THE POSSIBLE ROLE OF TRACE ELEMENTS IN THYROID HYPERTROPHIC AND ADENOMATOUS TRANSFORMATION

Background: Thyroid benign nodules (TBNs) are the most common diseases of this endocrine gland and are common worldwide. Among TBNs the colloid goiter (CG) and thyroid adenoma (TA) are very frequentdiseases. Evaluation of variant of TBNs is clinically important for subsequent therapeutic interventions, as well as for a clearer understanding the etiology of these disorders. The aim of this exploratory study was to examine differences in the content offifty trace elements (TE) in CG and TA tissues. Methods: Thyroid tissue levels of TE have prospectively evaluated in 46 patients with CG and 19 patients with TA. Measurements have performed using a combination of non-destructive and destructive methods: instrumental neutron activation analysis with high resolution spectrometry of long-lived radionuclides (INAA-LLR) and inductively coupled plasma mass spectrometry (ICPMS), respectively. Tissue samples were divided into two portions. One was used for morphological study while the other was intended for TE analysis. Results: It was observed that in both CG and TA tissues the contents of Ag, Al, Cr, Hg, Mn, Th, and Zn increased, whereas the levels of Au, Be, Cs, Pb, Rb, Sb, Sc, Th, Yb, and Zr were unchanged in comparison with normal thyroid tissue. No differences were found between the TE contents of CG and TA. Conclusions: From results obtained, it was possible to conclude that the common characteristics of CG and TA tissue samples were of a high level of Ag, Al, Cr, Hg, Mn, Th, and Zn in comparison with normal thyroid and, therefore, these TE could be involved in etiology and pathogenesis of thyroid disorders such as CG and TA. Peer Review History: Received: 12 November 2021; Revised: 15 December; Accepted: 31 December, Available online: 15 January 2022 Academic Editor: Ahmad Najib, Universitas Muslim Indonesia, Indonesia, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Prof. Dr. Hassan A.H. Al-Shamahy, Sana'a University, Yemen, [email protected] Rima Benatoui, Laboratory of Applied Neuroendocrinology, Department of Biology, Faculty of Science, Badji Mokhtar University Annaba, BP12 E L Hadjar–Algeria, [email protected] Similar Articles: COMPARISON OF LEVELS OF TWENTY CHEMICAL ELEMENTS IN NORMAL THYROID TISSUE AND HYPERTROPHIC THYROID TISSUE

Comparison of Chemical Element Contents in Thyroid Goiter, Adenoma, and Thyroiditis investigated using Neutron Activation Analysis

Thyroid benign nodules (TBNs) are the most common lesions of this endocrine gland. Among TBNs the colloid goiter (CG), thyroiditis (T), and thyroid adenoma (TA) are the most frequent diseases. An evaluation of the variant of TBNs is clinically important for subsequent therapeutic interventions, as well as for more clear understanding the etiology of these disorders. The aim of this exploratory study was to examine differences in the content of bromine (Br), calcium (Ca), chlorine (Cl), iodine (I), potassium (K), magnesium (Mg), manganese (Mn), and sodium (Na) in tissues of CG, TA, and T. Thyroid tissue levels of eight chemical elements (ChE) were prospectively evaluated in 46 patients with CG, 19 patients with TA, and 12 patients with T. Measurements were performed using non-destructive instrumental neutron activation analysis with high resolution spectrometry of short-lived radionuclides. Tissue samples were divided into two portions. One was used for morphological study while the other was intended for ChE analysis. It was observed that in CG, TA and T tissues content of Br was significantly higher, while level of I was lower than in normal thyroid tissue. I accumulation in T tissue was lower than in normal thyroid and CG. Abnormal increase in Br level and decrease in I level in all TBNs might demonstrate an involvement of these ChE in etiology and pathogenesis of TBNs. It was suosed that great losses of I in thyroid with T, in contract to little reduced levels of I content in thyroid with CG and TA, could possibly be explored for differencial diagnosis of T.

Ferroptosis-related gene signature predicts the prognosis of papillary thyroid carcinoma

Background Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC), accounting for more than 80% of all cases. Ferroptosis is a novel iron-dependent and Reactive oxygen species (ROS) reliant type of cell death which is distinct from the apoptosis, necroptosis and pyroptosis. Considerable studies have demonstrated that ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in PTC remains unclear. This study aims at exploring the expression of ferroptosis-related genes (FRG) and their prognostic values in PTC. Methods A ferroptosis-related gene signature was constructed using lasso regression analysis through the PTC datasets of the Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the bioinformatics functions of significantly different genes (SDG) of ferroptosis. Additionally, the correlations of ferroptosis and immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT database. Finally, SDG were test in clinical PTC specimens and normal thyroid tissues. Results LASSO regression model was utilized to establish a novel FRG signature with 10 genes (ANGPTL7, CDKN2A, DPP4, DRD4, ISCU, PGD, SRXN1, TF, TFRC, TXNRD1) to predicts the prognosis of PTC, and the patients were separated into high-risk and low-risk groups by the risk score. The high-risk group had poorer survival than the low-risk group (p < 0.001). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Multivariate regression analysis identified the prognostic signature-based risk score was an independent prognostic indicator for PTC. The functional roles of the DEGs in the TGCA PTC cohort were explored using GO enrichment and KEGG pathway analyses. Immune related analysis demonstrated that the most types of immune cells and immunological function in the high-risk group were significant different with those in the low-risk group. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) verified the SDG have differences in expression between tumor tissue and normal thyroid tissue. In addition, cell experiments were conducted to observe the changes in cell morphology and expression of signature’s genes with the influence of ferroptosis induced by sorafenib. Conclusions We identified differently expressed FRG that may involve in PTC. A ferroptosis-related gene signature has significant values in predicting the patients’ prognoses and targeting ferroptosis may be an alternative for PTC’s therapy.

A Case of Neonatal Thyrotoxicosis with Cardiac Insufficiency

Neonatal thyrotoxicosis is rare and most of the cases are secondary to maternal Graves’ disease. It is usually transient, but can be associated with significant morbidity and mortality if not recognized promptly and treated adequately. Neonates born to mothers treated with antithyroid drugs or those who receive maternal thyroid blocking antibodies may exhibit normal thyroid function or even hypothyroidism at birth. Since there may not be any obvious symptoms of hyperthyroidism at birth, it may be overlooked. Therefore, such neonates should be evaluated properly and monitored regularly to prevent serious complications of hyperthyroidism. We report a case of a 21-day-old male infant who developed thyrotoxicosis with dyspnea, irritability, tachycardia, and cardiac insufficiency. He was born to a mother who was treated for Graves’ disease with antithyroid drugs during pregnancy. We have also discussed the importance of careful examination and monitoring to prevent the development of clinical hyperthyroidism.

Feasibility of Quantitative Tissue Characterization Using Novel Parameters Extracted From Photoacoustic Power Spectrum Considering Multiple Absorbers

Frequency domain analysis of radio frequency signal is performed to differentiate between different tissue categories in terms of spectral parameters. However, due to complex relationship between the absorber size and spectral parameters, they cannot be used for quantitative tissue characterization. In an earlier study, we showed that using linear relationship between absorber size and two new spectral parameters namely number of lobes and average lobe width, absorber size can be successfully recovered from photoacoustic signal generated by single absorber. As actual biological tissue contains multiple absorbers, in this study we extended the application of these two new spectral parameters for computing absorber size from signals generated by multiple PA absorbers. We revisited our analytical model to establish two new linear relationships between the absorber radius and number of lobes as well as average lobe width considering multiple absorbers with bandlimited acquisition. A simulation study was performed to validate these linear relationships. A retrospective ex vivo study, in which the spectral parameters were computed using multiwavelength photoacoustic signals, was performed with freshly exercised thyroid specimens from 38 actual human patients undergoing thyroidectomy after having a diagnosis of suspected thyroid lesions. From statistical analysis it is shown that both the parameters were significantly different between malignant and non-malignant thyroid and malignant and normal thyroid tissue. Performance of the supervised classification with the computed spectral parameters showed that the extracted parameters could be successfully used to differentiate malignant thyroid tissue from normal thyroid tissue with reasonable degree of accuracy.

COMPARISON BETWEEN BROMINE, CALCIUM, CHLORINE, IODINE, POTASSIUM, MAGNESIUM, MANGANESE, AND SODIUM CONTENTS IN MACRO- AND MICRO-FOLLICULAR COLLOID GOITER

Objective: Colloid nodular goiter (CNG) is the most common disease of the thyroid, even in non-endemic regions, but the etiology of CNG is unclear. It is known that not merely iodine (I) but other chemical elements (ChE) are involved in goitrogenesis. The current study was performed to clarify the preferential accumulation of some ChE either in the colloid or in cells of the thyroid gland. Methods: Eight ChE: Bromine, calcium, chlorine (Cl), I, potassium, magnesium, manganese, and sodium (Na) in the thyroid tissues with diagnosed CNG were prospectively evaluated in 16 patients with macrofollicular CNG and 13 patients with microfollicular CNG. The control group included thyroid tissue samples from 105 healthy individuals. Measurements were conducted using non-destructive instrumental neutron activation analysis with high-resolution spectrometry of short-lived radionuclides. Results: It was found that in macrofollicular CNG, the mass fraction of Cl and Na was 2.57 and 1.82 times, respectively, higher than in tissues of the normal thyroid. In microfollicular CNG, the mass fraction of I was 59% lower, whereas the mass fraction of Na was 67% higher than in tissues of the normal thyroid. The level of I in macrofollicular goiter was 2.08 times higher than in microfollicular goiter Conclusion: There are substantial changes in ChE contents in the goitrous transformed tissue of the thyroid, which depend on the histology of the goiter.

Ferroptosis-Related Gene Signature Predicts The Prognosis of Papillary Thyroid Carcinoma

Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC), accounting for more than 80% of all cases. Ferroptosis is a novel iron-dependent and Reactive oxygen species (ROS) reliant type of cell death which is distinct from the apoptosis, necroptosis and pyroptosis. Considerable studies have demonstrated that ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in PTC remains unclear. This study aims at exploring the expression of ferroptosis-related genes (FRG) and their prognostic values in PTC. Methods: A ferroptosis-related gene signature was constructed using lasso regression analysis through the PTC datasets of the Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the bioinformatics functions of significantly different genes (SDG) of ferroptosis. Additionally, the correlations of ferroptosis and immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT database. Finally, SDG were test in clinical PTC specimens and normal thyroid tissues. Results: LASSO regression model was utilized to establish a novel FRG signature with 10 genes (ANGPTL7, CDKN2A, DPP4, DRD4, ISCU, PGD, SRXN1, TF, TFRC, TXNRD1) to predicts the prognosis of PTC, and the patients were separated into high-risk and low-risk groups by the risk score. The high-risk group had poorer survival than the low-risk group(p<0.001). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Multivariate regression analysis identified the prognostic signature-based risk score was an independent prognostic indicator for PTC. The functional roles of the DEGs in the TGCA PTC cohort were explored using GO enrichment and KEGG pathway analyses. Immune related analysis demonstrated that the most types of immune cells and immunological function in the high-risk group were significant different with those in the low-risk group. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) verified the SDG have differences in expression between tumor tissue and normal thyroid tissue. Conclusions: We identified differently expressed FRG that may involve in PTC. A ferroptosis-related gene signature has significant values in predicting the patients’ prognoses and targeting ferroptosis may be an alternative for PTC’s therapy.

Identification of Biomarkers Related To The Diagnosis And Prognosis of Thyroid Cancer Through Bioinformatics Analysis

Background: Thyroid cancer is the most common malignant tumor of the head and neck. In recent years, the incidence of thyroid cancer (THCA) worldwide has rapidly increased and shows a trend in the younger generation. This study attempted to screen key genes and potential prognostic biomarkers for thyroid cancer using bioinformatics analysis.Methods: This study attempted to screen key genes and potential prognostic biomarkers for thyroid cancer using bioinformatics analysis. 101 cases of thyroid cancer and 78 cases of normal thyroid tissue were collected from three Gene Expression Omnibus (GEO) databases, then we identified the differentially expressed genes (DEGs) and conducted downstream analyses. Moreover, we screened hub genes by constructing a protein‐protein interaction (PPI) network. Finally, we assessed the expression level of hub genes in thyroid cancer tissue and its normal tissue using GEPIA and qRT-PCR respectively. Results: 159 upregulated and 251 downregulated genes were determined after gene integration of these three GEO data sets. Through PPI analysis, we consider the top 20 DEGs with high connectivity as the hub genes of THCA. After that, this study verified 20 central genes through the GEPIA database and found that only four hub genes (TOP2A, FN1, TIMP1, and MMP9) had significantly higher expression levels in thyroid cancer tissues than in normal thyroid tissues. We further analyzed the correlation between these four hub genes and the prognosis of patients with thyroid cancer, which suggests that FN1, MMP9, TIMP1 help assess the prognosis of patients with thyroid cancer. We performed GSEA analysis on these 4 hub genes simultaneously, found that the high expression of these 4 hub genes enriched the "cell cycle." Subsequently, we collected thyroid cancer tissue specimens, verified these four hub gene expression levels by RT-PCR, and found that only FN1 and TIMP1 genes in thyroid cancer tissues had significantly higher mRNA levels than normal tissues. Conclusions: Our research has identified 20 hub genes that may be related to the occurrence and development of thyroid cancer through multiple gene expression profile data sets and a series of comprehensive bioinformatics analyses. Further database and tissue validation analysis revealed that only 2 hub genes may be considered as potential prognostic biomarkers, including FN1 and TIMP1. In addition, these two hub genes are involved in the cell cycle, suggesting that they may play a role in the occurrence and development of thyroid cancer.

Relationship of Trimester-Specific Maternal Thyroid Function With Gestational Weight Gain And Birth Weight In Pregnant Women With Normal Thyroid Autoimmunity

Background: Gestational weight gain (GWG) and birth weight are important indicators of maternal and infant health outcomes. Thyroid function may affect body composition and fetal growth during pregnancy. So far, on the premise of excluding thyroid autoimmunity interference, the correlation of thyroid function in different pregnancy with neonatal birth weight and maternal weight gain is still controversial. Methods: This study used data from a prospective birth cohort in Shanghai, China. Serum concentration of TSH, total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb) were determined using chemiluminescence assay. Maternal GWG and neonatal sex-specific birth weight-for-gestational age Z-score was calculated.Results: Subjects with a higher BMI before pregnancy turned to have a lower GWG and an infant with a higher birth weight. GWG was negatively associated with maternal FT4 at the first and third trimester (p<0.05), and TT4 at the third trimester (p<0.05). GWG was positively associated with maternal FT3 at the second trimester (p<0.05). Lower birth weight Z-score were associated with higher FT4 at the second and third trimester (p<0.05), and higher TT4 at the second trimester (p<0.05). Conclusions: In the general pregnant population with normal thyroid autoimmunity, higher maternal FT4 and TT4 and lower FT3 are associated with less GWG. Higher maternal FT4 and TT4 have an infant with lower birth weight.