PMID: 

Biochem Cell Biol. 2019 Dec 9. Epub 2019 Dec 9. PMID: 31815524

Abstract Title: 

Active Vitamin D activates chondrocyte autophagy to reduce osteoarthritis via mediating the AMPK/mTOR signaling pathway.

Abstract: 

Osteoarthritis (OA) is a common joint degenerative disease. Vitamin D (VD) is essential for bone function in human body. We hypothesized that active VD may play key functions in OA treatment. Low level of serum 25-hydroxyvitamin D (25(OH)D) was found in OA patients, and the serum VD level might be supportive for OA diagnosis. OA mouse models were established. HE and SafraninO/Fast Green staining suggested that active VD reduced OA symptoms in mice. VD treatment elevated p-AMPK/AMPK and decreased p-mTOR/mTOR, and it increased LC3II/LC3I, increased the protein level of Beclin-1, but decreased p62 according to Western blot analysis. Besides, VD reduced the contents of tumor necrosis factor-α and interleukin-6 both in cartilage tissues and in chondrocytes. Meanwhile, AMPK inhibitor Compound C and autophagy inhibitor 3-methyladenine (3-MA) reversed these changes following VD treatment. In addition, mRFP-GFP-LC3 transfection identified that active VD led to autophagosome aggregation inOA chondrocytes. 3-MA inhibited cell autophagy and promoted OA inflammation. This study provided evidence that active VD might activate chondrocyte autophagy to reduce OA inflammation via activating the AMPK/mTOR signaling pathway. Active OA treatment might serve as a novel therapeutic option for OAtreatment.

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PMID: 

Caspian J Intern Med. 2019 ;10(4):377-382. PMID: 31814934

Abstract Title: 

Are 25(OH) D concentrations associated with asthma control and pulmonary function test?

Abstract: 

Background: The relationship between vitamin D and asthma is still under investigation. We aimed to evaluate the association between serum vitamin D levels and clinical characteristics of asthma, and the impact of vitamin D deficiency on the clinical manifestations, as them being the issues of debate.Methods: Patients who were admitted to the outpatient clinics of Chest Diseases Department of Akdeniz University Hospital between January 2014 and December 2014, have been diagnosed as asthma according to the GINA 2014 guidelines were included in this study. Subjects with COPD, bronchiectasis, pneumonia or tuberculosis were excluded. Asthma exacerbation was defined, according to the GINA guidelines, as episodes of progressive shortness of breath, cough, wheezing or chest tightness accompanied by PFT abnormalities such as decreased PEF or FEV1.Results: A total of 158 patients with mean age of 48.8 years were included in the study. Twenty-seven (17.08%) of the patients demonstrated sufficient vitamin D serum levels (i.e.≥30 ng/mL), while the remaining 131 (82.92%) patients had vitamin D insufficiency (i.e.

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PMID: 

J Alzheimers Dis. 2019 Dec 2. Epub 2019 Dec 2. PMID: 31815694

Abstract Title: 

Circulating Vitamin D Levels and Alzheimer's Disease: A Mendelian Randomization Study in the IGAP and UK Biobank.

Abstract: 

Observational studies strongly supported the association of low levels of circulating 25-hydroxyvitamin D (25OHD) and cognitive impairment or dementia in aging populations. However, randomized controlled trials have not shown clear evidence that vitamin D supplementation could improve cognitive outcomes. In fact, some studies reported the association between vitamin D and cognitive impairment based on individuals aged 60 years and over. However, it is still unclear that whether vitamin D levels are causally associated with Alzheimer's disease (AD) risk in individuals aged 60 years and over. Here, we performed a Mendelian randomization (MR) study to investigate the causal association between vitamin D levels and AD using a large-scale vitamin D genome-wide association study (GWAS) dataset and two large-scale AD GWAS datasets from the IGAP and UK Biobank with individuals aged 60 years and over. Our results showed that genetically increased 25OHD levels were significantly associated with reduced AD risk individuals aged 60 years and over. Hence, our findings in combination with previous literature indicate that maintaining adequate vitamin D status in older people especially aged 60 years and over, may contribute to slow down cognitive decline and to forestall AD. Long-term randomized controlled trials are required to test whether vitamin D supplementation may prevent AD in older people especially those aged 60 years and may be recommended as preventive agents.

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PMID: 

Cell Death Dis. 2019 Dec 9 ;10(12):936. Epub 2019 Dec 9. PMID: 31819048

Abstract Title: 

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3.

Abstract: 

Chemoresistance is a major cause of cancer progression and the mortality of cancer patients. Developing a safe strategy for enhancing chemosensitivity is a challenge for biomedical science. Recent studies have suggested that vitamin D supplementation may decrease the risk of many cancers. However, the role of vitamin D in chemotherapy remains unknown. We found that vitamin D sensitised oral cancer cells to cisplatin and partially reversed cisplatin resistance. Using RNA-seq, we discovered that lipocalin 2 (LCN2) is an important mediator. Cisplatin enhanced the expression of LCN2 by decreasing methylation at the promoter, whereas vitamin D enhanced methylation and thereby inhibited the expression of LCN2. Overexpression of LCN2 increased cell survival and cisplatin resistance both in vitro and in vivo. High LCN2 expression was positively associated with differentiation, lymph node metastasis, and T staging and predicted a poor prognosis in oral squamous cell carcinoma (OSCC) patients. LCN2 was also associated with post-chemotherapy recurrence. Moreover, we found that LCN2 promoted the activation of NF-κB by binding to ribosomal protein S3 (RPS3) and enhanced the interaction between RPS3 and p65. Our study reveals that vitamin D can enhance cisplatin chemotherapy and suggests that vitamin D should be supplied during chemotherapy; however, more follow-up clinical studies are needed.

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PMID: 

Int J Biochem Cell Biol. 2019 Dec 7:105665. Epub 2019 Dec 7. PMID: 31821883

Abstract Title: 

Vitamin D deficiency induces the excitation/inhibition brain imbalance and the proinflammatory shift.

Abstract: 

Vitamin Dis among the major neurosteroids whose role in developing and adult brain is intensely studied now. Its active form 1,25(OH)Dregulates the expression and functioning of a range of brain-specific proteins, which orchestrates the neurotransmitter turnover, neurogenesis and neuroplasticity. Despite numerous studies of the vitamin D role in normal and pathological brain function, there is little evidence on the mechanisms of alterations in excitatory and inhibitory neurotransmission under vitamin D deficiency (VDD). Using the animal model we characterized the dysfunction of excitatory and inhibitory neurotransmission under alimentary VDD. The shift between unstimulated and evoked GABA release under VDD was largely reversed after treatment of VDD, whereas the impairments in glutamatergic system were only partially recovered after 1-month vitamin Dsupplementation. The increase of the external glutamate level and unstimulated GABA release in brain nerve terminals was associated with intensified ROS production and higher [Ca]in presynapse. The negative allosteric modulation of presynaptic mGlu7 receptors significantly enhanced exocytotic GABA release, which was decreased under VDD, thereby suggesting the neuroprotective effect of such modulation of inhibitory neurotransmission. Synaptic plasma membranes and cytosolic proteins contribute to the decreased stimulated release of neurotransmitter, by being the crucial components, whose functional state is impaired under VDD. The critical changes with synaptic vesicles occurred at the docking step of the process, whereas malfunctioning of synaptic cytosolic proteins impacted the fusion event foremost. The decreased amplitude of exocytosis was inherent for non-excitable cells as well, as evidenced by lower platelet degranulation. Our data suggest the presynaptic dysfunction and proinflammatory shift as the early events in the pathogenesis of VDD-associated disorders and provide evidences for the neuroprotective role of vitamin D

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PMID: 

Rev Invest Clin. 2019 ;71(6):381-386. PMID: 31823966

Abstract Title: 

ASSOCIATION OF VITAMIN D WITH MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DEMENTIA IN OLDER MEXICAN ADULTS.

Abstract: 

Background: It has been proposed that Vitamin D helps reduce the accumulation of cerebralβ-amyloid-42 by innate immune stimulation and phagocytosis activation. An association between low Vitamin D levels and Alzheimer's dementia (AD) has been established. We determined the association between Vitamin D, mild cognitive impairment (MCI), and AD in older Mexican adults (>65 years).Methods: Cross-sectional study conducted at the memory clinic in a tertiary-level hospital in Mexico City. We evaluated subjects with MCI, AD, and normal cognition (NC) with available serum Vitamin D [25(OH)D] levels (past 6 months). Three categories were assigned according to 25(OH)D levels: sufficiency (>30 ng/mL), insufficiency (21-29 ng/mL), and deficiency (≤ 20 ng/mL). Descriptive statistics, means and standard deviations were used. Logistic regression analyses adjusted by age, sex, and educational level were performed.Results: We evaluated 208 patients. Mean age was 79± 1 year, 65% (n = 136) were female; and mean educational level was 6.7 ± 2.3 years. Thirty-one subjects (14%) had NC; 42% (n = 88) had MCI; and 43% (n = 89) had AD. Prevalence of Vitamin D deficiency was 54%, more frequent in the AD group (64%) followed by the MCI (59%) and NC (13%) (p

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PMID: 

Asia Pac J Clin Nutr. 2019 ;28(4):689-694. PMID: 31826364

Abstract Title: 

Vitamin D and depression: mechanisms, determination and application.

Abstract: 

Depression is the most common debilitating psychiatric disease, the pathological mechanisms of which are associated with multiple aspects of neural function. While recent evidence has consistently suggested that a suboptimal vitamin D status is frequently observed in patients with depression, the results concerning whether vitamin D insufficiency is a causal factor of depression or is secondary to depressive behavior are conflicting; additionally, the lack of consistency of the method of vitamin D determination between labs has further worsened this confusion. Herein, we reviewed the neuroactivities of vitamin D that may be associated with depression and the current studies and clinical investigations to provide a full overview on the use of vitamin D in the treatment and prevention of depression.

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PMID: 

J Mol Neurosci. 2019 Dec 13. Epub 2019 Dec 13. PMID: 31836995

Abstract Title: 

Vitamin D Supplementation Ameliorates Severity of Major Depressive Disorder.

Abstract: 

Major depressive disorder is a serious neuropsychiatric disease that leads to significant impairment in social functioning and increased morbidity and mortality. Low vitamin D (25-OH D) levels have been hypothesized to contribute to the pathophysiology of MDD. To investigate the therapeutic role of vitamin D in MDD, we recruited 62 male and female patients diagnosed with MDD and randomized them into two groups: the first group (49 patients) received vitamin D supplementation as cholecalciferol vitamin D(50,000 I.U.) for 3 months, in addition to standard of care (SOC) which included pharmacological treatment and psychological support, and the second group (13 patients) received only SOC without vitamin D supplementation for 3 months. The Beck depression inventory (BDI) scale was used to assess the severity of MDD symptoms. Immunoassays were utilized to determine levels of serum vitamin Dand serotonin in all patients. The results showed significant gender differences; female patients showed the most improvement in their depressive symptoms after 3-month vitamin D supplementation. Females with moderate, severe, and extreme depression had significantly lower BDI scores after vitamin D treatment (p 

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PMID: 

Brain Behav. 2019 Dec 13:e01498. Epub 2019 Dec 13. PMID: 31837111

Abstract Title: 

Vitamin D increases remyelination by promoting oligodendrocyte lineage differentiation.

Abstract: 

INTRODUCTION: Several experimental studies have suggested the potential remyelinating effects of vitamin D (VitD) supplements regardless of the presence of VitD deficiency. This study aims to analyze neurogenesis in a model of toxic demyelination in order to evaluate the effects of VitD on demyelination and remyelination.MATERIAL AND METHODS: We used 24 male Wistar rats that had received surgical lesions to the corpus callosum and were injected with lysolecithin. Rats were divided into three groups: Group 1 included eight rats with lesions to the corpus callosum but not lysolecithin injections (sham group), group 2 included eight rats with lesions to the corpus callosum that were injected with lysolecithin (lysolecithin group), and group 3 included eight rats with lesions that were injected with lysolecithin and received VitD (VitD group). We analyzed neurogenesis both in the subventricular zone and at the lesion site.RESULTS: Administration of VitD promotes the proliferation and differentiation of neural stem cells in the subventricular zone and the migration of these cells to the lesion site in the corpus callosum; these cells subsequently differentiate into oligodendrocyte lineage cells and produce myelin basic protein. This phenomenon was not caused by microglial activation, which was less marked in rats receiving VitD. Megalin expression did not increase at the lesion site, which suggests that VitD is internalized by other mechanisms.CONCLUSION: Our results support the hypothesis that regardless of the presence of VitD deficiency, treatment with VitD may contribute to remyelination by promoting the proliferation of oligodendrocyte precursor cells.

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PMID: 

J Rheumatol. 2019 Dec 15. Epub 2019 Dec 15. PMID: 31839594

Abstract Title: 

Association between Vitamin D deficiency and disease activity, disability and radiographic progression in early rheumatoid arthritis. The ESPOIR cohort.

Abstract: 

OBJECTIVE: To evaluate the association of baseline serum level of vitamin D (vitD) with disease activity, disability and radiographic damage over the first year in early rheumatoid arthritis (RA).METHODS: Among early arthritis patients included in the ESPOIR cohort, patients with early RA were evaluated. 25OH vitamin D2D3 level was measured at baseline. Baseline associations between vitD level and DAS28-ESR, Health Assessment Questionnaire Disability Index (HAQ-DI) and van der Heijde-modified total Sharp score (mTSS) were assessed. Bivariate analysis was used to assess the association between vitD level and radiographic progression (mTSS increased by≥1 point) or disability (HAQ-DI ≥0.5) over 12 months. Forward stepwise multiple logistic regression was used to evaluate the independent association of baseline variables and outcomes.RESULTS: Among 813 patients with early arthritis, data for 645 RA patients were analyzed. VitD level was

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