Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical regi...Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.展开更多
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
Scurs is a horn phenotype that exhibits as small corneous structures on the skull due to the deformed development of horn tissues. Previous genome-wide association analysis of scurs in Soay sheep showed a significant ...Scurs is a horn phenotype that exhibits as small corneous structures on the skull due to the deformed development of horn tissues. Previous genome-wide association analysis of scurs in Soay sheep showed a significant association to the polled locus, relaxin-like receptor 2(RXFP2). However, the molecular mechanism underlying the development of scurs remains largely unknown. In the present study, we performed an i TRAQ-based quantitative proteomic analysis of horn tissues from both scurs and normal two-horned and four-horned individuals among Altay sheep to identify the differentially expressed proteins(DEPs) responsible for the scurs phenotype. In total, 232 proteins showed significant differential expression, and the most significant Gene ontology categories were the adhesion processes(biological adhesion(P=4.07×10–17) and cell adhesion(P=3.7×10–16)), multicellular organismal process(single-multicellular organism process(P=2.06×10–11) and multicellular organismal process(P=2.29×10–11)) and extracellular processes(extracellular matrix organization(P=4.77×10–16) and extracellular structure organization(P=4.93×10–16)). Kyoto encyclopedia of genes and genomes(KEGG) analysis showed that extracellular matrix(ECM)-receptor interactions and focal adhesion pathways were the most significant pathways. This finding is consistent with the reduced formation of extracellular matrix in scurs and the development of deformed horn tissues. Our study helps to elucidate the inheritance pattern of sheep horn traits from the perspectives of downstream expressed proteins.展开更多
Immune cells are indispensable defenders of the human body,clearing exogenous pathogens and toxicities or endogenous malignant and aging cells.Immune cell dysfunction can cause an inability to recognize,react,and remo...Immune cells are indispensable defenders of the human body,clearing exogenous pathogens and toxicities or endogenous malignant and aging cells.Immune cell dysfunction can cause an inability to recognize,react,and remove these hazards,resulting in cancers,inflammatory diseases,autoimmune diseases,and infections.Immune cells regulation has shown great promise in treating disease,and immune agonists are usually used to treat cancers and infections caused by immune suppression.In contrast,immunosuppressants are used to treat inflammatory and autoimmune diseases.However,the key to maintaining health is to restore balance to the immune system,as excessive activation or inhibition of immune cells is a common complication of immunotherapy.Nanoparticles are efficient drug delivery systems widely used to deliver small molecule inhibitors,nucleic acid,and proteins.Using nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell function.In this review,we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.展开更多
Tumor necrosis factor receptors(TNFRs)are promising targets for cancer therapy.However,activating their downstream signaling requires cross-linking of TNFRs.Herein,to devise strong agonists of TNFRs,ligands targeting ...Tumor necrosis factor receptors(TNFRs)are promising targets for cancer therapy.However,activating their downstream signaling requires cross-linking of TNFRs.Herein,to devise strong agonists of TNFRs,ligands targeting TNFRs,such as OX40L and tumor necrosis factor-related apoptosis-inducing ligand(TRAIL),were fused with a multivalent protein scaffold(MV)to prepare multivalent agonists for cross-linking TNFRs.The nano-clustered multivalent-OX40L(MV-OX40L)and MV-TRAIL could promote T cell activation and directly induce tumor cell apoptosis.Moreover,to develop a universal nano-adaptor for the rapid preparation of multivalent agonists of different TNFRs,the Fc receptor that could immobilize antibodies was fused with MV to prepare MV-FcR,which could multimerize commercial agonist antibodies targeting TNFRs,such as anti-OX40 antibody(αOX40).Simply incubatingαOX40 with MV-FcR could prepare MV-αOX40 to enhance its antitumor efficacy.In addition,MV-FcR could multimerize with other therapeutic antibodies,such as anti-PD-L1 antibody,to enhance their valency.This study provides a promising strategy for engineering multivalent antitumor protein drugs.展开更多
文摘Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.
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.
基金supported by the National Natural Science Foundations of China (31402033, U1603232)the Special Fund for Basic Scientific Research of Institute of Animal Sciences,the Chinese Academy of Agricultural Sciences (2017ywf-zd-11, Y2017JC03)the Agricultural Science and Technology Innovation Program of China (ASTIPIAS01)
文摘Scurs is a horn phenotype that exhibits as small corneous structures on the skull due to the deformed development of horn tissues. Previous genome-wide association analysis of scurs in Soay sheep showed a significant association to the polled locus, relaxin-like receptor 2(RXFP2). However, the molecular mechanism underlying the development of scurs remains largely unknown. In the present study, we performed an i TRAQ-based quantitative proteomic analysis of horn tissues from both scurs and normal two-horned and four-horned individuals among Altay sheep to identify the differentially expressed proteins(DEPs) responsible for the scurs phenotype. In total, 232 proteins showed significant differential expression, and the most significant Gene ontology categories were the adhesion processes(biological adhesion(P=4.07×10–17) and cell adhesion(P=3.7×10–16)), multicellular organismal process(single-multicellular organism process(P=2.06×10–11) and multicellular organismal process(P=2.29×10–11)) and extracellular processes(extracellular matrix organization(P=4.77×10–16) and extracellular structure organization(P=4.93×10–16)). Kyoto encyclopedia of genes and genomes(KEGG) analysis showed that extracellular matrix(ECM)-receptor interactions and focal adhesion pathways were the most significant pathways. This finding is consistent with the reduced formation of extracellular matrix in scurs and the development of deformed horn tissues. Our study helps to elucidate the inheritance pattern of sheep horn traits from the perspectives of downstream expressed proteins.
基金supported by the National Key R&D Program of China(2022YFB3808100)the National Natural Science Foundation of China(82072048,52130301,and 32271442)+2 种基金Guangdong Basic and Applied Basic Research Foundation(2022B1515020025)the Science and Technology Program of Guangzhou,China(202103030004)the Fundamental Research Funds for the Central Universities(2022ZYGXZR102).
文摘Immune cells are indispensable defenders of the human body,clearing exogenous pathogens and toxicities or endogenous malignant and aging cells.Immune cell dysfunction can cause an inability to recognize,react,and remove these hazards,resulting in cancers,inflammatory diseases,autoimmune diseases,and infections.Immune cells regulation has shown great promise in treating disease,and immune agonists are usually used to treat cancers and infections caused by immune suppression.In contrast,immunosuppressants are used to treat inflammatory and autoimmune diseases.However,the key to maintaining health is to restore balance to the immune system,as excessive activation or inhibition of immune cells is a common complication of immunotherapy.Nanoparticles are efficient drug delivery systems widely used to deliver small molecule inhibitors,nucleic acid,and proteins.Using nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell function.In this review,we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.
基金National Key R&D Program of China,Grant/Award Number:2022YFB3808100National Natural Science Foundation of China,Grant/Award Numbers:32271442,52130301,82072048+2 种基金Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2022B1515020025Science and Technology Program of Guangzhou,China,Grant/Award Number:202103030004Fundamental Research Funds for the Central Universities,Grant/Award Number:2022ZYGXZR102。
文摘Tumor necrosis factor receptors(TNFRs)are promising targets for cancer therapy.However,activating their downstream signaling requires cross-linking of TNFRs.Herein,to devise strong agonists of TNFRs,ligands targeting TNFRs,such as OX40L and tumor necrosis factor-related apoptosis-inducing ligand(TRAIL),were fused with a multivalent protein scaffold(MV)to prepare multivalent agonists for cross-linking TNFRs.The nano-clustered multivalent-OX40L(MV-OX40L)and MV-TRAIL could promote T cell activation and directly induce tumor cell apoptosis.Moreover,to develop a universal nano-adaptor for the rapid preparation of multivalent agonists of different TNFRs,the Fc receptor that could immobilize antibodies was fused with MV to prepare MV-FcR,which could multimerize commercial agonist antibodies targeting TNFRs,such as anti-OX40 antibody(αOX40).Simply incubatingαOX40 with MV-FcR could prepare MV-αOX40 to enhance its antitumor efficacy.In addition,MV-FcR could multimerize with other therapeutic antibodies,such as anti-PD-L1 antibody,to enhance their valency.This study provides a promising strategy for engineering multivalent antitumor protein drugs.
