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.

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.

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.

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 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.

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

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 ß-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 (STZß = 0.208, P = 0.037) and subcutaneous (STZß = 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 (STZß = 0.227, P = 0.023; STZß = 0.346, P < 0.001, respectively) and subcutaneous (STZß = 0.227, P = 0.026; STZß = 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.

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

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 (ß = 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.

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

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.

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

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.

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

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.

Alteration in follistatin gene expression detected in prenatally androgenized rats.

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.

Reliability and validity of the Iranian version of the QAPACE in adolescents.

PURPOSE: The aim of this study was to determine the reliability and validity of the Iranian version of the Quantification de l'Activite Physique en Altitude Chez les Enfants (QAPACE) in adolescents. METHODS: After linguistic validation, the Iranian version of the QAPACE was completed by 359 (52.4 % girls) schoolchildren, aged 15-18 years. Test-retest reliability of the questionnaire was determined by intraclass correlation coefficients (ICCs). For validation purposes, two methods were used for (1) the correlation between VO2peak and the DEE and (2) known-group validity, which was examined by comparing the normal weight adolescents and those who were overweight/obese. RESULTS: ICCs for test-retest ranged from 0.79 to 0.98. The mean scores in test-retest surveys for total score and all of the subscores were significant (p < 0.05). Sex-specific analysis showed a significant correlation between VO2peak and DEE over 12-month, school, and vacation periods in girls (p < 0.05). The mean values for all activities except for transportation, other activities in school, personal artistic activities, sport competition, and home activities were significantly lower in overweight/obese group than normal group. CONCLUSION: Our results support the initial reliability and validity of the Iranian version of QAPACE as a daily physical activity measure in adolescents.

The age effect on the association between the scavenger receptor class B type I (SR-BI) polymorphism and HDL-C level: Tehran Lipid and Glucose Study.

INTRODUCTION: The scavenger receptor class B type I (SR-BI) is a key component in the reverse cholesterol transportation. The aim of this study was to assess the association between exon1 (G → A) polymorphism of SR-BI gene and lipid profiles among the Tehran Lipid and Glucose Study (TLGS) population. MATERIALS AND METHODS: This cross-sectional study included 774 adults (322 males and 452 females) aged 20-70 years who were randomly selected from among TLGS population. Anthropometrical and biochemical variables for participants were measured. Selected SR-BI gene polymorphism was determined with restriction fragment length polymorphism, via Alu restriction enzyme. RESULTS: Minor allele frequency for SR-BI polymorphism in the selected population was 0.159. Allele frequencies were in conformity with Hardy-Weinberg equilibrium. Association between (G → A) SR-BI polymorphism and high density lipoprotein cholesterol (HDL-C) and HDL3 was significant only after adjustment for age as a potential covariate (p = 0.046, 0.041, respectively); however, the results did not improve after adjustment for sex. DISCUSSION: The result of this study confirms the role of age as a potential confounder which could modify the association between the SR-BI single nucleotide polymorphism and HDL-C level.

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.

Insulin resistance-related circulating predictive markers in the metabolic syndrome: a systematic review in the Iranian population.

Background: Specific biomarkers for metabolic syndrome (MetS) may improve diagnostic specificity for clinical information. One of the main pathophysiological mechanisms of MetS is insulin resistance (IR). This systematic review aimed to summarize IR-related biomarkers that predict MetS and have been investigated in Iranian populations. Methods: An electronic literature search was done using the PubMed and Scopus databases up to June 2022. The risk of bias was assessed for the selected articles using the instrument suggested by the Joanna Briggs Institute (JBI). This systematic review protocol was registered with PROSPERO (registration number CRD42022372415). Results: Among the reviewed articles, 46 studies investigated the association between IR biomarkers and MetS in the Iranian population. The selected studies were published between 2009 and 2022, with the majority being conducted on adults and seven on children and adolescents. The adult treatment panel III (ATP III) was the most commonly used criteria to define MetS. At least four studies were conducted for each IR biomarker, with LDL-C being the most frequently evaluated biomarker. Some studies have assessed the diagnostic potency of markers using the area under the curve (AUC) with sensitivity, specificity, and an optimal cut-off value. Among the reported values, lipid ratios and the difference between non-HDL-C and LDL-C levels showed the highest AUCs (≥ 0.80) for predicting MetS. Conclusions: Considering the findings of the reviewed studies, fasting insulin, HOMA-IR, leptin, HbA1c, and visfatin levels were positively associated with MetS, whereas adiponectin and ghrelin levels were negatively correlated with this syndrome. Among the investigated IR biomarkers, the association between adiponectin levels and components of MetS was well established. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01347-6.

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.

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.

Energy and macronutrient intake heritability: A systematic review and meta-analysis of twin and family-based studies.

BACKGROUND/AIMS: The current meta-analysis aimed to examine the heritability and familial resemblance of dietary intakes, including energy and macronutrients in both twin and family-based studies. METHODS: The online literature databases, including PubMed, Scopus, and Web of Science were searched comprehensively until 2023 to identify the relevant studies. The heritability index in family studies was h2 and the heritability indices for twin studies were h2, A2, and E2. Three weighted methods were used to calculate the mean and SE of heritability dietary intakes. RESULTS: Eighteen papers including 8 studies on familial population and 12 for twin population studies were included in the present meta-analysis. The heritability of dietary intakes in twin studies (range of pooled estimated h2, A2, and E2 was 30-55%, 14-42%, and 52-79%, respectively) was higher than family studies (range of pooled estimated h2 = 16-39%). In family studies, the highest and lowest heritability for various nutrients was observed for the fat (%Kcal) (h2 range:36-38%) and carbohydrate in g (h2 range:16-18%), respectively. In twin studies, based on mean h2, the highest and lowest heritability for various nutrients was reported for the fat (%Kcal) (h2 range:49-55%) and protein intake in g (h2 range:30-35%), respectively. Also, based on the mean of A2, the highest and lowest heritability was observed for carbohydrates (% Kcal) (A2 range:42-42%), and protein (% Kcal) (A2 range:14-16%), respectively. Furthermore, in twin studies, the highest and lowest mean of E2 was shown for saturated fats (E2 range:74-79%) and energy intake (E2 range:52-57%), respectively. CONCLUSION: Our analysis indicated that both environmental factors and genetics have noticeable contributions in determining the heritability of dietary intakes. Also, we observed higher heritability in twins compared to family studies.

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.

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.