Background Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species （ROS） and reactiv...Background Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species （ROS） and reactive nitrogen species （RNS） during and after noise exposure. This study was designed to investigate the noise exposure induced nitrotyrosine change and the mechanism of outer hair cells death in guinea pig cochlea. Method Thirty guinea pigs were used in this study. The experimental animals were either exposed for 4 hours per day to broadband noise at 122 dB SPL （A-weighted） for 2 consecutive days or perfused cochleae with 5 mg/ml of the SIN1 solutions, an exogenous NO and superoxide donor, for 30 minutes. Then the cochleae of the animals were dissected. Propidium iodide （PI）, a DNA intercalating fluorescent probe, was used to trace morphological changes in OHC nuclei. The distribution of nitrotyrosine （NT） in the organ of Corti and the cochlear lateral wall tissue from the guinea pigs were examined using fluorescence immunohistochemistry method. Whole mounts of organ of Corti were prepared. Morphological and fluorescent changes were examined under a confocal microscope. Results Either after noise exposure or after SIN1 perfusion, outer hair cells （OHCs） death with characteristics of both apoptotic and necrotic degradation appeared. Nitrotyrosine immunolabeling could be observed in the OHCs from the control animals. After noise exposure, NT immunostaining became much greater than the control animals in OHCs. The apoptotic OHC has significant increase of nitrotyrosine in and around the nucleus following noise exposure. In the normal later wall of cochleae, relatively weak nitrotyrosine immunolabeling could be observed. After noise exposure, nitrotyrosine immunoactivity became stronger in stria vascularis. Conclusion Noise exposure induced increase of nitrotyrosine production is associated with OHCs death suggesting reactive nitrogen species participation in the cochlear pathophysiolo展开更多
Stochastic bifurcations of the SD （smooth and discontinuous） oscillator with additive and/or multiplicative bounded noises are studied by the generalized cell mapping method using digraph analysis algorithm. From th...Stochastic bifurcations of the SD （smooth and discontinuous） oscillator with additive and/or multiplicative bounded noises are studied by the generalized cell mapping method using digraph analysis algorithm. From the global viewpoint, stochastic bifur- cation can be described as a sudden change in shape and size of a random attractor as the system parameter valies. The evolu- tionary process of stochastic bifurcation in the SD oscillator is shown in detail. Meanwhile, we show the phenomenon that un- der stochastic excitation the shape and size of random attractor and random saddle change along with the direction of unstable manifold. A plane stochastic bifurcation diagram is included.展开更多
目的:通过观察丝状肌动蛋白(F-actin)在不同阶段凋亡、坏死毛细胞中的变化,揭示噪声性耳蜗毛细胞损伤早期的细胞形态学特征。方法:青年SD大鼠20只,接触噪声暴露的实验组及未接触噪声暴露的正常对照组动物各10只。将动物暴露于110 dB SPL...目的:通过观察丝状肌动蛋白(F-actin)在不同阶段凋亡、坏死毛细胞中的变化,揭示噪声性耳蜗毛细胞损伤早期的细胞形态学特征。方法:青年SD大鼠20只,接触噪声暴露的实验组及未接触噪声暴露的正常对照组动物各10只。将动物暴露于110 dB SPL,4 kHz窄带噪声,持续暴露8 h。稳态噪声暴露后接触155 dB SPL的脉冲噪声75次。噪声暴露前及噪声暴露后即刻、2周应用电反应测听仪检测不同频率短纯音(5、10和20 kHz)诱发的动物双侧听性脑干反应阈值(ABR)。听觉功能检测后处死动物,解剖取双侧耳蜗。采用DNA荧光染料碘化丙锭(PI)标记毛细胞核,异硫氰酸荧光素标记的鬼笔环肽染色毛细胞纤毛、表皮板的丝状肌动蛋白。以对照组动物耳蜗为对照,荧光显微镜下观察噪声暴露后大鼠耳蜗不同程度核固缩、核肿胀毛细胞的纤毛、表皮板F-actin表达的变化。结果:噪声暴露后即刻和2周不同频率短纯音诱发的ABR阈值均升高。荧光显微镜下观察发现,外毛细胞核肿胀时未见F-actin染色的改变;外毛细胞核型正常,但PI染色加深时,也未见F-actin的变化。外毛细胞核轻微固缩时,F-actin表达正常或轻度增强。外毛细胞核中度、重度毛细胞固缩时,F-actin染色变浅;外细胞核完全消失后,F-actin表达明显减弱或消失。结论:噪声暴露后耳蜗中凋亡、坏死的外毛细胞核变化早于纤毛及表皮板。F-actin可能在毛细胞凋亡中存在聚合和解聚2个过程,但其与毛细胞坏死过程无关。展开更多
This paper reports that the synchronous integer multiple oscillations of heart-cell networks or clusters are observed in the biology experiment. The behaviour of the integer multiple rhythm is a transition between sup...This paper reports that the synchronous integer multiple oscillations of heart-cell networks or clusters are observed in the biology experiment. The behaviour of the integer multiple rhythm is a transition between super- and sub- threshold oscillations, the stochastic mechanism of the transition is identified. The similar synchronized oscillations are theoretically reproduced in the stochastic network composed of heterogeneous cells whose behaviours are chosen as excitable or oscillatory states near a Hopf bifurcation point. The parameter regions of coupling strength and noise density that the complex oscillatory rhythms can be simulated are identified. The results show that the rhythm results from a simple stochastic alternating process between super- and sub-threshold oscillations. Studies on single heart cells forming these clusters reveal excitable or oscillatory state nearby a Hopf bifurcation point underpinning the stochastic alternation. In discussion, the results are related to some abnormal heartbeat rhythms such as the sinus arrest.展开更多
Studies have shown that phosphatase and tensin homolog deleted on chromosome ten(PTEN)participates in the regulation of cochlear hair cell survival.Bisperoxovanadium protects against neurodegeneration by inhibiting PT...Studies have shown that phosphatase and tensin homolog deleted on chromosome ten(PTEN)participates in the regulation of cochlear hair cell survival.Bisperoxovanadium protects against neurodegeneration by inhibiting PTEN expression.However,whether bisperoxovanadium can protect against noise-induced hearing loss and the underlying mechanism remains unclear.In this study,we established a mouse model of noise-induced hearing loss by exposure to 105 dB sound for 2 hours.We found that PTEN expression was increased in the organ of Corti,including outer hair cells,inner hair cells,and lateral wall tissues.Intraperitoneal administration of bisperoxovanadium decreased the auditory threshold and the loss of cochlear hair cells and inner hair cell ribbons.In addition,noise exposure decreased p-PI3K and p-Akt levels.Bisperoxovanadium preconditioning or PTEN knockdown upregulated the activity of PI3K-Akt.Bisperoxovanadium also prevented H_(2)O_(2)-induced hair cell death by reducing mitochondrial reactive oxygen species generation in cochlear explants.These findings suggest that bisperoxovanadium reduces noise-induced hearing injury and reduces cochlear hair cell loss.展开更多
基金This research was supported by the grants from National Natural Science Foundation of China，Nuttal Alfred's Grant (NIH NIDCD DC 000105 and Shi Xiaorui's Grant
文摘Background Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species （ROS） and reactive nitrogen species （RNS） during and after noise exposure. This study was designed to investigate the noise exposure induced nitrotyrosine change and the mechanism of outer hair cells death in guinea pig cochlea. Method Thirty guinea pigs were used in this study. The experimental animals were either exposed for 4 hours per day to broadband noise at 122 dB SPL （A-weighted） for 2 consecutive days or perfused cochleae with 5 mg/ml of the SIN1 solutions, an exogenous NO and superoxide donor, for 30 minutes. Then the cochleae of the animals were dissected. Propidium iodide （PI）, a DNA intercalating fluorescent probe, was used to trace morphological changes in OHC nuclei. The distribution of nitrotyrosine （NT） in the organ of Corti and the cochlear lateral wall tissue from the guinea pigs were examined using fluorescence immunohistochemistry method. Whole mounts of organ of Corti were prepared. Morphological and fluorescent changes were examined under a confocal microscope. Results Either after noise exposure or after SIN1 perfusion, outer hair cells （OHCs） death with characteristics of both apoptotic and necrotic degradation appeared. Nitrotyrosine immunolabeling could be observed in the OHCs from the control animals. After noise exposure, NT immunostaining became much greater than the control animals in OHCs. The apoptotic OHC has significant increase of nitrotyrosine in and around the nucleus following noise exposure. In the normal later wall of cochleae, relatively weak nitrotyrosine immunolabeling could be observed. After noise exposure, nitrotyrosine immunoactivity became stronger in stria vascularis. Conclusion Noise exposure induced increase of nitrotyrosine production is associated with OHCs death suggesting reactive nitrogen species participation in the cochlear pathophysiolo
基金supported by the National Natural Science Foundation of China (Grant Nos.10932009 and 11172233)the Natural Science Foundation of Shaanxi Province (Grant No.2012JQ1004)the Northwestern Polytechnical University Foundation for Fundamental Research (Grant Nos.JC201266 and JC20110228)
文摘Stochastic bifurcations of the SD （smooth and discontinuous） oscillator with additive and/or multiplicative bounded noises are studied by the generalized cell mapping method using digraph analysis algorithm. From the global viewpoint, stochastic bifur- cation can be described as a sudden change in shape and size of a random attractor as the system parameter valies. The evolu- tionary process of stochastic bifurcation in the SD oscillator is shown in detail. Meanwhile, we show the phenomenon that un- der stochastic excitation the shape and size of random attractor and random saddle change along with the direction of unstable manifold. A plane stochastic bifurcation diagram is included.
文摘目的:通过观察丝状肌动蛋白(F-actin)在不同阶段凋亡、坏死毛细胞中的变化,揭示噪声性耳蜗毛细胞损伤早期的细胞形态学特征。方法:青年SD大鼠20只,接触噪声暴露的实验组及未接触噪声暴露的正常对照组动物各10只。将动物暴露于110 dB SPL,4 kHz窄带噪声,持续暴露8 h。稳态噪声暴露后接触155 dB SPL的脉冲噪声75次。噪声暴露前及噪声暴露后即刻、2周应用电反应测听仪检测不同频率短纯音(5、10和20 kHz)诱发的动物双侧听性脑干反应阈值(ABR)。听觉功能检测后处死动物,解剖取双侧耳蜗。采用DNA荧光染料碘化丙锭(PI)标记毛细胞核,异硫氰酸荧光素标记的鬼笔环肽染色毛细胞纤毛、表皮板的丝状肌动蛋白。以对照组动物耳蜗为对照,荧光显微镜下观察噪声暴露后大鼠耳蜗不同程度核固缩、核肿胀毛细胞的纤毛、表皮板F-actin表达的变化。结果:噪声暴露后即刻和2周不同频率短纯音诱发的ABR阈值均升高。荧光显微镜下观察发现,外毛细胞核肿胀时未见F-actin染色的改变;外毛细胞核型正常,但PI染色加深时,也未见F-actin的变化。外毛细胞核轻微固缩时,F-actin表达正常或轻度增强。外毛细胞核中度、重度毛细胞固缩时,F-actin染色变浅;外细胞核完全消失后,F-actin表达明显减弱或消失。结论:噪声暴露后耳蜗中凋亡、坏死的外毛细胞核变化早于纤毛及表皮板。F-actin可能在毛细胞凋亡中存在聚合和解聚2个过程,但其与毛细胞坏死过程无关。
基金supported by the National Natural Science Foundation of China (Grant Nos. 10772101 and 30670533)the National High Technology Research and Development Program of China (Grant No. 2007AA02Z310)the Fundamental Research Funds for the Central Universities (Grant No. GK200902025)
文摘This paper reports that the synchronous integer multiple oscillations of heart-cell networks or clusters are observed in the biology experiment. The behaviour of the integer multiple rhythm is a transition between super- and sub- threshold oscillations, the stochastic mechanism of the transition is identified. The similar synchronized oscillations are theoretically reproduced in the stochastic network composed of heterogeneous cells whose behaviours are chosen as excitable or oscillatory states near a Hopf bifurcation point. The parameter regions of coupling strength and noise density that the complex oscillatory rhythms can be simulated are identified. The results show that the rhythm results from a simple stochastic alternating process between super- and sub-threshold oscillations. Studies on single heart cells forming these clusters reveal excitable or oscillatory state nearby a Hopf bifurcation point underpinning the stochastic alternation. In discussion, the results are related to some abnormal heartbeat rhythms such as the sinus arrest.
基金supported by the National Natural Science Foundation of China,Nos.81670925(to FQC),81870732(to DJZ),81800918(to WL),81900933(to YLS)Department of Science and Technology Key Industry Innovation Chain Social Development Field Fund of Shaanxi Province,No.2021ZDLSF02-12(to FQC)the Natural Science Foundation of Shaanxi Province,No.2019JM-009(to JC).
文摘Studies have shown that phosphatase and tensin homolog deleted on chromosome ten(PTEN)participates in the regulation of cochlear hair cell survival.Bisperoxovanadium protects against neurodegeneration by inhibiting PTEN expression.However,whether bisperoxovanadium can protect against noise-induced hearing loss and the underlying mechanism remains unclear.In this study,we established a mouse model of noise-induced hearing loss by exposure to 105 dB sound for 2 hours.We found that PTEN expression was increased in the organ of Corti,including outer hair cells,inner hair cells,and lateral wall tissues.Intraperitoneal administration of bisperoxovanadium decreased the auditory threshold and the loss of cochlear hair cells and inner hair cell ribbons.In addition,noise exposure decreased p-PI3K and p-Akt levels.Bisperoxovanadium preconditioning or PTEN knockdown upregulated the activity of PI3K-Akt.Bisperoxovanadium also prevented H_(2)O_(2)-induced hair cell death by reducing mitochondrial reactive oxygen species generation in cochlear explants.These findings suggest that bisperoxovanadium reduces noise-induced hearing injury and reduces cochlear hair cell loss.
