Search Results (20)

Endocrine-Disrupting Chemicals (EDCs) disrupt thyroid hormone (TH) synthesis, transport, metabolism, and action, thereby perturbing systemic endocrine homeostasis. Transthyretin (TTR) is a key TH transport protein that regulates circulating hormone distribution and tissue availability, particularly during critical developmental windows. Chemical interference with TTR-binding may alter TH bioavailability and represent a transport-mediated molecular initiating event within thyroid-axis perturbation. Despite widespread exposure, many thyroidal EDCs remain unidentified, and their health effects are difficult to assess due to multiple simultaneous exposures. To support endocrine hazard identification and chemical prioritization within risk assessment frameworks, we developed machine learning-based QSAR models during the Tox24 challenge, using a dataset of 1512 chemicals to predict TTR-binding affinity. Of these, 67% were used for training, 13% for testing, and 20% for validation. Molecular descriptors were selected by first removing highly correlated features and then ranking the remaining descriptors using mutual information regression. The leverage approach was applied to define the models’ applicability domain (AD). Five machine learning algorithms, including gradient boosting regressor (GBR), Random Forest, Lasso Regression, Support Vector Machine (SVM), and regularized SVM models, were developed. The GBR model demonstrated the best overall performance. This model achieved an R² of 0.89 on the training set, 0.58 on the test set, and 0.55 on the validation set. The molecular descriptor analysis highlights hydrophobicity, steric effects, branching, connectivity, and ionization/electronic effects as the mechanistic basis for TTR disruption and stabilization, providing structural insight into features associated with thyroid hormone displacement. The AD analysis indicated that 97.5% of the test set and 96.0% of the validation set fell within the reliable descriptor space. Importantly, these predictions extend beyond model benchmarking by informing weight-of-evidence evaluations of thyroid-axis perturbation and supporting the prioritization of chemicals for targeted testing within non-animal new approach methodologies. Overall, this work highlights the application of in silico approaches for screening EDCs, supporting the prioritization and identification of potentially harmful chemicals. Full article

Diabetic foot complications represent a major global health burden and arise from a multifactorial interaction between neuropathy, ischemia, infection, and impaired wound repair. Increasing evidence suggests that, beyond traditional vascular and metabolic risk factors, endocrine dysregulation plays a central role in shaping vascular dysfunction and tissue vulnerability in patients with diabetes. This narrative review provides an updated overview of the endocrine–vascular axis in the development, progression, and healing of diabetic foot ulcers (DFUs), integrating evidence from experimental and clinical studies identified through targeted searches of PubMed, Embase, and Scopus. We examine how alterations in insulin signaling, relative glucagon excess, adipokine imbalance, dysregulation of stress hormones, and thyroid dysfunction interact with chronic hyperglycemia, dyslipidemia, mitochondrial dysfunction, and low-grade inflammation to impair endothelial homeostasis. These disturbances promote oxidative stress, reduce nitric oxide bioavailability, and compromise microvascular perfusion, thereby creating a pro-ischemic and pro-inflammatory tissue environment that limits angiogenesis, extracellular matrix (ECM) remodeling, immune coordination, and effective wound repair. By linking pathophysiological mechanisms to clinical relevance, this review highlights potential biomarkers of endocrine–vascular dysfunction, implications for risk stratification, and emerging therapeutic perspectives targeting metabolic optimization, endothelial protection, and hormonal modulation. Finally, key knowledge gaps and priority areas for future translational and clinical research are discussed, supporting the development of integrated endocrine-based strategies aimed at improving DFU prevention, healing outcomes, and long-term limb preservation in patients with diabetes. Full article

Background/Objectives: Iodine plays a key role in thyroid hormone synthesis and metabolic regulation in vertebrates. This study aimed to evaluate the in vivo bioavailability of iodine and assess selected biochemical parameters and thyroid-related gene expression in male Wistar rats fed lettuce (Lactuca sativa L.) biofortified with iodoquinolines (8-hydroxy-7-iodo-5-quinolinesulfonic acid or 5,7-diiodo-8-quinolinol) or potassium iodate. Methods: Two iodine intake levels were applied, a nutritionally adequate iodine level and a supranutritional level, to evaluate the nutritional safety of iodine obtained from biofortified vegetables. Results: A diet containing lettuce biofortified with iodoquinolines at the adequate level had no significant effect on thyroid hormone concentrations, the expression of Dio1, Dio2, Slc5a5, and Tpo genes, or thyroid morphology. While supranutritional iodine intake led to increased levels of T4, fT4, T3, and fT3, all hormone concentrations remained within the physiological range. No elevation in liver enzyme activity (ALT, AST, ALP) was observed, indicating the absence of hepatotoxic effects from high-iodine diets based on biofortified lettuce. Compared to potassium iodate, iodoquinolines demonstrated superior bioavailability, as evidenced by enhanced iodine accumulation in tissues and more efficient thyroid hormone synthesis. Conclusions: To the best of our knowledge, this is the first in vivo nutritional study assessing the physiological effects of supranutritional iodine intake from a biofortified plant source. These findings confirm the nutritional safety and efficacy of iodine biofortification using iodoquinolines and highlight the need for further research, including human nutritional clinical trials. Full article

Selenium (Se) is an essential trace element involved in antioxidant redox regulation, thyroid hormone metabolism, and cancer prevention. Among its different forms, elemental selenium (Se⁰), particularly at the nanoscale, has gained growing attention in food, feed, and biomedical applications due to its lower toxicity and higher bioavailability compared to inorganic selenium species. However, the detection of Se⁰ in real samples remains challenging as current analytical methods are time-consuming, labour-intensive, and often unsuitable for rapid analysis. In this study, we developed a method for rapidly measuring Se⁰ using carbon nanodots (CNDs) produced from the Maillard reaction between glucose and glycine. The fabricated CNDs were water-dispersible and strongly fluorescent, with an average particle size of 3.90 ± 1.36 nm. Comprehensive characterisation by transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), fluorescence spectroscopy, and Raman spectroscopy confirmed their structural and optical properties. The CNDs were employed as fluorescent probes for the selective detection of Se⁰. The sensor showed a wide linear detection range (0–12.665 mmol L⁻¹), with a low detection limit (LOD) of 0.381 mmol L⁻¹ and a quantification limit (LOQ) of 0.465 mmol L⁻¹. Validation with spiked real samples—including ultra-pure water, tap water, and soft drinks—yielded high recoveries (98.6–108.1%) and low relative standard deviations (<3.4%). These results highlight the potential of CNDs as a simple, reliable, and environmentally friendly sensing platform for trace-level Se⁰ detection in complex food and beverage matrices. Full article

Objective: This study evaluated the systemic bioavailability of L-thyroxine (L-T4) in healthy women following repeated cutaneous application of a new gel formulation containing L-T4 and escin. Plasma concentrations of free triiodothyronine (FT3), reverse triiodothyronine (rT3), and thyroid-stimulating hormone (TSH) were also assessed, along with local and systemic tolerability. Methods: Thirty healthy women participated in a single-group, open-label trial. L-thyroxine gel was applied at 20 g/day for the first 2 days and 10 g/day for the following 26 days (equivalent to 20 mg/day and 10 mg/day of L-T4, respectively). Blood samples were collected at Baseline, 5 and 24 h after the first application, and on Days 14, 28 (End of Treatment, EOT), and 42 (End of Study, EOS). Tolerability and safety were monitored throughout. Results: Plasma FT4 concentrations remained stable throughout the study, with no clinically significant changes from Baseline (1.13 ± 0.15 ng/dL) to EOT (1.11 ± 0.13 ng/dL). FT3 and TSH levels also remained within physiological ranges, with only a transient, non-clinically relevant decrease observed 5 h after the first application. No changes in rT3 concentrations were detected at any time point. No serious adverse events were reported. Conclusions: This study confirms that repeated application of L-thyroxine/escin gel over 28 days (total exposure of 300 g) does not affect systemic thyroid hormone levels and is well tolerated in healthy women. These findings support the hypothesis that intact skin acts as an effective barrier to transdermal L-T4 absorption. Full article

SHBG is a glycoprotein that not only controls serum sex hormone levels but is also strongly correlated with metabolic syndrome, cardiovascular risk, thyroid function, gynecological conditions, and even the process of carcinogenesis. Synthesis of SHBG is controlled by many factors related to obesity, lipogenesis, inflammatory status, and genetic predisposition. By influencing the bioavailability of sex hormones, SHBG regulates their effects not only on the reproductive system, but also cardiomyocytes, vascular epithelium, and more. In this review, we aim to gather and summarize current knowledge on the physiology of SHBG and its association with cardiovascular disease, metabolic syndrome, DM 2, thyroid function, PCOS, hypogonadism, infertility, and its correlations with oral contraception. What is more, genetic alterations are mentioned to highlight SHBG as a potential new diagnostic marker. Furthermore, we assess the clinical usefulness of this parameter in the diagnosis and treatment of patients suffering from the above-specified conditions. Full article

Iodine is a key micronutrient essential for the synthesis of thyroid hormone, which regulates metabolic processes and maintains overall health. Despite its importance, iodine deficiency is a global health issue, leading to disorders such as goiter, hypothyroidism, and developmental abnormalities. Biofortification of crops with iodine is a promising strategy to enhance the dietary iodine intake, providing an alternative to iodized salt. Curly kale (Brassica oleracea var. sabellica) is a nutrient-rich vegetable high in vitamins A, C, K; minerals; fiber; and bioactive compounds with antioxidant, anti-inflammatory, and detoxifying properties. This study evaluates the effects of diets containing iodine-biofortified curly kale (‘Oldenbor F₁’ and ‘Redbor F₁’) on iodine content, tissue iodine levels, and various biochemical parameters in laboratory rats. The biofortified curly kale was enriched with 5,7-diiodo-8-quinolinol. The iodine content in the AIN-93G (control) diet and the non-biofortified curly kale diets did not differ significantly. However, diets with 5,7-diiodo-8-quinolinol biofortified kale showed significantly higher iodine levels compared with the control diets. Tissue analysis revealed the highest iodine concentrations in the liver and kidneys of rats fed diets with biofortified curly kale, indicating better iodine bioavailability. Biochemical analysis showed that rats fed the biofortified kale diet had lower total cholesterol (TC) and triglyceride (TG) levels compared with rats fed the control diet. Additionally, the biofortified diet improved the liver function markers (ALAT, ASAT) and reduced oxidative stress markers (TBARS). The study also investigated the expression of thyroid-related genes (Slc5A5, Tpo, Dio1, Dio2) in response to diets containing biofortified kale. The results demonstrated significant changes in gene expression, indicating adaptive mechanisms to dietary iodine levels and the presence of bioactive compounds in the biofortified kale. The study also observed variations in uric acid levels, with lower concentrations in rats fed a diet with biofortified curly kale. Biofortified curly kale supports thyroid function and improves liver and kidney health by reducing oxidative stress and modulating key biochemical and genetic markers. These findings suggest that biofortified curly kale can effectively increase dietary iodine intake as a nutritional intervention to address iodine deficiency and promote overall health. Full article

Aging affects the structure and functions of all organs and systems in the organism. In the elderly, significant changes in hormonal levels are observed. These translate to a predisposition for chronic diseases, including cardiovascular, neurodegenerative, and metabolic disorders. Therefore, tremendous scientific effort is focused on investigating molecular mechanisms and drugs with the potential to reduce hormonal changes in old age and their impact. Sirtuin 1 (SIRT1), a member of the sirtuin family of deacetylases, has been extensively studied as a regulator of multiple pathways related to antioxidant properties, optimal immune response, and metabolism. SIRT1 plays a key role in regulating various hormonal pathways and maintaining homeostasis. In the present study, we review the interplay between SIRT1 and hormonal regulations, including the endocrine role of the hypothalamic–pituitary–thyroid, –adrenal, –gonadal, and –liver axes, of other endocrine glands, and of non-endocrine tissues in the aging organism. The application of natural SIRT1 activators, such as resveratrol, curcumin, paeonol, and Buyang Huanwu Decoction, for the treatment of aging and senescence is discussed. SIRT1 activators improve mitochondrial function, reduce oxidative stress, and promote longevity, but their clinical application is limited by low bioavailability and poor permeability across biological barriers. For this reason, advanced delivery strategies are being considered, including nose-to-brain drug delivery and nanotechnology-based formulations. Full article

In recent years, selenium nanoparticles (SeNPs) have attracted expanding consideration, particularly in the nanotechnology field. This element participates in important biological processes, such as antioxidant defense, immune function, and thyroid hormone regulation, protecting cells from oxidative damage. Selenium in the form of nanoscale particles has drawn attention for its biocompatibility, bioavailability, and low toxicity; thus, it has found several biomedical applications in diagnosis, treatment, and monitoring. Green methods for SeNP synthesis using plant extracts are considered to be single-step, inexpensive, and eco-friendly processes. Besides acting as natural reductants, compounds from plant extracts can also serve as natural capping agents, stabilizing the size of nanoparticles and contributing to the enhanced biological properties of SeNPs. This brief overview presents the recent developments in this area, focusing on the synthesis conditions and the characteristics of the obtained SeNPs. Full article

Thyroid diseases affect a considerable portion of the population, with hypothyroidism being one of the most commonly reported thyroid diseases. Levothyroxine (T4) is clinically used to treat hypothyroidism and suppress thyroid stimulating hormone secretion in other thyroid diseases. In this work, an attempt to improve T4 solubility is made through the synthesis of ionic liquids (ILs) based on this drug. In this context, [Na][T4] was combined with choline [Ch]⁺ and 1-(2-hydroxyethyl)-3-methylimidazolium [C₂OHMiM]⁺ cations in order to prepare the desired T4-ILs. All compounds were characterized by NMR, ATR-FTIR, elemental analysis, and DSC, aiming to check their chemical structure, purities, and thermal properties. The serum, water, and PBS solubilities of the T4-ILs were compared to [Na][T4], as well as the permeability assays. It is important to note an improved adsorption capacity, in which no significant cytotoxicity was observed against L929 cells. [C₂OHMiM][T4] seems to be a good alternative to the commercial levothyroxine sodium salt with promising bioavailability. Full article

Dietary selenium (Se) intake within the physiological range is critical to maintain various biological functions, including antioxidant defence, redox homeostasis, growth, reproduction, immunity, and thyroid hormone production. Chemical forms of dietary Se are diverse, including organic Se (selenomethionine, selenocysteine, and selenium-methyl-selenocysteine) and inorganic Se (selenate and selenite). Previous studies have largely investigated and compared the health impacts of dietary Se on agricultural stock and humans, where dietary Se has shown various benefits, including enhanced growth performance, immune functions, and nutritional quality of meats, with reduced oxidative stress and inflammation, and finally enhanced thyroid health and fertility in humans. The emergence of nanoparticles presents a novel and innovative technology. Notably, Se in the form of nanoparticles (SeNPs) has lower toxicity, higher bioavailability, lower excretion in animals, and is linked to more powerful and superior biological activities (at a comparable Se dose) than traditional chemical forms of dietary Se. As a result, the development of tailored SeNPs for their use in intensive agriculture and as candidate for therapeutic drugs for human pathologies is now being actively explored. This review highlights the biological impacts of SeNPs on growth and reproductive performances, their role in modulating heat and oxidative stress and inflammation and the varying modes of synthesis of SeNPs. Full article

The aim of this study was to examine the influence of the level (1, 3, and 5 mg I/kg) and source of iodine (KI, Ca(IO₃)₂, and KIO₃) on thyroid hormone and immunoglobulin concentrations in the blood serum of laying hens alongside a histological picture of the thyroid. In the first, birds were fed grain–soybean meal mixtures, and in the second, two kinds of diets based on corn–soybean or corn–soybean–rapeseed meal were applied. In the experiments, we determined the levels of the blood serum thyroid hormones fT₃ and fT₄, as well as the morphological structure of the thyroid gland. In the second experiment, the concentration of immunoglobulins in blood serum was assayed. In both experiments, no influence of iodine source on thyroid hormone concentration was observed. However, increasing the iodine level in the full mixture and adding rapeseed meal in both experiments caused an increase in fT₃ concentration. Increasing I-addition in both experiments led to a decrease in thyroid gland follicle diameter. Rapeseed meal inclusion (at a level of 10%) to the complete hen mixture led to an increase in thyroid gland follicle diameter. Applying KIO₃ as an iodine source in both experiments caused a decrease in the thyroid gland height of follicle epithelial cells. Immunoglobulin concentrations in the serum were not affected by experimental factors. The results suggest that the methodologies of studies on the bioavailability of minerals and the corresponding analytical methods require unification. The lack of such standardization makes it impossible to engage in a satisfactory discussion of the results and exchange experiences. Full article

Suboptimal iodine status is a prominent public health issue in several European coun-tries. Brown algae have a high iodine content that, upon intake, may exceed the recommended dietary intake level, but iodine bioavailability has been reported to be lower than from potassium iodide (KI) and highly depends on algae species. Further, potential negative effects from other components in algae, such as cadmium (Cd) and arsenic (As), have also been addressed. In this study, we observed a lower bioavailability of iodine from farmed sugar kelp (Saccharina latissima) than from KI in female Wistar IGS rats. Urinary iodine excretion was 94–95% in rats fed KI and 73–81% in rats fed sugar kelp, followed by increased faecal iodine levels in rats fed sugar kelp. No effects on body weight, feed efficiency, or plasma markers for liver or kidney damage were detected. The highest dose of iodine reduced plasma free thyroxine (fT4) and total T4 levels, but no significant effects on circulating levels of thyroid-stimulating hormone (TSH) and free triiodo-thyronine (fT3) were detected. Faeces and urine measurements indicate that 60–80% of total As and 93% of Cd ingested were excreted in rats fed 0.5 and 5% kelp. Liver metabolomic profiling demonstrates that a high inclusion of sugar kelp in the diet for 13 weeks of feeding modulates metabolites with potential antioxidant activity and phytosterols. Full article

Thyroid hormone is essential for fetal (brain) development. Plasma membrane transporters control the intracellular bioavailability of thyroid hormone. In the past few decades, 15 human thyroid hormone transporters have been identified, and among them, mutations in monocarboxylate transporter (MCT)8 and organic anion transporting peptide (OATP)1C1 are associated with clinical phenotypes. Different animal and human models have been employed to unravel the (patho)-physiological role of thyroid hormone transporters. However, most studies on thyroid hormone transporters focus on postnatal development. This review summarizes the research on the thyroid hormone transporters in pregnancy and fetal development, including their substrate preference, expression and tissue distribution, and physiological and pathophysiological role in thyroid homeostasis and clinical disorders. As the fetus depends on the maternal thyroid hormone supply, especially during the first half of pregnancy, the review also elaborates on thyroid hormone transport across the human placental barrier. Future studies may reveal how the different transporters contribute to thyroid hormone homeostasis in fetal tissues to properly facilitate development. Employing state-of-the-art human models will enable a better understanding of their roles in thyroid hormone homeostasis. Full article

Levothyroxine (LT4) is a standard therapy in hypothyroidism; however, its bioavailability and therapeutic effects might be affected by many factors. Data shows that therapy with liquid LT4 characterized by quicker pharmacokinetics provides better thyroid hormones control than tablet LT4. We addressed the quality of life (QoL) and efficacy of the new ethanol-free formula of liquid LT4 (Tirosint^®SOL) treatment in 76 euthyroid patients with primary (PH, n = 46) and central hypothyroidism (CH, n = 30), and compared the results to retrospective data on equivalent doses of tablet L-T4 therapy. After 8 weeks of liquid LT4 therapy, we found a significant improvement in QoL in both PH and CH patients. TSH levels were unaltered in PH patients. Free hormone levels (fT4 and fT3) increased in all the patients, with the exception of fT3 in the CH group. SHBG and low-density lipoprotein (LDL) also improved. Liquid LT4 therapy provided a better thyroid hormone profile and improvement in patients’ QoL than the tablet form, which was possibly due to the more favorable pharmacokinetics profile resulting in better absorption, as suggested by the increased free thyroid hormone levels. In summary, this is the first study addressing the QoL in hypothyroid patients, including primary and central hypothyroidism, treated with liquid LT4 formula in everyday practice. Full article