A method for simultaneously analyzing altemariol(AOH), altemariol monomethyl ether (AME) and zearalenone(ZEA) by particle beam LC/MS was established, LC separation was accompiished with a solvent system of methanol an...A method for simultaneously analyzing altemariol(AOH), altemariol monomethyl ether (AME) and zearalenone(ZEA) by particle beam LC/MS was established, LC separation was accompiished with a solvent system of methanol and water (80:20 v/v). The followed particle beam LC/MS analysis gave searchable spectra of AOH. AME and ZEA. Application of this technique to analysis of an alternaria culture confirmed the presence of AOH and AME.展开更多
Dimethyl fumarate （DMF） is a new drug used to treat multiple sclerosis （MS） patients. Here, we examined the effects of DMF and the DMF metabolite monomethyl fumarate （MMF） on various activities of natural killer...Dimethyl fumarate （DMF） is a new drug used to treat multiple sclerosis （MS） patients. Here, we examined the effects of DMF and the DMF metabolite monomethyl fumarate （MMF） on various activities of natural killer （NK） cells. We demonstrated that MMF augments the primary CD56^＋, but not CD56^-, NK cell lysis of K562 and RAJI tumor cells. MMF induced NKp46 expression on the surface of CD56^＋, but not CD56^-, NK cells after incubation for 24 h. This effect was closely correlated with the upregulation of CD107a expression on the surface of CD56＋ NK cells and the induction of Granzyme B release from these cells through this metabolite. An anti-NKp46 antibody inhibited the MMF-induced upregulation of CD107a and the lysis of tumor cells through CD56^＋ NK cells. Thus, these results are the first to show that MMF augments CD56^＋ NK cell lysis of tumor target cells, an effect mediated through NKp46. This novel effect suggests the use of MMF for therapeutic and/or preventive protocols in cancer.展开更多
Protein lysine methylation is a prevalent post-translational modification(PTM)and plays critical roles in all domains of life.However,its extent and function in photosynthetic organisms are still largely unknown.Cyano...Protein lysine methylation is a prevalent post-translational modification(PTM)and plays critical roles in all domains of life.However,its extent and function in photosynthetic organisms are still largely unknown.Cyanobacteria are a large group of prokaryotes that carry out oxygenic photosynthesis and are applied extensively in studies of photosynthetic mechanisms and environmental adaptation.Here we integrated propionylation of monomethylated proteins,enrichment of the modified peptides,and mass spectrometry(MS)analysis to identify monomethylated proteins in Synechocystis sp.PCC 6803(Synechocystis).Overall,we identified 376 monomethylation sites in270 proteins,with numerous monomethylated proteins participating in photosynthesis and carbon metabolism.We subsequently demonstrated that Cpc M,a previously identified asparagine methyltransferase in Synechocystis,could catalyze lysine monomethylation of the potential aspartate aminotransferase Sll0480 both in vivo and in vitro and regulate the enzyme activity of Sll0480.The loss of Cpc M led to decreases in the maximum quantum yield in primary photosystemⅡ(PSⅡ)and the efficiency of energy transfer during the photosynthetic reaction in Synechocystis.We report the first lysine monomethylome in a photosynthetic organism and present a critical database for functional analyses of monomethylation in cyanobacteria.The large number of monomethylated proteins and the identification of Cpc M as the lysine methyltransferase in cyanobacteria suggest that reversible methylation may influence the metabolic process and photosynthesis in both cyanobacteria and plants.展开更多
Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody dru...Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody drug conjugate(ADC)of MMAE is currently used in clinical practice.However,the safety issues of MMAE-based ADC,such as high drug toxicity and poor bioavailability,still exist when using it for anticancer therapy.A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects.Herein,PLGA-b-PEG 2000 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy.The sustained release effect and the immunogenic cell death(ICD)effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments.The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention(EPR)effect,inducing cell apoptosis and causing a certain degree of immune response.The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC.Overall,this study provides a safe and effective chemotherapeutic approach,as well as a simple and effective synthetic process for MMAE-based nanoparticles,improving their therapeutic efficacy and safety.展开更多
文摘A method for simultaneously analyzing altemariol(AOH), altemariol monomethyl ether (AME) and zearalenone(ZEA) by particle beam LC/MS was established, LC separation was accompiished with a solvent system of methanol and water (80:20 v/v). The followed particle beam LC/MS analysis gave searchable spectra of AOH. AME and ZEA. Application of this technique to analysis of an alternaria culture confirmed the presence of AOH and AME.
文摘Dimethyl fumarate （DMF） is a new drug used to treat multiple sclerosis （MS） patients. Here, we examined the effects of DMF and the DMF metabolite monomethyl fumarate （MMF） on various activities of natural killer （NK） cells. We demonstrated that MMF augments the primary CD56^＋, but not CD56^-, NK cell lysis of K562 and RAJI tumor cells. MMF induced NKp46 expression on the surface of CD56^＋, but not CD56^-, NK cells after incubation for 24 h. This effect was closely correlated with the upregulation of CD107a expression on the surface of CD56＋ NK cells and the induction of Granzyme B release from these cells through this metabolite. An anti-NKp46 antibody inhibited the MMF-induced upregulation of CD107a and the lysis of tumor cells through CD56^＋ NK cells. Thus, these results are the first to show that MMF augments CD56^＋ NK cell lysis of tumor target cells, an effect mediated through NKp46. This novel effect suggests the use of MMF for therapeutic and/or preventive protocols in cancer.
基金the National Natural Science Foundation of China(Grant No.31570829)the Chinese Academy of Sciences Grant QYZDY-SSW-SMC004+1 种基金the CAS Key Technology Talent Program(to MKY)the Open Fund of Key Laboratory of Experimental Marine Biology,Chinese Academy of Sciences(Grant No.KF2017NO3)。
文摘Protein lysine methylation is a prevalent post-translational modification(PTM)and plays critical roles in all domains of life.However,its extent and function in photosynthetic organisms are still largely unknown.Cyanobacteria are a large group of prokaryotes that carry out oxygenic photosynthesis and are applied extensively in studies of photosynthetic mechanisms and environmental adaptation.Here we integrated propionylation of monomethylated proteins,enrichment of the modified peptides,and mass spectrometry(MS)analysis to identify monomethylated proteins in Synechocystis sp.PCC 6803(Synechocystis).Overall,we identified 376 monomethylation sites in270 proteins,with numerous monomethylated proteins participating in photosynthesis and carbon metabolism.We subsequently demonstrated that Cpc M,a previously identified asparagine methyltransferase in Synechocystis,could catalyze lysine monomethylation of the potential aspartate aminotransferase Sll0480 both in vivo and in vitro and regulate the enzyme activity of Sll0480.The loss of Cpc M led to decreases in the maximum quantum yield in primary photosystemⅡ(PSⅡ)and the efficiency of energy transfer during the photosynthetic reaction in Synechocystis.We report the first lysine monomethylome in a photosynthetic organism and present a critical database for functional analyses of monomethylation in cyanobacteria.The large number of monomethylated proteins and the identification of Cpc M as the lysine methyltransferase in cyanobacteria suggest that reversible methylation may influence the metabolic process and photosynthesis in both cyanobacteria and plants.
基金funded by the Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(No.820LH027)the Hainan Provincial Natural Science Foundation of China(No.823RC472)+1 种基金the Open Project Program of Wuhan National Laboratory for Optoelectronics(No.2021WNLOKF008)the Hainan University Scientific Research Foundation(KYQD(ZR)19107).
文摘Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody drug conjugate(ADC)of MMAE is currently used in clinical practice.However,the safety issues of MMAE-based ADC,such as high drug toxicity and poor bioavailability,still exist when using it for anticancer therapy.A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects.Herein,PLGA-b-PEG 2000 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy.The sustained release effect and the immunogenic cell death(ICD)effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments.The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention(EPR)effect,inducing cell apoptosis and causing a certain degree of immune response.The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC.Overall,this study provides a safe and effective chemotherapeutic approach,as well as a simple and effective synthetic process for MMAE-based nanoparticles,improving their therapeutic efficacy and safety.
