Sara Sheikholeslami

Effect of pomegranate seed oil on serum TNF-α level in dyslipidemic patients.

Pomegranate punicic acid and pomegranate fruit extracts have the potential effects in inhibiting tumour necrosis factor-α (TNF-α) and inflammatory diseases. The aim of this study was to evaluate the effect of pomegranate seed oil (PSO) consumption on serum TNF-α level in dyslipidemic patients. Fifty-one subjects with serum total cholesterol concentration >200 mg/dl and serum triglyceride concentrations >150 mg/dl were randomly assigned into the PSO (n = 25) and placebo (n = 26) groups. Subjects were given 400 mg PSO or placebo capsules twice daily for 4 weeks. Six patients were excluded because of complications or lack of compliance. Serum TNF-α level was measured at baseline and after 4 weeks. Mean (SD) serum concentration of TNF-α decreased from 14.73 ± 5.25 to 13.28 ± 3.79 pg/ml in the PSO group (P = NS). Corresponding values in the placebo group were 12.46 ± 1.67 versus 13.14 ± 1.67 pg/ml (P = NS). In conclusion, administration of PSO in dyslipidemic patients does not affect the serum TNF-α.

RET proto oncogene mutation detection and medullary thyroid carcinoma prevention.

Thyroid cancer is the most common endocrine neoplasia. The medullary thyroid carcinoma (MTC) is one of the most aggressive forms of thyroid malignancy,accounting for up to 10% of all types of this disease. The mode of inheritance of MTC is autosomal dominantly and gain of function mutations in the RET proto-oncogene are well known to contribute to its development. MTC occurs as hereditary (25%) and sporadic (75%) forms. Hereditary MTC has syndromic (multiple endocrine neoplasia type 2A, B; MEN2A, MEN2B) and non-syndromic (Familial MTC, FMTC) types. Over the last two decades, elucidation of the genetic basis of tumorigenesis has provided useful screening tools for affected families. Advances in genetic screening of the RET have enabled early detection of hereditary MTCs and prophylactic thyroidectomy for relatives who may not show any symptom sof the disease. In this review we emphasize the main RET mutations in syndromic and non syndromic forms of MTC, and focus on the importance of RET genetic screening for early diagnosis and management of MTC patients, based on American Thyroid Association guidelines and genotype-phenotype correlation.

Diversity of mutations in the RET proto-oncogene and its oncogenic mechanism in medullary thyroid cancer.

Abstract Thyroid cancer is the most common endocrine malignancy and accounts for nearly 1% of all of human cancer. Thyroid cancer has four main histological types: papillary, follicular, medullary, and anaplastic. Papillary, follicular, and anaplastic thyroid carcinomas are derived from follicular thyroid cells, whereas medullary thyroid carcinoma (MTC) originates from the neural crest parafollicular cells or C-cells of the thyroid gland. MTC represents a neuroendocrine tumor and differs considerably from differentiated thyroid carcinoma. MTC is one of the aggressive types of thyroid cancer, which represents 3–10% of all thyroid cancers. It occurs in hereditary (25%) and sporadic (75%) forms. The hereditary form of MTC has an autosomal dominant mode of inheritance. According to the present classification, hereditary MTC is classified as a multiple endocrine neoplasi type 2 A & B (MEN2A & MEN2B) and familial MTC (FMTC). The RET proto-oncogene is located on chromosome 10q11.21. It is composed of 21 exons and encodes a transmembrane receptor tyrosine kinase. RET regulates a complex network of signal transduction pathways during development, survival, proliferation, differentiation, and migration of the enteric nervous system progenitor cells. Gain of function mutations in RET have been well demonstrated in MTC development. Variants of MTC result from different RET mutations, and they have a good genotype–phenotype correlation. Various MTC related mutations have been reported in different exons of the RET gene. We proposed that RET genetic mutations may be different in distinct populations. Therefore, the aim of this study was to find a geographical pattern of RET mutations in different populations.

Apolipoprotein E polymorphisms status in Iranian patients with multiple sclerosis

BACKGROUND Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system. Evidences linking apolipoprotein E (APOE) to myelin repair, neuronal plasticity, and cerebral inflammatory processes suggest that it may be relevant in MS. The main goal of this study was to determine whether the APOE genotypes and alleles are associated with MS patients. MATERIALS AND METHODS In total, 147 MS cases and 168 control subjects from Iranian population were genotyped for APOE gene using PCR-RFLP method. RESULTS The frequency of APOE-ε2ε3 genotype was significantly higher in controls than cases (14.3% vs. 6.1%, P=0.009, OR=0.39) whereas APOE-ε3ε4 genotype frequency was significantly higher in cases compared with controls (8.2% vs. 3.6%, P=0.03, OR=2.4). APOE-ε2 allele frequency in cases was significantly lower than that of controls (4.4% vs. 8.0%, P=0.03, OR=0.52). Also male controls were significantly more likely to have APOE-ε2 allele (7.8% vs. 1%, P=0.01, OR=0.11). APOE-ε4 allele frequency in cases was significantly higher than control group (4.8% versus 2.1%, P=0.03, OR=2.35). CONCLUSION It seems that individuals carrying APOE-ε4 allele and/or APOE-ε3ε4 genotype develop MS two times more than non-carriers. Also APOE-ε2ε3 genotype or APOE-ε2 allele may have a protective role against MS development in Iranian population. Further investigation would be warranted to understand the role of APOE alleles and genotypes and risk of MS.

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

Context The Tehran Lipid and Glucose Study (TLGS) is a community-based study to reveal the frequency of non-communicable diseases (NCDs) in Tehrans 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.

The Physical Activity and Non-Communicable Diseases Risk Factors: 20 Years of the TLGS Findings

Context Low physical activity is one of the major risk factors for non-communicable diseases (NCD) such as cardiovascular disease and type 2 diabetes. The current paper reviews the main findings from Tehran lipid and glucose study (TLGS) that focus on physical activity and its association with cardiometabolic risk factors over the past two decades. Evidence Acquisition We conducted a literature search for articles from 1999 to December 2017 using the search terms: (Physical activity, leisure time physical activity, non-communicable disease, and TLGS). Results The prevalence of low physical activity was 69.8% during phase ΙΙ of TLGS (2000 - 2004). During 6.5 years of follow up, the prevalence of low physical activity in the total population decreased significantly between phases II (2000 - 2004) and IV of TLGS (2008 - 2010) (P < 0.05). Overweight individuals with sedentary lifestyles had a higher risk of metabolic syndrome, compared to those who had high levels of leisure-time physical activity in phase IV of TLGS (2008 - 2010); in the obese group, systolic blood pressure, and triglyceride levels differed significantly between different leisure-time physical activity categories (106.9 ± 14.3 vs. 119.1 ± 17.2 mmHg, P = 0.03) and (111.4 ± 1.6 vs. 147.1 ± 1.6 mg/dL, P = 0.01), respectively. Conclusions The present review highlights the impact of low physical activity on the health of the TLGS community from adolescence to adulthood. The decreased prevalence of low physical activity from phase ΙΙ to phase ΙV of TLGS indicates the necessity for lifestyle interventions as a potentially effective strategy, which could have a positive impact on various risk factors and indicators of non-communicable diseases such as body mass index, waist circumference, systolic blood pressure, and lipid profiles.

Plasma Calcitonin Levels and miRNA323 Expression in Medullary Thyroid Carcinoma Patients with or without RET Mutation

Background: Medullary thyroid cancer (MTC) is an endocrine tumor featuring parafollicular or C-cell differentiation, with calcitonin as a specific biomarker in MTC diagnosis. Germline mutations in the RET proto-oncogene are considered responsible for its familial occurrence and somatic mutations can cause sporadic lesions. MicroRNAs can act as oncogenes or tumor suppressors by inhibiting the expression of target genes.. The aim of this study was to investigate relationships between plasma levels of calcitonin and miRNA323 expression in MTC patients with or without RET mutation. Methods: In this cross-sectional study, MTC lesions (based on pathological confirmation) were investigated. Genomic DNA was extracted and Exons 10 and 11 of RET were genotyped using PCR-sequencing. Division was into two groups of 43 cases each with or without mutation. Plasma levels of calcitonin were determined in both. Results: miRNA323 was measured using real-time-PCR. After performing normality tests, independent T-tests and Mann Whitney tests were used for the statistical comparison of parametric and nonparametric data, respectively. Plasma levels of calcitonin were significantly higher in MTC cases without a RET mutation compared to those with a mutation. Conclusion: There was no significant difference between the two groups regarding the expression of miRNA323 so that this parameter could not be used as a bio-index germ line mutations in MTCs. However, determination of calcitonin levels in plasma might be helpful in this regard.