Interleukin 17A(IL-17A)was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications.However,the role of IL-17A in diabetic encephalopathy remains poorly understood.In this...Interleukin 17A(IL-17A)was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications.However,the role of IL-17A in diabetic encephalopathy remains poorly understood.In this study,we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a-/-mice with spontaneously diabetic Ins2^(Akita)(Akita)mice.Blood glucose levels and body weights were monitored from 2-32 weeks of age.When mice were 32 weeks of age,behavioral tests were performed,including a novel object recognition test for assessing short-term memory and learning and a Morris water maze test for evaluating hippocampus-dependent spatial learning and memory.IL-17A levels in the serum,cerebrospinal fluid,and hippocampus were detected with enzyme-linked immunosorbent assays and real-time quantitative polymerase chain reaction.Moreover,proteins related to cognitive dysfunction(amyloid precursor protein,β-amyloid cleavage enzyme 1,p-tau,and tau),apoptosis(caspase-3 and-9),inflammation(inducible nitric oxide synthase and cyclooxygenase 2),and occludin were detected by western blot assays.Pro-inflammatory cytokines including tumor necrosis factor-α,interleukin-1β,and interferon-γin serum and hippocampal tissues were measured by enzyme-linked immunosorbent assays.Microglial activation and hippocampal neuronal apoptosis were detected by immunofluorescent staining.Compared with that in wild-type mice,mice with diabetic encephalopathy had higher IL-17A levels in the serum,cerebrospinal fluid,and hippocampus;downregulation of occludin expression;lower cognitive ability;greater loss of hippocampal neurons;increased microglial activation;and higher expression of inflammatory factors in the serum and hippocampus.IL-17A knockout attenuated the abovementioned changes in mice with diabetic encephalopathy.These findings suggest that IL-17A participates in the pathological process of diabetic encephalopathy.Furthermore,IL-17A deficiency reduces diabetic encephalopathy-mediated neuroinflammation and cognitive defects.These results highlight a role for IL-17A as a mediator of diabetic encephalopathy and potential target for the treatment of cognitive impairment induced by diabetic encephalopathy.展开更多
An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery.Our previous ...An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery.Our previous study has identified transient receptor potential channel 3(TRPC3)and TRPC6 as cation channels through which most of the damaging calcium enters,aggravates pathological changes in vivo and increases ischemia/reperfusion(I/R)injury in mice.This study aimed to verify the effects of TRPC3 inhibitor Pyr3 on myocardial I/R injury in mice.C57BL/6J wild-type male mice(8 to 12 weeks old)were anesthetized with 3.3%chloral hydrate.A murine I(30 min)/R(24 h)injury model was established by temporary occlusion of the left anterior descending(LAD)coronary artery.Pyr3 was administered at concentrations of 0,2.5,5,or 10 mg/kg via the right jugular vein 5 min before reperfusion.We observed that the selective TRPC3 inhibitor,10 mg/kg Pyr3,significantly decreased the infarct size of left ventricle,and reduced the myocardial cell apoptosis rate and inflammatory response in mice.In a conclusion,TRPC3 can function as a candidate target for I/R injury prevention,and Pyr3 may directly bind to TRPC3 channel protein,inhibit TRPC3 channel activity,and improve TRPC3-related myocardial I/R injury.Pyr3 may be used for clarification of TRPC3 functions and for treatments of TRPC3-mediated diseases.展开更多
A novel asymmetric Ni/PVC film has been developed by solution casting method. The structure, electrical conductivity, electromagnetic interference (EMI) shielding, and impact resistance were investigated. The result...A novel asymmetric Ni/PVC film has been developed by solution casting method. The structure, electrical conductivity, electromagnetic interference (EMI) shielding, and impact resistance were investigated. The results showed that the Ni particles were asymmetrically distributed along the thickness direction in the film. The top surface resistivity increased with film thickness, while the bottom surface exhibited the different trend. EMI shielding effectiveness (SE) depended on formation of closed packed conductive Ni network, which was influenced by both Ni content and film thickness. A linear relationship was observed between EMI SE and film thickness. The films with lower Ni content showed the faster increasing rate of EMI SE with film thickness. Some of the films show appreciably high EMI SE (〉 40 dB), indicating the promising application in EMI shielding field. Moreover, the films exhibit different impact performance under different impacting directions. All the experimental facts demonstrate that the asymmetric structure endows the film achieving high-performance EMI shielding function.展开更多
基金supported by the Natural Science Foundation of Jiangsu Province of China, No.BK20180948(to ZL)Nantong Applied Research Program of China, No.MS12019011(to XXF)Science and Technology Project of Nantong University of China, No.TDYXY2019007(to XXF)
文摘Interleukin 17A(IL-17A)was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications.However,the role of IL-17A in diabetic encephalopathy remains poorly understood.In this study,we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a-/-mice with spontaneously diabetic Ins2^(Akita)(Akita)mice.Blood glucose levels and body weights were monitored from 2-32 weeks of age.When mice were 32 weeks of age,behavioral tests were performed,including a novel object recognition test for assessing short-term memory and learning and a Morris water maze test for evaluating hippocampus-dependent spatial learning and memory.IL-17A levels in the serum,cerebrospinal fluid,and hippocampus were detected with enzyme-linked immunosorbent assays and real-time quantitative polymerase chain reaction.Moreover,proteins related to cognitive dysfunction(amyloid precursor protein,β-amyloid cleavage enzyme 1,p-tau,and tau),apoptosis(caspase-3 and-9),inflammation(inducible nitric oxide synthase and cyclooxygenase 2),and occludin were detected by western blot assays.Pro-inflammatory cytokines including tumor necrosis factor-α,interleukin-1β,and interferon-γin serum and hippocampal tissues were measured by enzyme-linked immunosorbent assays.Microglial activation and hippocampal neuronal apoptosis were detected by immunofluorescent staining.Compared with that in wild-type mice,mice with diabetic encephalopathy had higher IL-17A levels in the serum,cerebrospinal fluid,and hippocampus;downregulation of occludin expression;lower cognitive ability;greater loss of hippocampal neurons;increased microglial activation;and higher expression of inflammatory factors in the serum and hippocampus.IL-17A knockout attenuated the abovementioned changes in mice with diabetic encephalopathy.These findings suggest that IL-17A participates in the pathological process of diabetic encephalopathy.Furthermore,IL-17A deficiency reduces diabetic encephalopathy-mediated neuroinflammation and cognitive defects.These results highlight a role for IL-17A as a mediator of diabetic encephalopathy and potential target for the treatment of cognitive impairment induced by diabetic encephalopathy.
基金This study was supported by grants from the National Natural Science Foundation of China(No.81800266)Cultivating Project for Young Scholars at Hubei University of Medicine(No.2017QDJZR04 and No.2018QDJZR10).
文摘An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery.Our previous study has identified transient receptor potential channel 3(TRPC3)and TRPC6 as cation channels through which most of the damaging calcium enters,aggravates pathological changes in vivo and increases ischemia/reperfusion(I/R)injury in mice.This study aimed to verify the effects of TRPC3 inhibitor Pyr3 on myocardial I/R injury in mice.C57BL/6J wild-type male mice(8 to 12 weeks old)were anesthetized with 3.3%chloral hydrate.A murine I(30 min)/R(24 h)injury model was established by temporary occlusion of the left anterior descending(LAD)coronary artery.Pyr3 was administered at concentrations of 0,2.5,5,or 10 mg/kg via the right jugular vein 5 min before reperfusion.We observed that the selective TRPC3 inhibitor,10 mg/kg Pyr3,significantly decreased the infarct size of left ventricle,and reduced the myocardial cell apoptosis rate and inflammatory response in mice.In a conclusion,TRPC3 can function as a candidate target for I/R injury prevention,and Pyr3 may directly bind to TRPC3 channel protein,inhibit TRPC3 channel activity,and improve TRPC3-related myocardial I/R injury.Pyr3 may be used for clarification of TRPC3 functions and for treatments of TRPC3-mediated diseases.
基金financially supported by the National Natural Science Foundation of China(Nos.21274007 and 51021064)the Project of Science and Technology Innovation Platform of Beijing Municipal Education Commission(No.PXM2012-014213-000025)+1 种基金the Tribology Science Fund of State Key Laboratory of Tribology(No.SKLTKF12A10)Beijing Technology and Business University Natural Science Youth Foundation(No.QNJJ2012-29)
文摘A novel asymmetric Ni/PVC film has been developed by solution casting method. The structure, electrical conductivity, electromagnetic interference (EMI) shielding, and impact resistance were investigated. The results showed that the Ni particles were asymmetrically distributed along the thickness direction in the film. The top surface resistivity increased with film thickness, while the bottom surface exhibited the different trend. EMI shielding effectiveness (SE) depended on formation of closed packed conductive Ni network, which was influenced by both Ni content and film thickness. A linear relationship was observed between EMI SE and film thickness. The films with lower Ni content showed the faster increasing rate of EMI SE with film thickness. Some of the films show appreciably high EMI SE (〉 40 dB), indicating the promising application in EMI shielding field. Moreover, the films exhibit different impact performance under different impacting directions. All the experimental facts demonstrate that the asymmetric structure endows the film achieving high-performance EMI shielding function.