Regulation Of Thyroid Function Research Articles

CD147 protein molecule expression and chromosomal instability in the pathogenesis and prognosis of thyroid cancer

Low-coverage whole genome sequencing was performed for tissue samples from thyroid patients who received surgery treatment from 2015 to 2021. The potential biological significance of CD147 protein in thyroid cancer was explored through correlation analysis of CD147 protein expression level and clinical features of thyroid cancer patients. Low coverage whole genome sequencing was performed on the extracted DNA samples. The copy number analysis software was used to analyze the sequencing data, calculate the copy number of CD147 gene, further verify the expression of CD147 gene, and analyze its association with clinical features. The relationship between CIN and high risk was evaluated in the internal cohort. The association of CIN with the disease-free survival was validated in the cohort from The Cancer Genome Atlas Program. Thyroglobulin plays a key role in regulating thyroid function and maintaining normal metabolic rate. By sequencing tissue samples from this study, we can gain a deeper understanding of the association between cin and thyroid disease. The percentage of high risk patients in the multiple CIN group (77.8 %) was significantly higher than that in the 22q negative group (31.3 %), BRAF V600E group (22.2 %) and all negative group (25.0 %; p = 0.043).

The Immune Suppressor IGSF1 as a Potential Target for Cancer Immunotherapy.

The development of first-generation immune-checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 ushered in a new era in anticancer therapy. Although immune-checkpoint blockade therapies have shown clinical success, a substantial number of patients yet fail to benefit. Many studies are under way to discover next-generation immunotherapeutic targets. Immunoglobulin superfamily member 1 (IGSF1) is a membrane glycoprotein proposed to regulate thyroid function. Despite containing 12 immunoglobin domains, a possible role for IGSF1, in immune response, remains unknown. Here, our studies revealed that IGSF1 is predominantly expressed in tumors but not normal tissues, and increased expression is observed in PD-L1low non-small cell lung cancer (NSCLC) cells as compared with PD-L1high cells. Subsequently, we developed and characterized an IGSF1-specific human monoclonal antibody, WM-A1, that effectively promoted antitumor immunity and overcame the limitations of first-generation immune-checkpoint inhibitors, likely via a distinct mechanism of action. We further demonstrated high WM-A1 efficacy in humanized peripheral blood mononuclear cells (PBMC), and syngeneic mouse models, finding additive efficacy in combination with an anti-PD-1 (a well-characterized checkpoint inhibitor). These findings support IGSF1 as an immune target that might complement existing cancer immunotherapeutics.

The Potential Role of Pyrroloquinoline Quinone to Regulate Thyroid Function and Gut Microbiota Composition of Graves' Disease in Mice.

Graves' disease (GD) is an autoimmune disorder disease, and its prevalence continues to increase worldwide. Pyrroloquinoline quinone (PQQ) is a naturally antioxidant compound in milk, vegetables, and meat. We aim to identify the treatment efficacy of PQQ on GD and its regulatory effect on intestinal microbiota. The GD mice model was built by an adenovirus expressing autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). Fecal samples were collected for 16S rDNA sequencing after PQQ pretreatments (20, 40, or 60 mg/kg BW/day) for 4 weeks. Thyroid and intestine functions were measured. The levels of serum TSHR and T4 were significantly raised, and the thyroid gland size was typically enlarged in the GD group than in controls, reversed by PQQ therapy. After PQQ replenishment, IL6 and TNFα levels in small intestine tissues were lower than those in the GD group, with Nrf2 and HO1 levels improved. Also, the PQQ supplement could maintain the mucosal epithelial barrier impaired by GD. In microbial analyses, PQQ treatment could prompt the diversity recovery of gut microbiota and reconstruct the microbiota composition injured by GD. Lactobacillus served as the most abundant genus in all groups, and the abundance of Lactobacillus was increased in the GD group than in control and PQQ groups. Besides, Lactobacillus was highly correlative with all samples and the top 50 genera. PQQ supplementation regulates thyroid function and relieves intestine injury. PQQ changes the primary composition and abundance of GD's intestine microbiota by moderating Lactobacillus, which may exert in the pathogenesis and progression of GD.

TSH Pulses Finely Tune Thyroid Hormone Release and TSH Receptor Transduction.

Detection of circulating TSH is a first-line test of thyroid dysfunction, a major health problem (affecting about 5% of the population) that, if untreated, can lead to a significant deterioration of quality of life and adverse effects on multiple organ systems. Human TSH levels display both pulsatile and (nonpulsatile) basal TSH secretion patterns; however, the importance of these in regulating thyroid function and their decoding by the thyroid is unknown. Here, we developed a novel ultra-sensitive ELISA that allows precise detection of TSH secretion patterns with minute resolution in mouse models of health and disease. We characterized the patterns of ultradian TSH pulses in healthy, freely behaving mice over the day-night cycle. Challenge of the thyroid axis with primary hypothyroidism because of iodine deficiency, a major cause of thyroid dysfunction worldwide, results in alterations of TSH pulsatility. Induction in mouse models of sequential TSH pulses that mimic ultradian TSH profiles in periods of minutes were more efficient than sustained rises in basal TSH levels at increasing both thyroid follicle cAMP levels, as monitored with a genetically encoded cAMP sensor, and circulating thyroid hormone. Hence, this mouse TSH assay provides a powerful tool to decipher how ultradian TSH pulses encode thyroid outcomes and to uncover hidden parameters in the TSH-thyroid hormone set-point in health and disease.

Exploring the oral-gut microbiota during thyroid cancer: Factors affecting the thyroid functions and cancer development.

Thyroid cancer (TC) is categorized into papillary, follicular, medullary, and anaplastic. The TC is increasing in several countries, including China, the United States, the United Kingdom, Canada, France, Australia, Germany, Japan, Spain, and Italy. Thus, this review comprehensively covers the factors that affect thyroid gland function, TC types, risk factors, and symptoms. Lifestyle factors (such as nutrient consumption and smoking) and pollutants (such as chemicals and heavy metals) increased the thyroid-stimulating hormone (TSH) levels which are directly related to TC prevalence. The conventional and recent TC treatments are also highlighted. The role of the oral and gut microbiota as well as the application of probiotics on TC are also discussed. The variations in the composition of oral and gut microbes influence the thyroid function indirectly through alteration in metabolites (such as short-chain fatty acids) that are eminent for cellular energy metabolism. Maintenance of healthy gut and oral microbiota can help in regulating thyroid function by regulating iodine uptake. Oral or gut microbial dysbiosis can be considered as an early diagnosis factor or TC marker. High TSH during TC can increase the oral microbial diversity while disrupting the high ratio of Firmicutes and Bacteroidetes in the gut. Supplementation of probiotics as an adjuvant in TC treatment is beneficial. However, needs more extensive research to explore the direct effect of probiotics on thyroid function.

Assessment of the association between genetic factors regulating thyroid function and microvascular complications in diabetes: A two-sample Mendelian randomization study in the European population.

Observational studies have identified a possible link between thyroid function and diabetic microangiopathy, specifically in diabetic kidney disease (DKD) and diabetic retinopathy (DR). However, it is unclear whether this association reflects a causal relationship. To assess the potential direct effect of thyroid characteristics on DKD and DR based on Mendelian randomization (MR). We conducted an MR study using genetic variants as an instrument associated with thyroid function to examine the causal effects on DKD and DR. The study included the analysis of 4 exposure factors associated with thyroid hormone regulation and 5 outcomes. Genomewide significant variants were used as instruments for standardized freethyroxine (FT4) and thyroid-stimulating hormone (TSH) levels within the reference range, standardized free triiodothyronine (FT3):FT4 ratio, and standardized thyroid peroxidase antibody (TPOAB) levels. The primary outcomes were DKD and DR events, and secondary outcomes were estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR) in diabetes, and proliferative diabetic retinopathy (PDR). Satisfying the 3 MR core assumptions, the inverse-variance weighted technique was used as the primary analysis, and sensitivity analysis was performed using MR-Egger, weighted median, and MR pleiotropy residual sum and outlier techniques. All outcome and exposure instruments were selected from publicly available GWAS data conducted in European populations. In inverse-variance weighted random-effects MR, gene-based TSH with in the reference range was associated with DKD (OR 1.44; 95%CI 1.04, 2.41; P = 0.033) and eGFR (β: -0.031; 95%CI: -0.063, -0.001; P = 0.047). Gene-based increased FT3:FT4 ratio, decreased FT4 with in the reference range were associated with increased ACR with inverse-variance weighted random-effects β of 0.178 (95%CI: 0.004, 0.353; P = 0.046) and -0.078 (95%CI: -0.142, -0.014; P = 0.017), respectively, and robust to tests of horizontal pleiotropy. However, all thyroid hormone instruments were not associated with DR and PDR at the genetic level. In diabetic patients, an elevated TSH within the reference range was linked to a greater risk of DKD and decreased eGFR. Similarly, decreased FT4 and an increased FT3:FT4 ratio within the reference range were associated with increased ACR in diabetic patients. However, gene-based thyroid hormones were not associated with DR, indicating a possible pathway involving the thyroid-islet-renal axis. However, larger population studies are needed to further validate this conclusion.

Effects of Aloe vera on the Regulation of Thyroxine Release in FRTL-5 Thyroid Cells

To determine whether Aloe vera (AV), a traditional herbal medicine, could maintain homeostasis, we investigated its ability to regulate the production of hormones, particularly thyroid hormones. T4 ELISA assay with (6H media) and without thyrotropin (TSH) (5H media) showed that AV functions to maintain endocrine homeostasis. To understand the mechanisms by which AV regulates thyroxine release, we confirmed the protein expression of key upstream factors of thyroid hormone synthesis, such as phosphorylated extracellular signal-regulated kinase (ERK), phosphorylated cAMP response element binding protein (CREB), and phosphorylated protein kinase B (p-Akt). Although the protein expression of phosphorylated ERK and CREB were decreased in 6H media, they were increased and unchanged, respectively, in 5H media. However, protein expression of phosphorylated Akt was not changed by AV in both 6H and 5H media. Furthermore, inhibition of protein kinase A (PKA) by H89 eliminated AV-induced phosphorylation of ERK in 5H media. However, the inhibition of protein kinase C (PKC) by GF 109203X did not eliminate AV-induced ERK phosphorylation in 5H media. These results suggested that AV has TSH-like activity and could regulate thyroxine release through the TPO and PKA pathways. AV may regulate thyroid function to maintain a constant level of thyroid hormones in the body, and could be a candidate for thyroid disease therapies.

Influence of selenium deficiency on the development of thyroid disorders - a literature review

Introduction and purpose: Selenium is essential for the proper course of many physiological and biochemical processes in the human body. It plays a large role in ensuring proper immunoendocrine function. The organ with the greatest amount of selenium per gram of tissue is the thyroid gland. This element builds enzymes involved in antioxidant processes - peroxidase, as well as deiodinases involved in the metabolism of thyroid hormones. There are scientific reports showing a beneficial effect of selenium supplementation in autoimmune diseases of the thyroid gland. The aim of this study is to summarize the current knowledge on the relationship between selenium deficiency and the development of thyroid dysfunction. Description of the state of knowledge: There is a correlation between selenium deficiency and the functioning of the thyroid gland. It has been shown that selenium levels are often lowered in patients with autoimmune thyroiditis. Research shows that selenium supplementation may lower TPOAb and TgAb antibody levels in patients with Hashimoto's disease. In patients with Graves' orbitopathy, administration of selenium resulted in delayed progression of orbitopathy and less disease severity. There are reports that supplementation with this element may also increase the effectiveness of antithyroid drugs in patients with Graves-Basedow disease. There was also an association between selenium deficiency and the development of goiter and thyroid nodules. Conclusions: Selenium plays an important role in the proper functioning of the thyroid gland. Although the specific role of selenium in the pathogenesis of thyroid disease is still under investigation, there are numerous reports saying that its deficiency may affect it. More research is needed on the relationship between selenium concentration and the regulation of thyroid function, because introducing it into the treatment regimen of thyroid disorders may give hope for better therapeutic effects.

Sox9 is involved in the thyroid differentiation program and is regulated by crosstalk between TSH, TGF\u03b2 and thyroid transcription factors

While the signaling pathways and transcription factors involved in the differentiation of thyroid follicular cells, both in embryonic and adult life, are increasingly well understood, the underlying mechanisms and potential crosstalk between the thyroid transcription factors Nkx2.1, Foxe1 and Pax8 and inductive signals remain unclear. Here, we focused on the transcription factor Sox9, which is expressed in Nkx2.1-positive embryonic thyroid precursor cells and is maintained from embryonic development to adulthood, but its function and control are unknown. We show that two of the main signals regulating thyroid differentiation, TSH and TGFβ, modulate Sox9 expression. Specifically, TSH stimulates the cAMP/PKA pathway to transcriptionally upregulate Sox9 mRNA and protein expression, a mechanism that is mediated by the binding of CREB to a CRE site within the Sox9 promoter. Contrastingly, TGFβ signals through Smad proteins to inhibit TSH-induced Sox9 transcription. Our data also reveal that Sox9 transcription is regulated by the thyroid transcription factors, particularly Pax8. Interestingly, Sox9 significantly increased the transcriptional activation of Pax8 and Foxe1 promoters and, consequently, their expression, but had no effect on Nkx2.1. Our study establishes the involvement of Sox9 in thyroid follicular cell differentiation and broadens our understanding of transcription factor regulation of thyroid function.

Association between thyroid hormone levels and frailty in an older inpatient cohort: a cross-sectional study.

Frailty is a common biological syndrome in elderly people, and the aging process regulates thyroid function. The present study aimed to determine the prevalence of frailty in an older inpatient cohort using the FRAIL scale and to evaluate the association of frailty with thyroid hormone levels. This cross-sectional study was performed in the Department of Geriatrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China. From November 2019 to April 2020, 146 inpatients aged ≥65 years were recruited for the study and demographic data, frailty, geriatric assessment, and thyroid hormone levels were evaluated. Frailty was determined by the FRAIL scale, and geriatric assessment was based on activities of daily living (ADL) and instrumental activities of daily living (IADL). The data were analyzed using appropriate parametric and nonparametric statistical tests. At enrollment, 31 (21.23%) of the total participants were robust, 31 (21.23%) were pre-frail, and 84 (57.53%) were frail. The frail patients were significantly older than the robust patients and pre-frail patients (P<0.001 for both). The percentages of ADL disability differed significantly among the patients for frail versus robust, frail versus pre-frail, and pre-frail versus robust, as did the percentages of IADL disability among patients for frail versus robust and frail versus pre-frail (P<0.01 for all). In binary logistic regression analyses adjusted for age, sex, body mass index, HbA1c (%), and smoking, frailty was significantly associated with serum thyroid stimulating hormone (TSH) concentration [odds ratio (OR): 1.704], T3 concentration (OR: 0.102), ADL score (OR: 0.793), and IADL score (OR: 0.413). In our study population, the prevalence of frailty was higher in older geriatric inpatients in China than other studies. Inpatients with high TSH levels were at increased risk of frailty. Conduction of future longitudinal studies is warranted to determine the relationship between thyroid hormone levels and frailty.

Association Between Serum Nitric Oxide Level and Changes in Thyroid Function Test in a Population-based Study: Tehran Thyroid Study Participants (TTS).

BackgroundNitric oxide (NO) plays a key role in thyroid function regulation through the inhibition of iodide (I) uptake at the thyroidal sodium-iodide symporter (NIS) and impacts on the thyroid vascularity and blood flow.ObjectivesThis study aimed to evaluate the association between serum NO metabolites (NOx) and thyroid-stimulating hormone (TSH), free thyroxin (FT4), and anti-thyroid peroxidase (TPOAb) changes. Also, it aimed at evaluating the correlation between serum NOx and the incidence of clinical hypothyroidism, characterized by elevated TSH level and decreased FT4 concentration, and subclinical hypothyroidism, characterized by mildly elevated TSH level despite FT4 concentration within the normal range, over three years of follow-up.MethodsThis study included 1,137 participants of the Tehran Thyroid study (TTS), aged > 20 years old, for whom data on serum TSH, FT4, and TPOAb in the third and fourth phases, and serum NOx in the third phase were available. Changes in TSH (ΔTSH), FT4 (ΔFT4), and TPOAb (ΔTPO) between the third and fourth phases were calculated, and the associations between serum NOx and ΔTSH, ΔFT4, and ΔTPOAb were assessed after multivariable adjustment using linear regression analysis.ResultsNo significant association was found between serum NOx and ΔTSH, ΔFT4, and ΔTPOAb after the multivariable adjustment; neither was any observed in TPOAb split groups after multivariable adjustment. No significant association was found between serum NOx tertiles and clinical and subclinical hypothyroidism incidence in the fourth phase of TTS.ConclusionsThere was no association between serum NOx levels and changes in TSH, FT4, and TPOAb and clinical and subclinical hypothyroidism incidence.

Associations between artificial light at night and risk for thyroid cancer: A large US cohort study.

Light at night (LAN) inhibits nighttime secretion of melatonin and may cause circadian disruption, which may be a risk factor for cancer. Recent studies have linked high LAN exposure with elevated breast cancer risk. Given that breast cancer may share a common hormone-dependent etiology with thyroid cancer and that circadian rhythms play a role in regulating thyroid function, the authors hypothesized that exposure to LAN is positively associated with thyroid cancer incidence. This study examined the association between LAN and thyroid cancer incidence in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. LAN exposure was estimated from satellite data and was linked to residential addresses at the baseline. Incident thyroid cancer cases were ascertained via linkage to state cancer registries. Cox regression was used to determine the relationship between LAN and thyroid cancer risk, with adjustments made for sociodemographic, lifestyle, and other environmental factors. Among 464,371 participants, a positive association was found between LAN and thyroid cancer risk. Specifically, in comparison with the lowest quintile of LAN, the highest quintile was associated with a 55% increase in risk (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.18-2.02). The association was primarily driven by papillary thyroid cancer and was stronger in women (HR, 1.81; 95% CI, 1.26-2.60) than men (HR, 1.29; 95% CI, 0.86-1.94). In women, the association was stronger for localized cancer, whereas in men, the association was stronger for a more advanced stage. Results were consistent across different tumor sizes. LAN was positively associated with thyroid cancer risk. Future studies are needed to confirm this association and identify underlying biological mechanisms.

17β-Estradiol activates Cl− channels via the estrogen receptor α pathway in human thyroid cells

ABSTRACT Estradiol regulates thyroid function, and chloride channels are involved in the regulation of thyroid function. However, little is known about the role of chloride channels in the regulation of thyroid functions by estrogen. In this study, the effects of estrogen on chloride channel activities in human thyroid Nthy-ori3-1 cells were therefore investigated using the whole cell patch-clamp technique. The results showed that the extracellular application of 17β-estradiol (E2) activated Cl− currents, which reversed at a potential close to Cl− equilibrium potential and showed remarkable outward rectification and an anion permeability of I− > Br− > Cl− > gluconate. The Cl− currents were inhibited by the chloride channel blockers, NPPB and tamoxifen. Quantitative Real-time PCR results demonstrated that ClC-3 expression was highest in ClC family member in Nthy-ori3-1 cells. The down-regulation of ClC-3 expression by ClC-3 siRNA inhibited E2-induced Cl− current. The Cl− current was blocked by the estrogen receptor antagonist, ICI 182780 (fulvestrant). Estrogen receptor alpha (ERα) and not estrogen receptor beta was the protein expressed in Nthy-ori3-1 cells, and the knockdown of ERα expression with ERα siRNA abolished E2-induced Cl− currents. Estradiol can promote the accumulation of ClC-3 in cell membrane. ERα and ClC-3 proteins were partially co-localized in the cell membrane of Nthy-ori3-1 cells after estrogen exposure. The results suggest that estrogen activates chloride channels via ERα in normal human thyroid cells, and ClC-3 proteins play a pivotal role in the activation of E2-induced Cl− current.

Associations between maternal thyroid function in pregnancy and child neurodevelopmental outcomes at 20 months in the Seychelles Child Development Study, Nutrition Cohort 2 (SCDS NC2).

Maternal thyroid hormones facilitate optimal foetal neurodevelopment; however, the exact role of the thyroid hormones on specific cognitive outcomes is unknown. The present study aimed to investigate associations between maternal thyroid function and neurodevelopmental outcomes in the Seychelles Child Development Study (SCDS) Nutrition 2 cohort (n 1328). Maternal free thyroid hormones (fT3, fT4 and fTSH) were assessed at 28 weeks' gestation with a range of child cognitive outcomes analysed at 20 months. Dietary iodine intake was analysed for a subset of women through a Food Frequency Questionnaire. Linear regression analysis was used to test associations between serum concentrations of maternal thyroid hormones and child neurodevelopment outcomes. Thyroid hormones were analysed as continuous data and categorised as quintiles. 95% of mothers had optimal thyroid function based on fTSH concentrations. Overall, the present study shows that maternal thyroid function is not associated with neurodevelopmental outcomes in this high fish-eating population. However, a positive association, using quintiles for fT3, was reported for the Mental Developmental Index, between Q3 v. Q4 (β 0⋅073; P 0⋅043) and for Q3 v. Q5 (β value 0⋅086; P 0⋅018). To conclude, mothers in our cohort, who largely have optimal thyroid function and iodine intakes, appear able to regulate thyroid function throughout pregnancy to meet neurodevelopmental needs. However, it is possible that minor imbalances of fT3, as indicated from our secondary analysis, may impact offspring neurodevelopment. Further investigation of the relationship between maternal thyroid function and infant neurodevelopment is warranted, particularly in populations with different dietary patterns and thereby iodine intakes.

Expression of Caveolin-1 Is Associated With Thyroid Function in Patients With Human Papillary Thyroid Carcinoma.

Objective:The aim of this study was to evaluate the levels of caveolin-1 in thyroid follicular epithelial cells of papillary thyroid cancer, follicular thyroid cancer, and nonmalignant thyroid nodule benign follicular adenoma, as well as to explore the relationship between the levels of caveolin-1 and thyroid function.Methods:Thirty cases of papillary thyroid cancer, 10 cases of follicular thyroid cancer, 32 cases of nonmalignant thyroid nodule benign follicular adenoma, and 30 controls were enrolled in this study. Caveolin-1 expression in tissue specimens obtained from these cases was evaluated by immunohistochemistry and Western blotting.Results:Caveolin-1 expression in thyroid epithelial cells of patients with papillary thyroid cancer, particularly female patients, was significantly higher than that in patients with follicular thyroid cancer and nonmalignant thyroid nodule benign follicular adenoma (P < .005). Serum thyroid-stimulating hormone (TSH) levels in the caveolin-1-positive expression group were lower than that in the caveolin-1-negative expression group, and the lowest expression of caveolin-1 was detected in tissues of patients with Graves’ disease. The serum TSH level was associated with caveolin-1 expression in thyroid epithelial cells.Conclusion:Caveolin-1 may participate in regulating thyroid function and is a potential biomarker of follicular thyroid cancer.

Expression of thyroglobulin by regulatory T cells in thyroid tissue.

The follicles are the minimal functional unit of the thyroid; the morphology and the function of each follicle can vary significantly. However, the reasons for the apparent follicular heterogeneity are poorly understood. Some tissue-resident regulatory T cells (Tregs) have a special phenotype that expresses unique molecules related to local tissue and regulates the tissue functions. The aim of this study was to identify the phenotype of thyroid Tregs and the roles of thyroid Tregs in thyroid physiological regulation. Thyroid tissue and peripheral blood samples were obtained from patients with benign thyroid nodules. Microarray-based gene expression, flow cytometry, immunofluorescence microscopy, and functional analysis of thyroid Tregs were performed. Here, we demonstrated that human thyroid Tregs expressed high level of thyroglobulin (Tg), both gene and protein. The immunofluorescence microscopy of thyroid section showed that the FOXP3+Tg+ cells concentrated in some of the thyroid follicles, at the side of the thyroid follicle. The peripheral blood Tregs expressed minimal levels of Tg, and low levels of Tg could effectively induce peripheral blood Tregs to express Tg, which was independent of thyrotropin simulation. Furthermore, the Tg secreted freely from thyroid Tregs that negatively regulated some thyroid-related genes expression. Our results revealed that the thyroid Tregs was a distinct population of Tregs, which expressed high level of Tg. The thyroid Tregs regulate thyroid function by Tg that is paracrine from the cells.

Regulation of thyroid function by autonomic reflex

Regulation of thyroid function by autonomic reflex

Short Call Abstracts

Short Call Abstracts

Iodine consumption and cognitive performance: Confirmation of adequate consumption.

Iodine, a dynamic nutrient present in thyroid hormones, is responsible for regulating thyroid function, supporting a healthy metabolism, and aiding growth and development. Iodine is also essential for brain development during specific time windows influencing neurogenesis, neuronal and glial cell differentiation, myelination, neuronal migration, and synaptogenesis. About 1.5 billion people in 130 countries live in areas at risk of iron deficiencies (IDs). Reduced mental ability due to IDs occurs in almost 300 million people. Ensuring the consumption of minimum recommended daily allowances of iodine remains challenging. The effects of ID disorders range from high mortality of fetuses and children to inhibited mental development (cretinism). Poor socioeconomic development and impaired school performance are also notable. Currently, ID disorders are the single greatest contributor to preventable brain damage in fetuses and infants and arrested psychomotor development in children. Iodized salt may help fulfill iodine requirements. Increases in food salt iodization programs can help overcome ID disorders. Dietary plans can be well adjusted to incorporate iodinated foods. Maternal iodine supplementation for offspring requires adequate attention. Fruits, vegetables, bread, eggs, legumes (beans and peas), nuts, seeds, seafood, lean meats and poultry, and soy products provide small quantities of iodine. Nutrient‐dense foods containing essential vitamins and minerals such as iodine may confer positive effects. To some extent, fortified foods and daily dietary supplements can be provided for different nutrients including iodine; otherwise, iodine may be consumed in less than the recommended amounts. This review focuses on aspects of adequate iodine consumption to avoid cognitive impairments.

Intravenous and Intratracheal Thyrotropin Releasing Hormone and Its Analog Taltirelin Reverse Opioid-Induced Respiratory Depression in Isoflurane Anesthetized Rats.

Thyrotropin releasing hormone (TRH) is a tripeptide hormone and a neurotransmitter widely expressed in the central nervous system that regulates thyroid function and maintains physiologic homeostasis. Following injection in rodents, TRH has multiple effects including increased blood pressure and breathing. We tested the hypothesis that TRH and its long-acting analog, taltirelin, will reverse morphine-induced respiratory depression in anesthetized rats following intravenous or intratracheal (IT) administration. TRH (1 mg/kg plus 5 mg/kg/h, i.v.) and talitrelin (1 mg/kg, i.v.), when administered to rats pretreated with morphine (5 mg/kg, i.v.), increased ventilation from 50% ± 6% to 131% ± 7% and 45% ± 6% to 168% ± 13%, respectively (percent baseline; n = 4 ± S.E.M.), primarily through increased breathing rates (from 76% ± 9% to 260% ± 14% and 66% ± 8% to 318% ± 37%, respectively). By arterial blood gas analysis, morphine caused a hypoxemic respiratory acidosis with decreased oxygen and increased carbon dioxide pressures. TRH decreased morphine effects on arterial carbon dioxide pressure, but failed to impact oxygenation; taltirelin reversed morphine effects on both arterial carbon dioxide and oxygen. Both TRH and talirelin increased mean arterial blood pressure in morphine-treated rats (from 68% ± 5% to 126% ± 12% and 64% ± 7% to 116% ± 8%, respectively; n = 3 to 4). TRH, when initiated prior to morphine (15 mg/kg, i.v.), prevented morphine-induced changes in ventilation; and TRH (2 mg/kg, i.v.) rescued all four rats treated with a lethal dose of morphine (5 mg/kg/min, until apnea). Similar to intravenous administration, both TRH (5 mg/kg, IT) and taltirelin (2 mg/kg, IT) reversed morphine effects on ventilation. TRH or taltirelin may have clinical utility as an intravenous or inhaled agent to antagonize opioid-induced cardiorespiratory depression.