BACKGROUND： Complex learning tasks result in a greater number of paradoxical sleep phases, which can improve memory. The effect of paradoxical sleep deprivation, induced by ＂flower pot＂ technique, on spatial refere...BACKGROUND： Complex learning tasks result in a greater number of paradoxical sleep phases, which can improve memory. The effect of paradoxical sleep deprivation, induced by ＂flower pot＂ technique, on spatial reference memory and working memory require further research. OBJECTIVE： To observe the effect of progressive paradoxical sleep deprivation in rats, subsequent to learning, on memory using the Morris Water Maze. DESIGN, TIME AND SETTING： Controlled observation experiment. The experiment was performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from December 2006 to October 2007. MATERIALS： Twenty-eight, male, Wistar rats, 3-4 months old, were provided by the Experimental Animal Center of Lanzhou University. The Morris Water Maze and behavioral analyses system was purchased from Genheart Company, Beijing, China. METHODS： All animals, according to a random digits table, were randomly divided into paradoxical sleep deprivation, tank control, and home cage control groups. Paradoxical sleep deprivation was induced by the ＂flower pot＂ technique for 72 hours, housing the rats on small platforms over water. Rats in the ＂tank control＂ and ＂home cage control＂ groups were housed either in a tank with large platforms over the water or in normal cages without paradoxical sleep deprivation. MAIN OUTCOME MEASURES： Morris Water Maze was employed for task learning and spatial memory testing. Rats in all groups were placed at six random starting points each day for four consecutive days. Each placement was repeated for two trials; the first trial represented reference memory and the second working memory. Rats in the first trial were allowed to locate the submerged platform within 120 seconds. Data, including swimming distance, escape latency, swimming velocity, percentage of time in correct quarter, and memory scores were recorded and analyzed automatically by behavioral analyses systems for Morris Water Maze. RESULTS： Twenty-eight rats were included in the final analysis, without any loss. In the first trial, between day 2 and 4, escape latency and swimming distance increased significantly in the paradoxical sleep deprivation group compared to the home cage control and tank control groups （P 〈 0.01）; percentage of time in correct quarter and memory scores, however, decreased in the paradoxical sleep deprivation group compared to the home cage control and tank control groups （P 〈 0.01）. The escape latency, swimming distance, percentage of time in correct quarter, and memory scores in the second trial was not significantly different among the three groups （P 〉 0.05）. CONCLUSION： Paradoxical sleep deprivation inhibits spatial reference memory, but not working memory.展开更多
Various factors can induce cell degeneration by altering the phenotype and metabolism of cells.Mitochondria play an essential role in cellular homeostasis and function,rendering aging processes highly associated with ...Various factors can induce cell degeneration by altering the phenotype and metabolism of cells.Mitochondria play an essential role in cellular homeostasis and function,rendering aging processes highly associated with mitochondrial function and status.Herein,we describe an aging-prone phenotype of murine skin cells caused by depletion of Rad6B(Ube2b),an E2 ubiquitin-conjugating enzyme.In this study,using Masson’s trichrome,we showed that loss of Rad6B causes physiological structure changes in mouse skin with age.In addition,a combination of western blotting experiments,transmission electron microscopy and employment of immunofluorescence staining revealed that depletion of Rad6B was characterized by an abnormal mitochondrial metabolic profile,including decreased mitochondrial biosynthesis and mitochondrial complex activities,increased ROS production and suppressed mitophagy resulting in metabolic disorders.Taken together,these results highlight an important relationship between Rad6B and skin senescence,suggesting that Rad6B plays an indispensable role in maintaining a healthy mitochondrial network and intracellular homeostasis.展开更多
Background: Histone deacetylase inhibitors (HDACI) are promising class of drugs acting as antiproliferative agents by promoting differentiation as well as inducing apoptosis. Vorinostat (suberoylanilide hydroxamic aci...Background: Histone deacetylase inhibitors (HDACI) are promising class of drugs acting as antiproliferative agents by promoting differentiation as well as inducing apoptosis. Vorinostat (suberoylanilide hydroxamic acid, SAHA) is the first among this new class of anticancer drugs to be approved by FDA for the treatment of cancer but only for cutaneous T cell lymphoma (CTCL). The objective of this study is to investigate the inhibitory effect of SAHA on the viability of human bladder cancer cells and its synergetic effect with chemotherapy agents in vitro and in vivo. Methods: The cell viability of human bladder cancer cell lines after treated with SAHA or SAHA combining mitomycin c (MMC), Cisplatin (DDP) and Adriamycin (ADM) were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Hoechst staining was used to observe cell morphology for apoptotic cells. The survivin protein and acetylated histone H3 levels in bladder cancer were quantified by Western blot analysis. In vivo tumor growth inhibition of intravesical inject SAHA was determined in rats with N-methyl-N-nitrosourea (MNU) induced bladder cancer. Results: SAHA significantly inhibited growth of bladder cancer cell lines with concentration and time dependent manner. Furthermore, better results of tumor inhibition would be achieved when it was combined with chemotherapeutic agents in vitro and in vivo. Survivin expression decreased and acetylated histone H3 expression increased in bladder cancer cells lines after SAHA treatment. Intravesically injections of SAHA can inhibit tumor progress when combined with DDP. Conclusions: SAHA can act as HDACI which has direct anti-cancer effect and can enhance the action of several chemotherapy agents markedly. SAHA may sensitize bladder cancer to anti cancer drugs by down regulating survivin expression. Intravesically injections of SAHA can prevent tumor progression in MNU induced bladder cancer.展开更多
基金the National Natural Science Foundation of China, No.30670677
文摘BACKGROUND： Complex learning tasks result in a greater number of paradoxical sleep phases, which can improve memory. The effect of paradoxical sleep deprivation, induced by ＂flower pot＂ technique, on spatial reference memory and working memory require further research. OBJECTIVE： To observe the effect of progressive paradoxical sleep deprivation in rats, subsequent to learning, on memory using the Morris Water Maze. DESIGN, TIME AND SETTING： Controlled observation experiment. The experiment was performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from December 2006 to October 2007. MATERIALS： Twenty-eight, male, Wistar rats, 3-4 months old, were provided by the Experimental Animal Center of Lanzhou University. The Morris Water Maze and behavioral analyses system was purchased from Genheart Company, Beijing, China. METHODS： All animals, according to a random digits table, were randomly divided into paradoxical sleep deprivation, tank control, and home cage control groups. Paradoxical sleep deprivation was induced by the ＂flower pot＂ technique for 72 hours, housing the rats on small platforms over water. Rats in the ＂tank control＂ and ＂home cage control＂ groups were housed either in a tank with large platforms over the water or in normal cages without paradoxical sleep deprivation. MAIN OUTCOME MEASURES： Morris Water Maze was employed for task learning and spatial memory testing. Rats in all groups were placed at six random starting points each day for four consecutive days. Each placement was repeated for two trials; the first trial represented reference memory and the second working memory. Rats in the first trial were allowed to locate the submerged platform within 120 seconds. Data, including swimming distance, escape latency, swimming velocity, percentage of time in correct quarter, and memory scores were recorded and analyzed automatically by behavioral analyses systems for Morris Water Maze. RESULTS： Twenty-eight rats were included in the final analysis, without any loss. In the first trial, between day 2 and 4, escape latency and swimming distance increased significantly in the paradoxical sleep deprivation group compared to the home cage control and tank control groups （P 〈 0.01）; percentage of time in correct quarter and memory scores, however, decreased in the paradoxical sleep deprivation group compared to the home cage control and tank control groups （P 〈 0.01）. The escape latency, swimming distance, percentage of time in correct quarter, and memory scores in the second trial was not significantly different among the three groups （P 〉 0.05）. CONCLUSION： Paradoxical sleep deprivation inhibits spatial reference memory, but not working memory.
基金funded by the National Natural Science Foundation of China(Grant Nos.82071695 and 81772907 to DW and No.82060535 to YT)the Fundamental Research Funds for the Central Universities(Grant lzujbky-2017-k12 to DW).
文摘Various factors can induce cell degeneration by altering the phenotype and metabolism of cells.Mitochondria play an essential role in cellular homeostasis and function,rendering aging processes highly associated with mitochondrial function and status.Herein,we describe an aging-prone phenotype of murine skin cells caused by depletion of Rad6B(Ube2b),an E2 ubiquitin-conjugating enzyme.In this study,using Masson’s trichrome,we showed that loss of Rad6B causes physiological structure changes in mouse skin with age.In addition,a combination of western blotting experiments,transmission electron microscopy and employment of immunofluorescence staining revealed that depletion of Rad6B was characterized by an abnormal mitochondrial metabolic profile,including decreased mitochondrial biosynthesis and mitochondrial complex activities,increased ROS production and suppressed mitophagy resulting in metabolic disorders.Taken together,these results highlight an important relationship between Rad6B and skin senescence,suggesting that Rad6B plays an indispensable role in maintaining a healthy mitochondrial network and intracellular homeostasis.
文摘Background: Histone deacetylase inhibitors (HDACI) are promising class of drugs acting as antiproliferative agents by promoting differentiation as well as inducing apoptosis. Vorinostat (suberoylanilide hydroxamic acid, SAHA) is the first among this new class of anticancer drugs to be approved by FDA for the treatment of cancer but only for cutaneous T cell lymphoma (CTCL). The objective of this study is to investigate the inhibitory effect of SAHA on the viability of human bladder cancer cells and its synergetic effect with chemotherapy agents in vitro and in vivo. Methods: The cell viability of human bladder cancer cell lines after treated with SAHA or SAHA combining mitomycin c (MMC), Cisplatin (DDP) and Adriamycin (ADM) were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Hoechst staining was used to observe cell morphology for apoptotic cells. The survivin protein and acetylated histone H3 levels in bladder cancer were quantified by Western blot analysis. In vivo tumor growth inhibition of intravesical inject SAHA was determined in rats with N-methyl-N-nitrosourea (MNU) induced bladder cancer. Results: SAHA significantly inhibited growth of bladder cancer cell lines with concentration and time dependent manner. Furthermore, better results of tumor inhibition would be achieved when it was combined with chemotherapeutic agents in vitro and in vivo. Survivin expression decreased and acetylated histone H3 expression increased in bladder cancer cells lines after SAHA treatment. Intravesically injections of SAHA can inhibit tumor progress when combined with DDP. Conclusions: SAHA can act as HDACI which has direct anti-cancer effect and can enhance the action of several chemotherapy agents markedly. SAHA may sensitize bladder cancer to anti cancer drugs by down regulating survivin expression. Intravesically injections of SAHA can prevent tumor progression in MNU induced bladder cancer.
