scholarly journals Could Glyphosate and Glyphosate-Based Herbicides Be Associated With Increased Thyroid Diseases Worldwide?

2021 ◽  
Vol 12 ◽  
Author(s):  
Renata Marino Romano ◽  
Jeane Maria de Oliveira ◽  
Viviane Matoso de Oliveira ◽  
Isabela Medeiros de Oliveira ◽  
Yohandra Reyes Torres ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Thyroid Function ◽  
Molecular Mechanisms ◽  
Atp Synthesis ◽  
Feedback Mechanism ◽  
Thyroid Diseases ◽  
Environmental Chemicals ◽  
Health Concern ◽  
High Exposure ◽  
Hpt Axis

The increased incidence of thyroid diseases raises a series of questions about what the main predisposing factors are nowadays. If dietary restriction of iodine was once a major global health concern, today, the processes of industrialization of food and high exposure to a wide variety of environmental chemicals may be affecting, directly or indirectly, thyroid function. The homeostasis of hypothalamus–pituitary–thyroid (HPT) axis is finely regulated through the negative feedback mechanism exerted by thyroid hormones. Allostatic mechanisms are triggered to adjust the physiology of HPT axis in chronic conditions. Glyphosate and glyphosate-based herbicides are pesticides with controversial endocrine disrupting activities and only few studies have approached their effects on HPT axis and thyroid function. However, glyphosate has an electrophilic and nucleophilic zwitterion chemical structure that may affect the mechanisms involved in iodide oxidation and organification, as well as the oxidative phosphorylation in the ATP synthesis. Thus, in this review, we aimed to: (1) discuss the critical points in the regulation of HPT axis and thyroid hormones levels balance, which may be susceptible to the toxic action of glyphosate and glyphosate-based herbicides, correlating the molecular mechanisms involved in glyphosate toxicity described in the literature that may, directly or indirectly, be associated to the higher incidence of thyroid diseases; and (2) present the literature regarding glyphosate toxicity in HPT axis.

scholarly journals Modern problems of thyroidology

2019 ◽  
Vol 45 (1) ◽  
pp. 3-8 ◽  
Author(s):  
V. I. Kandror
Keyword(s):  
Thyroid Hormones ◽  
Molecular Mechanisms ◽  
Thyroid Diseases ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Endocrine Diseases

Modern reports about molecular mechanisms of the effects of thyroid hormones and the pathogenesis of autoimmune thyroid diseases are reviewed. The significance of fundamental studies in thyroidology for deciphering the pathogenesis of the most prevalent endocrine and other than endocrine diseases is emphasized.

scholarly journals SAT-449 Factors Associated with Reduced Thyroid Hormones in Cushing Syndrome Patients Before and After Surgical Cure

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Skand Shekhar ◽  
Raven McGlotten ◽  
Lynnette K Nieman
Keyword(s):  
Thyroid Hormones ◽  
Thyroid Function ◽  
Cushing Syndrome ◽  
Hormone Secretion ◽  
Free T4 ◽  
Curative Surgery ◽  
Duration Of Symptoms ◽  
Free Cortisol ◽  
Hpt Axis ◽  
Pearson Correlations

Abstract Background: Hypercortisolemia adversely affects thyroid hormone secretion. We previously described the temporal pattern of thyroid function recovery in 23 patients (1). However, the factors leading to suppression and recovery of the hypothalamic-pituitary-thyroid (HPT) axis in Cushing’s syndrome (CS) are not fully understood. We performed two separate studies to investigate these factors. Methods: In study 1, we examined patients (pts, n=62) with CS who underwent curative surgery and recorded their serum morning and evening cortisol, ACTH, tumor volume and duration of symptoms and 24-hour urine free cortisol (UFC) at baseline and the morning serum free T4, TSH and T3 at six-month intervals after cure. Data were log-transformed and Pearson correlations were performed. Linear mixed models were used to study factors that predict recovery of thyroid function. In study 2, we examined the diurnal variation of TSH by performing hourly TSH measurement between 3—7 PM and 12—4 AM on a cohort of pts (n=45) before surgery. Wilcoxon Signed-Rank method was used for comparisons of mean TSH across time and Pearson correlations were performed on log-transformed data. P values <.05 were considered significant. Results: Study 1: In this larger cohort, we confirmed previous findings of suppressed or low normal fT4 and TSH values with active hypercortisolism, with normalization after cure that reflected changes in the T3:TSH, fT4:TSH and T3:fT4 ratios. There were inverse linear correlations between log10 UFC, serum AM and PM cortisol; and log10 TT3, fT4 and TSH before surgery. Independent negative prognosticators of circulating fT4 recovery included UFC greater than 1000mcg/day (nl: 3.5—45mcg/day), duration of symptoms of less than one year, and ACTH levels greater than 60pg/mL(nl: 5—45pg/mL) Study 2: The nocturnal (12 - 4AM) TSH surge was reduced, so that the difference in day and night TSH values was not statistically significant; this contrasts with the 30—50% nocturnal TSH increase above daytime values seen in healthy subjects. There was an inverse relationship between UFC and nocturnal TSH, daytime TSH and TBG values, but there was no direct relationship between UFC and percent changes in nocturnal TSH values. Conclusions: Our findings suggest that a deficit in TSH stimulation of the thyroid gland may explain the reduction in T3 and T4 levels. There is a dose-response relationship between various measures of hypercortisolemia and both thyroid hormones and the pattern of TSH secretion. Finally, the severity of hypercortisolism correlates with a longer time to recovery of the HPT axis in pts with CS after curative surgery. 1. Shekhar S et al. HPG and HPT Axes in Cushing Syndrome. J Endocr Soc, 3 S1, April May 2019

High resolution mapping of nucleic acid containing complexes in vitro and in situ

1996 ◽  
Vol 54 ◽  
pp. 48-49
Author(s):  
D. P. Bazett-Jones ◽  
M. J. Hendzel
Keyword(s):  
Nucleic Acid ◽  
High Resolution ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Heavy Atom ◽  
Regulation Of Transcription ◽  
High Exposure ◽  
Resolution Mapping ◽  
Tata Sequence

Structural analysis of combinations of nucleosomes and transcription factors on promoter and enhancer elements is necessary in order to understand the molecular mechanisms responsible for the regulation of transcription initiation. Such complexes are often not amenable to study by high resolution crystallographic techniques. We have been applying electron spectroscopic imaging (ESI) to specific problems in molecular biology related to transcription regulation. There are several advantages that this technique offers in studies of nucleoprotein complexes. First, an intermediate level of spatial resolution can be achieved because heavy atom contrast agents are not necessary. Second, mass and stoichiometric relationships of protein and nucleic acid can be estimated by phosphorus detection, an element in much higher proportions in nucleic acid than protein. Third, wrapping or bending of the DNA by the protein constituents can be observed by phosphorus mapping of the complexes. Even when ESI is used with high exposure of electrons to the specimen, important macromolecular information may be provided. For example, an image of the TATA binding protein (TBP) bound to DNA is shown in the Figure (top panel). It can be seen that the protein distorts the DNA away from itself and much of its mass sits off the DNA helix axis. Moreover, phosphorus and mass estimates demonstrate whether one or two TBP molecules interact with this particular promoter TATA sequence.

THYROID DYSFUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: THE STATE OF THE PROBLEM AND THE WAYS OF SOLVING

2018 ◽  
Vol 22 (4) ◽  
pp. 40-49 ◽  
Author(s):  
A. R. Volkova ◽  
O. D. Dygun ◽  
B. G. Lukichev ◽  
S. V. Dora ◽  
O. V. Galkina
Keyword(s):  
Chronic Kidney Disease ◽  
Thyroid Gland ◽  
Kidney Disease ◽  
Thyroid Hormones ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
The Body ◽  
Type I ◽  
Low T3 ◽  
Iodine Excretion

Disturbance of the thyroid function is often detected in patients with different profiles. A special feature of patients with chronic kidney  disease is the higher incidence of various thyroid function  disturbances, especially hypothyroidism. It is known that in patients  with chronic kidney disease (CKD) iodine excretion from the body is  violated, since normally 90% of iodine is excreted in urine.  Accumulation of high concentrations of inorganic iodine leads to the  formation of the Wolf-Chaikoff effect: suppression of iodine  organization in the thyroid gland and disruption of the thyroid  hormones synthesis. Peripheral metabolism of thyroid hormones is  also disturbed, namely, deiodinase type I activity is suppressed and  peripheral conversion of T4 into T3 is inhibited (so-called low T3  syndrome). Therefore, patients with CKD are often diagnosed with  hypothyroidism, and the origin of hypothyroidism is not always  associated with the outcome of autoimmune thyroiditis. The article  presents an overview of a large number of population studies of  thyroid gland dysfunction in patients with CKD, as well as  experimental data specifying the pathogenetic mechanisms of  thyroid dysfunction in patients with CKD. Therapeutic tactics are still  not regulated. However, in a number of studies, replacement therapy with thyroid hormones in patients with CKD had some advantages.

scholarly journals Regulation of Store-Operated Ca2+ Entry by SARAF

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1887
Author(s):  
Inbal Dagan ◽  
Raz Palty
Keyword(s):  
Molecular Mechanisms ◽  
Feedback Mechanism ◽  
Cellular Biology ◽  
Excitable Cells ◽  
Major Pathway ◽  
Negative Feedback Mechanism ◽  
Crac Channels ◽  
Dependent Inactivation ◽  
Crac Channel ◽  
The One

Calcium (Ca2+) signaling plays a dichotomous role in cellular biology, controlling cell survival and proliferation on the one hand and cellular toxicity and cell death on the other. Store-operated Ca2+ entry (SOCE) by CRAC channels represents a major pathway for Ca2+ entry in non-excitable cells. The CRAC channel has two key components, the endoplasmic reticulum Ca2+ sensor stromal interaction molecule (STIM) and the plasma-membrane Ca2+ channel Orai. Physical coupling between STIM and Orai opens the CRAC channel and the resulting Ca2+ flux is regulated by a negative feedback mechanism of slow Ca2+ dependent inactivation (SCDI). The identification of the SOCE-associated regulatory factor (SARAF) and investigations of its role in SCDI have led to new functional and molecular insights into how SOCE is controlled. In this review, we provide an overview of the functional and molecular mechanisms underlying SCDI and discuss how the interaction between SARAF, STIM1, and Orai1 shapes Ca2+ signaling in cells.

scholarly journals Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3651
Author(s):  
Alexandru Blidisel ◽  
Iasmina Marcovici ◽  
Dorina Coricovac ◽  
Florin Hut ◽  
Cristina Adriana Dehelean ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Prediction Models ◽  
3D Models ◽  
Experimental Models ◽  
Health Concern ◽  
Liver Carcinoma ◽  
Tumor Type

Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

Thyroid hormones regulate phosphate homoeostasis through transcriptional control of the renal type IIa sodium-dependent phosphate co-transporter (Npt2a) gene

2010 ◽  
Vol 427 (1) ◽  
pp. 161-169 ◽  
Author(s):  
Mariko Ishiguro ◽  
Hironori Yamamoto ◽  
Masashi Masuda ◽  
Mina Kozai ◽  
Yuichiro Takei ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Critical Role ◽  
Serum Phosphate ◽  
Luciferase Assay ◽  
Mobility Shift ◽  
Intron 1 ◽  
Sodium Dependent

The type IIa renal sodium-dependent phosphate (Na/Pi) co-transporter Npt2a is implicated in the control of serum phosphate levels. It has been demonstrated previously that renal Npt2a protein and its mRNA expression are both up-regulated by the thyroid hormone T3 (3,3′,5-tri-iodothyronine) in rats. However, it has never been established whether the induction was mediated by a direct effect of thyroid hormones on the Npt2a promoter. To address the role of Npt2a in T3-dependent regulation of phosphate homoeostasis and to identify the molecular mechanisms by which thyroid hormones modulate Npt2a gene expression, mice were rendered pharmacologically hypo- and hyper-thyroid. Hypothyroid mice showed low levels of serum phosphate and a marked decrease in renal Npt2a protein abundance. Importantly, we also showed that Npt2a-deficient mice had impaired serum phosphate responsiveness to T3 compared with wild-type mice. Promoter analysis with a luciferase assay revealed that the transcriptional activity of a reporter gene containing the Npt2a promoter and intron 1 was dependent upon TRs (thyroid hormone receptors) and specifically increased by T3 in renal cells. Deletion analysis and EMSAs (electrophoretic mobility-shift assays) determined that there were unique TREs (thyroid-hormone-responsive elements) within intron 1 of the Npt2a gene. These results suggest that Npt2a plays a critical role as a T3-target gene, to control phosphate homoeostasis, and that T3 transcriptionally activates the Npt2a gene via TRs in a renal cell-specific manner.

scholarly journals MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3026
Author(s):  
Hyuk Moon ◽  
Simon-Weonsang Ro
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Erk Signaling ◽  
Health Concern ◽  
Alternative Mechanism ◽  
Major Health ◽  
Activating Mutations ◽  
Genetic Events

Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence is increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic and clinical researchers. The MAPK/ERK signaling pathway is activated in more than 50% of human HCC cases; however, activating mutations in RAS and RAF genes are rarely found in HCC, which are major genetic events leading to the activation of the MAPK/ERK signaling pathway in other cancers. This suggests that there is an alternative mechanism behind the activation of the signaling pathway in HCC. Here, we will review recent advances in understanding the cellular and molecular mechanisms involved in the activation of the MAPK/ERK signaling pathway and discuss potential therapeutic strategies targeting the signaling pathway in the context of HCC.

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