Publications by authors named "Maryam Zarkesh"

46 Publications

Application of Bacterial Nanocellulose in the Cancer Drug Delivery: A Review.

Curr Pharm Des 2021 Apr 12. Epub 2021 Apr 12.

Cellular and Molecular Endocrine Research Center, Research Institute of Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran. Iran.

Bacterial nanocellulose (BNC) is one of the natural biopolymers with unique features, the most important of which are nontoxicity, biocompatibility, high tensile profile, nanofiber structure, and purity. The current review aimed to summarize the latest development in BNC-based biomaterials in cancer drug delivery. The original articles were found by searching key databases including PubMed, Scopus, and Web of Scientific and using key terms such as "bacterial nanocellulose OR bacterial cellulose OR BNC" AND "cancer OR carcinoma OR tumor". The obtained data were in a wide timeframe and the English language. Totally, 350 articles were found from the three main databases (i.e., 106, 251, and 173 articles from PubMed, Scopus, and the Web of Science, respectively). In general, 32 articles met the inclusion criteria after duplicate removal and screening according to the aim of the present review study. In this review study, different applications of the bacterial nanocellulose were considered for cancer drug delivery in addition to describing advanced methods that may be applied to improve therapeutic potency while reducing the adverse effects of chemodrugs by decreasing their dosages. The high ratio of the surface area-to-volume and easy modifications of their chemical components lead BNC potential use as an appropriate matrix structure for the binding and controlled release of various pharmaceutical agents, specifically for topical or transdermal administrations. In addition, BNC-based products regulate the release of hydrophobic and hydrophilic compounds, therefore, provide appropriate materials related to cancer drug delivery. However, undoubtedly, further developments of BNC-based products as cancer drug delivery systems require more extensive investigations.
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http://dx.doi.org/10.2174/1381612827666210412150445DOI Listing
April 2021

Chromosomal regions strongly associated with waist circumference and body mass index in metabolic syndrome in a family-based study.

Sci Rep 2021 Mar 16;11(1):6082. Epub 2021 Mar 16.

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box, 19195-4763, Tehran, Iran.

Obesity is the most crucial phenotype in metabolic syndrome (MetS), and waist circumference (WC) and body mass index (BMI) are two common indexes to define obesity. It is an accepted fact that genetic and environmental interaction influence obesity and MetS. Microsatellites are a subcategory of tandem repeats with a length of 1 to 10 nucleotides. Tandem repeats make up repetitive genomic regions. Differences in the number of tandem repeats or their variation (alleles) result in microsatellite polymorphisms. Thus, we attempted to find microsatellite variation associated with WC and BMI in a family-based study. Twelve microsatellite markers were selected to investigate possible genes or chromosomal regions in 91 families with at least one affected MetS. The cut-off values for BMI and WC were considered 25 kg/m and 90 cm, respectively. In all members of the families, the strongest association was observed between the marker D11S1304 (allele 1) with both WC and BMI, independently, by the biallelic model in the family-based association test analysis (P < 0.05). Besides, when we compared high- and low-level groups in members with MetS, the markers D8S1743 and D11S1304 (allele 1) showed a strong association with WC (P = 0.0080) and BMI (P = 0.0074), respectively. When the simultaneous detection of the high WC and MetS status was used as a trait, the strongest association was observed with the marker D8S1743 (P = 0.0034). Moreover, when BMI with the high MetS status was used as a trait, the strongest association was observed with the marker D8S1743 (allele 4) (P = 0.0034). The obtained results showed a relationship between obesity and MetS with markers on the selected regions on chromosomes 8 and 11, and to a lesser degree, on chromosome 12.
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http://dx.doi.org/10.1038/s41598-021-85741-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966400PMC
March 2021

Does Dietary Intake Impact Omentin Gene Expression and Plasma Concentration? A Systematic Review.

Lifestyle Genom 2021 24;14(2):49-61. Epub 2021 Feb 24.

Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Omentin is an adipokine with anti-inflammatory and insulin-sensitizing effects that can play a protective role against cardiovascular disease and diabetes. The aim was to systematically review and summarize the existing evidence on the association between overall dietary intake and omentin gene expression and circulation.

Summary: A literature search was conducted in PubMed, Scopus, and Web of Science up to September 2019. Of the 1,940 retrieved articles, 20 relevant studies were included, 6 of which were observational, 11 were clinical trials in humans, and 3 were animal studies. Four randomized controlled trials (RCTs) had a high risk of bias (RoB), 1 had "some concerns", and 2 had a low RoB. Among the nonrandomized studies with comparators, 4 had a serious RoB and 2 had a moderate RoB. In the experimental animal studies with a moderate RoB, conflicting results for omentin serum concentration were found for high-fat and low-fat diets. A high-fat diet (HFD) was shown to reduce omentin gene expression in one animal study. In the observational studies, omentin serum concentration was reduced by Ramadan fasting and saturated fatty acid (SFA) intake, and an increase in omentin gene expression was observed with monounsaturated fatty acid (MUFA) intake. There was no association of dietary inflammatory index (DII), macronutrient intake, or total calorie intake with omentin plasma concentrations. In the human interventional studies, omentin plasma concentration increased with a long-term low-calorie, low-fat diet (LFD), and no change was seen with a HFD or a short-term low-calorie diet (LCD). Key Messages: It seems that a long-term diet with a lower fat content and a balanced distribution of fatty acids, i.e., a higher MUFA and lower SFA intake, may effectively increase omentin plasma concentration, possibly via improved insulin resistance and reduced inflammation, but more research is needed to confirm or refute this.
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http://dx.doi.org/10.1159/000513885DOI Listing
February 2021

Association of plasma fatty acids pattern with omentin gene expression in human adipose tissues: A cross-sectional study.

Nutr Metab Cardiovasc Dis 2021 03 27;31(3):894-901. Epub 2020 Nov 27.

Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background And Aims: Omentin, as an adipokine, has been reported to improve insulin resistance and inflammation may be related to fatty acids (FAs). Plasma FAs can be used as biomarkers of dietary FAs and endogenous FA exposure. We aimed to evaluate the association between plasma FAs pattern and omentin gene expression in adipose tissue (AT).

Methods And Results: Visceral and subcutaneous AT and fasting blood were gathered from 97 adults aged >18 years. Participants were already admitted to hospitals for elective abdominal surgery. Dietary intakes were assessed using a food frequency questionnaire. The relative omentin gene expression in visceral and subcutaneous AT was measured by Real-Time PCR and plasma FAs was determined by gas chromatography. The principal component analysis was performed to derive the FAs pattern from plasma individual FAs. Three patterns were derived from plasma FAs, 1) high de-novo lipogenesis (DNL), 2) high trans saturated fatty acids (SFA), and docosahexaenoic acid (trans-SFA/DHA), and 3) high long-chain SFA (LC-SFA). After adjustment for age, sex, and insulin concentration, only the LC-SFA pattern was associated with omentin gene expression in visceral AT (β = 2.25, P = 0.03). Other patterns were not associated with omentin gene expression in visceral and subcutaneous AT.

Conclusion: A pattern characterized by high levels of myristic acid (14:0), heptadecanoic acid (17:0), pentadecanoic acid (15:0), and Cis_heptadecanoic acid (17:1), which named LC-SFA was related to omentin gene expression in visceral AT.
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http://dx.doi.org/10.1016/j.numecd.2020.11.019DOI Listing
March 2021

Antineoplastic Activity of an Old Natural Antidiabetic Biguanoid on the Human Thyroid Carcinoma Cell Line.

Anticancer Agents Med Chem 2021 Jan 17. Epub 2021 Jan 17.

Cellular and Molecular Endocrine Research Center, Research Institute of Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran. Iran.

Background: In the last decades, metformin (Met), an herbal anti-diabetic medicine, has been proposed as an anti-cancer agent.

Objective: Thyroid cancers are the most common malignancy of the endocrine system. Therefore, the current study was performed to assess the effects of Met on cell proliferation and activation of the Phosphoinositide 3-Kinase (PI3K)/Protein kinase B (AKT)/Forkhead Box O1 (FOXO1) signaling pathway in the Medullary Thyroid Carcinoma (MTC) cells. The effects of Met on the expression of REarranged during Transfection (RET) proto-oncogene were also investigated.

Methods: MTC cell line (TT) was treated with 0, 2.5, 5, 10, 20, 30, 40, 50, and 60 mM concentrations of Met for 24, 48, and 72h. The viability and apoptosis of the treated cells were measured by the 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) and Annexin V- Propidium Iodide (PI) assays. The expression level of PI3K, AKT, FOXO1, and RET genes was investigated by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), and phosphorylation of their proteins was determined by the Enzyme-Linked Immunosorbent Assay (ELISA).

Results: Results showed that Met significantly decreased the viability of the MTC cells. Met also reduced the expression level of PI3K, AKT, and FOXO1 genes (P<0.05), whereas it elevated the expression level of RET proto-oncogene (P<0.05).

Conclusion: It seems that the Met has cytostatic effect on the TT cells. Our results showed that anti-tumoral effects of Met may be cell type-specific, and according to the induction of RET (as a proto-oncogene) and inhibition of FOXO1 (as a tumor suppressor gene), Met could not be an appropriate agent in treatment of MTC. The antineoplastic activity of Met has been confirmed against several malignancies in 'in vitro' and 'in vivo' studies. However, its molecular mechanisms in the treatment of different carcinomas particularly in thyroid cancers are not clearly understood and more studies are required to confirm its exact effect on the MTC.
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http://dx.doi.org/10.2174/1871520621666210118093532DOI Listing
January 2021

Dietary fat content and adipose triglyceride lipase and hormone-sensitive lipase gene expressions in adults' subcutaneous and visceral fat tissues.

Prostaglandins Leukot Essent Fatty Acids 2021 Feb 8;165:102244. Epub 2021 Jan 8.

Obesity Treatment Center, Department of Surgery, Shahed University, Tehran, Iran.

Introduction: We examined the association of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) gene expressions, as the key regulators of lipolysis, with dietary fat quantity and composition in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT).

Methods: In this observational study, samples were collected from patients undergoing elective abdominal surgery. Participants were categorized into two groups based on their body mass index (BMI) status. Dietary, anthropometric, and biochemical data were collected before surgery. Linear regression was performed to determine the association of dietary fat content with ATGL and HSL gene expressions in SAT and VAT.

Results: 152 individuals with a mean ± SD age of 40.7 ± 13.2 years and a median (inter-quartile range) BMI of 39.4 (26.5-45.3 kg/m) participated in this study, of whom 54 were non-obese (BMI<30 kg/m), and 98 were obese (BMI≥30 kg/m). Among non-obese participants, positive associations were observed between ATGL mRNA expression and reported intakes of total fatty acids (TFA) (β=0.306, P = 0.025), myristic (β=0.285, P = 0.038), palmitic (β=0.417, P = 0.002), oleic (β=0.333, P = 0.017), dairy trans (β=0.374, P = 0.006), and other trans FAs (β=0.369, P = 0.006) in SAT. In contrast, inverse associations between HSL mRNA expression and reported intakes of TFAs (β=-0.377, P = 0.005), myristic (β=-0.282, P = 0.039), palmitic (β=-0.372, P = 0.006), stearic (β=-0.314, P = 0.020), and oleic acid (β=-0.372, P = 0.007) were observed in SAT. No associations were observed among obese participants, nor in VAT among non-obese individuals.

Conclusion: ATGL and HSL mRNA expressions in SAT were associated with dietary fat quantity and composition among non-obese adults.
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http://dx.doi.org/10.1016/j.plefa.2021.102244DOI Listing
February 2021

The association of dietary and plasma fatty acid composition with FTO gene expression in human visceral and subcutaneous adipose tissues.

Eur J Nutr 2020 Nov 6. Epub 2020 Nov 6.

Department of Surgery, Tehran Obesity Treatment Center, Shahed University, Tehran, Iran.

Purpose: The human obesity susceptibility gene, FTO, associates with body mass and obesity in humans through regulation of energy expenditure and intake. We aimed to determine how fatty acids in plasma and in diet associate with FTO gene expression in subcutaneous and visceral adipose tissues.

Methods: In this study, 97 participants aged ≥ 18 years were selected from patients admitted to the hospital for abdominal surgeries. Habitual dietary intake of participants was collected using a valid and reliable food frequency questionnaire (FFQ), from which the intake of fatty acids was quantified. Plasma fatty acids were assessed by gas-liquid chromatography. The mRNA expression of the FTO gene in visceral and subcutaneous adipose tissues obtained by biopsy was measured by Real-Time Quantitative Reverse Transcription PCR. Standardized β-coefficients were calculated by multivariable linear regression.

Results: After adjusting for age, homeostasis model insulin resistance index (HOMA-IR), and body mass index, total fatty acid intake was significantly associated with FTO gene expression in visceral (STZβ = 0.208, P = 0.037) and subcutaneous (STZβ = 0.236, P = 0.020) adipose tissues. Dietary intake of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) had positive significant associations with the expression of FTO in visceral (STZβ = 0.227, P = 0.023; STZβ = 0.346, P < 0.001, respectively) and subcutaneous (STZβ = 0.227, P = 0.026; STZβ = 0.274, P = 0.006, respectively) adipose tissues. There were no associations between plasma fatty acids and FTO mRNA expression in either subcutaneous or visceral adipose tissues.

Conclusion: The weak association of dietary total fatty acids, MUFA, and PUFA with FTO gene expression in both adipose tissues may highlight the importance of dietary fatty acids composition along with total fat intake in relation to FTO gene expression.
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http://dx.doi.org/10.1007/s00394-020-02422-xDOI Listing
November 2020

Behavioral Interventions for Weight Management in Overweight and Obese Adolescents: A Comparison Between a Motivation-based Educational Program and Conventional Dietary Counseling.

Int J Endocrinol Metab 2020 Jan 1;18(1):e88192. Epub 2020 Feb 1.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objectives: This study aimed to compare the effects of a three-month motivation-based educational program and conventional dietary counseling on body composition and relevant outcomes among overweight and Obese adolescents.

Methods: A total of 115 overweight and obese adolescents (46% boys) were randomly assigned to either a motivation-based program or a conventional dietary counseling. The assessments were conducted at baseline and 3, 6, and 12 months after intervention.

Results: Mean age and body mass index (BMI) Z-score were 14.5 ± 1.2 and 2.42 ± 0.62, respectively. Considering time trend analysis, the two groups achieved significant improvements in BMI Z-score, wrist and waist circumferences, body composition indices, and HRQoL total scores after a one-year follow-up. Wrist circumference and the HRQoL reported by parents revealed significant differences between the study groups in favor of the motivation-based program.

Conclusions: Although both programs could improve anthropometric indices and HRQoL over time, the motivation-based program was more effective in reducing adolescents' wrist circumference and improving HRQoL, as the parents reported.
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http://dx.doi.org/10.5812/ijem.88192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144245PMC
January 2020

Association of dietary intake of fruit and green vegetables with PTEN and P53 mRNA gene expression in visceral and subcutaneous adipose tissues of obese and non-obese adults.

Gene 2020 Apr 21;733:144353. Epub 2020 Jan 21.

Tehran Obesity Treatment Center, Department of Surgery, Shahed University, Tehran, Iran. Electronic address:

Objective: The present study investigates the association of dietary intake of fruit and green Vegetables with PTEN and P53 mRNA gene expression in visceral (VAT) and subcutaneous adipose tissues (SAT) of obese and non-obese adults.

Methods: VAT and SAT were obtained from 151 individuals, aged ~40 years, who had undergone elective abdominal surgery. The participants were grouped according to their body mass index (BMI), as obese (BMI > 30 kg/m) and non-obese (BMI = 18.5-30 kg/m). Dietary intakes were obtained using a valid and reliable food-frequency questionnaire (FFQ). Real-time PCR was carried out for PTEN and P53 mRNA expressions. Associations between expression levels and dietary parameters were analyzed.

Results: P53 mRNA expression of obese participants was significantly higher than the non-obese, only in VAT (p < 0.001). After adjusting for total energy intake, age and BMI, fruit intake was inversely associated with P53 gene expression in both VAT (β = -0.38, P = 0.01) and SAT (β = -0.35, P = 0.03) among non-obese participants. Furthermore, fruit consumption was inversely associated with P53 gene expression in obese individuals, only in VAT (β = -0.21, P = 0.05). More so, intake of green vegetables in obese subjects was negatively associated with P53 gene expression in VAT (β = -0.27, P = 0.01) and SAT (β = -0.28, P < 0.001). On the other hand, after adjustment for total energy intake, age and BMI, a positive association was observed between fruit intake and PTEN in VAT (β = 0.27, P = 0.01) and SAT (β = 0.34, P < 0.001) among obese participants. In addition, dietary consumption of fruits in non-obese individuals was negatively associated withPTEN expression in SAT (β = -0.48, P < 0.001).

Conclusion: Dietary intake of fruit and green vegetables was associated with P53 gene expression in VAT and SAT of obese participants, suggesting their protective role in regulating P53 mRNA expression in adipose tissue. Furthermore, higher fruit intake was inversely associated with PTEN mRNA levels in non-obese participants, implying the anti-adipogenic role of PTEN gene expression.
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http://dx.doi.org/10.1016/j.gene.2020.144353DOI Listing
April 2020

Validation of Reference Genes for Normalization of Relative qRT-PCR Studies in Papillary Thyroid Carcinoma.

Sci Rep 2019 10 23;9(1):15241. Epub 2019 Oct 23.

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) in thyroid tumors require accurate data normalization, however, there are no sufficient studies addressing the suitable reference genes for gene expression analysis in malignant and normal thyroid tissue specimens. The purpose of this study was to identify valid internal control genes for normalization of relative qRT-PCR studies in human papillary thyroid carcinoma tissue samples. The expression characteristics of 12 candidate reference genes (GAPDH, ACTB, HPRT1, TBP, B2M, PPIA, 18SrRNA, HMBS, GUSB, PGK1, RPLP0, and PGM1) were assessed by qRT-PCR in 45 thyroid tissue samples (15 papillary thyroid carcinoma, 15 paired normal tissues and 15 multinodular goiters). These twelve candidate reference genes were selected by a systematic literature search. GeNorm, NormFinder, and BestKeeper statistical algorithms were applied to determine the most stable reference genes. The three algorithms were in agreement in identifying GUSB and HPRT1 as the most stably expressed genes in all thyroid tumors investigated. According to the NormFinder software, the pair of genes including 'GUSB and HPRT1' or 'GUSB and HMBS' or 'GUSB and PGM1' were the best combinations for selection of pair reference genes. The optimal number of genes required for reliable normalization of qPCR data in thyroid tissues would be three according to calculations made by GeNorm algorithm. These results suggest that GUSB and HPRT1 are promising reference genes for normalization of relative qRT-PCR studies in papillary thyroid carcinoma.
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http://dx.doi.org/10.1038/s41598-019-49247-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811563PMC
October 2019

Dietary glycemic index and dietary glycemic load is associated with apelin gene expression in visceral and subcutaneous adipose tissues of adults.

Nutr Metab (Lond) 2019 18;16:68. Epub 2019 Sep 18.

4Tehran Obesity Treatment Center, Department of Surgery, Shahed University, Tehran, Iran.

Background: Apelin, as an adipokine, plays an important role in the pathogenesis of insulin resistance and type 2 diabetes. This study aimed to determine whether the quality and quantity of dietary carbohydrates were associated with apelin gene expression in subcutaneous and visceral adipose tissues.

Methods: In this cross-sectional study, 102 adults who underwent minor abdominal surgery were selected. Approximately 100 mg of subcutaneous and visceral adipose tissues were collected during the surgery to measure apelin gene expression. Anthropometric measurment, blood samples, and dietary intakes were collected before surgery. The dietary carbohydrate intake, glycemic index (GI), and glycemic load (GL) were determined.

Results: The average apelin concentration was 269.6 ± 98.5(pg/mL), and 16.3% of participants were insulin resistant. There was a correlation between insulin (-value = 0.043), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)(-value = 0.045) and apelin gene expression in visceral adipose tissue. There was a positive association of apelin gene expression with dietary GI and GL after adjustment for age, sex, and waist circumference in visceral and subcutaneous adipose tissues( < 0.05). Apelin gene expression in visceral( = 0.002) and subcutaneous( = 0.003) adipose tissues was directly associated with foods with a higher GI. There was no association between total carbohydrate intake and apelin gene expression in both visceral and subcutaneous adipose tissues.

Conclusions: Dietary GI and GL, not total carbohydrate intake, were positively associated with apelin gene expression in both visceral and subcutaneous adipose tissues. Future studies are warranted to illustrate the chronic and acute effect of carbohydrate quality on apelin homeostasis.
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http://dx.doi.org/10.1186/s12986-019-0389-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751847PMC
September 2019

The association of dietary carbohydrate with FTO gene expression in visceral and subcutaneous adipose tissue of adults without diabetes.

Nutrition 2019 Jul - Aug;63-64:92-97. Epub 2019 Jan 2.

Tehran Obesity Treatment Center, Department of Surgery, Shahed University, Tehran, Iran.

Objectives: The aim of the present study was to investigate the association of dietary carbohydrates with fat mass and obesity-associated gene (FTO) expression in visceral and subcutaneous adipose tissue.

Methods: In this cross-sectional study, visceral and subcutaneous adipose tissues were gathered from 58 obese (body mass index ≥30 kg/m) and 44 non-obese (body mass index ≤18 to<30 kg/m) participants, aged ≥20 y, who had undergone elective abdominal surgery with minimal effect on dietary intake. Dietary intake was collected using a valid and reliable food frequency questionnaire, and daily intake of total carbohydrates, total sugar, sucrose, glucose, fructose, lactose, and maltose were calculated. The mRNA expression of the FTO gene in visceral and subcutaneous adipose tissues was measured by real-time quantitative polymerase chain reaction.

Results: No significant difference was observed for FTO gene expression in subcutaneous and visceral fat mass between non-obese and obese participants. After adjusting for age and sex, total carbohydrate intake was inversely associated with FTO gene expression in subcutaneous (β = -0.403; P = 0.003) adipose tissues among obese participants. Furthermore, higher intake of total sugars, sucrose, glucose, and lactose was inversely and higher intake fructose was directly associated with FTO mRNA expression in subcutaneous adipose tissue among participants with obesity.

Conclusion: Dietary intake of total sugars, sucrose, glucose, and lactose in obese participants only was inversely and dietary fructose was positively associated with FTO gene expression from the subcutaneous adipose tissue.
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http://dx.doi.org/10.1016/j.nut.2018.12.014DOI Listing
September 2020

BRAF V600E mutation and microRNAs are helpful in distinguishing papillary thyroid malignant lesions: Tissues and fine needle aspiration cytology cases.

Life Sci 2019 Apr 16;223:166-173. Epub 2019 Mar 16.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran. Electronic address:

Aims: Mutations of BRAF oncogene are considered to contribute in the invasiveness and poor clinicopathologic features of papillary thyroid cancer (PTC). As a step towards understanding the underlying molecular mechanisms of this contribution, we aimed to examine the association of four microRNAs' (miR-222, -137, -214, -181b) levels with BRAFV600E and clinicopathological features in PTC tissues and fine needle aspiration (FNA) specimens.

Methods: In total, 56 PTC and 27 benign with multinodular goiter tissue samples, 95 FNA samples, and B-CPAP and HEK293 cell lines were examined. BRAFV600E mutation was examined in PTC tissues and FNA samples. Expression of microRNAs was assessed by real-time quantitative reverse transcription-PCR.

Key Findings: The frequency of BRAFV600E in PTC tissues and FNA samples "suspicious for PTC" was 41.1 and 36.8%, respectively. MiR-222, -137, -214, and -181b were significantly upregulated in PTC tumors (P < 0.05) and in B-CPAP cell line (P < 0.001). In FNA, the expressions of miR-222, -181b and -214 were significantly elevated in patients suspected for PTC (P < 0.05), while there was no significant difference in miR-137. After adjustment for age and sex, miR-181b was associated with an increased risk of bearing BRAFV600E mutation (OR: 1.27; 95% CI: 1.01-1.61; P = 0.045) and risk of lymphovascular invasion (OR: 1.66; 95% CI: 1.01-2.72; P = 0.045); miR-137 was associated with the risk of larger tumor size (OR: 1.31; 95% CI: 1.04-1.65; P = 0.022); miR-222 was related to increase in extracapsular invasion (OR: 1.28; 95% CI: 1.04-1.57; P = 0.018).

Significance: Upregulation of miR-222, -214 and -181b has been confirmed in PTC tumors, FNA samples and cell line. MiR-137 upregulation has been confirmed in PTC tumors and cell line, but not in FNA samples. MiR-222, -137 and -181b showed an association with the degree of malignancy in PTC tumors.
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http://dx.doi.org/10.1016/j.lfs.2019.03.034DOI Listing
April 2019

Biochemical Assessment: Findings from 20 Years of the Tehran Lipid and Glucose Study.

Int J Endocrinol Metab 2018 Oct 16;16(4 Suppl):e84783. Epub 2018 Oct 16.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Context: The Tehran Lipid and Glucose Study (TLGS) is a community-based study to reveal the frequency of non-communicable diseases (NCDs) in Tehran's population. This research consists of two main parts, a cross-sectional study on the prevalence of cardiovascular risk factors and a 20-year-ongoing prospective cohort study, which was initiated in 1999 in several phases with an approximate duration of 3.6 years, and is still ongoing. The aim of the present study is review the 20 year biochemical findings of the TLGS related to the NCDs in a large sample.

Methods: All articles on biochemical assessments derived from the TLGS from the earliest publications (2002) until 30 January 2018 were reviewed for their findings on different risk factors of NCDs.

Results: According to the TLGS findings high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), homocysteine (Hcy), age, smoking, hypertension, and obesity were the most important risk factors of cardiovascular diseases (CVD). It was illustrated that in subjects with abdominal obesity, the hs-CRP and IL-6 serum levels were higher than in normal subjects. The most appropriate prognostic indexes and associations were for hs-CRP, IL-6, and Hcy with abdominal obesity, waist circumference, WHtR, and wrist circumference, respectively. Previous studies have demonstrated a direct relationship between obesity and serum levels of inflammatory factors.

Conclusions: According to the results of TLGS, serum levels of biochemical risk factors such as hs-CRP, IL-6, and Hcy could be beneficial in early diagnosis and effective treatment of cardiovascular, obesity and other metabolic diseases.
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http://dx.doi.org/10.5812/ijem.84783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289303PMC
October 2018

Genetic Identification for Non-Communicable Disease: Findings from 20 Years of the Tehran Lipid and Glucose Study.

Int J Endocrinol Metab 2018 Oct 27;16(4 Suppl):e84744. Epub 2018 Oct 27.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Context: Tehran Lipid and Glucose Study (TLGS), a longitudinal family based cohort study, is the oldest and largest longitudinal family based study in Iran, aimed at investigating effects of environmental, social and biological factors on the health of Tehranians over time. Considering the importance of genetic studies in this aspect, here we present a summary of the important genetic findings, and the potentiality of their contributions to future related projects.

Evidence Acquisition: For all related studies during the past 20 years the search sources were all prominent search engines such as PubMed, Scopus, and Google Scholar with the most proper Medical Subject Headings (MeSH).

Results: This review summarizes associations of 6 binary phenotypes and 17 quantitative traits with genetic markers in 26 genes. Of the 47 genetic markers, studied most were related to cardio metabolic risk factors. Results of heritability and linkage analysis were also collected and the highest heritability was found to be related to HDL-C (0.5).

Conclusion: Considering the opportunity provided by large-scale cohort studies to investigate molecular effects of genetic variants on causality and different omics' data, genetic studies conducted on TLGS population have had a remarkable success in identifying genetic variants that facilitating a unique genetic database on Iranian populations. The results of genome wide association studies in this population are currently facilitating investigations to define the Iranian genetic differences with other population.
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http://dx.doi.org/10.5812/ijem.84744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289296PMC
October 2018

The role of matrix metalloproteinase-9 as a prognostic biomarker in papillary thyroid cancer.

BMC Cancer 2018 Dec 3;18(1):1199. Epub 2018 Dec 3.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran.

Background: The aim of the present study was to investigate the association between matrix metalloproteinase-9 (MMP-9) expression with BRAF V600E mutation and clinicopathological features, in Iranian papillary thyroid cancer (PTC) patients.

Methods: In total, 90 participants including 60 PTC patients (15 males and 45 females) and 30 individuals with benign multinodular goiter (MNG) (5 males and 25 females) which were confirmed by surgical pathology, were investigated. MMP-9 was evaluated at both mRNA and protein levels, using SYBR-Green Real-Time PCR and enzyme-linked immune sorbent assay (ELISA), respectively. BRAF V600E mutation was detected by sequencing.

Results: Mean age of PTC and MNG patients was 37.6 ± 12.6 and 48.1 ± 13.3 years, respectively (P = 0.001). BRAF V600E mutation was found in 24 of the 60 (40%) PTC cases, with mean tumor size of 1.59 ± 1.20 cm. MMP-9 mRNA levels were elevated in tumoral compared to the adjacent non-tumoral tissues (P = 0.039); moreover, this rise was also observed in PTC patients compared to MNG patients (P = 0.001). The mRNA levels of MMP-9 increased in patients aged≥45 years (P = 0.015), those with lymphovascular invasion (P = 0.003), and higher tumor stages (III and IV) (P = 0.011). The protein level of MMP-9 increased in tumoral compared to adjacent non-tumoral tissues (P < 0.001); this increase was also found in PTC patients compared to MNG participants (P = 0.004). MMP-9 protein level was higher in patients aged≥45 years (P = 0.001), those with lymphovascular invasion (P = 0.036) and higher TNM stages (III and IV) (P = 0.001). Area under the ROC curve (AUC) was 0.70 (95%CI: 0.57-0.83, P = 0.003), with 91.4% sensitivity and 51.9% specificity at the cutoff value of 0.50.

Conclusion: The mRNA and protein levels of MMP-9 had no association with BRAF V600E mutation in Iranian PTC patients. These levels were associated with age, TNM stages, and lymphovascular invasion, being defined as malignant factors. Thus, elevated levels of MMP-9 in PTC patients compared to MNG participants illustrated that it can be used as a potential biomarker to differentiate PTC patients from those with MNG.
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http://dx.doi.org/10.1186/s12885-018-5112-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276227PMC
December 2018

Determinants of vitamin D receptor gene expression in visceral and subcutaneous adipose tissue in non-obese, obese, and morbidly obese subjects.

J Steroid Biochem Mol Biol 2019 03 6;187:82-87. Epub 2018 Nov 6.

Tehran Obesity Treatment Center, Department of Surgery, Shahed University, Tehran, Iran.

We aimed to illustrate determinants of VDR gene expression in visceral and subcutaneous adipose tissue among individuals without diabetes. We gathered visceral and subcutaneous adipose tissues during an elective abdominal surgery form 33 morbidly obese (BMI > 40 kg/m), 23 obese (BMI = 30-40 kg/m), and 35 non-obese (BMI<30 kg/m) participants who were free of diabetes. Participants were classified according to their degree of obesity. Before the surgery, habitual dietary intake, physical activity, 25(OH)D, body mass index (BMI), waist circumference (WC), and HOMA-IR was gathered. Non-obese participants had significantly lower mean VDR gene expression in visceral adipose tissues than both the obese and morbidly obese ones and had also lower expression in subcutaneous adipose tissues than the morbidly obese participants. In multiple linear regression models, BMI and HOMA-IR were the independent positive predictors of VDR gene expression in subcutaneous fat. Among non-obese subjects, WC and 25(OH)D were the positive and negative independent predictors of visceral adipose tissue VDR gene expression, respectively. Among obese participants, 25(OH)D was negatively, and BMI and HOMA-IR were positively associated with VDR mRNA levels in visceral adipose tissue. In morbidly obese participants, the independent positive predictors of VDR gene expression in visceral fat were BMI and HOMA-IR, and negative predictors were 25(OH)D and calcium intake. Our findings suggested that 25(OH)D concentrations are the fundamental elements to determine VDR gene expression in visceral fat which by increasing fat depots, the subsequent insulin resistance became another predictor of VDR gene expression.
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http://dx.doi.org/10.1016/j.jsbmb.2018.11.004DOI Listing
March 2019

Effects of metformin on the PI3K/AKT/FOXO1 pathway in anaplastic thyroid Cancer cell lines.

Daru 2018 Dec 21;26(2):93-103. Epub 2018 Sep 21.

Cellular and Molecular Endocrine Research Center, Research Institute of Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: The PI3K/AKT/FOXO signaling pathway plays an important role in the survival, proliferation and apoptosis of tumor cells. The aim of the present study was to explore whether metformin could affect insulin-promoting cell growth by regulation of this pathway.

Material And Methods: Anaplastic thyroid cancer cells were treated with 0-60 mM metformin for 24, 48 and 72 h. Cell viability, morphology, apoptosis and migration were investigated by MTT assay, microscopy observation, AnexinV-PI and the wound healing assay, respectively. Expression levels of PI3K, AKT and FOXO1 were detected by RT-qPCR, and proteins phosphorylated levels were determined by ELISA.

Results: Metformin decreased cell viability and migration in a significant time-and dose-dependent manner, and induced apoptosis and morphological changes in the cells. RT-qPCR results showed that expression levels of PI3K, AKT and FOXO1 was inhibited by metformin (P < 0.05). However, there was no significant change in the expression level of AKT following metformin treatment for C643 cell line (P > 0.05). ELISA results showed that metformin treatment had no significant effects on the phosphorylated levels of PI3K, AKT and FOXO1 (P > 0.05).

Conclusuion: The downregulation of FOXO1 was intensified by metformin, but no increase in cell viability was observed following FOXO1 downregulation by metformin. However, the exact molecular mechanism of metformin on inhibition of the PI3K/AKT pathway and subsequent decrease in cell viability remains unclear and further studies are required for its clarification.
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http://dx.doi.org/10.1007/s40199-018-0208-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279666PMC
December 2018

The Association of BRAF V600E Mutation With Tissue Inhibitor of Metalloproteinase-3 Expression and Clinicopathological Features in Papillary Thyroid Cancer.

Int J Endocrinol Metab 2018 Apr 10;16(2):e56120. Epub 2018 Feb 10.

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

Background: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The aim of this study was to investigate the association of tissue inhibitor metalloproteinase-3 (TIMP3) mRNA and protein levels in thyroid tissues, based on BRAF V600E status with the clinicopathologic characteristics of PTC.

Methods: A total of 60 fresh frozen tissue samples of PTC patients (15 male and 45 female) were collected during thyroidectomy. All clinicopathological information was obtained and samples were reviewed as well as confirmed by a pathologist; exon 15 of the BRAF gene was genotyped by sequencing, TIMP3 mRNA level was assessed using SYBR-Green Real-Time PCR, and TIMP3 protein level was measured using ELISA.

Results: Of 60 cases, BRAF mutation was found in 24 (40%). Larger tumor size and higher lymph node metastasis frequency were observed, significant in BRAF (+), compared to the BRAF (-) PTC group (P = 0.039 and P = 0.03, respectively). No significant difference was seen in the tumoral tissues of the TIMP3 mRNA level in BRAF (+), compared to BRAF (-) PTC samples. However, the mean TIMP3 protein level was significantly lower in tumoral tissues, compared to matched non-tumoral tissues in BRAF (+) PTC (P=0.003); TIMP3 protein level was significantly lower in tumoral tissues compared to matched non-tumoral tissues in BRAF (+), in subjects who had no lymph node metastasis and also in subjects with lymph node metastasis in both BRAF positive and negative PTC cases.

Conclusion: Our results showed that BRAF mutation was associated with a larger tumor size, higher frequency of lymph node metastasis, and lower TIMP3 protein levels. Lower TIMP3 protein level was associated with the lymph node metastasis in PTC patients.
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http://dx.doi.org/10.5812/ijem.56120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972213PMC
April 2018

Transient Congenital Hypothyroidism Alters Gene Expression of Glucose Transporters and Impairs Glucose Sensing Apparatus in Young and Aged Offspring Rats.

Cell Physiol Biochem 2017 27;43(6):2338-2352. Epub 2017 Oct 27.

Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background/aims: Transient congenital hypothyroidism (TCH) could disturb carbohydrate metabolism in adulthood. Aging is associated with increased risk of type 2 diabetes. This study aims to address effects of TCH on mRNA expressions of glucose transporters (GLUTs) and glucokinase (GcK) in islets and insulin target tissues of aged offspring rats.

Methods: The TCH group received water containing 0.025% 6-propyl-2-thiouracil during gestation. Offspring from control and TCH groups (n=6 in each group) were followed until month 19. Gene expressions of GLUTs and GcK were measured at months 3 and 19.

Results: Compared to controls, aged TCH rats had higher GLUT4 expression in heart (4.88 fold) and soleus (6.91 fold), while expression was lower in epididymal fat (12%). In TCH rats, GLUT2 and GcK expressions in islets were lower in young (12% and 10%, respectively) and higher in aged (10.85 and 8.42 fold, respectively) rats. In addition, liver GLUT2 and GcK expressions were higher in young (13.11 and 21.15 fold, respectively) and lower in aged rats (44% and 5%, respectively).

Conclusion: Thyroid hormone deficiency during fetal period impaired glucose sensing apparatus and changed glucose transporter expression in insulin-sensitive tissues of aged offspring rats. These changes may contribute to impaired carbohydrate metabolism.
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http://dx.doi.org/10.1159/000484386DOI Listing
January 2018

Habitual dietary intake of fatty acids are associated with leptin gene expression in subcutaneous and visceral adipose tissue of patients without diabetes.

Prostaglandins Leukot Essent Fatty Acids 2017 Nov 14;126:49-54. Epub 2017 Sep 14.

Tehran Obesity Treatment Center, Department of Surgery, Shahed University, Tehran, Iran.

The purpose of the study was to investigate the association of leptin gene expression in visceral and subcutaneous adipose tissues with habitual fatty acid intake and its subtypes in adults. Visceral and subcutaneous adipose tissues were gathered from 97 participants aged ≥ 20, who had undergone elective abdominal surgery. Dietary fatty acid intakes including total fatty acids (TFA), saturated fatty acid (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), n-3, n-6, and n-9 fatty acids were collected using a valid and reliable food-frequency questionnaire (FFQ). The leptin gene expression in visceral and subcutaneous adipose tissues was measured by Real-Time PCR. After controlling for body mass index (BMI) and insulin, energy-adjusted dietary intake of SFA was positively and MUFA and n-3 fatty acids were negatively associated with subcutaneous and visceral adipose tissues leptin gene expression. Besides, a significant negative association of PUFA, n-6, and n-9 fatty acids with leptin mRNA from visceral adipose tissue were observed. In order to better interpretations of the results, the participants were allocated two groups including non-obese (BMI < 30kg/m) and obese subjects (BMI ≥ 30kg/m). Among non-obese participants, the SFA had positive and PUFA had negative association with leptin gene expression in both adipose tissues. Furthermore, in obese participants, n-3, n-6, and n-9 fatty acids had a negative association with visceral leptin gene expression. Habitual intake of SFA, MUFA, and n-3 fatty acids were associated with leptin gene expression in visceral and subcutaneous adipose tissues, suggesting an important role of quality and quantity of fatty acids intake in adipose tissue to regulate leptin expression.
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http://dx.doi.org/10.1016/j.plefa.2017.09.010DOI Listing
November 2017

Altered Epigenetic Mechanisms in Thyroid Cancer Subtypes.

Mol Diagn Ther 2018 02;22(1):41-56

Cellular and Molecular Endocrine Research Center (CMERC), Research Institute for Endocrine Sciences of Shahid Beheshti University of Medical Sciences, 19395-4763, Tehran, Iran.

Thyroid carcinoma (TC) is the most frequent malignant neoplasm of the endocrine system. Molecular methods for diagnosis of invasive thyroid disease can be effectively adopted. Epigenetic factors play an important role in the diversity patterns of gene expression and the phenotypic and biological characteristics of TC subtypes. We aimed to review epigenetic changes in the main subtypes of TC, along with a presentation of the methods that have examined these changes, and active clinical trials for the treatment of advanced TCs targeting epigenetic changes. A literature analysis was performed in MEDLINE using PubMed, Elsevier, and Google Scholar for studies published up to 2016, using the keywords: "Epigenetic alterations" OR "Epigenetic changes", "thyroid cancers", "papillary thyroid cancer", "medullary thyroid cancer", "follicular thyroid cancer", and "anaplastic thyroid cancer", which resulted in 310 articles in English. All related abstracts were reviewed and studies were included that were published in English, had available full text, and determined the details of the methods and materials associated with the epigenetic patterns of TC and its subtypes (100 articles). Analysis of epigenetic alterations in TC subtypes helps to identify pathogenesis and can play an important role in the classification and diagnosis of tumors. Epigenetic mechanisms, especially aberrant methylation of DNA and microRNAs (miRs), are likely to play an important role in thyroid tumorigenesis. Further studies are required to elucidate the role of histone modification mechanisms in TC development.
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http://dx.doi.org/10.1007/s40291-017-0303-yDOI Listing
February 2018

Alteration in follistatin gene expression detected in prenatally androgenized rats.

Gynecol Endocrinol 2017 Jun 26;33(6):433-437. Epub 2017 Feb 26.

a Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences , Tehran , Iran.

Impaired ovarian follicle development, the hallmark of polycystic ovarian syndrome (PCOS), is believed to be due to the changes in expression of related genes such as follistatin (FST). Expression of FST gene and methylation level of its promoter in theca cells from adult female rats, prenatally exposed to androgen excess, during different phases of the estrus cycle was determined and compared with controls. Eight pregnant Wistar rats (experimental group) were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 8) received 500 ml solvent. Based on observed vaginal smear, adult female offspring of mothers were divided into three groups. Levels of serum steroidogenic sexual hormones and gonadotropins, expression and promoter methylation of the FST gene were measured using ELISA, cyber-green real-time PCR and bisulfite sequence PCR (BSP), respectively. Compared to controls, the relative expression of FST gene in the treated group decreased overall by 0.85 fold; despite significant changes in different phases, but no significant differences in methylation of FST promoter. Our results reveal that manifestation of PCOS-like phenotype following prenatal exposure to excess androgen is associated with irregularity in expression of the FST gene during the estrus cycle.
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http://dx.doi.org/10.1080/09513590.2017.1290067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724370PMC
June 2017

Is apelin gene expression and concentration affected by dietary intakes? A systematic review.

Crit Rev Food Sci Nutr 2018 Mar 12;58(4):680-688. Epub 2017 Jun 12.

e Obesity Treatment Center, Department of Surgery , Shahed University , Tehran , Iran.

Overproduction of apelin in obesity could be one of the last protective defenses before type 2 diabetes develops. To summarize the existing evidence on the association between dietary intake and apelin gene expression and concentration. We systematically searched MEDLINE, EMBASE, and google scholar and hand-searched bibliographies, including peer-reviewed articles with English abstracts, without restriction in publication date, updated until 21 February 2016 that reported the association between dietary intake and apelin gene expression or concentration. From a total of 1075 articles, we identified 12 relevant studies. There were 6 clinical trials in human and 6 studies in animals. Overall, two of three studies conducted in humans showed that calorie-restriction diet in obese subjects decreases apelin concentration. Five animal studies reported that higher intake of fatty acids and eicosapentaenoic acid (EPA) increased apelin expression and concentration. Given the paucity of data available, the heterogeneity of study designs used, and exposures tested, no quantitative meta-analysis was justified. Based on human studies, hypocaloric diet can reduce apelin concentration in obese individuals. In addition, higher intakes of total fatty acids and EPA may increase apelin gene expression and concentration.
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http://dx.doi.org/10.1080/10408398.2016.1262325DOI Listing
March 2018

Familial Aggregation of Metabolic Syndrome With Different Socio-Behavioral Characteristics: The Fourth Phase of Tehran Lipid and Glucose Study.

Iran Red Crescent Med J 2016 Aug 20;18(8):e30104. Epub 2016 Jun 20.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

Background: Since genetic and most environmental factors shape the context of families, some studies have been initiated to investigate the role of familial relationships in metabolic syndrome (MetS).

Objectives: To estimate the familial aggregation of MetS and its components by identifying both case and control probands among Tehranian adults with different socio-behavioral and reproductive characteristics.

Patients And Methods: This case-controlled/family-based study was conducted on 1,777 families (635 case probands) who participated in the Tehran Lipid and Glucose Study (TLGS). Socio-demographic and reproductive information including levels of education, marital status, occupation status, age at menarche, number of abortions, number of children, and lifestyle habits such as smoking, physical activity and regular diet were obtained from the TLGS data bank. Metabolic syndrome was defined according to the joint interim statement (JIS) criteria. To estimate the regression co-efficient for familial aggregation and environmental factors, the generalized estimation equation method was used.

Results: The risk of having MetS among family members for case versus control probands was 2.19 (95% CI: 1.68 - 2.84), which, after adjusting for potential confounders including age, sex, educational level, marital status, occupation, age at menarche and energy, soft drink and starchy vegetable intake, increased to 2.31 (95% CI: 1.81 - 2.94; P < 0.05). Compared to control probands, the risk of having MetS components increased significantly from OR = 1.28 for both high waist circumference (WC) and blood pressure (BP) to OR = 1.72 for high triglycerides in cases. Familial aggregation inherited from the father was significantly observed in all MetS components, from adjusted OR = 1.63 for hyperglycemia to adjusted OR = 2.69 for high WC, except for low HDL, after controlling for potential confounders.

Conclusions: Considering spouses and siblings, there was a higher risk for MetS components among families whose fathers and offspring had MetS components, implying the pivotal role of genetic inheritance in the incidence of the syndrome and its components.
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http://dx.doi.org/10.5812/ircmj.30104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065923PMC
August 2016

Elevated expression of steroidogenesis pathway genes; CYP17, GATA6 and StAR in prenatally androgenized rats.

Gene 2016 Nov 7;593(1):167-171. Epub 2016 Aug 7.

Cellular and Molecular Endocrine Research Center and Obesity Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

It is believed that excess androgen exposure of the fetus, via altered gene expression, causes hyperandrogenism a key feature of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate expression of Cytochrome P450-17 (CYP17), GATA-binding protein (GAGT6) and Steroidogenic acute regulatory protein (StAR), genes of adult female rats prenatally exposed to androgen excess, closely reflect endocrine and ovarian disturbances of PCOS in women, by comparing them during different phases of estrus cycle with those of non-treated rats. Both the adult prenatally testosterone exposed and control rats (n=23, each) were divided into four groups based on their observed vaginal smear (proestrus, estrus, metestrus and diestrus) and the relative expression of CYP17, GATA6 and StAR genes was measured in ovarian theca cells using Cyber-green Real-Time PCR. Serum sex steroid hormones and gonadotropins levels were measured using the ELISA method; a comparison of these two groups showed that there was an overall increase in the studied genes (CYP17; 2.39 fold change, 95% CI: 1.23-3.55; P<0.05, GATA6; 2.08 fold change, 95% CI: 1.62-2.55; P<0.0001, and StAR; 1.4 fold change, 95% CI: 1.02-1.78; P<0.05), despite variations in different phases with maximum elevation for all genes in diestrus. The changes observed may impair the normal development of ovaries that mediate the programming of adult PCOS.
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http://dx.doi.org/10.1016/j.gene.2016.07.067DOI Listing
November 2016

Involvement of inducible nitric oxide synthase in the loss of cardioprotection by ischemic postconditioning in hypothyroid rats.

Gene 2016 Apr 13;580(2):169-176. Epub 2016 Jan 13.

Endocrine Physiology Research Center and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Cardioprotection by ischemic postconditioning (IPost) is negated in hypothyroidism; the underlying mechanisms however are unknown. This study aimed at determining whether changes in Bax, Bcl-2, eNOS, and iNOS gene expressions are involved in the negating effects of IPost against ischemia-reperfusion (IR) injury in hypothyroidism. The hearts from control and hypothyroid rats were perfused in Langendorff apparatus and exposed to 30 min ischemia, followed by 120 min reperfusion and IPost. In a subgroup of hypothyroid rats, ischemia duration was extended to 40 min. Hemodynamic parameters, infarct size, and gene expressions were measured. Compared to controls, hypothyroid rats with 30 min ischemia had higher recovery of post-ischemic LVDP and ± dp/dt, confirmed by decreased CK and LDH levels (187 ± 16 vs. 485 ± 41 and 191 ± 9 vs. 702 ± 48 U/L, respectively; p<0.05), decreased infarct size (6.7 ± 1.1 vs. 46.1 ± 1.7%; p<0.05), and a reduced DNA laddering pattern. Recovery of post-ischemic LVDP and ± dp/dt decreased and infarct size increased following extension of ischemia period in hypothyroid rats. IPost increased eNOS and Bcl-2 expression by 3.2-fold and 3.7-fold and decreased Bax and iNOS expression by 79% and 38%, respectively; it also reduced IR-induced DNA laddering pattern in controls, whereas no change was observed in hypothyroid rats, regardless of the ischemia period. In conclusion, hearts from hypothyroid rats were resistant to IR injury, partly due to the lower expression of iNOS and subsequent reduction in apoptosis after IR. In hypothyroid rats, IPost was not associated with further reduction in iNOS expression and failed to provide additional cardioprotection against ischemia.
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http://dx.doi.org/10.1016/j.gene.2016.01.014DOI Listing
April 2016

Ischemic postconditioning provides cardioprotective and antiapoptotic effects against ischemia-reperfusion injury through iNOS inhibition in hyperthyroid rats.

Gene 2015 Oct 6;570(2):185-90. Epub 2015 Jun 6.

Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Ischemic postconditioning (IPost) is a strategy to provide protection against ischemia-reperfusion (IR) injury. The cardioprotective effects of IPost in cases of ischemic heart disease along with co-morbidities like hyperthyroidism remain unknown. The aim of this study was to investigate the effects of IPost on expression of eNOS, iNOS, Bax, and Bcl-2 genes in hyperthyroid male rats, subjected to myocardial IR. Hyperthyroidism was induced by adding thyroxine to drinking water for a period of 21 days. Using the Langendorff device hearts were perfused, then subjected to a 30-minute global ischemia which was followed by 120 min of reperfusion; subsequently IPost was induced immediately after ischemia. Results indicated that following IR, expression of eNOS and Bcl-2 decreased, whereas expression of iNOS and Bax increased in both the control and hyperthyroid groups. In hyperthyroid animals, IPost significantly increased expression of eNOS by 3.19 fold and Bcl-2 by 3.66 fold; it also decreased expression of Bax by 51%, and reduced IR-induced DNA laddering pattern and infarct size (45.7 ± 1.82% vs. 59.3 ± 1.83%, p<0.05) in the presence of aminoguanidine (AG), a selective iNOS inhibitor. In conclusion, IPost per se could not provide cardioprotection against myocardial ischemia in hyperthyroid rats, a loss of which however was restored by the combination of IPost and iNOS inhibition that acts by a decrease in Bax and an increase in both eNOS and Bcl-2 expression.
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http://dx.doi.org/10.1016/j.gene.2015.06.011DOI Listing
October 2015

Antimullerian hormone and its receptor gene expression in prenatally androgenized female rats.

Int J Endocrinol Metab 2015 Jan 30;13(1):e19511. Epub 2015 Jan 30.

Cellular and Molecular Endocrine Research Center, Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

Background: Anti-mullerian hormone (AMH) levels reflect the number of small antral follicles in ovaries and expression changes of AMH and its receptor are suspected to be involved in the pathogenesis of polycystic ovary syndrome (PCOS).

Objectives: The aim of this study was to evaluate gene expression of AMH and its receptor in immature and adult rats prenatally exposed to androgen excess.

Materials And Methods: Six pregnant Wistar rats in the experimental group were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 6) received only 500 mL of solvent. Female pups of each mother were randomly divided into three groups as day 0 (newborn), 10-day old and days 75-85 (adult). RNAs were extracted from ovarian tissues and relative expression levels for AMH and its receptor genes were measured using TaqMan Real-Time PCR. Serum AMH and testosterone levels were measured using ELISA method.

Results: Relative AMH expression decreased in newborns, 10-day olds and adults (0.806, 0.443 and 0.809 fold, respectively). AMHR expression was higher in newborns and adults (1.432 and 1.057 fold, respectively), while it decreased by 0.263 fold in 10-day olds, although none of them were significant (P > 0.05). In addition, AMH levels were consistent with the results of gene expression. Testosterone hormone levels from 10 day-olds to adults were significantly increased in both study groups (P = 0.016).

Conclusions: While AMH receptor expression was higher in experimental rats, their serum concentrations of AMH were decreased. Further researches with greater sample sizes and measurement of bioactive forms of hormones are recommended to confirm the findings of this study.
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http://dx.doi.org/10.5812/ijem.19511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338645PMC
January 2015

The association between inflammatory markers and obesity-related factors in Tehranian adults: Tehran lipid and glucose study.

Iran J Basic Med Sci 2014 Aug;17(8):577-82

Cellular and Molecular Research Center, Obesity Research Center, Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objectives: Obesity considered being a low-grade inflammatory disease. The objective of this study was to examine the association between inflammatory markers (IM) including C-reactive protein (hs-CRP), Interleukin-6 (IL-6), and homocystein (Hcy) and obesity-related factors (e.g. BMI, waist, hip) in adult participants of Tehran lipid and glucose study (TLGS).

Materials And Methods: In this cross-sectional study, 352 individuals (132 men and 220 women), age ≥19 years, were randomly recruited from participants of TLGS population. The serum levels of hs-CRP, IL-6, Hcy were determined using the enzyme linked immunosorbent assay (ELISA) method. Variables were compared by sample t-test. Bivariate linear correlation was estimated using Pearson's correlation coefficient. Linear regression analysis was applied to investigate the association between IMs and anthropometric and biochemical variables.

Results: The mean age of participants was 46.1±16.1 years. abdominal obesity was present in 199(56.5%) individuals. levels of hs-CRP and IL-6 increased in the abdominally obese group (1507±3.3 vs. 577.8±4.3 ng/ml P<0.001) (3.6±3.3 vs. 1.9±3.8 pg/ml P< 0.001), and in the same group, the best predictors for hs-CRP, IL-6 and Hcy were waist (WC), waist to height ratio (WHtR) and wrist respectively; hip and WHtR were the best predictors for Hcy and hs-CRP in the normal group. A linear augmentation in hs-CRP and IL-6 levels was observed in association with obesity categorizes.

Conclusion: This study provides evidence that abdominally obese individuals had higher levels of IMs. Wrist, waist and WHtR were the best predictors for Hcy, hs-CRP and IL-6 respectively in this group.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240791PMC
August 2014