scholarly journals Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Bassam Mahboub ◽  
Saba Al Heialy ◽  
Mahmood Yaseen Hachim ◽  
Rakhee K. Ramakrishnan ◽  
Ashraf Alzaabi ◽  
...  

Purpose. Vitamin D (VitD) deficiency is a significant public health concern in many areas around the globe and has been associated with many immune-mediated diseases, including asthma. Severe asthma has been linked to a decreased glucocorticoid receptor (GR) ratio (GR-α/GR-β ratio), indicating steroid hyporesponsiveness. Using a combination of in silico and in vivo approaches, we aimed to explore the immunomodulatory effect of VitD on asthmatic patients diagnosed with hypovitaminosis D. Methods. In silico tools were used to identify the regulatory effect of VitD supplementation on GR genes. We measured the expression levels of GR-α and the inactive isoform, GR-β, in the blood of adult asthmatics diagnosed with hypovitaminosis D before and after VitD supplementation. Moreover, the blood levels of inflammatory cytokines associated with asthma severity were determined. Results. Using an in silico approach, we identified specific genes commonly targeted by VitD as well as corticosteroids, the mainstay of asthma therapy. NR3C1 gene encoding GR was found to be significantly upregulated on Th2 CD4 cells and NK cells. Interestingly, blood expression level of NR3C1 was lower in severe asthmatics compared to nonsevere asthmatics and healthy controls, while the blood level of VitD receptor (VDR) was higher. Upon VitD supplementation of severe asthmatic patients, there was a significant increase in the blood levels of GR-α with no change in GR-β mRNA expression. VitD supplementation also suppressed the blood levels of IL-17F and IL-4. Conclusion. VitD may enhance steroid responsiveness by upregulating the expression of steroid receptor GR-α.

2019 ◽  
Vol 11 (2) ◽  
pp. 64-70
Author(s):  
Mohammed Haruna Yeldu ◽  
Mohammed Danjuma ◽  
Mainasara Abdullahi Sulaiman ◽  
Jiya Nma Muhammad ◽  
Garba Balkisu Illah ◽  
...  

Background: Asthma is a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms. It is characterized by the occurrence of bronchial hyper responsiveness, airflow obstruction and an underlying inflammation. Several studies have proposed the association of vitamin D with increased incidence of asthma symptoms. Aims and Objectives: This study aimed at determining the serum vitamin D status and biochemical parameters among asthmatic children in Sokoto-Nigeria. Materials and Methods: The study population consisted of 120 subjects including 80 asthmatic children and 40 age-and sex-matched apparently healthy controls from two tertiary Hospitals in Sokoto Metropolis. Serum vitamin D, calcium, parathyroid hormone (PTH), immunoglobulin E (IgE) and magnesium were measured using standard techniques. Results: Mean serum vitamin D and magnesium were significantly (p ˂ 0.05) lower, while serum PTH and IgE were significantly higher (p˂0.001) in asthmatic children than in controls. Vitamin D insufficiency was found to be prevalent among the asthmatic children. There was no significant relationship between the low level of vitamin D and asthma severity. Conclusion: This study observed that, hypovitaminosis D and hypomagnesaemia occurred among asthmatic children, and asthma was more prone in the younger children than in their older counterpart. It is recommended that in order to avoid or limit the rate of children having asthmatic episodes, vitamin D and magnesium supplements should be used in the management of asthmatic children.


Author(s):  
Ankita Kumari ◽  
Shaila Mitra ◽  
Harish C Tiwari ◽  
Reena Srivastav

Background: Hypovitaminosis D has been associated with a number of adverse pregnancy outcomes, and has been recognised as a public health concern. The objective of this study was to determine the impact of Vitamin D deficiency on maternal complications like gestational diabetes mellitus (GDM) and preeclampsia (PE) among pregnant women.Methods: This was a case control study undertaken at antenatal clinics and indoor of BRD Medical College, Gorakhpur, Uttar Pradesh, India. Two maternal blood samples, one at <20 weeks and other at term along with cord blood at delivery were taken. Patients were classified into preeclampsia (n=60), gestational diabetes mellitus (n=35) and control group (n=180) after abstracting past medical records at delivery. Vitamin D was estimated by 25- Hydroxyvitamin D125 RIA kit and categorized according to ACOG criteria. Statistical analysis was done by using chi square test, binary logistic regression and Pearson’s correlation coefficient to compare between two variables. P<0.05 was considered statistically significant.Results: Out of 275 women included in the study, 78% of women were Vitamin D deficient. Mean serum vitamin D was significantly lower among preeclamptic women 11.53±6.22 ng/ml and GDM women 12.62±6.69 ng/ml as compared to controls 24.25±14.44 ng/ml (median=18.2 ng/ml) (P<0.05). Vitamin D deficiency was significantly higher in pregnant women GDM (94.28% vs 68.3%) and preeclampsia (96.67% vs 68.3%) when compared to uncomplicated group.Conclusions: Maternal vitamin D deficiency is highly prevalent in early pregnancy and is significantly associated with elevated risk for GDM and preeclampsia.


2021 ◽  
Author(s):  
Gideon A. Gyebi ◽  
Oludare M. Ogunyemi ◽  
Ibrahim M. Ibrahim ◽  
Saheed O. Afolabi ◽  
Joseph O. Adebayo

Abstract The high morbidity and mortality rate of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection arises majorly from the Acute Respiratory Distress Syndrome and “cytokine storm” syndrome, which is sustained by an aberrant systemic inflammatory response and elevated pro-inflammatory cytokines. Thus, phytocompounds with broad-spectrum anti-inflammatory activity that target multiple SARS-CoV-2 proteins will enhance the development of effective drugs against the disease. In this study, an in-house library of 106 steriodal plant-derived pregnanes (PDPs) was docked in the active regions of human glucocorticoid receptors (hGRs) in a comparative molecular docking analysis. Based on the minimal binding energy and a comparative dexamethason binding mode analysis, a list of top twenty ranked PDPs docked in the agonist conformation of hGR, with binding energies ranging between -9.8 and -11.2 Kcal/mol, was obtained and analyzed for interactions with the human Janus kinases 1 and Interleukins-6 and SARS-CoV-2 3-chymotrypsin-like protease, Papain-like protease and RNA-dependent RNA polymerase. For each target protein, the top three ranked PDPs were selected. Eight PDPs (bregenin, hirundigenin, anhydroholantogenin, atratogenin A, atratogenin B, glaucogenin A, glaucogenin C and glaucogenin D) with high binding tendencies to the catalytic residues of multiple targets were identified. A high degree of structural stability was observed from the 100 ns molecular dynamics simulation analyses of glaucogenin C and hirundigenin complexes of hGR. The selected top-eight ranked PDPs demonstrated favourable druggable and in silico ADMET properties. Thus, the therapeutic potentials of glaucogenin C and hirundigenin can be explored for further in vitro and in vivo studies.


Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 20 ◽  
Author(s):  
Eugenio Cavalli ◽  
Emanuela Mazzon ◽  
Maria Sofia Basile ◽  
Santa Mammana ◽  
Manuela Pennisi ◽  
...  

We evaluated the in silico expression and circulating levels of interleukin (IL)37 in patients with different forms of multiple sclerosis (MS) and also upon treatment with different disease-modifying drugs. The combined interpretation of the resulting data strengthens and extends the current emerging concept that endogenous IL37 plays an important role in determining onset and progression of MS. The in silico analysis revealed that production of IL37 from cluster of differentiation (CD)4+ T cells from MS patients was reduced in vitro as compared to healthy controls. The analysis of the datasets also demonstrated that “higher” levels of IL37 production from PBMC entailed significant protection from MS relapses. In addition, the in vivo part of the study showed that IL37 was selectively augmented in the sera of MS patients during a relapse and that treatment with the high potency disease-modifying drug fingolimod significantly increased the frequency of patients with circulating blood levels of IL37 (6/9, 66%) as compared to patients receiving no treatment (n = 48) or platform therapy (n = 59) who had levels of IL37 below the limit of the sensitivity of the assay. This finding therefore anticipates that fingolimod may at least partially exert its beneficial effects in MS by upregulating the production of IL37.


2013 ◽  
Vol 09 (01) ◽  
pp. 40
Author(s):  
Fernanda Reis de Azevedo ◽  
Bruno Caramelli ◽  
◽  

Vitamin D has attracted much scientific interest in recent years, mostly due to its newly described roles in metabolism regulation and cell proliferation. Along with hypovitaminosis D, the incidence of obesity has risen and has become a public health concern. The association between these two conditions is not merely coincidence and is being deeply investigated regarding its prevalence, mechanism, and even a possible causal relation. The data are still inconclusive but there is important evidence indicating that vitamin D is involved with fat accumulation, the responsible mechanism however still the principal question. The three main hypotheses are: adipose tissue sequestration, genetic modulation, such as polymorphism of the vitamin D receptor (VDR), or an organism evolutionary adaptation to cold weather. In conclusion, more evidence is needed to determine what the correct direction of this connection is and the possible therapeutic strategies of vitamin D replenishment and obesity control.


2015 ◽  
Vol 85 (1-2) ◽  
pp. 50-60 ◽  
Author(s):  
Osama A. Kensarah ◽  
Abdelelah S. Jazar ◽  
Firas S. Azzeh

Abstract. Background: Vitamin D deficiency is common in Saudi Arabia. No sufficient data are available on the vitamin D status of preschool children. Aims: To investigate the vitamin D status among toddlers and preschool children and to evaluate the factors associated with hypovitaminosis D in Western Saudi Arabia. Methods: A cross-sectional study was conducted on 503 preschool children in Makkah. The children were divided into two age categories: 1 - 3 years (toddlers) and 3 - 6 years (preschool). Sociodemographic factors, life-style factors, eating habits, body mass index (BMI), 25-(OH)-vitamin D3, parathyroid hormone, calcium, phosphorous, and alkaline phosphatase concentrations were determined. Results: Sixty-three % of children had a vitamin D deficiency. Vitamin D in toddlers was significantly higher than in preschool children. Vitamin D levels were negatively correlated with BMI (r = - 0.419, P < 0.001), and duration of breast feeding (r = - 0.270, P = 0.027), but a significant positive correlation with vitamin D intake (r = 0.335, P = 0.021), calcium intake (r = 0.25, P = 0.029), duration of formula feeding (r = 0.354, P = 0.019), and outdoor physical activity (r = 0.381, P = 0.011) was found. Multivariable predictors of hypovitaminosis D were preschool age (OR = 11, [95 % CI: 2.78 - 43.57], P < 0.001), outdoor physical inactivity (OR = 2.44, [95 % CI: 0.93 - 14.12], P < 0.001), obesity (OR = 2.3, [95 % CI: 1.25 - 7.08], P = 0.008), overweight (OR = 2.16, [95 % CI: 1.18 - 6.01], P = 0.039), inadequate vitamin D intake (OR = 1.65, [95 % CI: 1.12 - 2.53], P = 0.012), exclusive formula feeding (OR = 0.53, [95 % CI: 0.41 - 0.72], P < 0.001), and breast and formula feeding (OR = 0.62 [95 % CI: 0.39 - 0.88], P = 0.002). Conclusion: Hypovitaminosis D is a public health concern, especially in preschool children. Possible determinants of low vitamin D status in preschool children in the Makkah region could be related to age, high BMI, inadequate vitamin D intake, exclusive breastfeeding, and outdoor physical inactivity.


2021 ◽  
Vol 20 (1) ◽  
pp. 1-6
Author(s):  
Saif Aboud M Alqahtani

Vitamin D deficiency is a major public health concern worldwide, resulting mainly due to insufficient sunlight exposure. The objective of this study was to assess the prevalence of vitamin D deficiency among the Saudi population living at different altitudes. A cross-sectional study was conducted to compare the level of vitamin D deficiency between 3402 (2110 female and 1292 male) population from Jeddah, 12 m above the sea level and with 3957 population (2202 female and 1755 male) from Asir, 2270 m above sea level. Data were collected from the biochemical investigation for total serum 25-hydroxyvitamin D and the serum calcium. Hypovitaminosis D (insufficiency and deficiency) was prevalent in 84.1% of females (n = 1775) and 81.7% of males (n = 1056) from Jeddah while 77.02% females (n = 1696) and 80% males (n = 1404) from Asir region. A negative correlation between Vitamin D and altitude was observed for gender (R = -0.894, P = 0.261) and age (R = -0.812, P = 0.382); the risk of hypovitaminosis D generally increases with decreasing altitude. The probability of Vitamin D deficiency was higher among female populations and study subjects living at the low altitudes, i.e., from the Jeddah region.


2021 ◽  
Author(s):  
Amira R Khattab ◽  
Mohamed Teleb ◽  
Mohamed S Kamel

Aim: The severity of COVID-19 has raised a great public health concern evoking an urgency for developing multitargeted therapeutics. Phlomis species was ethno-pharmacologically practiced for respiratory ailments. Materials & methods: An array of 15 phytoligands previously isolated from Phlomis aurea were subjected to molecular docking to explore their potential SARS-CoV-Spike-angiotensin-converting enzyme 2 complex inhibition, that is essential for virus entry to host cell. Results: Acteoside (11) showed the most potent in silico inhibition with an additional merit, over hesperidin (16), of not binding to angiotensin-converting enzyme 2 with well proven in vivo pulmonary protective role in acute lung injury, followed by chrysoeriol-7- O-β-glucopyranoside (12) and luteolin-7- O-β-glucopyranoside (14). Conclusion: Phytoligands (11, 12 and 14) were posed as promising candidates with potential prophylactic action against COVID-19. These phytoligands were prioritized for further biological experimentation because of their acceptable predicted ADME and drug-likeness parameters. Moreover, they could aid in developing multitargeted strategy for better management of COVID-19 using phytomedicines.


2010 ◽  
Vol 9 (2) ◽  
pp. 128 ◽  
Author(s):  
Fernanda Reis de Azevedo ◽  
Bruno Caramelli ◽  
◽  

Vitamin D has attracted much scientific interest in recent years, mostly due to its newly described roles in metabolism regulation and cell proliferation. Along with hypovitaminosis D, the incidence of obesity has risen and has become a public health concern. The association between these two conditions is not merely coincidence and is being deeply investigated regarding its prevalence, mechanism, and even a possible causal relation. The data are still inconclusive but there is important evidence indicating that vitamin D is involved with fat accumulation, the responsible mechanism however still the principal question. The three main hypotheses are: adipose tissue sequestration, genetic modulation, such as polymorphism of the vitamin D receptor (VDR), or an organism evolutionary adaptation to cold weather. In conclusion, more evidence is needed to determine what the correct direction of this connection is and the possible therapeutic strategies of vitamin D replenishment and obesity control.


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