Small non-protein coding micro-RNAs are regularly exported out of cells, both in health and disease. More than ninety percent of extracellular miRNAs are associated with lower-molecular-mass complexes bound to Argonau...Small non-protein coding micro-RNAs are regularly exported out of cells, both in health and disease. More than ninety percent of extracellular miRNAs are associated with lower-molecular-mass complexes bound to Argonaute 2 (Ago2), nucleophosmin-1 (NPM1) and high density lipoproteins (HDL), whereas the rest (~10%) are membrane-vesicle-encapsulated within exosomes, shedding microvesicles and apoptotic bodies. Regardless of the debate of the nature of circulating miRNA as byproducts of routine cell activities or mediators of cell-cell communication, proper understanding of the molecular behaviors of miRNA in health and disease, is expected to open a new gate for the discovery of new diagnostic tools and possibly therapeutic implementation in the near future.展开更多
The objective of the study was to analyse Streptococcus mutans biofilms grown under different dietary conditions by using multifaceted methodological approaches to gain deeper insight into the cariogenic impact of car...The objective of the study was to analyse Streptococcus mutans biofilms grown under different dietary conditions by using multifaceted methodological approaches to gain deeper insight into the cariogenic impact of carbohydrates. S. mutans biofilms were generated during a period of 24 h in the following media： Schaedler broth as a control medium containing endogenous glucose, Schaedler broth with an additional 5% sucrose, and Schaedler broth supplemented with 1% xylitol. The confocal laser scanning microscopy（CLSM）-based analyses of the microbial vitality, respiratory activity（5-cyano-2,3-ditolyl tetrazolium chloride, CTC） and production of extracellular polysaccharides（EPS） were performed separately in the inner, middle and outer biofilm layers. In addition to the microbiological sample testing, the glucose/sucrose consumption of the biofilm bacteria was quantified, and the expression of glucosyltransferases and other biofilm-associated genes was investigated. Xylitol exposure did not inhibit the viability of S. mutans biofilms, as monitored by the following experimental parameters： culture growth, vitality, CTC activity and EPS production. However,xylitol exposure caused a difference in gene expression compared to the control. Gtf C was upregulated only in the presence of xylitol.Under xylitol exposure, gtf B was upregulated by a factor of 6, while under sucrose exposure, it was upregulated by a factor of three.Compared with glucose and xylitol, sucrose increased cell vitality in all biofilm layers. In all nutrient media, the intrinsic glucose was almost completely consumed by the cells of the S. mutans biofilm within 24 h. After 24 h of biofilm formation, the multiparametric measurements showed that xylitol in the presence of glucose caused predominantly genotypic differences but did not induce metabolic differences compared to the control. Thus, the availability of dietary carbohydrates in either a pure or combined form seems to affect the cariogenic potential of S. mutans biofilms.展开更多
Each neuronal subtype is distinct in how it develops,responds to environmental cues,and whether it is capable of mounting a regenerative response following injury.Although the adult central nervous system（CNS） does ...Each neuronal subtype is distinct in how it develops,responds to environmental cues,and whether it is capable of mounting a regenerative response following injury.Although the adult central nervous system（CNS） does not regenerate,several experimental interventions have been trialled with successful albeit limited instances of axonal repair.We highlight here some of these approaches including extracellular matrix（ECM） modification,cellular grafting,gene therapy-induced replacement of proteins,as well as application of biomaterials.We also review the recent report demonstrating the failure of axonal localization and transport of growth-promoting receptors within certain classes of mature neurons.More specifically,we discuss an inability of integrin receptors to localize within the axonal compartment of mature motor neurons such as in the corticospinal and rubrospinal tracts,whereas in immature neurons of those pathways and in mature sensory tracts such as in the optic nerve and dorsal column pathways these receptors readily localize within axons.Furthermore we assert that this failure of axonal localization contributes to the intrinsic inability of axonal regeneration.We conclude by highlighting the necessity for both combined therapies as well as a targeted approach specific to both age and neuronal subtype will be required to induce substantial CNS repair.展开更多
To investigate the molecular mechanism of extracellular matrix overdeposition in hypertrophic scar tissues and to explore MMPs gene therapy for hypertrophic scar. Methods: Hypertrophic scarderived and normal skin-deri...To investigate the molecular mechanism of extracellular matrix overdeposition in hypertrophic scar tissues and to explore MMPs gene therapy for hypertrophic scar. Methods: Hypertrophic scarderived and normal skin-derived fibroblasts were cultured and a recombinant retrovirus vector containing MMP-3 gene was constructed and then transfected into hypertrophic scar fibroblasts. Expressive level of MMP-3 mRNA was detected by dot blotting, and the activity of MMPs was determined by DNP-peptide.Results: Lower expression of MMP-3 mRNA and fewer DNP-peptide hydrolyzed fragments were observed in hypertrophic scar-derived fibroblasts compared with normal skin-derived fibroblasts. Transfection of MMP-3gene into hypertrophic scar-derived fibroblasts could enhance the expression of MMP-3 mRNA (3. 4 fold)and the de novo capacity to hydrolyze DNP-peptide (2. 1 fold). Conclusion: Overdeposition of extracellular matrix in hypertrophic scar tissue was related to low expression of MMP-3 due to its down-degradation of extracellular matrix. MMP-3 gene transfection could be a better way to treat hypertrophic scars by degrading extracellular matrix.展开更多
为了评估华支睾吸虫(Clonorchis sinensis)细胞外膜囊泡中虫源miRNAs跨物种调控宿主基因的风险,试验利用miRBase数据库对华支睾吸虫细胞外膜囊泡和感染阳性宿主细胞共有的虫源miRNAs成熟体序列进行筛选,通过miRanda软件对细胞外膜囊泡...为了评估华支睾吸虫(Clonorchis sinensis)细胞外膜囊泡中虫源miRNAs跨物种调控宿主基因的风险,试验利用miRBase数据库对华支睾吸虫细胞外膜囊泡和感染阳性宿主细胞共有的虫源miRNAs成熟体序列进行筛选,通过miRanda软件对细胞外膜囊泡中表达量排在前10位的miRNAs进行靶基因预测,选取每个miRNAs评分排在前10位的靶基因作为候选靶基因,通过NCBI、Bing检索工具检索miRNAs候选靶基因的功能,利用GO功能注释及KEGG富集分析对靶基因进行生物信息学分析。结果表明:华支睾吸虫细胞外膜囊泡中的10种miRNAs共对应8128个与宿主相关的靶基因。有12个候选靶基因没有相关的功能报道,12个候选靶基因与肝功能有关,其余候选靶基因在癌症、信号转导、结构骨架、增殖和分化、迁移功能中发挥重要作用。候选靶基因Taf10和Onecut2与肝脏和肝胆管发育相关,候选靶基因Gng1和Hhip分别可参与致纤维化相关的丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)和Hedgehog信号通路。说明虫源miRNAs有靶向宿主细胞并参与致宿主肝纤维化和肝癌的风险。展开更多
文摘Small non-protein coding micro-RNAs are regularly exported out of cells, both in health and disease. More than ninety percent of extracellular miRNAs are associated with lower-molecular-mass complexes bound to Argonaute 2 (Ago2), nucleophosmin-1 (NPM1) and high density lipoproteins (HDL), whereas the rest (~10%) are membrane-vesicle-encapsulated within exosomes, shedding microvesicles and apoptotic bodies. Regardless of the debate of the nature of circulating miRNA as byproducts of routine cell activities or mediators of cell-cell communication, proper understanding of the molecular behaviors of miRNA in health and disease, is expected to open a new gate for the discovery of new diagnostic tools and possibly therapeutic implementation in the near future.
基金supported by the National Deutsche Gesellschaft fr Zahnerhaltung-GABA Scientific Fund, Germany
文摘The objective of the study was to analyse Streptococcus mutans biofilms grown under different dietary conditions by using multifaceted methodological approaches to gain deeper insight into the cariogenic impact of carbohydrates. S. mutans biofilms were generated during a period of 24 h in the following media： Schaedler broth as a control medium containing endogenous glucose, Schaedler broth with an additional 5% sucrose, and Schaedler broth supplemented with 1% xylitol. The confocal laser scanning microscopy（CLSM）-based analyses of the microbial vitality, respiratory activity（5-cyano-2,3-ditolyl tetrazolium chloride, CTC） and production of extracellular polysaccharides（EPS） were performed separately in the inner, middle and outer biofilm layers. In addition to the microbiological sample testing, the glucose/sucrose consumption of the biofilm bacteria was quantified, and the expression of glucosyltransferases and other biofilm-associated genes was investigated. Xylitol exposure did not inhibit the viability of S. mutans biofilms, as monitored by the following experimental parameters： culture growth, vitality, CTC activity and EPS production. However,xylitol exposure caused a difference in gene expression compared to the control. Gtf C was upregulated only in the presence of xylitol.Under xylitol exposure, gtf B was upregulated by a factor of 6, while under sucrose exposure, it was upregulated by a factor of three.Compared with glucose and xylitol, sucrose increased cell vitality in all biofilm layers. In all nutrient media, the intrinsic glucose was almost completely consumed by the cells of the S. mutans biofilm within 24 h. After 24 h of biofilm formation, the multiparametric measurements showed that xylitol in the presence of glucose caused predominantly genotypic differences but did not induce metabolic differences compared to the control. Thus, the availability of dietary carbohydrates in either a pure or combined form seems to affect the cariogenic potential of S. mutans biofilms.
基金support from the Morton Cure Paralysis Fund and Royal Society Research grant
文摘Each neuronal subtype is distinct in how it develops,responds to environmental cues,and whether it is capable of mounting a regenerative response following injury.Although the adult central nervous system（CNS） does not regenerate,several experimental interventions have been trialled with successful albeit limited instances of axonal repair.We highlight here some of these approaches including extracellular matrix（ECM） modification,cellular grafting,gene therapy-induced replacement of proteins,as well as application of biomaterials.We also review the recent report demonstrating the failure of axonal localization and transport of growth-promoting receptors within certain classes of mature neurons.More specifically,we discuss an inability of integrin receptors to localize within the axonal compartment of mature motor neurons such as in the corticospinal and rubrospinal tracts,whereas in immature neurons of those pathways and in mature sensory tracts such as in the optic nerve and dorsal column pathways these receptors readily localize within axons.Furthermore we assert that this failure of axonal localization contributes to the intrinsic inability of axonal regeneration.We conclude by highlighting the necessity for both combined therapies as well as a targeted approach specific to both age and neuronal subtype will be required to induce substantial CNS repair.
文摘To investigate the molecular mechanism of extracellular matrix overdeposition in hypertrophic scar tissues and to explore MMPs gene therapy for hypertrophic scar. Methods: Hypertrophic scarderived and normal skin-derived fibroblasts were cultured and a recombinant retrovirus vector containing MMP-3 gene was constructed and then transfected into hypertrophic scar fibroblasts. Expressive level of MMP-3 mRNA was detected by dot blotting, and the activity of MMPs was determined by DNP-peptide.Results: Lower expression of MMP-3 mRNA and fewer DNP-peptide hydrolyzed fragments were observed in hypertrophic scar-derived fibroblasts compared with normal skin-derived fibroblasts. Transfection of MMP-3gene into hypertrophic scar-derived fibroblasts could enhance the expression of MMP-3 mRNA (3. 4 fold)and the de novo capacity to hydrolyze DNP-peptide (2. 1 fold). Conclusion: Overdeposition of extracellular matrix in hypertrophic scar tissue was related to low expression of MMP-3 due to its down-degradation of extracellular matrix. MMP-3 gene transfection could be a better way to treat hypertrophic scars by degrading extracellular matrix.
文摘为了评估华支睾吸虫(Clonorchis sinensis)细胞外膜囊泡中虫源miRNAs跨物种调控宿主基因的风险,试验利用miRBase数据库对华支睾吸虫细胞外膜囊泡和感染阳性宿主细胞共有的虫源miRNAs成熟体序列进行筛选,通过miRanda软件对细胞外膜囊泡中表达量排在前10位的miRNAs进行靶基因预测,选取每个miRNAs评分排在前10位的靶基因作为候选靶基因,通过NCBI、Bing检索工具检索miRNAs候选靶基因的功能,利用GO功能注释及KEGG富集分析对靶基因进行生物信息学分析。结果表明:华支睾吸虫细胞外膜囊泡中的10种miRNAs共对应8128个与宿主相关的靶基因。有12个候选靶基因没有相关的功能报道,12个候选靶基因与肝功能有关,其余候选靶基因在癌症、信号转导、结构骨架、增殖和分化、迁移功能中发挥重要作用。候选靶基因Taf10和Onecut2与肝脏和肝胆管发育相关,候选靶基因Gng1和Hhip分别可参与致纤维化相关的丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)和Hedgehog信号通路。说明虫源miRNAs有靶向宿主细胞并参与致宿主肝纤维化和肝癌的风险。
