, Bennett, Khalil, Pathophysiology of pregnancy-induced hypertension, Am J Hypertens, doi:10.1016/s0895-7061(01)02086-6

Grover, Brandt, Reddy, Ananth, Chronic hypertension, perinatal mortality and the impact of preterm delivery: a population-based study, BJOG, doi:10.1111/1471-0528.16932

Hoffmann, Kleine-Weber, Schroeder, Kruger, Herrler et al., SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor, Cell, doi:10.1016/j.cell.2020.02.052

Hosier, Farhadian, Morotti, Deshmukh, Lu-Culligan et al., SARS-CoV-2 infection of the placenta, J Clin Invest, doi:10.1172/JCI139569

Iwata-Yoshikawa, Okamura, Shimizu, Hasegawa, Takeda et al., TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection, J Virol, doi:10.1128/JVI.01815-18

Jackson, Farzan, Chen, Choe, Mechanisms of SARS-CoV-2 entry into cells, Nat Rev Mol Cell Biol, doi:10.1038/s41580-021-00418-x

Kliman, Nestler, Sermasi, Sanger, Strauss, 3rd. Purification, characterization, and in vitro differentiation of cytotrophoblasts from human term placentae, Endocrinology

Kristal-Boneh, Froom, Harari, Ribak, Association of calcitriol and blood pressure in normotensive men, Hypertension, doi:10.1161/01.hyp.30.5.1289

Lai, Chang, Yang, Lin, Lai et al., The role of micronutrient and immunomodulation effect in the vaccine era of COVID-19, J Chin Med Assoc, doi:10.1097/JCMA.0000000000000587

Li, Kong, Wei, Chen, Liu et al., 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system, J Clin Invest, doi:10.1172/JCI15219

Li, Qiao, Uskokovic, Xiang, Zheng et al., Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure, J Steroid Biochem Mol Biol, doi:10.1016/j.jsbmb.2004.03.004

Li, Vitamin D regulation of the renin-angiotensin system, J Cell Biochem, doi:10.1002/jcb.10343

Lin, Ferguson, White, Wang, Vessella et al., Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2, Cancer Res

Lind, Hanni, Lithell, Hvarfner, Sorensen et al., Vitamin D is related to blood pressure and other cardiovascular risk factors in middle-aged men, Am J Hypertens, doi:10.1016/0895-7061(95)00154-H

Lind, Lithell, Skarfors, Wide, Ljunghall, Reduction of blood pressure by treatment with alphacalcidol. A double-blind, placebo-controlled study in subjects with impaired glucose tolerance, Acta Med Scand

Lind, Wengle, Wide, Ljunghall, Reduction of blood pressure during long-term treatment with active vitamin D (alphacalcidol) is dependent on plasma renin activity and calcium status. A double-blind, placebo-controlled study, Am J Hypertens, doi:10.1093/ajh/2.1.20

Liu, Kaplan, Lagishetty, Ouyang, Ouyang et al., Vitamin D and the regulation of placental inflammation, J Immunol, doi:10.4049/jimmunol.1003332

Liu, Kaplan, Low, Nguyen, Liu et al., Vitamin D induces innate antibacterial responses in human trophoblasts via an intracrine pathway, Biol Reprod, doi:10.1095/biolreprod.108.073577

Lye, Dunk, Zhang, Wei, Nakpu et al., ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth, Cells, doi:10.3390/cells10071724

Ma, Gu, Zhao, Sun, Groome et al., Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies, Am J Physiol Endocrinol Metab, doi:10.1152/ajpendo.00279.2012

Marques, Pringle, Conquest, Hirst, Markus et al., Molecular characterization of renin-angiotensin system components in human intrauterine tissues and fetal membranes from vaginal delivery and cesarean section, Placenta, doi:10.1016/j.placenta.2010.12.006

Molina, Tsai, Dai, Soto, Rosenthal et al., Comparison of Pregnancy and Birth Outcomes Before vs During the COVID-19 Pandemic, JAMA Netw Open, doi:10.1001/jamanetworkopen.2022.26531

Moukayed, A Narrative Review on the Potential Role of Vitamin D(3) in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19, Curr Nutr Rep, doi:10.1007/s13668-023-00471-2

Olmos-Ortiz, Garcia-Quiroz, Avila, Caldino-Soto, Halhali et al., Lipopolysaccharide and cAMP modify placental calcitriol biosynthesis reducing antimicrobial peptides gene expression, Am J Reprod Immunol, doi:10.1111/aji.12841

Olmos-Ortiz, Olivares-Huerta, Garcia-Quiroz, Avila, Halhali et al., Cord Serum Calcitriol Inversely Correlates with Maternal Blood Pressure in Urinary Tract Infection-Affected Pregnancies: Sex-Dependent Immune Implications, Nutrients, doi:10.3390/nu13093114

Pagliaro, Penna, ACE/ACE2 Ratio: A Key Also in 2019 Coronavirus Disease (Covid-19)?, Front Med, doi:10.3389/fmed.2020.00335

Patane, Morotti, Giunta, Sigismondi, Piccoli et al., Vertical transmission of coronavirus disease 2019: severe acute respiratory syndrome coronavirus 2 RNA on the fetal side of the placenta in pregnancies with coronavirus disease 2019-positive mothers and neonates at birth, Am J Obstet Gynecol MFM, doi:10.1016/j.ajogmf.2020.100145

Pfeifer, Begerow, Minne, Nachtigall, Hansen, Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women, J Clin Endocrinol Metab, doi:10.1210/jcem.86.4.7393

Pringle, Tadros, Callister, Lumbers, The expression and localization of the human placental prorenin/renin-angiotensin system throughout pregnancy: roles in trophoblast invasion and angiogenesis?, Placenta, doi:10.1016/j.placenta.2011.09.020

Qayyum, Mohammad, Slominski, Hassan, Tuckey et al., Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 replication machinery enzymes, Am J Physiol Endocrinol Metab, doi:10.1152/ajpendo.00174.2021

Qayyum, Slominski, Raman, Slominski, Novel CYP11A1-Derived Vitamin D and Lumisterol Biometabolites for the Management of COVID-19, Nutrients, doi:10.3390/nu14224779

Ruan, Ye, Yuan, Li, Zhang et al., Human early syncytiotrophoblasts are highly susceptible to SARS-CoV-2 infection, Cell Rep Med, doi:10.1016/j.xcrm.2022.100849

Rysz, Al-Saadi, Sjostrom, Farm, Campoccia Jalde et al., COVID-19 pathophysiology may be driven by an imbalance in the reninangiotensin-aldosterone system, Nat Commun, doi:10.1038/s41467-021-22713-z

Schwartz, Baldewijns, Benachi, Bugatti, Collins et al., Chronic Histiocytic Intervillositis With Trophoblast Necrosis Is a Risk Factor Associated With Placental Infection From Coronavirus Disease 2019 (COVID-19) and Intrauterine Maternal-Fetal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission in Live-Born and Stillborn Infants, Arch Pathol Lab Med, doi:10.5858/arpa.2020-0771-SA

Shen, Mao, Wu, Tanaka, Zhang, TMPRSS2: A potential target for treatment of influenza virus and coronavirus infections, Biochimie, doi:10.1016/j.biochi.2017.07.016

Shoemark, Colenso, Toelzer, Gupta, Sessions et al., Molecular Simulations suggest Vitamins, Retinoids and Steroids as Ligands of the Free Fatty Acid Pocket of the SARS-CoV-2 Spike Protein*, Angew Chem Int Ed Engl, doi:10.1002/anie.202015639

Shook, Bordt, Meinsohn, Pepin, De Guzman et al., Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?, J Infect Dis

Siblini, Kulkarni, Aslam, Coronavirus Disease 2019 (COVID-19) and Hypertensive Disorders of Pregnancy: Is the Placenta the Problem?, doi:10.17632/8tbym9x6md.1

Song, Qayyum, Greer, Slominski, Raman et al., Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study, J Biomol Struct Dyn, doi:10.1080/07391102.2021.1964601

Sriram, Insel, A hypothesis for pathobiology and treatment of COVID-19: The centrality of ACE1/ACE2 imbalance, Br J Pharmacol, doi:10.1111/bph.15082

Stephanou, Ross, Handwerger, Regulation of human placental lactogen expression by 1,25-dihydroxyvitamin D3, Endocrinology, doi:10.1210/endo.135.6.7988455

Taglauer, Benarroch, Rop, Barnett, Sabharwal et al., Consistent localization of SARS-CoV-2 spike glycoprotein and ACE2 over TMPRSS2 predominance in placental villi of 15 COVID-19 positive maternal-fetal dyads, Placenta, doi:10.1016/j.placenta.2020.08.015

Takimoto, Ishida, Sugiyama, Horiguchi, Murakami et al., Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen, Science, doi:10.1126/science.274.5289.995

Tamanna, Lumbers, Morosin, Delforce, Pringle, ACE2: a key modulator of the reninangiotensin system and pregnancy, Am J Physiol Regul Integr Comp Physiol, doi:10.1152/ajpregu.00211.2021

Valdespino-Vazquez, Helguera-Repetto, Leon-Juarez, Villavicencio-Carrisoza, Flores-Pliego et al., Fetal and placental infection with SARS-CoV-2 in early pregnancy, J Med Virol, doi:10.1002/jmv.26965

Vanegas-Cedillo, Bello-Chavolla, Ramirez-Pedraza, Rodriguez Encinas, Perez Carrion et al., Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity and Mortality Independent of Whole-Body and Visceral Adiposity, Front Nutr, doi:10.3389/fnut.2022.813485

Zhang, Dong, Liu, Gao, Risk and Protective Factors for COVID-19 Morbidity, Severity, and Mortality, Clin Rev Allergy Immunol, doi:10.1007/s12016-022-08921-5

{ 'indexed': { 'date-parts': [[2024, 11, 7]], 'date-time': '2024-11-07T05:13:23Z', 'timestamp': 1730956403401, 'version': '3.28.0'}, 'reference-count': 77, 'publisher': 'Elsevier BV', 'license': [ { 'start': { 'date-parts': [[2024, 11, 1]], 'date-time': '2024-11-01T00:00:00Z', 'timestamp': 1730419200000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'}, { 'start': { 'date-parts': [[2024, 11, 1]], 'date-time': '2024-11-01T00:00:00Z', 'timestamp': 1730419200000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://www.elsevier.com/legal/tdmrep-license'}, { 'start': { 'date-parts': [[2024, 11, 1]], 'date-time': '2024-11-01T00:00:00Z', 'timestamp': 1730419200000}, 'content-version': 'stm-asf', 'delay-in-days': 0, 'URL': 'https://doi.org/10.15223/policy-017'}, { 'start': { 'date-parts': [[2024, 11, 1]], 'date-time': '2024-11-01T00:00:00Z', 'timestamp': 1730419200000}, 'content-version': 'stm-asf', 'delay-in-days': 0, 'URL': 'https://doi.org/10.15223/policy-037'}, { 'start': { 'date-parts': [[2024, 11, 1]], 'date-time': '2024-11-01T00:00:00Z', 'timestamp': 1730419200000}, 'content-version': 'stm-asf', 'delay-in-days': 0, 'URL': 'https://doi.org/10.15223/policy-012'}, { 'start': { 'date-parts': [[2024, 11, 1]], 'date-time': '2024-11-01T00:00:00Z', 'timestamp': 1730419200000}, 'content-version': 'stm-asf', 'delay-in-days': 0, 'URL': 'https://doi.org/10.15223/policy-029'}, { 'start': { 'date-parts': [[2024, 11, 1]], 'date-time': '2024-11-01T00:00:00Z', 'timestamp': 1730419200000}, 'content-version': 'stm-asf', 'delay-in-days': 0, 'URL': 'https://doi.org/10.15223/policy-004'}], 'content-domain': {'domain': ['elsevier.com', 'sciencedirect.com'], 'crossmark-restriction': True}, 'published-print': {'date-parts': [[2024, 11]]}, 'DOI': '10.1016/j.jsbmb.2024.106625', 'type': 'journal-article', 'created': {'date-parts': [[2024, 11, 6]], 'date-time': '2024-11-06T08:16:30Z', 'timestamp': 1730880990000}, 'page': '106625', 'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Calcitriol prevents SARS-CoV Spike-induced inflammation in human trophoblasts through ' 'downregulating ACE2 and TMPRSS2 expression', 'prefix': '10.1016', 'author': [ {'given': 'Rafael', 'family': 'Vargas-Castro', 'sequence': 'first', 'affiliation': []}, {'given': 'Janice', 'family': 'García-Quiroz', 'sequence': 'additional', 'affiliation': []}, {'given': 'Andrea', 'family': 'Olmos-Ortiz', 'sequence': 'additional', 'affiliation': []}, {'given': 'Euclides', 'family': 'Avila', 'sequence': 'additional', 'affiliation': []}, {'given': 'Fernando', 'family': 'Larrea', 'sequence': 'additional', 'affiliation': []}, {'given': 'Lorenza', 'family': 'Díaz', 'sequence': 'additional', 'affiliation': []}], 'member': '78', 'reference': [ { 'key': '10.1016/j.jsbmb.2024.106625_bib1', 'doi-asserted-by': 'crossref', 'first-page': '78', 'DOI': '10.1016/j.jaut.2017.07.007', 'article-title': 'Modulation of inflammatory and immune responses by vitamin D', 'volume': '85', 'author': 'Colotta', 'year': '2017', 'journal-title': 'J Autoimmun'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib2', 'doi-asserted-by': 'crossref', 'first-page': '17', 'DOI': '10.1016/j.jri.2009.02.005', 'article-title': 'Calcitriol inhibits TNF-alpha-induced inflammatory cytokines in human ' 'trophoblasts', 'volume': '81', 'author': 'Diaz', 'year': '2009', 'journal-title': 'J Reprod Immunol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib3', 'doi-asserted-by': 'crossref', 'first-page': '5968', 'DOI': '10.4049/jimmunol.1003332', 'article-title': 'Vitamin D and the regulation of placental inflammation', 'volume': '186', 'author': 'Liu', 'year': '2011', 'journal-title': 'J Immunol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib4', 'doi-asserted-by': 'crossref', 'first-page': '881', 'DOI': '10.2310/JIM.0b013e31821b8755', 'article-title': 'Vitamin D and the immune system', 'volume': '59', 'author': 'Aranow', 'year': '2011', 'journal-title': 'J Investig Med'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib5', 'first-page': '398', 'article-title': 'Vitamin D induces innate antibacterial responses in human trophoblasts ' 'via an intracrine pathway, Biol Reprod', 'volume': '80', 'author': 'Liu', 'year': '2009'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib6', 'doi-asserted-by': 'crossref', 'first-page': '529', 'DOI': '10.1016/j.jsbmb.2006.12.097', 'article-title': 'Estradiol and progesterone synthesis in human placenta is stimulated by ' 'calcitriol', 'volume': '103', 'author': 'Barrera', 'year': '2007', 'journal-title': 'J Steroid Biochem Mol Biol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib7', 'doi-asserted-by': 'crossref', 'first-page': '3', 'DOI': '10.1186/1477-7827-6-3', 'article-title': 'Calcitriol affects hCG gene transcription in cultured human ' 'syncytiotrophoblasts', 'volume': '6', 'author': 'Barrera', 'year': '2008', 'journal-title': 'Reprod Biol Endocrinol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib8', 'doi-asserted-by': 'crossref', 'first-page': '2651', 'DOI': '10.1210/endo.135.6.7988455', 'article-title': 'Regulation of human placental lactogen expression by ' '1,25-dihydroxyvitamin D3', 'volume': '135', 'author': 'Stephanou', 'year': '1994', 'journal-title': 'Endocrinology'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib9', 'doi-asserted-by': 'crossref', 'first-page': '229', 'DOI': '10.1172/JCI0215219', 'article-title': '1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the ' 'renin-angiotensin system', 'volume': '110', 'author': 'Li', 'year': '2002', 'journal-title': 'J Clin Invest'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib10', 'doi-asserted-by': 'crossref', 'first-page': '327', 'DOI': '10.1002/jcb.10343', 'article-title': 'Vitamin D regulation of the renin-angiotensin system', 'volume': '88', 'author': 'Li', 'year': '2003', 'journal-title': 'J Cell Biochem'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib11', 'doi-asserted-by': 'crossref', 'first-page': '387', 'DOI': '10.1016/j.jsbmb.2004.03.004', 'article-title': 'Vitamin D: a negative endocrine regulator of the renin-angiotensin ' 'system and blood pressure', 'volume': '89-90', 'author': 'Li', 'year': '2004', 'journal-title': 'J Steroid Biochem Mol Biol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib12', 'doi-asserted-by': 'crossref', 'DOI': '10.3389/fimmu.2022.957224', 'article-title': 'SARS-CoV-2 modulates virus receptor expression in placenta and can ' 'induce trophoblast fusion, inflammation and endothelial permeability', 'volume': '13', 'author': 'Agostinis', 'year': '2022', 'journal-title': 'Front Immunol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib13', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.gene.2020.145102', 'article-title': 'Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 ' 'outcome', 'volume': '762', 'author': 'Gomez', 'year': '2020', 'journal-title': 'Gene'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib14', 'doi-asserted-by': 'crossref', 'first-page': '289 e217', 'DOI': '10.1016/j.ajog.2021.05.014', 'article-title': 'Preeclampsia and COVID-19: results from the INTERCOVID prospective ' 'longitudinal study', 'volume': '225', 'author': 'Papageorghiou', 'year': '2021', 'journal-title': 'Am J Obstet Gynecol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib15', 'doi-asserted-by': 'crossref', 'first-page': '226', 'DOI': '10.1080/10641955.2021.1965621', 'article-title': 'Coronavirus disease 2019 (COVID-19) and the risk of hypertensive ' 'disorders of pregnancy: a retrospective cohort study', 'volume': '40', 'author': 'Baracy', 'year': '2021', 'journal-title': 'Hypertens Pregnancy'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib16', 'doi-asserted-by': 'crossref', 'DOI': '10.1001/jamanetworkopen.2022.26531', 'article-title': 'Comparison of Pregnancy and Birth Outcomes Before vs During the ' 'COVID-19 Pandemic', 'volume': '5', 'author': 'Molina', 'year': '2022', 'journal-title': 'JAMA Netw Open'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib17', 'doi-asserted-by': 'crossref', 'first-page': '801', 'DOI': '10.1159/000520179', 'article-title': 'Frequent Placental SARS-CoV-2 in Patients with COVID-19-Associated ' 'Hypertensive Disorders of Pregnancy', 'volume': '48', 'author': 'Fabre', 'year': '2021', 'journal-title': 'Fetal Diagn Ther'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib18', 'doi-asserted-by': 'crossref', 'first-page': '13', 'DOI': '10.1111/1756-185X.14477', 'article-title': 'Vitamin D-A prominent immunomodulator to prevent COVID-19 infection', 'volume': '26', 'author': 'Ashique', 'year': '2023', 'journal-title': 'Int J Rheum Dis'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib19', 'doi-asserted-by': 'crossref', 'first-page': '231', 'DOI': '10.1080/14787210.2021.1941871', 'article-title': 'Vitamin D attenuates COVID-19 complications via modulation of ' 'proinflammatory cytokines, antiviral proteins, and autophagy', 'volume': '20', 'author': 'Gilani', 'year': '2022', 'journal-title': 'Expert Rev Anti Infect Ther'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib20', 'doi-asserted-by': 'crossref', 'first-page': '215', 'DOI': '10.1007/s13668-023-00471-2', 'article-title': 'A Narrative Review on the Potential Role of Vitamin D(3) in the ' 'Prevention, Protection, and Disease Mitigation of Acute and Long ' 'COVID-19', 'volume': '12', 'author': 'Moukayed', 'year': '2023', 'journal-title': 'Curr Nutr Rep'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib21', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.lfs.2022.120909', 'article-title': 'Vitamin D modulates systemic inflammation in patients with severe ' 'COVID-19', 'volume': '307', 'author': 'Sharif-Askari', 'year': '2022', 'journal-title': 'Life Sci'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib22', 'doi-asserted-by': 'crossref', 'first-page': '779', 'DOI': '10.1161/HYPERTENSIONAHA.111.00659', 'article-title': 'Effect of vitamin D supplementation on blood pressure in blacks', 'volume': '61', 'author': 'Forman', 'year': '2013', 'journal-title': 'Hypertension'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib23', 'doi-asserted-by': 'crossref', 'first-page': '1289', 'DOI': '10.1161/01.HYP.30.5.1289', 'article-title': 'Association of calcitriol and blood pressure in normotensive men', 'volume': '30', 'author': 'Kristal-Boneh', 'year': '1997', 'journal-title': 'Hypertension'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib24', 'doi-asserted-by': 'crossref', 'first-page': '894', 'DOI': '10.1016/0895-7061(95)00154-H', 'article-title': 'Vitamin D is related to blood pressure and other cardiovascular risk ' 'factors in middle-aged men', 'volume': '8', 'author': 'Lind', 'year': '1995', 'journal-title': 'Am J Hypertens'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib25', 'doi-asserted-by': 'crossref', 'first-page': '211', 'DOI': '10.1111/j.0954-6820.1988.tb15789.x', 'article-title': 'Reduction of blood pressure by treatment with alphacalcidol. A ' 'double-blind, placebo-controlled study in subjects with impaired ' 'glucose tolerance', 'volume': '223', 'author': 'Lind', 'year': '1988', 'journal-title': 'Acta Med Scand'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib26', 'doi-asserted-by': 'crossref', 'first-page': '20', 'DOI': '10.1093/ajh/2.1.20', 'article-title': 'Reduction of blood pressure during long-term treatment with active ' 'vitamin D (alphacalcidol) is dependent on plasma renin activity and ' 'calcium status. A double-blind, placebo-controlled study', 'volume': '2', 'author': 'Lind', 'year': '1989', 'journal-title': 'Am J Hypertens'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib27', 'first-page': '1633', 'article-title': 'Effects of a short-term vitamin D(3) and calcium supplementation on ' 'blood pressure and parathyroid hormone levels in elderly women', 'volume': '86', 'author': 'Pfeifer', 'year': '2001', 'journal-title': 'J Clin Endocrinol Metab'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib28', 'doi-asserted-by': 'crossref', 'DOI': '10.3390/nu13093114', 'article-title': 'Cord Serum Calcitriol Inversely Correlates with Maternal Blood Pressure ' 'in Urinary Tract Infection-Affected Pregnancies: Sex-Dependent Immune ' 'Implications', 'volume': '13', 'author': 'Olmos-Ortiz', 'year': '2021', 'journal-title': 'Nutrients'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib29', 'doi-asserted-by': 'crossref', 'first-page': '572', 'DOI': '10.1111/1471-0528.16932', 'article-title': 'Chronic hypertension, perinatal mortality and the impact of preterm ' 'delivery: a population-based study', 'volume': '129', 'author': 'Grover', 'year': '2022', 'journal-title': 'BJOG'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib30', 'doi-asserted-by': 'crossref', 'first-page': 'R833', 'DOI': '10.1152/ajpregu.00211.2021', 'article-title': 'ACE2: a key modulator of the renin-angiotensin system and pregnancy', 'volume': '321', 'author': 'Tamanna', 'year': '2021', 'journal-title': 'Am J Physiol Regul Integr Comp Physiol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib31', 'doi-asserted-by': 'crossref', 'first-page': '214', 'DOI': '10.1016/j.placenta.2010.12.006', 'article-title': 'Molecular characterization of renin-angiotensin system components in ' 'human intrauterine tissues and fetal membranes from vaginal delivery ' 'and cesarean section', 'volume': '32', 'author': 'Marques', 'year': '2011', 'journal-title': 'Placenta'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib32', 'doi-asserted-by': 'crossref', 'first-page': '956', 'DOI': '10.1016/j.placenta.2011.09.020', 'article-title': 'The expression and localization of the human placental ' 'prorenin/renin-angiotensin system throughout pregnancy: roles in ' 'trophoblast invasion and angiogenesis?', 'volume': '32', 'author': 'Pringle', 'year': '2011', 'journal-title': 'Placenta'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib33', 'doi-asserted-by': 'crossref', 'first-page': '69', 'DOI': '10.1016/j.placenta.2020.08.015', 'article-title': 'Consistent localization of SARS-CoV-2 spike glycoprotein and ACE2 over ' 'TMPRSS2 predominance in placental villi of 15 COVID-19 positive ' 'maternal-fetal dyads', 'volume': '100', 'author': 'Taglauer', 'year': '2020', 'journal-title': 'Placenta'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib34', 'doi-asserted-by': 'crossref', 'first-page': '3', 'DOI': '10.1038/s41580-021-00418-x', 'article-title': 'Mechanisms of SARS-CoV-2 entry into cells', 'volume': '23', 'author': 'Jackson', 'year': '2022', 'journal-title': 'Nat Rev Mol Cell Biol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib35', 'doi-asserted-by': 'crossref', 'first-page': '4947', 'DOI': '10.1172/JCI139569', 'article-title': 'SARS-CoV-2 infection of the placenta', 'volume': '130', 'author': 'Hosier', 'year': '2020', 'journal-title': 'J Clin Invest'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib36', 'doi-asserted-by': 'crossref', 'first-page': '271', 'DOI': '10.1016/j.cell.2020.02.052', 'article-title': 'SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a ' 'Clinically Proven Protease Inhibitor', 'volume': '181', 'author': 'Hoffmann', 'year': '2020', 'journal-title': 'Cell'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib37', 'doi-asserted-by': 'crossref', 'DOI': '10.3389/fnut.2022.813485', 'article-title': 'Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity ' 'and Mortality Independent of Whole-Body and Visceral Adiposity', 'volume': '9', 'author': 'Vanegas-Cedillo', 'year': '2022', 'journal-title': 'Front Nutr'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib38', 'doi-asserted-by': 'crossref', 'first-page': '1523', 'DOI': '10.3389/fimmu.2020.01523', 'article-title': 'Vitamin D Supplementation: A Potential Approach for ' 'Coronavirus/COVID-19 Therapeutics?', 'volume': '11', 'author': 'Arboleda', 'year': '2020', 'journal-title': 'Front Immunol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib39', 'doi-asserted-by': 'crossref', 'DOI': '10.1111/aji.12841', 'article-title': 'Lipopolysaccharide and cAMP modify placental calcitriol biosynthesis ' 'reducing antimicrobial peptides gene expression', 'volume': '79', 'author': 'Olmos-Ortiz', 'year': '2018', 'journal-title': 'Am J Reprod Immunol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib40', 'doi-asserted-by': 'crossref', 'first-page': '1567', 'DOI': '10.1210/endo-118-4-1567', 'article-title': '3rd, Purification, characterization, and in vitro differentiation of ' 'cytotrophoblasts from human term placentae', 'volume': '118', 'author': 'Kliman', 'year': '1986', 'journal-title': 'Endocrinology'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib41', 'series-title': 'Maternal Placental Interface: Methods and Protocols', 'first-page': '47', 'article-title': 'In Vitro Culturing of Human Trophoblasts from Term Placenta', 'author': 'Díaz', 'year': '2024'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib42', 'doi-asserted-by': 'crossref', 'first-page': '25', 'DOI': '10.1016/j.cytogfr.2020.05.003', 'article-title': 'The cytokine storm in COVID-19: An overview of the involvement of the ' 'chemokine/chemokine-receptor system', 'volume': '53', 'author': 'Coperchini', 'year': '2020', 'journal-title': 'Cytokine Growth Factor Rev'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib43', 'doi-asserted-by': 'crossref', 'first-page': '202', 'DOI': '10.1002/uog.24798', 'article-title': 'Increased levels of soluble fms-like tyrosine kinase-1 are associated ' 'with adverse outcome in pregnant women with COVID-19', 'volume': '59', 'author': 'Torres-Torres', 'year': '2022', 'journal-title': 'Ultrasound Obstet Gynecol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib44', 'doi-asserted-by': 'crossref', 'first-page': '2252', 'DOI': '10.1210/jc.2009-0945', 'article-title': 'Preeclampsia and soluble fms-like tyrosine kinase 1', 'volume': '94', 'author': 'Roberts', 'year': '2009', 'journal-title': 'J Clin Endocrinol Metab'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib45', 'doi-asserted-by': 'crossref', 'DOI': '10.3390/cells10071724', 'article-title': 'ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in ' 'Infection-Associated Preterm Birth', 'volume': '10', 'author': 'Lye', 'year': '2021', 'journal-title': 'Cells'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib46', 'doi-asserted-by': 'crossref', 'first-page': '335', 'DOI': '10.3389/fmed.2020.00335', 'article-title': 'ACE/ACE2 Ratio: A Key Also in 2019 Coronavirus Disease (Covid-19)?', 'volume': '7', 'author': 'Pagliaro', 'year': '2020', 'journal-title': 'Front Med (Lausanne)'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib47', 'doi-asserted-by': 'crossref', 'DOI': '10.3390/ijerph20054393', 'article-title': 'Effects of PM2.5 Exposure on the ACE/ACE2 Pathway: Possible Implication ' 'in COVID-19 Pandemic', 'volume': '20', 'author': 'Botto', 'year': '2023', 'journal-title': 'Int J Environ Res Public Health'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib48', 'doi-asserted-by': 'crossref', 'first-page': '298 e291', 'DOI': '10.1016/j.ajog.2020.08.055', 'volume': '224', 'author': 'Bloise', 'year': '2021', 'journal-title': 'Am J Obstet Gynecol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib49', 'doi-asserted-by': 'crossref', 'first-page': '4480', 'DOI': '10.1002/jmv.26965', 'article-title': 'Fetal and placental infection with SARS-CoV-2 in early pregnancy', 'volume': '93', 'author': 'Valdespino-Vazquez', 'year': '2021', 'journal-title': 'J Med Virol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib50', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.ajogmf.2020.100145', 'article-title': 'Vertical transmission of coronavirus disease 2019: severe acute ' 'respiratory syndrome coronavirus 2 RNA on the fetal side of the ' 'placenta in pregnancies with coronavirus disease 2019-positive mothers ' 'and neonates at birth', 'volume': '2', 'author': 'Patane', 'year': '2020', 'journal-title': 'Am J Obstet Gynecol MFM'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib51', 'doi-asserted-by': 'crossref', 'first-page': '387', 'DOI': '10.1177/10668969221102534', 'article-title': 'Placental Pathology After SARS-CoV-2 Infection in the Pre-Variant of ' 'Concern, Alpha / Gamma, Delta, or Omicron Eras', 'volume': '31', 'author': 'Shanes', 'year': '2023', 'journal-title': 'Int J Surg Pathol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib52', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.bbadis.2022.166582', 'article-title': 'Functional consequences of SARS-CoV-2 infection in pregnant women, ' 'fetoplacental unit, and neonate', 'volume': '1869', 'author': 'Carvajal', 'year': '2023', 'journal-title': 'Biochim Biophys Acta Mol Basis Dis'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib53', 'article-title': 'Human early syncytiotrophoblasts are highly susceptible to SARS-CoV-2 ' 'infection', 'volume': '3', 'author': 'Ruan', 'year': '2022', 'journal-title': 'Cell Rep Med'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib54', 'doi-asserted-by': 'crossref', 'first-page': '1223', 'DOI': '10.1038/s41556-023-01182-0', 'article-title': 'A placental model of SARS-CoV-2 infection reveals ACE2-dependent ' 'susceptibility and differentiation impairment in syncytiotrophoblasts', 'volume': '25', 'author': 'Chen', 'year': '2023', 'journal-title': 'Nat Cell Biol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib55', 'doi-asserted-by': 'crossref', 'DOI': '10.3390/biomedicines8050129', 'volume': '8', 'author': 'Glinsky', 'year': '2020', 'journal-title': 'Biomedicines'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib56', 'doi-asserted-by': 'crossref', 'DOI': '10.1128/JVI.01815-18', 'article-title': 'TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways ' 'of Murine Models after Coronavirus Infection', 'volume': '93', 'author': 'Iwata-Yoshikawa', 'year': '2019', 'journal-title': 'J Virol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib57', 'first-page': '4180', 'article-title': 'Prostate-localized and androgen-regulated expression of the ' 'membrane-bound serine protease TMPRSS2', 'volume': '59', 'author': 'Lin', 'year': '1999', 'journal-title': 'Cancer Res'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib58', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1016/j.biochi.2017.07.016', 'article-title': 'TMPRSS2: A potential target for treatment of influenza virus and ' 'coronavirus infections', 'volume': '142', 'author': 'Shen', 'year': '2017', 'journal-title': 'Biochimie'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib59', 'doi-asserted-by': 'crossref', 'DOI': '10.1136/bmjopen-2020-040129', 'article-title': 'Sex difference in coronavirus disease (COVID-19): a systematic review ' 'and meta-analysis', 'volume': '10', 'author': 'Abate', 'year': '2020', 'journal-title': 'BMJ Open'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib60', 'doi-asserted-by': 'crossref', 'first-page': '90', 'DOI': '10.1007/s12016-022-08921-5', 'article-title': 'Risk and Protective Factors for COVID-19 Morbidity, Severity, and ' 'Mortality', 'volume': '64', 'author': 'Zhang', 'year': '2023', 'journal-title': 'Clin Rev Allergy Immunol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib61', 'doi-asserted-by': 'crossref', 'first-page': 'S647', 'DOI': '10.1093/infdis/jiab335', 'article-title': 'Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute ' 'Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses ' 'Mediated by Fetal Sex?', 'volume': '224', 'author': 'Shook', 'year': '2021', 'journal-title': 'J Infect Dis'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib62', 'doi-asserted-by': 'crossref', 'first-page': '173', 'DOI': '10.1016/j.jsbmb.2016.05.017', 'article-title': 'Evidence of sexual dimorphism in placental vitamin D metabolism: ' 'Testosterone inhibits calcitriol-dependent cathelicidin expression', 'volume': '163', 'author': 'Olmos-Ortiz', 'year': '2016', 'journal-title': 'J Steroid Biochem Mol Biol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib63', 'doi-asserted-by': 'crossref', 'first-page': '591', 'DOI': '10.1016/j.medj.2021.04.016', 'article-title': 'Maternal respiratory SARS-CoV-2 infection in pregnancy is associated ' 'with a robust inflammatory response at the maternal-fetal interface', 'volume': '2', 'author': 'Lu-Culligan', 'year': '2021', 'journal-title': 'Med'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib64', 'doi-asserted-by': 'crossref', 'DOI': '10.1038/s41598-023-41115-3', 'article-title': 'SARS-CoV-2 spike protein induces endothelial inflammation via ACE2 ' 'independently of viral replication', 'volume': '13', 'author': 'Montezano', 'year': '2023', 'journal-title': 'Sci Rep'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib65', 'doi-asserted-by': 'crossref', 'first-page': '11594', 'DOI': '10.1080/07391102.2021.1964601', 'article-title': 'Vitamin D3 and its hydroxyderivatives as promising drugs against ' 'COVID-19: a computational study', 'volume': '40', 'author': 'Song', 'year': '2022', 'journal-title': 'J Biomol Struct Dyn'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib66', 'doi-asserted-by': 'crossref', 'DOI': '10.3390/nu14224779', 'article-title': 'Novel CYP11A1-Derived Vitamin D and Lumisterol Biometabolites for the ' 'Management of COVID-19', 'volume': '14', 'author': 'Qayyum', 'year': '2022', 'journal-title': 'Nutrients'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib67', 'doi-asserted-by': 'crossref', 'first-page': '7098', 'DOI': '10.1002/anie.202015639', 'article-title': 'Molecular Simulations suggest Vitamins, Retinoids and Steroids as ' 'Ligands of the Free Fatty Acid Pocket of the SARS-CoV-2 Spike Protein⁎', 'volume': '60', 'author': 'Shoemark', 'year': '2021', 'journal-title': 'Angew Chem Int Ed Engl'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib68', 'doi-asserted-by': 'crossref', 'first-page': 'E246', 'DOI': '10.1152/ajpendo.00174.2021', 'article-title': 'Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 ' 'replication machinery enzymes', 'volume': '321', 'author': 'Qayyum', 'year': '2021', 'journal-title': 'Am J Physiol Endocrinol Metab'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib69', 'doi-asserted-by': 'crossref', 'first-page': '995', 'DOI': '10.1126/science.274.5289.995', 'article-title': 'Hypertension induced in pregnant mice by placental renin and maternal ' 'angiotensinogen', 'volume': '274', 'author': 'Takimoto', 'year': '1996', 'journal-title': 'Science'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib70', 'doi-asserted-by': 'crossref', 'unstructured': 'T.K. Siblini, S. Aslam, M. Baracy, M.G., COVID-19 and Hypertensive ' 'Disorders of Pregnancy: Is the Placenta the Problem?, 72nd Annual ' 'Clinical and Scientific Meeting of the American College of Obstetrics ' 'and Gynecologists, San Francisco, CA, USA, 2024, pp. 37S.', 'DOI': '10.1097/01.AOG.0001013440.68477.8d'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib71', 'doi-asserted-by': 'crossref', 'first-page': '178S', 'DOI': '10.1016/S0895-7061(01)02086-6', 'article-title': 'Pathophysiology of pregnancy-induced hypertension', 'volume': '14', 'author': 'Granger', 'year': '2001', 'journal-title': 'Am J Hypertens'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib72', 'doi-asserted-by': 'crossref', 'first-page': '170', 'DOI': '10.1016/S0895-7061(01)02255-5', 'article-title': 'Tumor necrosis factor-alpha-induced hypertension in pregnant rats ' 'results in decreased renal neuronal nitric oxide synthase expression', 'volume': '15', 'author': 'Alexander', 'year': '2002', 'journal-title': 'Am J Hypertens'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib73', 'doi-asserted-by': 'crossref', 'first-page': '517', 'DOI': '10.5858/arpa.2020-0771-SA', 'volume': '145', 'author': 'Schwartz', 'year': '2021', 'journal-title': 'Arch Pathol Lab Med'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib74', 'first-page': '1021', 'article-title': '[Regulatory Effect of Vitamin D on Renin Expression at Maternal-Fetal ' 'Interface]', 'volume': '53', 'author': 'Chen', 'year': '2022', 'journal-title': 'Sichuan Da Xue Xue Bao Yi Xue Ban'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib75', 'doi-asserted-by': 'crossref', 'first-page': '2417', 'DOI': '10.1038/s41467-021-22713-z', 'article-title': 'COVID-19 pathophysiology may be driven by an imbalance in the ' 'renin-angiotensin-aldosterone system', 'volume': '12', 'author': 'Rysz', 'year': '2021', 'journal-title': 'Nat Commun'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib76', 'doi-asserted-by': 'crossref', 'first-page': '4825', 'DOI': '10.1111/bph.15082', 'article-title': 'A hypothesis for pathobiology and treatment of COVID-19: The centrality ' 'of ACE1/ACE2 imbalance', 'volume': '177', 'author': 'Sriram', 'year': '2020', 'journal-title': 'Br J Pharmacol'}, { 'key': '10.1016/j.jsbmb.2024.106625_bib77', 'doi-asserted-by': 'crossref', 'first-page': '821', 'DOI': '10.1097/JCMA.0000000000000587', 'article-title': 'The role of micronutrient and immunomodulation effect in the vaccine ' 'era of COVID-19', 'volume': '84', 'author': 'Lai', 'year': '2021', 'journal-title': 'J Chin Med Assoc'}], 'container-title': 'The Journal of Steroid Biochemistry and Molecular Biology', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S0960076024001730?httpAccept=text/xml', 'content-type': 'text/xml', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://api.elsevier.com/content/article/PII:S0960076024001730?httpAccept=text/plain', 'content-type': 'text/plain', 'content-version': 'vor', 'intended-application': 'text-mining'}], 'deposited': { 'date-parts': [[2024, 11, 6]], 'date-time': '2024-11-06T08:16:58Z', 'timestamp': 1730881018000}, 'score': 1, 'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S0960076024001730'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 11]]}, 'references-count': 77, 'alternative-id': ['S0960076024001730'], 'URL': 'http://dx.doi.org/10.1016/j.jsbmb.2024.106625', 'relation': {}, 'ISSN': ['0960-0760'], 'subject': [], 'container-title-short': 'The Journal of Steroid Biochemistry and Molecular Biology', 'published': {'date-parts': [[2024, 11]]}, 'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'}, { 'value': 'Calcitriol prevents SARS-CoV Spike-induced inflammation in human trophoblasts ' 'through downregulating ACE2 and TMPRSS2 expression', 'name': 'articletitle', 'label': 'Article Title'}, { 'value': 'The Journal of Steroid Biochemistry and Molecular Biology', 'name': 'journaltitle', 'label': 'Journal Title'}, { 'value': 'https://doi.org/10.1016/j.jsbmb.2024.106625', 'name': 'articlelink', 'label': 'CrossRef DOI link to publisher maintained version'}, {'value': 'article', 'name': 'content_type', 'label': 'Content Type'}, { 'value': '© 2024 Elsevier Ltd. All rights are reserved, including those for text and data ' 'mining, AI training, and similar technologies.', 'name': 'copyright', 'label': 'Copyright'}], 'article-number': '106625'}

Download Image

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.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0