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Thyroid Cancer (TC) is the most common malignant tumor of the endocrine system. Cystatin M/E (CST6) has been demonstrated to have a multifaceted role in several types of cancers. However, its potential mechanisms in the progression of TC have not been fully identified. Our results revealed that CST6 expressions were upregulated in TC tissues and cells compared with normal thyroid tissues and cells. High expression of CST6 was negatively correlated with poor prognosis of thyroid cancer patients. Functional assays showed that CST6 promoted TC cells malignant phenotype, including proliferation, colony formation, migration, and invasion. Inhibition of CST6 remarkably alleviated tumor growth and metastasis of ATC xenografts in nude mouse and zebrafish model. CST6 showed interaction with cathepsin B (CTSB). CTSB knockdown profoundly inhibited the aggressive behavior of TC cells. Of note, loss of CST6 attenuated the activity of CTSB, which led to the decrease of autophagy progress. Collectively, our findings demonstrated an essential role of CST6 in the development of TC through CTSB-mediated autophagy.

Hashimoto’s thyroiditis (HT) is an autoimmune illness caused by a combination of genetic, epigenetic, and environmental factors. The pathogenesis of HT is not fully elucidated, especially in epigenetics. The epigenetic regulator Jumonji domain-containing protein D3 (JMJD3) has been extensively investigated in immunological disorders. This study has been performed to explore the roles and potential mechanisms of JMJD3 in HT. Thyroid samples from patients and healthy subjects were collected. We first analyzed the expression of JMJD3 and chemokines in the thyroid gland using real-time PCR and immunohistochemistry. In vitro, the apoptosis effect of the JMJD3-specific inhibitor GSK-J4 on the thyroid epithelial cell line Nthy-ori 3-1 was evaluated using FITC Annexin V Detection kit. Reverse transcription-polymerase chain reaction and Western blotting were applied to examine the inhibitory effect of GSK-J4 on the inflammation of thyrocytes. In the thyroid tissue of HT patients, JMJD3 messenger RNA and protein levels were substantially greater than in controls (P < 0.05). Chemokines C–X–C motif chemokine ligand 10 (CXCL10) and C–C motif chemokine ligand 2 (CCL2) were elevated in HT patients, and thyroid cells with stimulation of tumor necrosis factor α (TNF-α). GSK-J4 could suppress TNF-α-induced synthesis of chemokines CXCL10 and CCL2 and prohibit thyrocyte apoptosis. Our results shed light on the potential role of JMJD3 in HT and indicate that JMJD3 may become a novel therapeutic target in HT treatment and prevention.

Xixuan Lu,1,&ast; Qiang Wang,2,&ast; Haiyan Liang,1 Li Xu,3 Liping Sha,1 Yuemei Wu,1 Liting Ma,1 Ping Yang,1 Hong Lei1 1Department of Endocrinology, Cardiovascular and Cerebrovascular Disease Hospital, Ningxia Medical University General Hospital, Yinchuan, Ningxia, People’s Republic of China; 2Department of Medical Office, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia, People’s Republic of China; 3Department of Radiology, People’s Liberation Army’s Joint Service for the 942nd Hospital, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xixuan LuDepartment of Endocrinology, Cardiovascular and Cerebrovascular Disease Hospital, Ningxia Medical University General Hospital, No. 804, Shengli South Street, Xingqing District, Yinchuan, 750004, Ningxia, People’s Republic of ChinaTel +860951-6746645Email xixuan86@163.comBackground: This study has been conducted to explore the correlation between phenotypes of obesity and metabolic comorbidities.Methods: This cross-sectional study recruited 14,724 adults aged ≥ 18 years with a randomized stratified sampling strategy. Obesity was classified into four types according to body mass index (BMI) and waist-to-height ratio (WHtR): normal weight with central obesity (NWCO) and without (NW) CO, and obese or overweight with (OBCO) and without (OB) central obesity. Uric acid (UA), fasting blood glucose (FBG), and lipid profile were measured.Results: The prevalence of hyperuricemia in the 4 groups (NW, NWCO, OB and OBCO) was 3.7%, 5.6%, 8.7% and 12.4%, whilst the prevalence of hypertriglyceridemia was 13.4%, 27.4%, 30.3% and 43.7%, separately. The prevalence of hypo-high-density lipoprotein cholesterolemia (hypo-HDL emia) was 20.1%, 21.4%, 30.8% and 27.9%, while the prevalence of hyper-low-density lipoprotein cholesterolemia (hyper-LDL emia) was 9.8%, 24.4%, 12.3% and 27.9%. The prevalence of hypercholesterolemia was 11.2%, 23.5%, 14.7%, 28.5% and the prevalence of hyperglycemia was 9.7%, 22.6%, 18.5%, and 27.0%, respectively. The prevalence of hypertension was 6.9%, 13.1%, 14.7%, and 20.6%. For various metabolic abnormalities, OBCO have the highest risks compared with NW (hyperuricemia: adjusted OR (aOR)= 2.60; hypertriglyceridemia: aOR= 3.19; hypercholesterolemia: aOR= 1.48; hyper LDLemia: aOR= 2.21; hypo HDLemia: aOR= 1.42; hyperglycemia: aOR= 1.95; hypertension: aOR= 2.16). The risk of hyper LDLemia, hypercholesterolemia and hyperglycemia in the NWCO group was higher than that in the OB group (hyperLDLemia: aOR: 1.69 vs 0.97; hypercholesterolemia: aOR: 1.27 vs 1.24; hyperglycemia: aOR: 1.62 vs 1.28).Conclusion: Different phenotypes of obesity are significantly associated with metabolic abnormalities. NWCO is more closely associated with hypercholesterolemia, hyperglycemia and hyper LDLemia. General obesity and central obesity have a synergistic effect on the diseases.Keywords: obesity, central obesity, metabolic abnormalities, BMI, WHtR

Extensive infiltration of tumor-associated macrophages was correlated poor prognosis in anaplastic thyroid cancer (ATC). However, the heterogeneity and characteristics of the ATC-associated macrophages (ATAMs) in ATC remain far from clear. We combined single-cell RNA-sequencing analysis and gene expression microarray datasets to assess the molecular signature of ATAMs. Compared with normal thyroid-associated macrophages (NTAMs), 778 differentially expressed genes (DEGs) significantly changed in ATAMs compared with NTAMs. These DEGs were correlated with oxidative phosphorylation (M2 phenotype) and phagocytosis (M1 phenotype). Moreover, ATAMs highly expressed pro-tumor genes associated with angiogenesis, fibrosis, metalloprotease activity, and metastasis. Notably, we identified one ATC-specific subset, IL2RA

OBJECTIVE: To investigate the molecular mechanism of resveratrol inhibiting the metastasis of liver cancer in vitro. METHODS: HepG2 and Huh7 cells were treated with different concentrations of resveratrol, and the cell viability was determined by CCK-8 assay to determine the optimal concentration of resveratrol for subsequent experiments. The expressions of miR-186-5p in liver cancer tissues and liver cancer cells were determined by quantitative real-time RT-PCR. The migration and invasion of HepG2 and Huh7 cells were detected by wound healing assay and Transwell assay, and the expression levels of epithelial-mesenchymal transition (EMT) related proteins were determined by Western blotting. RESULTS: Resveratrol with concentration of 6.25 μmol/L had no effect on the viability of HepG2 and Huh7 cells, so the concentration of resveratrol in subsequent experiments was 6.25 μmol/L. Resveratrol inhibited the wound healing and invasion of liver cancer cells; increased the expression of E-cadherin, and decreased the expression of vimentin and Twist1. The expression of miR-186-5p was significantly down-regulated in liver cancer tissues and cells compared with the adjacent tissues and normal liver cells (both P

Anaplastic thyroid carcinoma (ATC) is the most malignant tumor of endocrine system, which is an urgent medical problem to be solved. At present, immunotherapy studies on ATC mainly include cutting off the recruitment of tumor-associated macrophage (TAM), inducing the reprogramming of TAM and restoring its phagocytic function, targeting related immune checkpoints on T cells and natural killer cells, tumor vaccines based on oncolytic viruses and dendritic cells, and adoptive immunotherapy. Among them, immunotherapy strategies represented by targeted blocking of programmed death-1/programmed death ligand-1 at immune checkpoint have been preliminarily confirmed to benefit ATC patients, especially the combination of molecular targeted inhibitors and immunotherapy has shown excellent therapeutic effects. Due to the great heterogeneity of ATC, it is expected to provide more therapeutic strategies for patients of ATC by carrying out various immunotherapy studies including biological, immune and cellular therapies and exploring the therapeutic potential of the next generation of immune checkpoint inhibitors. This article reviews the potential immunotherapeutic targets of ATC and the progress of immunotherapy.

The human placenta is an important organ that forms a barrier where maternal and fetal exchange takes place. The placenta transport iodine to the fetal circulation by transfer of maternal iodine and deiodination of thyroid hormones (THs). The aim of the study was to examine the distribution of iodine and thyroid hormone transporters in the maternal and fetal sides of human-term placenta. A cross-sectional study was performed at the First Affiliated Hospital of China Medical University. Placental samples (maternal and fetal surfaces) were collected from 113 healthy-term pregnant women. The iodine content; the concentration of thyroxine (T4), triiodothyronine (T3), and reverse T3 (rT3); and the enzyme activity of placental type 2 iodothyronine deiodinase (D2) and D3 were examined. The mRNA and protein localization/expression of iodine and thyroid hormone transporters in the placenta were also studied. We also analyzed the association between expression level of Na+/I- symporter (NIS), thyroid hormone transporter protein, D3 activity in maternal and fetal surfaces of placenta with iodine content, and thyroid hormone levels. Iodine levels in placental samples from the maternal side were significantly higher than those in samples from the fetal side. T3 and T4 expression in fetal placenta was significantly lower than in maternal placenta. D3 activity in the fetal side of the placentas was significantly higher than that in the maternal side. The mRNA and protein expression of monocarboxylate transporters 8 (MCT8), L-amino acid transporters 1 (LAT1), organic anion transporting polypeptides 4A1 (OATP4A1), and TH binding protein transthyretin (TTR) were significantly increased in maternal side, while the NIS expression was higher in fetal side of human-term placenta. In conclusion, the enzymatic deiodination of thyroid hormones forms a barrier which reduces transplacental passage of the hormones and that the maternal part of the placenta is the primary factor in the mechanism regulating the hormonal transfer.

Type 2 diabetes mellitus (T2DM) is a chronic disease that seriously threatens human health with high incidence and various complications. Circular RNA has become a research hotspot in recent years due to its high stability and wide expression, and has been found to be related to many diseases. The main purpose of this study was to investigate the expression of serum hsa_circ_0054633 in T2DM patients and explore the potential role of serum hsa_circ_0054633 in T2DM diagnosis and its association with clinical characteristics.This retrospective case-control study enrolled 88 participants including 44 patients with T2DM and 44 age- and sex-matched controls between January 2018 and March 2019 at Ningxia Medical University General Hospital. Serum hsa_circ_0054633 levels were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) with absolute quantification. Baseline information including clinical background, glucose control and biochemical variables were collected. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic effect.We found that serum expression of hsa_circ_0054633 was dramatically increased in patients with T2DM. Serum hsa_circ_0054633 levels had high sensitivity (75.0%) and specificity (95.5%) for differentiating T2DM. Besides, serum expression of circ_0054633 was significantly correlated with fasting blood glucose (Serum hsa_circ_0054633 is a potential noninvasive biomarker in discerning T2DM and is associated with changes in blood glucose and lipid.

Iodine is one of the most important trace elements in the human body. It is not only the main component of thyroid hormones but also has extrathyroid biological functions. To date, there have been no large-scale epidemiological studies on the relationship between hyperuricemia and iodine intake, although both are closely related to health. A population-based epidemiological survey in China offers such an opportunity. This population-based cross-sectional study recruited 75,653 adults aged ≥ 18 years from 2015 to 2017 with a randomized, multistage, stratified sampling strategy. Serum uric acid levels and urinary iodine concentrations (UICs) were measured. Stratified by UIC, the prevalence of hyperuricemia was 17.8%, 18.8%, 16.0% and 13.7% in the UIC

Background Graves' disease (GD) is a common autoimmune disease characterized by genetic and environmental factors. Fcγ receptors (FcγRs) are involved in several autoimmune disorders through recognizing immunoglobulin (Ig) G antibodies and mediating immune response. The study on the expression of FcγRs in GD patients is scarce. The purpose of this study was to evaluate the expression of three different types of FcγRs in patients with active and remissive GD. Methods Blood samples of patients and healthy subjects were collected to analyze the percentage of FcγRI (CD64), FcγRII (CD32), and FcγRIII (CD16) on peripheral blood mononuclear cells (PBMCs) and monocytes by flow cytometry and Western blotting. CD32 isotypes were also examined in cases and controls by real‐time PCR. Results The cell percentages expressed CD32 and protein expressions of CD32 on PBMCs, and monocytes from patients with active GD were significantly reduced compared to controls and patients with remissive GD. In particular, the expression of CD32B on PBMC was also decreased in active GD patients. However, the cell percentages expressed CD16 and CD64 from PBMCs and monocytes were comparable between three groups. Besides, the percentages of CD14+CD32+ cells were negatively correlated with TRAb titers in active GD patients (r = −0.5825, P ＜ 0.001). Conclusion These results suggested that CD32 may act as a novel marker for active GDs. The expression of monocytic CD32, in particular CD32B, in GD patients might play a crucial role in maintaining FcγRs function and be a therapeutic target in GD patients.

Objectives Maintenance of functional beta cell mass is critical for prevention of diabetes. The transforming growth factor-beta (TGF-β) receptor signalling pathway plays an essential role in pancreatic development. However, its involvement in control of post-natal beta cell growth has only been recently reported. Materials and methods Here, we studied the role of TGF-β receptor signalling in beta cell proliferation after 50% partial pancreatectomy (PPx), using beta cell-specific TGF-β receptor II (TBR2)-mutated mice. Results Consistent with previous reports, we found that inhibition of TGF-β receptor signalling in beta cells resulted in slightly higher beta cell mass 1 week after PPx, due to greater beta cell proliferation. However, beta cell mass in these beta cell-specific TBR2-mutated mice significantly decreased by 12 weeks after PPx, resulting from increase in beta cell apoptosis. Conclusions Our data thus suggest that TGF-β receptor signalling may be required for prevention of beta cell death after proliferation, and highlight this pathway as an essential regulator during post-natal beta cell homoeostasis.