Fusobacterium nucleatum(F.nucleatum)is an early pathogenic colonizer in periodontitis,but the host response to infection with this pathogen remains unclear.In this study,we built an F.nucleatum infectious model with h...Fusobacterium nucleatum(F.nucleatum)is an early pathogenic colonizer in periodontitis,but the host response to infection with this pathogen remains unclear.In this study,we built an F.nucleatum infectious model with human periodontal ligament stem cells(PDLSCs)and showed that F.nucleatum could inhibit proliferation,and facilitate apoptosis,ferroptosis,and inflammatory cytokine production in a dose-dependent manner.The F.nucleatum adhesin Fad A acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β,IL-6 and IL-8.Further study showed that Fad A could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways.Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F.nucleatum infection.NFκB1 and NFκB2 upregulated after 3 h of F.nucleatum-infection,and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time.Using computational drug repositioning analysis,we predicted and validated that two potential drugs(piperlongumine and fisetin)could attenuate the negative effects of F.nucleatum-infection.Collectively,this study unveils the potential pathogenic mechanisms of F.nucleatum and the host inflammatory response at the early stage of F.nucleatum infection.展开更多
In the previous research,when the economic factor forecasting solution of Urbanization was used into practice,the users almost always ignored the effects of the lagged economic development factors.The accuracy of the ...In the previous research,when the economic factor forecasting solution of Urbanization was used into practice,the users almost always ignored the effects of the lagged economic development factors.The accuracy of the forecasting should be decreased seriously by this way.In this paper,taking Gansu province as an example,the authors try to improve the forecasting accuracy on the basis of the unrestricted PDL(Polynomial Distributed Lag)Models.In the context,the ARIMA Models and CPPS software are also applied to finish the forecasting more accurately.展开更多
基金foundation support of the National Natural Science Foundation of China(Grant No.82071122)the Program of Taishan Young from Shandong Province+3 种基金Major Innovation Projects in Shandong Province(No.2021SFGC0502)Oral Microbiome Innovation Team of Young Scientist Project of Shandong Province(Grant No.2020KJK001)and Jinan City(2021GXRC021)The National High-level Young Scientist Project Foundation(2019)Excellent Young Scientist Foundation of Shandong Province(Grant No.ZR202102230369)。
文摘Fusobacterium nucleatum(F.nucleatum)is an early pathogenic colonizer in periodontitis,but the host response to infection with this pathogen remains unclear.In this study,we built an F.nucleatum infectious model with human periodontal ligament stem cells(PDLSCs)and showed that F.nucleatum could inhibit proliferation,and facilitate apoptosis,ferroptosis,and inflammatory cytokine production in a dose-dependent manner.The F.nucleatum adhesin Fad A acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β,IL-6 and IL-8.Further study showed that Fad A could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways.Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F.nucleatum infection.NFκB1 and NFκB2 upregulated after 3 h of F.nucleatum-infection,and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time.Using computational drug repositioning analysis,we predicted and validated that two potential drugs(piperlongumine and fisetin)could attenuate the negative effects of F.nucleatum-infection.Collectively,this study unveils the potential pathogenic mechanisms of F.nucleatum and the host inflammatory response at the early stage of F.nucleatum infection.
文摘In the previous research,when the economic factor forecasting solution of Urbanization was used into practice,the users almost always ignored the effects of the lagged economic development factors.The accuracy of the forecasting should be decreased seriously by this way.In this paper,taking Gansu province as an example,the authors try to improve the forecasting accuracy on the basis of the unrestricted PDL(Polynomial Distributed Lag)Models.In the context,the ARIMA Models and CPPS software are also applied to finish the forecasting more accurately.
文摘目的探讨恒河猴来源的PDL1Ig在体外混合淋巴细胞反应中的作用。方法在Gen Bank中检索到恒河猴目的基因PDL1和Ig G1Fc的序列,采用重叠延伸PCR法合成该目的基因,与p GEM-T连接转化感受态E.coli TOP10,经鉴定得到PDL1Ig基因,p Shuttle-CMV线性化后连接目的基因转化感受态E.coli TOP10,克隆p Shuttle-CMV/PDL1Ig重组穿梭质粒。将p Ad Easy-1和线性p Shuttle-CMV/PDL1Ig共电转至BJ5183细胞中同源重组,构建重组腺病毒载体p Ad Easy-1/PDL1Ig骨架,以脂质体2000将p Ad Easy-1/PDL1Ig转染至293细胞中包装成有活性的重组腺病毒。感染恒河猴肝细胞,RT-PCR和Western blotting检测目的基因的表达。混合淋巴细胞反应(MLR)测定其生物学活性。结果成功构建了PDL1Ig重组腺病毒载体,能感染恒河猴肝细胞,RT-PCR和Western blotting检测有目的基因表达,在混合淋巴细胞反应中其能抑制T细胞增殖。结论成功构建了p Ad Easy-1/PDL1Ig重组腺病毒载体,其可在恒河猴肝细胞中高效表达,该重组蛋白可在体外通过PD-1/PDL1通路抑制T淋巴细胞增殖。
