PMID: 

Calcif Tissue Int. 2019 Aug 21. Epub 2019 Aug 21. PMID: 31435709

Abstract Title: 

Asiatic Acid Attenuates Bone Loss by Regulating Osteoclastic Differentiation.

Abstract: 

Anti-resorptive agents like bisphosphonates have been widely used for the treatment of postmenopausal osteoporosis. However, their long-term safety and efficacy are still controversial. This study is to examine the effect of Asiatic acid (AA) in osteoclastic differentiation, and further to investigate its effect on bone quality in animals. Effect of AA on osteoclastic differentiation was measured by Tartrate-resistant acid phosphatase stain, bone resorption pit assays, and quantitative real-time polymerase chain reaction. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor-β (TGF-β) signaling were measured by western blot before and after AA treatment. Ovariectomized (OVX) wild-type or Smad7 partially knock out mice were used to evaluate the effects of AA on bone quality by micro-computed tomography, mechanical test, and histomorphometry. Results revealed a dose-dependent inhibitory effect of AA on osteoclastic differentiation. After AA treatment, Smad7 was upregulated, while NF-κB and TGF-β signaling were inhibited during osteoclastic differentiation. Results from animal study revealed that AA prevented bone from furtherloss caused by OVX and increased the mechanical properties of femur in wild-type animals. AA also prevented bone loss in the Smad7-deficient animals. When combining with OVX in the Smad7-deficient mice, AA could only partially preserve their bone mass. Taken together, we found that AA effectively inhibited osteoclastic differentiation and attenuated osteoporosis, which effects may be through TGF-β and NF-κB pathways. This study reveals that AA may be a potential anti-resorptive agent for postmenopausal osteoporosis.

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PMID: 

Food Funct. 2019 Sep 9. Epub 2019 Sep 9. PMID: 31497826

Abstract Title: 

Urolithin A targets the PI3K/Akt/NF-κB pathways and prevents IL-1β-induced inflammatory response in human osteoarthritis: in vitro and in vivo studies.

Abstract: 

Osteoarthritis (OA) is a degenerative joint disease, whose progression is closely related to the inflammatory environment. Urolithin A (UA), a natural metabolite of a class of compounds (ellagitannins and ellagic acid) found in pomegranates and other fruits and nuts, has been proved to exert anti-inflammatory effects in a variety of diseases. However, the exact role of UA in OA development is still unclear. In the present study, we examined the latent mechanism of UA and its protective role in the progression of OA by both in vitro and in vivo experiments. In vitro, UA inhibited the interleukin-1 beta (IL-1β) induced over-production of nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in a concentration-dependent manner in human OA chondrocytes. Furthermore, by downregulating theexpression of metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5), UA attenuated the degradation of the extracellular matrix (ECM) induced by IL-1β. Mechanistically, UA was found to suppress the activation of PI3K/Akt/NF-κB pathways. In vivo, in a surgically induced mouse OA model,UA-induced protective effects in OA development could be detected. In summary, this research suggested that UA may be adopted as a new therapeutic agent for the treatment of OA.

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PMID: 

Oncol Lett. 2019 Sep ;18(3):3195-3201. Epub 2019 Jul 25. PMID: 31452796

Abstract Title: 

Shikonin potentiates paclitaxel antitumor efficacy in esophageal cancer cells via the apoptotic pathway.

Abstract: 

Shikonin is a natural naphthoquinone pigment that can suppress the growth of a number of cancer cell types. Paclitaxel is an antineoplastic chemotherapy drug, which is used for the treatment of various types of solid tumor cancer. However, acquired paclitaxel resistance results in the failure of therapy, and consequent metastasis and relapse. The aim of the present study was to investigate whether shikonin can sensitize esophageal cancer cells to paclitaxel-treatment and to elucidate the underlying mechanisms. The biological effects of these two agents on esophageal cancer cell lines KYSE270 and KYSE150 were investigated by MTT assay, cell cycle analysis, Annexin-V apoptosis assay, western blotting and reverse transcription-quantitative polymerase chain reaction. The results demonstrated that shikonin could significantly increase the cell growth inhibition effect induced by paclitaxel in the examined cell lines (P

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PMID: 

Nutrients. 2019 Sep 5 ;11(9). Epub 2019 Sep 5. PMID: 31491877

Abstract Title: 

Low Serum Vitamin D Concentrations Are Associated with Insulin Resistance in Mexican Children and Adolescents.

Abstract: 

Previous studies in the Mexican adult population have suggested a relationship between low levels of serum concentrations of serum vitamin D with impaired glucose tolerance, metabolic syndrome, and diabetes, regardless of the presence of obesity. The aim of this study is to investigate the relationship between serum vitamin D levels and the factors linked to insulin resistance. A total of 533 children and adolescents from the"Reference Values of Body Composition in the Pediatric Population of Mexico City"study are assessed. Body composition, dietary, and lifestyle data are obtained. Serum vitamin D, insulin, and glucose are also measured. Associations are tested using multiple linear and logistic regression models. Approximately 90% of children and adolescents in this study have sub-optimal vitamin D levels (

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PMID: 

Oral Dis. 2019 Sep 6. Epub 2019 Sep 6. PMID: 31493304

Abstract Title: 

Is vitamin D deficiency a risk factor for recurrent aphthous stomatitis? A systematic review and meta-analysis.

Abstract: 

OBJECTIVES: A few studies have associated vitamin D deficiency with the occurrence of recurrent aphthous stomatitis (RAS). Hence, the aim of the present systematic review and meta-analysis is to explore such a potential association.METHODS: A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted in June 2019.The inclusion criteria were: 1) observational studies that assessed the relationship between vitamin D and RAS, and 2) the outcome measures reported quantitative vitamin D levels. Studies without control groups, case series, case reports, experimental studies, letter to editors, reviews, were excluded. The random-effects model was conducted for meta-analyses using RevMan 5.3 software.RESULTS: Five studies comprising 208 RAS patients and 241 healthy individuals were included. All studies except one reported significantly lower levels of vitamin D in RAS patients compared to the healthy individuals. The results of the pooled 5 studies revealed statistically significant lower levels of vitamin D in RAS patients (Mean Difference (MD) = -9.67 ng/mL, 95% CI= -15.68, -3.65; P˂ 0.002).CONCLUSION: The present meta-analysis suggests a significant association between low vitamin D levels and RAS. Further well-designed studies with adequate sample sizes are required to elucidate the role of vitamin D in pathogenesis of RAS. This article is protected by copyright. All rights reserved.

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PMID: 

Clin Nutr. 2019 Aug 27. Epub 2019 Aug 27. PMID: 31495735

Abstract Title: 

Association between vitamin D status and sepsis in children: A meta-analysis of observational studies.

Abstract: 

BACKGROUND: The consequences of vitamin D deficiency regarding sepsis in children remain controversial. We conducted a meta-analysis of studies evaluating the association between vitamin D status and sepsis in children.METHODS: We used EMBASE, Ovid Medline and Cochrane Library to conduct a meta-analysis of studies published in English before November 21, 2017.RESULTS: Among 1146 initially identified studies, we included 13 studies according to predefined inclusion criteria comprising 975 patients and 770 control participants. According to a random effects model, the mean difference in 25(OH)D levels (nmol/L) between participants with sepsis (444) and controls (528) was (mean difference, -18.55; 95% confidence interval (CI), -19.45 to -17.66, p 

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PMID: 

Int J Diabetes Clin Res. 2018 ;5(3). Epub 2018 Sep 29. PMID: 31497649

Abstract Title: 

The Effect of Vitamin D Supplementation on Blood Lipids in Minorities with Type 2 Diabetes.

Abstract: 

Introduction: Vitamin D deficiency and type 2 diabetes are common among Hispanics and African Americans in the US. The aim of the study was to determine the effect of supplemental vitamin D intake (4000 IU/day or 6000 IU/day of vitamin D3 over a 6-month period) on blood lipids in a sample of African Americans and Hispanics with type 2 diabetes and vitamin D insufficiency.Materials and methods: Participants (n = 75) were recruited by community outreach. Participants in both groups were required to take either 4000 IU or 6000 IU of vitamin D (Cholecalciferol) per day given in the form of a pill in a single daily dose. Mixed model was used to compare treatment effects (4000 IU vs. 6000 IU) on the outcome variables. Bonferroni multiple comparison test was used to detect significant changes from baseline, 3 months, and 6 months.Results: A significant decrease in total cholesterol (from 193.88± 41.03 to 180.48 ± 27.53 mg/dl,= 0.040) and triglycerides (from 201.44± 91.35 to 172.92 ± 76.87 mg/dl,= 0.037) was found for the 6000 IU group at 6 months. The significance was lost after adjusting for confounders.Conclusion: Our results suggest that the positive effect of vitamin D supplementation on lipid profile may be mediated by other cofactors related to vitamin D metabolism among Hispanic and African American participants with type 2 diabetes.

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PMID: 

Nutr Rev. 2019 Sep 5. Epub 2019 Sep 5. PMID: 31504857

Abstract Title: 

Prebiotics may reduce serum concentrations of C-reactive protein and ghrelin in overweight and obese adults: a systematic review and meta-analysis.

Abstract: 

CONTEXT: Biochemical markers correlate positively with the development and severity of obesity, depression, and anxiety, and can be modulated by changes in intestinal microbiota composition.OBJECTIVE: A systematic review and meta-analysis was conducted to determine the effects of prebiotics or synbiotics on blood biomarkers of obesity, depression, and anxiety (including: ACTH [adrenocorticotropic hormone], cortisol, leptin, ghrelin, TSH [thyroid-stimulating hormone], PTH [parathyroid hormone], vitamin D, BDNF [brain-derived neurotrophic factor], and PCR [polymerase chain reaction]) in individuals with overweight or obesity.DATA SOURCES: MEDLINE, Web of Science, Scopus, and CENTRAL databases were searched, along with the reference lists of included articles. Authors were contacted for unpublished data.STUDY SELECTION: RCT in individuals with overweight or obesity, supplemented with prebiotics or synbiotics, assessing any of the outcomes of interest.DATA EXTRACTION: Data were extracted independently by three researchers.RESULTS: Thirteen studies were identified up to March 7, 2018. Regarding outcomes, 1 study assessed leptin, 4 studies assessed ghrelin, and 10 studies assessed CRP (C-reactive protein). Meta-analysis showed reduction in serum concentrations of ghrelin (-37.17 pg/mL; 95%CI = -69.62, -4.73; P = 0.025) and CRP (SMD [standardized mean difference] = -0.31; 95%CI = -0.58, -0.04; P = 0.027) after supplementation of inulin-type fructans.CONCLUSIONS: Prebiotics may help regulate blood concentrations of ghrelin and CRP in overweight or obese individuals.

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PMID: 

PLoS Med. 2019 Sep ;16(9):e1002907. Epub 2019 Sep 11. PMID: 31509529

Abstract Title: 

Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis.

Abstract: 

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.
METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D<50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as>75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D<25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies.
CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

PMID: 

Biomolecules. 2019 Sep 10 ;9(9). Epub 2019 Sep 10. PMID: 31509973

Abstract Title: 

Effects of Vitamin D Deficiency on Proliferation and Autophagy of Ovarian and Liver Tissues in a Rat Model of Polycystic Ovary Syndrome.

Abstract: 

AIM: We aimed to examine the alterations of the insulin signaling pathway, autophagy, nitrative stress and the effect of vitamin D supplementation in the liver and ovaries of vitamin D deficient hyperandrogenic rats.METHODS: Female Wistar rats received eight weeks of transdermal testosterone treatment and lived on a low vitamin D diet (D-T+). Vitamin D supplementation was achieved by oral administration of vitamin D3 (D+T+). Sham-treated (D+T-) and vitamin D deficient animals (D-T-) served as controls. (N = 10-12 per group).RESULTS: D-T+ animals showed decreased LC3 II levels in the liver and increased p-Akt/Akt and p-eNOS/eNOS ratios with decreased insulin receptor staining in the ovaries. Vitamin D supplementation prevented the increase of Akt phosphorylation in the ovaries. Vitamin D deficiency itself also led to decreased LC3 II levels in the liver and decreased insulin receptor staining in the ovaries. D-T+ group showed no increase in nitrotyrosine staining; however, the ovaries of D-T- rats and the liver of D+T+ animals showed increased staining intensity.CONCLUSION: Vitamin D deficiency itself might lead to disrupted ovarian maturation and autophagy malfunction in the liver. Preventing Akt phosphorylation may contribute to the beneficial effect of vitamin D treatment on ovarian function in hyperandrogenism.

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