Confirmation of sustained syndrome of inappropriate secretion of thyrotropin (SITSH) is a milestone in diagnosis of β type of resistance to thyroid hormone (RTHβ). The differential diagnoses of RTHβ include TSH-producing pituitary adenoma (TSHoma) and familial dysalbuminemic hyperthyroxinemia (FDH), which also present SITSH. Recently, patients with RTHα caused by a mutation in thyroid hormone receptor α were reported and they did not present SITSH but a decline in the serum T4/T3 ratio. This review was aimed to overview thyroid function tests in RTH and related disorders. First, the characteristics of the thyroid function in RTHβ, TSHoma, and FDH obtained from a Japanese database are summarized. Second, the degrees of SITSH in patients with truncations and frameshifts were compared with those in patients with single amino acid deletions and single amino acid substitutions obtained from the literature. Third, the degrees of SITSH in homozygous patients were compared with those in heterozygous patients with cognate mutations. Finally, the FT3/FT4 ratios in RTHα are summarized. In principle, the TSH values in FDH were within the normal range and apparent FT4 values in FDH were much higher than in RTHβ and TSHoma. The FT3/FT4 values in RTHβ were significantly lower than in TSHoma. The degrees of SITSH in patients with truncations and frameshifts were more severe than those in patients with single amino acid deletions and single amino acid substitutions, and those in homozygous patients were more severe than those in heterozygous patients with cognate mutations. The FT3/FT4 ratios in RTHα were higher than 1.0.

Long noncoding RNAs (lncRNAs) have been reported to play critical role in the development of diabetic nephropathy (DN). However, the effects and mechanism of plasmacytoma variant translocation 1 (PVT1) remain poorly understood. The expression of PVT1, miR-23b-3p, early growth response factor 1 (EGR1), Fibronectin (FN), Collagen IV (Col IV), alpha smooth muscle actin (α-SMA), E-cadherin, and vimentin, transforming growth factor (TGF)-β1 was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed by Cell Counting-8 (CCK-8) assay. Western blot assay was conducted to measure the protein levels of FN, Col IV, E-cadherin, α-SMA, vimentin, TGF-β1, and EGR1. The interaction between miR-23b-3p and PVT1 or EGR1 was predicted by starBase or TargetScan and confirmed by the dual luciferase reporter assay. The oxidative stress factors were analyzed by corresponding kits. We found that the expression of PVT1 and EGR1 was increased and miR-23b-3p was decreased in serum samples of DN patients and HG-induced HRMCs. Knockdown of PVT1 significantly inhibited HG-induced proliferation, extracellular matrix (ECM) accumulation, epithelial-mesenchymal transition (EMT), and oxidative stress in HRMCs, while these effects were abated by inhibiting miR-23b-3p. In addition, EGR1 was confirmed as downstream target of miR-23b-3p and miR-23b-3p could specially bind to PVT1. Besides, downregulation of PVT1 inhibited the progression of DN partially via upregulating miR-23b-3p and downregulating EGR1. In conclusion, our results suggested that PVT1 knockdown suppressed DN progression though functioning as ceRNA of miR-23b-3p to regulate EGR1 expression in vitro, providing potential value for the treatment of DN.

This study investigated the effects and mechanisms of miR-132 related to the permeability and mobility of human retinal pigment epithelium ARPE-19 cells in high-glucose (HG) condition. ARPE-19 cells were cultured in normal and HG condition and identified by immunofluorescence staining. Cell viability was assessed by the MTT assay, cell permeability was assessed by the FITC-dextran assay and cell mobility was assessed by the wound healing assay. Different miRNA and mRNA expression levels were determined by quantitative real-time polymerase chain reaction (RT-qPCR). The expression of tight junction-related proteins was determined by Western blot assay and immunofluorescence. The interaction between occludin and miR-132 was confirmed by a dual-luciferase reporter assay. We revealed that HG-treated ARPE-19 cells exhibited significantly increased miR-132 expression, decreased expression of the tight-junction markers including occludin and E-cadherin, and increased cell mobility and permeability. Occludin is a direct target of miR-132, which could regulate cell viability, mobility and permeability under HG condition through the JAK/STAT3 signaling pathway. These are the first data to suggest that miR-132 may contribute to the progression of diabetic retinopathy (DR) and that targeting the effect of miR-132 on occudin and the JAK/STAT3 pathway could represent a novel effective DR-treatment strategy.

CircRNAs have been implicated in the progression of human cancers, including papillary thyroid carcinoma (PTC). Although circ_0008274 has been demonstrated as a potential oncogenic circRNA in PTC, our understanding of its molecular determinants is limited. The levels of circ_0008274, miR-154-3p and solute carrier family 7 member 11 (SLC7A11) mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR). SLC7A11 protein level was assessed by western blot. Cell apoptosis, migration, and adhesion capacities were examined by flow cytometry, transwell and cell adhesion assays, respectively. The targeted correlations among circ_0008274, miR-154-3p and SLC7A11 were confirmed by a dual-luciferase reporter assay. Animal studies were performed to observe the role of circ_0008274 in tumor growth in vivo. Our data showed that the high levels of circ_0008274 and SLC7A11 were associated with poor prognosis of PTC patients. The knockdown of circ_0008274 or SLC7A11 enhanced PTC cell apoptosis and repressed cell migration and adhesion in vitro. Circ_0008274 knockdown suppressed tumor growth in vivo. Mechanistically, circ_0008274 modulated SLC7A11 expression by acting as a sponge of miR-154-3p. SLC7A11 was a functional mediator of circ_0008274 in regulating PTC cell apoptosis, migration and adhesion in vitro, and miR-154-3p overexpression repressed PTC progression in vitro by targeting SLC7A11. Our findings identified that the knockdown of circ_0008274 repressed PTC malignant progression at least in part through regulating the miR-154-3p/SLC7A11 axis, providing a promising therapeutic opportunity for PTC treatment.

Pre-emptive evacuation orders following the accident at the Fukushima Daiichi Nuclear Power Station (FDNPS) in March 2011 and subsequent regulatory limits regarding contaminated food, milk, and water minimized the external and internal radiation exposure doses of nearby residents. However, with regard to implementation of iodine thyroid blocking (ITB), residents were confused because no information on the matter was released by the central and/or local governments. Based on lessons learned from the FDNPS accident, many countries have revised their guidelines regarding ITB during nuclear disasters. To adequately revise such guidelines and ensure effective ITB implementation during a nuclear disaster, however, residents’ perceptions of ITB must be clarified. In this study, the perception of risks associated with ITB was investigated in mothers residing near the Sendai Nuclear Power Plant (SNPP) in Kagoshima Prefecture, Japan. Of the 520 mothers surveyed, 467 (89.8%) expressed anxiety regarding the administration of potassium iodine (KI) to their children. Logistic regression analysis revealed that the mothers’ anxiety regarding the administration of KI to their children was positively correlated with their wish to consult an expert about KI and their hesitation to let their children eat foods produced in Fukushima, and negatively correlated with having confidence about administering KI to their children. Careful communication of potential risks to mothers residing near nuclear power plants is thus critical for implementing effective ITB in children.

Pituitary tumors are discovered either incidentally by imaging studies (incidentalomas) or via evaluation of certain clinical symptoms (symptomatic tumors). In this study, we first surveyed patients with incidentalomas who underwent surgery. Cases included 62.3% non-functioning adenomas (NFPAs), 14.5% functioning adenomas, and 13.8% Rathke’s cleft cysts. Next, we compared the clinical features and surgical outcomes of 145 patients whose preoperative diagnosis was NFPA (incidentalomas [n = 79] vs. symptomatic tumors [n = 66]). The patients with incidentalomas were older (59.9 vs. 55.3 years, p < 0.05) and had smaller tumors compared with the patients with symptomatic tumors (mean maximum diameter: 23.1 vs. 27.5 mm, p < 0.01). The main reason for undergoing imaging studies was headache (n = 25) in the incidentaloma group and visual disturbance (n = 46) in the symptomatic tumor group. The incidence of preoperative pituitary hormone deficiencies was lower in the incidentaloma than symptomatic tumor group (growth hormone deficiency: 37.7% vs. 66.7%, p < 0.01; gonadotropin deficiency: 19.0% vs. 39.4%, p < 0.01; adrenocorticotropic hormone deficiency: 3.8% vs. 18.2%, p < 0.01; thyroid stimulating hormone deficiency: 6.3% vs. 12.1%, p = 0.25). Postoperative pituitary function was better preserved in the incidentaloma than symptomatic tumor group (no deficiency: 58.2% vs. 28.8%, p < 0.01). The difference in postoperative complications between groups was not statistically significant (incidentalomas vs. symptomatic tumors: 21.5% vs. 19.7%, p = 0.84). In conclusion, incidentalomas were detected while smaller size and lower incidence of hormone deficiency than symptomatic tumors, and the pituitary hormones were also preserved after surgery. It is important to observe incidentalomas carefully and to judge whether to operate appropriately before they become symptomatic tumors.

Thyroid nodules (TN) are common in the general population, and the clinical importance of diagnosing thyroid nodules is based on excluding the possibility of thyroid cancer, which occurs in 7–15% of cases. The thyroid gland, owing to its superficial location, is easily accessible via thermography, a noninvasive method of recording body temperature that measures infrared radiation emitted by the body surface. Therefore, this study aimed to evaluate the temperature differences between benign and malignant TN by using thermography. We conducted a cross-sectional study where 147 TN were divided into two groups: the first group included 120 benign nodules and the other included 27 malignant nodules. All the nodules were subjected to ultrasound, fine needle aspiration biopsy, and thermography. On analyzing the thermography results, the benign nodules had a higher temperature at the beginning of the thermography evaluation, and the malignant nodules showed a higher temperature in the middle and at the end (Ft). Using the relationships, it was observed that the temperature delta (ΔT), ΔT nodule/ΔT healthy, ΔT nodule minus ΔT healthy, and nodule Ft minus Ft of the healthy region were higher in malignant nodules. The ROC curve analysis of ΔT demonstrated a cutoff point of 2.38°C, with a sensitivity of 0.963 and specificity of 0.992. Malignant nodules have higher temperatures than benign nodules on thermographic evaluation. This finding suggests that thermography can be a useful tool in the diagnosis of thyroid nodules.

The increasing incidence of papillary thyroid cancer (PTC) has attracted many researchers to investigate the mechanism underlying PTC progression. This study explored the growth and apoptosis of PTC cells based on an lncRNA regulatory mechanism. The expression of nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) in PTC cell lines and PTC tissues was analyzed by qRT-PCR. The mutual binding site between NNT-AS1 and miR-199a-5p was predicted by starBase and confirmed by dual-luciferase reporter assay. The correlation between NNT-AS1 and miR-199a-5p was shown by Pearson correlation test. The viability, clone formation, migration, invasion and apoptosis of TPC-1 and IHH-4 cells were examined by CCK-8, colony formation, wound-healing, transwell, and flow cytometry assays, respectively. The expressions of Bax, cleaved Caspase-3, Bcl-2, E-Cadherin, N-Cadherin and SNAIL in TPC-1 and IHH-4 cells were determined by Western blot or qRT-PCR. NNT-AS1 expression was upregulated in PTC cells and tissues. In TPC-1 cells, silencing NNT-AS1 inhibited viability, clone formation, migration, and invasion as well as the expressions of N-Cadherin, SNAIL and Bcl-2, but promoted the expressions of E-Cadherin, Bax, and cleaved caspase-3. The effects of NNT-AS1 overexpression on IHH-4 cells were opposite to those of silencing NNT-AS1. In PTC tissues, miR-199a-5p was low-expressed and targeted by NNT-AS1, and it was negatively correlated with NNT-AS1. MiR-199a-5p inhibitor promoted TPC-1 cell progression, but miR-199a-5p mimic inhibited IHH-4 cell progression. NNT-AS1 and miR-199a-5p exerted opposite effects on PTC cells. Silencing NNT-AS1 inhibited PTC cell proliferation, migration and invasion, but promoted apoptosis via upregulation of miR-199a-5p.

In this study, we compared the efficacy of a dipeptidyl peptidase–4 inhibitor (DPP4i) to improve glucose control in patients with type 2 diabetes mellitus (T2DM) with or without Hashimoto’s thyroiditis (HT). First, we compared the change in glycated hemoglobin (HbA1c) between the hypothyroid condition (before levothyroxine sodium hydrate [LT4] treatment) and euthyroid condition (after LT4 treatment when patients had achieved euthyroidism for at least six months) in patients with T2DM and HT. Next, we compared the change in HbA1c levels before and six months of DPP4i treatment in patients with T2DM with and without HT. In hypothyroid condition the change in HbA1c after six months of DPP4i treatment was 0.13% ± 0.86%. The change in HbA1c levels from when patients first achieved euthyroidism to after six months in the euthyroid condition was 0.26% ± 0.90%. DPP4i efficacy in patients with T2DM and HT was reduced compared to patients with T2DM but without HT (–0.40 ± 0.90 vs. –0.99 ± 0.5, p = 0.0032). These data suggest that hypothyroidism does not impact on DPP4i efficacy. However, the effect of DPP4i in patients with T2DM and HT was reduced compared to that in T2DM patients without HT. An estimation of thyroid function before prescribing DPP4i may be useful tool for predicting the efficacy of DPP4i, allowing the ruling out complications from HT.

Primary ovarian insufficiency (POI) is a highly heterogeneous condition, and its underlying causes remain to be clarified in a large fraction of patients. Congenital disorders of glycosylation (CDG) are multisystem diseases caused by mutations of a number of genes involved in N-glycosylation or O-glycosylation, and the most frequent form is PMM2-CDG (alias, CDG-Ia) resulting from biallelic mutations in PMM2 encoding phosphomannomutase-2 involved in N-glycosylation. Here, we examined a 46,XX Japanese female with syndromic POI accompanied by an undetectable level of serum anti-Müllerian hormone (AMH). Whole exome sequencing identified biallelic pathogenic mutations of PMM2 (a novel c.34G>C:p.(Asp12His) of maternal origin and a recurrent c.310C>G:p.(Leu104Val) of paternal origin) (NM_000303.3), and N-glycosylation studies detected asialotransferrin and disialotransferrin characteristic of PMM2-CDG, in addition to normally glycosylated tetrasialotransferrin. Clinical assessment showed cerebellar hypotrophy, which is a fairly characteristic and highly prevalent feature in PMM2-CDG, together with multiple non-specific features reported in PMM2-CDG such as characteristic face, intellectual disability, skeletal abnormalities, and low blood antithrombin III value. These results including the undetectable level of serum AMH, in conjunction with previously reported findings suggestive of the critical role of glycosylation in oocyte development and function, imply that PMM2-CDG almost invariably leads to POI primarily because of the defective oogenesis and/or oocyte-dependent early folliculogenesis rather than the compromised bioactivity of FSH/LH with defective glycosylation. Thus, it is recommended to examine PMM2 in patients with syndromic POI, especially in those with cerebellar ataxia/hypotrophy.

The programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis is vital for immune resistance during tumor development, while PD-L1 inhibitors can also inhibit the PD-L1/B7-1 (CD80) interaction, indicating one of the molecular differences between PD-1 and PD-L1 inhibitors. However, the clinical benefits of PD-L1 inhibitors in patients previously treated with PD-1 inhibitors remain unknown. In this study, we retrospectively analyzed the clinical data of eight patients with non-small cell lung cancer who received the PD-L1 inhibitor atezolizumab and previously treated with the PD-1 inhibitor nivolumab. The median progression-free survival was 2.1 months (1.8–18.7 months), and 4 of 8 patients achieved at least stable disease. In two of these patients, atezolizumab treatment resulted in longer progression-free survival (PFS) compared with that of nivolumab. Conversely, one patient exhibited grade 4 diabetic ketoacidosis (DKA) within 2 weeks after the initial administration of atezolizumab. Another patient had developed type 1 diabetes mellitus (T1DM) during the prior nivolumab treatment and then developed DKA due to an infection after the initiation of atezolizumab. Both of them had high-risk human leukocyte antigen-DR/DQ types relevant to T1DM. These results demonstrate the potential efficacy of PD-L1 inhibitors to some tumors that have acquired resistance to PD-1 inhibitors and suggest that appropriate managements are required for not only a newly onset of T1DM but also blood glucose control after the development of T1DM during a reiteration of the PD-1/PD-L1 blockade.