The recent outbreak of the human Zaire ebolavirus(EBOV)epidemic is spiraling out of control in West Africa.Human EBOV hemorrhagic fever has a case fatality rate of up to 90%.The EBOV is classified as a biosafety level...The recent outbreak of the human Zaire ebolavirus(EBOV)epidemic is spiraling out of control in West Africa.Human EBOV hemorrhagic fever has a case fatality rate of up to 90%.The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention,with no approved therapies and vaccines available for its treatment apart from supportive care.Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial,the current epidemic might be outpacing the speed at which drugs and vaccines can be produced.Like all viruses,the EBOV largely relies on host cell factors and physiological processes for its entry,replication,and egress.We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies.Most of the therapeutic agents in this review are directed against non-mutable targets of the host,which is independent of viral mutation.These medications are approved by the Food and Drug Administration(FDA)for the treatment of other diseases.They are available and stockpileable for immediate use.They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV.展开更多
The gut microbiota plays a key role in metabolic diseases.Gut-microbiota-derived metabolites are found in different dietary sources,including:Carbohydrate(acetate,propionate,butyrate,also known as short-chain fatty ac...The gut microbiota plays a key role in metabolic diseases.Gut-microbiota-derived metabolites are found in different dietary sources,including:Carbohydrate(acetate,propionate,butyrate,also known as short-chain fatty acids,as well as succinate);protein(hydrogen sulfide,indole,and phenylacetic acid);and lipids(resveratrol-,ferulic acid-,linoleic acid-,catechin-and berry-derived metabolites).Insulin resistance,which is a global pandemic metabolic disease that progresses to type 2 diabetes mellitus,can be directly targeted by these metabolites.Gutmicrobiota-derived metabolites have broad effects locally and in distinct organs,in particular skeletal muscle,adipose tissue,and liver.These metabolites can modulate glucose metabolism,including the increase in glucose uptake and lipid oxidation in skeletal muscle,and decrease in lipogenesis and gluconeogenesis associated with lipid oxidation in the liver through activation of phosphatidylinositol 3-kinase-serine/threonine-protein kinase B and AMP-activated protein kinase.In adipose tissue,gut-microbiota-derived metabolites stimulate adipogenesis and thermogenesis,inhibit lipolysis,and attenuate inflammation.Importantly,an increase in energy expenditure and fat oxidation occurs in the whole body.Therefore,the therapeutic potential of current pharmacological and non-pharmacological approaches used to treat diabetes mellitus can be tested to target specific metabolites derived from intestinal bacteria,which may ultimately ameliorate the hyperglycemic burden.展开更多
Micro RNAs(mi RNAs) are small noncoding RNAs. More than 2500 mature mi RNAs are detected in plants, animals and several types of viruses. Hepatitis C virus(HCV), which is a positive-sense, singlestranded RNA virus, do...Micro RNAs(mi RNAs) are small noncoding RNAs. More than 2500 mature mi RNAs are detected in plants, animals and several types of viruses. Hepatitis C virus(HCV), which is a positive-sense, singlestranded RNA virus, does not encode viral mi RNA. However, HCV infection alters the expression of host mi RNAs, either in cell culture or in patients with liver disease progression, such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. In turn, host mi RNAs regulate HCV life cycle through directly binding to HCV RNAs or indirectly targeting cellular m RNAs. Increasing evidence demonstrates that mi RNAs are one of the centered factors in the interaction network between virus and host. The competitive viral and host RNA hypothesis proposes a latent cross-regulation pattern between host m RNAs and HCV RNAs. High loads of HCV RNA sequester and de-repress host mi RNAs from their normal host targets and thus disturb host gene expression, indicating a means of adaptation for HCV to establish a persistent infection. Some special mi RNAs are closely correlated with liver-specific disease progression and the changed levels of mi RNAs are even higher sensitivity and specificity than those of traditional proteins. Therefore, some of them can serve as novel diagnostic/prognostic biomarkers in HCVinfected patients with liver diseases. They are also attractive therapeutic targets for development of new anti-HCV agents.展开更多
文摘The recent outbreak of the human Zaire ebolavirus(EBOV)epidemic is spiraling out of control in West Africa.Human EBOV hemorrhagic fever has a case fatality rate of up to 90%.The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention,with no approved therapies and vaccines available for its treatment apart from supportive care.Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial,the current epidemic might be outpacing the speed at which drugs and vaccines can be produced.Like all viruses,the EBOV largely relies on host cell factors and physiological processes for its entry,replication,and egress.We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies.Most of the therapeutic agents in this review are directed against non-mutable targets of the host,which is independent of viral mutation.These medications are approved by the Food and Drug Administration(FDA)for the treatment of other diseases.They are available and stockpileable for immediate use.They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV.
基金Supported by São Paulo Research Foundation,No.2013/19560-6 and No.2017/23195-2EFSD(European Foundation for the Study of Diabetes)/Sanofi(to RangelÉB).
文摘The gut microbiota plays a key role in metabolic diseases.Gut-microbiota-derived metabolites are found in different dietary sources,including:Carbohydrate(acetate,propionate,butyrate,also known as short-chain fatty acids,as well as succinate);protein(hydrogen sulfide,indole,and phenylacetic acid);and lipids(resveratrol-,ferulic acid-,linoleic acid-,catechin-and berry-derived metabolites).Insulin resistance,which is a global pandemic metabolic disease that progresses to type 2 diabetes mellitus,can be directly targeted by these metabolites.Gutmicrobiota-derived metabolites have broad effects locally and in distinct organs,in particular skeletal muscle,adipose tissue,and liver.These metabolites can modulate glucose metabolism,including the increase in glucose uptake and lipid oxidation in skeletal muscle,and decrease in lipogenesis and gluconeogenesis associated with lipid oxidation in the liver through activation of phosphatidylinositol 3-kinase-serine/threonine-protein kinase B and AMP-activated protein kinase.In adipose tissue,gut-microbiota-derived metabolites stimulate adipogenesis and thermogenesis,inhibit lipolysis,and attenuate inflammation.Importantly,an increase in energy expenditure and fat oxidation occurs in the whole body.Therefore,the therapeutic potential of current pharmacological and non-pharmacological approaches used to treat diabetes mellitus can be tested to target specific metabolites derived from intestinal bacteria,which may ultimately ameliorate the hyperglycemic burden.
基金Supported by National Natural Science Foundation of China No.81321004 and No.81322050National Mega-Project for“R&D for Innovative Drugs”+3 种基金Ministry of Science and TechnologyChina No.2012ZX09301-002-001Ministry of EducationChina No.NCET-12-0072
文摘Micro RNAs(mi RNAs) are small noncoding RNAs. More than 2500 mature mi RNAs are detected in plants, animals and several types of viruses. Hepatitis C virus(HCV), which is a positive-sense, singlestranded RNA virus, does not encode viral mi RNA. However, HCV infection alters the expression of host mi RNAs, either in cell culture or in patients with liver disease progression, such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. In turn, host mi RNAs regulate HCV life cycle through directly binding to HCV RNAs or indirectly targeting cellular m RNAs. Increasing evidence demonstrates that mi RNAs are one of the centered factors in the interaction network between virus and host. The competitive viral and host RNA hypothesis proposes a latent cross-regulation pattern between host m RNAs and HCV RNAs. High loads of HCV RNA sequester and de-repress host mi RNAs from their normal host targets and thus disturb host gene expression, indicating a means of adaptation for HCV to establish a persistent infection. Some special mi RNAs are closely correlated with liver-specific disease progression and the changed levels of mi RNAs are even higher sensitivity and specificity than those of traditional proteins. Therefore, some of them can serve as novel diagnostic/prognostic biomarkers in HCVinfected patients with liver diseases. They are also attractive therapeutic targets for development of new anti-HCV agents.
