The role of vitamin D deficiency in antituberculous protection

BACKGROUND. The main task of modern phthysiology is a comprehensive search for ways to optimize the etiotropic and the pathogenetic treatment of tuberculosis (TB). The search for improved treatment in addition to etiotropic antimicrobial therapy lies in the plane of improving pathogenetic therapy. Analysis of the available scientific sources suggests that the efficacy of TB treatment can be improved by adding vitamin D to the pathogenetic treatment, as vitamin D metabolites support the innate immune response to Mycobacterium tuberculosis. OBJECTIVE. To determine the role of vitamin D in the immunopathogenesis of the inflammatory response in pulmonary TB and to assess the prospects of its impact on improving the effectiveness of treatment by analyzing information from available scientific sources on this topic. MATERIALS AND METHODS. The study was performed for the period December 2020 – August 2021. The search was conducted by Keywords: pulmonary tuberculosis, vitamin D, mechanism of action, pathogenesis, treatment. Access to various full-text and abstract databases was used as the main source of research. RESULTS AND DISCUSSION. A large number of studies conducted so far prove the link between vitamin D deficiency and the occurrence of pulmonary TB. Vitamin D receptors have been found to be present on various surfaces of immune cells, including T and B cells, indicating that they need vitamin D to perform cellular functions. Vitamin D has been shown to increase the phagocytic activity of macrophages, and that monocytes incubated with cholecalciferol (vitamin D3) metabolites induce anti-TB activity. A number of studies have shown that vitamin D increases the body’s production of the antimicrobial/antimycobacterial peptide LL-37, a member of the cathelicidin petelide family. Therefore, the narrowly analyzed analysis according to the literature suggests that in the conditions of full vitamin D status of the human body the course of TB will be favorable, and in case of vitamin D deficiency – which is primarily associated with genetic polymorphisms, the course of TB may be unfavorable. CONCLUSIONS. Vitamin D functionates as one of the activators of macrophages and plays a role in the immune defense of the human body against mycobacterial TB. The inclusion of vitamin D in the program of complex treatment of TB infection is promising, as it enhances the production of antimicrobial/antimycobacterial peptide LL-37. It can be used as one of the components of TB prevention in children.

Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology

Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and restricted-repetitive patterns of behavior, interests, or activities. ASD is generally associated with chronic inflammatory states, which are linked to immune system dysfunction and/or hyperactivation. The latter might be considered as one of the factors damaging neuronal cells. Several cell types trigger and sustain such neuroinflammation. In this study, we traced different markers of immune system activation on both cellular (immune cell phenotypes) and mediatory levels (production of cytokines) alongside adverse hematology and biochemistry screening in a group of autistic children. In addition, we analyzed the main metabolic pathways potentially involved in ASD development: energy (citric acid cycle components), porphyrin, and neurotransmitter metabolism. Several ASD etiological factors, like heavy metal intoxication, and risk factors—genetic polymorphisms of the relevant neurotransmitters and vitamin D receptors—were also analyzed. Finally, broad linear regression analysis allowed us to elucidate the possible scenario that led to the development of chronic inflammation in ASD patients. Obtained data showed elevated levels of urinary cis-aconitate, isocitrate, alfa-ketoglutarate, and HMG. There were no changes in levels of metabolites of monoamine neurotransmitters, however, the liver-specific tryptophan kinurenine pathway metabolites showed increased levels of quinolinate (QUIN) and picolinate, whereas the level of kynurenate remained unchanged. Abovementioned data demonstrate the infringement in energy metabolism. We found elevated levels of lead in red blood cells, as well as altered porphyrin metabolism, which support the etiological role of heavy metal intoxication in ASD. Lead intoxication, the effect of which is intensified by a mutation of the VDR-Taq and MAO-A, leads to quinolinic acid increase, resulting in energy metabolism depletion and mitochondrial dysfunction. Moreover, our data backing the CD4+CD3+ T-cell dependence of mitochondrial dysfunction development in ASD patients reported in our previous study leads us to the conclusion that redox-immune cross-talk is considered a main functional cell damaging factor in ASD patients.

Molecular Predictors of Effective Implantation and Live Birth in IVF Programs

The aim of the study was to improve the possibilities of predicting blastocyst implantation and live birth of ART programs in women of late reproductive age with tubal-peritoneal infertility based on immunohistochemical markers of the endometrium. Methods and Results: The results of IVF and IVF/ICSI programs were analyzed in 68 patients of late reproductive age (36-44 years of age) with tubal-peritoneal factor of infertility. Morphological examination of the endometrium was performed on Day 7 after confirmed ovulation in the cycle preceding ART. The expression of vitamin D receptors (VDR) and HOXA11 in endometrial stromal cells was assessed by immunohistochemical method. The effectiveness of using the endometrial markers VDR and HOXA11 as potential predictors of ART programs efficiency was confirmed by prognostic models. The levels of the stromal expression of VDR<8.7% and HOXA11<6.1% (probability >0.27) were determined to be favorable for successful blastocyst implantation. The expression levels of VDR<8.3% and HOXA11<6.1% in endometrial stromal cells are prognostically favorable for live birth (probability >0.19) in women of late reproductive age with tubal-peritoneal infertility who undergoing ART treatment with their own oocytes.

Atopinio dermatito sąsajos su filagrino geno mutacija bei vitaminu D. Literatūros apžvalga

Atopinis dermatitas (AD) – tai lėtinė uždegiminė odos liga, kuriai būdingas stiprus odos niežėjimas, sausumas, ligai paūmėjus, pūslelės, edema bei šašai. Šio straipsnio tikslas – apžvelgti AD, vitamino D ir filagrino mutacijos sąsajas, kurios yra reikšmingos ligos patogenezei. Metodika. Literatūros apžvalga parengta remiantis „PubMed“ duomenų bazės mokslinių straipsnių atranka pagal reikšminius žodžius: atopic dermatitis, filaggrin gene mutation, vitamin D receptors. Naudoti tokie įtraukimo kriterijai: klinikinių tyrimų rezultatų straipsniai, publikacijos anglų kalba, publikacijos ne senesnės nei 10 metų. Rezultatai. Dažniausios FLG mutacijos yra R501X ir 2282del4 ir su jomis nustatyta sąsaja tarp AD ligos eigos sunkumo. Skirtingos FLG geno mutacijos, susijusios su pacientų rase, AD rizikos veiksniais ir asmens odos mikrobiotos savybėmis. Vitaminas D veikia per keratinocitų vitamino D receptorius (VDR). VDR genų (ApaI, BsmI, FokI TaqI) polimorfizmas reguliuoja odos keratinocitų homeostazę ir epidermio barjerinę funkciją. BsmI geno turėjimas padidina riziką susirgti AD. Išvados. Atvejo ir kontrolės tyrimų duomenimis, sergantieji sunkios eigos AD dažniau turi VDR geno polimorfizmą ir FLG mutacijas priklausomai nuo rasės ir aplinkos veiksnių. Apie tai tyrimų rezultatų Baltijos šalyse nėra.

Perspectives of personalized approach to prevention and treatment of anticonvulsant-induced osteoporosis via action on vitamin D exchange and VDR expression

Anticonvulsant-induced osteoporosis (AIO) and associated pain syndromes and patient disabilities are an important interdisciplinary medical problem generated by various molecular, genetic and pathophysiological mechanisms. AIO are the most important pathological processes associated with chronic pain in adults with epilepsy. Standard approaches to their prevention and treatment do not always solve the problem of the progression of the pathological process and chronicity of AIO. This is the reason for the search for new personalized strategies for the prevention and treatment of AIO. Vitamin D metabolism, expression and specificity of vitamin D receptors (VDRs) may play a key role in the development of AIO and chronic back pain in patients with epilepsy. The aim of the study was to review publications on changes in the vitamin D system in patients with AIO. We searched for articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar. The search was carried out by key-words and their combinations. The role of vitamin D and VDR in the development of AIO and the chronicity of back pain has been demonstrated mainly in animal models and humans. Associative genetic studies have shown that single nucleotide variants (SNVs) of the VDR gene encoding VDR may be associated with the development of osteoporosis of the spine (including those associated with the intake of an anticonvulsants). The prospects for the use of vitamin D preparations for modulating the effect of anticonvulsants used to treat epilepsy are discussed. Genetic association studies of VDR gene SNVs are important for understanding the genetic predictors of AIO and chronic back pain in patients with epilepsy, as well as for developing new personalized pharmacotherapy strategies.

The Role of Vitamin D in Gastrointestinal Diseases: Inflammation, Gastric Cancer, and Colorectal Cancer

: Vitamin D as a prohormone is converted into the active form in vivo and binds to vitamin D receptors, exercising a wide range of biological functions. Recent studies strongly support that vitamin D supplementation is associated with reduced cancer risk and a good prognosis. Gastrointestinal cancer is the leading cause of cancer-related deaths worldwide. The key role of vitamin D in the development of gastrointestinal cancer has been observed. Moreover, Vitamin D can also affect innate immunity and perform anti-inflammation and anti-infection actions. Given the intimate relationship between cancer and inflammation, we herein summarize epidemiological and preclinical studies of vitamin D and the underlying mechanism of its action in inflammation, gastric and colorectal cancer by our group and other researchers. A beneficial effect of vitamin D in cancer and inflammatory disease has been supported by different studies. More controlled and larger clinical trials are needed before a reliable conclusion and realization of vitamin D supplementation in the adjunct treatment of gastrointestinal inflammation and cancer.

Role of Vitamin D in Cognitive Dysfunction: New Molecular Concepts and Discrepancies between Animal and Human Findings

Purpose of review: increasing evidence suggests that besides the several metabolic, endocrine, and immune functions of 1alpha,25-dihydroxyvitamin D (1,25(OH)2D), the neuronal effects of 1,25(OH)2D should also be considered an essential contributor to the development of cognition in the early years and its maintenance in aging. The developmental disabilities induced by vitamin D deficiency (VDD) include neurological disorders (e.g., attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia) characterized by cognitive dysfunction. On the other hand, VDD has frequently been associated with dementia of aging and neurodegenerative diseases (e.g., Alzheimer’s, Parkinson’s disease). Recent findings: various cells (i.e., neurons, astrocytes, and microglia) within the central nervous system (CNS) express vitamin D receptors (VDR). Moreover, some of them are capable of synthesizing and catabolizing 1,25(OH)2D via 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1) and 25-hydroxyvitamin D 24-hydroxylase (CYP24A1) enzymes, respectively. Both 1,25(OH)2D and 25-hydroxyvitamin D were determined from different areas of the brain and their uneven distribution suggests that vitamin D signaling might have a paracrine or autocrine nature in the CNS. Although both cholecalciferol and 25-hydroxyvitamin D pass the blood–brain barrier, the influence of supplementation has not yet demonstrated to have a direct impact on neuronal functions. So, this review summarizes the existing evidence for the action of vitamin D on cognitive function in animal models and humans and discusses the possible pitfalls of therapeutic clinical translation.

Study of Vitamin D Receptor Levels in Children with Immune Thrombocytopenic Purpura

Background: Vitamin D, affecting many tissues and organs of the body. It exerts many of its effects through contact with Vitamin D receptor (VDR) It Is Important especially in immune system; Immune thrombocytopenia is one of the most common causes of symptomatic thrombocytopenia in children. Aim: The main objective of our study was to study vitamin D receptor level in children with immune thrombocytopenic purpura and effect of vitamin D supplementation upon the response of the thrombocytopenia to conventional therapy of ITP. Subjects and Methods: This is a case control study which included 30 ITP children, who would be attendants to Hematology and Oncology Unit, Pediatric Department, Tanta University Hospital in Egypt. This study would include also 30 apparently healthy children matched in age and sex as a control group. The duration of the study ranges from 6 to 12 months, for all patients and controls the following were done: complete blood count, bone marrow aspiration, serum level of Vitamin D receptors, serum calcium level, serum phosphorus level, serum alkaline phosphatase level and serum parathyroid hormone level. Results: the results revealed that mean ± SD of Vitamin D receptors in case group is 132.43 ± 14.58 and there was statistical difference between groups regarding Vitamin D receptor. There was statistical difference between platelets count and Serum total Ca (mg/dl) with negative correlation, while there was no statistical difference between platelets count and Vitamin D receptor. There was statistically significant difference in platelets count in patient with ITP before and after conventional treatment and platelets count in patient with ITP under conventional treatment plus vitamin D supplementation. Conclusion: VD receptors elevation is very common in ITP. Supplementing VD might diminish recurrence. Further research is needed.

Recent Advance on Vitamin D in Athletes

PURPOSE: Vitamin D plays important roles in calcium homeostasis and bone metabolism. Since vitamin D receptors (VDRs) are located in a variety of organs, including skeletal muscle, vitamin D has potentially widespread effects. The purpose of this review was to summarize the current understanding of the effects of vitamin D on muscle function and exercise performance in athletes.METHODS: In this narrative review, we summarized previous studies by searching the literature in the PubMed, Google Scholar, and Science Direct databases.RESULTS: Vitamin D has been shown to regulate multiple actions in skeletal muscle tissue, such as myocyte proliferation and growth via genomic and non-genomic molecular pathways. Higher levels of vitamin D are associated with improved skeletal muscle function and exercise performance. Moreover, in some studies, vitamin D supplementation has beneficial effects on muscle strength in athletes, especially those who are vitamin D-deficient.CONCLUSIONS: Vitamin D appears to have beneficial effects on muscle and exercise performance in athletes. However, more studies are needed to clarify the action and dosage of vitamin D in athletes.

Association between Serum Brain-derived Neurotrophic Factor and 25-OH Vitamin D Levels with Vitamin D Receptors Gene Polymorphism (rs2228570) in Patients with Autoimmune Thyroiditis and Hypothyroidism

BACKGROUND: Different polymorphisms in Vitamin D receptors (VDRs) have an important role in autoimmune thyroiditis (AIT) risk. Hashimoto’s thyroiditis (HT) is the most recurrent autoimmune thyroid disorder. Patients with HT may suffer from cognitive impairment brain-derived neurotrophic factor (BDNF) which has been identified as an important growth factor that is involved in learning and memory. AIM: This study examined the linkage of VDR gene polymorphism (rs2228570) with blood serum levels of BDNF and 25-OH Vitamin D in thyroid pathology of patients in the West Ukrainian population. METHODS: This research is a case–control study was performed in HSEEU “Bukovinian State Medical University,” Chernivtsi Regional Endocrinology Center, and I. Horbachevsky Ternopil National Medical University, Ukraine, from September 2017 to December 2020. The study involved a total of 153 patients with post-operative hypothyroidism, hypothyroidism induced by AIT, and patients with both AIT and elevated serum antibodies anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase. BDNF levels in the sera of the patients and healthy individuals were quantified using enzyme-linked immunosorbent assay (ELISA) with highly sensitive Human BDNF ELISA Kit. Genotyping of the VDR (rs2228570) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) on CFX96™ Real-Time Polymerase Chain Reaction (PCR) Detection System (Bio-Rad Laboratories, Inc., USA). PCR for TaqMan genotyping was carried out according to the kit instructions (Applied Biosystems, USA). RESULTS: Our study revealed a significant decrease in the BDNF level in the study group in carriers of the AA and AG genotypes by 1.58 and 2.39 times, corresponding, compared with carriers of the AA genotype in the control group. Concurrently, there was no significant difference in the BDNF level between different genotypes of VDR rs2228570 in the research group. In our study, analysis of the correlation between serum BDNF levels and 25-OH Vitamin D concentration shows a moderate direct relationship (r = 0.4) between BDNF and 25-OH Vitamin D (p = 0.006). CONCLUSIONS: The rs2228570 VDR polymorphism is not a risk factor for decreased serum BDNF levels. At the same time, our study found a moderate direct relationship between serum BDNF levels and 25-OH Vitamin D.