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
AIM： To investigate the cyclooxygenase-2 （COX-2） expression level in human HepG2, Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2 selective inhibitor celecoxib-induced cell growth in...AIM： To investigate the cyclooxygenase-2 （COX-2） expression level in human HepG2, Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2 selective inhibitor celecoxib-induced cell growth inhibition and cell apoptosis. METHODS： Hepatoma cells were cultured and treated with celecoxib. Cell in situ hybridization （ISH） and immunocytochemistry were used to detect COX-2 mRNA and protein expression. Proliferating cell nuclear antigen and phosphorylated Akt were also detected by immunocytochemistry assay. Cell growth rates were assessed by 3-（4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium （MTT） bromide colorimetric assay. Celecoxib- induced cell apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） and flow cytometry （FCM）. The phosphorylated Akt and activated fragments of caspase-9, caspase-3 were examined by Western blotting analysis. RESULTS： Increased COX-2 mRNA and protein expression were detected in all three hepatoma cell lines. Celecoxib could significantly inhibit cell growth and the inhibitory effect was in a dose- and time-dependent manner evidenced by MTT assays and morphological changes. The apoptotic index measured by TUNEL increased correspondingly with the increased concentration of celecoxib and the reaction time. With 50 μmol/L celecoxib treatment for 24 h, the apoptotic index of HepG2, BEL-7402 and SMMC-7721 cells was 25.01±3.08%, 26.40±3.05%,and 30.60±2.89%, respectively. Western blotting analysis showed remarkable activation of caspase-9, caspase-3 and dephosphorylation of Akt （Thr^308）. Immunocytochemistry also showed the reduction of PCNA expression and phosphorylation Akt （Thr^308） after treatment with celecoxib. CONCLUSION： COX-2 mRNA and protein overexpression in HepG2, Bel-7402 and SMMC-7721 cell lines correlate with the increased cell growth rate. Celecoxib can inhibit proliferation and induce apoptosis of hepatoma cell strains in a dose- and time-dependent manner.展开更多
A new type of vascular stent is designed for treating stenotic vessels. Aiming at overcoming the shortcomings of existing equipment and technology for preparing a bioabsorbable vascular stent （BVS）, a new method whi...A new type of vascular stent is designed for treating stenotic vessels. Aiming at overcoming the shortcomings of existing equipment and technology for preparing a bioabsorbable vascular stent （BVS）, a new method which combines 3D bio-printing and electrospinning to prepare the composite bioabsorbable vascular stent （CBVS） is proposed. The inner layer of the CBVS can be obtained through 3D bio- printing using poly-p-dioxanone （PPDO）. The thin nanofiber film that serves as the outer layer can be built through electrospinning using mixtures of chitosan-PVA （poly （vinyl alcohol））. Tests of mechanical properties show that the stent prepared through 3D bio-printing combined with electrospinning is better than that prepared through 3D bio- printing alone. Cells cultivated on the CBVS adhere and proliferate better due to the natural, biological chitosan in the outer layer. The proposed complex process and method can provide a good basis for preparing a controllable drug-carrying vascular stent. Overall, the CBVS can be a good candidate for treating stenotic vessels.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.
基金Supported by Medical Science Research Foundation of Jiangsu Health Bureau Grant Z200314 (to JL)Medical Science Research Foundation of Nanjing Medical University Grant NY1999023 (to NBL) and CX2003012 (to JL)
文摘AIM： To investigate the cyclooxygenase-2 （COX-2） expression level in human HepG2, Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2 selective inhibitor celecoxib-induced cell growth inhibition and cell apoptosis. METHODS： Hepatoma cells were cultured and treated with celecoxib. Cell in situ hybridization （ISH） and immunocytochemistry were used to detect COX-2 mRNA and protein expression. Proliferating cell nuclear antigen and phosphorylated Akt were also detected by immunocytochemistry assay. Cell growth rates were assessed by 3-（4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium （MTT） bromide colorimetric assay. Celecoxib- induced cell apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） and flow cytometry （FCM）. The phosphorylated Akt and activated fragments of caspase-9, caspase-3 were examined by Western blotting analysis. RESULTS： Increased COX-2 mRNA and protein expression were detected in all three hepatoma cell lines. Celecoxib could significantly inhibit cell growth and the inhibitory effect was in a dose- and time-dependent manner evidenced by MTT assays and morphological changes. The apoptotic index measured by TUNEL increased correspondingly with the increased concentration of celecoxib and the reaction time. With 50 μmol/L celecoxib treatment for 24 h, the apoptotic index of HepG2, BEL-7402 and SMMC-7721 cells was 25.01±3.08%, 26.40±3.05%,and 30.60±2.89%, respectively. Western blotting analysis showed remarkable activation of caspase-9, caspase-3 and dephosphorylation of Akt （Thr^308）. Immunocytochemistry also showed the reduction of PCNA expression and phosphorylation Akt （Thr^308） after treatment with celecoxib. CONCLUSION： COX-2 mRNA and protein overexpression in HepG2, Bel-7402 and SMMC-7721 cell lines correlate with the increased cell growth rate. Celecoxib can inhibit proliferation and induce apoptosis of hepatoma cell strains in a dose- and time-dependent manner.
基金The National Natural Science Foundation of China(No.51475281,51375292)the National Natural Science Foundation for Young Scholar of China(No.51105239)
文摘A new type of vascular stent is designed for treating stenotic vessels. Aiming at overcoming the shortcomings of existing equipment and technology for preparing a bioabsorbable vascular stent （BVS）, a new method which combines 3D bio-printing and electrospinning to prepare the composite bioabsorbable vascular stent （CBVS） is proposed. The inner layer of the CBVS can be obtained through 3D bio- printing using poly-p-dioxanone （PPDO）. The thin nanofiber film that serves as the outer layer can be built through electrospinning using mixtures of chitosan-PVA （poly （vinyl alcohol））. Tests of mechanical properties show that the stent prepared through 3D bio-printing combined with electrospinning is better than that prepared through 3D bio- printing alone. Cells cultivated on the CBVS adhere and proliferate better due to the natural, biological chitosan in the outer layer. The proposed complex process and method can provide a good basis for preparing a controllable drug-carrying vascular stent. Overall, the CBVS can be a good candidate for treating stenotic vessels.
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.
