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Galdo-Torres D, Andreu S, Caballero O, Hernández-Ruiz I, Ripa I, Bello-Morales R, López-Guerrero JA. Immune Modulatory Effects of Vitamin D on Herpesvirus Infections. Int J Mol Sci 2025; 26:1767. [PMID: 40004230 PMCID: PMC11855552 DOI: 10.3390/ijms26041767] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 02/14/2025] [Accepted: 02/17/2025] [Indexed: 02/27/2025] Open
Abstract
In addition to its classical role in calcium and phosphate metabolism regulation, vitamin D also has an important impact on immunity modulation. Vitamin D regulates the immune response, shifting from a proinflammatory state to a more tolerogenic one by increasing the release of anti-inflammatory cytokines while downregulating proinflammatory cytokines. Thus, low levels of vitamin D have been associated with an increased risk of developing autoimmune diseases like multiple sclerosis and type 1 diabetes. Furthermore, this prohormone also enhances the release of well-known antimicrobial peptides, like cathelicidin LL-37 and β-defensins; therefore, it has been proposed that vitamin D serum levels might be related to the risk of well-known pathogen infections, including herpesviruses. These are a group of widely spread viral pathogens that can cause severe encephalitis or tumors like Kaposi's sarcoma and Burkitt lymphoma. However, there is no consensus on the minimum levels of vitamin D or the recommended daily dose, making it difficult to establish a possible association between these two factors. This narrative non-systematic review will analyze the mechanisms by which vitamin D regulates the immune system and recent studies about whether there is an association between vitamin D serum levels and herpesvirus infections.
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Affiliation(s)
| | | | | | | | | | - Raquel Bello-Morales
- Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid, Spain; (D.G.-T.); (O.C.); (I.R.); (J.A.L.-G.)
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Zhao Y, Zhu X, Lan Q, Wei Z, Shang P, Song L, Hu S, Chen L, Gan M, Niu L, Wang Y, Shen L, Zhu L. 1α,25-hydroxyvitamin D 3 alleviated rotavirus infection induced ferroptosis in IPEC-J2 cells by regulating the ATF3-SLC7A11-GPX4 axis. Int J Biol Macromol 2024; 283:137484. [PMID: 39528192 DOI: 10.1016/j.ijbiomac.2024.137484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 11/04/2024] [Accepted: 11/08/2024] [Indexed: 11/16/2024]
Abstract
Rotavirus (RV) mainly infects mature intestinal epithelial cells and impairs intestinal absorption function, which leads to the death of infected cells and eventually fatal diarrhea. Ferroptosis is a novel regulatory cell death pattern, which can be caused by virus infection. 1α,25-hydroxyvitamin D3 (1,25D3) has an anti-RV infection effect and can regulate ferroptosis. However, whether RV infection can induce ferroptosis, and whether 1,25D3 can inhibit RV infection by regulating ferroptosis has not yet been studied. Present study shows that RV infection or erastin treatment induces IPEC-J2 cell death, which results in mitochondrial shrinkage, decreased mitochondrial membrane potential (MMP) and glutathione (GSH) content, increased MMP, intracellular Fe2+, reactive oxygen species (ROS), and malondialdehyde (MDA) contents. Meanwhile, ferrostatin-1 (Fer-1), liproxstatin-1 (Lip-1), and deferoxamine (DFO) treatment can effectively reverse the increase of intracellular Fe2+, ROS and MDA levels induced by RV infection. Moreover, RV infection increases activating transcription factor 3 (ATF3) mRNA and protein expressions, and inhibited SLC7A11 and glutathione peroxidase 4 (GPX4) expressions, which was partially alleviated by siATF3. 1,25D3 treatment significantly eliminates RV induced ferroptosis via ATF3-SLC7A11-GPX4 axis. Therefore, these results reveals that RV infection induces ferroptosis in IPEC-J2 cell and 1,25D3 alleviates RV induced ferroptosis by regulating the ATF3-SLC7A11-GPX4 axis.
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Affiliation(s)
- Ye Zhao
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Xiaoxiao Zhu
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Qingyuan Lan
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Ziang Wei
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Pan Shang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Lei Song
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Shijie Hu
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Lei Chen
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Mailin Gan
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Lili Niu
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Yan Wang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Linyuan Shen
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Li Zhu
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
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Fedora K, Setyoningrum RA, Aina Q, Rosyidah LN, Ni’mah NL, Titiharja FF. Vitamin D supplementation decrease asthma exacerbations in children: a systematic review and meta-analysis of randomized controlled trials. Ann Med 2024; 56:2400313. [PMID: 39421966 PMCID: PMC11492411 DOI: 10.1080/07853890.2024.2400313] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 11/04/2023] [Accepted: 07/03/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Observational studies have linked low vitamin D (VD) levels to increased asthma attacks in children. Subsequent meta-analyses of adults and children revealed that VD treatment might benefit asthmatic patients by reducing the incidence of exacerbations. Therefore, this review aims to analyze the effects of VD supplementation in reducing asthma exacerbations in children. METHODS Published reports from PubMed, Cochrane, and Google Scholar were systematically searched until April 2023. The study protocol was registered in the PROSPERO database CRD42023411796. Randomized controlled trial studies were included in this review. Meta-analysis was performed using Cochrane RevMan 5.1 and presented with 95% confidence intervals (CIs). RESULTS Ten relevant studies enrolled 1243 asthmatic children (631 children receiving vitamin D3 supplementation, 612 children receiving placebo) were included in this review. Our pooled analysis found that VD supplementation had a significant effect on lowering the total number of asthma exacerbations (RR 0.62; 95% CI: 0.44, 0.87; p = 0.01). Subgroup analysis revealed that a daily dose of VD given based on standard daily dose recommendation had a significant improvement on asthma exacerbations [(RR 0.41; 95% CI: 0,18, 0,92; p = 0.03). CONCLUSIONS Vitamin D supplementation can lower the occurrence of exacerbations in children with asthma, along with the improvement of FEV1.
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Affiliation(s)
- Katherine Fedora
- Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
- Department of Child Health, Dr. Soetomo General Hospital, Surabaya, East Java, Indonesia
| | - Retno Asih Setyoningrum
- Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
- Department of Child Health, Dr. Soetomo General Hospital, Surabaya, East Java, Indonesia
| | - Qorri’ Aina
- Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
| | - Laili Nur Rosyidah
- Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
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Karonova TL, Mikhaylova AA, Golovatyuk KA, Chernikova AT, Korobova ZR, Liubimova NE, Starshinova AA, Kudlay DA, Totolian AA, Shlyakhto EV. Vitamin D Metabolism Parameters and Cytokine Profile in COVID-19 Patients with Bolus Cholecalciferol Supplementation. Diagnostics (Basel) 2024; 14:1408. [PMID: 39001298 PMCID: PMC11240998 DOI: 10.3390/diagnostics14131408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 06/28/2024] [Accepted: 06/30/2024] [Indexed: 07/16/2024] Open
Abstract
UNLABELLED Recent studies have demonstrated the relationship between vitamin D deficiency, infection severity and mortality from COVID-19. This study aimed to analyze the vitamin D metabolites and cytokine expression levels of COVID-19 patients who were hospitalized with bolus cholecalciferol supplementation. MATERIALS AND METHODS This study represents the next stage of the open-label randomized pilot conducted by the Almazov National Medical Research Centre. A total of 44 hospitalized patients, comparable in demographic, clinical, laboratory and instrumental baseline characteristics, with moderate/severe COVID-19 were included. All patients had similar doses of concomitant corticosteroid therapy. Twenty-two patients received 50,000 IU cholecalciferol on the first and eighth days of hospitalization. The serum 25(OH)D, 1,25(OH)2D and 28 plasma cytokines were estimated for each group initially and on the ninth day of hospitalization. RESULTS Initially, there were no differences in the 1,25(OH)2D and cytokine levels in patients with vitamin D deficiency and normal 25(OH)D. Bolus cholecalciferol therapy at a total dose of 100,000 IU led to an increase in 25(OH)D levels in hospitalized patients with COVID-19, while the levels of the active metabolite (1,25(OH)2D) did not show significant differences between the groups or in its increased level over time, regardless of cholecalciferol supplementation. Furthermore, cholecalciferol supplementation at a total dose of 100,000 IU did not affect the majority of the cytokines estimated on the ninth day of hospitalization, except for the pro-inflammatory marker IL-1b, the concentration of which was lower in the group of patients without vitamin D supplementation. CONCLUSIONS The 25(OH)D level was positively associated with an anti-inflammatory immune response, but cholecalciferol supplementation at a total dose of 100,000 IU did not affect the active-form vitamin D or cytokine expression levels. This fact may be explained by the impact of corticosteroid therapy, and it requires further investigation in a post-COVID-19 context.
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Affiliation(s)
- Tatiana L. Karonova
- Almazov National Medical Research Centre, 2, Akkuratov Str., St. Petersburg 197341, Russia; (T.L.K.); (A.A.M.); (K.A.G.); (A.T.C.); (E.V.S.)
| | - Arina A. Mikhaylova
- Almazov National Medical Research Centre, 2, Akkuratov Str., St. Petersburg 197341, Russia; (T.L.K.); (A.A.M.); (K.A.G.); (A.T.C.); (E.V.S.)
| | - Ksenia A. Golovatyuk
- Almazov National Medical Research Centre, 2, Akkuratov Str., St. Petersburg 197341, Russia; (T.L.K.); (A.A.M.); (K.A.G.); (A.T.C.); (E.V.S.)
| | - Alena T. Chernikova
- Almazov National Medical Research Centre, 2, Akkuratov Str., St. Petersburg 197341, Russia; (T.L.K.); (A.A.M.); (K.A.G.); (A.T.C.); (E.V.S.)
| | - Zoia R. Korobova
- Saint Petersburg Pasteur Institute, Saint-Petersburg 197101, Russia; (Z.R.K.); (N.E.L.); (A.A.T.)
| | - Natalia E. Liubimova
- Saint Petersburg Pasteur Institute, Saint-Petersburg 197101, Russia; (Z.R.K.); (N.E.L.); (A.A.T.)
| | - Anna A. Starshinova
- Almazov National Medical Research Centre, 2, Akkuratov Str., St. Petersburg 197341, Russia; (T.L.K.); (A.A.M.); (K.A.G.); (A.T.C.); (E.V.S.)
| | - Dmitry A. Kudlay
- Department of Pharmacognosy and Industrial Pharmacy, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow 119991, Russia;
- Institute of Immunology, Moscow 115478, Russia
| | - Areg A. Totolian
- Saint Petersburg Pasteur Institute, Saint-Petersburg 197101, Russia; (Z.R.K.); (N.E.L.); (A.A.T.)
| | - Evgeny V. Shlyakhto
- Almazov National Medical Research Centre, 2, Akkuratov Str., St. Petersburg 197341, Russia; (T.L.K.); (A.A.M.); (K.A.G.); (A.T.C.); (E.V.S.)
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Hernández-Sarmiento LJ, Valdés-López JF, Urcuqui-Inchima S. Zika virus infection suppresses CYP24A1 and CAMP expression in human monocytes. Arch Virol 2024; 169:135. [PMID: 38839691 PMCID: PMC11153301 DOI: 10.1007/s00705-024-06050-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 03/27/2024] [Indexed: 06/07/2024]
Abstract
Monocytes are the primary targets of Zika virus (ZIKV) and are associated with ZIKV pathogenesis. Currently, there is no effective treatment for ZIKV infection. It is known that 1,25-dihydroxy vitamin D3 (VitD3) has strong antiviral activity in dengue virus-infected macrophages, but it is unknown whether VitD3 inhibits ZIKV infection in monocytes. We investigated the relationship between ZIKV infection and the expression of genes of the VitD3 pathway, as well as the inflammatory response of infected monocytes in vitro. ZIKV replication was evaluated using a plaque assay, and VitD3 pathway gene expression was analyzed by RT-qPCR. Pro-inflammatory cytokines/chemokines were quantified using ELISA. We found that VitD3 did not suppress ZIKV replication. The results showed a significant decrease in the expression of vitamin D3 receptor (VDR), cytochrome P450 family 24 subfamily A member 1 (CYP24A1), and cathelicidin antimicrobial peptide (CAMP) genes upon ZIKV infection. Treatment with VitD3 was unable to down-modulate production of pro-inflammatory cytokines, except TNF-α, and chemokines. This suggests that ZIKV infection inhibits the expression of VitD3 pathway genes, thereby preventing VitD3-dependent inhibition of viral replication and the inflammatory response. This is the first study to examine the effects of VitD3 in the context of ZIKV infection, and it has important implications for the role of VitD3 in the control of viral replication and inflammatory responses during monocyte infection.
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Affiliation(s)
| | - Juan Felipe Valdés-López
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia
| | - Silvio Urcuqui-Inchima
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
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Jia H, Sheng F, Yan Y, Liu X, Zeng B. Vitamin D supplementation for prevention of acute respiratory infections in older adults: A systematic review and meta-analysis. PLoS One 2024; 19:e0303495. [PMID: 38787821 PMCID: PMC11125479 DOI: 10.1371/journal.pone.0303495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 04/25/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND Acute respiratory infections (ARIs) have a substantial impact on morbidity, healthcare utilization, and functional decline among older adults. Therefore, we systematically reviewed evidence from randomized controlled trials (RCTs) to evaluate the efficacy and safety of vitamin D supplementation in preventing ARIs in older adults. METHODS PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched until 1 February 2024. RCTs evaluating the use of vitamin D supplements to protect older adults from ARIs were included. Two reviewers independently screened papers, extracted the data and assessed the risk of bias. Data were summarised as relative risks (RRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Random effects meta-analyses were used to synthesise the results. GRADE was used to evaluate the quality of evidence. All the analysis were performed with Stata version 17. RESULTS Twelve trials (41552 participants) were included in the meta-analysis. It showed that vitamin D supplementation probably does not reduce the incidence of ARIs (RR, 0.99; 95% CI, 0.97-1.02, I2 = 0%; moderate certainty). No significant effect of vitamin D supplementation on the risk of ARI was observed for any of the subgroups defined by baseline 25(OH)D concentration, control treatments, dose frequency, study duration, and participants' condition. However, there was a possibility, although not statistically significant, that vitamin D may reduce the risk of ARI in patients with a baseline 25(OH)D concentration <50 nmol/L (OR, 0.90; 95% CI, 0.79-1.04, I2 = 14.7%). Additionally, vitamin D supplements might result in little to no difference in death due to any cause, any adverse event, hypercalcinemia, and kidney stones. CONCLUSIONS Vitamin D supplementation among older adults probably results in little to no difference in the incidence of ARIs. However, further evidence is needed, particularly for individuals with vitamin D deficiency and populations residing in low and middle income countries. TRIAL REGISTRATION This study was registered on PROSPERO (CRD42023451265).
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Affiliation(s)
- Hao Jia
- Drug Clinical Trial Institution, Tianjin Fifth Central Hospital (Peking University Binhai Hospital), Tianjin, China
| | - Feng Sheng
- Department of Education and Science, Tianjin Fifth Central Hospital (Peking University Binhai Hospital), Tianjin, China
| | - Yulan Yan
- Department of Education and Science, Tianjin Fifth Central Hospital (Peking University Binhai Hospital), Tianjin, China
| | - Xiaozhi Liu
- Central Laboratory, Tianjin Fifth Central Hospital (Peking University Binhai Hospital), Tianjin, China
- Tianjin Key Laboratory of Epigenetic for Organ Development of Preterm Infants, Tianjin Fifth Central Hospital, Tianjin, China
- High Altitude Characteristic Medical Research Institute, Huangnan Tibetan Autonomous Prefecture People’s Hospital, Huangnan Prefecture, Qinghai, China
| | - Baoqi Zeng
- Central Laboratory, Tianjin Fifth Central Hospital (Peking University Binhai Hospital), Tianjin, China
- Emergency Department of Tianjin Fifth Central Hospital, Tianjin, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China
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Dong H, Hao Y, Gao P. Vitamin D level in COVID-19 patients has positive correlations with autophagy and negative correlations with disease severity. Front Pharmacol 2024; 15:1388348. [PMID: 38783947 PMCID: PMC11112027 DOI: 10.3389/fphar.2024.1388348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 04/23/2024] [Indexed: 05/25/2024] Open
Abstract
Background and Objectives There is still incomplete understanding of the pathogenesis of COVID-19. Calcitriol, the main form of vitamin D in serum, regulates immune responses and increases resistance to pathogens, but the mechanism by which it protects against COVID-19 is uncertain. Autophagy has antiviral effects and helps to maintain homeostasis, but its specific role in COVID-19 is also uncertain. Both vitamin D and autophagy have important functions in the lung microenvironment. This study examined the relationship of serum vitamin D and autophagy-related proteins in patients with COVID-19 and evaluated their potential use as biomarkers. Methods Blood samples from COVID-19 patients at the Second Hospital of Jilin University were collected. The levels of vitamin D, autophagy-related proteins (Becline 1 [BECN1] and autophagy-related 7 [ATG7]), and inflammatory markers (TNF-α and IL-1β) were measured using enzyme-linked immunosorbent assays. Results We examined 25 patients with mild/moderate COVID-19 and 27 patients with severe/critical COVID-19. The group with severe/critical COVID-19 had more abnormalities in many laboratory indicators, including lower levels of autophagy markers (BECN1 and ATG7) and vitamin D, and higher levels of inflammatory markers (TNF-α and IL-1β). Partial correlation analysis showed that vitamin D had strong positive correlations with ATG7 (r = 0.819, p < 0.001) and BECN1 (r = 0.900, p < 0.001). Conclusion Our results demonstrated that the vitamin D level had significant negative correlations with COVID-19 severity and strong positive correlations with autophagy. These findings enhance our understanding of the pathogenesis of COVID-19, and provide a theoretical basis for clinical interventions that target autophagy and vitamin D.
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Affiliation(s)
| | | | - Peng Gao
- Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
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Figgins EL, Arora P, Gao D, Porcelli E, Ahmed R, Daep CA, Keele G, Ryan LK, Diamond G. Enhancement of innate immunity in gingival epithelial cells by vitamin D and HDAC inhibitors. FRONTIERS IN ORAL HEALTH 2024; 5:1378566. [PMID: 38567313 PMCID: PMC10986367 DOI: 10.3389/froh.2024.1378566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 03/05/2024] [Indexed: 04/04/2024] Open
Abstract
Introduction The human host defense peptide LL-37 is a component of the innate immune defense mechanisms of the oral cavity against colonization by microbes associated with periodontal disease. We have previously shown that the active form of vitamin D, 1,25(OH)2D3, can induce the expression of LL-37 in gingival epithelial cells (GEC), and prevent the invasion and growth of periopathogenic bacteria in these cells. Further, experimental vitamin D deficiency resulted in increased gingival inflammation and alveolar bone loss. Epidemiological studies have shown associations between vitamin D deficiency and periodontal disease in humans, suggesting application of vitamin D could be a useful therapeutic approach. Further, since we have shown the local activation of vitamin D by enzymes expressed in the GEC, we hypothesized that we could observe this enhancement with the stable, and inexpensive inactive form of vitamin D, which could be further increased with epigenetic regulators. Methods We treated 3-dimensional primary cultures of GEC topically with the inactive form of vitamin D, in the presence and absence of selected histone deacetylase (HDAC) inhibitors. LL-37 mRNA levels were quantified by quantitative RT-PCR, and inhibition of invasion of bacteria was measured by fluorescence microscopy. Results Vitamin D treatment led to an induction of LL-37 mRNA levels, as well as an inhibition of pro-inflammatory cytokine secretion. This effect was further enhanced by HDAC inhibitors, most strongly when the HDAC inhibitor, phenyl butyrate (PBA) was combined with Vitamin D3. This was observed both in solution and in a prototype gel formulation using sodium butyrate. Finally, this combination treatment led to an increase in the antimicrobial activity against infection by Porphyromonas gingivalis and Filifactor alocis, bacteria associated with periodontal lesions, as well as herpes simplex virus, which has also been shown to be associated with periodontal lesions. Conclusions Our results demonstrate that a combination of inactive vitamin D and sodium butyrate could be developed as a safe treatment for periodontal disease.
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Affiliation(s)
- Erika L. Figgins
- Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL, United States
- Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United States
| | - Payal Arora
- Global Technology Center, Colgate Palmolive Company, Piscataway, NJ, United States
| | - Denny Gao
- Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United States
| | - Emily Porcelli
- Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL, United States
| | - Rabab Ahmed
- Global Technology Center, Colgate Palmolive Company, Piscataway, NJ, United States
| | - Carlo Amorin Daep
- Global Technology Center, Colgate Palmolive Company, Piscataway, NJ, United States
| | - Garrett Keele
- Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United States
| | - Lisa K. Ryan
- Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United States
- Division of Infectious Disease and Global Medicine, Department of Medicine, University of Florida College of Medicine, Gainesville, FL, United States
- Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY, United States
| | - Gill Diamond
- Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL, United States
- Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United States
- Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY, United States
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Kalia V, Sarkar S. Vitamin D and antiviral immunity. FELDMAN AND PIKE'S VITAMIN D 2024:1011-1034. [DOI: 10.1016/b978-0-323-91338-6.00045-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Moatasim Y, Kutkat O, Osman AM, Gomaa MR, Okda F, El Sayes M, Kamel MN, Gaballah M, Mostafa A, El-Shesheny R, Kayali G, Ali MA, Kandeil A. Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E. Microorganisms 2023; 11:2777. [PMID: 38004788 PMCID: PMC10673013 DOI: 10.3390/microorganisms11112777] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 10/26/2023] [Accepted: 11/09/2023] [Indexed: 11/26/2023] Open
Abstract
Repurposing vitamins as antiviral supporting agents is a rapid approach used to control emerging viral infections. Although there is considerable evidence supporting the use of vitamin supplementation in viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the specific role of each vitamin in defending against coronaviruses remains unclear. Antiviral activities of available vitamins on the infectivity and replication of human coronaviruses, namely, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus 229E (HCoV-229E), were investigated using in silico and in vitro studies. We identified potential broad-spectrum inhibitor effects of Hydroxocobalamin and Methylcobalamin against the three tested CoVs. Cyanocobalamin could selectively affect SARS-CoV-2 but not MERS-CoV and HCoV-229E. Methylcobalamin showed significantly higher inhibition values on SARS-CoV-2 compared with Hydroxocobalamin and Cyanocobalamin, while Hydroxocobalamin showed the highest potent antiviral activity against MERS-CoV and Cyanocobalamin against HCoV-229E. Furthermore, in silico studies were performed for these promising vitamins to investigate their interaction with SARS-CoV-2, MERS-CoV, and HCoV-229E viral-specific cell receptors (ACE2, DPP4, and hAPN protein, respectively) and viral proteins (S-RBD, 3CL pro, RdRp), suggesting that Hydroxocobalamin, Methylcobalamin, and Cyanocobalamin may have significant binding affinity to these proteins. These results show that Methylcobalamin may have potential benefits for coronavirus-infected patients.
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Affiliation(s)
- Yassmin Moatasim
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (Y.M.); (O.K.); (M.R.G.); (M.E.S.); (M.N.K.); (M.G.); (A.M.); (R.E.-S.)
| | - Omnia Kutkat
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (Y.M.); (O.K.); (M.R.G.); (M.E.S.); (M.N.K.); (M.G.); (A.M.); (R.E.-S.)
| | - Ahmed M. Osman
- Biochemistry Department, Faculty of Science, Cairo University, Cairo 12613, Egypt;
| | - Mokhtar R. Gomaa
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (Y.M.); (O.K.); (M.R.G.); (M.E.S.); (M.N.K.); (M.G.); (A.M.); (R.E.-S.)
| | - Faten Okda
- Veterinary Research Institute, National Research Centre, Giza 12622, Egypt;
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
| | - Mohamed El Sayes
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (Y.M.); (O.K.); (M.R.G.); (M.E.S.); (M.N.K.); (M.G.); (A.M.); (R.E.-S.)
| | - Mina Nabil Kamel
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (Y.M.); (O.K.); (M.R.G.); (M.E.S.); (M.N.K.); (M.G.); (A.M.); (R.E.-S.)
| | - Mohamed Gaballah
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (Y.M.); (O.K.); (M.R.G.); (M.E.S.); (M.N.K.); (M.G.); (A.M.); (R.E.-S.)
| | - Ahmed Mostafa
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (Y.M.); (O.K.); (M.R.G.); (M.E.S.); (M.N.K.); (M.G.); (A.M.); (R.E.-S.)
| | - Rabeh El-Shesheny
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (Y.M.); (O.K.); (M.R.G.); (M.E.S.); (M.N.K.); (M.G.); (A.M.); (R.E.-S.)
| | | | - Mohamed A. Ali
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (Y.M.); (O.K.); (M.R.G.); (M.E.S.); (M.N.K.); (M.G.); (A.M.); (R.E.-S.)
| | - Ahmed Kandeil
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (Y.M.); (O.K.); (M.R.G.); (M.E.S.); (M.N.K.); (M.G.); (A.M.); (R.E.-S.)
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11
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Johnson CR, Thacher TD. Vitamin D: immune function, inflammation, infections and auto-immunity. Paediatr Int Child Health 2023; 43:29-39. [PMID: 36857810 DOI: 10.1080/20469047.2023.2171759] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 10/12/2022] [Indexed: 03/03/2023]
Abstract
Vitamin D plays an active role beyond mineral metabolism and skeletal health, including regulation of the immune system. Vitamin D deficiency is widely prevalent, and observational studies link low vitamin D status to a risk of infections and auto-immune disorders. Reports indicate an inverse relationship between vitamin D status and such conditions. This review details vitamin D signalling interactions with the immune system and provides experimental and clinical evidence evaluating vitamin D status, vitamin D supplementation and host susceptibility to infections, inflammation and auto-immunity. The published literature including related reviews, systematic reviews, meta-analyses, randomised controlled trials (RCTs), observational studies and basic science reports have been synthesised. Meta-analyses of observational studies have demonstrated a link between low vitamin D status and risk of acute respiratory infections, COVID-19 disorders, multiple sclerosis, type 1 diabetes (T1DM), inflammatory bowel disease (IBD), systemic lupus erythematosus and other auto-immune disorders. Observational studies suggest that vitamin D supplementation may protect against several infectious and auto-immune conditions. Meta-analyses of RCTs had mixed results, demonstrating a small protective role for vitamin D supplementation against acute respiratory infections, especially in those with vitamin D deficiency and children, and providing modest benefits for the management of T1DM and IBD. Vitamin D status is inversely associated with the incidence of several infectious and auto-immune conditions. Supplementation is recommended for those with vitamin D deficiency or at high risk of deficiency, and it might provide additional benefit in acute respiratory infections and certain auto-immune conditions.
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Affiliation(s)
- Casey R Johnson
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Tom D Thacher
- Department of Family Medicine, Mayo Clinic, Rochester, New York, USA
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12
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Komba S, Hase M, Kotake-Nara E. Organic Synthesis of New Secosteroids from Fucosterol, Its Intestinal Absorption by Caco-2 Cells, and Simulation of the Biological Activities of Vitamin D. Mar Drugs 2023; 21:540. [PMID: 37888475 PMCID: PMC10608315 DOI: 10.3390/md21100540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 10/12/2023] [Accepted: 10/12/2023] [Indexed: 10/28/2023] Open
Abstract
We previously examined the cellular uptake of six types of vitamin D in human intestinal Caco-2 cells. Since vitamins D5-D7 were commercially unavailable, we synthesized these compounds organically before studying them. This process led us to understand that new secosteroids could be generated as vitamin D candidates, depending on the sterol used as the starting material. We obtained two new secosteroids-compounds 3 and 4-from fucosterol in the current study. We investigated the intestinal absorption of these compounds using Caco-2 cells cultured in Transwells and compared the results with vitamin D3, a representative secosteroid. The intestinal absorption of compound 4 was comparable to that of vitamin D3. Compound 3 showed similar uptake levels but transported about half as much as vitamin D3. These compounds demonstrated intestinal absorption at the cellular level. Vitamin D is known for its diverse biological activities manifest after intestinal absorption. Using PASS online simulation, we estimated the biological activity of compound 3's activated form. In several items indicated by PASS, compound 3 exhibited stronger biological activity than vitamins D2-D7 and was also predicted to have unique biological activities.
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Affiliation(s)
- Shiro Komba
- Institute of Food Research, National Agriculture and Food Research Organization, 2-1-12 Kannondai, Tsukuba 305-8642, Ibaraki, Japan
| | - Megumi Hase
- Institute of Food Research, National Agriculture and Food Research Organization, 2-1-12 Kannondai, Tsukuba 305-8642, Ibaraki, Japan
| | - Eiichi Kotake-Nara
- Institute of Food Research, National Agriculture and Food Research Organization, 2-1-12 Kannondai, Tsukuba 305-8642, Ibaraki, Japan
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13
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Gao N, Raduka A, Rezaee F. Vitamin D 3 protects against respiratory syncytial virus-induced barrier dysfunction in airway epithelial cells via PKA signaling pathway. Eur J Cell Biol 2023; 102:151336. [PMID: 37354621 PMCID: PMC10773979 DOI: 10.1016/j.ejcb.2023.151336] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/19/2023] [Accepted: 06/21/2023] [Indexed: 06/26/2023] Open
Abstract
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection in infants and young children globally and is responsible for hospitalization and mortality in the elderly population. Virus-induced airway epithelial barrier damage is a critical step during RSV infection, and emerging studies suggest that RSV disrupts the tight junctions (TJs) and adherens junctions (AJs) between epithelial cells, increasing the permeability of the airway epithelial barrier. The lack of commercially available vaccines and effective antiviral drugs for RSV emphasizes the need for new management strategies. Vitamin D3 is a promising intervention for viral infection due to its critical role in modulating innate immune responses. However, there is limited evidence on the effect of vitamin D3 on RSV pathogenies. Here, we investigated the impact of vitamin D3 on RSV-induced epithelial barrier dysfunction and the underlying mechanisms. We found that pre-incubation with 1,25(OH)2D3, the active form of vitamin D3, alleviated RSV-induced epithelial barrier disruption in a dose-dependent manner without affecting viability in 16HBE cells. 1,25(OH)2D3 induced minor changes in the protein expression level of TJ/AJ proteins in RSV-infected cells. We observed increased CREB phosphorylation at Ser133 during 1,25(OH)2D3 exposure, indicating that vitamin D3 triggered protein kinase A (PKA) activity in 16HBE. PKA inhibitors modified the restoration of barrier function by 1,25(OH)2D3 in RSV-infected cells, implying that PKA signaling is responsible for the protective effects of vitamin D3 against RSV-induced barrier dysfunction in airway epithelial cells. Our findings suggest vitamin D3 as a prophylactic intervention to protect the respiratory epithelium during RSV infections.
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Affiliation(s)
- Nannan Gao
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Andjela Raduka
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Fariba Rezaee
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA; Center for Pediatric Pulmonary Medicine, Cleveland Clinic Children's, Cleveland, OH, USA.
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14
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Partap U, Sharma KK, Marathe Y, Wang M, Shaikh S, D’Costa P, Gupta G, Bromage S, Hemler EC, Mistry N, Kain KC, Dholakia Y, Fawzi WW. Vitamin D and Zinc Supplementation to Improve Treatment Outcomes among COVID-19 Patients in India: Results from a Double-Blind Randomized Placebo-Controlled Trial. Curr Dev Nutr 2023; 7:101971. [PMID: 37560461 PMCID: PMC10407567 DOI: 10.1016/j.cdnut.2023.101971] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/05/2023] [Accepted: 07/07/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND There remains a need to identify low-cost interventions to improve coronavirus disease 2019 (COVID-19) outcomes. Vitamin D and zinc play a role in respiratory infections and could hold value as part of therapeutic regimens. OBJECTIVES To determine the effect of vitamin D or zinc supplementation on recovery from COVID-19. METHODS We conducted a double-blind, randomly assigned 2 x 2 factorial placebo-controlled trial with 1:1:1:1 allocation ratio, enrolling nonpregnant adults with COVID-19 from hospitals in Mumbai and Pune, India (NCT04641195). Participants (N = 181) were randomly assigned to vitamin D3 (180,000 IU bolus, then 2000 IU daily), zinc (40 mg daily), vitamin D3 and zinc, or placebo, for 8 wk. Participants were followed until 8 wk. The primary outcome was time to resolution of fever, cough, and shortness of breath. Secondary outcomes were duration of individual symptoms; need for assisted ventilation; duration of hospital stay; all-cause mortality; and blood biomarkers, including nutritional, inflammatory, and immunological markers. RESULTS We observed no effect of vitamin D or zinc supplementation on time to resolution of all 3 symptoms [vitamin D hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.66, 1.30; P = 0.650; zinc HR: 0.94; 95% CI: 0.67, 1.33; P = 0.745)]. Neither vitamin D nor zinc supplementation was associated with secondary outcomes, except for increased endline serum vitamin D with vitamin D supplementation [median (interquartile range) difference between endline and baseline for vitamin D: 5.3 ng/mL (-2.3 to 13.7); for no vitamin D: -1.4 ng/mL (-5.6 to 3.9); P = 0.003]. We observed nonsignificant increases in serum zinc at endline following zinc supplementation. There was no evidence of interaction between vitamin D and zinc supplementation, no effect of either on hypercalcemia, and no adverse events. CONCLUSIONS Results suggest that neither vitamin D nor zinc supplementation improves COVID-19 treatment outcomes in this population. However, much larger-scale evidence, particularly from populations with vitamin D or zinc deficiency and severe infection, is required to corroborate our findings. This trial was registered at ClinicalTrials.gov and the Clinical Trials Registry of India as NCT04641195 and CTRI/2021/04/032593 respectively.
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Affiliation(s)
- Uttara Partap
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | | | | | - Molin Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Sanaa Shaikh
- The Foundation for Medical Research, Mumbai, India
| | - Pradeep D’Costa
- King Edward Memorial Hospital and Research Centre, Pune, India
| | | | - Sabri Bromage
- Institute of Nutrition, Mahidol University, Salaya, Thailand
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Elena C. Hemler
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | | | - Kevin C. Kain
- Department of Medicine, University of Toronto and University Health Network, Toronto, Ontario, Canada
| | | | - Wafaie W. Fawzi
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
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15
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Zhao X, Hu M, Zhou H, Yang Y, Shen S, You Y, Xue Z. The role of gut microbiome in the complex relationship between respiratory tract infection and asthma. Front Microbiol 2023; 14:1219942. [PMID: 37577440 PMCID: PMC10413575 DOI: 10.3389/fmicb.2023.1219942] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 06/19/2023] [Indexed: 08/15/2023] Open
Abstract
Asthma is one of the common chronic respiratory diseases in children, which poses a serious threat to children's quality of life. Respiratory infection is a risk factor for asthma. Compared with healthy children, children with early respiratory infections have a higher risk of asthma and an increased chance of developing severe asthma. Many clinical studies have confirmed the correlation between respiratory infections and the pathogenesis of asthma, but the underlying mechanism is still unclear. The gut microbiome is an important part of maintaining the body's immune homeostasis. The imbalance of the gut microbiome can affect the lung immune function, and then affect lung health and cause respiratory diseases. A large number of evidence supports that there is a bidirectional regulation between intestinal flora and respiratory tract infection, and both are significantly related to the development of asthma. The changes of intestinal microbial components and their metabolites in respiratory tract infection may affect the occurrence and development of asthma through the immune pathway. By summarizing the latest advancements in research, this review aims to elucidate the intricate connection between respiratory tract infections and the progression of asthma by highlighting its bridging role of the gut microbiome. Furthermore, it offers novel perspectives and ideas for future investigations into the mechanisms that underlie the relationship between respiratory tract infections and asthma.
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Affiliation(s)
| | | | | | | | | | - Yannan You
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zheng Xue
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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16
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Schichlein KD, Smith GJ, Jaspers I. Protective effects of inhaled antioxidants against air pollution-induced pathological responses. Respir Res 2023; 24:187. [PMID: 37443038 DOI: 10.1186/s12931-023-02490-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 07/06/2023] [Indexed: 07/15/2023] Open
Abstract
As the public health burden of air pollution continues to increase, new strategies to mitigate harmful health effects are needed. Dietary antioxidants have previously been explored to protect against air pollution-induced lung injury producing inconclusive results. Inhaled (pulmonary or nasal) administration of antioxidants presents a more promising approach as it could directly increase antioxidant levels in the airway surface liquid (ASL), providing protection against oxidative damage from air pollution. Several antioxidants have been shown to exhibit antioxidant, anti-inflammatory, and anti-microbial properties in in vitro and in vivo models of air pollution exposure; however, little work has been done to translate these basic research findings into practice. This narrative review summarizes these findings and data from human studies using inhaled antioxidants in response to air pollution, which have produced positive results, indicating further investigation is warranted. In addition to human studies, cell and murine studies should be conducted using more relevant models of exposure such as air-liquid interface (ALI) cultures of primary cells and non-aqueous apical delivery of antioxidants and pollutants. Inhalation of antioxidants shows promise as a protective intervention to prevent air pollution-induced lung injury and exacerbation of existing lung disease.
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Affiliation(s)
- Kevin D Schichlein
- Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, 116 Manning Drive, Chapel Hill, NC, 27599-7310, USA
| | - Gregory J Smith
- Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, 116 Manning Drive, Chapel Hill, NC, 27599-7310, USA
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Ilona Jaspers
- Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, 116 Manning Drive, Chapel Hill, NC, 27599-7310, USA.
- Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
- Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
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17
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Nathan J, Shameera R, Ramachandran A. Impact of nutraceuticals on immunomodulation against viral infections-A review during COVID-19 pandemic in Indian scenario. J Biochem Mol Toxicol 2023; 37:e23320. [PMID: 36799127 DOI: 10.1002/jbt.23320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 12/13/2022] [Accepted: 02/02/2023] [Indexed: 02/18/2023]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China, in early December 2019 is a censorious global emergency after World War II. Research on the coronavirus uncovered essential information that aided in the development of the vaccine, and specific coronavirus disease 2019 (COVID-19) vaccines were later developed and were approved for usage in humans. But then, mutations in the coronavirus gave rise to new variants and questioned the vaccine's efficacy against them. On the other hand, the investigation of traditional medicine was also on its path to find a novel outcome against COVID-19. On a comparative analysis between India and the United States, India had low death rate and high recovery rate than the latter. The dietary regulation of immunity may be the factor that makes the above difference. The immunity gained from the regular diet of Indian culture nourishes Indian people with essential phytochemicals that support immunity and metabolism. Dietary phytochemicals or nutraceuticals possess antioxidant, anti-inflammatory, and anticancer properties, out of which our concern will be on immune-boosting phytochemicals from our daily nutritional supplements. In several case studies, dietary substance like lemon, ginger, and spinach was reported in the recovery of COVID-19 patients. Thus in this review, we discuss coronavirus and its available variants, vaccines, and the effect of nutraceuticals against the coronavirus. Further, we denote that the immunity of the Indian population may be high because of their diet, which adds natural phytochemicals to boost their immunity and metabolism.
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Affiliation(s)
- Jhansi Nathan
- AUKBC Research Centre for Emerging Technologies, Anna University, Chennai, Tamil Nadu, India
| | - Rabiathul Shameera
- AUKBC Research Centre for Emerging Technologies, Anna University, Chennai, Tamil Nadu, India
| | - Arunkumar Ramachandran
- Multidisciplinary Research Unit (MRU), Madras Medical College, Chennai, Tamil Nadu, India
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18
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Hamza FN, Daher S, Fakhoury HMA, Grant WB, Kvietys PR, Al-Kattan K. Immunomodulatory Properties of Vitamin D in the Intestinal and Respiratory Systems. Nutrients 2023; 15:nu15071696. [PMID: 37049536 PMCID: PMC10097244 DOI: 10.3390/nu15071696] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 03/28/2023] [Accepted: 03/29/2023] [Indexed: 04/03/2023] Open
Abstract
Vitamin D plays a crucial role in modulating the innate immune response by interacting with its intracellular receptor, VDR. In this review, we address vitamin D/VDR signaling and how it contributes to the regulation of intestinal and respiratory microbiota. We additionally review some components of the innate immune system, such as the barrier function of the pulmonary and intestinal epithelial membranes and secretion of mucus, with their respective modulation by vitamin D. We also explore the mechanisms by which this vitamin D/VDR signaling mounts an antimicrobial response through the transduction of microbial signals and the production of antimicrobial peptides that constitute one of the body’s first lines of defense against pathogens. Additionally, we highlight the role of vitamin D in clinical diseases, namely inflammatory bowel disease and acute respiratory distress syndrome, where excessive inflammatory responses and dysbiosis are hallmarks. Increasing evidence suggests that vitamin D supplementation may have potentially beneficial effects on those diseases.
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Affiliation(s)
- Fatheia N. Hamza
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
| | - Sarah Daher
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
| | - Hana M. A. Fakhoury
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
- Correspondence:
| | - William B. Grant
- Sunlight, Nutrition, and Health Research Center, P.O. Box 641603, San Francisco, CA 94164-1603, USA
| | - Peter R. Kvietys
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
| | - Khaled Al-Kattan
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
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19
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Chatterjee S, Nalla LV, Sharma M, Sharma N, Singh AA, Malim FM, Ghatage M, Mukarram M, Pawar A, Parihar N, Arya N, Khairnar A. Association of COVID-19 with Comorbidities: An Update. ACS Pharmacol Transl Sci 2023; 6:334-354. [PMID: 36923110 PMCID: PMC10000013 DOI: 10.1021/acsptsci.2c00181] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Indexed: 03/03/2023]
Abstract
Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which was identified in Wuhan, China in December 2019 and jeopardized human lives. It spreads at an unprecedented rate worldwide, with serious and still-unfolding health conditions and economic ramifications. Based on the clinical investigations, the severity of COVID-19 appears to be highly variable, ranging from mild to severe infections including the death of an infected individual. To add to this, patients with comorbid conditions such as age or concomitant illnesses are significant predictors of the disease's severity and progression. SARS-CoV-2 enters inside the host cells through ACE2 (angiotensin converting enzyme2) receptor expression; therefore, comorbidities associated with higher ACE2 expression may enhance the virus entry and the severity of COVID-19 infection. It has already been recognized that age-related comorbidities such as Parkinson's disease, cancer, diabetes, and cardiovascular diseases may lead to life-threatening illnesses in COVID-19-infected patients. COVID-19 infection results in the excessive release of cytokines, called "cytokine storm", which causes the worsening of comorbid disease conditions. Different mechanisms of COVID-19 infections leading to intensive care unit (ICU) admissions or deaths have been hypothesized. This review provides insights into the relationship between various comorbidities and COVID-19 infection. We further discuss the potential pathophysiological correlation between COVID-19 disease and comorbidities with the medical interventions for comorbid patients. Toward the end, different therapeutic options have been discussed for COVID-19-infected comorbid patients.
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Affiliation(s)
- Sayan Chatterjee
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 382355, India
| | - Lakshmi Vineela Nalla
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 382355, India.,Department of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Andhra Pradesh 522302, India
| | - Monika Sharma
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 382355, India
| | - Nishant Sharma
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 382355, India
| | - Aditya A Singh
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 382355, India
| | - Fehmina Mushtaque Malim
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 382355, India
| | - Manasi Ghatage
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 382355, India
| | - Mohd Mukarram
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 382355, India
| | - Abhijeet Pawar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 382355, India
| | - Nidhi Parihar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 382355, India
| | - Neha Arya
- Department of Translational Medicine, All India Institute of Medical Sciences (AIIMS), Bhopal, Bhopal 462020, India
| | - Amit Khairnar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 382355, India.,International Clinical Research Center, St. Anne's University Hospital Brno, Brno 602 00, Czech Republic.,ICRC-FNUSA Brno 656 91, Czech Republic.,Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 753/5, 62500 Brno, Czechia
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20
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Vasheghani M, Rekabi M, Sadr M. Protective role of vitamin D status against COVID-19: a mini-review. Endocrine 2023; 79:235-242. [PMID: 36258153 PMCID: PMC9579655 DOI: 10.1007/s12020-022-03203-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 09/17/2022] [Indexed: 02/04/2023]
Abstract
An outbreak of pneumonia caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is called COVID-19 and has led to a pandemic worldwide. It is reasonable to investigate and control factors affecting disease severity and mortality. The relation between vitamin D and viral pneumonia has been previously reported. Vitamin D deficiency is common and may increase hospital admission and mortality rate in patients with COVID-19. This mini-review examines the pathways that show the association between vitamin D and COVID-19. On the other hand, it deals with the available evidence related to the relationship between vitamin D deficiency and the effect of vitamin D supplementation on the prevalence, severity, and mortality of COVID-19. Also, we described the pathophysiology of the organs' involvement in COVID-19 and the effect of vitamin D on these outcomes. Vitamin D strengthens the innate and adaptive immune system, modulates immune responses, prevents lung and cardiovascular system damage, and reduces thrombotic events. Vitamin D exerts these effects in several pathways. Vitamin D prevents virus entry and replication by maintaining the integrity of the body's physical barrier. Vitamin D reduces the damage to vital organs and thrombotic events by increasing the level of Angiotensin-converting enzyme 2 (ACE2), nitric oxide, and antioxidants or by reducing inflammatory cytokines and free radicals. Sufficient vitamin D may be reduced morbidity and mortality due to COVID-19. However, this issue should be investigated and confirmed by further research in the future.
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Affiliation(s)
- Maryam Vasheghani
- Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Rekabi
- Pediatric Respiratory Disease Research Center (PRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Makan Sadr
- Virology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
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21
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Notz Q, Herrmann J, Schlesinger T, Kranke P, Sitter M, Helmer P, Stumpner J, Roeder D, Amrein K, Stoppe C, Lotz C, Meybohm P. Vitamin D deficiency in critically ill COVID-19 ARDS patients. Clin Nutr 2022; 41:3089-3095. [PMID: 33745749 PMCID: PMC7937427 DOI: 10.1016/j.clnu.2021.03.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 02/16/2021] [Accepted: 03/01/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND & AIMS Vitamin D's pleiotropic effects include immune modulation, and its supplementation has been shown to prevent respiratory tract infections. The effectivity of vitamin D as a therapeutic intervention in critical illness remains less defined. The current study analyzed clinical and immunologic effects of vitamin D levels in patients suffering from coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). METHODS This was a single-center retrospective study in patients receiving intensive care with a confirmed SARS-CoV-2 infection and COVID-19 ARDS. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels, pro- and anti-inflammatory cytokines and immune cell subsets were measured on admission as well as after 10-15 days. Clinical parameters were extracted from the patient data management system. Standard operating procedures included the daily administration of vitamin D3 via enteral feeding. RESULTS A total of 39 patients with COVID-19 ARDS were eligible, of which 26 were included in this study as data on vitamin D status was available. 96% suffered from severe COVID-19 ARDS. All patients without prior vitamin D supplementation (n = 22) had deficient serum levels of 25-hydroxyvitamin D. Vitamin D supplementation resulted in higher serum levels of 25-hydroxyvitamin D but not did not increase 1,25-dihydroxyvitamin D levels after 10-15 days. Clinical parameters did not differ between patients with sufficient or deficient levels of 25-hydroxyvitamin D. Only circulating plasmablasts were higher in patients with 25-hydroxyvitamin D levels ≥30 ng/ml (p = 0.029). Patients with 1,25-dihydroxyvitamin D levels below 20 pg/ml required longer mechanical ventilation (p = 0.045) and had a worse acute physiology and chronic health evaluation (APACHE) II score (p = 0.048). CONCLUSION The vast majority of COVID-19 ARDS patients had vitamin D deficiency. 25-hydroxyvitamin D status was not related to changes in clinical course, whereas low levels of 1,25-dihydroxyvitamin D were associated with prolonged mechanical ventilation and a worse APACHE II score.
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Affiliation(s)
- Quirin Notz
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Germany,Corresponding author. Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Oberduerrbacher Str. 6, 97080, Wuerzburg, Germany. Fax: +49 0 931 201 30019
| | - Johannes Herrmann
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Germany
| | - Tobias Schlesinger
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Germany
| | - Peter Kranke
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Germany
| | - Magdalena Sitter
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Germany
| | - Philipp Helmer
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Germany
| | - Jan Stumpner
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Germany
| | - Daniel Roeder
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Germany
| | - Karin Amrein
- Division of Endocrinology and Diabetology, Medical University of Graz, Austria
| | - Christian Stoppe
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Germany
| | - Christopher Lotz
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Germany
| | - Patrick Meybohm
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Wuerzburg, Germany
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22
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Asghari A, Jafari F, Jameshorani M, Chiti H, Naseri M, Ghafourirankouhi A, Kooshkaki O, Abdshah A, Parsamanesh N. Vitamin D role in hepatitis B: focus on immune system and genetics mechanism. Heliyon 2022; 8:e11569. [PMID: 36411916 PMCID: PMC9674901 DOI: 10.1016/j.heliyon.2022.e11569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 08/01/2022] [Accepted: 11/07/2022] [Indexed: 11/16/2022] Open
Abstract
According to the World Health Organization (WHO) report, viral hepatitis has been a problem in human society. Vitamins play a significant role in preventing the hepatocarcinoma and liver cirrhosis. In this report, we will first focus on the vitamin D function in the immune system reactions, and then investigate its role in the viral infections and the signaling pathway of hepatitis B virus. The existence of the cytochrome P450 (CYP) 27B1 enzyme, which is involved in vitamin D synthesis in immune system cells, has drawn researchers ' attention to the field of immune system. Toll like receptor (TLR) play a significant role in the immune system, and are one of the primary receptors of the innate immune system. In addition, the synthesis of inflammatory cytokines, such as Interferon γ (IFNγ) and Interleukin-2 (IL-2) is one of the key roles of T helper type 1 (Th1) cells; these cells can suppress two cited cytokines via vitamin D. In the chronic phase of hepatitis B, Cytotoxic T lymphocytes (CTLs) cells have weaker performance than the acute phase of the disease. The association between vitamin D physiologies with viral infections is also confirmed by genetic studies, carried out on genetic variations of vitamin D receptor (VDR) R-encoding disease susceptibility gene. Vitamin D affects different phases of the disease. Therefore, further experiments in this area are proposed.
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Affiliation(s)
- Arghavan Asghari
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
- Birjand University of Medical Sciences, Birjand, Iran
| | - Fatemeh Jafari
- Radiation Oncology Research Center, Iran Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
- Department of Radiation Oncology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Jameshorani
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Science, Zanjan, Iran
- Department of Internal Medicine, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran
| | - Hossein Chiti
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Science, Zanjan, Iran
| | - Mohsen Naseri
- Department of Immunology, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | | | | | - Alireza Abdshah
- School of Medicine, Tehran University of Medical Science, Tehran, Iran
| | - Negin Parsamanesh
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Science, Zanjan, Iran
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23
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Sharma KK, Partap U, Mistry N, Marathe Y, Wang M, Shaikh S, D'Costa P, Gupta G, Bromage S, Hemler EC, Kain KC, Dholakia Y, Fawzi WW. Randomised trial to determine the effect of vitamin D and zinc supplementation for improving treatment outcomes among patients with COVID-19 in India: trial protocol. BMJ Open 2022; 12:e061301. [PMID: 36038172 PMCID: PMC9437735 DOI: 10.1136/bmjopen-2022-061301] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 08/08/2022] [Indexed: 12/01/2022] Open
Abstract
INTRODUCTION Presently, there are few population-level strategies to address SARS-CoV-2 infection except preventive measures such as vaccination. Micronutrient deficiency, particularly vitamin D and zinc deficiency, has been associated with dysregulated host responses, and may play an important role in COVID-19. METHODS AND ANALYSIS We have designed a 2×2 factorial, randomised, double-blind, multi-centre placebo-controlled trial to evaluate the effect of vitamin D and zinc on COVID-19 outcomes in Maharashtra, India. COVID-19 positive individuals are recruited from hospitals in Mumbai and Pune. Participants are provided (1) vitamin D3 bolus (180 000 IU) maintained by daily dose of 2000 IU and/or (2) zinc gluconate (40 mg daily), versus placebo for 8 weeks. Participants undergo a detailed assessment at baseline and at 8 weeks, and are monitored daily in hospital or every 3 days after leaving the hospital to assess symptoms and other clinical measures. A final follow-up telephone call occurs 12 weeks post-enrolment to assess long-term outcomes. The primary outcome of the study is to time to recovery, defined as time to resolution of all of fever, cough and shortness of breath. Secondary outcomes include: duration of hospital stay, all-cause mortality, necessity of assisted ventilation, change in blood biomarker levels and individual symptoms duration. Participant recruitment commenced on April 2021. ETHICS AND DISSEMINATION Ethical approval was obtained from institutional ethical committees of all participating institutions. The study findings will be presented in peer-reviewed medical journals. TRIAL REGISTRATION NUMBERS NCT04641195, CTRI/2021/04/032593, HMSC (GOI)-2021-0060.
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Affiliation(s)
| | - Uttara Partap
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Nerges Mistry
- The Foundation for Medical Research, Mumbai, Maharashtra, India
| | - Yogesh Marathe
- The Foundation for Medical Research, Mumbai, Maharashtra, India
| | - Molin Wang
- Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Sanaa Shaikh
- The Foundation for Medical Research, Mumbai, Maharashtra, India
| | - Pradeep D'Costa
- King Edward Memorial Hospital and Research Centre, Pune, Maharashtra, India
| | | | - Sabri Bromage
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Elena C Hemler
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Kevin C Kain
- Department of Medicine, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Yatin Dholakia
- The Foundation for Medical Research, Mumbai, Maharashtra, India
| | - Wafaie W Fawzi
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
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24
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Golec M, Lemieszek MK, Dutkiewicz J, Milanowski J, Barteit S. A Scoping Analysis of Cathelicidin in Response to Organic Dust Exposure and Related Chronic Lung Illnesses. Int J Mol Sci 2022; 23:8847. [PMID: 36012117 PMCID: PMC9408003 DOI: 10.3390/ijms23168847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 08/06/2022] [Accepted: 08/07/2022] [Indexed: 11/21/2022] Open
Abstract
Over two billion people worldwide are exposed to organic dust, which can cause respiratory disorders. The discovery of the cathelicidin peptide provides novel insights into the lung's response to organic dust; however, its role in the lung's response to organic dust exposure and chronic lung diseases remains limited. We conducted a scoping review to map the current evidence on the role of cathelicidin LL-37/CRAMP in response to organic dust exposure and related chronic lung diseases: hypersensitivity pneumonitis (HP), chronic obstructive pulmonary disease (COPD) and asthma. We included a total of n = 53 peer-reviewed articles in this review, following the process of (i) a preliminary screening; (ii) a systematic MEDLINE/PubMed database search; (iii) title, abstract and full-text screening; (iv) data extraction and charting. Cathelicidin levels were shown to be altered in all clinical settings investigated; its pleiotropic function was confirmed. It was found that cathelicidin contributes to maintaining homeostasis and participates in lung injury response and repair, in addition to exerting a positive effect against microbial load and infections. In addition, LL-37 was found to sustain continuous inflammation, increase mucus formation and inhibit microorganisms and corticosteroids. In addition, studies investigated cathelicidin as a treatment modality, such as cathelicidin inhalation in experimental HP, which had positive effects. However, the primary focus of the included articles was on LL-37's antibacterial effect, leading to the conclusion that the beneficial LL-37 activity has not been adequately examined and that further research is required.
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Affiliation(s)
- Marcin Golec
- Heidelberg Institute of Global Health (HIGH), Faculty of Medicine and University Hospital, Heidelberg University, 69117 Heidelberg, Germany
| | - Marta Kinga Lemieszek
- Department of Medical Biology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland
| | - Jacek Dutkiewicz
- Department of Biological Health Hazards and Parasitology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland
| | - Janusz Milanowski
- Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Sandra Barteit
- Heidelberg Institute of Global Health (HIGH), Faculty of Medicine and University Hospital, Heidelberg University, 69117 Heidelberg, Germany
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25
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Migliorini F, Vaishya R, Eschweiler J, Oliva F, Hildebrand F, Maffulli N. Vitamins C and D and COVID-19 Susceptibility, Severity and Progression: An Evidence Based Systematic Review. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:941. [PMID: 35888660 PMCID: PMC9318801 DOI: 10.3390/medicina58070941] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/02/2022] [Accepted: 07/12/2022] [Indexed: 04/07/2023]
Abstract
Background and Objectives: Starting in early December 2019, the novel Coronavirus Disease (COVID-19) from infection with COVID-19 has caused a global pandemic. Many aspects of its pathogenesis and related clinical consequences are still unclear. Early diagnosis and dynamic monitoring of prognostic factors are essential to improve the ability to manage COVID-19 infection. This study aimed to provide an account of the role played by vitamins C and D on the onset, progression and severity of COVID-19. Clinical features and infection-related risk factors are also briefly discussed. Material and Methods: In March 2022, the main online databases were accessed. All the articles that investigate the possible role of vitamins C and D on COVID-19 susceptibility, severity and progression were considered. Results: The current evidence on vitamin C and D supplementation in patients with COVID-19 infection is inconsistent and controversial. In some studies, vitamins were used as coadjuvant of a formal experimental therapy, while in others as main treatment. Ethnicity and hospital setting (inpatient/outpatient) were also variable. Moreover, there was no consensus between studies in administration protocol: high heterogeneity in dosage, administration, and duration of the treatment were evident. Finally, some studies administered vitamins pre- and/or during COVID infection, in patients with different risk factors and infection severity. Conclusions: While waiting to develop a targeted, safe and effective therapy, it is important to investigate individual predisposition and proper disease management. Concluding, available data on the use of nutraceuticals in COVID-19 are inconsistent. However, there is a lack of evidence-based guidelines which recommend vitamin C and D supplementation in patients with COVID-19, and results from high quality randomised controlled trials (RCTs) are inconsistent. Current investigations so far are mostly observational, and include a relatively small sample size which can lead to biased results. Large-scale multicentre studies are therefore needed.
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Affiliation(s)
- Filippo Migliorini
- Department of Orthopaedic, Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany; (J.E.); (F.H.)
| | - Raju Vaishya
- Department of Orthopaedics, Indraprastha Apollo Hospitals Institutes of Orthopaedics, New Delhi 110076, India;
| | - Jörg Eschweiler
- Department of Orthopaedic, Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany; (J.E.); (F.H.)
| | - Francesco Oliva
- Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi, Italy; (F.O.); (N.M.)
| | - Frank Hildebrand
- Department of Orthopaedic, Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany; (J.E.); (F.H.)
| | - Nicola Maffulli
- Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi, Italy; (F.O.); (N.M.)
- School of Pharmacy and Bioengineering, Keele University Faculty of Medicine, Thornburrow Drive, Stoke on Trent ST5 5BG, UK
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Centre for Sports and Exercise Medicine, Mile End Hospital, 275 Bancroft Road, London E1 4DG, UK
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26
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Abstract
PURPOSE OF REVIEW To review the mechanisms by which vitamin D and its metabolites regulate the immune system to facilitate the ability of the body to prevent and/or treat SARS-CoV2 and other respiratory infections and encourage further research into the role that vitamin D supplementation plays in preventing/treating such infections. RECENT FINDINGS Vitamin D deficiency is associated with an increased risk of SARS-CoV2 and other respiratory infections. Clinical trials in general demonstrate that correction of vitamin D deficiency reduces the risk of hospitalization, ICU admission, and death from SARS-CoV2 infection. The airway epithelium and alveolar macrophages express the enzyme, CYP27B1, that produces the active metabolite of vitamin D, 1,25(OH)2D, and the vitamin D receptor, VDR. Vitamin D and its metabolites promote the innate immune response, which provides the first line of defense against viral and bacterial infections while restricting the adaptive immune response, which if unchecked promotes the inflammatory response leading to the acute respiratory distress syndrome and death. The rationale for treating vitamin D deficiency to reduce the risk of SARS-CoV2 infection and supplementing patients with vitamin D early in the course of SARS-CoV2 infection rests primarily on the ability of vitamin D metabolites to promote an effective immune response to the infection.
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Affiliation(s)
- Daniel D Bikle
- Veterans Affairs Medical Center, University of California San Francisco, 1700 Owens St, San Francisco, CA, 94158, USA.
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27
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Castillo JA, Giraldo DM, Smit JM, Rodenhuis-Zybert IA, Urcuqui-Inchima S. Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection. Pathog Dis 2022; 80:6581314. [PMID: 35512569 DOI: 10.1093/femspd/ftac014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 04/26/2022] [Accepted: 05/03/2022] [Indexed: 11/13/2022] Open
Abstract
Epidemics of dengue, an acute and potentially severe disease caused by mosquito-borne dengue virus (DENV), pose a major challenge to clinicians and health care services across the sub(tropics). Severe disease onset is associated with a dysregulated inflammatory response to the virus and there are currently no drugs to alleviate disease symptoms. LL-37 is a potent antimicrobial peptide with a wide range of immunoregulatory properties. In this study, we assessed the effect of LL-37 on DENV-2-induced responses in human monocyte-derived macrophages (MDMs). We show that simultaneous exposure of exogenous LL-37 and DENV-2 resulted in reduced replication of the virus in MDMs, while the addition of LL-37 post-exposure to DENV-2 did not. Interestingly, the latter condition reduced the production of IL-6 and increased the expression of genes involved in virus sensing and antiviral response. Finally, we demonstrate that low endogenous levels and limited production of LL-37 in MDMs in response to DENV-2 infection can be increased by differentiating MDMs in the presence of Vitamin D (VitD3). Taken together, this study demonstrates that in addition to its antimicrobial properties, LL-37 has immunomodulatory properties in the curse of DENV infection and its production can be increased by VitD3.
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Affiliation(s)
- Jorge Andrés Castillo
- Grupo Inmunovirología. Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia.,Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Diana Marcela Giraldo
- Grupo Inmunovirología. Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia
| | - Jolanda M Smit
- Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Izabela A Rodenhuis-Zybert
- Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Silvio Urcuqui-Inchima
- Grupo Inmunovirología. Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia
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28
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Niemeyer BF, Benam KH. Untapping host-targeting cross-protective efficacy of anticoagulants against SARS-CoV-2. Pharmacol Ther 2022; 233:108027. [PMID: 34718070 PMCID: PMC8552695 DOI: 10.1016/j.pharmthera.2021.108027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 10/13/2021] [Accepted: 10/25/2021] [Indexed: 02/07/2023]
Abstract
Responding quickly to emerging respiratory viruses, such as SARS-CoV-2 the causative agent of coronavirus disease 2019 (COVID-19) pandemic, is essential to stop uncontrolled spread of these pathogens and mitigate their socio-economic impact globally. This can be achieved through drug repurposing, which tackles inherent time- and resource-consuming processes associated with conventional drug discovery and development. In this review, we examine key preclinical and clinical therapeutic and prophylactic approaches that have been applied for treatment of SARS-CoV-2 infection. We break these strategies down into virus- versus host-targeting and discuss their reported efficacy, advantages, and disadvantages. Importantly, we highlight emerging evidence on application of host serine protease-inhibiting anticoagulants, such as nafamostat mesylate, as a potentially powerful therapy to inhibit virus activation and offer cross-protection against multiple strains of coronavirus, lower inflammatory response independent of its antiviral effect, and modulate clotting problems seen in COVID-19 pneumonia.
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Affiliation(s)
- Brian F Niemeyer
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Kambez H Benam
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
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29
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Abstract
Covid-19 has to date infected a confirmed 275 million people with 5.4 million, now dead, with the count rising every day. Although the virus, SARS-CoV2, causing Covid-19 infects many cells in the body, its infection of the upper and lower respiratory tract (upper airway epithelia and pulmonary alveolar pneumocytes and macrophages) causing what is now called a cytokine storm in the lungs is the major cause of morbidity and mortality. This results from a dysregulation of the innate immune system with an outpouring of proinflammatory cytokines and chemokines leading to abnormal activation of the adaptive immune pathway. Airway epithelia constitutively expresses CYP27B1, the enzyme producing the active vitamin D metabolite, 1,25(OH)2D, and the vitamin D receptor (VDR) for which 1,25(OH)2D is the ligand. Pulmonary alveolar macrophages, on the other hand, are induced to express both CYP27B1 and VDR by various pathogens including viruses and cytokines released from infected epithelia and other immune cells. Although not demonstrated for corona viruses like SARS-CoV2, for other viruses and other respiratory pathogens activation of innate immunity leading to increased local 1,25(OH)2D production has been shown to enhance viral neutralization and clearance while modulating the subsequent proinflammatory response. Whether such will be the case for SARS-CoV2 remains to be seen, but is currently being proposed and investigated. This mini review will discuss some of the mechanisms by which vitamin D may help reduce morbidity and mortality in this devastating pandemic.
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Affiliation(s)
- Daniel D Bikle
- Veterans Affairs Medical Center and University of California San Francisco, 4150 Clement Street (111N), San Francisco, CA, 94121, USA.
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30
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Abstract
Vitamin D, best known for its role in skeletal health, has emerged as a key regulator of innate immune responses to microbial threat. In immune cells such as macrophages, expression of CYP27B1, the 25-hydroxyvitamin D 1α-hydroxylase, is induced by immune-specific inputs, leading to local production of hormonal 1,25-dihydroxyvitamin D (1,25D) at sites of infection, which in turn directly induces the expression of genes encoding antimicrobial peptides. Vitamin D signaling is active upstream and downstream of pattern recognition receptors, which promote front-line innate immune responses. Moreover, 1,25D stimulates autophagy, which has emerged as a mechanism critical for control of intracellular pathogens such as M. tuberculosis. Strong laboratory and epidemiological evidence links vitamin D deficiency to increased rates of conditions such as dental caries, as well as inflammatory bowel diseases arising from dysregulation of innate immune handling intestinal flora. 1,25D is also active in signaling cascades that promote antiviral innate immunity; 1,25D-induced expression of the antimicrobial peptide CAMP/LL37, originally characterized for its antibacterial properties, is a key component of antiviral responses. Poor vitamin D status is associated with greater susceptibility to viral infections, including those of the respiratory tract. Although the severity of the COVID-19 pandemic has been alleviated in some areas by the arrival of vaccines, it remains important to identify therapeutic interventions that reduce disease severity and mortality, and accelerate recovery. This review outlines of our current knowledge of the mechanisms of action of vitamin D signaling in the innate immune system. It also provides an assessment of the therapeutic potential of vitamin D supplementation in infectious diseases, including an up-to-date analysis of the putative benefits of vitamin D supplementation in the ongoing COVID-19 crisis.
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Affiliation(s)
- Aiten Ismailova
- Departments of Physiology, McGill University, Montreal, Qc, Canada
| | - John H White
- Departments of Physiology, McGill University, Montreal, Qc, Canada.
- Departments of Medicine, McGill University, Montreal, Qc, Canada.
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Serré J, Mathyssen C, Ajime TT, Heigl T, Verlinden L, Maes K, Verstuyf A, Cataldo D, Vanoirbeek J, Vanaudenaerde B, Janssens W, Gayan-Ramirez G. Local nebulization of 1α,25(OH)2D3 attenuates LPS-induced acute lung inflammation. Respir Res 2022; 23:76. [PMID: 35351141 PMCID: PMC8966160 DOI: 10.1186/s12931-022-01997-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 03/17/2022] [Indexed: 12/29/2022] Open
Abstract
Background Evidence supports a critical role of vitamin D status on exacerbation in chronic obstructive pulmonary disease, indicating the need to avoid vitamin D deficiency in these patients. However, oral vitamin D supplementation is limited by the potential risk for hypercalcemia. In this study, we investigated if local delivery of vitamin D to the lungs improves vitamin D-mediated anti-inflammatory action in response to acute inflammation without inducing hypercalcemia. Methods We studied vitamin D sufficient (VDS) or deficient (VDD) mice in whom 1α,25(OH)2D3 (0.2 μg/kg) or a vehicle followed by lipopolysaccharide (LPS 25 µg) were delivered to the lung as a micro-spray. Results Local 1α,25(OH)2D3 reduced LPS-induced inflammatory cells in bronchoalveolar lavage (BAL) in VDS (absolute number of cells: − 57% and neutrophils − 51% p < 0.01) and tended to diminish LPS-increased CXCL5 BAL levels in VDS (− 40%, p = 0.05) while it had no effect on CXCL1 and CXCL2 in BAL and mRNA in lung of VDS and VDD. It also significantly attenuated the increased IL-13 in BAL and lung, especially in VDD mice (− 41 and − 75%, respectively). mRNA expression of Claudin-18 in lung was significantly lower in VDS mice with local 1α,25(OH)2D3 while Claudin-3, -5 and -8 mRNA levels remained unchanged. Finally, in VDD mice only, LPS reduced lung mRNA expression of adhesion junction Zona-occludens-1, in addition to increasing uric acid and total protein in BAL, which both were prevented by local 1α,25(OH)2D3. Conclusion Under normal levels of vitamin D, local 1α,25(OH)2D3 nebulization into the lung efficiently reduced LPS induction of inflammatory cells in BAL and slightly attenuated LPS-increase in CXCL5. In case of severe vitamin D deficiency, although local 1α,25(OH)2D3 nebulization failed to significantly minimize cellular inflammation in BAL at this dose, it prevented epithelial barrier leakage and damage in lung. Additional research is needed to determine the potential long-term beneficial effects of local 1α,25(OH)2D3 nebulization on lung inflammation. Supplementary Information The online version contains supplementary material available at 10.1186/s12931-022-01997-9.
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Diyya ASM, Thomas NV. Multiple Micronutrient Supplementation: As a Supportive Therapy in the Treatment of COVID-19. BIOMED RESEARCH INTERNATIONAL 2022; 2022:3323825. [PMID: 35355818 PMCID: PMC8960013 DOI: 10.1155/2022/3323825] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 02/03/2022] [Accepted: 02/24/2022] [Indexed: 12/13/2022]
Abstract
During the infection and treatment of the SARS-CoV-2 viral infection, age and comorbidities play a major role in the successful management of COVID-19. The nutritional status changes which occur in the body vary with the age and underlying conditions and has a vital role in the functioning of the immune system and cellular membrane integrity, thus minimizing the vulnerability to the infection. Considering the data already published by eminent researchers, a few micronutrients have shown outstanding results as supportive therapies in the treatment of viral infections. Micronutrient like zinc improves the membrane barrier integrity, has anti-inflammatory activity, and is involved in antibody production. Vitamin A supports the phagocytic activity of macrophages, while vitamin C reduces the worsening of respiratory tract infections by restoring the dysfunctional epithelial barrier of the lungs. Vitamin D, vitamin E, selenium, and omega-3 fatty acid metabolites play a major role in immunomodulation and in the inhibition of proinflammatory cytokine production. Magnesium is involved in the synthesis of antibodies, while copper, vitamin B12, and folate have significant effects on immune cells. A few researchers suggest that iron supplementation has reduced the risk of acquiring respiratory tract infections in children. As the age of the patient increases, the need for micronutrients increases, thus leading to an imbalanced nutritional status which in turn increases the risk and fatality of the infections. The use of micronutrients in modulating the inflammatory, immune responses, and the epithelial barrier integrity is explored during the treatment of viral infections for faster recovery.
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Affiliation(s)
- A Salomy Monica Diyya
- College of Medicine, Department of Pharmacy, Komar University of Science and Technology, Sulaymaniyah, Kurdistan, Iraq
| | - Noel Vinay Thomas
- College of Science, Department of Biomedical Science, Komar University of Science and Technology, Sulaymaniyah, Kurdistan, Iraq
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Cho H, Myung SK, Cho HE. Efficacy of Vitamin D Supplements in Treatment of Acute Respiratory Infection: A Meta-Analysis for Randomized Controlled Trials. Nutrients 2022; 14:nu14061144. [PMID: 35334804 PMCID: PMC8955452 DOI: 10.3390/nu14061144] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 02/28/2022] [Accepted: 03/03/2022] [Indexed: 12/10/2022] Open
Abstract
BACKGROUND Recent randomized controlled trials (RCTs) have reported inconsistent findings regarding the efficacy of vitamin D supplementation in the treatment of acute respiratory infections (ARIs). This study aimed to investigate the efficacy of vitamin D supplementation in the treatment of ARIs using a meta-analysis of RCTs. METHODS PubMed, EMBASE, and the Cochrane Library were searched for relevant articles in June 2021. Two of the authors independently assessed the eligibility of the trials. RESULTS Out of 390 articles retrieved from the databases, we included 18 RCTs, which involved 3648 participants, with 1838 in an intervention group and 1810 in a control group in the final analysis. In the meta-analysis of all the trials, vitamin D supplements had a beneficial effect in the treatment of ARIs (relative risk (RR) = 1.07; 95% confidence interval (CI), 1.01-1.13; I2 = 66.9%). Publication bias was observed in the funnel plot. In the subgroup meta-analysis of high-quality RCTs, no significant efficacy of vitamin D supplements was found (RR = 1.02; 95% CI, 0.98-1.06; I2 = 24.0%). Although statistically significant changes of 7% in the treatment effects were observed, they are not considered as clinically substantial ones. CONCLUSIONS The current meta-analysis suggests that vitamin D supplements are not clinically effective in the treatment of ARIs.
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Affiliation(s)
- Herim Cho
- Department of Medicine, College of Medicine, Ewha Womans University, Seoul 07804, Korea; (H.C.); (H.-E.C.)
| | - Seung-Kwon Myung
- Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang 10408, Korea
- Cancer Epidemiology Branch, Division of Cancer Data Science, National Cancer Center Research Institute, Goyang 10408, Korea
- Department of Family Medicine and Center for Cancer Prevention and Detection, National Cancer Center Hospital, Goyang 10408, Korea
- Correspondence: ; Tel.: +82-31-920-0479
| | - Hae-Eun Cho
- Department of Medicine, College of Medicine, Ewha Womans University, Seoul 07804, Korea; (H.C.); (H.-E.C.)
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Bokobza I, El Hadi N, Bush A, Makrinioti H. Can vitamin D 3 supplementation reduce the time to severe asthma exacerbations in children with asthma? Breathe (Sheff) 2022; 17:210071. [PMID: 35035547 PMCID: PMC8753645 DOI: 10.1183/20734735.0071-2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 07/14/2021] [Indexed: 11/05/2022] Open
Abstract
Vitamin D deficiency in children needs to be treated irrespective of asthma benefits. The VDKA trial showed that vitamin D supplementation in school-age asthmatic children with vitamin D insufficiency did not improve asthma control. https://bit.ly/2UF3j61.
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Affiliation(s)
- Idan Bokobza
- West Middlesex University Hospital, Chelsea, and Westminster Foundation Trust, London, UK
| | - Nour El Hadi
- West Middlesex University Hospital, Chelsea, and Westminster Foundation Trust, London, UK
| | - Andrew Bush
- Imperial Centre for Paediatrics and Child Health, Imperial College, London, UK.,National Heart and Lung Institute, Imperial College, London, UK
| | - Heidi Makrinioti
- West Middlesex University Hospital, Chelsea, and Westminster Foundation Trust, London, UK.,Imperial Centre for Paediatrics and Child Health, Imperial College, London, UK
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Mitra S, Paul S, Roy S, Sutradhar H, Bin Emran T, Nainu F, Khandaker MU, Almalki M, Wilairatana P, Mubarak MS. Exploring the Immune-Boosting Functions of Vitamins and Minerals as Nutritional Food Bioactive Compounds: A Comprehensive Review. Molecules 2022; 27:555. [PMID: 35056870 PMCID: PMC8779769 DOI: 10.3390/molecules27020555] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 01/04/2022] [Accepted: 01/10/2022] [Indexed: 02/06/2023] Open
Abstract
Food components have long been recognized to play a fundamental role in the growth and development of the human body, conferring protective functionalities against foreign matter that can be severe public health problems. Micronutrients such as vitamins and minerals are essential to the human body, and individuals must meet their daily requirements through dietary sources. Micronutrients act as immunomodulators and protect the host immune response, thus preventing immune evasion by pathogenic organisms. Several experimental investigations have been undertaken to appraise the immunomodulatory functions of vitamins and minerals. Based on these experimental findings, this review describes the immune-boosting functionalities of micronutrients and the mechanisms of action through which these functions are mediated. Deficiencies of vitamins and minerals in plasma concentrations can lead to a reduction in the performance of the immune system functioning, representing a key contributor to unfavorable immunological states. This review provides a descriptive overview of the characteristics of the immune system and the utilization of micronutrients (vitamins and minerals) in preventative strategies designed to reduce morbidity and mortality among patients suffering from immune invasions or autoimmune disorders.
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Affiliation(s)
- Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh; (S.M.); (S.P.); (S.R.); (H.S.)
| | - Shyamjit Paul
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh; (S.M.); (S.P.); (S.R.); (H.S.)
| | - Sumon Roy
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh; (S.M.); (S.P.); (S.R.); (H.S.)
| | - Hriday Sutradhar
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh; (S.M.); (S.P.); (S.R.); (H.S.)
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh;
| | - Firzan Nainu
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Sulawesi Selatan, Indonesia;
| | - Mayeen Uddin Khandaker
- Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, Bandar Sunway 47500, Selangor, Malaysia;
| | - Mohammed Almalki
- Department of Nursing, Faculty of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia;
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
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Endogenous cathelicidin is required for protection against ZIKV-caused testis damage via inactivating virons. Antiviral Res 2022; 198:105248. [PMID: 35038500 DOI: 10.1016/j.antiviral.2022.105248] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/04/2022] [Accepted: 01/10/2022] [Indexed: 12/18/2022]
Abstract
Cathelicidins have been shown to effectively inhibit flavivirus replication in vitro. However, the effects of mouse and human endogenous cathelicidins on flavivirus infection in vivo are rarely known. We herein found that mouse endogenous cathelicidin CRAMP was significantly up-regulated upon Zika virus (ZIKV) infection. CRAMP deficiency markedly exacerbated ZIKV replication in testis, and aggravated ZIKV-induced testicular damage and ZIKV-induced spermatic damage in mice, indicating that endogenous cathelicidin is required for protection against ZIKV-caused male infertility in mice. In vitro antiviral assay showed that both mouse cathelidin CRAMP and human cathelicidin LL-37 obviously reduced ZIKV-caused cytopathic effect and inhibited ZIKV replication in Vero cells. Antiviral mechanism revealed that they both directly inactivated ZIKV virons by binding to ZIKV virons and inducing the leakage of ZIKV genomic RNA, consequently inactivated ZIKV virons. In vivo antiviral assay indicated that both of them effectively inhibited ZIKV replication in C57BL/6J and IFNα/β receptor-deficient (Ifnar1-/-) mice when CRAMP or LL-37 was intravenously injected in parallel with or at 1 h after intravenous injection of ZIKV, implying that mouse cathelidin CRAMP and human cathelicidin LL-37 effectively inactivated ZIKV particles and exhibited therapeutic potential against ZIKV infection in vivo. Our findings reveal that endogenous cahtelicidin CRAMP and LL-37 act as inactivators of ZIKV, and effectively protect against ZIKV replication and ZIKV-induced male infertility, highlighting their potential for therapy of ZIKV infection.
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Esneau C, Duff AC, Bartlett NW. Understanding Rhinovirus Circulation and Impact on Illness. Viruses 2022; 14:141. [PMID: 35062345 PMCID: PMC8778310 DOI: 10.3390/v14010141] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/08/2022] [Accepted: 01/10/2022] [Indexed: 01/27/2023] Open
Abstract
Rhinoviruses (RVs) have been reported as one of the main viral causes for severe respiratory illnesses that may require hospitalization, competing with the burden of other respiratory viruses such as influenza and RSV in terms of severity, economic cost, and resource utilization. With three species and 169 subtypes, RV presents the greatest diversity within the Enterovirus genus, and despite the efforts of the research community to identify clinically relevant subtypes to target therapeutic strategies, the role of species and subtype in the clinical outcomes of RV infection remains unclear. This review aims to collect and organize data relevant to RV illness in order to find patterns and links with species and/or subtype, with a specific focus on species and subtype diversity in clinical studies typing of respiratory samples.
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Affiliation(s)
| | | | - Nathan W. Bartlett
- Hunter Medical Research Institute, College of Health Medicine and Wellbeing, University of Newcastle, New Lambton Heights, NSW 2305, Australia; (C.E.); (A.C.D.)
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Cimmino G, Conte S, Morello M, Pellegrino G, Marra L, Morello A, Nicoletti G, De Rosa G, Golino P, Cirillo P. Vitamin D Inhibits IL-6 Pro-Atherothrombotic Effects in Human Endothelial Cells: A Potential Mechanism for Protection against COVID-19 Infection? J Cardiovasc Dev Dis 2022; 9:27. [PMID: 35050236 PMCID: PMC8781542 DOI: 10.3390/jcdd9010027] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/06/2022] [Accepted: 01/11/2022] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Thrombosis with cardiovascular involvement is a crucial complication in COVID-19 infection. COVID-19 infects the host by the angiotensin converting enzyme-2 receptor (ACE2r), which is expressed in endothelial cells too. Thus, COVID-related thrombotic events might be due to endothelial dysfunction. IL-6 is one of the main cytokines involved in the COVID-19 inflammatory storm. Some evidence indicates that Vitamin D (VitD) has a protective role in COVID-19 patients, but the molecular mechanisms involved are still debated. Thus, we investigated the effect of VitD on Tissue Factor and adhesion molecules (CAMs) in IL-6-stimulated endothelial cells (HUVEC). Moreover, we evaluated levels of the ACE2r gene and proteins. Finally, we studied the modulation of NF-kB and STAT3 pathways. METHODS HUVEC cultivated in VitD-enriched medium were stimulated with IL-6 (0.5 ng/mL). The TF gene (RT-PCR), protein (Western blot), surface expression (FACS) and procoagulant activity (FXa generation assay) were measured. Similarly, CAMs soluble values (ELISA) and ACE2r (RT-PCR and Western blot) levels were assessed. NF-kB and STAT3 modulation (Western blot) were also investigated. RESULTS VitD significantly reduced TF expression at both gene and protein levels as well as TF-procoagulant activity in IL-6-treated HUVEC. Similar effects were observed for CAMs and ACE2r expression. IL-6 modulates these effects by regulating NF-κB and STAT3 pathways. CONCLUSIONS IL-6 induces endothelial dysfunction with TF and CAMs expression via upregulation of ACE2r. VitD prevented these IL-6 deleterious effects. Thus, it might be speculated that this is one of the hypothetical mechanism(s) by which VitD exerts its beneficial effects in COVID-19 infection.
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Affiliation(s)
- Giovanni Cimmino
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (G.C.); (P.G.)
| | - Stefano Conte
- Department of Translational Medical Sciences, Section of Lung Disease, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Mariarosaria Morello
- Department of Advanced Biomedical Sciences, Section of Cardiology, University of Naples “Federico II”, 80131 Naples, Italy; (M.M.); (G.N.); (G.D.R.)
| | - Grazia Pellegrino
- Department of Woman, Child and General and Specialized Surgery, Section of Anesthesiology, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | - Laura Marra
- Department of Cell Biology and Biotherapy Research, Istituto Nazionale Tumori IRCCS—Fondazione G. Pascale, 80131 Naples, Italy;
| | - Andrea Morello
- Biochemical Unit, A. S. Re. M. (Azienda Sanitaria Regionale del Molise), Antonio Cardarelli Hospital, 86100 Campobasso, Italy;
| | - Giuseppe Nicoletti
- Department of Advanced Biomedical Sciences, Section of Cardiology, University of Naples “Federico II”, 80131 Naples, Italy; (M.M.); (G.N.); (G.D.R.)
| | - Gennaro De Rosa
- Department of Advanced Biomedical Sciences, Section of Cardiology, University of Naples “Federico II”, 80131 Naples, Italy; (M.M.); (G.N.); (G.D.R.)
| | - Paolo Golino
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (G.C.); (P.G.)
| | - Plinio Cirillo
- Department of Advanced Biomedical Sciences, Section of Cardiology, University of Naples “Federico II”, 80131 Naples, Italy; (M.M.); (G.N.); (G.D.R.)
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White JH. Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity. Nutrients 2022; 14:284. [PMID: 35057465 PMCID: PMC8779757 DOI: 10.3390/nu14020284] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/04/2022] [Accepted: 01/08/2022] [Indexed: 02/06/2023] Open
Abstract
Vitamin D deficiency, characterized by low circulating levels of calcifediol (25-hydroxyvitamin D, 25D) has been linked to increased risk of infections of bacterial and viral origin. Innate immune cells produce hormonal calcitriol (1,25-dihydroxyvitamin D, 1,25D) locally from circulating calcifediol in response to pathogen threat and an immune-specific cytokine network. Calcitriol regulates gene expression through its binding to the vitamin D receptor (VDR), a ligand-regulated transcription factor. The hormone-bound VDR induces the transcription of genes integral to innate immunity including pattern recognition receptors, cytokines, and most importantly antimicrobial peptides (AMPs). Transcription of the human AMP genes β-defensin 2/defensin-β4 (HBD2/DEFB4) and cathelicidin antimicrobial peptide (CAMP) is stimulated by the VDR bound to promoter-proximal vitamin D response elements. HDB2/DEFB4 and the active form of CAMP, the peptide LL-37, which form amphipathic secondary structures, were initially characterized for their antibacterial actively. Notably, calcitriol signaling induces secretion of antibacterial activity in vitro and in vivo, and low circulating levels of calcifediol are associated with diverse indications characterized by impaired antibacterial immunity such as dental caries and urinary tract infections. However, recent work has also provided evidence that the same AMPs are components of 1,25D-induced antiviral responses, including those against the etiological agent of the COVID-19 pandemic, the SARS-CoV2 coronavirus. This review surveys the evidence for 1,25D-induced antimicrobial activity in vitro and in vivo in humans and presents our current understanding of the potential mechanisms by which CAMP and HBD2/DEFB4 contribute to antiviral immunity.
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Affiliation(s)
- John H White
- Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada
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Min J, Jo H, Chung YJ, Song JY, Kim MJ, Kim MR. Vitamin D and the Immune System in Menopause: A Review. J Menopausal Med 2022; 27:109-114. [PMID: 34989184 PMCID: PMC8738846 DOI: 10.6118/jmm.21011] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 08/31/2021] [Accepted: 10/26/2021] [Indexed: 12/18/2022] Open
Abstract
Menopause is a normal phenomenon in a woman’s life cycle involving multiple health-related issues that contribute to physical instability. Changes in the immune system in postmenopausal women are caused by estrogen deprivation along with age. Increased proinflammatory serum marker levels, cytokine responses in body cells, decreased CD4 T and B lymphocyte levels, and natural killer cell cytotoxic activity are also observed during postmenopause. Moreover, vitamin D, in addition to its classical effects on calcium homeostasis and bone density, plays an important role. Current evidence indicates that vitamin D regulates innate and adaptive immune responses; however, vitamin D deficiency is linked to increased autoimmune activity and infection susceptibility. This review provides an overview of the consequences of immune alterations as an outcome of aging in postmenopausal women and the benefit of vitamin D supplementation.
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Affiliation(s)
- Jaeyoung Min
- Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hagyeong Jo
- Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Youn-Jee Chung
- Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jae Yen Song
- Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Min Jeong Kim
- Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Mee-Ran Kim
- Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Gayan‐Ramirez G, Janssens W. Vitamin D Actions: The Lung Is a Major Target for Vitamin D, FGF23, and Klotho. JBMR Plus 2021; 5:e10569. [PMID: 34950829 PMCID: PMC8674778 DOI: 10.1002/jbm4.10569] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 09/29/2021] [Accepted: 10/09/2021] [Indexed: 11/16/2022] Open
Abstract
Vitamin D is well known for its role as a calcium regulator and in maintenance of phosphate homeostasis in musculoskeletal health, and fibroblast growth factor 23 (FGF23) and its coreceptor α-klotho are known for their roles as regulators of serum phosphate levels. However, apart from these classical actions, recent data point out a relevant role of vitamin D and FGF23/klotho in lung health. The expression of the vitamin D receptor by different cell types in the lung and the fact that those cells respond to vitamin D or can locally produce vitamin D indicate that the lung represents a target for vitamin D actions. Similarly, the presence of the four FGF receptor isoforms in the lung and the ability of FGF23 to stimulate pulmonary cells support the concept that the lung is a target for FGF23 actions, whereas the contribution of klotho is still undetermined. This review will give an overview on how vitamin D or FGF23/klotho may act on the lung and interfere positively or negatively with lung health. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Ghislaine Gayan‐Ramirez
- Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETAKU LeuvenLeuvenBelgium
| | - Wim Janssens
- Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETAKU LeuvenLeuvenBelgium
- Clinical Department of Respiratory DiseasesUZ LeuvenLeuvenBelgium
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Ranjbar M, Karbalaie Niya MH, Roham M, Rezaie N, Yadollahzadeh M, Farrokhpour M, Azimi M, Motamed N, Perumal D, Tameshkel FS, Dadras F, Madani NH, Ghanbari B, Faraji A, Nikkhah M, Rahmani S, Golgiri F, Emadi SY, Abbasi R, Mohseni I, Babaei MR, Eskandari R, Ataee M, Panahi M, Zamani F, Makiani MJ, Laali A. Serum level of Vitamin D is associated with COVID-19 mortality rate in hospitalized patients. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2021; 26:112. [PMID: 35126575 PMCID: PMC8765512 DOI: 10.4103/jrms.jrms_1151_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 03/28/2021] [Accepted: 06/09/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Due to widespread of coronavirus disease 2019 (COVID-19) infection, identification of its risk factors and clinical characteristics are important. The aim of the present study was to assess Vitamin D levels in individuals with severe acute respiratory syndrome coronavirus-19 infection and to report on its potential as a predictive marker. MATERIALS AND METHODS All patients, diagnosed with COVID-19 infection from February 16 to March 21, 2020, and referred to Firoozgar Hospital, Tehran, Iran, were enrolled in this study. Vitamin D analysis was undertaken on patient serum samples using a commercial kit (Pars Azmoon Co., Tehran, Iran). SPSS v. 22 was used for statistical analysis. RESULTS Vitamin D serum concentration was analyzed in a total of 317 patients whose mean age ± standard deviation was 62.05 ± 15 years and with 62.5% being male. A significant association of Vitamin D level and death was observed. Higher levels of serum Vitamin D had protection against death (odds ratio = 0.955 [95% confidence interval = 0.923-0.988], P = 0.008). CONCLUSION As a preliminary study in the Iranian population who suffered COVID-19 disease, we identified that Vitamin D deficiency was associated with a higher death rate and intensive care unit admission.
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Affiliation(s)
- Mitra Ranjbar
- Department of Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | | | - Maryam Roham
- Department of Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
- Antimicrobial Resistant Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Nader Rezaie
- Department of Pulmonology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Mahdi Yadollahzadeh
- Department of Internal Medicine, School of Medicine, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Farrokhpour
- Department of Internal Medicine, School of Medicine, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Mehdi Azimi
- Department of Internal Medicine, School of Medicine, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Nima Motamed
- Department of Social Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Dhayaneethie Perumal
- Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences Pharmacy and Chemistry, Kingston University, London, United Kingdom
| | | | - Farahnaz Dadras
- Department of Nephrology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Nahid Hashemi Madani
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Behrooz Ghanbari
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Faraji
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mehdi Nikkhah
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Shahrzad Rahmani
- Department of Nephrology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Fatemah Golgiri
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Seyed Yadollah Emadi
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Rowshanak Abbasi
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Iman Mohseni
- Department of Interventional Radiology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Babaei
- Department of Interventional Radiology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Ramin Eskandari
- Department of Cardiology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Manizhe Ataee
- Department of Interventional Radiology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Mahshid Panahi
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Farhad Zamani
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mahin Jamshidi Makiani
- Department of Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
- Antimicrobial Resistant Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Azadeh Laali
- Department of Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
- Antimicrobial Resistant Research Center, Iran University of Medical Sciences, Tehran, Iran
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43
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Banerjee A, Ganguly U, Saha S, Chakrabarti S, Saini RV, Rawal RK, Saso L, Chakrabarti S. Vitamin D and immuno-pathology of COVID-19: many interactions but uncertain therapeutic benefits. Expert Rev Anti Infect Ther 2021; 19:1245-1258. [PMID: 33739215 PMCID: PMC8022339 DOI: 10.1080/14787210.2021.1905519] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 03/16/2021] [Indexed: 02/06/2023]
Abstract
Introduction: COVID-19 pandemic has caused huge loss of human lives and extensive socio-economic damages. The immuno-pathology of this disease is neither clearly understood nor there are effective drugs for severe cases of COVID-19. Repurposing of available drugs for the treatment of COVID-19 is imperative.Areas Covered: This review has gathered the evidence from PubMed, Google Scholar, WHO, and other reliable websites on COVID-19 and summarized the existing knowledge of the immuno-pathology of COVID-19. We elucidated how vitamin D through its diverse actions on immune effector cells, epithelial cells, or renin-angiotensin-aldosterone system could have a modulatory role on the pathogenic mechanisms of COVID-19. The epidemiological evidence associating vitamin D deficiency with the severity and incidence of COVID-19 is also presented. However, the evidence of clinical benefit to patients of COVID-19 from randomized controlled trials with vitamin D has not come as yet.Expert opinion: It is now established that fatality of COVID-19 is primarily determined by hyperactivation of the host's innate immune system in response to SARS-CoV-2 invasion, and thus the research on the immuno-modulatory and other roles of vitamin D against viral infections should be pursued vigorously. This would be also useful for future pandemics caused by other novel viruses.
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Affiliation(s)
- Anindita Banerjee
- Department of Biochemistry, Institute of Post Graduate Medical Education and Research, Kolkata, India
| | - Upasana Ganguly
- Department of Biochemistry & Central Research Cell, M.M. Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to Be University), Mullana, India
| | - Sarama Saha
- Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, India
| | | | - Reena V Saini
- Department of Biotechnology, M.M Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana, India
| | - Ravindra K Rawal
- Department of Chemistry, M.M Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana, India
| | - Luciano Saso
- Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, Rome, Italy
| | - Sasanka Chakrabarti
- Department of Biochemistry & Central Research Cell, M.M. Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to Be University), Mullana, India
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44
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Vaghari-Tabari M, Mohammadzadeh I, Qujeq D, Majidinia M, Alemi F, Younesi S, Mahmoodpoor A, Maleki M, Yousefi B, Asemi Z. Vitamin D in respiratory viral infections: a key immune modulator? Crit Rev Food Sci Nutr 2021; 63:2231-2246. [PMID: 34470511 DOI: 10.1080/10408398.2021.1972407] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Respiratory viral infections are common respiratory diseases. Influenza viruses, RSV and SARS-COV2 have the potential to cause severe respiratory infections. Numerous studies have shown that unregulated immune response to these viruses can cause excessive inflammation and tissue damage. Therefore, regulating the antiviral immune response in the respiratory tract is of importance. In this regard, recent years studies have emphasized the importance of vitamin D in respiratory viral infections. Although, the most well-known role of vitamin D is to regulate the metabolism of phosphorus and calcium, it has been shown that this vitamin has other important functions. One of these functions is immune regulation. Vitamin D can regulate the antiviral immune response in the respiratory tract in order to provide an effective defense against respiratory viral infections and prevention from excessive inflammatory response and tissue damage. In addition, this vitamin has preventive effects against respiratory viral infections. Some studies during the COVID-19 pandemic have shown that vitamin D deficiency may be associated with a higher risk of mortality and sever disease in patients with COVID-19. Since, more attention has recently been focused on vitamin D. In this article, after a brief overview of the antiviral immune response in the respiratory system, we will review the role of vitamin D in regulating the antiviral immune response comprehensively. Then we will discuss the importance of this vitamin in influenza, RSV, and COVID-19.
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Affiliation(s)
- Mostafa Vaghari-Tabari
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.,Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Iraj Mohammadzadeh
- Non-Communicable Pediatric Diseases Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Durdi Qujeq
- Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran.,Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Maryam Majidinia
- Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran
| | - Forough Alemi
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Simin Younesi
- Schoole of Health and Biomedical Sciences, RMIT University, Melborne, VIC, Australia
| | - Ata Mahmoodpoor
- Department of Anesthesiology and Intensive Care, School of Medicine, Tabriz University of Medical Science and Health Services, Tabriz, Iran
| | - Masomeh Maleki
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Bahman Yousefi
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.,Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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45
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Chiu SK, Tsai KW, Wu CC, Zheng CM, Yang CH, Hu WC, Hou YC, Lu KC, Chao YC. Putative Role of Vitamin D for COVID-19 Vaccination. Int J Mol Sci 2021; 22:8988. [PMID: 34445700 PMCID: PMC8396570 DOI: 10.3390/ijms22168988] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/11/2021] [Accepted: 08/18/2021] [Indexed: 01/18/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 is a new, highly pathogenic virus that has recently elicited a global pandemic called the 2019 coronavirus disease (COVID-19). COVID-19 is characterized by significant immune dysfunction, which is caused by strong but unregulated innate immunity with depressed adaptive immunity. Reduced and delayed responses to interferons (IFN-I/IFN-III) can increase the synthesis of proinflammatory cytokines and extensive immune cell infiltration into the airways, leading to pulmonary disease. The development of effective treatments for severe COVID-19 patients relies on our knowledge of the pathophysiological components of this imbalanced innate immune response. Strategies to address innate response factors will be essential. Significant efforts are currently underway to develop vaccines against SARS-CoV-2. COVID-19 vaccines, such as inactivated DNA, mRNA, and protein subunit vaccines, have already been applied in clinical use. Various vaccines display different levels of effectiveness, and it is important to continue to optimize and update their composition in order to increase their effectiveness. However, due to the continuous emergence of variant viruses, improving the immunity of the general public may also increase the effectiveness of the vaccines. Many observational studies have demonstrated that serum levels of vitamin D are inversely correlated with the incidence or severity of COVID-19. Extensive evidence has shown that vitamin D supplementation could be vital in mitigating the progression of COVID-19 to reduce its severity. Vitamin D defends against SARS-CoV-2 through a complex mechanism through interactions between the modulation of innate and adaptive immune reactions, ACE2 expression, and inhibition of the renin-angiotensin system (RAS). However, it remains unclear whether Vit-D also plays an important role in the effectiveness of different COVID-19 vaccines. Based on analysis of the molecular mechanism involved, we speculated that vit-D, via various immune signaling pathways, plays a complementary role in the development of vaccine efficacy.
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Affiliation(s)
- Sheng-Kang Chiu
- Division of Infection, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan;
- School of Medicine, Tzu Chi University, Hualien 970, Taiwan
- Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
| | - Kuo-Wang Tsai
- Department of Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan;
| | - Chia-Chao Wu
- Department of Internal Medicine, Division of Nephrology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan;
- Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan
| | - Cai-Mei Zheng
- Division of Nephrology, Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, New Taipei City 235, Taiwan;
| | - Chung-Hsiang Yang
- Department of Pediatrics, Taoyuan Armed Forces General Hospital, Taoyuan City 325, Taiwan;
| | - Wan-Chung Hu
- Department of Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan;
| | - Yi-Chou Hou
- Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 234, Taiwan;
| | - Kuo-Cheng Lu
- Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan;
| | - You-Chen Chao
- Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan;
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McCartney DM, O'Shea PM, Faul JL, Healy MJ, Byrne G, Griffin TP, Walsh JB, Byrne DG, Kenny RA. Vitamin D and SARS-CoV-2 infection-evolution of evidence supporting clinical practice and policy development : A position statement from the Covit-D Consortium. Ir J Med Sci 2021; 190:1253-1265. [PMID: 33219912 PMCID: PMC7679797 DOI: 10.1007/s11845-020-02427-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 10/29/2020] [Indexed: 12/22/2022]
Affiliation(s)
- Daniel M McCartney
- School of Biological and Health Sciences, College of Sciences & Health, Technological University Dublin - City Campus, Dublin 8, Ireland.
| | - Paula M O'Shea
- Department of Clinical Biochemistry, Galway University Hospitals, Galway, Ireland
- School of Medicine, National University of Ireland Galway, Galway, Ireland
| | - John L Faul
- James Connolly Memorial Asthma Research Centre, Royal College of Surgeons in Ireland, Connolly Hospital Blanchardstown, Dublin 15, Ireland
| | - Martin J Healy
- Biochemistry Department, St. James's Hospital, Dublin 8, Ireland
| | - Greg Byrne
- School of Biological and Health Sciences, College of Sciences & Health, Technological University Dublin - City Campus, Dublin 8, Ireland
| | - Tomás P Griffin
- Regenerative Medicine Institute at CÚRAM SFI Research Centre, School of Medicine, National University of Ireland Galway, Galway, Ireland
- Centre for Endocrinology, Diabetes and Metabolism, Galway University Hospitals, Galway, Ireland
| | - James Bernard Walsh
- Mercer's Institute for Successful Ageing, St James's Hospital, Dublin 8, Ireland
- Department of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin 2, Ireland
| | - Declan G Byrne
- Department of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin 2, Ireland
- Medicine Directorate, St. James's Hospital, Dublin 8, Ireland
| | - Rose Anne Kenny
- Mercer's Institute for Successful Ageing, St James's Hospital, Dublin 8, Ireland
- Department of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin 2, Ireland
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47
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Daoust L, Pilon G, Marette A. Perspective: Nutritional Strategies Targeting the Gut Microbiome to Mitigate COVID-19 Outcomes. Adv Nutr 2021; 12:1074-1086. [PMID: 33783468 PMCID: PMC8083677 DOI: 10.1093/advances/nmab031] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 02/12/2021] [Accepted: 03/01/2021] [Indexed: 02/07/2023] Open
Abstract
More than a year has passed since the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection in the city of Wuhan in China's Hubei Province. Until now, few antiviral medications (e.g., remdesivir) or drugs that target inflammatory complications associated with SARS-CoV2 infection have been considered safe by public health authorities. By the end of November 2020, this crisis had led to >1 million deaths and revealed the high susceptibility of people with pre-existing comorbidities (e.g., obesity, diabetes, coronary heart disease, hypertension) to suffer from a severe form of the disease. Elderly people have also been found to be highly susceptible to SARS-CoV2 infection and morbidity. Gastrointestinal manifestations and gut microbial alterations observed in SARS-CoV2-infected hospitalized patients have raised awareness of the potential role of intestinal mechanisms in increasing the severity of the disease. It is therefore critically important to find alternative or complementary approaches, not only to prevent or treat the disease, but also to reduce its growing societal and economic burden. In this review, we explore potential nutritional strategies that implicate the use of polyphenols, probiotics, vitamin D, and ω-3 fatty acids with a focus on the gut microbiome, and that could lead to concrete recommendations that are easily applicable to both vulnerable people with pre-existing metabolic comorbidities and the elderly, but also to the general population.
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Affiliation(s)
- Laurence Daoust
- Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada
| | - Geneviève Pilon
- Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada
| | - André Marette
- Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada
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48
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Feketea G, Vlacha V, Tsiros G, Voila P, Pop RM, Bocsan IC, Stanciu LA, Zdrenghea M. Vitamin D Levels in Asymptomatic Children and Adolescents with Atopy during the COVID-19 Era. J Pers Med 2021; 11:jpm11080712. [PMID: 34442356 PMCID: PMC8400733 DOI: 10.3390/jpm11080712] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/20/2021] [Accepted: 07/23/2021] [Indexed: 12/15/2022] Open
Abstract
This study assessed vitamin D status in asymptomatic children and adolescents in Greece, with and without atopy, and possible changes during the coronavirus disease 2019 (COVID-19) pandemic. Serum levels of 25-hydroxy-vitamin D (25(OH)D) and total immunoglobulin E (IgE), and eosinophil count were measured in 340 asymptomatic children and adolescents (155 males, 185 females), mean age 8.6 ± 4.6 years, recruited over a period of 24 months (February 2019–January 2021). Atopy, defined by high level of IgE for age, was associated with vitamin D deficient status (p = 0.041). Subjects with and without atopy showed similar rates of insufficient and normal levels of 25(OH)D. The median level of 25(OH)D was significantly higher in subjects recruited during the pandemic, when home confinement rules were observed, than before the pandemic, and significantly more children had normal levels of 25(OH)D (p < 0.001), but no differences were noticed for IgE levels or eosinophil count. These results support a link between vitamin D and allergic and infectious inflammations, and specifically the association of vitamin D deficiency with asymptomatic atopy, defined as increased IgE level for age.
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Affiliation(s)
- Gavriela Feketea
- Department of Haematology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (G.F.); (M.Z.)
- Hospital Unit of Amaliada, Department of Paediatrics, 27200 Amaliada, Greece
| | - Vasiliki Vlacha
- Department of Paediatrics, Karamandanio Children’s Hospital, 26331 Patras, Greece;
- Department of Early Years Learning and Care, University of Ioannina, 26331 Ioannina, Greece
| | - Georgios Tsiros
- Gastouni Health Centre, Department of Family Medicine, 27300 Gastouni, Greece;
| | - Panagiota Voila
- Private Medical Laboratory, Clinical Chemistry Department, 27200 Amaliada, Greece;
| | - Raluca Maria Pop
- Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania;
| | - Ioana Corina Bocsan
- Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania;
- Correspondence:
| | | | - Mihnea Zdrenghea
- Department of Haematology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (G.F.); (M.Z.)
- Ion Chiricuta Oncology Institute, Republicii Str., No. 34-36, 400010 Cluj-Napoca, Romania
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49
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Santos Ferreira RD, Dos Santos C, Maranhão Mendonça LAB, Espinola Carvalho CM, Franco OL. Immunonutrition effects on coping with COVID-19. Food Funct 2021; 12:7637-7650. [PMID: 34286803 DOI: 10.1039/d1fo01278a] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
COVID-19 implications are still a threat to global health. In the face of this pandemic, food and nutrition are key issues that can boost the immune system. The bioactivity of functional foods and nutrients (probiotics, prebiotics, water- and fat-soluble vitamins, minerals, flavonoids, glutamine, arginine, nucleotides, and PUFAs) contributes to immune system modulation, which establishes the status of nutrients as a factor of immune competence. These foods can contribute, especially during a pandemic, to the minimization of complications of SARS-CoV-2 infection. Therefore, it is important to support the nutritional strategies for strengthening the immune status, associated with good eating habits, as a way to confront COVID-19.
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Affiliation(s)
- Rosângela Dos Santos Ferreira
- S-Inova Biotech. Post Graduate Program in Biotechnology, Catholic University Dom Bosco-UCDB, MS 79117-010 Campo Grande, Brazil.
| | - Cristiane Dos Santos
- S-Inova Biotech. Post Graduate Program in Biotechnology, Catholic University Dom Bosco-UCDB, MS 79117-010 Campo Grande, Brazil.
| | | | | | - Octávio Luiz Franco
- S-Inova Biotech. Post Graduate Program in Biotechnology, Catholic University Dom Bosco-UCDB, MS 79117-010 Campo Grande, Brazil. and Center of Proteomic and Biochemical Analysis, Post Graduate Program in Genomic Sciences and Biotechnology, Catholic University of Brasilia, Brasilia, Distrito Federal, Brazil
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50
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Coultas JA, Cafferkey J, Mallia P, Johnston SL. Experimental Antiviral Therapeutic Studies for Human Rhinovirus Infections. J Exp Pharmacol 2021; 13:645-659. [PMID: 34276229 PMCID: PMC8277446 DOI: 10.2147/jep.s255211] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 06/01/2021] [Indexed: 12/17/2022] Open
Abstract
Rhinovirus infection is common and usually causes mild, self-limiting upper respiratory tract symptoms. Rhinoviruses can cause exacerbation of chronic respiratory diseases, such as asthma or chronic obstructive pulmonary disease, leading to a significant burden of morbidity and mortality. There has been a great deal of progress in efforts to understand the immunological basis of rhinovirus infection. However, despite a number of in vitro and in vivo attempts, there have been no effective treatments developed. This review article summarises the up to date virological and immunological understanding of these infections. We discuss the challenges researchers face, and key solutions, in their work to investigate potential therapies including in vivo rhinovirus challenge studies. Finally, we explore past and present experimental therapeutic strategies employed in the treatment of rhinovirus infections and highlight promising areas of future work.
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Affiliation(s)
- James A Coultas
- National Heart and Lung Institute, Imperial College London, London, UK
| | - John Cafferkey
- Respiratory Medicine, St Mary's Hospital, Imperial College Healthcare Foundation Trust, London, UK
| | - Patrick Mallia
- National Heart and Lung Institute, Imperial College London, London, UK
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