Aortic aneurysm(AA)is a common health problem with high mortality and no effective drugs.Transforming growth factor-β(TGF-β)superfamily members regulate various cellular processes,and TGF-βsignaling has key roles i...Aortic aneurysm(AA)is a common health problem with high mortality and no effective drugs.Transforming growth factor-β(TGF-β)superfamily members regulate various cellular processes,and TGF-βsignaling has key roles in development,tissue homeo-stasis,and diseases.Interest in the role of TGF-βsignaling in the pathogenesis of AAs has recently emerged,particularly since genetic studies demonstrated an association between gene mutations in components of TGF-βsignaling and AAs.However,paradoxical discoveries have implicated dysregulated TGF-βsignaling in aneurysm formation,complicating the precise functional role for TGF-βin aneurysm development and progression.Furthermore,interventions targeting towards TGF-βsignaling using losartan,which may represent a suitable therapeutic option for AAs,were subject to skepticism especially because of conflicting experimental results obtained from TGF-βantibody treatment without knowledge of the underlying mechanism.We propose a TGF-βaneurysm paradox,which would provide a good opportunity for the development of genetic mouse models of AA.These models would be used to clarify the mechanisms underlying TGF-βsignaling,which would translate into novel pharmacologic therapies based on the new molecular discoveries.展开更多
Effective prophylactic and therapeutic interventions are urgentlyneeded to address the coronavirus disease 2019(COVID-19)pandemic.Various antiviral drugs have recently been tested.Type I interferon(IFN)is a regulatory...Effective prophylactic and therapeutic interventions are urgentlyneeded to address the coronavirus disease 2019(COVID-19)pandemic.Various antiviral drugs have recently been tested.Type I interferon(IFN)is a regulatory protein involved in the innate immune response,with broad-spectrum antiviral activities and the ability to directly block viral replication and support the immune response to eliminate virus infection.Insufficient virus-induced type I IFN production is characteristic of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,because SARS-CoV-2 suppresses the IFN response by interacting with essential IFN signaling pathways.Exogenous type I IFN is recommended for treating COVID-19.Unexpectedly however,angiotensin converting enzyme-2(ACE2)receptor,which acts as a SARS-CoV-2 receptor,was shown to be stimulated by IFN,raising doubts about the suitability of IFN use.However,further studies have excluded concerns regarding IFN administration.Type I IFNs,including IFN-α1b,have been used clinically as antiviral drugs for many years and have shown strong antiviral activity against SARS-CoV-2in vitro.Preliminary clinical studies of type I IFNs,especially when delivered via aerosol inhalation,have demonstrated efficacy for the treatment and prevention of COVID-19.Randomized controlled trials of IFN for COVID-19 treatment are ongoing.展开更多
基金supported by the grants from State Key Laboratory of Proteomics(No.SKLP-K200902)Chinese Key Program for Drug Invention(No.2009ZX09501-027)Chinese National Key Program on Basic Research(Nos.2005CB522506,2006CB943501 and 2006BAI23B01-3)
文摘Aortic aneurysm(AA)is a common health problem with high mortality and no effective drugs.Transforming growth factor-β(TGF-β)superfamily members regulate various cellular processes,and TGF-βsignaling has key roles in development,tissue homeo-stasis,and diseases.Interest in the role of TGF-βsignaling in the pathogenesis of AAs has recently emerged,particularly since genetic studies demonstrated an association between gene mutations in components of TGF-βsignaling and AAs.However,paradoxical discoveries have implicated dysregulated TGF-βsignaling in aneurysm formation,complicating the precise functional role for TGF-βin aneurysm development and progression.Furthermore,interventions targeting towards TGF-βsignaling using losartan,which may represent a suitable therapeutic option for AAs,were subject to skepticism especially because of conflicting experimental results obtained from TGF-βantibody treatment without knowledge of the underlying mechanism.We propose a TGF-βaneurysm paradox,which would provide a good opportunity for the development of genetic mouse models of AA.These models would be used to clarify the mechanisms underlying TGF-βsignaling,which would translate into novel pharmacologic therapies based on the new molecular discoveries.
文摘Effective prophylactic and therapeutic interventions are urgentlyneeded to address the coronavirus disease 2019(COVID-19)pandemic.Various antiviral drugs have recently been tested.Type I interferon(IFN)is a regulatory protein involved in the innate immune response,with broad-spectrum antiviral activities and the ability to directly block viral replication and support the immune response to eliminate virus infection.Insufficient virus-induced type I IFN production is characteristic of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,because SARS-CoV-2 suppresses the IFN response by interacting with essential IFN signaling pathways.Exogenous type I IFN is recommended for treating COVID-19.Unexpectedly however,angiotensin converting enzyme-2(ACE2)receptor,which acts as a SARS-CoV-2 receptor,was shown to be stimulated by IFN,raising doubts about the suitability of IFN use.However,further studies have excluded concerns regarding IFN administration.Type I IFNs,including IFN-α1b,have been used clinically as antiviral drugs for many years and have shown strong antiviral activity against SARS-CoV-2in vitro.Preliminary clinical studies of type I IFNs,especially when delivered via aerosol inhalation,have demonstrated efficacy for the treatment and prevention of COVID-19.Randomized controlled trials of IFN for COVID-19 treatment are ongoing.
