Objective： To establish a convenient and economic method to determine hepatoma-specific α-fetoprotein （HS- AFP） for diagnosis of hepatocellular carcinoma （HCC）. Methods： HS-AFP from serum of HCC patients was se...Objective： To establish a convenient and economic method to determine hepatoma-specific α-fetoprotein （HS- AFP） for diagnosis of hepatocellular carcinoma （HCC）. Methods： HS-AFP from serum of HCC patients was separated by a mini-column Lens culinaris agglutinin （LCA）-affinity chromatography. The levels of serum total AFP and separated HS-AFP were detected by radioimmunoassay （RIA）. Results： Circulating AFP was separated into three peaks （AFP-1, AFP-2, and AFP-3） by LCA-affinity chromatography. Dunng the elution course, the AFP-1 and AFP-2 could be eluted with TE buffer. HSAFP （AFP-3） from sera of HCC patients was eluted clearly on the LCA-sepharose gel mini-column with a solution containing α-methyI-D-mannoside. It was a part of total AFP and only found in sera of HCC patients. A ratio of more than 15% for HS-AFP to total AFP in serum was considered as a specific marker for HCC diagnosis with higher sensitivity （92.7%） and specificity （88.2%）. Conclusion： The new assay for circulating HS-AFP analysis is more sensitive, repeatable, and convenient. Its clinical application would be useful to early diagnosis of HCC.展开更多
Hsp90 is a specialized molecular chaperone that is capable of buffering the expression of abnormal phenotypes. Inhibition of Hsp90 activity results in the expression of these phenotypes that are otherwise masked. Sele...Hsp90 is a specialized molecular chaperone that is capable of buffering the expression of abnormal phenotypes. Inhibition of Hsp90 activity results in the expression of these phenotypes that are otherwise masked. Selection of offspring from the crossing of affected progenies results in inheritance and enrichment of these phenotypes, which can become independent of their original stimuli. The current combined evidence favours a model involving the interplay between genetics and epigenetics. The recent proteomics efforts to characterize the Hsp90 interaction networks provide further clues into the molecular mechanisms behind this complex phenomenon. This review summarizes the most recent experimental observations and briefly discusses the genetic and epigenetic views used in explaining the different observations.展开更多
Maternal stress during pregnancy is prevailing worldwide, which exposes fetuses to intrauterine hyper glucocorticoids(GC), programming offspring to obesity and metabolic diseases. Despite the importance of brown adipo...Maternal stress during pregnancy is prevailing worldwide, which exposes fetuses to intrauterine hyper glucocorticoids(GC), programming offspring to obesity and metabolic diseases. Despite the importance of brown adipose tissue(BAT) in maintaining long-term metabolic health, impacts of prenatal hyper GC on postnatal BAT thermogenesis and underlying regulations remain poorly defined. Pregnant mice were administrated with synthetic GC dexamethasone(DEX) at levels comparable to fetal GC exposure of stressed mothers. Prenatal GC exposure dose-dependently reduced BAT thermogenic activity, contributing to lower body temperature and higher mortality of neonates;such difference was abolished under thermoneutrality, underscoring BAT deficiency was the major contributor to adverse changes in postnatal thermogenesis due to excessive GC. Prenatal GC exposure highly activated Redd1 expression and reduced Ppargc1 a transcription from the alternative promoter(Ppargc1 a-AP) in neonatal BAT. During brown adipocyte differentiation, ectopic Redd1 expression reduced Ppargc1 a-AP expression and mitochondrial biogenesis;and the inhibitory effects of GC on mitochondrial biogenesis and Ppargc1 a-AP expression were blocked by Redd1 ablation. Redd1 reduced protein kinase A phosphorylation and suppressed cyclic adenosine monophosphate(c AMP)-responsive element-binding protein(CREB) binding to the c AMP regulatory element(CRE) in Ppargc1 a-AP promoter, leading to Ppargc1 a-AP inactivation. In summary, excessive maternal GC exposure during pregnancy dysregulates Redd1-Ppargc1 a-AP axis, which impairs fetal BAT development, hampering postnatal thermogenic adaptation and metabolic health of offspring.展开更多
基金grant from the Project of the Bureau of Science and Technology of Nantong (S30033).
文摘Objective： To establish a convenient and economic method to determine hepatoma-specific α-fetoprotein （HS- AFP） for diagnosis of hepatocellular carcinoma （HCC）. Methods： HS-AFP from serum of HCC patients was separated by a mini-column Lens culinaris agglutinin （LCA）-affinity chromatography. The levels of serum total AFP and separated HS-AFP were detected by radioimmunoassay （RIA）. Results： Circulating AFP was separated into three peaks （AFP-1, AFP-2, and AFP-3） by LCA-affinity chromatography. Dunng the elution course, the AFP-1 and AFP-2 could be eluted with TE buffer. HSAFP （AFP-3） from sera of HCC patients was eluted clearly on the LCA-sepharose gel mini-column with a solution containing α-methyI-D-mannoside. It was a part of total AFP and only found in sera of HCC patients. A ratio of more than 15% for HS-AFP to total AFP in serum was considered as a specific marker for HCC diagnosis with higher sensitivity （92.7%） and specificity （88.2%）. Conclusion： The new assay for circulating HS-AFP analysis is more sensitive, repeatable, and convenient. Its clinical application would be useful to early diagnosis of HCC.
文摘Hsp90 is a specialized molecular chaperone that is capable of buffering the expression of abnormal phenotypes. Inhibition of Hsp90 activity results in the expression of these phenotypes that are otherwise masked. Selection of offspring from the crossing of affected progenies results in inheritance and enrichment of these phenotypes, which can become independent of their original stimuli. The current combined evidence favours a model involving the interplay between genetics and epigenetics. The recent proteomics efforts to characterize the Hsp90 interaction networks provide further clues into the molecular mechanisms behind this complex phenomenon. This review summarizes the most recent experimental observations and briefly discusses the genetic and epigenetic views used in explaining the different observations.
基金This work was supported by the National Institute of Health(NIH R01-HD067449)。
文摘Maternal stress during pregnancy is prevailing worldwide, which exposes fetuses to intrauterine hyper glucocorticoids(GC), programming offspring to obesity and metabolic diseases. Despite the importance of brown adipose tissue(BAT) in maintaining long-term metabolic health, impacts of prenatal hyper GC on postnatal BAT thermogenesis and underlying regulations remain poorly defined. Pregnant mice were administrated with synthetic GC dexamethasone(DEX) at levels comparable to fetal GC exposure of stressed mothers. Prenatal GC exposure dose-dependently reduced BAT thermogenic activity, contributing to lower body temperature and higher mortality of neonates;such difference was abolished under thermoneutrality, underscoring BAT deficiency was the major contributor to adverse changes in postnatal thermogenesis due to excessive GC. Prenatal GC exposure highly activated Redd1 expression and reduced Ppargc1 a transcription from the alternative promoter(Ppargc1 a-AP) in neonatal BAT. During brown adipocyte differentiation, ectopic Redd1 expression reduced Ppargc1 a-AP expression and mitochondrial biogenesis;and the inhibitory effects of GC on mitochondrial biogenesis and Ppargc1 a-AP expression were blocked by Redd1 ablation. Redd1 reduced protein kinase A phosphorylation and suppressed cyclic adenosine monophosphate(c AMP)-responsive element-binding protein(CREB) binding to the c AMP regulatory element(CRE) in Ppargc1 a-AP promoter, leading to Ppargc1 a-AP inactivation. In summary, excessive maternal GC exposure during pregnancy dysregulates Redd1-Ppargc1 a-AP axis, which impairs fetal BAT development, hampering postnatal thermogenic adaptation and metabolic health of offspring.
