Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of m...Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of medicine,food,and agriculture.However,efficiently screening AMPs from natural sources poses several challenges,including low efficiency and high antibiotic resistance.This review focuses on the action mechanisms of AMPs,both through membrane and non-membrane routes.We thoroughly examine various highly efficient AMP screening methods,including whole-bacterial adsorption binding,cell membrane chromatography(CMC),phospholipid membrane chromatography binding,membranemediated capillary electrophoresis(CE),colorimetric assays,thin layer chromatography(TLC),fluorescence-based screening,genetic sequencing-based analysis,computational mining of AMP databases,and virtual screening methods.Additionally,we discuss potential developmental applications for enhancing the efficiency of AMP discovery.This review provides a comprehensive framework for identifying AMPs within complex natural product systems.展开更多
Background Broiler chickens are most vulnerable immediately after hatching due to their immature immune systems,making them susceptible to infectious diseases.The yolk plays an important role in early immune defence b...Background Broiler chickens are most vulnerable immediately after hatching due to their immature immune systems,making them susceptible to infectious diseases.The yolk plays an important role in early immune defence by showing relevant antioxidant and passive immunity capabilities during broiler embryonic development.The immunomodulatory effects of phytogenic compound carvacrol have been widely reported.After in ovo delivery in the amniotic fluid during embryonic development carvacrol is known to migrate to the yolk sac.However,it is unknown whether carvacrol in the yolk could enhance defence responsiveness in the yolk sac.Therefore,the aim of this study was to improve early immune function in chicken embryos,and it was hypothesized that in ovo delivery of carvacrol would result in immunomodulatory effects in the yolk sac,potentially improving post-hatch resilience.Methods On embryonic day(E)17.5,either a saline(control)or carvacrol solution was injected into the amniotic fluid.Yolk sac tissue samples were collected at E19.5,and transcriptomic analyses using RNA sequencing were performed,following functional enrichment analyses comparing the control(saline)and carvacrol-injected groups.Results The results showed that 268 genes were upregulated and 174 downregulated in the carvacrol group compared to the control(P<0.05;logFC<-0.5 or log FC>0.5).Functional analyses of these differentially expressed genes,using KEGG,REACTOME,and Gene Ontology databases,showed enrichment of several immune-related pathways.This included the pathways‘Antimicrobial peptides’(P=0.001)and‘Chemoattractant activity’(P=0.004),amongst others.Moreover,the‘NOD-like receptor signaling’pathway was enriched(P=0.002).Antimicrobial peptides are part of the innate immune defence and are amongst the molecules produced after the nucleotide oligomeriza-tion domain(NOD)-like receptor pathway activation.While these responses may be associated with an inflammatory reaction to an exogenous threat,they could also indicate that in ovo delivery of carvacrol could prepare the newly hatched chick against bacterial pathogens by potentially promoting antimicrobial peptide production through acti-vation of NOD-like receptor signaling in the yolk sac.Conclusion In conclusion,these findings suggest that in ovo delivery of carvacrol has the potential to enhance anti-pathogenic and pro-inflammatory responses in the yolk sac via upregulation of antimicrobial peptides,and NOD-like receptor pathways.展开更多
Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for...Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for targeted therapeutics for multidrug-resistant cancer is more important than ever.Peptides,as emerging alternatives to current anticancer drugs,offer exquisite versatility in facilitating the design of novel oncology drugs,with the core superiorities of good biocompatibility and a low tendency to induce drug resistance.This review comprehensively introduces the pharmacological mechanisms of peptide-based drugs and strategies for overcoming multidrug resistance(MDR)in cancers,including inducing cell membrane lysis,targeting organelles,activating anticancer immune responses,enhancing drug uptake,targeting ATP-binding cassette(ABC)transporters,and targeting B-cell lymphoma-2(BCL-2)family proteins.Additionally,the current clinical applications of representative peptides in combating MDR cancers and their potential directions for medicinal chemistry research have been thoroughly discussed.This review offers essential insights into the novel treatment approaches for MDR cancers and highlights the trends and perspectives in this field.展开更多
The rising prevalence of drug-resistant Gram-positive pathogens,particularly methicillin-resistant Staphy-lococcus aureus(MRSA)and vancomycin-resistant Enterococci(VRE),poses a substantial clinical challenge.Biofilm-a...The rising prevalence of drug-resistant Gram-positive pathogens,particularly methicillin-resistant Staphy-lococcus aureus(MRSA)and vancomycin-resistant Enterococci(VRE),poses a substantial clinical challenge.Biofilm-associated infections exacerbate this problem due to their inherent antibiotic resistance and complex structure.Current antibiotic treatments struggle to penetrate biofilms and eradicate persister cells,leading to prolonged antibiotic use and increased resistance.Host defense peptides(HDPs)have shown promise,but their clinical application is limited by factors such as enzymatic degradation and difficulty in largescale preparation.Synthetic HDP mimics,such as poly(2-oxazoline),have emerged as effective alter-natives.Herein,we found that the poly(2-oxazoline),Gly-POX_(20),demonstrated rapid and potent activity against clinically isolated multidrug-resistant Gram-positive strains.Gly-POX_(20) showed greater stability under physiological conditions compared to natural peptides,including resistance to protease degradation.Importantly,Gly-POX_(20) inhibited biofilm formation and eradicated mature biofilm and demonstrated superior in vivo therapeutic efficacy to vancomycin in a MRSA biofilm-associated mouse keratitis model,suggesting its potential as a novel antimicrobial agent against drug-resistant Gram-positive bacteria,especially biofilm-associated infections.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
Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ab...Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.展开更多
In order to study the effects of Saussurea laniceps polysaccharides(SLPs)on the expression of inflammatory factors and antimicrobial peptide LL-37 in UVB-induced keratinocytes,SLPs were extracted by the ethanol therma...In order to study the effects of Saussurea laniceps polysaccharides(SLPs)on the expression of inflammatory factors and antimicrobial peptide LL-37 in UVB-induced keratinocytes,SLPs were extracted by the ethanol thermal reflux method,and SLPs at different concentrations were used to examine the inhibitory effect of COX-2(a key mediator of inflammatory pathway).A cell model of UVB irradiation-induced inflammation was established to determine the influence of SLPs on prostaglandin E2(PGE-2),TNF-αand IL-1βinflammatory factors,as well as the relationships of SLPs with LL-37 expression.An enzyme-linked immunosorbent assay(ELISA)and western blot analysis were used to detect the production of inflammatory factors and LL-37 antimicrobial peptide.The results showed that the inhibition rate of COX-2 was 82.41%at 1000μg/mL,and the expression of PGE-2,TNF-αand IL-1βinflammatory factors in HaCaT cells was significantly downregulated at 100μg/mL(P<0.01).In addition,SLPs at 50μg/mL and 100μg/mL concentrations enhanced the expression of LL-37 antimicrobial peptide(P<0.01),thereby down-regulating the expression of TNF-αand IL-1βinflammatory factors,then reducing skin inflammation.Conclusion:SLP can significantly inhibit the inflammatory response induced by UVB,and can further slow down the damage caused by inflammation to the skin by regulating LL-37 antimicrobial peptides,which has the potential to prevent skin inflammatory damage caused by UVB irradiation.展开更多
This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use o...This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.展开更多
Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy,which is often plagued by poor selectivity,off-target effects,and drug resistance.Among the various targeting agents in devel...Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy,which is often plagued by poor selectivity,off-target effects,and drug resistance.Among the various targeting agents in development,peptides stand out for their unique advantages,including minimal immunogenicity,high tissue penetration,and ease of modification.Their small size,specificity,and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively.Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery,improving tumor imaging,and reducing adverse effects.With cancer responsible for millions of deaths worldwide,the development of peptide-based therapeutics offers new hope in addressing the limitations of current treatments.As detailed studies on different aspects of targeting peptides are crucial for optimizing drug development,this review provides a comprehensive overview of the literature on tumor-targeting peptides,including their structure,sources,modes of action,and their application in cancer therapy—both as standalone agents and in fusion drugs.Additionally,various computational tools for peptide-based tumor-targeting drug design and validation are explored.The promising results from these studies highlight peptides as ideal candidates for targeted cancer therapies,offering valuable insights for researchers and accelerating the discovery of novel anti-tumor peptide base drug candidates.展开更多
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidom...The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidomics and bioinformatics were used to screen flavor peptides from Inner Mongolian cheese and further assess their antioxidant and angiotensin I-converting enzyme(ACE)inhibitory properties.According to sensory data,YH8 and IL7 had detectable bitter tastes with low thresholds of 0.03 and 0.06 mmol/L,respectively.With an umami threshold range of 0.24‒0.81 mmol/L,VQ6,FK13,HP13 and QT14 exhibited a range of flavors dominated by umami,including sweet,bitter,salty,sour and kokumi.Antioxidant activity wise,YH8,VQ6,HP13 and QT14 were well represented.The above-mentioned peptides all had some ACE inhibitory effect.The bitter peptide IL7(IC_(50)=0.08 mmol/L)had the highest level of ACE inhibitory activity,followed by YH8(IC_(50)=0.33 mmol/L).These multi-functional peptides,which have been assessed for bioactive and taste features in Inner Mongolian cheese,may have positive impacts on health and harmonize the cheese’s overall flavor.These results suggest that some flavor peptides produced in fermented foods might be with bioactivities while providing a basis for the exploration and application of multi-functional peptides.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
The cosmetic sector is a multibillion-dollar industry that requires constant attention being paid to innovative product development and engagement.Notably,its market value is projected to exceed 750 billion U.S.dollar...The cosmetic sector is a multibillion-dollar industry that requires constant attention being paid to innovative product development and engagement.Notably,its market value is projected to exceed 750 billion U.S.dollars by 2025,and it is expanding as novel,climate-friendly,green,and sustainable components from natural sources are incorporated.This review is written based on the numerous reports on the potential applications of food-derived peptides while focusing on their possible uses in the formulation of cosmeceutical and skincare products.First,the production methods of bioactive peptides linked to cosmeceutical uses are described.Then,we discuss the obtainment and characterization of different anti-inflammatory,antimicrobial,antioxidant,anti-aging,and other pleiotropic peptides with their specific mechanisms,from various food sources.The review concludes with salient considerations of the cost of production and pilot scale operation,stability,compatibility,user safety,site-specificity,and delivery methods,when designing or developing biopeptide-based cosmeceutical products.展开更多
[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
Umami peptides play important roles in the flavor of fermented broad bean paste(FBBP),and proteases produced by microorganisms contributed to the production of umami peptides.In order to reveal the formation of umami ...Umami peptides play important roles in the flavor of fermented broad bean paste(FBBP),and proteases produced by microorganisms contributed to the production of umami peptides.In order to reveal the formation of umami peptides and their relationships with protease-producing microorganisms during the natural fermentation of FBBP,peptidomics and virtual screening were used to identify and screen umami peptides.Meanwhile,macrogenomics was used to analyze the abundance of microbial-derived protease genes during FBBP fermentation.Then,based on the Pearson correlation coefficient,the correlation network diagram of each protease-producing microorganism with umami peptides was constructed.The results showed that a total of two exopeptidases and four endopeptidases were annotated from FBBP.Staphylococcus,Lactobacillus,Aspergillus,and Weissella can produce most proteases.The species Lactobacillus curvatus,Dyella jiangningensis,Erythrobacter sp.,and unclassified_g_Pantoea had strong correlation with umami peptides,and they may contribute to the process of protein hydrolysis to produce umami peptides.This study is expected to reveal the formation mechanism of umami peptides in FBBP,and the results of this study provided a better understanding of the relationship between proteases,microbiota,and core umami peptides in FBBP,which could help to improve the umami taste of Pixian Douban paste during fermentation.展开更多
Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttra...Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.展开更多
Hypoxic-ischemic encephalopathy(HIE)is a prominent cause of neuronal damage and neonatal death,and effective treatment strategies remain limited.In a prior investigation,we purified a novel peptide(designated MIP-15)f...Hypoxic-ischemic encephalopathy(HIE)is a prominent cause of neuronal damage and neonatal death,and effective treatment strategies remain limited.In a prior investigation,we purified a novel peptide(designated MIP-15)from the rare mushroom Morchella importuna,demonstrating its notable free radical scavenging activity.Nevertheless,the potential neuroprotective role of MIP-15 in neonatal hypoxic-ischemic brain damage(HIBD)and its underlying mechanism remain elusive.The purpose of this study was to evaluate whether MIP-15 exerts neuroprotective effects by inhibiting the mitochondrial apoptotic pathway after HIBD.A HIBD model in 7-day-old(P7)rats was established by the Rice-Vannucci method to evaluate the effect of MIP-15 on the neurological damage severity and space cognitive ability of rats.Subsequently,an oxygen glucose deprivation/reoxygenation(OGD/R)model was established in rat primary hippocampal neurons to explore the mechanism of MIP-15 action.Both in vivo and in vitro data showed that MIP-15 markedly restored endogenous antioxidative activity,decreased brain water content,and ameliorated pathological abnormalities following HIBD.The spatial cognitive ability and motor function of HIBD rats were also repaired.Moreover,in primary hippocampal neurons after OGD/R,MIP-15 increased cell viability by inhibiting the mitochondrial-dependent apoptosis pathway,as manifested by stabilization of the mitochondrial membrane potential,prevention of the release of cytochrome c,upregulation of Bcl-2/Bax,and reduction in the triggering of caspase proteins.These data indicate that MIP-15 may have the potential to act as a neuroprotective agent.展开更多
Ganoderma lingzhi is a new species of the prize medicinal mushroom Ganoderma(Agaricomycetes).Using angiotensin I-converting enzyme(ACE)as a target,a tripeptide Ser-Tyr-Pro(SYP)was discovered with preponderant ACE inhi...Ganoderma lingzhi is a new species of the prize medicinal mushroom Ganoderma(Agaricomycetes).Using angiotensin I-converting enzyme(ACE)as a target,a tripeptide Ser-Tyr-Pro(SYP)was discovered with preponderant ACE inhibitory activity with an 50%inhibiting concentration(IC_(50))value of 62.50μg/mL attribute to the formed salt bridge and hydrogen bonds between SYP and ACE.SYP even maintained superior bioactivity after intestinal digestion,and exerted no cytotoxicity,but presented incomplete bioavailability in blood of spontaneous hypertensive rats(SHRs).Furthermore,it performed antihypertensive effect in vivo by inhibiting the influx of Ca^(2+)through activating endothelial NO synthase(e NOS)/NO/guanosine 3',5'-cyclic monophosphate(c GMP)pathway,accompanied by attenuating angiotensin II(Ang II)/NADPH oxidase(NOX)/reactive oxygen species(ROS)pathway.This work not only discoverers a novel pharmacological ingredient from medicinal mushroom G.lingzhi for hypertension therapy,but also provides an insight into molecular mechanism of the ACE inhibitory peptide(ACEIP)on lowering blood pressure.展开更多
Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety...Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.展开更多
Background Elevated N-terminal pro-brain natriuretic peptide(NT-pro-BNP)is a recognized predictor of poor prognosis in heart failure and infectious diseases.We aimed to investigate its predictive value for short-term ...Background Elevated N-terminal pro-brain natriuretic peptide(NT-pro-BNP)is a recognized predictor of poor prognosis in heart failure and infectious diseases.We aimed to investigate its predictive value for short-term mortality in patients with infective endocarditis(IE)complicated by sepsis.Methods A total of 416 consecutive patients diagnosed with IE and sepsis at Guangdong Provincial People's Hospital were enrolled.The patients were divided into three groups according to the tertiles of NT-pro-BNP level of the first blood collection within 24 hours after admission:<2000 pg/mL(n=138),2000-7167 pg/mL(n=140),and>7167 pg/mL(n=138).Univariate and multivariate regression analysis were used to explore the predictive value of NT-pro-BNP for short-term mortality,and the best cut-off value was determined by receiver operating characteristic(ROC)curve.Results In-hospital and 6-month death occurred in 65 and 94 patients,respectively.Higher in-hospital mortality was found in patients with higher serum NT-pro-BNP levels(9.4%vs.13.6%vs.23.9%,P=0.003).ROC curve analysis identified an optimal NT-pro-BNP cutoff level of 1357 pg/mL[area under curve(AUC):0.652,95%CI:0.588-0.717,P<0.001].Multivariate regression analysis showed that both log-transformed NT-pro-BNP(in-hospital mortality:OR:1.987,95%CI:1.045-3.778,P=0.036;6-month mortality:HR:1.714,95%CI:1.072-2.7400,P=0.025)and NT-pro-BNP>1357 pg/mL(in-hospital mortality:OR:8.059,95%CI:1.813-35.818,P=0.006;6-month mortality:HR:5.193,95%CI:1.806-14.938,P=0.002)were both independent risk factors for in-hospital and 6-month mortality.Conclusions Serum NT-pro-BNP could serve as an independent predictor of in-hospital and 6-month mortality in patients with IE complicated with sepsis.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82373835,82304437,and 82173781)Regional Joint Fund Project of Guangdong Basic and Applied Basic Research Fund,China(Grant Nos.:2023A1515110417 and 2023A1515140131)+2 种基金Regional Joint Fund-Key Project of Guangdong Basic and Applied Basic Research Fund,China(Grant No.:2020B1515120033)the Key Field Projects of General Universities in Guangdong Province,China(Grant Nos.:2020ZDZX2057 and 2022ZDZX2056)Medical Scientific Research Foundation of Guangdong Province of China(Grant No.:A2022061).
文摘Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of medicine,food,and agriculture.However,efficiently screening AMPs from natural sources poses several challenges,including low efficiency and high antibiotic resistance.This review focuses on the action mechanisms of AMPs,both through membrane and non-membrane routes.We thoroughly examine various highly efficient AMP screening methods,including whole-bacterial adsorption binding,cell membrane chromatography(CMC),phospholipid membrane chromatography binding,membranemediated capillary electrophoresis(CE),colorimetric assays,thin layer chromatography(TLC),fluorescence-based screening,genetic sequencing-based analysis,computational mining of AMP databases,and virtual screening methods.Additionally,we discuss potential developmental applications for enhancing the efficiency of AMP discovery.This review provides a comprehensive framework for identifying AMPs within complex natural product systems.
基金support by AgriFutures Australia’s Chicken Meat Program[grant number PRJ-011584]is gratefully acknowledged.
文摘Background Broiler chickens are most vulnerable immediately after hatching due to their immature immune systems,making them susceptible to infectious diseases.The yolk plays an important role in early immune defence by showing relevant antioxidant and passive immunity capabilities during broiler embryonic development.The immunomodulatory effects of phytogenic compound carvacrol have been widely reported.After in ovo delivery in the amniotic fluid during embryonic development carvacrol is known to migrate to the yolk sac.However,it is unknown whether carvacrol in the yolk could enhance defence responsiveness in the yolk sac.Therefore,the aim of this study was to improve early immune function in chicken embryos,and it was hypothesized that in ovo delivery of carvacrol would result in immunomodulatory effects in the yolk sac,potentially improving post-hatch resilience.Methods On embryonic day(E)17.5,either a saline(control)or carvacrol solution was injected into the amniotic fluid.Yolk sac tissue samples were collected at E19.5,and transcriptomic analyses using RNA sequencing were performed,following functional enrichment analyses comparing the control(saline)and carvacrol-injected groups.Results The results showed that 268 genes were upregulated and 174 downregulated in the carvacrol group compared to the control(P<0.05;logFC<-0.5 or log FC>0.5).Functional analyses of these differentially expressed genes,using KEGG,REACTOME,and Gene Ontology databases,showed enrichment of several immune-related pathways.This included the pathways‘Antimicrobial peptides’(P=0.001)and‘Chemoattractant activity’(P=0.004),amongst others.Moreover,the‘NOD-like receptor signaling’pathway was enriched(P=0.002).Antimicrobial peptides are part of the innate immune defence and are amongst the molecules produced after the nucleotide oligomeriza-tion domain(NOD)-like receptor pathway activation.While these responses may be associated with an inflammatory reaction to an exogenous threat,they could also indicate that in ovo delivery of carvacrol could prepare the newly hatched chick against bacterial pathogens by potentially promoting antimicrobial peptide production through acti-vation of NOD-like receptor signaling in the yolk sac.Conclusion In conclusion,these findings suggest that in ovo delivery of carvacrol has the potential to enhance anti-pathogenic and pro-inflammatory responses in the yolk sac via upregulation of antimicrobial peptides,and NOD-like receptor pathways.
基金supported by the Science and Technology Innovation Program of Hunan Province(No.2022RC1168)National Natural Science Foundation of China(Nos.82322073,82173846,82304533)+12 种基金CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2023-I2M-3-009)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)China Postdoctoral Science Foundation(No.2021M702215)Oriental Scholars of Shanghai Universities(No.TP2022081)Jiangxi Province Thousand Talents Program(No.jxsq2023102168)Young Talent Lifting Project of China Association of Chinese Medicine(No.CACM-(2021-QNRC2-A08))Shanghai Rising-Star Program(No.22QA1409100)Shanghai Sailing Program(No.22YF1445000)2021 Shanghai Science and Technology Innovation Action Plan(No.21S11902800)Three-year Action Plan for Shanghai TCM Development and Inheritance Program(Nos.ZY(2021-2023)-0208,ZY(2021-2023)-0401)High level Key Discipline of National Administration of Traditional Chinese Medicine(No.71)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202004)Innovation team of high-level local universities in Shanghai:Strategic Innovation Team of TCM Chemical Biology。
文摘Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for targeted therapeutics for multidrug-resistant cancer is more important than ever.Peptides,as emerging alternatives to current anticancer drugs,offer exquisite versatility in facilitating the design of novel oncology drugs,with the core superiorities of good biocompatibility and a low tendency to induce drug resistance.This review comprehensively introduces the pharmacological mechanisms of peptide-based drugs and strategies for overcoming multidrug resistance(MDR)in cancers,including inducing cell membrane lysis,targeting organelles,activating anticancer immune responses,enhancing drug uptake,targeting ATP-binding cassette(ABC)transporters,and targeting B-cell lymphoma-2(BCL-2)family proteins.Additionally,the current clinical applications of representative peptides in combating MDR cancers and their potential directions for medicinal chemistry research have been thoroughly discussed.This review offers essential insights into the novel treatment approaches for MDR cancers and highlights the trends and perspectives in this field.
基金financially supported by the National Key Research and Development Program of China(no.2022YFC2303100)National Natural Science Foundation of China(nos.T2325010,22305082,52203162,and 22075078)+1 种基金Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission),the Fundamental Research Funds for the Central Universities(nos.JKVD1241029 and JKD01241701)Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry(Changchun Institute of Applied Chemistry,Chinese Academy of Sciences),the Open Project of Engineering Research Center of Dairy Quality and Safety Control Technology(Ministry of Education,no.R202201).
文摘The rising prevalence of drug-resistant Gram-positive pathogens,particularly methicillin-resistant Staphy-lococcus aureus(MRSA)and vancomycin-resistant Enterococci(VRE),poses a substantial clinical challenge.Biofilm-associated infections exacerbate this problem due to their inherent antibiotic resistance and complex structure.Current antibiotic treatments struggle to penetrate biofilms and eradicate persister cells,leading to prolonged antibiotic use and increased resistance.Host defense peptides(HDPs)have shown promise,but their clinical application is limited by factors such as enzymatic degradation and difficulty in largescale preparation.Synthetic HDP mimics,such as poly(2-oxazoline),have emerged as effective alter-natives.Herein,we found that the poly(2-oxazoline),Gly-POX_(20),demonstrated rapid and potent activity against clinically isolated multidrug-resistant Gram-positive strains.Gly-POX_(20) showed greater stability under physiological conditions compared to natural peptides,including resistance to protease degradation.Importantly,Gly-POX_(20) inhibited biofilm formation and eradicated mature biofilm and demonstrated superior in vivo therapeutic efficacy to vancomycin in a MRSA biofilm-associated mouse keratitis model,suggesting its potential as a novel antimicrobial agent against drug-resistant Gram-positive bacteria,especially biofilm-associated infections.
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.
文摘Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.
文摘In order to study the effects of Saussurea laniceps polysaccharides(SLPs)on the expression of inflammatory factors and antimicrobial peptide LL-37 in UVB-induced keratinocytes,SLPs were extracted by the ethanol thermal reflux method,and SLPs at different concentrations were used to examine the inhibitory effect of COX-2(a key mediator of inflammatory pathway).A cell model of UVB irradiation-induced inflammation was established to determine the influence of SLPs on prostaglandin E2(PGE-2),TNF-αand IL-1βinflammatory factors,as well as the relationships of SLPs with LL-37 expression.An enzyme-linked immunosorbent assay(ELISA)and western blot analysis were used to detect the production of inflammatory factors and LL-37 antimicrobial peptide.The results showed that the inhibition rate of COX-2 was 82.41%at 1000μg/mL,and the expression of PGE-2,TNF-αand IL-1βinflammatory factors in HaCaT cells was significantly downregulated at 100μg/mL(P<0.01).In addition,SLPs at 50μg/mL and 100μg/mL concentrations enhanced the expression of LL-37 antimicrobial peptide(P<0.01),thereby down-regulating the expression of TNF-αand IL-1βinflammatory factors,then reducing skin inflammation.Conclusion:SLP can significantly inhibit the inflammatory response induced by UVB,and can further slow down the damage caused by inflammation to the skin by regulating LL-37 antimicrobial peptides,which has the potential to prevent skin inflammatory damage caused by UVB irradiation.
文摘This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.
文摘Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy,which is often plagued by poor selectivity,off-target effects,and drug resistance.Among the various targeting agents in development,peptides stand out for their unique advantages,including minimal immunogenicity,high tissue penetration,and ease of modification.Their small size,specificity,and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively.Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery,improving tumor imaging,and reducing adverse effects.With cancer responsible for millions of deaths worldwide,the development of peptide-based therapeutics offers new hope in addressing the limitations of current treatments.As detailed studies on different aspects of targeting peptides are crucial for optimizing drug development,this review provides a comprehensive overview of the literature on tumor-targeting peptides,including their structure,sources,modes of action,and their application in cancer therapy—both as standalone agents and in fusion drugs.Additionally,various computational tools for peptide-based tumor-targeting drug design and validation are explored.The promising results from these studies highlight peptides as ideal candidates for targeted cancer therapies,offering valuable insights for researchers and accelerating the discovery of novel anti-tumor peptide base drug candidates.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
基金supported by the central government and guides local funds for science and technology development(2022ZY0109).
文摘The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidomics and bioinformatics were used to screen flavor peptides from Inner Mongolian cheese and further assess their antioxidant and angiotensin I-converting enzyme(ACE)inhibitory properties.According to sensory data,YH8 and IL7 had detectable bitter tastes with low thresholds of 0.03 and 0.06 mmol/L,respectively.With an umami threshold range of 0.24‒0.81 mmol/L,VQ6,FK13,HP13 and QT14 exhibited a range of flavors dominated by umami,including sweet,bitter,salty,sour and kokumi.Antioxidant activity wise,YH8,VQ6,HP13 and QT14 were well represented.The above-mentioned peptides all had some ACE inhibitory effect.The bitter peptide IL7(IC_(50)=0.08 mmol/L)had the highest level of ACE inhibitory activity,followed by YH8(IC_(50)=0.33 mmol/L).These multi-functional peptides,which have been assessed for bioactive and taste features in Inner Mongolian cheese,may have positive impacts on health and harmonize the cheese’s overall flavor.These results suggest that some flavor peptides produced in fermented foods might be with bioactivities while providing a basis for the exploration and application of multi-functional peptides.
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.
文摘The cosmetic sector is a multibillion-dollar industry that requires constant attention being paid to innovative product development and engagement.Notably,its market value is projected to exceed 750 billion U.S.dollars by 2025,and it is expanding as novel,climate-friendly,green,and sustainable components from natural sources are incorporated.This review is written based on the numerous reports on the potential applications of food-derived peptides while focusing on their possible uses in the formulation of cosmeceutical and skincare products.First,the production methods of bioactive peptides linked to cosmeceutical uses are described.Then,we discuss the obtainment and characterization of different anti-inflammatory,antimicrobial,antioxidant,anti-aging,and other pleiotropic peptides with their specific mechanisms,from various food sources.The review concludes with salient considerations of the cost of production and pilot scale operation,stability,compatibility,user safety,site-specificity,and delivery methods,when designing or developing biopeptide-based cosmeceutical products.
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 Science and Technology Department of Sichuan Province,China(2020YFN0151,23ZDYF3100)Chongqing Science and Technology Commission(cstc2021jscx-cylhX0014).
文摘Umami peptides play important roles in the flavor of fermented broad bean paste(FBBP),and proteases produced by microorganisms contributed to the production of umami peptides.In order to reveal the formation of umami peptides and their relationships with protease-producing microorganisms during the natural fermentation of FBBP,peptidomics and virtual screening were used to identify and screen umami peptides.Meanwhile,macrogenomics was used to analyze the abundance of microbial-derived protease genes during FBBP fermentation.Then,based on the Pearson correlation coefficient,the correlation network diagram of each protease-producing microorganism with umami peptides was constructed.The results showed that a total of two exopeptidases and four endopeptidases were annotated from FBBP.Staphylococcus,Lactobacillus,Aspergillus,and Weissella can produce most proteases.The species Lactobacillus curvatus,Dyella jiangningensis,Erythrobacter sp.,and unclassified_g_Pantoea had strong correlation with umami peptides,and they may contribute to the process of protein hydrolysis to produce umami peptides.This study is expected to reveal the formation mechanism of umami peptides in FBBP,and the results of this study provided a better understanding of the relationship between proteases,microbiota,and core umami peptides in FBBP,which could help to improve the umami taste of Pixian Douban paste during fermentation.
基金the National Natural Science Foundation of China(Nos.82373722,22077144)Hunan Provincial Natural Science Foundation of China(No.2023JJ30527)+2 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023B1515040006)Guangdong Provincial Key Laboratory of Construction Foundation(No.2023B1212060022)Key Research and Development Program of Guangdong Province(No.2020B1111110003).
文摘Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.
基金supported by Natural Science Foundation of Sichuan Province(2022NSFSC0112)the International Communication and Collaboration Project of Sichuan Academy of Agricultural Sciences(2022ZSSFGH09)the Independent Innovation Project of Sichuan Academy of Agricultural Sciences(2022ZZCX028)。
文摘Hypoxic-ischemic encephalopathy(HIE)is a prominent cause of neuronal damage and neonatal death,and effective treatment strategies remain limited.In a prior investigation,we purified a novel peptide(designated MIP-15)from the rare mushroom Morchella importuna,demonstrating its notable free radical scavenging activity.Nevertheless,the potential neuroprotective role of MIP-15 in neonatal hypoxic-ischemic brain damage(HIBD)and its underlying mechanism remain elusive.The purpose of this study was to evaluate whether MIP-15 exerts neuroprotective effects by inhibiting the mitochondrial apoptotic pathway after HIBD.A HIBD model in 7-day-old(P7)rats was established by the Rice-Vannucci method to evaluate the effect of MIP-15 on the neurological damage severity and space cognitive ability of rats.Subsequently,an oxygen glucose deprivation/reoxygenation(OGD/R)model was established in rat primary hippocampal neurons to explore the mechanism of MIP-15 action.Both in vivo and in vitro data showed that MIP-15 markedly restored endogenous antioxidative activity,decreased brain water content,and ameliorated pathological abnormalities following HIBD.The spatial cognitive ability and motor function of HIBD rats were also repaired.Moreover,in primary hippocampal neurons after OGD/R,MIP-15 increased cell viability by inhibiting the mitochondrial-dependent apoptosis pathway,as manifested by stabilization of the mitochondrial membrane potential,prevention of the release of cytochrome c,upregulation of Bcl-2/Bax,and reduction in the triggering of caspase proteins.These data indicate that MIP-15 may have the potential to act as a neuroprotective agent.
基金supported by the National Natural Science Foundation of China(32071673 and 32202573)the Program of Hunan Science and Technology Innovation Team(2021RC4063)+1 种基金the Natural Science Foundation of Hunan Province(2021JJ31151 and 2022JJ50028)the Key Scientific Research Project of Hunan Education Department(22A0538)。
文摘Ganoderma lingzhi is a new species of the prize medicinal mushroom Ganoderma(Agaricomycetes).Using angiotensin I-converting enzyme(ACE)as a target,a tripeptide Ser-Tyr-Pro(SYP)was discovered with preponderant ACE inhibitory activity with an 50%inhibiting concentration(IC_(50))value of 62.50μg/mL attribute to the formed salt bridge and hydrogen bonds between SYP and ACE.SYP even maintained superior bioactivity after intestinal digestion,and exerted no cytotoxicity,but presented incomplete bioavailability in blood of spontaneous hypertensive rats(SHRs).Furthermore,it performed antihypertensive effect in vivo by inhibiting the influx of Ca^(2+)through activating endothelial NO synthase(e NOS)/NO/guanosine 3',5'-cyclic monophosphate(c GMP)pathway,accompanied by attenuating angiotensin II(Ang II)/NADPH oxidase(NOX)/reactive oxygen species(ROS)pathway.This work not only discoverers a novel pharmacological ingredient from medicinal mushroom G.lingzhi for hypertension therapy,but also provides an insight into molecular mechanism of the ACE inhibitory peptide(ACEIP)on lowering blood pressure.
基金supported by the National Natural Science Foundation of China (Nos. 82173674 and 82204195)。
文摘Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.
文摘Background Elevated N-terminal pro-brain natriuretic peptide(NT-pro-BNP)is a recognized predictor of poor prognosis in heart failure and infectious diseases.We aimed to investigate its predictive value for short-term mortality in patients with infective endocarditis(IE)complicated by sepsis.Methods A total of 416 consecutive patients diagnosed with IE and sepsis at Guangdong Provincial People's Hospital were enrolled.The patients were divided into three groups according to the tertiles of NT-pro-BNP level of the first blood collection within 24 hours after admission:<2000 pg/mL(n=138),2000-7167 pg/mL(n=140),and>7167 pg/mL(n=138).Univariate and multivariate regression analysis were used to explore the predictive value of NT-pro-BNP for short-term mortality,and the best cut-off value was determined by receiver operating characteristic(ROC)curve.Results In-hospital and 6-month death occurred in 65 and 94 patients,respectively.Higher in-hospital mortality was found in patients with higher serum NT-pro-BNP levels(9.4%vs.13.6%vs.23.9%,P=0.003).ROC curve analysis identified an optimal NT-pro-BNP cutoff level of 1357 pg/mL[area under curve(AUC):0.652,95%CI:0.588-0.717,P<0.001].Multivariate regression analysis showed that both log-transformed NT-pro-BNP(in-hospital mortality:OR:1.987,95%CI:1.045-3.778,P=0.036;6-month mortality:HR:1.714,95%CI:1.072-2.7400,P=0.025)and NT-pro-BNP>1357 pg/mL(in-hospital mortality:OR:8.059,95%CI:1.813-35.818,P=0.006;6-month mortality:HR:5.193,95%CI:1.806-14.938,P=0.002)were both independent risk factors for in-hospital and 6-month mortality.Conclusions Serum NT-pro-BNP could serve as an independent predictor of in-hospital and 6-month mortality in patients with IE complicated with sepsis.
