Disrupted gut microecology after high-dose 131I therapy and radioprotective effects of arachidonic acid supplementation.

BACKGROUND: Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment. METHODS: A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses. RESULTS: 131I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1. CONCLUSION: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.

Body composition changes in patients with differentiated thyroid cancer after iodine-131 treatment and short-term levothyroxine replacement and suppression therapy.

PURPOSE: The purposes of this study were to assess the changes in body composition in patients who underwent thyroidectomy due to differentiated thyroid cancer (DTC) after radioactive iodine therapy (RAI) and short-term levothyroxine (LT4) supplementation and to explore the correlations between body composition distribution and corresponding blood indices. METHODS: Fifty-seven thyroidectomized DTC patients were included. Serum was tested for several biochemical indices of thyroid function, lipids, and bone metabolism, and body composition parameters were measured via dual-energy X-ray absorptiometry before and 4-6 weeks after RAI and LT4 supplementation. RESULTS: The body composition of DTC patients changed after RAI. Fat mass in all parts of the body decreased (range of relative change (RRC) -12.97--2.80%). Bone mineral content (BMC) increased throughout the body (relative change (RC) 12.12%), head (RC 36.23%), pelvis (RC 9.00%), and legs (RC 3.15%). Similarly, bone mineral density (BMD) increased in different regions (RRC 3.60-26.43%), except for the arms. Notably, lean mass in the arms (RC 4.30%) and legs (RC 3.67%) increased, while that in the head decreased (RC -2.75%), while total lean mass did not change at 4-6 weeks after LT4 supplementation. Furthermore, changes in fat distribution in the android region were related to the changes in total cholesterol (r = -0.390) and low-density lipoprotein cholesterol (r = -0.354), and changes in the BMC and BMD of the lumbar spine were positively associated with the changes in calcitonin (r = 0.302 and 0.325, respectively). CONCLUSIONS: After RAI and short-term LT4 supplementation in DTC patients, body composition rapidly and positively changed and was characterized by decreased fat mass and increased BMC and BMD.

Integrated microbiome and metabolome analysis reveals a distinct microbial and metabolic signature in Graves' disease and hypothyroidism.

Recent studies reveal that imbalanced microbiota is related to thyroid diseases. However, studies on the alterations in fecal metabolites in Graves' disease and clinical hypothyroidism patients are insufficient. Here, we identified 21 genera and 53 metabolites that were statistically significant among Graves' disease patients, hypothyroidism patients, and controls integrating microbiome and untargeted metabolome analysis. Disease groups revealed a decreased abundance in butyrate-producing microbiota and an increased abundance in potentially pathogenic microbiota. Lipids molecules were the major differential metabolites identified in all fecal samples. Network analysis recognized that microbiota may affect thyroid function by targeting specific metabolites. We further identified specific microbiota and metabolites that could distinguish Graves' disease patients, hypothyroidism patients, and controls. Our study reveals a distinct microbial and metabolic signature in hypothyroidism patients and Graves' disease patients and further validates the potential role of microbiota in thyroid diseases, providing new ideas for future research into the etiology and clinical intervention of thyroid diseases.

CCL22 and CCL26 are potential biomarkers for predicting distant metastasis in thyroid carcinoma.

OBJECTIVES: Chemokines have been suggested to play significant roles in the progression of malignant cancers. This study aimed to identify the chemokines related to malignant progression in thyroid carcinoma. METHODS: The mRNA expression levels of 52 chemokines were compared between differentiated thyroid cancer (DTC) samples and normal thyroid tissues from The Cancer Genome Atlas database; survival analysis was then performed on the basis of differentially expressed chemokines. A retrospective study was conducted on the level of differentially expressed chemokines in 76 DTC patients. Functional pathway analysis was performed to explore chemokine-related regulatory mechanisms. RESULTS: We identified 20 chemokines with differentially expressed mRNA levels through publicly available data. High levels of CCL22 and CCL26 were found to be related with metastasis in clinical DTC samples. High levels of CCL22 were found to be significantly related to poor prognosis in DTC patients. Pathway analyses revealed that cytokines might affect cancer progression through cytokine-cytokine receptor and cytokine-interleukin interactions. CONCLUSIONS: CCL22 and CCL26 could serve as prognostic biomarkers in thyroid carcinoma.

Anxiety and depression status prior to radioactive iodine therapy among differentiated thyroid cancer patients during the COVID­19 pandemic.

OBJECTION: The psychological health of thyroid cancer patients cannot be ignored; however, few studies have been conducted on the psychological status and influencing factors of thyroid cancer patients before radioactive iodine (RAI) therapy. The aim of this study was to investigate the incidence and risk factors for anxiety and depression in thyroid cancer patients prior to RAI therapy. METHODS: Clinical data were collected from patients with differentiated thyroid cancer (DTC) patients preparing for RAI therapy. Anxiety and depression were measured before RAI therapy using the Generalized Anxiety Disorder Questionnaire (GAD-7) and Patient Health Questionnaire (PHQ-9). We used the chi-square test and logistic regression analysis to identify independent risk factors for anxiety and depression. RESULTS: A total of 112 patients with thyroid cancer were included. Of these, 72.32% (n = 81) were female, with a mean age of 41.50 years. Anxiety and depression were reported by 46 (41.08%) and 38 (33.93%) patients, respectively. Based on the chi-square test and univariate logistic regression analysis, being female and having ever-experienced RAI therapy were significant risk factors for anxiety and depression among DTCs prior to RAI therapy. On multivariable analysis, the results of model 2 which included age, sex, education level, and ever suffering radioactive iodine therapy showed that being female was markedly associated with anxiety and depression in these patients, while having ever undergone RAI therapy was significantly related to anxiety but not depression. CONCLUSIONS: The incidence of anxiety and depression among patients with DTC prior to RAI therapy were 41.08% and 33.93%, respectively. Being female and having ever experienced RAI therapy significantly influenced anxiety and depression. Based on these findings, anxiety and depression assessment should be an important part of pre-RAI therapy in patients with DTC, and appropriate psychological nursing intervention can be carried out for key patients.

Effect of low-dose radiation on thyroid function and the gut microbiota.

BACKGROUND: The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. AIM: To investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice. METHODS: Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. RESULTS: We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls, and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups. And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. CONCLUSION: LDR can change thyroid function and the gut microbiota, and changes in the abundances of bacteria are correlated with the radiation dose.

Evaluation and analysis of anxiety and depression symptoms for college students during COVID-19 pandemic.

BACKGROUND: The mental health of students is affected by COVID-19. We aim to evaluate the anxiety and depression symptoms among college students during COVID-19 pandemic, analyze the influence factors that contribute to college students' anxiety and depression symptoms, and provide some suggestions for improving the mental health of college students. METHODS: With 179 college students participating, an online questionnaire consisting of a general questionnaire, Generalized Anxiety Disorder (GAD-7), and Patient Health Questionnaire (PHQ-9) was conducted in universities in Shanghai. The anxiety and depression symptoms among college students were evaluated using GAD-7 and PHQ-9 scales, and influence factors were analyzed using an unordered multi-class Logistic regression model. RESULTS: The reliability and validity of the GAD-7 and PHQ-9 scales were good (reliability ≥ 0.9, validity = 100%). The incidence of anxiety was 32.4%, of which were 23.5%, 8.4%, and 0.6% in mild, moderate, and severe, respectively; and the incidence of depression was 46.40%, of which in mild, moderate, moderate to severe, and severe were 28.5%, 10.1%, 7.3%, and 0.6%, respectively. Multivariate analysis revealed that male students with strong psychological quality, who were not easily affected by the COVID-19 pandemic, who received less negative or false information, and who had a strong grasp of psychology and related knowledge were less likely to suffer from mild or moderate anxiety symptoms [OR (95% CI) 0.18 (0.04, 0.81), 0.12 (0.05, 0.33), 0.23 (0.06, 0.89) and 0.07 (0.01, 0.74)]. Furthermore, college students who were not affected by the COVID-19 pandemic were less likely to suffer from mild, moderate, and moderate to severe depression symptoms [OR (95% CI) 0.23 (0.08, 0.65), 0.22 (0.05, 0.93), 0.10 (0.02, 0.54)]. CONCLUSION: The GAD-7 and PHQ-9 scales are suitable for evaluating anxiety and depression symptoms in college students. The COVID-19 pandemic was associated with a high incidence of anxiety and depression symptoms among college students, although gender and mental state fluctuations during the pandemic, negative and false information, and exposure to psychology and related courses were the main influencing factors.

Alterations of Gut Microbiome and Metabolite Profiles Associated With Anabatic Lipid Dysmetabolism in Thyroid Cancer.

Background: Currently, the high morbidity of individuals with thyroid cancer (TC) is an increasing health care burden worldwide. The aim of our study was to investigate the relationship among the gut microbiota community, metabolites, and the development of differentiated thyroid cancer. Methods: 16S rRNA gene sequencing and an integrated LC-MS-based metabolomics approach were performed to obtain the components and characteristics of fecal microbiota and metabolites from 50 patients with TC and 58 healthy controls (HCs). Results: The diversity and richness of the gut microbiota in the TC patients were markedly decreased. The composition of the gut microbiota was significantly altered, and the Bacteroides enterotype was the dominant enterotype in TC patients. Additionally, the diagnostic validity of the combined model (three genera and eight metabolites) and the metabolite model (six metabolites) were markedly higher than that of the microbial model (seven genera) for distinguishing TC patients from HCs. LEfSe analysis demonstrated that genera (g_Christensenellaceae_R-7_group, g_Eubacterium_coprostanoligenes_group) and metabolites [27-hydroxycholesterol (27HC), cholesterol] closely related to lipid metabolism were greatly reduced in the TC group. In addition, a clinical serum indicator (total cholesterol) and metabolites (27HC and cholesterol) had the strongest influence on the sample distribution. Furthermore, functional pathways related to steroid biosynthesis and lipid digestion were inhibited in the TC group. In the microbiota-metabolite network, 27HC was significantly related to metabolism-related microorganisms (g_Christensenellaceae_R-7_group). Conclusions: Our research explored the characteristics of the gut microecology of patients with TC. The findings of this study will help to discover risk factors that affect the occurrence and development of TC in the intestinal microecology.

Poorly differentiated thyroid carcinoma: a clinician's perspective.

Poorly differentiated thyroid carcinoma (PDTC) is a rare thyroid carcinoma originating from follicular epithelial cells. No explicit consensus can be achieved to date due to sparse clinical data, potentially compromising the outcomes of patients. In this comprehensive review from a clinician's perspective, the epidemiology and prognosis are described, diagnosis based on manifestations, pathology, and medical imaging are discussed, and both traditional and emerging therapeutics are addressed as well. Turin consensus remains the mainstay diagnostic criteria for PDTC, and individualized assessments are decisive for treatment option. The prognosis is optimal if complete resection is performed at early stage but dismal in nearly half of patients with locally advanced and/or distant metastatic diseases, in which adjuvant therapies such as 131I therapy, external beam radiation therapy, and chemotherapy should be incorporated. Emerging therapeutics including molecular targeted therapy, differentiation therapy, and immunotherapy deserve further investigations to improve the prognosis of PDTC patients with advanced disease.

Gut microbiota changes and its potential relations with thyroid carcinoma.

Introduction: Emerging evidence suggests that the essence of life is the ecological balance of the neural, endocrine, metabolic, microbial, and immune systems. Gut microbiota have been implicated as an important factor affecting thyroid homeostasis. Objectives: This study aims to explore the relationship between gut microbiota and the development of thyroid carcinoma. Methods: Stool samples were collected from 90 thyroid carcinoma patients (TCs) and 90 healthy controls (HCs). Microbiota were analyzed using 16S ribosomal RNA gene sequencing. A cross-sectional study of an exploratory cohort of 60 TCs and 60 HCs was conducted. The gut microbiota signature of TCs was established by LEfSe, stepwise logistic regression, lasso regression, and random forest model analysis. An independent cohort of 30 TCs and 30 HCs was used to validate the findings. Functional prediction was achieved using Tax4Fun and PICRUSt2. TC patients were subsequently divided into subgroups to analyze the relationship between microbiota and metastatic lymphadenopathy. Results: In the exploratory cohorts, TCs had reduced richness and diversity of gut microbiota compared to HCs. No significant difference was found between TCs and HCs on the phylum level, though 70% of TCs had increased levels of Proteobacteria-types based on dominant microbiota typing. A prediction model of 10 genera generated with LEfSe analysis and lasso regression distinguished TCs from HCs with areas under the curves of 0.809 and 0.746 in the exploration and validation cohorts respectively. Functional prediction suggested that the microbial changes observed in TCs resulted in a decline in aminoacyl-tRNA biosynthesis, homologous recombination, mismatch repair, DNA replication, and nucleotide excision repair. A four-genus microbial signature was able to distinguish TC patients with metastatic lymphadenopathy from those without metastatic lymphadenopathy. Conclusion: Our study shows that thyroid carcinoma patients demonstrate significant changes in gut microbiota, which will help delineate the relationship between gut microbiota and TC pathogenesis.

Analysis of Genetic Alterations Related to DNA Methylation in Testicular Germ Cell Tumors Based on Data Mining.

Embryonal carcinoma (EC) and seminoma (SE) are both derived from germ cell neoplasia in situ but show big differences in growth patterns and clinical prognosis. Epigenetic regulation may play an important role in the development of EC and SE. This study investigated the DNA methylation-based genetic alterations between EC and SE by analyzing the datasets of mRNA expression and DNA methylation profiling. The datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified between EC and SE by limma package in R environment. Gene function enrichment analysis of the DEGs was performed on the DAVID tool, the results of which suggested differences in capability of pluripotency and genomic stability between EC and SE. The minfi package and wANNOVAR tool were used to identify differentially methylated genes. A total of 37 genes were discovered with both mRNA expression and the accordant DNA methylation changes. The findings were verified by the sequencing data from The Cancer Genome Atlas database, and Kaplan-Meier survival analysis was performed. Finally, 5 genes (PRDM1, LMO2, FAM53B, HCN4, and FAM124B) were found that showed both low expression and high methylation in EC, and were significantly associated with relapse-free survival. The findings of methylation-based genetic features between EC and SE might be helpful in studying the role of DNA methylation in cancer development.

Gut Microbiota May Play a Significant Role in the Pathogenesis of Graves' Disease.

Background: Gut microbiota are considered to be intrinsic regulators of thyroid autoimmunity. We designed a cross-sectional study to examine the makeup and metabolic function of microbiota in Graves' disease (GD) patients, with the ultimate aim of offering new perspectives on the diagnosis and treatment of GD. Methods: The 16S ribosomal RNA (rRNA) V3-V4 DNA regions of microbiota were obtained from fecal samples collected from 45 GD patients and 59 controls. Microbial differences between the two groups were subsequently analyzed based on high-throughput sequencing. Results: Compared with controls, GD patients had reduced alpha diversity (p < 0.05). At the phylum level, GD patients had a significantly lower proportion of Firmicutes (p = 0.008) and a significantly higher proportion of Bacteroidetes (p = 0.002) compared with the controls. At the genus level, GD patients had greater numbers of Bacteroides and Lactobacillus, although fewer Blautia, [Eubacterium]_hallii_group, Anaerostipes, Collinsella, Dorea, unclassified_f_Peptostreptococcaceae, and [Ruminococcus]_torques_group than controls (all p < 0.05). Subgroup analysis of GD patients revealed that Lactobacillus may play a key role in the pathogenesis of autoimmune thyroid diseases. Nine distinct genera showed significant correlations with certain thyroid function tests. Functional prediction revealed that Blautia may be an important microbe in certain metabolic pathways that occur in the hyperthyroid state. In addition, linear discriminant analysis (LDA) and effect size (LEfSe) analysis showed that there were significant differences in the levels of 18 genera between GD patients and controls (LDA >3.0, all p < 0.05). A diagnostic model using the top nine genera had an area under the curve of 0.8109 [confidence interval: 0.7274-0.8945]. Conclusions: Intestinal microbiota are different in GD patients. The microbiota we identified offer an alternative noninvasive diagnostic methodology for GD. Microbiota may also play a role in thyroid autoimmunity, and future research is needed to further elucidate the role.

The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion.

The long noncoding RNA (lncRNA), HOX antisense intergenic RNA myeloid 1 (HOTAIRM1), has been shown to act as a tumor suppressor in various human cancers. However, the overall biological roles and clinical significance of HOTAIRM1 in papillary thyroid cancer (PTC) have not been investigated. In this study, we used quantitative reverse transcription PCR (qRT-PCR) to show that HOTAIRM1 was significantly downregulated in PTC tissues and low HOTAIRM1 expression levels were associated with lymph node metastasis and advanced TNM stage. We performed Cell Counting Kit-8, plate colony-formation, flow cytometric apoptosis, transwell, and scratch wound healing assays. Overexpression of HOTAIRM1 was found to inhibit PTC cell proliferation, invasion, and migration in vitro. Additionally, we identified miR-107 as a target of HOTAIRM1 using online bioinformatics tools. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm that HOTAIRM1 acted as a competing endogenous RNA of miR-107. Furthermore, enhancement of miR-107 could potentially reverse the effects of HOTAIRM1 overexpression in vitro. Inhibition of miR-107 suppressed PTC cell proliferation, invasion, and migration in vitro. HOTAIRM1 overexpression and miR-107 inhibition impaired tumorigenesis in vivo in mouse xenografts. Bioinformatics prediction and a dual-luciferase reporter gene assay demonstrated the binding between miR-107 and the 3'-untranslated region of TDG. The results of qRT-PCR and western blotting assays suggested that HOTAIRM1 could regulate the expression of TDG in an miR-107-meditated manner. In conclusion, we validated HOTAIRM1 as a novel tumor-suppressor lncRNA in PTC and proposed that the HOTAIRM1/miR-107/TDG axis may serve as a therapeutic target for PTC.

False-Positive Uptake of 131I Due to Tubal Ligation in a Patient With Papillary Thyroid Cancer.

A 39-year-old woman with papillary thyroid cancer underwent I therapy after thyroidectomy. Posttherapeutic I whole-body scan accidentally showed symmetric "hot spots" in the pelvic region beyond known bone metastases. SPECT/CT was immediately added and revealed metal artifacts with I accumulation in the nearby uterus. Further inquiry discovered that she underwent tubal ligation 19 years ago. Our case demonstrates that I accumulation can occur at the site of oviducts many years after tubal ligation, which should be distinguished from I-avid metastases.