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Pharmaceuticals
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Drug Insight: Vitamin D and Its Analogs
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Drug Insight: Vitamin D and Its Analogs

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 42406

Special Issue Editor

Prof. Julia O. Fedotova

E-Mail Website
Guest Editor
1. Laboratory of Neuroendocrinology, I.P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Emb. Makarova, 199034 St. Petersburg, Russia
2. International Research Centre "Biotechnologies of the Third Millennium", ITMO University, 9 Lomonosova Str., 191002 St. Petersburg, Russia
Interests: brain; behavior; anxiety; depression; memory; learning; schizophrenia; nutrients; nutraceuticals; vitamin D; estrogens; progesterone; DHEA; menopause; thyroid hormones; androgens; fertility; pharmacotherapy; psychology; psychoneuropharmacology; nutraceutical psychiatry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vitamin D is an exciting topic for many issues in the scientific research. The first evidence of a compound D formation in the course of biological evolution dates back to probably more than 500 million years ago, although this dating may be questionable. It is surely one of the first hormones, or even the very first one, that was produced on Earth. Many preclinical and clinical studies have strongly suggested that hormone D plays several physiological key roles in different areas. However, many questions still remain and will likely fuel ongoing investigation and debate. These questions will likely keep the story open on the pleiotropic effects of Vitamin D for the future.

This Special Issue of Pharmaceuticals on “Vitamin D and its Analogs” will include both experimental/clinical articles and reviews focused on the most recent advances in the research into Vitamin D and its analogs used in medicine, highlighting their beneficial effects in different disorders. The major focus will be on Vitamin D and its analogs’ effects on different diseases, including studies concerning their pathophysiological and molecular mechanisms. Special attention will be addressed to the design, synthesis, characterization, and preclinical studies of novel Vitamin D analogs.

With the aim of offering a dedicated forum open to all scientists engaged in this interdisciplinary research field, we particularly welcome contributions dealing with the following:

  • The beneficial effects of Vitamin D and its analogs as therapeutic tools for the treatment of neuroendocrinological and neuroimmunological impairments;
  • Vitamin D and its analogs as supplementations (design, synthesis, characterization, preclinical studies, clinical trials, etc.) for the treatment of different disorders, particularly with applications in anticancer treatment, reproduction, cognition, psychotropics, neurology, autoimmunity, and for the treatment of cardiovascular disorders, metabolic and hormonal diseases, etc.;
  • The beneficial effects of Vitamin D and its analogs as neuroprotective agents;

Antioxidant, antihypoxic, and anti-aging effects of Vitamin D and its analogs in the preclinical and clinical studies.

Among others research topics, the Special issue will provide a scientific view on the potential role of vitamin D in the treatment of the SARS-CoV-2 virus/COVID-19 disease:

  • Studies of the mechanism of antiviral action of Vitamin D, with a special focus on the its molecular and biochemical mechanisms in SARS-CoV-2 virus/COVID-19 disease;
  • Studies on the different treatments with Vitamin D in the complex therapy of COVID-19.

Dr. Julia O. Fedotova
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vitamin D
  • vitamin D analogs
  • endocrine system
  • immune system
  • cognitive disorders
  • affective-related disorders
  • neurological disorders
  • metabolic disorders
  • reproductive and hormonal disorders
  • neuroprotection
  • anti-aging
  • antioxidants
  • SARS-CoV-2
  • COVID-19

Published Papers (4 papers)

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13 pages, 1219 KiB  
Article
Impaired Vitamin D Metabolism in Hospitalized COVID-19 Patients
by Alexandra Povaliaeva, Viktor Bogdanov, Ekaterina Pigarova, Larisa Dzeranova, Nino Katamadze, Natalya Malysheva, Vitaliy Ioutsi, Larisa Nikankina, Liudmila Rozhinskaya and Natalia Mokrysheva
Pharmaceuticals 2022, 15(8), 906; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15080906 - 22 Jul 2022
Cited by 4 | Viewed by 2661
Abstract
There is increasing data regarding the association between vitamin D and COVID-19. This study aimed to reveal the alterations of vitamin D metabolism in the setting of COVID-19. We examined 119 adult COVID-19 inpatients and 44 apparently healthy adult individuals with similar serum [...] Read more.
There is increasing data regarding the association between vitamin D and COVID-19. This study aimed to reveal the alterations of vitamin D metabolism in the setting of COVID-19. We examined 119 adult COVID-19 inpatients and 44 apparently healthy adult individuals with similar serum 25OH-D3 levels as a reference group. The assessment included serum biochemical parameters (total calcium, albumin, phosphorus, creatinine), parathyroid hormone (PTH), vitamin D-binding protein (DBP), vitamin D metabolites (25OH-D3, 25OH-D2, 1,25(OH)2D3, 3-epi-25OH-D3, 24,25(OH)2D3 and D3) and free 25OH-D. COVID-19 patients had in general very low vitamin D levels (median 25OH-D3 equals 10.8 ng/mL), accompanied by an increased production of the active vitamin D metabolite (1,25(OH)2D3), estimated as higher 1,25(OH)2D3 serum levels (61 [44; 81] vs. 40 [35; 50] pg/mL, p < 0.001) and lower 25OH-D3/1,25(OH)2D3 ratio (175 [112; 260] vs. 272 [200; 433], p < 0.001) which is presumably aimed at preventing hypocalcemia. Patients with COVID-19 also had elevated DBP (450 [386; 515] vs. 392 [311; 433] mg/L, p < 0.001) and low free 25OH-D levels (<LoB vs. 3.9 [3.2; 4.4] pg/mL, p < 0.001). Follow-up assessment of the COVID-19 inpatients showed recovery of the observed changes. Overall, hospitalized patients with an acute course of COVID-19 have not only very low levels of 25OH-D but also profound abnormalities in the metabolism of vitamin D regardless of the clinical course of the disease. These alterations might exacerbate existing vitamin D deficiency and its negative impact. Full article
(This article belongs to the Special Issue Drug Insight: Vitamin D and Its Analogs)
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16 pages, 6230 KiB  
Article
Vitamin D Status and Immune Response in Hospitalized Patients with Moderate and Severe COVID-19
by Tatiana L. Karonova, Igor V. Kudryavtsev, Ksenia A. Golovatyuk, Arthur D. Aquino, Olga V. Kalinina, Alena T. Chernikova, Ekaterina K. Zaikova, Denis A. Lebedev, Ekaterina S. Bykova, Alexey S. Golovkin and Evgeny V. Shlyakhto
Pharmaceuticals 2022, 15(3), 305; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15030305 - 02 Mar 2022
Cited by 10 | Viewed by 3944
Abstract
A low 25-hydroxyvitamin D (25(OH)D) level is considered as an independent risk factor for COVID-19 severity. However, the association between vitamin D status and outcomes in COVID-19 is controversial. In the present study we investigate the association between the serum 25(OH)D level, immune [...] Read more.
A low 25-hydroxyvitamin D (25(OH)D) level is considered as an independent risk factor for COVID-19 severity. However, the association between vitamin D status and outcomes in COVID-19 is controversial. In the present study we investigate the association between the serum 25(OH)D level, immune response, and clinical disease course in patients with COVID-19. A total of 311 patients hospitalized with COVID-19 were enrolled. For patients with a vitamin D deficiency/insufficiency, the prevalence of severe COVID-19 was higher than in those with a normal 25(OH)D level (p < 0.001). The threshold of 25(OH)D level associated with mortality was 11.4 ng/mL (p = 0.003, ROC analysis). The frequency of CD3+CD4+ T helper (Th) cells was decreased in patients with 25(OH)D level ≤ 11.4 ng/mL, compared to healthy controls (HCs). There were no differences in the frequency of naive, central memory (CM), effector memory (EM), and terminally differentiated effector memory Th cells in patients with COVID-19 compared to HCs. The frequency of T-follicular helpers was decreased both in patients with 25(OH)D level > 11.4 ng/mL (p < 0.001) and 25(OH)D level ≤ 11.4 ng/mL (p = 0.003) compared to HCs. Patients with 25(OH)D level > 11.4 ng/mL had an increased frequency of Th2 CM (p = 0.010) and decreased Th17 CM (p < 0.001). While the frequency of Th2 EM was significantly increased, the frequency of Th17 EM was significantly decreased in both groups compared to HCs. Thus, 25(OH)D level is an independent risk factor for the disease severity and mortality in patients with COVID-19. We demonstrate that the serum 25(OH)D level ≤ 11.4 ng/mL is associated with the stimulation of Th2 and the downregulation of Th17 cell polarization of the adaptive immunity in patients with COVID-19. Full article
(This article belongs to the Special Issue Drug Insight: Vitamin D and Its Analogs)
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26 pages, 6750 KiB  
Article
Vitamin D3 Prevents the Deleterious Effects of Testicular Torsion on Testis by Targeting miRNA-145 and ADAM17: In Silico and In Vivo Study
by Doaa I. Mohamed, Doaa A. Abou-Bakr, Samar F. Ezzat, Hanaa F. Abd El-Kareem, Hebatallah H. Abo Nahas, Hosam A. Saad, Amir E. Mehana and Essa M. Saied
Pharmaceuticals 2021, 14(12), 1222; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14121222 - 25 Nov 2021
Cited by 37 | Viewed by 3820
Abstract
Testicular torsion (TT) is the most common urological emergency in children and young adults that can lead to infertility in many cases. The ischemia-reperfusion (IR) injury due to TT has been implicated in the pathogenesis of testicular damage. The main pathological mechanisms of [...] Read more.
Testicular torsion (TT) is the most common urological emergency in children and young adults that can lead to infertility in many cases. The ischemia-reperfusion (IR) injury due to TT has been implicated in the pathogenesis of testicular damage. The main pathological mechanisms of contralateral injury after ipsilateral TT are not fully understood. In the presented study, we investigated the molecular and microscopic basis of ipsilateral and contralateral testicular injury following ipsilateral testicular torsion detorsion (T/D) and explored the possible protective role of vitamin D3. The biochemical analysis indicated that IR injury following T/D significantly decreased the activity of testicular glutathione peroxidase (GPx) enzyme, level of serum testosterone, serum inhibin B, and expression of testicular miRNA145, while increased the activity of testicular myeloperoxidase (MPO) enzyme, level of testicular malondialdehyde (MDA), level of serum antisperm-antibody (AsAb), and expression of ADAM-17. The histological and semen analysis revealed that torsion of the testis caused damages on different tissues in testis. Interestingly, administration of vitamin D3 prior to the IR injury reversed the deterioration effect of IR injury on the testicular tissues as indicated by biochemical and histological analysis which revealed normal appearance of the seminiferous tubules with an apparent decrease in collagen fiber deposition in both ipsilateral and contralateral testes. Our results revealed that the protective effect of vitamin D3 treatment could be attributed to target miRNA145 and ADAM17 protein. To further investigate these findings, we performed a detailed molecular modelling study in order to explore the binding affinity of vitamin D3 toward ADAM17 protein. Our results revealed that vitamin D3 has the ability to bind to the active site of ADAM17 protein via a set of hydrophobic and hydrophilic interactions with high docking score. In conclusion, this study highlights the protective pharmacological application of vitamin D3 to ameliorate the damages of testicular T/D on the testicular tissues via targeting miRNA145 and ADAM17 protein. Full article
(This article belongs to the Special Issue Drug Insight: Vitamin D and Its Analogs)
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15 pages, 4393 KiB  
Systematic Review
Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis
by Christiano Argano, Raffaella Mallaci Bocchio, Giuseppe Natoli, Salvatore Scibetta, Marika Lo Monaco and Salvatore Corrao
Pharmaceuticals 2023, 16(1), 130; https://0-doi-org.brum.beds.ac.uk/10.3390/ph16010130 - 16 Jan 2023
Cited by 23 | Viewed by 30970
Abstract
Background: The COVID-19 pandemic represents one of the world’s most important challenges for global public healthcare. Various studies have found an association between severe vitamin D deficiency and COVID-19-related outcomes. Vitamin D plays a crucial role in immune function and inflammation. Recent data [...] Read more.
Background: The COVID-19 pandemic represents one of the world’s most important challenges for global public healthcare. Various studies have found an association between severe vitamin D deficiency and COVID-19-related outcomes. Vitamin D plays a crucial role in immune function and inflammation. Recent data have suggested a protective role of vitamin D in COVID-19-related health outcomes. The purpose of this meta-analysis and trial sequential analysis (TSA) was to better explain the strength of the association between the protective role of vitamin D supplementation and the risk of mortality and admission to intensive care units (ICUs) in patients with COVID-19. Methods: We searched four databases on 20 September 2022. Two reviewers screened the randomized clinical trials (RCTs) and assessed the risk of bias, independently and in duplicate. The pre-specified outcomes of interest were mortality and ICU admission. Results: We identified 78 bibliographic citations. After the reviewers’ screening, only five RCTs were found to be suitable for our analysis. We performed meta-analyses and then TSAs. Vitamin D administration results in a decreased risk of death and ICU admission (standardized mean difference (95% CI): 0.49 (0.34–0.72) and 0.28 (0.20–0.39), respectively). The TSA of the protective role of vitamin D and ICU admission showed that, since the pooling of the studies reached a definite sample size, the positive association is conclusive. The TSA of the protective role of vitamin D in mortality risk showed that the z-curve was inside the alpha boundaries, indicating that the positive results need further studies. Discussion: The results of the meta-analyses and respective TSAs suggest a definitive association between the protective role of vitamin D and ICU hospitalization. Full article
(This article belongs to the Special Issue Drug Insight: Vitamin D and Its Analogs)
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