The effects of high doses of vitamin D on the composition of the gut microbiome of adolescent girls.

BACKGROUND: Animal studies suggest that vitamin D can change the gut microbiome. The primary aim of this study was to evaluate the effect of a high dose supplementation of vitamin D on the composition of the gut microbiome. METHODS: After DNA extraction, TaqMan assays were used for the quantitation of selected microbiome in the feces of 50 adolescent girls before and after vitamin D supplementation. RESULTS: The expression fold changes for Enterococcus, Bifidobacterium, Lactobacillus, Bacteroidetes and Firmicutes were; 1.05, 1.20, 0.76, 0.28 and 1.50 respectively. Bacteroidetes and Lactobacillus fell by 72% (P < 0.0001) and 24% (P = 0.006) respectively, whilst Firmicutes and Bifidobacterium were increased by 1.5 (P < 0.0001), 1.2 (P < 0.0001) fold after supplementation. CONCLUSION: Our results suggested that a high dose supplementation of vitamin D alter the human gut microbiome composition. Future studies are required for a better understanding of the mechanisms by which vitamin D affects the gut microbiome.

Prevalence of CCR5delta32 in Northeastern Iran.

BACKGROUND: A 32-base pair deletion (∆32) in the open reading frame (ORF) of C-C motif chemokine receptor 5 (CCR5) seems to be a protective variant against immune system diseases, especially human immunodeficiency virus type 1 (HIV-1). We aimed to assess the frequency of CCR5∆32 in the healthy Iranian population. METHODS: In this study, 400 normal samples from Khorasan, northeastern Iran, were randomly selected. The frequency of CCR5∆32 carriers was investigated using PCR analysis. Allele prevalence and the fit to the Hardy-Weinberg equilibrium were analyzed. RESULTS: The prevalence of CCR5∆32 in the northeastern population of Iran was 0.016. Four hundred samples were studied, among which one with CCR5∆32/∆32 and 11 with CCR5Wild/∆32 genotype were detected. CONCLUSION: This study was the first investigation for an assessment of the prevalence of CCR5∆32 in northeastern Iran. The low prevalence of CCR5∆32 allele in the Iranian population may result in the increased susceptibility to HIV-1. In addition, this prevalence is the same as that of reported in East Asia, while is lower than that in the Europeans.

New anthropometric indices in the definition of metabolic syndrome in pediatrics.

Pediatrics metabolic syndrome (MetS) may be associated with the risk of development of chronic diseases in adulthood; however, the definition of pediatric MetS is unclear, and may vary with ethnicity. The primary goal of this study was to determine the best anthropometric predictors for pediatric MetS. For this purpose, 988 high school girls were recruited. Anthropometric indices and biochemical parameters were measured using standard procedures. The adapted MetS for pediatrics, including the IDF, NCEP, and two modified-NCEPs (Cook's and DeFerranti's) were used to establish a diagnosis of MetS. Statistical analysis was performed using SPSS and MedCalc softwares. Except for body frame size (r), the values for anthropometric indices were significantly lower in an individual without MetS. Waist to height (WHtR), BMI and hip circumference (HiC) showed the strongest association with the different MetS definitions. For the IDF definition, the highest sensitivity and specificity were observed for HiC (100.0, 85.2) and WHtR (100.0, 84.7); while for the NCEP definition, the r index showed the highest sensitivity (85.0); but low specificity made it inapplicable. For the Cook's definition of MetS, wrist circumference (WrC), HiC, WHtR, BMI and SR had similar sensitivity values with WC (92.9%), and HiC (85.3%) have the highest specificity. WHtR (86.05, 80.5), SR (86.05, 82.7) and HiC (76.7, 87.0) sensitivity and specificity were the best indexes for DeFerranti's criteria. Based on this date, we concluded that HiC and WHtR might be helpful as auxiliary indexes for pediatric MetS definition; however, further studies are required in both genders.

The clinical importance of CD4+ CD7- in human diseases.

The CD7 antigen is a member of the immunoglobulin superfamily that expresses on the surface of all thymocytes, a majority of mature T cells, and also natural killer cells. Interestingly, under physiological and different pathological conditions, the loss of CD7 antigen occurred in the subset of CD4+ memory T cells. Various functions have been proposed for CD7, including its role in the activation and intercellular adhesiveness of T cells. Several studies indicate that the number of CD4+ CD7- T cells increases in diseases such as chronic inflammation and T-cell malignancies, these being skin inflammatory lesions. Therefore, this can be useful for the diagnosis of cancer cells, especially with reference to blood origin, treatment monitoring, and establishment of new therapies. Therefore, a comprehensive review could be useful to increase our knowledge about the clinical importance of these cells in human disease.

A Western dietary pattern is associated with elevated level of high sensitive C-reactive protein among adolescent girls.

BACKGROUND: Serum high sensitive C-reactive protein (hs-CRP), is an indicator of low-grade inflammation, and is associated with several non-communicable diseases. The effects of diet on inflammation have not been extensively investigated, particularly among adolescents. We aimed to examine the association between major dietary patterns and elevated serum level of hs-CRP among Iranian adolescent girls. MATERIALS AND METHODS: In this cross-sectional study, a total of 670 adolescent girls were recruited from several schools in different areas of Mashhad and Sabzevar cities, Iran. The dietary intakes of study participants were collected using a 147-item food frequency questionnaire. To identify major dietary patterns based on the 40 food groups, we used principal component analysis. Serum concentration of hs-CRP was measured using commercial kits and the BT-3000 auto-analyser. To investigate the association between dietary patterns and elevated serum level of hs-CRP, we used logistic regression analysis. RESULTS: Three specific dietary patterns were identified: (i) healthy, (ii) traditional and (iii) western dietary patterns. A significant association was found between more adherence to Western dietary pattern and elevated serum level of hs-CRP (OR: 1.58; 95% CI: 1.02-2.42, P-trend = .03); these association remained significant after adjustment for potential confounders. However, there was no significant relationship between healthy and traditional dietary patterns and elevated serum level of hs-CRP. CONCLUSION: Our results indicate that there is a significant positive association between more adherence to Western dietary pattern and higher serum levels of hs-CRP among Iranian adolescent girls. Further studies, particularly longitudinal intervention studies may be required to clarify these relationships.

High-dose vitamin D supplementation is associated with an improvement in several cardio-metabolic risk factors in adolescent girls: a nine-week follow-up study.

Background Vitamin D deficiency is a prevalent and important global health problem. Because of its role in growth and development, vitamin D status is likely to be particularly important in adolescent girls. Here, we explored the effects of high-dose vitamin D supplementation on cardio-metabolic risk factors. Methods We have examined the effects of vitamin D supplementation on cardio-metabolic risk factors in 988 healthy adolescent girls in Iran. Fasting blood samples and anthropometric measurements were obtained at baseline and after supplementation with high-dose vitamin D. All individuals took a capsule of 50,000 IU vitamin D/week for nine weeks. The study was completed by 940 participants. Results The prevalence of vitamin D deficiency was 90% at baseline, reducing to 16.3% after vitamin D supplementation. Vitamin supplementation was associated with a significant increase in serum concentrations of 25 (OH) vitamin D and calcium. There were significant reductions in diastolic blood pressure, heart rate, waist circumference and serum fasting blood glucose, total- and low-density lipoprotein-cholesterol after the nine-week period on vitamin D treatment, but no significant effects were observed on body mass index, systolic blood pressure or serum high-density lipoprotein cholesterol and triglyceride. Conclusion Vitamin D supplementation had beneficial effects on cardio-metabolic profile in adolescent girls.

There is an association between serum high-sensitivity C-reactive protein (hs-CRP) concentrations and depression score in adolescent girls.

BACKGROUND: Whilst there is evidence of an association between depression and inflammation in adults, there is limited data on this in adolescents particularly in non-westernized populations. The primary aim of this study was to evaluate the association between serum hs-CRP level and depression score in adolescent girls living in northwestern Iran. METHOD: Serum hs-CRP was measured in 563 adolescent girls aged 12-18 years. Depression score was assessed using the Beck's depression inventory II (BDI-II). RESULTS: Serum hs-CRP was 0.61 (0.30-0.88) mg/L [median (interquartile range)] in the non-depressed group, 0.97 (0.50-1.82) mg/L in the group with a mild depression score, 1.04 (0.57-1.60) mg/L in those with a moderate depression score, and 0.84 (0.45-2.64) mg/L in girls with severe depression (Kruskal-Wallis test, P<0.001). It has shown that hs-CRP is significantly higher in depressed groups. Multinomial logistic regression analysis, controlling for age, BMI, waist circumference, social class, alcohol consumption, smoking or being passive smoker and recent infections, showed that depression scores were positively associated with serum hs-CRP level (OR=1.93, P<0.001). Using a linear model after adjustment, B (the unstandardized beta) of hs-CRP according to the depression score was 1.43, P<0.001. CONCLUSION: There is a significant association between serum hs-CRP and depression score in adolescent girls. The cross sectional study design does not allow us to conclude that there is a direct relationship between inflammation and depression, and this would need to be tested in an intervention study.

The current status and perspectives regarding the clinical implication of intracellular calcium in breast cancer.

Calcium ions (Ca2+ ) act as second messengers in intracellular signaling. Ca2+ pumps, channels, sensors, and calcium binding proteins, regulate the concentrations of intracellular Ca2+ as a key regulator of important cellular processes such as gene expression, proliferation, differentiation, DNA repair, apoptosis, metastasis, and hormone secretion. Intracellular Ca2+ also influences the functions of several organelles, that include: the endoplasmic reticulum, mitochondria, the Golgi, and cell membrane both in normal and breast cancer cells. In breast cancer, the disruption of intracellular: Ca2+ homeostasis may cause tumor progression by affecting key factors/pathways including phospholipase C (PLC), inositol 1,4,5-trisphosphate (IP3), calmodulin (CaM), nuclear factor of activated T-cells (NFAT), calpain, calmodulin-dependent protein kinase II (CaMKII), mitogen-activated protein kinase (MAPK), epithelial-mesenchymal transition (EMT), vascular endothelial growth factor (VEGF), poly (ADP-Ribose) polymerase-1 (PARP1), estrogen, and estrogen receptor. Because the foregoing molecules play crucial roles in breast cancer, the factors/pathways influencing intracellular Ca2+ concentrations are putative targets for cancer treatment, using drugs such as Mephebrindole, Tilapia piscidin 4, Nifetepimine, Paricalcitol, and Prednisolone. We have explored the factors/pathways which are related to breast cancer and Ca2+ homeostasis and signaling in this review, and also discussed their potential as biomarkers for breast cancer staging, prognosis, and therapy.

The 9p21 Locus and its Potential Role in Atherosclerosis Susceptibility; Molecular Mechanisms and Clinical Implications.

Cardiovascular disease (CVD) is the leading cause of global mortality. Although extensive efforts have been made to identify valid biomarkers for CVD risk, relatively few are of proven clinical utility. It is recognized that genetic factors play a major role in determining the susceptibility to CVD. Recent genome-wide-association-studies have demonstrated common genetic variants in a region on chromosome 9p21 associated with an increased risk of CVD. Several genetic-polymorphisms have been identified in this region that are highly associated with CVD, and these are clustered around the gene loci for CDKN2B (coding for p15ink4b), CDKN2A (coding for p16ink4a and p14ARF) and the 3' end of CDKN2BAS, which has been termed antisense noncoding RNA in the INK4 locus (ANRIL). Targeted deletion of the 9p21 locus reduces the cardiac expression of CDKN2A/B and is the most frequent mechanism for methylthioadenosine phosphorylase inactivation, leading to a less stable plaque phenotype in the artery. Further investigations will be essential to explore the clinical utility of emerging-markers in larger and multicenter setting in order to establish their values for risk stratification or prediction a chance of future CVD events. The aim of the current review was to provide an overview of the possible molecular mechanisms by which the chromosome 9p21 locus may confer CVD risk, and the consequential clinical implications with particular emphasis on preclinical/clinical trials on genetic changes of this locus and CVD risk.

Purification and characterization of a novel extracellular halophilic and organic solvent-tolerant amylopullulanase from the haloarchaeon, Halorubrum sp. strain Ha25.

A halophilic archaeon, Halorubrum sp. strain Ha25, produced extracellular halophilic organic solvent-tolerant amylopullulanase. The maximum enzyme production was at high salt concentration, 3-4 M NaCl. Optimum pH and temperature for enzyme production were 7.0 and 40 °C, respectively. Molecular mass of purified enzyme was estimated to be about 140 kDa by SDS-PAGE. This enzyme was active on pullulan and starch as substrates. The apparent Km for the enzyme activity on pullulan was 4 mg/ml and for soluble starch was 1.8 mg/ml. Optimum temperature for amylolytic and pullulytic activities was 50 °C. Optimum pH for amylolytic activity was 7 and for pullulytic activity was 7.5. This enzyme was active over a wide range of concentrations (0-4.5 M) of NaCl. The effect of organic solvents on the enzyme activities showed that this enzyme was more stable in the presence of non-polar organic solvents than polar solvents. This study is the first report on amylopullulanase production in halophilic bacteria and archaea.