OBJECTIVE: Dopamine agonist (DA) treatment is effective for hyperprolactinemia and reduces tumor size in patients with prolactinoma; however, prolonged DA administration without prolactinoma causes fibrosis around tumor tissues. Therefore, we aimed to identify circulating microRNAs (miRNAs) as potential biomarkers to predict prolactinoma in patients with hyperprolactinemia and pituitary tumors. DESIGN: Plasma samples were collected from 3 comparison groups: (1) patients clinically diagnosed with prolactinoma vs nonfunctioning pituitary adenoma (NFPA) based on response to cabergoline treatment, (2) patients with surgically confirmed prolactinoma vs NFPA, and (3) patients before and after cabergoline treatment. Candidate miRNAs from the initial nCounter assay were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in a larger cohort of 247 patients with hyperprolactinemia and 37 controls. METHODS: The nCounter assay was used for miRNA expression profiling, and the qRT-PCR validated the candidate miRNAs in the plasma and tumor tissue samples. Total RNA sequencing was conducted on pituitary tumor tissues to identify transcriptomic alterations. Furthermore, candidate miRNA target genes and their biological roles were analyzed using prolactinoma cell lines. RESULTS: Three miRNA candidates (miR-20a-5p, miR-424-5p, and miR-514a-5p) were selected by analyzing 3 sets of expression comparisons between the 2 groups. Furthermore, the relative miR-20a-5p expression significantly increased in prolactinoma compared with that in normal pituitary glands, NFPA, growth hormone-secreting pituitary adenoma, and adrenocorticotropic hormone-secreting pituitary adenoma. In MMQ and GH4 cells, miR-20a-5p inhibition decreased prolactinoma cell proliferation and prolactin secretion. CONCLUSIONS: Circulating miR-20a-5p is a potential biomarker for prolactinoma, which could be associated with responsiveness to DAs.

Objective: ) is an inducible negative regulator of the JAK/STAT pathway, implicated in various inflammatory diseases. In this study, we investigated the role of SOCS3 in the inflammatory and adipogenic pathogenesis of GO. Methods: expression was analyzed in IL-1β-, and IGF-1-stimulated orbital fibroblasts using quantitative real-time polymerase chain reaction and western blot analysis. Knockdown of SOCS3 using siRNA transfection was performed to assess the effect of SOCS3 on the production of proinflammatory cytokines and adipogenic phenotype. Results: at mRNA and protein levels. Silencing of SOCS3 suppressed the levels of IL-1β-induced proinflammatory cytokines, including IL-6, IL-8, and ICAM-1. Phosphorylation of NF-kB and Akt was suppressed and adipogenic differentiation was significantly attenuated by SOCS3 knockdown. Conclusions: may be a therapeutic target for controlling the inflammatory and adipogenic mechanisms in GO.

Our novel mouse model for GD, which showed the histological features of GO, was successfully established using the Cre-loxP system. This animal model offers improved insights and contributes to advancing methodological developments for GD and GO.

Objective: Improved molecular testing for common somatic mutations and the identification of mRNA and microRNA expression classifiers are promising approaches for the diagnosis of thyroid nodules. However, there is a need to improve the diagnostic accuracy of such tests for identifying thyroid cancer. Recent findings have revealed a crucial role of long non-coding RNAs (lncRNAs) in gene modulation. Thus, we aimed to evaluate the diagnostic value of selected lncRNAs from The Atlas of Noncoding RNAs in Cancer (TANRIC) thyroid cancer dataset. Methods: LncRNAs in TANRIC thyroid cancer dataset that have significantly increased or decreased expression in papillary thyroid cancer (PTC) tissues were selected as candidates for PTC diagnosis. Surgical specimens from patients who underwent thyroidectomy were used to determine the separation capability of candidate lncRNAs between malignant and benign nodules. Fine needle aspiration samples were obtained and screened for candidate lncRNAs to verify their diagnostic value. Results: LRRC52-AS1, LINC02471, LINC02082, UNC5B-AS1, LINC02408, MPPED2-AS1, LNCNEF, LOC642484, ATP6V0E2-AS1, and LOC100129129 were selected as the candidate lncRNAs. LRRC52-AS1, LINC02082, UNC5B-AS1, MPPED2-AS1, LNCNEF, and LOC100129129 expression levels were significantly increased or decreased in malignant nodules compared to those in benign nodules and paired normal thyroid tissues. The combination of LRRC52-AS1, LINC02082, and UNC5B-AS1 showed favorable results for the diagnosis of PTC from fine needle aspirates, with 88.9% sensitivity and 100.0% specificity. Conclusions: LncRNA expression analysis is a promising approach for advancing the molecular diagnosis of PTC. Further studies are needed to identify lncRNAs of additional diagnostic value.

OBJECTIVE: Dopamine agonist (DA) treatment is effective for hyperprolactinemia and reduces tumor size in patients with prolactinoma; however, prolonged DA administration without prolactinoma causes fibrosis around tumor tissues. Therefore, we aimed to identify circulating microRNAs (miRNAs) as potential biomarkers to predict prolactinoma in patients with hyperprolactinemia and pituitary tumors. DESIGN: Plasma samples were collected from 3 comparison groups: (1) patients clinically diagnosed with prolactinoma vs nonfunctioning pituitary adenoma (NFPA) based on response to cabergoline treatment, (2) patients with surgically confirmed prolactinoma vs NFPA, and (3) patients before and after cabergoline treatment. Candidate miRNAs from the initial nCounter assay were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in a larger cohort of 247 patients with hyperprolactinemia and 37 controls. METHODS: The nCounter assay was used for miRNA expression profiling, and the qRT-PCR validated the candidate miRNAs in the plasma and tumor tissue samples. Total RNA sequencing was conducted on pituitary tumor tissues to identify transcriptomic alterations. Furthermore, candidate miRNA target genes and their biological roles were analyzed using prolactinoma cell lines. RESULTS: Three miRNA candidates (miR-20a-5p, miR-424-5p, and miR-514a-5p) were selected by analyzing 3 sets of expression comparisons between the 2 groups. Furthermore, the relative miR-20a-5p expression significantly increased in prolactinoma compared with that in normal pituitary glands, NFPA, growth hormone-secreting pituitary adenoma, and adrenocorticotropic hormone-secreting pituitary adenoma. In MMQ and GH4 cells, miR-20a-5p inhibition decreased prolactinoma cell proliferation and prolactin secretion. CONCLUSIONS: Circulating miR-20a-5p is a potential biomarker for prolactinoma, which could be associated with responsiveness to DAs.

Objective: ) is an inducible negative regulator of the JAK/STAT pathway, implicated in various inflammatory diseases. In this study, we investigated the role of SOCS3 in the inflammatory and adipogenic pathogenesis of GO. Methods: expression was analyzed in IL-1β-, and IGF-1-stimulated orbital fibroblasts using quantitative real-time polymerase chain reaction and western blot analysis. Knockdown of SOCS3 using siRNA transfection was performed to assess the effect of SOCS3 on the production of proinflammatory cytokines and adipogenic phenotype. Results: at mRNA and protein levels. Silencing of SOCS3 suppressed the levels of IL-1β-induced proinflammatory cytokines, including IL-6, IL-8, and ICAM-1. Phosphorylation of NF-kB and Akt was suppressed and adipogenic differentiation was significantly attenuated by SOCS3 knockdown. Conclusions: may be a therapeutic target for controlling the inflammatory and adipogenic mechanisms in GO.

Our novel mouse model for GD, which showed the histological features of GO, was successfully established using the Cre-loxP system. This animal model offers improved insights and contributes to advancing methodological developments for GD and GO.

Objective: Improved molecular testing for common somatic mutations and the identification of mRNA and microRNA expression classifiers are promising approaches for the diagnosis of thyroid nodules. However, there is a need to improve the diagnostic accuracy of such tests for identifying thyroid cancer. Recent findings have revealed a crucial role of long non-coding RNAs (lncRNAs) in gene modulation. Thus, we aimed to evaluate the diagnostic value of selected lncRNAs from The Atlas of Noncoding RNAs in Cancer (TANRIC) thyroid cancer dataset. Methods: LncRNAs in TANRIC thyroid cancer dataset that have significantly increased or decreased expression in papillary thyroid cancer (PTC) tissues were selected as candidates for PTC diagnosis. Surgical specimens from patients who underwent thyroidectomy were used to determine the separation capability of candidate lncRNAs between malignant and benign nodules. Fine needle aspiration samples were obtained and screened for candidate lncRNAs to verify their diagnostic value. Results: LRRC52-AS1, LINC02471, LINC02082, UNC5B-AS1, LINC02408, MPPED2-AS1, LNCNEF, LOC642484, ATP6V0E2-AS1, and LOC100129129 were selected as the candidate lncRNAs. LRRC52-AS1, LINC02082, UNC5B-AS1, MPPED2-AS1, LNCNEF, and LOC100129129 expression levels were significantly increased or decreased in malignant nodules compared to those in benign nodules and paired normal thyroid tissues. The combination of LRRC52-AS1, LINC02082, and UNC5B-AS1 showed favorable results for the diagnosis of PTC from fine needle aspirates, with 88.9% sensitivity and 100.0% specificity. Conclusions: LncRNA expression analysis is a promising approach for advancing the molecular diagnosis of PTC. Further studies are needed to identify lncRNAs of additional diagnostic value.

mice but showed resistance against streptozotocin-induced hyperglycemia. The ectopic olfactory signaling events in pancreatic α-cells suggest that olfactory receptor pathways could be therapeutic targets for reducing excessive glucagon levels.

Thyrogen, a recombinant human thyroid-stimulating hormone (rhTSH), has a short half-life in the bloodstream, which necessitates multiple doses during treatment. Therefore, we developed a new long-acting rhTSH using anti-serum albumin Fab-associated (SAFA) technology to validate its biological activity through in vitro assays, pharmacokinetic studies in healthy mice and pharmacodynamics studies in a thyroid-stimulating hormone (TSH)-suppressed mouse model. SAFA-TSH was produced using a Chinese hamster ovary expression system. To verify its biological activity, we generated Nthy-ori 3-1 cells stably overexpressing TSHR and measured the production of cyclic adenosine monophosphate (cAMP). In a rat study, slow-release triiodothyronine (T3) pellets were implanted 3 days before administering Thyrogen or SAFA-TSH to measure the amount of thyroxine (T4) release alone resulting from exogenous administration. SAFA-TSH increased cAMP production dose-dependently, but less effectively than Thyrogen at similar concentrations. SAFA-TSH required six times the dose of Thyrogen to achieve similar cAMP levels, likely due to differences in molecular weight and relative bioactivity. In a rat study, SAFA-TSH produced elevated thyroid hormone levels well after the decline in the response to Thyrogen. SAFA-TSH had significantly higher cumulative effects on T4 and free T4 levels compared with Thyrogen, as observed by a more than two-fold higher average area under the effect curve of 262.56 vs 118.89 μg × h/dL and 127.47 vs 60.75 μg × h/dL, respectively. SAFA technology created successful long-acting TSH that demonstrated bioactivity. These findings endorse the continued development of SAFA-TSH for clinical use, highlighting its potential as a significant advancement treating thyroid cancer patients.

Metformin is widely used as a first-line therapy for type 2 diabetes mellitus. However, the molecular mechanisms by which it modulates intestinal glucose metabolism remain incompletely defined. Here metformin was orally administered to male C57BL/6 mice, followed by intraperitoneal glucose tolerance testing and fluorine-18 fluorodeoxyglucose tracing to evaluate glucose homeostasis. To investigate changes in intestinal glucose metabolism, IEC6 and Caco-2 cell lines were used for in vitro analysis, with organoid experiments conducted for further validation. qRT-PCR, western blotting, flow cytometry and immunohistochemistry were performed to elucidate the effects of metformin on glucose metabolism pathways. Metformin enhanced glucose uptake and excretion in the distal intestine, particularly in the ileum and colon. Mechanistically, metformin upregulated the expression and membrane localization of glucose transporter 1 (GLUT1) by downregulating thioredoxin-interacting protein (TXNIP) expression. Consistently, intestinal-specific overexpression of TXNIP abolished metformin-induced improvements in glucose tolerance, while pharmacological inhibition of GLUT1 similarly negated metformin's glucose-lowering effects. Our findings identified intestinal glucose excretion, mediated through the intestinal TXNIP-GLUT1 regulatory axis, as a previously unrecognized contributor to metformin's glucoregulatory action. These results highlight a novel intestinal mechanism underlying metformin's efficacy and provide insights for potential therapeutic strategies beyond traditional glucose regulation.