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
Objective:To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved,specifically focusing on the role of the caspase-3/gasdermin E(GSDME)signaling path...Objective:To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved,specifically focusing on the role of the caspase-3/gasdermin E(GSDME)signaling pathway and the impact of endoplasmic reticulum(ER)stress and autophagy.Methods: Necrostatin-1(Nec-1),lactate dehydrogenase release(LDH)assay,and Hoechst/propidium iodide(PI)double staining were employed to validate the mode of cell death.Western blot was used to detect the cleavage of GSDME and the expression of light chain 3(LC3)and BIP.Results: Celastrol induced cell swelling with large bubbles,which is consistent with the pyroptotic phenotype.Moreover,treatment with celastrol induced GSDME cleavage,indicating the activation of GSDME-mediated pyroptosis.GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells.In addition,cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells,suggesting that GSDME activation was induced by caspase-3.Mechanistically,celastrol induced endoplasmic reticulum(ER)stress and autophagy in HeLa cells,and other ER stress inducers produced effects consistent with those of celastrol.Conclusion: These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress,which may shed light on the potential antitumor clinical applications of celastrol.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
The newly invented farming method, Fenlong technology, uses self-propelled powder-ridging mechanical screw-type drill for the deep-cultivation and deep tillage of soil, and it can enhance the double tillering depth th...The newly invented farming method, Fenlong technology, uses self-propelled powder-ridging mechanical screw-type drill for the deep-cultivation and deep tillage of soil, and it can enhance the double tillering depth than the conventional tillage. Moreover, the tilth soil is uniform in size and in small, broken bits and loose. It expands the new soil ＂four warehouses＂ （namely soil nutrient warehouse, water warehouse, oxygen warehouse and microbial warehouse）, and under the conditions of ＂three no increase＂ in chemical fertilizer and pesticide, irrigation water and labor input, various crops show a increase of 10%-30% in yield （average increase by 25.48% in the 23 rice, wheat and corn planting areas of several provinces）, 5% in quality, and 1 time in water retention. And the sustainable production-increasing ef- fect lasts 2-3 years after once Fenlong tillage, with the comparative efficiency reaching about 20%. It is suggested using Fenlong to activate the arable land, saline land grassland and rivers resources, so as to drive the construction of green agriculture ＂3＋1＂ industrial system, which can promote the realization of the increases in available agricultural resource stock, quality food resource stock and available water resource stock in China and even in the world, realize the ＂two responses＂ to ecological environment deterioration and climate warming, and achieve the harmonious coexistence of human beings and nature.展开更多
A variety of spherical and structured activated charcoal supported Pt/Fe3O4 composites with an average particle size of ~100 nm have been synthesized by a self-assembly method using the difference of reduction potenti...A variety of spherical and structured activated charcoal supported Pt/Fe3O4 composites with an average particle size of ~100 nm have been synthesized by a self-assembly method using the difference of reduction potential between Pt （Ⅳ） and Fe （Ⅱ） precursors as driving force. The formed Fe3O4 nanoparticles （NPs） effectively prevent the aggregation of Pt nanocrystallites and promote the dispersion of Pt NPs on the surface of catalyst, which will be favorable for the exposure of Pt active sites for high-efficient adsorption and contact of substrate and hydrogen donor. The electron-enrichment state of Pt NPs donated by Fe304 nanocrystallites is corroborated by XPS measurement, which is responsible for promoting and activating the terminal C=O bond of adsorbed substrate via a vertical configuration. The experimental results show that the activated charcoal supported Pt/Fe3O4 catalyst exhibits 94.8% selectivity towards cinnamyl alcohol by the transfer hydrogenation of einnamaldehyde with Pt loading of 2.46% under the optimum conditions of 120 ℃ for 6 h, and 2-propanol as a hydrogen donor. Additionally, the present study demonstrates that a high-efficient and recyclable catalyst can be rapidly separated from the mixture due to its natural magnetism upon the application of magnetic field.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.
基金supported by grants from startup fund program at Beijing University of Chinese Medicine(90011451310011)key research fund for drug discovery in Chinese medicine at Beijing University of Chinese Medicine(1000061223476)startup fund program at Beijing University of Chinese Medicine(90020361220006).
文摘Objective:To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved,specifically focusing on the role of the caspase-3/gasdermin E(GSDME)signaling pathway and the impact of endoplasmic reticulum(ER)stress and autophagy.Methods: Necrostatin-1(Nec-1),lactate dehydrogenase release(LDH)assay,and Hoechst/propidium iodide(PI)double staining were employed to validate the mode of cell death.Western blot was used to detect the cleavage of GSDME and the expression of light chain 3(LC3)and BIP.Results: Celastrol induced cell swelling with large bubbles,which is consistent with the pyroptotic phenotype.Moreover,treatment with celastrol induced GSDME cleavage,indicating the activation of GSDME-mediated pyroptosis.GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells.In addition,cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells,suggesting that GSDME activation was induced by caspase-3.Mechanistically,celastrol induced endoplasmic reticulum(ER)stress and autophagy in HeLa cells,and other ER stress inducers produced effects consistent with those of celastrol.Conclusion: These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress,which may shed light on the potential antitumor clinical applications of celastrol.
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 Major Special Project for Science and Technology of Guangxi Province(Guike AA16380017)the Key Science and Technology Planning Project for Agriculture of Guangxi Province(201503)the Achievements Transformation of Guangxi Academy of Agricultural Sciences(Nongzhuancheng 201405)~~
文摘The newly invented farming method, Fenlong technology, uses self-propelled powder-ridging mechanical screw-type drill for the deep-cultivation and deep tillage of soil, and it can enhance the double tillering depth than the conventional tillage. Moreover, the tilth soil is uniform in size and in small, broken bits and loose. It expands the new soil ＂four warehouses＂ （namely soil nutrient warehouse, water warehouse, oxygen warehouse and microbial warehouse）, and under the conditions of ＂three no increase＂ in chemical fertilizer and pesticide, irrigation water and labor input, various crops show a increase of 10%-30% in yield （average increase by 25.48% in the 23 rice, wheat and corn planting areas of several provinces）, 5% in quality, and 1 time in water retention. And the sustainable production-increasing ef- fect lasts 2-3 years after once Fenlong tillage, with the comparative efficiency reaching about 20%. It is suggested using Fenlong to activate the arable land, saline land grassland and rivers resources, so as to drive the construction of green agriculture ＂3＋1＂ industrial system, which can promote the realization of the increases in available agricultural resource stock, quality food resource stock and available water resource stock in China and even in the world, realize the ＂two responses＂ to ecological environment deterioration and climate warming, and achieve the harmonious coexistence of human beings and nature.
基金This work is supported by the National Natural Science Foundation of China （No.51372248, No.51432009 and No.51502297）, Instrument Developing Project of the Chinese Academy of Sciences （No.yz201421）, the CAS/SAFEA International Partnership Program for Creative Research Teams of Chinese Academy of Sciences, China.
文摘A variety of spherical and structured activated charcoal supported Pt/Fe3O4 composites with an average particle size of ~100 nm have been synthesized by a self-assembly method using the difference of reduction potential between Pt （Ⅳ） and Fe （Ⅱ） precursors as driving force. The formed Fe3O4 nanoparticles （NPs） effectively prevent the aggregation of Pt nanocrystallites and promote the dispersion of Pt NPs on the surface of catalyst, which will be favorable for the exposure of Pt active sites for high-efficient adsorption and contact of substrate and hydrogen donor. The electron-enrichment state of Pt NPs donated by Fe304 nanocrystallites is corroborated by XPS measurement, which is responsible for promoting and activating the terminal C=O bond of adsorbed substrate via a vertical configuration. The experimental results show that the activated charcoal supported Pt/Fe3O4 catalyst exhibits 94.8% selectivity towards cinnamyl alcohol by the transfer hydrogenation of einnamaldehyde with Pt loading of 2.46% under the optimum conditions of 120 ℃ for 6 h, and 2-propanol as a hydrogen donor. Additionally, the present study demonstrates that a high-efficient and recyclable catalyst can be rapidly separated from the mixture due to its natural magnetism upon the application of magnetic field.
