Class A scavenger receptor(SR-A) plays an important role in foam cell formation.However, the mechanism underlying the internalization of the receptor-ligand complexes remains unclear.The aim of the present study was t...Class A scavenger receptor(SR-A) plays an important role in foam cell formation.However, the mechanism underlying the internalization of the receptor-ligand complexes remains unclear.The aim of the present study was to investigate the molecular mechanism to regulate SR-A-mediated intracellular lipid accumulation in macrophages A pull-clown assay was performed and glucoseregulated protein 78(GRP78) was identified to bind with the cytoplasmic domain of SR-A(CSR-A).Immunoprecipitation and artificially expressed protein binding assay demonstrated the direct specific binding of GRP78 with SR-A in cells.Indirect immunofluorescence assay and western blot analysis showed their co-localization in membrane and cytoplasm.Over-expression of GRP78 specifically inhibited SR-A-mediated uptake of fluorescent acetylated low-density lipoprotein, a specific ligand for SR-A, without altering cellular SR-A expression and binding ability, and significantly inhibited cholesterol ester accumulation in cells, which can be partly attributed to the suppression of c-Jun-NH2-terminal kinase signaling pathway.These results suggest that GRP78 may act as an inhibitor of SR-A-mediated internalization of modified low-density lipoprotein into macrophages(C) 2009 Elsevier Inc.All rights reserved.展开更多
Objective To explore the relationship between different obesity indicators and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 1 762 T2DM patients who visited ...Objective To explore the relationship between different obesity indicators and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 1 762 T2DM patients who visited the Endocrinology Department of Changzhou Second People’s Hospital Affiliated to Nanjing Medical University and the Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Traditional Chinese Medicine from January2019 to February 2022 were enrolled in this study.展开更多
AIM: To investigate the role of perioperative chemoradiotherapy (CRT) in the treatment of locally advanced thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Using preoperative computed tomography (CT)-based...AIM: To investigate the role of perioperative chemoradiotherapy (CRT) in the treatment of locally advanced thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Using preoperative computed tomography (CT)-based staging criteria, 238 patients with ESCC (stage ⅡⅢ ) were enrolled in this prospective study between January 1997 and June 2004. With informed consent, patients were randomized into 3 groups: preoperative CRT (80 cases), postoperative CRT (78 cases) and surgery alone (S) (80 cases). The 1-, 3-, 5and 10-year survival were followed up. Progressionfree survival (PFS) was chosen as the primary endpoint by treatment arm measured from study entry until documented progression of disease or death from any cause. The secondary endpoint was overall survival (OS) determined as the time (in months) between the date of therapy and the date of death. Other objectives were surgical and adjuvant therapy complications.RESULTS: With median follow-up of 45 mo for all the enrolled patients, significant differences in the 1-, 3-, 5-, 10-year OS (91.3%, 63.5%, 43.5%, 24.5% vs 91%, 62.8%, 42.3%, 24.4% vs 87.5%, 51.3%, 33.8%, 12.5%, P = 0.0176) and PFS (89.3%, 61.3%, 37.5%, 18.1% vs 89.1%, 61.1%, 37.2%, 17.8% vs 84.5%, 49.3%, 25.9%, 6.2%, P = 0.0151) were detected among the 3 arms. There were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm (P > 0.05). For the patients who had radical resection, significant differences in median PFS (48 mo vs 61 mo vs 39.5 mo, P = 0.0331) and median OS (56.5 mo vs 72 mo vs 41.5 mo, P = 0.0153) were detected among the 3 arms, but there were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm (P > 0.05). The local recurrence rates in the preoperative CRT, postoperative CRT group and S group were 11.3%, 14.1% and 35%, respectively (P < 0.05). No significant differences were detected among the 3 groups when comparing complications but tended to be in favor of the postoperative CRT and S groups (P > 0.05). Toxicities of CRT in the preoperative or postoperative CRT arms were mostly moderate, and could be quickly alleviated by adequate therapy. CONCLUSION: Rational application of preoperative or postoperative CRT can provide a benefit in PFS and OS in patients with locally advanced ESCC.展开更多
文摘Class A scavenger receptor(SR-A) plays an important role in foam cell formation.However, the mechanism underlying the internalization of the receptor-ligand complexes remains unclear.The aim of the present study was to investigate the molecular mechanism to regulate SR-A-mediated intracellular lipid accumulation in macrophages A pull-clown assay was performed and glucoseregulated protein 78(GRP78) was identified to bind with the cytoplasmic domain of SR-A(CSR-A).Immunoprecipitation and artificially expressed protein binding assay demonstrated the direct specific binding of GRP78 with SR-A in cells.Indirect immunofluorescence assay and western blot analysis showed their co-localization in membrane and cytoplasm.Over-expression of GRP78 specifically inhibited SR-A-mediated uptake of fluorescent acetylated low-density lipoprotein, a specific ligand for SR-A, without altering cellular SR-A expression and binding ability, and significantly inhibited cholesterol ester accumulation in cells, which can be partly attributed to the suppression of c-Jun-NH2-terminal kinase signaling pathway.These results suggest that GRP78 may act as an inhibitor of SR-A-mediated internalization of modified low-density lipoprotein into macrophages(C) 2009 Elsevier Inc.All rights reserved.
文摘Objective To explore the relationship between different obesity indicators and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 1 762 T2DM patients who visited the Endocrinology Department of Changzhou Second People’s Hospital Affiliated to Nanjing Medical University and the Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Traditional Chinese Medicine from January2019 to February 2022 were enrolled in this study.
文摘AIM: To investigate the role of perioperative chemoradiotherapy (CRT) in the treatment of locally advanced thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Using preoperative computed tomography (CT)-based staging criteria, 238 patients with ESCC (stage ⅡⅢ ) were enrolled in this prospective study between January 1997 and June 2004. With informed consent, patients were randomized into 3 groups: preoperative CRT (80 cases), postoperative CRT (78 cases) and surgery alone (S) (80 cases). The 1-, 3-, 5and 10-year survival were followed up. Progressionfree survival (PFS) was chosen as the primary endpoint by treatment arm measured from study entry until documented progression of disease or death from any cause. The secondary endpoint was overall survival (OS) determined as the time (in months) between the date of therapy and the date of death. Other objectives were surgical and adjuvant therapy complications.RESULTS: With median follow-up of 45 mo for all the enrolled patients, significant differences in the 1-, 3-, 5-, 10-year OS (91.3%, 63.5%, 43.5%, 24.5% vs 91%, 62.8%, 42.3%, 24.4% vs 87.5%, 51.3%, 33.8%, 12.5%, P = 0.0176) and PFS (89.3%, 61.3%, 37.5%, 18.1% vs 89.1%, 61.1%, 37.2%, 17.8% vs 84.5%, 49.3%, 25.9%, 6.2%, P = 0.0151) were detected among the 3 arms. There were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm (P > 0.05). For the patients who had radical resection, significant differences in median PFS (48 mo vs 61 mo vs 39.5 mo, P = 0.0331) and median OS (56.5 mo vs 72 mo vs 41.5 mo, P = 0.0153) were detected among the 3 arms, but there were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm (P > 0.05). The local recurrence rates in the preoperative CRT, postoperative CRT group and S group were 11.3%, 14.1% and 35%, respectively (P < 0.05). No significant differences were detected among the 3 groups when comparing complications but tended to be in favor of the postoperative CRT and S groups (P > 0.05). Toxicities of CRT in the preoperative or postoperative CRT arms were mostly moderate, and could be quickly alleviated by adequate therapy. CONCLUSION: Rational application of preoperative or postoperative CRT can provide a benefit in PFS and OS in patients with locally advanced ESCC.
