peptide

摘要： Objective:The morbidity of malignant melanoma keeps increasing annually.It has high risks of metastasis,drug resistance,and poor prognosis in clinics.Moreover,the available medicines used commonly,such as dacarbazine,temozolomide,the v-Raf murine sarcoma viral oncogene homolog B1(BRAF)inhibitor vemurafenib,and the programmed cell death protein 1 inhibitor pembrolizumab,have some limitations at some extent.Therefore,a more effective therapeutic strategy is still urgently necessary.Methods:In this study,Brucea javanica(L.)Merr.globulins were hydrolyzed with pepsin,then ultra-filtrated to collect small molecular peptides(≤3 kDa).The peptides were then analyzed by antiproliferative assay,cell-cycle distribution,apoptosis assay,and in vitro wound-scratch assay.Finally,western blotting was conducted to elucidate the underlying anti-melanoma mechanism.Results:The small molecular peptide from B.javanica significantly inhibited malignant melanoma cell proliferation with the IC_(50) of 2.72 mg/mL for 72 h.Further analysis indicated that B.javanica peptides arrested cell cycle at the S and G2/M phases and induced apoptosis by upregulating p21,p53,Bax,caspase-3,and cleaved PARP while downregulating Bcl-2 expression.The inhibitory migration effects were also confirmed by wound-healing assay.Conclusion:The small molecular biopeptides from B.javanica may be a promising bioactive agent candidate for melanoma treatment.

摘要： Ulcerative colitis(UC)is an incurable and highly complex digestive disease affecting millions of people worldwide.Compared to the current therapeutic drugs,bioactive peptides are more promising and safe substances as functional foods or drugs for the prevention and treatment of UC.The alcohol-soluble components from fermentation broth by fresh wheat germ and apple(AC-WGAF)were found to be effective in UC prevention in dextran sulfate sodium-induced mice in vivo.Herein,4 novel peptides are identifi ed from AC-WGAF by membrane ultrafi ltration,recycling preparative high-performance liquid chromatography,and matrix-assisted laser desorption–ionization time-of-fl ight/time-of-fl ight mass spectrometry,possessing anticolitis activity via using an in vitro model.One of those peptides named T24(PVLGPVRGPFPLL)exhibited the most remarkable anti-colitis activity by preventing tight junction protein loss,maintaining epithelial barrier integrity,and promoting cell proliferation during in vitro and in vivo studies by regulating mitogen-activated protein kinase signaling pathways.Thus,T24 is a promising peptide as a functional food or novel drug for UC prevention and treatment.

摘要： Intrauterine adhesion(IUA)is a common clinical endometrial disease,which can severely damage the fertility and quality of life in women.This study aims to find the differentially expressed endogenous peptides and their possible roles in IUA.Liquid chromatography-mass spectrometry was used to identify the peptidomic profiling of IUA tissues,and the differentially expressed peptides were screened out.Using real-time quantitative PCR,Western blotting,and immunocytochemistry staining,the function of six endogenous peptides was verified in vitro.It was found that peptide 6(T6)(peptide sequence:TFGGAPGFPLGSPLSSVFPR)could inhibit the expression of TGF-β1-induced cell fibrosis in human endometrial stromal cell line and primary human endometrial stromal cell at a concentration of 50μmol/L.This study provides new targets for further clarifying the formation and prevention of IUA.

摘要： Background:Digestive disorders in weaning pigs remain a major challenge for swine producers.Different types of commercial feed additives have been developed to promote gut health and development in young pigs,but their effects on resident gut microbial communities remain largely unexplored.The aim of this study was to investigate the impact of a peptide-based product(Peptiva)in combination with mannose oligosaccharides(MOS)and an exogenous protease on the performance and fecal microbiome of nursery pigs.Methods:A total of 1097 weaned pigs were divided into 44 pens(24-26 pigs/pen)with each pen randomly assigned to one of four experimental diets as part of Phase Ⅱ and Phase Ⅲ of a standard nursery phase feeding program.Fecal samples collected from representative control and treatment pigs were used to investigate bacterial composition profiles by high throughput sequencing of PCR-generated amplicons targeting the V1-V3 region of the 16S rRNA gene.Results:Higher gain:feed was observed for pigs fed Peptiva and MOS compared to Controls during the period when experimental diets were fed,but the benefits of supplementation were not maintained after pigs were transitioned to a non-supplemented diet.Three candidate bacterial species,identified as Operational Taxonomic Units(OTUs),were found to have significantly different abundances between control samples and treatment samples during the same phase.In Phase Ⅲ samples,SD_Ssd-00039,predicted to be a strain of Streptococcus alactolyticus based on nucleotide sequence identity,was the most highly represented of these OTUs with an average abundance in pigs fed Peptiva,MOS and protease that was 3.9 times higher than in Controls.The report also presents evidence of microbial succession that occurred during the trial,with 16 of the 32 most abundant OTUs found to vary between Phase Ⅱ and Phase Ⅲ samples for the same dietary treatment.Conclusions:Dietary supplementation with a combination of a peptide-based product,MOS,and protease increased the growth performance of weaned pigs compared to control animals during the nursery phase,but these benefits were no longer observed within 2 weeks after all animals were transitioned to a non-supplemented diet.Supplementation with these feed additives was found to modulate the composition of the swine gut microbiome during this period.

摘要： The present study aimed at making a rational usage for European eel bone by-products by preparing Europen eel bone peptide chelated calcium(EBPC-Ca).Nutritional properties and bioactivity of EBPC-Ca were evaluated.Results showed that nutritional properties of calcium ions will cause intra-and inter-molecular folding and aggregation of peptide to uniformly form EBPC-Ca chelate.The chelated compound of EBPC and calcium ion triggered a strong apoptosis in heterogeneous human epithelial colorectal adenocarcinoma(Caco-2)in concentration-and time-dependent manners.Western blot analysis revealed that the EBPC-Ca induced apoptosis may be the result of a blocked autophagy flux through mitochondrial-dependent pathway.Additionally,the increase in FGF-23 protein expression inhibited the absorption of calcium ions and alleviated cell apoptosis.It was also found that the cell apoptosis occurs with significant increases in the levels of reactive oxygen species(ROS)and Ca^(2+)in the cells,indicating the anti-tumor potential of EBPC-Ca may involve multiple channels.

摘要： Precisely analyzing the target materials in living cells can reveal the essence and mystery of life at a deeper level,which will provide reliable theoretical basis for the occurrence,development,treatment and prognosis of major diseases.However,because living cells are in the dynamic process of metabolism,there are several challenges existed in accurate analysis,including subcellular compartment heterogeneity,plasma membrane interface barrier,and cell cycle regulation.In this regard,our group has designed and synthesized a series of multifunctional aggregates by mainly integrating the peptide elements,nucleic acid elements and aggregation elements to overcome the barriers.This article summarizes the latest developments of multifunctional aggregates for precise cell analysis by our group,and systematically introduces them according to different design concepts and targeting dimensions,such as space,efficiency as well as time.We hope this work could contribute to analyzing the biomarkers in cells through constructing the multifunctional aggregates,understanding the operation mechanism of cells,finally inspiring technology breakthroughs in biomedical fields.

摘要： Estrogen receptor alpha(ERα/ESR1)is overexpressed in over half of all breast cancers and is considered a valuable therapeutic target in ERαpositive breast cancer.Here,we designed a membrane-permeant Chaperonemediated Autophagy Targeting Chimeras(CMATAC)peptide to knockdown endogenous ERαprotein through chaperone-mediated autophagy.The peptide contains a cell membrane-penetrating peptide(TAT)that allows the peptide to by-pass the plasma membrane,anαI peptide as a protein-binding peptide(PBD)that binds specifically to ERα,and CMA-targeting peptide(CTM)that targeting chaperone-mediated autophagy.We validated that ERαtargeting peptide was able to target and degrade ERαto reduce the viability of ERαpositive breast cancer cells.Taken together,our studies provided a new method to reduce the level of intracellular ERαprotein via CMATAC,and thus may provide a new strategy for the treatment of ERαpositive breast cancer.

摘要： Aim: Assess upper and lower limb functions in elderly with heart failure (HF) and evaluate its relation to HF severity. Methods: Handgrip strength (HGS) in kilograms (kgs.) of both hands using handle mechanical dynamometer and counting the repetitions (rep.) of stand and sit on a chair during 30 seconds [the 30 seconds chair-stand test (CST)] were used in 71 elderly (≥65 years old) patients with clinically stable HF and other matched 32 healthy elderly as a control. HF was diagnosed clinically, by plasma B-Type natriuretic peptide (BNP) and by echocardiography. The New York Heart Association (NYHA) functional classification of HF was used to obtain two groups: NYHA class I-II (33 patients), and NYHA class III (38 patients). Results: Showed significant decrease in both HGS and CST score in all HF patients (9.7 ± 4.4 kgs., 8.8 ± 3.1 rep., respectively) compared to controls (77.8 ± 11 kgs., 13.5 ± 1.1 rep., respectively, p Conclusion: Upper and lower limb muscles?strength, assessed by two easy andinexpensive tests (HGS and CST), may reflect clinical severity of HF in elderly patients who cannot usually perform exercise tests. Its prognostic value requires further follow-up studies to verify.

摘要： OBJECTIVE Alzheimer disease(AD) is the most common type of dementia and is featured by the accumulation of β-amyloid peptide(Aβ) in the brain. The Alpha 7 nicotinic acetylcholine receptor family(α7 nAChR) was widely considered to interact with that Aβ, mediate neuroprotection and improve cognitive performance. However, the mechanisms underlying these interactions remain elusive. The present study aimed to determine how this interaction contribute to AD pathology. METHODS In vitro model of AD(primary culture of mice hippocampus treated with Aβ) andin vivo, a mouse model of AD(APPswe/PSEN1 d E9 double transgenic mice, APP/PS1_DT mice) were used to study to the possible inter-action of α7 nAChR and Aβ in the pathogenesis of AD. In vitro experiments, the primary hippocampal neurons cell was exposed to Aβ1-42 peptides in combination with PNU. In vivo experiments, different drugs/operations was applied to APP/PS1_DT mice for setting up of the following groups: WP group, wild-type C57 mice treated with PNU(α7 nAChR specific agonist);AP group, APP/PS1_DT mice treated with PNU;APP/PS1 group, the APP/PS1_DT mice injected intraperitoneally with the same amount of normal saline for 5 d;Control group, wild-type C57 mice injected intraperitoneally with the same amount of normal saline for 5 d. A transmission electron microscope was used to observed the synaptic morphological changes of hippocampal neurons. Reverse transcription quantitative PCR(RT-q PCR) and Western blot analysis were used to detect the expression levels of synaptic-associated proteins(SYN, SNAP25 etc). The learning and memory abilities of mice were detected by Morris water maze. RESULTS In vitro, it was found that α7 nAChR acts as an anti-Aβ-induced synaptic injury to nerve cell by increased the expression of synaptic-associated proteins and attenuated apoptosis induced by Aβ oligomers. In vivo, α7 nAChR attenuated synaptic loss induced by Aβ1-42, reduced the deposition of Aβ1-42 in the hippocampus and maintained the integrity of synaptic structures in the hippocampus. Furthermore, in the Morris water maze test, α7 nAChR improved the learning and memory ability of the APP/PS1_DT mice. CONCLUSION Theα7 nAChR attenuate the toxic effect of Aβ in vivo and in vitro, eg reduced the deposition of Aβ in the hippocampus,prevented the synaptic loss, partially restored the expression levels of synaptic-associated proteins, and improved the learning and memory abilities of APP/PS1_DT mice. Our results also suggested that the α7 nAChR interacted with Aβby mediated by Ca M-Ca MKⅡ-CREB signalling pathway, which was imbalanced by deposition of Aβ.

摘要： 本发明提供了一种线性‑树状共聚物，所述线性‑树状共聚物的结构如式I所示。本发明还提供了一种给药系统，所述给药系统是上述线性‑树状共聚物与光敏剂发生偶联反应后得到的。研究表明，本发明的给药系统PPDP可在选择性溶剂中自组装形成尺寸均一、单分散性良好、稳定性高且带弱负电荷的纳米颗粒，其不仅具有优良的光物理特性，还能有效地产生ROS实现对肿瘤细胞的杀灭；其显著降低了光敏剂的皮肤光毒性；其不仅表现出较好的生物安全性、优异的荧光成像功能、血液长循环功能和长时间和高浓度的肿瘤靶向和富集效应，还具有显著的抗肿瘤活性，在制备抗肿瘤药物中显示出良好的应用前景。

摘要： 本发明提供了一种给药系统，所述给药系统中载有光敏剂焦脱镁叶绿酸a，所述给药系统的结构如式I所示。本发明还提供了一种光动力‑化疗联用给药系统，所述光动力‑化疗联用给药系统是以上述给药系统与阿霉素盐酸盐为原料制得的。本发明构建的光动力‑化疗联用的给药系统不仅进一步延长了药物的血液循环时间和滞留时间，提高了其在肿瘤部位的富集强度，还达到了肿瘤光动力和化疗协同增效的目的，同时也实现了对肿瘤治疗过程的实时监测和评估，最终在体内抗肿瘤实验中取得了显著的抑瘤效果。因此，本发明以PEG‑Peptide线性‑树状共聚物为载体材料构建的光动力‑化疗联用的给药系统是一种高安全且能有效地抑制恶性肿瘤的治疗手段，在制备抗肿瘤药物上具有很好的前景。

摘要： 本发明属于药物载体高分子聚合物材料技术领域，公开了一种酶敏感性两亲性聚酯(MePEG‑Peptide‑PER‑CL)纳米粒的制备方法。其制备分两步进行：1)两亲性聚酯(MePEG‑Peptide‑PER‑CL)的制备；2)姜黄素与MePEG‑Peptide‑PER‑CL按比例混合，加入丙酮溶解形成脂相；吐温‑85、泊洛沙姆‑188(P‑188)、聚乙烯醇(PVA)和十二烷基磺酸钠等表面活性剂溶于水形成水相；将脂相慢慢滴入水相，通过乳化溶剂挥发法搅拌0.5～8h，制备纳米粒。目的得到平均粒径100～280nm，多分散指数(PDI)小于0.30，包封率大于65％的姜黄素‑纳米粒。该类纳米给药载体可作为一种载姜黄素缓释载体系统，具有靶向性强、生物利用度高、毒副作用小等优点，适用于静脉注射、口服等多种给药方式。

摘要： 本发明提供了一种线性‑树状共聚物，所述线性‑树状共聚物的结构如式I所示。本发明还提供了一种给药系统，所述给药系统是上述线性‑树状共聚物与光敏剂发生偶联反应后得到的。研究表明，本发明的给药系统PPDP可在选择性溶剂中自组装形成尺寸均一、单分散性良好、稳定性高且带弱负电荷的纳米颗粒，其不仅具有优良的光物理特性，还能有效地产生ROS实现对肿瘤细胞的杀灭；其显著降低了光敏剂的皮肤光毒性；其不仅表现出较好的生物安全性、优异的荧光成像功能、血液长循环功能和长时间和高浓度的肿瘤靶向和富集效应，还具有显著的抗肿瘤活性，在制备抗肿瘤药物中显示出良好的应用前景。

摘要： 本发明提供了一种给药系统，所述给药系统中载有光敏剂焦脱镁叶绿酸a，所述给药系统的结构如式I所示。本发明还提供了一种光动力‑化疗联用给药系统，所述光动力‑化疗联用给药系统是以上述给药系统与阿霉素盐酸盐为原料制得的。本发明构建的光动力‑化疗联用的给药系统不仅进一步延长了药物的血液循环时间和滞留时间，提高了其在肿瘤部位的富集强度，还达到了肿瘤光动力和化疗协同增效的目的，同时也实现了对肿瘤治疗过程的实时监测和评估，最终在体内抗肿瘤实验中取得了显著的抑瘤效果。因此，本发明以PEG‑Peptide线性‑树状共聚物为载体材料构建的光动力‑化疗联用的给药系统是一种高安全且能有效地抑制恶性肿瘤的治疗手段，在制备抗肿瘤药物上具有很好的前景。

摘要： 本发明属于药物载体高分子聚合物材料技术领域，公开了一种酶敏感性两亲性聚酯(MePEG‑Peptide‑PER‑CL)纳米粒的制备方法。其制备分两步进行：1)两亲性聚酯(MePEG‑Peptide‑PER‑CL)的制备；2)姜黄素与MePEG‑Peptide‑PER‑CL按比例混合，加入丙酮溶解形成脂相；吐温‑85、泊洛沙姆‑188(P‑188)、聚乙烯醇(PVA)和十二烷基磺酸钠等表面活性剂溶于水形成水相；将脂相慢慢滴入水相，通过乳化溶剂挥发法搅拌0.5～8h，制备纳米粒。目的得到平均粒径100～280nm，多分散指数(PDI)小于0.30，包封率大于65％的姜黄素‑纳米粒。该类纳米给药载体可作为一种载姜黄素缓释载体系统，具有靶向性强、生物利用度高、毒副作用小等优点，适用于静脉注射、口服等多种给药方式。