Background and Objectives:This study investigated the iodine status of pregnant women at an average altitude of approximately 2000 meters in Qujing,China.The relationship between iodine and thyroid function in differe...Background and Objectives:This study investigated the iodine status of pregnant women at an average altitude of approximately 2000 meters in Qujing,China.The relationship between iodine and thyroid function in different trimesters as well as adverse pregnancy and fetal outcomes were also investigated.Methods and Study Design:A total of 1,025 pregnant women who were admitted to Qujing Affiliated Hospital of Kunming Medical Univer sity from January 2019 to August 2021 were included.Urinary iodine concentration(UIC)was detected by color imetric method,and serum thyroid function was detected by chemiluminescence.Among them,537 pregnant women were followed up to analyze the association of iodine with adverse pregnancy and fetal outcomes.Re sults:The median UIC was 127μg/L.Serum triiodothyronine,thyroxine,free triiodothyronine,and free thyrox ine were negatively associated with urinary iodine concentration in the first and second trimesters of pregnancy.The proportion of pregnant women testing positive for thyroid peroxidase antibody(TPO-Ab)and the prevalence of thyroid autoimmunity(TAI)increased significantly in more-than-adequate iodine and excess iodine groups.Logistic regression analysis showed maternal iodine was not associated with adverse pregnancy and fetal out comes.Conclusions:Mild iodine deficiency is common among pregnant women in plateau areas of China.The relationship between iodine and thyroid function is significant in the first and second trimesters of pregnancy,es pecially in those with moderate to severe iodine deficiency.Abnormal iodine level in pregnant women was not significantly associated with adverse pregnancy and fetal outcomes in areas with predominantly mild iodine defi ciency.展开更多
The activation of hepatic stellate cells(HSCs),characterized by transdifferentiation from a quiescent state to a fibrogenic phenotype,is a core process of liver fibrosis.The metabolic reprogramming of HSCs plays a maj...The activation of hepatic stellate cells(HSCs),characterized by transdifferentiation from a quiescent state to a fibrogenic phenotype,is a core process of liver fibrosis.The metabolic reprogramming of HSCs plays a major role in this process to meet the high energy demands of myofibroblastic HSCs with multiple functions,such as extracellular matrix synthesis,migration,and proliferation.AMP-activated protein kinase(AMPK)is a gatekeeper of intracellular energy homeostasis,but its role in the activation of HSCs and the progression of liver fibrosis remains unclear.Here,we found that the phosphorylation of AMPK in HSCs was upregulated in liver tissues from metabolic dysfunction-associated steatohepatitis patients and from mice treated with carbon tetrachloride(CCl4)or bile duct ligation(BDL).HSC-specific deletion of two catalyticα-subunits of AMPK attenuated liver fibrosis in the CCl4 or BDL mouse model.In vitro analysis demonstrated that AMPK promoted HSC activation upon various profibrogenic stimuli.The activation of AMPKα-deficient HSCs was impaired due to the decreased mitochondrial oxidative phosphorylation but restored after treatment with the mitophagy inducer rapamycin.Mechanistically,both the AMPK–ULK1 and AMPK–Raptor pathways contribute to the maintenance of the mitophagy pathway and mitochondrial quality.These findings provide direct evidence of the crucial role of AMPK–mitophagy signaling in ensuring mitochondrial health and sufficient energy supply during HSC activation.In this study,AMPK was modulated in HSCs prior to activation,which is distinguished from previous investigations and thus provides new insights into the role of AMPK during distinct phases of HSC activation.展开更多
基金supported by Yunnan Province Basic Re search Special Program-Kunming Medical University Joint Special Program-Superficial Program(202101AY070001-226)Yunnan Provincial Science and Technology Talents and Plat form Program(202305AD160002)Kunming Medical Uni versity"14th Five-Year Plan"Key Discipline Construction Pro jects.The funders supported the costs of this study.
文摘Background and Objectives:This study investigated the iodine status of pregnant women at an average altitude of approximately 2000 meters in Qujing,China.The relationship between iodine and thyroid function in different trimesters as well as adverse pregnancy and fetal outcomes were also investigated.Methods and Study Design:A total of 1,025 pregnant women who were admitted to Qujing Affiliated Hospital of Kunming Medical Univer sity from January 2019 to August 2021 were included.Urinary iodine concentration(UIC)was detected by color imetric method,and serum thyroid function was detected by chemiluminescence.Among them,537 pregnant women were followed up to analyze the association of iodine with adverse pregnancy and fetal outcomes.Re sults:The median UIC was 127μg/L.Serum triiodothyronine,thyroxine,free triiodothyronine,and free thyrox ine were negatively associated with urinary iodine concentration in the first and second trimesters of pregnancy.The proportion of pregnant women testing positive for thyroid peroxidase antibody(TPO-Ab)and the prevalence of thyroid autoimmunity(TAI)increased significantly in more-than-adequate iodine and excess iodine groups.Logistic regression analysis showed maternal iodine was not associated with adverse pregnancy and fetal out comes.Conclusions:Mild iodine deficiency is common among pregnant women in plateau areas of China.The relationship between iodine and thyroid function is significant in the first and second trimesters of pregnancy,es pecially in those with moderate to severe iodine deficiency.Abnormal iodine level in pregnant women was not significantly associated with adverse pregnancy and fetal outcomes in areas with predominantly mild iodine defi ciency.
基金supported by grants from the National Natural Science Foundation of China(82130099 to J.L.)the Key New Drug Creation and Manufacturing Program of China(2019zX09201001-003-010 to Y.Z.)+2 种基金Shanghai Institute of Materia Medica(CASIMM0120225006-2 to J.L.)Taishan Scholar Foundation of Shandong Province(tstp0648 to J.L.)the Natural Science Foundation of Shandong Province(ZR2024QC378 to Hanmin Wang).
文摘The activation of hepatic stellate cells(HSCs),characterized by transdifferentiation from a quiescent state to a fibrogenic phenotype,is a core process of liver fibrosis.The metabolic reprogramming of HSCs plays a major role in this process to meet the high energy demands of myofibroblastic HSCs with multiple functions,such as extracellular matrix synthesis,migration,and proliferation.AMP-activated protein kinase(AMPK)is a gatekeeper of intracellular energy homeostasis,but its role in the activation of HSCs and the progression of liver fibrosis remains unclear.Here,we found that the phosphorylation of AMPK in HSCs was upregulated in liver tissues from metabolic dysfunction-associated steatohepatitis patients and from mice treated with carbon tetrachloride(CCl4)or bile duct ligation(BDL).HSC-specific deletion of two catalyticα-subunits of AMPK attenuated liver fibrosis in the CCl4 or BDL mouse model.In vitro analysis demonstrated that AMPK promoted HSC activation upon various profibrogenic stimuli.The activation of AMPKα-deficient HSCs was impaired due to the decreased mitochondrial oxidative phosphorylation but restored after treatment with the mitophagy inducer rapamycin.Mechanistically,both the AMPK–ULK1 and AMPK–Raptor pathways contribute to the maintenance of the mitophagy pathway and mitochondrial quality.These findings provide direct evidence of the crucial role of AMPK–mitophagy signaling in ensuring mitochondrial health and sufficient energy supply during HSC activation.In this study,AMPK was modulated in HSCs prior to activation,which is distinguished from previous investigations and thus provides new insights into the role of AMPK during distinct phases of HSC activation.
