Archives of biochemistry and biophysics最新文献

筛选
英文 中文
Corrigendum to “LncRNA ZNF649-AS1 promotes trastuzumab resistance and TAM-dependent PD-L1 expression in breast cancer by regulating EXOC7 alternative splicing” [Archiv. Biochem. Biophys. 761 (2024) 110128] “LncRNA ZNF649-AS1通过调节EXOC7选择性剪接促进曲妥珠单抗耐药和tami依赖性PD-L1在乳腺癌中的表达”的更正。物化学。生物工程学报,2016,32(2):389 - 389。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-02-01 DOI: 10.1016/j.abb.2024.110220
Huaying Dong, Jing Han, Xiang Chen, Hening Sun, Mingli Han, Wei Wang
{"title":"Corrigendum to “LncRNA ZNF649-AS1 promotes trastuzumab resistance and TAM-dependent PD-L1 expression in breast cancer by regulating EXOC7 alternative splicing” [Archiv. Biochem. Biophys. 761 (2024) 110128]","authors":"Huaying Dong, Jing Han, Xiang Chen, Hening Sun, Mingli Han, Wei Wang","doi":"10.1016/j.abb.2024.110220","DOIUrl":"10.1016/j.abb.2024.110220","url":null,"abstract":"","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110220"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805695","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
Differential effect of cerium nanoparticles on the viability, redox-status and Ca2+-signaling system of cancer cells of various origins 铈纳米颗粒对不同来源癌细胞活力、氧化还原状态和Ca2+信号系统的差异影响。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-02-01 DOI: 10.1016/j.abb.2024.110261
Elena G. Varlamova , Sergey V. Gudkov , Egor A. Turovsky
{"title":"Differential effect of cerium nanoparticles on the viability, redox-status and Ca2+-signaling system of cancer cells of various origins","authors":"Elena G. Varlamova ,&nbsp;Sergey V. Gudkov ,&nbsp;Egor A. Turovsky","doi":"10.1016/j.abb.2024.110261","DOIUrl":"10.1016/j.abb.2024.110261","url":null,"abstract":"<div><div>The present study aims to understand the molecular mechanism underlying the therapeutic effect of cerium nanoparticles (CeNPs) in oncology. Cancer cells were treated with different concentrations of pure nanocerium of different sizes synthesized by laser ablation. Due to the not insignificant influence of surface defects and oxygen species on the ROS-modulating properties of cerium nanoparticles, the nanoparticles were not coated with surfactants or organic molecules during synthesis, which could potentially inhibit a number of pro-oxidative effects. Reactive oxygen species (ROS) production, expression of genes encoding redox-status proteins, selenoproteins and proteins regulating cell death and endoplasmic reticulum stress (ER-stress) were investigated as indicators of the molecular mechanism of cancer cell death. Studies were conducted on the effects of cerium nanoparticles on the Ca<sup>2+</sup> signaling system of cancer cells of different origins. Mouse fibroblasts (L-929 cell line) were used as non-cancerous (“normal”) cells for which a whole series of experiments were performed, and a comparative analysis of the effects of nanoceria. It was found that 75 nm-sized cerium nanoparticles did not affect the redox-status and ROS production of cancer cells. In fibroblast cells, however, this nanoparticle diameter led to a deterioration of the cellular redox status and ROS production in a wide range of nanoparticle concentrations. Larger nanoparticles (100 nm-sized and 160 nm-sized), on the other hand, showed a different effect on cancer cells of different origins. In mouse fibroblast L-929 cells, however, 100 nm-sized or 160 nm-sized CeNPs acted in a high concentration range to disrupt mitochondrial membrane potential and activate early apoptosis. High concentrations of CeNPs were required to increase ROS production, reduce redox-status and induce apoptosis in human A-172 glioblastoma cells compared to the hepatocellular carcinoma cell line HepG2 and the breast cancer cell line MCF-7. In the A-172 glioblastoma cells, ER-stress was also not activated and their Ca<sup>2+</sup> signaling system was activated by a significantly higher concentration of CeNPs, which could also contribute to the formation of tolerance of this cancer cell line to nanoceria. The Ca<sup>2+</sup> signaling system of mouse fibroblasts was found to be highly sensitive to activation by nanoceria and the cells produced Ca2+ signals with higher amplitude compared to A-172 and MCF-7 cells.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110261"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790958","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
MD simulations for rational design of high-affinity HDAC4 inhibitors – Analysis of non-bonding interaction energies for building new compounds 高亲和HDAC4抑制剂合理设计的MD模拟——构建新化合物的非键相互作用能分析。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-02-01 DOI: 10.1016/j.abb.2024.110262
Varun Dewaker , Pratik Narain Srivastava , Utsab Debnath , Ajay Kumar Srivastava , Yenamandra S. Prabhakar
{"title":"MD simulations for rational design of high-affinity HDAC4 inhibitors – Analysis of non-bonding interaction energies for building new compounds","authors":"Varun Dewaker ,&nbsp;Pratik Narain Srivastava ,&nbsp;Utsab Debnath ,&nbsp;Ajay Kumar Srivastava ,&nbsp;Yenamandra S. Prabhakar","doi":"10.1016/j.abb.2024.110262","DOIUrl":"10.1016/j.abb.2024.110262","url":null,"abstract":"<div><div>This study investigates the contributions of non-bonding energy (NBE) to the efficacy of four HDAC4 co-crystallized inhibitors (<strong>HA3</strong>, <strong>9F4</strong>, <strong>EBE</strong>, and <strong>TFG</strong>) through 100ns Molecular Dynamics (MD) simulations. These inhibitors contain hydroxamic acid (<strong>HA3</strong>, <strong>9F4</strong>, <strong>EBE</strong>) or diol (<strong>TFG</strong>) as zinc-binding groups. In PDBs 2VQJ and 2VQM, the HDAC4 catalytic domain is in the 'open' conformation, while in PDBs 4CBT and 6FYZ, the same is in the 'closed' conformation. We identified <strong>HA3</strong> as a weaker inhibitor because of the unfavorable NBE contributions from its carbonyl fragment (<strong>FR3</strong>) and hydroxamic fragment (<strong>FR1</strong>). To enhance NBE efficacy, we designed novel <strong>HA3</strong> analogs (<strong>H01</strong>–<strong>H16</strong>) by introducing diverse fragments (–CF3, 2-hydroxyacetic acid, -NH-CH2-, 5-fluoro-2-phenyl pyrimidine, and chloroquinoline moieties). MD simulations revealed promising analogs (<strong>H02</strong>, <strong>H07</strong>, <strong>H08</strong>, <strong>H15</strong>) with strong NBEs and stable ligand-zinc retention (2.07–2.33 Å). These analogs exhibited strong relative binding free energies within their catalytic sites, highlighting their potential as novel HDAC4 inhibitors. The current study provides medicinal chemists with insights into non-covalent interactions, identifies key fragments for optimization, and offers a rational design strategy for developing more effective HDAC4 inhibitors.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110262"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811786","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
Differential structural characteristics, physicochemical properties, and calcium-binding capabilities of annexin A2 wild-type versus E53A, E96A, D162A, E247A and D322A mutants 附件蛋白 A2 野生型与 E53A、E96A、D162A、E247A 和 D322A 突变体的不同结构特征、理化性质和钙结合能力。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-02-01 DOI: 10.1016/j.abb.2024.110267
Sunisa Yoodee, Sirikanya Plumworasawat, Thanyalak Malaitad, Paleerath Peerapen, Visith Thongboonkerd
{"title":"Differential structural characteristics, physicochemical properties, and calcium-binding capabilities of annexin A2 wild-type versus E53A, E96A, D162A, E247A and D322A mutants","authors":"Sunisa Yoodee,&nbsp;Sirikanya Plumworasawat,&nbsp;Thanyalak Malaitad,&nbsp;Paleerath Peerapen,&nbsp;Visith Thongboonkerd","doi":"10.1016/j.abb.2024.110267","DOIUrl":"10.1016/j.abb.2024.110267","url":null,"abstract":"<div><div>Annexin A2 (ANXA2) is a Ca<sup>2+</sup>-dependent multifunctional protein containing five Ca<sup>2+</sup>-binding domains, but their functional significance and difference remain unclear. Herein, glutamic acid (E) or aspartic acid (D) in five Ca<sup>2+</sup>-binding domains of canine ANXA2 (98.82 % and 96.76–99.41 % identical to ANXA2 from human and other mammals, respectively) was substituted by alanine (A) using site-directed mutagenesis. Recombinant ANXA2 wild-type (WT) and E53A, E96A, D162A, E247A and D322A mutants were constructed and expressed using a bacterial expression system followed by high-affinity purification using nickel-nitrilotriacetic acid (Ni-NTA) matrix. Efficacies of their expression and purification were confirmed by SDS-PAGE and Western blotting. Their amino acid sequences were verified by nanoLC-ESI-Qq-TOF tandem mass spectrometry. ATR-FTIR spectroscopy revealed that their secondary structure significantly differed (α-helix decreased but random coil increased in all mutants). Analyses of physicochemical properties revealed that molecular weight slightly decreased, whereas isoelectric point, aliphatic index, grand average of hydropathicity, electrostatic potential and molecular hydrophobicity potential slightly increased in all the mutants compared with WT. Interestingly, Ca<sup>2+</sup>-binding capability of these mutants (particularly E96A and D322A) significantly decreased from that of WT. In summary, secondary structure, physicochemical properties, and Ca<sup>2+</sup>-binding capability of E53A, E96A, D162A, E247A and D322A mutants of ANXA2 significantly differed from its WT, consistent with the loss of negatively charged E/D. In particular, E96A and D322A exhibited the lowest Ca<sup>2+</sup>-binding capability. These data and recombinant proteins would be useful for further investigations of the Ca<sup>2+</sup>-dependent functions of individual Ca<sup>2+</sup>-binding domains in ANXA2.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110267"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823942","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
Identification of ABC transporter Cdr1 inhibitors of Candida glabrata 秃念珠菌ABC转运蛋白Cdr1抑制剂的鉴定。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-02-01 DOI: 10.1016/j.abb.2024.110270
Mohd Waseem , Shubhashis Das , Debarati Mondal , Anuj Kumari , Ritu Kulshreshtha , Jitendra K. Thakur , Naidu Subbarao
{"title":"Identification of ABC transporter Cdr1 inhibitors of Candida glabrata","authors":"Mohd Waseem ,&nbsp;Shubhashis Das ,&nbsp;Debarati Mondal ,&nbsp;Anuj Kumari ,&nbsp;Ritu Kulshreshtha ,&nbsp;Jitendra K. Thakur ,&nbsp;Naidu Subbarao","doi":"10.1016/j.abb.2024.110270","DOIUrl":"10.1016/j.abb.2024.110270","url":null,"abstract":"<div><div><em>Candida glabrata is</em> one of the most common causes of invasive candidiasis. Rising treatment failures from resistance to current antifungal drugs highlight the need for new antifungals. Overexpression of efflux pump transporter genes is significantly associated with the development of multidrug resistance. In this study, we have identified novel and potential inhibitors of ABC transporter Cdr1 of <em>Candida glabrata</em> (<em>Cg</em>Cdr1) by employing high throughput virtual screening of large chemical datasets from five different chemical libraries (ZINC, DrugBank, ChemDiv antifungal, ChemDiv Kinases, and ChEMBL bioassay). As a result many molecules were predicted to have higher binding affinity toward the <em>Cg</em>Cdr1, in which a naturally occurring compound, pentagalloyl glucose, was identified to significantly reduce the growth of <em>Candida glabrata</em> with an IC<sub>50</sub> value of 16.97 ± 2.1 μM. Molecular dynamics studies showed stable binding of pentagalloyl glucose with <em>Cg</em>Cdr1 protein. In summary, our research identifies pentagalloyl glucose as a novel antifungal compound that has the potential to be used for inhibiting the growth of <em>Candida glabrata</em>.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110270"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833759","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
MiR-495 reverses in the mechanical unloading, random rotating and aging induced muscle atrophy via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 axis MiR-495通过靶向MyoD和激活Myostatin/TGF-β/Smad3轴,逆转了机械卸载、随机旋转和老化诱导的肌肉萎缩。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-02-01 DOI: 10.1016/j.abb.2024.110273
Chenyan Zhang , Yile Tian , Xinli Liu , Xuezhou Yang , Shanfeng Jiang , Ge Zhang , Changqing Yang , Wenjing Liu , Weihong Guo , Wenzhe Zhao , Dachuan Yin
{"title":"MiR-495 reverses in the mechanical unloading, random rotating and aging induced muscle atrophy via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 axis","authors":"Chenyan Zhang ,&nbsp;Yile Tian ,&nbsp;Xinli Liu ,&nbsp;Xuezhou Yang ,&nbsp;Shanfeng Jiang ,&nbsp;Ge Zhang ,&nbsp;Changqing Yang ,&nbsp;Wenjing Liu ,&nbsp;Weihong Guo ,&nbsp;Wenzhe Zhao ,&nbsp;Dachuan Yin","doi":"10.1016/j.abb.2024.110273","DOIUrl":"10.1016/j.abb.2024.110273","url":null,"abstract":"<div><div>Mechanical unloading can lead to homeostasis imbalance and severe muscle disease, in which muscle atrophy was one of the disused diseases. However, there were limited therapeutic targets for such diseases. In this study, miR-495 was found dramatically reduced in atrophic skeletal muscle induced by mechanical unloading models both <em>in vitro</em> and <em>in vivo</em>, including the random positioning model (RPM), tail-suspension (TS) model, and aged mice model. Enforced miR-495 expression by its mimic could enormously facilitate the differentiation and regeneration of both mouse myoblast C2C12 cells and muscle satellite cells<em>.</em> Furthermore, MyoD was proved as the directly interacted gene of miR-495, and their interaction was crucial for myotube formation. Enforced miR-495 expression could intensively strengthen the muscle mass, <em>in situ</em> muscular electrophysiological indexes, including peak tetanic tension (Po) and peak twitch tension (Pt), and the cross-sectional areas (CSA) of muscle fibers via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 signaling pathway, indicating that miR-495 can be proposed as an effective target for muscle atrophy treatment induced by in the mechanical unloading, random rotating and aging.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110273"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862909","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
Lactamase β reprograms lipid metabolism to inhibit the progression of endometrial cancer through attenuating MDM2-mediated p53 ubiquitination and degradation 内酰胺酶β重编程脂质代谢,通过减弱mdm2介导的p53泛素化和降解来抑制子宫内膜癌的进展。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-02-01 DOI: 10.1016/j.abb.2024.110287
Ting Zhou , Xiaorong Li , Fangfang Zhao , Jing Zhou , Binghui Sun
{"title":"Lactamase β reprograms lipid metabolism to inhibit the progression of endometrial cancer through attenuating MDM2-mediated p53 ubiquitination and degradation","authors":"Ting Zhou ,&nbsp;Xiaorong Li ,&nbsp;Fangfang Zhao ,&nbsp;Jing Zhou ,&nbsp;Binghui Sun","doi":"10.1016/j.abb.2024.110287","DOIUrl":"10.1016/j.abb.2024.110287","url":null,"abstract":"<div><h3>Background</h3><div>Lactamase β (LACTB) inhibits the metastasis and progression of multiple malignant tumors. However, little is known about its role in endometrial cancer (EC). Our study aimed to investigate the function and potential molecular mechanism of LACTB in modulating EC progression.</div></div><div><h3>Methods</h3><div>LACTB expression was measured via immunohistochemistry staining, Western blot and qRT-PCR. The role of LACTB in EC was investigated both in vivo and in vitro by employing xenograft mice models and using colony formation, EdU, and Transwell assays, along with flow cytometric analysis. In addition, to assess LACTB function on lipid metabolism, lipid droplets in EC cells were labeled with Nile red. Western blot, immunofluorescence staining, co-immunoprecipitation, ubiquitination assay, and cycloheximide chase assay and rescue experiments were performed to confirm the interaction between LACTB, p53, and MDM2 in EC.</div></div><div><h3>Results</h3><div>LACTB expression was downregulated in EC. LACTB inhibited the malignant phenotypes and reprogramed lipid metabolism in EC cells. Moreover, LACTB significantly upregulated p53 by attenuating the MDM2-mediated ubiquitination and degradation of p53. Besides, LACTB silencing facilitated the malignant phenotypes and reprogramed lipid metabolism in EC cells; this was reversed with p53 overexpression. LACTB knockdown facilitated EC progression via downregulating p53 in vivo.</div></div><div><h3>Conclusion</h3><div>LACTB repressed EC cell proliferation and metastasis, and reprogramed lipid metabolism via attenuating the MDM2-mediated ubiquitination and degradation of p53.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110287"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920680","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
Exosomal signaling in cancer metastasis: Molecular insights and therapeutic opportunities 肿瘤转移中的外泌体信号传导:分子洞察和治疗机会。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-02-01 DOI: 10.1016/j.abb.2024.110277
Manasi S. Pote, Rajesh N. Gacche
{"title":"Exosomal signaling in cancer metastasis: Molecular insights and therapeutic opportunities","authors":"Manasi S. Pote,&nbsp;Rajesh N. Gacche","doi":"10.1016/j.abb.2024.110277","DOIUrl":"10.1016/j.abb.2024.110277","url":null,"abstract":"<div><div>Exosomes are membrane-bound extracellular vesicles that play a role in exchanging biological products across membranes and serve as intermediaries in intercellular communication to maintain normal homeostasis. Numerous molecules, including lipids, proteins, and nucleic acids are enclosed in exosomes. Exosomes are constantly released into the extracellular environment and exhibit distinct characteristics based on the secreted cells that produce them. Exosome-mediated cell-to-cell communication has reportedly been shown to affect multiple cancer hallmarks, such as immune response modulation, pre-metastatic niche formation, angiogenesis, stromal cell reprogramming, extracellular matrix architecture remodeling, or even drug resistance, and eventually the development and metastasis of cancer cells. Exosomes can be used as therapeutic targets and possible diagnostic biomarkers by selectively loading oncogenic molecules into them. We highlight the important roles that exosomes play in cancer development in this review, which may lead to the development of fresh approaches for future clinical uses.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110277"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871093","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
Discovery of anti-tumor small molecule lead compounds targeting the SH3 domain of c-Src protein through virtual screening and biological evaluation 通过虚拟筛选和生物学评价发现靶向c-Src蛋白SH3结构域的抗肿瘤小分子先导化合物。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-02-01 DOI: 10.1016/j.abb.2024.110286
Haifang Hao , Yuan Bian , Na Yang , Xingzhao Ji , Jie Bao , Kongkai Zhu
{"title":"Discovery of anti-tumor small molecule lead compounds targeting the SH3 domain of c-Src protein through virtual screening and biological evaluation","authors":"Haifang Hao ,&nbsp;Yuan Bian ,&nbsp;Na Yang ,&nbsp;Xingzhao Ji ,&nbsp;Jie Bao ,&nbsp;Kongkai Zhu","doi":"10.1016/j.abb.2024.110286","DOIUrl":"10.1016/j.abb.2024.110286","url":null,"abstract":"<div><div>c-Src, also known as cellular Src, is a non-receptor tyrosine kinase that plays a crucial role in various cellular processes, including cell proliferation, adhesion, and migration. Its dysregulation has been implicated in the development and progression of several diseases, particularly cancer. Current therapeutic agents targeting c-Src are primarily small molecules binding to its kinase domain. However, drug resistance often reduces the effectiveness of these drugs. The SH3 domain of c-Src is a highly conserved functional region with a low propensity for developing drug resistance, whereas there are no existing anti-cancer drugs specifically binding to this domain. In this study, structure-based virtual screening and thermal shift experimental verification identified three molecules that showed potent binding affinity with SH3 domain of c-Src. Subsequent kinase activity assay validated the inhibitory activity of these compounds against c-Src, with IC<sub>50</sub> values ranging from 60.42 to 122.2 nM. Next, cell-level assays and preliminary study were conducted to further evaluate the efficacy of the identified active compounds. In conclusion, the present work has provided new chemical templates as lead structures for the future development of new antitumor therapeutics targeting the c-Src SH3 domain to overcome drug resistance.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110286"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913626","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
Radiosensitization impact assessment of silica-layered iron oxide nanocomposites with various shell thickness 不同壳厚的二氧化硅层氧化铁纳米复合材料的辐射敏化影响评估
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-02-01 DOI: 10.1016/j.abb.2024.110257
Mohamed M. Fathy, Omnia A. Saad, Heba M. Fahmy
{"title":"Radiosensitization impact assessment of silica-layered iron oxide nanocomposites with various shell thickness","authors":"Mohamed M. Fathy,&nbsp;Omnia A. Saad,&nbsp;Heba M. Fahmy","doi":"10.1016/j.abb.2024.110257","DOIUrl":"10.1016/j.abb.2024.110257","url":null,"abstract":"<div><div>Silica shell is considered to be a promising design that enhances nanocomposite stability, cellular internalization, and consequentially therapeutic impacts by overcoming their aggregation under physiological conditions. This study addressed synthesizing silica-layered iron oxide-based nanoparticles (SCINPs) with different shell thicknesses (1-SCINPs, 2-SCINPs, 3-SCINPs, and 4-SCINPs). Also, the impact of shell thickness on the nanoparticle's cellular internalization and the radio-sensitizing effect of prepared nano-formulations were assessed. The physical properties of the synthesized nanoparticles were examined using transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), vibrating sample magnetometry (VSM), and X-ray diffraction (XRD). Cytotoxicity assay, oxidative stress parameters, and comet assay were used to investigate the radio-sensitizing effect of various nanoformulations. Results revealed that the mean diameter of prepared oxide-based nanoparticles (INPs) was about 12.63 ± 1.36 nm, and the shell thickness for 1-SCINPs, 2-SCINPs, 3-SCINPs, and 4-SCINPs was 22.58 ± 3.51, 26.13 ± 1.40, 46.95 ± 3.10 and 60.30 ± 4.30 nm, respectively. Interestingly, we found that in cells treated with 40 μg/ml of INPs, their viability decreased to 44.6 %. Meanwhile, the viability was 41.69 % and 39.4 % for cells treated with 1-SCINPs and 2-SCINPs, respectively. This means that a thicker silica shell led to a decreased impact on radiosensitization. This was attributed to the influence of surface properties and size of SCINPs on their cellular uptake and the secondary electrons' entrapment within thicker shells upon radiation exposure. Cell viability test, comet assay and oxidative stress parameters show that 2-SCINPs formulations had the most potent radiosensitizing effect (with the highest dose enhancement factor equal to 2.1) when combined with radio-treatment. The results suggest that optimizing the silica shell thickness is critical for maximizing the therapeutic efficacy of SCINPs, with 2-SCINPs showing the highest radiosensitization effect.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110257"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823974","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信