Polymyxins are the last line of defense against multidrug-resistant(MDR)Gram-negative bacterial infections.However,this last resort has been threatened by the emergence of superbugs carrying the mobile colistin resist...Polymyxins are the last line of defense against multidrug-resistant(MDR)Gram-negative bacterial infections.However,this last resort has been threatened by the emergence of superbugs carrying the mobile colistin resistance gene-1(mcr-1).Given the high concentration of matrix metalloproteinase 3(MMP-3)in bacterial pneumonia,limited plasma accumulation of colistin(CST)in the lung,and potential toxicity of ionic silver(Ag+),we designed a feasible clinical transformation platform,an MMP-3 high-performance lung-targeted bio-responsive delivery system,which we named“CST&Ag@CNMS”.This system exhibited excellent lung-targeting ability(>80%in lungs),MMP-3 bio-responsive release property(95%release on demand),and synergistic bactericidal activity in vitro(2-4-fold minimum inhibitory concentration reduction).In the mcr-1+CST-resistant murine pneumonia model,treatment with CST&Ag@CNMS improved survival rates(70%vs.20%),reduced bacteria burden(2-3 log colony-forming unit[CFU]/g tissue),and considerably mitigated inflammatory response.In this study,CST&Ag@CNMS performed better than the combination of free CST and AgNO3.We also demonstrated the superior biosafety and biodegradability of CST&Ag@CNMS both in vitro and in vivo.These findings indicate the clinical translational potential of CST&Ag@CNMS for the treatment of lung infections caused by CST-resistant bacteria carrying mcr-1.展开更多
To editor:Hypertriglyceridemia is a major risk factor for cardiovascu-lar disease and acute pancreatitis.1Accordingly,during preg-nancy,the growing serum lipid levels have potentially critical implications.2,3However,...To editor:Hypertriglyceridemia is a major risk factor for cardiovascu-lar disease and acute pancreatitis.1Accordingly,during preg-nancy,the growing serum lipid levels have potentially critical implications.2,3However,the management of gestational hypertriglyceridemia is further complicated because of the lackof safety data for most of the lipid-lowering agents.展开更多
Preeclampsia(PE)is a principal cause of maternal and newborn mortality that poses financial and physical burdens to tens of thousands of families each year.Unfortunately,there is no effective management to arrest the ...Preeclampsia(PE)is a principal cause of maternal and newborn mortality that poses financial and physical burdens to tens of thousands of families each year.Unfortunately,there is no effective management to arrest the progression of this disease unless delivery.Therefore,standardized management or preventive treatments are needed urgently.PE is closely associated with placental hypoxia,which increases the secretion of soluble fms-like tyrosine kinase 1(sFlt-1)as well as soluble endoglin(sEng)into the maternal circulation.Metformin has been found to inhibit those anti-angiogenic factors so it might be a candidate to prevent or treat PE.Women who are diagnosed with gestational diabetes mellitus(GDM)are more likely to have complications of hypertension or PE,so this review aims to demonstrate that the application of metformin in GDM might prevent the onset or progression of PE complicated with GDM.展开更多
基金supported by the Natural Science Foundation of Shanghai[grant number 23ZR1456800]the Interdisciplinary Program of Shanghai Jiao Tong University[grant number YG2021ZD07]+4 种基金the Science and Technology Commission of Shanghai Municipality[grant number 20Y11901100]the Clinical Science and Technology Innovation Project of SHCD[grant number SHDC22021212]the National Natural Science Foundation of China[grant number 82002188]the Scientific Research Project Plan of Shanghai Municipal Health Commission[grant number 20204Y0145]the Guangci Discipline Group Construction of Public Health and Disaster Emergency Center[grant number XKQ-09].
文摘Polymyxins are the last line of defense against multidrug-resistant(MDR)Gram-negative bacterial infections.However,this last resort has been threatened by the emergence of superbugs carrying the mobile colistin resistance gene-1(mcr-1).Given the high concentration of matrix metalloproteinase 3(MMP-3)in bacterial pneumonia,limited plasma accumulation of colistin(CST)in the lung,and potential toxicity of ionic silver(Ag+),we designed a feasible clinical transformation platform,an MMP-3 high-performance lung-targeted bio-responsive delivery system,which we named“CST&Ag@CNMS”.This system exhibited excellent lung-targeting ability(>80%in lungs),MMP-3 bio-responsive release property(95%release on demand),and synergistic bactericidal activity in vitro(2-4-fold minimum inhibitory concentration reduction).In the mcr-1+CST-resistant murine pneumonia model,treatment with CST&Ag@CNMS improved survival rates(70%vs.20%),reduced bacteria burden(2-3 log colony-forming unit[CFU]/g tissue),and considerably mitigated inflammatory response.In this study,CST&Ag@CNMS performed better than the combination of free CST and AgNO3.We also demonstrated the superior biosafety and biodegradability of CST&Ag@CNMS both in vitro and in vivo.These findings indicate the clinical translational potential of CST&Ag@CNMS for the treatment of lung infections caused by CST-resistant bacteria carrying mcr-1.
文摘To editor:Hypertriglyceridemia is a major risk factor for cardiovascu-lar disease and acute pancreatitis.1Accordingly,during preg-nancy,the growing serum lipid levels have potentially critical implications.2,3However,the management of gestational hypertriglyceridemia is further complicated because of the lackof safety data for most of the lipid-lowering agents.
文摘Preeclampsia(PE)is a principal cause of maternal and newborn mortality that poses financial and physical burdens to tens of thousands of families each year.Unfortunately,there is no effective management to arrest the progression of this disease unless delivery.Therefore,standardized management or preventive treatments are needed urgently.PE is closely associated with placental hypoxia,which increases the secretion of soluble fms-like tyrosine kinase 1(sFlt-1)as well as soluble endoglin(sEng)into the maternal circulation.Metformin has been found to inhibit those anti-angiogenic factors so it might be a candidate to prevent or treat PE.Women who are diagnosed with gestational diabetes mellitus(GDM)are more likely to have complications of hypertension or PE,so this review aims to demonstrate that the application of metformin in GDM might prevent the onset or progression of PE complicated with GDM.
