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Recovery of Proteases and Protease Inhibitors from Ganoderma spp. Cultivated in Amazonian Lignocellulose Wastes. 从亚马逊木质纤维素废料中培养的灵芝中回收蛋白酶和蛋白酶抑制剂。
IF 1.9 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-24 DOI: 10.2174/0113892037297181240605112831
Larissa Ramos Chevreuil, Vítor Alves Pessoa, Giovanna Lima da Silva, Paula Romenya Dos Santos Gouvêa, Larissa Batista do Nascimento Soares, Ceci Sales-Campos

Background: Ganoderma spp. are a great source of bioactive molecules. The production and recovery of bioactive molecules vary according to strain, growth substrate, and extraction solution. Variations in protease and their inhibitors in basidiomata from a commercial strain (G. lingzhi) and an Amazonian isolate (Ganoderma sp.) cultivated in Amazonian lignocellulosic wastes and extracted with different solutions are plausible and were investigated in our study.

Methods: Basidiomata from cultivation in substrates based on açaí seed, guaruba-cedro sawdust and three lots of marupá sawdust were submitted to extraction in water, Tris-HCl, and sodium phosphate. Protein content, proteases, and protease inhibitors were estimated through different assays. The samples were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR).

Results: Tris-HCl provided higher protein extraction from Ganoderma sp. and higher caseinolytic, gelatinolytic, and fibrinolytic activity for G. lingzhi cultivated in açaí. Water extracts of Ganoderma sp., in general, exhibited higher trypsin and papain inhibitor activities compared to G. lingzhi. Extracts in Tris-HCl and sodium phosphate showed more intense protein bands in SDS-- PAGE, highlighting bands of molecular weights around 100, 50, and 30 kDa. FTIR spectra showed patterns for proteins in all extracts, with variation in transmittance according to substrate and extractor.

Conclusion: Water extract from Amazonian Ganoderma sp. cultivated in marupá wastes are promising as a source of protease inhibitors, while the Tris-HCL extract of G. lingzhi from açaí cultivation stands out as a source of proteases with fibrinolytic, caseinolytic, and gelatinolytic activities.

背景:灵芝是生物活性分子的重要来源。生物活性分子的产生和回收因菌株、生长基质和提取液的不同而不同。我们的研究调查了在亚马逊木质纤维素废物中培养并用不同溶液提取的商业菌株(灵芝)和亚马逊分离菌株(灵芝孢子菌)基原体中蛋白酶及其抑制剂的变化:在基于阿萨伊种子、瓜鲁巴-雪松锯屑和三个批次的马鲁巴锯屑的基质中培养出的基生菌在水、Tris-HCl 和磷酸钠中进行提取。通过不同的检测方法对蛋白质含量、蛋白酶和蛋白酶抑制剂进行了评估。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)和傅立叶变换红外光谱衰减全反射(FTIR-ATR)对样品进行表征:在阿萨伊中培养的灵芝具有更高的酪蛋白溶解、明胶溶解和纤维蛋白溶解活性。与灵芝相比,灵芝的水提取物一般具有更高的胰蛋白酶和木瓜蛋白酶抑制活性。三羟甲基丙烷和磷酸钠提取物在 SDS PAGE 中显示出更强的蛋白质条带,突出的是分子量在 100、50 和 30 kDa 左右的条带。傅立叶变换红外光谱显示了所有提取物中蛋白质的模式,透射率随底物和提取物的不同而变化:结论:在马鲁帕废物中栽培的亚马逊灵芝的水提取物有望成为蛋白酶抑制剂的来源,而从阿萨伊栽培的灵芝中提取的 Tris-HCL 提取物则是具有纤维蛋白溶解、酪蛋白溶解和明胶溶解活性的蛋白酶来源。
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引用次数: 0
Recent Advancement in Novel Wound Healing Therapies by Using Antimicrobial Peptides Derived from Humans and Amphibians 利用从人类和两栖动物中提取的抗菌肽开发新型伤口愈合疗法的最新进展
IF 2.8 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-06 DOI: 10.2174/0113892037288051240319052435
Trilochan Satapathy, Yugal Kishore, Ravindra Kumar Pandey, Shiv Shankar Shukla, Shiv Kumar Bhardwaj, Beena Gidwani
: The skin is the biggest organ in the human body. It is the first line of protection against invading pathogens and the starting point for the immune system. The focus of this review is on the use of amphibian-derived peptides and antimicrobial peptides (AMPs) in the treatment of wound healing. When skin is injured, a chain reaction begins that includes inflammation, the formation of new tissue, and remodelling of existing tissue to aid in the healing process. Collaborating with non-immune cells, resident and recruited immune cells in the skin remove foreign invaders and debris, then direct the repair and regeneration of injured host tissues. Restoration of normal structure and function requires the healing of damaged tissues. However, a major issue that slows wound healing is infection. AMPs are just one type of host-defense chemicals that have developed in multicellular animals to regulate the immune response and limit microbial proliferation in response to various types of biological or physical stress. Therefore, peptides isolated from amphibians represent novel therapeutic tools and approaches for regenerating damaged skin. Peptides that speed up the healing process could be used as therapeutic lead molecules in future research into novel drugs. AMPs and amphibian-derived peptides may be endogenous mediators of wound healing and treat non-life-threatening skin and epithelial lesions. Hence, this article describes different peptides used in wound healing, theirmethods of preparation, and their routes of administration.
:皮肤是人体最大的器官。它是抵御病原体入侵的第一道防线,也是免疫系统的起点。本综述的重点是两栖动物肽和抗菌肽(AMPs)在伤口愈合治疗中的应用。当皮肤受伤时,一连串的反应就会开始,包括炎症、新组织的形成和现有组织的重塑,以帮助伤口愈合。皮肤中的常驻和招募免疫细胞与非免疫细胞合作,清除外来入侵者和碎片,然后指导受伤宿主组织的修复和再生。恢复正常结构和功能需要受损组织的愈合。然而,减缓伤口愈合的一个主要问题是感染。AMPs 只是宿主防御化学物质的一种,它在多细胞动物中发展起来,用于调节免疫反应和限制微生物增殖,以应对各种类型的生物或物理压力。因此,从两栖动物体内分离出的肽是再生受损皮肤的新型治疗工具和方法。加速愈合过程的肽可作为治疗先导分子,用于未来的新型药物研究。AMPs 和两栖动物提取的肽可能是伤口愈合的内源性介质,可治疗不危及生命的皮肤和上皮损伤。因此,本文介绍了用于伤口愈合的各种肽、其制备方法和给药途径。
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引用次数: 0
Influences of Ipomoea batatas Anti-Cancer Peptide on Tomato Defense Genes Ipomoea batatas 抗癌肽对番茄防御基因的影响
IF 2.8 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-03 DOI: 10.2174/0113892037299818240408053000
Hsin-Hung Lin, Kuan-Hung Lin, Yung-Lin Tsai, Rong-Jane Chen, Yen-Chang Lin, Yu-Chi Chen
Aims: This study investigates the impact of IbACP (Ipomoea batatas anti-cancer peptide) on defense-related gene expression in tomato leaves, focusing on its role in plant defense mechanisms. Background: IbACP was isolated from sweet potato leaves, and it was identified as a peptide capable of inducing an alkalinization response in tomato suspension culture media. Additionally, IbACP was found to regulate the proliferation of human pancreatic adenocarcinoma cells. Objective: Elucidate IbACP's molecular influence on defense-related gene expression in tomato leaves using next-generation sequencing analysis. method: To assess the impact of IbACP on defense-related gene expression, transcriptome data were analyzed, encompassing various functional categories such as photosynthesis, metabolic processes, and plant defense. Semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis was employed to verify transcription levels of defense-related genes in tomato leaves treated with IbACP. Method: To assess the impact of IbACP on defense-related gene expression, transcriptome data were analyzed, encompassing various functional categories such as photosynthesis, metabolic processes, and plant defense. Semi-quantitative reverse-transcription polymerase chain reaction analysis was employed to verify transcription levels of defense-related genes in tomato leaves treated with IbACP for durations ranging from 0 h (control) to 24 h. Results: IbACP induced jasmonic acid-related genes (LoxD and AOS) at 2 h, with a significant up-regulation of salicylic acid-dependent gene NPR1 at 24 h. This suggested a temporal antagonistic effect between jasmonic acid and salicylic acid during the early hours of IbACP treatment. Downstream ethylene-responsive regulator genes (ACO1, ETR4, and ERF1) were consistently down-regulated by IbACP at all times. Additionally, IbACP significantly up-regulated the gene expressions of suberization-associated anionic peroxidases (TMP1 and TAP2) at all time points, indicating enhanced suberization of the plant cell wall to prevent pathogen invasion. Conclusion: IbACP enhances the synthesis of defense hormones and up-regulates downstream defense genes, improving the plant's resistance to biotic stresses.
目的:本研究调查了 IbACP(Ipomoea batatas 抗癌肽)对番茄叶片防御相关基因表达的影响,重点研究其在植物防御机制中的作用。背景:IbACP 从甘薯叶片中分离出来,经鉴定,它是一种能诱导番茄悬浮培养基碱化反应的多肽。此外,研究还发现 IbACP 能调节人类胰腺癌细胞的增殖。研究目的利用新一代测序分析,阐明 IbACP 对番茄叶片中防御相关基因表达的分子影响:为了评估 IbACP 对防御相关基因表达的影响,分析了包括光合作用、代谢过程和植物防御等各种功能类别的转录组数据。采用半定量反转录聚合酶链反应(RT-PCR)分析来验证 IbACP 处理的番茄叶片中防御相关基因的转录水平。方法:为了评估 IbACP 对防御相关基因表达的影响,分析了包括光合作用、代谢过程和植物防御等各种功能类别的转录组数据。采用半定量反转录聚合酶链反应分析法验证了番茄叶片在 IbACP 处理 0 小时(对照)至 24 小时期间防御相关基因的转录水平:这表明在 IbACP 处理的早期,茉莉酸和水杨酸之间存在时间上的拮抗作用。乙烯反应调控因子的下游基因(ACO1、ETR4 和 ERF1)在所有时间段都被 IbACP 一致下调。此外,IbACP 在所有时间点都显著上调了与琥珀化相关的阴离子过氧化物酶(TMP1 和 TAP2)的基因表达,这表明植物细胞壁的琥珀化作用增强,可防止病原体入侵。结论IbACP 可增强防御激素的合成并上调下游防御基因,从而提高植物对生物胁迫的抵抗力。
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引用次数: 0
Dominant Circulating Cell-free Mycobacterial Proteins in in-use Machining Fluid and their Antigenicity Potential 使用中加工液中的主要循环无细胞分枝杆菌蛋白及其抗原性潜力
IF 2.8 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-03 DOI: 10.2174/0113892037291635240405042554
Harish Chandra, Bethany Ahlers, Ying Wai Lam, Jagjit S. Yadav
Background: Occupational exposure to industrial Metalworking Fluid (MWF) colonized by Mycobacterium immunogenum (MI) has been associated with immune lung disease hypersensitivity pneumonitis (HP) in machinists. This warrants regular fluid monitoring for early detection of mycobacterial proteins, especially those with antigenic potential. Objective: To detect and identify dominant MI proteins and antigens directly from the field-drawn in-use MWF using an integrated immunoproteomic and immunoinformatic approach. Methods: An MI-positive MWF selected by DNA-based screening of several field-drawn MWF samples were cultured to isolate the colonizing strain and profiled for dominant circulating cell- free (ccf) MI proteins, including antigens using an integrated immunoproteomic (1D- and 2Dgel fractionation of seroreactivity proteins combined with shotgun proteomic analysis using LC-MS/ MS) and immunoinformatic strategy. Results: A new MI strain (MJY-27) was identified. The gel fractionated MI protein bands (1Dgel) or spots (2D-gel) seroreactive with anti-MI sera probes (Rabbit and Patient sera) yielded 86 MI proteins, 29 of which showed peptide abundance. T-cell epitope analysis revealed high (90-100%) binding frequency for HLA-I& II alleles for 13 of the 29 proteins. Their antigenicity analysis revealed the presence of 6 to 37 antigenic determinants. Interestingly, one of the identified candidates corresponded to an experimentally validated strong B- and T-cell antigen (AgD) from our laboratory culture-based studies. result: A new MI strain (MJY-27) was identified. The gel fractionated MI protein bands (1D-gel) or spots (2D-gel) seroreactive with anti-MI sera probes (Rabbit and Patient sera) yielded 86 MI proteins, 29 of which showed peptide abundance. T-cell epitope analysis revealed high (90-100%) binding frequency for HLA-I&amp; II alleles for 13 of the 29 proteins. Their antigenicity analysis revealed presence of 6 to 37 antigenic determinants. Interestingly, one of the identified candidates corresponded to an experimentally validated strong B- and T- cell antigen (AgD) from our laboratory culture-based studies. Conclusion: This first report on dominant proteins, including putative antigens of M. immunogenum prevalent in field in-use MWF, is a significant step towards the overall goal of developing fluid monitoring for exposure and disease risk assessment for HP development in machining environments. conclusion: This first report on dominant proteins including putative antigens of M. immunogenum prevalent in field in-use MWF is a significant step towards the overall goal of development of fluid monitoring for exposure and disease risk assessment for HP development in machining environments.
背景:机械师在工作中接触到由免疫分枝杆菌(MI)定植的工业金属加工液(MWF)与免疫性肺部疾病超敏性肺炎(HP)有关。因此,有必要对金属加工液进行定期监测,以便及早发现分枝杆菌蛋白,尤其是具有抗原潜力的分枝杆菌蛋白。目标:检测并确定主要的分枝杆菌蛋白采用免疫蛋白组学和免疫形式学综合方法,直接从现场抽取的使用中的 MWF 中检测和鉴定主要的分枝杆菌蛋白和抗原。研究方法:通过对多个野外提取的 MWF 样品进行 DNA 筛选,筛选出 MI 阳性的 MWF,对其进行培养以分离出定植菌株,并使用综合免疫蛋白组学(血清反应蛋白的一维和二维凝胶分馏,结合使用 LC-MS/ MS 的霰弹枪蛋白质组分析)和免疫形式化策略分析主要的循环游离细胞 (ccf) MI 蛋白,包括抗原。结果:确定了一种新的 MI 株系(MJY-27)。用抗 MI 血清探针(兔血清和患者血清)进行血清反应的凝胶分馏 MI 蛋白带(1D-凝胶)或点(2D-凝胶)得到了 86 个 MI 蛋白,其中 29 个显示了肽丰度。T细胞表位分析显示,29种蛋白质中有13种与HLA-I& II等位基因的结合频率很高(90%-100%)。其抗原性分析表明存在 6 至 37 个抗原决定因子。有趣的是,其中一个候选抗原与我们实验室培养研究中实验验证的强 B 细胞和 T 细胞抗原(AgD)相对应:确定了一种新的 MI 菌株(MJY-27)。用抗 MI 血清探针(兔血清和患者血清)对凝胶分馏的 MI 蛋白带(1D-凝胶)或点(2D-凝胶)进行血清反应,得到了 86 个 MI 蛋白,其中 29 个显示了肽丰度。T细胞表位分析显示,29种蛋白质中有13种与HLA-I&amp;II等位基因的结合频率很高(90%-100%)。其抗原性分析表明存在 6 至 37 个抗原决定因子。有趣的是,其中一种候选蛋白与我们实验室培养研究中实验验证的强 B 细胞和 T 细胞抗原(AgD)相对应。结论:这份关于主要蛋白质(包括现场使用中的 MWF 中普遍存在的免疫原疟原虫的假定抗原)的首次报告,是朝着为机械加工环境中的 HP 开发流体接触监测和疾病风险评估的总体目标迈出的重要一步:该报告首次介绍了野外使用的 MWF 中普遍存在的主要蛋白质(包括免疫原疟原虫的假定抗原),这是为机械加工环境中的 HP 开发开发流体监测暴露和疾病风险评估总体目标迈出的重要一步。
{"title":"Dominant Circulating Cell-free Mycobacterial Proteins in in-use Machining Fluid and their Antigenicity Potential","authors":"Harish Chandra, Bethany Ahlers, Ying Wai Lam, Jagjit S. Yadav","doi":"10.2174/0113892037291635240405042554","DOIUrl":"https://doi.org/10.2174/0113892037291635240405042554","url":null,"abstract":"Background: Occupational exposure to industrial Metalworking Fluid (MWF) colonized by Mycobacterium immunogenum (MI) has been associated with immune lung disease hypersensitivity pneumonitis (HP) in machinists. This warrants regular fluid monitoring for early detection of mycobacterial proteins, especially those with antigenic potential. Objective: To detect and identify dominant MI proteins and antigens directly from the field-drawn in-use MWF using an integrated immunoproteomic and immunoinformatic approach. Methods: An MI-positive MWF selected by DNA-based screening of several field-drawn MWF samples were cultured to isolate the colonizing strain and profiled for dominant circulating cell- free (ccf) MI proteins, including antigens using an integrated immunoproteomic (1D- and 2Dgel fractionation of seroreactivity proteins combined with shotgun proteomic analysis using LC-MS/ MS) and immunoinformatic strategy. Results: A new MI strain (MJY-27) was identified. The gel fractionated MI protein bands (1Dgel) or spots (2D-gel) seroreactive with anti-MI sera probes (Rabbit and Patient sera) yielded 86 MI proteins, 29 of which showed peptide abundance. T-cell epitope analysis revealed high (90-100%) binding frequency for HLA-I&amp; II alleles for 13 of the 29 proteins. Their antigenicity analysis revealed the presence of 6 to 37 antigenic determinants. Interestingly, one of the identified candidates corresponded to an experimentally validated strong B- and T-cell antigen (AgD) from our laboratory culture-based studies. result: A new MI strain (MJY-27) was identified. The gel fractionated MI protein bands (1D-gel) or spots (2D-gel) seroreactive with anti-MI sera probes (Rabbit and Patient sera) yielded 86 MI proteins, 29 of which showed peptide abundance. T-cell epitope analysis revealed high (90-100%) binding frequency for HLA-I&amp;amp; II alleles for 13 of the 29 proteins. Their antigenicity analysis revealed presence of 6 to 37 antigenic determinants. Interestingly, one of the identified candidates corresponded to an experimentally validated strong B- and T- cell antigen (AgD) from our laboratory culture-based studies. Conclusion: This first report on dominant proteins, including putative antigens of M. immunogenum prevalent in field in-use MWF, is a significant step towards the overall goal of developing fluid monitoring for exposure and disease risk assessment for HP development in machining environments. conclusion: This first report on dominant proteins including putative antigens of M. immunogenum prevalent in field in-use MWF is a significant step towards the overall goal of development of fluid monitoring for exposure and disease risk assessment for HP development in machining environments.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Carboxylic Group Functionalized Carbon Quantum Dots inhibit Hen Egg White Lysozyme Amyloidogenesis, leading to the Formation of Spherical Aggregates with Reduced Toxicity and ROS Generation. 羧基功能化碳量子点可抑制母鸡卵白溶菌酶淀粉样蛋白生成,从而形成球形聚集体,降低毒性和 ROS 生成。
IF 2.8 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-24 DOI: 10.2174/0113892037294778240328041907
M. P. Prabhu, Shreya Chrungoo, N. Sarkar
INTRODUCTIONProteinopathies are a group of diseases where the protein structure has been altered. These alterations are linked to the production of amyloids, which are persistent, organized clumps of protein molecules through inter-molecular interactions. Several disorders, including Alzheimer's and Parkinson's, have been related to the presence of amyloids. Highly ordered beta sheets or beta folds are characteristic of amyloids; these structures can further self- -assemble into stable fibrils.METHODProtein aggregation is caused by a wide variety of environmental and experimental factors, including mutations, high pH, high temperature, and chemical modification. Despite several efforts, a cure for amyloidosis has yet to be found. Due to its advantageous semi-conducting characteristics, unique optical features, high surface area-to-volume ratio, biocompatibility, etc., carbon quantum dots (CQDs) have lately emerged as key instruments for a wide range of biomedical applications. To this end, we have investigated the effect of CQDs with a carboxyl group on their surface (CQD-CA) on the in vitro amyloidogenesis of hen egg white lysozyme (HEWL).RESULTBy generating a stable compound that is resistant to fibrillation, our findings show that CQD-CA can suppress amyloid and disaggregate HEWL. In addition, CQD-CA caused the creation of non-toxic spherical aggregates, which generated much less reactive oxygen species (ROS).CONCLUSIONOverall, our results show that more research into amyloidosis treatments, including surface functionalized CQDs, is warranted.
简介蛋白质病是一组蛋白质结构发生改变的疾病。这些改变与淀粉样蛋白的产生有关,淀粉样蛋白是蛋白质分子通过分子间相互作用而形成的持久的、有组织的团块。包括阿尔茨海默氏症和帕金森氏症在内的多种疾病都与淀粉样蛋白的存在有关。高度有序的贝塔片或贝塔折叠是淀粉样蛋白的特征;这些结构可进一步自我组装成稳定的纤维。尽管经过多次努力,但淀粉样变性的治疗方法仍未找到。碳量子点(CQDs)因其优越的半导电特性、独特的光学特征、高表面积体积比、生物相容性等优点,近年来已成为广泛生物医学应用的关键工具。为此,我们研究了表面带有羧基的碳量子点(CQD-CA)对母鸡卵白溶菌酶(HEWL)体外淀粉样蛋白生成的影响。结果表明,通过生成一种抗纤维化的稳定化合物,CQD-CA 可以抑制淀粉样蛋白并分解 HEWL。此外,CQD-CA 还能产生无毒的球形聚集体,其产生的活性氧(ROS)也要少得多。总之,我们的研究结果表明,有必要对淀粉样变性治疗方法(包括表面功能化 CQDs)进行更多研究。
{"title":"Carboxylic Group Functionalized Carbon Quantum Dots inhibit Hen Egg White Lysozyme Amyloidogenesis, leading to the Formation of Spherical Aggregates with Reduced Toxicity and ROS Generation.","authors":"M. P. Prabhu, Shreya Chrungoo, N. Sarkar","doi":"10.2174/0113892037294778240328041907","DOIUrl":"https://doi.org/10.2174/0113892037294778240328041907","url":null,"abstract":"INTRODUCTION\u0000Proteinopathies are a group of diseases where the protein structure has been altered. These alterations are linked to the production of amyloids, which are persistent, organized clumps of protein molecules through inter-molecular interactions. Several disorders, including Alzheimer's and Parkinson's, have been related to the presence of amyloids. Highly ordered beta sheets or beta folds are characteristic of amyloids; these structures can further self- -assemble into stable fibrils.\u0000\u0000\u0000METHOD\u0000Protein aggregation is caused by a wide variety of environmental and experimental factors, including mutations, high pH, high temperature, and chemical modification. Despite several efforts, a cure for amyloidosis has yet to be found. Due to its advantageous semi-conducting characteristics, unique optical features, high surface area-to-volume ratio, biocompatibility, etc., carbon quantum dots (CQDs) have lately emerged as key instruments for a wide range of biomedical applications. To this end, we have investigated the effect of CQDs with a carboxyl group on their surface (CQD-CA) on the in vitro amyloidogenesis of hen egg white lysozyme (HEWL).\u0000\u0000\u0000RESULT\u0000By generating a stable compound that is resistant to fibrillation, our findings show that CQD-CA can suppress amyloid and disaggregate HEWL. In addition, CQD-CA caused the creation of non-toxic spherical aggregates, which generated much less reactive oxygen species (ROS).\u0000\u0000\u0000CONCLUSION\u0000Overall, our results show that more research into amyloidosis treatments, including surface functionalized CQDs, is warranted.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140664139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive Overview of Treponema pallidum Outer Membrane Proteins. 苍白螺旋体外膜蛋白综合概述
IF 2.8 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-24 DOI: 10.2174/0113892037293502240328042224
Sirui Wu, Lan Luo, Fei Ye, Yuanfang Wang, Dongdong Li
Treponema pallidum, the causative agent of syphilis, is a sexually transmitted microorganism that exhibits remarkable motility capabilities, allowing it to affect various systems. Despite its structural resemblance to gram-negative bacteria due to its dual-membrane, T. pallidum possesses a lower abundance of outer membrane proteins (OMPs), which enables it to effectively conceal itself. This review presents a comprehensive analysis of the clinical diagnostic potential associated with the OMPs of T. pallidum. Furthermore, the known OMPs in T. pallidum that are responsible for mediating host interactions have been progressively elucidated. This review aims to shed light on the pathogenesis of syphilis, encompassing aspects such as vascular inflammation, chancre self-healing, neuroinvasion, and reinfection. Additionally, this review offers a detailed overview of the current state and prospects of development in the field of syphilis vaccines, with the ultimate goal of establishing a foundation for understanding the pathogenesis and implementing effective prevention strategies against syphilis.
苍白螺旋体是梅毒的病原体,是一种通过性传播的微生物,具有显著的运动能力,可以影响各种系统。尽管其双膜结构与革兰氏阴性菌相似,但苍白螺旋体拥有较少的外膜蛋白(OMPs),这使其能够有效地隐藏自己。本综述全面分析了与苍白螺旋体外膜蛋白相关的临床诊断潜力。此外,苍白螺旋体中负责介导宿主相互作用的已知 OMPs 也已被逐步阐明。本综述旨在阐明梅毒的发病机制,包括血管炎症、硬下疳自愈、神经入侵和再感染等方面。此外,本综述还详细概述了梅毒疫苗领域的现状和发展前景,最终目的是为了解梅毒的发病机制和实施有效的预防策略奠定基础。
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引用次数: 0
Knockdown of Ubiquitin-Conjugating Enzyme E2 T Abolishes the Progression of Head and Neck Squamous Cell Carcinoma by Inhibiting NF-Κb Signaling and inducing Ferroptosis 通过抑制NF-Κb信号和诱导铁凋亡敲除泛素结合酶E2 T可阻止头颈部鳞状细胞癌的进展
IF 2.8 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-15 DOI: 10.2174/0113892037287640240322084946
Feng Cai, Hongbo Xu, Shilong Song, Gengming Wang, Yajun Zhang, Jing Qian, Lu Xu
Background: Ubiquitin-conjugating enzyme 2T (UBE2T) has been reported to be associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. However, the understanding of its regulatory role in the carcinogenesis of Head And Neck Squamous Cell Carcinoma (HNSC) is limited. background: Ubiquitin-conjugating enzyme 2T (UBE2T) has been associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. Methods: UBE2T expression in HNSC patient samples and the correlation between its expression and patients’ survival rates were evaluated using The Cancer Genome Atlas (TCGA) database. Cell survival and proliferation were investigated in UM-SCC1 and UM-SCC15 cells infected with control and shUBE2T lentivirus. The xenograft mouse model was established using UM-SCC15 cells to examine HNSC tumorigenesis with or without UBE2T. Western blot, qRT-PCR, and ferroptosis assays were carried out to disclose the interaction between UBE2T and NF-κB signaling and ferroptosis. objective: To study the understanding of its regulatory role in the carcinogenesis of head and neck squamous cell carcinoma (HNSC). Results: The increased expression of UBE2T was noted in tumor tissues of patients with HNSC, correlating with a significantly reduced overall survival time in this patient cohort. Knockdown of UBE2T inhibited HNSC tumorigenesis and tumor growth. Mechanistically, inhibition of UBE2T suppressed NF-κB signaling and induced ferroptosis in HNSC. method: UBE2T expression in HNSC patient samples and the correlation between its expression and patients’ survival rates were evaluated using TCGA database. Cell survival and proliferation were investigated in UM-SCC1 and UM-SCC15 cells infected with control and shUBE2T-derived lentivirus. Cell line-derived xenograft mouse model was established using UM-SCC15 cells to examine HNSC tumorigenesis with or without UBE2T. Western blot, qRT-PCR, and ferroptosis assays were carried out to disclose the interaction between UBE2T and NF-κB signaling and ferroptosis. Conclusion: Our study underscores the multifaceted role of UBE2T in HNSC, illuminating its potential as a biomarker and therapeutic target. result: High expression of UBE2T were consistently observed in HNSC tumor tissues, which correlated with a significantly shortened overall survival time among HNSC patients. Knockdown of UBE2T inhibited HNSC tumorigenesis and tumor growth. Mechanistically, inhibition of UBE2T suppressed NF-κB signaling activation and induced ferroptosis in HNSC.
背景:据报道,泛素结合酶 2T(UBE2T)与多种癌症类型中不受控制的细胞生长和肿瘤发生有关。然而,人们对其在头颈部鳞状细胞癌(HNSC)发生过程中的调控作用了解有限:泛素结合酶 2T (UBE2T) 与多种癌症类型中不受控制的细胞生长和肿瘤发生有关。方法:利用癌症基因组图谱(TCGA)数据库评估 UBE2T 在 HNSC 患者样本中的表达及其与患者生存率之间的相关性。研究了用对照组和 shUBE2T 慢病毒感染的 UM-SCC1 和 UM-SCC15 细胞的存活和增殖情况。利用 UM-SCC15 细胞建立了异种移植小鼠模型,以检测有无 UBE2T 的 HNSC 肿瘤发生。进行了 Western 印迹、qRT-PCR 和铁突变试验,以揭示 UBE2T 与 NF-κB 信号传导和铁突变之间的相互作用:研究了解其在头颈部鳞状细胞癌(HNSC)发生过程中的调控作用。结果:UBE2T在 HNSC 患者的肿瘤组织中发现 UBE2T 的表达增加,这与该患者群的总生存时间显著缩短有关。敲除 UBE2T 可抑制 HNSC 肿瘤发生和肿瘤生长。从机制上讲,抑制 UBE2T 可抑制 NF-κB 信号传导并诱导 HNSC 中的铁变态反应:利用 TCGA 数据库评估 UBE2T 在 HNSC 患者样本中的表达及其与患者生存率之间的相关性。用对照组和 shUBE2T 衍生慢病毒感染 UM-SCC1 和 UM-SCC15 细胞,研究细胞存活和增殖情况。利用 UM-SCC15 细胞建立了细胞系衍生异种移植小鼠模型,以研究有无 UBE2T 的 HNSC 肿瘤发生情况。通过Western印迹、qRT-PCR和铁变态反应实验揭示了UBE2T与NF-κB信号传导和铁变态反应之间的相互作用。结论我们的研究强调了 UBE2T 在 HNSC 中的多方面作用,揭示了其作为生物标志物和治疗靶点的潜力:在 HNSC 肿瘤组织中持续观察到 UBE2T 的高表达,这与 HNSC 患者总生存时间的显著缩短相关。敲除 UBE2T 可抑制 HNSC 肿瘤发生和肿瘤生长。从机制上讲,抑制 UBE2T 可抑制 HNSC 中 NF-κB 信号的激活并诱导铁变态反应。
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引用次数: 0
Targeted Delivery of Diphtheria Toxin into VEGFR1/VEGFR2 Overexpressing Cells Induces Anti-angiogenesis Activity 向血管内皮生长因子受体1/血管内皮生长因子受体2过表达细胞靶向输送白喉毒素可诱导抗血管生成活性
IF 2.8 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-20 DOI: 10.2174/0113892037292385240222074908
Fatemeh Kazemi-Lomedasht, Farzad Taghizadeh-Hesary, Zahra Faal, Mahdi Behdani
Background: Vascular Endothelial Growth Factor Receptors (VEGFR1 and VEGFR2) are tyrosine kinase receptors expressed on endothelial cells and tumor vessels and play an important role in angiogenesis. In this study, three repeats of VEGFR1 and VEGFR2 binding peptide (VGB3) were genetically fused to the truncated diphtheria toxin (TDT), and its in vitro activity was evaluated. Methods: The recombinant construct (TDT-triVGB3) was expressed in bacteria cells and purified with nickel affinity chromatography. The binding capacity and affinity of TDT-triVGB3 were evaluated using the enzyme-linked immunosorbent assay. The inhibitory activity of TDT-triVGB3 on viability, migration, and tube formation of human endothelial cells was evaluated using MTT, migration, and tube formation assays. Results: TDT-triVGB3 selectively detected VEGFR1 and VEGFR2 with high affinity in an enzyme- linked immunosorbent assay and significantly inhibited viability, migration, and tube formation of human endothelial cells. Conclusion: The developed TDT-triVGB3 is potentially a novel agent for targeting VEGFR1/ VEGFR2 over-expressing cancer cells.
背景:血管内皮生长因子受体(VEGFR1 和 VEGFR2)是内皮细胞和肿瘤血管上表达的酪氨酸激酶受体,在血管生成中发挥着重要作用。本研究将 VEGFR1 和 VEGFR2 结合肽(VGB3)的三个重复序列与截短的白喉毒素(TDT)进行基因融合,并对其体外活性进行了评估。方法在细菌细胞中表达重组构建体(TDT-triVGB3),并用镍亲和层析法纯化。用酶联免疫吸附试验评估了 TDT-triVGB3 的结合能力和亲和力。使用 MTT、迁移和管形成试验评估了 TDT-triVGB3 对人内皮细胞活力、迁移和管形成的抑制活性。结果显示在酶联免疫吸附试验中,TDT-triVGB3 能以高亲和力选择性地检测到血管内皮生长因子受体 1 和血管内皮生长因子受体 2,并能显著抑制人内皮细胞的活力、迁移和管形成。结论开发的 TDT-triVGB3 有可能成为靶向 VEGFR1/ VEGFR2 过度表达癌细胞的新型药物。
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引用次数: 0
The Disulfide Bond-Mediated Cyclization of Oral Peptides 二硫键介导的口服肽环化反应
IF 2.8 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-29 DOI: 10.2174/0113892037280719231214095428
Chenguang Yao, Guoguo Ye, Qing Yang, Zhenwang Chen, Minghui Yang
: ‘Structure determines function’ is a consensus in the current biological community, but the structural characteristics corresponding to a certain function have always been a hot field of scientific exploration. A peptide is a bio-active molecule that is between the size of an antibody and a small molecule. Still, the gastrointestinal barrier and the physicochemical properties of peptides have always limited the oral administration of peptides. Therefore, we analyze the main ways oral peptide conversion strategies of peptide modification and permeation enhancers. Based on our analysis of the structure of natural oral peptides, which can be absorbed through the gastrointestinal tract, we believe that the design strategy of natural stapled peptides based on disulfide bonds is good for oral peptide design. This cannot only be used to identify anti-gastrointestinal digestive structural proteins in nature but also provide a solid structural foundation for the construction of new oral peptide drugs.
结构决定功能 "是当前生物学界的共识,但与某种功能相对应的结构特征一直是科学探索的热点领域。多肽是一种生物活性分子,其大小介于抗体和小分子之间。然而,多肽的胃肠道屏障和理化特性一直限制着多肽的口服给药。因此,我们分析了多肽修饰和渗透促进剂的主要口服多肽转化策略。基于对天然口服肽结构的分析,我们认为基于二硫键的天然钉合肽设计策略有利于口服肽的设计。这不仅可用于鉴定自然界中的抗胃肠道消化结构蛋白,还可为构建新型口服多肽药物提供坚实的结构基础。
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引用次数: 0
Current Stage and Future Perspectives for Homology Modeling, Molecular Dynamics Simulations, Machine Learning with Molecular Dynamics, and Quantum Computing for Intrinsically Disordered Proteins and Proteins with Intrinsically Disordered Regions 同源性建模、分子动力学模拟、分子动力学机器学习以及量子计算在本质上无序蛋白质和具有本质上无序区蛋白质方面的当前阶段和未来前景
IF 2.8 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-02 DOI: 10.2174/0113892037281184231123111223
Orkid Coskuner-Weber, Vladimir N. Uversky
The structural ensembles of intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs) cannot be easily characterized using conventional experimental techniques. Computational techniques complement experiments and provide useful insights into the structural ensembles of IDPs and proteins with IDRs. Herein, we discuss computational techniques such as homology modeling, molecular dynamics simulations, machine learning with molecular dynamics, and quantum computing that can be applied to the studies of IDPs and hybrid proteins with IDRs. We also provide useful future perspectives for computational techniques that can be applied to IDPs and hybrid proteins containing ordered domains and IDRs.
使用传统的实验技术难以表征本征无序蛋白(IDPs)和具有本征无序区(IDRs)的蛋白质的结构组合。计算技术是对实验的补充,能为了解本质无序蛋白和具有本质无序区的蛋白质的结构组合提供有用的见解。在此,我们将讨论可应用于 IDPs 和具有 IDRs 的混合蛋白质研究的计算技术,如同源建模、分子动力学模拟、分子动力学机器学习和量子计算。我们还为可应用于含有有序结构域和 IDR 的 IDPs 和杂交蛋白的计算技术提供了有用的未来展望。
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引用次数: 0
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Current protein & peptide science
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