Chemico-biological interactions最新文献

In vitro evaluation of isatin-pyridine oxime hybrids as potential acetylcholinesterase inhibitors for nerve agent prophylaxis. isatin-吡啶肟复合物作为潜在的乙酰胆碱酯酶抑制剂用于神经毒剂预防的体外评价。

Chemico-biological interactions Pub Date : 2025-06-12 DOI: 10.1016/j.cbi.2025.111605

Munique C J da Silva, Amanda M V Pinto, Mariana de A Balthar, Ana Beatriz de A Correa, Dipanjan Bhattacharyya, Alessandro B C Simas, Kamil Kuča, Pat Forgione, Tanos C C França, Samir F de A Cavalcante, Daniel A S Kitagawa

引用次数: 0

Insights into the diagnostic and prognostic value of paraoxonase 1-related variables and inflammatory markers in community-acquired pneumonia. 对氧磷酶1相关变量和炎症标志物在社区获得性肺炎中的诊断和预后价值

Chemico-biological interactions Pub Date : 2025-06-12 DOI: 10.1016/j.cbi.2025.111606

Frederic Ballester, Xavier Gabaldó-Barrios, Andrea Jiménez-Franco, Isabel Pujol, Simona Iftimie, Jordi Camps, Sandra Parra, Antoni Castro, Jorge Joven

{"title":"Insights into the diagnostic and prognostic value of paraoxonase 1-related variables and inflammatory markers in community-acquired pneumonia.","authors":"Frederic Ballester, Xavier Gabaldó-Barrios, Andrea Jiménez-Franco, Isabel Pujol, Simona Iftimie, Jordi Camps, Sandra Parra, Antoni Castro, Jorge Joven","doi":"10.1016/j.cbi.2025.111606","DOIUrl":"https://doi.org/10.1016/j.cbi.2025.111606","url":null,"abstract":"Community-acquired pneumonia (CAP) remains a major health concern, with oxidative stress and inflammation playing key roles in its pathophysiology. This study examines the potential of paraoxonase-1 (PON1)-related variables as biomarkers for diagnosing and managing CAP. A prospective case-control study included 78 patients with community-acquired pneumonia (CAP) who were hospitalized and 80 healthy controls. Serum PON1 concentration (PON1c), PON1 arylesterase (ARE) and paraoxonase (PARX) activities, and inflammatory markers (C-reactive protein, procalcitonin, and C-C motif chemokine ligand) were measured and compared with lipid profiles and clinical severity scores. Receiver operating characteristic curve analysis was used to assess their diagnostic and prognostic value. CAP patients exhibited significantly lower ARE and PARX activities but higher PON1c levels than controls, with these changes correlating with increased inflammatory markers and decreased total and high-density lipoprotein cholesterol concentrations. PON1-related variables demonstrated strong diagnostic accuracies (areas under the curve > 0.90), outperforming traditional inflammatory markers. However, although these variables provided insights into disease severity and pathophysiology, their prognostic value and ability to differentiate microbial etiologies were limited. These findings suggest that PON1-related variables may serve as promising diagnostic biomarkers for CAP, but their role in prognosis and guiding antimicrobial therapy requires further investigation. Future studies should validate these results in larger and more diverse populations while exploring the mechanistic involvement of PON1 in CAP progression.","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111606"},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of a gene expression biomarker predictive of hypoxia-inducible factor-1 modulation. 预测缺氧诱导因子-1调节的基因表达生物标志物的表征。

Chemico-biological interactions Pub Date : 2025-06-09 DOI: 10.1016/j.cbi.2025.111595

J Christopher Corton, Brian Chorley, Jie Liu

{"title":"Characterization of a gene expression biomarker predictive of hypoxia-inducible factor-1 modulation.","authors":"J Christopher Corton, Brian Chorley, Jie Liu","doi":"10.1016/j.cbi.2025.111595","DOIUrl":"https://doi.org/10.1016/j.cbi.2025.111595","url":null,"abstract":"We describe here a gene expression biomarker that can accurately identify chemicals and genetic conditions that perturb hypoxia-inducible factor-1 (HIF-1), a transcription factor critical for the cellular response to hypoxia involved in the pathophysiology of cancer, inflammation, and ischemia. The HIF-1 biomarker genes were identified from transcript profiles in a variety of human cell lines after hypoxia as well as genetic knockdown of the HIF1A gene. The HIF-1 biomarker of 122 genes was found to be enriched for: genes bound by HIF-1 using ChIP-Seq, metabolic pathways regulated by HIF-1 (e.g., gluconeogenesis). Using Ingenuity Pathway Analysis, HIF-1 was the top predicted regulator of the genes. The biomarker could identify activation of HIF-1 by overexpression of the HIF1A gene or suppression of the negative regulator, von-Hipple Lindau (VHL) gene; suppression of HIF-1 occurred by inhibition of the expression of HIF1A or the heterodimer partner aryl hydrocarbon receptor nuclear translocator (ARNT). The biomarker was specific for HIF-1 activation, as activation or suppression of the HIF-2 gene was not detected by the biomarker. Using a reference chemical set with 180 positives and 45 negatives, the balanced accuracy of the HIF-1 biomarker to identify activation was 94.1%. An in-silico screen of a gene expression compendium identified hundreds of potential activators. Eleven of these were selected for verification and all were found to activate HIF-1 biomarker genes in wild-type but not HIF1A-null cells. The HIF-1 biomarker will be a useful tool to identify environmentally relevant chemicals that affect HIF-1 in high-throughput transcriptomics screening studies.","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111595"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comprehensive Transcriptomic Analysis in Wild-type and ATM Knockout Lung Cancer Cells: Influence of Cisplatin on Oxidative Stress-Induced Senescence. 野生型和ATM敲除肺癌细胞的综合转录组学分析：顺铂对氧化应激诱导的衰老的影响。

Chemico-biological interactions Pub Date : 2025-05-16 DOI: 10.1016/j.cbi.2025.111563

Ayşegül Varol, Sabine M Klauck, Susan P Lees-Miller, Thomas Efferth

{"title":"Comprehensive Transcriptomic Analysis in Wild-type and ATM Knockout Lung Cancer Cells: Influence of Cisplatin on Oxidative Stress-Induced Senescence.","authors":"Ayşegül Varol, Sabine M Klauck, Susan P Lees-Miller, Thomas Efferth","doi":"10.1016/j.cbi.2025.111563","DOIUrl":"https://doi.org/10.1016/j.cbi.2025.111563","url":null,"abstract":"Genetic mutations and impaired DNA repair mechanisms in cancer not only facilitate tumor progression but also reduce the effectiveness of chemotherapeutic agents, particularly cisplatin. Combination therapy has emerged as a promising strategy to overcome resistance. Comprehensive transcriptomic analyses, supported by integrated comparative bioinformatics and experimental approaches, are essential for identifying biomarkers and novel therapeutic targets underlying drug resistance. In this study, we performed overall survival and mutation analyses, examining 23 double-strand break repair proteins across more than 7,500 tumors spanning 23 distinct cancer types. Our findings identify ATM (ataxia-telangiectasia mutated) as a key protein with the highest mutation frequency. Using CRISPR/Cas9, we investigated the effects of ATM mutations on signalling pathways that influence the cellular response to cisplatin. ATM knockout enhanced cisplatin cytotoxicity by activating alternative cell death pathways, including oxidative stress-induced senescence and necroptosis. Microarray analysis revealed a regulatory interplay between ATM and NRF2 in the activation of oxidative stress-induced senescence. Specifically, ATM knockoutpromoted senescence by increasing reactive oxygen species (ROS) accumulation and downregulating NRF2 expression. To enhance combination therapy, integrating genetic profiling with advanced tools such as CRISPR/Cas9 to target oxidative stress-induced senescence may provide innovative strategies to overcome drug resistance, thereby advancing personalized cancer treatment. These approaches lay the foundation for the development of personalized cancer therapies tailored to the unique mutational landscape of individual patients, offering promising prospects for improving treatment outcomes.","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111563"},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to testicular damage and impaired spermatogenesis in Wilson disease. 铜暴露会通过 TLR4/NF-κB 信号通路诱发炎症和 PAN 细胞凋亡，导致威尔逊氏病患者的睾丸损伤和精子发生障碍。

Chemico-biological interactions Pub Date : 2024-06-01 Epub Date: 2024-05-17 DOI: 10.1016/j.cbi.2024.111060

Dan Zhao, Limin Wu, Xinru Fang, Luyao Wang, Qianzhuo Liu, Pengyu Jiang, Zhihui Ji, Nian Zhang, Miaozhu Yin, Hui Han

{"title":"Copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to testicular damage and impaired spermatogenesis in Wilson disease.","authors":"Dan Zhao, Limin Wu, Xinru Fang, Luyao Wang, Qianzhuo Liu, Pengyu Jiang, Zhihui Ji, Nian Zhang, Miaozhu Yin, Hui Han","doi":"10.1016/j.cbi.2024.111060","DOIUrl":"10.1016/j.cbi.2024.111060","url":null,"abstract":"Copper is a toxic heavy metal that causes various damage when it accumulates in the body beyond the physiological threshold. Wilson disease (WD) is an inherited disorder characterized by impaired copper metabolism. Reproductive damage in male patients with WD is gradually attracting attention. However, the underlying mechanisms of copper toxicity are unclear. In this study, we investigated the role of inflammation and PANoptosis in testicular damage and impaired spermatogenesis caused by copper deposition using the WD model toxic milk (TX) mice. Copper chelator-penicillamine and toll-like receptor 4 (TLR4) inhibitor-eritoran were used to intervene in TX mice in our animal experiment methods. Testis samples were collected from mice for further analysis. The results showed that the morphology and ultrastructure of the testis and epididymis in TX mice were damaged, and the sperm counts decreased significantly. The TLR4/nuclear factor kappa-B (NF-κB) signaling pathway was activated by copper deposition, which led to the upregulation of serum and testicular inflammatory factors in TX mice. Meanwhile, pyroptosis, apoptosis, and necroptosis were significant in the testis of TX mice. Both chelated copper or inhibited TLR4 expression markedly suppressed the TLR4/NF-κB signaling pathway, thereby reducing the expression of inflammatory factors. PANoptosis in the testis of TX mice was also reversed. Our study indicated that pathological copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to toxic testicular damage and impaired spermatogenesis in WD.","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111060"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elucidating the Molecular Mechanisms of Pterostilbene Against Cervical Cancer Through an Integrated Bioinformatics and Network Pharmacology Approach 通过综合生物信息学和网络药理学方法阐明紫檀芪抗宫颈癌的分子机制

Chemico-biological interactions Pub Date : 2024-05-01 DOI: 10.1016/j.cbi.2024.111058

Xiang Li, Dequan Yu, Qiming Wang, Yating Chen, Hanbing Jiang

引用次数: 0

Assessment of anti-hyperglycemic and anti-hyperlipidemic effects of thiazolidine-2,4-dione derivatives in HFD-STZ diabetic animal model 评估噻唑烷-2,4-二酮衍生物在 HFD-STZ 糖尿病动物模型中的降血糖和降血脂作用

Chemico-biological interactions Pub Date : 2024-02-01 DOI: 10.1016/j.cbi.2024.110902

S. Fettach, Fatima Zahra Thari, Khalid Karrouchi, Laila Benbacer, Learn-Han Lee, Abdelhakim Bouyahya, Y. Cherrah, Hassan Sefrioui, Khalid Bougrin, M. El Abbes Faouzi

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Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin VRK1缺失会改变DNA损伤对多柔比星反应的核磷酸蛋白组

Chemico-biological interactions Pub Date : 2024-02-01 DOI: 10.1016/j.cbi.2024.110908

Elena Navarro-Carrasco, Aurora Campos-Díaz, Eva Monte-Serrano, F. Rolfs, Richard de Goeij-de Haas, T. Pham, S. Piersma, Connie R. Jimenez, Pedro A. Lazo

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Neurotoxicity of Pyrethroids in exacerbating neurodegenerative diseases: From animals' models to humans’ studies 拟除虫菊酯在加剧神经退行性疾病方面的神经毒性：从动物模型到人体研究

Chemico-biological interactions Pub Date : 2024-02-01 DOI: 10.1016/j.cbi.2024.110911

Rafael Arsuffi-Marcon, Lizandra Gomes Souza, Artur Santos-Miranda, J. Joviano-Santos

引用次数: 0