The alpha1 adrenoreceptor antagonist tamsulosin is primarily used to treat benign prostatic hypertrophy. In this study, we intragastrically administered rats with 0.01,0.1 and 1 mg/kg tamsulosin to investigate the eff...The alpha1 adrenoreceptor antagonist tamsulosin is primarily used to treat benign prostatic hypertrophy. In this study, we intragastrically administered rats with 0.01,0.1 and 1 mg/kg tamsulosin to investigate the effects of tamsulosin on memory function, and hippocampal cell apoptosis and proliferation following intracerebral hemorrhage. Step-down avoidance task results showed that tamsulosin treatment markedly alleviated intracerebral hemorrhage- induced short-term memory impairment. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results showed that tamsulosin treatment markedly suppressed intracerebral hemorrhage-induced caspase-3 expression in the hippocampal CA1 region and cell proliferation in the hippocampal dentate gyrus. Tamsulosin treatment at a dose of 0.01 mg/kg exhibited the most potent inhibitory effects on cell apoptosis and proliferation. These findings suggest that tamsulosin treatment facilitates the recovery of rat memory function by inhibiting hippocampal cell apoptosis and proliferation followincl intracerebral hemorrhaQe.展开更多
Energy metabolism is significantly reprogrammed in many human cancers, and these alterations confer many advantages to cancer cells, including the pro- motion of biosynthesis, ATP generation, detoxification and suppor...Energy metabolism is significantly reprogrammed in many human cancers, and these alterations confer many advantages to cancer cells, including the pro- motion of biosynthesis, ATP generation, detoxification and support of rapid proliferation. The pentose phos- phate pathway （PPP） is a major pathway for glucose catabolism. The PPP directs glucose flux to its oxi- dative branch and produces a reduced form of nico- tinamide adenine dinucleotide phosphate （NADPH）, an essential reductant in anabolic processes. It has become clear that the PPP plays a critical role in regulating cancer cell growth by supplying cells with not only ribose-5-phosphate but also NADPH for detoxification of intracellular reactive oxygen species, reductive biosynthesis and ribose biogenesis. Thus, alteration of the PPP contributes directly to cell pro- liferation, survival and senescence. Furthermore, recent studies have shown that the PPP is regulated oncogenically and/or metabolically by numerous fac- tors, including tumor suppressors, oncoproteins and intracellular metabolites. Dysregulation of PPP flux dramatically impacts cancer growth and survival. Therefore, a better understanding of how the PPP is reprogrammed and the mechanism underlying the balance between glycolysis and PPP flux in cancer will be valuable in developing therapeutic strategies targeting this pathway.展开更多
Background： Glehnia littoralis has been used for traditional Asian medicine, which has diverse therapeutic activities. However, studies regarding neurogenic effects of G. littoralis have not yet been considered. Ther...Background： Glehnia littoralis has been used for traditional Asian medicine, which has diverse therapeutic activities. However, studies regarding neurogenic effects of G. littoralis have not yet been considered. Therefore, in this study, we examined effects of G. littoralis extract on cell proliferation, neuroblast differentiation, and the maturation of newborn neurons in the hippocampus of adult mice. Methods： A total of 39 male ICR mice （12 weeks old） were randomly assigned to vehicle-treated and 100 and 200 mg/kg G. littoralis extract-treated groups （n = 13 in each group）. Vehicle and G. littoralis extract were orally administrated for 28 days. To examine neurogenic effects ofG. litmralis extract, we performed immunohistochemistry tbr 5-bromo-2-deoxyuridine （BrdU, an indicator for cell proliferation） and doublecortin （DCX, an immature neuronal marker） and double immunofluorescence staining for BrdU and neuronal nuclear antigen （NeuN, a mature neuronal marker）. In addition, we examined expressional changes of brain-derived neurotrophic factor （BDNF） and its major receptor tropomyosin-related kinase B （TrkB） using Western blotting analysis. Results： Treatment with 200 mg/kg, not 100 mg/kg, significantly increased number of BrdU-immunoreactive （＋） and DCX＋ cells （48.0 ±3.1and 72.0 ± 3.8 cells/section, respectively） in the subgranular zone （SGZ） of the dentate gyrus （DG） and BrdU＊/NeuN＋ cells （17.0 ±1.5 cells/section） in the granule cell layer as well as in the SGZ. In addition, protein levels of BDNF and YrkB （about 232% and 244% of the vehicle-treated group, respectively） were significantly increased in the DG of the mice treated with 200 mg/kg ofG. littoralis extract. Conclusion： G. littoralis extract promots cell proliferation, neuroblast differentiation, and neuronal maturation in the hippocampal DG, and neurogenic effects might be closely related to increases ofBDN F and TrkB proteins by G. littoralis extract treatment.展开更多
基金the National Research Foundation of Korea Grant funded by the Korean Government, No. 2010-0003794the Research Fund, 2010 of Gachon University Gil Hospital
文摘The alpha1 adrenoreceptor antagonist tamsulosin is primarily used to treat benign prostatic hypertrophy. In this study, we intragastrically administered rats with 0.01,0.1 and 1 mg/kg tamsulosin to investigate the effects of tamsulosin on memory function, and hippocampal cell apoptosis and proliferation following intracerebral hemorrhage. Step-down avoidance task results showed that tamsulosin treatment markedly alleviated intracerebral hemorrhage- induced short-term memory impairment. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results showed that tamsulosin treatment markedly suppressed intracerebral hemorrhage-induced caspase-3 expression in the hippocampal CA1 region and cell proliferation in the hippocampal dentate gyrus. Tamsulosin treatment at a dose of 0.01 mg/kg exhibited the most potent inhibitory effects on cell apoptosis and proliferation. These findings suggest that tamsulosin treatment facilitates the recovery of rat memory function by inhibiting hippocampal cell apoptosis and proliferation followincl intracerebral hemorrhaQe.
基金We apologize to those authors whose excellent work could not be cited due to space constraints. This work was supported by the Start-Up Package Fund from Tsinghua University to J.P. and the grant （Grants No. 2010CB912804 and 31030046 to WM） from National Natural Science Foundation of China.
文摘Energy metabolism is significantly reprogrammed in many human cancers, and these alterations confer many advantages to cancer cells, including the pro- motion of biosynthesis, ATP generation, detoxification and support of rapid proliferation. The pentose phos- phate pathway （PPP） is a major pathway for glucose catabolism. The PPP directs glucose flux to its oxi- dative branch and produces a reduced form of nico- tinamide adenine dinucleotide phosphate （NADPH）, an essential reductant in anabolic processes. It has become clear that the PPP plays a critical role in regulating cancer cell growth by supplying cells with not only ribose-5-phosphate but also NADPH for detoxification of intracellular reactive oxygen species, reductive biosynthesis and ribose biogenesis. Thus, alteration of the PPP contributes directly to cell pro- liferation, survival and senescence. Furthermore, recent studies have shown that the PPP is regulated oncogenically and/or metabolically by numerous fac- tors, including tumor suppressors, oncoproteins and intracellular metabolites. Dysregulation of PPP flux dramatically impacts cancer growth and survival. Therefore, a better understanding of how the PPP is reprogrammed and the mechanism underlying the balance between glycolysis and PPP flux in cancer will be valuable in developing therapeutic strategies targeting this pathway.
文摘Background： Glehnia littoralis has been used for traditional Asian medicine, which has diverse therapeutic activities. However, studies regarding neurogenic effects of G. littoralis have not yet been considered. Therefore, in this study, we examined effects of G. littoralis extract on cell proliferation, neuroblast differentiation, and the maturation of newborn neurons in the hippocampus of adult mice. Methods： A total of 39 male ICR mice （12 weeks old） were randomly assigned to vehicle-treated and 100 and 200 mg/kg G. littoralis extract-treated groups （n = 13 in each group）. Vehicle and G. littoralis extract were orally administrated for 28 days. To examine neurogenic effects ofG. litmralis extract, we performed immunohistochemistry tbr 5-bromo-2-deoxyuridine （BrdU, an indicator for cell proliferation） and doublecortin （DCX, an immature neuronal marker） and double immunofluorescence staining for BrdU and neuronal nuclear antigen （NeuN, a mature neuronal marker）. In addition, we examined expressional changes of brain-derived neurotrophic factor （BDNF） and its major receptor tropomyosin-related kinase B （TrkB） using Western blotting analysis. Results： Treatment with 200 mg/kg, not 100 mg/kg, significantly increased number of BrdU-immunoreactive （＋） and DCX＋ cells （48.0 ±3.1and 72.0 ± 3.8 cells/section, respectively） in the subgranular zone （SGZ） of the dentate gyrus （DG） and BrdU＊/NeuN＋ cells （17.0 ±1.5 cells/section） in the granule cell layer as well as in the SGZ. In addition, protein levels of BDNF and YrkB （about 232% and 244% of the vehicle-treated group, respectively） were significantly increased in the DG of the mice treated with 200 mg/kg ofG. littoralis extract. Conclusion： G. littoralis extract promots cell proliferation, neuroblast differentiation, and neuronal maturation in the hippocampal DG, and neurogenic effects might be closely related to increases ofBDN F and TrkB proteins by G. littoralis extract treatment.
