Dopamine agonists (DA) are a first-line therapy for prolactinomas (PA). However, nearly 10% of prolactinomas do not respond to DA therapy. A considerable number of studies have shown that estrogen plays an importa...Dopamine agonists (DA) are a first-line therapy for prolactinomas (PA). However, nearly 10% of prolactinomas do not respond to DA therapy. A considerable number of studies have shown that estrogen plays an important role in the development of prolactinomas. However, the expression of estrogen receptors (ER) in prolactinomas has not been fully explored. Accordingly, we examined the levels of ESR1 and its subtypes A5-DeI-ESR1 and ESR2 mRNA in prolactinomas. In the present study,展开更多
In the present study, 7 day postnatal C57/BL6 wild-type mice (hyperoxia group) and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice (NR3A KO group) were exposed to 75% oxygen and 15% nitrogen...In the present study, 7 day postnatal C57/BL6 wild-type mice (hyperoxia group) and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice (NR3A KO group) were exposed to 75% oxygen and 15% nitrogen in a closed container for 5 days. Wild-type mice raised in normoxia served as controls. TdT-mediated dUTP nick end labeling (TUNEL)/neuron-specific nuclear protein (NeuN) and 5-bromo-2'-deoxyuridine (BrdU)/NeuN immunofluorescence staining showed that the number of apoptotic cells and the number of proliferative cells in the dentate subgranular zone significantly increased in the hyperoxia group compared with the control group. However, in the same hyperoxia environment, the number of apoptotic cells and the number of proliferative cells significantly decreased in the NR3A KO group compared with hyperoxia group. TUNEL+/NeuN+ and BrdU+/NeuN~ cells were observed in the NR3A KO and the hyperoxia groups. These results demonstrated that the NR3A gene can promote cell apoptosis and mediate the potential damage in the developing brain induced by exposure to non-physiologically high concentrations of oxygen.展开更多
To explore the functions of very low density lipoprotein receptor (VLDL-R) subtype II in lipoprotein metabolism and foam cells formation, the recombinant plasmid with the two subtypes cDNA was constructed respectively...To explore the functions of very low density lipoprotein receptor (VLDL-R) subtype II in lipoprotein metabolism and foam cells formation, the recombinant plasmid with the two subtypes cDNA was constructed respectively, the ldl-A7 cell lines were transfected and two cell lines expressing VLDL-R were obtained: one stably expressing the VLDLR with the O-linked sugar region (type I VLDLR) and the other without the O-linked sugar region (type II VLDLR). In the study on binding of VLDLR to their nuclein labeled natural ligands (VLDL and β-VLDL), it was found that surface binding of 125I-VLDL or 125I-β-VLDL of ldl-A7 cells transfected with type I VLDLR recombinant (ldl-A7-VRI) was more higher than that of ldl-A7 cells transfected with type II VLDLR recombinant (ldl-A7-VRII). After being incubated with VLDL for different time, the contents of triglyceride and total cholesterol in cells were mensurated, and the formation of foam cells and accumulation of lipid in cells was observed by oil-red O staining. The results showed that the contents of triglyceride and total cholesterol in ldl-A7-VR I were much higher than those in ldl-A7-VR II, and ldl-A7-VR I could transform into foam cells notably. It was suggested that type I VLDLR binds with relative higher affinity to VLDL and β-VLDL, and internalizes much more lipoprotein into cells. As a result, we can conclude that type I VLDLR plays a more important role in lipoprotein metabolism and foam cells formation than type II VLDLR.展开更多
3-Arylisothiazolo[5,4-b]quinolin-4(9H)-ones and 3-arylisoxazolo[5,4-b]quinolin-4(9H)-ones were synthesized and assayed for affinity for the benzodiazepine binding site of the GABAA receptors. While the 3-arylisothiazo...3-Arylisothiazolo[5,4-b]quinolin-4(9H)-ones and 3-arylisoxazolo[5,4-b]quinolin-4(9H)-ones were synthesized and assayed for affinity for the benzodiazepine binding site of the GABAA receptors. While the 3-arylisothiazoloquinolin-4-ones were found to be potent ligands, with affinities (expressed as the affinity Ki value) down to 1 nM, the 3-arylisoxazoloquinolin-4-ones are less potent. This is suggested to depend on sterical repulsive interaction of the 3-arylisoxazoloquinolin-4-ones with the receptor essential volume of the binding site, and a higher electron density at the nitrogen in the azole ring (N-2) as well as the carbonyl oxygen in the isothiazoloquinolin-4-ones enabling them to interact stronger with hydrogen bond donor sites at the binding site.展开更多
According to the classification presented by Lehmann BD(2016),triple-negative breast cancer(TNBC)is a heterogeneous group of malignant tumors with four specific subtypes:basal-like(subtype 1 and subtype 2),mesenchymal...According to the classification presented by Lehmann BD(2016),triple-negative breast cancer(TNBC)is a heterogeneous group of malignant tumors with four specific subtypes:basal-like(subtype 1 and subtype 2),mesenchymal,and luminal androgen receptor(LAR)subtypes.The basal-like subtypes of carcinomas predominate in this group,accounting for up to 80%of all cases.Despite the significantly lower proportions of mesenchymal and LAR variants in the group of breast carcinomas with a TNBC profile,such tumors are characterized by aggressive biological behavior.To this end,the LAR subtype is of particular interest,since the literature on such tumors presents different and even contradictory data concerning the disease course and prognosis.This review is devoted to the analysis of the relevant literature,reflecting the main results of studies on the molecular properties and clinical features of the disease course of LAR-type TNBC carcinomas.展开更多
Objective: To investigate in chronic hibernating myocardium in rabbits and the influence and significance of captopril, betaloc, valsartan in angiotensin Ⅱ subtype 1 receptor(AT1R), angiotensin Ⅱ subtype 2 recep...Objective: To investigate in chronic hibernating myocardium in rabbits and the influence and significance of captopril, betaloc, valsartan in angiotensin Ⅱ subtype 1 receptor(AT1R), angiotensin Ⅱ subtype 2 receptor(AT2R), extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase(JNK). Methods: The model of chronic hibernating myocardium(CHM) was established. The changes of AT1R, AT2R, ERK1/2, JNK in different groups were assessed by western blotting and immunohistochemistry. Results: The amount of AT1R decreased while AT2R increased in the CON group compared with in sham group, and both AT1R and AT2R decreased in drug groups compared with the CON group. The content of ERK had no change in each group, while that of "expression" p-ERK increased in CON group compared with in sham group, and was lower in drug intervention groups than in CON and sham groups. The contents of JNK and p-JNK decreased in CON and drug intervention groups compared with in sham group. The protein levels of JNK, p-JNK in drug intervention groups were lower than in the CON group. Three drugs can inhibit interstitial fibrosis and reduce apoptotic cells. The expression levels in the groups(with different doses) had statistical difference as well as between groups of captopril and other drugs; however the results between betaloc and valsartan had no significant difference. Conclusion: AT1R, AT2R may be the upper stream receptor of ERK and JNK and may participate in generation and evolution of CHM. Captopril, valsartan and betaloc may preserve CHM by inhibiting ATIR, AT2R and JNK activity.展开更多
基金supported by the Research Special Fund for Public Welfare Industry of Health(201402008)
文摘Dopamine agonists (DA) are a first-line therapy for prolactinomas (PA). However, nearly 10% of prolactinomas do not respond to DA therapy. A considerable number of studies have shown that estrogen plays an important role in the development of prolactinomas. However, the expression of estrogen receptors (ER) in prolactinomas has not been fully explored. Accordingly, we examined the levels of ESR1 and its subtypes A5-DeI-ESR1 and ESR2 mRNA in prolactinomas. In the present study,
基金supported by the National Institutes of Health, USA, No. NS 045810, NS 057255the BasicClinical Scientific Research Foundation Program of the Capital Medical University, China, No. 2006JL19
文摘In the present study, 7 day postnatal C57/BL6 wild-type mice (hyperoxia group) and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice (NR3A KO group) were exposed to 75% oxygen and 15% nitrogen in a closed container for 5 days. Wild-type mice raised in normoxia served as controls. TdT-mediated dUTP nick end labeling (TUNEL)/neuron-specific nuclear protein (NeuN) and 5-bromo-2'-deoxyuridine (BrdU)/NeuN immunofluorescence staining showed that the number of apoptotic cells and the number of proliferative cells in the dentate subgranular zone significantly increased in the hyperoxia group compared with the control group. However, in the same hyperoxia environment, the number of apoptotic cells and the number of proliferative cells significantly decreased in the NR3A KO group compared with hyperoxia group. TUNEL+/NeuN+ and BrdU+/NeuN~ cells were observed in the NR3A KO and the hyperoxia groups. These results demonstrated that the NR3A gene can promote cell apoptosis and mediate the potential damage in the developing brain induced by exposure to non-physiologically high concentrations of oxygen.
基金This project was supported by a grant from National Natu-ral Sciences Foundation of China (No .30300134)
文摘To explore the functions of very low density lipoprotein receptor (VLDL-R) subtype II in lipoprotein metabolism and foam cells formation, the recombinant plasmid with the two subtypes cDNA was constructed respectively, the ldl-A7 cell lines were transfected and two cell lines expressing VLDL-R were obtained: one stably expressing the VLDLR with the O-linked sugar region (type I VLDLR) and the other without the O-linked sugar region (type II VLDLR). In the study on binding of VLDLR to their nuclein labeled natural ligands (VLDL and β-VLDL), it was found that surface binding of 125I-VLDL or 125I-β-VLDL of ldl-A7 cells transfected with type I VLDLR recombinant (ldl-A7-VRI) was more higher than that of ldl-A7 cells transfected with type II VLDLR recombinant (ldl-A7-VRII). After being incubated with VLDL for different time, the contents of triglyceride and total cholesterol in cells were mensurated, and the formation of foam cells and accumulation of lipid in cells was observed by oil-red O staining. The results showed that the contents of triglyceride and total cholesterol in ldl-A7-VR I were much higher than those in ldl-A7-VR II, and ldl-A7-VR I could transform into foam cells notably. It was suggested that type I VLDLR binds with relative higher affinity to VLDL and β-VLDL, and internalizes much more lipoprotein into cells. As a result, we can conclude that type I VLDLR plays a more important role in lipoprotein metabolism and foam cells formation than type II VLDLR.
基金Financial support from the Swedish Board for Scientific Research(VR),the Knut and Alice Wallenberg Foundation,the Research School for Pharmaceutical Sciences at Lund University,Carlsberg Foundation,Denmark,and the NeuroScience PharmaBiotec Research Center,Den-mark,is gratefully acknowledged.
文摘3-Arylisothiazolo[5,4-b]quinolin-4(9H)-ones and 3-arylisoxazolo[5,4-b]quinolin-4(9H)-ones were synthesized and assayed for affinity for the benzodiazepine binding site of the GABAA receptors. While the 3-arylisothiazoloquinolin-4-ones were found to be potent ligands, with affinities (expressed as the affinity Ki value) down to 1 nM, the 3-arylisoxazoloquinolin-4-ones are less potent. This is suggested to depend on sterical repulsive interaction of the 3-arylisoxazoloquinolin-4-ones with the receptor essential volume of the binding site, and a higher electron density at the nitrogen in the azole ring (N-2) as well as the carbonyl oxygen in the isothiazoloquinolin-4-ones enabling them to interact stronger with hydrogen bond donor sites at the binding site.
文摘According to the classification presented by Lehmann BD(2016),triple-negative breast cancer(TNBC)is a heterogeneous group of malignant tumors with four specific subtypes:basal-like(subtype 1 and subtype 2),mesenchymal,and luminal androgen receptor(LAR)subtypes.The basal-like subtypes of carcinomas predominate in this group,accounting for up to 80%of all cases.Despite the significantly lower proportions of mesenchymal and LAR variants in the group of breast carcinomas with a TNBC profile,such tumors are characterized by aggressive biological behavior.To this end,the LAR subtype is of particular interest,since the literature on such tumors presents different and even contradictory data concerning the disease course and prognosis.This review is devoted to the analysis of the relevant literature,reflecting the main results of studies on the molecular properties and clinical features of the disease course of LAR-type TNBC carcinomas.
基金the Natural Science Fundfor Colleges and Universities in Jiangsu Province(03KJB320145)the Science and Technology projects fund of Xuzhou city(X2002036)
文摘Objective: To investigate in chronic hibernating myocardium in rabbits and the influence and significance of captopril, betaloc, valsartan in angiotensin Ⅱ subtype 1 receptor(AT1R), angiotensin Ⅱ subtype 2 receptor(AT2R), extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase(JNK). Methods: The model of chronic hibernating myocardium(CHM) was established. The changes of AT1R, AT2R, ERK1/2, JNK in different groups were assessed by western blotting and immunohistochemistry. Results: The amount of AT1R decreased while AT2R increased in the CON group compared with in sham group, and both AT1R and AT2R decreased in drug groups compared with the CON group. The content of ERK had no change in each group, while that of "expression" p-ERK increased in CON group compared with in sham group, and was lower in drug intervention groups than in CON and sham groups. The contents of JNK and p-JNK decreased in CON and drug intervention groups compared with in sham group. The protein levels of JNK, p-JNK in drug intervention groups were lower than in the CON group. Three drugs can inhibit interstitial fibrosis and reduce apoptotic cells. The expression levels in the groups(with different doses) had statistical difference as well as between groups of captopril and other drugs; however the results between betaloc and valsartan had no significant difference. Conclusion: AT1R, AT2R may be the upper stream receptor of ERK and JNK and may participate in generation and evolution of CHM. Captopril, valsartan and betaloc may preserve CHM by inhibiting ATIR, AT2R and JNK activity.