In Alzheimer’s disease (AD) there is a loss of neurons in different areas of the brain, including hippocampus, temporal and frontal cortex. Molecular mechanism of neuronal death in AD is not clear. It seems that apop...In Alzheimer’s disease (AD) there is a loss of neurons in different areas of the brain, including hippocampus, temporal and frontal cortex. Molecular mechanism of neuronal death in AD is not clear. It seems that apoptosis is a major form of neuronal cell death in this neurodegenerative disease. Neurons in both experimental animals and AD brains showed apoptotic changes, including DNA fragmentation, microRNA expression and caspase-3 activation. Activated caspase-3 may lead to amyloid precursor protein (APP) cleavage, extracellular senile plaques (SPs) and intracellular neurofibrillary tangles (NFTs) formation and neuronal loss, and it contributes to synaptic plasticity and cognitive dysfunction, especially in early stage of AD. Moreover, changes of caspase-3 activity were observed after therapy with memantine (NMDA receptor antagonist), donepezil and ladostigil (acetylcholinesterase inhibitors) in AD patients. It has been shown that both mementine and acetylcholinesterase inhibitors protect neurons from the caspase-3 activation. It seems that caspase-3 may be a potential diagnostic factor and target for pharmacotherapy of AD patients.展开更多
目的探讨三黄连合剂通过NOD样受体蛋白3(NOD-like receptor protein domain associated protein 3,NLRP3)/凋亡相关颗粒样蛋白(apoptosis-associated speck-like protein containing a CARD,ASC)/半胱氨酸天冬氨酸蛋白酶1(cysteine aspa...目的探讨三黄连合剂通过NOD样受体蛋白3(NOD-like receptor protein domain associated protein 3,NLRP3)/凋亡相关颗粒样蛋白(apoptosis-associated speck-like protein containing a CARD,ASC)/半胱氨酸天冬氨酸蛋白酶1(cysteine aspartic acid specific protease-1,Caspase-1)通路对哮喘患儿气道炎症的作用及机制。方法选取2021年1月—2023年10月就诊的90例哮喘患儿,采用数字表法随机分为观察组与对照组,各45例。观察2组哮喘患儿不良反应、1 s用力呼气容积(forced expiratory volume in the first second,FEV_(1)%)、最大呼气流量(peak expiratory flow,PEF)、用力肺活量(forced vital capacity,FVC)、白细胞介素-1β(interleukin-1β,IL-1β)及TNF-α(tumor necrosis factor-α,TNF-α)表达水平差异。结果观察组不良反应发生率为6.66%,对照组为11.11%,差异无统计学意义(P>0.05)。观察组总有效率为95.56%,高于对照组的80.00%(P<0.05)。治疗后FEV_(1)%、PEF、FVC、哮喘控制测试表(asthma control test,ACT)评分高于对照组(P<0.05)。治疗后观察组血清IL-1β、IL-6、IL-8、IL-17、IL-18水平低于对照组(P<0.05)。治疗后观察组患儿血清NLRP3、ASC、Caspase-1、IL-1β蛋白表达水平低于对照组(P<0.05)。结论三黄连合剂治疗能减轻哮喘患儿气道炎症反应,降低炎症因子水平,改善肺功能,减轻病情,提高疗效,其可能通过NLRP3/ASC/Caspase-1通路发挥作用。展开更多
Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid ...Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.展开更多
文摘In Alzheimer’s disease (AD) there is a loss of neurons in different areas of the brain, including hippocampus, temporal and frontal cortex. Molecular mechanism of neuronal death in AD is not clear. It seems that apoptosis is a major form of neuronal cell death in this neurodegenerative disease. Neurons in both experimental animals and AD brains showed apoptotic changes, including DNA fragmentation, microRNA expression and caspase-3 activation. Activated caspase-3 may lead to amyloid precursor protein (APP) cleavage, extracellular senile plaques (SPs) and intracellular neurofibrillary tangles (NFTs) formation and neuronal loss, and it contributes to synaptic plasticity and cognitive dysfunction, especially in early stage of AD. Moreover, changes of caspase-3 activity were observed after therapy with memantine (NMDA receptor antagonist), donepezil and ladostigil (acetylcholinesterase inhibitors) in AD patients. It has been shown that both mementine and acetylcholinesterase inhibitors protect neurons from the caspase-3 activation. It seems that caspase-3 may be a potential diagnostic factor and target for pharmacotherapy of AD patients.
文摘目的探讨三黄连合剂通过NOD样受体蛋白3(NOD-like receptor protein domain associated protein 3,NLRP3)/凋亡相关颗粒样蛋白(apoptosis-associated speck-like protein containing a CARD,ASC)/半胱氨酸天冬氨酸蛋白酶1(cysteine aspartic acid specific protease-1,Caspase-1)通路对哮喘患儿气道炎症的作用及机制。方法选取2021年1月—2023年10月就诊的90例哮喘患儿,采用数字表法随机分为观察组与对照组,各45例。观察2组哮喘患儿不良反应、1 s用力呼气容积(forced expiratory volume in the first second,FEV_(1)%)、最大呼气流量(peak expiratory flow,PEF)、用力肺活量(forced vital capacity,FVC)、白细胞介素-1β(interleukin-1β,IL-1β)及TNF-α(tumor necrosis factor-α,TNF-α)表达水平差异。结果观察组不良反应发生率为6.66%,对照组为11.11%,差异无统计学意义(P>0.05)。观察组总有效率为95.56%,高于对照组的80.00%(P<0.05)。治疗后FEV_(1)%、PEF、FVC、哮喘控制测试表(asthma control test,ACT)评分高于对照组(P<0.05)。治疗后观察组血清IL-1β、IL-6、IL-8、IL-17、IL-18水平低于对照组(P<0.05)。治疗后观察组患儿血清NLRP3、ASC、Caspase-1、IL-1β蛋白表达水平低于对照组(P<0.05)。结论三黄连合剂治疗能减轻哮喘患儿气道炎症反应,降低炎症因子水平,改善肺功能,减轻病情,提高疗效,其可能通过NLRP3/ASC/Caspase-1通路发挥作用。
基金supported by the National Natural Science Foundation of China(NSFC)(81973316,82173807)the China Postdoctoral Science Foundation(2020M681914)+1 种基金the Fund from Tianjin Municipal Health Commission(ZC200093)the Open Fund of Tianjin Central Hospital of Obstetrics and Gynecology/Tianjin Key Laboratory of human development and reproductive regulation(2021XHY01)。
文摘Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.