Mimetic seeds attract birds to disperse seeds mainly by mimicking fleshy fruits or arillate seeds,however,they provide little nutritive reward for bird dispersers.The key characteristics of mimetic seeds are conspicuo...Mimetic seeds attract birds to disperse seeds mainly by mimicking fleshy fruits or arillate seeds,however,they provide little nutritive reward for bird dispersers.The key characteristics of mimetic seeds are conspicuous seed color,hard seed coat,certain toxic secondary metabolites,and perhaps smooth waxy layer.In this review,we discuss the global distribution of mimetic seeds,the interaction of mimetic seeds with bird dispersers,and secondary metabolites that underlie key characteristics of mimetic seeds.Mimetic-seed species mainly occur in the tropics,with large numbers distributed along coastal areas.The interaction between mimetic-seed species and bird dispersers can be antagonistic,mutualistic,or both.These interactions are generally established by conspicuous visual cues and hard tactile cues from mimetic seeds.The formation and variation of key characteristics of mimetic seeds may contribute to the metabolism of several kind of secondary compounds.Here,we also discuss mimetic-seed dispersal in the context of an evolutionary game,and propose several aspects of mimetic-seed dispersal that remain unstudied.While this review is based on preliminary findings and does not account for other potential influencing factors such as climate,it is expected to contribute to an improved understanding of mimetic-seed dispersal.展开更多
BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and tech...BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and technology.Surgical techniques,primarily involving the use of mesh to cover the abdominal wall gap,are widely used as a standard intervention strategy.AIM To examine the regeneration of the aponeurosis defect in the anterior abdominal wall in rats using regenerative mimetic factors of the extracellular matrix[ReGeneraTing Agent(RGTA)],adipose tissue micrografts(ATM),and platelet rich plasma(PRP)as regenerative agents.METHODS Regenerative agents such as RGTA,ATM,and PRP are gaining popularity.ATM involves autologous adipose tissue cells with mesenchymal stem cell markers and a high percentage of stromal vascular fraction cells.RGTAs are heparan sulfate(HS)mimetics that replace degraded HSs in damaged tissue,enhancing the quality and speed of repair.PRP is a concentrated plasma preparation containing seven fundamental proteins responsible for tissue production.An acellular dermal matrix is a biological implant free of cellular or antigenic components,making it an excellent material for reconstructive surgery.Polyglactin is a synthetic,absorbable mesh that loses 50%of its strength after fourteen days,providing initial support for new tissue regeneration before being completely absorbed.RESULTS Rats will undergo a laparotomy with a precise 2 cm by 2 cm excision of the anterior abdominal wall fascia below the umbilicus.They will be divided into sixteen groups,each receiving different combinations of regenerative factor injections into the denervated area in both non-contaminated and contaminated environments.A collagenelastin matrix will be used to join the aponeurosis edges,with an absorbable polyglactin mesh anchored over it.Samples will be taken for macroscopic,histological,and immunohistochemical evaluation of tissue regeneration.CONCLUSION Our study aims to demonstrate how these factors promote cell proliferation and healing of the denervated anterior abdominal wall,potentially reducing the frequency and complications of incisional hernias.This approach could offer a more economical and efficient treatment option compared to current costly methods.展开更多
Since the catalytic activity of most nanozymes is still far lower than the corresponding natural enzymes,there is urgent need to discover novel highly efficient enzyme-like materials.In this work,Co_(3)V_(2)O_(8)with ...Since the catalytic activity of most nanozymes is still far lower than the corresponding natural enzymes,there is urgent need to discover novel highly efficient enzyme-like materials.In this work,Co_(3)V_(2)O_(8)with hollow hexagonal prismatic pencil structures were prepared as novel artificial enzyme mimics.They were then decorated by photo-depositing Ag nanoparticles(Ag NPs)on the surface to further improve its catalytic activities.The Ag NPs decorated Co_(3)V_(2)O_(8)(ACVPs)showed both excellent oxidase-and peroxidase-like catalytic activities.They can oxidize the colorless 3,3’,5,5’-tetramethylbenzidine rapidly to induce a blue change.The enhanced enzyme mimetic activities can be attributed to the surface plasma resonance(SPR)effect of Ag NPs as well as the synergistic catalytic effect between Ag NPs and Co_(3)V_(2)O_(8),accelerating electron transfer and promoting the catalytic process.ACVPs were applied in constructing a colorimetric sensor,validating the occurrence of the Fenton reaction,and disinfection,presenting favorable catalytic performance.The enzyme-like catalytic mechanism was studied,indicating the chief role of⋅O_(2)-radicals in the catalytic process.This work not only discovers a novel functional material with double enzyme mimetic activity but also provides a new insight into exploiting artificial enzyme mimics with highly efficient catalytic ability.展开更多
Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanopa...Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanoparticles have been reported, but the underlying mechanism remains largely unknown. In our study, we aim to understand the safety of paclitaxel （PTX） loaded bovine albumin nanoparticles （BNPs） and active targeted PTX loaded BNPs to normal vital organ or tissue in vivo. The anti-human epidermal growth factor receptor 2 （HER2/neu） peptide mimetic （AHNP） was covalent bound to surface of BNPs （AHNP-BNPs） to exert selected delivery to HER2＋ cells. In HER2＋ tumor xenographs, saline （control）, PTX traditional formula （medium of Cremophor EL-ethanol）, BNPs, and AHNP-BNPs were administrated to evaluate the toxicity. There is no severe neutropenia or anemia with treatment of BNPs and AHNP-BNPs compared with traditional PTX injection. We also evaluated their damage on normal organs, including liver, kidney, spleen, lung and heart to fully estimate the safety of AHNP-BNPs and BNPs delivery systems. We observed similar toxicity in liver and lung in mice treated with BNPs or PTX injection, but decreased liver damage in mice treated with AHNP-BNPs. Further studies are rcouired to confirm our conclusion.展开更多
Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8%of the world's population and is anticipated to cross 5.4%by the year 2025.Since long back herbal medicines have been the highly este...Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8%of the world's population and is anticipated to cross 5.4%by the year 2025.Since long back herbal medicines have been the highly esteemed source of medicine therefore,they have become a growing part of modern,high-tech medicine.In view of the above aspects the present review provides profiles of plants(65 species) with hypoglycaemic properties,available through literature source from various database with proper categorization according to the parts used,mode of reduction in blood glucose(insulinomimetic or insulin secretagugues activity) and active phyloconsliluents having insulin mimetics activity.From the review it was suggested that,plant showing hypoglycemic potential mainly belongs to the family Leguminoseae,Lamiaceae,Liliaceae,Cucurbitaceae, Asteraceae,Moraceae,Rosaceae and Araliaceae.The most active plants are Allium sativum. Gymnema sylvestre,Citrullus colocynthis,Trigonella foenum greacum,Momordica charantia and Ficuts bengalensis.The review describes some new bioactive drugs and isolated compounds from plants such as roseoside,epigallocatechin gallate,beta-pyrazol-1-ylalanine,cinchonain Ib,leucocyandin 3-O-beta-d-galactosyl cellobioside,leucopelargonidin-3- O-alpha-L rhamuoside,glycyrrhetinic acid,dehydrotrametenolic acid,strictinin,isostrictinin,pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents.Thus,from the review majorly,the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols,flavonoida, terpenoids,coumarins and other constituents which show reduction in blood glucose levels.The review also discusses the management aspect of diabetes mellitus using these plants and their active principles.展开更多
Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(...Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(6'-SL),which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6'-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin.Indeed,lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6'-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H_20_2-induced oxidative stress.The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China(approval No.SUMC 2014-004)on February 20,2014.展开更多
Iron(Ⅱ) tetrasulfophthalocyanine(FeTSPc) ,as a novel mimetic enzyme of peroxidase,was used in the synthesis of a conducting polyaniline(PANI) /sodium dodecylsulfate(SDS) complex in SDS aqueous micellar solutions. The...Iron(Ⅱ) tetrasulfophthalocyanine(FeTSPc) ,as a novel mimetic enzyme of peroxidase,was used in the synthesis of a conducting polyaniline(PANI) /sodium dodecylsulfate(SDS) complex in SDS aqueous micellar solutions. The effects of pH,concentrations of aniline,SDS and H2O2,and reaction time on polymerization of aniline were studied in this case as shown by UV-Vis absorption spectroscopy. The results show that a wide range of pH(0.5-4.0) is required to produce the conducting PANI,and the optimal pH is 1.0 in SDS micelle. The optimal concentrations of aniline,SDS and H2O2 in feed,and reaction time in this case for the production of conducting PANI are respectively 10 mmol/L,10 mmol/L,25 mmol/L,and 15 h. FT-IR spectrum,elemental analysis,conductivity,cyclic voltammetry and thermogravimetric analysis confirm the thermal stability and electroactive form of PANI.展开更多
Hemoglobin was used as a mimetic enzyme for peroxidase to catalyze the oxidative reaction of o-phenylenediamine with H2O2 which functioned as an oxidant. The relationship between physicochemical properties of the inte...Hemoglobin was used as a mimetic enzyme for peroxidase to catalyze the oxidative reaction of o-phenylenediamine with H2O2 which functioned as an oxidant. The relationship between physicochemical properties of the intermediate and enzymatic activity of hemoglobin was studied. Since the solubility of the intermediate in the reaction is higher in butanol phase than in water phase, the intermediate itself diffused from the aqueous phase to the butanol phase. The experimental results showed that the rate of product and the stability of intermediate were associated with the temperature and the pH value of the buffer. The formation rate of intermediate and half-life period reveal the maximal in pH7, nevertheless, the whole rate of the catalytic reaction is the greatest in pH5, which the ratio of the initial rate in final product formation compared to that intermediate formation is the greatest.展开更多
In this study, Mn(Ⅱ) as a mimetic enzyme of horseradish peroxidase (HRP) was applied to the determination of hydrogen peroxide (H2O2). The method introduced in this paper is based on Mn(Ⅱ)’s catalytic effect on t...In this study, Mn(Ⅱ) as a mimetic enzyme of horseradish peroxidase (HRP) was applied to the determination of hydrogen peroxide (H2O2). The method introduced in this paper is based on Mn(Ⅱ)’s catalytic effect on the oxidation of 4-aminoantipyrine(4-AAP) with modified Trinder’s reagent N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3, 5-dimethoxyaniline(DAOS) by H2O2. By coupling this mimetic catalytic reaction with the catalytic reaction of glucose oxidase (GOD), glucose can be detected. Under optimum conditions, the calibration graphs for the determination of H2O2 and glucose are in the range of 1.0×10-3?1.0×10-1 mol/L and 1.0×10-3?14×10-3 mol/L respectively. The detection limit is 5.9×10-4 mol/L for H2O2 and is 9.2×10-4 mol/L for glucose. The feasibility of Mn ( II ) as a HRP mimetic enzyme in practical clinical analysis has been proven in the determination of glucose in human serum. So far, Mn ( II ) is the simplest and the most inexpensive mimetic enzyme.展开更多
Glucagon-like peptide 1（GLP-1）is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors（GLP-1Rs）on pancrea...Glucagon-like peptide 1（GLP-1）is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors（GLP-1Rs）on pancreaticβcells.Several GLP-1 mimetics,such as exenatide（exendin-4（Ex-4））,liraglutide,and lixisenatide,have been developed and approved as treatments for patients with type 2 diabetes.These peptides show bioactiv-ities almost identical to those of GLP- 1 and have a substantially longer plasma half-life than GLP-1 because of their resistance to dipeptidyl peptidase-4, a GLP-1 degrading enzyme.展开更多
The development of small molecule nerve growth factor (NGF) mimetics is a promising approach to overcome limitations in the use of the neurotrophin as a drug, which are poor pharmacokinetics and undesirable side effec...The development of small molecule nerve growth factor (NGF) mimetics is a promising approach to overcome limitations in the use of the neurotrophin as a drug, which are poor pharmacokinetics and undesirable side effects. We designed dimeric dipeptide called GK-2 (bis(N-succinyl-L-glutamyl-L-lysine)hexametylendiamide) on the base of beta-turn sequence of NGF loop4 which most exposed to solvent and hence can play the major role in the interaction of NGF with the receptor. It was shown, that GK-2 stimulates phosphorylation of TrkA receptor, selectively activates PI3K/Akt signaling cascade that is important for cell survival, and does not activate MAPK/Erk pathway, associated not only with cell survival but also with cell differentiation. According to these data, GK-2 in vitro prevented H2O2- or MPTP- or glutamate-induced neuronal cell death at nanomolar concentrations, but did not provoke neurite outgrowth in PC12 cells. In vivo GK-2 exhibits therapeutic effects in models of Parkinson’s disease, Alzheimer’s disease, brain ischemia and diabetes mellitus. GK-2 shows activity in doses 0.01 - 5 mg/kg intraperitoneally and retains the activity after oral administration in dose 10 mg/kg. GK-2 has no side effects accompanying NGF treatment namely hyperalgesia and weight loss. Thus, the designed dimeric substituted dipeptide provides promising drug candidate and a molecular tool for investigating the possibility of divergence in NGF therapeutic and adverse effects.展开更多
β-Cyclodextrin (β-CD) and its cross-linked polymer (β-CDP) were known as the mimetic models. Metalloporphyrin had been widely used in the enzymatic method of analysis and molecular recognition. In present work, it ...β-Cyclodextrin (β-CD) and its cross-linked polymer (β-CDP) were known as the mimetic models. Metalloporphyrin had been widely used in the enzymatic method of analysis and molecular recognition. In present work, it was investigation that supramolecular recognition for halogenated phenols, three crosols, three nitrophenols and three aminophenols, served respectively as the substrate of the mimetic receptor, iron-5, 10, 15, 20-tetrakis (sulforphenyl)-21H, 23H-porphine (FeTPPS) or FeTPPS-β-CDP. Supramolecular complex, FeTPPS-β-CDP with function of mult i-recognition and induced-fit, was a advanced kind of mimetic peroxidase; Methyl phenol or polyphenol was the substitute of chlorophenic acid, while aminophenols and other phenols were suggested not to be utilized to enzymatic assay of H2O2. Being a mimetic enzyme mimicking the space structure of overall proteinase, beaimed by immobilized mimetic enzyme with a large number of β-CD interior cavities, chlorophenol was identified optimal substrate in the system tested.展开更多
The characteristic of Myoglobin as mimetic enzyme was studied and applied in the determination of HeO2 with o-phenylenediamine as substrate. The absorbanee obtained at 40 ℃ was found to be proportional to the concent...The characteristic of Myoglobin as mimetic enzyme was studied and applied in the determination of HeO2 with o-phenylenediamine as substrate. The absorbanee obtained at 40 ℃ was found to be proportional to the concentration of H2O2 in the range of 2.0×10^-5- 2.0×10^-7 mol/L, with a correlation coefficient of 0.999 1. The proposed meth od is simple and highly sensitive to a detection limit of 2.7 × 10^-8 mol/L. The relative standard deviations were within 5% for the determination of different concentrations of H2O2. Satisfied results were obtained in the determination of H2O2 in rainwater by this method, and the recoveries were at the range of 97.2%-105.4%.展开更多
Intrinsic fluorescence emission maxima of hemoglobin(Hb) was investigated in relation to peroxidase property of Hb. The peroxidase activity of Hb was based on its ca\| talytic activity for oxidation of o \|pheny...Intrinsic fluorescence emission maxima of hemoglobin(Hb) was investigated in relation to peroxidase property of Hb. The peroxidase activity of Hb was based on its ca\| talytic activity for oxidation of o \|phenylenediamine by hydrogen peroxide. Hb was treated in the condition (temperature, ethanol and salt) that tetramer\|dimer equilibrium of Hb is shifted to the dimer state and its fluorescence spectrum was measured . When Hb treated in temperature (60\|70 ℃), ethanol concentration (60%\|70%) and NaCl concentration (2.5\|3.0 mol/L), the fluorescence emission maxima of Hb shifted towards red wavelength and its activity decreased quickly. Experimental results revealed that the activity and stability of Hb as mimetic peroxidase was closely relative to the hydrophobic environment of active center of Hb, and when Hb (Fe Ⅱ ) converted into met Hb (Fe Ⅲ ), its activity was 1.6 times as much as that of Hb.展开更多
In this paper,we study a theory of gravity called mimetic f(R,T)in the presence of swampland dS conjecture.For this purpose,we introduce several inflation solutions of the Hubble parameter H(N)from f(R,T)=R+δT gravit...In this paper,we study a theory of gravity called mimetic f(R,T)in the presence of swampland dS conjecture.For this purpose,we introduce several inflation solutions of the Hubble parameter H(N)from f(R,T)=R+δT gravity model,in which R is Ricci scalar,and T denotes the trace of the energy–momentum tensor.Also,δand N are the free parameter and a number of e-fold,respectively.Then we calculate quantities such as potential,Lagrange multiplier,slow-roll,and some cosmological parameters such as nsand r.Then we challenge the mentioned inflationary model from the swampland dS conjecture.We discuss the stability of the model and investigate the compatibility or incompatibility of this inflationary scenario with the latest Planck observable data.展开更多
The mimetic peroxidase iron-tetrakis(3-N-methylpyridyl)- porphyrin (Fe-T(3MPy)P)can be used as a catalyst in the spectrophoto- metric determination of H_2O_2 and glucose.The method is based on the formation of crystal...The mimetic peroxidase iron-tetrakis(3-N-methylpyridyl)- porphyrin (Fe-T(3MPy)P)can be used as a catalyst in the spectrophoto- metric determination of H_2O_2 and glucose.The method is based on the formation of crystal violet from leuco crystal violet.The glucose in human serum is determined by this reaction combined with catalytic reaction of glucose oxidase.展开更多
Several important PDE systems,like magnetohydrodynamics and computational electrodynamics,are known to support involutions where the divergence of a vector field evolves in divergence-free or divergence constraint-pre...Several important PDE systems,like magnetohydrodynamics and computational electrodynamics,are known to support involutions where the divergence of a vector field evolves in divergence-free or divergence constraint-preserving fashion.Recently,new classes of PDE systems have emerged for hyperelasticity,compressible multiphase flows,so-called firstorder reductions of the Einstein field equations,or a novel first-order hyperbolic reformulation of Schrödinger’s equation,to name a few,where the involution in the PDE supports curl-free or curl constraint-preserving evolution of a vector field.We study the problem of curl constraint-preserving reconstruction as it pertains to the design of mimetic finite volume(FV)WENO-like schemes for PDEs that support a curl-preserving involution.(Some insights into discontinuous Galerkin(DG)schemes are also drawn,though that is not the prime focus of this paper.)This is done for two-and three-dimensional structured mesh problems where we deliver closed form expressions for the reconstruction.The importance of multidimensional Riemann solvers in facilitating the design of such schemes is also documented.In two dimensions,a von Neumann analysis of structure-preserving WENOlike schemes that mimetically satisfy the curl constraints,is also presented.It shows the tremendous value of higher order WENO-like schemes in minimizing dissipation and dispersion for this class of problems.Numerical results are also presented to show that the edge-centered curl-preserving(ECCP)schemes meet their design accuracy.This paper is the first paper that invents non-linearly hybridized curl-preserving reconstruction and integrates it with higher order Godunov philosophy.By its very design,this paper is,therefore,intended to be forward-looking and to set the stage for future work on curl involution-constrained PDEs.展开更多
For a long time, fermented dairy products have been consumed for human’s nutrition and health. Recently, consumption of whole dairy products, such as full fat yoghurt, has declined due to the awareness of probable ha...For a long time, fermented dairy products have been consumed for human’s nutrition and health. Recently, consumption of whole dairy products, such as full fat yoghurt, has declined due to the awareness of probable harmful effects of fat on consumers’ health, resulting change of market interest in favor of low or non fat dairy products. It is a challenge for food scientists to produce a suitable fat substitute providing the functionality of the missing fat. The present investigation was carried out to examine the effect of 0 to 50% renneted skim milk (RSM) as a fat mimetic upon the physico-chemical, physical, rheological and sensory characteristics of nonfat yoghurt in comparison to control samples (full fat and skim yoghurt). By increasing RSM content, the chemical characteristics (titratable acidity, pH as well as the content of fat and total protein) of yoghurts did not alter except decrease of total solid in sample with 50% RSM. The yoghurts with more content of RSM exhibited higher b*and a* values, while the highest L* value, viscosity, water holding capacity (WHC), firmness and lowest syneresis were found in sample containing 30% RSM. It seems that new interaction in gel network of yoghurts containing RSM, exhibited greater ability to bind water than control skim yoghurt. In addition, probably new bridges between milk proteins (interacting partially hydrolyzed casein with casein) can increase the number of bounds between protein particles leading to lower syneresis. However, excessive RSM content (higher than 30%) did not increase the L* value, viscosity and WHC of samples probably because of too much aggregation of casein. Sensory results revealed that sample containing 30% RSM was exactly alike to full fat yoghurt in terms of overall sensory attributes. New formulation of palatable skim yoghurt was developed using 3% RSM successfully.展开更多
The dimeric dipeptide mimetics of the brain derived neurotrophic factor (BDNF) loops 1 and 4 and nerve growth factor (NGF) loop 4 were designed and synthesized at the Zakusov Research Institute of Pharmacology. There ...The dimeric dipeptide mimetics of the brain derived neurotrophic factor (BDNF) loops 1 and 4 and nerve growth factor (NGF) loop 4 were designed and synthesized at the Zakusov Research Institute of Pharmacology. There are respectively bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylenediamide(GSB-214), bis-(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide (GSB-106) and bis-(N-monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide (GK-2). All of the ob-tained compounds activated a corresponding specific NGF or BDNF tyrosine kinase receptor (TrkA or TrkB), but had different postreceptor signaling patterns. GSB-106 activated the ERK and AKT, whereas GSB-214 and GK-2 only activated the AKT kinase. Here we report a comparative analysis of neuroprotective activity of these dipeptides in a model of ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The all three dimeric dipeptides showed a statistically significant decrease of infarct volumes with the treatment beginning 4 hour after surgery. In the experiment with BDNF mimetics, GSB-106 reduced this volume by 66% and GSB-214 by 26%. NGF GK-2 reduced the cerebral infarct volume by 45%. Thus, BDNF mimetic, which activated both the ERK and AKT, and NGF mimetic, which selectively activated PI3K/AKT, showed high neuroprotective efficacy. In addition, we studied neuroprotective effects of GK-2 at the beginning of the treatment 6, 8 and 24 hours after reperfusion. The neuroprotective effect of GK-2 persisted in all these conditions. The effectiveness of GK-2 at a delayed start of administration suggests that the dipeptide has neuroregenerative properties. The results obtained suggest a potential role for the dimeric dipeptide NGF and BDNF mimetics as therapeutic agents useful in the treatment of a stroke.展开更多
Is physical fatigue one of the major causes of motor vehicle accidents？ Our study results challenged this traditional belief, and indicated that motor vehicle induced whole body vibration （WBV） is the actual cause....Is physical fatigue one of the major causes of motor vehicle accidents？ Our study results challenged this traditional belief, and indicated that motor vehicle induced whole body vibration （WBV） is the actual cause. In this study, rats were subjected to simulated WBV. After 2 weeks all rats were evaluated by multiple physiological tests. Results indicated that WBV for short periods impaired the animal＇s mental judgment capabilities as well as sensory and motor functions. The primary reason for this is that WBV caused vasoconstriction, which decreased the cerebral blood flow as shown by Doppler imaging. This reduction in blood flow impaired the animal＇s ability to run a maze. Nerve functions were affected as well. This was shown by a reduction in nerve conduction velocity （NCV）. An increase in tail flick and Von Frey withdrawal times showed sensory deficits. Grip strength was also reduced. 4F （human apolipoprotein A-I molecule mimetic） conditioning has shown preventive effects against WBV injury as indicated by the above functional tests. This animal model simulated the most common motor vehicle travel vibration and validated the biological cause and mechanism of physiological impairment from WBV, which can be translated into a practical application for motor vehicle accident prevention.展开更多
基金supported by the Yunnan Ten Thousand Talents Plan Young&Elite Talents Project(YNWR-QNBJ-2018-017)the National Natural Science Foundation of China(32371564)+2 种基金the Key Project of Basic Research of Yunnan Province,China(202101AS070035202301AS070001)to G.ChenYunnan Provincial Science and Technology Talent and Platform Plan(202305AM070005).
文摘Mimetic seeds attract birds to disperse seeds mainly by mimicking fleshy fruits or arillate seeds,however,they provide little nutritive reward for bird dispersers.The key characteristics of mimetic seeds are conspicuous seed color,hard seed coat,certain toxic secondary metabolites,and perhaps smooth waxy layer.In this review,we discuss the global distribution of mimetic seeds,the interaction of mimetic seeds with bird dispersers,and secondary metabolites that underlie key characteristics of mimetic seeds.Mimetic-seed species mainly occur in the tropics,with large numbers distributed along coastal areas.The interaction between mimetic-seed species and bird dispersers can be antagonistic,mutualistic,or both.These interactions are generally established by conspicuous visual cues and hard tactile cues from mimetic seeds.The formation and variation of key characteristics of mimetic seeds may contribute to the metabolism of several kind of secondary compounds.Here,we also discuss mimetic-seed dispersal in the context of an evolutionary game,and propose several aspects of mimetic-seed dispersal that remain unstudied.While this review is based on preliminary findings and does not account for other potential influencing factors such as climate,it is expected to contribute to an improved understanding of mimetic-seed dispersal.
文摘BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and technology.Surgical techniques,primarily involving the use of mesh to cover the abdominal wall gap,are widely used as a standard intervention strategy.AIM To examine the regeneration of the aponeurosis defect in the anterior abdominal wall in rats using regenerative mimetic factors of the extracellular matrix[ReGeneraTing Agent(RGTA)],adipose tissue micrografts(ATM),and platelet rich plasma(PRP)as regenerative agents.METHODS Regenerative agents such as RGTA,ATM,and PRP are gaining popularity.ATM involves autologous adipose tissue cells with mesenchymal stem cell markers and a high percentage of stromal vascular fraction cells.RGTAs are heparan sulfate(HS)mimetics that replace degraded HSs in damaged tissue,enhancing the quality and speed of repair.PRP is a concentrated plasma preparation containing seven fundamental proteins responsible for tissue production.An acellular dermal matrix is a biological implant free of cellular or antigenic components,making it an excellent material for reconstructive surgery.Polyglactin is a synthetic,absorbable mesh that loses 50%of its strength after fourteen days,providing initial support for new tissue regeneration before being completely absorbed.RESULTS Rats will undergo a laparotomy with a precise 2 cm by 2 cm excision of the anterior abdominal wall fascia below the umbilicus.They will be divided into sixteen groups,each receiving different combinations of regenerative factor injections into the denervated area in both non-contaminated and contaminated environments.A collagenelastin matrix will be used to join the aponeurosis edges,with an absorbable polyglactin mesh anchored over it.Samples will be taken for macroscopic,histological,and immunohistochemical evaluation of tissue regeneration.CONCLUSION Our study aims to demonstrate how these factors promote cell proliferation and healing of the denervated anterior abdominal wall,potentially reducing the frequency and complications of incisional hernias.This approach could offer a more economical and efficient treatment option compared to current costly methods.
基金supported by National Natural Science Foundation of China(52208272,41706080 and 51702328)the Basic Scientific Fund for National Public Research Institutes of China(2020S02 and 2019Y03)+3 种基金the Basic Frontier Science Research Program of Chinese Academy of Sciences(ZDBS-LY-DQC025)the Young Elite Scientists Sponsorship Program by CAST(No.YESS20210201)the Strategic Leading Science&Technology Program of the Chinese Academy of Sciences(XDA13040403)the Key Research and Development Program of Shandong Province(Major Scientific and Technological Innovation Project)(2019JZZY020711).
文摘Since the catalytic activity of most nanozymes is still far lower than the corresponding natural enzymes,there is urgent need to discover novel highly efficient enzyme-like materials.In this work,Co_(3)V_(2)O_(8)with hollow hexagonal prismatic pencil structures were prepared as novel artificial enzyme mimics.They were then decorated by photo-depositing Ag nanoparticles(Ag NPs)on the surface to further improve its catalytic activities.The Ag NPs decorated Co_(3)V_(2)O_(8)(ACVPs)showed both excellent oxidase-and peroxidase-like catalytic activities.They can oxidize the colorless 3,3’,5,5’-tetramethylbenzidine rapidly to induce a blue change.The enhanced enzyme mimetic activities can be attributed to the surface plasma resonance(SPR)effect of Ag NPs as well as the synergistic catalytic effect between Ag NPs and Co_(3)V_(2)O_(8),accelerating electron transfer and promoting the catalytic process.ACVPs were applied in constructing a colorimetric sensor,validating the occurrence of the Fenton reaction,and disinfection,presenting favorable catalytic performance.The enzyme-like catalytic mechanism was studied,indicating the chief role of⋅O_(2)-radicals in the catalytic process.This work not only discovers a novel functional material with double enzyme mimetic activity but also provides a new insight into exploiting artificial enzyme mimics with highly efficient catalytic ability.
基金the National Natural Science Foundation of China(Grant No.30970785,81273454)Beijing Natural Science Foundation(Grant No.7132113)+2 种基金National Basic Research Program(Grant No.2009CB930303,2013CB932501)Doctoral Foundation of the Ministry of Education(Grant No.20100001110056)Innovation Team of Ministry of Education(Grant No.BMU20110263)
文摘Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanoparticles have been reported, but the underlying mechanism remains largely unknown. In our study, we aim to understand the safety of paclitaxel （PTX） loaded bovine albumin nanoparticles （BNPs） and active targeted PTX loaded BNPs to normal vital organ or tissue in vivo. The anti-human epidermal growth factor receptor 2 （HER2/neu） peptide mimetic （AHNP） was covalent bound to surface of BNPs （AHNP-BNPs） to exert selected delivery to HER2＋ cells. In HER2＋ tumor xenographs, saline （control）, PTX traditional formula （medium of Cremophor EL-ethanol）, BNPs, and AHNP-BNPs were administrated to evaluate the toxicity. There is no severe neutropenia or anemia with treatment of BNPs and AHNP-BNPs compared with traditional PTX injection. We also evaluated their damage on normal organs, including liver, kidney, spleen, lung and heart to fully estimate the safety of AHNP-BNPs and BNPs delivery systems. We observed similar toxicity in liver and lung in mice treated with BNPs or PTX injection, but decreased liver damage in mice treated with AHNP-BNPs. Further studies are rcouired to confirm our conclusion.
基金financially supported by University Grants Commission,New Delhi
文摘Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8%of the world's population and is anticipated to cross 5.4%by the year 2025.Since long back herbal medicines have been the highly esteemed source of medicine therefore,they have become a growing part of modern,high-tech medicine.In view of the above aspects the present review provides profiles of plants(65 species) with hypoglycaemic properties,available through literature source from various database with proper categorization according to the parts used,mode of reduction in blood glucose(insulinomimetic or insulin secretagugues activity) and active phyloconsliluents having insulin mimetics activity.From the review it was suggested that,plant showing hypoglycemic potential mainly belongs to the family Leguminoseae,Lamiaceae,Liliaceae,Cucurbitaceae, Asteraceae,Moraceae,Rosaceae and Araliaceae.The most active plants are Allium sativum. Gymnema sylvestre,Citrullus colocynthis,Trigonella foenum greacum,Momordica charantia and Ficuts bengalensis.The review describes some new bioactive drugs and isolated compounds from plants such as roseoside,epigallocatechin gallate,beta-pyrazol-1-ylalanine,cinchonain Ib,leucocyandin 3-O-beta-d-galactosyl cellobioside,leucopelargonidin-3- O-alpha-L rhamuoside,glycyrrhetinic acid,dehydrotrametenolic acid,strictinin,isostrictinin,pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents.Thus,from the review majorly,the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols,flavonoida, terpenoids,coumarins and other constituents which show reduction in blood glucose levels.The review also discusses the management aspect of diabetes mellitus using these plants and their active principles.
基金supported by the National Natural Science Foundation of China,No.81471279 and No.81171138(to WJZ)Talent Support Grant from Shantou University Medical College,China,No.2501220118(to WJZ)the Li Kashing Foundation,No.LD030302(to MS)
文摘Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(6'-SL),which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6'-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin.Indeed,lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6'-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H_20_2-induced oxidative stress.The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China(approval No.SUMC 2014-004)on February 20,2014.
基金Project(07JJ6020) supported by the Hunan Provincial Natural Science Foundation of ChinaProject(2007-24-3) supported by the Huaihua Key Science and Technology Program, China
文摘Iron(Ⅱ) tetrasulfophthalocyanine(FeTSPc) ,as a novel mimetic enzyme of peroxidase,was used in the synthesis of a conducting polyaniline(PANI) /sodium dodecylsulfate(SDS) complex in SDS aqueous micellar solutions. The effects of pH,concentrations of aniline,SDS and H2O2,and reaction time on polymerization of aniline were studied in this case as shown by UV-Vis absorption spectroscopy. The results show that a wide range of pH(0.5-4.0) is required to produce the conducting PANI,and the optimal pH is 1.0 in SDS micelle. The optimal concentrations of aniline,SDS and H2O2 in feed,and reaction time in this case for the production of conducting PANI are respectively 10 mmol/L,10 mmol/L,25 mmol/L,and 15 h. FT-IR spectrum,elemental analysis,conductivity,cyclic voltammetry and thermogravimetric analysis confirm the thermal stability and electroactive form of PANI.
基金Supported by the National Natural Science F oundation of China( No.39770 2 0 0 )
文摘Hemoglobin was used as a mimetic enzyme for peroxidase to catalyze the oxidative reaction of o-phenylenediamine with H2O2 which functioned as an oxidant. The relationship between physicochemical properties of the intermediate and enzymatic activity of hemoglobin was studied. Since the solubility of the intermediate in the reaction is higher in butanol phase than in water phase, the intermediate itself diffused from the aqueous phase to the butanol phase. The experimental results showed that the rate of product and the stability of intermediate were associated with the temperature and the pH value of the buffer. The formation rate of intermediate and half-life period reveal the maximal in pH7, nevertheless, the whole rate of the catalytic reaction is the greatest in pH5, which the ratio of the initial rate in final product formation compared to that intermediate formation is the greatest.
文摘In this study, Mn(Ⅱ) as a mimetic enzyme of horseradish peroxidase (HRP) was applied to the determination of hydrogen peroxide (H2O2). The method introduced in this paper is based on Mn(Ⅱ)’s catalytic effect on the oxidation of 4-aminoantipyrine(4-AAP) with modified Trinder’s reagent N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3, 5-dimethoxyaniline(DAOS) by H2O2. By coupling this mimetic catalytic reaction with the catalytic reaction of glucose oxidase (GOD), glucose can be detected. Under optimum conditions, the calibration graphs for the determination of H2O2 and glucose are in the range of 1.0×10-3?1.0×10-1 mol/L and 1.0×10-3?14×10-3 mol/L respectively. The detection limit is 5.9×10-4 mol/L for H2O2 and is 9.2×10-4 mol/L for glucose. The feasibility of Mn ( II ) as a HRP mimetic enzyme in practical clinical analysis has been proven in the determination of glucose in human serum. So far, Mn ( II ) is the simplest and the most inexpensive mimetic enzyme.
基金supported by a Grant-in-aid for Scientific Research from the Ministry of EducationScience+3 种基金Sports and Culture of Japan(grant number:25430056)the fund from Nukada Institute for Medical and Biological ResearchChibaJapan
文摘Glucagon-like peptide 1（GLP-1）is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors（GLP-1Rs）on pancreaticβcells.Several GLP-1 mimetics,such as exenatide（exendin-4（Ex-4））,liraglutide,and lixisenatide,have been developed and approved as treatments for patients with type 2 diabetes.These peptides show bioactiv-ities almost identical to those of GLP- 1 and have a substantially longer plasma half-life than GLP-1 because of their resistance to dipeptidyl peptidase-4, a GLP-1 degrading enzyme.
文摘The development of small molecule nerve growth factor (NGF) mimetics is a promising approach to overcome limitations in the use of the neurotrophin as a drug, which are poor pharmacokinetics and undesirable side effects. We designed dimeric dipeptide called GK-2 (bis(N-succinyl-L-glutamyl-L-lysine)hexametylendiamide) on the base of beta-turn sequence of NGF loop4 which most exposed to solvent and hence can play the major role in the interaction of NGF with the receptor. It was shown, that GK-2 stimulates phosphorylation of TrkA receptor, selectively activates PI3K/Akt signaling cascade that is important for cell survival, and does not activate MAPK/Erk pathway, associated not only with cell survival but also with cell differentiation. According to these data, GK-2 in vitro prevented H2O2- or MPTP- or glutamate-induced neuronal cell death at nanomolar concentrations, but did not provoke neurite outgrowth in PC12 cells. In vivo GK-2 exhibits therapeutic effects in models of Parkinson’s disease, Alzheimer’s disease, brain ischemia and diabetes mellitus. GK-2 shows activity in doses 0.01 - 5 mg/kg intraperitoneally and retains the activity after oral administration in dose 10 mg/kg. GK-2 has no side effects accompanying NGF treatment namely hyperalgesia and weight loss. Thus, the designed dimeric substituted dipeptide provides promising drug candidate and a molecular tool for investigating the possibility of divergence in NGF therapeutic and adverse effects.
基金the National Natural Science Foundation of China
文摘β-Cyclodextrin (β-CD) and its cross-linked polymer (β-CDP) were known as the mimetic models. Metalloporphyrin had been widely used in the enzymatic method of analysis and molecular recognition. In present work, it was investigation that supramolecular recognition for halogenated phenols, three crosols, three nitrophenols and three aminophenols, served respectively as the substrate of the mimetic receptor, iron-5, 10, 15, 20-tetrakis (sulforphenyl)-21H, 23H-porphine (FeTPPS) or FeTPPS-β-CDP. Supramolecular complex, FeTPPS-β-CDP with function of mult i-recognition and induced-fit, was a advanced kind of mimetic peroxidase; Methyl phenol or polyphenol was the substitute of chlorophenic acid, while aminophenols and other phenols were suggested not to be utilized to enzymatic assay of H2O2. Being a mimetic enzyme mimicking the space structure of overall proteinase, beaimed by immobilized mimetic enzyme with a large number of β-CD interior cavities, chlorophenol was identified optimal substrate in the system tested.
基金Supported by the National Natural Science Foun-dation of China (20275027) the Natural Science Foundation ofHubei Province (2004ABA182) .
文摘The characteristic of Myoglobin as mimetic enzyme was studied and applied in the determination of HeO2 with o-phenylenediamine as substrate. The absorbanee obtained at 40 ℃ was found to be proportional to the concentration of H2O2 in the range of 2.0×10^-5- 2.0×10^-7 mol/L, with a correlation coefficient of 0.999 1. The proposed meth od is simple and highly sensitive to a detection limit of 2.7 × 10^-8 mol/L. The relative standard deviations were within 5% for the determination of different concentrations of H2O2. Satisfied results were obtained in the determination of H2O2 in rainwater by this method, and the recoveries were at the range of 97.2%-105.4%.
文摘Intrinsic fluorescence emission maxima of hemoglobin(Hb) was investigated in relation to peroxidase property of Hb. The peroxidase activity of Hb was based on its ca\| talytic activity for oxidation of o \|phenylenediamine by hydrogen peroxide. Hb was treated in the condition (temperature, ethanol and salt) that tetramer\|dimer equilibrium of Hb is shifted to the dimer state and its fluorescence spectrum was measured . When Hb treated in temperature (60\|70 ℃), ethanol concentration (60%\|70%) and NaCl concentration (2.5\|3.0 mol/L), the fluorescence emission maxima of Hb shifted towards red wavelength and its activity decreased quickly. Experimental results revealed that the activity and stability of Hb as mimetic peroxidase was closely relative to the hydrophobic environment of active center of Hb, and when Hb (Fe Ⅱ ) converted into met Hb (Fe Ⅲ ), its activity was 1.6 times as much as that of Hb.
文摘In this paper,we study a theory of gravity called mimetic f(R,T)in the presence of swampland dS conjecture.For this purpose,we introduce several inflation solutions of the Hubble parameter H(N)from f(R,T)=R+δT gravity model,in which R is Ricci scalar,and T denotes the trace of the energy–momentum tensor.Also,δand N are the free parameter and a number of e-fold,respectively.Then we calculate quantities such as potential,Lagrange multiplier,slow-roll,and some cosmological parameters such as nsand r.Then we challenge the mentioned inflationary model from the swampland dS conjecture.We discuss the stability of the model and investigate the compatibility or incompatibility of this inflationary scenario with the latest Planck observable data.
文摘The mimetic peroxidase iron-tetrakis(3-N-methylpyridyl)- porphyrin (Fe-T(3MPy)P)can be used as a catalyst in the spectrophoto- metric determination of H_2O_2 and glucose.The method is based on the formation of crystal violet from leuco crystal violet.The glucose in human serum is determined by this reaction combined with catalytic reaction of glucose oxidase.
基金Dinshaw S.Balsara acknowledges support via NSF grants NSF-19-04774,NSFAST-2009776 and NASA-2020-1241Michael Dumbser acknowledges the financial support received from the Italian Ministry of Education,University and Research(MIUR)in the frame of the Departments of Excellence Initiative 2018-2022 attributed to DICAM of the University of Trento(grant L.232/2016)and in the frame of the PRIN 2017 project Innovative numerical methods for evolutionary partial differential equations and applications.
文摘Several important PDE systems,like magnetohydrodynamics and computational electrodynamics,are known to support involutions where the divergence of a vector field evolves in divergence-free or divergence constraint-preserving fashion.Recently,new classes of PDE systems have emerged for hyperelasticity,compressible multiphase flows,so-called firstorder reductions of the Einstein field equations,or a novel first-order hyperbolic reformulation of Schrödinger’s equation,to name a few,where the involution in the PDE supports curl-free or curl constraint-preserving evolution of a vector field.We study the problem of curl constraint-preserving reconstruction as it pertains to the design of mimetic finite volume(FV)WENO-like schemes for PDEs that support a curl-preserving involution.(Some insights into discontinuous Galerkin(DG)schemes are also drawn,though that is not the prime focus of this paper.)This is done for two-and three-dimensional structured mesh problems where we deliver closed form expressions for the reconstruction.The importance of multidimensional Riemann solvers in facilitating the design of such schemes is also documented.In two dimensions,a von Neumann analysis of structure-preserving WENOlike schemes that mimetically satisfy the curl constraints,is also presented.It shows the tremendous value of higher order WENO-like schemes in minimizing dissipation and dispersion for this class of problems.Numerical results are also presented to show that the edge-centered curl-preserving(ECCP)schemes meet their design accuracy.This paper is the first paper that invents non-linearly hybridized curl-preserving reconstruction and integrates it with higher order Godunov philosophy.By its very design,this paper is,therefore,intended to be forward-looking and to set the stage for future work on curl involution-constrained PDEs.
文摘For a long time, fermented dairy products have been consumed for human’s nutrition and health. Recently, consumption of whole dairy products, such as full fat yoghurt, has declined due to the awareness of probable harmful effects of fat on consumers’ health, resulting change of market interest in favor of low or non fat dairy products. It is a challenge for food scientists to produce a suitable fat substitute providing the functionality of the missing fat. The present investigation was carried out to examine the effect of 0 to 50% renneted skim milk (RSM) as a fat mimetic upon the physico-chemical, physical, rheological and sensory characteristics of nonfat yoghurt in comparison to control samples (full fat and skim yoghurt). By increasing RSM content, the chemical characteristics (titratable acidity, pH as well as the content of fat and total protein) of yoghurts did not alter except decrease of total solid in sample with 50% RSM. The yoghurts with more content of RSM exhibited higher b*and a* values, while the highest L* value, viscosity, water holding capacity (WHC), firmness and lowest syneresis were found in sample containing 30% RSM. It seems that new interaction in gel network of yoghurts containing RSM, exhibited greater ability to bind water than control skim yoghurt. In addition, probably new bridges between milk proteins (interacting partially hydrolyzed casein with casein) can increase the number of bounds between protein particles leading to lower syneresis. However, excessive RSM content (higher than 30%) did not increase the L* value, viscosity and WHC of samples probably because of too much aggregation of casein. Sensory results revealed that sample containing 30% RSM was exactly alike to full fat yoghurt in terms of overall sensory attributes. New formulation of palatable skim yoghurt was developed using 3% RSM successfully.
文摘The dimeric dipeptide mimetics of the brain derived neurotrophic factor (BDNF) loops 1 and 4 and nerve growth factor (NGF) loop 4 were designed and synthesized at the Zakusov Research Institute of Pharmacology. There are respectively bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylenediamide(GSB-214), bis-(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide (GSB-106) and bis-(N-monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide (GK-2). All of the ob-tained compounds activated a corresponding specific NGF or BDNF tyrosine kinase receptor (TrkA or TrkB), but had different postreceptor signaling patterns. GSB-106 activated the ERK and AKT, whereas GSB-214 and GK-2 only activated the AKT kinase. Here we report a comparative analysis of neuroprotective activity of these dipeptides in a model of ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The all three dimeric dipeptides showed a statistically significant decrease of infarct volumes with the treatment beginning 4 hour after surgery. In the experiment with BDNF mimetics, GSB-106 reduced this volume by 66% and GSB-214 by 26%. NGF GK-2 reduced the cerebral infarct volume by 45%. Thus, BDNF mimetic, which activated both the ERK and AKT, and NGF mimetic, which selectively activated PI3K/AKT, showed high neuroprotective efficacy. In addition, we studied neuroprotective effects of GK-2 at the beginning of the treatment 6, 8 and 24 hours after reperfusion. The neuroprotective effect of GK-2 persisted in all these conditions. The effectiveness of GK-2 at a delayed start of administration suggests that the dipeptide has neuroregenerative properties. The results obtained suggest a potential role for the dimeric dipeptide NGF and BDNF mimetics as therapeutic agents useful in the treatment of a stroke.
文摘Is physical fatigue one of the major causes of motor vehicle accidents？ Our study results challenged this traditional belief, and indicated that motor vehicle induced whole body vibration （WBV） is the actual cause. In this study, rats were subjected to simulated WBV. After 2 weeks all rats were evaluated by multiple physiological tests. Results indicated that WBV for short periods impaired the animal＇s mental judgment capabilities as well as sensory and motor functions. The primary reason for this is that WBV caused vasoconstriction, which decreased the cerebral blood flow as shown by Doppler imaging. This reduction in blood flow impaired the animal＇s ability to run a maze. Nerve functions were affected as well. This was shown by a reduction in nerve conduction velocity （NCV）. An increase in tail flick and Von Frey withdrawal times showed sensory deficits. Grip strength was also reduced. 4F （human apolipoprotein A-I molecule mimetic） conditioning has shown preventive effects against WBV injury as indicated by the above functional tests. This animal model simulated the most common motor vehicle travel vibration and validated the biological cause and mechanism of physiological impairment from WBV, which can be translated into a practical application for motor vehicle accident prevention.
