Abnormal accumulation ofα-synuclein contributes to the formation of Lewy bodies in the substantia nigra,which is considered the typical pathological hallmark of Parkinson's disease.Recent research indicates that ...Abnormal accumulation ofα-synuclein contributes to the formation of Lewy bodies in the substantia nigra,which is considered the typical pathological hallmark of Parkinson's disease.Recent research indicates that angiotensin-(1-7)plays a crucial role in several neurodegenerative disorders,including Parkinson's disease,but the underlying mechanisms remain elusive.In this study,we used intraperitoneal administration of rotenone to male Sprague-Dawley rats for 4 weeks to establish a Parkinson's disease model.We investigated whether angiotensin-(1-7)is neuroprotective in this model by continuous administration of angiotensin-(1-7)into the right substantia nigra for 4 weeks.We found that angiotensin-(1-7)infusion relieved characteristic parkinsonian behaviors and reducedα-synuclein aggregation in the substantia nigra.Primary dopaminergic neurons were extracted from newborn Sprague-Dawley rat substantia nigras and treated with rotenone,angiotensin-(1-7),and/or the Mas receptor blocker A-779 for 24 hours.After binding to the Mas receptor,angiotensin-(1-7)attenuated apoptosis andα-synuclein aggregation in rotenone-treated cells.Primary dopaminergic neurons were also treated with angiotensin-(1-7)and/or the autophagy inhibitor 3-methyladenine for 24 hours.Angiotensin-(1-7)increasedα-synuclein removal and increased the autophagy of rotenone-treated cells.We conclude that angiotensin-(1-7)reducesα-synuclein aggregation by alleviating autophagy dysfunction in Parkinson's disease.Therefore,the angiotensin-(1-7)/Mas receptor axis plays an important role in the pathogenesis of Parkinson's disease and angiotensin-(1-7)has potential therapeutic value for Parkinson's disease.All experiments were approved by the Biological Research Ethics Committee of Nanjing First Hospital(approval No.DWSY-2000932)in January 2020.展开更多
AIM: To demonstrate the feasibility of mesenchymal stem cell(MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport of hypoxiainducible factor-1α small interfering RNA(HIF-1...AIM: To demonstrate the feasibility of mesenchymal stem cell(MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport of hypoxiainducible factor-1α small interfering RNA(HIF-1α si RNA) between MSCs and retinal pigment epithelial cells(RPE) under hypoxia environment.METHODS: Plasmid and lentivirus targeting the human HIF-1α gene were designed and constructed. HIF-1α si RNA was encapsulated into poly(lactic-co-glycolic acid) nanoparticles(PLGA-NPs) through the water-in-oil-in-water(w/o/w) multiple emulsion technique. The effect of PLGANPs uptake on the expression of HIF-1α m RNA was tested in RPE cells by real-time quantitative polymerase chain reaction(q PCR) and additional transfected conditions were used as control, including lentivirus group, nude plasmid group and blank PLGA group. MSCs were transfected with the NPs and the transfection efficacy was evaluated by flow cytometry. Transwell co-culture system of transfected MSCs and RPE cells was constructed under hypoxia environment. The effects of MSC-loaded HIF-1α si RNA PLGA-NPs on proliferation, apoptosis, and migration of RPE cells were then evaluated. The effect of transfected MSCs on HIF-1α expression of RPE cells was analyzed by using q PCR at the time points 24h, 3d, and 7d.RESULTS: The average diameter of PLGA-NPs loaded with HIF si RNA was 314.1 nm and the zeta potential was-0.36 m V. The transfection efficiency of PLGA-NPs was 67.3%±5.2% into MSCs by using flow cytometry. Compared with the lentivirus group, the PLGA-NPs loaded with HIF-1α si RNA can effectively reduce the expression of HIF-1α m RNA up to 7d in RPE(0.63±0.05 at 7d, P<0.001). In the Transwell co-culture system of transfected MSCs and RPE, the abilities of proliferation(2.34±0.17, 2.40±0.28, 2.47±0.24 at 48h, F=0.23, P=0.80), apoptosis(14.83%±2.43%, 12.94%±2.19%, 12.39%±3.21%;F=0.70, P=0.53) and migration(124.5±7.78, 119.5±5.32, 130±9.89, F=1.33, P=0.33) of the RPE cells had no differences between MSCloaded HIF-1α si RNA PLGA-NPs and other groups. The inhibition of PLGA on the HIF-1α m RNA expression in RPE cells could continue until the 7th day, the level of HIF-1α m RNA was lower than that of other groups(F=171.98, P<0.001). CONCLUSION: The delivery of PLGA-NPs loaded with HIF-1α si RNA carried by MSCs is found to be beneficial temporally for HIF-1α m RNA inhibition in RPE cells under hypoxia environment. The MSC-based bio-mimetic delivery of HIF-1α si RNA nanoparticles is a potential method for therapy against choroidal neovascularization.展开更多
The dipole species transformation and polarization relaxation configuration are achieved by changing the cobalt ion stoichiometry,which precisely tailors the electromagnetic attenuation performance of bismuth iron cob...The dipole species transformation and polarization relaxation configuration are achieved by changing the cobalt ion stoichiometry,which precisely tailors the electromagnetic attenuation performance of bismuth iron cobalt oxide.When the stoichiometric ratio of Fe:Co is 19:1,the optimal reflection loss reaches-60 dB.The high electromagnetic attenuation performance significantly improve the linear sensitivity of the strain response and active customized stealth capability of the designed multifunctional capacitor-like structure.Therefore,the wireless multifunctional design integrates energy attenuaten of electromagnetic wave with the wireless sensing and active camouflage functions for the first time.The work provides an important step for the realization of electromagnetical multifunctional applications including electromag-netic protection and electromagnetic sensing in artificial beings,medical health and even space travel.展开更多
基金supported by the National Natural Science Foundation of China,No.81801263(to QG)。
文摘Abnormal accumulation ofα-synuclein contributes to the formation of Lewy bodies in the substantia nigra,which is considered the typical pathological hallmark of Parkinson's disease.Recent research indicates that angiotensin-(1-7)plays a crucial role in several neurodegenerative disorders,including Parkinson's disease,but the underlying mechanisms remain elusive.In this study,we used intraperitoneal administration of rotenone to male Sprague-Dawley rats for 4 weeks to establish a Parkinson's disease model.We investigated whether angiotensin-(1-7)is neuroprotective in this model by continuous administration of angiotensin-(1-7)into the right substantia nigra for 4 weeks.We found that angiotensin-(1-7)infusion relieved characteristic parkinsonian behaviors and reducedα-synuclein aggregation in the substantia nigra.Primary dopaminergic neurons were extracted from newborn Sprague-Dawley rat substantia nigras and treated with rotenone,angiotensin-(1-7),and/or the Mas receptor blocker A-779 for 24 hours.After binding to the Mas receptor,angiotensin-(1-7)attenuated apoptosis andα-synuclein aggregation in rotenone-treated cells.Primary dopaminergic neurons were also treated with angiotensin-(1-7)and/or the autophagy inhibitor 3-methyladenine for 24 hours.Angiotensin-(1-7)increasedα-synuclein removal and increased the autophagy of rotenone-treated cells.We conclude that angiotensin-(1-7)reducesα-synuclein aggregation by alleviating autophagy dysfunction in Parkinson's disease.Therefore,the angiotensin-(1-7)/Mas receptor axis plays an important role in the pathogenesis of Parkinson's disease and angiotensin-(1-7)has potential therapeutic value for Parkinson's disease.All experiments were approved by the Biological Research Ethics Committee of Nanjing First Hospital(approval No.DWSY-2000932)in January 2020.
基金Supported by Key Research and Development Program of Shaanxi ProvinceChina (No.2020SF-267)+3 种基金the Natural Science Basis Research Plan in Shaanxi Province of China (No.2022JM-514)Bethune·Lumitin Research Funding for the Young and Middle-aged Ophthalmologists (No.BJ-LM2021011J)Xi’an Science and Technology Project [No.20YXYJ0008(3)]Research Incubation Fund of Xi’an People’s Hospital (Xi’an Fourth Hospital)(No.ZD-5, ZD-7, and ZD-8)。
文摘AIM: To demonstrate the feasibility of mesenchymal stem cell(MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport of hypoxiainducible factor-1α small interfering RNA(HIF-1α si RNA) between MSCs and retinal pigment epithelial cells(RPE) under hypoxia environment.METHODS: Plasmid and lentivirus targeting the human HIF-1α gene were designed and constructed. HIF-1α si RNA was encapsulated into poly(lactic-co-glycolic acid) nanoparticles(PLGA-NPs) through the water-in-oil-in-water(w/o/w) multiple emulsion technique. The effect of PLGANPs uptake on the expression of HIF-1α m RNA was tested in RPE cells by real-time quantitative polymerase chain reaction(q PCR) and additional transfected conditions were used as control, including lentivirus group, nude plasmid group and blank PLGA group. MSCs were transfected with the NPs and the transfection efficacy was evaluated by flow cytometry. Transwell co-culture system of transfected MSCs and RPE cells was constructed under hypoxia environment. The effects of MSC-loaded HIF-1α si RNA PLGA-NPs on proliferation, apoptosis, and migration of RPE cells were then evaluated. The effect of transfected MSCs on HIF-1α expression of RPE cells was analyzed by using q PCR at the time points 24h, 3d, and 7d.RESULTS: The average diameter of PLGA-NPs loaded with HIF si RNA was 314.1 nm and the zeta potential was-0.36 m V. The transfection efficiency of PLGA-NPs was 67.3%±5.2% into MSCs by using flow cytometry. Compared with the lentivirus group, the PLGA-NPs loaded with HIF-1α si RNA can effectively reduce the expression of HIF-1α m RNA up to 7d in RPE(0.63±0.05 at 7d, P<0.001). In the Transwell co-culture system of transfected MSCs and RPE, the abilities of proliferation(2.34±0.17, 2.40±0.28, 2.47±0.24 at 48h, F=0.23, P=0.80), apoptosis(14.83%±2.43%, 12.94%±2.19%, 12.39%±3.21%;F=0.70, P=0.53) and migration(124.5±7.78, 119.5±5.32, 130±9.89, F=1.33, P=0.33) of the RPE cells had no differences between MSCloaded HIF-1α si RNA PLGA-NPs and other groups. The inhibition of PLGA on the HIF-1α m RNA expression in RPE cells could continue until the 7th day, the level of HIF-1α m RNA was lower than that of other groups(F=171.98, P<0.001). CONCLUSION: The delivery of PLGA-NPs loaded with HIF-1α si RNA carried by MSCs is found to be beneficial temporally for HIF-1α m RNA inhibition in RPE cells under hypoxia environment. The MSC-based bio-mimetic delivery of HIF-1α si RNA nanoparticles is a potential method for therapy against choroidal neovascularization.
基金supported by the National Natural Science Foun-dation of China(Nos.51977009,11774027,51132002,11604237,52177014,and 51372282).
文摘The dipole species transformation and polarization relaxation configuration are achieved by changing the cobalt ion stoichiometry,which precisely tailors the electromagnetic attenuation performance of bismuth iron cobalt oxide.When the stoichiometric ratio of Fe:Co is 19:1,the optimal reflection loss reaches-60 dB.The high electromagnetic attenuation performance significantly improve the linear sensitivity of the strain response and active customized stealth capability of the designed multifunctional capacitor-like structure.Therefore,the wireless multifunctional design integrates energy attenuaten of electromagnetic wave with the wireless sensing and active camouflage functions for the first time.The work provides an important step for the realization of electromagnetical multifunctional applications including electromag-netic protection and electromagnetic sensing in artificial beings,medical health and even space travel.
