Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and li...Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver cancer.Numerous studies showed that metabolic dysfunction can promote NAFLD development.Linggui Zhugan Decoction(LGZGD)has therapeutic effects on NAFLD.The mechanism of LGZGD still remains unclear.This study was to examine the impact of LGZGD on the metabolic processes involved in the development of NAFLD.Methods:A mice model of NAFLD was treated with LGZGD.The therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of NAFLD.Additionally,this study also evaluated the influence of LGZGD on liver inflammation and oxidative stress.Results:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD mice.LGZGD improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the liver.Untargeted metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate cycle.Further RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.展开更多
AIM:To investigate whether retinal nerve fiber layer defects(RNFLDs)is a potential risk factor for chronic kidney disease(CKD)in Chinese adults.METHODS:The Kailuan Eye Study was a populationbased study that included 1...AIM:To investigate whether retinal nerve fiber layer defects(RNFLDs)is a potential risk factor for chronic kidney disease(CKD)in Chinese adults.METHODS:The Kailuan Eye Study was a populationbased study that included 14440 participants.All participants underwent detailed assessments,RNFLDs were diagnosed using color fundus photographs.RESULTS:Overall,12507 participants[8533 males(68.23%)]had complete systemic examination data and at least one evaluable fundus photograph.RNFLDs were found in 621 participants[5.0%;95%confidence interval(CI):4.6%-5.34%],and 70 cases of multiple RNFLDs were found(11.27%).After adjusting multiple factors,RNFLDs was significantly associated with CKD severity,the ORs of CKD stage 3,stage 4 and stage 5 were 1.698,4.167,and 9.512,respectively.Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors,the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively.Furthermore,2294 participants had CKD(18.34%,95%CI:17.68%-18.99%).After adjusting for other factors,CKD presence was significantly correlated with the presence of RNFLDs.CONCLUSION:The strongest risk factors for RNFLDs are CKD and hypertension.Conversely,RNFLDs can be an ocular feature in patients with CKD.Fundoscopy can help detect systemic diseases,and assessment for RNFLDs should be considered in CKD patients.展开更多
Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in I...Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in ICU patients.Lung injury is a common organ damage observed in sepsis patients.Macrophages and Th17 cells,as crucial components of innate and adaptive immunity,play pivotal roles in the development of sepsis-induced acute lung injury(ALI).This review summarizes the alterations and mechanisms of macrophages and Th17 cells in sepsis-induced ALI.By focusing on the“cross-talk”between macrophages and Th17 cells,this review aims to provide a solid theoretical foundation for further exploring the therapeutic targets of traditional Chinese medicine formulas in the treatment of sepsis complicated with ALI,thereby offering insights and guidance for the clinical application of traditional Chinese medicine in managing sepsis-associated ALI.展开更多
AIM:To evaluate the efficacy and safety of high-dose ultrasound cyclo-plasty(UCP)for the treatment of refractory glaucoma in Chinese patients.METHODS:In this 6-month retrospective study,37 eyes of 37 patients sufferin...AIM:To evaluate the efficacy and safety of high-dose ultrasound cyclo-plasty(UCP)for the treatment of refractory glaucoma in Chinese patients.METHODS:In this 6-month retrospective study,37 eyes of 37 patients suffering from severe glaucoma with uncontrolled intraocular pressure(IOP)of≥21 mm Hg underwent 8-s ultrasonic cyclocoagulation with ten active piezoelectric elements.A complete ophthalmic examination was performed before and at 1 d,1,3,6 mo after UCP.Therapeutic success was defined as IOP reduction from baseline≥20%and IOP≥5 mm Hg without adding new glaucoma medication compare to baseline at the 6-month follow-up visit.In addition to mean IOP at each followup visit,medications used and complications were also detected and compared to baseline.RESULTS:After UCP procedure,the mean IOP was significantly reduced(P<0.01)from the preoperative 44.1±11.9 mm Hgto postoperative 26.7±11.8 mm Hg at 3 mo,and 30.4±14.5 mm Hg at 6 mo.The overall mean IOP reductions achieved at 3 and 6 mo were 39%and 31%compared to baseline IOP.Sixty-one percent of patients responded well to UCP treatment with a mean IOP reduction of 48%at 3 mo and 42%at 6 mo.Ocular pain in most of patients were alleviated.No serious intraoperative or postoperative complications occurred.CONCLUSION:High-dose UCP treatment is an effective and safe procedure to reduce IOP in Chinese patients with severe glaucoma.展开更多
AIM:To investigate the risk and protective factors associated with the retinal nerve fiber layer defect(RNFLD)in a Chinese adult population.METHODS:This study was a cross-sectional populationbased investigation includ...AIM:To investigate the risk and protective factors associated with the retinal nerve fiber layer defect(RNFLD)in a Chinese adult population.METHODS:This study was a cross-sectional populationbased investigation including employees and retirees of a coal mining company in Kailuan City,Hebei Province.All the study participants underwent a comprehensive systemic and ophthalmic examination.RNFLD was diagnosed on fundus photographs.Binary logistic regression was used to investigate the risk and protective factors associated with the RNFLD.RESULTS:The community-based study included 14440 participants.There were 10473 participants in our study,including 7120 males(68.0%)and 3353 females(32.0%).The age range was 45-108y,averaging 59.56±8.66y.Totally 568 participants had RNFLD and the prevalence rate was 5.42%.A higher prevalence of RNFLD was associated with older age[P<0.001,odds ratio(OR):1.032;95%confidence interval(CI):1.018-1.046],longer axial length(P=0.010,OR:1.190;95%CI:1.042-1.359),hypertension(P=0.007,OR:0.639;95%CI:0.460-0.887),and diabetes mellitus(P=0.019,OR:0.684;95%CI:0.499-0.939).The protective factors of RNFLD were visual acuity(P=0.038,OR:0.617;95%CI:0.391-0.975),and central anterior chamber depth(P=0.046,OR:0.595;95%CI:0.358-0.990).CONCLUSION:In our cross-sectional community-based study,with an age range of 45-108y,RNFLD is associated with older age,longer axial length,hypertension,and diabetes mellitus.The protective factors of RNFLD are visual acuity and central anterior chamber depth.These can help to predict and evaluate RNFLD related diseases and identify high-risk populations early.展开更多
The soft-hard tissue interface of the human periodontium is responsible for periodontal homeostasis and is essential for normal oral activities.This softhard tissue interface is formed by the direct insertion of fibro...The soft-hard tissue interface of the human periodontium is responsible for periodontal homeostasis and is essential for normal oral activities.This softhard tissue interface is formed by the direct insertion of fibrous ligaments into the bone tissue.It differs from the unique four-layer structure of the fibrocartilage interface.This interface is formed by a combination of physical,chemical,and biological factors.The physiological functions of this interface are regulated by different signaling pathways.The unique structure of this soft-hard tissue interface has inspired scientists to construct biomimetic gradient structures.These biomimetic systems include nanofiber scaffolds,cell sheets,and hydrogels.Exploring methods to repair this soft-hard tissue interface can help solve clinically unresolved problems.The present review examines the structure of the soft-hard tissue interface of the periodontium and the factors that influence the development of this interface.Relevant regulatory pathways and biomimetic reconstruction methods are also presented to provide ideas for future research on interfacial tissue engineering.展开更多
The functional concept of using synthetic entities to supplement or replace certain functions or structures of biological cells is realized by the development of atypical artificial cells using a bottom-up approach.Tr...The functional concept of using synthetic entities to supplement or replace certain functions or structures of biological cells is realized by the development of atypical artificial cells using a bottom-up approach.Tremendous progress has been achieved over the past 5 years that focuses on the therapeutic applications of atypical artificial cells,especially in the anticancer arena.Artificial cell-based anticancer strategies have demon-strated eminent advantages over conventional anticancer tactics,with excellent biocompatibility and targeting capability.The present review commences with introducing the constructing principles and classification of artificial cells.Artificial cell-based applications in cancer prophylaxis,diagnosis,and treatment are subsequently highlighted.These stimulating outcomes may inspire the development of next-generation anticancer ther-apeutic strategies.展开更多
Sensory nerves promote osteogenesis through the release of neuropeptides.However,the potential application and mechanism in which sensory nerves promote healing of bone defects in the presence of biomaterials remain e...Sensory nerves promote osteogenesis through the release of neuropeptides.However,the potential application and mechanism in which sensory nerves promote healing of bone defects in the presence of biomaterials remain elusive.The present study identified that new bone formation was more abundantly produced after implantation of silicified collagen scaffolds into defects created in the distal femur of rats.The wound sites were accompanied by extensive nerve innervation and angiogenesis.Sensory nerve dysfunction by capsaicin injection resulted in significant inhibition of silicon-induced osteogenesis in the aforementioned rodent model.Application of extracellular silicon in vitro induced axon outgrowth and increased expression of semaphorin 3 A(Sema3A)and semaphorin 4D(Sema4D)in the dorsal root ganglion(DRG),as detected by the upregulation of signaling molecules.Culture medium derived from silicon-stimulated DRG cells promoted proliferation and differentiation of bone marrow mesenchymal stem cells and endothelial progenitor cells.These effects were inhibited by the use of Sema3A neutralizing antibodies but not by Sema4D neutralizing antibodies.Knockdown of Sema3A in DRG blocked silicon-induced osteogenesis and angiogenesis almost completely in a femoral defect rat model,whereas overexpression of Sema3A promoted the silicon-induced phenomena.Activation of“mechanistic target of rapamycin”(mTOR)pathway and increase of Sema3A production were identified in the DRG of rats that were implanted with silicified collagen scaffolds.These findings support the role of silicon in inducing Sema3A production by sensory nerves,which,in turn,stimulates osteogenesis and angiogenesis.Taken together,silicon has therapeutic potential in orthopedic rehabilitation.展开更多
Osteoimmunology has gained momentum in recent years,focusing on the crosstalk between the skeleton and the immune system.Extracellular vesicles(EVs)are nanoscale vesicles that are potential candidates for cell-free ti...Osteoimmunology has gained momentum in recent years,focusing on the crosstalk between the skeleton and the immune system.Extracellular vesicles(EVs)are nanoscale vesicles that are potential candidates for cell-free tissue regeneration strategies.They may be used for repairing damaged tissues and regulating the body’s immune system and bone-related metabolic activities.Because of the ability of EVs to deliver bioactive signals and mediate intercellular communication,they can decipher the complex mechanisms of interaction within the“osteoimmune system”at the molecular level.To address the lack of targeting ability caused by vesicle heterogeneity in the clinical applications of EVs,these nanoscopical entities may be modified by bioengineering techniques to optimize the interaction between bone repair and immunomodulation for improving treatment efficacy,specificity and safety.In the present review,the endogenous properties that make EVs natural delivery agents are outlined.Properties that may be improved by bioengineering are highlighted.The therapeutic applications of EVs in the rehabilitation of bone defects are discussed.The opportunities and challenges that need to be addressed for translating this field of research into clinical practice are brought into perspectives.展开更多
Ectopic mineralization refers to the deposition of mineralized complexes in the extracellular matrix of soft tissues.Calcific aortic valve disease,vascular calcification,gallstones,kidney stones,and abnormal mineraliz...Ectopic mineralization refers to the deposition of mineralized complexes in the extracellular matrix of soft tissues.Calcific aortic valve disease,vascular calcification,gallstones,kidney stones,and abnormal mineralization in arthritis are common examples of ectopic mineralization.They are debilitating diseases and exhibit excess mortality,disability,and morbidity,which impose on patients with limited social or financial resources.Recent recognition that inflammation plays an important role in ectopic mineralization has attracted the attention of scientists from different research fields.In the present review,we summarize the origin of inflammation in ectopic mineralization and different channels whereby inflammation drives the initiation and progression of ectopic mineralization.The current knowledge of inflammatory milieu in pathological mineralization is reviewed,including how immune cells,pro-inflammatory mediators,and osteogenic signaling pathways induce the osteogenic transition of connective tissue cells,providing nucleating sites and assembly of aberrant minerals.Advances in the understanding of the underlying mechanisms involved in inflammatory-mediated ectopic mineralization enable novel strategies to be developed that may lead to the resolution of these enervating conditions.展开更多
基金supported by the National Natural Science Foundation of China(82274424).
文摘Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver cancer.Numerous studies showed that metabolic dysfunction can promote NAFLD development.Linggui Zhugan Decoction(LGZGD)has therapeutic effects on NAFLD.The mechanism of LGZGD still remains unclear.This study was to examine the impact of LGZGD on the metabolic processes involved in the development of NAFLD.Methods:A mice model of NAFLD was treated with LGZGD.The therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of NAFLD.Additionally,this study also evaluated the influence of LGZGD on liver inflammation and oxidative stress.Results:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD mice.LGZGD improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the liver.Untargeted metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate cycle.Further RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.
基金Supported by the National Natural Science Foundation of China(No.82220108017,No.82141128)the Capital Health Research and Development of Special(No.2020-1-2052)Science&Technology Project of Beijing Municipal Science&Technology Commission(No.Z201100005520045,No.Z181100001818003).
文摘AIM:To investigate whether retinal nerve fiber layer defects(RNFLDs)is a potential risk factor for chronic kidney disease(CKD)in Chinese adults.METHODS:The Kailuan Eye Study was a populationbased study that included 14440 participants.All participants underwent detailed assessments,RNFLDs were diagnosed using color fundus photographs.RESULTS:Overall,12507 participants[8533 males(68.23%)]had complete systemic examination data and at least one evaluable fundus photograph.RNFLDs were found in 621 participants[5.0%;95%confidence interval(CI):4.6%-5.34%],and 70 cases of multiple RNFLDs were found(11.27%).After adjusting multiple factors,RNFLDs was significantly associated with CKD severity,the ORs of CKD stage 3,stage 4 and stage 5 were 1.698,4.167,and 9.512,respectively.Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors,the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively.Furthermore,2294 participants had CKD(18.34%,95%CI:17.68%-18.99%).After adjusting for other factors,CKD presence was significantly correlated with the presence of RNFLDs.CONCLUSION:The strongest risk factors for RNFLDs are CKD and hypertension.Conversely,RNFLDs can be an ocular feature in patients with CKD.Fundoscopy can help detect systemic diseases,and assessment for RNFLDs should be considered in CKD patients.
基金supported by the National Natural Science Foundation of China(No.82104581,No.82060864).
文摘Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in ICU patients.Lung injury is a common organ damage observed in sepsis patients.Macrophages and Th17 cells,as crucial components of innate and adaptive immunity,play pivotal roles in the development of sepsis-induced acute lung injury(ALI).This review summarizes the alterations and mechanisms of macrophages and Th17 cells in sepsis-induced ALI.By focusing on the“cross-talk”between macrophages and Th17 cells,this review aims to provide a solid theoretical foundation for further exploring the therapeutic targets of traditional Chinese medicine formulas in the treatment of sepsis complicated with ALI,thereby offering insights and guidance for the clinical application of traditional Chinese medicine in managing sepsis-associated ALI.
基金Supported by the Anhui Medical University Research Fund Project(No.2018xkj042)the Second Hospital of Anhui Medical University Incubation Project of NSFC(No.2019GQFY04)Science and Technology New Star Training Project(No.2018KA08)。
文摘AIM:To evaluate the efficacy and safety of high-dose ultrasound cyclo-plasty(UCP)for the treatment of refractory glaucoma in Chinese patients.METHODS:In this 6-month retrospective study,37 eyes of 37 patients suffering from severe glaucoma with uncontrolled intraocular pressure(IOP)of≥21 mm Hg underwent 8-s ultrasonic cyclocoagulation with ten active piezoelectric elements.A complete ophthalmic examination was performed before and at 1 d,1,3,6 mo after UCP.Therapeutic success was defined as IOP reduction from baseline≥20%and IOP≥5 mm Hg without adding new glaucoma medication compare to baseline at the 6-month follow-up visit.In addition to mean IOP at each followup visit,medications used and complications were also detected and compared to baseline.RESULTS:After UCP procedure,the mean IOP was significantly reduced(P<0.01)from the preoperative 44.1±11.9 mm Hgto postoperative 26.7±11.8 mm Hg at 3 mo,and 30.4±14.5 mm Hg at 6 mo.The overall mean IOP reductions achieved at 3 and 6 mo were 39%and 31%compared to baseline IOP.Sixty-one percent of patients responded well to UCP treatment with a mean IOP reduction of 48%at 3 mo and 42%at 6 mo.Ocular pain in most of patients were alleviated.No serious intraoperative or postoperative complications occurred.CONCLUSION:High-dose UCP treatment is an effective and safe procedure to reduce IOP in Chinese patients with severe glaucoma.
基金Supported by the National Natural Science Foundation of China(No.82220108017,No.82141128)The Capital Health Research and Development of Special(No.2020-1-2052)Science&Technology Project of Beijing Municipal Science&Technology Commission(No.Z201100005520045,No.Z181100001818003)。
文摘AIM:To investigate the risk and protective factors associated with the retinal nerve fiber layer defect(RNFLD)in a Chinese adult population.METHODS:This study was a cross-sectional populationbased investigation including employees and retirees of a coal mining company in Kailuan City,Hebei Province.All the study participants underwent a comprehensive systemic and ophthalmic examination.RNFLD was diagnosed on fundus photographs.Binary logistic regression was used to investigate the risk and protective factors associated with the RNFLD.RESULTS:The community-based study included 14440 participants.There were 10473 participants in our study,including 7120 males(68.0%)and 3353 females(32.0%).The age range was 45-108y,averaging 59.56±8.66y.Totally 568 participants had RNFLD and the prevalence rate was 5.42%.A higher prevalence of RNFLD was associated with older age[P<0.001,odds ratio(OR):1.032;95%confidence interval(CI):1.018-1.046],longer axial length(P=0.010,OR:1.190;95%CI:1.042-1.359),hypertension(P=0.007,OR:0.639;95%CI:0.460-0.887),and diabetes mellitus(P=0.019,OR:0.684;95%CI:0.499-0.939).The protective factors of RNFLD were visual acuity(P=0.038,OR:0.617;95%CI:0.391-0.975),and central anterior chamber depth(P=0.046,OR:0.595;95%CI:0.358-0.990).CONCLUSION:In our cross-sectional community-based study,with an age range of 45-108y,RNFLD is associated with older age,longer axial length,hypertension,and diabetes mellitus.The protective factors of RNFLD are visual acuity and central anterior chamber depth.These can help to predict and evaluate RNFLD related diseases and identify high-risk populations early.
基金Shaanxi Key Scientific and Technological Innovation Team of China,Grant/Award Number:2020TD-033National Key Research and Development Program of China,Grant/Award Numbers:2022YFC2405900,2022YFC2405901+1 种基金National Natural Science Foundation of China,Grant/Award Numbers:81870805,82325012National Clinical Research Center for Oral Diseases of China,Grant/Award Number:LCA202004。
文摘The soft-hard tissue interface of the human periodontium is responsible for periodontal homeostasis and is essential for normal oral activities.This softhard tissue interface is formed by the direct insertion of fibrous ligaments into the bone tissue.It differs from the unique four-layer structure of the fibrocartilage interface.This interface is formed by a combination of physical,chemical,and biological factors.The physiological functions of this interface are regulated by different signaling pathways.The unique structure of this soft-hard tissue interface has inspired scientists to construct biomimetic gradient structures.These biomimetic systems include nanofiber scaffolds,cell sheets,and hydrogels.Exploring methods to repair this soft-hard tissue interface can help solve clinically unresolved problems.The present review examines the structure of the soft-hard tissue interface of the periodontium and the factors that influence the development of this interface.Relevant regulatory pathways and biomimetic reconstruction methods are also presented to provide ideas for future research on interfacial tissue engineering.
基金National Clinical Research Center for Oral Diseases,Grant/Award Number:LCA202004National Natural Science Foundation of China,Grant/Award Numbers:82301043,82325012Shaanxi Key Scientific and Technological Innovation Team,Grant/Award Number:2020TD-033。
文摘The functional concept of using synthetic entities to supplement or replace certain functions or structures of biological cells is realized by the development of atypical artificial cells using a bottom-up approach.Tremendous progress has been achieved over the past 5 years that focuses on the therapeutic applications of atypical artificial cells,especially in the anticancer arena.Artificial cell-based anticancer strategies have demon-strated eminent advantages over conventional anticancer tactics,with excellent biocompatibility and targeting capability.The present review commences with introducing the constructing principles and classification of artificial cells.Artificial cell-based applications in cancer prophylaxis,diagnosis,and treatment are subsequently highlighted.These stimulating outcomes may inspire the development of next-generation anticancer ther-apeutic strategies.
基金This work was supported by grants 81722015,81870805,81870787,81671012 and 81720108011 from National Nature Science Foundation of China,grant 2020TD-033 from the Shaanxi Key Scientific and Technological Innovation Team and by the Youth Innovation Team of Shaanxi Universities.
文摘Sensory nerves promote osteogenesis through the release of neuropeptides.However,the potential application and mechanism in which sensory nerves promote healing of bone defects in the presence of biomaterials remain elusive.The present study identified that new bone formation was more abundantly produced after implantation of silicified collagen scaffolds into defects created in the distal femur of rats.The wound sites were accompanied by extensive nerve innervation and angiogenesis.Sensory nerve dysfunction by capsaicin injection resulted in significant inhibition of silicon-induced osteogenesis in the aforementioned rodent model.Application of extracellular silicon in vitro induced axon outgrowth and increased expression of semaphorin 3 A(Sema3A)and semaphorin 4D(Sema4D)in the dorsal root ganglion(DRG),as detected by the upregulation of signaling molecules.Culture medium derived from silicon-stimulated DRG cells promoted proliferation and differentiation of bone marrow mesenchymal stem cells and endothelial progenitor cells.These effects were inhibited by the use of Sema3A neutralizing antibodies but not by Sema4D neutralizing antibodies.Knockdown of Sema3A in DRG blocked silicon-induced osteogenesis and angiogenesis almost completely in a femoral defect rat model,whereas overexpression of Sema3A promoted the silicon-induced phenomena.Activation of“mechanistic target of rapamycin”(mTOR)pathway and increase of Sema3A production were identified in the DRG of rats that were implanted with silicified collagen scaffolds.These findings support the role of silicon in inducing Sema3A production by sensory nerves,which,in turn,stimulates osteogenesis and angiogenesis.Taken together,silicon has therapeutic potential in orthopedic rehabilitation.
基金supported by grant 2019KB01 from the State Key Laboratory of Military Stomatology,China,grant 81870805 from the National Nature Science Foundation of China,grant 2020TD-033 from the Shaanxi Key Scientific and Technological Innovation Team and by Innovative research team of high-level local universities in shanghai,Oral and maxillofacial regeneration and functional restoration.
文摘Osteoimmunology has gained momentum in recent years,focusing on the crosstalk between the skeleton and the immune system.Extracellular vesicles(EVs)are nanoscale vesicles that are potential candidates for cell-free tissue regeneration strategies.They may be used for repairing damaged tissues and regulating the body’s immune system and bone-related metabolic activities.Because of the ability of EVs to deliver bioactive signals and mediate intercellular communication,they can decipher the complex mechanisms of interaction within the“osteoimmune system”at the molecular level.To address the lack of targeting ability caused by vesicle heterogeneity in the clinical applications of EVs,these nanoscopical entities may be modified by bioengineering techniques to optimize the interaction between bone repair and immunomodulation for improving treatment efficacy,specificity and safety.In the present review,the endogenous properties that make EVs natural delivery agents are outlined.Properties that may be improved by bioengineering are highlighted.The therapeutic applications of EVs in the rehabilitation of bone defects are discussed.The opportunities and challenges that need to be addressed for translating this field of research into clinical practice are brought into perspectives.
基金grants 81870805 from the National Natural Science Foundation of China,grant 2020TD-033 from the Shaanxi Key Scientific and Technological Innovation Team and by the Youth Innovation Team of Shaanxi Universities.
文摘Ectopic mineralization refers to the deposition of mineralized complexes in the extracellular matrix of soft tissues.Calcific aortic valve disease,vascular calcification,gallstones,kidney stones,and abnormal mineralization in arthritis are common examples of ectopic mineralization.They are debilitating diseases and exhibit excess mortality,disability,and morbidity,which impose on patients with limited social or financial resources.Recent recognition that inflammation plays an important role in ectopic mineralization has attracted the attention of scientists from different research fields.In the present review,we summarize the origin of inflammation in ectopic mineralization and different channels whereby inflammation drives the initiation and progression of ectopic mineralization.The current knowledge of inflammatory milieu in pathological mineralization is reviewed,including how immune cells,pro-inflammatory mediators,and osteogenic signaling pathways induce the osteogenic transition of connective tissue cells,providing nucleating sites and assembly of aberrant minerals.Advances in the understanding of the underlying mechanisms involved in inflammatory-mediated ectopic mineralization enable novel strategies to be developed that may lead to the resolution of these enervating conditions.