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The Role of circRNA-miRNA-mRNA Regulatory Network and its Potential Biomarker Function in Colorectal Cancer. circRNA-miRNA-mRNA调控网络在结直肠癌中的作用及其潜在的生物标志物功能
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.2174/0109298665263662231108053654
Xutang Fu, Pengpeng Chen, Hao Wang

Background: Revealing the process and mechanism of colorectal cancer will facilitate the discovery of new biomarkers and contribute to the development of targeted drugs.

Objectives: This study aimed to explore the potentially functional circRNA-miRNA-mRNA network in colorectal cancer (CRC), and further explore its mechanism.

Methods: Bioinformatics analysis was used to identify the differentially expressed circRNAs and mRNAs. Gene set enrichment analysis and KEGG pathways analysis were used to screen out the differentially expressed genes and observe crucial pathways that might have a strong association with CRC. Then, a network targeting circRNA, miRNA, and mRNA has been built by using the Cytoscape software. In addition, the expression of circRNA_0001573, miR-382-5p, and FZD3 was detected by qRT-PCR in CRC tissues and cells (SW480, HCT116, and HT29).

Results: Abnormal expressions of circRNAs and mRNAs were obtained by bioinformatics analysis and visualized by Volcano plot and Heatmap. A series of highly correlated pathways were enriched by KEGG analysis. The interaction network of circRNA_0001573/miR-382-5p/FZD3 axis was predicted. The expressions of circRNA_0001573 and FZD3 were highly upregulated and the miR- 382-5p expression level was decreased in CRC tissues and cell lines (SW480, HCT116, and HT29).

Conclusion: Our study suggests that circRNA_0001573 and circRNA_0001573/miR-382-5p/FZD3 regulatory networks might provide a potential diagnosis for colorectal cancer.

背景:揭示结直肠癌的发病过程和机制将有助于发现新的生物标志物,有助于开发靶向药物。目的:本研究旨在探索结直肠癌(CRC)中潜在功能的circRNA-miRNA-mRNA网络,并进一步探讨其作用机制。方法:采用生物信息学分析鉴定差异表达的环状rna和mrna。通过基因集富集分析和KEGG通路分析,筛选差异表达基因,观察可能与结直肠癌密切相关的关键通路。然后,利用Cytoscape软件构建了一个靶向circRNA、miRNA和mRNA的网络。此外,通过qRT-PCR检测CRC组织和细胞(SW480、HCT116和HT29)中circRNA_0001573、miR-382-5p和FZD3的表达。结果:通过生物信息学分析获得环状rna和mrna的异常表达,并通过Volcano图和Heatmap可视化。KEGG分析富集了一系列高度相关的通路。预测circRNA_0001573/miR-382-5p/FZD3轴的相互作用网络。circRNA_0001573和FZD3在CRC组织和细胞系(SW480、HCT116和HT29)中表达高度上调,miR382-5p表达水平降低。结论:我们的研究表明circRNA_0001573和circRNA_0001573/miR-382-5p/FZD3调控网络可能为结直肠癌提供潜在的诊断。
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引用次数: 0
The Emerging Roles of circRNAs in Papillary Thyroid Carcinoma: Molecular Mechanisms and Biomarker Potential. 环状rna在甲状腺乳头状癌中的新作用:分子机制和生物标志物潜力。
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.2174/0929866530666230804104057
Haihan Ye, Xiaoyang Sun, Qianyun Ding, Enyu Yang, Shuo Zhao, Xiaowei Fan, Meiyu Fang, Xianfeng Ding

Papillary thyroid carcinoma (PTC) is a common endocrine malignant tumor. The incidence of PTC has increased in the past decades and presents a younger trend. Accumulating evidence indicates that circular RNAs (circRNAs), featured with non-linear, closed-loop structures, play pivotal roles in tumorigenesis and regulate cell biological processes, such as proliferation, migration, and invasion, by acting as microRNA (miRNA) sponges. Additionally, due to their unique stability, circRNAs hold promising potential as diagnostic biomarkers and effective therapeutic targets for PTC treatment. In this review, we systematically arrange the expression level of circRNAs, related clinical characteristics, circRNA-miRNA-mRNA regulatory network, and molecular mechanisms. Furthermore, related signaling pathways and their potential ability of diagnostic biomarkers and therapeutic targets are discussed, which might provide a new strategy for PTC diagnosis, monitoring, and prognosis.

甲状腺乳头状癌是一种常见的内分泌恶性肿瘤。近几十年来,PTC发病率呈上升趋势,且呈低龄化趋势。越来越多的证据表明,环状rna (circRNAs)具有非线性、闭环结构的特点,在肿瘤发生过程中发挥关键作用,并通过充当microRNA (miRNA)海绵来调节细胞增殖、迁移和侵袭等生物学过程。此外,由于其独特的稳定性,环状rna作为PTC治疗的诊断生物标志物和有效治疗靶点具有很大的潜力。在这篇综述中,我们系统地梳理了circrna的表达水平、相关临床特征、circRNA-miRNA-mRNA调控网络以及分子机制。此外,本文还讨论了相关信号通路及其作为诊断生物标志物和治疗靶点的潜在能力,为PTC的诊断、监测和预后提供了新的策略。
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引用次数: 0
Heterologous Expression and Function of Cholesterol Oxidase: A Review. 胆固醇氧化酶的异源表达及功能研究进展
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.2174/0929866530666230525162545
Haoran Cui, Mohamad Hesam Shahrajabian, Yue Kuang, Haiyan Zhang, Wenli Sun

Cholesterol was first found in gallstones as an animal sterol; hence it is called cholesterol. Cholesterol oxidase is the chief enzyme in the process of cholesterol degradation. Its role is obtained by the coenzyme FAD, which catalyzes the isomerization and oxidation of cholesterol to produce cholesteric 4-ene-3-ketone and hydrogen peroxide at the same time. Recently, a great advance has been made in the discovery of the structure and function of cholesterol oxidase, and it has proven added value in clinical discovery, medical care, food and biopesticides development and other conditions. By recombinant DNA technology, we can insert the gene in the heterologous host. Heterologous expression (HE) is a successful methodology to produce enzymes for function studies and manufacturing applications, where Escherichia coli has been extensively used as a heterologous host because of its economical cultivation, rapid growth, and efficiency in offering exogenous genes. Heterologous expression of cholesterol oxidase has been considered for several microbial sources, such as Rhodococcus equi, Brevibacterium sp., Rhodococcus sp., Streptomyces coelicolor, Burkholderia cepacia ST-200, Chromobacterium, and Streptomyces spp. All related publications of numerous researchers and scholars were searched in ScienceDirect, Scopus, PubMed, and Google Scholar. In this article, the present situation and promotion of heterologous expression of cholesterol oxidase, the role of protease, and the perspective of its possible applications were reviewed.

胆固醇最初是作为动物固醇在胆结石中发现的;因此它被称为胆固醇。胆固醇氧化酶是胆固醇降解过程中的主要酶。它的作用是由辅酶FAD获得的,它催化胆固醇的异构化和氧化,同时产生胆固醇甾体4-烯-3-酮和过氧化氢。近年来,胆固醇氧化酶的结构和功能的发现取得了很大的进展,并在临床发现、医疗保健、食品和生物农药开发等方面证明了它的附加价值。通过重组DNA技术,我们可以将该基因插入到异源宿主中。异源表达(HE)是一种成功的酶的功能研究和生产应用的方法,大肠杆菌因其经济的培养、快速的生长和提供外源基因的效率而被广泛用作异源宿主。胆固醇氧化酶的异源表达已被考虑用于几种微生物来源,如马红球菌、短杆菌、红球菌、彩色链霉菌、洋葱伯氏菌ST-200、嗜铬杆菌和链霉菌等。在ScienceDirect、Scopus、PubMed和Google Scholar中检索了众多研究人员和学者的相关出版物。本文综述了胆固醇氧化酶异种表达的研究现状、促进作用、蛋白酶的作用以及对其应用前景的展望。
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引用次数: 0
Ultrasonication Induced Alterations in Physicochemical and Functional Properties of Myosin. 超声诱导肌球蛋白理化和功能特性的改变。
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.2174/0929866530666230124093804
Rashid Saleem, Riaz Ahmad

Background: Several reports have indicated that ultrasonication can change the solubility of muscle proteins and improves the functional properties of meat and isolated muscle proteins. Moreover, available literature suggests that ultrasonication can significantly improve the gelling properties of muscle proteins.

Objectives: The present study was carried out to investigate the effect of low-frequency ultrasonication on the secondary structure of myosin and the impact of these structural changes on solubility and gelling ability.

Methods: Myosin from breast muscles (Pectoralis major) of broiler chicken was extracted and exposed to low-frequency ultrasonication for 30 min. Four aliquots collected at the interval of 5, 10, 20, and 30 min were analysed for change in ATPase activity, sulfhydryl content, surface hydrophobicity, alpha-helicity. The possible impact of these changes on heat-induced gelation was observed through electron micrographs.

Results: Ultrasonication reduced the enzymatic activity of myosin and increased the reactive sulfhydryl content. Decreased α-helicity and increased intrinsic fluorescence displayed significant structural changes at the secondary and tertiary levels. Myosin aggregation, as indicated by electron micrographs, showed a marked decrease. The microstructure of myosin gels displayed a distinct correlation with ultrasonication-induced structural changes. Furthermore, improved microstructure led to a significant increase in the water retention capacity of myosin gels.

Conclusion: In conclusion, ultrasonication of myosin caused a marked change in structure at the tertiary and secondary levels. Structural changes apparently confined within the globular head region and rod portion of myosin were displayed by reduced enzymatic activity and improved gelation/solubility. Results of our study convincingly showed that ultrasonication improved the microstructure of myosin gels resulting in increased WHC.

背景:一些报道表明,超声可以改变肌肉蛋白的溶解度,改善肉和分离肌肉蛋白的功能特性。此外,现有文献表明,超声可以显著改善肌肉蛋白的胶凝特性。目的:探讨低频超声对肌球蛋白二级结构的影响,以及这些结构变化对肌球蛋白溶解度和胶凝能力的影响。方法:从肉仔鸡胸肌(胸大肌)中提取肌球蛋白,经低频超声处理30min,分别于5、10、20、30min取4份,分析其atp酶活性、巯基含量、表面疏水性、α -螺旋度的变化。通过电子显微镜观察了这些变化对热诱导凝胶的可能影响。结果:超声处理降低了肌球蛋白的酶活性,提高了活性巯基含量。α-螺旋度降低,本征荧光增加,二级和三级结构发生显著变化。电镜显示肌凝蛋白聚集明显减少。肌球蛋白凝胶的微观结构与超声诱导的结构变化有明显的相关性。此外,微观结构的改善使肌球蛋白凝胶的保水能力显著提高。结论:超声可引起肌球蛋白三级和二级结构的明显改变。结构变化明显局限于肌球蛋白的球形头部区域和棒状部分,表现为酶活性降低和凝胶化/溶解度提高。我们的研究结果令人信服地表明,超声改善了肌球蛋白凝胶的微观结构,导致WHC增加。
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引用次数: 0
An Indicating Role of Antioxidant System Enzymes at the Stage of Active Structural Anomalies Formation in Karelian Birch (Betula pendula Roth var. carelica (Mercl.) Hämet-Ahti). 抗氧化系统酶在卡累利阿桦木(Betula pendula Roth var. carelica)活性结构异常形成阶段的指示作用Hamet-Ahti)。
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.2174/0929866530666230228113430
Kseniya Mihajlovna Nikerova, Natalia Alekseevna Galibina, Irina Nikolaevna Sofronova, Marina Nikolaevna Borodina, Yuliya Leonidovna Moshchenskaya, Tatiana Vladimirovna Tarelkina, Anna Vladimirovna Klimova, Ludmila Lyudvigovna Novitskaya

Introduction: A complex study of the antioxidant system enzymes (AOS) is an important subject of biochemical research; changes in the activity of these enzymes can be used as a biochemical marker of various processes in plants. At the same time, practically little attention has been paid to describing the regularities of these enzymatic reactions in different wood formation processes, such as xylogenesis. This article discusses the outcomes of different behaviors of AOS enzymes, which are involved in both the redistribution of the ROS balance and phenolic compounds at the early stages of wood formation in young plants of silver birch (Betula pendula Roth) with straight-grained wood and Karelian birch (Betula pendula Roth var. carelica (Merckl.) Hamet-Ahti) with non-figured and figured parts within the single trunk.

Background: Spectrophotometric determination of AOS enzymes' activity can be used as a biochemical marker in the different wood formation processes, including xylogenesis. In this study, we studied structural anomalies of the woody plant trunk of Karelian birch (Betula pendula Roth var. carelica (Merckl.) Hamet- Ahti).

Objective: This study aimed to study AOS enzymes' activity in 12-year-old plants of silver birch (Betula pendula Roth) with straight-grained wood and Karelian birch (Betula pendula Roth var. carelica (Merckl.) Hamet-Ahti) with non-figured and figured parts within the single trunk.

Methods: Plant tissues were ground in liquid nitrogen to a uniform mass and homogenized at 4°C in the buffer containing 50 mM HEPES (pH 7.5), 1 mM EDTA, 1 mM EGTA, 3 mM DTT, 5 mM MgCl2, and 0.5 mM PMSF. After 20 min extraction, the homogenate was centrifuged at 10000 g for 20 min (MPW-351R, Poland). The sediment was washed in the buffer thrice. The pooled supernatant and sediment were dialyzed at 4°C for 18-20 h against a tenfold diluted homogenization buffer. The enzymes' activity was determined spectrophotometrically (Spectrophotometer SF-2000, OKB Spectr, Russia). Proteins in the extracts were quantified by the method of Bradford.

Results: We observed different behaviors of the studied enzymes involved in both the redistribution of the ROS balance and phenolic compounds with subsequent lignification even at the early stages of wood formation in young plants and even in different trunk parts within a tree, which was consistent with results obtained earlier on adult plants. High SOD activity in the phloem compared to the activity in the xylem was accompanied by higher CAT activity. The POD/SOD ratio was significantly higher in the figured trunk parts in Karelian birch compared to other variants in the xylem and higher in Karelian birch plants compared to plants of common birch in the phloem. The CAT/POD ratio was significantly higher in plants with no signs of anomalies. The high POD and PPO

摘要抗氧化系统酶(AOS)的复杂研究是生物化学研究的一个重要课题;这些酶活性的变化可以作为植物各种过程的生化标志。与此同时,几乎很少有人注意描述这些酶反应在不同木材形成过程中的规律,如木质化。本文讨论了直纹白桦(Betula pendula Roth)和卡累利阿桦树(Betula pendula Roth var. carelica (Merckl.))幼树成材早期活性氧平衡和酚类化合物再分配中AOS酶不同行为的结果。Hamet-Ahti)在单个主干内具有非图形和图形部分。背景:分光光度法测定AOS酶活性可作为木材不同形成过程(包括木质学)的生化指标。本文对卡累利阿白桦(Betula pendula Roth var. carelica, Merckl.)木本植物树干的结构异常进行了研究。原作者- Ahti)。目的:研究直纹白桦(Betula pendula Roth)和卡累利阿桦木(Betula pendula Roth var. carelica (Merckl.)) 12年株AOS酶的活性。Hamet-Ahti)在单个主干内具有非图形和图形部分。方法:植物组织在液氮中研磨至均匀质量,并在4°C下均质,缓冲液中含有50 mM HEPES (pH 7.5), 1 mM EDTA, 1 mM EGTA, 3 mM DTT, 5 mM MgCl2和0.5 mM PMSF。提取20分钟后,匀浆10000 g离心20分钟(MPW-351R,波兰)。沉积物在缓冲液中被冲洗了三次。池中的上清和沉淀物在4°C下透析18-20 h,使用稀释10倍的均质缓冲液。用分光光度法测定酶的活性(分光光度计SF-2000, OKB光谱,俄罗斯)。用Bradford法定量提取液中的蛋白质。结果:我们观察到,即使在幼树木材形成的早期阶段,甚至在树木的不同树干部位,所研究的酶参与活性氧平衡和酚类化合物的再分配以及随后的木质化的不同行为,这与之前在成年植物上获得的结果一致。与木质部相比,韧皮部SOD活性较高,CAT活性也较高。在木质部中,卡累利阿桦树主干部分的POD/SOD比显著高于其他变异,在韧皮部中,卡累利阿桦树植株的POD/SOD比显著高于普通桦树植株。在没有异常迹象的植物中,CAT/POD比值显著高于其他植物。木质部有形和无形木质部韧皮部POD和PPO活性高可能与外质体转化酶活性高有关。结论:本研究表明,在卡累利阿桦树幼树形态树干部位结构异常活跃形成阶段,过氧化氢利用主要是由于POD活性的增加。花型植物主干中PPO活性的增加也可以被认为是结构异常形成的一个指标。同时,在发育异常木材的区域,POD/SOD比值升高,CAT/POD比值降低,说明超氧自由基和过氧化氢之间的平衡发生了微调,当这种平衡发生变化时,可能会调节木质部分化向增殖方向的重排。
{"title":"An Indicating Role of Antioxidant System Enzymes at the Stage of Active Structural Anomalies Formation in Karelian Birch (<i>Betula pendula</i> Roth var. <i>carelica</i> (Mercl.) Hämet-Ahti).","authors":"Kseniya Mihajlovna Nikerova,&nbsp;Natalia Alekseevna Galibina,&nbsp;Irina Nikolaevna Sofronova,&nbsp;Marina Nikolaevna Borodina,&nbsp;Yuliya Leonidovna Moshchenskaya,&nbsp;Tatiana Vladimirovna Tarelkina,&nbsp;Anna Vladimirovna Klimova,&nbsp;Ludmila Lyudvigovna Novitskaya","doi":"10.2174/0929866530666230228113430","DOIUrl":"https://doi.org/10.2174/0929866530666230228113430","url":null,"abstract":"<p><strong>Introduction: </strong>A complex study of the antioxidant system enzymes (AOS) is an important subject of biochemical research; changes in the activity of these enzymes can be used as a biochemical marker of various processes in plants. At the same time, practically little attention has been paid to describing the regularities of these enzymatic reactions in different wood formation processes, such as xylogenesis. This article discusses the outcomes of different behaviors of AOS enzymes, which are involved in both the redistribution of the ROS balance and phenolic compounds at the early stages of wood formation in young plants of silver birch (<i>Betula pendula</i> Roth) with straight-grained wood and Karelian birch (Betula pendula Roth var. <i>carelica</i> (Merckl.) Hamet-Ahti) with non-figured and figured parts within the single trunk.</p><p><strong>Background: </strong>Spectrophotometric determination of AOS enzymes' activity can be used as a biochemical marker in the different wood formation processes, including xylogenesis. In this study, we studied structural anomalies of the woody plant trunk of Karelian birch (<i>Betula pendula</i> Roth var. <i>carelica</i> (Merckl.) Hamet- Ahti).</p><p><strong>Objective: </strong>This study aimed to study AOS enzymes' activity in 12-year-old plants of silver birch (Betula pendula Roth) with straight-grained wood and Karelian birch (<i>Betula pendula</i> Roth var. <i>carelica</i> (Merckl.) Hamet-Ahti) with non-figured and figured parts within the single trunk.</p><p><strong>Methods: </strong>Plant tissues were ground in liquid nitrogen to a uniform mass and homogenized at 4°C in the buffer containing 50 mM HEPES (pH 7.5), 1 mM EDTA, 1 mM EGTA, 3 mM DTT, 5 mM MgCl2, and 0.5 mM PMSF. After 20 min extraction, the homogenate was centrifuged at 10000 g for 20 min (MPW-351R, Poland). The sediment was washed in the buffer thrice. The pooled supernatant and sediment were dialyzed at 4°C for 18-20 h against a tenfold diluted homogenization buffer. The enzymes' activity was determined spectrophotometrically (Spectrophotometer SF-2000, OKB Spectr, Russia). Proteins in the extracts were quantified by the method of Bradford.</p><p><strong>Results: </strong>We observed different behaviors of the studied enzymes involved in both the redistribution of the ROS balance and phenolic compounds with subsequent lignification even at the early stages of wood formation in young plants and even in different trunk parts within a tree, which was consistent with results obtained earlier on adult plants. High SOD activity in the phloem compared to the activity in the xylem was accompanied by higher CAT activity. The POD/SOD ratio was significantly higher in the figured trunk parts in Karelian birch compared to other variants in the xylem and higher in Karelian birch plants compared to plants of common birch in the phloem. The CAT/POD ratio was significantly higher in plants with no signs of anomalies. The high POD and PPO ","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9549813","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
Deuterium Solvent Kinetic Isotope Effect on Enzymatic Methyl Transfer Catalyzed by Catechol O-methyltransferase. 氘溶剂动力学同位素对邻苯二酚甲基转移酶催化甲基转移的影响。
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.2174/0929866530666230228100703
Zhao Zipeng, Li Fangya, Zhang Jianyu

Introduction: Catechol o-methyltransferase plays a key role in the metabolism of catecholamine neurotransmitters. At present, its catalytic mechanism, overall structure, and kinetic characteristics have been basically clarified, but few people have paid attention to the function of solvents on enzymatic methyl transfer reactions. The influence of solvents on enzymatic reactions has always been a fuzzy hot topic. In addition, as a well-studied typical methyltransferase, COMT is a good test bed for exploring the source of the solvent isotope effect, which is a powerful tool in enzymatic mechanism research.

Methods: We have measured the kinetic parameters of methyl transfer catalyzed by COMT in both normal water (H2O) and heavy water (D2O) by high-performance liquid chromatography (HPLC) in the range of pL 6 ~ 11.

Results: The kinetic characteristics of COMT in H2O and D2O were significantly different under different pH/pD conditions. Significant solvent kinetic isotope effects (SKIE) were obtained, especially inverse solvent kinetic isotope effects (SKIE < 1) were observed in this methyl transfer reaction for the first time.

Conclusion: Traditional factors which could interpret the solvent isotope effect were ruled out. It's suggested that the solvent might affect the overall conformation as well as the flexibility of protein through non-covalent forces, thus altering the catalytic activity of COMT and leading to the solvent isotope effect.

儿茶酚o-甲基转移酶在儿茶酚胺类神经递质代谢中起关键作用。目前,其催化机理、总体结构、动力学特性等方面已基本阐明,但溶剂在酶促甲基转移反应中的作用却很少有人关注。溶剂对酶促反应的影响一直是一个模糊的热点问题。此外,COMT作为一种被充分研究的典型甲基转移酶,是探索溶剂同位素效应来源的良好实验平台,是酶机制研究的有力工具。方法:采用高效液相色谱法(HPLC)测定了COMT在正常水(H2O)和重水(D2O)中催化甲基转移的动力学参数,范围为pL 6 ~ 11。结果:不同pH/pD条件下COMT在H2O和D2O中的动力学特性有显著差异。得到了显著的溶剂动力学同位素效应(SKIE),特别是首次在甲基转移反应中观察到反溶剂动力学同位素效应(SKIE < 1)。结论:排除了解释溶剂同位素效应的传统因素。提示溶剂可能通过非共价力影响蛋白质的整体构象和柔韧性,从而改变COMT的催化活性,导致溶剂同位素效应。
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引用次数: 0
A Mini-review on Potentials Proteins/Peptides Applied for Serodiagnosis of Human Monkeypox Infection and Future Trends. 应用于人类猴痘感染血清诊断的潜在蛋白/肽及未来趋势小综述
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.2174/0929866530666230328094425
Fellipe Alexandre Alves Moraes, Caíque Lopes Duarte, Gabriel Oliveira Fernandes, Lucas Antônio Lisboa Ribeiro, Luciana Martins Rodrigues, Junivania Aparecida Dos Santos Lacerda, Líria Souza Silva, Jonatas Oliveira da Silva, Michelli Dos Santos, Alessandra da Silva Dantas, Miguel Angel Chávez-Fumagalli, Mariana Campos-da-Paz, Rodolfo Cordeiro Giunchetti, Eduardo Antônio Ferraz Coelho, Juliana Martins Machado, Alexsandro Sobreira Galdino

Monkeypox is a zoonosis that re-emerged in 2022, generating cases in non-endemic countries for the disease and creating a public health issue. The rapid increase in the number of cases kindles a need for quick, inexpensive diagnostic tests for the epidemiological control of the disease. The high cost of molecular tests can make this control more difficult to access in poorer regions, with immunological tests being a more viable option. In this mini-review, a search was conducted in the main databases for peptide and protein options that could be used in the development of serological diagnostic tests. Nine viable registres were found, and seven were selected (two patents and five studies). The main studies used the B21R peptide sequence as it is a high immunogenic epitope. In addition, studies on the improvement of these sequences were also found to avoid cross-reactions against other viruses of the same family, proposing a rational approach using multiepitope recombinant proteins. These approaches demonstrated high sensitivity and specificity values and are seen as viable options for developing new tests. New effective serological testing options, when combined with awareness, disease surveillance, early diagnosis, and rapid communication, form a set of key strategies used by health systems to control the spread of the monkeypox virus.

猴痘是一种人畜共患病,于 2022 年再次出现,在该疾病的非流行国家也出现了病例,并引发了公共卫生问题。病例数量的迅速增加激发了对快速、廉价诊断检测的需求,以便对该疾病进行流行病学控制。分子检测的高昂成本会使贫困地区更难获得这种控制,而免疫学检测则是更可行的选择。在这篇小型综述中,我们在主要数据库中搜索了可用于开发血清学诊断测试的多肽和蛋白质。共找到 9 个可行的注册表,并从中选出 7 个(2 项专利和 5 项研究)。主要研究使用了 B21R 肽序列,因为它是一种高免疫原性表位。此外,对这些序列进行改进的研究还发现,为了避免与同族其他病毒发生交叉反应,提出了一种使用多表位重组蛋白的合理方法。这些方法的灵敏度和特异性都很高,被视为开发新检测方法的可行选择。新的有效血清学检测方法与宣传、疾病监测、早期诊断和快速沟通相结合,构成了卫生系统用于控制猴痘病毒传播的一套关键策略。
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引用次数: 0
Protein Engineering, a Robust Tool to Engineer Novel Functions in Protein. 蛋白质工程:设计蛋白质新功能的强大工具。
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.2174/0929866530666230519122612
Nancy, Sudarshan Singh Lakhawat, Sanjeev Chandel, Sunil Kumar Jaswal, Pushpender Kumar Sharma

Designing effective diagnostics, biotherapeutics, and biocatalysts are a few interesting potential outcomes of protein engineering. Despite being just a few decades old, the discipline of de novo protein designing has provided a foundation for remarkable outcomes in the pharmaceuticals and enzyme industries. The technologies that will have the biggest impact on current protein therapeutics include engineered natural protein variants, Fc fusion protein, and antibody engineering. Furthermore, designing protein scaffolds can be used in developing next-generation antibodies and in transplanting active sites in the enzyme. The article highlights the important tools and techniques used in protein engineering and their application in the engineering of enzymes and therapeutic proteins. This review further sheds light on the engineering of superoxide dismutase, an enzyme responsible for catalyzing the conversion of superoxide radicals to oxygen and hydrogen peroxide by catalyzing a redox reaction at the metal center while concurrently oxidizing and reducing superoxide free radicals.

设计有效的诊断、生物治疗和生物催化剂是蛋白质工程的几个有趣的潜在成果。尽管只有几十年的历史,从头开始的蛋白质设计学科已经为制药和酶工业的显著成果奠定了基础。将对当前蛋白质治疗产生最大影响的技术包括工程天然蛋白质变体、Fc融合蛋白和抗体工程。此外,设计蛋白质支架可以用于开发下一代抗体和移植酶的活性位点。本文重点介绍了蛋白质工程中的重要工具和技术,以及它们在酶和治疗蛋白工程中的应用。超氧化物歧化酶是一种通过在金属中心催化氧化还原反应,同时氧化和还原超氧化物自由基,从而催化超氧化物自由基转化为氧和过氧化氢的酶。
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引用次数: 0
Polymorphic Variants of ASS1 Gene Related to Arginine Metabolism and the Risk of HCC. 与精氨酸代谢和HCC风险相关的ASS1基因多态性变异
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.2174/0929866530666230529143121
Kulsoom Bibi, Tehseen Fatima, Saba Sohrab, Ghulam Haider, Shamshad Zarina, Amber Ilyas

Background: Hepatocellular carcinoma is a primary liver cancer and 6th most common cancer globally. Inefficient diagnostic strategies and the limited availability of treatments are the foremost reasons. Variable factors directly impact the disease burden, among them, molecular alterations have been found to play a significant role. In liver, argininosuccinate synthase-1 is a center of arginine metabolism and rate limiting enzyme of urea cycle. It also triggers multiple mechanisms that lead to HCC pathogenesis.

Objectives: The aim of this study is to analyze the ASS1 gene expression, its polymorphic genotype and microsatellite instability among HCC patients from our Pakistani population.

Method: Blood samples were collected from disease and healthy control individuals. Allele-Specific PCR was performed for SNP analysis. MSI of tri and tetra nucleotide repeats were analyzed by PCR. The differential expression of ASS1 gene was also investigated. Furthermore, the reactome database and STRING software were utilized for finding correlations between ASS1 gene with other associated gene/proteins.

Results: The GG wild-type genotype was more prevailed in the disease group as compared to the control. Significant downregulation in ASS1 and NOS2 genes was observed. Bioinformatics analysis reveals the correlation between ASS1 polymorphism and HCC development appears to be linked with the EMT pathway and polyamine production. Furthermore, MSI significantly resided in the disease group. Results were analyzed statistically to calculate the significance of obtained results.

Conclusion: Study concludes that the insight of HCC mechanism through population-specific genetic mutations and altered gene expression of ASS1 might be helpful in early diagnostic and therapeutic purposes.

背景:肝细胞癌是一种原发性肝癌,是全球第六大常见癌症。低效的诊断策略和有限的治疗是最主要的原因。多种因素直接影响疾病负担,其中分子改变已被发现起重要作用。在肝脏中,精氨酸琥珀酸合酶-1是精氨酸代谢的中心和尿素循环的限速酶。它还触发导致HCC发病的多种机制。目的:本研究的目的是分析巴基斯坦人群HCC患者中ASS1基因表达、多态性基因型和微卫星不稳定性。方法:采集疾病和健康对照者的血液样本。采用等位基因特异性PCR进行SNP分析。用PCR方法分析三核苷酸和四核苷酸重复序列的MSI。我们还研究了ASS1基因的差异表达。此外,利用反应组数据库和STRING软件寻找ASS1基因与其他相关基因/蛋白的相关性。结果:与对照组相比,疾病组GG野生型基因型更为普遍。ASS1和NOS2基因显著下调。生物信息学分析显示,ASS1多态性与HCC发展之间的相关性似乎与EMT途径和多胺产生有关。此外,MSI明显存在于疾病组。对结果进行统计学分析,计算所得结果的显著性。结论:研究表明,通过人群特异性基因突变和ASS1基因表达改变来了解HCC的发病机制可能有助于早期诊断和治疗。
{"title":"Polymorphic Variants of <i>ASS1</i> Gene Related to Arginine Metabolism and the Risk of HCC.","authors":"Kulsoom Bibi,&nbsp;Tehseen Fatima,&nbsp;Saba Sohrab,&nbsp;Ghulam Haider,&nbsp;Shamshad Zarina,&nbsp;Amber Ilyas","doi":"10.2174/0929866530666230529143121","DOIUrl":"https://doi.org/10.2174/0929866530666230529143121","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma is a primary liver cancer and 6th most common cancer globally. Inefficient diagnostic strategies and the limited availability of treatments are the foremost reasons. Variable factors directly impact the disease burden, among them, molecular alterations have been found to play a significant role. In liver, argininosuccinate synthase-1 is a center of arginine metabolism and rate limiting enzyme of urea cycle. It also triggers multiple mechanisms that lead to HCC pathogenesis.</p><p><strong>Objectives: </strong>The aim of this study is to analyze the <i>ASS1</i> gene expression, its polymorphic genotype and microsatellite instability among HCC patients from our Pakistani population.</p><p><strong>Method: </strong>Blood samples were collected from disease and healthy control individuals. Allele-Specific PCR was performed for SNP analysis. MSI of tri and tetra nucleotide repeats were analyzed by PCR. The differential expression of <i>ASS1</i> gene was also investigated. Furthermore, the reactome database and STRING software were utilized for finding correlations between <i>ASS1</i> gene with other associated gene/proteins.</p><p><strong>Results: </strong>The GG wild-type genotype was more prevailed in the disease group as compared to the control. Significant downregulation in <i>ASS1</i> and <i>NOS2</i> genes was observed. Bioinformatics analysis reveals the correlation between <i>ASS1</i> polymorphism and HCC development appears to be linked with the EMT pathway and polyamine production. Furthermore, MSI significantly resided in the disease group. Results were analyzed statistically to calculate the significance of obtained results.</p><p><strong>Conclusion: </strong>Study concludes that the insight of HCC mechanism through population-specific genetic mutations and altered gene expression of <i>ASS1</i> might be helpful in early diagnostic and therapeutic purposes.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10473406","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
Rise of Bacterial Small Proteins and Peptides in Therapeutic Applications. 细菌小蛋白和多肽在治疗应用中的兴起。
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.2174/0929866530666230118144723
Ruby Shelin, Shanmugaraja Meenakshi

Background: Polypeptides that comprise less than 100 amino acids (50 amino acids in some cases) are referred to as small proteins (SPs), however, as of date, there is no strict definition. In contrast to the small polypeptides that arise due to proteolytic activity or abrupt protein synthesis, SPs are coded by small open reading frames (sORFs) and are conventionally synthesized by ribosomes.

Purpose of the review: Although proteins that contain more than 100 amino acids have been studied exquisitely, studies on small proteins have been largely ignored, basically due to the unsuccessful detection of these SPs by traditional methodologies/techniques. Serendipitous observation of several small proteins and elucidation of their vital functions in cellular processes opened the floodgate of a new area of research on the new family of proteins called "Small proteins". Having known the significance of such SPs, several advanced techniques are being developed to precisely identify and characterize them.

Conclusion: Bacterial small proteins (BSPs) are being intensely investigated in recent days and that has brought the versatile role of BSPs into the limelight. In particular, identification of the fact that BSPs exhibit antimicrobial activity has further expanded its scope in the area of therapeutics. Since the microbiome plays an inevitable role in determining the outcome of personalized medicine, studies on the secretory small proteins of the microbiome are gaining momentum. This review discusses the importance of bacterial small proteins and peptides in terms of their therapeutic applications.

背景:包含少于100个氨基酸(在某些情况下为50个氨基酸)的多肽被称为小蛋白质(SPs),然而,截至目前,没有严格的定义。与由于蛋白质水解活性或突然蛋白质合成而产生的小多肽相反,SPs由小的开放阅读框(sorf)编码,通常由核糖体合成。综述目的:尽管对含有100多种氨基酸的蛋白质进行了细致的研究,但对小蛋白质的研究在很大程度上被忽视了,这主要是由于传统方法/技术无法检测到这些SPs。对几种小蛋白质的偶然观察和对它们在细胞过程中的重要功能的阐明,打开了对被称为“小蛋白质”的新蛋白质家族研究的新领域的闸门。在了解了这些SPs的重要性之后,正在开发几种先进的技术来精确地识别和表征它们。结论:近年来,人们对细菌小蛋白(BSPs)的研究越来越深入,BSPs的多用途作用也越来越受到关注。特别是,BSPs具有抗菌活性的事实的鉴定进一步扩大了其在治疗学领域的范围。由于微生物组在决定个性化医疗的结果中起着不可避免的作用,因此对微生物组分泌小蛋白的研究正在蓬勃发展。本文综述了细菌小蛋白和肽在治疗应用方面的重要性。
{"title":"Rise of Bacterial Small Proteins and Peptides in Therapeutic Applications.","authors":"Ruby Shelin,&nbsp;Shanmugaraja Meenakshi","doi":"10.2174/0929866530666230118144723","DOIUrl":"https://doi.org/10.2174/0929866530666230118144723","url":null,"abstract":"<p><strong>Background: </strong>Polypeptides that comprise less than 100 amino acids (50 amino acids in some cases) are referred to as small proteins (SPs), however, as of date, there is no strict definition. In contrast to the small polypeptides that arise due to proteolytic activity or abrupt protein synthesis, SPs are coded by small open reading frames (sORFs) and are conventionally synthesized by ribosomes.</p><p><strong>Purpose of the review: </strong>Although proteins that contain more than 100 amino acids have been studied exquisitely, studies on small proteins have been largely ignored, basically due to the unsuccessful detection of these SPs by traditional methodologies/techniques. Serendipitous observation of several small proteins and elucidation of their vital functions in cellular processes opened the floodgate of a new area of research on the new family of proteins called \"Small proteins\". Having known the significance of such SPs, several advanced techniques are being developed to precisely identify and characterize them.</p><p><strong>Conclusion: </strong>Bacterial small proteins (BSPs) are being intensely investigated in recent days and that has brought the versatile role of BSPs into the limelight. In particular, identification of the fact that BSPs exhibit antimicrobial activity has further expanded its scope in the area of therapeutics. Since the microbiome plays an inevitable role in determining the outcome of personalized medicine, studies on the secretory small proteins of the microbiome are gaining momentum. This review discusses the importance of bacterial small proteins and peptides in terms of their therapeutic applications.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9116589","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: 2
期刊
Protein and Peptide Letters
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