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Keywords = thyroid hormone

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11 pages, 226 KB  
Article
Cardiorenal Biomarkers and Cerebrovascular Risk in Patients with Congenital Heart Disease
by Efrén Martínez-Quintana and Fayna Rodríguez-González
J. Clin. Med. 2026, 15(6), 2440; https://doi.org/10.3390/jcm15062440 (registering DOI) - 23 Mar 2026
Abstract
Background/Objectives: Adults with congenital heart disease (CHD) have a substantially higher risk of ischemic stroke than the general population. Circulating biomarkers such as N-terminal pro B-type natriuretic peptide (NT-pro-BNP), high-sensitivity C-reactive protein (hs-CRP), and microalbuminuria have been associated with adverse cardiovascular outcomes [...] Read more.
Background/Objectives: Adults with congenital heart disease (CHD) have a substantially higher risk of ischemic stroke than the general population. Circulating biomarkers such as N-terminal pro B-type natriuretic peptide (NT-pro-BNP), high-sensitivity C-reactive protein (hs-CRP), and microalbuminuria have been associated with adverse cardiovascular outcomes in CHD, but their role in predicting cerebrovascular events remains uncertain. Methods: Prospective cohort study including 372 adults with CHD [median age 34 years (IQR 23–42); 57.8% male] followed at a tertiary center between 2017 and 2022. Baseline assessments included demographic characteristics, CHD anatomical complexity, cardiovascular risk factors, NT-pro-BNP, hs-CRP, lipid profile, and 24-h urinary albumin excretion. The primary endpoint was incident ischemic stroke during a median follow-up of 6.3 years (IQR 3.9–8.3). Univariable Cox proportional hazards models were used to identify predictors of stroke. Results: During follow-up, 13 patients (3.5%) experienced ischemic stroke. Patients with stroke were significantly older [51 (46–64) vs. 30 (23–40) years; p < 0.001] and had a higher prevalence of dyslipidemia (61.5% vs. 15.0%; p < 0.001). NT-pro-BNP levels were markedly higher in patients with stroke [369 (218–604) vs. 64 (21–172) pg/mL; p < 0.001]. No significant differences were observed between groups in renal function parameters, hs-CRP, thyroid-stimulating hormone, or urinary albumin excretion rate. In Cox analyses, older age and dyslipidemia were the strongest predictors of stroke (p < 0.001). Arterial hypertension, diabetes mellitus, and higher NT-pro-BNP levels were also associated with increased stroke risk (p < 0.05), whereas CHD anatomical complexity, NYHA functional class, and cyanosis were not. Conclusions: In adults with CHD, ischemic stroke was mainly associated with traditional cardiovascular risk factors and elevated NT-pro-BNP levels rather than anatomical disease complexity or functional status. Full article
(This article belongs to the Special Issue Current Challenges in Adult Congenital Heart Diseases)
10 pages, 262 KB  
Article
Management of Hypothyroidism in Pregnancy and Its Impact on Maternal and Perinatal Outcomes: A Single-Center Retrospective Cohort Study
by Chinnu George Samuel, Asma Jamil, Mohamed Bashir, Hala Abdullahi and Ibrahim Ibrahim
Life 2026, 16(3), 527; https://doi.org/10.3390/life16030527 (registering DOI) - 22 Mar 2026
Abstract
Background: Hypothyroidism is one of the most common endocrine conditions during pregnancy and has been associated with poor obstetric and perinatal outcomes. There is still a lack of data from Middle Eastern populations, despite its clinical significance. This study aimed to evaluate thyroid [...] Read more.
Background: Hypothyroidism is one of the most common endocrine conditions during pregnancy and has been associated with poor obstetric and perinatal outcomes. There is still a lack of data from Middle Eastern populations, despite its clinical significance. This study aimed to evaluate thyroid management patterns during pregnancy and examine the association between thyroid function control and maternal and perinatal outcomes in women with hypothyroidism at a tertiary care center in Qatar. Methods: A retrospective cohort study including 379 pregnant women with hypothyroidism diagnosed between January 2019 and November 2022 was conducted at Sidra Medicine in Doha, Qatar. Based on trimester-specific Thyroid-stimulating hormone (TSH )reference values, participants were categorized as having adequately or inadequately controlled thyroid function. Data on obstetrics, biochemistry, and demographics were taken from electronic medical records (EMR). Statistical analyses were performed using chi-square tests for categorical variables and t-tests for continuous variables, with a significance threshold of p < 0.05. Results: Participants had a mean Body Mass Index (BMI) of 30.33 ± 6.14 kg/m2 and an average age of 32.65 ± 4.99 years; 54% of them were Qataris. Of the patients, 58.5% had positive thyroid antibodies and 55.7% had pre-gestational hypothyroidism. Women with pre-gestational hypothyroidism required significantly higher levothyroxine doses compared with those with gestational hypothyroidism (93.2 ± 47.5 mcg/day vs. 67.6 ± 30.1 mcg/day; p < 0.001). Treatment adjustment was demonstrated by the improvement in TSH normalization from 51.3% in the first trimester to 64.2% in the third trimester (p = 0.041). No significant associations were observed with pre-eclampsia, preterm delivery, hypertension, or placental abruption. However, women with normal third-trimester TSH had a higher prevalence of gestational diabetes mellitus (GDM) compared with those with elevated TSH (51.6% vs. 36.8%; p = 0.013). Conclusions: Appropriate trimester-specific monitoring and timely levothyroxine titration was associated with improved biochemical control without adverse maternal outcomes. Greater levothyroxine requirements in women with pre-gestational hypothyroidism emphasize the importance of early intervention. These findings highlight the potential benefit of structured thyroid monitoring and multidisciplinary care approaches in pregnancy and may help inform future regional clinical practice guidelines. Full article
(This article belongs to the Section Medical Research)
17 pages, 868 KB  
Article
Low fT3 Syndrome, Dialysis Inadequacy, and Death Occurrence in Hemodialysis Patients: Evidence of a Vicious Circle from a Prospective Bi-Center Observational Study
by Aleksandra Młodożeniec, Małgorzata Rodzoń-Norwicz, Renata Orłowska-Florek, Krystyna Tęcza, Piotr Młodożeniec, Krzysztof Gargasz and Agnieszka Gala-Błądzińska
J. Clin. Med. 2026, 15(6), 2400; https://doi.org/10.3390/jcm15062400 (registering DOI) - 21 Mar 2026
Abstract
Background/Objectives: Non-thyroidal illness syndrome (NTIS) also known as low FT3 syndrome is characterized by altered thyroid hormone levels during severe illness, is common in end-stage renal disease, and reflects metabolic and inflammatory stress. This study evaluated the thyroid hormone profiles of patients undergoing [...] Read more.
Background/Objectives: Non-thyroidal illness syndrome (NTIS) also known as low FT3 syndrome is characterized by altered thyroid hormone levels during severe illness, is common in end-stage renal disease, and reflects metabolic and inflammatory stress. This study evaluated the thyroid hormone profiles of patients undergoing maintenance hemodialysis, assessing relationships between NTIS severity and dialysis adequacy while accounting for mineral and bone metabolism markers, anemia status, duration of dialysis therapy, and their association with the number of deaths during follow-up. Methods: This prospective bi-center study included adults receiving maintenance hemodialysis for at least 3 months. Patients treated for thyroid disease or taking medications affecting the hypothalamus–pituitary–thyroid axis were excluded. Thyroid-stimulating hormone, free triiodothyronine (fT3), and free thyroxine (fT4) levels were measured, and dialysis adequacy was assessed using spKt/V. Patients were classified as euthyroid or having NTIS (stratified by severity), and associations between clinical characteristics and the number of deceased patients during a 6-month observation period were analyzed using receiver operating characteristic (ROC) curves to determine prognostic cut-off values for thyroid hormones. Results: Among 74 patients, 50% had NTIS and exhibited significantly lower dialysis adequacy than euthyroid individuals (median spKt/V 1.0 vs. 1.1; p = 0.03), with spKt/V declining as NTIS severity increased (stages I–III, p = 0.008). NTIS severity correlated with age and pulmonary comorbidities, while mineral and bone metabolism markers were comparable between the groups. During the 6-month follow-up, 23% of the patients died, exhibiting significantly lower fT3 and fT4 levels than survivors. ROC analysis identified clinically relevant fT3 and fT4 cut-off values that were associated with the number of deaths. Conclusions: NTIS in hemodialysis patients correlates with reduced dialysis adequacy and appears to be a prognostic factor for risk of death. NTIS severity correlated with declining spKt/V, potentially reflecting disease burden, and thyroid hormone assessment may provide prognostic information. Full article
(This article belongs to the Section Nephrology & Urology)
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16 pages, 2002 KB  
Article
Genetic Variants and Molecular Components Associated with Metabolic Dysfunctional-Associated Steatotic Liver Disease and Depression: Shared Association of ADAMTS7 and THRAP3
by Eron G. Manusov, Vincent P. Diego, Marcio Almeida, Jacob A. Galan, Kathryn Herklotz, Edwardo Abrego III, Habiba Sultana, Luis Pena Marquez, Marco A. Arriaga, Marcelo Leandro, Juan Peralta, Ana C. Leandro, Tom E. Howard, Joanne E. Curran, Sandra Laston, John Blangero and Sarah Williams-Blangero
Genes 2026, 17(3), 343; https://doi.org/10.3390/genes17030343 - 19 Mar 2026
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and depression frequently occur together. Identifying the genes that influence both MASLD and depression may facilitate the discovery of biological pathways associated with disease risk. Methods: We recruited 525 participants from Mexican American families [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and depression frequently occur together. Identifying the genes that influence both MASLD and depression may facilitate the discovery of biological pathways associated with disease risk. Methods: We recruited 525 participants from Mexican American families living in the Rio Grande Valley of south Texas. We collected clinical data, biometric measurements, hepatic health assessments using Vibration-Controlled Transient Elastography (VCTE), and depression evaluations determined with the Beck Depression Inventory-II. We estimated the heritability (h2) of MASLD-related measures, depression status, aspartate aminotransferase (AST), alanine aminotransferase (ALT), the AST/ALT ratio, and Vibration-Controlled Transient Elastography measurements. For each gene, we derived a genetic endophenotype representing its expression level. We then performed functional network and gene ontology enrichment analyses to characterize the underlying protein pathways. Results: We observed significant associations between the expression of two genes, Thyroid Hormone Receptor-Associated Protein 3 (THRAP3) (h2 = 0.56 [0.45, 0.67]) and ADAM Metallopeptidase with Thrombospondin Type 1 Motif 7 (ADAMTS7) (h2 = 0.66 [0.55, 0.77]), with depression and multiple MASLD-related phenotypes. We identified 351 genes with expression levels significantly correlated with one or more MASLD phenotypes and depression. Among these, five genes—ADAMTS7, THRAP3, CHPM4A, RAB9A, and PDIA3—were jointly associated with three phenotypes: AST/ALT, ALT, and Controlled Attenuation Parameter (CAP kPa). Based on the Fisher Combined Test, only THRAP3 (p = 3.0 × 10−2) and ADAMTS7 (p = 2 × 10−2) were jointly significant for depression (BDI-II) and AST, ALT, AST/ALT ratio, FAST, and CAP (kPa). We present a protein–protein interaction network comprising nodes (proteins) and edges (interactions), and a gene ontology enrichment analysis of cellular components. Discussion: Our findings highlight pleiotropic genes underlying MASLD and depression. Two genes, ADAMTS7 and THRAP3, warrant further investigation as potential targets for therapeutic interventions to manage MASLD and depression among Mexican Americans. These results may improve our understanding of the pathways involved in these two diseases, advance current research, and contribute to improvements in personalized medicine. Conclusion: We identified possible shared gene expression phenotypes linking MASLD and depression, which may provide insight into a common molecular underpinning. Pathway enrichment and gene analysis were used to help refine networks and enhance our understanding of complex gene-environmental interactions and their implications for precision medicine. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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14 pages, 2242 KB  
Article
Euthyroid Sick Syndrome (ESS) and Monocyte-to-Lymphocyte Ratio (MLR) Are Predictors of Complications in Geriatric Hip Fractures: A Single-Center Retrospective Analysis
by Giacomo Capece, Doriana Di Costa, Elisa Pesare, Michele Pomponi, Valeria Maccauro, Rocco Maria Comodo, Rami Kaplan, Umberto Capece, Pasquale Farsetti, Marcello Covino, Giulio Maccauro and Raffaele Vitiello
J. Clin. Med. 2026, 15(6), 2282; https://doi.org/10.3390/jcm15062282 - 17 Mar 2026
Viewed by 134
Abstract
Background: Euthyroid Sick Syndrome (ESS) is a clinical condition characterized by reduced free triiodothyronine (FT3) levels in response to acute or chronic stress. Proximal femur fractures in geriatric patients are associated with high morbidity and mortality rates and ESS may influence outcomes [...] Read more.
Background: Euthyroid Sick Syndrome (ESS) is a clinical condition characterized by reduced free triiodothyronine (FT3) levels in response to acute or chronic stress. Proximal femur fractures in geriatric patients are associated with high morbidity and mortality rates and ESS may influence outcomes in this population. This study aimed to investigate the role of ESS as a predictor of complications in elderly patients with hip fractures, analyzing its association with inflammatory and nutritional markers, including the Monocyte-to-Lymphocyte Ratio (MLR), Controlling Nutritional Status (CONUT) score and Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score. Materials and Methods: We conducted a single-center retrospective analysis of patients aged 65 and older who were admitted with proximal femur fractures requiring surgical intervention. Thyroid hormone profiles, inflammatory markers and other clinical variables were analyzed preoperatively (T0) and on the first (T1) and third (T2) postoperative days. Logistic regression was used to identify predictors of complications and transfusion requirements. Results: The study included 103 patients (72 men, 31 women; mean age 85 ± 6.27 years). ESS was present in 30 patients (29%) and was associated with longer surgery duration (83.9 ± 35.5 vs. 68.9 ± 21.3 min; p = 0.042). At admission (T0), ESS patients had lower FT3 (1.91 ± 0.25 vs. 2.75 ± 0.28 pmol/L; p < 0.001) and higher TSH (1.55 ± 0.75 vs. 1.20 ± 0.80 mIU/L; p = 0.057). Postoperatively, MLR was significantly altered at T1 (p = 0.026) and T2 (p = 0.040). ESS was a significant predictor of complications at T0 but lost significance postoperatively, while MLR emerged as a key predictor at T2 (p = 0.003). Logistic regression confirmed MLR at T2 as an independent predictor of complications. Hemoglobin levels at T0 (p < 0.001), T1 (p < 0.001), and T2 (p < 0.001), along with albumin at T1 (2.67 ± 0.34 vs. 2.94 ± 0.33 g/dL; p = 0.001) and calcium at T1 (p = 0.006), were significant predictors of transfusion requirements. Nutritional and inflammatory scores were not predictive. Conclusions: ESS is a significant initial predictor of complications in geriatric patients with hip fractures, but inflammatory markers such as MLR assume greater relevance in the postoperative period. These findings emphasize the importance of monitoring ESS and MLR to enhance risk stratification and guide personalized management strategies. Full article
(This article belongs to the Section Orthopedics)
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12 pages, 261 KB  
Article
Assessment of the Thyroid Profile in the Iberian Lynx (Lynx pardinus)
by Adriana Maia, Rodrigo Serra, Ana C. Silvestre-Ferreira, Jaume Ródon, Guillermo López and Felisbina Pereira Queiroga
Vet. Sci. 2026, 13(3), 278; https://doi.org/10.3390/vetsci13030278 - 17 Mar 2026
Viewed by 131
Abstract
The Iberian lynx (Lynx pardinus), once considered the most endangered felid, has shown demographic recovery thanks to intensive conservation measures. Over the past two decades, large physiological datasets have supported both clinical management and research, yet thyroid function has remained comparatively [...] Read more.
The Iberian lynx (Lynx pardinus), once considered the most endangered felid, has shown demographic recovery thanks to intensive conservation measures. Over the past two decades, large physiological datasets have supported both clinical management and research, yet thyroid function has remained comparatively underexplored. This study provides the first reference intervals (RI) for total thyroxine (TT4) and thyroid-stimulating hormone (TSH) in captive and wild lynxes, and assesses the effects of age, sex, and environment. Serum samples from 71 individuals (32 captive, 39 wild; 32 females, 39 males) were analysed, including 32 young adults, 14 adults, and 25 geriatric animals. TT4 was measured by enzyme immunoassay, and TSH using chemiluminescence. TT4 RI was 0.80–2.00 µg/dl (captive) and 0.70–2.20 µg/dl (wild) (p = 0.065). TSH RI was 0.00–1.10 ng/ml (captive) and 0.00–0.10 ng/ml (wild), showing a significant difference (p < 0.001). Captive males had higher TT4 than females (p = 0.018), while no sex difference appeared in wild lynxes (p = 0.408). Age had no significant effect on TT4 (p = 0.462) or TSH (p = 0.739). Findings confirmed that environment and sex (captivity) influenced thyroid parameters, while age did not. These values are crucial for health monitoring and endocrine assessment in this endangered species. Full article
(This article belongs to the Special Issue Wildlife Health and Disease in Conservation—2nd Edition)
22 pages, 581 KB  
Article
Low-Carbohydrate (Ketogenic) Diet in Children with Obesity: Part 2—Hormonal Effects of the Ketogenic Diet
by Ivanka N. Paskaleva, Nartsis N. Kaleva, Teodora D. Dimcheva and Ivan S. Ivanov
Children 2026, 13(3), 406; https://doi.org/10.3390/children13030406 - 14 Mar 2026
Viewed by 289
Abstract
Background: For decades, the ketogenic diet has been successfully used for the treatment of obesity, metabolic syndrome, and type 2 diabetes. The mechanisms through which it affects metabolism are not fully understood, but the hormonal changes that occur during ketogenic nutrition are likely [...] Read more.
Background: For decades, the ketogenic diet has been successfully used for the treatment of obesity, metabolic syndrome, and type 2 diabetes. The mechanisms through which it affects metabolism are not fully understood, but the hormonal changes that occur during ketogenic nutrition are likely to play an important role. Objectives: To investigate the effect of the ketogenic diet on various hormones associated with obesity and the accompanying metabolic disorders in childhood. Methods: One hundred children aged 8–18 years with obesity were enrolled. After baseline anthropometric, biochemical, and hormonal testing, they followed a 4-month “well-formulated ketogenic diet.” Fifty-eight of them successfully completed the study with follow-up assessments. Among them, 8 girls had polycystic ovary syndrome (PCOS) and 7 children had Hashimoto’s autoimmune thyroiditis. Results: At the end of the 4-month period, there was a significant decrease in basal insulinemia (p < 0.0001) and in mean morning cortisol levels (p = 0.04), as well as an increase in adiponectin levels (p = 0.04). All girls with PCOS experienced spontaneous menstrual cycles, accompanied by a reduction in testosterone levels. TSH levels showed no change for the whole group (p = 0.13), but there was a significant decrease in T3 (p < 0.0001) and a mild increase in T4 (p = 0.05). Among patients with Hashimoto’s thyroiditis, TSH levels were significantly higher at the end of the study. Conclusions: A short-term, well-formulated ketogenic diet in children with obesity is associated with hormonal changes that support weight loss and improve insulin sensitivity. The diet shows particularly beneficial effects in girls with PCOS and may be considered as part of a comprehensive therapeutic approach in these patients. Monitoring thyroid function during ketogenic nutrition is advisable in patients with hypothyroidism and thyroid disorders. Full article
(This article belongs to the Section Pediatric Endocrinology & Diabetes)
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19 pages, 425 KB  
Article
Variations in Circulating Thyroid Hormone Profiles Across Age, Sex, and Pregnancy Outcomes in Killer Whales (Orcinus orca) Under Human Care
by Todd R. Robeck, Karen J. Steinman, Gisele A. Montano, Steve Paris and Janine L. Brown
Animals 2026, 16(6), 907; https://doi.org/10.3390/ani16060907 - 13 Mar 2026
Viewed by 216
Abstract
The study examined how season, age, sex, and pregnancy outcomes influenced serum total thyroxine (TT4) and triiodothyronine (TT3) levels in killer whales (Orcinus orca). Total T4 and TT3 concentrations were quantified in 1513 serum samples collected voluntarily over ~40 years from [...] Read more.
The study examined how season, age, sex, and pregnancy outcomes influenced serum total thyroxine (TT4) and triiodothyronine (TT3) levels in killer whales (Orcinus orca). Total T4 and TT3 concentrations were quantified in 1513 serum samples collected voluntarily over ~40 years from 14 males and 24 females (ages 1–54) under managed care. Data were analyzed using LMM to determine the effects of age, sex, season, and pregnancy status (normal vs. abnormal outcomes). Age, season, and pregnancy significantly influenced thyroid hormone concentrations, while sex did not. Juveniles exhibited higher concentrations consistent with increased thermoregulatory needs and growth demands. Seasonal analysis showed TT4 peaked in summer and declined in winter suggesting thermoregulatory adaptation. Pregnancies with abnormal outcomes (abortion, dystocia, stillbirth) were associated with atypical thyroid hormone profiles; specifically, dystocia was linked to consistently low TT3/TT4, while stillbirths correlated with elevated late-term TT3. Females experiencing abortion showed decreased TT3 and TT4 during the late gestation. These findings suggest that in pregnancies with adverse outcomes, metabolic imbalances or transient hyperthyroid-like states may negatively impact fetal health. Consequently, in killer whales, variation in thyroid hormone levels may reflect a complex interplay between environmental adaptation, reproductive status, and underlying evolutionary physiology. Full article
(This article belongs to the Section Mammals)
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18 pages, 2895 KB  
Article
An Enhanced Electrochemiluminescence Immunoassay Platform via Optimized Magnetic Bead Uniformity for Reliable Thyroid-Stimulating Hormone Monitoring
by Hengbo Lei, Xinyu Huang, Xiang Cao, Yuguo Tang and Yang Ge
Bioengineering 2026, 13(3), 333; https://doi.org/10.3390/bioengineering13030333 - 13 Mar 2026
Viewed by 200
Abstract
Electrochemiluminescence immunoassay (ECLIA) is widely used in clinical diagnostics owing to its high sensitivity, broad dynamic range, and excellent analytical stability. However, the influence of magnetic bead deposition behavior on electrochemiluminescence (ECL) signal performance remains insufficiently characterized. In this study, a quantitative evaluation [...] Read more.
Electrochemiluminescence immunoassay (ECLIA) is widely used in clinical diagnostics owing to its high sensitivity, broad dynamic range, and excellent analytical stability. However, the influence of magnetic bead deposition behavior on electrochemiluminescence (ECL) signal performance remains insufficiently characterized. In this study, a quantitative evaluation method for magnetic bead distribution uniformity on the electrode surface was established and applied to optimize fluidic parameters in an ECLIA measurement system. By combining microscopic imaging with image analysis, magnetic bead spreading behavior under different flow conditions was systematically characterized and correlated with luminescence signal intensity. Optimization of the flow rate (18.46 µL·s−1) improved bead distribution uniformity and resulted in a 26.32% increase in luminescence intensity without altering bead coverage or assay chemistry. The optimized system was further validated using thyroid-stimulating hormone (TSH) detection, showing a linear response over 0.016–120 µIU·mL−1 (R2 > 0.996) and high consistency with a commercial analyzer (R2 = 0.998) from Roche. These results demonstrate that quantitative control of magnetic bead distribution provides an effective strategy for improving ECLIA performance and offers a general optimization framework for bead-based electrochemiluminescence systems. Full article
(This article belongs to the Section Biosignal Processing)
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9 pages, 247 KB  
Article
Iron Overload and Endocrine Dysfunction in Adults with Transfusion-Dependent Beta-Thalassemia and Growth Retardation: A Correlational Study
by Muhammad Hammad, Sadaf Fardoos, Khadija Shakoor and Ali Nasir
Thalass. Rep. 2026, 16(1), 5; https://doi.org/10.3390/thalassrep16010005 - 11 Mar 2026
Viewed by 158
Abstract
Background and Objective: Iron overload remains a significant clinical concern in patients with transfusion-dependent beta-thalassemia (TDT). This study aims to characterize the iron load and endocrine profile of adult transfusion-dependent beta-thalassemia patients and to evaluate their correlation with growth retardation. Methods: [...] Read more.
Background and Objective: Iron overload remains a significant clinical concern in patients with transfusion-dependent beta-thalassemia (TDT). This study aims to characterize the iron load and endocrine profile of adult transfusion-dependent beta-thalassemia patients and to evaluate their correlation with growth retardation. Methods: A cross-sectional study was conducted at PIMS Hospital, Islamabad, involving 62 adult patients with homozygous or HbE beta-thalassemia receiving regular blood transfusions. Iron overload was assessed using serum ferritin (SF) and transferrin saturation (TS), while endocrine function was evaluated through measurements of thyroid-stimulating hormone-sensitive (TSH), free thyroxine (FT4), and insulin-like growth factor-1 (IGF-1). Data was analyzed using SPSS v26.0 and R v4.3.1, which included Pearson correlation, chi-square testing, and multivariable regression to explore associations between iron indices and endocrine dysfunction. Results: Serum ferritin demonstrated significant negative correlations with FT4 (r = −0.348, p = 0.005) and IGF-1 (r = −0.302, p = 0.015). MRI T2* pancreas values correlated positively with FT4 (r = 0.268, p = 0.037) and IGF-1 (r = 0.312, p = 0.015). Patients with ferritin > 5000 ng/mL exhibited a higher prevalence of low IGF-1 levels (89.2% vs. 64.0%, p = 0.018). No significant gender-based differences were observed in endocrine parameters. Conclusion: Pancreatic iron burden and elevated serum ferritin were significantly associated with impaired thyroid and growth axis function, highlighting the value of integrating MRI T2* and biochemical markers for early endocrine risk stratification in adult TDT patients. Full article
17 pages, 2959 KB  
Article
Sublethal Clothianidin Exposure Impairs Development, Thyroid Hormones, Locomotion and Predation in Fejervarya cancrivora from Rice Paddy Ecosystems
by Joko Pilianto, Amr Abou El-Ela, Asim Munawar, Xiangfen Zhang, Dun Wang, Abid Ali Soomro, Naved A. Ansari, Wenwu Zhou and Zengrong Zhu
Toxics 2026, 14(3), 243; https://doi.org/10.3390/toxics14030243 (registering DOI) - 11 Mar 2026
Viewed by 244
Abstract
Clothianidin (CLO) is a widely used neonicotinoid insecticide in agricultural systems and may pose risks to non-target aquatic organisms, including amphibians. Here, we evaluated acute and sublethal effects of CLO on Fejervarya cancrivora tadpoles, an important predator of insect pests in rice paddy [...] Read more.
Clothianidin (CLO) is a widely used neonicotinoid insecticide in agricultural systems and may pose risks to non-target aquatic organisms, including amphibians. Here, we evaluated acute and sublethal effects of CLO on Fejervarya cancrivora tadpoles, an important predator of insect pests in rice paddy ecosystems. Acute toxicity tests (96 h) yielded an LC50 of 50.41 mg a.i./L (with LC10, LC25 and LC30 values of 15.35, 31.96 and 36.07 mg a.i./L, respectively). Sublethal exposure at these concentrations significantly reduced body weight, whole-body length, and hindlimb length during metamorphosis. CLO also altered thyroid hormone regulation, with T4 showing a dose-dependent increase, while T3 was elevated relative to controls but showed comparatively limited additional sensitivity to concentration and exposure duration. Locomotor activity was impaired under sublethal CLO exposure, reflected by reduced swimming distance and speed. In addition, frogs that developed from CLO-exposed tadpoles exhibited decreased feeding efficiency on brown planthoppers (Nilaparvata lugens) across developmental stages 46–48. Together, these findings demonstrate that CLO can affect amphibian development, endocrine regulation, and behavior at sublethal levels, highlighting the need to incorporate sublethal endpoints into ecological risk assessment and to promote pest management strategies that reduce impacts on biodiversity and ecosystem services. Full article
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25 pages, 2354 KB  
Article
Machine Learning Prediction of Transthyretin Binding for Thyroid Hormone Transport Disruption for Chemical Risk Assessment
by Shuaikang Hou, Chao Ji, Christopher M. Reh and Patricia Ruiz
Toxics 2026, 14(3), 240; https://doi.org/10.3390/toxics14030240 - 10 Mar 2026
Viewed by 311
Abstract
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 [...] Read more.
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
(This article belongs to the Section Novel Methods in Toxicology Research)
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22 pages, 1014 KB  
Article
Prospective Monitoring of Serum Values of CBC, Total IgE, Thyroid Findings, D-Dimer, Vitamin D, and Inflammatory Molecules CRP, ESR, and IL-6 and Clinical Features of Chronic Spontaneous Urticaria Patients During Antihistamine Treatment
by Matea Kuna, Mario Štefanović, Ema Barac, Fran Ivan Madunić, Milena Hanžek and Liborija Lugović-Mihić
Int. J. Mol. Sci. 2026, 27(5), 2503; https://doi.org/10.3390/ijms27052503 - 9 Mar 2026
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Abstract
Having appropriate and meaningful diagnostic procedures is crucial in the approach to patients with chronic spontaneous urticaria (CSU), so we wanted to investigate relationships between CSU patients’ common serum factors and clinical CSU features, and their temporal trends during antihistamine treatment. In this [...] Read more.
Having appropriate and meaningful diagnostic procedures is crucial in the approach to patients with chronic spontaneous urticaria (CSU), so we wanted to investigate relationships between CSU patients’ common serum factors and clinical CSU features, and their temporal trends during antihistamine treatment. In this exploratory hypothesis-based study, we assessed disease severity and quality of life (QoL) in, initially, 41 CSU patients using UAS7, daily UAS, UCT, DLQI, and CU-Q2oL. Concurrently, we measured serum complete blood count (CBC), total IgE, thyroid antibodies and hormones, ANA, D-dimer, vitamin D, and the inflammatory molecules CRP, ESR and IL-6. We compared initial (T1) and follow-up findings (T2) (after 3 months of antihistamine therapy). Basophil concentration was the only examined serum factor useful in assessing current CSU severity/daily UAS (sensitivity 78.6%; specificity 63%; p = 0.028). Basopenia was more frequent in patients with moderate/severe CSU than in those with mild disease or remission, as measured by daily UAS (79% vs. 37%; p = 0.020). T4 values showed a significant dependence on CSU duration (r = −0.328; p = 0.036). ESR was the only examined serum factor significantly associated with weekly CSU severity (UAS7) (p = 0.038). Antihistamine treatment significantly reduced CSU activity (recorded by daily UAS and UAS7) and improved QoL (DLQI) (p = 0.006) and disease control/UCT (p = 0.005). After three months of treatment, only the CRP value correlated with CSU control/UCT (p = 0.014). We encourage the use of diagnostics employing basophil counts and clinical indices UAS7, daily UAS, UCT and DLQI for insight into a patient’s CSU clinical condition. Serum factor values did not change during the 3-month treatment period, so it is not useful to measure them repeatedly. Although this study involved a small cohort and has many limitations, these promising results highlight the need for replication with a greater number of CSU patients. Full article
(This article belongs to the Special Issue Allergic Reactions and Immune Factors)
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25 pages, 5393 KB  
Article
Potential of Zinc-L-Selenomethionine to Improve the Health of Weaned Piglets and Its Antioxidant Stress Mechanism Through Modulation of PI3K/AKT and Nrf2/Keap1 Signaling Pathways
by Shujie Liu, Yongming Li, Xin Tao, Siyuan Li, Jie Wu, Fei Ji, Ziwei Xu and Bo Deng
Int. J. Mol. Sci. 2026, 27(5), 2499; https://doi.org/10.3390/ijms27052499 - 9 Mar 2026
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Abstract
Zinc-L-selenomethionine (Zn-L-SeMet), a novel organic selenium (Se) source, shows great potential in alleviating oxidative stress. This study first evaluated the potential of Zn-L-SeMet to improve the health of weaned piglets and investigated underlying molecular mechanisms. In vivo, 240 weaned piglets were assigned to [...] Read more.
Zinc-L-selenomethionine (Zn-L-SeMet), a novel organic selenium (Se) source, shows great potential in alleviating oxidative stress. This study first evaluated the potential of Zn-L-SeMet to improve the health of weaned piglets and investigated underlying molecular mechanisms. In vivo, 240 weaned piglets were assigned to five dietary groups, namely, a control group (basal diet without Se) and four groups supplemented with Zn-L-SeMet (0.1, 0.2, 0.3, or 0.4 mg Se/kg in basal diet) for 42 days. In vitro, an oxidative stress model was established using hydrogen peroxide (H2O2) in porcine intestinal epithelial cells (IPEC-J2) to investigate the mechanisms of Zn-L-SeMet against oxidative damage. The results showed that Zn-L-SeMet improved growth performance, enhanced antioxidant and immune function, stimulated thyroid hormone secretion, and upregulated expression of selenoprotein genes. In vitro, Zn-L-SeMet reduced H2O2-induced apoptosis, promoted IPEC-J2 viability, and enhanced activities of antioxidant enzymes, while reducing lactate dehydrogenase release, malondialdehyde and reactive oxygen species levels. Furthermore, Zn-L-SeMet significantly increased the expression levels of Keap1, NQO1, HO-1, ARE, p-Nrf2, p-PI3K, and p-AKT, and protein ratio of p-Nrf2/Nrf2, PI3K/PI3K, and p-AKT/AKT compared to the H2O2 group (p < 0.05). In conclusion, Zn-L-SeMet improves health status with antioxidant potential in weaned piglets, and the mechanism is associated with activation of PI3K/AKT and Nrf2/Keap1 pathways. Full article
(This article belongs to the Special Issue Research on Trace Elements in Nutrition and Health)
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17 pages, 1404 KB  
Article
The Prognostic Significance of Low-Triiodothyronine Syndrome in Aneurysmal Subarachnoid Hemorrhage
by Adrianna Lebiedzińska, Małgorzata Burzyńska, Jowita Woźniak and Waldemar Goździk
Biomedicines 2026, 14(3), 603; https://doi.org/10.3390/biomedicines14030603 - 9 Mar 2026
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Abstract
Background: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high early mortality and long-term disability. Prognostic assessment relies mainly on neurological grading scales, which may incompletely capture the systemic metabolic response to acute brain injury. Non-thyroidal illness syndrome (NTIS), particularly low triiodothyronine syndrome (LT3S), [...] Read more.
Background: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high early mortality and long-term disability. Prognostic assessment relies mainly on neurological grading scales, which may incompletely capture the systemic metabolic response to acute brain injury. Non-thyroidal illness syndrome (NTIS), particularly low triiodothyronine syndrome (LT3S), is common in critical illness, but its prognostic relevance in aSAH remains unclear. Objectives: To evaluate the prognostic impact of early thyroid hormone alterations on 30-day mortality and early clinical outcomes including delayed cerebral ischemia (DCI) in patients with aSAH, with particular emphasis on the magnitude of triiodothyronine (T3) deficiency. Methods: We conducted a retrospective single-center observational cohort study of 157 consecutive adult patients admitted with confirmed aSAH between 2014 and 2025. Serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were measured within 72 h of admission. Hormone values were normalized to contemporaneous reference intervals to generate continuous reference-adjusted metrics (FT3_level, TSH_level). Associations with 30-day in-hospital mortality were analyzed using logistic regression and Cox proportional hazards models adjusted for admission variables including age, sex, APACHE II score, World Federation of Neurosurgical Societies grade, Fisher grade, and treatment modality. Results: Binary LT3S classification was frequent but not independently associated with 30-day mortality. In contrast, lower FT3_level values were significantly associated with increased mortality and shorter survival time. In logistic regression analyses, each 0.1 increase in FT3_level was associated with an 18% lower odds of death (adjusted OR 0.82, 95% CI 0.69–0.97). This association persisted after adjustment for established clinical severity measures and was concordant with time-to-event analyses. FT3_level was not correlated with TSH_level, consistent with NTIS. Endovascular coiling was associated with more pronounced peripheral fT3 deficiency (p < 0.05) but was not independently associated with mortality. FT3_level was not independently associated with early neurological status or functional outcome at hospital discharge. Conclusions: Lower FT3_level values were independently associated with higher 30-day mortality, indicating that early peripheral T3 reduction reflects clinically relevant metabolic vulnerability in aSAH. Full article
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