Osteomyelitis remains a global challenge in the field of orthopedics.Even after standard debridement and antibiotic-assisted treatment,the long-term recurrence rate remains at 20%-30%.Given the dynamic changes in immu...Osteomyelitis remains a global challenge in the field of orthopedics.Even after standard debridement and antibiotic-assisted treatment,the long-term recurrence rate remains at 20%-30%.Given the dynamic changes in immune responses and defense mechanisms during bone infection,as well as the complex“race for the surface”involving bacterial adhesion and host cells(macrophages and tissue cells)on implant surfaces,biomaterials with immunomodulatory functions have attracted considerable attention.Macrophages,as crucial components of the immune system,participate in the inflammatory regulation and tissue remodeling of bone infections through highly plastic polarization mechanisms after bacterial invasion.The different microenvironmental characteristics and therapeutic needs at different stages of bone infection highlight the promising applications of biomaterials capable of macrophage polarization remodeling and sequential regulation.In this review,we provide a detailed discussion of the complex immune regulatory patterns in the bone infection microenvironment and the critical functions of macrophage polarization.We then explore how implant surface properties influence bacterial adhesion and macrophage function,highlighting the importance of achieving precise and dynamic regulation of macrophage polarization based on the Race for the Surface theory.Furthermore,we focus on recent advances,potential challenges,and opportunities in biomaterial-mediated macrophage polarization remodeling and sequential modulation strategies across different stages of osteomyelitis,aiming to offer insights that may accelerate the clinical translation of novel biomaterial-based macrophage immunotherapies.展开更多
BACKGROUND Human mesenchymal stromal cells(MSCs)possess regenerative potential due to pluripotency and paracrine functions.However,their stemness and immunomod-ulatory capabilities are sub-optimal in conventional two-...BACKGROUND Human mesenchymal stromal cells(MSCs)possess regenerative potential due to pluripotency and paracrine functions.However,their stemness and immunomod-ulatory capabilities are sub-optimal in conventional two-dimensional(2D)culture.AIM To enhance the efficiency and therapeutic efficacy of MSCs,an in vivo-like 3D culture condition was applied.METHODS MSCs were cultured on polystyrene(2D)or in a gellan gum-based 3D system.In vitro,prostaglandin-endoperoxide synthase 2,indoleamine-2,3-dioxygenase,heme oxygenase 1,and prostaglandin E synthase gene expression was quantified by quantitative real-time polymerase chain reaction.MSCs were incubated with lipopolysaccharide(LPS)-treated mouse splenocytes,and prostaglandin E2 and tumor necrosis factor-alpha levels were measured by enzyme linked immuno-sorbent assay.In vivo,LPS was injected into the lateral ventricle of mouse brain,and MSCs were administered intravenously the next day.Animals were sacrificed and analyzed on days 2 and 6.RESULTS Gellan gum polymer-based 3D culture significantly increased expression of octamer-binding transcription factor 4 and Nanog homeobox stemness markers in human MSCs compared to 2D culture.This 3D environment also heightened expression of cyclooxygenase-2 and heme-oxygenase 1,enzymes known for immunomodulatory functions,including production of prostaglandins and heme degradation,respectively.MSCs in 3D culture secreted more prostaglandin E2 and effectively suppressed tumor necrosis factor-alpha release from LPS-stimulated splenocytes and surpassed the efficiency of MSCs cultured in 2D.In a murine neuroinflammation model,intravenous injection of 3D-cultured MSCs significantly reduced ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression,mitigating chronic inflammation more effectively than 2D-cultured MSCs.CONCLUSION The microenvironment established in 3D culture serves as an in vivo mimetic,enhancing the immunomodulatory function of MSCs.This suggests that engineered MSCs hold significant promise a potent tool for cell therapy.展开更多
Background:Ulcerative colitis(UC)is a chronic disease that often presents with abdominal pain,diarrhea,hematochezia,and significant morbidity.Gancao Xiexin decoction(GXD),a traditional Chinese medicine,has been applie...Background:Ulcerative colitis(UC)is a chronic disease that often presents with abdominal pain,diarrhea,hematochezia,and significant morbidity.Gancao Xiexin decoction(GXD),a traditional Chinese medicine,has been applied for the clinical treatment of UC,while its action mechanisms are unclear.Methods:The active ingredients and their targets of GXD,and UC-related targets,were derived from public databases.Protein-protein interaction,Gene Ontology(GO),and the Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to analyze the important active compounds,key targets,and signaling pathways.Then,molecular docking and animal experiments were performed to verify the findings.A total of 213 active compounds and 89 common targets of GXD for UC were obtained.Results:The hub gene network showed ALB,AKT1,IL6,TNF,VEGFA,TP53,CXCL8,MAPK1,PTGS2,and IL1βmay be potential targets of GXD against UC.GO and KEGG pathway enrichment analyses suggested that the action of GXD against UC was mainly related to response to oxygen levels,lipopolysaccharide,and molecule of bacterial origin,etc.,and achieved by advanced glycation endproducts/receptors for advanced glycation endproducts signaling pathway in diabetic complications,hypoxia-inducible factor(HIF)-1 signaling pathway,interleukin-17/HIF-1 signaling pathway,TNF signaling pathway,etc.Molecular docking results showed that the GXD had good potency of action with the hub target.In vivo experiments showed that GXD significantly alleviated the symptoms of UC and down-regulated the expression of inflammatory factors,nuclear factor-κB and signal transducer and activator of transcription 3.Conclusions:The anti-UC action of GXD is mainly attributed to its anti-oxidative stress,antiinflammatory,and immunomodulatory functions.展开更多
In this study,egg white peptides(EWP)were prepared using preheat treatment combined with a bienzymatic hydrolysis.Results on peptide yield and molecular weight distribution showed that preheat treatment could obviousl...In this study,egg white peptides(EWP)were prepared using preheat treatment combined with a bienzymatic hydrolysis.Results on peptide yield and molecular weight distribution showed that preheat treatment could obviously promote egg white hydrolysis.The yield of EWP obtained from neutral-alkaline protease treatment was 74.62%±0.23%and 92.69%of EWP was between 200 Da and 500 Da.Supplementation with 750 mg/kg/d EWP significantly alleviated the decrease of immune organ index in immunosuppressed male BLAB/c mice caused by cyclophosphamide.The pathological changes of spleen showed that EWP could also alleviate the damage of spleen tissue.The number of white blood cells in peripheral blood and the levels of serum cytokines(IL-6,IL-2 and TNF-α)in 750 mg/kg/d EWP group were significantly higher than the model group.The immunomodulatory effects of EWP might be related to the presence of abundant branched-chain amino acids,which were important components of immunomodulatory peptides.Eight possible immunomodulatory peptides were identified from EWP by High Performance Liquid Chromatography-Mass Spectrometry in combination with ProteinLynx Global SERVER and mass spectral database.Therefore,EWP may have potential as a natural immunomodulator for the prevention of immune damage caused by external influences.展开更多
基金supported by National Natural Science Foundation of China(Grant No.82072392)Yunnan Orthopedics and Sports Rehabilitation Clinical Medicine Research Center(Grant No.202102AA310068)+2 种基金Yunnan Clinical Medical Center for Traumatology and Orthopedics(Grant No.ZX20191001)Basic research project of Science and Technology Department of Yunnan Province(Grant No.202301AC070621)Scientific Research Fund Project Department of Education of Yunnan Province(Grant No.2024Y251)。
文摘Osteomyelitis remains a global challenge in the field of orthopedics.Even after standard debridement and antibiotic-assisted treatment,the long-term recurrence rate remains at 20%-30%.Given the dynamic changes in immune responses and defense mechanisms during bone infection,as well as the complex“race for the surface”involving bacterial adhesion and host cells(macrophages and tissue cells)on implant surfaces,biomaterials with immunomodulatory functions have attracted considerable attention.Macrophages,as crucial components of the immune system,participate in the inflammatory regulation and tissue remodeling of bone infections through highly plastic polarization mechanisms after bacterial invasion.The different microenvironmental characteristics and therapeutic needs at different stages of bone infection highlight the promising applications of biomaterials capable of macrophage polarization remodeling and sequential regulation.In this review,we provide a detailed discussion of the complex immune regulatory patterns in the bone infection microenvironment and the critical functions of macrophage polarization.We then explore how implant surface properties influence bacterial adhesion and macrophage function,highlighting the importance of achieving precise and dynamic regulation of macrophage polarization based on the Race for the Surface theory.Furthermore,we focus on recent advances,potential challenges,and opportunities in biomaterial-mediated macrophage polarization remodeling and sequential modulation strategies across different stages of osteomyelitis,aiming to offer insights that may accelerate the clinical translation of novel biomaterial-based macrophage immunotherapies.
基金Supported by National Research Foundation of Korea,No.RS-2024-00409554,No.2023R1A2C2006894,and No.2021R1A6A3A01088243.
文摘BACKGROUND Human mesenchymal stromal cells(MSCs)possess regenerative potential due to pluripotency and paracrine functions.However,their stemness and immunomod-ulatory capabilities are sub-optimal in conventional two-dimensional(2D)culture.AIM To enhance the efficiency and therapeutic efficacy of MSCs,an in vivo-like 3D culture condition was applied.METHODS MSCs were cultured on polystyrene(2D)or in a gellan gum-based 3D system.In vitro,prostaglandin-endoperoxide synthase 2,indoleamine-2,3-dioxygenase,heme oxygenase 1,and prostaglandin E synthase gene expression was quantified by quantitative real-time polymerase chain reaction.MSCs were incubated with lipopolysaccharide(LPS)-treated mouse splenocytes,and prostaglandin E2 and tumor necrosis factor-alpha levels were measured by enzyme linked immuno-sorbent assay.In vivo,LPS was injected into the lateral ventricle of mouse brain,and MSCs were administered intravenously the next day.Animals were sacrificed and analyzed on days 2 and 6.RESULTS Gellan gum polymer-based 3D culture significantly increased expression of octamer-binding transcription factor 4 and Nanog homeobox stemness markers in human MSCs compared to 2D culture.This 3D environment also heightened expression of cyclooxygenase-2 and heme-oxygenase 1,enzymes known for immunomodulatory functions,including production of prostaglandins and heme degradation,respectively.MSCs in 3D culture secreted more prostaglandin E2 and effectively suppressed tumor necrosis factor-alpha release from LPS-stimulated splenocytes and surpassed the efficiency of MSCs cultured in 2D.In a murine neuroinflammation model,intravenous injection of 3D-cultured MSCs significantly reduced ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression,mitigating chronic inflammation more effectively than 2D-cultured MSCs.CONCLUSION The microenvironment established in 3D culture serves as an in vivo mimetic,enhancing the immunomodulatory function of MSCs.This suggests that engineered MSCs hold significant promise a potent tool for cell therapy.
文摘Background:Ulcerative colitis(UC)is a chronic disease that often presents with abdominal pain,diarrhea,hematochezia,and significant morbidity.Gancao Xiexin decoction(GXD),a traditional Chinese medicine,has been applied for the clinical treatment of UC,while its action mechanisms are unclear.Methods:The active ingredients and their targets of GXD,and UC-related targets,were derived from public databases.Protein-protein interaction,Gene Ontology(GO),and the Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to analyze the important active compounds,key targets,and signaling pathways.Then,molecular docking and animal experiments were performed to verify the findings.A total of 213 active compounds and 89 common targets of GXD for UC were obtained.Results:The hub gene network showed ALB,AKT1,IL6,TNF,VEGFA,TP53,CXCL8,MAPK1,PTGS2,and IL1βmay be potential targets of GXD against UC.GO and KEGG pathway enrichment analyses suggested that the action of GXD against UC was mainly related to response to oxygen levels,lipopolysaccharide,and molecule of bacterial origin,etc.,and achieved by advanced glycation endproducts/receptors for advanced glycation endproducts signaling pathway in diabetic complications,hypoxia-inducible factor(HIF)-1 signaling pathway,interleukin-17/HIF-1 signaling pathway,TNF signaling pathway,etc.Molecular docking results showed that the GXD had good potency of action with the hub target.In vivo experiments showed that GXD significantly alleviated the symptoms of UC and down-regulated the expression of inflammatory factors,nuclear factor-κB and signal transducer and activator of transcription 3.Conclusions:The anti-UC action of GXD is mainly attributed to its anti-oxidative stress,antiinflammatory,and immunomodulatory functions.
基金supported by the National Natural Science Foundation for the Youth of China(No.31901642).
文摘In this study,egg white peptides(EWP)were prepared using preheat treatment combined with a bienzymatic hydrolysis.Results on peptide yield and molecular weight distribution showed that preheat treatment could obviously promote egg white hydrolysis.The yield of EWP obtained from neutral-alkaline protease treatment was 74.62%±0.23%and 92.69%of EWP was between 200 Da and 500 Da.Supplementation with 750 mg/kg/d EWP significantly alleviated the decrease of immune organ index in immunosuppressed male BLAB/c mice caused by cyclophosphamide.The pathological changes of spleen showed that EWP could also alleviate the damage of spleen tissue.The number of white blood cells in peripheral blood and the levels of serum cytokines(IL-6,IL-2 and TNF-α)in 750 mg/kg/d EWP group were significantly higher than the model group.The immunomodulatory effects of EWP might be related to the presence of abundant branched-chain amino acids,which were important components of immunomodulatory peptides.Eight possible immunomodulatory peptides were identified from EWP by High Performance Liquid Chromatography-Mass Spectrometry in combination with ProteinLynx Global SERVER and mass spectral database.Therefore,EWP may have potential as a natural immunomodulator for the prevention of immune damage caused by external influences.
