Oxygen/glucose deprivation （OGD） has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra＇, ...Oxygen/glucose deprivation （OGD） has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra＇, where residual blood flow remains oxygen and glucose supplies are at low levels. To model this pathological genesis, we developed a partial OGD （pOGD） protocol in a rat brain slice. This model met two requirements： oxygen was partially deprived and glucose was reduced in the perfusion buffer. Therefore we investigated the effect of pOGD on gama-aminobutyric acid （GABAA） receptor-mediated inhibitory postsynaptic currents （IPSCs） in CA1 neurons of a hippocampal slice through whole-cell patch-clamp technique. We found that the amplitude and decay time of IPSCs were increased immediately during pOGD treatment. And the enhancement of IPSCs amplitude resulted from an increase of the synaptic conductance without a significant change in the reversal potential of chloride. These results suggested that the nervous system could increase inhibitory neurotransmission to offset excitation by homeostasis mechanisms during the partial oxygen and glucose attack.展开更多
We conducted a systematic review and meta-analysis of randomized controlled trials（RCTs） to determine the effectiveness and safety of incretin-based therapies（IBTs） for the treatment of type 2 diabetes（T2DM） wit...We conducted a systematic review and meta-analysis of randomized controlled trials（RCTs） to determine the effectiveness and safety of incretin-based therapies（IBTs） for the treatment of type 2 diabetes（T2DM） with nonalcoholic fatty liver disease（NAFLD）. Electronic databases such as the Cochrane library, EMbase, Pub Med, and three Chinese databases were searched for RCTs that compared IBTs with other treatments or placebo for T2 DM with NAFLD. Two reviewers independently assessed the risk of bias, extracted, and analyzed the data. A meta-analysis was performed using Revman 5.2. Publication bias was evaluated. Seven RCTs involving 532 patients were ultimately included. The results of meta-analysis（random-effects model） revealed that IBTs had a significant reduction in serum ALT（WMD –12.30, 95% CI –17.53~–7.06） and BMI（WMD –2.64, 95% CI –4.35~–0.94）. However, there was no significant difference in other outcomes including Hb A1 c, AST, TC, TG and HOMA-RA. IBTs were well tolerated by patients but the evidence was limited. The significant decrease in hepatic biochemical markers following treatment with IBTs, as well as improvements in BMI, suggested that IBTs may be an effective option for T2 DM with NAFLD.展开更多
Human intestinal carboxyl esterase （hiCE） is a drug target for ameliorating irinotecan-induced diarrhea. By reducing irinotecan- induced diarrhea, hiCE inhibitors can improve the anti-cancer efficacy of irinotecan. ...Human intestinal carboxyl esterase （hiCE） is a drug target for ameliorating irinotecan-induced diarrhea. By reducing irinotecan- induced diarrhea, hiCE inhibitors can improve the anti-cancer efficacy of irinotecan. To find effective hiCE inhibitors, a new virtual screening protocol that combines pharmacophore models derived from the hiCE structure and its ligands has been pro- posed. The hiCE structure has been constructed through homology techniques using hCESI＇s crystal structure. The hiCE structure was optimized via molecular dynamics simulations with the most known active hiCE inhibitors docked into the structure. An optimized pharmacophore, derived from the receptor, was then generated. A ligand-based pharmacophore was also generated from a larger set of known hiCE inhibitors. The final hiCE inhibitor predictions were based upon the virtual screening hits from both ligand-based and receptor-based pharmacophore models. The hit rates from the ligand-based and receptor-based pharmacophore models are 88% and 86%, respectively. The final hit rate is 94%. The two models are highly consistent with one another （85%）. This proves that both models are reliable.展开更多
文摘Oxygen/glucose deprivation （OGD） has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra＇, where residual blood flow remains oxygen and glucose supplies are at low levels. To model this pathological genesis, we developed a partial OGD （pOGD） protocol in a rat brain slice. This model met two requirements： oxygen was partially deprived and glucose was reduced in the perfusion buffer. Therefore we investigated the effect of pOGD on gama-aminobutyric acid （GABAA） receptor-mediated inhibitory postsynaptic currents （IPSCs） in CA1 neurons of a hippocampal slice through whole-cell patch-clamp technique. We found that the amplitude and decay time of IPSCs were increased immediately during pOGD treatment. And the enhancement of IPSCs amplitude resulted from an increase of the synaptic conductance without a significant change in the reversal potential of chloride. These results suggested that the nervous system could increase inhibitory neurotransmission to offset excitation by homeostasis mechanisms during the partial oxygen and glucose attack.
文摘We conducted a systematic review and meta-analysis of randomized controlled trials（RCTs） to determine the effectiveness and safety of incretin-based therapies（IBTs） for the treatment of type 2 diabetes（T2DM） with nonalcoholic fatty liver disease（NAFLD）. Electronic databases such as the Cochrane library, EMbase, Pub Med, and three Chinese databases were searched for RCTs that compared IBTs with other treatments or placebo for T2 DM with NAFLD. Two reviewers independently assessed the risk of bias, extracted, and analyzed the data. A meta-analysis was performed using Revman 5.2. Publication bias was evaluated. Seven RCTs involving 532 patients were ultimately included. The results of meta-analysis（random-effects model） revealed that IBTs had a significant reduction in serum ALT（WMD –12.30, 95% CI –17.53~–7.06） and BMI（WMD –2.64, 95% CI –4.35~–0.94）. However, there was no significant difference in other outcomes including Hb A1 c, AST, TC, TG and HOMA-RA. IBTs were well tolerated by patients but the evidence was limited. The significant decrease in hepatic biochemical markers following treatment with IBTs, as well as improvements in BMI, suggested that IBTs may be an effective option for T2 DM with NAFLD.
基金funded in part of the National High-tech R&D Program of China(863 Program)(2012AA020307)the introduction of innovative R&D team program of Guangdong Province(2009010058)+1 种基金the National Natural Science Foundation of China(81001372,81173470)the Fundamental Research Funds for the Central Universities(10ykjc01)
文摘Human intestinal carboxyl esterase （hiCE） is a drug target for ameliorating irinotecan-induced diarrhea. By reducing irinotecan- induced diarrhea, hiCE inhibitors can improve the anti-cancer efficacy of irinotecan. To find effective hiCE inhibitors, a new virtual screening protocol that combines pharmacophore models derived from the hiCE structure and its ligands has been pro- posed. The hiCE structure has been constructed through homology techniques using hCESI＇s crystal structure. The hiCE structure was optimized via molecular dynamics simulations with the most known active hiCE inhibitors docked into the structure. An optimized pharmacophore, derived from the receptor, was then generated. A ligand-based pharmacophore was also generated from a larger set of known hiCE inhibitors. The final hiCE inhibitor predictions were based upon the virtual screening hits from both ligand-based and receptor-based pharmacophore models. The hit rates from the ligand-based and receptor-based pharmacophore models are 88% and 86%, respectively. The final hit rate is 94%. The two models are highly consistent with one another （85%）. This proves that both models are reliable.
