The arachidonic acid(AA)pathway plays a key role in cardiovascular biology,carcinogenesis,and many inflammatory diseases,such as asthma,arthritis,etc.Esterified AA on the inner surface of the cell membrane is hydrolyz...The arachidonic acid(AA)pathway plays a key role in cardiovascular biology,carcinogenesis,and many inflammatory diseases,such as asthma,arthritis,etc.Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2),which is in turn further metabolized by cyclooxygenases(COXs)and lipoxygenases(LOXs)and cytochrome P450(CYP)enzymes to a spectrum of bioactive mediators that includes prostanoids,leukotrienes(LTs),epoxyeicosatrienoic acids(EETs),dihydroxyeicosatetraenoic acid(diHETEs),eicosatetraenoic acids(ETEs),and lipoxins(LXs).Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases(CVD),cancers,and inflammatory diseases.This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer.progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2.Thus,we herein present a synopsis of AA metabolism in human health,cardiovascular and cancer biology,and the signaling pathways involved in these processes.To explore the role of the AA metabolism and potential therapies,we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.展开更多
We conducted a randomized,open-label,parallel-controlled,multicenter trial on the use of Shuanghuanglian(SHL),a traditional Chinese patent medicine,in treating cases of COVID-19.A total of 176 patients received SHL by...We conducted a randomized,open-label,parallel-controlled,multicenter trial on the use of Shuanghuanglian(SHL),a traditional Chinese patent medicine,in treating cases of COVID-19.A total of 176 patients received SHL by three doses(56 in low dose,61 in middle dose,and 59 in high dose)in addition to standard care.The control group was composed of 59 patients who received standard therapy alone.Treatment with SHL was not associated with a difference from standard care in the time to disease recovery.Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group(93.4%vs.73.9%,P=0.006).Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia,which was evaluated by density reduction of inflammatory focus from baseline,at day 7(mean difference(95%CI),−46.39(−86.83 to−5.94)HU;P=0.025)and day 14(mean difference(95%CI),−74.21(−133.35 to−15.08)HU;P=0.014).No serious adverse events occurred in the SHL groups.This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.展开更多
基金supported in part by National Nature Science Foundation of China(Nos.81790624,81700333,81900363,and 81900244)the Deutsche Forschungsgemeinschaft:SFB1039/A6(to I.F.).
文摘The arachidonic acid(AA)pathway plays a key role in cardiovascular biology,carcinogenesis,and many inflammatory diseases,such as asthma,arthritis,etc.Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2),which is in turn further metabolized by cyclooxygenases(COXs)and lipoxygenases(LOXs)and cytochrome P450(CYP)enzymes to a spectrum of bioactive mediators that includes prostanoids,leukotrienes(LTs),epoxyeicosatrienoic acids(EETs),dihydroxyeicosatetraenoic acid(diHETEs),eicosatetraenoic acids(ETEs),and lipoxins(LXs).Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases(CVD),cancers,and inflammatory diseases.This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer.progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2.Thus,we herein present a synopsis of AA metabolism in human health,cardiovascular and cancer biology,and the signaling pathways involved in these processes.To explore the role of the AA metabolism and potential therapies,we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.
基金This work was supported by the National Key R&D Program of China(No.2020YFC0841400)Tongji Hospital Clinical Research Project(Nos.XXGZBDYJ009 and 2019YBKY019).
文摘We conducted a randomized,open-label,parallel-controlled,multicenter trial on the use of Shuanghuanglian(SHL),a traditional Chinese patent medicine,in treating cases of COVID-19.A total of 176 patients received SHL by three doses(56 in low dose,61 in middle dose,and 59 in high dose)in addition to standard care.The control group was composed of 59 patients who received standard therapy alone.Treatment with SHL was not associated with a difference from standard care in the time to disease recovery.Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group(93.4%vs.73.9%,P=0.006).Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia,which was evaluated by density reduction of inflammatory focus from baseline,at day 7(mean difference(95%CI),−46.39(−86.83 to−5.94)HU;P=0.025)and day 14(mean difference(95%CI),−74.21(−133.35 to−15.08)HU;P=0.014).No serious adverse events occurred in the SHL groups.This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.