Three-month-old Alzheimer's disease model transgenic mice were immunized with Aβ1-42, Plp-Adenovirus [Ad]-X-CMV-(Aβ3-10)lo-CpG [AdCpG-(Aβ3-10)1] or AdCpG virus fluid via na- sal mucosal inhalation, respectivel...Three-month-old Alzheimer's disease model transgenic mice were immunized with Aβ1-42, Plp-Adenovirus [Ad]-X-CMV-(Aβ3-10)lo-CpG [AdCpG-(Aβ3-10)1] or AdCpG virus fluid via na- sal mucosal inhalation, respectively. ELISA analysis of serum showed Aβ42 antibody titers were significantly increased in mice immunized with Aβ1-42 and AdCpG-(Aβ3-10)10. Concanavalin A and AdCpG-(Aβ3-10)10 stimulation significantly increased the number of proliferating spleen cells cultured from AdCpG(Aβ3-10)Io and Aβ42 groups compared with the control group. In the AdCp- G(Aβ3-10)10 group, levels of interleukin (IL)-4 and IL-10 were increased, while those of IL-2 and interferon-y were decreased. In the A[342 group, levels of IL-4, IL-10, IL-2 and interferon-y were all increased. Experimental findings indicate that AdCpG-(Aβ3-10)10 vaccine can produce strong T helper 2 (Th2) humoral immune responses in addition to the production of Aβ42 antibody. The cellular immunologic response was weak and avoided Aβ1-42-mediated cytotoxicity.展开更多
Alzheimer’s disease is a neurodegenerative disease that accounts for most of the 50-million dementia cases worldwide in 2018.A large amount of evidence supports the amyloid cascade hypothesis,which states that amyloi...Alzheimer’s disease is a neurodegenerative disease that accounts for most of the 50-million dementia cases worldwide in 2018.A large amount of evidence supports the amyloid cascade hypothesis,which states that amyloid-beta accumulation triggers tau hyperphosphorylation and aggregation in form of neurofibrillary tangles,and these aggregates lead to inflammation,synaptic impairment,neuronal loss,and thus to cognitive decline and behavioral abnormalities.The poor correlation found between cognitive decline and amyloid plaques,have led the scientific community to question whether amyloid-beta accumulation is actually triggering neurodegeneration in Alzheimer’s disease.The occurrence of tau neurofibrillary tangles better correlates to neuronal loss and clinical symptoms and,although amyloid-beta may initiate the cascade of events,tau impairment is likely the effector molecule of neurodegeneration.Recently,it has been shown that amyloid-beta and tau cooperatively work to impair transcription of genes involved in synaptic function and,more importantly,that downregulation of tau partially reverses transcriptional perturbations.Despite mounting evidence points to an interplay between amyloid-beta and tau,some factors could independently affect both pathologies.Thus,the dual pathway hypothesis,which states that there are common upstream triggers causing both amyloid-beta and tau abnormalities has been proposed.Among others,the immune system seems to be strongly involved in amyloid-beta and tau pathologies.Other factors,as the apolipoprotein Eε4 isoform has been suggested to act as a link between amyloid-beta and tau hyperphosphorylation.Interestingly,amyloid-beta-immunotherapy reduces not only amyloid-beta but also tau levels in animal models and in clinical trials.Likewise,it has been shown that tau-immunotherapy also reduces amyloid-beta levels.Thus,even though amyloid-beta immunotherapy is more advanced than tau-immunotherapy,combined amyloid-beta and tau-directed therapies at early stages of the disease have recently been proposed as a strategy to stop the progression of Alzheimer’s disease.展开更多
Amyloid β peptide binding alcohol dehydrogenase (ABAD) decoy peptide (DP) can competitively antagonize binding of amyloid β peptide to ABAD and inhibit the cytotoxic effects of amyloid β peptide. Based on pepti...Amyloid β peptide binding alcohol dehydrogenase (ABAD) decoy peptide (DP) can competitively antagonize binding of amyloid β peptide to ABAD and inhibit the cytotoxic effects of amyloid β peptide. Based on peptide aptamers, the present study inserted ABAD-DP into the disulfide bond of human thioredoxin (TRX) using molecular cloning technique to construct a fusion gene that can express the TRX1-ABAD-DP-TRX2 aptamer. Moreover, adeno-associated virus was used to allow its stable expression. Immunofluorescent staining revealed the co-expression of the transduced fusion gene TRX1-ABAD-DP-TRX2 and amyloid β peptide in NIH-3T3 cells, indicating that the TRXl-ABAD-DP-TRX2 aptamer can bind amyloid β peptide within cells. In addition, cell morphology and MTT results suggested that TRX1-ABAD-DP-TRX2 attenuated amyloid β peptide-induced SH-SY5Y cell injury and improved cell viability. These findings confirmed the possibility of constructing TRX-based peptide aptamer using ABAD-DP. Moreover, TRXl-ABAD-DP-TRX2 inhibited the cytotoxic effect of amyloid β peptide.展开更多
Amyloid-beta peptide is the main component of amyloid plaques, which are found in Alzhei- mer's disease. The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Al...Amyloid-beta peptide is the main component of amyloid plaques, which are found in Alzhei- mer's disease. The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzheimer's disease. Lipid rafts are glycolipid-rich liquid domains of the plasma membrane, where certain types of protein tend to aggregate and intercalate. Lipid rafts are involved in the generation of amyloid-beta oligomers and the formation of amyloid-beta peptides. In this paper, we review the mechanism by which lipid rafts disturb the aberrant deg- radative autophagic-lysosomal pathway of amyloid-beta, which plays an important role in the pathological process of Alzheimer's disease. Moreover, we describe this mechanism from the view of the Two-system Theory of fasciology and thus, suggest that lipid rafts may be a new target of Alzheimer's disease treatment.展开更多
In this study, we treated PC12 cells with 0-20 μM amyloid-β peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 μM amyloid-β peptide (25-35) decreased PC12 cell viability, but adenosine tr...In this study, we treated PC12 cells with 0-20 μM amyloid-β peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 μM amyloid-β peptide (25-35) decreased PC12 cell viability, but adenosine triphosphate-sensitive potassium channel activator diazoxide suppressed the decrease in PC12 cell viability induced by amyloid-β peptide (25-35). Diazoxide protected PC12 cells against amyloid-β peptide (25-35)-induced increases in mitochondrial membrane potential and intracellular reactive oxygen species levels. These protective effects were reversed by the selective mitochondrial adenosine triphosphate-sensitive potassium channel blocker 5-hydroxydecanoate. An inducible nitric oxide synthase inhibitor, Nw-nitro-L-arginine, also protected PC12 cells from amyloid-β peptide (25-35)-induced increases in both mitochondrial membrane potential and intracellular reactive oxygen species levels. However, the H202-degrading enzyme catalase could not reverse the amyloid-β peptide (25-35)-induced increase in intracellular reactive oxygen species. A 24-hour exposure to amyloid-13 peptide (25-35) did not result in apoptosis or necrosis, suggesting that the increases in both mitochondrial membrane potential and reactive oxygen species levels preceded cell death. The data suggest that amyloid-β peptide (25-35) cytotoxicity is associated with adenosine triphosphate-sensitive potassium channels and nitric oxide. Regulation of adenosine triphosphate-sensitive potassium channels suppresses PC12 cell cytotoxicity induced by amyloid-β peptide (25-35).展开更多
Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami taste.In this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alc...Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami taste.In this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alcoholic extracts of the oyster using nano-HPLC-MS/MS analysis,i Umami-Scoring Card Method(i Umami-SCM)database and molecular docking(MD).Sensory evaluation and electronic tongue analysis were further used to confirm their tastes.The threshold of the three peptides ranged from 0.38 to 0.55 mg/m L.MD with umami receptors T1R1/T1R3 indicated that the electrostatic interaction and hydrogen bond interaction were the main forces involved.Besides,the Phe592 and Gln853 of T1R3 were the primary docking site for MD and played an important role in umami intensity.Peptides with two Glu residues at the terminus had stronger umami,especially at the C-terminus.These results contribute to the understanding of umami peptides in oysters and the interaction mechanism between umami peptides and umami receptors.展开更多
Wild edible Termitomyces mushrooms are popular in Southwest China and umami is important flavor qualities of edible mushrooms.This study aimed to understand the umami taste of Termitomyces intermedius and Termitomyces...Wild edible Termitomyces mushrooms are popular in Southwest China and umami is important flavor qualities of edible mushrooms.This study aimed to understand the umami taste of Termitomyces intermedius and Termitomyces aff.bulborhizus.Ten umami peptides from aqueous extracts were separated using a Sephadex G-15 gel filtration chromatography.The intense umami fraction was evaluated by both sensory evaluation and electronic tongue.They were identified as KLNDAQAPK,DSTDEKFLR,VGKGAHLSGEH,MLKKKKLA,SLGFGGPPGY,TVATFSSSTKPDD,AMDDDEADLLLLAM,VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK.Seven peptides,except VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK were selectively synthesized to verify their taste characteristics.All these 10 peptides had umami or salt taste.The 10 peptides were conducted by molecular docking to study their interaction with identified peptides and the umami taste receptor T1R1/T1R3.All these 10 peptides perfectly docked the active residues in the T1R3 subunit.Our results provide theoretical basis for the umami taste and address the umami mechanism of two wild edible Termitomyces mushrooms.展开更多
Two selenium(Se)-containing peptides from Se-enriched rice,TSeMMM and SeMDPGQQ,possess neuroprotective potency against lead(Pb2+)-induced cytotoxicity.However,the crosstalk between mRNA and microRNAs(miRNA)involved in...Two selenium(Se)-containing peptides from Se-enriched rice,TSeMMM and SeMDPGQQ,possess neuroprotective potency against lead(Pb2+)-induced cytotoxicity.However,the crosstalk between mRNA and microRNAs(miRNA)involved in the neuroprotection mechanism remains to be elucidated.In this study,RNA-sequencing and miRNA-sequencing were used to independently identify differentially expressed mRNAs and small RNAs profiles in Pb^(2+)-treated primary fetal rat cortical neurons and then the correlated miRNA-mRNA target pairs were obtained.It was found that 34 mRNAs related to oxidative phosphorylation could be reversed by pretreatment of TSeMMM and SeMDPGQQ.The protective effect of TSeMMM and SeMDPGQQ was mediated by upregulation of miR-107-3p,which downregulates the ATPase H+transporting V0 subunit e1(Atp6v0e1)mRNA level.A zebrafish model was applied to verify the relevance between the targeted mRNA and miRNA by real-time quantitative PCR.The results indicated that miR-107-3p was a potential therapeutic target to achieve neuroprotection of Se-containing peptides via stimulation of Atp6v0e1.展开更多
Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with ...Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with traditional pharmaceuticals while delivering superior anxiolytic and antidepressant effects.This review summarizes current research on food-derived anxiolytic and antidepressant protein hydrolysates and peptides,and subsequently analyses their physicochemical characteristics and elaborates on their mechanisms.The aim of this work is to contribute to the in-depth study and provide a theoretical foundation for the development of related products to better serve patients with anxiety and depression.展开更多
Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high ac...Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention.This article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability improvement.The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity evaluations.In addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical mechanism.Moreover,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement.Hopefully,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.展开更多
The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activati...The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migraine.展开更多
Alpha-lactalbumin(α-LA)is a major whey protein found in breast milk and plays a crucial role in the growth and development of infants.In this study,Bacillus subtilis RIK1285 harboring AprE signal peptide(SP)was selec...Alpha-lactalbumin(α-LA)is a major whey protein found in breast milk and plays a crucial role in the growth and development of infants.In this study,Bacillus subtilis RIK1285 harboring AprE signal peptide(SP)was selected as the original strain for the production ofα-LA.It was found thatα-LA was identified in the pellet after ultrasonic disruption and centrifugation instead of in the fermentation supernatant.The original strain most likely only producedα-LA intracellular,but not extracellular.To improve the expression and secretion ofα-LA in RIK1285,a library of 173 homologous SPs from the B.subtilis 168 genome was fused with target LALBA gene in the pBE-S vector and expressed extracellularly in RIK1285.SP YjcN was determined to be the best signal peptide.Bands in supernatant were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and purified by nickel column to calculate the highest yield signal peptide.In addition,different promoters(P_(aprE),P_(43),and P_(glv))were compared and applied.The results indicated that the strain RIK1285-pBE-P_(glv)-YjcN-LALBA had the highestα-LA yield,reaching 122.04μg/mL.This study demonstrates successful expression and secretion of humanα-LA in B.subtilis and establishes a foundation for simulating breast milk for infant formulas and developing bioengineered milk.展开更多
Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its progression.Antioxidant peptides may thus present therapeutic potential for PD.In...Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its progression.Antioxidant peptides may thus present therapeutic potential for PD.In this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for Cath-KP.In vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant properties.Using the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2-related factor 2(Nrf2)pathway activation.Both focal adhesion kinase(FAK)and p38 were also identified as regulatory elements.In the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated dyskinesia.To the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress.These findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.展开更多
The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is ...The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.展开更多
BACKGROUND:Streptococcus pneumoniae(S.pneumoniae)is a common pathogen that causes bacterial pneumonia.However,with increasing bacterial resistance,there is an urgent need to develop new drugs to treat S.pneumoniae inf...BACKGROUND:Streptococcus pneumoniae(S.pneumoniae)is a common pathogen that causes bacterial pneumonia.However,with increasing bacterial resistance,there is an urgent need to develop new drugs to treat S.pneumoniae infections.Nanodefensin with a 14-carbon saturated fatty acid(ND-C14)is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of humanα-defensin 5(HD5)via an amide bond.However,it is unclear whether ND-C14 is effective against lung infections caused by S.pneumoniae.METHODS:In vitro,three groups were established,including the control group,and the HD5 and ND-C14 treatment groups.A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S.pneumoniae.The morphological changes of S.pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy.In vivo,mice were divided into sham,vehicle,and ND-C14 treatment groups.Mice in the sham group were treated with 25μL of phosphate-buffered saline(PBS).Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25μL of bacterial suspension with 2×108 CFU/mL(total bacterial count:5×10^(6) CFU),and then the mice were given 25μL PBS or intratracheally injected with 25μL of ND-C14(including 20μg or 50μg),respectively.Survival rates were evaluated in the vehicle and ND-C14 treatment groups.Bacterial burden in the blood and bronchoalveolar lavage fluid were counted.The lung histology of the mice was assessed.A propidium iodide uptake assay was used to clarify the destructive eff ect of ND-C14 against S.pneumoniae.RESULTS:Compared with HD5,ND-C14 had a better bactericidal eff ect against S.pneumoniae because of its stronger ability to destroy the membrane structure of S.pneumoniae in vitro.In vivo,ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S.pneumoniae.ND-C14 reduced bacterial burden and lung tissue injury.Moreover,ND-C14 had a membrane permeation eff ect on S.pneumoniae,and its destructive ability increased with increasing ND-C14 concentration.CONCLUSION:The ND-C14 may improve bactericidal eff ects on S.pneumoniae both in vitro and in vivo.展开更多
The taste presentation and receptor perception mechanism of the salty peptide of Stropharia rugosoannulata were predicted and verified using peptide omics and molecular interaction techniques.The combination of aspart...The taste presentation and receptor perception mechanism of the salty peptide of Stropharia rugosoannulata were predicted and verified using peptide omics and molecular interaction techniques.The combination of aspartic acid(D)and glutamic acid(E),or peptide fragments composed of arginine(R),constitute the characteristic taste structural basis of salty peptides of S.rugosoannulata.The taste intensity of the salty peptide positively correlates with its concentration within a specific concentration range(0.25–1.0 mg/mL).The receptor more easily recognizes the first amino acid residue at the N-terminal of salty peptides and the aspartic acid residue in the peptides.GLU513,ASP707,and VAL508 are the critical amino acid residues for the receptor to recognize salty peptides.TRPV1 is specifically the receptor for recognizing salty peptides.Hydrogen bonds and electrostatic interactions are the main driving forces for the interactions between salty peptides and TRPV1 receptors.KSWDDFFTR has the most potent binding capacity with the receptor and has tremendous potential for application in sodium salt substitution.This study confirmed the taste receptor that specifically recognizes salty peptides,analyzed the receptor-peptide binding interaction,and provided a new idea for understanding the taste receptor perception of salty peptides.展开更多
Melittin,a classical antimicrobial peptide,is a highly potent antitumor agent.However,its significant toxicity seriously hampers its application in tumor therapy.In this study,we developed novel melittin analogs with ...Melittin,a classical antimicrobial peptide,is a highly potent antitumor agent.However,its significant toxicity seriously hampers its application in tumor therapy.In this study,we developed novel melittin analogs with pH-responsive,cell-penetrating and membranelytic activities by replacing arginine and lysine with histidine.After conjugation with camptothecin(CPT),CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic conditions.Notably,we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the N-terminus.CPT-AAM-1 significantly suppressed melanoma growth in vivo with relatively low toxicity.Collectively,the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.展开更多
Objective: This paper aims to investigate the effect of applying recombinant human brain natriuretic peptide in patients with heart failure combined with hypotension. Recombinant human brain natriuretic peptide is a s...Objective: This paper aims to investigate the effect of applying recombinant human brain natriuretic peptide in patients with heart failure combined with hypotension. Recombinant human brain natriuretic peptide is a synthetic polypeptide drug that is primarily used to treat acute heart failure. Its mechanism of action closely mimics that of human endogenous brain natriuretic peptide. By binding to receptors on cardiomyocytes, it exerts its pharmacological effects. Methods: For the study, 76 heart failure patients with hypotension were selected from our hospital between May 2022 and June 2023. These patients were divided into two groups: a control group and an observation group, each comprising 38 patients. The control group received dopamine treatment, while the observation group was treated with recombinant brain natriuretic peptide. The objective was to compare the effects of the treatments in both groups by analyzing cardiac function indices and levels of vasoactive substances to identify any significant differences in outcomes. Results: The overall response rate of the patients in the observation group and the control group was 94.74% and 73.68%, significantly higher as compared with the observation group (P 0.05). After the following treatment, BNP, ANNP and urine output in the observation group were significantly different compared with the control group, of the statistical significance (P Conclusion: For the treatment of heart failure patients with hypotension, the clinical application of recombinant human brain natriuretic peptide is the most ideal, and significantly improves the cardiac function of patients, which is worth popularizing.展开更多
Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanis...Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.展开更多
Walnut dreg protein hydrolysates(WDPHs)exhibit a variety of biological activities,however,the cyclooxygenase-2(COX-2)inhibitory peptide of WDPHs remain unclear.The aim of this study was to rapidly screen for such pept...Walnut dreg protein hydrolysates(WDPHs)exhibit a variety of biological activities,however,the cyclooxygenase-2(COX-2)inhibitory peptide of WDPHs remain unclear.The aim of this study was to rapidly screen for such peptides in WDPHs through a combination of in silico and in vitro analysis.In total,1262 peptide sequences were observed by nano liquid chromatography/tandem mass spectrometry(nano LC-MS/MS)and 4 novel COX-2 inhibitory peptides(AGFP,FPGA,LFPD,and VGFP)were identified.Enzyme kinetic data indicated that AGFP,FPGA,and LFPD displayed mixed-type COX-2 inhibition,whereas VGFP was a non-competitive inhibitor.This is mainly because the peptides form hydrogen bonds and hydrophobic interactions with residues in the COX-2 active site.These results demonstrate that computer analysis combined with in vitro evaluation allows for rapid screening of COX-2 inhibitory peptides in walnut protein dregs.展开更多
基金supported by the National Natural Science Foundation of China,No.30471927
文摘Three-month-old Alzheimer's disease model transgenic mice were immunized with Aβ1-42, Plp-Adenovirus [Ad]-X-CMV-(Aβ3-10)lo-CpG [AdCpG-(Aβ3-10)1] or AdCpG virus fluid via na- sal mucosal inhalation, respectively. ELISA analysis of serum showed Aβ42 antibody titers were significantly increased in mice immunized with Aβ1-42 and AdCpG-(Aβ3-10)10. Concanavalin A and AdCpG-(Aβ3-10)10 stimulation significantly increased the number of proliferating spleen cells cultured from AdCpG(Aβ3-10)Io and Aβ42 groups compared with the control group. In the AdCp- G(Aβ3-10)10 group, levels of interleukin (IL)-4 and IL-10 were increased, while those of IL-2 and interferon-y were decreased. In the A[342 group, levels of IL-4, IL-10, IL-2 and interferon-y were all increased. Experimental findings indicate that AdCpG-(Aβ3-10)10 vaccine can produce strong T helper 2 (Th2) humoral immune responses in addition to the production of Aβ42 antibody. The cellular immunologic response was weak and avoided Aβ1-42-mediated cytotoxicity.
基金supported by grant SAF2017-89613-R from the Ministerio de Economía y Competitividad(MINECO)/FEDER(Madrid,Spain)(to SV).
文摘Alzheimer’s disease is a neurodegenerative disease that accounts for most of the 50-million dementia cases worldwide in 2018.A large amount of evidence supports the amyloid cascade hypothesis,which states that amyloid-beta accumulation triggers tau hyperphosphorylation and aggregation in form of neurofibrillary tangles,and these aggregates lead to inflammation,synaptic impairment,neuronal loss,and thus to cognitive decline and behavioral abnormalities.The poor correlation found between cognitive decline and amyloid plaques,have led the scientific community to question whether amyloid-beta accumulation is actually triggering neurodegeneration in Alzheimer’s disease.The occurrence of tau neurofibrillary tangles better correlates to neuronal loss and clinical symptoms and,although amyloid-beta may initiate the cascade of events,tau impairment is likely the effector molecule of neurodegeneration.Recently,it has been shown that amyloid-beta and tau cooperatively work to impair transcription of genes involved in synaptic function and,more importantly,that downregulation of tau partially reverses transcriptional perturbations.Despite mounting evidence points to an interplay between amyloid-beta and tau,some factors could independently affect both pathologies.Thus,the dual pathway hypothesis,which states that there are common upstream triggers causing both amyloid-beta and tau abnormalities has been proposed.Among others,the immune system seems to be strongly involved in amyloid-beta and tau pathologies.Other factors,as the apolipoprotein Eε4 isoform has been suggested to act as a link between amyloid-beta and tau hyperphosphorylation.Interestingly,amyloid-beta-immunotherapy reduces not only amyloid-beta but also tau levels in animal models and in clinical trials.Likewise,it has been shown that tau-immunotherapy also reduces amyloid-beta levels.Thus,even though amyloid-beta immunotherapy is more advanced than tau-immunotherapy,combined amyloid-beta and tau-directed therapies at early stages of the disease have recently been proposed as a strategy to stop the progression of Alzheimer’s disease.
基金supported by the National Natural Science Foundation of China,No.30872721the National Natural Science Foundation for the Youth,No.30801211,30800338the Scientific Research Foundation for New Teachers of High Institutes,No.200801831073,200801831072
文摘Amyloid β peptide binding alcohol dehydrogenase (ABAD) decoy peptide (DP) can competitively antagonize binding of amyloid β peptide to ABAD and inhibit the cytotoxic effects of amyloid β peptide. Based on peptide aptamers, the present study inserted ABAD-DP into the disulfide bond of human thioredoxin (TRX) using molecular cloning technique to construct a fusion gene that can express the TRX1-ABAD-DP-TRX2 aptamer. Moreover, adeno-associated virus was used to allow its stable expression. Immunofluorescent staining revealed the co-expression of the transduced fusion gene TRX1-ABAD-DP-TRX2 and amyloid β peptide in NIH-3T3 cells, indicating that the TRXl-ABAD-DP-TRX2 aptamer can bind amyloid β peptide within cells. In addition, cell morphology and MTT results suggested that TRX1-ABAD-DP-TRX2 attenuated amyloid β peptide-induced SH-SY5Y cell injury and improved cell viability. These findings confirmed the possibility of constructing TRX-based peptide aptamer using ABAD-DP. Moreover, TRXl-ABAD-DP-TRX2 inhibited the cytotoxic effect of amyloid β peptide.
基金supported by a grant from Projects of High-tech Industrialization of Guangdong Province of China,No.2011B010500004a grant from National Financial Major Project of China
文摘Amyloid-beta peptide is the main component of amyloid plaques, which are found in Alzhei- mer's disease. The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzheimer's disease. Lipid rafts are glycolipid-rich liquid domains of the plasma membrane, where certain types of protein tend to aggregate and intercalate. Lipid rafts are involved in the generation of amyloid-beta oligomers and the formation of amyloid-beta peptides. In this paper, we review the mechanism by which lipid rafts disturb the aberrant deg- radative autophagic-lysosomal pathway of amyloid-beta, which plays an important role in the pathological process of Alzheimer's disease. Moreover, we describe this mechanism from the view of the Two-system Theory of fasciology and thus, suggest that lipid rafts may be a new target of Alzheimer's disease treatment.
基金supported by the Project Sponsored by Yantai Science and Technology Bureau,China,No.2010232
文摘In this study, we treated PC12 cells with 0-20 μM amyloid-β peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 μM amyloid-β peptide (25-35) decreased PC12 cell viability, but adenosine triphosphate-sensitive potassium channel activator diazoxide suppressed the decrease in PC12 cell viability induced by amyloid-β peptide (25-35). Diazoxide protected PC12 cells against amyloid-β peptide (25-35)-induced increases in mitochondrial membrane potential and intracellular reactive oxygen species levels. These protective effects were reversed by the selective mitochondrial adenosine triphosphate-sensitive potassium channel blocker 5-hydroxydecanoate. An inducible nitric oxide synthase inhibitor, Nw-nitro-L-arginine, also protected PC12 cells from amyloid-β peptide (25-35)-induced increases in both mitochondrial membrane potential and intracellular reactive oxygen species levels. However, the H202-degrading enzyme catalase could not reverse the amyloid-β peptide (25-35)-induced increase in intracellular reactive oxygen species. A 24-hour exposure to amyloid-13 peptide (25-35) did not result in apoptosis or necrosis, suggesting that the increases in both mitochondrial membrane potential and reactive oxygen species levels preceded cell death. The data suggest that amyloid-β peptide (25-35) cytotoxicity is associated with adenosine triphosphate-sensitive potassium channels and nitric oxide. Regulation of adenosine triphosphate-sensitive potassium channels suppresses PC12 cell cytotoxicity induced by amyloid-β peptide (25-35).
基金supported by the National Key Research and Development Program of China:Investigate the mechanism of formation and control technologies of Chinese traditional and ethnic food quality(2021YFD2100100)。
文摘Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami taste.In this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alcoholic extracts of the oyster using nano-HPLC-MS/MS analysis,i Umami-Scoring Card Method(i Umami-SCM)database and molecular docking(MD).Sensory evaluation and electronic tongue analysis were further used to confirm their tastes.The threshold of the three peptides ranged from 0.38 to 0.55 mg/m L.MD with umami receptors T1R1/T1R3 indicated that the electrostatic interaction and hydrogen bond interaction were the main forces involved.Besides,the Phe592 and Gln853 of T1R3 were the primary docking site for MD and played an important role in umami intensity.Peptides with two Glu residues at the terminus had stronger umami,especially at the C-terminus.These results contribute to the understanding of umami peptides in oysters and the interaction mechanism between umami peptides and umami receptors.
基金supported by the Yunnan Key Project of Science and Technology(202202AE090001)Postdoctoral Directional Training Foundation of Yunnan Province(E23174K2)Postdoctoral Research Funding Projects of Yunnan Province,China(E2313442)。
文摘Wild edible Termitomyces mushrooms are popular in Southwest China and umami is important flavor qualities of edible mushrooms.This study aimed to understand the umami taste of Termitomyces intermedius and Termitomyces aff.bulborhizus.Ten umami peptides from aqueous extracts were separated using a Sephadex G-15 gel filtration chromatography.The intense umami fraction was evaluated by both sensory evaluation and electronic tongue.They were identified as KLNDAQAPK,DSTDEKFLR,VGKGAHLSGEH,MLKKKKLA,SLGFGGPPGY,TVATFSSSTKPDD,AMDDDEADLLLLAM,VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK.Seven peptides,except VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK were selectively synthesized to verify their taste characteristics.All these 10 peptides had umami or salt taste.The 10 peptides were conducted by molecular docking to study their interaction with identified peptides and the umami taste receptor T1R1/T1R3.All these 10 peptides perfectly docked the active residues in the T1R3 subunit.Our results provide theoretical basis for the umami taste and address the umami mechanism of two wild edible Termitomyces mushrooms.
基金supported by the National Natural Science Foundation of China(32272319,31972020,32202032)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Two selenium(Se)-containing peptides from Se-enriched rice,TSeMMM and SeMDPGQQ,possess neuroprotective potency against lead(Pb2+)-induced cytotoxicity.However,the crosstalk between mRNA and microRNAs(miRNA)involved in the neuroprotection mechanism remains to be elucidated.In this study,RNA-sequencing and miRNA-sequencing were used to independently identify differentially expressed mRNAs and small RNAs profiles in Pb^(2+)-treated primary fetal rat cortical neurons and then the correlated miRNA-mRNA target pairs were obtained.It was found that 34 mRNAs related to oxidative phosphorylation could be reversed by pretreatment of TSeMMM and SeMDPGQQ.The protective effect of TSeMMM and SeMDPGQQ was mediated by upregulation of miR-107-3p,which downregulates the ATPase H+transporting V0 subunit e1(Atp6v0e1)mRNA level.A zebrafish model was applied to verify the relevance between the targeted mRNA and miRNA by real-time quantitative PCR.The results indicated that miR-107-3p was a potential therapeutic target to achieve neuroprotection of Se-containing peptides via stimulation of Atp6v0e1.
基金supported by the National Key Research and Development Program of China (2021YFD2100402)the National Natural Science Foundation of China (81903275)the Fund of the Cultivation Project of Double First-Class Disciplines of Food Science and Engineering,Beijing Technology&Business University (BTBUYXTD202203)。
文摘Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with traditional pharmaceuticals while delivering superior anxiolytic and antidepressant effects.This review summarizes current research on food-derived anxiolytic and antidepressant protein hydrolysates and peptides,and subsequently analyses their physicochemical characteristics and elaborates on their mechanisms.The aim of this work is to contribute to the in-depth study and provide a theoretical foundation for the development of related products to better serve patients with anxiety and depression.
基金sponsored by the National Natural Science Foundation China(32270115)National Key R&D Program of China(2018YFD0901102)+1 种基金Fundamental Research Funds for the Provincial Universities of Zhejiang(SJLY2021015)K.C.Wong Magna Fund of Ningbo University。
文摘Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention.This article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability improvement.The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity evaluations.In addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical mechanism.Moreover,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement.Hopefully,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.
基金supported by the European Union Grant Alehoop(H2020-BBIJTI-2019-887259)And from the Xunta de Galicia(Centro singular de Investigación de Galicia accreditation 2016-2019),ED431 G/02(to FM)。
文摘The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migraine.
基金This work was funded by National Natural Science Foundation of China(32272279)the Key R&D project of Qingdao Science and Technology Plan(22-3-3-hygg-29-hy).
文摘Alpha-lactalbumin(α-LA)is a major whey protein found in breast milk and plays a crucial role in the growth and development of infants.In this study,Bacillus subtilis RIK1285 harboring AprE signal peptide(SP)was selected as the original strain for the production ofα-LA.It was found thatα-LA was identified in the pellet after ultrasonic disruption and centrifugation instead of in the fermentation supernatant.The original strain most likely only producedα-LA intracellular,but not extracellular.To improve the expression and secretion ofα-LA in RIK1285,a library of 173 homologous SPs from the B.subtilis 168 genome was fused with target LALBA gene in the pBE-S vector and expressed extracellularly in RIK1285.SP YjcN was determined to be the best signal peptide.Bands in supernatant were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and purified by nickel column to calculate the highest yield signal peptide.In addition,different promoters(P_(aprE),P_(43),and P_(glv))were compared and applied.The results indicated that the strain RIK1285-pBE-P_(glv)-YjcN-LALBA had the highestα-LA yield,reaching 122.04μg/mL.This study demonstrates successful expression and secretion of humanα-LA in B.subtilis and establishes a foundation for simulating breast milk for infant formulas and developing bioengineered milk.
基金supported by the National Natural Science Foundation of China(31772476 and 31911530077 to X.X.,81870991 and U1603281 to S.Q.)Guangdong Basic and Applied Basic Research Foundation(2023A1515010914 to X.X.)Natural Science Foundation of Guangdong Province(2022A1515010352 to S.Q.)。
文摘Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its progression.Antioxidant peptides may thus present therapeutic potential for PD.In this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for Cath-KP.In vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant properties.Using the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2-related factor 2(Nrf2)pathway activation.Both focal adhesion kinase(FAK)and p38 were also identified as regulatory elements.In the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated dyskinesia.To the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress.These findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.
基金supported by the National Natural Science Foundation of China(No.31901635)。
文摘The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.
基金supported by the National Natural Science Foundation of China(82072148)Zhejiang Provincial Basic Public Welfare Research Program of Zhejiang Province(LGF21H150002)+1 种基金Zhejiang Medicine and Health Science and Technology Project(2022RC245&2023KY255)Ningbo Municipal Natural Science Foundation(2023J134).
文摘BACKGROUND:Streptococcus pneumoniae(S.pneumoniae)is a common pathogen that causes bacterial pneumonia.However,with increasing bacterial resistance,there is an urgent need to develop new drugs to treat S.pneumoniae infections.Nanodefensin with a 14-carbon saturated fatty acid(ND-C14)is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of humanα-defensin 5(HD5)via an amide bond.However,it is unclear whether ND-C14 is effective against lung infections caused by S.pneumoniae.METHODS:In vitro,three groups were established,including the control group,and the HD5 and ND-C14 treatment groups.A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S.pneumoniae.The morphological changes of S.pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy.In vivo,mice were divided into sham,vehicle,and ND-C14 treatment groups.Mice in the sham group were treated with 25μL of phosphate-buffered saline(PBS).Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25μL of bacterial suspension with 2×108 CFU/mL(total bacterial count:5×10^(6) CFU),and then the mice were given 25μL PBS or intratracheally injected with 25μL of ND-C14(including 20μg or 50μg),respectively.Survival rates were evaluated in the vehicle and ND-C14 treatment groups.Bacterial burden in the blood and bronchoalveolar lavage fluid were counted.The lung histology of the mice was assessed.A propidium iodide uptake assay was used to clarify the destructive eff ect of ND-C14 against S.pneumoniae.RESULTS:Compared with HD5,ND-C14 had a better bactericidal eff ect against S.pneumoniae because of its stronger ability to destroy the membrane structure of S.pneumoniae in vitro.In vivo,ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S.pneumoniae.ND-C14 reduced bacterial burden and lung tissue injury.Moreover,ND-C14 had a membrane permeation eff ect on S.pneumoniae,and its destructive ability increased with increasing ND-C14 concentration.CONCLUSION:The ND-C14 may improve bactericidal eff ects on S.pneumoniae both in vitro and in vivo.
基金funded by Natural Science Foundation of Shanghai,China(No.23ZR1426100)SAAS program for Excellent Research Team(No.G202203)。
文摘The taste presentation and receptor perception mechanism of the salty peptide of Stropharia rugosoannulata were predicted and verified using peptide omics and molecular interaction techniques.The combination of aspartic acid(D)and glutamic acid(E),or peptide fragments composed of arginine(R),constitute the characteristic taste structural basis of salty peptides of S.rugosoannulata.The taste intensity of the salty peptide positively correlates with its concentration within a specific concentration range(0.25–1.0 mg/mL).The receptor more easily recognizes the first amino acid residue at the N-terminal of salty peptides and the aspartic acid residue in the peptides.GLU513,ASP707,and VAL508 are the critical amino acid residues for the receptor to recognize salty peptides.TRPV1 is specifically the receptor for recognizing salty peptides.Hydrogen bonds and electrostatic interactions are the main driving forces for the interactions between salty peptides and TRPV1 receptors.KSWDDFFTR has the most potent binding capacity with the receptor and has tremendous potential for application in sodium salt substitution.This study confirmed the taste receptor that specifically recognizes salty peptides,analyzed the receptor-peptide binding interaction,and provided a new idea for understanding the taste receptor perception of salty peptides.
基金supported by the grants from the National Natural Science Foundation of China(Nos.81773566 and 21602092)Innovation Project of Medicine and Health Science and Technology of Chinese Academy of Medical Sciences(2019-I2M-5-074)+1 种基金the Funds for Fundamental Research Creative Groups of Gansu Province(No.20JR5RA310)the Fundamental Research Funds for the Central Universities(No.lzujbky-2021-38).
文摘Melittin,a classical antimicrobial peptide,is a highly potent antitumor agent.However,its significant toxicity seriously hampers its application in tumor therapy.In this study,we developed novel melittin analogs with pH-responsive,cell-penetrating and membranelytic activities by replacing arginine and lysine with histidine.After conjugation with camptothecin(CPT),CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic conditions.Notably,we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the N-terminus.CPT-AAM-1 significantly suppressed melanoma growth in vivo with relatively low toxicity.Collectively,the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.
文摘Objective: This paper aims to investigate the effect of applying recombinant human brain natriuretic peptide in patients with heart failure combined with hypotension. Recombinant human brain natriuretic peptide is a synthetic polypeptide drug that is primarily used to treat acute heart failure. Its mechanism of action closely mimics that of human endogenous brain natriuretic peptide. By binding to receptors on cardiomyocytes, it exerts its pharmacological effects. Methods: For the study, 76 heart failure patients with hypotension were selected from our hospital between May 2022 and June 2023. These patients were divided into two groups: a control group and an observation group, each comprising 38 patients. The control group received dopamine treatment, while the observation group was treated with recombinant brain natriuretic peptide. The objective was to compare the effects of the treatments in both groups by analyzing cardiac function indices and levels of vasoactive substances to identify any significant differences in outcomes. Results: The overall response rate of the patients in the observation group and the control group was 94.74% and 73.68%, significantly higher as compared with the observation group (P 0.05). After the following treatment, BNP, ANNP and urine output in the observation group were significantly different compared with the control group, of the statistical significance (P Conclusion: For the treatment of heart failure patients with hypotension, the clinical application of recombinant human brain natriuretic peptide is the most ideal, and significantly improves the cardiac function of patients, which is worth popularizing.
基金financially supported by Shenzhen Agricultural Development Special Fund(Fishery)Agricultural High-Tech Project([2021]735)the Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173207022)Youth Science Foundation Project(32101936)。
文摘Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.
基金supported by the Major Project of Science and Technology Department of Yunnan Province (202002AA100005 and 202102AE090027-2)the Project of Yunnan Province Food and Drug Homologous Resources Functional Food Innovation Team (A3032023057)+2 种基金the YEFICRC project of Yunnan provincial key programs (2019ZG009)Yunnan Province Ten Thousand Plan Industrial Technology Talents project (YNWR-CYJS-2020-010)the Yunnan Provincial Department of Science and Technology Agricultural Joint Special Project (202101BD070001-120)。
文摘Walnut dreg protein hydrolysates(WDPHs)exhibit a variety of biological activities,however,the cyclooxygenase-2(COX-2)inhibitory peptide of WDPHs remain unclear.The aim of this study was to rapidly screen for such peptides in WDPHs through a combination of in silico and in vitro analysis.In total,1262 peptide sequences were observed by nano liquid chromatography/tandem mass spectrometry(nano LC-MS/MS)and 4 novel COX-2 inhibitory peptides(AGFP,FPGA,LFPD,and VGFP)were identified.Enzyme kinetic data indicated that AGFP,FPGA,and LFPD displayed mixed-type COX-2 inhibition,whereas VGFP was a non-competitive inhibitor.This is mainly because the peptides form hydrogen bonds and hydrophobic interactions with residues in the COX-2 active site.These results demonstrate that computer analysis combined with in vitro evaluation allows for rapid screening of COX-2 inhibitory peptides in walnut protein dregs.