Objective: To investigate the effects of emulsified isoflurane on hypoxic pulmonary artery endothelial cells (HPAECs) injury and orphan nuclear receptor subfamily 4A1 (NR4A1) expression. Methods: HPAECs were divided i...Objective: To investigate the effects of emulsified isoflurane on hypoxic pulmonary artery endothelial cells (HPAECs) injury and orphan nuclear receptor subfamily 4A1 (NR4A1) expression. Methods: HPAECs were divided into normal control group, model group and test group. Normal control group was cultured under normoxia. Cells in model group and test group were treated in a hypoxic chamber with oxygen concentration of about 3% (95% N2+ 5% CO2) for 2 h. The final concentration of 1 mmol·L-1 emulsified isoflurane was added to the test group, and 30% Intralipid? was added to the normal control group and the model group. MTT method was used to detect cell proliferation, Hoechst 33258 nuclear staining was used to detect cell apoptosis, Griess method was used to detect the production of NO in cell supernatant, and real-time fluorescence quantitative PCR (q-RT-PCR) was used to detect the expression of NR4A1 in cells. Results: After 12 h of intervention, the cell viability of normal control group, model group and test group were (98.45±2.41)%, (15.46±2.69)%, (79.52±4.16)%, the apoptosis rate were (2.51±0.36)%, (50.12±3.36)%, (22.15±3.42)%respectively, the concentration of NO in the culture supernatant were (59.52±4.1) μmol·L^-1, (25.16±4.85) μmol·L^-1, (43.58±6.19) μmol·L^-1, and the relative expression of NR4A1 were 1.00±0.09, 5.89±0.41, 2.39±0.24, respectively. The difference was statistically significant (P<0.05). Conclusion: Emulsified isoflurane can promote the proliferation, inhibit apoptosis and increase NO production of hypoxic HPAECs. NR4A1 may be involved in the endogenous protective mechanism of endothelial cell injury after hypoxia.展开更多
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well ...Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease. However, due to the its subtle nature and concurring events PDAC cure remains elusive. Nuclear receptors (NR) are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism, to growth and development. Given the nature of their ligands, NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases. There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages; nonetheless many aspects of their role are not fully understood. The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors, retinoic acid receptors, retinoid X receptor, androgen receptor, estrogen receptors and the orphan NR Nur, chicken ovalbumin upstream promoter transcription factor II and the liver receptor homologue-1 receptor to PDAC development, connections that could lead to the identification of novel therapies for this disease.展开更多
E2A is involved in promoting forkhead box P3（FOXP3） and retinoid-related orphan receptor gamma t（RORγt） gene transcription, which are pivotal transcription factors of T regulatory cells and Th17 cells, respective...E2A is involved in promoting forkhead box P3（FOXP3） and retinoid-related orphan receptor gamma t（RORγt） gene transcription, which are pivotal transcription factors of T regulatory cells and Th17 cells, respectively. Little is known about the involvement of E2 A in pregnancy process. This study aimed to investigate the expression of E2 A, cytotoxic T-lymphocyte-associated protein 4（CTLA-4）, and Foxp3 in luteal phase endometrium of women suffering recurrent miscarriage（RM）（n=21） and control group（n=11） by immunohistochemistry, with the Vectra？ automated quantitative pathology imaging system for analysis. The percentage of E2 A＋ cells and CTLA-4＋ cells was significantly higher in the endometrium of women with RM than in the controls. There was positive correlation between E2 A and CTLA-4（r=0.523, P=0.002）, E2 A and FOXP3（r=0.380, P=0.032）, and FOXP3 and CTLA-4（r=0.625, P=0.000） in the mid-secretory phase of endometrium for all subjects. It was concluded that the abnormal expression of endometrial E2 A existed in mid-secretory endometrium of women with RM, and there was a positive correlation between E2 A and FOXP3, and E2 A and CTLA-4, suggesting the possible regulation role of E2 A involved in regulating endometrium receptivity.展开更多
基金supported by the Seed Fund Program of Shanghai University of Medicine&Health Sciences(Grant No.HMSF-16-22-026).
文摘Objective: To investigate the effects of emulsified isoflurane on hypoxic pulmonary artery endothelial cells (HPAECs) injury and orphan nuclear receptor subfamily 4A1 (NR4A1) expression. Methods: HPAECs were divided into normal control group, model group and test group. Normal control group was cultured under normoxia. Cells in model group and test group were treated in a hypoxic chamber with oxygen concentration of about 3% (95% N2+ 5% CO2) for 2 h. The final concentration of 1 mmol·L-1 emulsified isoflurane was added to the test group, and 30% Intralipid? was added to the normal control group and the model group. MTT method was used to detect cell proliferation, Hoechst 33258 nuclear staining was used to detect cell apoptosis, Griess method was used to detect the production of NO in cell supernatant, and real-time fluorescence quantitative PCR (q-RT-PCR) was used to detect the expression of NR4A1 in cells. Results: After 12 h of intervention, the cell viability of normal control group, model group and test group were (98.45±2.41)%, (15.46±2.69)%, (79.52±4.16)%, the apoptosis rate were (2.51±0.36)%, (50.12±3.36)%, (22.15±3.42)%respectively, the concentration of NO in the culture supernatant were (59.52±4.1) μmol·L^-1, (25.16±4.85) μmol·L^-1, (43.58±6.19) μmol·L^-1, and the relative expression of NR4A1 were 1.00±0.09, 5.89±0.41, 2.39±0.24, respectively. The difference was statistically significant (P<0.05). Conclusion: Emulsified isoflurane can promote the proliferation, inhibit apoptosis and increase NO production of hypoxic HPAECs. NR4A1 may be involved in the endogenous protective mechanism of endothelial cell injury after hypoxia.
基金Supported by Fondo per gli Investimenti della Ricerca di Base(FIRB)(RBAP10MY35_002)by Ente Cassa di Risparmio di Firenzeby FiorGen ONLUS to Galli A
文摘Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease. However, due to the its subtle nature and concurring events PDAC cure remains elusive. Nuclear receptors (NR) are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism, to growth and development. Given the nature of their ligands, NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases. There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages; nonetheless many aspects of their role are not fully understood. The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors, retinoic acid receptors, retinoid X receptor, androgen receptor, estrogen receptors and the orphan NR Nur, chicken ovalbumin upstream promoter transcription factor II and the liver receptor homologue-1 receptor to PDAC development, connections that could lead to the identification of novel therapies for this disease.
基金supported by the grants from National Natural Science Foundation of China(No.81401276,No.81771618 and No.81771662)the Fund Project of Health and Family Planning Commission of Hubei Province(No.WJ2015MA006 and No.WJ2015Q017)
文摘E2A is involved in promoting forkhead box P3（FOXP3） and retinoid-related orphan receptor gamma t（RORγt） gene transcription, which are pivotal transcription factors of T regulatory cells and Th17 cells, respectively. Little is known about the involvement of E2 A in pregnancy process. This study aimed to investigate the expression of E2 A, cytotoxic T-lymphocyte-associated protein 4（CTLA-4）, and Foxp3 in luteal phase endometrium of women suffering recurrent miscarriage（RM）（n=21） and control group（n=11） by immunohistochemistry, with the Vectra？ automated quantitative pathology imaging system for analysis. The percentage of E2 A＋ cells and CTLA-4＋ cells was significantly higher in the endometrium of women with RM than in the controls. There was positive correlation between E2 A and CTLA-4（r=0.523, P=0.002）, E2 A and FOXP3（r=0.380, P=0.032）, and FOXP3 and CTLA-4（r=0.625, P=0.000） in the mid-secretory phase of endometrium for all subjects. It was concluded that the abnormal expression of endometrial E2 A existed in mid-secretory endometrium of women with RM, and there was a positive correlation between E2 A and FOXP3, and E2 A and CTLA-4, suggesting the possible regulation role of E2 A involved in regulating endometrium receptivity.
