Gout is a metabolic bone and joint disease caused by purine metabolism disorder.The disturbance of inflammatory microenvironment caused by monosodium urate(MSU)deposition is an important pathological mechanism of gout...Gout is a metabolic bone and joint disease caused by purine metabolism disorder.The disturbance of inflammatory microenvironment caused by monosodium urate(MSU)deposition is an important pathological mechanism of gout occurrence and development.In the understanding of Traditional Chinese medicine(TCM),the interaction of"dampness","heat"and"stasis"is the main pathogenesis of gout,and the method of clearing heat and removing dampness is the main treatment method of TCM for gout.In recent years,studies have found that heat-clearing and dampness-removing method can improve the TCM symptom score of gout patients,especially in the body tiredness,dry mouth and dry throat,short yellow urine,thirsty,etc.,which are the characteristics of dampness and heat syndrome,this may be related to the fact that the TCM heat-clearing and dampness-removing method in the treatment of gout removes the appearance of dampness and heat,improves the inflammatory microenvironment of gout and restores the normal metabolic function of human body.This paper deeply explores the specific mechanism of TCM heat-clearing and dampness-removing method to improve the inflammatory microenvironment of gout,which can provide new ideas for the diagnosis and treatment of clinical gout.展开更多
Periodontitis is a complex chronic inflammatory disease.The invasion of pathogens induces the inflammatory microenvironment in periodontitis.Cell behavior changes in response to changes in the microenvironment,which i...Periodontitis is a complex chronic inflammatory disease.The invasion of pathogens induces the inflammatory microenvironment in periodontitis.Cell behavior changes in response to changes in the microenvironment,which in turn alters the local inflammatory microenvironment of the periodontium through factors secreted by cells.It has been confirmed that periodontal ligament stem cells(PDLSCs)are vital in the development of periodontal disease.Moreover,PDLSCs are the most effective cell type to be used for periodontium regeneration.This review focuses on changes in PDLSCs,their basic biological behavior,osteogenic differentiation,and drug effects caused by the inflammatory microenvironment,to provide a better understanding of the influence of these factors on periodontal tissue homeostasis.In addition,we discuss the underlying mechanism in detail behind the reciprocal responses of PDLSCs that affect the microenvironment.展开更多
Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chin...Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chinese medicine syndrome diagnoses(also called syndrome differentiation)in pancreatic ductal adenocarcinoma.Methods:128 pancreatic ductal adenocarcinoma patients with different syndrome diagnoses were retrospectively reviewed in this study.Long RNA sequencing was conducted to analyze the EV long RNA profile of plasma samples.Differentially regulated EV long RNAs were annotated and assessed for Gene Ontology pathway enrichment using DAVID.The online program xCell were used to perform the cell-type enrichment analysis.Results:An average of 15,000 annotated genes,mainly including messenger RNAs,were stably detected per sample.Different syndrome diagnoses exhibited unique EV mRNA expression profiles and therefore different enriched pathways.Gene Set Enrichment Analysis discovered transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation as the hallmarks of cancer with Shi-Re syndrome.Cell-type enrichment analysis also revealed a varied inflammation/immune cell type distribution among patients with or without Shi-Re diagnosis.Mast cells,platelets and Tregs were significantly enriched but basophils,common lymphoid progenitors,dendritic cells,and conventional dendritic cells were decreased in patients with Shi-Re diagnosis compared with patients without Shi-Re diagnosis.Conclusion:We identified the hallmarks of cancer with different syndrome diagnoses based on plasma EV long RNA sequencing.In particular,transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation were the hallmarks of Shi-Re syndrome,which contribute to shape an inflammatory/immune-suppressive tumor microenvironment in pancreatic ductal adenocarcinoma.展开更多
It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells(MSCs).However,the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflamm...It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells(MSCs).However,the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear.This study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on scaffolds.Cyclic mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7,14,or 21 days.At the predetermined time points,culture supernatant was collected for inflammatory mediator detection,and gene expression was analyzed by qRT-PCR.The results showed that the expression of inflammatory mediators(IL1B and IL8)was downregulated(p<0.05)and the expression of ALP(p<0.01)and COL1A1(p<0.05)was upregulated under mechanical loading.The cell-scaffold composites biofabricated with or without mechanical loading were freeze-dried to prepare extracellular matrix-based scaffolds(ECM-based scaffolds).Murine macrophages were seeded on the ECM-based scaffolds to evaluate their polarization.The ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying enhanced the expression of M2 polarization-related biomarkers(Arginase 1 and Mrc1,p<0.05)of macrophages in vitro and increased bone volume/total volume ratio in vivo.Overall,these findings demonstrated that mechanical loading could dually modulate the inflammatory responses and osteogenic differentiation of MSCs.Besides,the ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying facilitated the M2 polarization of macrophages in vitro and bone regeneration in vivo.Mechanical loading may be a promising biofabrication strategy for bone biomaterials.展开更多
Accumulating evidence suggests that chronic inflammation may play a critical role in various malignancies,including bladder cancer.This hypothesis stems in part from inflammatory cells observed in the urethral microen...Accumulating evidence suggests that chronic inflammation may play a critical role in various malignancies,including bladder cancer.This hypothesis stems in part from inflammatory cells observed in the urethral microenvironment.Chronic inflammation may drive neoplastic transformation and the progression of bladder cancer by activating a series of in-flammatory molecules and signals.Recently,it has been shown that the microbiome also plays an important role in the development and progression of bladder cancer,which can be mediated through the stimulation of chronic inflammation.In effect,the urinary microbiome can play a role in establishing the inflammatory urethral microenvironment that may facilitate the development and progression of bladder cancer.In other words,chronic inflammation caused by the urinary microbiome may promote the initiation and progression of bladder cancer.Here,we provide a detailed and comprehensive account of the link between chronic inflammation,the microbiome and bladder cancer.Finally,we highlight that targeting the urinary microbiome might enable the development of strategies for bladder cancer prevention and personalized treatment.展开更多
Current research data reveal microenvironment as a significant modifier of physical functions,pathologic changes,as well as the therapeutic effects of stem cells.When comparing regeneration potential of various stem c...Current research data reveal microenvironment as a significant modifier of physical functions,pathologic changes,as well as the therapeutic effects of stem cells.When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering,mesenchymal stem cells(MSCs)are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use.The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs,indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration.Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues,MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years.This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions,giving additional insight into the current clinical application of these cells.展开更多
Infected bone fractures remain a major clinical challenge for orthopedic surgeons.From a tissue regeneration perspective,biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired,while ...Infected bone fractures remain a major clinical challenge for orthopedic surgeons.From a tissue regeneration perspective,biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired,while advanced materials capable of mimicking the pathological microenvironment during the healing process of infected tissues remain an area deserving more research.Hematoma,the gel-like blood coagulum,plays an essential role in bone fracture repair because of its ability to serve as a dynamic and temporary scaffold with cytokines for both pathogen elimination and tissue healing.In light of this,we designed a dynamic hydrogel with hematoma-like antimicrobial or reparative performance for infected bone fracture repair in this study.The proposed dynamic hydrogel network was based on the reversible recognition of a natural glycopeptide antibiotic vancomycin(Van)and its target dipeptide D-Ala-D-Ala(AA),which could serve as a hematoma-like scaffold for obliterating bacteria in the fracture region and promoting bone repair by introducing an endogenous osteogenic peptide(OGP).In vivo experiments demonstrated that the hydrogel could rapidly eradicate bacteria,improve bone regeneration and restore the local inflammatory microenvironment.Together,findings from this study imply that the use of hematoma-like dynamic hydrogel could lead to a biomimetic revolution in surgical strategies against susceptible bone fractures.展开更多
Macroautophagy has been implicated in modulating the therapeutic function of mesenchymal stromal cells(MSCs).However,the biological function of chaperone-mediated autophagy(CMA)in MSCs remains elusive.Here,we found th...Macroautophagy has been implicated in modulating the therapeutic function of mesenchymal stromal cells(MSCs).However,the biological function of chaperone-mediated autophagy(CMA)in MSCs remains elusive.Here,we found that CMA was inhibited in MSCs in response to the proinflammatory cytokines interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α).In addition,suppression of CMA by knocking down the CMA-related lysosomal receptor lysosomal-associated membrane protein 2(LAMP-2A)in MSCs significantly enhanced the immunosuppressive effect of MSCs on T cell proliferation,and as expected,LAMP-2A overexpression in MSCs exerted the opposite effect on T cell proliferation.This effect of CMA on the immunosuppressive function of MSCs was attributed to its negative regulation of the expression of chemokine C-X-C motif ligand 10(CXCL10),which recruits inflammatory cells,especially T cells,to MSCs,and inducible nitric oxide synthase(iNOS),which leads to the subsequent inhibition of T cell proliferation via nitric oxide(NO).Mechanistically,CMA inhibition dramatically promoted IFN-γplus TNF-α-induced activation of NF-κB and STAT1,leading to the enhanced expression of CXCL10 and iNOS in MSCs.Furthermore,we found that IFN-γplus TNF-α-induced AKT activation contributed to CMA inhibition in MSCs.More interestingly,CMA-deficient MSCs exhibited improved therapeutic efficacy in inflammatory liver injury.Taken together,our findings established CMA inhibition as a critical contributor to the immunosuppressive function of MSCs induced by inflammatory cytokines nd highlighted a previously unknown function of CMA.展开更多
Periodontitis is recognized as the major cause of tooth loss in adults, posing an adverse impact on systemic health. In periodontitis, excessive production of reactive oxygen species (ROS) at the inflamed site culmina...Periodontitis is recognized as the major cause of tooth loss in adults, posing an adverse impact on systemic health. In periodontitis, excessive production of reactive oxygen species (ROS) at the inflamed site culminates in periodontal destruction. In this study, a novel ROS-responsive drug delivery system based on polydopamine (PDA) functionalized mesoporous silica nanoparticles was developed for delivering minocycline hydrochloride (MH) to treat periodontitis. The outer PDA layer and the inner MH of the nanoparticles acted as ROS scavengers and anti-inflammatory agents, respectively. Under the synergistic action of PDA and MH, macrophages were polarized from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. The in vitro experiments provided convincing evidence that PDA could scavenge ROS effectively, and the expression of pro-inflammatory cytokines was attenuated and the secretion of anti-inflammatory cytokines was enhanced through M1 to M2 polarization of macrophages with the cooperation of MH. In addition, the results obtained from the periodontitis rat models demonstrated that the synergetic effect of PDA and MH prevented alveolar bone loss without causing any adverse effect. Taken together, the results from the present investigation provide a new strategy to remodel the inflammatory microenvironment by inducing the polarization of macrophages from M1 toward M2 state for the treatment of periodontitis.展开更多
文摘Gout is a metabolic bone and joint disease caused by purine metabolism disorder.The disturbance of inflammatory microenvironment caused by monosodium urate(MSU)deposition is an important pathological mechanism of gout occurrence and development.In the understanding of Traditional Chinese medicine(TCM),the interaction of"dampness","heat"and"stasis"is the main pathogenesis of gout,and the method of clearing heat and removing dampness is the main treatment method of TCM for gout.In recent years,studies have found that heat-clearing and dampness-removing method can improve the TCM symptom score of gout patients,especially in the body tiredness,dry mouth and dry throat,short yellow urine,thirsty,etc.,which are the characteristics of dampness and heat syndrome,this may be related to the fact that the TCM heat-clearing and dampness-removing method in the treatment of gout removes the appearance of dampness and heat,improves the inflammatory microenvironment of gout and restores the normal metabolic function of human body.This paper deeply explores the specific mechanism of TCM heat-clearing and dampness-removing method to improve the inflammatory microenvironment of gout,which can provide new ideas for the diagnosis and treatment of clinical gout.
基金supported by the Jilin Provincial Department of Finance(No.jcsz2020304-9)the Guangzhou Medical University Student Innovation Ability Improvement Program(No.(2022)66-113),China。
文摘Periodontitis is a complex chronic inflammatory disease.The invasion of pathogens induces the inflammatory microenvironment in periodontitis.Cell behavior changes in response to changes in the microenvironment,which in turn alters the local inflammatory microenvironment of the periodontium through factors secreted by cells.It has been confirmed that periodontal ligament stem cells(PDLSCs)are vital in the development of periodontal disease.Moreover,PDLSCs are the most effective cell type to be used for periodontium regeneration.This review focuses on changes in PDLSCs,their basic biological behavior,osteogenic differentiation,and drug effects caused by the inflammatory microenvironment,to provide a better understanding of the influence of these factors on periodontal tissue homeostasis.In addition,we discuss the underlying mechanism in detail behind the reciprocal responses of PDLSCs that affect the microenvironment.
基金supported by the National Natural Science Foundation of China(82230122,82025035,82104612)Shanghai Municipal Health Commission program(ZY(2021-2023)-0205-02)the Science Foundation for Young Scholars of Zhongshan Hospital,Fudan University(grant No.2021ZSQN70).
文摘Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chinese medicine syndrome diagnoses(also called syndrome differentiation)in pancreatic ductal adenocarcinoma.Methods:128 pancreatic ductal adenocarcinoma patients with different syndrome diagnoses were retrospectively reviewed in this study.Long RNA sequencing was conducted to analyze the EV long RNA profile of plasma samples.Differentially regulated EV long RNAs were annotated and assessed for Gene Ontology pathway enrichment using DAVID.The online program xCell were used to perform the cell-type enrichment analysis.Results:An average of 15,000 annotated genes,mainly including messenger RNAs,were stably detected per sample.Different syndrome diagnoses exhibited unique EV mRNA expression profiles and therefore different enriched pathways.Gene Set Enrichment Analysis discovered transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation as the hallmarks of cancer with Shi-Re syndrome.Cell-type enrichment analysis also revealed a varied inflammation/immune cell type distribution among patients with or without Shi-Re diagnosis.Mast cells,platelets and Tregs were significantly enriched but basophils,common lymphoid progenitors,dendritic cells,and conventional dendritic cells were decreased in patients with Shi-Re diagnosis compared with patients without Shi-Re diagnosis.Conclusion:We identified the hallmarks of cancer with different syndrome diagnoses based on plasma EV long RNA sequencing.In particular,transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation were the hallmarks of Shi-Re syndrome,which contribute to shape an inflammatory/immune-suppressive tumor microenvironment in pancreatic ductal adenocarcinoma.
基金This research was supported by the National Natural Science Foundation of China(Grant no.32071351,81772400 and 31900583,32071341)the Fundamental Research Funds for the Central Universities(Grant no.19ykzd05)+3 种基金the Committee for Science and Technology Innovation of Shenzhen(Grant no.JCYJ20190809142211354 and GJHZ20180929160004704)the Sanming Project of Medicine in Shenzhen(Grant no.SZSM201911002)the Natural Science Foundation of Guangzhou City(Grant no.201807010031,201704030082)the Beijing Municipal Health Commission(Grant no.BMHC-2019-9,BMHC-2018-4,PXM2020_026275_000002).
文摘It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells(MSCs).However,the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear.This study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on scaffolds.Cyclic mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7,14,or 21 days.At the predetermined time points,culture supernatant was collected for inflammatory mediator detection,and gene expression was analyzed by qRT-PCR.The results showed that the expression of inflammatory mediators(IL1B and IL8)was downregulated(p<0.05)and the expression of ALP(p<0.01)and COL1A1(p<0.05)was upregulated under mechanical loading.The cell-scaffold composites biofabricated with or without mechanical loading were freeze-dried to prepare extracellular matrix-based scaffolds(ECM-based scaffolds).Murine macrophages were seeded on the ECM-based scaffolds to evaluate their polarization.The ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying enhanced the expression of M2 polarization-related biomarkers(Arginase 1 and Mrc1,p<0.05)of macrophages in vitro and increased bone volume/total volume ratio in vivo.Overall,these findings demonstrated that mechanical loading could dually modulate the inflammatory responses and osteogenic differentiation of MSCs.Besides,the ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying facilitated the M2 polarization of macrophages in vitro and bone regeneration in vivo.Mechanical loading may be a promising biofabrication strategy for bone biomaterials.
基金This research was supported by grants from National Natural Science Foundation of China[grant numbers 81630080,91129714,81874380,81730108,81973635 and 82022075]Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars[grant number LR18H160001]+1 种基金the National Key R&D Program of China[grant numbers 2018YFC1704100 and 2018YFC1704106]Zhejiang province science and technology project of TCM[grant number 2019ZZ016].
文摘Accumulating evidence suggests that chronic inflammation may play a critical role in various malignancies,including bladder cancer.This hypothesis stems in part from inflammatory cells observed in the urethral microenvironment.Chronic inflammation may drive neoplastic transformation and the progression of bladder cancer by activating a series of in-flammatory molecules and signals.Recently,it has been shown that the microbiome also plays an important role in the development and progression of bladder cancer,which can be mediated through the stimulation of chronic inflammation.In effect,the urinary microbiome can play a role in establishing the inflammatory urethral microenvironment that may facilitate the development and progression of bladder cancer.In other words,chronic inflammation caused by the urinary microbiome may promote the initiation and progression of bladder cancer.Here,we provide a detailed and comprehensive account of the link between chronic inflammation,the microbiome and bladder cancer.Finally,we highlight that targeting the urinary microbiome might enable the development of strategies for bladder cancer prevention and personalized treatment.
基金the Ministry of Education,Science and Technological Development,Republic of Serbia,No.451-03-9/2021-14/200015.
文摘Current research data reveal microenvironment as a significant modifier of physical functions,pathologic changes,as well as the therapeutic effects of stem cells.When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering,mesenchymal stem cells(MSCs)are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use.The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs,indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration.Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues,MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years.This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions,giving additional insight into the current clinical application of these cells.
基金the National Natural Science Foundation of China(32222041,82102619,81925027,21875092)the Natural Science Foundation of Jiangsu Province(BK20220059)the National Key Research and Development Program of China(2019YFA0112000)。
文摘Infected bone fractures remain a major clinical challenge for orthopedic surgeons.From a tissue regeneration perspective,biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired,while advanced materials capable of mimicking the pathological microenvironment during the healing process of infected tissues remain an area deserving more research.Hematoma,the gel-like blood coagulum,plays an essential role in bone fracture repair because of its ability to serve as a dynamic and temporary scaffold with cytokines for both pathogen elimination and tissue healing.In light of this,we designed a dynamic hydrogel with hematoma-like antimicrobial or reparative performance for infected bone fracture repair in this study.The proposed dynamic hydrogel network was based on the reversible recognition of a natural glycopeptide antibiotic vancomycin(Van)and its target dipeptide D-Ala-D-Ala(AA),which could serve as a hematoma-like scaffold for obliterating bacteria in the fracture region and promoting bone repair by introducing an endogenous osteogenic peptide(OGP).In vivo experiments demonstrated that the hydrogel could rapidly eradicate bacteria,improve bone regeneration and restore the local inflammatory microenvironment.Together,findings from this study imply that the use of hematoma-like dynamic hydrogel could lead to a biomimetic revolution in surgical strategies against susceptible bone fractures.
基金supported by the Ministry of Science and Technology of China(2015CB943300 and 2011CB966200)the National Natural Science Foundation of China(81873447 and 81670540)+1 种基金The Program of Science and Technology Commission of Shanghai Municipality(19ZR1409200 and 19ZR1430900)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA01040000).
文摘Macroautophagy has been implicated in modulating the therapeutic function of mesenchymal stromal cells(MSCs).However,the biological function of chaperone-mediated autophagy(CMA)in MSCs remains elusive.Here,we found that CMA was inhibited in MSCs in response to the proinflammatory cytokines interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α).In addition,suppression of CMA by knocking down the CMA-related lysosomal receptor lysosomal-associated membrane protein 2(LAMP-2A)in MSCs significantly enhanced the immunosuppressive effect of MSCs on T cell proliferation,and as expected,LAMP-2A overexpression in MSCs exerted the opposite effect on T cell proliferation.This effect of CMA on the immunosuppressive function of MSCs was attributed to its negative regulation of the expression of chemokine C-X-C motif ligand 10(CXCL10),which recruits inflammatory cells,especially T cells,to MSCs,and inducible nitric oxide synthase(iNOS),which leads to the subsequent inhibition of T cell proliferation via nitric oxide(NO).Mechanistically,CMA inhibition dramatically promoted IFN-γplus TNF-α-induced activation of NF-κB and STAT1,leading to the enhanced expression of CXCL10 and iNOS in MSCs.Furthermore,we found that IFN-γplus TNF-α-induced AKT activation contributed to CMA inhibition in MSCs.More interestingly,CMA-deficient MSCs exhibited improved therapeutic efficacy in inflammatory liver injury.Taken together,our findings established CMA inhibition as a critical contributor to the immunosuppressive function of MSCs induced by inflammatory cytokines nd highlighted a previously unknown function of CMA.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.21804072 and 82071838)the Natural Science Foundation of Jiangsu Province(No.BK20180941)+3 种基金China Postdoctoral Science Foundation(No.2018M642297)Science and technology Project of Nantong City(No.MS12019022)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(Nos.KYCX19-2080 and KYCX19-2078)Jiangsu Students’Program for Innovation and Entrepreneurship Training(No.201910304031Z).
文摘Periodontitis is recognized as the major cause of tooth loss in adults, posing an adverse impact on systemic health. In periodontitis, excessive production of reactive oxygen species (ROS) at the inflamed site culminates in periodontal destruction. In this study, a novel ROS-responsive drug delivery system based on polydopamine (PDA) functionalized mesoporous silica nanoparticles was developed for delivering minocycline hydrochloride (MH) to treat periodontitis. The outer PDA layer and the inner MH of the nanoparticles acted as ROS scavengers and anti-inflammatory agents, respectively. Under the synergistic action of PDA and MH, macrophages were polarized from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. The in vitro experiments provided convincing evidence that PDA could scavenge ROS effectively, and the expression of pro-inflammatory cytokines was attenuated and the secretion of anti-inflammatory cytokines was enhanced through M1 to M2 polarization of macrophages with the cooperation of MH. In addition, the results obtained from the periodontitis rat models demonstrated that the synergetic effect of PDA and MH prevented alveolar bone loss without causing any adverse effect. Taken together, the results from the present investigation provide a new strategy to remodel the inflammatory microenvironment by inducing the polarization of macrophages from M1 toward M2 state for the treatment of periodontitis.
