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.

Causal effect of serum 25 hydroxyvitamin D concentration on cardioembolic stroke: Evidence from two-sample Mendelian randomization.

BACKGROUND AND AIMS: The putative association between serum 25-hydroxyvitamin D concentration [25(OH)D] and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES. METHODS AND RESULTS: The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Our results unveiled a causal relationship between 25(OH)D and CES using IVW [OR = 0.82, 95% CI: 0.67-0.98, p = 0.037]. Horizontal pleiotropy was not seen [MR-Egger intercept = 0.001; p = 0.792], suggesting an absence of horizontal pleiotropy. Cochrane's Q [Q = 78.71, p-value = 0.924], Rucker's Q [Q = 78.64, p-value = 0.913], and I2 = 0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity. This result remained consistent using different MR methods and sensitivity analyses, including Maximum likelihood [OR = 0.82, 95%CI: 0.67-0.98, p-value = 0.036], Constrained maximum likelihood [OR = 0.76, 95%CI: 0.64-0.90, p-value = 0.002], Debiased inverse-variance weighted [OR = 0.82, 95%CI: 0.68-0.99, p-value = 0.002], MR-PRESSO [OR = 0.82, 95%CI 0.77-0.87, p-value = 0.022], RAPS [OR = 0.82, 95%CI 0.67-0.98, p-value = 0.038], MR-Lasso [OR = 0.82, 95%CI 0.68-0.99, p-value = 0.037]. CONCLUSION: Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.

The effect of Apigenin on glycometabolism and cell death in an anaplastic thyroid cancer cell line.

AIMS AND BACKGROUND: A more pronounced characteristic of cancer cells is the energy dependence on glucose, which mitigated by glucose transporters. The comprehension of the regulatory mechanisms behind the Warburg effect holds promise for developing therapeutic interventions for cancers. Studies are lacking which targeted the GLUTs for treatment of malignancy of thyroid tumors. In our current investigation, we have undertaken this study to determine the potential of Apigenin, plant derived flavonoid in modulating tumor apoptosis by targeting GLUTs expression in SW1736 cell line of anaplastic thyroid carcinoma. MATERIAL METHODS: Flow cytometry with propidium iodide staining was used to determine cell apoptosis. For glucose uptake detection, the "GOD-PAP" enzymatic colorimetric test was used to measure the direct glucose levels inside the cells. To determine the expression of GLUT1 and GLUT3 mRNA in the SW1736 cell line qRT-PCR was employed. Protein levels of GLUT1 and GLUT3 in the SW1736 cell line were detected with western blotting. Also, the scratch wound healing assay was conducted for cell migration. RESULTS: According to qRT-PCR analysis, the levels of GLUT1 and GLUT3 mRNA were lower in the group that received Apigenin relative to the control group. The Apigenin treatment of SW1736 cells decreased protein expression of the GLUT1 and GLUT3 levels in conformity to qRT-PCR. The scratch assays revealed that Apigenin treatment of cancer cell lines inhibited cell migration as compared to control. CONCLUSION: These findings demonstrate the possibility of targeting the glucose facilitators' pathway for making thyroid cancer cells more susceptible to programmed cell death.

Investigating the Effects of Maternal Separation on Hypothalamic-Pituitary-Adrenal Axis and Glucose Homeostasis under Chronic Social Defeat Stress in Young Adult Male Rat Offspring.

INTRODUCTION: Given the suggested metabolic regulatory effects of stress-responsive genes and based on the impacts of early-life stress on HPA axis development, this study aimed to characterize the maternal separation (MS) impact on the communication between glucose metabolism and HPA axis dysregulations under chronic social defeat stress (CSDS). METHODS: During the first 2 weeks of life, male Wistar rats were either exposed to MS or left undisturbed with their mothers (Std). Starting on postnatal day 50, the animals of each group were either left undisturbed in the standard group housing (Con) or underwent CSDS for 3 weeks. There were four groups (n = 10/group): Std-Con, MS-Con, Std-CSDS, and MS-CSDS. RESULTS: Early and/or adult life adversity reduced ß-cell number, muscular FK506-binding protein 51 (FKBP51) content, and BMI in adulthood. The reduction of ß-cell number and BMI in the MS-CSDS rats were more profound than MS-Con group. CSDS either alone or in combination with MS reduced locomotor activity and increased and decreased corticotropin-releasing factor type 1 receptor (CRFR1) content, respectively, in hypothalamus and pancreas. Although, under CSDS, MS intensified HPA axis overactivity and reduced isolated islets' insulin secretion, it could promote resilience to depression symptoms. No differences were observed in hypothalamic Fkbp5 gene DNA methylation and glucose tolerance among groups. CONCLUSION: MS exacerbated HPA axis overactivity and the endocrine pancreas dysfunctions under CSDS. The intensified corticosterone secretion and the diminished content of pancreatic CRFR1 protein could be involved in the reduced ß-cell number and islets' insulin secretion under CSDS. The decreased muscular FKBP51 content might be a homeostatic response to slow down insulin resistance development under chronic stress.

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.

Association of LDL-cholesterol subfractions with cardiovascular disorders: a systematic review.

BACKGROUND: Cardiovascular disorders (CVDs) are the leading cause of death worldwide. This study aimed to evaluate the association between low-density lipoprotein (LDL) subfractions and cardiovascular disorders. METHODS: To ensure the rigor of the systematic review, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. For this systematic review, a comprehensive search strategy was performed in important databases including PubMed, Scopus, Embase, International Statistical Institute (ISI) Web of Science, and google scholar from 2009 to February 2021. The following terms were used for systematic search: low-density lipoprotein, LDL, subfractions, subclasses, nuclear magnetic resonance, NMR, chromatography, high-pressure liquid, HPLC, cardiovascular disease, cerebrovascular, and peripheral vascular disease. Also, for evaluating the risk of bias, the Newcastle-Ottawa scale was employed. RESULTS: At the end of the search process, 33 articles were included in this study. The results of most of the evaluated studies revealed that a higher LDL particle number was consistently associated with increased risk for cardiovascular disease, independent of other lipid measurements. Also, small dense LDL was associated with an increased risk of CVDs. There was no association between LDL subfraction and CVDs in a small number of studies. CONCLUSIONS: Overall, it seems that the evaluation of LDL subclasses can be used as a very suitable biomarker for the assessment and diagnosis of cardiovascular diseases. However, further studies are required to identify the mechanisms involved.

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.

Recent developments in cell shipping methods.

As opposed to remarkable advances in the cell therapy industry, research reveal inexplicable difficulties associated with preserving and post-thawing cell death. Post cryopreservation apoptosis is a common occurrence that has attracted the attention of scientists to use apoptosis inhibitors. Transporting cells without compromising their survival and function is crucial for any experimental cell-based therapy. Preservation of cells allows the safe transportation of cells between distances and improves quality control testing in clinical and research applications. The vitality of transported cells is used to evaluate the efficacy of transportation strategies. For many decades, the conventional global methods of cell transfer were not only expensive but also challenging and had adverse effects. The first determination of some projects is optimizing cell survival after cryopreservation. The new generation of cryopreservation science wishes to find appropriate and alternative methods for cell transportation to ship viable cells at an ambient temperature without dry ice or in media-filled flasks. The diversity of cell therapies demands new cell shipping methodologies and cryoprotectants. In this review, we tried to summarize novel improved cryopreservation methods and alternatives to cryopreservation with safe and viable cell shipping at ambient temperature, including dry preservation, hypothermic preservation, gel-based methods, encapsulation methods, fibrin microbeads, and osmolyte solution compositions.

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.

Serum adiponectin and cortisol levels are not affected by studied ADIPOQ gene variants: Tehran lipid and glucose study.

BACKGROUND: Obesity is a major public health concern in developed and even developing countries worldwide. Adiponectin is a protein secreted by adipose tissue that modulates many metabolic processes and plays a vital role in obesity. This study aimed to determine the association of four variants of the ADIPOQ gene with serum adiponectin, cortisol levels and obesity status. METHODS: This case-control study was performed on 164 obese individuals compared by 156 control from the Tehran Lipid and Glucose Study (TLGS). Standard procedures obtained anthropometric measures and metabolic parameters. Cortisol and adiponectin levels were measured by ELISA method. rs1501299, rs266729, rs17300539, and rs17366743 on the ADIPOQ gene were genotyped using the PCR-RFLP. The correlation between adiponectin gene SNPs and obesity were calculated by Additive, dominant, and recessive genetic models. Pearson's or Spearman's found correlations between adiponectin levels and metabolic and anthropometric variables. Data were analyzed using SPSS software Version 20. RESULTS: Adiponectin and cortisol levels were significantly lower in obese subjects compared to the control group (p < 0.05). There was a significant negative correlation between serum adiponectin level and BMI, waist circumference (WC), waist-hip ratio, hip circumference (HC), Fasting blood sugar (FBS) Triglyceride (TG), Total cholesterol (TC), Systolic blood pressure (SBP), Diastolic blood pressure (DBP) (r = - 0.147, r = - 0.324, r = 0.371, r = - 0.179, r = - 0.299, r = - 0.277, r = - 0.041, r = - 0.134, and r = - 0.149, respectively). A positive correlation was found between adiponectin and high-density lipoprotein cholesterol (HDL-C) (r = 0.29), but no significant correlations were found between adiponectin and Low-density lipoprotein cholesterol(LDL-C) and cortisol. ADIPOQ variant rs1501299 was significantly associated with cortisol levels in subjects with BMI ≥ 25 (P-value =0.039). CONCLUSIONS: Adiponectin and cortisol levels were associated with obesity. No ADIPOQ gene variants and haplotypes were associated with cortisol, Adiponectin, and obesity.

Iodine Status of Preterm Infants Born in an Area of Iodine Sufficiency: Are They at Risk of Iodine Deficiency?

OBJECTIVE: To the assess the iodine status of preterm infants born in an area of iodine sufficiency using the urinary iodine concentration (UIC) and thyroid-stimulating hormone (TSH) levels and compare these values across different feeding practices during the first 7 days of life. METHODS: In this cross-sectional study, 88 preterm infants born at 30 to 34 weeks of gestation and admitted to the neonatal intensive care unit of a referral hospital in Tehran (Iran) were included. The infant UIC and TSH levels and breast milk iodine concentration in mothers who were exclusively breastfeeding were measured. RESULTS: Median (interquartile range [IQR]) UIC and TSH levels in the study population were 81 (39-189) µg/L and 1.60 (0.80-2.85) mIU/L, respectively. When preterm infants were stratified by the type of feeding, the median (IQR) UICs were 64 (42-126) µg/L in parenteral nutrition, 125 (41-195) µg/L in exclusively breastfeeding, 57 (28-123) µg/L in formula feeding, and 45 (35-132) µg/L in mixed feeding, with no statistically significant difference between the groups (P = .31). The median (IQR) breast milk iodine concentration was 271 (177-521) µg/L in preterm infants exclusively fed their mothers' own milk. There was no significant difference in the proportion of the TSH levels of >5 mIU/L between preterm infants who received enteral and parenteral nutrition (P = .27). CONCLUSION: Preterm infants are at risk of iodine deficiency even in an area where the general population has adequate iodine. Only the preterm infants who received exclusively their mothers' own milk had marginally adequate iodine status. Further studies are warranted to determine the necessity of iodine supplementation for this vulnerable group.

The interactive effect of vitamin D3 supplementation and vitamin D receptor polymorphisms on weight and body composition in overweight women with hypovitaminosis D: a randomized, double-blind, placebo-controlled clinical trial.

Different responses to vitamin D supplementation may be due to genes involved in vitamin D metabolism, including the vitamin D receptor (VDR) gene. The present study aimed to determine the interactive effect of vitamin D supplementation and VDR polymorphisms, including FokI (rs2228570) and BsmI (1544410) on weight and body composition in overweight women with hypovitaminosis D. This study comprised two phases: a double-blind, randomized and a before-after clinical trial. In the first phase, 50 healthy overweight women aged 20-45 years with hypovitaminosis D were randomly categorized into intervention and control groups and were given 50 000 IU/w vitamin D3 or placebo for 12 weeks. In the second phase, 75 women received 50 000 IU/w of vitamin D3 for 12 weeks. All variables were measured at baseline and after 12 weeks. Circulating 25(OH)D was measured using an ELISA kit. Anthropometric indices were calculated according to standard protocol (WHO-TRH-854). Body composition was determined using the body impedance analysis method. The VDR polymorphisms were detected using the PCR sequence. Supplementation resulted in a significant increase in the level of 25(OH)D in the intervention group but did not affect the anthropometric profile of the subjects. When considering FokI genotypes, carriers of the FF genotype had higher fat mass reduction than carriers of Ff + ff genotypes.

Umbilical cord blood concentration of connecting peptide (C-peptide) and pregnancy outcomes.

BACKGROUND: C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration. METHODS: For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration. RESULTS: In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 - 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 - 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 - 0.42, p < 0.001; and Coef.= 0.34, 95% CI: 0.06 - 0.63, p = 0.02, respectively). CONCLUSION: UC blood concentration of C-peptide is significantly associated with the incidence of maternal GDM and neonatal macrosomia. Using stratification for maternal BMI and gestational weight gain (GWG) and investigating molecular markers like Leptin and IGF-1 in the future might lay the ground to better understand the link between metabolic disturbances of pregnancy and UC blood C-peptide concentration.

Maternal serum adiponectin and leptin levels and their gene expression, postpartum body mass index, and breastfeeding duration based on mode of delivery: A prospective study.

BACKGROUND: Adipokines are involved in inflammatory responses, associated with body mass index whose concentrations may change in response to inflammatory conditions, including surgery and delivery. We examined adiponectin and leptin levels and their gene expression at birth, body mass index, and breastfeeding duration at 24 months postpartum according to mode of delivery. METHODS: In this study, 90 normal pregnant women were investigated. Blood samples were collected after delivery. Serum levels and gene expression of adiponectin and leptin were evaluated. Body mass index and breastfeeding duration were calculated at 24 months postpartum. Data were analyzed using SPSS-16 and p < 0.05 was considered as significant. RESULTS: Serum leptin level was significantly higher in vaginal delivery than in cesarean section (p = 0.033). No significant difference was found between two groups regarding adiponectin level and gene expression, while leptin gene expression was significantly higher in cesarean (p = 0.005). Postpartum body mass index did not differ between the two groups (p = 0.14). On the other hand, postpartum body mass index was significantly higher than the equivalent prepregnancy index in both groups (p < 0.001) and was associated with serum leptin and adiponectin in vaginal delivery (r = 0.46, p = 0.001, and r = -0.3, p = 0.04, respectively). The duration of breastfeeding was longer in vaginal delivery (p = 0.008). CONCLUSION: Cesarean section was associated with lower maternal leptin levels and shorter breast-feeding duration compared to vaginal delivery. Leptin gene expression was significantly higher in cesarean section than in vaginal delivery. Postpartum body mass index, adiponectin level, and gene expression did not differ between the two groups.

Elevated miR-143 and miR-34a gene expression in human visceral adipose tissue are associated with insulin resistance in non-diabetic adults: a cross-sectional study.

OBJECTIVE: We aimed to evaluate the association of miR-143 and miR-34a expression in human visceral (VAT) and subcutaneous (SAT) adipose tissues with insulin resistance (IR). METHODS: VAT and SAT were obtained from 176 participants without diabetes. miR-143 and miR-34a expressions in VAT and SAT were measured using qRT-PCR. Fasting serum insulin and glucose concentration, homeostatic model assessment of IR index (HOMA-IR) and ß-cell function (HOMA-B), and quantitative insulin-sensitivity check index (QUICKI) were calculated. RESULTS: After adjustment for age, sex and body mass index (BMI), VAT miR-143 expression was positively associated with fasting plasma glucose (FPG), insulin, and HOMA-IR, and negatively associated with HOMA-B and QUICKI. miR-34a expression in VAT was directly associated with FPG, insulin, and HOMA-IR and negatively associated with QUICKI. In SAT, miR-34a expression was positively associated with insulin and negatively associated with QUICKI. The interaction terms of HOMA-IR and BMI categories were significant for both miR gene expressions in VAT. After stratifying participants based on BMI, the association of miR-143 and miR-34a expressions in VAT with IR indices remained significant only in obese patients. CONCLUSION: miR-143 and miR-34a expressions in VAT were independent predictors of IR in people without diabetes, and that this association was conditional on the degree of obesity. LEVEL OF EVIDENCE: Level of evidence III, cross-sectional analytic study.

Interplay between SARS-CoV-2 and human long non-coding RNAs.

The long non-coding RNAs (lncRNAs) play a critical regulatory role in the host response to the viral infection. However, little is understood about the transcriptome architecture, especially lncRNAs pattern during the SARS-CoV-2 infection. In the present study, using publicly available RNA sequencing data of bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) samples from COVID-19 patients and healthy individuals, three interesting findings highlighted: (a) More than half of the interactions between lncRNAs-PCGs of BALF samples established by three trans-acting lncRNAs (HOTAIRM1, PVT1 and AL392172.1), which also exhibited the high affinity for binding to the SARS-CoV-2 genome, suggesting the major regulatory role of these lncRNAs during the SARS-CoV-2 infection. (b) lncRNAs of MALAT1 and NEAT1 are possibly contributed to the inflammation development in the SARS-CoV-2 infected cells. (c) In contrast to the 3' part of the SARS-CoV-2 genome, the 5' part can interact with many human lncRNAs. Therefore, the mRNA-based vaccines will not show any side effects because of the off-label interactions with the human lncRNAs. Overall, the putative functionalities of lncRNAs can be promising to design the non-coding RNA-based drugs and to inspect the efficiency of vaccines to overcome the current pandemic.

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 different pathologic subtypes of growth hormone producing pituitary adenoma and remission in acromegaly patients: a retrospective cohort study.

BACKGROUND: Regarding the inconclusive results of previous investigations, this study aimed to determine the association between pathology, as a possible predictor, with remission outcomes, to know the role of pathology in the personalized decision making in acromegaly patients. METHODS: A retrospective cohort study was performed on the consecutive surgeries for growth hormone (GH) producing pituitary adenomas from February 2015 to January 2021. Seventy-one patients were assessed for granulation patterns and prolactin co-expression as dual staining adenomas. The role of pathology and some other predictors on surgical remission was evaluated using logistic regression models. RESULTS: Among 71 included patients, 34 (47.9%) patients had densely granulated (DG), 14 (19.7%) had sparsely granulated (SG), 23 (32.4%) had dual staining pituitary adenomas. The remission rate was about 62.5% in the patients with SG and DG adenomas named single staining and 52.2% in dual staining groups. Postoperative remission was 1.53-folds higher in the single staining adenomas than dual staining-one (non-significant). The remission rate was doubled in DG group compared to two other groups (non-significant). By adjusting different predictors, cavernous sinus invasion and one-day postoperative GH levels decreased remission rate by 91% (95% CI: 0.01-0.67; p = 0.015) and 64% (95% CI: 0.19-0.69; p < 0.001), respectively. Responses to the medications were not significantly different among three groups. CONCLUSION: Various pathological subtypes of pituitary adenomas do not appear to have a predictive role in estimating remission outcomes. Cavernous sinus invasion followed by one-day postoperative GH is the strongest parameter to predict biochemical remission.

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.

Gym and home-based combined training in men with primary hypertension: are they equally effective on functional fitness profile, body composition components, and biochemical parameters of hypertension?

OBJECTIVE: This study aimed to compare the effects of 10 weeks of gym versus home-based combined training on the functional fitness, body composition, and biochemical parameters of hypertension in primary hypertensive men. METHODS: Forty-six patients (age 48 ± 9 years, BMI 30 ± 4 kg/m2) assigned into three groups: a gym-based combined training (GBCTr: n = 16; resistance at 60-80% of 1RM, using pin-loaded resistance equipment, aerobic at 40-60% HRR, and stretching), home-based combined training (HBCTr: n = 15; resistance at 12-15 RPE, using an elastic exercise band, aerobic at 40-60% HRR, and stretching), and control (CTR, n = 15). RESULTS: Following GBCTr and HBCTr, the functional aerobic capacity (P = .005 and P = .004, respectively), flexibility (P = .01 and P = .004, respectively), and lower limb muscle strength (P = .01 and P = .02, respectively) was increased significantly compared with the CTR group. The body weight (P = .02), body mass index (P = .008), hip circumference (P = .02), and nitric oxide level in GBCTr and HBCTr group (P = .002 and P = .02, respectively) was decreased significantly compared with the CTR group. No significant changes found in the plasma levels of NADPH oxidase 5, thioredoxin-2, thioredoxin reductase-2, and resting blood pressure after GBCTr and HBCTr compared with the CTR group. CONCLUSION: These results suggest that in hypertensive men, HBCTr equally to GBCTr improved functional fitness and body composition remarkably without necessarily reducing resting blood pressure. Therefore, they can be advisable substitutes for gaining health benefits.