AIM:To investigate whether hepatitis B virus(HBV) exacerbates hepatic cholesterol accumulation,and explore the underlying mechanisms.METHODS:HepG2 cells were infected with adenovirus(Ad) containing 1.3-fold overlength...AIM:To investigate whether hepatitis B virus(HBV) exacerbates hepatic cholesterol accumulation,and explore the underlying mechanisms.METHODS:HepG2 cells were infected with adenovirus(Ad) containing 1.3-fold overlength HBV genome.Realtime polymerase chain reaction and Western blotting were used to measure mRNA and protein expression of target genes.Cholesterol accumulation was measured by fluorescence microscopy.Cell toxicity due to Ad-HBV treatment was determined by the mitochondrial tetrazolium assay.The protein levels of toll-like receptors(TLRs) were determined by Western blotting.RESULTS:Ad-HBV increased hepatic cholesterol accumulation and enhanced the mRNA and protein levels oflow-density lipoprotein receptor(LDLR) and 3-hydroxy3-methylglutharyl-coenzyme A reductase(HMGCoAr) mRNA and protein expression in HepG2 cells.In addition,these inductive effects were partly offset by suppressing TLR2 expression levels by small interfering RNA in HepG2 cells.CONCLUSION:Ad-HBV increases LDLR and HMGCoAr expression,resulting in exacerbated cholesterol accumulation in HepG2 cells,which was mediated via the TLR2 pathway.展开更多
Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neu...Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection.However,recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions.Accordingly,neutrophils are emerging as highly versatile cells that are able to acquire different,often opposite,functional capacities depending on the microenvironment and their differentiation status.Herein,we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT,from the hematopoietic stem cell(HSC)mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion.We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versushost disease(GVHD)prophylaxis.Finally,the potential involvement of neutrophils in alloHSCT-related complications,such as transplant-associated thrombotic microangiopathy(TA-TMA),acute and chronic GVHD,and cytomegalovirus(CMV)reactivation,is also discussed.Based on the data reviewed herein,the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role.However,much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.展开更多
基金Supported by The Youth Foundation of Hunan Provincial Education Department,No.11B110the Graduate Innovation Project of Hunan Provincial Education Department,No.CX2010B382
文摘AIM:To investigate whether hepatitis B virus(HBV) exacerbates hepatic cholesterol accumulation,and explore the underlying mechanisms.METHODS:HepG2 cells were infected with adenovirus(Ad) containing 1.3-fold overlength HBV genome.Realtime polymerase chain reaction and Western blotting were used to measure mRNA and protein expression of target genes.Cholesterol accumulation was measured by fluorescence microscopy.Cell toxicity due to Ad-HBV treatment was determined by the mitochondrial tetrazolium assay.The protein levels of toll-like receptors(TLRs) were determined by Western blotting.RESULTS:Ad-HBV increased hepatic cholesterol accumulation and enhanced the mRNA and protein levels oflow-density lipoprotein receptor(LDLR) and 3-hydroxy3-methylglutharyl-coenzyme A reductase(HMGCoAr) mRNA and protein expression in HepG2 cells.In addition,these inductive effects were partly offset by suppressing TLR2 expression levels by small interfering RNA in HepG2 cells.CONCLUSION:Ad-HBV increases LDLR and HMGCoAr expression,resulting in exacerbated cholesterol accumulation in HepG2 cells,which was mediated via the TLR2 pathway.
基金supported by grants from Associazione Italiana per la Ricerca sul Cancro(AIRC,IG-20339)Ministero delllstruzione,deirUniversitci e della Ricerca(MIUR-PRIN 20177J4E75_004)Fondazione Cariverona to MAC。
文摘Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection.However,recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions.Accordingly,neutrophils are emerging as highly versatile cells that are able to acquire different,often opposite,functional capacities depending on the microenvironment and their differentiation status.Herein,we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT,from the hematopoietic stem cell(HSC)mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion.We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versushost disease(GVHD)prophylaxis.Finally,the potential involvement of neutrophils in alloHSCT-related complications,such as transplant-associated thrombotic microangiopathy(TA-TMA),acute and chronic GVHD,and cytomegalovirus(CMV)reactivation,is also discussed.Based on the data reviewed herein,the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role.However,much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.
