Archives of biochemistry and biophysics最新文献_第6页

Microbial metabolite deoxycholic acid inhibits noncancerous NCM460 human colon cell proliferation: an inverse correlation between Bmal1:Clock gene expression and cell apoptosis 微生物代谢物脱氧胆酸抑制非癌性NCM460人结肠细胞增殖：Bmal1::Clock基因表达与细胞凋亡呈负相关

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics

Pub Date : 2025-12-05 DOI: 10.1016/j.abb.2025.110694

Huawei Zeng , Bryan D. Safratowich , Zhenhua Liu , Mary Briske-Anderson

High fat diets increase colonic deoxycholic acid (DCA) concentrations, which induce apoptosis, and subsequently enrich a compensatory DCA-resistant mutant colon cell subpopulation. While circadian Bmal1 and Clock genes are key regulators for cell proliferation, little is known about the relationship between DCA-induced apoptosis and circadian gene regulation in normal colon cells. In this study, we employed a noncancerous NCM460 human colon cell model to simulate the effect of DCA on cell proliferation in the colon and hypothesized that DCA-induced apoptosis is regulated by the Bmal1Clock complex in colon cells. Compared to the control cells, the treatment with DCA at 0.3- and 0.4-mM inhibited cell proliferation (via cell cycle arrest and apoptosis) by 19 % and 29 %, respectively. As the Bmal1Clock complex and Wnt signaling pathways are interlinked with apoptotic processes, we identified that 42 genes were differentially expressed in the Wnt signaling pathway; and there was a decrease (≥47 %) in Bmal1, Clock and Wee1 protein levels but an increase (≥172 %) in Rev-Erbα protein levels in DCA-treated cells compared to the control cells. At clinical levels, the mRNA levels of Bmal1 and Rev-Erbα were decreased by (≥) 15 % while Wee1 was increased by 38 % in cancerous colon tissues compared to normal ones. Collectively, DCA inhibits noncancerous NCM460 colon cell proliferation via cell cycle arrest and apoptosis accompanied with a drop of Bmal1Clock gene expression and altered Wnt signaling pathways. The Bmal1Clock regulatory network is relatively normal in the DCA-treated noncancerous NCM460 colon cells but not in colon cancer tissues.

高脂肪饮食增加结肠脱氧胆酸（DCA）浓度，诱导细胞凋亡，随后丰富代偿性DCA抗性突变结肠细胞亚群。虽然昼夜节律Bmal1和Clock基因是细胞增殖的关键调控因子，但在正常结肠细胞中，dca诱导的细胞凋亡与昼夜节律基因调控之间的关系尚不清楚。本研究采用非癌性NCM460人结肠细胞模型模拟DCA对结肠细胞增殖的影响，并假设DCA诱导的结肠细胞凋亡受Bmal1::Clock复合物调控。与对照细胞相比，0.3和0.4 mm的DCA处理分别抑制了19%和29%的细胞增殖（通过细胞周期阻滞和凋亡）。由于Bmal1::Clock复合体和Wnt信号通路与凋亡过程相互关联，我们发现42个基因在Wnt信号通路中差异表达；与对照细胞相比，dca处理的细胞Bmal1、Clock和Wee1蛋白水平降低（≥47%），Rev-Erbα蛋白水平升高（≥172%）。在临床水平上，癌性结肠组织中Bmal1和Rev-Erbα mRNA水平较正常结肠组织降低（≥）15%，而Wee1 mRNA水平较正常结肠组织升高38%。总的来说，DCA通过细胞周期阻滞和凋亡抑制非癌性NCM460结肠细胞增殖，同时降低Bmal1::Clock基因表达和改变Wnt信号通路。Bmal1::Clock调节网络在dca处理的非癌性NCM460结肠细胞中相对正常，而在结肠癌组织中则不正常。

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引用次数: 0

RHAU helicase affects testosterone synthesis by regulating the Star 3′ UTR region RHAU解旋酶通过调节Star 3' UTR区影响睾酮合成。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics

Pub Date : 2025-12-05 DOI: 10.1016/j.abb.2025.110690

Zhongyu Qin , Kaixia Li , Yang Song , Yuwen Wu , Haorui Wang , Xuanjie Li , Jiayi Huang , Shuaishuai Shi , Yiqiang Zhang

This study investigates the role and regulatory mechanism of RNA helicase and RNA-binding protein RHAU in testosterone synthesis. Using molecular biology techniques, such as circular dichroism spectroscopy, RNA-protein interaction assays, gene expression analysis, and ELISA functional assays, we explored the interaction between RHAU and the 3′ untranslated region of Star mRNA, and its effect on mRNA stability and translation efficiency. The results show that conditional knockdown of RHAU leads to decreased testosterone levels in mouse blood, reduced translation of steroidogenic acute regulatory protein (STAR), and significantly increased apoptosis of testicular interstitial cells. RHAU specifically binds to the G-quadruplex structure in the 3′ untranslated region of Star mRNA, regulating STAR expression and affecting testosterone synthesis. This study is the first to reveal the critical role of RHAU in testosterone synthesis and post-transcriptional regulation. Moreover, RHAU emerges as a potential therapeutic target for diseases related to testosterone imbalance.

本研究探讨了RNA解旋酶和RNA结合蛋白RHAU在睾酮合成中的作用及其调控机制。利用分子生物学技术，如圆二色光谱、rna -蛋白相互作用分析、基因表达分析和ELISA功能分析，我们探讨了RHAU与Star mRNA 3'非翻译区相互作用及其对mRNA稳定性和翻译效率的影响。结果表明，有条件地敲低RHAU可导致小鼠血液中睾酮水平降低，类固醇急性调节蛋白（STAR）翻译减少，睾丸间质细胞凋亡显著增加。RHAU特异性结合Star mRNA 3'非翻译区g -四重体结构，调节Star表达并影响睾酮合成。这项研究首次揭示了RHAU在睾酮合成和转录后调控中的关键作用。此外，RHAU成为睾酮失衡相关疾病的潜在治疗靶点。

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引用次数: 0

An in silico DNA binding investigation using DFT, molecular docking and molecular dynamics simulation on mono and tetra acetylated derivatives of quinalizarin to enable a comparison with experimental DNA binding data 利用DFT、分子对接和分子动力学模拟对喹那沙林单乙酰化衍生物和四乙酰化衍生物进行了硅DNA结合研究，以便与实验DNA结合数据进行比较。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics

Pub Date : 2025-12-04 DOI: 10.1016/j.abb.2025.110680

Tanmoy Saha , Sayantani Chatterjee , Saurabh Das

Following dissociation of phenolic–OH, quinalizarin generates anions that face repulsion from DNA posing a challenge to its use as an alternative to anthracyclines. An earlier attempt to prevent anion formation by converting all –OH groups to acetyl units had resulted in increased binding with DNA. Although such increase in binding with DNA compared to quinalizarin was observed, owing to a simultaneous increase in steric bulk, a doubt had remained as to whether it was a true manifestation of acetylation. The suspicion being, whether increase in binding constant overcoming repulsion was offset in any way by increase in steric bulk. This in silico DNA binding investigation aims to realize what would be the outcome if one exclusively acetylates the –OH responsible for mono-anion formation. Not having experimental binding information on mono-acetylated species, DNA binding was tried by an in silico approach. Analysis reveals tetra-acetylated quinalizarin was better than the mono-acetylated form; increase due to groove binding, rather than by intercalation being the correct manifestation. Three forms of quinalizarin and the standard drug doxorubicin were investigated by a general DNA model (PDBID:1BNA) and subsequently by intercalation specific (PDBID:1Z3F) and groove binding specific (PDBID:101D) models. ADMET profiles for drug-like properties were done. Information from in silico analysis suggest simpler analogues of anthracyclines are economical and acetylation of all –OH groups of quinalizarin is biologically significant.

在苯酚- oh解离后，喹那沙林产生阴离子，面临DNA的排斥，这对其作为蒽环类药物的替代品提出了挑战。早期尝试通过将所有-OH基团转化为乙酰基单元来阻止阴离子的形成，结果增加了与DNA的结合。虽然与喹那沙林相比，观察到与DNA结合的增加，但是，由于空间体积同时增加，对于这是否是乙酰化的真正表现仍然存在疑问。怀疑是，是否增加的结合常数克服排斥以任何方式抵消了空间体积的增加。这个硅DNA结合研究的目的是了解如果一个人完全乙酰化负责单阴离子形成的-OH会有什么结果。由于没有单乙酰化物种的实验结合信息，DNA结合采用了计算机方法。分析表明，四乙酰化的喹那沙林优于单乙酰化的喹那沙林；增加是通过凹槽结合，而不是通过插入来正确表现的。采用一般DNA模型（PDBID:1BNA）、插层特异性模型（PDBID:1Z3F）和凹槽结合特异性模型（PDBID:101D）对三种形式的喹那沙林、标准药物阿霉素进行了研究。ADMET对药物样性质进行了分析。来自计算机分析的信息表明，更简单的蒽环类药物类似物是经济的，喹那西林所有-OH基团的乙酰化具有重要的生物学意义。

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引用次数: 0

Nucleotide-dependent structural dynamics and domain motion in Coxiella burnetii EngA GTPases: Insights from molecular dynamics simulation 伯氏杆菌gtp酶的核苷酸依赖结构动力学和结构域运动：来自分子动力学模拟的见解。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics

Pub Date : 2025-12-04 DOI: 10.1016/j.abb.2025.110693

K.M. Kavya , Guruswaroop C , Upendra N , Krishnaveni S

EngA, a ribosome-associated bacterial GTPase essential for 50S subunit maturation and bacterial growth, lacks a human ortholog, making it an attractive antibacterial target. Its activity is governed by a nucleotide-dependent molecular switch: GTP binding promotes EngA association with the immature 50S subunit and facilitates rRNA processing, whereas GTP hydrolysis to GDP triggers dissociation from the ribosome. Structural studies on Bacillus subtilis EngA revealed that GTP-analog-bound EngA disrupts the GD1-KH interface required for 45S subunit association, while GDP-bound EngA retains these interactions. However, the molecular mechanism by which nucleotides regulate these transitions and whether similar mechanisms exist in other pathogenic species remain unclear. To address this, 1000 ns molecular dynamics simulations of Coxiella burnetii EngA was performed in four nucleotide-bound states: [GDP:GDP], [GDP:GTP-Mg²⁺], [GTP-Mg²⁺:GDP], and [GTP-Mg²⁺:GTP-Mg²⁺]. Analyses of principal components, interaction energies, and distance-angle parameters revealed nucleotide-dependent domain dynamics. In the [GTP-Mg²⁺:GTP-Mg²⁺] state, GD1 and KH domains moved apart, forming an open conformation, while in [GDP:GDP] they approached each other, forming a closed conformation consistent with cryo-EM structures. Community network analysis further showed that GDP binding to GD1 extends connectivity from the nucleotide to SwI, stabilizing SwI-KH interactions and restricting GD1 motion. In contrast, GTP-Mg²⁺ binding disrupts this network, enabling SwI-GD2 interactions that weaken the GD1-KH interface and promote an open conformation. Overall, the results highlight how nucleotide charge-dependent interactions regulate EngA allosteric network and drive its conformational switching mechanism.

EngA是一种核糖体相关的细菌GTPase，对50S亚基成熟和细菌生长至关重要，缺乏人类同源物，使其成为一个有吸引力的抗菌靶点。其活性受核苷酸依赖的分子开关控制：GTP结合促进EngA与未成熟的50S亚基结合并促进rRNA加工，而GTP水解为GDP则触发核糖体的解离。对枯草芽孢杆菌EngA的结构研究表明，gpp -类似物结合的EngA破坏了45S亚基结合所需的GD1-KH界面，而gdp -结合的EngA保留了这些相互作用。然而，核苷酸调节这些转变的分子机制以及其他致病物种中是否存在类似机制尚不清楚。为了解决这一问题，研究人员在4种核苷酸结合状态（[GDP:GDP]、[GDP:GTP-Mg2+]、[GTP-Mg2+:GDP]和[GTP-Mg2+:GTP-Mg2+]）下进行了1000 ns的伯氏杆菌EngA分子动力学模拟。主成分、相互作用能和距离角参数的分析揭示了核苷酸依赖的结构域动力学。在[GTP-Mg2+:GTP-Mg2+]状态下，GD1和KH结构域分开，形成一个开放的构象，而在[GDP:GDP]状态下，它们彼此靠近，形成一个封闭的构象，与低温电镜结构一致。社区网络分析进一步表明，GDP与GD1的结合扩展了从核苷酸到SwI的连通性，稳定了SwI- kh相互作用并限制了GD1的运动。相比之下，GTP-Mg2+的结合破坏了这个网络，使wi - gd2相互作用削弱了GD1-KH界面并促进了开放构象。总的来说，结果强调了核苷酸电荷依赖的相互作用如何调节EngA变构网络并驱动其构象转换机制。

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引用次数: 0

The role of miR-491-3p in early diagnosis and prognosis evaluation of acute myocardial infarction miR-491-3p在急性心肌梗死早期诊断及预后评价中的作用

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics

Pub Date : 2025-12-03 DOI: 10.1016/j.abb.2025.110691

Tai Dou , Lijie Qin , Peirong Zhang, Lijun Xu, Yanwei Cheng, Peng Wang

Aims

To investigate the expression characteristics, clinical implications, and underlying mechanisms of miR-491-3p in patients with acute myocardial infarction (AMI).

Methods

Serum samples were collected from patients with AMI and healthy controls. miR-491-3p expression was measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curves evaluated its diagnostic accuracy for AMI. Correlations between miR-491-3p levels and myocardial injury markers or inflammatory factors were analyzed. A one-year follow-up assessed its predictive value for major adverse cardiovascular events (MACE). A hypoxia/reoxygenation (H/R) model of human AC16 cardiomyocytes was established to explore the mechanism of miR-491-3p in H/R-induced injury via targeting aquaporin 9 (AQP9).

Results

Serum miR-491-3p was significantly downregulated in AMI patients, with an AUC of 0.893 for AMI diagnosis (sensitivity 83 %, specificity 79.5 %). Levels were negatively correlated with myocardial injury markers and inflammatory factors. AMI patients with low miR-491-3p expression had a higher incidence of MACE, and low expression was identified as a risk factor. In the H/R model, miR-491-3p was downregulated. Overexpression of miR-491-3p improved cell proliferation, reduced apoptosis, and decreased inflammatory factors by targeting and inhibiting AQP9.

Conclusions

miR-491-3p may be involved in the pathological process of AMI by targeting and regulating AQP9. This makes it a promising candidate as both a diagnostic and prognostic marker for AMI, as well as a potential therapeutic target.

目的：探讨miR-491-3p在急性心肌梗死（AMI）患者中的表达特征、临床意义及其机制。方法：分别采集AMI患者和健康对照者的血清样本。采用逆转录定量聚合酶链反应（RT-qPCR）检测miR-491-3p的表达。受试者工作特征（ROC）曲线评价其诊断AMI的准确性。分析miR-491-3p水平与心肌损伤标志物或炎症因子的相关性。1年随访评估其对主要不良心血管事件（MACE）的预测价值。建立人AC16心肌细胞缺氧/再氧化（H/R）模型，通过靶向水通道蛋白9 （AQP9）探讨miR-491-3p在H/R诱导损伤中的作用机制。结果：AMI患者血清miR-491-3p明显下调，AMI诊断AUC为0.893（敏感性83%，特异性79.5%）。其水平与心肌损伤标志物和炎症因子呈负相关。miR-491-3p低表达的AMI患者MACE发生率较高，低表达被认为是一个危险因素。在H/R模型中，miR-491-3p下调。过表达miR-491-3p通过靶向和抑制AQP9促进细胞增殖，减少细胞凋亡，降低炎症因子。结论：miR-491-3p可能通过靶向调控AQP9参与AMI的病理过程。这使其成为AMI的诊断和预后标志物，以及潜在的治疗靶点。

{"title":"The role of miR-491-3p in early diagnosis and prognosis evaluation of acute myocardial infarction","authors":"Tai Dou , Lijie Qin , Peirong Zhang, Lijun Xu, Yanwei Cheng, Peng Wang","doi":"10.1016/j.abb.2025.110691","DOIUrl":"10.1016/j.abb.2025.110691","url":null,"abstract":"<div><h3>Aims</h3><div>To investigate the expression characteristics, clinical implications, and underlying mechanisms of miR-491-3p in patients with acute myocardial infarction (AMI).</div></div><div><h3>Methods</h3><div>Serum samples were collected from patients with AMI and healthy controls. miR-491-3p expression was measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curves evaluated its diagnostic accuracy for AMI. Correlations between miR-491-3p levels and myocardial injury markers or inflammatory factors were analyzed. A one-year follow-up assessed its predictive value for major adverse cardiovascular events (MACE). A hypoxia/reoxygenation (H/R) model of human AC16 cardiomyocytes was established to explore the mechanism of miR-491-3p in H/R-induced injury via targeting aquaporin 9 (AQP9).</div></div><div><h3>Results</h3><div>Serum miR-491-3p was significantly downregulated in AMI patients, with an AUC of 0.893 for AMI diagnosis (sensitivity 83 %, specificity 79.5 %). Levels were negatively correlated with myocardial injury markers and inflammatory factors. AMI patients with low miR-491-3p expression had a higher incidence of MACE, and low expression was identified as a risk factor. In the H/R model, miR-491-3p was downregulated. Overexpression of miR-491-3p improved cell proliferation, reduced apoptosis, and decreased inflammatory factors by targeting and inhibiting AQP9.</div></div><div><h3>Conclusions</h3><div>miR-491-3p may be involved in the pathological process of AMI by targeting and regulating AQP9. This makes it a promising candidate as both a diagnostic and prognostic marker for AMI, as well as a potential therapeutic target.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"776 ","pages":"Article 110691"},"PeriodicalIF":3.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A comprehensive review of the structural basis for the selectivity of sulfonamide-based inhibitors for carbonic anhydrase isoforms IX and XII over carbonic anhydrase II based on the available high quality crystallographic data 基于现有的高质量晶体学数据，综述了基于磺胺类抑制剂对碳酸酐酶异构体IX和XII对碳酸酐酶II选择性的结构基础。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics

Pub Date : 2025-12-01 DOI: 10.1016/j.abb.2025.110682

Sarfraz Ahmad , Muhammad Usman Mirza , Mamoona Nazir , Lee Yean Kee , Noorsaadah Binti Abd Rahman , Iskandar Abdullah , John F. Trant

Hypoxia in solid tumours induces carbonic anhydrases (CAs) upregulation, notably CA IX and CA XII, to sustain pH homeostasis. While sulfonamide-based zinc binders show high affinity for these targets, achieving the required selectivity versus the ubiquitous CA II remains challenging. Fortunately, the efforts of the community in obtaining experimental structures of ligand-protein complexes have now generated sufficient samples to rationalize isoform preferences. Herein, we provide our detailed structure-annotated meta-analysis of sulfonamide binding across CA II, CA IX, and CA XII that standardizes residue numbering and interaction taxonomy. We examine 130 X-ray cocrystal structures, CA II (47), CA IX (55), and CA XII (28), to quantify Zn–sulfonamide geometry, entrance-zone contacts (Arg60, Thr199/Thr200, His64 π-cation), conserved water mediation, and occupancy/orientation within the 130s subpocket (residues 131/132/135) that provide the best opportunities for delivering selectivity. From these data, we extract concrete, structure-derived design rules: (i) lowering sulfonamide pKa boosts affinity across isoforms but does not confer selectivity; (ii) directing steric/hydrophobic bulk into the 130s subpocket exploits Phe131/Gly132/Val135 (CA II) versus Val131/Asp132/Leu135 (CA IX) versus Ala131/Ser132/Ser135 (CA XII) differences; (iii) favourable entrance-zone interactions, e.g., salt bridging to Arg60 (IX), halogen bonding to Thr199, and occasional His64 π-cation, enhances IX/XII bias; and (iv) compact, highly polar heads without tailored tails tend to default to preferring CA II. This critical synthesis consolidates the dispersed structural evidence into an isoform-resolved map of selectivity-enabling interactions. This provides public access to a very useful tool for CA IX/XII-selective inhibitor design.

实体肿瘤中的缺氧诱导碳酸酐酶（CAs）上调，特别是caix和caxii，以维持pH稳态。虽然基于磺胺的锌粘合剂对这些靶标具有很高的亲和力，但与普遍存在的CA II相比，实现所需的选择性仍然具有挑战性。幸运的是，该社区在获得配体-蛋白质复合物的实验结构方面的努力现在已经产生了足够的样品来合理化异构体偏好。在此，我们提供了详细的结构注释的磺胺结合CA II， CA IX和CA XII的meta分析，标准化残基编号和相互作用分类。我们研究了130个x射线共晶结构，CA II (47), CA IX（55）和CA XII(28)，以量化zn -磺胺的几何形状，入口区接触（Arg60, Thr199/Thr200， His64 π-阳离子），保守的水介质和130s子包内的占据/取向（残基131/132/135），为传递选择性提供了最佳机会。从这些数据中，我们提取了具体的，结构衍生的设计规则：(i)降低磺胺pKa提高了跨异构体的亲和力，但不赋予选择性；（ii）利用Phe131/Gly132/Val135 （CA ii）与Val131/Asp132/Leu135 （CA IX）和Ala131/Ser132/Ser135 （CA XII）的差异，将空间/疏水体导向130s子口袋；（iii）有利的入口区相互作用，如盐与Arg60 （IX）的桥接，卤素与Thr199的键合，以及偶尔的His64 π阳离子，增强了IX/XII偏置；（iv）紧凑，高度极性的头部，没有量身定制的尾巴，倾向于默认选择CA II。这一关键的综合将分散的结构证据整合成一个具有选择性的相互作用的同型分辨图。这为CA IX/ xii选择性抑制剂的设计提供了一个非常有用的工具。

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引用次数: 0

Predictive value of LncRNA LINC00667 in the development and prognosis of papillary thyroid carcinoma and its possible regulation of cellular processes via miR-34c-5p LncRNA LINC00667在甲状腺乳头状癌发生和预后中的预测价值及其可能通过miR-34c-5p调控细胞过程。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics

Pub Date : 2025-12-01 DOI: 10.1016/j.abb.2025.110683

Qinghua Zhang , Zhao Liu , Zhiyong Li , Xiancun Hou , Changli Ouyang

Background

As a major type of endocrine malignancy, thyroid cancer (THCA) has a relatively high occurrence rate around the world. However, the underlying mechanism through which LINC00667 acts in papillary thyroid carcinoma (PTC) remains unelucidated.

Methods

A total of 120 PTC patients were enrolled. The expression of LINC00667 was analyzed using reverse transcription-quantitative polymerase chain reaction. To evaluate the clinical significance of LINC00667, chi-square analysis was performed, a Kaplan-Meier survival curve was generated, and multivariate Cox analysis was conducted to determine its association with the clinical-pathological characteristics and prognostic outcomes of PTC. Cell Counting Kit-8 and Transwell assays evaluated changes in cellular processes. A dual luciferase reporter assay and RNA Immunoprecipitation were employed to analyze the binding relationship between LINC00667 and miR-34c-5p.

Results

LINC00667 exhibited significant up-regulation in PTC tissues, with elevated expression levels associated with tumor malignancy. Increased LINC00667 expression was a marker of unfavorable prognostic outcomes and functioned as an independent risk indicator for PTC. Knockdown of LINC00667 expression inhibited the proliferation, migration capability, and invasive properties of PTC cells. Furthermore, LINC00667 was identified to exert a negative regulatory effect on miR-34c-5p, and the silencing of miR-34c-5p weakened the inhibitory impacts induced by LINC00667 depletion on the malignant behaviors of PTC cells.

Conclusions

Up-regulated LINC00667 may serve as a biomarker for PTC. Knockdown of LINC00667 may inhibit the progression of PTC by regulating miR-34c-5p.

背景：甲状腺癌（THCA）是一种主要的内分泌恶性肿瘤，在世界范围内发病率较高。然而，LINC00667在甲状腺乳头状癌（PTC）中的作用机制尚不清楚。方法：共纳入120例PTC患者。采用逆转录-定量聚合酶链反应分析LINC00667的表达。为了评价LINC00667的临床意义，我们进行卡方分析，生成Kaplan-Meier生存曲线，并进行多因素Cox分析，以确定其与PTC临床病理特征及预后结局的相关性。细胞计数试剂盒-8和Transwell检测评估细胞过程的变化。采用双荧光素酶报告基因法和RNA免疫沉淀法分析LINC00667与miR-34c-5p的结合关系。结果：LINC00667在PTC组织中表达显著上调，表达水平升高与肿瘤恶性相关。升高的LINC00667表达是不良预后的标志，是PTC的独立风险指标。抑制LINC00667表达抑制PTC细胞的增殖、迁移能力和侵袭特性。此外，我们发现LINC00667对miR-34c-5p具有负调控作用，miR-34c-5p的沉默减弱了LINC00667缺失对PTC细胞恶性行为的抑制作用。结论：上调的LINC00667可能作为PTC的生物标志物。敲低LINC00667可能通过调节miR-34c-5p抑制PTC的进展。

{"title":"Predictive value of LncRNA LINC00667 in the development and prognosis of papillary thyroid carcinoma and its possible regulation of cellular processes via miR-34c-5p","authors":"Qinghua Zhang , Zhao Liu , Zhiyong Li , Xiancun Hou , Changli Ouyang","doi":"10.1016/j.abb.2025.110683","DOIUrl":"10.1016/j.abb.2025.110683","url":null,"abstract":"<div><h3>Background</h3><div>As a major type of endocrine malignancy, thyroid cancer (THCA) has a relatively high occurrence rate around the world. However, the underlying mechanism through which LINC00667 acts in papillary thyroid carcinoma (PTC) remains unelucidated.</div></div><div><h3>Methods</h3><div>A total of 120 PTC patients were enrolled. The expression of LINC00667 was analyzed using reverse transcription-quantitative polymerase chain reaction. To evaluate the clinical significance of LINC00667, chi-square analysis was performed, a Kaplan-Meier survival curve was generated, and multivariate Cox analysis was conducted to determine its association with the clinical-pathological characteristics and prognostic outcomes of PTC. Cell Counting Kit-8 and Transwell assays evaluated changes in cellular processes. A dual luciferase reporter assay and RNA Immunoprecipitation were employed to analyze the binding relationship between LINC00667 and miR-34c-5p.</div></div><div><h3>Results</h3><div>LINC00667 exhibited significant up-regulation in PTC tissues, with elevated expression levels associated with tumor malignancy. Increased LINC00667 expression was a marker of unfavorable prognostic outcomes and functioned as an independent risk indicator for PTC. Knockdown of LINC00667 expression inhibited the proliferation, migration capability, and invasive properties of PTC cells. Furthermore, LINC00667 was identified to exert a negative regulatory effect on miR-34c-5p, and the silencing of miR-34c-5p weakened the inhibitory impacts induced by LINC00667 depletion on the malignant behaviors of PTC cells.</div></div><div><h3>Conclusions</h3><div>Up-regulated LINC00667 may serve as a biomarker for PTC. Knockdown of LINC00667 may inhibit the progression of PTC by regulating miR-34c-5p.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"776 ","pages":"Article 110683"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Structure and reaction mechanisms of a two-component indole monooxygenase from Acinetobacter baumannii 鲍曼不动杆菌双组分吲哚单加氧酶的结构和反应机理。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics

Pub Date : 2025-11-29 DOI: 10.1016/j.abb.2025.110681

Kanyarat Suksomjaisaman , Konrawee Thananon , Montisa Mangkalee , Kittisak Thotsaporn , Ruchanok Tinikul , Albert Schulte , Kittikhun Wangkanont , Supaart Sirikantaramas , Jeerus Sucharitakul , Pimchai Chaiyen

The indole monooxygenase system from Acinetobacter baumannii is a two-component flavoprotein that catalyzes the monooxygenation of indole. The system consists of the flavoprotein reductase (IndR) and the oxygenase (IndOx). IndR generates reduced FAD (FADH⁻) to IndOx using NADH. The pre-equilibration of IndOx with FADH⁻ inhibits the formation of C4a-hydroperoxyflavin. In contrast, the presence of indole facilitates the formation of C4a-hydroperoxyflavin. The structural study reveals a dynamic loop at the active site, which has never been demonstrated in this class of enzyme, resulting in two conformations of IndOx. The closed conformation prevents the formation of the C4a-hydroperoxyflavin, whereas the binding of indole directs the open conformation, allowing for the formation of C4a-hydroperoxyflavin. The kinetic mechanism of both components was elucidated using rapid kinetics. The binding of indole to form a ternary complex is a preferential random-order mechanism in which indole preferentially binds to IndOx:C4a-hydroperoxyflavin, compared with IndOx:FADH⁻ complex. The turnover number in the presence of both components to produce 3-hydroxyindole demonstrated that either the release of oxidized FAD or the release of monooxygenated product from the IndOx active site, or partially both, entirely limits the catalytic reaction. The solvent isotope effect on the step of the structural rearrangement of the monooxygenated product to form 3-hydroxyindole in this study supports the previously proposed epoxide-dihydrodiol model. This step is significantly slower than the turnover number, indicating that the monooxygenated indole is released and then undergoes a non-enzymatic structural rearrangement outside the active site, leading to the formation of 3-hydroxyindole.

来自鲍曼不动杆菌的吲哚单加氧酶系统是一种催化吲哚单加氧的双组分黄蛋白。该系统由黄蛋白还原酶（IndR）和加氧酶（IndOx）组成。IndR利用NADH生成还原性FAD （FADH-）到IndOx。IndOx与FADH-的预平衡抑制了c4a -氢过氧黄素的形成。相反，吲哚的存在有利于c4a -氢过氧黄素的形成。结构研究揭示了活性位点的动态环，这在该类酶中从未被证实，导致IndOx的两种构象。封闭的构象阻止了c4a -氢过氧黄素的形成，而吲哚的结合引导了开放的构象，允许c4a -氢过氧黄素的形成。用快速动力学方法对两组分的动力学机理进行了分析。吲哚结合形成三元配合物是一种优先的随机顺序机制，与IndOx: c4a -氢过氧黄素复合物相比，吲哚优先与IndOx: c4a -氢过氧黄素结合。在这两种成分存在的情况下生成3-羟基吲哚的周转数表明，氧化FAD的释放或单氧产物从IndOx活性位点的释放，或两者的部分释放，完全限制了催化反应。本研究中溶剂同位素对单氧产物结构重排生成3-羟基吲哚步骤的影响支持了之前提出的环氧化物-二氢二醇模型。这一步骤明显慢于周转数，说明单氧吲哚被释放，然后在活性位点外进行非酶促结构重排，形成3-羟基吲哚。

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引用次数: 0

mmu_circ_0000684/hsa_circ_0067098 mediates renal tubular epithelial cells apoptosis to ischemia-reperfusion-induced acute kidney injury by targeting the mmu_miR_671-5p/ARID3B axis mmu_circ_0000684/hsa_circ_0067098通过靶向mmu_miR_671-5p/ARID3B轴介导肾小管上皮细胞凋亡至缺血再灌注诱导的急性肾损伤

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics

Pub Date : 2025-11-29 DOI: 10.1016/j.abb.2025.110679

Ben Yang , Qiang Zheng , Yan Pu , Yingying Hu , Dongshan Zhang

Objective

This investigation sought to explore the possible role of mmu_circ_0000684 and its homolog hsa_circ_0067098 in the evolution of ischemia-reperfusion-induced acute kidney injury (AKI), with an emphasis on their viability as therapeutic targets.

Method

A model was constructed employing Boston University mouse proximal tubule (BUMPT) cells, human renal tubular epithelial (HK-2) cells, and murine kidney tissue. The mmu_circ_0000684, miR-671-5p, and ARID3B mRNA levels, along with their corresponding protein expression, underwent quantification via real-time quantitative polymerase chain reaction and Western blot. A comprehensive examination of the biological roles and signaling cascade of mmu_circ_0000684 and hsa_circ_0067098 was executed utilizing bioinformatics prediction, luciferase reporter assays, fluorescence in situ hybridization, flow cytometry, hematoxylin and eosin staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining.

Results

Ischemic stress was observed to induce mmu_circ_0000684 expression. Functionally, mmu_circ_0000684 was implicated in promoting BUMPT cell apoptosis as a consequence of ischemia-reperfusion injury. Mechanistically, mmu_circ_0000684 acted as a molecular sponge for miR-671-5p, thereby facilitating the upregulation of ARID3B, which in turn contributed to apoptosis induction. Moreover, silencing mmu_circ_0000684 markedly mitigated ischemia-triggered AKI via modulation of the miR-671-5p/ARID3B axis. Notably, hsa_circ_0067098, the homolog of mmu_circ_0000684, exhibited an analogous regulatory role in HK-2 cells.

Conclusion

The mmu_circ_0000684, hsa_circ_0067098/miR-671-5p/ARID3B signaling cascade emerges as an essential mechanism during ischemic AKI progression. Consequently, hsa_circ_0067098 represents a promising therapeutic candidate for addressing ischemic AKI.

目的：本研究旨在探讨mmu_circ_00684及其同源基因hsa_circ_0067098在缺血-再灌注诱导的急性肾损伤（AKI）进化中的可能作用，并重点研究它们作为治疗靶点的可行性。方法：采用波士顿大学小鼠近端小管细胞（BUMPT）、人肾小管上皮细胞（HK-2）和小鼠肾组织构建模型。mmu_circ_0000684、miR-671-5p和ARID3B mRNA水平及其相应的蛋白表达通过实时定量聚合酶链反应和Western blot进行定量。利用生物信息学预测、荧光素酶报告基因测定、荧光原位杂交、流式细胞术、苏木精和伊红染色、末端脱氧核苷酸转移酶dUTP标记染色，对mmu_circ_0000684和hsa_circ_0067098的生物学作用和信号级联进行了全面的研究。结果：缺血应激诱导mmu_circ_0000684表达。功能上，mmu_circ_0000684参与促进BUMPT细胞因缺血再灌注损伤而凋亡。在机制上，mmu_circ_0000684作为miR-671-5p的分子海绵，从而促进ARID3B的上调，进而促进细胞凋亡的诱导。此外，沉默mmu_circ_0000684可通过调节miR-671-5p/ARID3B轴显著减轻缺血触发的AKI。值得注意的是，hsa_circ_0067098， mmu_circ_0000684的同源物，在HK-2细胞中表现出类似的调节作用。结论：mmu_circ_0000684， hsa_circ_0067098/miR-671-5p/ARID3B信号级联是缺血性AKI进展的重要机制。因此，hsa_circ_0067098代表了解决缺血性AKI的有希望的治疗候选者。

{"title":"mmu_circ_0000684/hsa_circ_0067098 mediates renal tubular epithelial cells apoptosis to ischemia-reperfusion-induced acute kidney injury by targeting the mmu_miR_671-5p/ARID3B axis","authors":"Ben Yang , Qiang Zheng , Yan Pu , Yingying Hu , Dongshan Zhang","doi":"10.1016/j.abb.2025.110679","DOIUrl":"10.1016/j.abb.2025.110679","url":null,"abstract":"<div><h3>Objective</h3><div>This investigation sought to explore the possible role of mmu_circ_0000684 and its homolog hsa_circ_0067098 in the evolution of ischemia-reperfusion-induced acute kidney injury (AKI), with an emphasis on their viability as therapeutic targets.</div></div><div><h3>Method</h3><div>A model was constructed employing Boston University mouse proximal tubule (BUMPT) cells, human renal tubular epithelial (HK-2) cells, and murine kidney tissue. The mmu_circ_0000684, miR-671-5p, and ARID3B mRNA levels, along with their corresponding protein expression, underwent quantification via real-time quantitative polymerase chain reaction and Western blot. A comprehensive examination of the biological roles and signaling cascade of mmu_circ_0000684 and hsa_circ_0067098 was executed utilizing bioinformatics prediction, luciferase reporter assays, fluorescence in situ hybridization, flow cytometry, hematoxylin and eosin staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining.</div></div><div><h3>Results</h3><div>Ischemic stress was observed to induce mmu_circ_0000684 expression. Functionally, mmu_circ_0000684 was implicated in promoting BUMPT cell apoptosis as a consequence of ischemia-reperfusion injury. Mechanistically, mmu_circ_0000684 acted as a molecular sponge for miR-671-5p, thereby facilitating the upregulation of ARID3B, which in turn contributed to apoptosis induction. Moreover, silencing mmu_circ_0000684 markedly mitigated ischemia-triggered AKI via modulation of the miR-671-5p/ARID3B axis. Notably, hsa_circ_0067098, the homolog of mmu_circ_0000684, exhibited an analogous regulatory role in HK-2 cells.</div></div><div><h3>Conclusion</h3><div>The mmu_circ_0000684, hsa_circ_0067098/miR-671-5p/ARID3B signaling cascade emerges as an essential mechanism during ischemic AKI progression. Consequently, hsa_circ_0067098 represents a promising therapeutic candidate for addressing ischemic AKI.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"776 ","pages":"Article 110679"},"PeriodicalIF":3.0,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Aromatic secondary metabolite interactions with nickel-dependent urease 芳香次级代谢物与镍依赖性脲酶的相互作用

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics

Pub Date : 2025-11-24 DOI: 10.1016/j.abb.2025.110677

Duygu İnci Özbağcı , Sevinç İlkar Erdağı , Rahmiye Aydın

Aromatic secondary metabolites, hydroxybenzoic acids (HBAs)—β-resorcylic (2,4-dihydroxybenzoic acid) and gallic acid (3,4,5-trihydroxybenzoic acid)—constitute a class of phenolic compounds with numerous bioactivities that are of pharmacological and therapeutic interest. Urease plays a critical role in various biological pathways, with its activation linked to medical conditions including nephrolithiasis and peptic ulcers. The pursuit of potent and safe urease inhibitors has become a key priority in the field of pharmaceutical research. The present study sought to explore the molecular interactions between HBAs and urease to better understand their binding behavior. To assess the impact of both HBAs on the structural integrity and enzymatic activity of urease, fluorescence spectroscopy, FTIR, and molecular docking were utilized. Both HBAs quenched urease fluorescence through static mechanisms and bound favorably to the Ni²⁺-centered catalytic site. In silico ADME and toxicity profiling confirmed their drug-likeness and low predicted toxicity. Gallic acid exhibited stronger antioxidant and urease inhibition activity than β-resorcylic acid, highlighting the importance of hydroxyl substituents in radical scavenging. These findings suggest HBAs as promising natural scaffolds for developing dual-function urease inhibitors with antioxidant potential.

芳香次生代谢产物羟基苯甲酸(HBAs) - β-间环酸（2,4-二羟基苯甲酸）和没食子酸（3,4,5-三羟基苯甲酸）-构成一类具有许多生物活性的酚类化合物，具有药理和治疗意义。脲酶在多种生物途径中起着关键作用，其激活与肾结石和消化性溃疡等疾病有关。追求有效和安全的脲酶抑制剂已成为制药研究领域的一个关键优先事项。本研究旨在探索HBAs与脲酶之间的分子相互作用，以更好地了解它们的结合行为。为了评估这两种HBAs对脲酶结构完整性和酶活性的影响，利用荧光光谱、FTIR和分子对接技术进行了研究。这两种HBAs通过静态机制淬灭脲酶荧光，并有利于结合到Ni2+中心的催化位点。在计算机上，ADME和毒性分析证实了它们的药物相似性和低预测毒性。没食子酸表现出比β-间环酸更强的抗氧化和脲酶抑制活性，突出了羟基取代基在自由基清除中的重要性。这些发现表明，HBAs是开发具有抗氧化潜力的双功能脲酶抑制剂的有希望的天然支架。

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引用次数: 0