There is an increasing interest in discovering new antibacterial agents derived from nature to enhance the treatment of various bacterial infections.Defensins and their derived peptide fragments exhibit significant an...There is an increasing interest in discovering new antibacterial agents derived from nature to enhance the treatment of various bacterial infections.Defensins and their derived peptide fragments exhibit significant antibacterial activity without any cytotoxic effects,making them attractive features for potential novel antibacterial therapeutics.Crassostrea gigas,a traditional seafood that has been used worldwide for centuries,has its shells applied in Chinese medicine as Ostreae concha.In this study,bioinformatics analysis was used to obtain a novel antibacterial peptide,CGD-1,derived from marine Chinese medicine Ostreae concha.The physicochemical characterization and circular dichroism analysis results demonstrated that CGD-1 assembled into anα-helical structure in a simulated membrane environment,and it displayed antibacterial action against Gram-negative bacteria.The minimal inhibitory concentrations against both Pseudomonas aeruginosa ATCC27853 and Escherichia coli ATCC25922 were 25μM.CGD-1 was able to efficiently permeate the cell membrane.Changes in bacterial cell morphology were evaluated using a field emission scanning electron microscope.The results suggested that CGD-1 exerted its antibacterial activity through permeabilizing and disrupting the bacterial cell membrane.Therefore,CGD-1 may have potential applications in fighting against pathogenic bacteria such as P.aeruginosa and E.coli.展开更多
AIM: To investigate the genetic background of human defensin expression in type 1 and 2 diabetes.METHODS: Associations between DEFA1/DEFA3 gene copy number polymorphism and diabetes as well as between the promoter pol...AIM: To investigate the genetic background of human defensin expression in type 1 and 2 diabetes.METHODS: Associations between DEFA1/DEFA3 gene copy number polymorphism and diabetes as well as between the promoter polymorphisms of DEFB1 and diabetes were studied. The copy number variation of the DEFA1/DEFA3 genes was determined in 257 diabetic patients(117 patients with type 1 and 140 with type 2 diabetes). The control group consisted of 221 age- and gender-matched healthy blood donors. The cumulative copy numbers of the DEFA1/DEFA3 genes were detected by using quantitative PCR analysis. To evaluate the HNP 1-3(human neutrophil peptide 1-3 or α-defensin) levels in the circulation, plasma HNP 1-3 concentrations were measured by ELISA. The expression of DEFA1/A3 in peripheral leukocytes of the diabetic patients was measured by quantitative RT PCR analysis. Three SNPs of the human DEFB1(human defensin β-1) gene: DEFB1 G-20A(rs11362), DEFB1 C-44G(rs1800972) and DEFB1 G-52A(rs1799946) were genotyped by Custom TaqMan? Real Time PCR assay.RESULTS: Significant differences were observed in HNP1-3 levels between the healthy subjects and both groups of diabetic patients. The mean ± SE was 28.78 ± 4.2 ng/mL in type 1 diabetes, and 29.82 ± 5.36 ng/mL in type 2 diabetes, vs 11.94 ± 2.96 ng/mL in controls; P < 0.01 respectively. There was no significant difference between patients with type 1 and type 2 diabetes in the high plasma concentrations of HNP1-3. The highest concentrations of α-defensin were found in diabetic patients with nephropathy(49.4 ± 4.8 ng/mL), neuropathy(38.7 ± 4.8 ng/mL) or cardiovascular complications(45.6 ± 1.45 ng/L). There was no significant difference in the cumulative copy numbers of DEFA1/DEFA3 genes between controls and patients, or between patients with the two types of diabetes. Comparisons of HNP 1-3 plasma level and DEFA1/A3 copy number of the same patient did not reveal significant relationship between defensin-α levels and the gene copy numbers(r2 = 0.01). Similarly, no positive correlation was observed between the copy numbers and the mRNA expression levels of DEFA1/A3. Regarding the C-44G polymorphism of DEFB1, the GG "protective" genotype was much less frequent(1%-2%) among both groups of patients than among controls(9%).CONCLUSION: Elevated HNP1-3 levels in diabetes are independent of DEFA1/DEFA3 copy numbers, but GG genotype of C-44G SNP in DEFB1 gene may result in decreased defensin β-1 production.展开更多
The epididymal β-defensins have evolved by repeated gene duplication and divergence to encode a family of proteins that provide direct protection against pathogens and also support the male reproductive tract in its ...The epididymal β-defensins have evolved by repeated gene duplication and divergence to encode a family of proteins that provide direct protection against pathogens and also support the male reproductive tract in its primary function. Male tract defensins also facilitate recovery from pathogen attack. The β-defensins possess ancient conserved sequence and structural features widespread in multi-cellular organisms, suggesting fundamental roles in species survival. Primate SPAG11, the functional fusion of two ancestrally independent β-defensin genes, produces a large family of alternatively spliced transcripts that are expressed according to tissue-specific and species-specific constraints. The complexity of SPAG11 varies in different branches of mammalian evolution. Interactions of human SPAG11D with host proteins indicate involvement in multiple signaling pathways. （Asian J Andro12007 July; 9： 453- 462）展开更多
基金This research work was financially supported National Natural Science Foundation of China(No.82003910)Guangdong Basic and Applied Basic Research Foundation(2020A1515110550)+2 种基金Funding Key R&D Program of Shandong Province(2022SFGC0105)Exploration Innovation Team(2021GXRC062),Jinan Talent Project for Universities(202228088)Key innovation Project of Qilu University of Technology(Shandong Academy of Sciences)(2022JBZ01-06).
文摘There is an increasing interest in discovering new antibacterial agents derived from nature to enhance the treatment of various bacterial infections.Defensins and their derived peptide fragments exhibit significant antibacterial activity without any cytotoxic effects,making them attractive features for potential novel antibacterial therapeutics.Crassostrea gigas,a traditional seafood that has been used worldwide for centuries,has its shells applied in Chinese medicine as Ostreae concha.In this study,bioinformatics analysis was used to obtain a novel antibacterial peptide,CGD-1,derived from marine Chinese medicine Ostreae concha.The physicochemical characterization and circular dichroism analysis results demonstrated that CGD-1 assembled into anα-helical structure in a simulated membrane environment,and it displayed antibacterial action against Gram-negative bacteria.The minimal inhibitory concentrations against both Pseudomonas aeruginosa ATCC27853 and Escherichia coli ATCC25922 were 25μM.CGD-1 was able to efficiently permeate the cell membrane.Changes in bacterial cell morphology were evaluated using a field emission scanning electron microscope.The results suggested that CGD-1 exerted its antibacterial activity through permeabilizing and disrupting the bacterial cell membrane.Therefore,CGD-1 may have potential applications in fighting against pathogenic bacteria such as P.aeruginosa and E.coli.
基金Supported by TáMOP-4.2.2.A-11-1-KONV-2012-0035 Research Grant
文摘AIM: To investigate the genetic background of human defensin expression in type 1 and 2 diabetes.METHODS: Associations between DEFA1/DEFA3 gene copy number polymorphism and diabetes as well as between the promoter polymorphisms of DEFB1 and diabetes were studied. The copy number variation of the DEFA1/DEFA3 genes was determined in 257 diabetic patients(117 patients with type 1 and 140 with type 2 diabetes). The control group consisted of 221 age- and gender-matched healthy blood donors. The cumulative copy numbers of the DEFA1/DEFA3 genes were detected by using quantitative PCR analysis. To evaluate the HNP 1-3(human neutrophil peptide 1-3 or α-defensin) levels in the circulation, plasma HNP 1-3 concentrations were measured by ELISA. The expression of DEFA1/A3 in peripheral leukocytes of the diabetic patients was measured by quantitative RT PCR analysis. Three SNPs of the human DEFB1(human defensin β-1) gene: DEFB1 G-20A(rs11362), DEFB1 C-44G(rs1800972) and DEFB1 G-52A(rs1799946) were genotyped by Custom TaqMan? Real Time PCR assay.RESULTS: Significant differences were observed in HNP1-3 levels between the healthy subjects and both groups of diabetic patients. The mean ± SE was 28.78 ± 4.2 ng/mL in type 1 diabetes, and 29.82 ± 5.36 ng/mL in type 2 diabetes, vs 11.94 ± 2.96 ng/mL in controls; P < 0.01 respectively. There was no significant difference between patients with type 1 and type 2 diabetes in the high plasma concentrations of HNP1-3. The highest concentrations of α-defensin were found in diabetic patients with nephropathy(49.4 ± 4.8 ng/mL), neuropathy(38.7 ± 4.8 ng/mL) or cardiovascular complications(45.6 ± 1.45 ng/L). There was no significant difference in the cumulative copy numbers of DEFA1/DEFA3 genes between controls and patients, or between patients with the two types of diabetes. Comparisons of HNP 1-3 plasma level and DEFA1/A3 copy number of the same patient did not reveal significant relationship between defensin-α levels and the gene copy numbers(r2 = 0.01). Similarly, no positive correlation was observed between the copy numbers and the mRNA expression levels of DEFA1/A3. Regarding the C-44G polymorphism of DEFB1, the GG "protective" genotype was much less frequent(1%-2%) among both groups of patients than among controls(9%).CONCLUSION: Elevated HNP1-3 levels in diabetes are independent of DEFA1/DEFA3 copy numbers, but GG genotype of C-44G SNP in DEFB1 gene may result in decreased defensin β-1 production.
文摘The epididymal β-defensins have evolved by repeated gene duplication and divergence to encode a family of proteins that provide direct protection against pathogens and also support the male reproductive tract in its primary function. Male tract defensins also facilitate recovery from pathogen attack. The β-defensins possess ancient conserved sequence and structural features widespread in multi-cellular organisms, suggesting fundamental roles in species survival. Primate SPAG11, the functional fusion of two ancestrally independent β-defensin genes, produces a large family of alternatively spliced transcripts that are expressed according to tissue-specific and species-specific constraints. The complexity of SPAG11 varies in different branches of mammalian evolution. Interactions of human SPAG11D with host proteins indicate involvement in multiple signaling pathways. （Asian J Andro12007 July; 9： 453- 462）
