The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer’s disease.Microglia are resident immune cells in the brain that may orchestrate communication between the centra...The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer’s disease.Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system,though the mechanisms are unclear.Here,we found that gamma-type immunoglobulin,a product originating from peripheral blood B cells,localized in the brain parenchyma of multiple mouse models with amyloid pathology,and was enriched on microglia but not on other brain cell types.Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes,including upregulation of pathways related to phagocytosis and immunity.Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc fragment,but not Fab fragment,fragment.Our data indicate that microglia,when exposed to gamma-type immunoglobulin,exhibit an enhanced capacity for clearing amyloid-beta fibrils,potentially via the gamma-type immunoglobulin Fc fragment signaling pathway.This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer’s disease by enhancing microglial function.展开更多
Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular st...Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular studies have demonstrated a consistent association between chronic viral infection and B-NHLs.Multiple pathogenic mechanisms have been implicated in lymphomagenesis,both direct and indirect,including chronic antigenic stimulation,direct infection of B cells,and viral protein-mediated oncogenic signaling,It is likely that a combination of several pathogenic conditions is required to eventually lead to the development of lymphoma.The prevalence of B-cell lymphomas among individuals with chronic HCV or HBV infection presents a complex pathogenetic scenario,given the tumor heterogeneity and variable clinical behavior,and poses therapeutic challenges,due to the partial efficacy of current treatment options.The advent of direct-acting antivirals(DAAs)for HCV and high-genetic barrier nucleos(t)ide analogues(NAs)for HBV has improved patient outcomes.In indolent HCV-associated B-NHLs,antiviral therapy with DAAs alone often achieves sustained virologic response and may lead to lymphoma regression.Conversely,aggressive subtypes like diffuse large B-cell lymphomas require combination treatment with immunochemotherapy.In the setting of HBV-associated lymphomas,antiviral prophylaxis with potent NAs(e.g.,entecavir or tenofovir)is essential to prevent HBV reactivation during rituximab-containing chemotherapy regimen.The integration of antiviral and anticancer therapies has been shown to enhance survival outcomes while mitigating hepatic toxicity.A comprehensive understanding of the biological interplay between chronic viral infection and B-cell transformation is critical for optimizing diagnostic and therapeutic strategies.Aim of this viewpoint is to provide evidence that early viral detection and prompt management remain the most effective strategies to improve survival rates and to reduce treatment-related morbidity in these patients.展开更多
Hyperglycemia resulting from diabetes mellitus(DM)exacerbates osteoporosis and fractures,damaging bone regeneration due to impaired healing capacity.Stem cell therapy offers the potential for bone repair,accelerating ...Hyperglycemia resulting from diabetes mellitus(DM)exacerbates osteoporosis and fractures,damaging bone regeneration due to impaired healing capacity.Stem cell therapy offers the potential for bone repair,accelerating the healing of bone defects by introducing stem cells with osteogenic differentiation ability.Dental follicle stem cells(DFSCs)are a newly emerging type of dental stem cells that not only have the potential for multipotent differentiation but also hold easy accessibility and can stand longterm storage.However,DM-associated oxidative stress and inflammation elevate the risk of DFSCs dysfunction and apoptosis,diminishing stem cell therapy efficacy.Recent nanomaterial advances,particularly in DNA nanostructures like tetrahedral framework nucleic acids(tFNAs),have been promising candidates for modulating cellular behaviors.Accumulating experiments have shown that tFNAs’cell proliferation and migration-promoting ability and induce osteogenic differentiation of stem cells.Meanwhile,tFNAs can scavenge reactive oxygen species(ROS)and downregulate the secretion of inflammatory factors by inhibiting various inflammation-related signaling pathways.Here,we applied tFNAs to modify DFSCs and observed enhanced osteogenic differentiation alongside ROS scavenging and anti-inflammatory effects mediated by suppressing the ROS/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa-B(NF-κB)signaling pathway.This intervention reduced stem cell apoptosis,bolstering stem cell therapy efficacy in DM.Our study establishes a simple yet potent tFNAs-DFSCs system,offering potential as a bone repair agent for future DM treatment.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171082(to ZX),32000727(to TZ),32370731(to YZ)Guangdong Basic and Applied Basic Research Foundation,No.2024A151501069(to ZX)+1 种基金Shenzhen Science and Technology Program,Nos.JCYJ20210324101603009(to ZX),GJHZ20220913142807015(to TZ),JCYJ20220531100204010(to TZ),JCYJ20230807091308018(to YZ)Shenzhen Medical Research Funds,No.A2303068(to TZ).
文摘The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer’s disease.Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system,though the mechanisms are unclear.Here,we found that gamma-type immunoglobulin,a product originating from peripheral blood B cells,localized in the brain parenchyma of multiple mouse models with amyloid pathology,and was enriched on microglia but not on other brain cell types.Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes,including upregulation of pathways related to phagocytosis and immunity.Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc fragment,but not Fab fragment,fragment.Our data indicate that microglia,when exposed to gamma-type immunoglobulin,exhibit an enhanced capacity for clearing amyloid-beta fibrils,potentially via the gamma-type immunoglobulin Fc fragment signaling pathway.This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer’s disease by enhancing microglial function.
基金supported by the National Italian Research Council(CNR)“Progetto DSB.AD007.305.001”to Monica Rinaldi。
文摘Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular studies have demonstrated a consistent association between chronic viral infection and B-NHLs.Multiple pathogenic mechanisms have been implicated in lymphomagenesis,both direct and indirect,including chronic antigenic stimulation,direct infection of B cells,and viral protein-mediated oncogenic signaling,It is likely that a combination of several pathogenic conditions is required to eventually lead to the development of lymphoma.The prevalence of B-cell lymphomas among individuals with chronic HCV or HBV infection presents a complex pathogenetic scenario,given the tumor heterogeneity and variable clinical behavior,and poses therapeutic challenges,due to the partial efficacy of current treatment options.The advent of direct-acting antivirals(DAAs)for HCV and high-genetic barrier nucleos(t)ide analogues(NAs)for HBV has improved patient outcomes.In indolent HCV-associated B-NHLs,antiviral therapy with DAAs alone often achieves sustained virologic response and may lead to lymphoma regression.Conversely,aggressive subtypes like diffuse large B-cell lymphomas require combination treatment with immunochemotherapy.In the setting of HBV-associated lymphomas,antiviral prophylaxis with potent NAs(e.g.,entecavir or tenofovir)is essential to prevent HBV reactivation during rituximab-containing chemotherapy regimen.The integration of antiviral and anticancer therapies has been shown to enhance survival outcomes while mitigating hepatic toxicity.A comprehensive understanding of the biological interplay between chronic viral infection and B-cell transformation is critical for optimizing diagnostic and therapeutic strategies.Aim of this viewpoint is to provide evidence that early viral detection and prompt management remain the most effective strategies to improve survival rates and to reduce treatment-related morbidity in these patients.
基金supported by the National Natural Science Foundation of China (Nos. 82101077, 82370929)Sichuan Science and Technology Program (Nos. 2023NSFSC1516, 2023NSFSC1706)+3 种基金Postdoctoral Science Foundation of China (Nos. 2021M692271, 2023T160455, BX20220220, 2022M722251)West China School/Hospital of Stomatology Sichuan University (No. RCDWJS2023–5)Fundamental Research Funds for the Central UniversitiesResearch and Develop Program, West China Hospital of Stomatology Sichuan University
文摘Hyperglycemia resulting from diabetes mellitus(DM)exacerbates osteoporosis and fractures,damaging bone regeneration due to impaired healing capacity.Stem cell therapy offers the potential for bone repair,accelerating the healing of bone defects by introducing stem cells with osteogenic differentiation ability.Dental follicle stem cells(DFSCs)are a newly emerging type of dental stem cells that not only have the potential for multipotent differentiation but also hold easy accessibility and can stand longterm storage.However,DM-associated oxidative stress and inflammation elevate the risk of DFSCs dysfunction and apoptosis,diminishing stem cell therapy efficacy.Recent nanomaterial advances,particularly in DNA nanostructures like tetrahedral framework nucleic acids(tFNAs),have been promising candidates for modulating cellular behaviors.Accumulating experiments have shown that tFNAs’cell proliferation and migration-promoting ability and induce osteogenic differentiation of stem cells.Meanwhile,tFNAs can scavenge reactive oxygen species(ROS)and downregulate the secretion of inflammatory factors by inhibiting various inflammation-related signaling pathways.Here,we applied tFNAs to modify DFSCs and observed enhanced osteogenic differentiation alongside ROS scavenging and anti-inflammatory effects mediated by suppressing the ROS/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa-B(NF-κB)signaling pathway.This intervention reduced stem cell apoptosis,bolstering stem cell therapy efficacy in DM.Our study establishes a simple yet potent tFNAs-DFSCs system,offering potential as a bone repair agent for future DM treatment.
