The apoptosis repressor with caspase recruitment domain(ARC)plays a critical role in extrinsic apoptosis initiation via death receptor ligands,physiological stress,infection response in a tissue-dependent manner,endop...The apoptosis repressor with caspase recruitment domain(ARC)plays a critical role in extrinsic apoptosis initiation via death receptor ligands,physiological stress,infection response in a tissue-dependent manner,endoplasmic reticulum(ER)stress,genotoxic drugs,ionizing radiation,oxidative stress,and hypoxia.Recent studies have suggested that regulating apoptosis-related pathways can improve outcomes for patients with neurological diseases,such as hemorrhagic stroke.ARC expression is significantly correlated with acute cerebral hemorrhage.However,the mechanism by which it mediates the anti-apoptosis pathway remains poorly known.Here,we discuss the function of ARC in hemorrhagic stroke and argue that it could serve as an effective target for the treatment of hemorrhagic stroke.展开更多
目的:研究半胱氨酸天冬氨酸蛋白酶招募域家族分子10(caspase recruitment domain family member 10,CARD10)在肝癌组织中的表达,及其对肝癌进展尤其是凋亡抵抗的作用和机制。方法:采集2008年至2010年海军军医大学东方肝胆外科医院收治的...目的:研究半胱氨酸天冬氨酸蛋白酶招募域家族分子10(caspase recruitment domain family member 10,CARD10)在肝癌组织中的表达,及其对肝癌进展尤其是凋亡抵抗的作用和机制。方法:采集2008年至2010年海军军医大学东方肝胆外科医院收治的129例肝癌患者手术切除的肝癌及其癌旁组织标本,采用实时定量PCR法检测癌旁和肝癌组织中CARD10的表达,以Spearman等级相关统计学分析CARD10表达与肝癌分期的相关性。在CARD10质粒转染过表达以及RNA干扰敲减表达后,采用流式细胞术Annexin-V/PI标记法检测肝癌细胞株的凋亡,采用Western blotting检测肝癌细胞株中NF-κB信号的活化。结果:CARD10在肝癌组织中的表达较癌旁组织显著增高(P<0.01),且肝癌组织中CARD10的表达增高与肝癌分期进展呈正相关(P<0.01)。CARD10过表达可以抑制肝癌细胞株SMMC-7721和BEL-7402的凋亡,而敲减CARD10能够促进肝癌细胞株凋亡。CARD10过表达能够增强肝癌细胞株中促生存的NF-κB信号的活化,而CARD10敲减能够抑制NF-κB信号活化。结论:CARD10在肝癌组织中表达显著增高并与肝癌进展呈正相关,CARD10能够通过活化NF-κB信号进而促进肝癌细胞凋亡抵抗。展开更多
Objective: To investigate the mechanism of Chinese herbal medicine Dioscorea nipponica for the treatment of monosodium urate crystals-induced gouty arthritis(GA) in rats. Methods: Sixty male Wistar rats were divided i...Objective: To investigate the mechanism of Chinese herbal medicine Dioscorea nipponica for the treatment of monosodium urate crystals-induced gouty arthritis(GA) in rats. Methods: Sixty male Wistar rats were divided into 6 groups: normal, model, indomethacin and three total saponin(900, 300 and 100 mg/kg) groups. The liver, kidney and serum levels of lysosomal enzymes, antioxidant capacities, and inflammatory factors were measured. In addition, the m RNA and protein levels of the NALP3 inflammasome components in the mononuclear cells of rats’ peripheral blood were analyzed using real-time polymerase chain reaction and Western blotting methods, respectively. Results: Total saponins groups could reduce the activities of β-galactosidase,β-N acetyl glucosamine enzyme,β-glucuronidase, acid phosphatase, and malonaldehyde as wel as the contents of TNF-α, IL-1β and IL-8(all P<0.05). They could also increase the activities of glutathione peroxidase and total superoxide dismutase(both P<0.05). Further studies showed that total saponins groups of high, middle and low doses could all increase the m RNA and protein levels of caspase-1, adapter apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC) and NALP3 in the mononuclear cells of peripheral blood(all P<0.05). Conclusion: Dioscorea nipponica may treat GA by regulating lysosomal enzymes, antioxidant capacities and the NALP3 inflammasome.展开更多
基金supported by the Shanghai Hospital Development Center(grant number:SHDC2020CR3021A,to YG)the National Natural Science Foundation of China(grant number:82072788,to YG).
文摘The apoptosis repressor with caspase recruitment domain(ARC)plays a critical role in extrinsic apoptosis initiation via death receptor ligands,physiological stress,infection response in a tissue-dependent manner,endoplasmic reticulum(ER)stress,genotoxic drugs,ionizing radiation,oxidative stress,and hypoxia.Recent studies have suggested that regulating apoptosis-related pathways can improve outcomes for patients with neurological diseases,such as hemorrhagic stroke.ARC expression is significantly correlated with acute cerebral hemorrhage.However,the mechanism by which it mediates the anti-apoptosis pathway remains poorly known.Here,we discuss the function of ARC in hemorrhagic stroke and argue that it could serve as an effective target for the treatment of hemorrhagic stroke.
文摘目的:研究半胱氨酸天冬氨酸蛋白酶招募域家族分子10(caspase recruitment domain family member 10,CARD10)在肝癌组织中的表达,及其对肝癌进展尤其是凋亡抵抗的作用和机制。方法:采集2008年至2010年海军军医大学东方肝胆外科医院收治的129例肝癌患者手术切除的肝癌及其癌旁组织标本,采用实时定量PCR法检测癌旁和肝癌组织中CARD10的表达,以Spearman等级相关统计学分析CARD10表达与肝癌分期的相关性。在CARD10质粒转染过表达以及RNA干扰敲减表达后,采用流式细胞术Annexin-V/PI标记法检测肝癌细胞株的凋亡,采用Western blotting检测肝癌细胞株中NF-κB信号的活化。结果:CARD10在肝癌组织中的表达较癌旁组织显著增高(P<0.01),且肝癌组织中CARD10的表达增高与肝癌分期进展呈正相关(P<0.01)。CARD10过表达可以抑制肝癌细胞株SMMC-7721和BEL-7402的凋亡,而敲减CARD10能够促进肝癌细胞株凋亡。CARD10过表达能够增强肝癌细胞株中促生存的NF-κB信号的活化,而CARD10敲减能够抑制NF-κB信号活化。结论:CARD10在肝癌组织中表达显著增高并与肝癌进展呈正相关,CARD10能够通过活化NF-κB信号进而促进肝癌细胞凋亡抵抗。
基金Supported by the National Natural Science Foundation of China(Nos.81173618,81403156)China Postdoctoral Science Foundation(No.2015M57036)+2 种基金Heilongjiang Postdoctoral Special Assisted Fund(Nos.LBH-TZ0520,LBH-Z13191)Scientific Fund of Heilongjiang University of Chinese Medicine(No.2013bs05)the Outstanding Innovative Talent Support Programs of Heilongjiang University of Chinese Medicine
文摘Objective: To investigate the mechanism of Chinese herbal medicine Dioscorea nipponica for the treatment of monosodium urate crystals-induced gouty arthritis(GA) in rats. Methods: Sixty male Wistar rats were divided into 6 groups: normal, model, indomethacin and three total saponin(900, 300 and 100 mg/kg) groups. The liver, kidney and serum levels of lysosomal enzymes, antioxidant capacities, and inflammatory factors were measured. In addition, the m RNA and protein levels of the NALP3 inflammasome components in the mononuclear cells of rats’ peripheral blood were analyzed using real-time polymerase chain reaction and Western blotting methods, respectively. Results: Total saponins groups could reduce the activities of β-galactosidase,β-N acetyl glucosamine enzyme,β-glucuronidase, acid phosphatase, and malonaldehyde as wel as the contents of TNF-α, IL-1β and IL-8(all P<0.05). They could also increase the activities of glutathione peroxidase and total superoxide dismutase(both P<0.05). Further studies showed that total saponins groups of high, middle and low doses could all increase the m RNA and protein levels of caspase-1, adapter apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC) and NALP3 in the mononuclear cells of peripheral blood(all P<0.05). Conclusion: Dioscorea nipponica may treat GA by regulating lysosomal enzymes, antioxidant capacities and the NALP3 inflammasome.
