DEAR EDITOR,Pore-forming proteins(PFPs)are widely distributed among all kingdoms of life and can oligomerize to form pores/channels in membrane systems.Extracellular vesicles(EVs)circulate in all biological fluids and...DEAR EDITOR,Pore-forming proteins(PFPs)are widely distributed among all kingdoms of life and can oligomerize to form pores/channels in membrane systems.Extracellular vesicles(EVs)circulate in all biological fluids and can trigger biological responses at a distance,thus emerging as an additional means of intercellular communication through the release of cellular cargo,such as lipids,nucleic acids,metabolites,and proteins.To date,however,the mechanism by which EV contents are released into extracellular space remains unclear.In our previous study on toads(Bombina maxima),we identified a PFP and trefoil factor complexβγ-CAT(βγ-crystallin fused aerolysin-like protein(α-subunit)and trefoil factor(β-subunit)complex,hence namedβγ-CAT),which assembled under strict regulation in response to environmental cues.Here,we observed that the PFPβγ-CAT colocalized with EVs in the skin of B.maxima in vivo.Using small EVs(sEVs)isolated from B.maxima dermal fibroblast cells and murine fibroblast cells,we found thatβγ-CAT could specifically target and oligomerize on purified EVs,rather than disrupt membrane integrity,and promote the release of different metabolites.Our analysis revealed that a secretory PFP drove metabolite release from EVs through channel formation,providing novel clues for the delivery of EV content into extracellular space.展开更多
Cationic antimicrobial peptides （AMPs） are considered as important candidate therapeutic agents, which exert potent microbicidal properties against bacteria, fungi and some viruses. Based on our previous findings ki...Cationic antimicrobial peptides （AMPs） are considered as important candidate therapeutic agents, which exert potent microbicidal properties against bacteria, fungi and some viruses. Based on our previous findings king cobra cathelicidin （OH-CATH） is a 34-amino acid peptide that exerts strong antibacterial and weak hemolytic activity. The aim of this research is to evaluate the efficacy of both OH-CATH30 and its analog D-OH-CATH30 against clinical isolates comparing with routinely utilized antibiotics in vitro. In this study, 584 clinical isolates were tested （spanning 2013-2016） and the efficacy of the candidate peptides and antibiotics were determined by a broth microdilution method according to the CLSI guidelines. Among the 584 clinical isolates, 85% were susceptible to OH-CATH30 and its analogs. Both L- and D-OH-CATH30 showed higher efficacy against （toward） Gram-positive bacteria and stronger antibacterial activity against nearly all Gram-negative bacteria tested compare with antibiotics. The highest bactericidal activity was detected against Acinetobacter spp., including multi-drug-resistant Acinetobacter baumannfi （MRAB） and methicillin-resistant Staphylococcus aureus （MRSA）. The overall efficacy of OH-CATH30 and its analogs was higher than that of the 9 routinely used antibiotics. OH-CATH30 is a promising candidate drug for the treatment of a wide variety of bacterial infections which are resistant to many routinely used antimicrobial agents.展开更多
As the oldest venomous animals,centipedes use their venom as a weapon to attack prey and for protection.Centipede venom,which contains many bioactive and pharmacologically active compounds,has been used for centuries ...As the oldest venomous animals,centipedes use their venom as a weapon to attack prey and for protection.Centipede venom,which contains many bioactive and pharmacologically active compounds,has been used for centuries in Chinese medicine,as shown by ancient records.Based on comparative analysis,we revealed the diversity of and differences in centipede toxin-like molecules between Scolopendra mojiangica,a substitute pharmaceutical material used in China,and S.subspinipes mutilans.More than 6000 peptides isolated from the venom were identified by electrospray ionization-tandem mass spectrometry(ESI-MS/MS)and inferred from the transcriptome.As a result,in the proteome of S.mojiangica,246 unique proteins were identified:one in five were toxin-like proteins or putative toxins with unknown function,accounting for a lower percentage of total proteins than that in S.mutilans.Transcriptome mining identified approximately 10 times more toxin-like proteins,which can characterize the precursor structures of mature toxinlike peptides.However,the constitution and quantity of the toxin transcripts in these two centipedes were similar.In toxicity assays,the crude venom showed strong insecticidal and hemolytic activity.These findings highlight the extensive diversity of toxin-like proteins in S.mojiangica and provide a new foundation for the medical-pharmaceutical use of centipede toxin-like proteins.展开更多
DEAR EDITOR,Extracellular vesicles(EVs)are important for the transport of biologically active materials and for intercellular communication.As an exposed mucosa,amphibian skin participates in many essential physiologi...DEAR EDITOR,Extracellular vesicles(EVs)are important for the transport of biologically active materials and for intercellular communication.As an exposed mucosa,amphibian skin participates in many essential physiological processes.To date,however,little is known about EVs in amphibian skin.Here,we successfully isolated EVs from the skin secretions of Bombina maxima,and characterized the EVs using nanoparticle tracking,western blotting,and electron microscopy.展开更多
The arachidonic acid(AA)metabolic pathway participates in various physiological processes as well as in the development of malignancies.We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atla...The arachidonic acid(AA)metabolic pathway participates in various physiological processes as well as in the development of malignancies.We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atlas(TCGA)prostate cancer(PCa)dataset and found that the gene encoding soluble epoxide hydrolase(EPHX2)is frequently deleted in PCa.EPHX2 mRNA and protein expression in PCa was examined in multiple datasets by differential gene expression analysis and in a tissue microarray by immunohistochemistry.The expression data were analyzed in conjunction with clinicopathological variables.Both the mRNA and protein expression levels of EPHX2 were significantly decreased in tumors compared with normal prostate tissues and were inversely correlated with the Gleason grade and disease-free survival time.Furthermore,EPHX2 mRNA expression was significantly decreased in metastatic and recurrent PCa compared with localized and primary PCa,respectively.In addition,EPHX2 protein expression correlated negatively with Ki67 expression.In conclusion,EPHX2 deregulation is significantly correlated with the clinical characteristics of PCa progression and may serve as a prognostic marker for PCa.展开更多
基金supported by the National Natural Science Foundation of China (31572268, U1602225, 31872226)Yunling Scholar Program to Y.Z.Basic Research of Yunnan Province(202101AT070292) to X.L.G.
文摘DEAR EDITOR,Pore-forming proteins(PFPs)are widely distributed among all kingdoms of life and can oligomerize to form pores/channels in membrane systems.Extracellular vesicles(EVs)circulate in all biological fluids and can trigger biological responses at a distance,thus emerging as an additional means of intercellular communication through the release of cellular cargo,such as lipids,nucleic acids,metabolites,and proteins.To date,however,the mechanism by which EV contents are released into extracellular space remains unclear.In our previous study on toads(Bombina maxima),we identified a PFP and trefoil factor complexβγ-CAT(βγ-crystallin fused aerolysin-like protein(α-subunit)and trefoil factor(β-subunit)complex,hence namedβγ-CAT),which assembled under strict regulation in response to environmental cues.Here,we observed that the PFPβγ-CAT colocalized with EVs in the skin of B.maxima in vivo.Using small EVs(sEVs)isolated from B.maxima dermal fibroblast cells and murine fibroblast cells,we found thatβγ-CAT could specifically target and oligomerize on purified EVs,rather than disrupt membrane integrity,and promote the release of different metabolites.Our analysis revealed that a secretory PFP drove metabolite release from EVs through channel formation,providing novel clues for the delivery of EV content into extracellular space.
基金supported by grants from the National Natural Sciences Foundation of China(31572268,31560596)the Key Research Program of the Chinese Academy of Sciences(KJZD-EW-L03)+3 种基金"Yunnan Scholar"Programthe Yunnan Applied Basic Research Projects(2016FD076)the National Training Program of Innovation and Entrepreneurship for Undergraduates(201510685001201610685001)Puer University(RCXM003&CXTD011)
文摘Cationic antimicrobial peptides （AMPs） are considered as important candidate therapeutic agents, which exert potent microbicidal properties against bacteria, fungi and some viruses. Based on our previous findings king cobra cathelicidin （OH-CATH） is a 34-amino acid peptide that exerts strong antibacterial and weak hemolytic activity. The aim of this research is to evaluate the efficacy of both OH-CATH30 and its analog D-OH-CATH30 against clinical isolates comparing with routinely utilized antibiotics in vitro. In this study, 584 clinical isolates were tested （spanning 2013-2016） and the efficacy of the candidate peptides and antibiotics were determined by a broth microdilution method according to the CLSI guidelines. Among the 584 clinical isolates, 85% were susceptible to OH-CATH30 and its analogs. Both L- and D-OH-CATH30 showed higher efficacy against （toward） Gram-positive bacteria and stronger antibacterial activity against nearly all Gram-negative bacteria tested compare with antibiotics. The highest bactericidal activity was detected against Acinetobacter spp., including multi-drug-resistant Acinetobacter baumannfi （MRAB） and methicillin-resistant Staphylococcus aureus （MRSA）. The overall efficacy of OH-CATH30 and its analogs was higher than that of the 9 routinely used antibiotics. OH-CATH30 is a promising candidate drug for the treatment of a wide variety of bacterial infections which are resistant to many routinely used antimicrobial agents.
基金supported by grants from the Chinese National Natural Science Foundation(81860696,31560596,81373945,and 31360516)Yunnan Applied Basic Research Projects(2016FD076)+2 种基金Key Research Program of the Chinese Academy of Sciences(KJZD-EW-L03)"Yunling Scholar"Program,Yunnan Provincial Training Programs of Youth Leader in Academic and Technical Reserve Talent(2019HB058)Puer University(2017XJKT12&CXTD011)。
文摘As the oldest venomous animals,centipedes use their venom as a weapon to attack prey and for protection.Centipede venom,which contains many bioactive and pharmacologically active compounds,has been used for centuries in Chinese medicine,as shown by ancient records.Based on comparative analysis,we revealed the diversity of and differences in centipede toxin-like molecules between Scolopendra mojiangica,a substitute pharmaceutical material used in China,and S.subspinipes mutilans.More than 6000 peptides isolated from the venom were identified by electrospray ionization-tandem mass spectrometry(ESI-MS/MS)and inferred from the transcriptome.As a result,in the proteome of S.mojiangica,246 unique proteins were identified:one in five were toxin-like proteins or putative toxins with unknown function,accounting for a lower percentage of total proteins than that in S.mutilans.Transcriptome mining identified approximately 10 times more toxin-like proteins,which can characterize the precursor structures of mature toxinlike peptides.However,the constitution and quantity of the toxin transcripts in these two centipedes were similar.In toxicity assays,the crude venom showed strong insecticidal and hemolytic activity.These findings highlight the extensive diversity of toxin-like proteins in S.mojiangica and provide a new foundation for the medical-pharmaceutical use of centipede toxin-like proteins.
基金supported by the National Natural Science Foundation of China(31572268,U1602225,31872226)Yunling Scholar Program to Y.Z.,and the Basic Research of Yunnan Province(202101AT070292)to X.L.G.
文摘DEAR EDITOR,Extracellular vesicles(EVs)are important for the transport of biologically active materials and for intercellular communication.As an exposed mucosa,amphibian skin participates in many essential physiological processes.To date,however,little is known about EVs in amphibian skin.Here,we successfully isolated EVs from the skin secretions of Bombina maxima,and characterized the EVs using nanoparticle tracking,western blotting,and electron microscopy.
基金Financial support for this study was supported by Yunnan Fundamental Research Projects(No.2019FE001[-277]and 2019FE001[-005])the Project for Innovation Team of Yunnan Provincial Science and Technology Department,China(No.2018HC005)Qujing Affiliated Hospital of Kunming Medical University(2019YJKT11 and 2020YJKT03).
文摘The arachidonic acid(AA)metabolic pathway participates in various physiological processes as well as in the development of malignancies.We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atlas(TCGA)prostate cancer(PCa)dataset and found that the gene encoding soluble epoxide hydrolase(EPHX2)is frequently deleted in PCa.EPHX2 mRNA and protein expression in PCa was examined in multiple datasets by differential gene expression analysis and in a tissue microarray by immunohistochemistry.The expression data were analyzed in conjunction with clinicopathological variables.Both the mRNA and protein expression levels of EPHX2 were significantly decreased in tumors compared with normal prostate tissues and were inversely correlated with the Gleason grade and disease-free survival time.Furthermore,EPHX2 mRNA expression was significantly decreased in metastatic and recurrent PCa compared with localized and primary PCa,respectively.In addition,EPHX2 protein expression correlated negatively with Ki67 expression.In conclusion,EPHX2 deregulation is significantly correlated with the clinical characteristics of PCa progression and may serve as a prognostic marker for PCa.
