Association of a genetic variant in angiopoietin-like 3 with serum HDL-C and risk of cardiovascular disease: A study of the MASHAD cohort over 6 years.

BACKGROUND: Loss-of-function (LOF) variants of the angiopoietin-like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations and thereby affect the risk of cardiovascular disease (CVD). OBJECTIVE: In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. METHODS: One thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow-up. After a 12-h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra-ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20. RESULTS: Individuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01-2.02, p = 0.041). There was a 1.3-fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non-carriers (OR = 1.32, 95%CI = 1.06-1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL-C. CONCLUSION: We have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.

Evaluation of rs10811661 polymorphism in CDKN2A / B in colon and gastric cancer.

One of the causes of colon and gastric cancer is the dysregulation of carcinogenic genes, tumor inhibitors, and micro-RNA. The purpose of this study is to apply rs10811661 polymorphism in CDKN2A /B gene as an effective biomarker of colon cancer and early detection of gastric cancer. As a result,400 blood samples, inclusive of 200 samples from healthy individuals and 200 samples (100 samples from intestinal cancer,100 samples from stomach cancer) from the blood of someone with these cancers, to determine the genotype of genes in healthful and ill people through PCR-RFLP approach and Allelic and genotypic tests of SPSS software. To observe the connection between gastric cancer and bowel cancer risk and genotypes, the t-student test for quantitative variables and Pearson distribution for qualitative variables have been tested and the results have been evaluated using the Chi-square test. The effects confirmed that the highest frequency of TT genotypes is in affected individuals and CC genotype is in healthful individuals. In addition, it confirmed that women were more inclined than men to T3 tumor invasion and most grade II and III colon cancers, and in older sufferers with gastric cancer, the grade of tumor tended to be grade I. Among genetic variety and rs10811661, with invasiveness, there is a tumor size and degree in the affected person. In summary, our findings suggest that the rs10811661 polymorphism of the CDKN2A / B gene is strongly associated with the occurrence of intestinal cancer and stomach is linked to its potential role as a prognostic biomarker for the management of bowel cancer and stomach.

Double blind control trial of vitamin D fortified milk on the expression of lncRNAs and adiponectin for patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (Mets) is a common metabolic disorder in which hypoadiponectinemia is one of the consequences for the body caused by inflammation, and vitamin D may help improve inflammatory symptoms. LncRNAs (long non-coding RNA) play several different regulatory roles in the body. The goal of this study was to see how adding vitamin D to milk affected the levels of adiponectin and inflammatory lncRNAs in the serum of people with Mets. METHODS: This clinical trial was conducted on staff and students between the ages of 30 and 50 at Mashhad University of Medical Sciences and met the International Diabetes Federation's criteria for Mets. Eighty-two Mets were assigned randomly to one of two groups for ten weeks: fortified milk (FM) with 1500 IU vitamin D or non-fortified milk (NFM). Total RNA was extracted from both frozen clinical samples using Trizol reagent. APQ AS and MALAT1 lncRNA gene expression were measured by Real-Time PCR. RESULTS: Serum adiponectin levels in the FM group increased significantly compared to the NFM group (p = 0.01). Also, the expression of APQ AS and MALAT1 genes decreased after ten weeks, which showed a significant decrease in APQ AS (p = 0.036). CONCLUSION: As in FM, vitamin D may have anti-inflammatory effects and increase adiponectin levels in people with Mets via decreasing APQ AS gene expression.

Upregulation of the c-MYC oncogene and adjacent long noncoding RNAs PVT1 and CCAT1 in esophageal squamous cell carcinoma.

BACKGROUND: All cell types express long non-coding RNAs (lncRNAs), which have the potential to play a role in carcinogenesis by altering the levels of their expression. Squamous cell carcinoma of the esophagus (ESCC) is a deadly disease with a poor prognosis and a high frequency of lymphatic metastases. Understanding the functional role and signaling pathways of two neighboring lncRNAs, CCAT1 and PVT1, in this oncogene's pathogenesis may help us determine ESCC. Furthermore, it is still unclear whether these lncRNAs are linked to the clinicopathological characteristics of patients with ESCC. METHODS: For this study, we used biopsy from the Imam Khomeini Cancer Institute's tumor bank in Tehran, Iran to obtain 40 ESCC tumor samples and their normal margin counterparts. The expression levels of the CCAT1, PVT1, and c-MYC genes were assessed using quantitative Real-Time RT-PCR. Additionally, demographic data and clinical-pathologic characteristics, such as tumor grade, tumor stage, lymph node, and metastasis, were taken into consideration. Graphpad prism version 8 was used for bioinformatics analyses. RESULTS: Comparing ESCC tissues to non-tumor tissues, we found significant upregulation of PVT1, CCAT1, and c-MYC. Patients with ESCC who had increased PVT1 expression also had higher rates of advanced stage and lymph node metastasis, whereas increased CCAT1 expression was only linked to advanced stage and wasn't associated with lymph node metastasis. In predicting ESCC, CCAT1 (p < 0.05) was found to be an important factor. Overall survival was reduced by c-MYC and PVT1 overexpression (p < 0.001), according to Kaplan-Meier analysis. PVT1, CCAT1, and c-MYC were found to interact with 23 miRNAs with high and medium score classes, as shown in a bioinformatics study. We summarized the experimentally proven interactions between c-MYC, PVT1, and CCAT1 and other miRNAs, lncRNAs, and proteins. CONCLUSION: This is the first report that CCAT1, PVT1 and c-MYC have been found to be up-regulated simultaneously in ESCC. It is possible that these genes may be involved in ESCC as a result of these findings. Therefore, as consequence, more research is needed to determine whether or not these lncRNAs play an oncogenic role in ESCC development and progression, as well as the regulatory mechanisms that control them.

Association between Inflammatory Factors, Vitamin D, Long Non-Coding RNAs, MALAT1, and Adiponectin Antisense in Individuals with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a common clustering of cardiovascular risk factors associated with increased inflammation. Long non-coding RNA (LncRNA) are involved in many of the body's metabolic activities, including inflammation. Vitamin D may play a vital role in preventing metabolic syndrome risk factors. This study aimed to evaluate the status of inflammation and expression of LncRNA and their relationship with serum vitamin D levels in patients with metabolic syndrome. METHOD: This cross-sectional study included staff and Mashhad University of Medical Sciences students between 30 and 50 years old who met the International Diabetes Federation criteria for Mets. Total RNA was extracted from both frozen clinical samples using the Trizol reagent. RESULTS: A total of eighty people were recruited into the two groups, with and without MetS. Inflammatory markers were higher in the individuals in the MetS group, and linear regression showed an inverse association between serum vitamin D and LncRNAs. There was a positive association between inflammatory biomarkers, lipid profiles and Adiponectin Antisense (APQ AS) expression. CONCLUSION: APQ AS and MALAT1 levels are positively associated with inflammatory biomarkers and inverse relation between MALAT1 and serum 25 (OH) D concentration.

The Effects of Vitamin D Fortified Products on Bone Biomarkers: A Systematic Review and Meta-Analysis.

Background: Vitamin D plays an essential role in the regulation of bone metabolism. The current meta-analysis aimed to assess the effectiveness of vitamin D fortification on special bone biomarkers. Methods: Five main databases (PubMed/Medline, ISI Web of Knowledge, Science Direct, Scopus, Cochrane Library as well as Science Direct, and Scopus) were considered for this systematic review, until Jan 2020. All randomized controlled trials were included to evaluate the probable relationship between consumption of vitamin D fortification products and bone biomarkers profile in this review. Results: Among serum bone biomarkers (osteocalcin and telopeptides of type-1 collagen) investigated, only the level of telopeptides of type-1 collagen significantly decreased after fortification of vitamin D in the intervention group. A significant increase in vitamin D was seen in those older than 18 yr old, while the increase in younger children was not statistically significant between intervention and control groups. Conclusion: Vitamin D fortification was not associated with a significant improvement in bone mass density (BMD), while it resulted in decreased PTH levels. Vitamin D fortified foods have some benefits on bone health due to increase in the level of vitamin D and IGF-1; and decreasing PTH and CTx levels.

Long non-coding RNAs: a valuable biomarker for metabolic syndrome.

Long non-coding RNAs (lncRNAs) have become important regulators of gene expression because they affect a wide range of biological processes, such as cell growth, death, differentiation, and aging. More and more evidence suggests that lncRNAs play a role in maintaining metabolic homeostasis. When certain lncRNAs are out of balance, metabolic disorders like diabetes, obesity, and heart disease get worse. In this review, we talk about what we know about how lncRNAs control metabolism, with a focus on diseases caused by long-term inflammation and the characteristics of the metabolic syndrome. We looked at lncRNAs and their molecular targets in the pathogenesis of signaling pathways. We also talked about how lncRNAs are becoming more and more interesting as diagnostic and therapeutic targets for improving metabolic homeostasis.

Low expression of LncRNA-CAF attributed to the high expression of HIF1A in esophageal squamous cell carcinoma and gastric cancer patients.

PURPOSE: Cancer-associated fibroblasts (CAFs) are major components of tumor microenvironment that stimulate ESCC and GC progression. The LncRNA-CAF, FLJ22447, is located in the vicinity of HIF1A, while their association remains unclear. This study aims to assess the FLJ22447 expression in the ESCC and GC patients and evaluate its association with the HIF1A gene. METHODS: Fresh ESCC and GC tumor samples and their adjacent non-tumor tissues were collected from patients who underwent surgery in Imam Khomeini Hospital, Tehran, Iran. The expression of FLJ22447, HIF1A, and VEGF was evaluated using qRT-PCR test. The association of their expression with tumor clinicopathological features in ESCC patients was assessed. System biology tools were then applied for the possible biological subsequences of the FLJ22447. RESULTS: A significant reduction in FLJ22447 expression was observed in ESCC and GC tissues than adjacent non-tumor tissues, while, the expression of HIF1A and VEGF were increased. Low expression of FLJ22447 was significantly correlated with HIF1A (P = 2.4e-73, R = 0.63) and VEGF (P = 0.00019, R = 0.15) expression. A significant relationship was detected between the high expression of HIF1A and tumor stages (I-II) and it was related to the reduced survival of ESCC patients. Conversely, increased VEGF expression was linked to the advanced stages (III-IV) and metastasis in ESCC. The analysis of FLJ22447-interacted proteins showed that MYC, JUN, SMRCA4, PPARG, AR, FOS, and CEBPA are the hub genes. These proteins were implicated in the cancer related pathways. Among them, SPI1, E2F1, TCF7L2, and STAT1 were significantly expressed in esophageal and gastric cancers that were functionally involved in the proliferation, apoptosis, and angiogenesis pathways in cancer. CONCLUSION: The results suggested that FLJ22447 may have a regulatory function on the HIF1A expression. We identified the FLJ22447-interacted proteins and their molecular function in cancer pathogenesis. Further research emphasis is to realize the association of FLJ22447 with its protein partners in progression of cancer. These may provide an insight into the FLJ22447 activity that could introduce it as a potential value in tumor gene therapy.

Interaction between the genetic variant of rs696217-ghrelin and food intake and obesity and dyslipidemia.

In this study, we aimed to investigate the relationship between the genetic variant of rs696217-ghrelin and fasted lipid profile, indices of obesity, and environmental parameters. Amplification refractory mutation system-polymerase chain reaction (ARMs-PCR) was used for genotyping 1118 individuals recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. The interaction between the presence of the genetic variant of rs696217-ghrelin and nutritional intake and other major determinants of obesity and lipid profile was examined in the MASHAD study population. Individuals with the TT genotype at the locus had the lowest prevalence of obesity compared to other genotypes among the individuals. No significant relationship was found between the two groups regarding the lipid profile and TT genotype. Furthermore, no significant association was found between dietary intake and the genetic variant of rs696217-ghrelin in the population under study. Individuals with a TT or GT genotype appear to be at a higher risk of obesity, compared to those with a GG genotype. The results of the current study revealed a significant association between the genetic variant of rs696217-ghrelin and obesity; however, this gene did not correlate with the risk factors of cardiovascular diseases and dyslipidemia in the Iranian population.

The association between a Fatty Acid Binding Protein 1 (FABP1) gene polymorphism and serum lipid abnormalities in the MASHAD cohort study.

INTRODUCTION: Dyslipidemia is a known risk factor for cardiovascular disease and is partially determined by genetic variations in the genes involved in lipoprotein metabolism. Therefore, we aimed to assess the association between a polymorphism of the Fatty Acid Binding Protein1 (rs2241883) gene locus and dyslipidemia in an Iranian cohort. MATERIALS AND METHODS: This is a case-control study 2737 individuals were recruited (2203 subjects with dyslipidemia and 534 controls). Dyslipidemia was defined as total cholesterol≥200 mg/dl, or TG≥150 mg/dl, or LDL-C≥130 mg/dl, or HDL-C<40 mg/dl in males and <50 mg/dl in females. Serum lipid profile was determined using a Alcyon Abbott biochemical auto analyzer, USA. Genotyping was made through double amplification refractory mutation system polymerase chain reaction (ARMs PCR). RESULT: The frequency of TT, CT, CC genotypes of rs2241883 polymorphism of FABP1 gene were 65.5, 33.4, 5.1 in subjects with dyslipidemia and 56.9%, 40.4%, 2.6% in subjects without dyslipidemia, respectively. Using a dominant genetic model, subjects carrying C allele (CC&CT genotypes) had a 22% lower risk of dyslipidemia (OR: 0.78, CI 95%: 0.62-0.98 P, 0.03). Individuals with CT vs. TT genotypes had a significantly lower risk of a high serum TC and LDL level. Further analysis showed that there was a positive association between FABP1 genotype (CT) and isolated HTG as well as combined dyslipidemia. The change of a polar amino acid (threonine) in position T94A to a hydrophobic amino acid (alanine) can cause transformation protein. CONCLUSIONS: A CC genotype of the rs2241883 polymorphism of the FABP1 gene appears to confer a higher risk of dyslipidemia in our representative cohort of Iranian individuals.

Association between serum Vitamin E concentrations and the presence of Metabolic Syndrome: A population-based cohort study.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of clinical and metabolic features that include central obesity, dyslipidemia, hypertension and impaired glucose tolerance. These features are accompanied by increased oxidative stress and impaired antioxidant defenses. Vitamin E is a major factor in the non-enzymatic antioxidant defenses. The aim of present study was to investigate the association between serum levels of vitamin E and the presence of MetS and its components in a sample population of Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study. METHODS: This cross-sectional study was carried out in 128 subjects with MetS and 235 subjects without MetS. MetS was defined according to the International-Diabetes-Federation criteria. Serum levels of vitamin E were measured using the HPLC method. Anthropometric and biochemical parameters were measured using standard protocols.  Results. MetS patients had significantly lower serum levels of vitamin E (Vit E), Vit E/Total cholesterol (TC), and Vit E/ (TC+triglyceride(TG)) compared to the control group (P < 0.05).  Vit E/ (TG+TC) was also significantly lower in diabetics or those with elevated levels of high sensitive C-reactive protein (hs-CRP). Additionally, there was a significant association between Vit E/ (TG + Total Cho) and the number of components of the metabolic syndrome (p= 0.02) Conclusions. There is a significant inverse association between indices of Vit E status and the presence of MetS. Moreover, a significantly lower Vit E/ (TC+TG) was observed along with individuals with increasing numbers of components of the MetS.

Association between a genetic variant in scavenger receptor class B type 1 and its role on codon usage bias with increased risk of developing coronary artery disease.

OBJECTIVE: Coronary artery disease (CAD) as an important cause of morbidity and mortality globally. The scavenger receptor class B type 1 (SCARB1) plays an essential role in the reverse cholesterol transport. We have explored the association between a genetic variant, rs5888, in the SCARB1 gene with CAD and serum HDL-C levels. METHODS: Patients were categorized into two groups' angiogram positive (>50% coronary stenosis) and angiogram negative (<50% coronary stenosis). Genotyping was carried out using polymerase chain reaction-amplification refractory mutation system. The association between the SNP rs5888 and serum HDL-C was analyzed using a logistic regression model. RESULTS: The results showed that the subjects carrying a T allele was associated with a decreased serum HDL-C levels compared to the C allele in total population (p < 0.001). The risk of angiogram positivity in subjects carrying a T allele was 3.1-fold higher than for the control group (p < 0.001). CONCLUSION: CVD patients carrying the T allele of rs5888 variant in the SCARB1 gene was associated with decreased serum level of HDL.

Association of vitamin D status with liver and kidney disease: A systematic review of clinical trials, and cross-sectional and cohort studies.

Background: Vitamin D deficiency (VDD) is a major public health problem. There are few comprehensive systematic reviews about the relationship between Vitamin D status and liver and renal disease in Iran. Methods: We systemically searched the following databases: Web of Science; PubMed; Cochrane Library; Scopus; Science Direct; Google Scholar and two Iranian databases (Scientific Information Database (SID) and IranMedex) up until November 2017 to identify all randomized control trials (RCTs), case control, cross-sectional and cohort studies investigating the association between vitamin D and any form of liver or kidney disease. Results: Vitamin D insufficiency, or deficiency (VDD), is highly prevalent in Iran, reports varying between 44.4% in Isfahan to 98% in Gorgan. There is also a high prevalence of VDD among patients with liver or kidney disease, and the administration of vitamin D supplements may have beneficial effects on lipid profile, blood glucose, liver function and fatty liver disease, and bone health. Low serum vitamin D levels are related with abnormalities in these laboratory and clinical parameters. Conclusion: VDD is prevalent in patients with chronic liver or renal disease in Iran. There appear to be several beneficial effects of vitamin D supplementation in vitamin D deficient patients with liver or kidney disease.

The effect of vitamin D fortified products on anthropometric indices: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The reported effects of vitamin D on anthropometric indices have been inconsistent. This meta-analysis was conducted in order to assess the impact of vitamin D fortified food on weight, body mass index (BMI), fat mass, waist circumference (WC), hip circumference (HC) and waist to hip ratio (WHR). MATERIALS AND METHODS: PubMed/Medline, ISI Web of Knowledge, ScienceDirect, Scopus, Cochrane Library and Google Scholar were searched up to the end of 2019. We selected only randomized controlled trials in which vitamin D fortified food was used as the intervention, and a regular diet was used in the control group. RESULTS: Vitamin D fortified products appeared to have a significant effect on WC (MD: -1.283; 95% CI,-1.892 to -0.674) and WHR (MD: -0.020; 95%CI: -0.035 to -0.004). CONCLUSION: This meta-an-alysis showed that whilst a diet containing vitamin D fortified foods does not reduce body weight or BMI, it has beneficial effect on WHR and WC.

Association of a genetic variant in the AKT gene locus and cardiovascular risk factors.

Cardiovascular disease (CVDs) is the leading cause of morbidity and death worldwide. Most genetic variants could be identified by several genome-wide-association-studies (GWAS), including within genes encoding proteins involved in the AKT/PI3K pathways that are related with an increased risk of metabolic syndrome and CVDs. Therefore, due to the importance of genetic variants in the prognosis of diseases, we examined the genetic polymorphism of AKT-rs1130233 located on chromosome 14 with cardiovascular risk factors. In this cross-sectional study, 721 subjects recruited from the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort study. The participants including 257 subjects with metabolic syndrome, 144 subjects with cardiovascular disease and 320 subjects as a control group. Anthropometric, biochemical and demographic information measures were prepared. Dietary assessment was managed by 24h dietary recall. DNA extraction and genotyping were carried out by using the TaqMan real-time-PCR based method. The association of AKT rs1130233 locus with dietary intakes, metabolic syndrome and cardiovascular risk factors were assessed. Data were analyzed by using SPSS 21 software. Frequencies of genotypes AA, AG and GG of the AKT rs1130233 polymorphism were 12.6%, 44.5% and 42.9% in subjects with metabolic syndrome and 9.7%, 39.6% and 50.7% in subjects with cardiovascular disease, respectively. The frequency of allele A and G in cardiovascular disease and metabolic syndrome population were 29.5%, 70.5% and 34.8%, 65.2%, respectively. We have found no significant association between the AKT rs1130233 polymorphism with cardiovascular risk factors and metabolic syndrome. The results of dietary intake showed that the levels of phosphorus intake (p=0.008), calcium intake (p=0.007) and iodine intake (p=0.04) were different in subjects with and without metabolic syndrome. And also, energy intake was significantly different in subjects with cardiovascular disease (p=0.01) compared to the control group. Our findings suggest that AKT rs1130233 was not associated with the risk of metabolic syndrome and cardiovascular disease in the Iranian population. More studies are needed to validate our results. We did functional analysis, due to certify our investigation about value of this genetic biomarker for CVD risk.

A systematic review and meta-analysis of the effect of Vitamin D-fortified food on glycemic indices.

Some reports indicated that Vitamin D may improve glycaemia indices in diabetic patients. The aim of this systematic and meta-analysis was to evaluate effects of Vitamin D fortification on indices of glycemic control. Six databases (PubMed/Medline, ISI Web of Knowledge, Cochrane Library, Science Direct, Scopus, and Google Scholar) were searched, for randomized controlled trials that were published up to September 2018 and that compared the effect of Vitamin D-fortified food versus regular diet in relation to glycemic control. Of the 4,379 studies originally found, 11 articles remained to be assessed for meta-analysis. Vitamin D fortification was associated with a significant improvement in fasting serum glucose (mean difference [MD]: -2.772; 95% confidence interval [CI]: -5.435 to -0.109) and fasting serum insulin (MD: -2.937; 95% CI: -4.695 to -1.178) in patients with Type 2 diabetes mellitus. A diet with food enriched with Vitamin D was associated with a significant improvement in homeostatic model assessment of insulin resistance (MD: -1.608; 95% CI: -3.138 to -0.079) but was not associated with a significant reduction in hemoglobin A1C (MD: 0.034; 95% CI: -0.655 to 0.069). This meta-analysis indicates that Vitamin D fortification improves indices of glycemic control. Hence, food fortified with Vitamin D may be of potential therapeutic value in diabetic patients, as an adjuvant therapy.

Exosomes: New insights into cancer mechanisms.

Exosomes are mobile extracellular vesicles with a diameter 40 to 150 nm. They play a critical role in several processes such as the development of cancers, intercellular signaling, drug resistance mechanisms, and cell-to-cell communication by fusion onto the cell membrane of recipient cells. These vesicles contain endogenous proteins and both noncoding and coding RNAs (microRNA and messenger RNAs) that can be delivered to various types of cells. Furthermore, exosomes exist in body fluids such as plasma, cerebrospinal fluid, and urine. Therefore, they could be used as a novel carrier to deliver therapeutic nucleic-acid drugs for cancer therapy. It was recently documented that, hypoxia promotes exosomes secretion in different tumor types leading to the activation of vascular cells and angiogenesis. Cancer cell-derived exosomes (CCEs) have been used as prognostic and diagnostic markers in many types of cancers because exosomes are stable at 4°C and -70°C. CCEs have many functional roles in tumorigenesis, metastasis, and invasion. Consequently, this review presents the data about the therapeutic application of exosomes and the role of CCEs in cancer invasion, drug resistance, and metastasis.

Scavenger receptor Class B type I as a potential risk stratification biomarker and therapeutic target in cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of mortality globally. There are few useful markers available for CVD risk stratification that has proven clinical utility. Scavenger receptor B type I (SR-BI) is a cell surface protein that plays a major role in cholesterol homeostasis through its interaction with high-density lipoprotein-cholesterol (HDL-C) esters (CE). HDL delivers CE to the liver through selective uptake by the SR-BI. SR-BI also regulates the inflammatory response. It has been shown that SR-BI overexpression has beneficial, protective effects in atherogenesis, and there is considerable interest in developing antiatherogenic strategies that involve SR-BI-mediated increases in reverse cholesterol transport through HDL and/or low-density lipoprotein. Further investigations are essential to explore the clinical utility of this approach. Moreover, there is growing evidence showing associations between genetic variants with modulation of SR-BI function that may, thereby, increase CVD risk. The aim of the current review was to provide an overview of the possible molecular mechanisms by which SR-BI may affect CVD risk, and the clinical implications of this, with particular emphasis on preclinical studies on genetic changes of SR-BI and CVD risk.

The effects of vitamin D supplementation on indices of glycemic control in Iranian diabetics: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: This systematic review and meta-analysis aimed to assess the effects of vitamin D supplements on indices of glycemic control [homeostatic model assessment-insulin resistance (HOMA-IR), hemoglobin A1C (HbA1C), fasting blood glucose (FBG), and quantitative insulin-sensitivity check index (QUICKI) and lipid profile in diabetic patients. METHODS: Eight databases were searched, for randomized controlled trials (RCTs) or cross-sectional and cohort studies that have been published up to December 2017. We used the comprehensive meta-analysis (CMA) software for all statistical analysis and used the I2 index for assessing heterogeneity. A p value of <0.05 was considered as statistically significant. RESULTS: We found 621 articles, and after the exclusion of ineligible publications, 82 studies remained to be assessed of which 37 were used for meta-analysis. Vitamin D supplementation was associated with a significant improvement in FBG (p = 0.001 and 95% CI: -0.526 to -0.136) and HbA1C (p = 0.003 and 95% CI: 1.719 to -0.361) in individuals with type 2 diabetes mellitus (T2DM); while in women with gestational diabetes mellitus (GDM) the reduction in FBG (p = 0.071 and 95% CI: -0.873 to -0.035) and HbA1C (p = 0.199 and 95% CI: 3.270 to 0.681) failed to reach statistical significance. Treatment with vitamin D supplements was associated with an improvement in HOMA-IR in pregnant diabetic women (p = 0.028 and 95% CI: 0.924 to -0.053) and for individuals with diabetes mellitus (p = 0.005 and 95% CI: 1.772 to -0.319). The pooled result of the cross-sectional meta-analysis indicated that serum vitamin D concentrations were significantly lower in diabetic patients than in healthy controls (p = 0.018 and 95% CI: 0.587 to -0.054). CONCLUSION: This meta-analysis suggests that vitamin D supplementation improves indices of glycemic control (FBG, HOMA-IR, and HbA1C) in patients with diabetes mellitus. Hence, vitamin D supplements may be of potential therapeutic value in diabetic patients, as an adjuvant therapy along with other treatments.

WDR7 up-regulation upon knocking down of neighboring non-coding RNA using siRNAs encapsulated in polyamidoamine dendrimers.

OBJECTIVES: Breast cancer is the second leading cause of cancer death in females. Understanding molecular mechanisms in cancer cells compared with normal cells is crucial for diagnostic and therapeutic strategies. Long intergenic non-protein coding RNA, a regulator of reprogramming (lincRNA-RoR) is a noncoding RNA which initially was detected in induced pluripotent stem cells, and it has an important role in cell reprogramming and highly expressed in breast cancer cells. A key point in successful gene silencing is the usage of siRNA delivery system that is safe and efficient. MATERIALS AND METHODS: In this study, the fifth-generation of PAMAM dendrimer is used as a nanocarrier for entering siRNA molecules for gene silencing of lincRNA-RoR. WDR7 is the gene encoding adjacent of lincRNA-RoR, which has an important role in apoptosis and cell cycle. Gel retardation assay was used to find the best Negative/Positive (N/P) molar charge ratio of siRNA- PAMAM transfected into MDA-MB 231 cells. MTT assay was performed 24 hr after transfection revealed the IC50 value (half maximal inhibitory concentrations) about 100 nanomolar for lincRNA-ROR siRNA. RESULTS: The lincRNA-RoR and WDR7 gene expression changes were evaluated by real-time PCR after siRNA treatment and showed an increase in the gene expression of WDR7. CONCLUSION: This study showed that PAMAM dendrimer G5/ siRNA could be a useful system delivery for future gene therapy approaches.