Search Results (5,247)

Anxiety, a common mental disorder, is epidemiologically linked to high dietary sugar intake. However, the underlying neural mechanisms remain poorly understood. Here, using male C57BL/6 mice (n ≥ 10 per group), we show that two-week consumption of sugar-sweetened drinks reliably induced anxiety-like behavior, characterized by reduced center time in the open field test and less open arm exploration in the elevated plus maze. Notably, consumption of sucrose, glucose, or the non-metabolizable glucose analog methyl-α-D-glucopyranoside induced anxiety-like behavior, whereas intake of the artificial sweetener acesulfame potassium (Ace-K) did not. Moreover, after two weeks of exposure to sucrose or glucose but not to Ace-K, c-Fos expression was elevated in glutamatergic neurons of the nucleus of the solitary tract (NTS). Mechanistically, high glucose activated intrinsic excitability and the amplitude of spontaneous excitatory postsynaptic currents in NTS glutamatergic neurons; congruently, selective activation of NTS glutamatergic neurons mimicked anxiety-like behavior in mice, while chemogenetic silencing of these neurons abolished glucose-induced anxiety. Together, our findings demonstrate that NTS glutamatergic neurons activation mediates sugar-induced anxiety. These results suggest that this anxiogenic effect is driven by glucose-related signaling rather than artificial sweet taste perception alone, shedding light on a novel clinical therapy against anxiety. Full article

Depression is one of the most prevalent psychiatric disorders worldwide, with a steadily increasing incidence and complex, multifactorial pathophysiology. Beyond classical neurochemical mechanisms, growing evidence points to the role of systemic low-grade inflammation and immuno-metabolic disturbances in its development. Gut microbiota dysbiosis has emerged as a key factor linking metabolic, immune, and neuroendocrine pathways, potentially exacerbating neuroinflammation and contributing to the onset and progression of depressive symptoms. Immune activation, which is a result of gut dysbiosis, may play a crucial role in the pathogenesis of immuno-metabolic depression. Thyroid dysfunction appears to be an important, yet insufficiently understood component of this network. Thyroid hormones play a crucial role in regulating metabolism, immune responses, and central nervous system function. Alterations in thyroid function, even within subclinical ranges, have been associated with mood disturbances and may share common inflammatory and metabolic pathways with depression. Furthermore, emerging data suggest that gut microbiota may influence thyroid hormone metabolism, including deiodinase activity, linking dysbiosis with thyroid axis dysregulation. Despite these insights, the integrated interactions between thyroid function, gut microbiota, metabolic syndrome, and inflammation in depression remain largely unexplored. This review explores current evidence to highlight gaps in existing research and synthesizes current knowledge, aiming to clarify mechanisms underlying immuno-metabolic depression. Understanding these relationships may provide a rationale for redefining depression as an immuno-metabolic disorder and support the development of more integrative therapeutic strategies targeting not only the brain, but also the gut-thyroid axis. Full article

Selenium (Se) is an essential trace element. The bioactivity of Se arises from its incorporation into the 21st amino acid, selenocysteine (Sec). Twenty-five human genes have been identified that encode selenoproteins, each of which contains at least one Sec residue. Selenoprotein functions include antioxidant responses, thyroid hormone synthesis, and maintenance of cellular redox homeostasis. Due to its role in critical cellular functions, Se deficiency is associated with morbidities of the cardiovascular system and connective tissue in regions of countries with low soil Se content. While these morbidities are geography-specific and have been mitigated in adults through public health interventions, preterm infants remain susceptible to Se deficiency worldwide. Infants born preterm are deprived of fetal Se accrual in the 3rd trimester of pregnancy, a deficiency compounded by higher Se needs than term infants and older infants and dependence on parenteral nutrition (PN) and fortification. In addition, the composition of selenoproteins and selenometabolites in human milk is different from that in formula and PN, yet little is known about the biological impact of these differences. The knowledge gap in optimal Se supplementation is reflected in discrepant guidelines between North American and European/Chinese nutrition societies, whose recommended Se supplementation in preterm infants differs by more than 2-fold. In this review, we describe the biosynthesis, metabolism, and maternal-fetal transfer of Se. In addition, we address how developmentally regulated aspects of metabolism may impact how preterm infants respond to supplementation with different forms of Se. Lastly, we highlight current challenges and recommendations for optimizing Se levels in neonates based on available data. Full article

Background: Papillary thyroid cancer (PTC) is the most common form of thyroid malignancy, with an incidence that has been steadily rising globally. Early and accurate diagnosis remains crucial for effective treatment and improved outcomes. MicroRNAs (miRNAs), small non-coding RNA molecules that regulate gene expression, have emerged as promising biomarkers in cancer research due to their stability and accessibility in serum. In this pilot study we compared the expression of 84 consistently reported, malignancy-associated serum miRNAs in patients with PTC (PTC group) and benign thyroid disease (Control group) as potential PTC markers. Methods: A focused panel containing primer assays for 84 human miRNAs that are consistently reported in the literature as being detectable and differentially expressed in serum in various organ-specific cancers was used to measure miRNA levels in serum samples from PTC (n = 8) and benign thyroid disease (n = 6) patients prior to thyroidectomy. Results: Among the 84 miRNAs analyzed, a panel of ten miRNAs showed numerical trends of differential expression between the two groups, including three upregulated (hsa-miR-150-5p, hsa-miR-21-5p, hsa-miR-23a-3p) and seven downregulated miRNAs (hsa-miR-17-5p, hsa-miR-17-3p, hsa-miR-200c-3p, hsa-miR-296-5p, hsa-miR-574-3p, hsa-miR-885-5p, hsa-miR-130-3p). The serum expression levels of hsa-miR-23a-3p were markedly elevated in patients with malignant nodules compared with those with benign lesions, while hsa-miR-574-3p was significantly downregulated in the PTC group. Conclusions: These findings warrant further investigation of hsa-miR-23a-3p and hsa-miR-574-3p in larger cohorts of patients with PTC to validate their potential clinical relevance. Full article

Iodine is an essential micronutrient required for the synthesis of thyroid hormones and the maintenance of metabolic, neurodevelopmental and immune function. As iodine cannot be synthesized endogenously, adequate intake depends on dietary sources and environmental availability. Despite decades of progress in improving iodine supply, both iodine deficiency and excess remain significant global public health challenges. This review summarizes iodine physiology, covering both its role in thyroid hormone synthesis and emerging evidence for extrathyroidal immunomodulatory and antioxidant actions. It summarizes major dietary sources, global intake patterns and current approaches to iodine status assessment, including urinary biomarkers, salivary iodide measurement and dietary screening tools. The clinical consequences of iodine imbalance are examined, ranging from goiter, hypothyroidism and impaired neurocognitive development associated with deficiency, to iodine-induced thyroid dysfunction, autoimmunity and adverse systemic effects linked to excess intake. Special attention is given to vulnerable populations, particularly pregnant women and infants. This review further evaluates public health strategies, including salt iodization and targeted supplementation, while addressing the emerging challenge posed by salt-reduction initiatives. Achieving optimal iodine intake remains essential for thyroid health and population well-being, underscoring the need for coordinated monitoring and policy adaptation. Full article

This case highlights a novel genotype–phenotype correlation in the field of endocrinology. Specific endocrine and imaging assessment, in addition to next-generation sequencing (NGS), was performed on the Illumina MiSeq platform, using a TruSight One Sequencing Panel kit for genomic analysis of coding regions of 4813 genes. A 54-year-old female was confirmed with a papillary thyroid carcinoma after total thyroidectomy and underwent radioiodine ablative therapy. Three years later, a left femoral enchondroma of almost 3 cm was identified at computed tomography (CT) scan and magnetic resonance imaging (MRI). She experienced hypertension (in addition to obesity, dyslipidaemia and impaired glucose tolerance) and was later confirmed with ACTH-independent cortisol excess [lack of cortisol suppression at 1 mg dexamethasone testing of 13.9 (normal < 1.8 µg/dL)], noting bilateral adrenal tumors, of 4.7 cm (right), respectively, and of 1.6 cm (left) at CT. Right laparoscopic adrenalectomy was performed with post-operative adrenal insufficiency, requiring glucocorticoid replacement and stopping the anti-hypertensive medication. Pathology report confirmed an adrenocortical adenoma (a Ki67 proliferation index of 2%). Noting the unusual association of the mentioned conditions, NGS was performed in the peripheral blood and identified a heterozygote missense variant of the APC gene (c.5759G>A, p.Arg1920Gln), a heterozygote missense variant of the MSH6 gene (c.2092C>G, p.Gln698Glu), and an incidental additional finding: a heterozygote stop gain pathogenic variant of the CACNA1S gene (c.2707C>T, p.Arg903*). The first two are currently classified as variants of uncertain significance. Whether the co-presence of a triple mutation may change the clinical picture and the life-long outcomes across reciprocal influence is still an open matter. Further research will point out the clinical implications of this genotype–phenotype association, which, to our best knowledge, has not been previously reported. Full article

Objectives: The mechanism of action of genes related to lactate metabolism in papillary thyroid carcinoma (PTC) is still unclear. In this study, key genes that play a role in PTC were selected from the known genes related to lactate metabolism, and their roles in promoting lactate metabolism in PTC cells were investigated. Methods: Through bioinformatics analysis and cell experiments, the roles of the relevant genes in lactate metabolism and their roles in the occurrence and development of PTC were verified. Results: Through bioinformatics analysis, 12 candidate genes were obtained. Through qRT-PCR experiments, it was confirmed that the expressions of TIMP1 and DPP4 were higher in thyroid papillary carcinoma than in normal PTC cells. By inhibiting the expression of TIMP1 and DPP4 using siRNA, the invasion and proliferation abilities of PTC could be reduced. Compared with normal thyroid cells, the contents of lactic acid and LDHA in PTC cells were higher. Knocking down the expression of TIMP1 and DPP4 would reduce the lactate production ability of PTC cells, and TIMP1 and DPP4 promoted the accumulation of lactate in PTC cells.Conclusions: In this study, by screening the differentially expressed lactate metabolism genes in PTC, different prognostic subtypes were constructed based on the molecular expression patterns. Multi-group student’s t-tests were conducted on the differential signaling pathways and tumor immune regulation of the prognostic subtypes, and a PTC prognosis prediction model was constructed. It was further confirmed that the lactate metabolism genes TIMP1 and DPP4 are highly expressed in PTC and can regulate the proliferation, invasion, metastasis and lactate metabolism of PTC cells. Full article

Thyroid hormones regulate a complex and interconnected network of metabolic signaling. Thyroid dysfunction is, at present, defined and monitored through circulating thyroid-stimulating hormone (TSH) and free thyroid hormones. However, biochemical normalization does not entirely indicate restoration of metabolic homeostasis. This discrepancy highlights a critical limitation of the current TSH-centric paradigm, which also fails to explain the heterogeneity in cardiometabolic outcomes observed among patients with similar biochemical profiles. Metabolomics, through the analysis of tissue-specific biofluids, could aid in capturing the complex metabolic perturbations that characterize this disease. In this review, we summarize metabolomic signatures typical of thyroid dysfunction, perform a critical evaluation of limitations and variability across studies, and explore the clinical and translational implications of metabolomics in thyroid pathology. In addition, five metabolic hubs influenced by thyroid hormone activity are summarized: (i) lipid and lipoprotein remodeling; (ii) mitochondrial energetics and redox balance; (iii) amino acid metabolism and protein turnover; (iv) gut–liver–thyroid axis and (v) biological impact of subclinical thyroid diseases. Taken together, these findings challenge the sufficiency of a diagnostic model based on TSH measurement and pose metabolomics as a promising tool to refine risk stratification, uncover subclinical vulnerability and guide patient-centered management of thyroid disease. Despite its promise, clinical adoption of metabolomics is hindered by a lack of standardization and complex data interpretation. To overcome these limitations, coupling metabolomics with genomics and transcriptomics may allow its translation into practical application. Full article

Objective: Primary extranodal lymphomas of the head and neck region are relatively rare and represent a biologically distinct subset. The diagnosis and differential diagnosis of head and neck lymphomas are important and deserve special attention. The aim of the present study was to retrospectively evaluate patients diagnosed with primary head and neck lymphomas at the Department of Pathology between January 2020 and January 2026. Histopathological subtypes, localization, relative frequencies, and overall survival were analyzed. Materials and Methods: This retrospective study included 31 cases diagnosed with lymphoma involving the head and neck region. Medical records were reviewed. Histopathological slides were re-evaluated under light microscopy by experienced pathologists. All cases were classified according to the current World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues. An extensive immunohistochemical panel was applied. Statistical analysis was performed using SPSS statistical software (version 27.0; IBM Corp., Armonk, NY, USA). Results: The study group included 31 patients with head and neck lymphoma. The most common histological type was diffuse large B-cell lymphoma (DLBCL) (54.8%). Other histological subtypes included follicular lymphoma (FL), mantle cell lymphoma (MCL), extranodal NK/T-cell lymphoma (NKTCL), anaplastic large cell lymphoma (ALCL), and Hodgkin lymphoma (HL). The most common location was the tonsil (38.7%). Other locations included the nasopharynx, oral cavity, nasal cavity, salivary glands, and thyroid. Epstein–Barr virus (EBV) positivity was detected in two patients (6.5%), and human immunodeficiency virus (HIV) infection was identified in two patients (6.5%). At the time of the last follow-up, 27 patients (87.1%) were alive, whereas four patients (12.9%) had died. The mortality rate was 12.9%. The median overall survival was 28 months (95% CI: 10–45). Conclusions: Malignant lymphoma should be considered when evaluating head and neck masses, and histopathological assessment of the affected tissue remains the cornerstone of diagnosis. Full article

Thyroid cancer (TC) is the most common endocrine malignancy, and challenges persist in preoperative diagnosis of indeterminate nodules and postoperative monitoring when thyroglobulin (Tg) assays are compromised by interfering anti-Tg antibodies (Tg-Ab). Extracellular vesicles (EVs) carry molecular cargo reflective of cells of origin and are increasingly explored as biomarker sources. In this study, we investigated whether thyroid-derived EVs retain the expression of thyroid-specific thyrotropin-receptor (TSHR), a suitable target in immunoaffinity-based EV isolation, and explored the presence of Tg in EV cargo as potential surrogate for serum Tg. EVs from thyroid cell lines (Nthy-Ori 3-1, TPC-1, OCUT2) and plasma of patients with benign, malignant tumors and recurrent TC were isolated by differential ultracentrifugation and characterized via nanoparticle tracking and Dot and Western blot analyses. EVs derived from Nthy-Ori 3-1 and TPC-1 cell lines were positive for surface TSHR and vesicular Tg, but not OCUT2. All plasma-derived EVs were positive for TSHR and Tg, while their electrophoretic profiles from vesicles differed compared to tissue lysate. Tg was detectable in EVs isolated from recurrent TC samples, even in Tg-Ab positive cases. Together, these results support the use of TSHR for targeted EV isolation and point to vesicular Tg as a potential recurrence marker. Full article

Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignancy arising in the thyroid or neck, with an uncertain cellular origin that complicates both diagnosis and treatment. To better understand its molecular underpinnings and identify potential therapeutic avenues, we conducted integrated whole-exome and transcriptome sequencing on six CASTLE and six thymic carcinoma samples. Whole-exome sequencing (WES) was performed on all 12 samples, while RNA sequencing was successful for 1 CASTLE and 6 thymic carcinoma samples. Our analysis included somatic mutation profiling, mutational signature deconvolution, differential gene expression, and characterization of tumor microenvironment for the cases with available data, with comparisons to genomic data from other thyroid cancers. CASTLE tumors demonstrated a higher median tumor mutational burden than thymic carcinoma and lacked the common BRAF and RAS mutations typically found in thyroid cancers. They harbored alterations in genes such as TRHDE, cilia-associated genes (ANKS6, CFAP46, DNAH6), and Wnt signaling components (TRRAP, BCL9L), as well as mutational signatures suggestive of mismatch repair deficiency and oxidative damage. MSIsensor-pro analysis of the WES data provided support for the potential for mismatch repair deficiency in a subset of CASTLE samples. Exploratory transcriptomic analysis from a single CASTLE case showed downregulation of thyroid follicular markers and an “immune-hot”, lymphocyte-rich microenvironment, closely resembling that of thymic carcinoma. While these findings require validation in larger cohorts, they support a thymic origin for CASTLE and establish its molecular distinction from follicular-derived thyroid cancers. The immunogenic tumor landscape suggests that immune checkpoint inhibitors, particularly those targeting PD-1/PD-L1, may be a promising therapeutic strategy, alongside emerging targets for precision oncology. Full article

Background: Surgical trauma disrupts hormone networks, but the duration required for these systems to recover remains unclear. We hypothesize that significant perioperative stress would trigger protracted abnormalities of the thyroid axis extending past 28 days. Methods: This retrospective exploratory study analyzed opportunistically obtained thyroid-related laboratory values (free T3 [FT3], free T4 [FT4], and thyroid-stimulating hormone [TSH]) and serum albumin from electronic medical records of patients undergoing CABG, AVR, or PCI between 2017 and 2022. Preprocedural baseline values were compared with post-procedural serum levels measured during the acute peri-procedural period (0–30 days), early recovery (31–90 days), intermediate recovery (91–180 days), late recovery (181–365 days), medium-term follow-up (1–2 years), and long-term follow-up (>2 years). Results: Free T3 demonstrated early suppression across all procedures, most pronounced in CABG during the acute peri-procedural period, with partial recovery at later timepoints. AVR showed moderate suppression at early and long-term follow-up, while PCI demonstrated minimal and inconsistent changes. Free T4 remained relatively stable across procedures, with limited significant post hoc differences after adjustment. TSH showed significant temporal variability in CABG and AVR but not in PCI. Serum albumin demonstrated marked early decline, most pronounced in CABG, with partial recovery over time, whereas AVR showed delayed long-term suppression. Data availability declined substantially at later timepoints across all biomarkers. Conclusions: In this retrospective exploratory analysis, CABG was associated with the most pronounced early perturbations in thyroid and albumin trajectories, while PCI and AVR demonstrated more heterogeneous temporal patterns. These findings are hypothesis-generating and should be interpreted cautiously given non-protocolized laboratory follow-up, substantial missingness, and potential selection bias. Full article

Background/Objectives: Chronic urticaria (CU) is a heterogeneous inflammatory disorder generally attributed to mast cell activation. However, emerging evidence suggests that metabolic reprogramming and systemic immune dysregulation also contribute to the disease pathophysiology. This study aimed to investigate the interplay between epithelial barrier integrity, innate immune regulation, metabolic activity, and mast cell effector mechanisms in CU. Methods: Forty CU patients and 40 healthy controls were evaluated. Clinical parameters included disease severity, disease subtype, antihistamine response, IgE levels, anti-TPO status, gastrointestinal symptoms, and angioedema. Serum levels of histamine, intestinal fatty acid-binding protein (IFABP), soluble CD14 (sCD14), diamine oxidase (DAO), D-lactic acid, endotoxin, zonulin, calprotectin, and related ratios were measured. Disease activity and control were assessed using the UAS7 and UCT scores. Results: CU patients exhibited significantly higher DAO (p = 0.003) and lactic acid (p = 0.004) levels compared to controls, whereas other markers showed no significant differences. In anti-TPO-positive patients, sCD14 levels were reduced (p = 0.024), while histamine/sCD14 (p = 0.005), lactic acid/sCD14 (p = 0.014), IFABP/sCD14 (p = 0.008), and zonulin/sCD14 (p = 0.027) were significantly elevated, suggesting relative amplification of metabolic and barrier-related signals under impaired innate immune regulation. Severe anti-TPO-positive patients exhibited lower sCD14 (p = 0.022) and NLR (p = 0.013) but higher UAS7 (p = 0.032), histamine (p = 0.011), calprotectin (p = 0.041), and CD14-normalized ratios, including histamine (p = 0.003), IFABP (p = 0.028), lactic acid (p = 0.019), zonulin (p = 0.029), and calprotectin (p = 0.011) compared with severe anti-TPO-negative patients, indicating a mast cell-dominant and metabolically active inflammatory phenotype. The lactic acid/DAO ratio was significantly lower in controlled versus uncontrolled CU (p = 0.013) and showed discriminatory potential for disease control. Patients with angioedema had higher CRP (p = 0.038) and UAS7 scores (p < 0.001). Conclusions: CU exhibits marked immunometabolic heterogeneity. Elevated DAO and lactic acid indicate increased histamine turnover and metabolic activation, whereas altered sCD14-normalized biomarker profiles reveal immune dysregulation in anti-TPO-positive patients. Severe CU with features suggestive of thyroid autoimmunity manifests as a mast cell-dominant, metabolically active phenotype with relative suppression of innate immune modulators, contrasting with alternative pathways in other CU phenotypes. The lactic acid/DAO ratio may serve as a candidate biomarker of disease control. These results underscore the importance of phenotype-tailored therapeutic strategies in CU. Full article