Repressor Proteins

抑制蛋白
  • 文章类型: Journal Article
    背景:人工智能(AI)在医学中显示出巨大的潜力,聊天生成预训练变压器(ChatGPT)已在该领域用于不同的目的。然而,它可能不符合某些医疗场景的复杂性和细微差别。这项研究评估了ChatGPT3.5和4在提供有关前列腺切除术后尿失禁(PPUI)的管理建议方面的准确性。考虑前列腺治疗后尿失禁:AUA/SUFU指南作为最佳实践基准。
    方法:准备了一组基于AUA/SUFU指南的问题。查询包括10个概念性问题和10个基于案例的问题。所有问题都是开放的,并输入了ChatGPT,并建议将答案限制为200字,为了更大的客观性。回答被评为正确(1分);部分正确(0.5分),或不正确(0分)。针对概念性和基于案例的问题,对ChatGPT版本3.5和4的性能进行了整体和单独分析。
    结果:ChatGPT3.5在20分中获得11.5分(准确率为57.5%),而ChatGPT4得分为18(90.0%;p=0.031)。在概念性问题中,ChatGPT3.5提供了六个问题的准确答案,以及一个部分正确的答案和三个不正确的答案。最终得分为6.5分。相比之下,ChatGPT4对八个问题提供了正确答案,对两个问题提供了部分正确答案,得分为9.0。在基于案例的问题中,ChatGPT3.5得分为5.0,而ChatGPT4得分为9.0。ChatGPT表现最差的领域是评估,治疗方案,手术并发症,和特殊情况。
    结论:与ChatGPT3.5相比,ChatGPT4在提供PPUI管理建议方面表现优异,使用AUA/SUFU指南作为基准。持续监测对于评估AI生成的医疗信息的开发和精度至关重要。
    BACKGROUND: Artificial intelligence (AI) shows immense potential in medicine and Chat generative pretrained transformer (ChatGPT) has been used for different purposes in the field. However, it may not match the complexity and nuance of certain medical scenarios. This study evaluates the accuracy of ChatGPT 3.5 and 4 in providing recommendations regarding the management of postprostatectomy urinary incontinence (PPUI), considering The Incontinence After Prostate Treatment: AUA/SUFU Guideline as the best practice benchmark.
    METHODS: A set of questions based on the AUA/SUFU Guideline was prepared. Queries included 10 conceptual questions and 10 case-based questions. All questions were open and entered into the ChatGPT with a recommendation to limit the answer to 200 words, for greater objectivity. Responses were graded as correct (1 point); partially correct (0.5 point), or incorrect (0 point). Performances of versions 3.5 and 4 of ChatGPT were analyzed overall and separately for the conceptual and the case-based questions.
    RESULTS: ChatGPT 3.5 scored 11.5 out of 20 points (57.5% accuracy), while ChatGPT 4 scored 18 (90.0%; p = 0.031). In the conceptual questions, ChatGPT 3.5 provided accurate answers to six questions along with one partially correct response and three incorrect answers, with a final score of 6.5. In contrast, ChatGPT 4 provided correct answers to eight questions and partially correct answers to two questions, scoring 9.0. In the case-based questions, ChatGPT 3.5 scored 5.0, while ChatGPT 4 scored 9.0. The domains where ChatGPT performed worst were evaluation, treatment options, surgical complications, and special situations.
    CONCLUSIONS: ChatGPT 4 demonstrated superior performance compared to ChatGPT 3.5 in providing recommendations for the management of PPUI, using the AUA/SUFU Guideline as a benchmark. Continuous monitoring is essential for evaluating the development and precision of AI-generated medical information.
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  • 文章类型: Journal Article
    目的:术后放疗(RT)联合化疗(CT)对淋巴结阳性(LN+)三阴性乳腺癌(TNBC)的作用仍存在争议。SUV39H1介导的表观遗传调控与癌细胞迁移有关,入侵,转移,和治疗阻力。本研究旨在明确SUV39H1在TNBC中的作用。
    方法:总的来说,从TCGA-BRCA中检索并分析了498个具有SUV39H1RNA-seq谱的TNBC;使用X-tile算法将群体分层为低,中间,和高SUV39H1。此外,我们使用MDA-MB-231细胞系进行了体外克隆细胞存活测定,以评估SUV39H1对细胞应答的影响.
    结果:结果显示,TNBC中SUV39H1明显高于正常组织和管腔亚型乳腺癌。值得注意的是,SUV39H1在基底样1(BL1)和免疫调节(IM)亚组中显著表达,与其他亚型相比。与SUV39H1低或中表达的患者相比,省略RT只会使SUV39H1高表达的患者的无病生存率(DFS)恶化。实验结果表明,si-SUV39H1抑制了SUV39H1,MDA-MB-231-IV2-1细胞中SUV39H1的敲低增强了阿霉素和紫杉醇的细胞毒性。
    结论:靶向SUV39H1可能提供省略RT的潜在指导指示,以避免TNBC的过度治疗和化学敏感性。
    OBJECTIVE: The role of postoperative radiotherapy (RT) combined with chemotherapy (CT) for lymph node-positive (LN+) triple-negative breast cancer (TNBC) remains controversial. SUV39H1-mediated epigenetic regulation is associated with cancer cell migration, invasion, metastasis, and treatment resistance. This study aims to identify the role of SUV39H1 in TNBCs.
    METHODS: Overall, 498 TNBCs with SUV39H1 RNA-seq profiles were retrieved from TCGA-BRCA and analyzed; the X-tile algorithm was used to stratify the population into low, intermediate, and high SUV39H1. Furthermore, we performed an in vitro clonogenic cell survival assay using the MDA-MB-231 cell line to assess the effects of SUV39H1 on cellular responses.
    RESULTS: The results showed that SUV39H1 was significantly higher in TNBC than normal tissue and luminal subtype breast cancer. Notably, SUV39H1 is significantly expressed in the basal-like 1 (BL1) and immunomodulatory (IM) subgroups, compared to other subtypes. Compared to patients with a low or medium expression of SUV39H1, omitting RT only worsens disease-free survival (DFS) in those with high SUV39H1 expression. The experimental results showed SUV39H1 was suppressed by si-SUV39H1, and SUV39H1 knockdown in MDA-MB-231-IV2-1 cells enhanced the cellular toxicity of doxorubicin and paclitaxel.
    CONCLUSIONS: Targeting SUV39H1 may provide a potential guiding indication of omitting RT to avoid over-treatment and chemosensitivity for TNBC.
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  • 文章类型: Systematic Review
    目的:本指南的目的是提供一种用于诊断的临床结构,咨询,女性压力性尿失禁(SUI)的治疗。
    方法:2017版SUI指南的主要证据来源是ECRI研究所进行的系统文献综述。最初的搜索涵盖了2005年1月至2015年12月的文献,并在2016年9月之前进行了更新的摘要搜索。当前的修正案是对2017年迭代的首次更新,包括到2022年2月发布的更新文献。
    结果:对该指南进行了修订,以反映自2017年以来文献的变化和补充。小组坚持认为,索引患者和非索引患者之间的区别仍然很重要。索引患者是健康女性,脱垂很少或没有脱垂,需要手术治疗纯SUI或压力性混合性尿失禁。非指标患者有可能影响其治疗方案和结果的因素,如高度脱垂(3级或4级),急迫性混合性尿失禁,神经源性下尿路功能障碍,膀胱排空不完全,排尿功能失调,SUI在抗失禁治疗后,网状并发症,高体重指数,或高龄。
    结论:虽然在该领域取得了进展,以支持新的诊断方法,治疗,以及对SUI患者的随访,该领域继续扩大。因此,未来将对该指南进行审查,以保持最高水平的患者护理。
    The purpose of this guideline is to provide a clinical structure with which to approach the diagnosis, counseling, and treatment of female patients with stress urinary incontinence (SUI).
    The primary source of evidence for the 2017 version of the SUI guideline was the systematic literature review conducted by the ECRI Institute. The initial search spanned literature from January 2005 to December 2015, with an additional updated abstract search through September 2016. The current amendment represents the first update to the 2017 iteration and includes updated literature published through February 2022.
    This guideline has been amended to reflect changes in and additions to the literature since 2017. The Panel maintained that the differentiation between index and non-index patients remained important. The index patient is a healthy female with minimal or no prolapse who desires surgical therapy for treatment of pure SUI or stress-predominant mixed urinary incontinence. Non-index patients have factors that may affect their treatment options and outcomes, such as high grade prolapse (grade 3 or 4), urgency-predominant mixed incontinence, neurogenic lower urinary tract dysfunction, incomplete bladder emptying, dysfunctional voiding, SUI following anti-incontinence treatment, mesh complications, high body mass index, or advanced age.
    While gains have been made in the field to support new methods for the diagnosis, treatment, and follow-up of patients with SUI, the field continues to expand. As such, future reviews of this guideline will take place to stay in keeping with the highest levels of patient care.
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  • 文章类型: Journal Article
    2019年,美国泌尿外科协会(AUA)发布了基于证据的指南“女性复发性无并发症尿路感染:AUA/CUA/SUFU指南”。“支持该指南的信息来自太平洋西北循证实践中心(EPC)为AUA准备的2019年系统证据审查。AUA使用EPC报告中11个关键问题(附录C)的证据得出16个准则声明。2021年,EPC进行了更新文献综述(ULR),评估了自2019年系统综述以来发表的新研究的摘要。AUA要求EPC进一步评估ULR报告中包含的一部分研究,支持2019年指南的潜在变化。
    一项系统评价利用了俄勒冈健康与科学大学的研究。PacificNorthwestEPC被用来更新2019年AUA关于女性rUTI的指南,并在2021年之前发布了新的证据。
    进行了更新,以反映自2019年以来文献的变化。更新包括最近关于抗生素预防的出版物,非抗生素预防,和雌激素疗法.
    rUTI的存在对患者的健康至关重要,其影响必须考虑到社会福利。随着有关当前治疗和未来治疗选择的知识不断扩展,本文件将进行更新。.
    OBJECTIVE: In 2019 the American Urological Association (AUA) released the evidence-based guideline \"Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline.\" Information supporting the guideline came from a 2019 systematic evidence review prepared for the AUA by the Pacific Northwest Evidence-based Practice Center (EPC). The AUA used evidence found for 11 Key Questions (Appendix C) in the EPC\'s report to derive 16 Guideline Statements. In 2021 the EPC conducted an Update Literature Review (ULR) assessing abstracts from new studies published since the 2019 systematic review. The AUA asked the EPC to further assess a subset of studies included in the ULR report, to support potential changes to the 2019 guideline.
    METHODS: A systematic-review utilized research from the Oregon Health & Science University. Pacific Northwest EPC was used to update the 2019 AUA Guideline on rUTI in women with new evidence published through 2021.
    RESULTS: Updates were made to reflect changes in literature since 2019. Updates include recent publications on antibiotic prophylaxis, non-antibiotic prophylaxis, and estrogen therapy.
    CONCLUSIONS: The presence of rUTI is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand. .
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  • 文章类型: Editorial
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    铜对细菌具有广泛的毒性。因此,细菌已经进化出专门的铜输出系统(cop操纵子),通常由DNA结合/铜响应调节因子(可以是阻遏物或激活剂)组成,一个铜伴侣,一个铜出口商。对于那些使用DNA结合铜阻遏物的细菌,很少有研究研究了该操纵子对抑制子结合所需的操纵子DNA序列的调节。在肺炎链球菌(肺炎球菌)中,CopY是警察操纵子的铜抑制子。以前,肺炎球菌CopY同源物的特征是结合10个碱基的共有序列T/GACANNTGTA,称为copbox。使用这个主题,我们试图确定cop操纵子之外的基因是否也受CopY阻遏因子的调节,我们发现肺炎链球菌CopY在体外不与这些候选基因上游的cop算子结合。我们发现,cop框序列是必要的,但不足以进行CopY绑定。这里,我们提出肺炎链球菌cop操纵子的更新操纵子序列为ATTGACAAATGTAGAT结合CopY,解离常数(Kd)为28nM。我们证明了一些CopY蛋白和CopY算子之间的强跨物种相互作用,表明了强大的进化保守性。结合我们的结合研究和生物信息学数据,我们提出了细菌CopR-CopY铜阻遏同源物的共识算子RNYKACANNYGTMRNY。重要性许多革兰氏阳性细菌通过上调由铜敏感阻遏物控制的铜输出系统对铜胁迫的反应,CopR-CopY.该蛋白质家族的先前操纵子序列已被鉴定为TACANNTGTA。这里,使用几种重组蛋白和各种DNA片段中的突变,我们将这10个碱基定义为必要的,但不足以进行绑定,将cop操纵子运算符细化为16个碱基的序列RNYKACANNTGTMRNY。由于据说与原始10个碱基结合的阻遏物数量众多,包括许多抗生素抗性抑制物,如BlaI和MecI,我们认为,这项研究强调需要重新检查过去的许多网站,并在未来使用更严格的方式来验证运营商。
    Copper is broadly toxic to bacteria. As such, bacteria have evolved specialized copper export systems (cop operons) often consisting of a DNA-binding/copper-responsive regulator (which can be a repressor or activator), a copper chaperone, and a copper exporter. For those bacteria using DNA-binding copper repressors, few studies have examined the regulation of this operon regarding the operator DNA sequence needed for repressor binding. In Streptococcus pneumoniae (the pneumococcus), CopY is the copper repressor for the cop operon. Previously, homologs of pneumococcal CopY have been characterized to bind a 10-base consensus sequence T/GACANNTGTA known as the cop box. Using this motif, we sought to determine whether genes outside the cop operon are also regulated by the CopY repressor, which was previously shown in Lactococcus lactis We found that S. pneumoniae CopY did not bind to cop operators upstream of these candidate genes in vitro During this process, we found that the cop box sequence is necessary but not sufficient for CopY binding. Here, we propose an updated operator sequence for the S. pneumoniae cop operon to be ATTGACAAATGTAGAT binding CopY with a dissociation constant (Kd ) of ∼28 nM. We demonstrate strong cross-species interaction between some CopY proteins and CopY operators, suggesting strong evolutionary conservation. Taken together with our binding studies and bioinformatics data, we propose the consensus operator RNYKACANNYGTMRNY for the bacterial CopR-CopY copper repressor homologs.IMPORTANCE Many Gram-positive bacteria respond to copper stress by upregulating a copper export system controlled by a copper-sensitive repressor, CopR-CopY. The previous operator sequence for this family of proteins had been identified as TACANNTGTA. Here, using several recombinant proteins and mutations in various DNA fragments, we define those 10 bases as necessary but not sufficient for binding and in doing so, refine the cop operon operator to the 16-base sequence RNYKACANNTGTMRNY. Due to the sheer number of repressors that have been said to bind to the original 10 bases, including many antibiotic resistance repressors such as BlaI and MecI, we feel that this study highlights the need to reexamine many of these sites of the past and use added stringency for verifying operators in the future.
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  • 文章类型: Journal Article
    弥漫大B细胞淋巴瘤(DLBCL)是非霍奇金淋巴瘤(NHL)最常见的亚型,病态,和具有高度可变的临床结果的分子异质性疾病。目前,目前仍缺乏有效的DLBCL预后标志物.优化靶向治疗,改善DLBCL的预后,建议的生物标志物的性能需要在多个队列中进行评估,新的生物标志物需要在大数据集中进行研究。这里,我们为弥漫性大B细胞淋巴瘤开发了一个一致的在线生存分析网络服务器,缩写为OSdlbcl,评估个体基因的预后价值。要构建OSdlbcl,我们从癌症基因组图谱(TCGA)和基因表达综合(GEO)数据库中收集了1100份具有基因表达谱和临床随访信息的样本.此外,还从TCGA数据库收集DNA突变数据。总生存期(OS),无进展生存期(PFS),疾病特异性生存率(DSS),无病间隔(DFI),无进展间期(PFI)是反映OSdlbcl生存率的重要终点。此外,将临床特征整合到OSdlbcl中,以便根据用户的特殊需要进行数据分层.通过输入官方基因符号并选择所需的标准,生存分析结果可以通过具有风险比(HR)和log-rankp值的Kaplan-Meier(KM)图以图形方式呈现。作为概念验证演示,先前报道的23种生存相关生物标志物的预后价值,在OSdlbcl中评估了转录因子FOXP1和BCL2,发现它们与所报告的生存率显着相关(HR=1.73,P<.01;HR=1.47,P=.03)。总之,OSdlbcl是一个新的网络服务器,集成了公共基因表达,基因突变数据,和临床随访信息,为DLBCL的生物标志物开发提供预后评估。OSdlbclWeb服务器可在https://bioinfo获得。henu.edu.cn/DLBCL/DLBCLList。jsp.
    Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL) and is a clinical, pathological, and molecular heterogeneous disease with highly variable clinical outcomes. Currently, valid prognostic biomarkers in DLBCL are still lacking. To optimize targeted therapy and improve the prognosis of DLBCL, the performance of proposed biomarkers needs to be evaluated in multiple cohorts, and new biomarkers need to be investigated in large datasets. Here, we developed a consensus Online Survival analysis web server for Diffuse Large B-Cell Lymphoma, abbreviated OSdlbcl, to assess the prognostic value of individual gene. To build OSdlbcl, we collected 1100 samples with gene expression profiles and clinical follow-up information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In addition, DNA mutation data were also collected from the TCGA database. Overall survival (OS), progression-free survival (PFS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) are important endpoints to reflect the survival rate in OSdlbcl. Moreover, clinical features were integrated into OSdlbcl to allow data stratifications according to the user\'s special needs. By inputting an official gene symbol and selecting desired criteria, the survival analysis results can be graphically presented by the Kaplan-Meier (KM) plot with hazard ratio (HR) and log-rank p value. As a proof-of-concept demonstration, the prognostic value of 23 previously reported survival associated biomarkers, such as transcription factors FOXP1 and BCL2, was evaluated in OSdlbcl and found to be significantly associated with survival as reported (HR = 1.73, P < .01; HR = 1.47, P = .03, respectively). In conclusion, OSdlbcl is a new web server that integrates public gene expression, gene mutation data, and clinical follow-up information to provide prognosis evaluations for biomarker development for DLBCL. The OSdlbcl web server is available at https://bioinfo.henu.edu.cn/DLBCL/DLBCLList.jsp.
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  • 文章类型: Journal Article
    Histone deacetylases (HDAC) are being targeted for a number of diseases such as cancer, inflammatory disease, and neurological disorders. Within this family of 18 isozymes, HDAC4 is a prime target for glioma, one of the most aggressive brain tumors reported. Thus, the development of HDAC4 inhibitors could present a novel therapeutic route for glioma. In this work, molecular docking studies on cyclopropane hydroxamic acid derivatives identified five novel molecular interactions to the HDAC4 receptor that could be harnessed to enhance inhibitor binding. Thus, design guidelines for the optimization of potent HDAC4 inhibitors were developed which can be utilized to further the development of HDAC4 inhibitors. Using the developed guidelines, eleven novel cyclopropane hydroxamic acid derivatives were designed that outcompeted all original cyclopropane hydroxamic acids HDAC4 inhibitors studied in silico. The results of this work will be an asset to paving the way for further design and optimization of novel potent HDAC4 inhibitors for gliomas.
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