[ Objective] The aim was to predict the secondary structure and B cell epitope of growth hormone （GH） protein from Acipenser sinensis. [Method] With the amino acid sequence of GH protein from A. sinensis as the base...[ Objective] The aim was to predict the secondary structure and B cell epitope of growth hormone （GH） protein from Acipenser sinensis. [Method] With the amino acid sequence of GH protein from A. sinensis as the base, the secondary structure of GH protein from A. sinensis was predicted by the method of Gamier-Robson, Chou-Fasman and Karpius-Schulz, and its cell epitope was predicted by the method of Kyte- Doolittle, Emini and Jameson-Wolf. [Result] The sections of 18 -23, 55 -55, 67 -73, 83 -86,112 -114,151 -157 and 209 -211 in the N terminal of GH protein molecule had softer structure and these sections could sway or fold to produce more complex tertiary structure. The sections of 19 -23, 51 -71,84 -95, 128 -139, 164 -176 and 189 -195 in the N terminal of GH protein could be the epitope of B cell and there were flexible regions in these sections or near these sections of GH protein molecule. So the dominant regions could be in these sections or near these sections. [ Conclusion] The research provided the basis for the preparation of monoctonal antibody of GH protein from A. sinensis and provided the reference for the discussion for the molecular regulation mechanism of A. sinensis.展开更多
Background： A major shortcoming in tissue engineered blood vessels （TEBVs） is the lack of healthy and easily attainable smooth muscle cells （SMCs）. Smooth muscle progenitor cells （SPCs）, especially from periphe...Background： A major shortcoming in tissue engineered blood vessels （TEBVs） is the lack of healthy and easily attainable smooth muscle cells （SMCs）. Smooth muscle progenitor cells （SPCs）, especially from peripheral blood, may offer an alternative cell source for tissue engineering involving a less invasive harvesting technique. Methods： SPCs were isolated from 5-ml fresh rat peripheral blood by density-gradient centrifugation and cultured for 3 weeks in endothelial growth medium-2-MV （EGM-2-MV） medium containing platelet-derived growth factoroBB （PDGF BB）. Before seeded on the synthesized scaffold, SPC-derived smooth muscle outgrowth cell （SOC） phenotypes were assessed by immuno-fluorescent staining, Western blot analysis, and reverse transcription polymerase chain reaction （RT-PCR）. The cells were seeded onto the silk fibroin-modified poly（3-hydroxybutyrate-co-3-hydroxyhexanoate） （SF-PHBHHx） scaflblds by 6× 10^4 cells/cm^2 and cultured under the static condition for 3 weeks. The growth and proliferation of the seeded cells on the scaffold were analyzed by 3-（4,5-dimethylthiazol-2-yl）-diphenyltetrazolium bromide （MTT） assay, scanning electron microscope （SEM）, and 4,6-diamidino-2-phenylindole （DAPI） staining. Results： SOCs displayed specific ＂hill and valley＂ morphology, expressed the specific markers of the SMC lineage： smooth muscle （SM） a-actin, calponin and smooth muscle myosin heavy chain （SM MHC） at protein and messenger ribonucleic acid （mRNA） levels. RT-PCR results demonstrate that SOCs also expressed smooth muscle protein 22a （SM22a, a contractile protein, and extracellular matrix components elastin and matrix Gla protein （MGP）, as well as vascular endothelial growth factor （VEGF）. After seeded on the SF-PHBHHx scaffold, the cells showed excellent metabolic activity and proliferation. Conclusion： SPCs isolated from peripheral blood can be differentiated the SMCs in vitro and have an impressive growth potential in the biodegradable synthesized scaffold. Thus, SPCs may be a promising cell sointo urce for constructing TEBVs.展开更多
Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great...Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.展开更多
The term epigenetics refers to heritable changes not encoded by DNA. The organization of DNA into chromatin fibers affects gene expression in a heritable manner and is therefore one mechanism of epigenetic inheritance...The term epigenetics refers to heritable changes not encoded by DNA. The organization of DNA into chromatin fibers affects gene expression in a heritable manner and is therefore one mechanism of epigenetic inheritance. Large parts of eukaryotic genomes consist of constitutively highly condensed heterochromatin, important for maintaining genome integrity but also for silencing of genes within. Small RNA, together with factors typically associated with RNA interference （RNAi） targets homologous DNA sequences and recruits factors that modify the chromatin, com- monly resulting in formation of heterochromatin and silencing of target genes. The scope of this review is to provide an overview of the roles of small RNA and the RNAi components, Dicer, Argonaute and RNA dependent polymerases in epigenetic inheritance via heterochromatin formation, exemplified with pathways from unicellular eukaryotes, plants and animals.展开更多
Adsorption reactions between surfaces of nanodiamond and nanosilica with diameter of 100 nm prepared as suspension solutions of 0.25μg/μL and lysozyme molecule with different concentrations of 7 mmol/L PPBS at pH=7,...Adsorption reactions between surfaces of nanodiamond and nanosilica with diameter of 100 nm prepared as suspension solutions of 0.25μg/μL and lysozyme molecule with different concentrations of 7 mmol/L PPBS at pH=7, 9, 11, and 13 have been investigated by fluores- cence spectroscopy. Adsorption reaction constants and coverages of lysozyme with different concentrations of 0-1000 nmol/L under the influences of different pH values have been ob- tained. Helicities and conformations of the adsorbed lysozyme molecules, free spaces of every adsorbed lysozyme molecule on the surfaces of nanopartieles at different concentrations and pH values have been deduced and discussed. The highest adsorption capabilities for both sys- tems and conformational efficiency of the adsorbed lysozyme molecule at pH=13 have been obtained. Lysozyme molecules can be prepared, adsorbed and carried with optimal activity and helicity, with 2 and 10 mg/m2 on unit nanosurface, 130 and 150 mg/g with respect to the weight of nanoparticle, within the linear regions of the coverages at around 150-250 nmol/L and four pH values for nanodiamond and nanosilica, respectively. They can be prepared in the tightest packed form, with 20 and 55 mg/m2, 810-1680 and 580-1100 mg/g at threshold concentrations and four pH values for nanodiamond and nanosilica, respectively.展开更多
Talin是一类位于黏着斑上连接整合素及微丝细胞骨架的蛋白,具有承载和传递细胞内外应力的作用.其蛋白内部2个结构域F3和RS相互作用可以形成分子内自抑制构象,从而抑制与整合素的结合.使用原子力显微镜测量talin自抑制复合物两结构域间...Talin是一类位于黏着斑上连接整合素及微丝细胞骨架的蛋白,具有承载和传递细胞内外应力的作用.其蛋白内部2个结构域F3和RS相互作用可以形成分子内自抑制构象,从而抑制与整合素的结合.使用原子力显微镜测量talin自抑制复合物两结构域间的结合强度,发现2者键寿命随作用力呈现弱的逆锁键特性,即在小力区间不随力的增加而减少,只有当力超过一定数值(10 p N)后,才迅速降低.另外,分子动力学模拟研究发现了另一种除该自抑制复合物晶体结构之外的稳定构象.进一步分析显示,外力可能会调节这2种构象状态间的平衡关系,从而导致了生存几率的多重指数减小趋势.本实验发现了一种talin激活的负调节机制,为更好理解talin在黏着斑中的作用提供了新思路.展开更多
The capability to image, as well as control and manipulate single molecules such as nucleic acids(DNA or RNA) can greatly enrich our knowledge of the roles of individual biomolecules in cellular processes and their be...The capability to image, as well as control and manipulate single molecules such as nucleic acids(DNA or RNA) can greatly enrich our knowledge of the roles of individual biomolecules in cellular processes and their behavior in native environments. Here we summarize the recent advances of single nucleic acid imaging based on optical observation and force manipulation. We start by discussing the superiority of single molecule image, the central roles nucleic acids play in biosystems, and the significance of single molecule image towards nucleic acids. We then list a series of representative examples in brief to illustrate how nucleic acid of various morphologies has been imaged from different aspects, and what can be learned from such characterizations. Finally,concluding remarks on parts of which should be improved and outlook are outlined.展开更多
Although microbes primarily are single-cell organisms,they are not isolated individuals.Microbes use various means to communicate with one another.Based on the communication,microbes establish a social interaction wit...Although microbes primarily are single-cell organisms,they are not isolated individuals.Microbes use various means to communicate with one another.Based on the communication,microbes establish a social interaction with their neighbors in a specific ecological niche,and cooperative behaviors are normally performed to provide benefits on the population and species levels.In the microbiome era,in order to better understand the behaviors of microbes,deep understanding of the social communication between microbes hence becomes a key to interpret microbe behaviors.Here we summarize the molecular mechanisms that underlie the cell-to-cell communication in prokaryotic and eukaryotic microorganisms,the recent discoveries and novel technologies in understanding the interspecies and interkingdom communication,and discuss new concepts of the sociomicrobiology.展开更多
Revealing the behavior of single molecules in single live cells provides a fundamental approach to understand cellular organization and dynamics.With the rapid merging of biotechnology and nanotechnology in recent yea...Revealing the behavior of single molecules in single live cells provides a fundamental approach to understand cellular organization and dynamics.With the rapid merging of biotechnology and nanotechnology in recent years,single plasmonic nanoparticle sensors have endowed a new dimension to the imaging scale given their comparable size to biomolecules such as nucleic acids or antibodies.展开更多
Photocurable systems, which offer advantages such as microfabrication and in situ fabrication, have been widely used as dental restorative materials. Because the visible light-curable(VLC) system causes no biological ...Photocurable systems, which offer advantages such as microfabrication and in situ fabrication, have been widely used as dental restorative materials. Because the visible light-curable(VLC) system causes no biological damage, it is popular as a dental material and is being investigated by many researchers for other medical applications. Here, the principle of the VLC system is explained and recent progress in key components including photoinitiators, monomers, macromers, and prepolymers is discussed. Finally, biomedical applications for drug delivery and soft tissue engineering are reviewed. Considering the recent development of VLC systems, its importance in the field of medical applications is expected to continue to increase in the future.展开更多
文摘[ Objective] The aim was to predict the secondary structure and B cell epitope of growth hormone （GH） protein from Acipenser sinensis. [Method] With the amino acid sequence of GH protein from A. sinensis as the base, the secondary structure of GH protein from A. sinensis was predicted by the method of Gamier-Robson, Chou-Fasman and Karpius-Schulz, and its cell epitope was predicted by the method of Kyte- Doolittle, Emini and Jameson-Wolf. [Result] The sections of 18 -23, 55 -55, 67 -73, 83 -86,112 -114,151 -157 and 209 -211 in the N terminal of GH protein molecule had softer structure and these sections could sway or fold to produce more complex tertiary structure. The sections of 19 -23, 51 -71,84 -95, 128 -139, 164 -176 and 189 -195 in the N terminal of GH protein could be the epitope of B cell and there were flexible regions in these sections or near these sections of GH protein molecule. So the dominant regions could be in these sections or near these sections. [ Conclusion] The research provided the basis for the preparation of monoctonal antibody of GH protein from A. sinensis and provided the reference for the discussion for the molecular regulation mechanism of A. sinensis.
基金supported by Shanghai Science Committee Fund for Key Research Project (No. 04JC14012)Fudan University Med-X Fund, China
文摘Background： A major shortcoming in tissue engineered blood vessels （TEBVs） is the lack of healthy and easily attainable smooth muscle cells （SMCs）. Smooth muscle progenitor cells （SPCs）, especially from peripheral blood, may offer an alternative cell source for tissue engineering involving a less invasive harvesting technique. Methods： SPCs were isolated from 5-ml fresh rat peripheral blood by density-gradient centrifugation and cultured for 3 weeks in endothelial growth medium-2-MV （EGM-2-MV） medium containing platelet-derived growth factoroBB （PDGF BB）. Before seeded on the synthesized scaffold, SPC-derived smooth muscle outgrowth cell （SOC） phenotypes were assessed by immuno-fluorescent staining, Western blot analysis, and reverse transcription polymerase chain reaction （RT-PCR）. The cells were seeded onto the silk fibroin-modified poly（3-hydroxybutyrate-co-3-hydroxyhexanoate） （SF-PHBHHx） scaflblds by 6× 10^4 cells/cm^2 and cultured under the static condition for 3 weeks. The growth and proliferation of the seeded cells on the scaffold were analyzed by 3-（4,5-dimethylthiazol-2-yl）-diphenyltetrazolium bromide （MTT） assay, scanning electron microscope （SEM）, and 4,6-diamidino-2-phenylindole （DAPI） staining. Results： SOCs displayed specific ＂hill and valley＂ morphology, expressed the specific markers of the SMC lineage： smooth muscle （SM） a-actin, calponin and smooth muscle myosin heavy chain （SM MHC） at protein and messenger ribonucleic acid （mRNA） levels. RT-PCR results demonstrate that SOCs also expressed smooth muscle protein 22a （SM22a, a contractile protein, and extracellular matrix components elastin and matrix Gla protein （MGP）, as well as vascular endothelial growth factor （VEGF）. After seeded on the SF-PHBHHx scaffold, the cells showed excellent metabolic activity and proliferation. Conclusion： SPCs isolated from peripheral blood can be differentiated the SMCs in vitro and have an impressive growth potential in the biodegradable synthesized scaffold. Thus, SPCs may be a promising cell sointo urce for constructing TEBVs.
文摘Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.
文摘The term epigenetics refers to heritable changes not encoded by DNA. The organization of DNA into chromatin fibers affects gene expression in a heritable manner and is therefore one mechanism of epigenetic inheritance. Large parts of eukaryotic genomes consist of constitutively highly condensed heterochromatin, important for maintaining genome integrity but also for silencing of genes within. Small RNA, together with factors typically associated with RNA interference （RNAi） targets homologous DNA sequences and recruits factors that modify the chromatin, com- monly resulting in formation of heterochromatin and silencing of target genes. The scope of this review is to provide an overview of the roles of small RNA and the RNAi components, Dicer, Argonaute and RNA dependent polymerases in epigenetic inheritance via heterochromatin formation, exemplified with pathways from unicellular eukaryotes, plants and animals.
文摘Adsorption reactions between surfaces of nanodiamond and nanosilica with diameter of 100 nm prepared as suspension solutions of 0.25μg/μL and lysozyme molecule with different concentrations of 7 mmol/L PPBS at pH=7, 9, 11, and 13 have been investigated by fluores- cence spectroscopy. Adsorption reaction constants and coverages of lysozyme with different concentrations of 0-1000 nmol/L under the influences of different pH values have been ob- tained. Helicities and conformations of the adsorbed lysozyme molecules, free spaces of every adsorbed lysozyme molecule on the surfaces of nanopartieles at different concentrations and pH values have been deduced and discussed. The highest adsorption capabilities for both sys- tems and conformational efficiency of the adsorbed lysozyme molecule at pH=13 have been obtained. Lysozyme molecules can be prepared, adsorbed and carried with optimal activity and helicity, with 2 and 10 mg/m2 on unit nanosurface, 130 and 150 mg/g with respect to the weight of nanoparticle, within the linear regions of the coverages at around 150-250 nmol/L and four pH values for nanodiamond and nanosilica, respectively. They can be prepared in the tightest packed form, with 20 and 55 mg/m2, 810-1680 and 580-1100 mg/g at threshold concentrations and four pH values for nanodiamond and nanosilica, respectively.
文摘Talin是一类位于黏着斑上连接整合素及微丝细胞骨架的蛋白,具有承载和传递细胞内外应力的作用.其蛋白内部2个结构域F3和RS相互作用可以形成分子内自抑制构象,从而抑制与整合素的结合.使用原子力显微镜测量talin自抑制复合物两结构域间的结合强度,发现2者键寿命随作用力呈现弱的逆锁键特性,即在小力区间不随力的增加而减少,只有当力超过一定数值(10 p N)后,才迅速降低.另外,分子动力学模拟研究发现了另一种除该自抑制复合物晶体结构之外的稳定构象.进一步分析显示,外力可能会调节这2种构象状态间的平衡关系,从而导致了生存几率的多重指数减小趋势.本实验发现了一种talin激活的负调节机制,为更好理解talin在黏着斑中的作用提供了新思路.
基金supported by the National Natural Science Foundation of China (21525523, 21574048, 21375042, 21405054)the National Basic Research Program of China (2015CB932600, 2013CB933000)+1 种基金the Special Fund for Strategic New Industry Development of Shenzhen, China (JCYJ20150616144425376)1000 Young Talent (to Fan Xia)
文摘The capability to image, as well as control and manipulate single molecules such as nucleic acids(DNA or RNA) can greatly enrich our knowledge of the roles of individual biomolecules in cellular processes and their behavior in native environments. Here we summarize the recent advances of single nucleic acid imaging based on optical observation and force manipulation. We start by discussing the superiority of single molecule image, the central roles nucleic acids play in biosystems, and the significance of single molecule image towards nucleic acids. We then list a series of representative examples in brief to illustrate how nucleic acid of various morphologies has been imaged from different aspects, and what can be learned from such characterizations. Finally,concluding remarks on parts of which should be improved and outlook are outlined.
基金supported by the National Natural Science Foundation of China(31571288)CAS Interdisciplinary Innovation Team and the Newton Advanced Fellowship(NA140085)from the Royal Society
文摘Although microbes primarily are single-cell organisms,they are not isolated individuals.Microbes use various means to communicate with one another.Based on the communication,microbes establish a social interaction with their neighbors in a specific ecological niche,and cooperative behaviors are normally performed to provide benefits on the population and species levels.In the microbiome era,in order to better understand the behaviors of microbes,deep understanding of the social communication between microbes hence becomes a key to interpret microbe behaviors.Here we summarize the molecular mechanisms that underlie the cell-to-cell communication in prokaryotic and eukaryotic microorganisms,the recent discoveries and novel technologies in understanding the interspecies and interkingdom communication,and discuss new concepts of the sociomicrobiology.
文摘Revealing the behavior of single molecules in single live cells provides a fundamental approach to understand cellular organization and dynamics.With the rapid merging of biotechnology and nanotechnology in recent years,single plasmonic nanoparticle sensors have endowed a new dimension to the imaging scale given their comparable size to biomolecules such as nucleic acids or antibodies.
基金supported by the Foreign Postdoctoral Researcher program of RIKEN and JSPS KAKENHI(22220009)
文摘Photocurable systems, which offer advantages such as microfabrication and in situ fabrication, have been widely used as dental restorative materials. Because the visible light-curable(VLC) system causes no biological damage, it is popular as a dental material and is being investigated by many researchers for other medical applications. Here, the principle of the VLC system is explained and recent progress in key components including photoinitiators, monomers, macromers, and prepolymers is discussed. Finally, biomedical applications for drug delivery and soft tissue engineering are reviewed. Considering the recent development of VLC systems, its importance in the field of medical applications is expected to continue to increase in the future.
