The neural cell adhesion molecule NrCAM regulates development of hypothalamic tanycytes

Hypothalamic tanycytes are neural stem and progenitor cells, but little is known of how they are regulated. Here we provide evidence that the cell adhesion molecule, NrCAM, regulates tanycytes in the adult niche. NrCAM is strongly expressed in adult mouse tanycytes. Immunohistochemical and in situ hybridization analysis revealed that NrCAM loss of function leads to both a reduced number of tanycytes and reduced expression of tanycyte-specific cell markers, along with a small reduction in tyrosine hydroxylase-positive arcuate neurons. Similar analyses of NrCAM mutants at E16 identify few changes in gene expression or cell composition, indicating that NrCAM regulates tanycytes, rather than early embryonic hypothalamic development. Neurosphere and organotypic assays support the idea that NrCAM governs cellular homeostasis. Single-cell RNA sequencing (scRNA-Seq) shows that tanycyte-specific genes, including a number that are implicated in thyroid hormone metabolism, show reduced expression in the mutant mouse. However, the mild tanycyte depletion and loss of markers observed in NrCAM-deficient mice were associated with only a subtle metabolic phenotype.

Mitochondrial And Myogenic Gene Expression Pathways Are Influenced By The Exercise Mimetic Formoterol In Human Myotubes

Background: Exercise is an effective treatment for establishing and maintaining skeletal muscle (SKM) health. The interconnected cascade of gene expression pathways related to myogenesis, mitochondrial homeostasis, and thyroid hormone metabolism are critical to SKM health. This in vitro study was conducted to investigate the effects of exercise mimetic (formoterol) stimulation on human SKM cell signaling during myogenesis, and to provide insight on potential targets for future studies exploring therapies for SKM atrophy.Methods: Human myoblasts were cultured and differentiated to evaluate the effects of exercise mimetic stimulation on gene expression during mid and late myogenesis. We characterized the expression of 24 genes related to myogenesis, mitochondrial biogenesis, thyroid hormone metabolism, and cellular homeostasis.Results: Formoterol stimulated the gene expression for SKM pathways related to mitochondrial biogenesis, thyroid metabolism, and cellular homeostasis. Additionally, formoterol resulted in a myogenic program that appears to favor prolonged myoblast proliferation and delayed myotube maturation.Conclusion: Robust, yet differential effects of exercise mimetic stimulation on gene expression during mid-myogenesis and at terminal differentiation were found. The results of our study support the groundwork for establishing further experiments utilizing exercise signaling as a therapeutic treatment in models targeting dysfunctional SKM cell growth.

Pharmacological properties of selenium and its preparations: from antioxidant to neuroprotector

Selenium is an essential component of more than two dozen enzymes and other selenoproteins that play critical roles in reproduction, DNA synthesis, thyroid hormone metabolism, and protection from oxidative damage and infection. Selenium has a protective action against some forms of cancer and cardiovascular diseases, modulates levels of inflammatory mediators, promotes to maintain bone homeostasis and protects against bone loss. Selenium significance as a cardioprotective agent may be associated not only with its antioxidant properties, but also with its ability to prevent inflammation, autophagy, as well as the intrinsic and extrinsic apoptosis pathways. Signaling pathways, such as p-AMPK, PARP, Nrf2, STAT, are involved in the protective effects of selenium. Selenium protects against cardiovascular damage by increasing the survival rate of cardiomyocytes, including a mitochondria-dependent pathway and autophagy through peroxisome proliferator-activated receptors. Research demonstrating neuroprotective and cardioprotective effects of selenium preparations – selenoline, selenocysteine and selenomethionine – is growing at a rapid rate. It has been established that these compounds are able to normalize the levels of heat shock proteins (HSP70), which limit the cytotoxic effects of free radicals, produce energotropic action, prevent a decrease in the membrane mitochondria charge, and the opening of the mitochondrial pore. Also regulate the expression of transmembrane factors NF-kB, c-fos, which is associated with their main biological function of chaperone proteins, providing protection of neurons from damage. In this review, we want to emphasize pharmacological role of Selenium and its derivatives on human health is very complex and has yet to be fully understood.

Thyroid

This chapter covers the anatomy and physiology of the thyroid, and the molecular action of the thyroid hormone. It explains tests of hormone concentration and homeostatic control, and rare genetic disorders associated with thyroid hormone metabolism. It covers antibody screens and screening for thyroid disease, ultrasound scanning, fine needle aspiration cytology, computed tomography, positron emission tomography, and other laboratory investigations. It then covers various thyroid-associated diseases, their treatment (medical and surgical when necessary), and any follow-up management programmes.

The Impact of Selenium Deficiency on Cardiovascular Function

Selenium (Se) is an essential trace element that is necessary for various metabolic processes, including protection against oxidative stress, and proper cardiovascular function. The role of Se in cardiovascular health is generally agreed upon to be essential yet not much has been defined in terms of specific functions. Se deficiency was first associated with Keshan’s Disease, an endemic disease characterized by cardiomyopathy and heart failure. Since then, Se deficiency has been associated with multiple cardiovascular diseases, including myocardial infarction, heart failure, coronary heart disease, and atherosclerosis. Se, through its incorporation into selenoproteins, is vital to maintain optimal cardiovascular health, as selenoproteins are involved in numerous crucial processes, including oxidative stress, redox regulation, thyroid hormone metabolism, and calcium flux, and inadequate Se may disrupt these processes. The present review aims to highlight the importance of Se in cardiovascular health, provide updated information on specific selenoproteins that are prominent for proper cardiovascular function, including how these proteins interact with microRNAs, and discuss the possibility of Se as a potential complemental therapy for prevention or treatment of cardiovascular disease.

Effect of Micronutrients on Thyroid Parameters

Micronutrients are involved in various vital cellular metabolic processes including thyroid hormone metabolism. This study aimed to investigate the correlation between serum levels of micronutrients and their effects on thyroid parameters. The correlation of serum levels of micronutrients and thyroid markers was studied in a group of 387 healthy individuals tested for thyroid markers (T4, T3, FT4, FT3, TSH, anti-TPO, RT3, and anti-Tg) and their micronutrient profile at Vibrant America Clinical Laboratory. The subjects were rationalized into three groups (deficient, normal, or excess levels of micronutrients), and the levels of their thyroid markers were compared. According to our results, deficiency of vitamin B2, B12, and B9 and Vit-D25[OH] ( p < 0.05 ) significantly affected thyroid functioning. Other elemental micronutrients such as calcium, copper, choline, iron, and zinc ( p < 0.05 ) have a significant correlation with serum levels of free T3. Amino acids asparagine (r = 0.1765, p < 0.001 ) and serine (r = 0.1186, p < 0.05 ) were found to have a strong positive correlation with TSH. Valine, leucine, and arginine ( p < 0.05 ) also exhibited a significant positive correlation with serum levels of T4 and FT4. No other significant correlations were observed with other micronutrients. Our study suggests strong evidence for the association of the levels of micronutrients with thyroid markers with a special note on the effect of serum levels of certain amino acids.

THYROID DISORDER AND HYPERTENSION

Arterial hypertension represents a major global health concern; more than one fourth of the population is affected by high blood pressure. Albeit the underlying cause of the disease remains unclear in the vast majority of the cases, ~10% are of secondary origin. Endocrine disorders are common illnesses and some of them may lead to elevated blood pressure, among which thyroid diseases are of high prevalence and often overlooked, especially in mild cases. Overt and subclinical hyper- and hypothyroidism can both lead to (mostly mild) hypertension; however, the underlying mechanisms are only partially understood. The results of clinical studies are often controversial. During the past decades, some genetic mutations in the hypothalamus-pituitary-thyroid axis with cardiovascular consequences were revealed. Atherosclerotic changes resulting from lipid abnormalities due to thyroid dysfunction also affect the vasculature and can cause elevated blood pressure. The review gives a synopsis of our knowledge how thyroid hormone metabolism and functional thyroid diseases affect the cardiovascular system, their negative impact and causative role in the development of hypertension.

Molecular cloning and characterization of common marmoset SULT1C subfamily members that catalyze the sulfation of thyroid hormones

Cytosolic sulfotransferase SULT1C subfamily is one of the most flexible gene subfamily during mammalian evolution. The physiological functions of SULT1C enzymes still remain to be fully understood. In this study, common marmoset (Callithrix jacchus), a promising primate animal model, was used to investigate the functional relevance of the SULT1C subfamily. Gene database search revealed three intact SULT1C genes and a pseudogene in its genome. These four genes were named SULT1C1, SULT1C2, SULT1C3P, and SULT1C5, according to the sequence homology and gene location. Since SULT1C5 is the orthologous gene for human SULT1C2P, we propose, here, to revisit the designation of human SULT1C2P to SULT1C5P. Purified recombinant SULT1C enzymes showed sulfating activities toward a variety of xenobiotic compounds and thyroid hormones. Kinetic analysis revealed high catalytic activities of SULT1C1 and SULT1C5 for 3,3’-T2. It appears therefore that SULT1C isoforms may play a role in the thyroid hormone metabolism in common marmoset.

Liver Proteome Profile of Growth Restricted and Appropriately Grown Newborn Wistar Rats Associated With Maternal Undernutrition

BackgroundFetal growth restriction (FGR) has been associated with adverse perinatal outcomes and epigenetic modifications that impact gene expression leading to permanent changes of fetal metabolic pathways and thereby influence development of disease in childhood and adult life. In this study, we investigated the result of maternal food restriction on liver protein expression in Wistar male newborn pups.Materials &amp; MethodsTen (n = 10) timed pregnant Wistar rats on their 14th day of gestation were randomly assigned to either control (n = 4) or food restricted group (n = 6). The control group had ad libitum access to food. In the food restricted group, maternal diet was limited in a moderate fashion (50%) from day 15 of pregnancy until delivery. All rats delivered spontaneously on day 21 and newborn pups were immediately weighed. Pups born to normally nourished mothers were considered as controls, while pups born to food restricted mothers were subdivided into two groups, based on their birth weight: growth restricted (FGR) and appropriately grown (non-FGR). Rats were euthanized immediately after birth and liver tissues of 11 randomly selected male offspring (FGR n = 4, non-FGR n = 4, control n = 3) were collected and analyzed using quantitative proteomics.ResultsIn total 6,665 proteins were profiled. Of these, 451 and 751 were differentially expressed in FGR and non-FGR vs. control, respectively, whereas 229 proteins were commonly expressed. Bioinformatics analysis of the differentially expressed proteins (DEPs) in FGR vs. control revealed induction of the super-pathway of cholesterol biosynthesis and inhibition of thyroid hormone metabolism, fatty acid beta oxidation and apelin liver signaling pathway. Analysis of DEPs in non-FGR vs. control groups showed inhibition of thyroid hormone metabolism, fatty acid beta oxidation, and apelin liver signaling pathway.ConclusionThis study demonstrates the impact of prenatal food restriction on the proteomic liver profile of FGR and non-FGR offspring underlying the importance of both prenatal adversities and birth weight on liver-dependent postnatal disease.