This study represents a significant advancement in the search for natural compounds that can inhibit the activity of Gingipain K(KGP),a key virulence factor secreted by Porphyromonas gingivalis.At present,there are fe...This study represents a significant advancement in the search for natural compounds that can inhibit the activity of Gingipain K(KGP),a key virulence factor secreted by Porphyromonas gingivalis.At present,there are few studies on the inhibition of gingipains by natural products,and there is an urgent need to find more candidate compounds.By employing molecular docking technology,the researchers screened a large number of natural compounds to assess their binding ability to KGP proteins.As a result,14 flavonoid compounds were identified as potential inhibitors of KGP.The findings from molecular docking analysis revealed a close relationship between the inhibitory effect of candidate compounds and their molecular structures.Further investigation on their inhibitory abilities against KGP proteins was in accordance with the molecular docking results.Among them,trilobatin showed the highest inhibitory rate on the proteolytic ability of KGP(54.86%),while hesperetin 7-O-glucoside showed the highest inhibitory rate on the hemolytic ability of KGP(46.47%).The MIC of phloretin is 12.5μg/mL,followed by trilobatin,phlorizin,and hesperetin dihydrochalcone(50μg/mL),and then naringenin 7-O-glucoside and naringenin(100μg/mL).In further validation,replacing hemoglobin with heme in culture medium increases the MIC of some flavonoids to 2-4 times,indicating the loss of the open-ring structure on the C-ring will lead to a decrease in inhibitory ability.This is the first report of the role of these flavonoids in this field,which will help discover food ingredients to develop products that can help solve the problem of P.gingivalis.展开更多
BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relation...BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.展开更多
目的分析牙龈卟啉单胞菌及其毒力因子牙龈蛋白K在青少年正畸治疗早期的变化。方法随机收集青少年正畸牙龈正常者45例,分别取矫治器戴入前,戴入后1、2、3、6个月龈沟液标本,应用16S r DNA PCR技术检测各样本中的牙龈卟啉单胞菌及其毒力...目的分析牙龈卟啉单胞菌及其毒力因子牙龈蛋白K在青少年正畸治疗早期的变化。方法随机收集青少年正畸牙龈正常者45例,分别取矫治器戴入前,戴入后1、2、3、6个月龈沟液标本,应用16S r DNA PCR技术检测各样本中的牙龈卟啉单胞菌及其毒力因子牙龈蛋白K;采用SPSS17.0软件包对数据进行统计分析,牙龈卟啉单胞菌及牙龈蛋白K各组间检出率比较用χ2检验;牙龈卟啉单胞菌、牙龈蛋白K的检出率与牙龈炎症之间的关系用Spearman等级相关分析。结果牙龈卟啉单胞菌在矫治前与戴入后1个月有显著性差异(P<0.05),与2个月、3个月之间有极显著性差异(P<0.01);戴入后1个月与2个月之间有显著性差异(P<0.05);牙龈蛋白K在矫治器戴入前与戴入后1个月、6个月之间无显著性差异,与戴入后2个月、3个月之间有显著性差异(P<0.05);从第2个月开始牙龈卟啉单胞菌与牙龈蛋白K的检出率下降,到6个月时检出率已基本接近矫治器戴入前。结论青少年正畸治疗过程中在矫治器戴入早期可引发牙龈卟啉单胞菌及牙龈蛋白K的增加,出现牙龈炎症反应,当增加到一定时间即2个月后开始逐渐下降,到6个月时已基本接近矫治器戴入前。展开更多
目的:分析牙龈蛋白K(gingipain K,Kgp)在正畸治疗中对牙龈炎性反应的影响。方法:选择青少年牙龈健康者45例,分别取矫治器戴入前与矫治器戴入后3个月的龈沟液,应用16S r DNA PCR技术检测各样本中的牙龈卟啉单胞菌(P.g)及Kgp,采用SPSS17....目的:分析牙龈蛋白K(gingipain K,Kgp)在正畸治疗中对牙龈炎性反应的影响。方法:选择青少年牙龈健康者45例,分别取矫治器戴入前与矫治器戴入后3个月的龈沟液,应用16S r DNA PCR技术检测各样本中的牙龈卟啉单胞菌(P.g)及Kgp,采用SPSS17.0软件包对数据进行统计学分析。结果:矫治器戴入前Kgp检出率为35.71%,矫治器戴入后Kgp检出率为67.86%,两者之间差异显著(P<0.05)。结论:正畸治疗患者在矫治器戴入后Kgp检出率增加,出现牙龈炎性反应。展开更多
基金supported by the National Natural Science Foundation of China(No.22278159)the Natural Science Foundation of Guangdong Province(No.2024A1515011105).
文摘This study represents a significant advancement in the search for natural compounds that can inhibit the activity of Gingipain K(KGP),a key virulence factor secreted by Porphyromonas gingivalis.At present,there are few studies on the inhibition of gingipains by natural products,and there is an urgent need to find more candidate compounds.By employing molecular docking technology,the researchers screened a large number of natural compounds to assess their binding ability to KGP proteins.As a result,14 flavonoid compounds were identified as potential inhibitors of KGP.The findings from molecular docking analysis revealed a close relationship between the inhibitory effect of candidate compounds and their molecular structures.Further investigation on their inhibitory abilities against KGP proteins was in accordance with the molecular docking results.Among them,trilobatin showed the highest inhibitory rate on the proteolytic ability of KGP(54.86%),while hesperetin 7-O-glucoside showed the highest inhibitory rate on the hemolytic ability of KGP(46.47%).The MIC of phloretin is 12.5μg/mL,followed by trilobatin,phlorizin,and hesperetin dihydrochalcone(50μg/mL),and then naringenin 7-O-glucoside and naringenin(100μg/mL).In further validation,replacing hemoglobin with heme in culture medium increases the MIC of some flavonoids to 2-4 times,indicating the loss of the open-ring structure on the C-ring will lead to a decrease in inhibitory ability.This is the first report of the role of these flavonoids in this field,which will help discover food ingredients to develop products that can help solve the problem of P.gingivalis.
文摘BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.
文摘目的分析牙龈卟啉单胞菌及其毒力因子牙龈蛋白K在青少年正畸治疗早期的变化。方法随机收集青少年正畸牙龈正常者45例,分别取矫治器戴入前,戴入后1、2、3、6个月龈沟液标本,应用16S r DNA PCR技术检测各样本中的牙龈卟啉单胞菌及其毒力因子牙龈蛋白K;采用SPSS17.0软件包对数据进行统计分析,牙龈卟啉单胞菌及牙龈蛋白K各组间检出率比较用χ2检验;牙龈卟啉单胞菌、牙龈蛋白K的检出率与牙龈炎症之间的关系用Spearman等级相关分析。结果牙龈卟啉单胞菌在矫治前与戴入后1个月有显著性差异(P<0.05),与2个月、3个月之间有极显著性差异(P<0.01);戴入后1个月与2个月之间有显著性差异(P<0.05);牙龈蛋白K在矫治器戴入前与戴入后1个月、6个月之间无显著性差异,与戴入后2个月、3个月之间有显著性差异(P<0.05);从第2个月开始牙龈卟啉单胞菌与牙龈蛋白K的检出率下降,到6个月时检出率已基本接近矫治器戴入前。结论青少年正畸治疗过程中在矫治器戴入早期可引发牙龈卟啉单胞菌及牙龈蛋白K的增加,出现牙龈炎症反应,当增加到一定时间即2个月后开始逐渐下降,到6个月时已基本接近矫治器戴入前。
文摘目的:分析牙龈蛋白K(gingipain K,Kgp)在正畸治疗中对牙龈炎性反应的影响。方法:选择青少年牙龈健康者45例,分别取矫治器戴入前与矫治器戴入后3个月的龈沟液,应用16S r DNA PCR技术检测各样本中的牙龈卟啉单胞菌(P.g)及Kgp,采用SPSS17.0软件包对数据进行统计学分析。结果:矫治器戴入前Kgp检出率为35.71%,矫治器戴入后Kgp检出率为67.86%,两者之间差异显著(P<0.05)。结论:正畸治疗患者在矫治器戴入后Kgp检出率增加,出现牙龈炎性反应。
