Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases ...Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.展开更多
Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2...Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.展开更多
Glutamate-induced excitotoxicity plays a critical role in the neurological impairment caused by middle cerebral artery occlusion.Achyranthes bidentata polypeptides have been shown to protect against neurological funct...Glutamate-induced excitotoxicity plays a critical role in the neurological impairment caused by middle cerebral artery occlusion.Achyranthes bidentata polypeptides have been shown to protect against neurological functional damage caused by middle cerebral artery occlusion,but the underlying neuroprotective mechanisms and the relationship to glutamate-induced excitotoxicity remain unclear.Therefore,in the current study,we investigated the protective effects of Achyranthes bidentata polypeptides against glutamate-induced excitotoxicity in cultured hippocampal neurons.Hippocampal neurons were treated with Mg^2+-free extracellular solution containing glutamate(300μM)for 3 hours as a model of glutamate-mediated excitotoxicity(glutamate group).In the normal group,hippocampal neurons were incubated in Mg^2+-free extracellular solution.In the Achyranthes bidentata polypeptide group,hippocampal neurons were incubated in Mg^2+-free extracellular solution containing glutamate(300μM)and Achyranthes bidentata polypeptide at different concentrations.At 24 hours after exposure to the agents,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Hoechst 33258 staining were used to assess neuronal viability and nuclear m'orphology,respectively.Caspase-3 expression and activity were evaluated using western blot assay and colorimetric enzymatic assay,respectively.At various time points after glutamate treatment,reactive oxygen species in cells were detected by H2 DCF-DA,and mitochondrial membrane potential was detected by rhodamine 123 staining.To examine the effect of Achyranthes bidentata polypeptides on glutamate receptors,electrophysiological recording was used to measure the glutamate-induced inward current in cultured hippocampal neurons.Achyranthes bidentata polypeptide decreased the percentage of apoptotic cells and reduced the changes in caspase-3 expression and activity induced by glutamate.In addition,Achyranthes bidentata polypeptide attenuated the amplitude of the glutamate-induced current.Furthermore,the glutamate-induced increase in intracellular reactive oxygen species and reduction in mitochondrial membrane potential were attenuated by Achyranthes bidentata polypeptide treatment.These findings collectively suggest that Achyranthes bidentata polypeptides exert a neuroprotective effect in cultured hippocampal neurons by suppressing the overactivation of glutamate receptors and inhibiting the caspase-3-dependent mitochondrial apoptotic pathway.All animal studies were approved by the Animal Care and Use Committee,Nantong University,China(approval No.20120216-001)on February 16,2012.展开更多
Two kinds of polypeptides were tethered onto the surface of polypropylene microporous membrane (PPMM) through a ring opening polymerization of L-glutamate N-carboxyanhydride initiated by amino groups which were intr...Two kinds of polypeptides were tethered onto the surface of polypropylene microporous membrane (PPMM) through a ring opening polymerization of L-glutamate N-carboxyanhydride initiated by amino groups which were introduced by ammonia plasma and y-aminopropyl triethanoxysilane treatments. X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared spectroscopy (FT-IR/ATR), scanning electron microscopy (SEM), together with water contact angle measurements were used to characterize the modified membranes. XPS analyses and FT-IR/ATR spectra demonstrated that polypeptides are actually grafted onto the membrane surface. The wettability of the membrane surface increases at first and then decreases with the increase in grafting degrees of polypeptide. Platelet adhesion and murine macrophage attachment experiments reveal an enhanced hemocompatibility for the polypeptide modified PPMMs. All these results give evidence that polypeptide grafting can simultaneously improve the hemocompatibility as well as reserve the hydrophobicity for the membrane, which will provide a potential approach to improve the performance of polypropylene hollow fiber microporous membrane used in artificial oxygenator.展开更多
Two artificial minic polypeptides which are synthetic analogues of natural products with DNA affinity were synthesized, and theirs cleavage activity with DNA were examined. The structures of these compounds was confir...Two artificial minic polypeptides which are synthetic analogues of natural products with DNA affinity were synthesized, and theirs cleavage activity with DNA were examined. The structures of these compounds was confirmed by ^1H NMR, MS and IR.展开更多
(a)NCA polymerization initiated by LiHMDS or other initiators in THF,initiator i)n-hexylamine,ii)HMDS,iii)bipyNi(COD);(b)LiHMDS-initiated open vessel polymerization of BLGNCA at 26 mg and 2 g scale;(c)GPC traces of po...(a)NCA polymerization initiated by LiHMDS or other initiators in THF,initiator i)n-hexylamine,ii)HMDS,iii)bipyNi(COD);(b)LiHMDS-initiated open vessel polymerization of BLGNCA at 26 mg and 2 g scale;(c)GPC traces of poly-BLG at variable DP;(d)Reaction rates of LiHMDS and hexylamine initiated BLGNCA polymerization in THF with NCA:initiator ratio of 100∶1 and initial NCA concentration at 0.2 mol/L;(e)CD spectra of poly-BLG at variable DP prepared from LiHMDS-initiated NCA polymerization.展开更多
Two expressing plasmids have been constructed and used to express two bifunctional-domain recombinant polypeptides of human fibronectin (FN) in E. coli. One was CH50 (Pro1239-Ser1515 of FN linked with Ala1690-Thr1960 ...Two expressing plasmids have been constructed and used to express two bifunctional-domain recombinant polypeptides of human fibronectin (FN) in E. coli. One was CH50 (Pro1239-Ser1515 of FN linked with Ala1690-Thr1960 of FN through Met) and the other was CH56 (Pro1239-Thr1960 of FN). Both of two polypeptides were capable of binding heparin and were purified by heparin-a-garose affinity chromatography. The purified products were capable of binding cells. The production of CH50 and CH56 polypeptides provided a fundamental basis for further study of the anti-metastatic function of recombinant fibronectin polypeptides.展开更多
Nanomaterials are materials in which at least one of the dimensions of the particles is 100 nm and below.There are many types of nanomaterials,but noble metal nanoparticles are of interest due to their uniquely large ...Nanomaterials are materials in which at least one of the dimensions of the particles is 100 nm and below.There are many types of nanomaterials,but noble metal nanoparticles are of interest due to their uniquely large surface-to-volume ratio,high surface area,optical and electronic properties,high stability,easy synthesis,and tunable surface functionalization.More importantly,noble metal nanoparticles are known to have excellent compatibility with bio-materials,which is why they are widely used in biological applications.The synthesis method of noble metal nanoparticles conventionally involves the reduction of the noble metal salt precursor by toxic reaction agents such as NaBH4,hydrazine,and formaldehyde.This is a major drawback for researchers involved in biological application researches.Hence,the bio-synthesis of noble metal nanoparticles(NPs)by bio-materials via bio-reduction provides an alternative method to synthesize noble metal nanoparticles which are potentially non-toxic and safer for biological application.In this review,the bio-synthesis of noble metal nanoparticle including gold nanoparticle(AuNPs),silver nanoparticle(AgNPs),platinum nanoparticle(PtNPs),and palladium nanoparticle(PdNPs)are first discussed.This is followed by a discussion of these biosynthesized noble metal in biological applications including antimicrobial,wound healing,anticancer drug,and bioimaging.Based on these,it can be concluded that the study on bio-synthesized noble metal nanoparticles will expand further involving bio-reduction by unexplored bio-materials.However,many questions remain on the feasibility of bio-synthesized noble metal nanoparticles to replace existing methods on various biological applications.Nevertheless,the current development of the biological application by bio-synthesized noble metal NPs is still intensively ongoing,and will eventually reach the goal of full commercialization.展开更多
The molecular conformations of four silk fibroin crystalline analogues [GAGAG-X] 16(G,Gly;A,Ala;X=Ala,Ser,Tyr or Val,designated eGA,eGS,eGY or eGV),carried out using molecular design and expressed by Escherichia coil(...The molecular conformations of four silk fibroin crystalline analogues [GAGAG-X] 16(G,Gly;A,Ala;X=Ala,Ser,Tyr or Val,designated eGA,eGS,eGY or eGV),carried out using molecular design and expressed by Escherichia coil(E.coli),were evaluated by Raman spectra analysis.The abilities of forming β-sheet structure were determined by thioflavin T(ThT) fluorescence spectra analysis.In terms of molecular conformation,except eGY that could not form significant typical molecular conformation,eGS and eGV were mainly composed of β-sheets while eGA tended to form β-turn.β-turn was also present in eGY and absent in eGS and eGV.In terms of β-sheet structure,eGS had the highest β-sheet content,followed by eGV,and eGA had the lowest content,furthermore,β-sheet structures were more stable in eGS and eGV than those in eGA and eGY.展开更多
OBJECTIVE To explore the therapeutic effects and underlying mechanisms of velvet antler polypeptides(VVAPs)in CCl4-induced experimental hepatic fibrosis in rats.METHODS Anti-hepatic fibrosis properties of VAPs were te...OBJECTIVE To explore the therapeutic effects and underlying mechanisms of velvet antler polypeptides(VVAPs)in CCl4-induced experimental hepatic fibrosis in rats.METHODS Anti-hepatic fibrosis properties of VAPs were tested by Subcutaneous injection(SC)into male Wistar rats of CCl4- induced experimental hepatic fibrosis.After SC injections for 45 consecutive days at doses of 5mg·kg-1(low dose,VAPsL),10mg·kg-1(mid-dose,VAPsM)and 20mg·kg-1(high-dose,VAPsH),the rats were sacrificed and the various indicators were evaluated and tested.Observed hepatic cells degeneration and necrosis,inflammatory infiltration and levels of serum enzymes to assess treatment of VAPs;The expression levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),MDA,and hydroxyproline(HYP)in liver tissue were analyzed;RT-PCR analysis was carried out to detect the expression levels of matrix metalloproteinases2(MMP-2)and tissue inhibitor of metalloproteinases 1(TIMP-1)in liver tissue.RESULTS VAPs has obvious anti-hepatic fibrosis effects.Hepatocyte swelling,fatty degeneration was significantly reduced,reducing infiltration of inflammatory cells.Release of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)decreased significantly,reduction of hyaluronic acid(HA)and laminin(LN)obviously,at the same time,the content of total protein and albumin increased significantly in serum.Activity of SOD and GSH-Px was significantly raised and the content of MDA and HYP was reduced significantly in liver tissue.Expression levels of MMP-2and TIMP-1 mRNA in liver were decreased significantly.These improvements were more significant in high-dos and mid-dose groups(P<0.05 or P<0.01 vs model group).CONCLUSION These findings suggest VAPs can significant treat the hepatic fibrosis,which may be due to protect liver cells and improve liver functions by hydroxyl radical scavenging activity and great effect of antioxidation,and decrease the gene expression of MMP-2,improving exist-environment of liver cells and decreasing the gene expression of TIMP-1,prompting degradation of extracellular matrix.展开更多
Achyranthes bidentata polypeptides(ABPP) have been reported to inhibit apoptosis of retinal ganglion cells(RGCs).The present study investigated the protective effects of ABPP on RGCs in a rat model of optic nerve ...Achyranthes bidentata polypeptides(ABPP) have been reported to inhibit apoptosis of retinal ganglion cells(RGCs).The present study investigated the protective effects of ABPP on RGCs in a rat model of optic nerve injury.With prolonged injury time,RGC densities were gradually decreased.ABPP(5 μg) significantly increased RGC densities and upregulated growth associated protein 43 expression in rats with optic nerve injury.Results demonstrate that ABPP can protect RGCs and promote axonal growth after optic nerve crush.展开更多
Integrins are heterodimeric cell surface receptors that bind to ligands on another cell,e.g.intercellular adhesion molecule 1(ICAM-1),or the extracellular matrix.Integrins play an important role in immune system,and t...Integrins are heterodimeric cell surface receptors that bind to ligands on another cell,e.g.intercellular adhesion molecule 1(ICAM-1),or the extracellular matrix.Integrins play an important role in immune system,and they participate in inflammation,thrombosis,and proliferation,migration and apoptosis of tumor cells.They mediate adhesion and transduce signals across the membrane usually under the influence of forces.A recent study has shown that integrins bind and activate transforming growth factorβisoform(TGF-β)which is involved in tumor suppression and growth,and blocking the binding of TGF-βto integrin can inhibit tumor growth.RGD(arginine-glycine-aspartate)small peptide,which competitively inhibits ligand binding to integrins,has been approved as an injectable drug.However,when the RGD is used to block cancer-related extracellular signaling pathways,it will also cause activation of integrins for a period,and stimulate the transduction of intracellular signals constantly.Therefore,it is necessary to explore for new drugs that can selectively control conformational state of integrins without activating or blocking all of them.In this study,we selected two small peptides,KQAGDV and RTDLDSLRT,that combined with integrins and do not contain an RGD sequence.The non-RGD polypeptide RTDLDSLRT has been reported to have a binding site with integrins and the binding affinity is on nanomolar scale.For the motif of the fibrinogen y chain C-terminal KQAGDV,it can adhere to the head of the integrins.The micropipette aspiration technique and electron microscopy techniques were used to study the adhesion and activation of integrins by peptides,respectively.Micropipette aspiration technique was used to investigate the adhesion frequency of peptide and integrin on Jurkat cell.The pressure system was used to supply a controllable negative pression to the microtube,and two micropipettes were used to absorb red blood cells and Jurkat cells,respectively.The red blood cells were coated with small peptides and can serve as a force sensor after being sucked when two cells were connected.The binding kinetics of integrin and peptides interactions was determined by fitting the curves constructed using adhesion probability between two cells as a function of time.The curves were fitted using a small system probabilistic kinetic model to estimate a pair of kinetic parameters,including the zero force reverse rate kr0,and the cellular binding affinity Acmrm1Ka0.The adhesion frequency yielded P(t)=75%and 57%for RGD and KQAG DV peptides,respectively.We obtained Acmrm1Ka0=1.40 and kr0=0.32 s-1,for RGD,and Acmrm1Ka0=0.85 and kr0=0.54 s-1 for KQAGDV.The RGD peptide has a higher adhesion frequency and lower dissociation rate than the KQAGDV peptide.Electron microscopy techniques was used to observe the activation of integrins by peptides.Jurkat cell expressing integrins was bound to a magnetic bead and bottom plate which were coated with different integrin-binding peptides.Then,we manipulated the beads in a controlled direction by changing the magnetic field nearby,and the forces were applied to the cell.The target cells were fixed and then observed by scanning electron microscope or transmission electron microscope.Jurkat cells contain abundant flexible microvilli of which there are many parallel bundles of actin filaments inside.By electron microscopy analysis,the cell connected with magnetic bead coated with RGD were found to be protruded and the size of microvilli increased up to#-fold of the length of the KQAGDV sample.The microvilli exhibited a curved agglomerate structure under a force-free condition.Moreover,a higher proportion of cells were activated in the presence of RGD than KQAGDV.In conclusion,the binding affinity of KQAGDV to integrin is weaker than RGD,and KQAGDV can bind with integrins effectively with a lower activated proportion.Our results indicate the peptides may selectively bind to integrins without activating them.展开更多
Some striking differences in relative polypeptide abundanceof crystallins were observed in normal and galactose-induced cataractouslenses of rat by means of SDS-PAGE.In the cataractous lenses aprominent band appeared ...Some striking differences in relative polypeptide abundanceof crystallins were observed in normal and galactose-induced cataractouslenses of rat by means of SDS-PAGE.In the cataractous lenses aprominent band appeared at about 25 kDa and the αA chain increasedmarkedly,whereas the relative amount of the 31 kDa band decreasedsubstantially.These alterations are similar to the changes observed duringthe incubation of young mouse lenses in glucose-free medium.Eye Science1993;9:143-145.展开更多
Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid po...Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid polypeptide,that accompanies the pathophysiology of type 2 diabetes mellitus.Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia,including Alzheimer’s disease and vascular dementia,but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear.In this review,we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage,ultimately leading to the clinical symptoms of dementia.We discuss the evidence for islet amyloid polypeptide deposition in the brain,islet amyloid polypeptide interaction with other amyloids implicated in neurodegeneration,neuroinflammation caused by islet amyloid polypeptide deposition,vascular damage induced by islet amyloid polypeptide accumulation,and islet amyloid polypeptide-induced cytotoxicity.There are very few therapies approved for the treatment of dementia,and of these,clinical responses have been controversial at best.Therefore,investigating new,targetable pathways is vital for identifying novel therapeutic strategies for treating dementia.As such,we conclude this review by discussing islet amyloid polypeptide accumulation as a potential therapeutic target not only in treating type 2 diabetes mellitus but as a future target in treating or even preventing dementia associated with type 2 diabetes mellitus.展开更多
Background: Two differently charged polypeptides, α-poly-L-lysine and poly-L-glutamate, have previously been shown to effectively reduce postoperative intraabdominal adhesions. Though α-poly-L-lysine showed toxicity...Background: Two differently charged polypeptides, α-poly-L-lysine and poly-L-glutamate, have previously been shown to effectively reduce postoperative intraabdominal adhesions. Though α-poly-L-lysine showed toxicity in doses too close to the lowest therapeutic dose, the aim in the present study was to investigate the possible antiadhesive effect of another four cationic polypeptides. Materials/Methods: 125 mice were studied with a standardized and reproducible adhesion model and given epsilon poly-L-lysine, lactoferrin, lysozyme and polyarginine respectively in a combination with poly-L-glutamate. Epsilon poly-L-lysine was also tested in different concentrations and as single treatment. Results: All four cationic polypeptides above showed a significantly better anti-adhesive effect than the controls receiving saline (p<0.05). Epsilon poly-L-lysine had the best antiadhesive effect of the new substances tested in the experiment. Single treatment with the epsilon poly-L-lysine showed toxic side effects. Discussion: We have shown that epsilon poly-L-lysine, polyarginine, lysozyme and lactoferrin, in descending order, all can reduce postoperative intraabdominal adhesions in mice when combined with poly-L-glutamate. There were side effects of epsilon poly-L-lysine resembling those of α-poly-L-lysine, although less toxic. The antiadhesive effect of epsilon poly-L-lysine did not reach the level of α-poly-L-lysine. Further studies will concentrate on additional investigation, trying to modify the α-poly-L-lysine to lower its toxicity. The less toxic epsilon poly-L-lysine also needs further attention in our research of antiadhesive bioactive polypeptides.展开更多
基金sponsored by the National Key R&D Program of China (2018YFD0901102)the Natural Science Foundation of Zhejiang Province (LQ22D060002)+2 种基金the Fund of State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products (ZS20190105)the Fundamental Research Funds for the Provincial Universities of Zhejiang (SJLY2021015)the K.C.Wong Magna Fund of Ningbo University。
文摘Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.
文摘Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.
基金supported by the National Natural Science Foundation of China,No.81073079(to HMS)the Natural Science Foundation of the Jiangsu Higher Education Institute of China,No.18KJA180009(to HMS)the Science Foundation of Nantong City of China,No.MS12018043(to HMS)
文摘Glutamate-induced excitotoxicity plays a critical role in the neurological impairment caused by middle cerebral artery occlusion.Achyranthes bidentata polypeptides have been shown to protect against neurological functional damage caused by middle cerebral artery occlusion,but the underlying neuroprotective mechanisms and the relationship to glutamate-induced excitotoxicity remain unclear.Therefore,in the current study,we investigated the protective effects of Achyranthes bidentata polypeptides against glutamate-induced excitotoxicity in cultured hippocampal neurons.Hippocampal neurons were treated with Mg^2+-free extracellular solution containing glutamate(300μM)for 3 hours as a model of glutamate-mediated excitotoxicity(glutamate group).In the normal group,hippocampal neurons were incubated in Mg^2+-free extracellular solution.In the Achyranthes bidentata polypeptide group,hippocampal neurons were incubated in Mg^2+-free extracellular solution containing glutamate(300μM)and Achyranthes bidentata polypeptide at different concentrations.At 24 hours after exposure to the agents,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Hoechst 33258 staining were used to assess neuronal viability and nuclear m'orphology,respectively.Caspase-3 expression and activity were evaluated using western blot assay and colorimetric enzymatic assay,respectively.At various time points after glutamate treatment,reactive oxygen species in cells were detected by H2 DCF-DA,and mitochondrial membrane potential was detected by rhodamine 123 staining.To examine the effect of Achyranthes bidentata polypeptides on glutamate receptors,electrophysiological recording was used to measure the glutamate-induced inward current in cultured hippocampal neurons.Achyranthes bidentata polypeptide decreased the percentage of apoptotic cells and reduced the changes in caspase-3 expression and activity induced by glutamate.In addition,Achyranthes bidentata polypeptide attenuated the amplitude of the glutamate-induced current.Furthermore,the glutamate-induced increase in intracellular reactive oxygen species and reduction in mitochondrial membrane potential were attenuated by Achyranthes bidentata polypeptide treatment.These findings collectively suggest that Achyranthes bidentata polypeptides exert a neuroprotective effect in cultured hippocampal neurons by suppressing the overactivation of glutamate receptors and inhibiting the caspase-3-dependent mitochondrial apoptotic pathway.All animal studies were approved by the Animal Care and Use Committee,Nantong University,China(approval No.20120216-001)on February 16,2012.
基金This project was supported by the National Natural Science Foundation of China (No. 20074033)the National Basic Research Program of China (No. 2003CB15705).
文摘Two kinds of polypeptides were tethered onto the surface of polypropylene microporous membrane (PPMM) through a ring opening polymerization of L-glutamate N-carboxyanhydride initiated by amino groups which were introduced by ammonia plasma and y-aminopropyl triethanoxysilane treatments. X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared spectroscopy (FT-IR/ATR), scanning electron microscopy (SEM), together with water contact angle measurements were used to characterize the modified membranes. XPS analyses and FT-IR/ATR spectra demonstrated that polypeptides are actually grafted onto the membrane surface. The wettability of the membrane surface increases at first and then decreases with the increase in grafting degrees of polypeptide. Platelet adhesion and murine macrophage attachment experiments reveal an enhanced hemocompatibility for the polypeptide modified PPMMs. All these results give evidence that polypeptide grafting can simultaneously improve the hemocompatibility as well as reserve the hydrophobicity for the membrane, which will provide a potential approach to improve the performance of polypropylene hollow fiber microporous membrane used in artificial oxygenator.
文摘Two artificial minic polypeptides which are synthetic analogues of natural products with DNA affinity were synthesized, and theirs cleavage activity with DNA were examined. The structures of these compounds was confirmed by ^1H NMR, MS and IR.
文摘(a)NCA polymerization initiated by LiHMDS or other initiators in THF,initiator i)n-hexylamine,ii)HMDS,iii)bipyNi(COD);(b)LiHMDS-initiated open vessel polymerization of BLGNCA at 26 mg and 2 g scale;(c)GPC traces of poly-BLG at variable DP;(d)Reaction rates of LiHMDS and hexylamine initiated BLGNCA polymerization in THF with NCA:initiator ratio of 100∶1 and initial NCA concentration at 0.2 mol/L;(e)CD spectra of poly-BLG at variable DP prepared from LiHMDS-initiated NCA polymerization.
文摘Two expressing plasmids have been constructed and used to express two bifunctional-domain recombinant polypeptides of human fibronectin (FN) in E. coli. One was CH50 (Pro1239-Ser1515 of FN linked with Ala1690-Thr1960 of FN through Met) and the other was CH56 (Pro1239-Thr1960 of FN). Both of two polypeptides were capable of binding heparin and were purified by heparin-a-garose affinity chromatography. The purified products were capable of binding cells. The production of CH50 and CH56 polypeptides provided a fundamental basis for further study of the anti-metastatic function of recombinant fibronectin polypeptides.
基金This work was financially supported by the National Natural Science Foundation of China(No.21536010).
文摘Nanomaterials are materials in which at least one of the dimensions of the particles is 100 nm and below.There are many types of nanomaterials,but noble metal nanoparticles are of interest due to their uniquely large surface-to-volume ratio,high surface area,optical and electronic properties,high stability,easy synthesis,and tunable surface functionalization.More importantly,noble metal nanoparticles are known to have excellent compatibility with bio-materials,which is why they are widely used in biological applications.The synthesis method of noble metal nanoparticles conventionally involves the reduction of the noble metal salt precursor by toxic reaction agents such as NaBH4,hydrazine,and formaldehyde.This is a major drawback for researchers involved in biological application researches.Hence,the bio-synthesis of noble metal nanoparticles(NPs)by bio-materials via bio-reduction provides an alternative method to synthesize noble metal nanoparticles which are potentially non-toxic and safer for biological application.In this review,the bio-synthesis of noble metal nanoparticle including gold nanoparticle(AuNPs),silver nanoparticle(AgNPs),platinum nanoparticle(PtNPs),and palladium nanoparticle(PdNPs)are first discussed.This is followed by a discussion of these biosynthesized noble metal in biological applications including antimicrobial,wound healing,anticancer drug,and bioimaging.Based on these,it can be concluded that the study on bio-synthesized noble metal nanoparticles will expand further involving bio-reduction by unexplored bio-materials.However,many questions remain on the feasibility of bio-synthesized noble metal nanoparticles to replace existing methods on various biological applications.Nevertheless,the current development of the biological application by bio-synthesized noble metal NPs is still intensively ongoing,and will eventually reach the goal of full commercialization.
基金National Natural Science Foundation of China (No. 51075422)Natural Science Foundation of Jiangsu Province,China(No. BK2009147,No. BK2010253)+1 种基金Society Development Foundation of Suzhou City,China (No. SYG201001)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
文摘The molecular conformations of four silk fibroin crystalline analogues [GAGAG-X] 16(G,Gly;A,Ala;X=Ala,Ser,Tyr or Val,designated eGA,eGS,eGY or eGV),carried out using molecular design and expressed by Escherichia coil(E.coli),were evaluated by Raman spectra analysis.The abilities of forming β-sheet structure were determined by thioflavin T(ThT) fluorescence spectra analysis.In terms of molecular conformation,except eGY that could not form significant typical molecular conformation,eGS and eGV were mainly composed of β-sheets while eGA tended to form β-turn.β-turn was also present in eGY and absent in eGS and eGV.In terms of β-sheet structure,eGS had the highest β-sheet content,followed by eGV,and eGA had the lowest content,furthermore,β-sheet structures were more stable in eGS and eGV than those in eGA and eGY.
基金The project supported by National Natural Science Foundation of China(U1204826)
文摘OBJECTIVE To explore the therapeutic effects and underlying mechanisms of velvet antler polypeptides(VVAPs)in CCl4-induced experimental hepatic fibrosis in rats.METHODS Anti-hepatic fibrosis properties of VAPs were tested by Subcutaneous injection(SC)into male Wistar rats of CCl4- induced experimental hepatic fibrosis.After SC injections for 45 consecutive days at doses of 5mg·kg-1(low dose,VAPsL),10mg·kg-1(mid-dose,VAPsM)and 20mg·kg-1(high-dose,VAPsH),the rats were sacrificed and the various indicators were evaluated and tested.Observed hepatic cells degeneration and necrosis,inflammatory infiltration and levels of serum enzymes to assess treatment of VAPs;The expression levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),MDA,and hydroxyproline(HYP)in liver tissue were analyzed;RT-PCR analysis was carried out to detect the expression levels of matrix metalloproteinases2(MMP-2)and tissue inhibitor of metalloproteinases 1(TIMP-1)in liver tissue.RESULTS VAPs has obvious anti-hepatic fibrosis effects.Hepatocyte swelling,fatty degeneration was significantly reduced,reducing infiltration of inflammatory cells.Release of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)decreased significantly,reduction of hyaluronic acid(HA)and laminin(LN)obviously,at the same time,the content of total protein and albumin increased significantly in serum.Activity of SOD and GSH-Px was significantly raised and the content of MDA and HYP was reduced significantly in liver tissue.Expression levels of MMP-2and TIMP-1 mRNA in liver were decreased significantly.These improvements were more significant in high-dos and mid-dose groups(P<0.05 or P<0.01 vs model group).CONCLUSION These findings suggest VAPs can significant treat the hepatic fibrosis,which may be due to protect liver cells and improve liver functions by hydroxyl radical scavenging activity and great effect of antioxidation,and decrease the gene expression of MMP-2,improving exist-environment of liver cells and decreasing the gene expression of TIMP-1,prompting degradation of extracellular matrix.
基金the Priority Academic Program Development of Jiangsu Higher Education Institutions (PADA)
文摘Achyranthes bidentata polypeptides(ABPP) have been reported to inhibit apoptosis of retinal ganglion cells(RGCs).The present study investigated the protective effects of ABPP on RGCs in a rat model of optic nerve injury.With prolonged injury time,RGC densities were gradually decreased.ABPP(5 μg) significantly increased RGC densities and upregulated growth associated protein 43 expression in rats with optic nerve injury.Results demonstrate that ABPP can protect RGCs and promote axonal growth after optic nerve crush.
基金supported by the National Science Foundation of China ( 11772133, 11372116)
文摘Integrins are heterodimeric cell surface receptors that bind to ligands on another cell,e.g.intercellular adhesion molecule 1(ICAM-1),or the extracellular matrix.Integrins play an important role in immune system,and they participate in inflammation,thrombosis,and proliferation,migration and apoptosis of tumor cells.They mediate adhesion and transduce signals across the membrane usually under the influence of forces.A recent study has shown that integrins bind and activate transforming growth factorβisoform(TGF-β)which is involved in tumor suppression and growth,and blocking the binding of TGF-βto integrin can inhibit tumor growth.RGD(arginine-glycine-aspartate)small peptide,which competitively inhibits ligand binding to integrins,has been approved as an injectable drug.However,when the RGD is used to block cancer-related extracellular signaling pathways,it will also cause activation of integrins for a period,and stimulate the transduction of intracellular signals constantly.Therefore,it is necessary to explore for new drugs that can selectively control conformational state of integrins without activating or blocking all of them.In this study,we selected two small peptides,KQAGDV and RTDLDSLRT,that combined with integrins and do not contain an RGD sequence.The non-RGD polypeptide RTDLDSLRT has been reported to have a binding site with integrins and the binding affinity is on nanomolar scale.For the motif of the fibrinogen y chain C-terminal KQAGDV,it can adhere to the head of the integrins.The micropipette aspiration technique and electron microscopy techniques were used to study the adhesion and activation of integrins by peptides,respectively.Micropipette aspiration technique was used to investigate the adhesion frequency of peptide and integrin on Jurkat cell.The pressure system was used to supply a controllable negative pression to the microtube,and two micropipettes were used to absorb red blood cells and Jurkat cells,respectively.The red blood cells were coated with small peptides and can serve as a force sensor after being sucked when two cells were connected.The binding kinetics of integrin and peptides interactions was determined by fitting the curves constructed using adhesion probability between two cells as a function of time.The curves were fitted using a small system probabilistic kinetic model to estimate a pair of kinetic parameters,including the zero force reverse rate kr0,and the cellular binding affinity Acmrm1Ka0.The adhesion frequency yielded P(t)=75%and 57%for RGD and KQAG DV peptides,respectively.We obtained Acmrm1Ka0=1.40 and kr0=0.32 s-1,for RGD,and Acmrm1Ka0=0.85 and kr0=0.54 s-1 for KQAGDV.The RGD peptide has a higher adhesion frequency and lower dissociation rate than the KQAGDV peptide.Electron microscopy techniques was used to observe the activation of integrins by peptides.Jurkat cell expressing integrins was bound to a magnetic bead and bottom plate which were coated with different integrin-binding peptides.Then,we manipulated the beads in a controlled direction by changing the magnetic field nearby,and the forces were applied to the cell.The target cells were fixed and then observed by scanning electron microscope or transmission electron microscope.Jurkat cells contain abundant flexible microvilli of which there are many parallel bundles of actin filaments inside.By electron microscopy analysis,the cell connected with magnetic bead coated with RGD were found to be protruded and the size of microvilli increased up to#-fold of the length of the KQAGDV sample.The microvilli exhibited a curved agglomerate structure under a force-free condition.Moreover,a higher proportion of cells were activated in the presence of RGD than KQAGDV.In conclusion,the binding affinity of KQAGDV to integrin is weaker than RGD,and KQAGDV can bind with integrins effectively with a lower activated proportion.Our results indicate the peptides may selectively bind to integrins without activating them.
文摘Some striking differences in relative polypeptide abundanceof crystallins were observed in normal and galactose-induced cataractouslenses of rat by means of SDS-PAGE.In the cataractous lenses aprominent band appeared at about 25 kDa and the αA chain increasedmarkedly,whereas the relative amount of the 31 kDa band decreasedsubstantially.These alterations are similar to the changes observed duringthe incubation of young mouse lenses in glucose-free medium.Eye Science1993;9:143-145.
基金supported by The Mike Hogg FundBaylor College of Medicine Medical Scientist Training Program,NICHD R01HD099252(to RJP)and R01HD098131(to RJP)the NHLBI T32 HL092332(to ASB)。
文摘Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid polypeptide,that accompanies the pathophysiology of type 2 diabetes mellitus.Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia,including Alzheimer’s disease and vascular dementia,but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear.In this review,we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage,ultimately leading to the clinical symptoms of dementia.We discuss the evidence for islet amyloid polypeptide deposition in the brain,islet amyloid polypeptide interaction with other amyloids implicated in neurodegeneration,neuroinflammation caused by islet amyloid polypeptide deposition,vascular damage induced by islet amyloid polypeptide accumulation,and islet amyloid polypeptide-induced cytotoxicity.There are very few therapies approved for the treatment of dementia,and of these,clinical responses have been controversial at best.Therefore,investigating new,targetable pathways is vital for identifying novel therapeutic strategies for treating dementia.As such,we conclude this review by discussing islet amyloid polypeptide accumulation as a potential therapeutic target not only in treating type 2 diabetes mellitus but as a future target in treating or even preventing dementia associated with type 2 diabetes mellitus.
文摘Background: Two differently charged polypeptides, α-poly-L-lysine and poly-L-glutamate, have previously been shown to effectively reduce postoperative intraabdominal adhesions. Though α-poly-L-lysine showed toxicity in doses too close to the lowest therapeutic dose, the aim in the present study was to investigate the possible antiadhesive effect of another four cationic polypeptides. Materials/Methods: 125 mice were studied with a standardized and reproducible adhesion model and given epsilon poly-L-lysine, lactoferrin, lysozyme and polyarginine respectively in a combination with poly-L-glutamate. Epsilon poly-L-lysine was also tested in different concentrations and as single treatment. Results: All four cationic polypeptides above showed a significantly better anti-adhesive effect than the controls receiving saline (p<0.05). Epsilon poly-L-lysine had the best antiadhesive effect of the new substances tested in the experiment. Single treatment with the epsilon poly-L-lysine showed toxic side effects. Discussion: We have shown that epsilon poly-L-lysine, polyarginine, lysozyme and lactoferrin, in descending order, all can reduce postoperative intraabdominal adhesions in mice when combined with poly-L-glutamate. There were side effects of epsilon poly-L-lysine resembling those of α-poly-L-lysine, although less toxic. The antiadhesive effect of epsilon poly-L-lysine did not reach the level of α-poly-L-lysine. Further studies will concentrate on additional investigation, trying to modify the α-poly-L-lysine to lower its toxicity. The less toxic epsilon poly-L-lysine also needs further attention in our research of antiadhesive bioactive polypeptides.