Bacterial adherence to the acquired dental pellicle, important in dental caries (caries), is mediated by receptor-adhesins such as salivary agglutinin binding to Streptococcus mutans antigen I/II (I/II). Ten selected ...Bacterial adherence to the acquired dental pellicle, important in dental caries (caries), is mediated by receptor-adhesins such as salivary agglutinin binding to Streptococcus mutans antigen I/II (I/II). Ten selected I/II epitopes were chosen to determine their reactivity to human salivary IgA. Previous studies suggested that a specific HLA biomarker group (HLA-DRB1*04) may have differential influence of immune responses to I/II. However, it was not known whether secretory IgA (SIgA) responses to the selected epitopes from HLA-DRB1*04 positive subjects were different compared to controls, or across other caries-related factors such as total IgA (TIgA). Thirty-two total subjects were matched according to HLA type, gender, ethnicity and age. HLA genotyping, oral bacterial, immunoglobulin and antibody analyses were performed. A large observed difference emerged with regard to the natural immune reservoir of TIgA in HLA-DRB1*04 positive subjects, specifically, a 27.6% reduction compared to controls. In contrast to all other epitopes studied, HLA-DRB1*04 positive subjects also exhibited reduced reactivity to I/II epitope 834-853. HLA-DRB1*04 positive subjects exhibited lower specific SIgA activity/TIgA to 834-853 and also a lower specific reactivity to 834-853/whole cell S. mutans UA159. Furthermore, HLA-DRB1*04 positive subjects exhibited lower responses to I/II in its entirety. The large observed difference in TIgA and the 834-853 reactivity pattern across multiple measures suggest potentially important connections pertaining to the link between HLA-DRB1*04 and caries.展开更多
Dental caries,a chronic disease characterized by tooth decay,occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria,especially Streptococcus mutans,because of its acidog...Dental caries,a chronic disease characterized by tooth decay,occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria,especially Streptococcus mutans,because of its acidogenic,aciduric,and biofilm-forming capabilities.Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents.The current study represents an up-to-date review of in silico approaches of drug design against dental caries,which have emerged more and more powerful complementary to biochemical attempts.Firstly,we categorize the in silico approaches into computer-aided drug design(CADD)and AI-assisted drug design(AIDD)and highlight the specific methods and models they contain respectively.Subsequently,we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S.mutans,such as glucosyltransferases(Gtfs),antigen I/II(AgI/II),sortase A(SrtA),the VicRK signal transduction system and superoxide dismutases(SODs).Finally,we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.展开更多
The taxonomic status of Papilio maackii and P.syfanius has long been disputed.We conducted a molecular phylogenetic study to evaluate the taxonomic status of P.maackii and P.syfanius.A total of twenty-four P.maackii i...The taxonomic status of Papilio maackii and P.syfanius has long been disputed.We conducted a molecular phylogenetic study to evaluate the taxonomic status of P.maackii and P.syfanius.A total of twenty-four P.maackii individuals from six localities and sixteen P.syfanius individuals from two localities were analyzed.We sequenced the partial region of the CO-I gene（about 579 bp） and partial CO-II gene sequence（about 655bp） of the two species.The Kimura-2-Parameter distances among P.maackii and P.syfanius ranged from 0 to 0.6%.Fifteen haplotypes were obtained based on the combined data set.The results strongly supported that all P.maackii individuals and all P.syfanius individuals formed a large clade,and could not be divided into separated clades.This research indicated that the two species have only very recently undergone speciation.展开更多
文摘Bacterial adherence to the acquired dental pellicle, important in dental caries (caries), is mediated by receptor-adhesins such as salivary agglutinin binding to Streptococcus mutans antigen I/II (I/II). Ten selected I/II epitopes were chosen to determine their reactivity to human salivary IgA. Previous studies suggested that a specific HLA biomarker group (HLA-DRB1*04) may have differential influence of immune responses to I/II. However, it was not known whether secretory IgA (SIgA) responses to the selected epitopes from HLA-DRB1*04 positive subjects were different compared to controls, or across other caries-related factors such as total IgA (TIgA). Thirty-two total subjects were matched according to HLA type, gender, ethnicity and age. HLA genotyping, oral bacterial, immunoglobulin and antibody analyses were performed. A large observed difference emerged with regard to the natural immune reservoir of TIgA in HLA-DRB1*04 positive subjects, specifically, a 27.6% reduction compared to controls. In contrast to all other epitopes studied, HLA-DRB1*04 positive subjects also exhibited reduced reactivity to I/II epitope 834-853. HLA-DRB1*04 positive subjects exhibited lower specific SIgA activity/TIgA to 834-853 and also a lower specific reactivity to 834-853/whole cell S. mutans UA159. Furthermore, HLA-DRB1*04 positive subjects exhibited lower responses to I/II in its entirety. The large observed difference in TIgA and the 834-853 reactivity pattern across multiple measures suggest potentially important connections pertaining to the link between HLA-DRB1*04 and caries.
基金supported by the Sichuan Science and Technology Program,China(Grant Nos.:2023ZYD0105 and 2023YFS0343)。
文摘Dental caries,a chronic disease characterized by tooth decay,occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria,especially Streptococcus mutans,because of its acidogenic,aciduric,and biofilm-forming capabilities.Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents.The current study represents an up-to-date review of in silico approaches of drug design against dental caries,which have emerged more and more powerful complementary to biochemical attempts.Firstly,we categorize the in silico approaches into computer-aided drug design(CADD)and AI-assisted drug design(AIDD)and highlight the specific methods and models they contain respectively.Subsequently,we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S.mutans,such as glucosyltransferases(Gtfs),antigen I/II(AgI/II),sortase A(SrtA),the VicRK signal transduction system and superoxide dismutases(SODs).Finally,we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.
基金National Natural Science Foundation of China (30870359)Anhui Scholar Special Fund in Science and Technology (KJ2009B015)
文摘The taxonomic status of Papilio maackii and P.syfanius has long been disputed.We conducted a molecular phylogenetic study to evaluate the taxonomic status of P.maackii and P.syfanius.A total of twenty-four P.maackii individuals from six localities and sixteen P.syfanius individuals from two localities were analyzed.We sequenced the partial region of the CO-I gene（about 579 bp） and partial CO-II gene sequence（about 655bp） of the two species.The Kimura-2-Parameter distances among P.maackii and P.syfanius ranged from 0 to 0.6%.Fifteen haplotypes were obtained based on the combined data set.The results strongly supported that all P.maackii individuals and all P.syfanius individuals formed a large clade,and could not be divided into separated clades.This research indicated that the two species have only very recently undergone speciation.
