Chemico-Biological Interactions最新文献_第5页

4-Hydroxybenzoic acid restrains Nlrp3 inflammasome priming and activation via disrupting PU.1 DNA binding activity and direct antioxidation 4-羟基苯甲酸通过破坏 PU.1 DNA 结合活性和直接抗氧化来抑制 Nlrp3 炎症小体的启动和激活。

IF 4.7 2区医学

Chemico-Biological Interactions Pub Date : 2024-10-09 DOI: 10.1016/j.cbi.2024.111262

Yanbo Kou , Qiyue Jing , Xiaoqing Yan , Junru Chen , Yusi Shen , Yulu Ma , Yaoyao Xiang , Xiangyang Li , Xiangye Liu , Zhuanzhuan Liu , Yanxia Wei , Yugang Wang

{"title":"4-Hydroxybenzoic acid restrains Nlrp3 inflammasome priming and activation via disrupting PU.1 DNA binding activity and direct antioxidation","authors":"Yanbo Kou , Qiyue Jing , Xiaoqing Yan , Junru Chen , Yusi Shen , Yulu Ma , Yaoyao Xiang , Xiangyang Li , Xiangye Liu , Zhuanzhuan Liu , Yanxia Wei , Yugang Wang","doi":"10.1016/j.cbi.2024.111262","DOIUrl":"10.1016/j.cbi.2024.111262","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) production is considered central to triggering the nucleotide-binding domain-like receptor family pyrin domain containing 3 (Nlrp3) inflammasome activation and the subsequent inflammatory responses. Coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>) plays a critical role in maintaining intracellular ROS homeostasis and inhibiting excessive Nlrp3 inflammasome activation. However, direct supplementation of CoQ<sub>10</sub> showed unsatisfactory clinical improvement due to its limited absorption and bioavailability. Therefore, stimulating endogenous CoQ<sub>10</sub> biosynthesis by supplementing CoQ<sub>10</sub> precursors may provide a more promising therapeutic approach. In this study, we described the role of 4-hydroxybenzoic acid (4-HBA), a precursor of CoQ<sub>10</sub>, in attenuating excessive inflammatory responses. We found that while supplementation of 4-HBA inhibited the priming and activation of Nlrp3 inflammasome, this effect was independent of its metabolic transformation into CoQ<sub>10</sub>. 4-HBA itself exhibits antioxidative activities. Furthermore, 4-HBA can disrupt the binding activity of PU.1 on the promoters of <em>Tlr4</em> and <em>Md2</em>, thereby directly suppressing Nlrp3 inflammasome priming during LPS-induced inflammatory responses. Therefore, strategically utilizing 4-HBA or increasing 4-HBA intake may represent a potential strategy for reducing excessive inflammation.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"404 ","pages":"Article 111262"},"PeriodicalIF":4.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the effects of pemetrexed on drug resistance mechanisms in human lung adenocarcinoma and its association with PGRMC1 探索培美曲塞对人类肺腺癌耐药机制的影响及其与 PGRMC1 的关联。

IF 4.7 2区医学

Chemico-Biological Interactions Pub Date : 2024-10-03 DOI: 10.1016/j.cbi.2024.111259

Ssu-Yun Wu , En-Chi Liao , Yueh-Feng Wen , Yi-Shiuan Wang , Han Meng , Hsiu-Chuan Chou , Hong-Lin Chan

{"title":"Exploring the effects of pemetrexed on drug resistance mechanisms in human lung adenocarcinoma and its association with PGRMC1","authors":"Ssu-Yun Wu , En-Chi Liao , Yueh-Feng Wen , Yi-Shiuan Wang , Han Meng , Hsiu-Chuan Chou , Hong-Lin Chan","doi":"10.1016/j.cbi.2024.111259","DOIUrl":"10.1016/j.cbi.2024.111259","url":null,"abstract":"<div><div>According to the 2022 cancer statistics of the World Health Organization, lung cancer ranks among the top ten causes of death, with lung adenocarcinoma being the most prevalent type. Despite significant advancements in lung cancer therapeutics, many clinical limitations remain, primarily due to the development of drug resistance. The present study investigated the effects of pemetrexed on the drug resistance mechanisms in human lung adenocarcinoma and its association with progesterone receptor membrane component 1 (PGRMC1) expression. Given that KRAS-mutant lung adenocarcinoma cell lines (e.g., A549) exhibit a high folate synthesis activity, pemetrexed, which is structurally similar to folate, was selected as the therapeutic drug. The present study used a lung adenocarcinoma cell line (A549) and established a drug-resistant lung adenocarcinoma cell line (A549/PEM). The findings demonstrated that PGRMC1 expression was elevated in the A549/PEM cells. It has been hypothesized that PGRMC1 regulates iron absorption through heme binding, resulting in a preference for iron-related cell death pathways (ferroptosis). Our findings indicate that drug-resistant lung adenocarcinoma cells with high PGRMC1 levels exhibit elevated antioxidant activity on the cell membrane and increased reliance on iron-dependent cell death pathways. This suggests a correlation between PGRMC1 and pemetrexed-induced iron-dependent cell death. Our study contributes to the development of more effective therapeutic strategies to improve the prognosis of patients with lung adenocarcinoma, particularly those facing drug resistance challenges.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111259"},"PeriodicalIF":4.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Homocysteine decreases VEGF, EGF, and TrkB levels and increases CCL5/RANTES in the hippocampus: Neuroprotective effects of rivastigmine and ibuprofen 同型半胱氨酸会降低海马中血管内皮生长因子、表皮生长因子和 TrkB 的水平，并增加 CCL5/RANTES：利伐斯的明和布洛芬的神经保护作用。

IF 4.7 2区医学

Chemico-Biological Interactions Pub Date : 2024-10-01 DOI: 10.1016/j.cbi.2024.111260

Osmar Vieira Ramires Júnior , Josiane Silva Silveira , Darlan Gusso , Gustavo Ricardo Krupp Prauchner , Bruna Ferrary Deniz , Wellington de Almeida , Lenir Orlandi Pereira , Angela TS. Wyse

{"title":"Homocysteine decreases VEGF, EGF, and TrkB levels and increases CCL5/RANTES in the hippocampus: Neuroprotective effects of rivastigmine and ibuprofen","authors":"Osmar Vieira Ramires Júnior , Josiane Silva Silveira , Darlan Gusso , Gustavo Ricardo Krupp Prauchner , Bruna Ferrary Deniz , Wellington de Almeida , Lenir Orlandi Pereira , Angela TS. Wyse","doi":"10.1016/j.cbi.2024.111260","DOIUrl":"10.1016/j.cbi.2024.111260","url":null,"abstract":"<div><div>Homocysteine (Hcy) is produced through methionine transmethylation. Elevated Hcy levels are termed Hyperhomocysteinemia (HHcy) and represent a risk factor for neurodegenerative conditions such as Alzheimer's disease. This study aimed to explore the impact of mild HHcy and the neuroprotective effects of ibuprofen and rivastigmine via immunohistochemical analysis of glial markers (Iba-1 and GFAP). Additionally, we assessed levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), chemokine ligand 5 (CCL5/RANTES), CX3C chemokine ligand 1 (CX3CL1), and the NGF/p75NTR/tropomyosin kinase B (TrkB) pathway in the hippocampus of adult rats. Mild chronic HHcy was induced chemically in Wistar rats by subcutaneous administration of Hcy (4 mg/kg body weight) twice daily for 30 days. Rivastigmine (0.5 mg/kg) and ibuprofen (40 mg/kg) were administered intraperitoneally once daily. Results revealed elevated levels of CCL5/RANTES and reduced levels of VEGF, EGF, and TrkB in the hippocampus of HHcy-exposed rats. Rivastigmine mitigated the neurotoxic effects of HHcy by increasing TrkB and VEGF levels. Conversely, ibuprofen attenuated CCL5/RANTES levels against the neurotoxicity of HHcy, significantly reducing this chemokine's levels. HHcy-induced neurochemical impairment in the hippocampus may jeopardize neurogenesis, synapse formation, axonal transport, and inflammatory balance, leading to neurodegeneration. Treatments with rivastigmine and ibuprofen alleviated some of these detrimental effects. Reversing HHcy-induced damage through these compounds could serve as a potential neuroprotective strategy against brain damage.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111260"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Silicon dioxide particles induce DNA oxidative damage activating the AIM2-mediated PANoptosis in mice cerebellum 二氧化硅颗粒诱导 DNA 氧化损伤，激活 AIM2 介导的小鼠小脑泛凋亡。

IF 4.7 2区医学

Chemico-Biological Interactions Pub Date : 2024-10-01 DOI: 10.1016/j.cbi.2024.111258

Hao Cai , Meichen Gao , Tong Xu , Ke Li , Yuanxin Zhou , Chencong Lyu , Shiwen Xu

{"title":"Silicon dioxide particles induce DNA oxidative damage activating the AIM2-mediated PANoptosis in mice cerebellum","authors":"Hao Cai , Meichen Gao , Tong Xu , Ke Li , Yuanxin Zhou , Chencong Lyu , Shiwen Xu","doi":"10.1016/j.cbi.2024.111258","DOIUrl":"10.1016/j.cbi.2024.111258","url":null,"abstract":"<div><div>Silicon dioxide (SiO<sub>2</sub>) particles are novel materials with wide-ranging applications across various fields, posing potential neurotoxic effects. This study investigates the toxicological mechanisms of SiO<sub>2</sub> particles of different sizes on murine cerebellar tissue and cells. Six-week-old C57BL/6 mice were orally administered SiO<sub>2</sub> particles of three sizes (1 μm, 300 nm, 50 nm) for 21 days to establish an in vivo model, and mice cerebellar astrocytes (C8-D1A cells) were cultured in vitro. Indicators of oxidative stress, DNA damage, and the PANoptosis pathway were detected using methods such as immunofluorescence staining, comet assay, western blotting, and qRT-PCR. The results show that SiO<sub>2</sub> particles induce oxidative stress leading to DNA oxidative damage. The aberrant DNA is recognized by AIM2 (absent in melanoma 2), which activates the assembly of the PANoptosome complex, subsequently triggering PANoptosis. Furthermore, the extent of damage is inversely correlated with the size of SiO<sub>2</sub> particles. This study elucidates the toxicological mechanism of SiO<sub>2</sub> particles causing cerebellar damage via PANoptosis, extending research on PANoptosis in neurotoxicology, and aiding in the formulation of stricter safety standards and protective measures to reduce the potential toxic risk of SiO<sub>2</sub> particles to humans.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111258"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PP2 suppresses proliferation and migration of C6 Glioma and MDA-MB-231 cells by targeting both fibroblast growth factor receptor 1 and Src PP2 通过靶向成纤维细胞生长因子受体 1 和 Src，抑制 C6 胶质瘤和 MDA-MB-231 细胞的增殖和迁移

IF 4.7 2区医学

Chemico-Biological Interactions Pub Date : 2024-09-26 DOI: 10.1016/j.cbi.2024.111252

Yanyan Yang , Ningning Tang , Yan Liu , Wooram Choi , Ji Hye Kim , Han Gyung Kim , Tao Yu , Jae Youl Cho

{"title":"PP2 suppresses proliferation and migration of C6 Glioma and MDA-MB-231 cells by targeting both fibroblast growth factor receptor 1 and Src","authors":"Yanyan Yang , Ningning Tang , Yan Liu , Wooram Choi , Ji Hye Kim , Han Gyung Kim , Tao Yu , Jae Youl Cho","doi":"10.1016/j.cbi.2024.111252","DOIUrl":"10.1016/j.cbi.2024.111252","url":null,"abstract":"<div><div>Fibroblast growth factor (FGF) is involved in the progression of glioma, a most common type of brain tumor, and breast tumors. In this study, we aim to evaluate the effects of the inhibitor PP2 on cell proliferation and migration in glioma and breast tumor cells, and to characterize the molecular mechanisms involved in these processes. The inhibitory effect of PP2 on the tumorigenic potential of C6 glioma and MDA-MB-231 cells was examined by proliferation, migration, and invasion assays, and apoptotic analysis. The molecular mechanism behind the anti-glioma activity of PP2 was investigated by immunoblotting, immunoprecipitation, phosphoprotein assay, cellular thermal shift assay (CETSA), and molecular docking modeling. PP2 suppressed the proliferation and migration of C6 glioma and MDA-MB-231 cells via FGF2. Moreover, PP2 directly blocked the enzyme activity of FGF receptor 1 (FGFR1) and Src, subsequently affecting the nuclear factor-κB and activator protein-1 signaling pathways. CETSA analysis and the docking model indicated that the TK1 domains (Val 492 ad Glu 486) of FGFR2 could be binding sites of PP2. Collectively, therefore, our findings suggest that PP2 mediates antitumor effects by targeting both FGFR1 and Src and may have applications as a therapeutic inhibitor for the treatment of glioma.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111252"},"PeriodicalIF":4.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142326776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endocytic pathways and metabolic fate of colloidal bismuth subcitrate in human renal cells 胶体次柠檬酸铋在人肾细胞中的内吞途径和代谢命运

IF 4.7 2区医学

Chemico-Biological Interactions Pub Date : 2024-09-26 DOI: 10.1016/j.cbi.2024.111256

Yang Yang , Mengfei Tan , Jinbin Cui, He Liu, Hezhang Meng, Xiaju Cheng, Yangyun Wang, Yong Wang, Leshuai W. Zhang

{"title":"Endocytic pathways and metabolic fate of colloidal bismuth subcitrate in human renal cells","authors":"Yang Yang , Mengfei Tan , Jinbin Cui, He Liu, Hezhang Meng, Xiaju Cheng, Yangyun Wang, Yong Wang, Leshuai W. Zhang","doi":"10.1016/j.cbi.2024.111256","DOIUrl":"10.1016/j.cbi.2024.111256","url":null,"abstract":"<div><div>Bismuth compounds, particularly colloidal bismuth subcitrate (CBS), have been widely used in the treatment of gastrointestinal diseases. However, overdose of CBS has been linked to cases of acute renal failure, primarily due to the intracellular accumulation of bismuth in the kidney. To date, the detailed mechanisms of CBS internalization and its metabolic fate remain unclear. In this study, CBS was characterized as a type of nano-object using transmission electron microscopy and dynamic light scattering. Renal cells internalized CBS primarily via clathrin-mediated endocytosis in an active transport manner. Gene knockdown techniques revealed that CBS binds to the transferrin receptor likely through complexing with transferrin before cellular uptake. Once internalized, CBS was sorted into early endosomes, late endosomes, and lysosomes, mediated by microtubules and the Golgi apparatus. Additionally, differentially expressed genes analysis revealed that CBS endocytosis stimulated oxidative stress, significantly affecting the metabolism of glutathione and cysteine within cells. This led to the formation of black bismuth sulfide particles as a result of CBS conjugating with intracellular glutathione. These findings provide crucial insights into the cellular mechanisms underlying excessive CBS exposure, which is essential for understanding and potentially mitigating the risks associated with the use of bismuth compounds in medical treatments.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111256"},"PeriodicalIF":4.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142326766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lanostane triterpenoids from Ganoderma calidophilum exhibit potent anti-tumor activity by inhibiting PTP1B 灵芝三萜类化合物通过抑制 PTP1B 显示出强大的抗肿瘤活性。

IF 4.7 2区医学

Chemico-Biological Interactions Pub Date : 2024-09-26 DOI: 10.1016/j.cbi.2024.111253

Chuan Chen , Ruixuan Xu , Chenxiao Guo , Xiangke Li , Youxing Zhao , Duqiang Luo

{"title":"Lanostane triterpenoids from Ganoderma calidophilum exhibit potent anti-tumor activity by inhibiting PTP1B","authors":"Chuan Chen , Ruixuan Xu , Chenxiao Guo , Xiangke Li , Youxing Zhao , Duqiang Luo","doi":"10.1016/j.cbi.2024.111253","DOIUrl":"10.1016/j.cbi.2024.111253","url":null,"abstract":"<div><div>The species <em>Ganoderma calidophilum</em> represents a distinct variety within the genus Ganoderma and used by the indigenous Li ethnic group as a medicinal agent for the prevention and treatment of cancer. However, the precise biological activity and role of <em>G. calidophilum</em> in antitumor treatment remain largely unresolved. Several lanostane triterpenoids have been isolated from <em>G</em>. <em>calidophilum</em>. The enzyme activity analysis revealed that four lanostane triterpenoids exhibited PTP1B inhibition activity, with minimal inhibition towards SHP2, SHP1, PTPN5, PTPRA, STEP and TCPTP. Molecular docking analysis demonstrated that these compounds primarily bind to the substrate recognition and entry regions of PTP1B. Further analysis indicated that among them, ganoderic aldehyde A (GAA) is a selective and non-competitive PTP1B inhibitor. GAA inhibited the proliferation, colony formation and migration of C33A and MDA-MB-231 cells in a dose-dependent manner. GAA has the capacity to induce apoptosis in a cell-type-specific manner, both in a caspase-dependent and -independent manner. PTP1B siRNA significantly reduced the cytotoxic effect of GAA, while overexpression of PTP1B significantly increased cell growth after GAA treatment. These findings confirm that PTP1B is a functional target of GAA. Research into the mechanisms of action of GAA has revealed that it could inhibit the activation of AKT by inhibiting PTP1B, while simultaneously activating p38, which promotes cell death. It is possible to develop specific PTP1B inhibitors based on the lanosterol triterpene skeleton. <em>G. calidophilum</em> has the potential to be developed into functional foods or drugs with the aim of preventing and treating cancer.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111253"},"PeriodicalIF":4.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative analysis of the interaction mechanism of γ-globulin and hemoglobin with spherical and rod-shaped gold nanoparticles γ-球蛋白和血红蛋白与球形和棒形金纳米粒子相互作用机制的比较分析。

IF 4.7 2区医学

Chemico-Biological Interactions Pub Date : 2024-09-26 DOI: 10.1016/j.cbi.2024.111257

Xiangrong Li , Xinzhe Wu , Yujie Sun , Zhizhi Song , Li Shi , Ze Dong

{"title":"Comparative analysis of the interaction mechanism of γ-globulin and hemoglobin with spherical and rod-shaped gold nanoparticles","authors":"Xiangrong Li , Xinzhe Wu , Yujie Sun , Zhizhi Song , Li Shi , Ze Dong","doi":"10.1016/j.cbi.2024.111257","DOIUrl":"10.1016/j.cbi.2024.111257","url":null,"abstract":"<div><div>The interaction mechanism of spherical gold nanoparticles (AuNPs) and rod-shaped gold nanoparticles (AuNRs) with γ-globulin and hemoglobin was comprehensively and comparatively analyzed. γ-Globulin and hemoglobin have high affinity with AuNPs, and with two different types of binding sites on AuNRs surface. Except hemoglobin interaction with the first binding site of AuNRs, the interaction between γ-globulin/hemoglobin and AuNPs/AuNRs is the spontaneous, endothermic and entropy-driven process, and hydrophobic interaction plays a dominant role. The molecular adsorption mechanism of γ-globulin/hemoglobin on AuNPs and AuNRs surface conforms to Langmuir model and Freundlich model, respectively. The kinetic molecular mechanism between them conforms to the pseudo-second-order model, and chemisorption is the rate-limiting step. AuNPs result in the loosening and unfolding of γ-globulin backbone. AuNRs have no significant effect on γ-globulin backbone. AuNPs/AuNRs result in no significant changes in hemoglobin structure and heme group microenvironment. AuNPs/AuNRs decrease the hydrophobicity of Trp microenvironment of γ-globulin, but there is an intramolecular energy transfer from Trp residue to Tyr residue of hemoglobin. The β-sheet of γ-globulin and the α-helix of hemoglobin reduce by increasing concentrations of AuNPs/AuNRs. Molecular docking is suggesting that the specific amino acid residues of γ-globulin and hemoglobin interaction with AuNPs/AuNRs, and validates the experimental results.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111257"},"PeriodicalIF":4.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure optimization, synthesis and bioactivity evaluation of novel BCR-ABL tyrosine kinase inhibitor targeting T315I mutation 针对 T315I 突变的新型 BCR-ABL 酪氨酸激酶抑制剂的结构优化、合成和生物活性评估。

IF 4.7 2区医学

Chemico-Biological Interactions Pub Date : 2024-09-25 DOI: 10.1016/j.cbi.2024.111248

Shuo Wang , Jingjing Chen , Rui Hou , Yijing Xiong , Huaihuai Shi , Zhesheng Chen , Jiazhong Li , Xin Wang

{"title":"Structure optimization, synthesis and bioactivity evaluation of novel BCR-ABL tyrosine kinase inhibitor targeting T315I mutation","authors":"Shuo Wang , Jingjing Chen , Rui Hou , Yijing Xiong , Huaihuai Shi , Zhesheng Chen , Jiazhong Li , Xin Wang","doi":"10.1016/j.cbi.2024.111248","DOIUrl":"10.1016/j.cbi.2024.111248","url":null,"abstract":"<div><div>Chronic Myeloid Leukemia (CML) is a malignant hematologic tumor caused by BCR-ABL fusion protein that binds with ATP to exert tyrosinase activity and persistently activates downstream phosphorylation pathways. The tyrosine kinase inhibitors (TKIs) represented by Imatinib are the key clinical therapy to the CML. While the mutations on the target lead to the serious drug resistance problems, especially the T315I mutation remains an unresolved challenge, and the cardiotoxicity has limited the clinical application of the third generation TKI Ponatinib despite its favorable efficacy against the T315I mutation. Even though, structural optimization of Ponatinib remains a potential strategy to overcome the resistance imposed by the mutation. Herein, we present a series of novel BCR-ABL/T315I tyrosine kinase inhibitors obtained by virtual screening using ZINC21710815, a BCR-ABL/T315I inhibitor reported earlier by our team, as a lead compound, and structural optimization of lead compounds against the T315I mutation, as well as screening of two novel compounds by activity evaluation and mechanistic studies, W4 and W8. W4 and W8 have better cell death-inducing effects and special selectivity against BaF3/T315I, which are worthy of further in-depth study to obtain more desirable anti-CML drugs as lead compounds.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111248"},"PeriodicalIF":4.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CGS-21680 defers cisplatin-induced AKI-CKD transition in C57/BL6 mice CGS-21680 可延缓 C57/BL6 小鼠顺铂诱导的 AKI-CKD 转化。

IF 4.7 2区医学

Chemico-Biological Interactions Pub Date : 2024-09-25 DOI: 10.1016/j.cbi.2024.111255

Menna A. Elbrolosy, Manar G. Helal, Mirhan N. Makled

{"title":"CGS-21680 defers cisplatin-induced AKI-CKD transition in C57/BL6 mice","authors":"Menna A. Elbrolosy, Manar G. Helal, Mirhan N. Makled","doi":"10.1016/j.cbi.2024.111255","DOIUrl":"10.1016/j.cbi.2024.111255","url":null,"abstract":"<div><div>Acute kidney injury (AKI), with a high mortality and morbidity, is known as a risk factor for developing progressive chronic kidney disease (CKD). Targeting transition of AKI to CKD displays an excellent therapeutic potential. This study aims at investigating the role of CGS-21680, selective A2AR agonist, in deferring <em>Cis</em>-induced AKI-CKD transition. The AKI-CKD transition model was induced in C57/BL6 mice by repeated low doses of Cis (2.5 mg/kg i.p for 5 consecutive days in two cycles with a recovery phase of 16 days between two cycles). CGS-21680 was administered daily for 6 weeks (0.1 mg/kg, i.p). Urine, blood, and kidney were collected at three different time points to track the disease progression. CGS-21680 administration preserved kidney function and attenuated tubular damage as evidenced by hematoxylin-eosin (H&E) histopathology. CGS-21680 significantly restored oxidative status as reflected by reduced malondialdehyde (MDA) content and increased total antioxidant capacity (TAC). CGS-21680 showed anti-inflammatory effect as indicated by decreased TNF-α and iNOS. Additionally, CGS-21680 ameliorated endothelial dysfunction and enhanced renal vasodilation as evidenced by upregulation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) expression and down regulation of endothelin-1 (ET-1) and its receptor endothelin-A (ET-A) receptor expression. CGS-21680 also attenuated renal fibrosis as reflected by the reduction of percentage of fibrosis in Masson's trichome-stained renal sections and down regulation of transforming growth factor beta1 (TGF-β1) protein expression in IHC-stained renal sections. In conclusion, CGS-21680 could defer <em>Cis</em>-induced AKI-CKD transition via its vasodilatory, antioxidant, anti-inflammatory, and anti-fibrotic effects.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111255"},"PeriodicalIF":4.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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