Thyroid Hormone Levels Research Articles

Association Between Maternal Thyroid Hormone Concentration with Normal Thyroid Function During Pregnancy and Preschoolers' Glycolipid Metabolism: A Birth Cohort Study.

Background: Thyroid hormones (THs) are essential endocrine hormones that play key roles in individual's growth and development. There is limited knowledge about the association between maternal TH concentrations variations with normal thyroid function during pregnancy and offspring's glycolipid metabolism. Methods: A total of 1130 mother-child pairs from the Ma'anshan birth cohort were included in this prospective study. Maternal TH levels and thyroid peroxidase antibodies were measured in the 1st, 2nd, and 3rd trimesters of pregnancy during the childhood follow-up period. Fasting venous blood was collected from children at 4-6 years of age and glycolipid metabolic indicators were assayed. Analyses were performed using Binary logistic regression models, linear regression models, and Generalized linear regression model. Results: Maternal TH trajectories were fitted via latent category growth models. During the 1st trimester of pregnancy, maternal T3 and free thyroxine (fT4) levels were positively associated with children's blood glucose levels (β = 0.007 [CI 0.028-0.181]; β = 0.022 [CI 0.004-0.040]), whereas high levels of fT4 may be associated with decreased risk of children's hypercholesterolemia (OR = 0.870 [CI 0.768-0.986]). Maternal T4 concentrations during the 3rd trimester of pregnancy were negatively associated with children's cholesterol levels (β = -0.002 [CI -0.003-0.00]). High maternal TH levels were associated with high fasting glucose level and low low-density lipoprotein concentrations in children. Conclusions: Maternal TH dynamic variations may be associated with glycolipid metabolism in preschoolers, even when women do not have clinically diagnosed thyroid disorders. The exact associations between maternal THs in specific trimesters of pregnancy under normal thyroid function conditions and glycolipid metabolism in offspring require further investigation.

Oral nicotinic acid administration effect on lipids, thyroid hormones, and oxidative stress in intact adult dogs.

Nicotinic acid (niacin, Vitamin B3) is one of the most effective medicines for improving high-density lipoprotein concentrations. Obesity and related diseases are life-threatening to dogs. This study investigated the niacin effect on triglyceride, cholesterol, lipoproteins, thyroid hormones, oxidative stress, and lipid peroxidation in intact adult dogs. Blood samples were taken from seven healthy, intact adult dogs as a control group (day 0). Then, the animals received 1000mg/dog of oral nicotinic acid tab daily for 42days, and blood sampling was performed on days 14, 28, 42, and 56. The results showed an increasing trend in high-density lipoprotein (HDL) concentration. The highest HDL concentration (138.85 ± 43.72mg/dl) was related to day 56; the HDL level followed a statistically significant increase between day 14 and 56. Unlike HDL, there was a decreasing trend in low-density lipoprotein (LDL) concentration. The lowest LDL concentration (21.85 ± 18.60mg/dl) was related to day 56. The concentration of apolipoprotein A-I (apoA1) was significantly increased during the study. The highest concentration of apoA1 (1.66 ± 0.06g/l) was on day 42. There was a significant increase in apoA1 concentrations between days 0 and 14, 42, and 56. The apoA1 was significantly increased between days 14 and 42 and 56. The apoA1 followed a statistically significant increase between days 28 and 42. Changes in thyroid hormone levels did not show any constant increasing or decreasing trend. On day 14, a decreasing trend in the concentrations of TT4, FT4, and T3 was observed. However, an increasing trend was detected in the concentrations of TT4, FT4, and T3 on days 28 and 42. However, the increase in the concentrations of TT4 and FT4 was less than that on day 0. After treatment (day 56), a decreasing trend was observed in thyroid hormone concentrations. The negative correlation was detected between apoA1 and triiodothyronine (T3), total thyroxine T4 (TT4)), and free T4 (FT4) concentrations on day 42. Furthermore, a significant negative relationship was observed between HDL and T4 on day 42. However, the relationship between triglyceride and T3 was statistically positive on day 14. There was an increasing trend in serum total antioxidant capacity (TAC). The highest TAC concentration (3.83 ± 0.62µmol /l) was on day 56; however, the malondialdehyde (MDA) concentration was decreased during the study. The total antioxidant level followed a statistically significant increase between days 0 and 56 compared to days 14 and 42. The study demonstrated the efficacy of nicotinic acid in improving serum HDL, apoA1, and TAC, as well as decreasing serum MDA and LDL concentrations.

Butyrate Ameliorates Graves' Orbitopathy Through Regulating Orbital Fibroblast Phenotypes and Gut Microbiota.

Graves' orbitopathy (GO), the common extrathyroidal complication of Graves' disease (GD), is characterized by orbital fibroblast stimulation, adipogenesis, and hyaluronan production. Recently, gut microbiota and its metabolites have garnered attention for their possible involvement in GO. This study utilized an animal model of GO and examined the effects of butyrate treatment on orbital fibroblast cells and gut microbiota. Ex vivo experiments were performed using orbital fibroblasts derived from healthy patients' and patients' with GO orbital tissue to evaluate vitality, activation, and adipogenesis in response to butyrate treatment. Gut microbiota diversity was also analyzed in butyrate-treated and untreated GO mice. In human orbital fibroblasts, butyrate treatment dramatically decreased the vitality of GO-derived fibroblasts without harming normal fibroblasts. Butyrate prevented activation and fibrotic processes induced by transforming growth factor beta 1 (TGF-β1) in GO and normal fibroblasts. Additionally, butyrate reduced lipid droplet formation and downregulated lipogenic markers in GO and normal orbital fibroblasts, inhibiting adipogenesis. In the GO mouse model, butyrate therapy improved orbital histological abnormalities and normalized serum thyroid hormone and antibody levels. The intestinal microbiome of butyrate-treated GO mice also changed significantly, with a reduction in certain bacteria (Bifidobacterium, GCA-900066575, and Parabacteroides) and an increase in others (Bacteroides and Rikenellaceae_RC9). Butyrate ameliorates several of the symptoms of GO, lowering GO orbital fibroblast viability, adipogenesis, and TGF-β1-induced fibrosis without damaging normal fibroblasts. Butyrate normalizes thyroid function in a GO mouse model, improves histopathological alterations, and transforms gut microbiota populations, proving its potential in treating GO through the gut-thyroid axis.

Autoimmune Thyroid Diseases in Chronic Spontaneous Urticaria: The Role of Hormones, Anti-Thyroid Antibodies, and Ultrasound

Background/Objectives: Chronic spontaneous urticaria (CSU) is an immune-mediated skin disorder, with increasing evidence suggesting its association with autoimmune thyroid diseases. The presence of antithyroid antibodies (anti-TPO and anti-TG) and autoimmune thyroid disease indicates shared immunological mechanisms in the pathogenesis of both conditions. This study examines the prevalence of autoimmune thyroid changes in patients with CSU. Methods: The study was conducted as a combined retrospective-prospective observational analysis. It included 43 patients with CSU and 50 healthy participants in the control group. Thyroid hormone levels (TSH, T3, T4), anti-TPO and anti-TG antibodies, as well as ultrasound characteristics of the thyroid gland, were analyzed. Results: In patients with CSU, a higher prevalence of hypothyroidism (27.9% vs. 4% in the control group), hypertension, asthma, and diabetes were observed. Elevated levels of anti-TPO antibodies were found in 51.2% of CSU patients, compared to only 6% in the control group (p < 0.001). Similarly, anti-TG antibodies were increased in 41.9% of CSU patients, compared to 4% in the control group. Additionally, ultrasound analysis revealed significant differences in thyroid morphology, with a heterogeneous structure observed in 72.1% of CSU patients, compared to only 14% in the control group (p < 0.001). Nodular changes were present in 34.88% of CSU patients, whereas the prevalence in the control group was only 6% (p < 0.001). Conclusions: Our results confirm a significant association between CSU and autoimmune thyroid diseases, including a high prevalence of anti-TPO and anti-TG antibodies, hypothyroidism, diffuse heterogeneity, and nodular changes. Additionally, elevated T3 hormone levels were common among CSU patients, while T4 levels did not differ significantly from those in the control group.

Assessment of Left Ventricular Strain Echocardiography in Individuals with Hashimoto’s Thyroiditis and Its Association with Serum TIMP-1 Concentration

Background: Hashimoto’s thyroiditis (HT), which is an autoimmune condition and the primary cause of hypothyroidism, has numerous impacts on the cardiovascular system. This research aimed to compare TIMP-1 levels and LV strain values in euthyroid HT, hypothyroid HT, and healthy control persons. Materials and Methods: This study included 40 hypothyroid HT patients, 42 HT patients who became euthyroid with thyroid hormone replacement therapy, and 40 healthy controls. All subjects had conventional echocardiography and STE. Global and segmental LV longitudinal strain values (LVGLS) were calculated. Participants’ blood was tested for TIMP-1, thyroid function, and anti-TPO. Results: Higher serum TIMP-1 levels were found in euthyroid and hypothyroid HT patients than in the control group. Additionally, patients with euthyroid and hypothyroid HT displayed lower segmental and global LV strain values than the control group. A negative correlation was observed between strain values and TIMP-1 and anti-TPO levels. No significant difference was observed in serum TIMP-1 and strain values between euthyroid and hypothyroid HT patients. Patients with hypothyroid HT exhibited impaired diastolic function and reduced ejection fraction when compared to both euthyroid HT and control groups. However, euthyroid HT patients and the controls had similar diastolic function and ejection fractions. Conclusions: Hashimoto’s thyroiditis causes impairment of LV strain, regardless of thyroid hormone levels. Additionally, the condition is associated with elevated TIMP-1 levels. The relationship between LV strain values and anti-TPO levels indicates that the autoimmune component of the disease may be responsible for the impaired LV strain.

Evaluation of the Relationship Between Thyroid Hormone Levels and Bisphenol A in Children Aged 6-14 Years.

The incidence of hypothyroidism in childhood is increasing. This study aimed to investigate the potential role of exposure to bisphenol A, an environmental endocrine disruptor, and its substitutes in the development of hypothyroidism. To this end, thyroid hormone levels and urinary bisphenol concentrations were compared in newly diagnosed hypothyroid children and a healthy control group. In this case-control study, 51 newly diagnosed hypothyroid children aged 6-14 years were matched with 51 healthy controls. The association between thyroid hormone levels and urinary bisphenol levels was investigated by measuring urinary bisphenol levels in both the case and control groups. There was no significant difference in age, sex or BMI percentile between the case and control groups. The groups were homogeneously distributed. When urinary bisphenol levels were examined, BPA, BPS, BPF and BPB were not detected in the control group. There was a significant difference between the groups in terms of urinary bisphenol BPS levels. The case group showed a mean total concentration of 16.5 ng/mL and a median of 5.8 ng/mL. Diagnosing hypothyroidism in the children can be considered by examining the bisphenol level. In the ROC analysis, if this level is over 1.3 and is considered positive for hypothyroidism, the sensitivity value is determined as 83.7% and the specificity value is 75%. This study demonstrated that at least 50% of the children in the case group had bisphenol concentrations exceeding the highest value recorded in the control group, suggesting that total BP levels could be used as a potential biomarker for hypothyroidism.

Population-level impact of COVID-19 on thyroid function tests: Results from a repeated cross-sectional study.

Population-level impact of COVID-19 on thyroid function tests: Results from a repeated cross-sectional study.

The hypothalamus-pituitary-thyroid axis is disrupted by exposure to a mix of tributyltin and bisphenol S.

The hypothalamus-pituitary-thyroid axis is disrupted by exposure to a mix of tributyltin and bisphenol S.

Application of Thyroid Hormones in Women’s Hair for the Non-Invasive Prediction of Graves’ Disease

Graves’ disease (GD) is an autoimmune disorder that can be difficult to distinguish from other diseases due to symptom similarity. The exacerbation of GD owing to delayed diagnosis is a serious issue, and a novel accessible health screening system is needed. Therefore, this study investigated the association between GD and thyroid hormone levels in women’s hair and evaluated the prediction accuracy of this non-invasive type of sample. By optimizing pretreatment and analysis techniques using liquid chromatography–mass spectrometry (LC-MS), free triiodothyronine (FT3) and thyroxine (FT4) could be detected in only 2 mg of hair with high sensitivity. Compared with healthy controls, the thyroid hormone levels in the hair of GD patients were significantly higher in correlation with blood levels. The predictive ability of hair thyroid hormones was analyzed using a receiver operating characteristic (ROC) curve, and the optimal cut-off value was determined via the Youden index. As a result, the area under the curve (AUC) was 0.974 (95% confidence interval (CI): 0.935–1.000) for FT3 and 0.900 (95% CI: 0.807–0.993) for FT4. The cut-off value was 0.133 pg/mg (sensitivity: 91.2%; specificity: 100%; positive predictive value (PPV): 100%; negative predictive value (NPV): 76.9%) for FT3 and 0.067 pg/mg (sensitivity: 70.6%; specificity: 100%; PPV: 100%; NPV: 50.0%) for FT4. Collectively, our new approach offers the possibility of accurately and non-invasively detecting GD using hair samples. Since hair can be stored and transported at room temperature, this system facilitates large-scale screening at locations including hair salons and homes, potentially enabling the early determination of GD outside of medical facilities.

The comparison study to Triiodothyronine (T3) levels in severe and non-severe covid-19 infections in Babylon province

In addition to evaluating thyroid hormone levels as a possible predictor of illness severity, this reading sought to regulate the reminder among disease severity and demographic characteristics (age, gender, blood group, vaccination status, and geographic distribution) in recovered COVID-19 patients. 76 COVID-19 patients who received treatment at Babylon Province's Merjan Teaching Hospital between November and December 2021 were examined. Age was significantly correlated with severity (p≤0.0001), with non-severe cases being more common in those under 30 and severe cases being more common in those over 40. Gender differences were not statistically significant, despite the fact that males outnumbered females (p˃0.0001). Although there were variations between rural and urban cases (p≤0.0357), geographic location had no discernible effect. While ABO blood type affected severity While ABO blood type had no effect on severity, vaccination status did (p˃0.0001). Significant differences in T3 levels between severe and non-severe patients point to a possible function in predicting the severity of the disease. These results shed light on the biological and demographic variables affecting COVID-19 outcomes.

Study of thyroid hormone status in severely malnourished children

Background: In 2022 globally, nearly half of deaths among children under 5 years of age are linked to undernutrition particularly in low- and middle-income countries. Reductive adaptation, the body’s physiological response to energy deficiency, can significantly impact various metabolic processes, including thyroid function immaturity. The present study has been conducted to study thyroid dysfunction in severe acute malnutrition (SAM); and its correlation with plasma protein levels. Methods: This prospective cross-sectional study at RNT medical college, Udaipur, involved 100 children (group A) with SAM and 100 non-SAM children (group B). Demographic, clinical, and anthropometric data were collected. Serum levels of thyroid hormones (FT3, FT4 and TSH) and total protein were measured and analyzed for correlations and differences. Results: Mean age of presentation of malnourished children was 16.14±9.16 months with male to female ratio 1.17:1. The mean value of FT3, FT4 and TSH in the group A was 2.39±1.50 pg/ml, 0.83±0.57ng/dl and 1.57±1.93 mIU/ml while of the group B was 4.55±1.88 pg/ml, 1.26±0.66 ng/dl and 2.12±1.17 mIU/ml respectively. The mean serum total protein was 5.58±0.93 g/dl in group A and 6.63±0.75 g/dl in group B. A significant correlation was found between FT3, FT4, and TSH levels with serum total protein levels. Conclusions: In our study, we found that children with SAM exhibited lower levels of thyroid hormone compared to children with non-SAM. Significant correlation (p<0.05) was noted between thyroid hormone levels and serum total protein levels.

Glycaemicparameters, Dyslipidaemia and Thyroid Hormone: An exploratory study of their interrelationship in Type 2 Diabetes Mellitus patients

Background: Diabetes mellitus and thyroid disorders may coexist and impacting each other. The thyroid gland function (hypo- and hyper-function) may affect the metabolism of carbohydrates. Both conditions have an impact on the lipid profile since insulin resistance or insufficiency alters important enzymes and pathways involved in lipid metabolism. Lipid abnormalities are common in diabetes mellitus. The purpose of this study is to determine how diabetes mellitus, hypothyroidism, and dyslipidaemia are related. Method: The study included 300 participants, 150 of whom were healthy controls and 150 of whom had diabetes mellitus and hypothyroidism. 150 people with diabetes were further divided into 75 people who had dyslipidemia and 75 people who did not. Serum lipid profiles and blood sugar levels were measured using the Mindray BS240 analyzer. Triiodothyronine [T3], thyroxine [T4], and thyroid stimulating hormone [TSH] were measured using chemiluminescence immunoassay. Result: The study found that female subjects with diabetes had a higher prevalence of dyslipidaemia. The TSH differences between the study and control groups were more significant (OR 3.147, P Value0.001*). Notable were the T4 (OR 1.734, P Value0.001*) and T3 (OR 2.031, P Value0.001*), mean differences as well. Higher levels of FBS, PPBS, and RBS were observed. The lipid profile total cholesterol (OR 3.120, P Value0.001*), triglycerides (OR 1.592, P Value0.001*), HDL (OR 2.173, P Value0.001*), LDL (OR 2.110, P Value0.001*), and VLDL (OR 2.194, P Value0.001*) is also significant compared to controls. Conclusion: This study shows that T2DM significantly affect thyroid function especially in female. It is crucial to take thyroid function into account in diabetic patients because changes in thyroid hormone levels may be caused by insulin resistance and altered glucagon levels.The results suggest a significant association between hypothyroidism and diabetes with dyslipidaemia.

The Impact of Acquired Hypothyroidism on the Growth and Metabolic Profiles of Pediatric Patients: A Retrospective Monocentric Study

Background: Hypothyroidism is the most common thyroid dysfunction in childhood, resulting from the decreased biological activity of thyroid hormones in tissues. Pediatric patients with hypothyroidism, when left untreated or when thyroid hormone levels fail to normalize despite treatment, may exhibit various complications such as growth retardation, obesity, and hypercholesterolemia. Aim: We conducted a monocentric retrospective study to evaluate potential differences in obesity rates and auxological parameters between healthy patients and children with hypothyroidism undergoing levothyroxine replacement therapy. Additionally, we examined possible differences in lipid and glucose metabolism between the two groups. Materials and Methods: We collected and analyzed data from the electronic medical records of 108 patients who were regularly followed up for thyroid dysfunction at the Pediatric Endocrinology Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS from January 2016 to June 2024. We also included 104 healthy controls who underwent thyroid function testing during the same period, followed up in the same department for regular auxological check-ups. Results: Our findings revealed that patients with acquired hypothyroidism had a lower height z-score compared to healthy controls (t(210) = −2.6; p = 0.01). Additionally, they exhibited higher blood glucose and triglyceride levels, although these values remained within the normal range. Conclusions: We highlight the critical importance of the early diagnosis of hypothyroidism to initiate levothyroxine replacement therapy promptly and mitigate the long-term effects of hypothyroidism on children’s growth.

Effects of organophosphate esters on thyroid function during pregnancy: Risk of endocrine disruptors during early- and mid-pregnancy.

Effects of organophosphate esters on thyroid function during pregnancy: Risk of endocrine disruptors during early- and mid-pregnancy.

The correlation between WMSDs and thyroid indicators in male large-scale mechanical maintenance workers

Objective: To investigate the status of work-related musculoskeletal disorders (WMSDs) in male large-scale mechanical maintenance workers, and to explore the relationship between WMSDs and thyroid indexes. Methods: From April to July 2022, male front-line maintenance workers in a large-scale mechanical maintenance enterprise who participated in occupational health examination were selected as the study subjects (n=2036). The occurrence of WMSDs was investigated by questionnaire. The levels of triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) in serum were detected. χ(2) test, t-test and Mann-Whitney U test were used to detect thyroid diseases and hormone levels of workers in WMSDs group and non-WMSDs group, and binary logistic regression model was used to analyze the relationship between thyroid disease, T3, T4, TSH and WMSDs. Results: The incidence of WMSDs among the male large-scale mechanical maintenance workers was 73.18% (1490/2036). The rate of thyroid disease in WMSDs group was higher than that in non-WMSDs group [8.26% (123/1490) vs. 4.95% (27/546), χ(2)=6.42, P=0.011], and the TSH value was lower than that in non-WMSDs group[1.66 (1.23, 2.26) μIU/ml vs. 1.75 (1.30, 2.42) μIU/ml, Z=-2.40, P=0.019]. There were no significant differences in the levels of T3, T4 and abnormal levels of 3 hormones between the two groups (P>0.05). After accounting for individual and occupational factors, workers with thyroid disease had an increased risk of WMSDs (OR=1.656, 95%CI: 1.072-2.559, P=0.023), while workers with increased TSH had a decreased risk of WMSDs (OR=0.897, 95% CI: 0.823-0.977, P=0.013) . Conclusion: The incidence of WMSDs in male workers of large-scale mechanical maintenance is high, and its incidence may be related to thyroid index. Thyroid disease may be a risk factor for WMSDs, and increased TSH may be a protective factor for WMSDs.

Differential levels of thyroid hormones, cortisol, and apolipoprotein M in fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), recently reclassified as metabolic dysfunction-associated fatty liver disease (MAFLD), can also manifest in patients classified as non-MAFLD who do not meet MAFLD criteria. The involvement of cortisol and thyroid hormones may play a role in the pathogenesis of FLD by modifying the metabolism of specific lipoproteins, particularly apolipoprotein M (Apo M). This study investigated cortisol and thyroid hormones levels and Apo M gene expression in white blood cells (WBCs) of individuals with MAFLD, non-MAFLD, and healthy controls. The serum and WBCs of the study subjects were collected from patients with FLD (n=99) including 58 MAFLD and 41 non-MAFLD and healthy individuals (n=23). To investigate the gene expression of Apo M and thyroid and cortisol hormones, qRT-PCR and ELISA methods were used, respectively. The Apo M gene expression was significantly lower in FLD patients, both non-MAFLD, and MAFLD patients compared to the control group (p<0.05). Total T4 and TSH hormone levels in the MAFLD patients were significantly decreased and increased compared to the control group, respectively (p<0.05). The cortisol level was significantly elevated in the FLD and MAFLD patients compared to the control group (p<0.01). Alterations in Apo M gene expression also cortisol and thyroid hormones levels in non-MAFLD patients were milder than MAFLD patients when compared to the control. Also, likely Apo M may be involved in FLD pathogenesis.

INFLUENCE OF DIFFERENT TYPES OF ALLOSTERIC REGULATORS ON THE BASAL AND HORMONE-STIMULATED ACTIVITY OF THE THYROID-STIMULATED HORMONE RECEPTOR IN VITRO AND IN VIVO

Background: Antithyroid drugs used to treat autoimmune hyperthyroidism lead to thyroid hormone deficiency when used for a long time. In this regard, it is relevant to develop thyroid-stimulating hormone receptor (TSHR) regulators capable of inhibiting TSHR activation by agonists acting on the orthosteric site of the receptor (TSH, autoantibodies to TSHR) and stimulating its basal activity. This function can be performed by allosteric TSHR regulators with agonist activity and negative allosteric modulators (ago-NAM).Aim: A comparative study of the effects of TPY4, a thieno[2,3-d]-pyrimidine derivative, and peptide 612–627-Lys(Palm)Ala, a derivative of the third cytoplasmic loop of TSHR, on basal and TSH-stimulated adenylate cyclase (AC) activity in thyroid membranes and on basal and thyrotropin-releasing hormone (TRH)-stimulated thyroid hormone levels when administered to male rats.Materials and methods: The activity of AC in membranes isolated from the rat thyroid gland was measured by the radioisotope method using [α-32P]-ATP as a substrate. The ability of the drugs to affect the basal and TRH-stimulated levels of thyroid hormones was assessed by treating rats with the peptide 612–627-Lys(Palm)Ala (750 μg/kg) and TPY4 (15 mg/kg). The concentrations of free thyroxine (FT4), total triiodothyronine (TT3), and TSH in the blood of rats were determined by enzyme immunoassay.Results: In rat thyroid membranes, TPY4 and 612–627-Lys(Palm)Ala in micromolar concentrations increased the basal activity of AC and decreased its stimulation by TSH (10-9 M), and TPY4 was more effective as an inhibitor of the TSH effect, while the peptide stimulated AC to a greater extent. When administered to rats, both compounds, although to varying degrees, increased the production of FT4 and TT3, but at the same time prevented its increase upon activation of the thyroid axis by TRH (100 μg/rat). They did not have a significant effect on the TRH-stimulated level of TSH in the blood, and this indicates that their targets are TSHR localized in thyrocytes.Conclusions: Structurally distinct allosteric ligands of TSHR, the thieno[2,3-d]-pyrimidine derivative TPY4 and the peptide 612–627-Lys(Palm)Ala, were characterized by a similar spectrum of pharmacological activity, functioning as an ago-NAM for TSHR. Their ability to prevent hyperactivation of TSHR without causing a decrease in thyroid hormone levels could be used to develop drugs for the treatment of autoimmune hyperthyroidism.

The Performance, Ingestive Behavior, Nutrient Digestibility, Ruminal Fermentation Profile, Health Status, and Gene Expression of Does Fed a Phytochemical-Lactobacilli Blend in Late Pregnancy.

This study investigated the effects of a phytochemical-Lactobacilli blend (PEL) on the performance and health of late-pregnant does. Thirty Zaraibi does (30.9 ± 0.37 kg body weight, 3-3.5 years old, 90 days pregnant) were randomly assigned to three experimental groups, ensuring equal distribution based on body weight, parity, litter size, and previous lactation milk production. The does were fed either a control diet (no supplementation) or a PEL-supplemented diet (control diet plus 2 g or 4 g of PEL per day) for 60 days. PEL supplementation linearly improved (p < 0.05) feed intake, nutrient digestibility, and ruminal concentrations of acetic and propionic acids, while significantly reducing (p < 0.05) ruminal ammonia-N concentrations. PEL supplementation linearly reduced (p < 0.05) feeding and rumination times while increasing idling time. Blood hematological parameters improved (p < 0.05) with PEL supplementation. Serum protein, liver and kidney function indicators, lipid metabolism, cortisol, and thyroid hormone levels were significantly improved (p < 0.01) in a linear manner with PEL supplementation. Antioxidant status, pro-inflammatory cytokines, and immune response were enhanced both linearly and quadratically (p < 0.05) with PEL treatment. Gene expression analysis revealed a linear upregulation (p < 0.05) of growth, immune, and antioxidant-related genes with PEL supplementation. These findings suggest that supplementing pregnant does with 4 g of PEL per day can effectively enhance their performance, health, and metabolic status.

Selective Therapeutic Potential of a H2O2 Inducible DNA Interstrand Cross-Linker in Anaplastic Thyroid Carcinoma.

We aimed to investigate Hydrogen Peroxide Inducible DNA Interstrand Cross-Linker (HP-ICL) as a targeted therapy for anaplastic thyroid cancer (ATC) due to its higher H2O2 content compared to normal cells. In vitro analysis included fluorescence microscopy for H2O2 levels, and exposure of ATC cells to various HP-ICL concentrations followed by assessment of cell viability, apoptosis, cell cycle, and DNA damage using MTT, flow cytometry, and a γH2AX assay. Protein levels related to apoptosis and the PI3K/AKT/mTOR pathway were measured by western blotting. An ATC xenograft mouse model was used to evaluate HP-ICL's in vivo effects. ATC cells had higher H2O2 levels than normal thyroid cells. HP-ICL treatment caused a dose-dependent decrease in cell viability and an increase in apoptosis, with a slight G2/M phase arrest. A 30 µM HP-ICL treatment doubled γH2AX foci. Bcl-2 levels decreased, while Bax, cleaved-Caspase 3 and PARP increased in a dose-dependent manner. It also inhibited p-PI3K, p-AKT, and p-mTOR. In vivo, HP-ICL significantly inhibited tumor growth while maintaining body weight and without causing organ damage or altering thyroid hormone levels. Additionally, tumor sections exhibited increased TUNEL staining, decreased Ki67 expression, and reduced levels of p-PI3K, p-AKT, and p-mTOR. HP-ICL significantly inhibited ATC both in vitro and in vivo, suggesting its potential as an effective therapy for ATC.

Substitution of an Ethyl Group with a Methyl Group in the Variable Moiety of TPY3m, a Thyroid-Stimulating Hormone Receptor Agonist, Modifies the Effect of This Analogue on the Basal and Thyroliberin-Stimulated Levels of Thyroid Hormones in Rats

Substitution of an Ethyl Group with a Methyl Group in the Variable Moiety of TPY3m, a Thyroid-Stimulating Hormone Receptor Agonist, Modifies the Effect of This Analogue on the Basal and Thyroliberin-Stimulated Levels of Thyroid Hormones in Rats