-
1.
PKM2, a potential target for regulating cancer.
Li, YH, Li, XF, Liu, JT, Wang, H, Fan, LL, Li, J, Sun, GP
Gene. 2018;:48-53
Abstract
Aberrated glucose metabolism is a key future of cancer cells. Unlike normal cells, tumor cells favor glycolysis even in the presence of sufficient oxygen. Pyruvate kinase (PK), a key glucose metabolic enzyme, converts phosphoenolpyruvate (PEP) to pyruvate by transferring the high-energy phosphate group to adenosine diphosphate (ADP) to produce adenosine triphosphate (ATP). Pyruvate kinase M2 (PKM2), one of the four isozyme of PK, which universally expressed in rapidly proliferating cells such as embryonic cells and cancer cells. Recent years, more and more research suggested PKM2 plays a crucial role in cancer progression through both metabolic and non-metabolic pathways. On the one hand, the middle product of glycolysis, such as amino acids, nucleotides, lipids is necessary to rapid growth of cancer cells. On the other hand, PKM2 supports tumor growth through regulating the expression of gene that involved in cell proliferation, migration and apoptosis. In this article, we review the recent advances to further understand the regulation and function of PKM2 in tumorigenesis. Given its multiple effects on cancer, PKM2 may be a potential target for cancer diagnosis and treatment.
-
2.
Micronutrients, iodine status and concentrations of thyroid hormones: a systematic review.
O'Kane, SM, Mulhern, MS, Pourshahidi, LK, Strain, JJ, Yeates, AJ
Nutrition reviews. 2018;(6):418-431
Abstract
CONTEXT The metabolism of thyroid hormones, which are essential for normal development, involves many proteins and enzymes. It requires iodine as a key component but is also influenced by several other micronutrients, including selenium, zinc, iron, and vitamin A. OBJECTIVE This systematic review was designed to investigate the effect of micronutrient status and supplementation on iodine status and thyroid hormone concentrations. DATA SOURCES Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, electronic databases were searched from their inception to April 2016. STUDY SELECTION Human studies published in English and reporting data on micronutrient status and iodine status and/or thyroid hormone concentrations were included. Studies that examined the effect of micronutrient supplementation on iodine status and/or thyroid hormone concentrations were also included. DATA EXTRACTION A predesigned and piloted data extraction form was used to compile data from individual studies. RESULTS A total of 57 studies were included: 20 intervention studies and 37 observational studies. Although observational evidence suggests that concentrations of selenium, zinc, and iron are positively associated with iodine status, data from randomized controlled trials fail to confirm this relationship. CONCLUSIONS Further studies are needed to provide greater understanding of the role of micronutrient status in iodine nutrition and thyroid function to ascertain the public health implications for populations worldwide.
-
3.
Black pepper-based beverage induced appetite-suppressing effects without altering postprandial glycaemia, gut and thyroid hormones or gastrointestinal well-being: a randomized crossover study in healthy subjects.
Zanzer, YC, Plaza, M, Dougkas, A, Turner, C, Östman, E
Food & function. 2018;(5):2774-2786
Abstract
Pleiotropic effects of spices on health, particularly on glucose metabolism and energy regulation, deserve further clinical investigation into their efficacy. The aim of the current study was to evaluate whether consumption of a black pepper-based beverage (BPB) preload containing 20 mg gallic acid equivalent (GAE) would exert any effect on postprandial glycaemia, appetite sensations, gut hormones, thyroid function, and gastrointestinal well-being after a white wheat bread (WWB) challenge meal containing 50 g available carbohydrates (CHO) compared to a control beverage. Sixteen healthy subjects (10 men; 6 women; 26 ± 0.9 years; BMI 22.93 ± 0.53 kg m-2) completed a randomized, crossover intervention study. The BPB's bioactive compounds were characterized using ultra high-performance liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer with an electrospray ionization source (UHPLC-DAD-ESI-QTOF-MS). Nine compounds tentatively identified in BPB include: dihydroxybenzoic acid hexoside-pentoside, decaffeoyl-acteoside, cynaroside A, apigenin 6,8-di-C-hexoside, luteolin 6-C-hexoside-8-C-rhamnoside, apigenin 8-C-hexoside-C-deoxyhexoside, kaempferol 3-rhamnoside-4'-xyloside, apigenin 7-neohesperidoside, and apigenin-8-C-arabinopyranoside-2''-rhamnoside. Blood glucose and serum insulin responses, insulin sensitivity and β-cell function were not affected during the acute intervention with BPB. Neither were effects on gastrointestinal well-being observed after BPB. However, BPB modulated overall acute appetite by lowering 'hunger', 'desire to eat', and 'prospective consumption', and increasing 'satiety' and 'fullness'. In contrast, there were no changes in gut (peptide tyrosine-tyrosine [PYY] and glucagon-like peptide-1 [GLP-1]) and thyroid (triiodothyronine [T3] and thyroxine [T4]) hormones after BPB compared to the control beverage. In conclusion, inclusion of BPB prior to the WWB challenge meal might be beneficial for appetite modulation, but we did not find supporting evidence in glycaemia, gut and thyroid hormones. Further studies are needed to elucidate the mechanisms of appetite-reducing pungent spices, such as black pepper.
-
4.
Thyrotropic hormones.
Mallya, M, Ogilvy-Stuart, AL
Best practice & research. Clinical endocrinology & metabolism. 2018;(1):17-25
Abstract
Thyroid hormones are crucial for normal cognition and neurodevelopment in children. The introduction of the screening programs for congenital hypothyroidism has decreased the incidence of untreated congenital hypothyroidism. As maternal thyroid disease is common, and may impact on thyroid gland development and function in the fetus, optimal management is crucial. This review discusses thyroid function and the impact of maternal thyroid disease on the fetus and neonate, as well as the influence of thyroid hormones, thyroid antibodies and the excretion of thyroid medication into breast milk on infant thyroid function.
-
5.
The Physiology of Childhood Growth: Hormonal Regulation.
Benyi, E, Sävendahl, L
Hormone research in paediatrics. 2017;(1):6-14
Abstract
The growth patterns of a child changes from uterine life until the end of puberty. Height velocity is highest in utero and declines after birth until puberty when it rises again. Important hormonal regulators of childhood growth are growth hormone, insulin-like growth factor 1, sex steroids, and thyroid hormone. This review gives an overview of these hormonal regulators of growth and their interplay with nutrition and other key players such as inflammatory cytokines.
-
6.
Thyroid and Glucocorticoid Hormones Promote Functional T-Tubule Development in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Parikh, SS, Blackwell, DJ, Gomez-Hurtado, N, Frisk, M, Wang, L, Kim, K, Dahl, CP, Fiane, A, Tønnessen, T, Kryshtal, DO, et al
Circulation research. 2017;(12):1323-1330
-
-
Free full text
-
Abstract
RATIONALE Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are increasingly being used for modeling heart disease and are under development for regeneration of the injured heart. However, incomplete structural and functional maturation of hiPSC-CM, including lack of T-tubules, immature excitation-contraction coupling, and inefficient Ca-induced Ca release remain major limitations. OBJECTIVE Thyroid and glucocorticoid hormones are critical for heart maturation. We hypothesized that their addition to standard protocols would promote T-tubule development and mature excitation-contraction coupling of hiPSC-CM when cultured on extracellular matrix with physiological stiffness (Matrigel mattress). METHODS AND RESULTS hiPSC-CM were generated using a standard chemical differentiation method supplemented with T3 (triiodothyronine) and/or Dex (dexamethasone) during days 16 to 30 followed by single-cell culture for 5 days on Matrigel mattress. hiPSC-CM treated with T3+Dex, but not with either T3 or Dex alone, developed an extensive T-tubule network. Notably, Matrigel mattress was necessary for T-tubule formation. Compared with adult human ventricular cardiomyocytes, T-tubules in T3+Dex-treated hiPSC-CM were less organized and had more longitudinal elements. Confocal line scans demonstrated spatially and temporally uniform Ca release that is characteristic of excitation-contraction coupling in the heart ventricle. T3+Dex enhanced elementary Ca release measured by Ca sparks and promoted RyR2 (ryanodine receptor) structural organization. Simultaneous measurements of L-type Ca current and intracellular Ca release confirmed enhanced functional coupling between L-type Ca channels and RyR2 in T3+Dex-treated cells. CONCLUSIONS Our results suggest a permissive role of combined thyroid and glucocorticoid hormones during the cardiac differentiation process, which when coupled with further maturation on Matrigel mattress, is sufficient for T-tubule development, enhanced Ca-induced Ca release, and more ventricular-like excitation-contraction coupling. This new hormone maturation method could advance the use of hiPSC-CM for disease modeling and cell-based therapy.
-
7.
Advances in applied homeostatic modelling of the relationship between thyrotropin and free thyroxine.
Hoermann, R, Midgley, JEM, Larisch, R, Dietrich, JWC
PloS one. 2017;(11):e0187232
Abstract
INTRODUCTION The relationship between pituitary TSH and thyroid hormones is central to our understanding of thyroid physiology and thyroid function testing. Here, we generated distribution patterns by using validated tools of thyroid modelling. METHODS We simulated patterns of individual set points under various conditions, based on a homeostatic model of thyroid feedback control. These were compared with observed data points derived from clinical trials. RESULTS A random mix of individual set points was reconstructed by simulative modelling with defined structural parameters. The pattern displayed by the cluster of hypothetical points resembled that observed in a natural control group. Moderate variation of the TSH-FT4 gradient over the functional range introduced further flexibility, implementing a scenario of adaptive set points. Such a scenario may be a realistic possibility for instance in treatment where relationships and equilibria between thyroid parameters are altered by various influences such as LT4 dose and conversion efficiency. CONCLUSIONS We validated a physiologically based homeostatic model that permits simulative reconstruction of individual set points. This produced a pattern resembling the observed data under various conditions. Applied modelling, although still experimental at this stage, shows a potential to aid our physiological understanding of the interplay between TSH and thyroid hormones. It should eventually benefit personalised clinical decision making.
-
8.
"With a little help from my friends" - The role of microbiota in thyroid hormone metabolism and enterohepatic recycling.
Virili, C, Centanni, M
Molecular and cellular endocrinology. 2017;:39-43
Abstract
The gut microbiota is composed of over 1200 species of anaerobes and aerobes bacteria along with bacteriophages, viruses and fungal species. Increasing evidence indicates that the intestinal microbiota, beside digestive equilibrium, is also crucial for immunologic, hormonal and metabolic homeostasis. The intestinal microbiota interacts with distant organs by signals which may be part of the bacteria themselves or their metabolites. Dysbiosis has been observed in inflammatory or autoimmune disorders such as multiple sclerosis or type 1 diabetes as well as in obesity and type 2 diabetes. Functional thyroid disorders were associated with bacterial overgrowth and a different microbial composition. Although thyroid metabolism was apparently disregarded, the interference of microbiota on peripheral iodothyronine homeostasis is an intriguing issue. In this review we focused on the interactions of intestinal microbiota with thyroid-related micronutrients and with the metabolic steps of endogenous and exogenous iodothyronines.
-
9.
Thyroid Hormones, Metabolic Syndrome and Its Components.
Delitala, AP, Fanciulli, G, Pes, GM, Maioli, M, Delitala, G
Endocrine, metabolic & immune disorders drug targets. 2017;(1):56-62
Abstract
Metabolic syndrome is a clustering of various metabolic parameters, which include diabetes, low high-density lipoprotein cholesterol, elevated triglycerides, abdominal obesity, and hypertension. It has merged as a worldwide epidemic and a major public health care concern. However, due to the different criteria used for the assessment, the frequency of metabolic syndrome in the general population is variable but it is more common in the older people. Metabolic syndrome is closely linked to cardiovascular risk and increases cardiovascular outcomes and all-cause mortality. Recent evidences showed that alterations of the thyroid function could have an impact on the components of the metabolic syndrome, suggesting that thyroid hormones have a variety of effects on energy homeostasis, lipid and glucose metabolism, and blood pressure. In this review, we summarize available data on the action of thyroid hormone on the components of metabolic syndrome.
-
10.
Metabolomic profile in hyperthyroid patients before and after antithyroid drug treatment: Correlation with thyroid hormone and TSH concentration.
Piras, C, Arisci, N, Poddighe, S, Liggi, S, Mariotti, S, Atzori, L
The international journal of biochemistry & cell biology. 2017;:119-128
Abstract
Hyperthyroidism (HT) is characterized by an intense metabolic impact which affects the lipid, carbohydrate and amino acids metabolism, with increased resting energy expenditure and thermogenesis. Metabolomics is a new comprehensive technique that allows to capture an instant metabolic picture of an organism, reflecting peculiar molecular and pathophysiological states. The aim of the present prospective study was to identify a distinct metabolomic profile in HT patients using 1H NMR spectroscopy before and after antithyroid drug treatment. This prospective study included 15 patients (10 female, 5 male) who were newly diagnosed hyperthyroidism. A nuclear magnetic resonance (1H NMR) based analysis was performed on plasma samples from the same patients at diagnosis (HypT0) and when they achieved euthyroidism (HypT1). The case groups were compared with a control group of 26 healthy volunteers (C). Multivariate statistical analysis was performed with Partial Least Squares-Discriminant Analysis (PLS-DA). PLS-DA identified a distinct metabolic profile between C and untreated hyperthyroid patients (R2X 0.638, R2Y 0.932, Q2 0.783). Interestingly, a significant difference was also found between C and euthyroid patients after treatment (R2X 0.510, R2Y 0.838, Q2 0.607), while similar cluster emerged comparing HypT0vs HypT1 patients. This study shows that metabolomic profile is deeply influenced by hyperthyroidism and this alteration persists after normalization of thyrotropin (TSH) and free thyroid hormone (FT3, FT4) concentration. This suggests that TSH, FT3 and FT4 assays may not be insufficient to detect long lasting peripheral effects of the thyroid hormones action. Further studies are needed to clarify whether and to what extent the evaluation of metabolomics profile may provide relevant information in the clinical management of hyperthyroidism.