Vitamin D Administration Research Articles

Vitamin D and Tinospora cordifolia modulate TLR3 and TLR4 pathways, reduce inflammation, and maintain antimicrobial peptide levels in infected mice

The activation of Toll-Like Receptor-3 (TLR3) and Toll-Like Receptor-4 (TLR4) signalling pathways is a regular pathway for immune system activation during infection. This study aimed to investigate the effects of vitamin D (VD) and Tinospora cordifolia ethanol extract (TC) on TLR3 and TLR4 receptor protein expression, proinflammatory cytokine (IL1 and IL-6) production, and antimicrobial peptide cathelicidin (CAP) production in CD11b+ cells of mice infected with Escherichia coli. The treatments consisted of administration of VD (0.325 µg/kg bw), TC (100 mg/kg bw), and a combination of both in the same dose for 28 days, followed by induction of E. coli infection on day 29. The flow cytometry method was analyzed of TLR3, TLR4, IL-1, IL-6, and CAP expression in CD11b+ cells of experimental animals. The following measurement results were compared with healthy controls and infected animals with the significance of differences between treatments analyzed by One-way ANOVA with p < 0.05. The results showed that administering VD, TC, and a combination of both reduced the expression of TLR3, TLR4, and IL-1 compared to treating infected animals. The combination treatment of VD + TC increased CAP production more than all other treatments. This significant finding suggests that the combination of VD + TC has the potential to control inflammation without disrupting the body’s defence mechanisms against infection, providing valuable insights for the field of immunology.

Acute calcitriol treatment mitigates vitamin D deficiency-associated mortality after intracerebral haemorrhage

ObjectiveVitamin D deficiency (VDD) is emerging as a predictor of poor prognosis in various neurological conditions, where clinical outcomes are often worse in stroke patients with VDD. This study aimed to provide experimental evidence on whether and how pre-existing VDD would affect survival and neurofunctional outcomes in intracerebral haemorrhage (ICH), and to evaluate whether acute vitamin D (VD) supplementation would improve post-stroke outcomes. MethodsExperimental ICH models were induced in mice with and without VDD. Haematoma size was measured using T2*-weighted MRI and haemoglobin concentration. Post-ICH mortality, neurofunctional outcomes and the extent of blood–brain barrier (BBB) leakage were assessed to identify their correlations with VD status. Therapeutic benefits of acute VD administration were also evaluated. ResultsMice with VDD exhibited significantly higher acute mortality rates and more severe motor deficits than mice without VDD post-ICH. Marked haematoma expansion and increased Evans blue extravasation were observed in VDD mice, suggesting that VDD was associated outcomes with increased BBB disruption. Acute treatment with a loading dose of VD (calcitriol) significantly improved outcomes in VDD mice. ConclusionThis study provides novel insights into the pathophysiological mechanisms at play in ICH concomitant with VDD and a scientific rationale for acute treatment with VD.

Vitamin D and Sulforaphane Decrease Inflammatory Oxidative Stress and Restore the Markers of Epithelial Integrity in an In Vitro Model of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is strictly linked to chronic oxidative stress, inflammation, loss of epithelial barrier integrity, and often with abnormal new blood vessel development. In this study, the retinal epithelial cell line ARPE-19 was treated with pro-inflammatory transforming growth factor-beta (TGF-β) to investigate the activity of vitamin D (VD) and sulforaphane (SF) in abating the consequences of oxidative stress and inflammation. The administration of VD and SF lowered reactive oxygen species (ROS) levels, and abated the related expression of the pro-inflammatory cytokines interleukin-6 and interleukin-8 induced by TGF-β. We evaluated mitochondrial respiration as a source of ROS production, and we discovered that the increased transcription of respiratory elements triggered by TGF-β was prevented by VD and SF. In this model of inflamed epithelium, the treatment with VD and SF also reduced the secretion of VEGF, a key angiogenic factor, and restored the markers of epithelial integrity. Remarkably, all the observed biological effects were potentiated by the co-stimulation with the two compounds and were not mediated by VD receptor expression but rather by the ERK 1/2 pathway. Altogether, the results of this study reveal the powerful synergistic anti-inflammatory activity of SF and VD and lay the foundation for future clinical assessment of their efficacy in AMD.

Vitamin D Supplementation at a Dose of 10 µg/Day in Institutionalized Children with Severe Motor and Intellectual Disabilities.

Vitamin D (VD) deficiency can lead to health-related consequences. This study determined the effects of VD administration in VD-deficient children with severe motor and intellectual disabilities (SMID). Twenty-eight subjects were included. Among them, 25 subjects with parental consent for VD administration were given 10 µg/day (400 IU/day) of VD in April 2021. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured at least 30 days after the start of VD administration. The total VD intake, serum 25(OH)D levels, and ultraviolet (UV) exposure before the blood tests were investigated. The results showed that the median serum 25(OH)D levels were 8.7 ng/mL (4.3-17.2) and 24.0 ng/mL (7.8-39 ng/mL) from March to May in 2020 and 2021, respectively. Among the 25 subjects, 22 with UV exposure had >20 ng/mL serum 25(OH)D level, and 2 without UV exposure had <20 ng/mL serum 25(OH)D level. Three subjects who did not receive VD supplementation had <20 ng/mL serum 25(OH)D level. Taken together, VD supplementation (10 µg/day) is effective in children with SMID in institutional care. Moreover, it may be sufficient for children with UV exposure, but not for those without.

The protective effects of Vitamin D against Cadmium-induced nephrotoxicity

BackgroundCadmium (Cd) is retained in the kidneys in large amounts thus inducing oxidative damage. Vitamin D (VD) is a potent antioxidant that is postulated to reverse the Cd-induced oxidative effects. AimThe present study aimed at investigating the effect of VD administration on reversing Cd-induced renal toxicity. Material and methodsTwenty-four male rats were assorted into three equal groups: Negative control (NC) group receiving drinking water only, Positive control (PC) group receiving Cadmium chloride (CdCl2) and VD group receiving VD injections in addition to CdCl2. The serum levels of creatinine, urea and 25-OH VD as well as renal tissue concentration of glutathione peroxidase (GPX) and malondialdehyde (MDA) were measured. Tissue sections were examined for signs of renal injury, immunostained for Vitamin D receptor (VDR), Cyp24a1 and Cyp27b1 and the apoptotic index was measured. ResultsCd administration resulted in higher serum levels of creatinine and urea as well as lower serum 25-OH VD level in addition to higher MDA and lower GPX renal concentration. VD supplementation showed improved renal functions, a remarkable improvement in the renal tissue with enhanced expression of VDR and Cyp27b1, lower Cyp24a1 expression and a lower apoptotic index. ConclusionVD administration can ameliorate Cd-induced nephrotoxicity.

Advances in the Administration of Vitamin D Analogues to Support Bone Health and Treat Chronic Diseases.

Vitamin D (VD) exerts a wide variety of biological actions in addition to its well-known roles in calcium homeostasis. Nutritional VD deficiency induces rachitic abnormalities in growing children and osteomalacia in adults, and it has been proposed to underlie the onset and development of multiple non-communicable chronic diseases. Therefore, the administration of VD or synthetic VD analogues represents a promising therapeutic strategy; indeed, VD and a VD agonist have shown clinical promise in mitigating osteoporosis and symptoms of insufficient calcium intake. However, even though high doses of VD analogues have shown pre-clinical efficacy against several diseases, including cancers, they have not yet had wide-spread clinical success. This difference may be due to limitation of clinical doses in light of the inherent calcemic action of VD. An approach to overcome this problem involves the development of VD analogues with lower calcemic activity, which could be administered in high doses to attenuate the onset and progress of disease. In a similar strategy, selective estrogen receptor modulators have had success as anti-osteoporosis drugs, and they have shown benefit for other estrogen target organs by serving as partial antagonists or agonists of estrogen receptor α. It is thus conceivable to generate synthetic partial antagonists or agonists for the VD receptor (VDR) that would exert beneficial effects on bone and other VD target organs. In this review, we discuss the molecular basis of the development of such synthetic VDR ligands from the viewpoint of roles of VDR in gene regulation.

Role of Vitamin D in Celiac Disease and Inflammatory Bowel Diseases

Vitamin D (VD) is a pro-hormone that has long been known as a key regulator of calcium homeostasis and bone health in both children and adults. In recent years, studies have shown that VD may exert many extra-skeletal functions, mainly through a relevant modulation of the innate and adaptive immune system. This has suggested that VD could play a fundamental role in conditioning development, clinical course, and treatment of several autoimmune disorders, including celiac disease (CD) and inflammatory bowel diseases (IBDs). The main aim of this review is to evaluate the relationships between VD, CD, and IBDs. Literature analysis showed a potential impact of VD on CD and IBDs can be reasonably assumed based on the well-documented in vitro and in vivo VD activities on the gastrointestinal tract and the immune system. The evidence that VD can preserve intestinal mucosa from chemical and immunological damage and that VD modulation of the immune system functions can contrast the mechanisms that lead to the intestinal modifications characteristic of gastrointestinal autoimmune diseases has suggested that VD could play a role in controlling both the development and the course of CD and IBDs. Administration of VD in already diagnosed CD and IBD cases has not always significantly modified disease course. However, despite these relevant problems, most of the experts recommend monitoring of VD levels in patients with CD and IBDs and administration of supplements in patients with hypovitaminosis.

Knowledge and behaviors of using vitamin D to boost immunity against COVID-19 pandemic: A cross-sectional study in Saudi Arabia.

The coronavirus 2019 (COVID-19) pandemic has globally impacted all aspects of life since its emergence and spread. There is a strong biological assumption and progressing epidemiological data supporting the role of vitamin D (VD) in COVID-19 infection. This study aims to determine the knowledge about VD supplements to boost immunity against COVID-19 and if participation in specific behaviors has increased the consumption of VD supplements during social distance restriction in Saudi Arabia (SA) in May 2021. This cross-sectional study used a structured online questionnaire for 2369 SA people, including demographic characteristics and knowledge about VD supplements to boost immunity against COVID-19 showed that there was a significant association between sex and vitamin D deficiency (VDD) (P = .000), and having VDD was strongly associated with having another vitamin deficiency (P = .008). Additionally, there was a statistically significant difference between VDD and cardiovascular (P = .027) and respiratory diseases (P = .019). Almost half of the participants used VD supplements to reduce or heal their COVID-19 symptoms. The adverse association between having VDD and understanding of COVID-19 symptoms was statistically significant (P = .01). Ginger is commonly used as an alternative medicine for the treatment of VD. The administration of VD is now known to be of physiological significance for general health, and evidence suggesting the beneficial role of VD in the prevention and/or treatment of diseases, particularly infectious diseases, such as COVID-19, is increasing.

Primary hyperparathyreoidism - diagnostic procedures and management

Hypercalcemia as a laboratory result is often diagnosed during evaluation for osteoporosis. Any form of hypercalcemia should be evaluated further. Owing to fluctuating calcium levels, the measurement should be repeated and corrected for elevated albumin levels by calculation or by measuring ionized calcium. In the diagnosis of primary hyperparathyroidism, measurement of parathyroid hormone, creatinine/glomerular filtration rate, phosphate, 25-OH vitamin D3 and 24-hour urine values are essential for differential diagnosis. Kidney ultrasound is used to detect nephrocalcinosis or kidney stones, and dual-energy X-ray absorptiometry (DXA) to determine bone mineral density (BMD) at the lumbar spine, femoral neck, total femur, and distal forearm. Complete cure is only possible through surgical resection of the adenoma(s). The indication for surgery is dependent on the age of the patient, existing complications, and the patient's preference. Diagnostic imaging should only be performed if surgery is planned. Typically, neck ultrasound and 99mTc MIBI scintigraphy are sufficient to localize the parathyroid adenoma. Presurgical diagnostic evaluation of the thyroid is reasonable for surgical planning. Vitamin-D deficiency should be normalized before surgery. Postsurgical calcium and vitamin-D administration will prevent postsurgical hypocalcemia and hungry-bone disease, and may optimize the outcome of BMD. Treatment of osteoporosis without fractures might not be necessary, owing to normalization of BMD several years after parathyroid surgery. The continuation of specific anti-osteoporotic treatment with bisphosphonates post-surgery did not have any advantage and hence cannot be recommended.

Vitamin D and green tea extracts for the treatment of uterine fibroids in late reproductive life: a pilot, prospective, daily-diary based study

Objective The beneficial effects of Vitamin D (VD) and Epigallocatechin gallate (EGCG), a polyphenol of green tea, on the growth of uterine fibroids (UF) were previously described in vitro and in vivo. We have decided to investigate their simultaneous administration in women with UFs in late reproductive life. Methods >40 years old n = 16 premenopausal women with intramural (IM) or subserosal (SS) UF of ≥3 cm or several UFs of different sizes, even smaller but with a total diameter ≥3 cm but <10 cm, without further concomitant organic causes of abnormal uterine bleeding, treated with EGCG 300 mg, Vitamin B6 10 mg and VD 50 µg/day for 90 days. Women completed a diary on a daily basis to obtain information about bleeding and pelvic pain. Results We have observed a significant reduction in UF’s mean size both at patient’s (−17.8%, p = .03) and at single UF’s level (−37.3%, p = .015). The effect was more evident in women with predominant IM (p = .016) in comparison to SS UFs. No significant changes were observed for uterine and ovarian volume and endometrial thickness during treatment. We reported a significant decrease in menstrual flow length of 0.9 day (p = .04) with no modification in cycle length, menstrual flow intensity and menstrual pain intensity. The satisfaction with treatment was in general very high, with no adverse effects reported. Conclusion The concomitant administration of VD and EGCG represents a promising treatment of UF in women of late reproductive life for which hormonal manipulation is not foreseen.

Vitamin D receptor activated by vitamin D administration alleviates Mycobacterium tuberculosis-induced bone destruction by inhibiting NFκB-mediated aberrant osteoclastogenesis.

Clinically, bone destruction caused by Mycobacterium tuberculosis was serious especially in patients with vitamin D (VD) deficiency. However, the role of VD in M. tuberculosis-induced bone destruction remains clear. In this context, we investigate the role of VD and vitamin D receptor (VDR) in the M. tuberculosis-induced bone destruction. First, we infected RAW264.7 and bone marrow-derived macrophages (BMMs) with Mycobacterium bovis Bacillus Calmette-Guérin (M. bovis BCG) in vitro. Then, we activated VDR through VD administration. TRAP and FAK staining, bone resorption assays, immunofluorescence staining, qPCR, and western blot were carried out. In vivo, the M. tuberculosis-induced osteolytic model on the murine skull was established and the μCT and histological analyses were performed. We found that VDR and TRAP were upregulated in bone tuberculosis tissue and proved that M. tuberculosis infection promoted osteoclastogenesis in RAW264.7 and BMMs. VD could inhibit osteoclasts differentiation, fusion, and bone resorption dose-dependently. However, when VDR was knocked down, the inhibitory effect of VD on osteoclasts disappeared. In mechanism, activation of VDR inhibits the phosphorylation of IκB α, thereby inhibiting NFκB signaling pathway and alleviating osteoclastogenesis. Furthermore, in the skull osteolysis model, VD administration reduced osteolysis, but not in VDR-/- mice. Our study, for the first time, demonstrates that activation of VDR by VD administration inhibits M. tuberculosis-induced bone destruction. Our results reveal that VD and VDR are potential therapeutic targets for M. tuberculosis-induced bone destruction, and are of great clinical significance for the development of new therapeutic strategies.

Effects of Vitamin D on doxorubucin-induced lung injury and TRPM2 immunoreactivity in rats

Aim: Although doxorubicin (DOX) is a commonly used chemotherapeutic agent, it causes significant toxic side effects on many organs. This study aims to investigate the effects of vitamin D (VD) on DOX-induced lung injury and expression of transient receptor potential melastatin 2 (TRPM2), a Ca2 + permeable cation channel. Methods: A total of 24 Wistar albino rats were separated into four groups of six rats, as follows: The control group received no medications. The VD group received 200 IU/kg VD via an oral dropper (o.d.) for 14-days. DOX group received a single dose of 10 mg/kg DOX intraperitoneally (i.p.) on day 8. DOX+VD group was administered 200 IU/kg VD via an o.d. for 14-days, and a single dose of 10 mg/kg DOX i.p. on day 8. At the end of the experiment, lung and serum samples from all rats were collected. Masson’s trichrome staining and streptavidin-biotin-peroxidase complex were applied to the lung tissue sections. Serum total antioxidant status (TAS) and total oxidant status (TOS) were assessed by enzyme-linked immunosorbent assay (ELISA) method. Results: Histopathological damage was observed in the DOX group compared to the control group, and biochemical and immunohistochemical evaluation revealed that TOS level and TRPM2 expression increased while TAS level decreased significantly (P<0.001). Additionally, compared to the DOX group VD administration significantly reversed these values in the DOX+VD group (P<0.001). Conclusion: VD showed a protective effect on lung damage induced by DOX. Our data also suggest that TRPM2 channel may have a role in the pathophysiology of DOX-induced lung damage.

Efecto de la suplementación con vitamina D en dosis única sobre el estado nutricional de vitamina D

El primer año de vida es un periodo de riesgo de deficiencia de vitamina D (VD). La administración de 400 UI diarias de VD no tiene una adherencia del 100%, en cambio dosis únicas de 100.000 UI de VD oral son seguras en recién nacidos.Objetivo: Comparar el efecto de la suplementación oral de VD en dosis única de 100.000 UI al mes de edad vs dosis diarias de 400 UI sobre las concentraciones séricas de VD, a los 6 meses de vida.Sujetos y Método: Ensayo clínico aleatorizado, sin enmascaramiento. Se incluyeron 84 lactantes sanos de 1 mes de vida, asignados al azar al grupo de estudio (GE) que recibió una dosis única de VD de 100.000 UI oral o al grupo control (GC), que recibió dosis diarias de VD de 400 UI oral del 1er al 6to mes de vida. A los 6 meses de edad se determinó la concentración sérica de VD.Resultados: 65 lactantes terminaron el estudio, 36 en GE y 29 en GC. No se encontró deficiencia de VD. La insuficiencia de VD fue de 5,5% y 6,8% en el GE y GC, respectivamente. La concentración sérica de VD a los 6 meses de vida, fue de 38,8 ± 5,2 ng/ml y 39,7 ± 6,3 ng/ml para GE y GC, respectivamente (NS).Conclusiones: La suplementación con 100.000 UI de VD única al mes de edad logra concentraciones séricas de VD a los 6 meses de vida, similares a dosis diarias de 400 UI de VD, del 1er al 6to mes.

Effect of vitamin D supplementation as a single dose on the nutritional status of vitamin D.

Infants are a group at risk of vitamin D (VD) deficiency. The administration of 400 IU of VD per day during the first year of life does not achieve 100% adherence. A single dose of 100,000 IU of oral VD is safe in newborns. To compare the effect of oral administration of VD between a single dose of 100,000 IU at one month of age vs daily doses of 400 IU on serum concentrations of VD, at 6 months of age. Randomized clinical trial, without masking. 84 healthy infants were included at 1 month of age, randomized to the study group (SG) receiving a single oral dose of 100,000 IU or to the control group (CG), who received daily oral doses of VD of 400 IU from the 1st to the 6th month of life. At 6 months of life, the serum concentration of VD was determined. 65 infants completed the study, 36 in SG and 29 in CG. No VD deficiency was found. VD insufficient was 5.5% and 6.8% in the SG and CG, respectively. The serum concentration of VD at six months of age was 38.8 ± 5.2 ng/ml and 39.7 ± 6.3 ng/ml for the SG and CG, respectively (NS). Supplementation of 100,000 IU of VD at one month age achieves serum concentrations of VD at 6 months of life similar to the administration of daily doses of 400 IU of VD from the 1st to the 6th month.

The Role of Vitamin D Deficiency in Children With Recurrent Wheezing-Clinical Significance.

Recurrent wheezing (RW) in infancy is one of the most frequent reasons for parents to consult health care providers and creates a significant global burden. Clinical course of RW is difficult to predict, also which infants will progress to asthma, since no valid biomarkers have been established. Identification of those infants with RW who are at risk of further recurrences and/or severe acute respiratory tract infection (ARTI) could help pediatricians to improve their therapeutic decisions. Increasing research interest is focused on the extra-skeletal actions of vitamin D (VD) and the clinical impact of VD insufficiency/deficiency. As VD deficiency could be a risk factor for causing RW in children, measurement of their serum level of 25-hydroxycholecalciferol [25(OH)D] is recommended. In the case of deficiency, VD administration is recommended in age-appropriate doses for at least 6 weeks, until achievement of normal blood 25(OH)D level, followed by supplementation as long as exposure to sun is inadequate. Higher doses of VD given in an attempt to prevent asthma development appear to be of no additional benefit. In children with severe ARTI, VD level is recommended to be assess.

Diminished Vitamin D Receptor Protein Levels in Crohn's Disease Fibroblasts: Effects of Vitamin D.

Vitamin D (VD) deficiency has been associated to Crohn’s disease (CD) pathogenesis, and the exogenous administration of VD improves the course of the disease, but the mechanistic basis of these observations remains unknown. Vitamin D receptor (VDR) mediates most of the biological functions of this hormone, and we aim to analyze here the expression of VDR in intestinal tissue, epithelial cells, and fibroblasts from CD patients. The effects of VD on a fibroblast wound healing assay and murine intestinal fibrosis are also analyzed. Our data show diminished VDR protein levels in surgical resections and epithelial cells from CD patients. In intestinal fibroblasts isolated from damaged tissue of CD patients, we detected enhanced migration and decreased VDR expression compared with both fibroblasts from non-damaged tissue of the same CD patient or control fibroblasts. Treatment with VD increased VDR protein levels, avoided the accelerated migration in CD fibroblasts, and prevented murine intestinal fibrosis induced by the heterotopic transplant model. In conclusion, our study demonstrates diminished VDR protein levels associated with enhanced migration in intestinal fibroblasts from damaged tissue of CD patients. In these cells, VD accumulates VDR and normalizes migration, which supports that CD patients would benefit from the VD anti-fibrotic therapeutic value that we demonstrate in a murine experimental model.

Vitamin D Protects Against Alcohol-Induced Liver Cell Injury Within an NRF2-ALDH2 Feedback Loop.

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. Oxidative stress induced during the alcohol metabolism plays a crucial role in ALD, and clinical evidence demonstrates the prevalence and risks of vitamin D (VD) deficiency in ALD. This study aims to explore the mechanism of VD administration to ameliorate alcohol-induced cell injury. VD activates NRF2 (nuclear factor erythroid 2 (NF-E2)-related factor 2) signals along with upregulation of ALDH2 expression. Knockdown of NRF2 eliminates the protective effects of VD treatment. ALDH2 knockdown not only partially affects this protection, but also mildly reduces NRF2 expression. ALDH2 overexpression enhances ERK phosphorylation and upregulated NRF2 transcription via a newly identified TRE in the exon 1 of NRF2. This study provides evidence that VD protects against alcohol-induced cell injury within an NRF2-ALDH2 feedback loop. NRF2 induced by VD could transcriptionally upregulate ALDH2 expression to help metabolize alcohol. TRE-driven transcriptional upregulation of NRF2 through ALDH2-ERK/MEK signals would further exert the anti-oxidant effects. The study explores a novel potential protection of VD in alcohol-induced liver cell injury, and contributes to alcohol-related liver disease nutritional therapies.

Vitamin D protects against particles-caused lung injury through induction of autophagy in an Nrf2-dependent manner.

Fine particulate matter is a well-known air pollutant threatening public health. Studies have confirmed long-term exposure to the particles could decrease the pulmonary function, induce asthma exacerbation, and chronic obstructive pulmonary disease, as well as increase the incidence and mortality of lung cancer. A clinical study has explored that the prevalence and risks of vitamin D (VD) deficiency in various chronic disease and toxins induced tissue damage. Our current study aimed to explore the mechanism and further therapeutic potential of VD administration to ameliorate fine particles exposure induced pulmonary damage in vivo and in vitro. To elucidate the effects and mechanisms of VD in particles-induced pulmonary damage, a murine model was established with fine particles intratracheal instillation along with VD intramuscular injection. Our study demonstrated that treatment with VD attenuated particles-induced pulmonary damage and promoted tissue repair by repressing of TGFβ1 signaling pathway and upregulation of MMP9 expression. VD treatment could also regulate the autophagy-related signals along with activation of Nrf2 transcription factor. Furthermore, the results from the in vitro study demonstrated that VD protected against particles-induced cells' damage through the induction of autophagy in an Nrf2-dependent manner. VD treatment caused the degradation of P62 and its bound Keap1, which decreased the Nrf2 ubiquitination and increasing its protein stability. Our work explored a novel potential mechanism in the protection of VD in particles-induced pulmonary injury and tissue repair, and could further bring insights into exploring antifine particles exposure caused inflammation among other natural products and contributes to inflammation disease medical therapies.

Comparison of Vitamin D Status for Hirsutism, Biochemical Hyperandrogenism, Glycemia and Dyslipidemia among Subjects with Polycystic Ovarian Syndrome (PCOS)

Background: Data indicates that Vitamin-D (VD) insufficiency (low level of serum VD) has a close association with many metabolic disorders. Polycystic Ovary Syndrome (PCOS) is considered to be a metabolic disorder and VD administration has been attempted to ameliorate PCOS. VD insufficiency has been reported to be present in women with PCOS. However, coexisting conditions with PCOS (hyperandrogenism, insulin resistance, obesity, glucose intolerance, and dyslipidemia) have prevented to confirm this association. Methods: We measured and compared serum VD level in patients with PCOS (n=169) vs. those without PCOS (n=164), who visited PNS HAFEEZ Hospital Islamabad between Jan 2018-July 2019. We also compared VD level in relation to the following: BMI (using General Linear Model (GLM)), glucose levels and lipid parameters for patients with vs. without PCOS. Free Androgen Index (FAI) and modified Ferriman Gallwey (mFG) scores were compared between VD groups using one-way ANOVA. GLM was used to compare the effects of VD status and presence or absence of PCOS on insulin resistance. Results: Patients with PCOS, compared with those without it, showed lower VD levels regardless of BMI. Similarly, Lower level of Vitamin-D was observed in hyper-androgenism (Free Androgen Index (FAI)) and hirsutism (modified FG scores). Using univariate GLM with insulin resistance as dependent (confirmed) variable and PCOS and VD defined groups as independent factors, an increase in insulin resistance was observed with lower VD and the presence of PCOS. Conclusion: Patients with PCOS had lower VD levels than those with non-PCOS.

The Prevention of a High Dose of Vitamin D or Its Combination with Sulforaphane on Intestinal Inflammation and Tumorigenesis in Apc1638N Mice Fed a High‐Fat Diet

The previous study shows that obesity-promoted inflammation is responsible for the activation of the intestinal tumorigenic Wnt-signaling. The present study aims to test a dietary strategy, dietary supplementation with a high dose of vitamin D (VD) or its combination with sulforaphane (SFN) to inhibit intestinal inflammation and obesity-associated tumorigenesis. Apc1638N mice are randomly divided into four groups: LF, a low-fat diet (10 kcal% fat) with 200 IU VD; HF, a high-fat diet (60 kcal% fat) with 200 IU VD; HFD, a high-fat diet with 5000 IU VD; and HFDS, a high-fat diet plus 5000 IU VD and 0.23 g SFN per ≈4000 kcal. VD administration decreased tumor incidence and size, and the co-administration with SFN (HFDS) magnified the effects. Inflammation and Wnt-signaling are suppressed by VD. The addition of SFN decreased the activity of histone deacetylase (HDAC) and increased autophagy. The administration of VD, at 5000 IU level, exerts an anti-inflammatory property and leads to suppressed intestinal Wnt-signaling and tumorigenesis in obese mice. The molecular function of SFN on a high dose of VD supplementation, although displayed on the inhibition of HDAC and the activation of autophagy, needs further investigation.