Objective To investigate the anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high- altitude exposure. Methods Totally 100 young male army members newly recruited from Sichuan province (400...Objective To investigate the anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high- altitude exposure. Methods Totally 100 young male army members newly recruited from Sichuan province (400 meters above sea level) were enrolled. They were randomly divided into two groups: 50 in aminophylline group (A group) and 50 in control group (C group). A group and C group orally took aminophylline and placebo respectively for 10 days, 7 days before entering Lhasa (3 658 meters above sea level) by air and 3 days after it. Several parameters were measured at three time points: before drug taken, 7 days after drug taken, and 3 days after ascending high altitude. These parameters included serum levels of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), hydrogen dioxide (H2O2), lactic acid (LA), as well as arterial oxygen saturation (SO2), arterial oxygen partial pressure (PaO2), and arterial carbon dioxide partial pressure (PaCO2). Statistical analysis was conducted to compare the difference between two groups with Stata 7.0 software system. Results There were no statistical differences between groups in hypoxia and oxidation indicators before and after drug taken in plain area. Three days after ascending high altitude, the serum levels of SOD, CAT, H2O2, LA, PaCO2 increased in both groups, yet to a much larger degree in C group than A group (P<0.01); and NO, SO2, PaO2 decreased more markedly in C group (P<0.05 for NO, P<0.0001 for SO2 and PaO2). Conclusion Aminophylline has significant anti-hypoxia and anti-oxidation effects at high altitude.展开更多
In order to overcome hypoxia induced sickness,a stable source of anti-hypoxia functional agents, Schizophyllum commune fermented broth has been developed in this study. Animal experiments were conducted to examine its...In order to overcome hypoxia induced sickness,a stable source of anti-hypoxia functional agents, Schizophyllum commune fermented broth has been developed in this study. Animal experiments were conducted to examine its anti-hypoxia activities and possible mechanisms involved. The acute hypoxic experiment showed that Schizophyllum commune fermented broth could significantly prolong the survival time of mice. The underlying mechanisms were associated with improved energy metabolism based on a study carried out in rats exposed to a low pressure chamber simulating the low pressure environment of 8 000 m altitude. It was concluded that the Schizophyllum commune fermented broth was an effective anti-hypoxia functional agent and could be greatly bene- ficial to those living and working at high altitudes,such as people who reside in the reconstruction regions of Yushu.展开更多
RNA interfering therapy has emerged as a promising therapeutic modality to treat cancer.The specific and efficient delivery of RNA into a tumor is crucial for achieving effective cancer gene therapy but remains a huge...RNA interfering therapy has emerged as a promising therapeutic modality to treat cancer.The specific and efficient delivery of RNA into a tumor is crucial for achieving effective cancer gene therapy but remains a huge challenge.Herein,we report a novel furin-responsive small interfering RNA(siRNA)delivery vehicle with multiple functions for colorectal tumor treatment.A peptide-based siRNA delivery vehicle RVRR-P18-Gd,consisting of furin enzyme-specific peptide substrate Arg-Val-Arg-Arg(RVRR)with positive charge for siRNA binding,a Gd(III)chelated 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid(DOTA)(DOTA-Gd)for magnetic resonance imaging,and purpurin 18 as photosensitizer for photodynamic therapy(PDT),was rationally designed and synthesized.Taking advantage of the cationic amphiphilic feature,RVRR-P18-Gd molecules spontaneously self-assembled with negatively charged Hif-1αsiRNA into stable nanoparticles via attractive electrostatic interaction,which effectively prevented siRNA degradation by nucleases,prolonged the circulation half-life,and enhanced tumor accumulation.Moreover,the specific release of Hif-1αsiRNA mediated by endogenous furin significantly downregulated Hif-1αexpression in colorectal cancer cells,resulting in enhanced therapeutic susceptibility,and with the PDT effect,effectively suppressed HCT116 tumor growth in living mice.This work highlights a powerful and universal approach to precisely deliver siRNA to targeted tumors for efficient synergistic therapy.展开更多
文摘Objective To investigate the anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high- altitude exposure. Methods Totally 100 young male army members newly recruited from Sichuan province (400 meters above sea level) were enrolled. They were randomly divided into two groups: 50 in aminophylline group (A group) and 50 in control group (C group). A group and C group orally took aminophylline and placebo respectively for 10 days, 7 days before entering Lhasa (3 658 meters above sea level) by air and 3 days after it. Several parameters were measured at three time points: before drug taken, 7 days after drug taken, and 3 days after ascending high altitude. These parameters included serum levels of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), hydrogen dioxide (H2O2), lactic acid (LA), as well as arterial oxygen saturation (SO2), arterial oxygen partial pressure (PaO2), and arterial carbon dioxide partial pressure (PaCO2). Statistical analysis was conducted to compare the difference between two groups with Stata 7.0 software system. Results There were no statistical differences between groups in hypoxia and oxidation indicators before and after drug taken in plain area. Three days after ascending high altitude, the serum levels of SOD, CAT, H2O2, LA, PaCO2 increased in both groups, yet to a much larger degree in C group than A group (P<0.01); and NO, SO2, PaO2 decreased more markedly in C group (P<0.05 for NO, P<0.0001 for SO2 and PaO2). Conclusion Aminophylline has significant anti-hypoxia and anti-oxidation effects at high altitude.
基金National Nature Science Foundation of China(No.31171662)"973"National Key Basic Research and Development Program(No.2012CB518202)Project of Qinghai Development of Science and Technology(No.2011-N-150)
文摘In order to overcome hypoxia induced sickness,a stable source of anti-hypoxia functional agents, Schizophyllum commune fermented broth has been developed in this study. Animal experiments were conducted to examine its anti-hypoxia activities and possible mechanisms involved. The acute hypoxic experiment showed that Schizophyllum commune fermented broth could significantly prolong the survival time of mice. The underlying mechanisms were associated with improved energy metabolism based on a study carried out in rats exposed to a low pressure chamber simulating the low pressure environment of 8 000 m altitude. It was concluded that the Schizophyllum commune fermented broth was an effective anti-hypoxia functional agent and could be greatly bene- ficial to those living and working at high altitudes,such as people who reside in the reconstruction regions of Yushu.
基金the National Science Foundation of China(grant no.22077092)the Open Project Program of the State Key Laboratory of Radiation Medicine and Protection(grant no.GZK1202140)+2 种基金Science and Technology Development Plan of Suzhou(grant no.SLJ2022018)Scientific Research Project of Suzhou Commission of Health(grant no.GSWS2020028)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘RNA interfering therapy has emerged as a promising therapeutic modality to treat cancer.The specific and efficient delivery of RNA into a tumor is crucial for achieving effective cancer gene therapy but remains a huge challenge.Herein,we report a novel furin-responsive small interfering RNA(siRNA)delivery vehicle with multiple functions for colorectal tumor treatment.A peptide-based siRNA delivery vehicle RVRR-P18-Gd,consisting of furin enzyme-specific peptide substrate Arg-Val-Arg-Arg(RVRR)with positive charge for siRNA binding,a Gd(III)chelated 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid(DOTA)(DOTA-Gd)for magnetic resonance imaging,and purpurin 18 as photosensitizer for photodynamic therapy(PDT),was rationally designed and synthesized.Taking advantage of the cationic amphiphilic feature,RVRR-P18-Gd molecules spontaneously self-assembled with negatively charged Hif-1αsiRNA into stable nanoparticles via attractive electrostatic interaction,which effectively prevented siRNA degradation by nucleases,prolonged the circulation half-life,and enhanced tumor accumulation.Moreover,the specific release of Hif-1αsiRNA mediated by endogenous furin significantly downregulated Hif-1αexpression in colorectal cancer cells,resulting in enhanced therapeutic susceptibility,and with the PDT effect,effectively suppressed HCT116 tumor growth in living mice.This work highlights a powerful and universal approach to precisely deliver siRNA to targeted tumors for efficient synergistic therapy.