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
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
Constructing high-performance nanozymes for specific biomolecules is crucial but challenging for practical applications and fundamental research.Herein,through the examination of the catalytic reaction paths of natura...Constructing high-performance nanozymes for specific biomolecules is crucial but challenging for practical applications and fundamental research.Herein,through the examination of the catalytic reaction paths of natural nicotinamide adenine dinucleotide(NADH)oxidase(NOX),a novel and efficient single-atom rhodium catalyst(Rh1/NC)was developed to mimic NOX.The Rh_(1)/NC demonstrated the ability to catalyze the dehydrogenation of NADH and transfer electrons to O_(2)to generate H_(2)O_(2)through the typical two-electron pathway.Furthermore,our findings revealed that Rh_(1)/NC exhibits the ability to catalyze the conversion of produced H_(2)O_(2)into OH under mildly acidic conditions.This process amplifies the oxidation of NADH,showcasing NADH peroxidase-like activity(NPx-like).As a paradigm,this unique dual enzyme-like property of Rh_(1)/NC with a positive feedback effect holds significance in disrupting cancer cellular homeostasis.Rh_(1)/NC can effectively consume NADH via cascade biocatalytic reactions within cancer cells,further triggering the elevation of reactive oxygen species(ROS),leading to impaired oxidative phosphorylation and decreased mitochondrial membrane potential,thus damaging the adenosine triphosphate(ATP)synthesis.The resulting'domino effect'interferes with the energy metabolism homeostasis of cancer cells,ultimately promoting cell apoptosis.This study provides potential guidance for the rational design of materials with greater capabilities.展开更多
In the past decades, enzyme mimetics based on ceria nanoparticles （nanoceria） have been developed as potential substitutes for nature enzymes. The mixed valence states of cerium and the patterns of oxygen vacancies ...In the past decades, enzyme mimetics based on ceria nanoparticles （nanoceria） have been developed as potential substitutes for nature enzymes. The mixed valence states of cerium and the patterns of oxygen vacancies on crystal planes result in different enzyme mimetic activities. In this review we survey the bio-applications of nanoceria-based enzyme mimetics as well as the underlying mechanisms. Factors influencing the enzyme mimetic activities and future perspective of nanoceria-based enzyme mimetics are also addressed.展开更多
Oxidative stress is associated with many acute and chronic inflammatory diseases.Development of nanomaterial-based enzyme mimetics for reactive oxygen species(ROS)scavenging is challenging,but holds great promise for ...Oxidative stress is associated with many acute and chronic inflammatory diseases.Development of nanomaterial-based enzyme mimetics for reactive oxygen species(ROS)scavenging is challenging,but holds great promise for the treatment of inflammatory diseases.Herein,we report the highly ordered manganese dioxide encapsulated selenium-melanin(Se@Me@MnO_(2))nanozyme with high efficiency for intracellular antioxidation and anti-inflammation.The Se@Me@MnO_(2)nanozyme is sequentially fabricated through the radical polymerization and the in-situ oxidation-reduction.In vitro experimental results demonstrated that the Se@Me@MnO_(2) nanozyme exhibits multiple enzyme activities to scavenge ROS,including catalase(CAT),glutathione peroxidase(GPx)and superoxide dismutase(SOD).Mechanism researches illustrated that the Se core possesses GPx-like catalytic activity,the Me and the MnO_(2) possess both the SOD-like and the CAT-like activities.What’s more,due to the stable unpaired electrons existing in the nanozyme,the Se,Me and MnO_(2) provide synergistic and fast electron transfer effect to achieve the quickly scavenging of hydrogen peroxide,hydroxyl radical,and superoxide anion.Further in vivo experimental results showed that this biocompatible nanozyme exhibits cytoprotective effects by resisting ROS-mediated damage,thereby alleviating the inflammation.This multienzyme mimetics is believed to be an excellent ROS scavenger and have a good potential in clinical therapy for ROS-related diseases.展开更多
Natural enzymes as biological catalysts possess remarkable advantages,especially their highly efficient and selective catalysis under mild conditions.However,most natural enzymes are proteins,thus exhibiting an inhere...Natural enzymes as biological catalysts possess remarkable advantages,especially their highly efficient and selective catalysis under mild conditions.However,most natural enzymes are proteins,thus exhibiting an inherent low durability to harsh reaction conditions.Artificial enzyme mimetics have been pursued extensively to avoid this drawback.Quite recently,some inorganic nanoparticles(NPs) have been found to exhibit unique enzyme mimetics.In addition,their much higher stability overcomes the inherent disadvantage of natural enzymes.Furthermore,easy mass-production and low cost endow them more benefits.As a new member of artificial enzyme mimetics,they have received intense attention.In this review article,major progress in this field is summarized and future perspectives are highlighted.展开更多
Passerine mimics often imitate various vocalizations from other bird species and incorporate these sounds into their song repertoires.While a few anecdotes reported that wild songbirds imitated human-associated sounds...Passerine mimics often imitate various vocalizations from other bird species and incorporate these sounds into their song repertoires.While a few anecdotes reported that wild songbirds imitated human-associated sounds,besides captive parrots and songbirds,systemic and quantitative studies on human-made sound mimicry in wild birds remain scarce.In this study,we investigated the mimetic accuracy and consistency of electric moped sounds imitated by an urban bird,the Chinese Blackbird(Turdus mandarinus).We found that:(1)Only one type of electric moped sound was imitated,i.e.,13 of 26 males mimicked the first part of the antitheft alarm,a phrase containing a series of identical notes.(2)The mimicry produced by male Chinese Blackbirds had fewer notes and lower consistency within phrases compared to the model alarms.(3)The mimicry of male Chinese Blackbirds was imperfect,i.e.,most of the acoustic parameters differed from the model alarms.Additionally,mimetic notes were lower in frequency than the models.Mimetic notes from two areas were also different in acoustic structures,suggesting Chinese Blackbirds might learn mimicry mainly from conspecific neighbors within each area respectively rather than electric mopeds,namely the secondary mimicry.Imperfect mimicry of human-made sounds could result from cost and physical constraints,associated with high consistency,frequency,and repetitions.Consequently,Chinese Blackbirds copied a simplified version of electric moped alarms.We recommend further attention to mimic species inhabiting urban ecosystems to better understand vocal mimicry's adaptation to ongoing urbanization.展开更多
Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-ad...Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-adhesion hydrogels combined with growth factors is a promising strategy to address endometrial injury.Insulin-like growth factor 1 is closely associated with endometrial growth and plays a crucial role in endometrial receptivity that is essential for fertility.However,its high cost,environmental sensitivity,and short biological half-life limit its practical applications.In this study,we developed a two-component peptide-based hydrogel consisting of a biotinylated peptide and an insulin-like growth factor 1(IGF-1)mimetic peptide,both of which were designed with self-assembly capabilities.The resultant hydrogel exhibited significant mechanical properties and retained its native IGF-1 bioactivity.In vivo experiments demonstrated that the hydrogel significantly facilitated proliferation and vascular restoration.Additionally,it effectively reduced fibrosis by decreasing collagen accumulation,restoring the expression of progesterone receptors,and enhancing endometrial receptivity,which are crucial for embryo implantation.These findings highlight the potential of the two-component peptide-based hydrogel as an innovative therapeutic approach for treating endometrial injury.展开更多
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
For the ultra-high water-cut reservoirs,after long-term water injection exploitation,the physical properties of the reservoir change and the heterogeneity of the reservoir becomes increasingly severe,which further agg...For the ultra-high water-cut reservoirs,after long-term water injection exploitation,the physical properties of the reservoir change and the heterogeneity of the reservoir becomes increasingly severe,which further aggravates the spatial difference of the flow field.In this study,the displacement experiments were employed to investigate the variations in core permeability,porosity,and relative permeability after a large amount of water injection.A relative permeability endpoint model was proposed by utilizing the alternating conditional expectation(ACE)transformation to describe the variation in relative permeability based on the experimental data.Based on the time dependent models for permeability and relative permeability,the traditional oil-water two-phase model was improved and discretized using the mimetic finite difference method(MFD).The two cases were launched to confirm the validation of the proposed model.The impact of time-varying physical features on reservoir production performance was studied in a real water flooding reservoir.The experimental results indicate that the overall relative permeability curve shifts to the right as water injection increases.This shift corresponds to a transition towards a more hydrophilic wettability and a decrease in residual oil saturation.The endpoint model demonstrates excellent accuracy and can be applied to time-varying simulations of reservoir physics.The impact of variations in permeability and relative permeability on the reservoir production performance yields two distinct outcomes.The time-varying permeability of the reservoir results in intensified water channeling and poor development effects.On the other hand,the time-varying relative permeability enhances the oil phase seepage capacity,facilitating oil displacement.The comprehensive time-varying behavior is the result of the combined influence of these two parameters,which closely resemble the actual conditions observed in oil field exploitation.The time-varying simulation technique of reservoir physical properties proposed in this paper can continuously and stably characterize the dynamic changes of reservoir physical properties during water drive development.This approach ensures the reliability of the simulation results regarding residual oil distribution.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
About two thousand years ago,Hippocrates observed that“walking is man's best medicine”[1],a notion increasingly validated in modern society.The benefits of physical activity in preventing chronic diseases and in...About two thousand years ago,Hippocrates observed that“walking is man's best medicine”[1],a notion increasingly validated in modern society.The benefits of physical activity in preventing chronic diseases and in improving longevity have been extensively studied[2].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
The evasion from controlled cell death induction has been considered as one of the hallmarks of cancer cells. Defects in cell death signaling are a fundamental phenomenon in colorectal cancer. Nearly any non-invasive ...The evasion from controlled cell death induction has been considered as one of the hallmarks of cancer cells. Defects in cell death signaling are a fundamental phenomenon in colorectal cancer. Nearly any non-invasive cancer treatment finally aims to induce cell death. However, apoptosis resistance is the major cause for insufficient therapeutic success and disease relapse in gastrointestinal oncology. Various compounds have been developed and evaluated with the aim to meet with this obstacle by triggering cell death in cancer cells. The aim of this review is to illustrate current approaches and future directions in targeting cell death signaling in colorectal cancer. The complex signaling network of apoptosis will be demonstrated and the “druggability” of targets will be identified. In detail, proteins regulating mitochondrial cell death in colorectal cancer, such as Bcl-2 and survivin, will be discussed with respect to potential therapeutic exploitation. Death receptor signaling and targeting in colorectal cancer will be outlined. Encouraging clinical trials including cell death based targeted therapies for colorectal cancer are under way and will be demonstrated. Our conceptual understanding of cell death in cancer is rapidly emerging and new types of controlled cellular death have been identified. To meet this progress in cell death research, the implication of autophagy and necroptosis for colorectal carcinogenesis and therapeutic approaches will also be depicted. The main focus of this topic highlight will be on the revelation of the complex cell death concepts in colorectal cancer and the bridging from basic research to clinical use.展开更多
Objective To examine the neuroprotective effects of a novel manganese porphyrin, manganese （Ill） meso-tetrakis （N,N＇-diethylimidazolium-2-yl） porphyrin （MnTDM）, in the mouse model of Parkinson＇s disease （PD）...Objective To examine the neuroprotective effects of a novel manganese porphyrin, manganese （Ill） meso-tetrakis （N,N＇-diethylimidazolium-2-yl） porphyrin （MnTDM）, in the mouse model of Parkinson＇s disease （PD） induced by paraquat （PQ）. Methods Male C57BL / 6 mice were subcutaneously injected with either saline or PQ at 2-day intervals for a total of 10 doses, MnTDM was subcutaneously injected with the PQ 2 h before treatment. Performance on the pole and swim test were measured 7 days after the last injection and animals were sacrificed one day later. Levels of dopamine （DA） and its metabolites in the striatum were measured by high-performance liquid chromatography with an electrochemical detector （HPLC-ECD）. Thiobarbituric acid （TBA） method was used to assay the lipid peroxidation product, malondialdehyde （MDA）, and the number of tyrosine hydroxylase （TH） positive neurons was estimated using immunohistochemistry. Results Pretreatment with MnTI）M significantly attenuated PQ-impaired behavioral performance, depleted dopamine content in striata, increased MDA, and dopaminergic neuron loss in the substantia nigra. Conclusions Oxidative stress plays an important role in PQ-induced neurotoxicity which can be potentially prevented by manganese porphyrin. These findings also propose a possible therapeutical strategy for neurodegenerative disorders associated with oxidative stress such as PD.展开更多
Diabetes mellitus(DM)is a chronic metabolic disease characterized by hyperglycemia.Type 2 diabetes(T2DM)accounting for 90%of cases globally.The worldwide prevalence of DM is rising dramatically over the last decades,f...Diabetes mellitus(DM)is a chronic metabolic disease characterized by hyperglycemia.Type 2 diabetes(T2DM)accounting for 90%of cases globally.The worldwide prevalence of DM is rising dramatically over the last decades,from 30 million cases in 1985 to 382 million cases in 2013.It’s estimated that 451 million people had diabetes in 2017.As the pathophysiology was understood over the years,treatment options for diabetes increased.Incretin-based therapy is one of them.Glucagon-like peptide-1 receptor agonist(GLP-1 RA)not only significantly lower glucose level with minimal risk of hypoglycemia but also,they have an important advantage in themanagement of cardiovascular risk and obesity.Thus,we will review here GLP-1 RAsrole in the treatment of diabetes.展开更多
In this work, metal-organic frameworks (MOFs) FJU-21 was synthesized by solvothermal method. The crystal structure of FJU-21 was characterized by XRD and BET and it was applied to the catalytic hydrolysis of bovine se...In this work, metal-organic frameworks (MOFs) FJU-21 was synthesized by solvothermal method. The crystal structure of FJU-21 was characterized by XRD and BET and it was applied to the catalytic hydrolysis of bovine serum albumin. The effects of reaction pH, temperature and reaction time on the catalytic activity of FJU-21 were studied. FJU-21 were found to possess an intrinsic enzyme mimicking activity similar to that found in trypsin. The Michaelis constant (Km) of the artificial protease (0.18 × 10-3 - 0.20 × 10-3 M-1) was about 15-fold lower than that free trypsin (2.7 × 10-3 M-1) and about 3-fold lower than that of soluble Cu(II) oxacyclen (0.54 × 10-3 M-1). The Kcat of FJU-21 is 102 times higher than that of soluble Cu(II) oxacyclen catalysts and, indicating a much higher affinity of BSA for FJU-21 surface. FJU-21 could be reused for eleven times without losing in its activity.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
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.
基金financially supported by the National Natural Science Foundation of China(No.22207066)Taishan Scholars Program of Shandong Province(No.TS201712065)+2 种基金the Academic Promotion Program of Shandong First Medical University(No.2019QL009)the Science and Technology Funding from Jinan(No.2020GXRC018)the Traditional Chinese Medicine Science and Technology Project of Shandong Province(No.Q-2022142)。
文摘Constructing high-performance nanozymes for specific biomolecules is crucial but challenging for practical applications and fundamental research.Herein,through the examination of the catalytic reaction paths of natural nicotinamide adenine dinucleotide(NADH)oxidase(NOX),a novel and efficient single-atom rhodium catalyst(Rh1/NC)was developed to mimic NOX.The Rh_(1)/NC demonstrated the ability to catalyze the dehydrogenation of NADH and transfer electrons to O_(2)to generate H_(2)O_(2)through the typical two-electron pathway.Furthermore,our findings revealed that Rh_(1)/NC exhibits the ability to catalyze the conversion of produced H_(2)O_(2)into OH under mildly acidic conditions.This process amplifies the oxidation of NADH,showcasing NADH peroxidase-like activity(NPx-like).As a paradigm,this unique dual enzyme-like property of Rh_(1)/NC with a positive feedback effect holds significance in disrupting cancer cellular homeostasis.Rh_(1)/NC can effectively consume NADH via cascade biocatalytic reactions within cancer cells,further triggering the elevation of reactive oxygen species(ROS),leading to impaired oxidative phosphorylation and decreased mitochondrial membrane potential,thus damaging the adenosine triphosphate(ATP)synthesis.The resulting'domino effect'interferes with the energy metabolism homeostasis of cancer cells,ultimately promoting cell apoptosis.This study provides potential guidance for the rational design of materials with greater capabilities.
文摘In the past decades, enzyme mimetics based on ceria nanoparticles （nanoceria） have been developed as potential substitutes for nature enzymes. The mixed valence states of cerium and the patterns of oxygen vacancies on crystal planes result in different enzyme mimetic activities. In this review we survey the bio-applications of nanoceria-based enzyme mimetics as well as the underlying mechanisms. Factors influencing the enzyme mimetic activities and future perspective of nanoceria-based enzyme mimetics are also addressed.
基金supported by the Innovation Zone Project(No.18-163-12-ZT-003-077-01)Health Major Project(Nos.BWS17J028 and AWS16J018)National Natural Science Foundation of China(Nos.81872835,21621003,and 21563010).
文摘Oxidative stress is associated with many acute and chronic inflammatory diseases.Development of nanomaterial-based enzyme mimetics for reactive oxygen species(ROS)scavenging is challenging,but holds great promise for the treatment of inflammatory diseases.Herein,we report the highly ordered manganese dioxide encapsulated selenium-melanin(Se@Me@MnO_(2))nanozyme with high efficiency for intracellular antioxidation and anti-inflammation.The Se@Me@MnO_(2)nanozyme is sequentially fabricated through the radical polymerization and the in-situ oxidation-reduction.In vitro experimental results demonstrated that the Se@Me@MnO_(2) nanozyme exhibits multiple enzyme activities to scavenge ROS,including catalase(CAT),glutathione peroxidase(GPx)and superoxide dismutase(SOD).Mechanism researches illustrated that the Se core possesses GPx-like catalytic activity,the Me and the MnO_(2) possess both the SOD-like and the CAT-like activities.What’s more,due to the stable unpaired electrons existing in the nanozyme,the Se,Me and MnO_(2) provide synergistic and fast electron transfer effect to achieve the quickly scavenging of hydrogen peroxide,hydroxyl radical,and superoxide anion.Further in vivo experimental results showed that this biocompatible nanozyme exhibits cytoprotective effects by resisting ROS-mediated damage,thereby alleviating the inflammation.This multienzyme mimetics is believed to be an excellent ROS scavenger and have a good potential in clinical therapy for ROS-related diseases.
基金supported by the National Natural Science Foundation of China (Grant No. 20773032)the National Basic Research Program of China (Grant No. 2011CB932802)
文摘Natural enzymes as biological catalysts possess remarkable advantages,especially their highly efficient and selective catalysis under mild conditions.However,most natural enzymes are proteins,thus exhibiting an inherent low durability to harsh reaction conditions.Artificial enzyme mimetics have been pursued extensively to avoid this drawback.Quite recently,some inorganic nanoparticles(NPs) have been found to exhibit unique enzyme mimetics.In addition,their much higher stability overcomes the inherent disadvantage of natural enzymes.Furthermore,easy mass-production and low cost endow them more benefits.As a new member of artificial enzyme mimetics,they have received intense attention.In this review article,major progress in this field is summarized and future perspectives are highlighted.
基金supported by the National Key Research and Development Program of China(2022YFC3202104)the Western LightKey Laboratory Cooperative Research Cross-Team Project of Chinese Academy of Sciences(xbzg-zdsys-202207)。
文摘Passerine mimics often imitate various vocalizations from other bird species and incorporate these sounds into their song repertoires.While a few anecdotes reported that wild songbirds imitated human-associated sounds,besides captive parrots and songbirds,systemic and quantitative studies on human-made sound mimicry in wild birds remain scarce.In this study,we investigated the mimetic accuracy and consistency of electric moped sounds imitated by an urban bird,the Chinese Blackbird(Turdus mandarinus).We found that:(1)Only one type of electric moped sound was imitated,i.e.,13 of 26 males mimicked the first part of the antitheft alarm,a phrase containing a series of identical notes.(2)The mimicry produced by male Chinese Blackbirds had fewer notes and lower consistency within phrases compared to the model alarms.(3)The mimicry of male Chinese Blackbirds was imperfect,i.e.,most of the acoustic parameters differed from the model alarms.Additionally,mimetic notes were lower in frequency than the models.Mimetic notes from two areas were also different in acoustic structures,suggesting Chinese Blackbirds might learn mimicry mainly from conspecific neighbors within each area respectively rather than electric mopeds,namely the secondary mimicry.Imperfect mimicry of human-made sounds could result from cost and physical constraints,associated with high consistency,frequency,and repetitions.Consequently,Chinese Blackbirds copied a simplified version of electric moped alarms.We recommend further attention to mimic species inhabiting urban ecosystems to better understand vocal mimicry's adaptation to ongoing urbanization.
基金the financial support from the Zhejiang Provincial Natural Science Foundation of China(No.LBY24H040012)Discipline Cluster of Oncology of Wenzhou Medical University(No.z1-2023007)+1 种基金the financial support from the National Natural Science Foundation of China(No.32401107)the financial support from the Discipline Cluster of Oncology of Wenzhou Medical University(No.z3-2023027)。
文摘Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-adhesion hydrogels combined with growth factors is a promising strategy to address endometrial injury.Insulin-like growth factor 1 is closely associated with endometrial growth and plays a crucial role in endometrial receptivity that is essential for fertility.However,its high cost,environmental sensitivity,and short biological half-life limit its practical applications.In this study,we developed a two-component peptide-based hydrogel consisting of a biotinylated peptide and an insulin-like growth factor 1(IGF-1)mimetic peptide,both of which were designed with self-assembly capabilities.The resultant hydrogel exhibited significant mechanical properties and retained its native IGF-1 bioactivity.In vivo experiments demonstrated that the hydrogel significantly facilitated proliferation and vascular restoration.Additionally,it effectively reduced fibrosis by decreasing collagen accumulation,restoring the expression of progesterone receptors,and enhancing endometrial receptivity,which are crucial for embryo implantation.These findings highlight the potential of the two-component peptide-based hydrogel as an innovative therapeutic approach for treating endometrial injury.
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 Research project of Shengli Oifield Exploration and Development Research Institute (Grant No.30200018-21-ZC0613-0125)。
文摘For the ultra-high water-cut reservoirs,after long-term water injection exploitation,the physical properties of the reservoir change and the heterogeneity of the reservoir becomes increasingly severe,which further aggravates the spatial difference of the flow field.In this study,the displacement experiments were employed to investigate the variations in core permeability,porosity,and relative permeability after a large amount of water injection.A relative permeability endpoint model was proposed by utilizing the alternating conditional expectation(ACE)transformation to describe the variation in relative permeability based on the experimental data.Based on the time dependent models for permeability and relative permeability,the traditional oil-water two-phase model was improved and discretized using the mimetic finite difference method(MFD).The two cases were launched to confirm the validation of the proposed model.The impact of time-varying physical features on reservoir production performance was studied in a real water flooding reservoir.The experimental results indicate that the overall relative permeability curve shifts to the right as water injection increases.This shift corresponds to a transition towards a more hydrophilic wettability and a decrease in residual oil saturation.The endpoint model demonstrates excellent accuracy and can be applied to time-varying simulations of reservoir physics.The impact of variations in permeability and relative permeability on the reservoir production performance yields two distinct outcomes.The time-varying permeability of the reservoir results in intensified water channeling and poor development effects.On the other hand,the time-varying relative permeability enhances the oil phase seepage capacity,facilitating oil displacement.The comprehensive time-varying behavior is the result of the combined influence of these two parameters,which closely resemble the actual conditions observed in oil field exploitation.The time-varying simulation technique of reservoir physical properties proposed in this paper can continuously and stably characterize the dynamic changes of reservoir physical properties during water drive development.This approach ensures the reliability of the simulation results regarding residual oil distribution.
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supported by grants from the National Natural Science Foundation of China(Nos.92057207,92357303,92254308,32271223,and 32021003)the National Key Research and Development Program of China(No.2024YFA1306102).
文摘About two thousand years ago,Hippocrates observed that“walking is man's best medicine”[1],a notion increasingly validated in modern society.The benefits of physical activity in preventing chronic diseases and in improving longevity have been extensively studied[2].
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BCK holds a Postdoctoral-Fellowship from the Medical Faculty of the University of Heidelberg,GermanyHSB receives grants from the German Research Foundation (DFG SCHU 1443/4-1)
文摘The evasion from controlled cell death induction has been considered as one of the hallmarks of cancer cells. Defects in cell death signaling are a fundamental phenomenon in colorectal cancer. Nearly any non-invasive cancer treatment finally aims to induce cell death. However, apoptosis resistance is the major cause for insufficient therapeutic success and disease relapse in gastrointestinal oncology. Various compounds have been developed and evaluated with the aim to meet with this obstacle by triggering cell death in cancer cells. The aim of this review is to illustrate current approaches and future directions in targeting cell death signaling in colorectal cancer. The complex signaling network of apoptosis will be demonstrated and the “druggability” of targets will be identified. In detail, proteins regulating mitochondrial cell death in colorectal cancer, such as Bcl-2 and survivin, will be discussed with respect to potential therapeutic exploitation. Death receptor signaling and targeting in colorectal cancer will be outlined. Encouraging clinical trials including cell death based targeted therapies for colorectal cancer are under way and will be demonstrated. Our conceptual understanding of cell death in cancer is rapidly emerging and new types of controlled cellular death have been identified. To meet this progress in cell death research, the implication of autophagy and necroptosis for colorectal carcinogenesis and therapeutic approaches will also be depicted. The main focus of this topic highlight will be on the revelation of the complex cell death concepts in colorectal cancer and the bridging from basic research to clinical use.
文摘Objective To examine the neuroprotective effects of a novel manganese porphyrin, manganese （Ill） meso-tetrakis （N,N＇-diethylimidazolium-2-yl） porphyrin （MnTDM）, in the mouse model of Parkinson＇s disease （PD） induced by paraquat （PQ）. Methods Male C57BL / 6 mice were subcutaneously injected with either saline or PQ at 2-day intervals for a total of 10 doses, MnTDM was subcutaneously injected with the PQ 2 h before treatment. Performance on the pole and swim test were measured 7 days after the last injection and animals were sacrificed one day later. Levels of dopamine （DA） and its metabolites in the striatum were measured by high-performance liquid chromatography with an electrochemical detector （HPLC-ECD）. Thiobarbituric acid （TBA） method was used to assay the lipid peroxidation product, malondialdehyde （MDA）, and the number of tyrosine hydroxylase （TH） positive neurons was estimated using immunohistochemistry. Results Pretreatment with MnTI）M significantly attenuated PQ-impaired behavioral performance, depleted dopamine content in striata, increased MDA, and dopaminergic neuron loss in the substantia nigra. Conclusions Oxidative stress plays an important role in PQ-induced neurotoxicity which can be potentially prevented by manganese porphyrin. These findings also propose a possible therapeutical strategy for neurodegenerative disorders associated with oxidative stress such as PD.
文摘Diabetes mellitus(DM)is a chronic metabolic disease characterized by hyperglycemia.Type 2 diabetes(T2DM)accounting for 90%of cases globally.The worldwide prevalence of DM is rising dramatically over the last decades,from 30 million cases in 1985 to 382 million cases in 2013.It’s estimated that 451 million people had diabetes in 2017.As the pathophysiology was understood over the years,treatment options for diabetes increased.Incretin-based therapy is one of them.Glucagon-like peptide-1 receptor agonist(GLP-1 RA)not only significantly lower glucose level with minimal risk of hypoglycemia but also,they have an important advantage in themanagement of cardiovascular risk and obesity.Thus,we will review here GLP-1 RAsrole in the treatment of diabetes.
文摘In this work, metal-organic frameworks (MOFs) FJU-21 was synthesized by solvothermal method. The crystal structure of FJU-21 was characterized by XRD and BET and it was applied to the catalytic hydrolysis of bovine serum albumin. The effects of reaction pH, temperature and reaction time on the catalytic activity of FJU-21 were studied. FJU-21 were found to possess an intrinsic enzyme mimicking activity similar to that found in trypsin. The Michaelis constant (Km) of the artificial protease (0.18 × 10-3 - 0.20 × 10-3 M-1) was about 15-fold lower than that free trypsin (2.7 × 10-3 M-1) and about 3-fold lower than that of soluble Cu(II) oxacyclen (0.54 × 10-3 M-1). The Kcat of FJU-21 is 102 times higher than that of soluble Cu(II) oxacyclen catalysts and, indicating a much higher affinity of BSA for FJU-21 surface. FJU-21 could be reused for eleven times without losing in its activity.
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.
