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36 pages, 6047 KiB  
Review
Prevalence and Levels of Thyroid Autoantibodies in Polycystic Ovary Syndrome—Impact of TSH- and BMI-Matched Comparisons: A Systematic Review and Meta-Analysis
by Jakub Kwiatkowski, Nicole Akpang, Lucja Zaborowska and Artur Ludwin
Int. J. Mol. Sci. 2025, 26(15), 7525; https://doi.org/10.3390/ijms26157525 (registering DOI) - 4 Aug 2025
Abstract
Polycystic ovary syndrome (PCOS) is a complex condition affecting women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, polycystic ovarian morphology, and low-grade inflammation accompanied by oxidative stress and increased autoimmune risk, particularly Hashimoto’s thyroiditis. Many studies have examined thyroid autoantibodies—anti-thyroid peroxidase antibodies [...] Read more.
Polycystic ovary syndrome (PCOS) is a complex condition affecting women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, polycystic ovarian morphology, and low-grade inflammation accompanied by oxidative stress and increased autoimmune risk, particularly Hashimoto’s thyroiditis. Many studies have examined thyroid autoantibodies—anti-thyroid peroxidase antibodies (anti-TPO) and anti-thyroglobulin antibodies (anti-TG)—in PCOS; however, observed differences in baseline thyroid-stimulating hormone (TSH) levels and body mass indices (BMIs) impede a direct interpretation of the results. This systematic review and meta-analysis aimed to summarize the available evidence on the prevalence and levels of anti-TPO and anti-TG in women with PCOS. We conducted a systematic search of PubMed, Scopus, and Embase, which yielded 40 eligible, observational studies including 6045 women with PCOS and 4527 controls. Subgroup analyses were conducted separately for TSH- and BMI-matched populations. Anti-TPO prevalence (odds ratio [OR] = 2.03; 95% confidence interval [CI]: 1.35–3.04; p = 0.0006) and levels (standardized mean difference [SMD] = 0.63; 95% CI: 0.37–0.88; p < 0.00001) were significantly higher in PCOS patients. Anti-TG prevalence (OR = 1.92; 95% CI: 1.23–3.01; p = 0.004) and levels (SMD = 0.41; 95% CI: 0.18–0.64; p = 0.0004) were also significantly elevated. In matched subgroups, prevalence differences were no longer significant, though anti-TPO levels remained significantly elevated and anti-TG levels were borderline significant in the TSH-matched subgroup of PCOS women. Although differences in thyroid autoantibody prevalence in women with PCOS appear to be driven by elevated TSH levels and BMIs, the persistently increased antibody levels in the majority of matched subgroups suggest that PCOS itself may contribute independently to heightened autoimmune activation. Full article
(This article belongs to the Section Molecular Oncology)
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13 pages, 2643 KiB  
Review
Primary Hyperparathyroidism: 18F-Fluorocholine PET/CT vs. 4D-CT for Parathyroid Identification: Toward a Comprehensive Diagnostic Framework—An Updated Review and Recommendations
by Gregorio Scerrino, Nunzia Cinzia Paladino, Giuseppa Graceffa, Giuseppina Melfa, Giuseppina Orlando, Renato Di Vuolo, Chiara Lo Cicero, Alessandra Murabito, Stefano Radellini, Pierina Richiusa and Antonio Lo Casto
J. Clin. Med. 2025, 14(15), 5468; https://doi.org/10.3390/jcm14155468 - 4 Aug 2025
Abstract
Introduction: Primary hyperparathyroidism (pHPT) is an endocrine disorder characterized by excessive parathyroid hormone production, typically due to adenomas, hyperplasia, or carcinoma. Preoperative imaging plays a critical role in guiding surgical planning, particularly in selecting patients for minimally invasive procedures. While first-line imaging [...] Read more.
Introduction: Primary hyperparathyroidism (pHPT) is an endocrine disorder characterized by excessive parathyroid hormone production, typically due to adenomas, hyperplasia, or carcinoma. Preoperative imaging plays a critical role in guiding surgical planning, particularly in selecting patients for minimally invasive procedures. While first-line imaging techniques, such as ultrasound and 99mTc-sestamibi scintigraphy, are standard, advanced second-line imaging modalities like 18F-fluorocholine PET/CT (FCH-PET) and four-dimensional computed tomography (4D-CT) have emerged as valuable tools when initial diagnostics are inconclusive. Methods: This article provides an updated review and recommendations of the role of these advanced imaging techniques in localizing parathyroid adenomas. Results: FCH-PET has shown exceptional sensitivity (94% per patient, 96% per lesion) and is particularly useful in detecting small or ectopic adenomas. Despite its higher sensitivity, it can yield false positives, particularly in the presence of thyroid disease. On the other hand, 4D-CT offers detailed anatomical imaging, aiding in the identification of parathyroids in challenging cases, including recurrent disease and ectopic glands. Studies suggest that FCH-PET and 4D-CT exhibit similar diagnostic performance and could be complementary in preoperative planning of most difficult situations. Conclusions: This article also emphasizes a multimodal approach, where initial imaging is followed by advanced techniques only in cases of uncertainty. Although 18F-fluorocholine PET/CT is favored as a second-line option, 4D-CT remains invaluable for its high spatial resolution and ability to guide surgery in complex cases. Despite limitations in evidence, these imaging modalities significantly enhance the accuracy of parathyroid localization, contributing to more targeted and minimally invasive surgery. Full article
(This article belongs to the Section General Surgery)
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16 pages, 575 KiB  
Article
Polycystic Ovary Syndrome Attenuates TSH-Lowering Effect of Metformin in Young Women with Subclinical Hypothyroidism
by Robert Krysiak, Karolina Kowalcze, Johannes Ott, Sofia Burgio, Simona Zaami and Bogusław Okopień
Pharmaceuticals 2025, 18(8), 1149; https://doi.org/10.3390/ph18081149 - 1 Aug 2025
Viewed by 176
Abstract
Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: [...] Read more.
Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis. Full article
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18 pages, 1782 KiB  
Review
Nutrition and Micronutrient Interactions in Autoimmune Thyroid Disorders: Implications for Cardiovascular Health
by Michał Mazur, Magdalena Szymańska, Agnieszka Malik, Wojciech Szlasa and Joanna Popiołek-Kalisz
Pathophysiology 2025, 32(3), 37; https://doi.org/10.3390/pathophysiology32030037 - 1 Aug 2025
Viewed by 141
Abstract
Thyroid hormones play a crucial role in regulating metabolism and cardiovascular function, with even mild dysfunction—such as subclinical hypothyroidism—negatively impacting heart health. While previous studies have confirmed the effects of iodine, selenium, and vitamin D on thyroid regulation and inflammation, the combined role [...] Read more.
Thyroid hormones play a crucial role in regulating metabolism and cardiovascular function, with even mild dysfunction—such as subclinical hypothyroidism—negatively impacting heart health. While previous studies have confirmed the effects of iodine, selenium, and vitamin D on thyroid regulation and inflammation, the combined role of these nutrients in reducing cardiovascular disease (CVD) risk in autoimmune thyroid disorders remains insufficiently understood. This review explores the influence of specific micronutrients—including selenium, iodine, and zinc—and dietary patterns, particularly the Mediterranean diet, on the pathophysiology of hypothyroidism and Hashimoto’s thyroiditis. We introduce a novel framework that integrates emerging data on sex-specific micronutrient interactions and nutritional immunomodulation. Unlike the existing literature, this review introduces original hypotheses related to sex-specific nutritional immunomodulation and proposes a novel framework for micronutrient-driven dietary intervention in Hashimoto’s thyroiditis. Full article
(This article belongs to the Section Metabolic Disorders)
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13 pages, 721 KiB  
Article
The Influence of Hyperthyroid Metabolic Status on the Coagulation and Fibrinolysis System and the Risk of Thrombosis: A Prospective Cohort Study
by Manuela Andrea Hoffmann, Anne Zinndorf, Florian Rosar, Inge Scharrer, Nicolas Fischer, Tobias Gruebl, Pia-Elisabeth Baqué, Stefan Reuss and Mathias Schreckenberger
Biomedicines 2025, 13(8), 1869; https://doi.org/10.3390/biomedicines13081869 - 1 Aug 2025
Viewed by 208
Abstract
Background: Risk assessment in hyperthyroidism remains challenging. The aim of the present study is to determine the influence of hyperthyroid metabolic status on blood clotting and an increased risk of thrombosis. Methods: This prospective study included 50 patients after radical thyroidectomy [...] Read more.
Background: Risk assessment in hyperthyroidism remains challenging. The aim of the present study is to determine the influence of hyperthyroid metabolic status on blood clotting and an increased risk of thrombosis. Methods: This prospective study included 50 patients after radical thyroidectomy and ablative radioiodine therapy because of thyroid carcinoma who were compared with 50 control subjects in a euthyroid metabolic state. Latent hyperthyroid patients with basal thyroid-stimulating hormone (TSH) ≤ 0.15 mU/L on levothyroxine hormone therapy were included. The control group was selected to match the patient group based on age and sex. The evaluation data were collected using laboratory coagulation tests and patient questionnaires. A bleeding and a thrombosis score were determined. Results: The coagulation parameters between the patient and control groups showed statistically significant differences. In particular, the patients’ group showed a significantly shortened activated partial thromboplastin time (aPTT/p = 0.009) and a significantly higher plasminogen activator inhibitor 1 (PAI-1/p < 0.001) compared to the control group. Age, sex, and medication use were not found to influence the patients’ laboratory results. Only body mass index was higher in the patient group than in the control group. Conclusions: Our results support a shift in the coagulation system in latent hyperthyroid metabolism towards increased coagulability and reduced fibrinolysis. A latent hyperthyroid metabolic state appears to be associated with an increased risk of thrombosis. Further prospective cohort studies with large patient populations are needed to verify the association between (latent) hyperthyroidism and thromboembolic events as well as to determine therapeutic anticoagulation or to adjust the indication for exogenous administration of thyroid hormone. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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17 pages, 666 KiB  
Review
Three Major Deficiency Diseases Harming Mankind (Protein, Retinoid, Iron) Operate Under Tryptophan Dependency
by Yves Ingenbleek
Nutrients 2025, 17(15), 2505; https://doi.org/10.3390/nu17152505 - 30 Jul 2025
Viewed by 173
Abstract
This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated [...] Read more.
This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article
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13 pages, 615 KiB  
Article
Euthyroid Sick Syndrome as an Index of Prognosis in Severe COVID-19 Disease
by Lambros Athanassiou, Ifigenia Kostoglou-Athanassiou, Georgia Kaiafa, Sofia Nikolakopoulou, Alexandra Konstantinou, Olga Mascha, Charilaos Samaras, Christos Savopoulos, Yehuda Shoenfeld and Panagiotis Athanassiou
Medicina 2025, 61(8), 1372; https://doi.org/10.3390/medicina61081372 - 29 Jul 2025
Viewed by 206
Abstract
Background and Objectives: Euthyroid sick syndrome, or non-thyroidal illness syndrome, has been observed in severely ill patients and has been found to be an index of prognosis. It has been detected in patients with severe infectious diseases, e.g., those with severe COVID-19 [...] Read more.
Background and Objectives: Euthyroid sick syndrome, or non-thyroidal illness syndrome, has been observed in severely ill patients and has been found to be an index of prognosis. It has been detected in patients with severe infectious diseases, e.g., those with severe COVID-19 infection. Prognostic indicators of the outcome of severe COVID-19 disease are important for the prognosis of individual as well as groups of patients. The aim of this study was to identify euthyroid sick syndrome in patients admitted for severe COVID-19 disease and its relationship to disease severity and outcome. Materials and Methods: In a cohort of patients admitted to hospital for severe COVID-19 disease, thyroid function in patients requiring hospitalization was evaluated by measuring TSH, FreeT3 (FT3), and FreeT4 (FT4) levels. Patients were classified into four groups: a group with uncompromised respiratory function (pO2 > 70 mmHg, without need of oxygen supplementation) (disease severity 1); a group with mild respiratory insufficiency (pO2 50–60 mmHg, in need of oxygen supplementation with nasal cannula) (disease severity 2); a group with severe respiratory insufficiency (pO2 < 50 mmHg, in need of oxygen supplementation with high flow oxygen) (disease severity 3); and a group with severe respiratory insufficiency requiring intubation (pO2 < 60 mmHg on high flow oxygen supplementation) (disease severity 4). Results: In this cohort, euthyroid sick syndrome was diagnosed in 57.1% of the patients. The presence of euthyroid sick syndrome was related to increased disease severity and adverse disease outcome, i.e., death. FT3 levels were inversely related to CRP levels. Conclusions: Euthyroid sick syndrome may be observed in severe COVID-19 disease and is related to increased disease severity and adverse outcomes. Measurement of thyroid hormones in patients hospitalized for severe COVID-19 infection may aid in the prognosis of the disease. Full article
(This article belongs to the Section Epidemiology & Public Health)
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27 pages, 1569 KiB  
Review
Bisphenols: Endocrine Disruptors and Their Impact on Fish: A Review
by Nikola Peskova and Jana Blahova
Fishes 2025, 10(8), 365; https://doi.org/10.3390/fishes10080365 - 29 Jul 2025
Viewed by 327
Abstract
Bisphenols (BPs), particularly bisphenol A (BPA) and its structural analogues, are synthetic compounds widely used in plastics and industrial materials. These substances are also recognised as endocrine-disrupting chemicals (EDCs) due to their ability to interfere with hormonal systems, which has significant implications for [...] Read more.
Bisphenols (BPs), particularly bisphenol A (BPA) and its structural analogues, are synthetic compounds widely used in plastics and industrial materials. These substances are also recognised as endocrine-disrupting chemicals (EDCs) due to their ability to interfere with hormonal systems, which has significant implications for aquatic organisms. This review summarises the occurrence, environmental distribution, and toxicity of BPs in fish, with a focus on estrogenic, androgenic, thyroid, and glucocorticoid disruptions. Studies consistently show that exposure to BPs leads to altered gene expression, developmental abnormalities, impaired reproduction, and disrupted hormonal signalling in various fish species. Although BPA alternatives like bisphenol S, bisphenol F, or bisphenol AF were introduced as safer options, emerging evidence suggests they may pose equal or greater risks. Regulatory measures are evolving, particularly within the European Union, but legislation remains limited for many bisphenol analogues. This review emphasises the need for comprehensive environmental monitoring, stricter regulatory frameworks, and the development of genuinely safer alternatives to minimise the ecological and health impacts of BPs in aquatic systems. Full article
(This article belongs to the Section Environment and Climate Change)
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16 pages, 3203 KiB  
Article
Green Synthesised Carbon Nanodots Using the Maillard Reaction for the Rapid Detection of Elemental Selenium in Water and Carbonated Beverages
by Arjun Muthu, Duyen H. H. Nguyen, Aya Ferroudj, József Prokisch, Hassan El-Ramady, Chaima Neji and Áron Béni
Nanomaterials 2025, 15(15), 1161; https://doi.org/10.3390/nano15151161 - 28 Jul 2025
Viewed by 185
Abstract
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 [...] Read more.
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
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19 pages, 1159 KiB  
Article
Multifactorial Refractory Acne in Women: Insights from a Case Series Involving Hormonal-, Metabolic-, and Corticosteroid-Related Triggers
by Alexa Florina Bungau, Ruxandra Cristina Marin, Delia Mirela Tit, Gabriela Bungau, Ada Radu, Daciana Elena Branisteanu and Laura Maria Endres
Life 2025, 15(8), 1196; https://doi.org/10.3390/life15081196 - 28 Jul 2025
Viewed by 424
Abstract
Acne vulgaris is a multifactorial inflammatory skin disorder that significantly impairs quality of life and may signal underlying systemic dysfunction, particularly in adult women with treatment-resistant or atypical presentations. This case series presents three clinically and etiologically distinct examples of persistent acne in [...] Read more.
Acne vulgaris is a multifactorial inflammatory skin disorder that significantly impairs quality of life and may signal underlying systemic dysfunction, particularly in adult women with treatment-resistant or atypical presentations. This case series presents three clinically and etiologically distinct examples of persistent acne in female patients, each associated with different contributing factors: long-term topical corticosteroid misuse, polycystic ovary syndrome (PCOS), and metabolic syndrome with autoimmune thyroiditis. All cases underwent comprehensive dermatologic evaluation, endocrine/metabolic assessments, and personalized therapeutic interventions, ranging from corticosteroid withdrawal and barrier repair to hormonal modulation and insulin-sensitizing therapy. Clinical progression was monitored for up to six months, revealing favorable responses in all cases, with substantial lesion clearance and improved skin quality. These real-world cases highlight the importance of an integrative, interdisciplinary diagnostic approach in refractory acne and support the need for individualized, long-term management strategies tailored to underlying systemic contributors. Full article
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10 pages, 1202 KiB  
Article
Incidence of Congenital Hypothyroidism Is Increasing in Chile
by Francisca Grob, Gabriel Cavada, Gabriel Lobo, Susana Valdebenito, Maria Virginia Perez and Gilda Donoso
Int. J. Neonatal Screen. 2025, 11(3), 58; https://doi.org/10.3390/ijns11030058 - 26 Jul 2025
Viewed by 264
Abstract
Congenital hypothyroidism (CH) is a leading preventable cause of neurocognitive impairment. Its incidence appears to be rising in several countries. We analysed 27 years of newborn-screening data (1997–2023) from the largest Chilean screening centre, covering 3,225,216 newborns (51.1% of national births), to characterise [...] Read more.
Congenital hypothyroidism (CH) is a leading preventable cause of neurocognitive impairment. Its incidence appears to be rising in several countries. We analysed 27 years of newborn-screening data (1997–2023) from the largest Chilean screening centre, covering 3,225,216 newborns (51.1% of national births), to characterise temporal trends and potential drivers of CH incidence. Annual CH incidence was modelled with Prais–Winsten regression to correct for first-order autocorrelation; additional models assessed trends in gestational age, sex, biochemical markers, and aetiological subtypes. We identified 1550 CH cases, giving a mean incidence of 4.9 per 10,000 live births and a significant yearly increase of 0.067 per 10,000 (95 % CI 0.037–0.098; p < 0.001). Mild cases (confirmation TSH < 20 mU/L) rose (+0.89 percentage points per year; p = 0.002). The program’s recall was low (0.05%). Over time, screening and diagnostic TSH values declined, total and free T4 concentrations rose, gestational age at diagnosis fell, and a shift from thyroid ectopy toward hypoplasia emerged; no regional differences were detected. The sustained increase in CH incidence, alongside falling TSH thresholds and growing detection of in situ glands, suggests enhanced recognition of milder disease. Ongoing surveillance should integrate environmental, iodine-nutrition, and genetic factors to clarify the causes of this trend. Full article
(This article belongs to the Special Issue Newborn Screening for Congenital Hypothyroidism)
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16 pages, 1038 KiB  
Article
Metabolic Profiles of Feline Obesity Revealed by Untargeted and Targeted Mass Spectrometry-Based Metabolomics Approaches
by Renata Barić Rafaj, Ivana Rubić, Josipa Kuleš, Dominik Prišćan, Alberto Muñoz-Prieto, Jelena Gotić, Luka Ećimović, Nada Kučer, Marko Samardžija, Mislav Kovačić and Vladimir Mrljak
Vet. Sci. 2025, 12(8), 697; https://doi.org/10.3390/vetsci12080697 - 25 Jul 2025
Viewed by 260
Abstract
Obesity is currently one of the major medical problems affecting humans and companion animals, including cats; however, a detailed understanding of the metabolic processes altered in feline obesity remains limited. This study aimed to investigate obesity-related changes in the serum metabolome of three [...] Read more.
Obesity is currently one of the major medical problems affecting humans and companion animals, including cats; however, a detailed understanding of the metabolic processes altered in feline obesity remains limited. This study aimed to investigate obesity-related changes in the serum metabolome of three groups of cats, metabolically healthy normal-weight (MHN) cats, metabolically healthy overweight (MHO) cats, and metabolically unhealthy overweight (MUO) cats. Metabolome changes were assessed using LC-MS (untargeted), LC-MS (targeted), and FIA-MS (targeted) methods. Untargeted analysis detected 141 significant annotated features, while targeted approach identified 48 metabolites significantly associated with obesity. Both untargeted and targeted analyses showed lower kynurenine levels in the MUO group compared to the MHN group. Targeted LC-MS analysis identified 11 significant metabolites, whereas the FIA-MS approach detected 37. Four metabolites—glycine, citrulline, and two phosphatidylcholines—were found at lower levels in the MHO group compared to the MHN group. Arginine and proline metabolism, along with methionine metabolism, were significantly altered pathways, while thyroid hormone synthesis was independently altered with the highest enrichment ratio. The obtained results suggest that cats with a healthy phenotype exhibit an intermediate-metabolic-risk profile and provide new insights into the metabolic mechanisms and pathways underlying feline obesity. Full article
(This article belongs to the Section Nutritional and Metabolic Diseases in Veterinary Medicine)
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18 pages, 3973 KiB  
Article
Identification and Characterization of Static Craniofacial Defects in Pre-Metamorphic Xenopus laevis Tadpoles
by Emilie Jones, Jay Miguel Fonticella and Kelly A. McLaughlin
J. Dev. Biol. 2025, 13(3), 26; https://doi.org/10.3390/jdb13030026 - 25 Jul 2025
Viewed by 309
Abstract
Craniofacial development is a complex, highly conserved process involving multiple tissue types and molecular pathways, with perturbations resulting in congenital defects that often require invasive surgical interventions to correct. Remarkably, some species, such as Xenopus laevis, can correct some craniofacial abnormalities during [...] Read more.
Craniofacial development is a complex, highly conserved process involving multiple tissue types and molecular pathways, with perturbations resulting in congenital defects that often require invasive surgical interventions to correct. Remarkably, some species, such as Xenopus laevis, can correct some craniofacial abnormalities during pre-metamorphic stages through thyroid hormone-independent mechanisms. However, the full scope of factors mediating remodeling initiation and coordination remain unclear. This study explores the differential remodeling responses of craniofacial defects by comparing the effects of two pharmacological agents, thioridazine-hydrochloride (thio) and ivermectin (IVM), on craniofacial morphology in X. laevis. Thio-exposure reliably induces a craniofacial defect that can remodel in pre-metamorphic animals, while IVM induces a permanent, non-correcting phenotype. We examined developmental changes from feeding stages to hindlimb bud stages and mapped the effects of each agent on the patterning of craniofacial tissue types including: cartilage, muscle, and nerves. Our findings reveal that thio-induced craniofacial defects exhibit significant consistent remodeling, particularly in muscle, with gene expression analysis revealing upregulation of key remodeling genes, matrix metalloproteinases 1 and 13, as well as their regulator, prolactin.2. In contrast, IVM-induced defects show no significant remodeling, highlighting the importance of specific molecular and cellular factors in pre-metamorphic craniofacial correction. Additionally, unique neuronal profiles suggest a previously underappreciated role for the nervous system in tissue remodeling. This study provides novel insights into the molecular and cellular mechanisms underlying craniofacial defect remodeling and lays the groundwork for future investigations into tissue repair in vertebrates. Full article
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18 pages, 4037 KiB  
Article
A Genetically-Engineered Thyroid Gland Built for Selective Triiodothyronine Secretion
by Cintia E. Citterio, Berenice Morales-Rodriguez, Xiao-Hui Liao, Catherine Vu, Rachel Nguyen, Jessie Tsai, Jennifer Le, Ibrahim Metawea, Ming Liu, David P. Olson, Samuel Refetoff and Peter Arvan
Int. J. Mol. Sci. 2025, 26(15), 7166; https://doi.org/10.3390/ijms26157166 - 24 Jul 2025
Viewed by 344
Abstract
Thyroid hormones (thyroxine, T4, and triiodothyronine, T3) are indispensable for sustaining vertebrate life, and their deficiency gives rise to a wide range of symptoms characteristic of hypothyroidism, affecting 5–10% of the world’s population. The precursor for thyroid hormone synthesis [...] Read more.
Thyroid hormones (thyroxine, T4, and triiodothyronine, T3) are indispensable for sustaining vertebrate life, and their deficiency gives rise to a wide range of symptoms characteristic of hypothyroidism, affecting 5–10% of the world’s population. The precursor for thyroid hormone synthesis is thyroglobulin (Tg), a large iodoglycoprotein consisting of upstream regions I-II-III (responsible for synthesis of most T4) and the C-terminal CholinEsterase-Like (ChEL) domain (responsible for synthesis of most T3, which can also be generated extrathyroidally by T4 deiodination). Using CRISPR/Cas9-mediated mutagenesis, we engineered a knock-in of secretory ChEL into the endogenous TG locus. Secretory ChEL acquires Golgi-type glycans and is properly delivered to the thyroid follicle lumen, where T3 is first formed. Homozygous knock-in mice are capable of thyroidal T3 synthesis but largely incompetent for T4 synthesis such that T4-to-T3 conversion contributes little. Instead, T3 production is regulated thyroidally by thyrotropin (TSH). Compared to cog/cog mice with conventional hypothyroidism (low serum T4 and T3), the body size of ChEL-knock-in mice is larger; although, these animals with profound T4 deficiency did exhibit a marked elevation of serum TSH and a large goiter, despite normal circulating T3 levels. ChEL knock-in mice exhibited a normal expression of hepatic markers of thyroid hormone action but impaired locomotor activities and increased anxiety-like behavior, highlighting tissue-specific differences in T3 versus T4 action, reflecting key considerations in patients receiving thyroid hormone replacement therapy. Full article
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13 pages, 573 KiB  
Review
Developmental Programming and Postnatal Modulations of Muscle Development in Ruminants
by Kiersten Gundersen and Muhammad Anas
Biology 2025, 14(8), 929; https://doi.org/10.3390/biology14080929 - 24 Jul 2025
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Abstract
Prenatal and postnatal skeletal muscle development in ruminants is coordinated by interactions between genetic, nutritional, epigenetic, and endocrine factors. This review focuses on the influence of maternal nutrition during gestation on fetal myogenesis, satellite cell dynamics, and myogenic regulatory factors expression, including MYF5 [...] Read more.
Prenatal and postnatal skeletal muscle development in ruminants is coordinated by interactions between genetic, nutritional, epigenetic, and endocrine factors. This review focuses on the influence of maternal nutrition during gestation on fetal myogenesis, satellite cell dynamics, and myogenic regulatory factors expression, including MYF5, MYOD1, and MYOG. Studies in sheep and cattle indicate that nutrient restriction or overnutrition alters muscle fiber number, the cross-sectional area, and the transcriptional regulation of myogenic genes in offspring. Postnatally, muscle hypertrophy is primarily mediated by satellite cells, which are activated via PAX7, MYOD, and MYF5, and regulated through mechanisms such as CARM1-induced chromatin remodeling and miR-31-mediated mRNA expression. Hormonal signaling via the GH–IGF1 axis and thyroid hormones further modulate satellite cell proliferation and protein accretion. Genetic variants, such as myostatin mutations in Texel sheep and Belgian Blue cattle, enhance muscle mass but may compromise reproductive efficiency. Nutritional interventions, including the plane of nutrition, supplementation strategies, and environmental stressors such as heat and stocking density, significantly influence muscle fiber composition and carcass traits. This review provides a comprehensive overview of skeletal muscle programming in ruminants, tracing the developmental trajectory from progenitor cell differentiation to postnatal growth and maturation. These insights underscore the need for integrated approaches combining maternal diet optimization, molecular breeding, and precision livestock management to enhance muscle growth, meat quality, and production sustainability in ruminant systems. Full article
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