Global change,which refers to large-scale changes in the earth system and human society,has been changing the outbreak and transmission mode of many infectious diseases.Climate change affects infectious diseases direc...Global change,which refers to large-scale changes in the earth system and human society,has been changing the outbreak and transmission mode of many infectious diseases.Climate change affects infectious diseases directly and indirectly.Meteorological factors including temperature,precipitation,humidity and radiation influence infectious disease by modulating pathogen,host and transmission pathways.Meteorological disasters such as droughts and floods directly impact the outbreak and transmission of infectious diseases.Climate change indirectly impacts infectious diseases by altering the ecological system,including its underlying surface and vegetation distribution.In addition,anthropogenic activities are a driving force for climate change and an indirect forcing of infectious disease transmission.International travel and rural-urban migration are a root cause of infectious disease transmission.Rapid urbanization along with poor infrastructure and high disease risk in the rural-urban fringe has been changing the pattern of disease outbreaks and mortality.Land use changes,such as agricultural expansion and deforestation,have already changed the transmission of infectious disease.Accelerated air,road and rail transportation development may not only increase the transmission speed of outbreaks,but also enlarge the scope of transmission area.In addition,more frequent trade and other economic activities will also increase the potential risks of disease outbreaks and facilitate the spread of infectious diseases.展开更多
The present study was designed to analyze the metabolites of all-trans-retinal(atRal) and compare the cytotoxicity of atRal versus its derivative all-trans-retinoic acid(atRA) in human retinal pigment epithelial(RPE) ...The present study was designed to analyze the metabolites of all-trans-retinal(atRal) and compare the cytotoxicity of atRal versus its derivative all-trans-retinoic acid(atRA) in human retinal pigment epithelial(RPE) cells. We confirmed that atRA was produced in normal pig neural retina and RPE. The amount of all-trans-retinol(atROL) converted from atRal was about 2.7 times that of atRal-derived atRA after incubating RPE cells with 10 μmol/L atRal for 24 h, whereas atRA in medium supernatant is more plentiful(91 vs. 29 pmol/mL), suggesting that atRA conversion ? facilitates elimination of excess atRal in the retina. Moreover, we found that mRNA expression of retinoic acid-specific hydroxylase CYP26 b1 was dose-dependently up-regulated by atRal exposure in RPE cells, indicating that atRA inactivation may be also initiated in atRal-accumulated RPE cells. Our data show that atRA-caused viability inhibition was evidently reduced compared with the equal concentration of its precursor atRal. Excess accumulation of atRal provoked intracellular reactive oxygen species(ROS) overproduction, heme oxygenase-1(HO-1) expression, and increased cleaved poly(ADP-ribose) polymerase 1(PARP1) expression in RPE cells. In contrast, comparable dosage of atRA-induced oxidative stress was much weaker, and it could not activate apoptosis in RPE cells. These results suggest that atRA generation is an antidotal metabolism pathway for atRal in the retina. Moreover, we found that in the eyes of ABCA4-/-RDH8-/-mice, a mouse model with atRal accumulation in the retina, the atRA content was almost the same as that in the wild type. It is possible that atRal accumulation simultaneously and equally promotes atRA synthesis and clearance in eyes of ABCA4-/-RDH8-/-mice, thus inhibiting the further increase of atRA in the retina. Our present study provides further insights into atRal clearance in the retina.展开更多
基金supported by the National Research Program of the Ministry of Science and Technology,China(Grant Nos.2010CB530300,2012CB955501,2013AA122003&2012AA12A407)the National Natural Science Foundation of China(Grant No.41271099)China Postdoctoral Science Foundation(Grant No.2012M510344)
文摘Global change,which refers to large-scale changes in the earth system and human society,has been changing the outbreak and transmission mode of many infectious diseases.Climate change affects infectious diseases directly and indirectly.Meteorological factors including temperature,precipitation,humidity and radiation influence infectious disease by modulating pathogen,host and transmission pathways.Meteorological disasters such as droughts and floods directly impact the outbreak and transmission of infectious diseases.Climate change indirectly impacts infectious diseases by altering the ecological system,including its underlying surface and vegetation distribution.In addition,anthropogenic activities are a driving force for climate change and an indirect forcing of infectious disease transmission.International travel and rural-urban migration are a root cause of infectious disease transmission.Rapid urbanization along with poor infrastructure and high disease risk in the rural-urban fringe has been changing the pattern of disease outbreaks and mortality.Land use changes,such as agricultural expansion and deforestation,have already changed the transmission of infectious disease.Accelerated air,road and rail transportation development may not only increase the transmission speed of outbreaks,but also enlarge the scope of transmission area.In addition,more frequent trade and other economic activities will also increase the potential risks of disease outbreaks and facilitate the spread of infectious diseases.
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LQ17H120001)the Medical Science and Technology Program of Zhejiang Province(Nos.2016KYA195 and 2017KY714)+1 种基金the National Natural Science Foundation of China(No.81801424)the 211 Talents Training Program of Taizhou,China
文摘The present study was designed to analyze the metabolites of all-trans-retinal(atRal) and compare the cytotoxicity of atRal versus its derivative all-trans-retinoic acid(atRA) in human retinal pigment epithelial(RPE) cells. We confirmed that atRA was produced in normal pig neural retina and RPE. The amount of all-trans-retinol(atROL) converted from atRal was about 2.7 times that of atRal-derived atRA after incubating RPE cells with 10 μmol/L atRal for 24 h, whereas atRA in medium supernatant is more plentiful(91 vs. 29 pmol/mL), suggesting that atRA conversion ? facilitates elimination of excess atRal in the retina. Moreover, we found that mRNA expression of retinoic acid-specific hydroxylase CYP26 b1 was dose-dependently up-regulated by atRal exposure in RPE cells, indicating that atRA inactivation may be also initiated in atRal-accumulated RPE cells. Our data show that atRA-caused viability inhibition was evidently reduced compared with the equal concentration of its precursor atRal. Excess accumulation of atRal provoked intracellular reactive oxygen species(ROS) overproduction, heme oxygenase-1(HO-1) expression, and increased cleaved poly(ADP-ribose) polymerase 1(PARP1) expression in RPE cells. In contrast, comparable dosage of atRA-induced oxidative stress was much weaker, and it could not activate apoptosis in RPE cells. These results suggest that atRA generation is an antidotal metabolism pathway for atRal in the retina. Moreover, we found that in the eyes of ABCA4-/-RDH8-/-mice, a mouse model with atRal accumulation in the retina, the atRA content was almost the same as that in the wild type. It is possible that atRal accumulation simultaneously and equally promotes atRA synthesis and clearance in eyes of ABCA4-/-RDH8-/-mice, thus inhibiting the further increase of atRA in the retina. Our present study provides further insights into atRal clearance in the retina.
