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LINC01836 Promotes Colorectal Cancer Progression and Functions as ceRNA to Target SLC17A9 by Sponging miR-1226-3p. LINC01836促进结直肠癌进展,并通过海绵miR-1226-3p作为ceRNA靶向SLC17A9。
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.2174/0109298665248028231122064831
Zhihua Xu, Yue Yu, Hao Ni, Wei Sun, Yuting Kuang

Background: Increasing evidence proves that long non-coding RNAs (lncRNAs) play a key role in the occurrence and development of colorectal cancer. However, the function and molecular mechanism of LINC01836 in CRC are still unknown.

Methods: The differentially expressed lncRNAs in colorectal cancer were obtained from the RNA sequencing data. The effects of LINC01836 on colorectal cancer cells were tested in in vitro experiments. The mechanism of LINC01836 action was investigated through western blot, RNA immunoprecipitation assay and luciferase reporter assay. Moreover, the xenograft mouse model was conducted to examine the effects of LINC01836 in vivo.

Results: In this study, we showed that LINC01836 was significantly elevated in colorectal cancer tissues and cells. Elevated LINC01836 expression significantly correlated with larger tumor size, positive lymph node metastasis, distant metastasis, advanced tumor-node-metastasis (TNM) stage, and poor prognosis. Furthermore, decreased expression of LINC01836 repressed proliferation, migration, and invasion in vitro and vivo, and high LINC01836 expression displayed the opposite effect. Further analysis revealed that LINC01836 could regulate the expression of SLC17A9 by competing with miR---1226-3p. Furthermore, down-regulation of LINC01836 or increased expression of miR-1226-3p markedly reversed the effects of SLC17A9 overexpression on colorectal cancer cells.

Conclusion: This study showed that LINC01836 regulated the expression of SLC17A9 through sponge miR-1226-3p by acting as a competitive endogenous RNA (ceRNA), promoted the progression of colorectal cancer, and suggested a new prognostic biomarker and potential cancer treatment target for colorectal cancer.

背景:越来越多的证据表明,长链非编码rna (long non-coding rna, lncRNAs)在结直肠癌的发生发展中起着关键作用。然而,LINC01836在结直肠癌中的功能和分子机制尚不清楚。方法:从RNA测序数据中获得结直肠癌中差异表达的lncRNAs。通过体外实验检测了LINC01836对结直肠癌细胞的作用。采用western blot、RNA免疫沉淀法和荧光素酶报告基因法研究LINC01836的作用机制。此外,我们还建立了异种移植小鼠模型来检验LINC01836在体内的作用。结果:在本研究中,我们发现LINC01836在结直肠癌组织和细胞中显著升高。LINC01836表达升高与肿瘤大小较大、淋巴结转移阳性、远处转移、肿瘤-淋巴结-转移(TNM)晚期、预后不良相关。此外,LINC01836的低表达抑制了体外和体内的增殖、迁移和侵袭,而LINC01836的高表达则表现出相反的效果。进一步分析发现,LINC01836可以通过与miR-1226-3p竞争来调节SLC17A9的表达。此外,下调LINC01836或增加miR-1226-3p的表达可显著逆转SLC17A9过表达对结直肠癌细胞的影响。结论:本研究表明,LINC01836通过海绵miR-1226-3p作为竞争性内源性RNA (ceRNA)调控SLC17A9的表达,促进结直肠癌的进展,提示结直肠癌新的预后生物标志物和潜在的癌症治疗靶点。
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引用次数: 0
Feasibility of Domain Segmentation of B19V VP1u Using Intein Technology for Structural Studies. 利用 Intein 技术对 B19V VP1u 进行结构研究的域分割可行性。
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.2174/0109298665277211231214065419
Renuk Varayil Lakshmanan, Mavis Agbandje-McKenna, Robert McKenna

Introduction: Parvovirus B19 (B19V) is a human pathogen, and the minor capsid protein of B19V possesses a unique N terminus called VP1u that plays a crucial role in the life cycle of the virus.

Objectives: The objective of this study was to develop a method for domain segmentation of B19 VP1u using intein technology, particularly its receptor binding domain (RBD) and phospholipase A2 (PLA2) domain.

Methods: RBD and PLA2 domains of VP1u were each fused to the DnaE split inteins derived from the Nostoc punctiforme. Each of these precursor proteins was expressed in E. coli. Combining the purified precursors in equal molar ratios resulted in the formation of full-length VP1u. Furthermore, Circular Dichroism (CD) spectroscopy and PLA2 assays were used to probe the structure and activity of the newly formed protein.

Results: The CD spectrum of the full length VP1u confirmed the secondary structure of protein, while the PLA2 assay indicated minimal disruption in enzymatic activity.

Conclusion: This method would allow for the selective incorporation of NMR-active isotopes into either of the VP1u domains, which can reduce signal overlap in NMR structural determination studies.

导言:Parvovirus B19(B19V)是一种人类病原体,B19V的小囊膜蛋白具有一个独特的N末端,称为VP1u,在病毒的生命周期中起着至关重要的作用:本研究的目的是利用intein技术开发一种对B19 VP1u进行结构域分割的方法,特别是其受体结合结构域(RBD)和磷脂酶A2(PLA2)结构域:方法:将 VP1u 的 RBD 和 PLA2 结构域分别与来自点状芽孢杆菌的 DnaE 分裂内含素融合。这些前体蛋白分别在大肠杆菌中表达。将纯化的前体蛋白以等摩尔比结合,形成了全长的 VP1u。此外,还使用了圆二色性(CD)光谱和 PLA2 试验来探究新形成的蛋白质的结构和活性:结果:全长 VP1u 的 CD 光谱证实了蛋白质的二级结构,而 PLA2 检测则表明酶活性受到的干扰极小:结论:这种方法可将核磁共振活性同位素选择性地加入到 VP1u 的任一结构域中,从而减少核磁共振结构测定研究中的信号重叠。
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引用次数: 0
The Features of Shared Genes among Transcriptomes Probed in Atopic Dermatitis, Psoriasis, and Inflammatory Acne: S100A9 Selection as the Target Gene. 特应性皮炎、银屑病和炎症性痤疮转录组中共享基因的特征:选择 S100A9 作为目标基因。
IF 1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.2174/0109298665290166240426072642
Wei Wang, Sungbo Hwang, Daeui Park, Yong-Doo Park

Background: Atopic dermatitis (AD), psoriasis (PS), and inflammatory acne (IA) are well-known as inflammatory skin diseases. Studies of the transcriptome with altered expression levels have reported a large number of dysregulated genes and gene clusters, particularly those involved in inflammatory skin diseases.

Objective: To identify genes commonly shared in AD, PS, and IA that are potential therapeutic targets, we have identified consistently dysregulated genes and disease modules that overlap with AD, PS, and IA.

Methods: Microarray data from AD, PS, and IA patients were downloaded from Gene Expression Omnibus (GEO), and identification of differentially expressed genes from microarrays of AD, PS, and IA was conducted. Subsequently, gene ontology and gene set enrichment analysis, detection of disease modules with known disease-associated genes, construction of the protein-protein interaction (PPI) network, and PPI sub-mapping analysis of shared genes were performed. Finally, the computational docking simulations between the selected target gene and inhibitors were conducted.

Results: We identified 50 shared genes (36 up-regulated and 14 down-regulated) and disease modules for each disease. Among the shared genes, 20 common genes in PPI network were detected such as LCK, DLGAP5, SELL, CEP55, CDC20, RRM2, S100A7, S100A9, MCM10, AURKA, CCNB1, CHEK1, BTC, IL1F7, AGTR1, HABP4, SERPINB13, RPS6KA4, GZMB, and TRIP13. Finally, S100A9 was selected as the target gene for therapeutics. Docking simulations between S100A9 and known inhibitors indicated several key binding residues, and based on this result, we suggested several cannabinoids such as WIN-55212-2, JZL184, GP1a, Nabilone, Ajulemic acid, and JWH-122 could be potential candidates for a clinical study for AD, PS, and IA via inhibition of S100A9-related pathway.

Conclusion: Overall, our approach may become an effective strategy for discovering new disease candidate genes for inflammatory skin diseases with a reevaluation of clinical data.

背景:特应性皮炎(AD)、银屑病(PS)和炎症性痤疮(IA)是众所周知的炎症性皮肤病。对表达水平改变的转录组的研究报告了大量失调基因和基因簇,尤其是那些涉及炎症性皮肤病的基因:为了确定 AD、PS 和 IA 中常见的潜在治疗靶点基因,我们确定了与 AD、PS 和 IA 重叠的持续失调基因和疾病模块:从基因表达总库(Gene Expression Omnibus,GEO)中下载了AD、PS和IA患者的芯片数据,并对AD、PS和IA芯片中的差异表达基因进行了鉴定。随后,进行了基因本体和基因组富集分析、已知疾病相关基因的疾病模块检测、蛋白质相互作用(PPI)网络的构建以及共享基因的PPI子图谱分析。最后,对选定的靶基因和抑制剂进行了计算对接模拟:结果:我们为每种疾病确定了 50 个共有基因(36 个上调,14 个下调)和疾病模块。在共享基因中,我们发现了 20 个 PPI 网络中的常见基因,如 LCK、DLGAP5、SELL、CEP55、CDC20、RRM2、S100A7、S100A9、MCM10、AURKA、CCNB1、CHEK1、BTC、IL1F7、AGTR1、HABP4、SERPINB13、RPS6KA4、GZMB 和 TRIP13。最后,S100A9 被选为治疗药物的靶基因。S100A9与已知抑制剂之间的对接模拟显示了几个关键的结合残基,基于这一结果,我们认为WIN-55212-2、JZL184、GP1a、Nabilone、Ajulemic acid和JWH-122等几种大麻素可能成为通过抑制S100A9相关途径治疗AD、PS和IA的临床研究候选药物:总之,通过对临床数据的重新评估,我们的方法可能成为发现炎症性皮肤病新疾病候选基因的有效策略。
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引用次数: 0
P53-induced GAP-43 Upregulation in Primary Cortical Neurons of Rats. 大鼠初级皮层神经元中 P53 诱导的 GAP-43 上调
IF 1 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.2174/0109298665263864231221071712
Tianxia Li, Yuexin Jia, Junxian Fu, Zhuo Fu, Zhidong Qiao, Xiaoyang Liu, Ting Lv, Rong Tang, Guanglu Yang

Objectives: In this study, we employed an in vitro culturing technique to investigate the impact of p53 on the modulation of growth-associated protein-43 (GAP-43) within the primary cortical neurons of rat specimens.

Methods: (1) Within the first 24 hours after birth, the bilateral cortex was extracted from newborn Wistar rats and primary cortical neurons were cultured and identified. (2) The changes in the mRNA and protein expressions of GAP-43 induced by p53 in rat primary cortical neurons cultured in vitro were identified utilizing real-time polymerase chain reaction and western blot techniques.

Results: (1) Lentiviral transfection of p53 within primary cortical neurons of rats elicited elevated levels of both mRNA and protein expressions of GAP-43, consequently culminating in a noteworthy augmentation of p53 expression. (2) The introduction of a p53 inhibitor in rat primary cortical neurons resulted in a reduction in both mRNA and protein expressions of GAP-43.

Conclusion: Within primary rat cortical neurons, p53 has the potential to prompt an augmentation in both the transcriptional and protein expression levels of the GAP-43 protein.

研究目的方法:1)在新生Wistar大鼠出生后24小时内,提取其双侧皮层,培养并鉴定大鼠原代皮层神经元。2)利用实时聚合酶链式反应和 Western 印迹技术鉴定 p53 诱导的 GAP-43 mRNA 和蛋白表达在体外培养的大鼠原代皮层神经元中的变化:1)慢病毒转染大鼠原代皮质神经元中的 p53 可引起 GAP-43 mRNA 和蛋白表达水平的升高,从而导致 p53 表达的显著增强。2)在大鼠原代皮层神经元中引入 p53 抑制剂会导致 GAP-43 的 mRNA 和蛋白表达量减少:结论:在原代大鼠大脑皮层神经元中,p53 有可能促使 GAP-43 蛋白的转录和蛋白表达水平增加。
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引用次数: 0
KIF20A Promotes CRC Progression and the Warburg Effect through the C-Myc/HIF-1α Axis. KIF20A通过C-Myc/HIF-1α轴促进结直肠癌进展和Warburg效应。
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.2174/0109298665256238231120093150
Min Wu, Xianqiang Wu, Jie Han

Background: Colorectal cancer (CRC) is a prevalent form of cancer globally, characterized by a high mortality rate. Therefore, discovering effective therapeutic approaches for CRC treatment is critical.

Methods: The levels of KIF20A in CRC clinical samples were determined using Western Blot and immunofluorescence assay. SW480 cells were transfected with siRNA targeting KIF20A, while HT-29 cells were transfected with a KIF20A overexpression vector. Cell viability and apoptosis of CRC cells were assessed using CCK-8 and TUNEL analysis. Migration ability was investigated using Transwell. The levels of pyruvate, lactate and ATP were determined through corresponding assay kits. Western Blot was applied to confirm the level of proteins associated with glycolysis, c- Myc, HIF-1α, PKM2 and LDHA. Subsequently, functional rescue experiments were conducted to investigate further the regulatory relationship between KIF20A, c-Myc, and HIF-1α in colorectal cancer (CRC), employing the c-Myc inhibitor 10058-F4 and c-Myc overexpression plasmids.

Results: KIF20A was up-regulated in vivo and in vitro in CRC. KIF20A knockdown inhibited cell viability and migration while promoting cell apoptosis in SW480 cells. Conversely, overexpression of KIF20A yielded contrasting effects in HT-29 cells. Moreover, inhibition of KIF20A restrained the pyruvate, lactate production and ATP level, whereas overexpression of KIF20A enhanced the Warburg effect. Western Blot indicated that knockdown KIF20A attenuated the levels of c-Myc, HIF-1α, PKM2 and LDHA. In addition, rescue experiments further verified that KIF20A enhanced the Warburg effect by the KIF20A/c-Myc/HIF-1α axis in CRC.

Conclusion: KIF20A, being a crucial regulator in the progression of CRC, has the potential to be a promising therapeutic target for the treatment of CRC.

背景:结直肠癌(CRC)是全球常见的一种癌症,其特点是死亡率高。因此,发现有效的结直肠癌治疗方法至关重要。方法:采用Western Blot和免疫荧光法检测结直肠癌临床标本中KIF20A的表达水平。用靶向KIF20A的siRNA转染SW480细胞,用KIF20A过表达载体转染HT-29细胞。采用CCK-8和TUNEL分析评估结直肠癌细胞的细胞活力和凋亡情况。利用Transwell对其迁移能力进行了研究。通过相应的检测试剂盒检测丙酮酸、乳酸和ATP水平。Western Blot检测糖酵解、cMyc、HIF-1α、PKM2和LDHA相关蛋白水平。随后,我们利用c-Myc抑制剂10058-F4和c-Myc过表达质粒,开展功能挽救实验,进一步探讨KIF20A、c-Myc和HIF-1α在结直肠癌(CRC)中的调控关系。结果:在结直肠癌中,KIF20A在体内和体外均表达上调。KIF20A敲低抑制SW480细胞的活力和迁移,同时促进细胞凋亡。相反,KIF20A过表达在HT-29细胞中产生相反的效果。此外,抑制KIF20A抑制了丙酮酸、乳酸的产生和ATP水平,而过表达KIF20A则增强了Warburg效应。Western Blot结果显示,敲低KIF20A可降低c-Myc、HIF-1α、PKM2和LDHA水平。此外,救援实验进一步验证了KIF20A通过KIF20A/c-Myc/HIF-1α轴在CRC中增强Warburg效应。结论:KIF20A作为CRC进展的关键调节因子,有潜力成为CRC治疗的有希望的治疗靶点。
{"title":"KIF20A Promotes CRC Progression and the Warburg Effect through the C-Myc/HIF-1α Axis.","authors":"Min Wu, Xianqiang Wu, Jie Han","doi":"10.2174/0109298665256238231120093150","DOIUrl":"10.2174/0109298665256238231120093150","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a prevalent form of cancer globally, characterized by a high mortality rate. Therefore, discovering effective therapeutic approaches for CRC treatment is critical.</p><p><strong>Methods: </strong>The levels of KIF20A in CRC clinical samples were determined using Western Blot and immunofluorescence assay. SW480 cells were transfected with siRNA targeting KIF20A, while HT-29 cells were transfected with a KIF20A overexpression vector. Cell viability and apoptosis of CRC cells were assessed using CCK-8 and TUNEL analysis. Migration ability was investigated using Transwell. The levels of pyruvate, lactate and ATP were determined through corresponding assay kits. Western Blot was applied to confirm the level of proteins associated with glycolysis, c- Myc, HIF-1α, PKM2 and LDHA. Subsequently, functional rescue experiments were conducted to investigate further the regulatory relationship between KIF20A, c-Myc, and HIF-1α in colorectal cancer (CRC), employing the c-Myc inhibitor 10058-F4 and c-Myc overexpression plasmids.</p><p><strong>Results: </strong>KIF20A was up-regulated <i>in vivo</i> and <i>in vitro</i> in CRC. KIF20A knockdown inhibited cell viability and migration while promoting cell apoptosis in SW480 cells. Conversely, overexpression of KIF20A yielded contrasting effects in HT-29 cells. Moreover, inhibition of KIF20A restrained the pyruvate, lactate production and ATP level, whereas overexpression of KIF20A enhanced the Warburg effect. Western Blot indicated that knockdown KIF20A attenuated the levels of c-Myc, HIF-1α, PKM2 and LDHA. In addition, rescue experiments further verified that KIF20A enhanced the Warburg effect by the KIF20A/c-Myc/HIF-1α axis in CRC.</p><p><strong>Conclusion: </strong>KIF20A, being a crucial regulator in the progression of CRC, has the potential to be a promising therapeutic target for the treatment of CRC.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462238","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
Heterogenous Expression and Purification of Lipid II Flippase from Staphylococcus aureus. 金黄色葡萄球菌脂质 II 翻转酶的异源表达与纯化
IF 1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.2174/0109298665316374240531113258
Yuan Yuan Zheng, Wai-Hong Chung, Yun-Chung Leung, Kwok-Yin Wong

Background: Staphylococcus aureus is a common pathogen with strains that are resistant to existing antibiotics. MurJ from S. aureus (SaMurJ), an integral membrane protein functioning as Lipid II flippase, is a potential target for developing new antibacterial agents against this pathogen. Successful expression and purification of this protein shall be useful in the development of drugs against this target.

Objective: In this study, we demonstrated the optimized expression and purification procedures of SaMurJ, identified suitable detergent for extracting and solubilizing the protein, and examined the peptidisc system to generate a detergent-free environment.

Methods: SaMurJ fused with N-terminal ten-His tag was expressed without induction. Six detergents were selected for screening the most efficient candidate for extraction and solubilization of the protein. The thermostability of the detergent-solubilized protein was assessed by evaluated temperature incubation. Different ratios of peptidisc bi-helical peptide (NSPr) to SaMurJ were mixed and the on-bead peptidisc assembly method was applied.

Results: SaMurJ expressed in BL21(DE3) was confirmed by peptide fingerprinting, with a yield of 1 mg SaMurJ per liter culture. DDM was identified as the optimum detergent for solubilization and the nickel affinity column enabled SaMurJ purification with a purity of ~88%. However, NSPr could not stabilize SaMurJ.

Conclusion: The expression and purification of SaMurJ were successful, with high purity and good yield. SaMurJ can be solubilized and stabilized by a DDM-containing buffer.

背景:金黄色葡萄球菌是一种常见病原体,其菌株对现有抗生素具有耐药性。来自金黄色葡萄球菌的 MurJ(SaMurJ)是一种具有脂质 II 翻转酶功能的整体膜蛋白,是针对该病原体开发新抗菌药物的潜在靶点。成功表达和纯化该蛋白将有助于开发针对这一靶点的药物:在这项研究中,我们展示了 SaMurJ 的优化表达和纯化程序,确定了提取和增溶该蛋白的合适去垢剂,并研究了产生无去垢剂环境的肽盘系统:方法:SaMurJ融合了N-末端十-His标签,无需诱导即可表达。方法:SaMurJ融合了N-端十-His标签,未经诱导表达,筛选出六种去垢剂,用于提取和溶解蛋白质。去垢剂溶解蛋白的热稳定性通过评估温度孵育进行评估。将不同比例的肽盘双螺旋肽(NSPr)与SaMurJ混合,并采用珠上肽盘组装法:结果:通过肽指纹图谱确认了在 BL21(DE3)中表达的 SaMurJ,每升培养物产率为 1 毫克 SaMurJ。DDM 被确定为最佳增溶去垢剂,镍亲和柱使 SaMurJ 的纯度达到约 88%。然而,NSPr 无法稳定 SaMurJ:结论:SaMurJ 的表达和纯化是成功的,纯度高,收率好。结论:SaMurJ 的表达和纯化均获得成功,纯度高、收率好。SaMurJ 可在含 DDM 的缓冲液中溶解和稳定。
{"title":"Heterogenous Expression and Purification of Lipid II Flippase from <i>Staphylococcus aureus</i>.","authors":"Yuan Yuan Zheng, Wai-Hong Chung, Yun-Chung Leung, Kwok-Yin Wong","doi":"10.2174/0109298665316374240531113258","DOIUrl":"10.2174/0109298665316374240531113258","url":null,"abstract":"<p><strong>Background: </strong><i>Staphylococcus aureus</i> is a common pathogen with strains that are resistant to existing antibiotics. MurJ from <i>S. aureus</i> (SaMurJ), an integral membrane protein functioning as Lipid II flippase, is a potential target for developing new antibacterial agents against this pathogen. Successful expression and purification of this protein shall be useful in the development of drugs against this target.</p><p><strong>Objective: </strong>In this study, we demonstrated the optimized expression and purification procedures of SaMurJ, identified suitable detergent for extracting and solubilizing the protein, and examined the peptidisc system to generate a detergent-free environment.</p><p><strong>Methods: </strong>SaMurJ fused with N-terminal ten-His tag was expressed without induction. Six detergents were selected for screening the most efficient candidate for extraction and solubilization of the protein. The thermostability of the detergent-solubilized protein was assessed by evaluated temperature incubation. Different ratios of peptidisc bi-helical peptide (NSPr) to SaMurJ were mixed and the on-bead peptidisc assembly method was applied.</p><p><strong>Results: </strong>SaMurJ expressed in BL21(DE3) was confirmed by peptide fingerprinting, with a yield of 1 mg SaMurJ per liter culture. DDM was identified as the optimum detergent for solubilization and the nickel affinity column enabled SaMurJ purification with a purity of ~88%. However, NSPr could not stabilize SaMurJ.</p><p><strong>Conclusion: </strong>The expression and purification of SaMurJ were successful, with high purity and good yield. SaMurJ can be solubilized and stabilized by a DDM-containing buffer.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring Potential Biomarkers of Early Thymoma based on Serum Proteomics. 基于血清蛋白质组学探索早期胸腺瘤的潜在生物标记物
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.2174/0109298665275655231103105924
Min Jin, Peng Liu, Guoyan Qi

Background: Early diagnosis remains difficult because the early symptoms of thymoma are atypical.

Objectives: This study aimed to analyze the changes of serum proteins in the early stage of thymoma (stage I/II) by proteomics method and to screen and validate candidate biomarkers.

Methods: Proteins were extracted from 8 sera patients with stage I/II thymoma and 9 healthy controls. The levels of serum proteins were detected by data-independent acquisition (DIA) quantitative proteomics techniques, and the differential proteins were identified. The proteomic results were verified by enzyme-linked immunosorbent assay. Additionally, differentially expressed proteins were analyzed using receiver operating characteristic curves (ROC).

Results: There were 80 differentially expressed proteins between the patients with thymoma and the healthy control group, among which 39 were up-regulated and 41 were down-regulated. Differential protein enrichment is involved in environmental information processing, signaling molecules and interactions, and in the body system and the immune system. The analysis of receptor working characteristic curves showed that the areas under the curve of CORO1A, SAA1 and LTA4H were all larger than 0.8, indicating that these proteins had good diagnostic value.

Conclusion: CORO1A, SAA1 and LTA4H may be new biomarkers for early screening of thymoma.

背景:由于胸腺瘤的早期症状不典型,因此早期诊断仍很困难:由于胸腺瘤的早期症状不典型,因此早期诊断仍很困难:本研究旨在通过蛋白质组学方法分析胸腺瘤早期(I/II期)血清蛋白的变化,并筛选和验证候选生物标志物:从8名I/II期胸腺瘤患者和9名健康对照者的血清中提取蛋白质。方法:从 8 例 I/II 期胸腺瘤患者和 9 例健康对照者的血清中提取蛋白质,采用数据独立获取(DIA)定量蛋白质组学技术检测血清蛋白水平,并鉴定差异蛋白。蛋白质组学结果通过酶联免疫吸附试验进行了验证。此外,还利用接收者操作特征曲线(ROC)对差异表达蛋白进行了分析:结果:胸腺瘤患者与健康对照组之间共有 80 个差异表达蛋白,其中 39 个上调,41 个下调。差异蛋白富集涉及环境信息处理、信号分子和相互作用、机体系统和免疫系统。受体工作特征曲线分析表明,CORO1A、SAA1和LTA4H的曲线下面积均大于0.8,表明这些蛋白质具有良好的诊断价值:结论:CORO1A、SAA1和LTA4H可能是早期筛查胸腺瘤的新生物标记物。
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引用次数: 0
Molecular Machinery of the Triad Holin, Endolysin, and Spanin: Key Players Orchestrating Bacteriophage-Induced Cell Lysis and their Therapeutic Applications. 三联体 Holin、Endolysin 和 Spanin 的分子机制:噬菌体诱导的细胞裂解及其治疗应用的关键角色。
IF 1.6 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.2174/0109298665181166231212051621
Safia Samir

Phage therapy, a promising alternative to combat multidrug-resistant bacterial infections, harnesses the lytic cycle of bacteriophages to target and eliminate bacteria. Key players in this process are the phage lysis proteins, including holin, endolysin, and spanin, which work synergistically to disrupt the bacterial cell wall and induce lysis. Understanding the structure and function of these proteins is crucial for the development of effective therapies. Recombinant versions of these proteins have been engineered to enhance their stability and efficacy. Recent progress in the field has led to the approval of bacteriophage-based therapeutics as drugs, paving the way for their clinical use. These proteins can be combined in phage cocktails or combined with antibiotics to enhance their activity against bacterial biofilms, a common cause of treatment failure. Animal studies and clinical trials are being conducted to evaluate the safety and efficacy of phage therapy in humans. Overall, phage therapy holds great potential as a valuable tool in the fight against multidrug- resistant bacteria, offering hope for the future of infectious disease treatment.

近年来,噬菌体疗法作为治疗多重耐药性(MDR)感染的一种可能替代疗法备受关注。溶解性噬菌体编码用于破坏细菌宿主包膜的蛋白质。噬菌体产生内溶素壁层酶,它们是噬菌体编码的肽聚糖水解酶(PGHs),可在噬菌体溶解繁殖周期结束时酶解宿主细菌的肽聚糖(PG)或金霉素层。噬菌体全蛋白调节内溶菌素进入肽聚糖的途径,在特定的 "溶解时钟 "时刻启动溶解过程。噬菌体spanins会破坏外膜。Holin/Endolysin/Spanin 可用作新型抗菌剂,以对抗细菌引起的感染。这些蛋白质正引起各行各业的兴趣,包括制药、食品、生物技术和医学等领域。在这篇综述中,我们强调了这些蛋白质的重要性及其在动物研究中的应用。此外,还提到了一些临床试验。
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引用次数: 0
Variable Surface Antigens of Plasmodium falciparum: Protein Families with Divergent Roles. 恶性疟原虫的可变表面抗原:具有不同作用的蛋白质家族。
IF 1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.2174/0109298665298567240530170924
Jasweer Kaur, Prakash Chandra Mishra, Rachna Hora

Malaria caused by Plasmodium falciparum (Pf) is an illness that contributes significantly to the global health burden. Pf makes significant alterations to the host cell to meet its metabolic demands and escape the immune response of the host. These include the export of a large number of parasite proteins to the infected Red Blood Cells (iRBC). Variable Surface Antigens (VSAs), which are highly polymorphic protein families with important roles in immune evasion, form an important component of the exported proteins. A total of five protein families constitute the VSAs, viz. PfEMP1 (Pf erythrocyte membrane protein 1), RIFIN (repetitive interspersed family), STEVOR (sub-telomeric open reading frame), SURFIN (surface-associated interspersed gene family), and PfMC-2TM (Pf Maurer's cleft two transmembrane). With orthologues present in various simian-infecting species, VSAs take up a variety of domain topologies and organizational structures while exhibiting differential expressions throughout the parasite life cycle. Their expression varies across clinical isolates and laboratory strains, which suggests their crucial role in host cell survival and defense. Members of VSAs are reported to contribute significantly to disease pathogenesis through immune evasion processes like cytoadherence, iRBC sequestration in the host vasculature, rosetting, reduced erythrocyte deformability, and direct immunosuppression. In this study, we have gathered information on various aspects of VSAs, like their orthologues, domain architecture, surface topology, functions and interactions, and three-dimensional structures, while emphasizing discoveries in the field. Considering the vast repertoire of Plasmodial VSAs with new emergent functions, a lot remains unknown about these families and, hence, malaria biology.

由恶性疟原虫(Plasmodium falciparum,Pf)引起的疟疾是一种严重影响全球健康的疾病。疟原虫会对宿主细胞进行重大改造,以满足其新陈代谢需求并逃避宿主的免疫反应。其中包括向受感染的红细胞(iRBC)输出大量寄生虫蛋白质。可变表面抗原(VSAs)是高度多态的蛋白质家族,在免疫逃避中发挥着重要作用,是输出蛋白质的重要组成部分。共有五个蛋白家族构成了 VSAs,即 PfEMP1(Pf 红细胞膜蛋白 1)、RIFIN(重复穿插家族)、STEVOR(亚端粒开放阅读框)、SURFIN(表面相关穿插基因家族)和 PfMC-2TM(Pf Maurer's cleft two transmembrane)。VSAs 在各种猿类感染物种中都有同源物,它们具有各种结构域拓扑和组织结构,同时在整个寄生虫生命周期中表现出不同的表达方式。它们在临床分离株和实验室菌株中的表达各不相同,这表明它们在宿主细胞的生存和防御中起着至关重要的作用。据报道,VSAs 成员通过免疫逃避过程,如细胞粘附、iRBC 在宿主血管中固着、轮集、降低红细胞变形性和直接免疫抑制等,对疾病的发病机制起着重要作用。在本研究中,我们收集了 VSAs 的各方面信息,如它们的同源物、结构域、表面拓扑、功能和相互作用以及三维结构,同时强调了该领域的新发现。考虑到具有新功能的质体 VSA 种类繁多,人们对这些家族以及疟疾生物学仍有很多未知之处。
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引用次数: 0
The Agonistic Activity of the Human Epidermal Growth Factor is Reduced by the D46G Substitution. 人表皮生长因子的激动活性因 D46G 取代而降低
IF 1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 DOI: 10.2174/0109298665297321240708044223
Anastasia Aleksandrovna Akunevich, Vladislav Victorovich Khrustalev, Tatyana Aleksandrovna Khrustaleva, Marina Anatolyevna Yermalovich

Background: Resistance to anti-tumor agents targeting the epidermal growth factor receptor (EGFR) reduces treatment response and requires the development of novel EGFR antagonists. Mutant epidermal growth factor (EGF) forms with reduced agonistic activity could be promising agents in cancer treatment.

Methods: EGF D46G affinity to EGFR domain III was assessed with affinity chromatography. EGF D46G acute toxicity in Af albino mice at 320 and 3200 μg/kg subcutaneous doses was evaluated. EGF D46G activity in human epidermoid carcinoma cells at 10 ng/mL concentration in serum-free medium and in subcutaneous Ehrlich ascites carcinoma mice model at 320 μg/kg dose was studied.

Results: The D46G substitution decreases the thermal stability of EGF complexes with EGFR domain III by decreasing the ability of the C-terminus to be released from the intermolecular β- sheet. However, with remaining binding sites for EGFR domain I, EGF D46G effectively competes with other EGF-like growth factors for binding to EGFR and does not demonstrate toxic effects in mice. EGF D46G inhibits the proliferation of human epidermoid carcinoma cells compared to native EGF. A single subcutaneous administration of EGF D46G along with Ehrlich carcinoma cells injection inhibits the proliferation of these cells and delays tumor formation for up to seven days.

Conclusion: EGF D46G can be defined as a partial EGFR agonist as this mutant form demonstrates reduced agonistic activity compared to native EGF. The study emphasizes the role of the EGF C-terminus in establishing interactions with EGFR domain III, which are necessary for EGFR activation and subsequent proliferation of cells.

背景:针对表皮生长因子受体(EGFR)的抗肿瘤药物的抗药性会降低治疗反应,因此需要开发新型的 EGFR 拮抗剂。激动活性降低的突变型表皮生长因子(EGF)可能成为治疗癌症的有效药物:方法:采用亲和层析法评估了 EGF D46G 与表皮生长因子受体结构域 III 的亲和性。以 320 和 3200 μg/kg 皮下注射剂量评估了 EGF D46G 对非洲白化小鼠的急性毒性。研究了 EGF D46G 在无血清培养基中浓度为 10 ng/mL 的人表皮样癌细胞中的活性,以及在皮下注射 320 μg/kg 剂量的艾氏腹水癌小鼠模型中的活性:结果:D46G取代会降低表皮生长因子受体结构域III与表皮生长因子受体复合物的热稳定性,因为它降低了C-末端从分子间β-薄片中释放出来的能力。然而,由于表皮生长因子受体结构域 I 仍有结合位点,表皮生长因子 D46G 能有效地与其他表皮生长因子样生长因子竞争与表皮生长因子受体的结合,而且不会对小鼠产生毒性作用。与原生表皮生长因子相比,EGF D46G 能抑制人类表皮样癌细胞的增殖。在注射艾氏癌细胞的同时皮下注射一次 EGF D46G,可抑制这些细胞的增殖并延缓肿瘤形成长达七天:结论:表皮生长因子受体 D46G 可被定义为部分表皮生长因子受体激动剂,因为与原生表皮生长因子受体相比,这种突变形式的表皮生长因子受体激动活性降低。这项研究强调了表皮生长因子受体 C 端在与表皮生长因子受体结构域 III 建立相互作用方面的作用,而这种作用是表皮生长因子受体活化及随后细胞增殖所必需的。
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引用次数: 0
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Protein and Peptide Letters
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