[Objectives]This study adopted a three-factor three-level orthogonal design to explore the effects of different application periods and methods of fish protein peptide on the fruit quality of‘Tieshanzha’.[Methods]Fa...[Objectives]This study adopted a three-factor three-level orthogonal design to explore the effects of different application periods and methods of fish protein peptide on the fruit quality of‘Tieshanzha’.[Methods]Factor A was set as the application period,with three levels:fruit-setting stage,core-hardening stage,and pre-coloring stage.Factor B was set as the application method,with three levels:root application,foliar spray,and root application+foliar spray.Factor C was set as the application concentration,with three levels:0,5 and 10 ml/L.[Results]Application period had an extremely significant effect on single fruit weight.Fertilization at the fruit-setting stage showed a single fruit weight as high as 13.36 g,which was 27.9%and 24%higher than those achieved by fertilization at the core-hardening stage and the pre-coloring stage,respectively.The factor that had the greatest impact on the internal quality of hawthorn fruit,specifically the Vc content,was application method.The optimal combination was foliar spray at the core-hardening stage with a concentration of 10 ml/L,which achieved the best fertilization effect.[Conclusions]This study provides a theoretical basis for improving fruit quality of‘Tieshanzha’.展开更多
Bioactive peptides and proteins(BAPPs)are promising therapeutic agents for tissue repair with considerable advantages,including multifunctionality,specificity,biocompatibility,and biodegradability.However,the high com...Bioactive peptides and proteins(BAPPs)are promising therapeutic agents for tissue repair with considerable advantages,including multifunctionality,specificity,biocompatibility,and biodegradability.However,the high complexity of tissue microenvironments and their inherent deficiencies such as short half-live and susceptibility to enzymatic degradation,adversely affect their therapeutic efficacy and clinical applications.Investigating the fundamental mechanisms by which BAPPs modulate the microenvironment and developing rational delivery strategies are essential for optimizing their administration in distinct tissue repairs and facilitating clinical translation.This review initially focuses on the mechanisms through which BAPPs influence the microenvironment for tissue repair via reactive oxygen species,blood and lymphatic vessels,immune cells,and repair cells.Then,a variety of delivery platforms,including scaffolds and hydrogels,electrospun fibers,surface coatings,assisted particles,nanotubes,two-dimensional nanomaterials,and nanoparticles engineered cells,are summarized to incorporate BAPPs for effective tissue repair,modification strategies aimed at enhancing loading efficiencies and release kinetics are also reviewed.Additionally,the delivery of BAPPs can be precisely regulated by endogenous stimuli(glucose,reactive oxygen species,enzymes,pH)or exogenous stimuli(ultrasound,heat,light,magnetic field,and electric field)to achieve on-demand release tailored for specific tissue repair needs.Furthermore,this review focuses on the clinical potential of BAPPs in facilitating tissue repair across various types,including bone,cartilage,intervertebral discs,muscle,tendons,periodontal tissues,skin,myocardium,nervous system(encompassing brain,spinal cord,and peripheral nerve),endometrium,as well as ear and ocular tissue.Finally,current challenges and prospects are discussed.展开更多
Peptide-and protein-based therapeutics offer realized and potential benefits to health,due to their potent bioactivity,high specificity,and favorable safety characteristics.However,their widespread clinical applicatio...Peptide-and protein-based therapeutics offer realized and potential benefits to health,due to their potent bioactivity,high specificity,and favorable safety characteristics.However,their widespread clinical application is constrained by inherent limitations,including rapid enzymatic degradation,poor membrane permeability,and a reliance on parenteral administration,which reduces patient adherence.To overcome these challenges,extensive research has explored non-invasive delivery strategies,including topical,transdermal,and oral formulations.Despite promising advances in these delivery strategies,they are yet to overcome substantial biological and physicochemical barriers in peptide and protein therapeutics,such as enzymatic degradation in the gastrointestinal tract,limited epithelial transport,and inherently low systemic bioavailability.This review provides a comprehensive and up-to-date analysis of the structural and physiological barriers influencing peptide and protein bioavailability and therapeutic efficacy.It critically examines key challenges associated with various administration routes,including topical,transdermal,oral(including delivery targeting the brain),and others.Furthermore,it explores innovative strategies to enhance peptide and protein stability and bioavailability,including chemical modifications,enzyme inhibitors,penetration enhancers,physical delivery technologies,and advanced nanoparticulate formulations.Additionally,emerging trends in formulation optimization,regulatory considerations,and translational pathways for clinical implementation are discussed.By addressing these critical challenges and highlighting recent advances,this review serves as a roadmap for the development of next-generation peptide and protein therapeutics with improved stability and efficacy,and enhanced patient adherence,which is needed to fully realize the true potential of this class of therapeutics.展开更多
OBJECTIVE: To study the efficacy and explore the mechanism of the anti-tumor immunity elicited by heat shock protein 70-peptide complexes (HSP70-PC) derived from tumor cells. METHODS: Cells culture, flow cytometric an...OBJECTIVE: To study the efficacy and explore the mechanism of the anti-tumor immunity elicited by heat shock protein 70-peptide complexes (HSP70-PC) derived from tumor cells. METHODS: Cells culture, flow cytometric analysis, affinity chromatography for protein purification, SDS-PAGE, Western-blotting and animal experiment were used. RESULTS: HSP70-PC immunization rendered protective effect to both naive tumorl-bearing mice. All of the naive mice obtained complete resistance to Hcaf cell attack; 40% of the tumor-bearing mice survived for over 90 days, whereas the mice of control group died within 2 weeks (P展开更多
Recent years have witnessed growing interest in the role of peptides in animal nutrition. Chemical, enzymatic, or microbial hydrolysis of proteins in animal by-products or plant-source feedstuffs before feeding is an ...Recent years have witnessed growing interest in the role of peptides in animal nutrition. Chemical, enzymatic, or microbial hydrolysis of proteins in animal by-products or plant-source feedstuffs before feeding is an attractive means of generating high-quality small or large peptides that have both nutritional and physiological or regulatory functions in livestock, poultry and fish. These peptides may also be formed from ingested proteins in the gastrointestinal tract, but the types of resultant peptides can vary greatly with the physiological conditions of the animals and the composition of the diets. In the small intestine, large peptides are hydrolyzed to small peptides,which are absorbed into enterocytes faster than free amino acids（AAs） to provide a more balanced pattern of AAs in the blood circulation. Some peptides of plant or animal sources also have antimicrobial, antioxidant,antihypertensive, and immunomodulatory activities. Those peptides which confer biological functions beyond their nutritional value are called bioactive peptides. They are usually 2–20 AA residues in length but may consist of 〉20AA residues. Inclusion of some（e.g. 2–8%） animal-protein hydrolysates（e.g., porcine intestine, porcine mucosa,salmon viscera, or poultry tissue hydrolysates） or soybean protein hydrolysates in practical corn-and soybean mealbased diets can ensure desirable rates of growth performance and feed efficiency in weanling pigs, young calves,post-hatching poultry, and fish. Thus, protein hydrolysates hold promise in optimizing the nutrition of domestic and companion animals, as well as their health（particularly gut health） and well-being.展开更多
Peptide and protein drugs with therapeutic effects suffer from their short half-life and low stability,albeit their high efficiency and specificity.To overcome these demerits,long-acting drug delivery systems have bee...Peptide and protein drugs with therapeutic effects suffer from their short half-life and low stability,albeit their high efficiency and specificity.To overcome these demerits,long-acting drug delivery systems have been developed,wherein poly(lactic-co-glycolic acid)(PLGA)implants are most preferred owing to their excellent biodegradability and biocompatibility.Dozens of PLGA based products have been approved since1986,when the first product,named Decapeptyl R,successfully marched into market.To meet the increasing demand for delivering various peptides and proteins,different kinds of technologies have been developed for lab-scale fabrication or industrial manufacture.This review aims to introduce recent advances of PLGA implants,and give a brief summary of fundamental properties of PLGA,fabrication technologies of peptides/proteins-loaded PLGA implants as well as factors influencing the drug release processes.Moreover,challenges and future perspectives are also highlighted.展开更多
Despite intensive research,most neurodegenerative diseases cannot be cured and for some of them no treatment is available to increase survival or quality of life.Among the latter are prion diseases,fatal and transmiss...Despite intensive research,most neurodegenerative diseases cannot be cured and for some of them no treatment is available to increase survival or quality of life.Among the latter are prion diseases,fatal and transmissible neurodegenerative diseases of humans and other animals.展开更多
Late-stage modification of peptides and proteins meets the increasing demand in biochemical and pharmaceutical communities. These modification strategies could provide functionalized nonproteinogenic analogues with en...Late-stage modification of peptides and proteins meets the increasing demand in biochemical and pharmaceutical communities. These modification strategies could provide functionalized nonproteinogenic analogues with enhanced biological activities or improved therapeutic capabilities compared to their natural counterparts. Recent years, transition-metal-promoted functionalization of ubiquitous C-H bonds has been emerged as a powerful and tunable tool in this area, both for backbone diversifications and labeling of specific moieties. These reactions were flexible and expedient in both academic and industrial laboratories, especially considering their atom and step-economy, good functional group compatibility, accurate site selectivity. This review surveys the progress achieved in the late-stage modification of peptides and proteins utilizing transition-metal-catalyzed C-H functionalization with C-C and C-X(F, Cl, O, N, B, etc.) bonds formation.展开更多
Objective The aim of this study was to enhance the treatment effect of tumor purified autogenous heat shock protein 70-peptide complexes(HSP70-PCs)on HER-3-overexpressing breast cancer.Methods In this study,we first s...Objective The aim of this study was to enhance the treatment effect of tumor purified autogenous heat shock protein 70-peptide complexes(HSP70-PCs)on HER-3-overexpressing breast cancer.Methods In this study,we first studied the expression of HER-3 in breast cancer tissues and its relationship with patient characteristics.We then purified HSP70-PCs from primary breast cancer cells with different HER-2 and HER-3 expression profiles and determined the cytotoxicity of autogenous dendritic cells(DCs)and CD8+T cells induced by these complexes.Third,recombinant human HSP70-HER-3 protein complexes were used to inhibit the autogenous HSP70-PCs purified from HER-3-overexpressing breast cancer cells,and the resulting immunological response was examined.Results The results show that HSP70-PCs can be combined with recombinant HSP70-HER-3 protein complexes to induce stronger immunological responses than autogenous HSP70-PCs alone and that these treatments induce autogenous CD8+T cell killing of HER-3-positive breast cancer cells.Conclusion These findings provide a new direction for HSP70-DC-based immunotherapy for patients with HER-3-overexpressing breast cancer.展开更多
A modified two-stage soft-docking procedure was developed for the theoretic researches on the recognition of protein-protein or protein-peptide complexes. Some systems have been used to test our program and the result...A modified two-stage soft-docking procedure was developed for the theoretic researches on the recognition of protein-protein or protein-peptide complexes. Some systems have been used to test our program and the results are encouraging.展开更多
Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen so...Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.展开更多
Antimicrobial proteins and peptides had been found from a wide variety of organisms in the last few years These molecules have attracted much research interest because of their biochemical diversity, broad specificity...Antimicrobial proteins and peptides had been found from a wide variety of organisms in the last few years These molecules have attracted much research interest because of their biochemical diversity, broad specificity on anti-viral, anti-bacterial, anti-fungi, anti-protozoan parasites, anti-tumoural, and wound-healing effects. Antimicrobial proteins and peptides play key roles in innate immunity. They interact directly with bacteria and kill them. The brown-spotted grouper, Epinephelusfario, is an important marine fish cultured in southem China. Recently, bacteria and virus have caused high mortality in E. fario cultures, but its endogenous antimicrobial peptides and proteins have not been explored. An antimicrobial component was found from the skin homogenate of E. fario. After the skin homogenate was digested with trypsin, its antimicrobial activity was lost, which showed that the antimicrobial component is a protein. The antimicrobial protein （Efap） was purified from the skin homogenate of E. fario by successive ion-exchange and gel filtration chromatography. Efap was demonstrated to be single protein band by SDS-PAGE, with the apparent molecular weight of 41 kD. Efap exhibited antimicrobial activity both for the Gram-positive bacteria, Staphylococcus aureus, Micrococcus luteus and Bacillus subtilis, and for the Gram-negative bacteria, Vibrio alginolyticus, Vibrio parahaemolyticus, Vibrio fluvialis, Pasteurella multocida, Aeromonas hydrophila, Eschrrichiu coli, and Pseudomonas aeruginosa. Except A. hydrophila, P. aeruginosa, and E. coli （MIC〉20 mol/L）, most of the tested Gram-negative bacteria were sensitive to Efap （MIC〈20 mol/L）. Interestingly, Efap showed potent antimicrobial activity against Gram-positive bacteria S. aureus （MIC 5-10 mol/L） but comparatively weak antimicrobial activity against M. luteus and B. subtilis. The broad antimicrobial activities of Efap suggest that it contributes to the innate host defence of E. fario.展开更多
[Objectives]To investigate the effects of three foliar fertilizers on photosynthetic characteristics,fruit quality and yield of hawthorn.[Methods]Taking hawthorn foliar fertilization as the reference,the photosyntheti...[Objectives]To investigate the effects of three foliar fertilizers on photosynthetic characteristics,fruit quality and yield of hawthorn.[Methods]Taking hawthorn foliar fertilization as the reference,the photosynthetic rate,transpiration rate,intercellular CO 2 concentration,stomatal conductance and single fruit weight of hawthorn leaves were measured under different concentrations of foliar fertilizer.[Results]The results showed that the photosynthetic rate,transpiration rate and stomatal conductance of hawthorn leaves increased significantly,while the intercellular CO 2 concentration decreased.Specifically,the fish protein peptide foliar fertilizer performed best,with net photosynthetic rate and transpiration rate increased by 57.22%and 57.51%,respectively.All the three foliar fertilizers significantly reduced the intercellular CO 2 concentration.In addition,fertilization significantly increased the single fruit weight of hawthorn,and the effect of fermented fulvic acid foliar fertilizer was the most significant,with the highest growth rate of 68.49%.[Conclusions]Spraying foliar fertilizer significantly increased the content of Vc,titratable acid,anthocyanin and soluble solids of hawthorn fruit,among which fermented fulvic acid foliar fertilizer had the optimal effect.展开更多
Proteins have been widely used in the biomedical field because of their well-defined architecture,accurate molecular weight,excellent biocompatibility and biodegradability,and easy-to-functionalization.Inspired by the...Proteins have been widely used in the biomedical field because of their well-defined architecture,accurate molecular weight,excellent biocompatibility and biodegradability,and easy-to-functionalization.Inspired by the wisdom of nature,increasing proteins/peptides that possess self-assembling capabilities have been explored and designed to generate nanoassemblies with unique structure and function,including spatially organized conformation,passive and active targeting,stimuli-responsiveness,and high stability.These characteristics make protein/peptide-based nanoassembly an ideal platform for drug delivery and vaccine development.In this review,we focus on recent advances in subsistent protein/peptide-based nanoassemblies,including protein nanocages,virus-like particles,self-assemblable natural proteins,and self-assemblable artificial peptides.The origin and characteristics of various protein/peptide-based assemblies and their applications in drug delivery and vaccine development are summarized.In the end,the prospects and challenges are discussed for the further development of protein/peptide-based nanoassemblies.展开更多
Our dynamic laser light scattering(LLS) study shows that the current widely used protocols of dissolving amyloidogenic protein/peptide do not really result in a true solution;namely,there always exist a trace amount o...Our dynamic laser light scattering(LLS) study shows that the current widely used protocols of dissolving amyloidogenic protein/peptide do not really result in a true solution;namely,there always exist a trace amount of interchain aggregates,which greatly affect the association kinetics,partially explaining why different kinetics were reported even for a solution with identical protein and solvent.Recently,using a combination of the conventional dissolution procedure and our newly developed ultra-filtration method,we have developed a novel protocol to prepare a true solution of amyloidogenic protein/peptide without any interchain aggregates.The resultant solutions remain in their monomeric state for at least one week,which is vitally important for further study of the very initial stage of the interchain association under the physiological conditions because more and more evidence suggests that it is those small oligomers rather than large fabric aggregates that are cytotoxic.In addition,this study shows that combining static and dynamic LLS can lead to more physical and microscopic information about the protein association instead of only the size distribution.展开更多
Background We showed in our previous study that the N-terminal 17-mer peptide of amyloid precursor protein （APP17-mer peptide）,an active peptide segment with trophic and antioxidative effects,protects skin fibroblas...Background We showed in our previous study that the N-terminal 17-mer peptide of amyloid precursor protein （APP17-mer peptide）,an active peptide segment with trophic and antioxidative effects,protects skin fibroblasts against ultraviolet （UV） damage and downregulates matrix metalloproteinase 1 （MMP-1） expression.The aim of the current study was to explore the protective effects of P165,the N-terminal 5-mer peptide analog of amyloid precursor protein that is resistant to enzymolysis,on UVA-induced damage in human dermal fibroblasts （HDFs）.Methods HDFs were cultured in Dulbecco＆#39;s modified Eagle＆#39;s medium without and with P165 （concentrations were 1,10,and 100 μJmol/L）.Then,15 J/cm2 UVA irradiation was used to obtain the UV-irradiated model.Cell proliferation was analyzed using MTT kit.The collagen type Ⅰ and MMP-1 contents in cell lysate were determined by enzyme-linked immunosorbent assay （ELISA）.Fluorometric assays were performed to detect the formation of intracellular reactive oxygen species （ROS） in the cells.Results P165 significantly protected the HDFs against UVA-induced cytotoxicity.Compared with the UVA-irradiated control,1,10,and 100 μmol/L P165 elevated cell proliferation by 14.98% （P〈0.05）,17.52% （P〈0.01） and 28.34% （P〈0.001）,respectively.Simultaneously,10 and 100 μmol/L P165 increased collagen type Ⅰ content （both P〈0.05）.Moreover,P165 treatment （all concentrations） also markedly suppressed the UVA-induced MMP-1 expression （all P〈0.001）.P165 at 1,10,and 100 μmol/L also reduced UVA-induced ROS generation by 11.27%,13.69% （both P〈0.05）,and 25.48% （P〈0.001）,respectively.Conclusions P165 could protect the HDFs against UVA-induced photodamage,including cytotoxicity,and MMP-1 generation.Furthermore,it also increased the collagen type Ⅰ content in the cells.The inhibitory effect on intracellular ROS generation might be involved in these photoprotective effects.Thus,P165 may be a useful candidate in the prevention and treatment of skin photoaging.展开更多
[Objective] The aim was to study if the fermentation broth of Kombucha has protein with antimicrobial activity. [Method] The effects of different cultivation time on cell concentration, pH, total protein concentration...[Objective] The aim was to study if the fermentation broth of Kombucha has protein with antimicrobial activity. [Method] The effects of different cultivation time on cell concentration, pH, total protein concentration and inhibition zone were studied. The fermentation broth of Kombucha on the sixth day was adjusted to different pH. Fermentation broth treated with protease was put into the plates of Escherichia co/i, Bacillus cereue and Staphylococcus aureus as control, as well as ampenicilin. The zone of broth inhibition was measured. [ Result] The concentration of general protein was of positive relevance to the antimicrobial activity of Kombucha fermentation broth. The zone of inhibition decreased with rising pH and was the lowest when pH was 7. Later, as pH increasing, it enlarged. The inhibition effect of processed protease reduced remarkably. [ Conclusion] The fermentation broth of Kombucha revealed antimicrobial proteins.展开更多
Background：To develop a vaccine-based immunotherapy for sarcoma,we evaluated a mixture of heat shock proteins （mHSPs） as a vaccine for sarcoma treatment in a mouse model.Heat shock protein/peptides （HSP/Ps） are a...Background：To develop a vaccine-based immunotherapy for sarcoma,we evaluated a mixture of heat shock proteins （mHSPs） as a vaccine for sarcoma treatment in a mouse model.Heat shock protein/peptides （HSP/Ps） are autoimmune factors that can induce both adaptive and innate immune responses;HSP/Ps isolated from tumors can induce antitumor immune activity when used as vaccines.Methods：In this study,we evaluated the effects of mHSP/Ps on prophylactic antitumor immunity.We extracted mHSP/Ps,including HSP60,HSP70,GP96,and HSP l 10,from the mouse sarcoma cell lines S 180 and MCA207 using chromatography.The immunity induced by mHSP/Ps was assessed using flow cytometry,ELISPOT,lactate dehydrogenase release,and enzyme-linked immunosorbent assay.Results：Of S180 sarcoma-beating mice immunized with mHSP/Ps isolated from S180 cells,41.2% showed tumor regression and long-term survival,with a tumor growth inhibition rate of 82.3% at 30 days.Of MCA207 sarcoma-bearing mice immunized with mHSP/Ps isolated from MCA207 cells,50% showed tumor regression and long-term survival with a tumor growth inhibition rate of 79.3%.All control mice died within 40 days.The proportions of natural killer cells,CD8＋,and interferon-γ-secreting cells and tumor-specific cytotoxic T-lymphocyte activity were increased in the immunized group.Conclusions：Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors.This mHSP/P vaccine exerted greater antitumor effects than did HSPT0,HSP60,or tumor lysates alone.展开更多
The intra and extracellular pathways of hepatic injury by coronavirus disease 2019(COVID-19)are still being studied.Understanding them is important to treat this viral disease and other liver and biliary tract disorde...The intra and extracellular pathways of hepatic injury by coronavirus disease 2019(COVID-19)are still being studied.Understanding them is important to treat this viral disease and other liver and biliary tract disorders.Thus,this paper aims to present three hypotheses about liver injury caused by COVID-19:(1)The interactions between severe acute respiratory syndrome coronavirus 2 spike protein and membrane receptors in the hepatocyte;(2)The dysbiosis and"gutliver axis"disruption in patients with serious clinical presentations of COVID-19;and(3)The inflammatory response exacerbated through the production of interleukins such as interleukin-6.However,despite these new perspectives,the pathophysiological process of liver injury caused by COVID-19 is still complex and multifactorial.Thus,understanding all these variables is a challenge to science but also the key to propose individualized and effective patient therapies.展开更多
A prerequisite for life is the ability to uphold electro-chemical imbalance across biomembranes. Ion trans- porting enzymes, known as specific pumps, are re-sponsible for the transport of various ions across cell memb...A prerequisite for life is the ability to uphold electro-chemical imbalance across biomembranes. Ion trans- porting enzymes, known as specific pumps, are re-sponsible for the transport of various ions across cell membranes to sustain the same. In all eukaryotes, the plasma membrane potential and secondary transport systems are maintained by the activity of P-type ion transporting enzymes, commonly known as ATPase membrane pumps. Malfunction of pumps leads to various cell disorders and subsequently diseases like cardiac problems, renal malfunctionings, diabetes, cataract, even cancer. Activities/functions of these pumps are regulated either by exogenous agents or by endogenous substances like proteins, peptides, hormones, etc., which are collectively known as mo- dulators. Some of these endogenous modulators may be useful for developing drugs depending on the na-ture of regulation. For more than last two decades, researchers across the globe are exploring the me- chanism of action of different endogenous modulators on these ion transporting enzymes with the aim of developing target-specific drugs. In this review, we have discussed recent advances in our understanding of ATPase pumps, e.g., Ca2+-, Na+, K+-, Ca2+, Mg2+-, H+, K+-ATPases, with the emphasis on their functional regulation by a number of endogenous modulators, and the implications of development of some of these modulators as potential drugs.展开更多
基金Supported by Key Research and Development Program of Hebei Province(23317102D).
文摘[Objectives]This study adopted a three-factor three-level orthogonal design to explore the effects of different application periods and methods of fish protein peptide on the fruit quality of‘Tieshanzha’.[Methods]Factor A was set as the application period,with three levels:fruit-setting stage,core-hardening stage,and pre-coloring stage.Factor B was set as the application method,with three levels:root application,foliar spray,and root application+foliar spray.Factor C was set as the application concentration,with three levels:0,5 and 10 ml/L.[Results]Application period had an extremely significant effect on single fruit weight.Fertilization at the fruit-setting stage showed a single fruit weight as high as 13.36 g,which was 27.9%and 24%higher than those achieved by fertilization at the core-hardening stage and the pre-coloring stage,respectively.The factor that had the greatest impact on the internal quality of hawthorn fruit,specifically the Vc content,was application method.The optimal combination was foliar spray at the core-hardening stage with a concentration of 10 ml/L,which achieved the best fertilization effect.[Conclusions]This study provides a theoretical basis for improving fruit quality of‘Tieshanzha’.
基金supported by the National Natural Science Foundation of China(82372405,81871752)the Key Research and Development Program of Hubei Province(2022BCA052)+2 种基金the Key Research and Development Program of Wuhan City(2024020702030105)the Fundamental Research Funds for the Central Universities(2042023kf0199)the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(ZNJC202014).
文摘Bioactive peptides and proteins(BAPPs)are promising therapeutic agents for tissue repair with considerable advantages,including multifunctionality,specificity,biocompatibility,and biodegradability.However,the high complexity of tissue microenvironments and their inherent deficiencies such as short half-live and susceptibility to enzymatic degradation,adversely affect their therapeutic efficacy and clinical applications.Investigating the fundamental mechanisms by which BAPPs modulate the microenvironment and developing rational delivery strategies are essential for optimizing their administration in distinct tissue repairs and facilitating clinical translation.This review initially focuses on the mechanisms through which BAPPs influence the microenvironment for tissue repair via reactive oxygen species,blood and lymphatic vessels,immune cells,and repair cells.Then,a variety of delivery platforms,including scaffolds and hydrogels,electrospun fibers,surface coatings,assisted particles,nanotubes,two-dimensional nanomaterials,and nanoparticles engineered cells,are summarized to incorporate BAPPs for effective tissue repair,modification strategies aimed at enhancing loading efficiencies and release kinetics are also reviewed.Additionally,the delivery of BAPPs can be precisely regulated by endogenous stimuli(glucose,reactive oxygen species,enzymes,pH)or exogenous stimuli(ultrasound,heat,light,magnetic field,and electric field)to achieve on-demand release tailored for specific tissue repair needs.Furthermore,this review focuses on the clinical potential of BAPPs in facilitating tissue repair across various types,including bone,cartilage,intervertebral discs,muscle,tendons,periodontal tissues,skin,myocardium,nervous system(encompassing brain,spinal cord,and peripheral nerve),endometrium,as well as ear and ocular tissue.Finally,current challenges and prospects are discussed.
文摘Peptide-and protein-based therapeutics offer realized and potential benefits to health,due to their potent bioactivity,high specificity,and favorable safety characteristics.However,their widespread clinical application is constrained by inherent limitations,including rapid enzymatic degradation,poor membrane permeability,and a reliance on parenteral administration,which reduces patient adherence.To overcome these challenges,extensive research has explored non-invasive delivery strategies,including topical,transdermal,and oral formulations.Despite promising advances in these delivery strategies,they are yet to overcome substantial biological and physicochemical barriers in peptide and protein therapeutics,such as enzymatic degradation in the gastrointestinal tract,limited epithelial transport,and inherently low systemic bioavailability.This review provides a comprehensive and up-to-date analysis of the structural and physiological barriers influencing peptide and protein bioavailability and therapeutic efficacy.It critically examines key challenges associated with various administration routes,including topical,transdermal,oral(including delivery targeting the brain),and others.Furthermore,it explores innovative strategies to enhance peptide and protein stability and bioavailability,including chemical modifications,enzyme inhibitors,penetration enhancers,physical delivery technologies,and advanced nanoparticulate formulations.Additionally,emerging trends in formulation optimization,regulatory considerations,and translational pathways for clinical implementation are discussed.By addressing these critical challenges and highlighting recent advances,this review serves as a roadmap for the development of next-generation peptide and protein therapeutics with improved stability and efficacy,and enhanced patient adherence,which is needed to fully realize the true potential of this class of therapeutics.
文摘OBJECTIVE: To study the efficacy and explore the mechanism of the anti-tumor immunity elicited by heat shock protein 70-peptide complexes (HSP70-PC) derived from tumor cells. METHODS: Cells culture, flow cytometric analysis, affinity chromatography for protein purification, SDS-PAGE, Western-blotting and animal experiment were used. RESULTS: HSP70-PC immunization rendered protective effect to both naive tumorl-bearing mice. All of the naive mice obtained complete resistance to Hcaf cell attack; 40% of the tumor-bearing mice survived for over 90 days, whereas the mice of control group died within 2 weeks (P
基金supported by the National Natural Science Foundation of China(31572416,31372319,31330075 and 31110103909)Hubei Provincial Key Project for Scientific and Technical Innovation(2014ABA022)+2 种基金Hubei Hundred Talent program,Natural Science Foundation of Hubei Province(2013CFA097)Agriculture and Food Research Initiative Competitive Grants(2014-67015-21770 and 2015-67015-23276)from the USDA National Institute of Food and AgricultureTexas A&M Agri Life Research(H-8200)
文摘Recent years have witnessed growing interest in the role of peptides in animal nutrition. Chemical, enzymatic, or microbial hydrolysis of proteins in animal by-products or plant-source feedstuffs before feeding is an attractive means of generating high-quality small or large peptides that have both nutritional and physiological or regulatory functions in livestock, poultry and fish. These peptides may also be formed from ingested proteins in the gastrointestinal tract, but the types of resultant peptides can vary greatly with the physiological conditions of the animals and the composition of the diets. In the small intestine, large peptides are hydrolyzed to small peptides,which are absorbed into enterocytes faster than free amino acids（AAs） to provide a more balanced pattern of AAs in the blood circulation. Some peptides of plant or animal sources also have antimicrobial, antioxidant,antihypertensive, and immunomodulatory activities. Those peptides which confer biological functions beyond their nutritional value are called bioactive peptides. They are usually 2–20 AA residues in length but may consist of 〉20AA residues. Inclusion of some（e.g. 2–8%） animal-protein hydrolysates（e.g., porcine intestine, porcine mucosa,salmon viscera, or poultry tissue hydrolysates） or soybean protein hydrolysates in practical corn-and soybean mealbased diets can ensure desirable rates of growth performance and feed efficiency in weanling pigs, young calves,post-hatching poultry, and fish. Thus, protein hydrolysates hold promise in optimizing the nutrition of domestic and companion animals, as well as their health（particularly gut health） and well-being.
基金the financial support from National Natural Science Foundation of China(Nos.82104082,81973247 and 82030107)Shanghai Municipal Commission of Science and Technology(Nos.19XD1400300 and 21430760800).
文摘Peptide and protein drugs with therapeutic effects suffer from their short half-life and low stability,albeit their high efficiency and specificity.To overcome these demerits,long-acting drug delivery systems have been developed,wherein poly(lactic-co-glycolic acid)(PLGA)implants are most preferred owing to their excellent biodegradability and biocompatibility.Dozens of PLGA based products have been approved since1986,when the first product,named Decapeptyl R,successfully marched into market.To meet the increasing demand for delivering various peptides and proteins,different kinds of technologies have been developed for lab-scale fabrication or industrial manufacture.This review aims to introduce recent advances of PLGA implants,and give a brief summary of fundamental properties of PLGA,fabrication technologies of peptides/proteins-loaded PLGA implants as well as factors influencing the drug release processes.Moreover,challenges and future perspectives are also highlighted.
基金funded by grants from the Alberta Prion Research Institutethe Alzheimer Society of Alberta and Northwest Territories+2 种基金the Natural Sciences and Engineering Research Council(NSERC)of Canadasupported by the Canada Research Chair programa postdoctoral fellowship from the German Research Foundation(DFG)
文摘Despite intensive research,most neurodegenerative diseases cannot be cured and for some of them no treatment is available to increase survival or quality of life.Among the latter are prion diseases,fatal and transmissible neurodegenerative diseases of humans and other animals.
基金the support from the National Key R&D Program of China(No. 2017YFA0505400)the National Natural Science Foundation of China (Nos. 21572214, 21702200)
文摘Late-stage modification of peptides and proteins meets the increasing demand in biochemical and pharmaceutical communities. These modification strategies could provide functionalized nonproteinogenic analogues with enhanced biological activities or improved therapeutic capabilities compared to their natural counterparts. Recent years, transition-metal-promoted functionalization of ubiquitous C-H bonds has been emerged as a powerful and tunable tool in this area, both for backbone diversifications and labeling of specific moieties. These reactions were flexible and expedient in both academic and industrial laboratories, especially considering their atom and step-economy, good functional group compatibility, accurate site selectivity. This review surveys the progress achieved in the late-stage modification of peptides and proteins utilizing transition-metal-catalyzed C-H functionalization with C-C and C-X(F, Cl, O, N, B, etc.) bonds formation.
基金Supported by a grant from the National Natural Science Foundation of China(No.81260392).
文摘Objective The aim of this study was to enhance the treatment effect of tumor purified autogenous heat shock protein 70-peptide complexes(HSP70-PCs)on HER-3-overexpressing breast cancer.Methods In this study,we first studied the expression of HER-3 in breast cancer tissues and its relationship with patient characteristics.We then purified HSP70-PCs from primary breast cancer cells with different HER-2 and HER-3 expression profiles and determined the cytotoxicity of autogenous dendritic cells(DCs)and CD8+T cells induced by these complexes.Third,recombinant human HSP70-HER-3 protein complexes were used to inhibit the autogenous HSP70-PCs purified from HER-3-overexpressing breast cancer cells,and the resulting immunological response was examined.Results The results show that HSP70-PCs can be combined with recombinant HSP70-HER-3 protein complexes to induce stronger immunological responses than autogenous HSP70-PCs alone and that these treatments induce autogenous CD8+T cell killing of HER-3-positive breast cancer cells.Conclusion These findings provide a new direction for HSP70-DC-based immunotherapy for patients with HER-3-overexpressing breast cancer.
文摘A modified two-stage soft-docking procedure was developed for the theoretic researches on the recognition of protein-protein or protein-peptide complexes. Some systems have been used to test our program and the results are encouraging.
基金supported by National Key Research and Development Program of China(Grant No.2021YFE0115200)the Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(Grant No.U22A20356).
文摘Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.
基金Key Research Program for International Cooperation(2005DFA30610)Program for New Century Excellent Talents in University(NCET-05-0755)+2 种基金National Natural Science Foundation(30700128)Natural Science Foundation of Hainan Province(80623)Research Foundation of Education Department of Hainan Province(Hj200731)
文摘Antimicrobial proteins and peptides had been found from a wide variety of organisms in the last few years These molecules have attracted much research interest because of their biochemical diversity, broad specificity on anti-viral, anti-bacterial, anti-fungi, anti-protozoan parasites, anti-tumoural, and wound-healing effects. Antimicrobial proteins and peptides play key roles in innate immunity. They interact directly with bacteria and kill them. The brown-spotted grouper, Epinephelusfario, is an important marine fish cultured in southem China. Recently, bacteria and virus have caused high mortality in E. fario cultures, but its endogenous antimicrobial peptides and proteins have not been explored. An antimicrobial component was found from the skin homogenate of E. fario. After the skin homogenate was digested with trypsin, its antimicrobial activity was lost, which showed that the antimicrobial component is a protein. The antimicrobial protein （Efap） was purified from the skin homogenate of E. fario by successive ion-exchange and gel filtration chromatography. Efap was demonstrated to be single protein band by SDS-PAGE, with the apparent molecular weight of 41 kD. Efap exhibited antimicrobial activity both for the Gram-positive bacteria, Staphylococcus aureus, Micrococcus luteus and Bacillus subtilis, and for the Gram-negative bacteria, Vibrio alginolyticus, Vibrio parahaemolyticus, Vibrio fluvialis, Pasteurella multocida, Aeromonas hydrophila, Eschrrichiu coli, and Pseudomonas aeruginosa. Except A. hydrophila, P. aeruginosa, and E. coli （MIC〉20 mol/L）, most of the tested Gram-negative bacteria were sensitive to Efap （MIC〈20 mol/L）. Interestingly, Efap showed potent antimicrobial activity against Gram-positive bacteria S. aureus （MIC 5-10 mol/L） but comparatively weak antimicrobial activity against M. luteus and B. subtilis. The broad antimicrobial activities of Efap suggest that it contributes to the innate host defence of E. fario.
基金Supported by Project of Hebei Provincial Department of Science and Technology"Key Technology Research and Industrialization Development Project of Hawthorn Industry in Xinglong County"(23317102D)Project of Hebei(Chengde)Hawthorn Industry Technology Research Institute.
文摘[Objectives]To investigate the effects of three foliar fertilizers on photosynthetic characteristics,fruit quality and yield of hawthorn.[Methods]Taking hawthorn foliar fertilization as the reference,the photosynthetic rate,transpiration rate,intercellular CO 2 concentration,stomatal conductance and single fruit weight of hawthorn leaves were measured under different concentrations of foliar fertilizer.[Results]The results showed that the photosynthetic rate,transpiration rate and stomatal conductance of hawthorn leaves increased significantly,while the intercellular CO 2 concentration decreased.Specifically,the fish protein peptide foliar fertilizer performed best,with net photosynthetic rate and transpiration rate increased by 57.22%and 57.51%,respectively.All the three foliar fertilizers significantly reduced the intercellular CO 2 concentration.In addition,fertilization significantly increased the single fruit weight of hawthorn,and the effect of fermented fulvic acid foliar fertilizer was the most significant,with the highest growth rate of 68.49%.[Conclusions]Spraying foliar fertilizer significantly increased the content of Vc,titratable acid,anthocyanin and soluble solids of hawthorn fruit,among which fermented fulvic acid foliar fertilizer had the optimal effect.
基金the National Key Research and Development Program of China(No.2019YFA0905200)the National Natural Science Foundation of China(No.82072045)the Natural Science Foundation of Jiangsu Province of China for Excellent Young Scholars(No.BK20190084).
文摘Proteins have been widely used in the biomedical field because of their well-defined architecture,accurate molecular weight,excellent biocompatibility and biodegradability,and easy-to-functionalization.Inspired by the wisdom of nature,increasing proteins/peptides that possess self-assembling capabilities have been explored and designed to generate nanoassemblies with unique structure and function,including spatially organized conformation,passive and active targeting,stimuli-responsiveness,and high stability.These characteristics make protein/peptide-based nanoassembly an ideal platform for drug delivery and vaccine development.In this review,we focus on recent advances in subsistent protein/peptide-based nanoassemblies,including protein nanocages,virus-like particles,self-assemblable natural proteins,and self-assemblable artificial peptides.The origin and characteristics of various protein/peptide-based assemblies and their applications in drug delivery and vaccine development are summarized.In the end,the prospects and challenges are discussed for the further development of protein/peptide-based nanoassemblies.
基金support of the National Natural Science Foundation of China Project(20934005)the Hong Kong Special Administration Region Earmarked Project(CUHK4046/08P,2160365+1 种基金CUHK4039/08P,2160361 CUHK4042/09P,2160396)
文摘Our dynamic laser light scattering(LLS) study shows that the current widely used protocols of dissolving amyloidogenic protein/peptide do not really result in a true solution;namely,there always exist a trace amount of interchain aggregates,which greatly affect the association kinetics,partially explaining why different kinetics were reported even for a solution with identical protein and solvent.Recently,using a combination of the conventional dissolution procedure and our newly developed ultra-filtration method,we have developed a novel protocol to prepare a true solution of amyloidogenic protein/peptide without any interchain aggregates.The resultant solutions remain in their monomeric state for at least one week,which is vitally important for further study of the very initial stage of the interchain association under the physiological conditions because more and more evidence suggests that it is those small oligomers rather than large fabric aggregates that are cytotoxic.In addition,this study shows that combining static and dynamic LLS can lead to more physical and microscopic information about the protein association instead of only the size distribution.
基金This work was supported in part by a grant from the National Natural Science Foundation of China
文摘Background We showed in our previous study that the N-terminal 17-mer peptide of amyloid precursor protein （APP17-mer peptide）,an active peptide segment with trophic and antioxidative effects,protects skin fibroblasts against ultraviolet （UV） damage and downregulates matrix metalloproteinase 1 （MMP-1） expression.The aim of the current study was to explore the protective effects of P165,the N-terminal 5-mer peptide analog of amyloid precursor protein that is resistant to enzymolysis,on UVA-induced damage in human dermal fibroblasts （HDFs）.Methods HDFs were cultured in Dulbecco＆#39;s modified Eagle＆#39;s medium without and with P165 （concentrations were 1,10,and 100 μJmol/L）.Then,15 J/cm2 UVA irradiation was used to obtain the UV-irradiated model.Cell proliferation was analyzed using MTT kit.The collagen type Ⅰ and MMP-1 contents in cell lysate were determined by enzyme-linked immunosorbent assay （ELISA）.Fluorometric assays were performed to detect the formation of intracellular reactive oxygen species （ROS） in the cells.Results P165 significantly protected the HDFs against UVA-induced cytotoxicity.Compared with the UVA-irradiated control,1,10,and 100 μmol/L P165 elevated cell proliferation by 14.98% （P〈0.05）,17.52% （P〈0.01） and 28.34% （P〈0.001）,respectively.Simultaneously,10 and 100 μmol/L P165 increased collagen type Ⅰ content （both P〈0.05）.Moreover,P165 treatment （all concentrations） also markedly suppressed the UVA-induced MMP-1 expression （all P〈0.001）.P165 at 1,10,and 100 μmol/L also reduced UVA-induced ROS generation by 11.27%,13.69% （both P〈0.05）,and 25.48% （P〈0.001）,respectively.Conclusions P165 could protect the HDFs against UVA-induced photodamage,including cytotoxicity,and MMP-1 generation.Furthermore,it also increased the collagen type Ⅰ content in the cells.The inhibitory effect on intracellular ROS generation might be involved in these photoprotective effects.Thus,P165 may be a useful candidate in the prevention and treatment of skin photoaging.
基金Supported by Scientific Research Fund of Beijing Educational DepartmentBeijing Higher School Personnel Teaching Program
文摘[Objective] The aim was to study if the fermentation broth of Kombucha has protein with antimicrobial activity. [Method] The effects of different cultivation time on cell concentration, pH, total protein concentration and inhibition zone were studied. The fermentation broth of Kombucha on the sixth day was adjusted to different pH. Fermentation broth treated with protease was put into the plates of Escherichia co/i, Bacillus cereue and Staphylococcus aureus as control, as well as ampenicilin. The zone of broth inhibition was measured. [ Result] The concentration of general protein was of positive relevance to the antimicrobial activity of Kombucha fermentation broth. The zone of inhibition decreased with rising pH and was the lowest when pH was 7. Later, as pH increasing, it enlarged. The inhibition effect of processed protease reduced remarkably. [ Conclusion] The fermentation broth of Kombucha revealed antimicrobial proteins.
文摘Background：To develop a vaccine-based immunotherapy for sarcoma,we evaluated a mixture of heat shock proteins （mHSPs） as a vaccine for sarcoma treatment in a mouse model.Heat shock protein/peptides （HSP/Ps） are autoimmune factors that can induce both adaptive and innate immune responses;HSP/Ps isolated from tumors can induce antitumor immune activity when used as vaccines.Methods：In this study,we evaluated the effects of mHSP/Ps on prophylactic antitumor immunity.We extracted mHSP/Ps,including HSP60,HSP70,GP96,and HSP l 10,from the mouse sarcoma cell lines S 180 and MCA207 using chromatography.The immunity induced by mHSP/Ps was assessed using flow cytometry,ELISPOT,lactate dehydrogenase release,and enzyme-linked immunosorbent assay.Results：Of S180 sarcoma-beating mice immunized with mHSP/Ps isolated from S180 cells,41.2% showed tumor regression and long-term survival,with a tumor growth inhibition rate of 82.3% at 30 days.Of MCA207 sarcoma-bearing mice immunized with mHSP/Ps isolated from MCA207 cells,50% showed tumor regression and long-term survival with a tumor growth inhibition rate of 79.3%.All control mice died within 40 days.The proportions of natural killer cells,CD8＋,and interferon-γ-secreting cells and tumor-specific cytotoxic T-lymphocyte activity were increased in the immunized group.Conclusions：Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors.This mHSP/P vaccine exerted greater antitumor effects than did HSPT0,HSP60,or tumor lysates alone.
文摘The intra and extracellular pathways of hepatic injury by coronavirus disease 2019(COVID-19)are still being studied.Understanding them is important to treat this viral disease and other liver and biliary tract disorders.Thus,this paper aims to present three hypotheses about liver injury caused by COVID-19:(1)The interactions between severe acute respiratory syndrome coronavirus 2 spike protein and membrane receptors in the hepatocyte;(2)The dysbiosis and"gutliver axis"disruption in patients with serious clinical presentations of COVID-19;and(3)The inflammatory response exacerbated through the production of interleukins such as interleukin-6.However,despite these new perspectives,the pathophysiological process of liver injury caused by COVID-19 is still complex and multifactorial.Thus,understanding all these variables is a challenge to science but also the key to propose individualized and effective patient therapies.
文摘A prerequisite for life is the ability to uphold electro-chemical imbalance across biomembranes. Ion trans- porting enzymes, known as specific pumps, are re-sponsible for the transport of various ions across cell membranes to sustain the same. In all eukaryotes, the plasma membrane potential and secondary transport systems are maintained by the activity of P-type ion transporting enzymes, commonly known as ATPase membrane pumps. Malfunction of pumps leads to various cell disorders and subsequently diseases like cardiac problems, renal malfunctionings, diabetes, cataract, even cancer. Activities/functions of these pumps are regulated either by exogenous agents or by endogenous substances like proteins, peptides, hormones, etc., which are collectively known as mo- dulators. Some of these endogenous modulators may be useful for developing drugs depending on the na-ture of regulation. For more than last two decades, researchers across the globe are exploring the me- chanism of action of different endogenous modulators on these ion transporting enzymes with the aim of developing target-specific drugs. In this review, we have discussed recent advances in our understanding of ATPase pumps, e.g., Ca2+-, Na+, K+-, Ca2+, Mg2+-, H+, K+-ATPases, with the emphasis on their functional regulation by a number of endogenous modulators, and the implications of development of some of these modulators as potential drugs.
