Versican belongs to the family of the large aggregating chondroitin sulfate proteoglycans located primarily within the extracellular matrix （ECM）. Versican, like other members of its family, has unique N- and C-term...Versican belongs to the family of the large aggregating chondroitin sulfate proteoglycans located primarily within the extracellular matrix （ECM）. Versican, like other members of its family, has unique N- and C-terminal globular regions, each with multiple motifs. A large glycosaminoglycan-binding region lies between them. This review will begin by outlining these structures, in the context of ECM proteoglycans. The diverse binding partners afforded to versican by virtue of its modular design will then be examined. These include ECM components, such as hyaluronan, type Ⅰ collagen, tenascin-R, fibulin-1, and -2, fibrillin-1, fibronectin, P- and L-selectins, and chemokines. Versican also binds to the cell surface proteins CD44, integrin β1, epidermal growth factor receptor, and P-selectin glycoprotein ligand-1. These multiple interactors play important roles in cell behaviour, and the roles of versican in modulating such processes are discussed.展开更多
Overexpression of receptor-interacting protein 140（RIP140） promotes neuronal differentiation of N2 a cells via extracellular regulated kinase 1/2（ERK1/2） signaling.However,involvement of RIP140 in human neural dif...Overexpression of receptor-interacting protein 140（RIP140） promotes neuronal differentiation of N2 a cells via extracellular regulated kinase 1/2（ERK1/2） signaling.However,involvement of RIP140 in human neural differentiation remains unclear.We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells.Moreover,RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation,and positively correlated with the neural stem cell marker Nestin during later stages.Thus,ERK1/2 signaling may provide the molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced.展开更多
Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-en...Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-engineered structures are intended to integrate with the patient’s body.Vascular tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered constructs.Bioinks have a specific role,representingthenecessarymedium for printability and vascular cell growth.This review aims to understand the requirements for the design of vascular bioinks.First,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth functions.This review describes the general structure of vascular walls with wall-specific cell and extracellular matrix(ECM)components and biomechanical properties and functions.Furthermore,the physiological role of vascular ECM components for their interaction with vascular cells and the mode of interaction is introduced.Diverse currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular bioprinting.The physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular structures.Finally,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are outlined.These concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.展开更多
目的:基于转录组测序(RNA-seq)技术分析益肾散结复方抑制阿霉素肾病肾小球硬化的作用机制。方法:将40只SD大鼠随机分为4组,分别为正常组、阿霉素模型组、盐酸贝那普利对照组和益肾散结复方组(以下统称正常组、模型组、对照组和复方组),...目的:基于转录组测序(RNA-seq)技术分析益肾散结复方抑制阿霉素肾病肾小球硬化的作用机制。方法:将40只SD大鼠随机分为4组,分别为正常组、阿霉素模型组、盐酸贝那普利对照组和益肾散结复方组(以下统称正常组、模型组、对照组和复方组),连续2次尾静脉注射盐酸阿霉素制备阿霉素大鼠肾病模型,对照组和复方组分别按10mg/kg/d盐酸贝那普利和6.24g/kg/d益肾散结复方煎剂灌胃6周,其余组灌胃予等剂量生理盐水,灌胃前后对比大鼠一般情况、24小时尿蛋白定量(24h UTP)、血尿素氮(BUN)及血肌酐(SCr)指标变化,电镜下观察大鼠肾脏病理改变;同时将复苏的HBZY-1大鼠肾小球系膜细胞分为以上4组,以40μM浓度阿霉素诱导大鼠肾脏系膜细胞凋亡模型,分别对应处理各组细胞,观察大鼠肾小球系膜细胞凋亡情况。在此基础上,对正常组、模型组、复方组细胞进行RNA测序,筛选差异表达基因(DEG),对共同DEG进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)富集分析。结果:动物实验研究显示益肾散结复方可改善阿霉素肾病大鼠便溏、反应迟钝、活动减少等精神状态,减少24h UTP、BUN和SCr水平( P <0.05),减少阿霉素肾病大鼠肾小球系膜区基质沉积,改善基底膜缺血、皱缩情况,从而抑制肾小球硬化程度;细胞实验研究显示:益肾散结复方可延缓阿霉素诱导的HBZY-1大鼠肾小球系膜细胞凋亡过程,从而对肾小球硬化起抑制作用。根据细胞RNA-seq结果,益肾散结复方抗阿霉素肾病肾小球硬化的共同DEG有863个,542个上调, 321个下调;GO分析显示这些DEG主要富集在生物过程、细胞成分和分子功能三个方面,其中与肾小球硬化相关的GO功能有:正向调节细胞迁移、细胞粘附、细胞外基质、整合素结合、CXCR趋化因子受体结合、趋化因子活动等;KEGG分析显示上述DEG富集在19条通路( P <0.05)中,其中细胞外基质(ECM)-受体相互作用、核转录因子κB(NF-κB)信号通路、钙信号通路与肾小球硬化关系密切。结论:益肾散结复方可通过抑制肾小球系膜细胞凋亡和减少系膜区基质沉积来抑制阿霉素肾病肾小球硬化过程,其作用可能通过正向调节肾小球系膜细胞迁移、参与有丝分裂细胞周期、促进细胞粘附等生物过程,作用于细胞外基质,发挥整合素结合、CXCR趋化因子受体结合和促进趋化因子活动等分子功能来实现,与调控ECM-受体相互作用、NF-κB信号通路、钙信号通路密切相关。展开更多
目的:探索应用细菌双杂交系统在细胞外蛋白质之间相互作用的可行性。方法:应用Stratagene BacterioMatch two hy-brid system,以pTRG构建编码TRAIL细胞外可溶性区域序列融合表达质粒;以pBT构建编码DR4、DR5、OPG等的细胞外区域序列融合...目的:探索应用细菌双杂交系统在细胞外蛋白质之间相互作用的可行性。方法:应用Stratagene BacterioMatch two hy-brid system,以pTRG构建编码TRAIL细胞外可溶性区域序列融合表达质粒;以pBT构建编码DR4、DR5、OPG等的细胞外区域序列融合表达质粒。重组质粒分别相应共转化报告菌株XL1-Blue MRF,报道基因产物以抗羧苄青霉素和β-半乳糖苷酶活性作为转录激活的指标。结果:pTRG-TRAIL与pBT-DR4,pTRG-TRAIL与pBT-DR5及对照组分别共转化后在高浓度羧苄青霉素(500μg/ml以上)筛选下宿主菌呈转录激活状态,pTRG-TRAIL与pBT-OPG组共转化后在低浓度羧苄青霉素(250μg/ml以下)筛选下宿主菌呈转录激活状态,用X-Gal-PETG平皿可以进一步验证阳性克隆。对照组pTRG-TRAIL与pBT-LGF2,pBT-DR4、pBT-DR5或pBT-OPG与pTRG-Gal114组共转化后呈阴性。结论:所用的双杂交序列皆为编码这些蛋白质的细胞外区域,而这些蛋白质本身的相互作用已有其他报道验证,所以细菌双杂交系统可以用于细胞外蛋白质的相互作用研究。展开更多
Direct observation of a wide range of natural microorganisms has revealed the fact that the majority of microbes persist as surface-attached communities surrounded by matrix materials, called biofilms. Biofilms can be...Direct observation of a wide range of natural microorganisms has revealed the fact that the majority of microbes persist as surface-attached communities surrounded by matrix materials, called biofilms. Biofilms can be formed by a single bacterial strain. However, most natural biofilms are actually formed by multiple bacterial species. Conventional methods for bacterial cleaning, such as applications of antibiotics and/or disinfectants are often ineffective for biofilm populations due to their special physiology and physical matrix barrier. It has been estimated that billions of dollars are spent every year worldwide to deal with damage to equipment, contamina- tions of products, energy losses, and infections in human beings resulted from microbial biofilms. Microorganisms compete, cooperate, and communicate with each other in multi-species biofilms. Understanding the mechanisms of multi-species hiofilm formation will facilitate the development of methods for combating bacterial hiofilms in clinical, environmental, industrial, and agricultural areas. The most recent advances in the understanding of multi-species biofilms are summarized and discussed in the review.展开更多
Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation ...Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.展开更多
With research burgeoning in nanoscience and nanotechnology,there is an urgent need to develop new biological models that can simulate native structure,function,and genetic properties of tissues to evaluate the adverse...With research burgeoning in nanoscience and nanotechnology,there is an urgent need to develop new biological models that can simulate native structure,function,and genetic properties of tissues to evaluate the adverse or beneficial effects of nanomaterials on a host.Among the current biological models,three-dimensional(3D)organoids have developed as powerful tools in the study of nanomaterial-biology(nano-bio)interactions,since these models can overcome many of the limitations of cell and animal models.A deep understanding of organoid techniques will facilitate the development of more efficient nanomedicines and further the fields of tissue engineering and personalized medicine.Herein,we summarize the recent progress in intestinal organoids culture systems with a focus on our understanding of the nature and influencing factors of intestinal organoid growth.We also discuss biomimetic extracellular matrices(ECMs)coupled with nanotechnology.In particular,we analyze the application prospects for intestinal organoids in investigating nano-intestine interactions.By integrating nanotechnology and organoid technology,this recently developed model will fill the gaps left due to the deficiencies of traditional cell and animal models,thus accelerating both our understanding of intestine-related nanotoxicity and the development of nanomedicines.展开更多
The nerves of the peripheral nervous system are not able to effectively regenerate in cases of severe neural injury.This can result in debilitating consequences,including morbidity and lifelong impairments affecting t...The nerves of the peripheral nervous system are not able to effectively regenerate in cases of severe neural injury.This can result in debilitating consequences,including morbidity and lifelong impairments affecting the quality of the patient’s life.Recent findings in neural tissue engineering have opened promising avenues to apply fibrous tissue-engineered scaffolds to promote tissue regeneration and functional recovery.These scaffolds,known as neural scaffolds,are able to improve neural regeneration by playing two major roles,namely,by being a carrier for transplanted peripheral nervous system cells or biological cues and by providing structural support to direct growing nerve fibers towards the target area.However,successful implementation of scaffold-based therapeutic approaches calls for an appropriate design of the neural scaffold structure that is capable of up-and down-regulation of neuron-scaffold interactions in the extracellular matrix environment.This review discusses the main challenges that need to be addressed to develop and apply fibrous tissue-engineered scaffolds in clinical practice.It describes some promising solutions that,so far,have shown to promote neural cell adhesion and growth and a potential to repair peripheral nervous system injuries.展开更多
文摘Versican belongs to the family of the large aggregating chondroitin sulfate proteoglycans located primarily within the extracellular matrix （ECM）. Versican, like other members of its family, has unique N- and C-terminal globular regions, each with multiple motifs. A large glycosaminoglycan-binding region lies between them. This review will begin by outlining these structures, in the context of ECM proteoglycans. The diverse binding partners afforded to versican by virtue of its modular design will then be examined. These include ECM components, such as hyaluronan, type Ⅰ collagen, tenascin-R, fibulin-1, and -2, fibrillin-1, fibronectin, P- and L-selectins, and chemokines. Versican also binds to the cell surface proteins CD44, integrin β1, epidermal growth factor receptor, and P-selectin glycoprotein ligand-1. These multiple interactors play important roles in cell behaviour, and the roles of versican in modulating such processes are discussed.
基金supported by the National Natural Science Foundation of China,No.31340024
文摘Overexpression of receptor-interacting protein 140（RIP140） promotes neuronal differentiation of N2 a cells via extracellular regulated kinase 1/2（ERK1/2） signaling.However,involvement of RIP140 in human neural differentiation remains unclear.We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells.Moreover,RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation,and positively correlated with the neural stem cell marker Nestin during later stages.Thus,ERK1/2 signaling may provide the molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced.
文摘Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-engineered structures are intended to integrate with the patient’s body.Vascular tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered constructs.Bioinks have a specific role,representingthenecessarymedium for printability and vascular cell growth.This review aims to understand the requirements for the design of vascular bioinks.First,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth functions.This review describes the general structure of vascular walls with wall-specific cell and extracellular matrix(ECM)components and biomechanical properties and functions.Furthermore,the physiological role of vascular ECM components for their interaction with vascular cells and the mode of interaction is introduced.Diverse currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular bioprinting.The physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular structures.Finally,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are outlined.These concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.
文摘目的:基于转录组测序(RNA-seq)技术分析益肾散结复方抑制阿霉素肾病肾小球硬化的作用机制。方法:将40只SD大鼠随机分为4组,分别为正常组、阿霉素模型组、盐酸贝那普利对照组和益肾散结复方组(以下统称正常组、模型组、对照组和复方组),连续2次尾静脉注射盐酸阿霉素制备阿霉素大鼠肾病模型,对照组和复方组分别按10mg/kg/d盐酸贝那普利和6.24g/kg/d益肾散结复方煎剂灌胃6周,其余组灌胃予等剂量生理盐水,灌胃前后对比大鼠一般情况、24小时尿蛋白定量(24h UTP)、血尿素氮(BUN)及血肌酐(SCr)指标变化,电镜下观察大鼠肾脏病理改变;同时将复苏的HBZY-1大鼠肾小球系膜细胞分为以上4组,以40μM浓度阿霉素诱导大鼠肾脏系膜细胞凋亡模型,分别对应处理各组细胞,观察大鼠肾小球系膜细胞凋亡情况。在此基础上,对正常组、模型组、复方组细胞进行RNA测序,筛选差异表达基因(DEG),对共同DEG进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)富集分析。结果:动物实验研究显示益肾散结复方可改善阿霉素肾病大鼠便溏、反应迟钝、活动减少等精神状态,减少24h UTP、BUN和SCr水平( P <0.05),减少阿霉素肾病大鼠肾小球系膜区基质沉积,改善基底膜缺血、皱缩情况,从而抑制肾小球硬化程度;细胞实验研究显示:益肾散结复方可延缓阿霉素诱导的HBZY-1大鼠肾小球系膜细胞凋亡过程,从而对肾小球硬化起抑制作用。根据细胞RNA-seq结果,益肾散结复方抗阿霉素肾病肾小球硬化的共同DEG有863个,542个上调, 321个下调;GO分析显示这些DEG主要富集在生物过程、细胞成分和分子功能三个方面,其中与肾小球硬化相关的GO功能有:正向调节细胞迁移、细胞粘附、细胞外基质、整合素结合、CXCR趋化因子受体结合、趋化因子活动等;KEGG分析显示上述DEG富集在19条通路( P <0.05)中,其中细胞外基质(ECM)-受体相互作用、核转录因子κB(NF-κB)信号通路、钙信号通路与肾小球硬化关系密切。结论:益肾散结复方可通过抑制肾小球系膜细胞凋亡和减少系膜区基质沉积来抑制阿霉素肾病肾小球硬化过程,其作用可能通过正向调节肾小球系膜细胞迁移、参与有丝分裂细胞周期、促进细胞粘附等生物过程,作用于细胞外基质,发挥整合素结合、CXCR趋化因子受体结合和促进趋化因子活动等分子功能来实现,与调控ECM-受体相互作用、NF-κB信号通路、钙信号通路密切相关。
文摘Direct observation of a wide range of natural microorganisms has revealed the fact that the majority of microbes persist as surface-attached communities surrounded by matrix materials, called biofilms. Biofilms can be formed by a single bacterial strain. However, most natural biofilms are actually formed by multiple bacterial species. Conventional methods for bacterial cleaning, such as applications of antibiotics and/or disinfectants are often ineffective for biofilm populations due to their special physiology and physical matrix barrier. It has been estimated that billions of dollars are spent every year worldwide to deal with damage to equipment, contamina- tions of products, energy losses, and infections in human beings resulted from microbial biofilms. Microorganisms compete, cooperate, and communicate with each other in multi-species biofilms. Understanding the mechanisms of multi-species hiofilm formation will facilitate the development of methods for combating bacterial hiofilms in clinical, environmental, industrial, and agricultural areas. The most recent advances in the understanding of multi-species biofilms are summarized and discussed in the review.
文摘Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.
基金supported by the National Key Research and Development Program of China(No.2021YFA1200900)the National Natural Science Foundation of China(NSFC,No.32271460)+7 种基金the Major instrument project of NSFC(No.22027810)NSFC Major Research Plan-Integrated Program(No.92143301)the Innovative Research Group Project of NSFC(No.11621505)the CAS international cooperative project(No.GJHZ201949)the CAS Interdisciplinary Innovation Team,the CAS Key Research Program for Frontier Sciences(No.QYZDJ-SSSLH022)the Research and Development Project in Key Areas of Guangdong Province(No.2019B090917011)CAMS Innovation Fund for Medical Sciences(No.CIFMS 2019-I2M-5-018)the Strategic Priority Research Program of Chinese Academy of Sciences(No.XDB36000000).
文摘With research burgeoning in nanoscience and nanotechnology,there is an urgent need to develop new biological models that can simulate native structure,function,and genetic properties of tissues to evaluate the adverse or beneficial effects of nanomaterials on a host.Among the current biological models,three-dimensional(3D)organoids have developed as powerful tools in the study of nanomaterial-biology(nano-bio)interactions,since these models can overcome many of the limitations of cell and animal models.A deep understanding of organoid techniques will facilitate the development of more efficient nanomedicines and further the fields of tissue engineering and personalized medicine.Herein,we summarize the recent progress in intestinal organoids culture systems with a focus on our understanding of the nature and influencing factors of intestinal organoid growth.We also discuss biomimetic extracellular matrices(ECMs)coupled with nanotechnology.In particular,we analyze the application prospects for intestinal organoids in investigating nano-intestine interactions.By integrating nanotechnology and organoid technology,this recently developed model will fill the gaps left due to the deficiencies of traditional cell and animal models,thus accelerating both our understanding of intestine-related nanotoxicity and the development of nanomedicines.
基金supported by a Garnett-Passe and Rodney Williams Memorial Foundation grant(to JE)a National Health and Medical Research Council grant,No.APP1183799(to JASJ and JAKE).
文摘The nerves of the peripheral nervous system are not able to effectively regenerate in cases of severe neural injury.This can result in debilitating consequences,including morbidity and lifelong impairments affecting the quality of the patient’s life.Recent findings in neural tissue engineering have opened promising avenues to apply fibrous tissue-engineered scaffolds to promote tissue regeneration and functional recovery.These scaffolds,known as neural scaffolds,are able to improve neural regeneration by playing two major roles,namely,by being a carrier for transplanted peripheral nervous system cells or biological cues and by providing structural support to direct growing nerve fibers towards the target area.However,successful implementation of scaffold-based therapeutic approaches calls for an appropriate design of the neural scaffold structure that is capable of up-and down-regulation of neuron-scaffold interactions in the extracellular matrix environment.This review discusses the main challenges that need to be addressed to develop and apply fibrous tissue-engineered scaffolds in clinical practice.It describes some promising solutions that,so far,have shown to promote neural cell adhesion and growth and a potential to repair peripheral nervous system injuries.
