Parent-child correlation in energy and macronutrient intakes: A meta-analysis and systematic review.

In the current study, we aimed to review the evidence from twin and family-based studies that have assessed the familial similarity in intakes of energy and macronutrients among various parent-child pairs. The online literature databases, including Web of Science, PubMed, and Scopus, were searched up to December 2022 to find potentially eligible studies. We converted Pearson's, Spearman's, or intra-class correlation coefficients to z's using Fisher's z transformation to obtain approximate normality and then calculated a mean and standard error (SE) of transformed correlation weighted by the sample sizes in the studies. We reported pooled r and 95% CI as our final results in five groups, including parent-child, mother-daughter, mother-son, father-daughter, and father-son. Twenty-one eligible studies were included in this meta-analysis, in which the sample size ranged from 33 and 4310. Our analysis showed that family resemblance in the intake of energy and macronutrients in various parent-offspring pairs was weak to moderate which could be different based on family pairs, nutrients, and studies. The highest similarity in dietary intakes was observed among the mother-daughter pair, which was for carbohydrate and protein intake, respectively. The lowest correlations in dietary intakes were found between mother-son or father-son pairs. Our meta-analysis suggested that family similarity for intakes of energy and macronutrients was not strong in parent-child pairs. The highest correlation in dietary intake was mostly found in mother-daughter pairs. The weak similarities in dietary intake among parent-child pairs indicate the noticeable effect of the environment outside the family on individuals' dietary choices.

Effect of long-term inorganic nitrate administration on myocardial ischemia-reperfusion injury in ovariectomized rats.

Introduction: Menopause is associated with reduced nitric oxide (NO) bioavailability and lower tolerance against myocardial ischemia-reperfusion (IR) injury. This study investigated whether long-term nitrate administration provides resistance against myocardial IR injury in ovariectomized (OVX) rats. Method: After ovariectomy, female rats were assigned to the OVX and the OVX + nitrate groups (n = 14/group); the latter group consumed nitrate (100 mg/L) for 9 months. At month 9, each group was divided into two subgroups (n = 7/subgroup), of which one subgroup was exposed to myocardial IR (IR+ hearts) and the other was not exposed (IR- hearts). The hearts of rats were isolated, and NO metabolite (NOx), oxidative stress indices, and mRNA expressions of endothelial (eNOS), inducible (iNOS), and neuronal (nNOS) NO synthases, as well as markers of apoptosis, were measured in the IR- and IR+ hearts. In the IR+ hearts, cardiac function indices (CFI) and the infarct size were also measured. Results: Nitrate increased catalase activity (97%) and eNOS expression (2.94-fold) in the IR- hearts. In the IR+ hearts, nitrate reduced left ventricular (LV) end-diastolic pressure (11.6%) and infarct size (26.2%) and increased recovery of LV developed pressure (44.0%) and peak rate of positive (28.9%) and negative (15.4%) changes in LV pressure. In addition, in the IR+ hearts, nitrate increased eNOS and B-cell lymphoma-2 (Bcl-2) as well as decreased iNOS, Bcl-2 associated X protein (Bax), caspase-3, caspase-8, caspase-9, and tumor necrosis factor-α (TNF-α) expression. Nitrate increased total antioxidant capacity (TAC) and catalase (CAT) activity and decreased malondialdehyde (MDA) levels at month nine in serum and IR+ hearts. Conclusion: The favorable effects of nitrate against IR injury were associated with higher eNOS and Bcl-2 expression, CAT activity, TAC, and lower iNOS, Bax, caspase-3, caspase-8, caspase-9 and TNF-α expression, and MDA in the heart tissue. Nitrate preconditioning alleviated IR-induced myocardial injury in OVX rats; this effect was associated with eNOS upregulation before IR and the blunting of OVX-induced eNOS downregulation, iNOS upregulation, apoptosis, and oxidative stress in heart tissue after IR.

The Tehran longitudinal family-based cardiometabolic cohort study sheds new light on dyslipidemia transmission patterns.

Dyslipidemia, as a metabolic risk factor, with the strongest and most heritable independent cause of cardiovascular diseases worldwide. We investigated the familial transmission patterns of dyslipidemia through a longitudinal family-based cohort, the Tehran Cardiometabolic Genetic Study (TCGS) in Iran. We enrolled 18,729 individuals (45% were males) aged > 18 years (mean: 38.15 (15.82)) and observed them over five 3-year follow-up periods. We evaluated the serum concentrations of total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol with the first measurement among longitudinal measures and the average measurements (AM) of the five periods. Heritability analysis was conducted using a mixed-effect framework with likelihood-based and Bayesian approaches. The periodic prevalence and heritability of dyslipidemia were estimated to be 65.7 and 42%, respectively. The likelihood of an individual having at least one dyslipidemic parent reveals an OR = 6.94 (CI 5.28-9.30) compared to those who do not have dyslipidemic parents. The most considerable intraclass correlation of family members was for the same-sex siblings, with ICC ~ 25.5%. For serum concentrations, heritability ranged from 33.64 to 60.95%. Taken together, these findings demonstrate that familial transmission of dyslipidemia in the Tehran population is strong, especially within the same-gender siblings. According to previous reports, the heritability of dyslipidemia in this population is considerably higher than the global average.

Thyroid cancer cell metabolism: A glance into cell culture system-based metabolomics approaches.

Thyroid cancer is the most common malignancy of the endocrine system and the seventh most prevalent cancer in women worldwide. It is a complex and diverse disease characterized by heterogeneity, underscoring the importance of understanding the underlying metabolic alterations within tumor cells. Metabolomics technologies offer a powerful toolset to explore and identify endogenous and exogenous biochemical reaction products, providing crucial insights into the intricate metabolic pathways and processes within living cells. Metabolism plays a central role in cell function, making metabolomics a valuable reflection of a cell's phenotype. In the OMICs era, metabolomics analysis of cells brings numerous advantages over existing methods, propelling cell metabolomics as an emerging field with vast potential for investigating metabolic pathways and their perturbation in pathophysiological conditions. This review article aims to look into recent developments in applying metabolomics for characterizing and interpreting the cellular metabolome in thyroid cancer cell lines, exploring their unique metabolic characteristics. Understanding the metabolic alterations in tumor cells can lead to the identification of critical nodes in the metabolic network that could be targeted for therapeutic intervention.

A systematic review of dysregulated microRNAs in Hashimoto's thyroiditis.

BACKGROUND: Plenty of evidence suggests that dysregulated microRNAs are linked to developing autoimmune thyroid diseases. In this study, we aimed to identify commonly linked dysregulated microRNAs in Hashimoto's thyroiditis(HT) and explore microRNA-targeted genes and the involved pathways. METHODS: Embase, PubMed, Web of Science, and Scopus databases were searched using the MeSH terms and free text terms, which yielded 11879 articles published up to July 2023. Two-step screening(first for titles and second for abstracts) was completed according to inclusion and exclusion criteria. The search strategy was formulated using the PEO format(Population, Exposure, and Outcome) for observational studies. The corresponding target genes and relevant signaling pathways were also identified using web servers of Diana Tools/its mirPath v.3 software, miRNA Enrichment Analysis, Mirpath DB2, miRPathDB 2.0, and miRmap. RESULTS: Review inclusion criteria were met by 16 studies. Thirty-three microRNAs were identified as differentially expressed in HT patients compared to a healthy control after qRT-PCR or RNA sequencing confirmation. Only three miR-146a, miR-142, and miR-301 showed significant results in more than two studies comparing HT cases with healthy controls. CONCLUSION: Three key microRNAs in HT were identified by systematic review; the corresponding target genes and signaling pathways involved in the target genes were also identified. These microRNAs regulate the immune response and inflammation and may favor the development and progression of HT. These data may be beneficial to make a step forward to understand the exact etiology of HT and use of these MicroRNAs as possible diagnostic and prognostic biomarkers and as target therapy.

Association of baseline and changes in adiponectin, homocysteine, high-sensitivity C-reactive protein, interleukin-6, and interleukin-10 levels and metabolic syndrome incidence: Tehran lipid and glucose study.

Background: Metabolic syndrome (MetS) is accompanied by chronic low-grade inflammation, and inflammatory markers like high-sensitivity C-reactive protein(hs-CRP), interleukin-6(IL-6), and homocysteine(Hcy) contribute to inflammation, obesity, and insulin resistance. Adiponectin(AdipoQ) and interleukin-10(IL-10) are anti-inflammatory markers that play protective roles in MetS. This study aimed to investigate the association between these biochemical marker changes and MetS in a sample of the Tehranian population during six years of follow-up. Methods: In this longitudinal study, 340 adults at baseline and after a six-year follow-up, aged ≥18 years, were selected randomly from the Tehran Lipid and Glucose Study (TLGS). MetS was defined according to the Joint Interim Statement (JIS) criteria. Individuals were categorized into four groups based on their MetS status at baseline and follow-up: 1) non-MetS: participants who did not have MetS at both baseline and follow-up; 2) incident MetS: participants who did not have MetS at baseline but developed MetS during the follow-up ; 3) recovery MetS: participants who had MetS at baseline but no longer had MetS during the follow-up; 4) persistent MetS: participants who had MetS both at baseline and follow-up. Results: The mean follow-up time was 6.1 years. There were 176 subjects in the non-MetS group, 35 in the incident MetS group, 41 in the recovery MetS group, and 88 in the persistent MetS group. Increases in the levels of both hs-CRP 1.40 (95% CI: 1.15, 1.71, p = 0.001) and IL-6 1.09 (95% CI: 1.03, 1.17, p = 0.004) significantly increased the odds of the incident and persistent MetS, respectively. The area under the ROC curve (AUC) was more than 0.69 (p < 0.000) for hs-CRP in predicting MetS incidence and more than 0.86 (p < 0.000) for IL-6 in predicting MetS persistence. Conclusion: After a six-year average follow-up, hs-CRP and IL-6 levels were deemed more reliable predictors of MetS incidence and persistence, respectively.

RET/PTC rearrangement in papillary thyroid carcinoma arising in malignant struma ovarii with abdominal wall metastasis and cervical thyroid gland: a case report and review of the literature.

BACKGROUND: Struma ovarii refers to rare mature cystic teratomas containing at least 50% of thyroid tissue, and malignant transformation is known to be even rarer. The synchronous development of malignant struma ovarii and cervical thyroid carcinoma are also scarce and poorly understood due to limited data about molecular features. Here, we present the first report of RET/PTC 1 rearrangement in synchronous metastatic malignant struma ovarii to the abdominal wall and cervical thyroid cancer. CASE PRESENTATION: We described a 47-year-old multigravida woman with bilateral adnexal and lower abdominal wall masses detected during the evaluation of abnormal uterine bleeding. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy, and surgical removal of abdominal wall mass. Then, the pathological evaluation revealed papillary thyroid carcinoma (PTC) within struma ovarii and metastatic PTC in the abdominal wall fibro adipose tissue. Further, cervical thyroid gland physical examination and ultrasound illustrated a nodule within the left lobe. Subsequently, a total thyroidectomy was performed, and a histological examination revealed PTC. Furthermore, all affected tissue, i.e., struma ovarii, abdominal wall metastasis, and cervical thyroid gland tested for BRAF and RAS mutations and RET/PTC 1 rearrangement. RET/PTC 1 rearrangement was identified among all three different sites. Finally, after six years of follow-up, the patient had no evidence of recurrence or distant metastasis. CONCLUSIONS: In light of these findings, malignant struma ovarii might yield a clue to cervical thyroid carcinoma, and the molecular analysis could provide valuable information for understanding the underlying mechanism, tumor clinicopathological behaviors, and prognosis.

Familial resemblance and family-based heritability of nutrients intake in Iranian population: Tehran cardiometabolic genetic study.

BACKGROUND: We aimed to investigate the familial resemblance of dietary intakes, including energy and nutrients, and the family-based heritability of dietary intake in different age-sex dyads of the Tehran cardiometabolic genetic study. METHODS: This cross-sectional study was conducted on 9,798 participants, aged ≥ 18 years, with complete data in each of the third, fourth, fifth, and sixth surveys of the Tehran Cardiometabolic Genetic study, who were eligible to enter the current study based on inclusion and exclusion criteria. Nutrient intake was determined using a valid and reliable food frequency questionnaire (FFQ). FCOR command of the S.A.G.E. software was used to estimate the intra-class correlation coefficients of all relative pairs to verify the family resemblance of dietary nutrient intakes. Classical likelihood-based is used to assess the family-based heritability of dietary nutrient traits. RESULTS: There were 4338 families with a mean family size of 3.20 ± 2.89, including 1 to 32 members (2567 constituent pedigrees and 1572 singletons) and 3627 sibships. The mean ± SD age of participants was 42.0 ± 15.2 years, and 44.5% were males. The heritability of nutrient intake ranged from 3 to 21%. The resemblance degree of energy intake and most nutrients between spouses or between parents and children is weak to moderate; however, a high resemblance of intake was observed for some food components, especially among spouses, including trans fatty acids (TFAs) (r:0.70), chromium (r:0.44), fiber(r:0.35), pantothenic acid (r:0.31), and vitamin C(r:0.31). Based on our findings, the resemblance of nutrient intake in spouses was greater than in parent-offspring. The similarity in parent-offspring nutrient intake was different, and the correlation in mother-girls nutrient intakes was greater than other parent-child correlations. Also, the lowest resemblance in nutrient intake was observed among siblings. CONCLUSIONS: Our findings suggested a weak-to-moderate similarity between the nutrient intakes of parents and offspring. The resemblance degree in nutrient intake varied between different family pairs; the strongest correlation of nutrients was observed between spouses, which includes TFAs, chromium, fiber, pantothenic acid, and vitamin C. The lowest correlation of nutrients was between siblings, such as carbohydrates, thiamine, niacin, and vitamin K. An individual's nutrient intake can somewhat be influenced by genetics, family relationships, and the effects of parents, although the significant influence of environmental factors should not be ignored.

Evidence of familial resemblance and family-based heritability of food intakes derived from a longitudinal cohort study.

We sought to investigate the familial aggregation and family-based heritability of dietary intakes among adults in a population-based longitudinal study of the Tehran Lipid and Glucose Study (TLSG). Total of 4359 males and 5439 females entered our study. We categorized foods into main groups based on the literature on main food groups and their subgroups among the Iranian dietary habits and food culture as follows: grains, fruits, vegetables, dairy, meats, legume, nuts, beverages, snacks, and fats. The intraclass correlation coefficients (ICC) are estimated to verify familial resemblance of dietary habits for all relative pairs and spouses. Family-based heritability is obtained using a mixed effect framework with likelihood-based approach. For almost all food groups, the correlation between parents and offsprings tended to be larger than those of siblings. Family-based heritability of food groups varies from the lowest 6.36% for snacks to the highest 25.67% for fruits, and 25.66% for legume. Our findings indicated weak-to-moderate similarities between parents' and offspring's food intakes; however, the similarity in parent-child food intakes was different, and the correlation in mother-daughter food intakes was stronger than other parent-child correlations, and almost all of dietary components showed strong family-based heritability.

Association of physical activity with increased PI3K and Akt mRNA levels in adipose tissues of obese and non-obese adults.

Phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway regulates glucose and lipid metabolism. We examined the association of PI3K and Akt expression in visceral (VAT) and subcutaneous adipose tissue (SAT) with daily physical activity (PA) in non-diabetic obese and non-obese adults. In this cross-sectional study, we included 105 obese (BMI ≥ 30 kg/m2) and 71 non-obese (BMI < 30 kg/m2) subjects (aged/ ≥ 18 years). PA was measured using a valid and reliable International Physical Activity Questionnaire(IPAQ)-long-form, and the metabolic equivalent of task(MET) was calculated. Real-time PCR was performed to analyze the mRNA relative expression. VAT PI3K expression had a lower level in obese compared to non-obese (P = 0.015), while its expression was higher in active individuals than inactive ones (P = 0.029). SAT PI3K expression was increased in active individuals compared to inactive ones (P = 0.031). There was a rise in VAT Akt expression in the actives compared to the inactive participants (P = 0.037) and in non-obese/active compared to non-obese/inactive individuals (P = 0.026). Obese individuals had a decreased expression level of SAT Akt compared to non-obsesses (P = 0.005). VAT PI3K was directly and significantly associated with PA in obsesses (ß = 1.457, P = 0.015). Positive association between PI3K and PA suggests beneficial effects of PA for obese individuals that can be partly described by PI3K/Akt pathway acceleration in adipose tissue.

Cohort profile update: Tehran cardiometabolic genetic study.

The Tehran cardiometabolic genetic study (TCGS) is a large population-based cohort study that conducts periodic follow-ups. TCGS has created a comprehensive database comprising 20,367 participants born between 1911 and 2015 selected from four main ongoing studies in a family-based longitudinal framework. The study's primary goal is to identify the potential targets for prevention and intervention for non-communicable diseases that may develop in mid-life and late life. TCGS cohort focuses on cardiovascular, endocrine, metabolic abnormalities, cancers, and some inherited diseases. Since 2017, the TCGS cohort has augmented by encoding all health-related complications, including hospitalization outcomes and self-reports according to ICD11 coding, and verifying consanguineous marriage using genetic markers. This research provides an update on the rationale and design of the study, summarizes its findings, and outlines the objectives for precision medicine.

Protective effects of long-term nitrate administration against ovariectomy-induced kidney dysfunction in rats.

BACKGROUND: Menopause is associated with higher risks of chronic kidney disease. We determined the effect of nitrate on ovariectomy-induced kidney dysfunction METHODS: Control, ovariectomized (OVX), control + nitrate, and OVX + nitrate female Wistar rats (n = 10/group); sodium nitrate (100 mg/L) administered in drinking water for 9 months. Glomerular filtration rate (GFR) and albumin excretion rate (AER) were calculated from serum and urine parameters. At month 9, serum and kidney levels of nitric oxide (NO) metabolites (NOx), oxidative stress indices, and mRNA expression of endothelial NO synthase (eNOS) were measured; with histological analyses of the kidney. RESULTS: Compared to controls, OVX rats had lower GFR (31%, p = 0.0079), higher glomerular tuft volume (30%, p = 0.0402), and Bowman's capsule space (39%, p = 0.0224). OVX rats had lower serum NOx (33%, p = 0.0061) and kidney eNOS mRNA expression (34%, p = 0.0368). Nitrate administration to: (i) control rats increased serum NOx (59%, p < 0.0001), with no effect on other parameters; (ii) OVX rats increased serum (85%, p < 0.0001) and kidney (106%, p = 0.0008) NOx values, and restored kidney eNOS expression to normal value. Nitrate administration to OVX rats increased GFR (36%, p = 0.0361) and restored glomerular tuft volume and Bowman's capsule space to normal values. In OVX rats, it also increased serum catalase (CAT) activity, serum and kidney total antioxidant capacity (TAC), and decreased serum malondialdehyde (MDA). CONCLUSIONS: Low-dose long-term nitrate administration protects against ovariectomy-induced kidney dysfunction in rats. This effect is associated with reducing ovariectomy-induced oxidative stress and restoring eNOS-derived NO deficiency in systemic circulation and the kidney.

Altered sialin mRNA gene expression in type 2 diabetic male Wistar rats: implications for nitric oxide deficiency.

Nitrate therapy has been suggested to boost nitric oxide (NO) levels in type 2 diabetes (T2D); however, little is known about nitrate transport across the membranes. This study aimed to assess changes in the mRNA expression of sialin, as a nitrate transporter, in the main tissues of rats with T2D. Rats were divided into two groups (n = 6/group): Control and T2D. A high-fat diet combined with a low dose of streptozotocin (STZ, 30 mg/kg) was used to induce T2D. At month 6, samples from the main tissues of rats were used to measure the mRNA expression of sialin and levels of NO metabolites. Rats with T2D had lower nitrate levels in the soleus muscle (66%), lung (48%), kidney (43%), aorta (30%), adrenal gland (58%), epididymal adipose tissue (eAT) (61%), and heart (37%) and had lower nitrite levels in the pancreas (47%), kidney (42%), aorta (33%), liver (28%), eAT (34%), and heart (32%). The order of sialin gene expression in control rats was: soleus muscle > kidney > pancreas > lung > liver > adrenal gland > brain > eAT > intestine > stomach > aorta > heart. Compared to controls, rats with T2D had higher sialin mRNA expressions in the stomach (2.1), eAT (2.0), adrenal gland (1.7), liver (8.9), and soleus muscle (3.4), and lower sialin expression in the intestine (0.56), pancreas (0.42), and kidney (0.44), all P values < 0.05. These findings indicate altered sialin mRNA expression in the main tissues of male T2D rats and may have implications for future NO-based treatment of T2D.

Physical Activity and Exercise Promote Peroxisome Proliferator-Activated Receptor Gamma Expression in Adipose Tissues of Obese Adults.

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) has recently been studied for its potential influence on the functional response of the human body to exercise. We aimed to investigate the association of habitual physical activity (PA) with PPARγ mRNA level in the visceral and subcutaneous adipose tissues (VAT and SAT) in non-obese and obese non-diabetic adults. Methods: VAT and SAT were obtained from 95 individuals, including 40 non-obese (BMI<30kg/m2) and 55 obese (BMI≥30kg/m2) who underwent elective abdominal surgery (Tehran, Iran, 2012-2015). The assessment of habitual PA was performed by a valid and reliable International PA Questionnaire-long form, and the metabolic equivalent of task (MET) was evaluated. Real-time quantitative reverse transcriptase-PCR evaluated the PPARγ expression in VAT and SAT. Results: PPARγ expression in both VAT (1.18 vs. 0.37 fold change, P<0.001) and SAT (2.07 vs. 0.29 fold change, P=0.004) among obese subjects was higher than the non-obese group. After controlling for age, sex, and total energy in-take, a positive association was found between total METs and PPARγ expression in both VAT and SAT among obese participants (ß=0.22, P=0.007 and ß=0.12, P<0.001, respectively). Among obese participants, there was a direct association between leisure time-related METs with VAT PPARγ expression (ß=0.05, P=0.026). Moreover, in this group, an association was observed between occupation-related METs with PPARγ in both fat tissues (ß=0.11, P=0.002 and ß=0.17, P=0.013, respectively), and household work-related METs with SAT PPARγ (ß=0.21, P=0.011). Conclusion: High PA as an indispensable part of a healthy lifestyle may exert its beneficial effect by regulating PPARγ expression.

Is Habitual Dietary Intake of Fats Associated with Apelin Gene Expression in Visceral and Subcutaneous Adipose Tissues and Its Serum Levels in Obese Adults?

INTRODUCTION: Apelin could be one of the last protective defenses before developing obesity-related disorders, including insulin resistance, type 2 diabetes, and hypertension, which can be modified by dietary intake. The present study investigated the association of habitual intake of total fatty acids (TFAs), saturated-, monounsaturated-, polyunsaturated FAs, n-3, and n-6 FAs with Apelin expression in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). METHODS: We obtained VAT and SAT from 168 participants (64 nonobese and 104 obese) who had undergone open abdominal surgery. Dietary intake information was gathered with a valid and reliable food frequency questionnaire. The mRNA expression of the Apelin gene was analyzed by real-time PCR. RESULTS: Apelin serum levels were increased in the obese subjects compared to the nonobese group (p = 0.016). The SAT and VAT Apelin mRNA levels were significantly elevated in the obese participants compared to the nonobese ones (p < 0.05). Based on BMI status, only obese subjects indicated a positive association between SAT and VAT Apelin expression and TFA intake (p < 0.001). However, this association was observed between SAT and VAT Apelin gene expression and polyunsaturated fatty acid (PUFA) and n-3 FA intakes in both obese and nonobese groups (p < 0.05). CONCLUSION: High Apelin gene expression was associated with TFA intake in obese subjects in both fat tissues. However, habitual intake of PUFA and n-3 FA was associated with Apelin gene expression in obese and nonobese individuals. Our results indicate a determinative role of the quality and quantity of FA intake on adipose tissue.

Metabolomics-A Tool to Find Metabolism of Endocrine Cancer.

Clinical endocrinology entails an understanding of the mechanisms involved in the regulation of tumors that occur in the endocrine system. The exact cause of endocrine cancers remains an enigma, especially when discriminating malignant lesions from benign ones and early diagnosis. In the past few years, the concepts of personalized medicine and metabolomics have gained great popularity in cancer research. In this systematic review, we discussed the clinical metabolomics studies in the diagnosis of endocrine cancers within the last 12 years. Cancer metabolomic studies were largely conducted using nuclear magnetic resonance (NMR) and mass spectrometry (MS) combined with separation techniques such as gas chromatography (GC) and liquid chromatography (LC). Our findings revealed that the majority of the metabolomics studies were conducted on tissue, serum/plasma, and urine samples. Studies most frequently emphasized thyroid cancer, adrenal cancer, and pituitary cancer. Altogether, analytical hyphenated techniques and chemometrics are promising tools in unveiling biomarkers in endocrine cancer and its metabolism disorders.

CpG island status as an epigenetic alteration for NIS promoter in thyroid neoplasms; a cross-sectional study with a systematic review.

BACKGROUND: Gene silence via methylation of the CpG islands is cancer's most common epigenetic modification. Given the highly significant role of NIS in thyroid cancer (TC) differentiation, this cross-sectional study aimed to investigate the DNA methylation pattern in seven CpG islands (CpG1-7 including +846, +918, +929, +947, +953, +955, and +963, respectively) of the NIS promoter in patients diagnosed with papillary (PTC), follicular (FTC), and multinodular goiter (MNG). Additionally, a systematic review of the literature was conducted to compare our results with studies concerning methylation of the NIS gene promoter. METHODS: Thyroid specimens from 64 patients met the eligibility criteria, consisting of 28 PTC, 9 FTC, and 27 benign MNG cases. The mRNA of NIS was tested by qRT-PCR. The bisulfite sequencing PCR (BSP) technique was performed to evaluate the promoter methylation pattern of the NIS gene. Sequencing results were received in chromatograph, FASTA, SEQ, and pdf formats and were analyzed using Chromas. The methylation percentage at each position and for each sample was calculated by mC/(mC+C) formula for all examined CpGs; following that, the methylation percentage was also calculated at each CpG site. Besides, a literature search was conducted without restricting publication dates. Nine studies met the eligibility criteria after removing duplicates, unrelated articles, and reviews. RESULTS: NIS mRNA levels decreased in tumoral tissues of PTC (P = 0.04) and FTC (P = 0.03) patients compared to their matched non-tumoral ones. The methylation of NIS promoter was not common in PTC samples, but it was frequent in FTC (P < 0.05). Significant differences were observed in the methylation levels in the 4th(+ 947), 6th(+ 955), and 7th(+ 963) CpGs sites in the forward strand of NIS promoter between FTC and MNG tissues (76.34 ± 3.12 vs 40.43 ± 8.42, P = 0.004, 69.63 ± 3.03 vs 23.29 ± 6.84, P = 0.001 and 50.33 ± 5.65 vs 24 ± 6.89, P = 0.030, respectively). There was no significant correlation between the expression and methylation status of NIS in PTC and FTC tissues. CONCLUSION: Perturbation in NIS promoter's methylation individually may have a potential utility in differentiating MNG and FTC tissues. The absence of a distinct methylation pattern implies the importance of other epigenetic processes, which may alter the production of NIS mRNA. In addition, according to the reversibility of DNA methylation, it is anticipated that the design of particular targeted demethylation medicines will lead to a novel cancer therapeutic strategy.

The Cross-Talk between Polyphenols and the Target Enzymes Related to Oxidative Stress-Induced Thyroid Cancer.

The most serious hallmark step of carcinogenesis is oxidative stress, which induces cell DNA damage. Although in normal conditions ROS are important second messengers, in pathological conditions such as cancer, due to imbalanced redox enzyme expression, oxidative stress can occur. Recent studies with firmly established evidence suggest an interdependence between oxidative stress and thyroid cancer based on thyroid hormone synthesis. Indeed, a reduced antioxidant defense system might play a part in several steps of progression in thyroid cancer. Based on studies that have been conducted previously, future drug designs for targeting enzymatic ROS sources, as a single agent or in combination, have to be tested. Polyphenols represent the potential for modulating biological events in thyroid cancer, including antioxidative activity. Targeting enzymatic ROS sources, without affecting the physiological redox state, might be an important purpose. As regards the underlying chemopreventive mechanisms of natural compounds that have been discussed in other cancer models, the confirmation of the influence of polyphenols on thyroid cancer is inconclusive and rarely available. Therefore, there is a need for further scientific investigations into the features of the antioxidative effects of polyphenols on thyroid cancer. The current review illustrates the association between some polyphenols and the key enzymes that take place in oxidation reactions in developing thyroid cancer cells. This review gives the main points of the enzymatic ROS sources act and redox signaling in normal physiological or pathological contexts and supplies a survey of the currently available modulators of TPO, LOX, NOX, DUOX, Nrf2, and LPO derived from polyphenols.

Association of miR-34a and miR-143 levels with PPARγ gene expression in adipose tissues of non-diabetic adults.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a promising therapeutic molecule. Epigenetic mechanisms, including non-coding RNAs, regulate the expression level of the PPARγ gene. OBJECTIVE: We aimed to examine the PPARγ expression in non-diabetic individuals in four body mass index (BMI) categories and its association with miR-34a and miR-143 expression. METHODS: Visceral and subcutaneous adipose tissues (VAT and SAT) samples were collected from patients undergoing bariatric or elective open abdominal surgeries. The subjects (mean age: 42±14.8 years) included 18 normal-weight, 19 overweight, 18 obese, and 19 morbidly obese individuals. The RNAs levels were determined by quantitative real-time PCR. RESULTS: The PPARγ expression was significantly upregulated in both adipose depots of the morbidly obese subjects compared to the normal group. SAT PPARγ level was significantly increased in the obese group compared to the normal-weight group (P<0.01); this increase was also significant in the SAT of morbidly obese subjects compared to the overweight cases (P=0.02). Differences in the regulation of PPARγ expression in both SAT and VAT were significant between the four groups (P<0.05). While miR-143 was overexpressed in the SAT of obese and morbidly obese individuals compared to the normal-weight group, the pairwise comparison showed no significant difference in the miR-34a expression of SAT between the four BMI groups (P>0.01). After controlling for the confounding factors, the expression of VAT PPARγ was directly associated with the miR-34a level in the normal-weight group (ß=0.311, P=0.010). A negative association was observed between the VAT PPARγ expression and miR-34a expression in obese cases (ß = - 0.594, P=0.039). CONCLUSION: The results also confirmed the regulatory function of microRNAs in the PPARγ expression and adipogenesis.

The relation of omentin gene expression and glucose homeostasis of visceral and subcutaneous adipose tissues in non-diabetic adults.

BACKGROUND: Adipose tissue (AT) is a passive reservoir for energy storage and an active endocrine organ responsible for synthesizing bioactive molecules called adipokines. Omentin is known as an anti-inflammatory adipokine that can modulate insulin sensitivity. The present study aimed to investigate the relationship between omentin mRNA expression and glucose homeostasis of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in non-diabetic adults. METHODS: VAT and SAT adipose tissues were collected from 137 adults aged ≥ 18 years hospitalized for abdominal surgery. Before surgery, preoperative blood samples were taken from the participants to measure fasting plasma glucose, insulin, and triglyceride. BMI, HOMA-IR, HOMA-B, and QUICKI were calculated. Insulin levels were measured with Mercodia kits using enzyme-linked immunosorbent assay (ELISA). In order to obtain omentin mRNA expression, real-time PCR was performed. RESULTS: Overall, 91 (66.4%) subjects were healthy [without insulin resistance (IR)], and 46 (33.6%) participants were with IR. In healthy and IR subjects, omentin gene expression was 1.04 and 2.32, respectively in VAT, and 3.06 and 1.30, respectively, in SAT (P > 0.05). After controlling for age and BMI, linear regression analysis indicated a significant positive association of SAT omentin expression with insulin concentration (ß = 0.048; 95% CI 0.009, 0.088, P = 0.017) and HOMA-IR (ß = 0.173; 95% CI 0.023, 0.323, P = 0.014). Moreover, a negative association of SAT omentin expression with HOMA-B (ß = - 0.001; 95% CI 0.002, - 0.001, P < 0.001) was observed. CONCLUSION: This study's finding confirms a direct association between IR with omentin mRNA levels in SAT. Besides, the indicator of insulin sensitivity had an inverse association with omentin gene expression in SAT. This aspect of research suggests that omentin secretion from SAT has a strong link with insulin regulation.