Food is a critical environmental factor that influences animal survival,especially for small passerines due to their high mass-specific metabolic rates.Basal metabolic rate(BMR)reflects the energy expended by endother...Food is a critical environmental factor that influences animal survival,especially for small passerines due to their high mass-specific metabolic rates.Basal metabolic rate(BMR)reflects the energy expended by endothermic animals for basic physiological processes and constitutes a major part of their daily energy budget.Some birds have been shown to employ compensatory mechanisms during food shortages,temporarily reducing these selfmaintenance expenditures without using hypothermia.However,the mechanisms of BMR adjustment remain unexplored.In the present study,we assessed the phenotypic variation in basal thermogenesis of Eurasian Tree Sparrows(Passer montanus)by comparing a control group to groups fasted for 6,12,18,and 24 h.We focused on the correlation between a reduction in energy metabolism and the alterations of cellular metabolic activities,mitochondrial substrate supply,and changes in serum thyroid hormones during fasting.Our data indicated that fasting groups had significantly lower body mass,BMR,body temperature,and body fat content.Furthermore,fasting groups had significantly lower glycogen levels,mitochondrial state 4 respiration and cytochrome c oxidase(CCO)activity in the liver,and CCO activity in pectoral muscle.The levels of avian uncoupling protein(avUCP)m RNA were significantly reduced,while the levels of myostatin protein in pectoral muscle were significantly increased in the fasting groups.Furthermore,the groups subjected to fasting exhibited significantly lower levels of serum glucose,triglyceride,thyroxine(T_(4)),and triiodothyronine(T_(3)).Positive correlations were observed between the following pairs of variables:log BMR and log body mass,log body mass and log body fat,log BMR and log state 4 respiration in the liver,log BMR and log CCO activity in the liver and muscle,log BMR and log av-UCP m RNA expression,whereas a negative correlation was observed between log BMR and log myostatin level.In addition,a positive correlation was also detected between log T_(3) and each of the following:log BMR,state 4 respiration,and log CCO activity in the liver.Our results suggested that decreased metabolic thermogenesis via down-regulation in cellular aerobic capacity of organs and serum thyroid hormones may be an important survival strategy for fasting Tree Sparrows to reduce energy expenditure.展开更多
Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regula...Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regulate gene transcription via nuclear receptors TRα/β,modulating proliferation,apoptosis,and AR signaling,while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K-Akt signaling,driving metabolic reprogramming,migration,and angiogenesis.Local DIO enzymes fine-tune T3/T4 levels,with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion.Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk,whereas experimental models show inconsistent effects,reflecting regulation by hormone levels,receptor distribution,and tumor molecular features.Bibliometric analyses reveal a shift from epidemiological studies to molecular,immune,and metabolic mechanistic research,though clinical translation remains limited.This review synthesizes current knowledge on THs in PCa,highlighting mechanistic insights,evidence gaps,and future directions,aiming to inform early detection,stratification,and therapeutic strategies.展开更多
Objective To examine the mechanistic of organochlorine-associated changes in lung function.Methods This study investigated 76 healthy older adults in Jinan,Shandong Province,over a fivemonth period.Personal exposure t...Objective To examine the mechanistic of organochlorine-associated changes in lung function.Methods This study investigated 76 healthy older adults in Jinan,Shandong Province,over a fivemonth period.Personal exposure to organochlorines was quantified using wearable passive samplers,while inflammatory factors and thyroid hormones were analyzed from blood samples.Participants’lung function was evaluated.After stratifying participants according to their thyroid hormone levels,we analyzed the differential effects of organochlorine exposure on lung function and inflammatory factors across the low and high thyroid hormone groups.Mediation analysis was further conducted to elucidate the relationships among organochlorine exposures,inflammatory factors,and lung function.Results Bis(2-chloro-1-methylethyl)ether(BCIE),was negatively associated with forced vital capacity(FVC,–2.05%,95%CI:–3.11%to–0.97%),and associated with changes in inflammatory factors such as interleukin(IL)-2,IL-7,IL-8,and IL-13 in the low thyroid hormone group.The mediation analysis indicated a mediating effect of IL-2(15.63%,95%CI:0.91%to 44.64%)and IL-13(13.94%,95%CI:0.52%to 41.07%)in the association between BCIE exposure and FVC.Conclusion Lung function and inflammatory factors exhibited an increased sensitivity to organochlorine exposure at lower thyroid hormone levels,with inflammatory factors potentially mediating the adverse effects of organochlorines on lung function.展开更多
Reverse cholesterol transport (RCT) is a complex process which transfers cholesterol from peripheral cells to the liver for subsequent elimination from the body via feces. Thyroid hormones (THs) affect growth, develop...Reverse cholesterol transport (RCT) is a complex process which transfers cholesterol from peripheral cells to the liver for subsequent elimination from the body via feces. Thyroid hormones (THs) affect growth, develop- ment, and metabolism in almost all tissues. THs exert their actions by binding to thyroid hormone receptors (TRs). There are two major subtypes of TRs, TRα and TRβ, and several isoforms (e.g. TRα1, TRα2, TRβ1, and TRβ2). Activation of TRα1 affects heart rate, whereas activation of TRβ1 has positive effects on lipid and lipoprotein metabolism. Consequently, particular interest has been focused on the development of thyromimetic compounds targeting TRβ1, not only because of their ability to lower plasma cholesterol but also due their ability to stimulate RCT, at least in pre-clinical models. In this review we focus on THs, TRs, and on the effects of TRβ1-modulating thyromimetics on RCT in various animal models and in humans.展开更多
Injury to peripheral nerves is often observed in the clinic and severe injuries may cause loss of motor and sensory functions.Despite extensive investigation,testing various surgical repair techniques and neurotrophic...Injury to peripheral nerves is often observed in the clinic and severe injuries may cause loss of motor and sensory functions.Despite extensive investigation,testing various surgical repair techniques and neurotrophic molecules,at present,a satisfactory method to ensuring successful recovery does not exist.For successful molecular therapy in nerve regeneration,it is essential to improve the intrinsic ability of neurons to survive and to increase the speed of axonal outgrowth.Also to induce Schwann cell phenotypical changes to prepare the local environment favorable for axonal regeneration and myelination.Therefore,any molecule that regulates gene expression of both neurons and Schwann cells could play a crucial role in peripheral nerve regeneration.Clinical and experimental studies have reported that thyroid hormones are essential for the normal development and function of the nervous system,so they could be candidates for nervous system regeneration.This review provides an overview of studies devoted to testing the effect of thyroid hormones on peripheral nerve regeneration.Also it emphasizes the importance of combining biodegradable tubes with local administration of triiodothyronine for future clinical therapy of human severe injured nerves.We highlight that the local and single administration of triiodothyronine within biodegradable nerve guide improves significantly the regeneration of severed peripheral nerves,and accelerates functional recovering.This technique provides a serious step towards future clinical application of triiodothyronine in human severe injured nerves.The possible regulatory mechanism by which triiodothyronine stimulates peripheral nerve regeneration is a rapid action on both axotomized neurons and Schwann cells.展开更多
The present study determined the thyroid hormone interference of tetrabromobisphenol A （TBBPA） in Sprague-Dawley （SD） rats, and the derived-reference dose （RfD） of different endpoint effects on mammals based on ...The present study determined the thyroid hormone interference of tetrabromobisphenol A （TBBPA） in Sprague-Dawley （SD） rats, and the derived-reference dose （RfD） of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine （T3）, thyroxine （T4）, and thyroid stimulating hormone （TSH） demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day.展开更多
BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has...BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.展开更多
Exposure to endocrine disruptors(EDCs) could disrupt thyroid hormone homeostasis. However, human epidemiological studies reported inconsistent observations, and scarce information on the effect of a mixture of chemica...Exposure to endocrine disruptors(EDCs) could disrupt thyroid hormone homeostasis. However, human epidemiological studies reported inconsistent observations, and scarce information on the effect of a mixture of chemicals. The aim of the present study was to examine the associations of multiple chemicals with thyroid hormones among adults from China. We measured serum levels of thyroid hormones and urinary levels of 11 EDCs, including six phthalate metabolites, bisphenol A(BPA), bisphenol F(BPF), bisphenol S(BPS), perchlorate, and thiocyanate among 177 healthy adults without occupational exposure. Associations of multiple urinary analytes with serum thyroid hormones were examined by performing general linear regression analysis and bayesian kernal machine regression analysis. These EDCs were detected in almost all samples. After adjusting for various covariates, we observed only BPF significantly associated with total thyroxin(TT4)(β=-0.27, 95% confidence interval(CI) [-0.41,-0.14]), total triiodothyronine(TT3)(β=-0.02 95% CI [-0.03,-0.01]), free T4(fT4)(β=-0.02, 95% CI [-0.03,-0.01]), and free T3(fT3)(β=-0.04, 95% CI [-0.07,-0.01]), and mono-(2-ethyl-5-oxohexyl) phthalate(MEOHP) and monoethyl phthalate(MEP) positively associated with TT4(β=0.24, 95% CI [0.01, 0.48]) and fT4(β=0.02, 95% CI [0.01, 0.04]), respectively. Moreover, we observed significant dose-response relationships between TT4 and the mixture of11 EDCs, and BPF was the main contributor to the mixture effect, suggesting the priority of potential effect of BPF on disrupting thyroid function under a real scenario of human exposure to multiple EDCs. Our findings supported the hypothesis that human exposure to low levels of EDCs could alter thyroid hormones homeostasis among non-occupational healthy adults.展开更多
[Objeclive] The comparison of levels of thyroid hormones （T3, T4 and FT3） in female ducks serum and embryo of different embryonic age between Gaoyou duck and Jinding duck were made to provide basic data for further ...[Objeclive] The comparison of levels of thyroid hormones （T3, T4 and FT3） in female ducks serum and embryo of different embryonic age between Gaoyou duck and Jinding duck were made to provide basic data for further research. [Method] The levels of thyroid hormones （T3, T4 and FT3） in female ducks serum, fertilized eggs, and 7, 11,15, 19, 22, 28-days embryo of Gaoyou duck and Jinding duck were analyzed with radioimmunoassay （RIA）. [ Result]The levels of thyroid hormones in fertilized eggs were higher than those in serum of female ducks; different em- bryonic age hormone level of Gaoyou duck and Jinding duck in serum had almost the same variation trend, which was low but relatively stable after 15 days. [Condusion] The result suggested that thyroid hormones play an important role in duck embryonic development, especially in the early peded.展开更多
We fed adult mink diets containing supplemental iodine, from 0 to 320 ppm, for one or seven months prior to breeding. Blood samples collected from the adults and their offspring (kits) at 4 wk post-partum were assayed...We fed adult mink diets containing supplemental iodine, from 0 to 320 ppm, for one or seven months prior to breeding. Blood samples collected from the adults and their offspring (kits) at 4 wk post-partum were assayed for total thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), and T4-binding indices. As expected T4 concentrations of the adult and kit mink varied inversely with the level of supplemental iodine. In addition, T3 and rT3 concentrations decreased gradually in kits from the long-term experiment in response to the increased dietary iodine of the dams. T3 concentrations of kits from dams fed iodine short-term decreased markedly while rTy concentrations were elevated greatly in response to increased dietary iodine of the dam. These decreases in hormone levels are due to serum iodine blocking the thyroid uptake of iodine and subsequent decrease of hormone synthesis. Excess iodine may also block the effect of thyroid stimulating hormone. The T4-binding indices of the adults, in general, were depressed, while the T4-binding indices of the kits were more variable. These effects are probably due to fluctuations in thyroglobulin.展开更多
The aim was to characterize thyroid function in Hispanic hypertensive population. Retrospective study of 1,023 individuals was performed, in which 68.23% had hypertension （74.21% women） and 37.25% had thyroid pathol...The aim was to characterize thyroid function in Hispanic hypertensive population. Retrospective study of 1,023 individuals was performed, in which 68.23% had hypertension （74.21% women） and 37.25% had thyroid pathology. Age, weight, blood pressure, biochemical measurements were recorded, mean age： 53.02 ± 14.80 yr, mean weight： 83.05 ±16.95 kg, thyrotropin-stimulating hormone （TSH） hypertensive patients： 5.55±1.63 μUI/mL and without hypertension： 3,72 ± 1.60 μUI/mL. TSH range concentration distributed by sex indicates： 1.50-2.49 μUI/mL men, 2.50-5.01 μUI/mL women. TSH categories vs. age were positively associated （r = ＋ 0.114, P = 0.044） and hypertension by age was also correlated （r = ＋ 0.178, P = 0.0001）. Significant positive association we found between TSH and diastolic blood pressure （r = ＋ 0.197, P = 0.008）. Systolic and diastolic blood pressure vs. age were positively increasing （r = ＋ 0.410,p = 0.0001; r = ＋0.285, P = 0.0001, respectively）. Prevalence of thyroid pathology in hypertensive subjects are hyperthyroidism 5.87%; hypothyroidism 20.34% （5.73% subclinic） and autoimmune disease 6.25%. High percentage of hypertensive population has concomitant thyroid diseases, more common in women （50-70 years）. Systematic surveillance for occult thyroid dysfunction in patients with hypertension could prevent future cardiovascular disease.展开更多
Background Thyroid hormones(THs) including thyroxine(T4) and triiodothyronine(T3) with high biological activities have important effects on cardiovascular system by acting on renin-angiotensin-aldosterone system(RAAS)...Background Thyroid hormones(THs) including thyroxine(T4) and triiodothyronine(T3) with high biological activities have important effects on cardiovascular system by acting on renin-angiotensin-aldosterone system(RAAS), oxidative stress, mitochondria, endothelial cells, vascular smooth muscle cells(VSMC), cardiomyocytes, thyroid hormone receptor(TRs), cholesterol metabolism, insulin sensitivity, blood coagulation, etc. Excess or lack of THs is detrimental to cardiovascular function, so this article reviews the mechanism of THs on cardiovascular system.[S Chin J Cardiol 2019;20(4):269-279]展开更多
Objective: There are clinical and laboratory associations between thyroid and liver diseases. Hepatitis C virus (HCV) is known to be responsible for both hepatic and extrahepatic diseases. The most frequent and clinic...Objective: There are clinical and laboratory associations between thyroid and liver diseases. Hepatitis C virus (HCV) is known to be responsible for both hepatic and extrahepatic diseases. The most frequent and clinically important endocrine extrahepatic diseases are thyroid disorders and type 2 diabetes mellitus. We aim to study the relationship between the serum level of thyroid hormones (THs) and the severity of liver disease in patients with chronic hepatitis C virus (CHC) infection. Methods: 60 patients with CHC infection were selected for the study. They were divided into two groups: with or without liver cirrhosis. Those with liver cirrhosis were further subdivided according to the Child-Turcotte-Pugh scoring system. Serum levels of free T3 (FT3), free T4 (FT4) and TSH were measured to all patients. Results: There was decrease in the FT3 and FT4 levels and increase in the TSH levels in patients with CHC with cirrhosis when compared to patients with CHC without cirrhosis. Conclusion: Thyroid profile abnormalities were seen in cirrhotic HCV patients when compared to non-cirrhotic patients. The abnormalities in the serum level of THs (decreased FT3, FT4, and increased TSH) are strongly associated with the severity of liver damage and advancing of the child score.展开更多
This study aimed to assess the systemic effect of LLLT on thyroid gland functioning and consequently on calcium regulation through Triiodothyronine (T3) and Thyroxine (T4) measurements in rabbits’ serum. A total of t...This study aimed to assess the systemic effect of LLLT on thyroid gland functioning and consequently on calcium regulation through Triiodothyronine (T3) and Thyroxine (T4) measurements in rabbits’ serum. A total of thirty two New Zealand male rabbits were randomly distributed in four groups with eight animals each: control group C (nonirradiated animals), group EI (5 J/cm2 per session), group EII (10 J/cm2 per session) and group EIII (20 J/cm2 per session). All animals underwent lower left incisor extraction followed by immediate insertion of an osseintegrated implant, providing an equality of initial clinical condition between the groups. The experimental groups were irradiated with aluminium gallium arsenide diode laser (GaAlAs, λ = 830 nm, 50 mW, CW), during 13 days at each 48 hours, totalizing 7 sessions. Laboratorial T3 and T4 measurements were done in four distinct moments (before surgical procedure, immediately after surgical procedure, after the first LLLT session and after the last LLLT session) in all animals. The results obtained showed statistically significant differences in Triiodothyronine values between the groups throughout the experiment. It was concluded that the LLLT, in the protocol of irradiation used in this study, promoted a significantly alteration on rabbits’ serum hormonal levels.展开更多
Thyroid metabolism is orchestrated by the action of various minerals and trace elements including iron, iodine, selenium, and zinc. Iron deficiency, specifically deficiency in serum ferritin levels, is one of the comm...Thyroid metabolism is orchestrated by the action of various minerals and trace elements including iron, iodine, selenium, and zinc. Iron deficiency, specifically deficiency in serum ferritin levels, is one of the common causes of thyroid dysfunction. Our objective was to evaluate the relationship between serum ferritin levels and circulating thyroid hormones. For this, a retrospective analysis was performed on 16,512 individuals who tested for serum levels of ferritin and thyroid profile at Vibrant America Clinical Laboratories. Subjects were stratified based on the serum levels of ferritin. Age (p −0.03232, p < 0.0001). Analysis of Linear association by Pearson’s correlation exhibited a considerable correlation between varying serum ferritin levels with all tested thyroid hormones. The study concludes that serum ferritin levels were associated with thyroid hormone synthesis and metabolism in individuals with optimal levels of circulating ferritin.展开更多
Objective To investigate the association between thyroid hormone sensitivity indices and metabolic dysfunction-associated fatty liver disease(MAFLD)in euthyroid Chinese adults.Methods This cohort study included 5,356 ...Objective To investigate the association between thyroid hormone sensitivity indices and metabolic dysfunction-associated fatty liver disease(MAFLD)in euthyroid Chinese adults.Methods This cohort study included 5,356 euthyroid patients.The peripheral and central thyroid hormone sensitivity indices were calculated.Cox regression models were used to evaluate associations with MAFLD risk,and restricted cubic splines were used to assess potential nonlinearity.Mediation analyses based on an accelerated failure-time model were used to examine the role of the triglycerideglucose(TyG)index.Results MAFLD incidence in euthyroid participants was 18.26%.After adjustment,higher free thyroxine(FT4)levels were inversely associated with MAFLD(HR=0.973,95%CI:0.948 to 0.999,P=0.043),whereas higher free triiodothyronine(FT3)levels increased MAFLD risk(HR=1.118,95%CI:1.000 to 1.250,P=0.050).Enhanced thyroid hormone sensitivity,as reflected by elevated FT3/FT4 levels and lower total thyroxine resistance index(TT4RI),thyroid stimulating hormone index(TSHI),and thyroid feedback quantile-based index(TFQIFT4),was also associated with a higher incidence(all P<0.05).Mediation analyses indicated that TyG partially mediated the FT3/FT4-MAFLD and TFQIFT4-MAFLD associations,with indirect effects of-96.27(95%CI:-124.67 to-70.42)and-4.95(95%CI:-8.29 to-2.10),respectively.Conclusion Increased FT3/FT4 and decreased TFQIFT4 levels were significantly associated with a higher MAFLD risk in euthyroid adults,with TyG acting as a partial mediator.展开更多
The uncorrected caption of Fig.2 read:Figure 2 Local conversion of T4 to T3 via D2 represses type I fibers,but stimulates the rapid type Ⅱ fibers.Thyroid hormones increase oxidative capacity due to increased mitochon...The uncorrected caption of Fig.2 read:Figure 2 Local conversion of T4 to T3 via D2 represses type I fibers,but stimulates the rapid type Ⅱ fibers.Thyroid hormones increase oxidative capacity due to increased mitochondrial content and protein activity.T3 stimulates UCP-3 expression that uncouples ATP synthesis(adapted from Shishmarev[59];Simonides and van Hardeveld[60]).展开更多
We investigated the effects of prenatal bisphenol A (BPA) exposure on maternal thyroid hormones and fetal growth outcomes within a cohort from Saudi Arabia. In this prospective study, 672 pregnant women provided 1957 ...We investigated the effects of prenatal bisphenol A (BPA) exposure on maternal thyroid hormones and fetal growth outcomes within a cohort from Saudi Arabia. In this prospective study, 672 pregnant women provided 1957 urine samples, which were analyzed for BPA concentrations using UPLC-MS/MS throughout three trimesters. We recorded BPA detection rates and median concentrations, using mixed-effects models to examine the influence on maternal thyroid hormones, specifically free thyroxine (FT4) and thyroid-stimulating hormone (TSH). Additionally, we explored the impact on fetal growth markers such as head circumference (HC) and placental weight (PWT) through multivariable regression, adjusting for confounders. Findings indicated that BPA was present in over 95 % of samples, with a notable decrease in median concentrations from the 1st to the 3rd trimester. Higher BPA exposure correlated with a 2.96 % increase in FT4 levels and a 14.58 % reduction in TSH in the top exposure quartile. Fetal growth analysis showed a decrease of 3.8 % in HC and 15.3 % in PWT associated with high first-trimester BPA levels. Furthermore, FT4 levels in the first and 2nd trimesters mediated the relationship between BPA exposure and fetal growth outcomes by 21.1 % for PWT and 19.1 % for HC, while gestational age mediated 12.1 % of the change in HC. The study highlights significant disruptions in thyroid function and detrimental effects on fetal development due to high BPA exposure, underscoring the need for rigorous monitoring and preventive measures during pregnancy.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most prevalent chronic liver disease worldwide,affecting approximately 32%-38%of the adult population and posing a growing public health bu...Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most prevalent chronic liver disease worldwide,affecting approximately 32%-38%of the adult population and posing a growing public health burden.MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),progressive hepatic fibrosis,cirrhosis,and ultimately hepatocellular carcinoma(HCC).The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis,characterized by an imbalance among de novo lipogenesis,fatty acidβ-oxidation,and very-low-density lipoprotein(VLDL)-mediated lipid export.This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression.Among the multiple regulatory pathways involved,thyroid hormone(TH)signaling has emerged as a central regulator of hepatic metabolic homeostasis.The liver is a major peripheral target organ of TH action,where TH predominantly exerts its metabolic effects through thyroid hormone receptorβ(TRβ).Large-scale epidemiological studies and metaanalyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence,more severe histological injury,and advanced hepatic fibrosis,suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum.At the molecular level,TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis,enhancement of mitochondrial fatty acid oxidation,and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβaxis and non-genomic signaling pathways.Across different stages of MASLD,TH signaling exerts stagedependent protective effects.In the steatosis stage,TH improves metabolic flexibility by modulating insulin sensitivity,glucose metabolism,and lipid droplet clearance,thereby alleviating early lipotoxic stress.During progression to MASH,TH attenuates inflammatory amplification by improving mitochondrial homeostasis,suppressing activation of the NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome,and modulating the gut-liver axis microenvironment.In advanced stages,TH signaling influences hepatic stellate cell activation and extracellular matrix deposition,partly through interaction with the transforming growth factor-β(TGF-β)/SMAD pathway,while alterations in intrahepatic TH availability,mediated by dynamic changes in iodothyronine deiodinase 1(DIO1),contribute to fibrosis progression and hepatocellular dedifferentiation.In hepatocellular carcinoma,coordinated downregulation of TRβand DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression.The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom,a liver-targeted TRβ-selective agonist,for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis(F2-F3).This approval represents a landmark transition from mechanistic understanding to metabolismcentered precision therapy in MASLD.Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints,including MASH resolution and fibrosis regression,but also favorably modulates atherogenic lipid profiles,highlighting the therapeutic potential of selectively targeting hepatic TH pathways.This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of THbased interventions,aiming to inform future mechanistic research and optimize clinical management strategies.展开更多
Studies have indicated the different effects of PM_(2.5)components on human health.However,specific components that influence the severity of disease in schizophrenia patients and their underlying mechanisms remain un...Studies have indicated the different effects of PM_(2.5)components on human health.However,specific components that influence the severity of disease in schizophrenia patients and their underlying mechanisms remain unclear.Therefore,a repeated measures study for schizophrenia was constructed based on Anhui Mental Health Center.We collected information,including demographics and thyroid hormones(TH)levels,on repeat admissions of schizophrenia patients during 2017−2020,assessing their illness severity by positive and negative symptom scales(PANSS).Concentrations from the nearest component monitoring station in the 3 months before admission were assigned as the participant’s exposure level.We assessed the effects of PM_(2.5)components individually and in combination on schizophrenia and explored the mediating role of THs.Results indicated that benzo[a]pyrene,sulfate,nitrate,chloride,ammonia,cadmium,chromium,lead,selenium,and thallium exposure were associated with increased PANSS scores,with more significant results observed in males.Mixed exposure to PM_(2.5)components was found to be associated with increased PANSS scores and decreased free triiodothyronine(FT3).Mediation analysis suggested that the reduction in FT3 might mediate the association between the PM_(2.5)components and PANSS scores.The findings emphasize the impacts of PM_(2.5)components on schizophrenia and the potential value of focusing on changes in THs.展开更多
基金financially supported by grants from the National Natural Science Foundation of China (Nos.32371573,32171497,and 31971420)。
文摘Food is a critical environmental factor that influences animal survival,especially for small passerines due to their high mass-specific metabolic rates.Basal metabolic rate(BMR)reflects the energy expended by endothermic animals for basic physiological processes and constitutes a major part of their daily energy budget.Some birds have been shown to employ compensatory mechanisms during food shortages,temporarily reducing these selfmaintenance expenditures without using hypothermia.However,the mechanisms of BMR adjustment remain unexplored.In the present study,we assessed the phenotypic variation in basal thermogenesis of Eurasian Tree Sparrows(Passer montanus)by comparing a control group to groups fasted for 6,12,18,and 24 h.We focused on the correlation between a reduction in energy metabolism and the alterations of cellular metabolic activities,mitochondrial substrate supply,and changes in serum thyroid hormones during fasting.Our data indicated that fasting groups had significantly lower body mass,BMR,body temperature,and body fat content.Furthermore,fasting groups had significantly lower glycogen levels,mitochondrial state 4 respiration and cytochrome c oxidase(CCO)activity in the liver,and CCO activity in pectoral muscle.The levels of avian uncoupling protein(avUCP)m RNA were significantly reduced,while the levels of myostatin protein in pectoral muscle were significantly increased in the fasting groups.Furthermore,the groups subjected to fasting exhibited significantly lower levels of serum glucose,triglyceride,thyroxine(T_(4)),and triiodothyronine(T_(3)).Positive correlations were observed between the following pairs of variables:log BMR and log body mass,log body mass and log body fat,log BMR and log state 4 respiration in the liver,log BMR and log CCO activity in the liver and muscle,log BMR and log av-UCP m RNA expression,whereas a negative correlation was observed between log BMR and log myostatin level.In addition,a positive correlation was also detected between log T_(3) and each of the following:log BMR,state 4 respiration,and log CCO activity in the liver.Our results suggested that decreased metabolic thermogenesis via down-regulation in cellular aerobic capacity of organs and serum thyroid hormones may be an important survival strategy for fasting Tree Sparrows to reduce energy expenditure.
基金Guangzhou Medical and Health Science and Technology Project(Project No.:20231A011103)General projects of Guangzhou municipal Science and Technology Bureau(Project No.:2023A04J0598)Guangdong Basic and Applied Basic Research Foundation(Project No.:2022A1515111122)。
文摘Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regulate gene transcription via nuclear receptors TRα/β,modulating proliferation,apoptosis,and AR signaling,while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K-Akt signaling,driving metabolic reprogramming,migration,and angiogenesis.Local DIO enzymes fine-tune T3/T4 levels,with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion.Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk,whereas experimental models show inconsistent effects,reflecting regulation by hormone levels,receptor distribution,and tumor molecular features.Bibliometric analyses reveal a shift from epidemiological studies to molecular,immune,and metabolic mechanistic research,though clinical translation remains limited.This review synthesizes current knowledge on THs in PCa,highlighting mechanistic insights,evidence gaps,and future directions,aiming to inform early detection,stratification,and therapeutic strategies.
基金supported by the National Key Research and Development Program of China(No.2022YFC3702700)the National Natural Science Foundation of China(No.82025030)the National Research Program for Key Issues in Air Pollution Control of China(No.DQGG0401)。
文摘Objective To examine the mechanistic of organochlorine-associated changes in lung function.Methods This study investigated 76 healthy older adults in Jinan,Shandong Province,over a fivemonth period.Personal exposure to organochlorines was quantified using wearable passive samplers,while inflammatory factors and thyroid hormones were analyzed from blood samples.Participants’lung function was evaluated.After stratifying participants according to their thyroid hormone levels,we analyzed the differential effects of organochlorine exposure on lung function and inflammatory factors across the low and high thyroid hormone groups.Mediation analysis was further conducted to elucidate the relationships among organochlorine exposures,inflammatory factors,and lung function.Results Bis(2-chloro-1-methylethyl)ether(BCIE),was negatively associated with forced vital capacity(FVC,–2.05%,95%CI:–3.11%to–0.97%),and associated with changes in inflammatory factors such as interleukin(IL)-2,IL-7,IL-8,and IL-13 in the low thyroid hormone group.The mediation analysis indicated a mediating effect of IL-2(15.63%,95%CI:0.91%to 44.64%)and IL-13(13.94%,95%CI:0.52%to 41.07%)in the association between BCIE exposure and FVC.Conclusion Lung function and inflammatory factors exhibited an increased sensitivity to organochlorine exposure at lower thyroid hormone levels,with inflammatory factors potentially mediating the adverse effects of organochlorines on lung function.
基金Supported by Research Award from KaroBio AB, Sweden (to Parini P)
文摘Reverse cholesterol transport (RCT) is a complex process which transfers cholesterol from peripheral cells to the liver for subsequent elimination from the body via feces. Thyroid hormones (THs) affect growth, develop- ment, and metabolism in almost all tissues. THs exert their actions by binding to thyroid hormone receptors (TRs). There are two major subtypes of TRs, TRα and TRβ, and several isoforms (e.g. TRα1, TRα2, TRβ1, and TRβ2). Activation of TRα1 affects heart rate, whereas activation of TRβ1 has positive effects on lipid and lipoprotein metabolism. Consequently, particular interest has been focused on the development of thyromimetic compounds targeting TRβ1, not only because of their ability to lower plasma cholesterol but also due their ability to stimulate RCT, at least in pre-clinical models. In this review we focus on THs, TRs, and on the effects of TRβ1-modulating thyromimetics on RCT in various animal models and in humans.
基金supported by the Swiss National Science FoundationSUVA foundationNovartis foundation
文摘Injury to peripheral nerves is often observed in the clinic and severe injuries may cause loss of motor and sensory functions.Despite extensive investigation,testing various surgical repair techniques and neurotrophic molecules,at present,a satisfactory method to ensuring successful recovery does not exist.For successful molecular therapy in nerve regeneration,it is essential to improve the intrinsic ability of neurons to survive and to increase the speed of axonal outgrowth.Also to induce Schwann cell phenotypical changes to prepare the local environment favorable for axonal regeneration and myelination.Therefore,any molecule that regulates gene expression of both neurons and Schwann cells could play a crucial role in peripheral nerve regeneration.Clinical and experimental studies have reported that thyroid hormones are essential for the normal development and function of the nervous system,so they could be candidates for nervous system regeneration.This review provides an overview of studies devoted to testing the effect of thyroid hormones on peripheral nerve regeneration.Also it emphasizes the importance of combining biodegradable tubes with local administration of triiodothyronine for future clinical therapy of human severe injured nerves.We highlight that the local and single administration of triiodothyronine within biodegradable nerve guide improves significantly the regeneration of severed peripheral nerves,and accelerates functional recovering.This technique provides a serious step towards future clinical application of triiodothyronine in human severe injured nerves.The possible regulatory mechanism by which triiodothyronine stimulates peripheral nerve regeneration is a rapid action on both axotomized neurons and Schwann cells.
基金supported by the National Natural Science Foundation of China(No.21377045)Joint Innovation Funding of Production and Research-a Prospective Joint Research Project(BY2015027-05)
文摘The present study determined the thyroid hormone interference of tetrabromobisphenol A （TBBPA） in Sprague-Dawley （SD） rats, and the derived-reference dose （RfD） of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine （T3）, thyroxine （T4）, and thyroid stimulating hormone （TSH） demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day.
基金Supported by the Xuanwu Hospital Capital Medical University Science Program for Fostering Young Scholars,No.YC20220113the Pilot Project for Public,No.Beijing Medical Research 2021-8.
文摘BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.
基金supported by the National Natural Science Foundation of China (Nos. 21976046, 21537001, and 21507018)by the National Key Research and Development Program of China (No. 2017YFC1600500)。
文摘Exposure to endocrine disruptors(EDCs) could disrupt thyroid hormone homeostasis. However, human epidemiological studies reported inconsistent observations, and scarce information on the effect of a mixture of chemicals. The aim of the present study was to examine the associations of multiple chemicals with thyroid hormones among adults from China. We measured serum levels of thyroid hormones and urinary levels of 11 EDCs, including six phthalate metabolites, bisphenol A(BPA), bisphenol F(BPF), bisphenol S(BPS), perchlorate, and thiocyanate among 177 healthy adults without occupational exposure. Associations of multiple urinary analytes with serum thyroid hormones were examined by performing general linear regression analysis and bayesian kernal machine regression analysis. These EDCs were detected in almost all samples. After adjusting for various covariates, we observed only BPF significantly associated with total thyroxin(TT4)(β=-0.27, 95% confidence interval(CI) [-0.41,-0.14]), total triiodothyronine(TT3)(β=-0.02 95% CI [-0.03,-0.01]), free T4(fT4)(β=-0.02, 95% CI [-0.03,-0.01]), and free T3(fT3)(β=-0.04, 95% CI [-0.07,-0.01]), and mono-(2-ethyl-5-oxohexyl) phthalate(MEOHP) and monoethyl phthalate(MEP) positively associated with TT4(β=0.24, 95% CI [0.01, 0.48]) and fT4(β=0.02, 95% CI [0.01, 0.04]), respectively. Moreover, we observed significant dose-response relationships between TT4 and the mixture of11 EDCs, and BPF was the main contributor to the mixture effect, suggesting the priority of potential effect of BPF on disrupting thyroid function under a real scenario of human exposure to multiple EDCs. Our findings supported the hypothesis that human exposure to low levels of EDCs could alter thyroid hormones homeostasis among non-occupational healthy adults.
基金funded by State Funds($31172194)Jiangsu Province Modern Agricultural Variety Innovation CX(11)(1030)+1 种基金Science and Technology Support Plan(BE2011329)Yangzhou City Science and Technology Research(YZ2010048)
文摘[Objeclive] The comparison of levels of thyroid hormones （T3, T4 and FT3） in female ducks serum and embryo of different embryonic age between Gaoyou duck and Jinding duck were made to provide basic data for further research. [Method] The levels of thyroid hormones （T3, T4 and FT3） in female ducks serum, fertilized eggs, and 7, 11,15, 19, 22, 28-days embryo of Gaoyou duck and Jinding duck were analyzed with radioimmunoassay （RIA）. [ Result]The levels of thyroid hormones in fertilized eggs were higher than those in serum of female ducks; different em- bryonic age hormone level of Gaoyou duck and Jinding duck in serum had almost the same variation trend, which was low but relatively stable after 15 days. [Condusion] The result suggested that thyroid hormones play an important role in duck embryonic development, especially in the early peded.
基金Supported in part by the Mink Farmers Research Foundation,Thiensville,WI and The Heger Company,North St.Paul,MN.
文摘We fed adult mink diets containing supplemental iodine, from 0 to 320 ppm, for one or seven months prior to breeding. Blood samples collected from the adults and their offspring (kits) at 4 wk post-partum were assayed for total thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), and T4-binding indices. As expected T4 concentrations of the adult and kit mink varied inversely with the level of supplemental iodine. In addition, T3 and rT3 concentrations decreased gradually in kits from the long-term experiment in response to the increased dietary iodine of the dams. T3 concentrations of kits from dams fed iodine short-term decreased markedly while rTy concentrations were elevated greatly in response to increased dietary iodine of the dam. These decreases in hormone levels are due to serum iodine blocking the thyroid uptake of iodine and subsequent decrease of hormone synthesis. Excess iodine may also block the effect of thyroid stimulating hormone. The T4-binding indices of the adults, in general, were depressed, while the T4-binding indices of the kits were more variable. These effects are probably due to fluctuations in thyroglobulin.
文摘The aim was to characterize thyroid function in Hispanic hypertensive population. Retrospective study of 1,023 individuals was performed, in which 68.23% had hypertension （74.21% women） and 37.25% had thyroid pathology. Age, weight, blood pressure, biochemical measurements were recorded, mean age： 53.02 ± 14.80 yr, mean weight： 83.05 ±16.95 kg, thyrotropin-stimulating hormone （TSH） hypertensive patients： 5.55±1.63 μUI/mL and without hypertension： 3,72 ± 1.60 μUI/mL. TSH range concentration distributed by sex indicates： 1.50-2.49 μUI/mL men, 2.50-5.01 μUI/mL women. TSH categories vs. age were positively associated （r = ＋ 0.114, P = 0.044） and hypertension by age was also correlated （r = ＋ 0.178, P = 0.0001）. Significant positive association we found between TSH and diastolic blood pressure （r = ＋ 0.197, P = 0.008）. Systolic and diastolic blood pressure vs. age were positively increasing （r = ＋ 0.410,p = 0.0001; r = ＋0.285, P = 0.0001, respectively）. Prevalence of thyroid pathology in hypertensive subjects are hyperthyroidism 5.87%; hypothyroidism 20.34% （5.73% subclinic） and autoimmune disease 6.25%. High percentage of hypertensive population has concomitant thyroid diseases, more common in women （50-70 years）. Systematic surveillance for occult thyroid dysfunction in patients with hypertension could prevent future cardiovascular disease.
基金supported Jining Medical University National Nature Fund Cultivation Fund(No.JYP201733)
文摘Background Thyroid hormones(THs) including thyroxine(T4) and triiodothyronine(T3) with high biological activities have important effects on cardiovascular system by acting on renin-angiotensin-aldosterone system(RAAS), oxidative stress, mitochondria, endothelial cells, vascular smooth muscle cells(VSMC), cardiomyocytes, thyroid hormone receptor(TRs), cholesterol metabolism, insulin sensitivity, blood coagulation, etc. Excess or lack of THs is detrimental to cardiovascular function, so this article reviews the mechanism of THs on cardiovascular system.[S Chin J Cardiol 2019;20(4):269-279]
文摘Objective: There are clinical and laboratory associations between thyroid and liver diseases. Hepatitis C virus (HCV) is known to be responsible for both hepatic and extrahepatic diseases. The most frequent and clinically important endocrine extrahepatic diseases are thyroid disorders and type 2 diabetes mellitus. We aim to study the relationship between the serum level of thyroid hormones (THs) and the severity of liver disease in patients with chronic hepatitis C virus (CHC) infection. Methods: 60 patients with CHC infection were selected for the study. They were divided into two groups: with or without liver cirrhosis. Those with liver cirrhosis were further subdivided according to the Child-Turcotte-Pugh scoring system. Serum levels of free T3 (FT3), free T4 (FT4) and TSH were measured to all patients. Results: There was decrease in the FT3 and FT4 levels and increase in the TSH levels in patients with CHC with cirrhosis when compared to patients with CHC without cirrhosis. Conclusion: Thyroid profile abnormalities were seen in cirrhotic HCV patients when compared to non-cirrhotic patients. The abnormalities in the serum level of THs (decreased FT3, FT4, and increased TSH) are strongly associated with the severity of liver damage and advancing of the child score.
文摘This study aimed to assess the systemic effect of LLLT on thyroid gland functioning and consequently on calcium regulation through Triiodothyronine (T3) and Thyroxine (T4) measurements in rabbits’ serum. A total of thirty two New Zealand male rabbits were randomly distributed in four groups with eight animals each: control group C (nonirradiated animals), group EI (5 J/cm2 per session), group EII (10 J/cm2 per session) and group EIII (20 J/cm2 per session). All animals underwent lower left incisor extraction followed by immediate insertion of an osseintegrated implant, providing an equality of initial clinical condition between the groups. The experimental groups were irradiated with aluminium gallium arsenide diode laser (GaAlAs, λ = 830 nm, 50 mW, CW), during 13 days at each 48 hours, totalizing 7 sessions. Laboratorial T3 and T4 measurements were done in four distinct moments (before surgical procedure, immediately after surgical procedure, after the first LLLT session and after the last LLLT session) in all animals. The results obtained showed statistically significant differences in Triiodothyronine values between the groups throughout the experiment. It was concluded that the LLLT, in the protocol of irradiation used in this study, promoted a significantly alteration on rabbits’ serum hormonal levels.
文摘Thyroid metabolism is orchestrated by the action of various minerals and trace elements including iron, iodine, selenium, and zinc. Iron deficiency, specifically deficiency in serum ferritin levels, is one of the common causes of thyroid dysfunction. Our objective was to evaluate the relationship between serum ferritin levels and circulating thyroid hormones. For this, a retrospective analysis was performed on 16,512 individuals who tested for serum levels of ferritin and thyroid profile at Vibrant America Clinical Laboratories. Subjects were stratified based on the serum levels of ferritin. Age (p −0.03232, p < 0.0001). Analysis of Linear association by Pearson’s correlation exhibited a considerable correlation between varying serum ferritin levels with all tested thyroid hormones. The study concludes that serum ferritin levels were associated with thyroid hormone synthesis and metabolism in individuals with optimal levels of circulating ferritin.
基金supported by the Beijing Natural Science Foundation(grant number 7202010).
文摘Objective To investigate the association between thyroid hormone sensitivity indices and metabolic dysfunction-associated fatty liver disease(MAFLD)in euthyroid Chinese adults.Methods This cohort study included 5,356 euthyroid patients.The peripheral and central thyroid hormone sensitivity indices were calculated.Cox regression models were used to evaluate associations with MAFLD risk,and restricted cubic splines were used to assess potential nonlinearity.Mediation analyses based on an accelerated failure-time model were used to examine the role of the triglycerideglucose(TyG)index.Results MAFLD incidence in euthyroid participants was 18.26%.After adjustment,higher free thyroxine(FT4)levels were inversely associated with MAFLD(HR=0.973,95%CI:0.948 to 0.999,P=0.043),whereas higher free triiodothyronine(FT3)levels increased MAFLD risk(HR=1.118,95%CI:1.000 to 1.250,P=0.050).Enhanced thyroid hormone sensitivity,as reflected by elevated FT3/FT4 levels and lower total thyroxine resistance index(TT4RI),thyroid stimulating hormone index(TSHI),and thyroid feedback quantile-based index(TFQIFT4),was also associated with a higher incidence(all P<0.05).Mediation analyses indicated that TyG partially mediated the FT3/FT4-MAFLD and TFQIFT4-MAFLD associations,with indirect effects of-96.27(95%CI:-124.67 to-70.42)and-4.95(95%CI:-8.29 to-2.10),respectively.Conclusion Increased FT3/FT4 and decreased TFQIFT4 levels were significantly associated with a higher MAFLD risk in euthyroid adults,with TyG acting as a partial mediator.
文摘The uncorrected caption of Fig.2 read:Figure 2 Local conversion of T4 to T3 via D2 represses type I fibers,but stimulates the rapid type Ⅱ fibers.Thyroid hormones increase oxidative capacity due to increased mitochondrial content and protein activity.T3 stimulates UCP-3 expression that uncouples ATP synthesis(adapted from Shishmarev[59];Simonides and van Hardeveld[60]).
基金funded by the King Salman Center for Disability Research(RCS-0011-2017-PR)The project was approved by the Research Advisory Council,King Faisal Specialist Hospital,and Research Centre(RAC#2180005).
文摘We investigated the effects of prenatal bisphenol A (BPA) exposure on maternal thyroid hormones and fetal growth outcomes within a cohort from Saudi Arabia. In this prospective study, 672 pregnant women provided 1957 urine samples, which were analyzed for BPA concentrations using UPLC-MS/MS throughout three trimesters. We recorded BPA detection rates and median concentrations, using mixed-effects models to examine the influence on maternal thyroid hormones, specifically free thyroxine (FT4) and thyroid-stimulating hormone (TSH). Additionally, we explored the impact on fetal growth markers such as head circumference (HC) and placental weight (PWT) through multivariable regression, adjusting for confounders. Findings indicated that BPA was present in over 95 % of samples, with a notable decrease in median concentrations from the 1st to the 3rd trimester. Higher BPA exposure correlated with a 2.96 % increase in FT4 levels and a 14.58 % reduction in TSH in the top exposure quartile. Fetal growth analysis showed a decrease of 3.8 % in HC and 15.3 % in PWT associated with high first-trimester BPA levels. Furthermore, FT4 levels in the first and 2nd trimesters mediated the relationship between BPA exposure and fetal growth outcomes by 21.1 % for PWT and 19.1 % for HC, while gestational age mediated 12.1 % of the change in HC. The study highlights significant disruptions in thyroid function and detrimental effects on fetal development due to high BPA exposure, underscoring the need for rigorous monitoring and preventive measures during pregnancy.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most prevalent chronic liver disease worldwide,affecting approximately 32%-38%of the adult population and posing a growing public health burden.MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),progressive hepatic fibrosis,cirrhosis,and ultimately hepatocellular carcinoma(HCC).The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis,characterized by an imbalance among de novo lipogenesis,fatty acidβ-oxidation,and very-low-density lipoprotein(VLDL)-mediated lipid export.This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression.Among the multiple regulatory pathways involved,thyroid hormone(TH)signaling has emerged as a central regulator of hepatic metabolic homeostasis.The liver is a major peripheral target organ of TH action,where TH predominantly exerts its metabolic effects through thyroid hormone receptorβ(TRβ).Large-scale epidemiological studies and metaanalyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence,more severe histological injury,and advanced hepatic fibrosis,suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum.At the molecular level,TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis,enhancement of mitochondrial fatty acid oxidation,and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβaxis and non-genomic signaling pathways.Across different stages of MASLD,TH signaling exerts stagedependent protective effects.In the steatosis stage,TH improves metabolic flexibility by modulating insulin sensitivity,glucose metabolism,and lipid droplet clearance,thereby alleviating early lipotoxic stress.During progression to MASH,TH attenuates inflammatory amplification by improving mitochondrial homeostasis,suppressing activation of the NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome,and modulating the gut-liver axis microenvironment.In advanced stages,TH signaling influences hepatic stellate cell activation and extracellular matrix deposition,partly through interaction with the transforming growth factor-β(TGF-β)/SMAD pathway,while alterations in intrahepatic TH availability,mediated by dynamic changes in iodothyronine deiodinase 1(DIO1),contribute to fibrosis progression and hepatocellular dedifferentiation.In hepatocellular carcinoma,coordinated downregulation of TRβand DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression.The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom,a liver-targeted TRβ-selective agonist,for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis(F2-F3).This approval represents a landmark transition from mechanistic understanding to metabolismcentered precision therapy in MASLD.Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints,including MASH resolution and fibrosis regression,but also favorably modulates atherogenic lipid profiles,highlighting the therapeutic potential of selectively targeting hepatic TH pathways.This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of THbased interventions,aiming to inform future mechanistic research and optimize clinical management strategies.
基金funded by the National Natural Science Foundation of China(Grant No.42375184)the Research Funds of Center for Big Data and Population Health of IHM(Grant No.JKS2022011)the Natural Science Research Key Project of University of Anhui Province(Grant No.2023AH050652).
文摘Studies have indicated the different effects of PM_(2.5)components on human health.However,specific components that influence the severity of disease in schizophrenia patients and their underlying mechanisms remain unclear.Therefore,a repeated measures study for schizophrenia was constructed based on Anhui Mental Health Center.We collected information,including demographics and thyroid hormones(TH)levels,on repeat admissions of schizophrenia patients during 2017−2020,assessing their illness severity by positive and negative symptom scales(PANSS).Concentrations from the nearest component monitoring station in the 3 months before admission were assigned as the participant’s exposure level.We assessed the effects of PM_(2.5)components individually and in combination on schizophrenia and explored the mediating role of THs.Results indicated that benzo[a]pyrene,sulfate,nitrate,chloride,ammonia,cadmium,chromium,lead,selenium,and thallium exposure were associated with increased PANSS scores,with more significant results observed in males.Mixed exposure to PM_(2.5)components was found to be associated with increased PANSS scores and decreased free triiodothyronine(FT3).Mediation analysis suggested that the reduction in FT3 might mediate the association between the PM_(2.5)components and PANSS scores.The findings emphasize the impacts of PM_(2.5)components on schizophrenia and the potential value of focusing on changes in THs.
