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Abatacept: A Promising Repurposed Solution for Myocardial Infarction-Induced Inflammation in Rat Models 阿巴他赛普大鼠模型中心肌梗死诱发炎症的有望再利用解决方案
2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-13 DOI: 10.1155/2024/3534104
Vipin Kumar Verma, Ekta Mutneja, Salma Malik, Anil Kumar Sahu, Vaishali Prajapati, Priya Bhardwaj, Ruma Ray, Tapas Chandra Nag, Jagriti Bhatia, Dharamvir Singh Arya
Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and myocardial damage. However, after a perilous period, ischemia-reperfusion (IR) itself causes the generation of oxygen free radicals, disturbance in cation homeostasis, depletion of cellular energy stores, and activation of innate and adaptive immune responses. The present study employed Abatacept (ABT), which is an anti-inflammatory drug, originally used as an antirheumatic response agent. To investigate the cardioprotective potential of ABT, primarily, the dose was optimized in a chemically induced model of myocardial necrosis. Thereafter, ABT optimized the dose of 5 mg/kg s.c. OD was investigated for its cardioprotective potential in a surgical model of myocardial IR injury, where animals (n = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT perse. ABT and telmisartan were administered for 21 days. On the 21st day, animals were subjected to LAD coronary artery occlusion for 60 min, followed by reperfusion for 45 min. Further, the cardioprotective potential was assessed through hemodynamic parameters, oxidant–antioxidant biochemical enzymatic parameters, cardiac injury, inflammatory markers, histopathological analysis, TUNEL assay, and immunohistochemical evaluation, followed by immunoblotting to explore signaling pathways. The statistics were performed by one-way analysis of variance, followed by the Tukey comparison post hoc tests. Noteworthy, 21 days of ABT pretreatment amended the hemodynamic and ventricular functions in the rat models of MI. The cardioprotective potential of ABT is accompanied by inhibiting MAP kinase signaling and modulating Nrf-2/HO-1 proteins downstream signaling cascade. Overall, the present work bolsters the previously known anti-inflammatory role of ABT in MI and contributes a mechanistic insight and application of clinically approved drugs in averting the activation of inflammatory response.
心肌梗死(MI)是由于长时间缺血/缺氧对心肌组织造成的不可逆损伤,随后导致收缩功能丧失和心肌损伤。然而,在危险期过后,缺血再灌注(IR)本身会导致氧自由基的产生、阳离子平衡的紊乱、细胞能量储存的耗竭以及先天性和适应性免疫反应的激活。本研究采用的阿巴他赛普(ABT)是一种抗炎药物,最初用作抗风湿反应剂。为了研究 ABT 的心脏保护潜力,首先在化学诱导的心肌坏死模型中优化了剂量。此后,在心肌红外损伤的手术模型中,将动物(n = 30)随机分为五组,以 5 mg/kg s.c. OD 的剂量对 ABT 的心脏保护潜力进行了研究:Sham 组、IR-C 组、Telmi10 + IR 组(替米沙坦,10 毫克/千克口服)、ABT5 + IR 组、ABT perse.ABT和替米沙坦给药21天。第21天,对动物进行LAD冠状动脉闭塞60分钟,然后再灌注45分钟。此外,还通过血液动力学参数、氧化-抗氧化生化酶学参数、心脏损伤、炎症标志物、组织病理学分析、TUNEL检测和免疫组织化学评估来评估心脏保护潜力,然后通过免疫印迹来探索信号通路。统计采用单因素方差分析,然后进行Tukey比较事后检验。值得注意的是,ABT 预处理 21 天可改善心肌梗死大鼠模型的血液动力学和心室功能。ABT的心脏保护潜力伴随着抑制MAP激酶信号转导和调节Nrf-2/HO-1蛋白下游信号级联。总之,本研究加强了之前已知的 ABT 在心肌梗死中的抗炎作用,并有助于从机理上深入了解和应用临床批准的药物来避免炎症反应的激活。
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引用次数: 0
ACA-28, an ERK MAPK Signaling Modulator, Exerts Anticancer Activity through ROS Induction in Melanoma and Pancreatic Cancer Cells ERK MAPK 信号调节剂 ACA-28 通过诱导黑色素瘤和胰腺癌细胞中的 ROS 发挥抗癌作用
2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-11 DOI: 10.1155/2024/7683793
Teruaki Takasaki, Yasuyuki Hamabe, Kenta Touchi, Golam Iftakhar Khandakar, Takeshi Ueda, Hitoshi Okada, Kazuko Sakai, Kazuto Nishio, Genzoh Tanabe, Reiko Sugiura
The extracellular signal-regulated kinase (ERK) MAPK pathway is dysregulated in various human cancers and is considered an attractive therapeutic target for cancer. Therefore, several inhibitors of this pathway are being developed, and some are already used in the clinic. We have previously identified an anticancer compound, ACA-28, with a unique property to preferentially induce ERK-dependent apoptosis in melanoma cells. To comprehensively understand the biological cellular impact induced by ACA-28, we performed a global gene expression analysis of human melanoma SK-MEL-28 cells exposed to ACA-28 using a DNA microarray. The transcriptome analysis identified nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcription factor that combats oxidative stress, as the most upregulated genetic pathway after ACA-28 treatment. Consistently, ACA-28 showed properties to increase the levels of reactive oxygen species (ROS) as well as Nrf2 protein, which is normally repressed by proteasomal degradation and activated in response to oxidative stresses. Furthermore, the ROS scavenger N-acetyl cysteine significantly attenuated the anticancer activity of ACA-28. Thus, ACA-28 activates Nrf2 signaling and exerts anticancer activity partly via its ROS-stimulating property. Interestingly, human A549 cancer cells with constitutively high levels of Nrf2 protein showed resistance to ACA-28, as compared with SK-MEL-28. Transient overexpression of Nrf2 also increased the resistance of cells to ACA-28, while knockdown of Nrf2 exerted the opposite effect. Thus, upregulation of Nrf2 signaling protects cancer cells from ACA-28-mediated cell death. Notably, the Nrf2 inhibitor ML385 substantially enhanced the cell death-inducing property of ACA-28 in pancreatic cancer cells, T3M4 and PANC-1. Our data suggest that Nrf2 plays a key role in determining cancer cell susceptibility to ACA-28 and provides a novel strategy for cancer therapy to combine the Nrf2 inhibitor and ACA-28.
在各种人类癌症中,细胞外信号调节激酶(ERK)MAPK 通路失调,被认为是一种有吸引力的癌症治疗靶点。因此,该通路的几种抑制剂正在开发中,其中一些已经应用于临床。我们之前发现了一种抗癌化合物 ACA-28,它具有一种独特的特性,能优先诱导黑色素瘤细胞发生 ERK 依赖性凋亡。为了全面了解 ACA-28 对生物细胞的影响,我们使用 DNA 微阵列对暴露于 ACA-28 的人黑色素瘤 SK-MEL-28 细胞进行了全基因表达分析。转录组分析发现,ACA-28 处理后上调最多的基因通路是核因子红细胞 2 相关因子 2(Nrf2),这是一种对抗氧化应激的主转录因子。同样,ACA-28 还具有提高活性氧(ROS)和 Nrf2 蛋白水平的特性,而 Nrf2 蛋白通常会被蛋白酶体降解所抑制,并在氧化应激时被激活。此外,ROS 清除剂 N- 乙酰半胱氨酸会显著削弱 ACA-28 的抗癌活性。因此,ACA-28 可激活 Nrf2 信号,并部分通过其刺激 ROS 的特性发挥抗癌活性。有趣的是,与SK-MEL-28相比,人A549癌细胞的Nrf2蛋白组成水平较高,对ACA-28表现出抗性。瞬时过表达 Nrf2 也会增加细胞对 ACA-28 的抵抗力,而敲除 Nrf2 则会产生相反的效果。因此,上调 Nrf2 信号可保护癌细胞免受 ACA-28 介导的细胞死亡。值得注意的是,Nrf2抑制剂ML385大大增强了ACA-28在胰腺癌细胞T3M4和PANC-1中诱导细胞死亡的特性。我们的数据表明,Nrf2在决定癌细胞对ACA-28的易感性方面起着关键作用,并为结合Nrf2抑制剂和ACA-28的癌症治疗提供了一种新策略。
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引用次数: 0
BACE1 Inhibition Utilizing Organic Compounds Holds Promise as a Potential Treatment for Alzheimer’s and Parkinson’s Diseases 利用有机化合物抑制 BACE1有望成为阿尔茨海默氏症和帕金森氏症的潜在治疗方法
2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-22 DOI: 10.1155/2024/6654606
Razieh Amini, Shadi Moradi, Rezvan Najafi, Mehrdokht Mazdeh, Amir Taherkhani
Background. Neurological disorders like Alzheimer’s disease (AD) and Parkinson’s disease (PD) manifest through gradually deteriorating cognitive functions. An encouraging strategy for addressing these disorders involves the inhibition of precursor-cleaving enzyme 1 (BACE1). Objectives. In the current research, a virtual screening technique was employed to identify potential BACE1 inhibitors among selected herbal isolates. Methods. This study evaluated 79 flavonoids, anthraquinones (AQs), and cinnamic acid derivatives for their potential blood–brain barrier (BBB) permeability. Using the AutoDock 4.0 tool, molecular docking analysis was conducted to determine the binding affinity of BBB permeable compounds to the BACE1 active site. Molecular dynamics (MD) simulations were performed to assess the stability of the docked poses of the most potent inhibitors. The interactions between the most effective plant-based inhibitors and the residues within the BACE1 catalytic site were examined before and after MD simulations. Results. Ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine were among the highest-ranking BACE1 inhibitors, with inhibition constant values calculated in the nanomolar range. Furthermore, during 10 ns simulations, the docked poses of these ligands were observed to be stable. Conclusion. The findings propose that ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine might serve as potential choices for the treatment of AD and PD, laying the groundwork for the creation of innovative BACE1 inhibitors.
背景。阿尔茨海默病(AD)和帕金森病(PD)等神经系统疾病表现为认知功能逐渐恶化。解决这些疾病的一个令人鼓舞的策略是抑制前体分解酶 1 (BACE1)。研究目的在目前的研究中,我们采用了虚拟筛选技术,从选定的草药分离物中找出潜在的 BACE1 抑制剂。方法。本研究评估了 79 种黄酮类化合物、蒽醌类化合物 (AQ) 和肉桂酸衍生物的潜在血脑屏障 (BBB) 渗透性。使用 AutoDock 4.0 工具进行了分子对接分析,以确定 BBB 可渗透化合物与 BACE1 活性位点的结合亲和力。还进行了分子动力学(MD)模拟,以评估最有效抑制剂对接姿势的稳定性。在进行 MD 模拟之前和之后,研究了最有效的植物抑制剂与 BACE1 催化位点内残基之间的相互作用。结果显示椪柑素、丹参酮、菊花酚和 N-对香豆酰酪胺是排名最靠前的 BACE1 抑制剂,其抑制常数的计算值在纳摩尔范围内。此外,在 10 ns 模拟期间,还观察到这些配体的对接位置是稳定的。结论研究结果表明,芒柄蜡素、丹参酮、金丝桃醇和N-对香豆酰酪胺可能成为治疗AD和PD的潜在选择,为创造创新的BACE1抑制剂奠定了基础。
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引用次数: 0
Synergistic Cytotoxicity of Extracts of Chaga Mushroom and Microalgae against Mammalian Cancer Cells In Vitro 查加蘑菇和微藻提取物对哺乳动物体外癌细胞的协同细胞毒性
2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-17 DOI: 10.1155/2024/7944378
Sajeev Wagle, Julie Anne Lee, H. P. Vasantha Rupasinghe
Chaga mushroom (Inonotus obliquus) contains bioactive metabolites and has been used to treat various ailments, including cancer. Similarly, marine microalgae are considered a sustainable food supplement with anticancer and antioxidant properties. This study investigated the cytotoxicity of different extracts prepared from I. obliquus and microalgae using cultured human and canine cancer cell lines (MCF-7, HepG2, HOS, D-17, and DH-82). MTS cell viability assay was used to study the cytotoxicity of I. obliquus and microalgae extracts, and a synergy matrix effect was used to study the combined effect of the extracts. Isobologram analysis and the highest single agent synergy model were applied to study and validate the synergy between the extracts from I. obliquus and microalgae. Ethanol-based extraction and supercritical water extract significantly inhibited the growth of various mammalian cancer cells compared to aqueous extracts. Osteosarcoma cells were more susceptible to the supercritical extracts of I. obliquus and chlorophyll-free and sugar-free ethanol extracts of microalgae. A combination of ethanol-based I. obliquus extract and chlorophyll-free microalgae extract resulted in a synergistic interaction with various tested cancer cells. This study provides experimental evidence supporting the potential therapeutic application of I. obliquus and microalgae extracts with a synergistic effect to inhibit the growth of various mammalian cancer cells. Additional in vivo studies are required to fully explore possible therapeutic applications of these unique mixtures to be used in treating cancers.
Chaga 蘑菇(Inonotus obliquus)含有生物活性代谢物,被用于治疗包括癌症在内的各种疾病。同样,海洋微藻也被认为是一种具有抗癌和抗氧化特性的可持续食品补充剂。本研究使用培养的人类和犬癌细胞系(MCF-7、HepG2、HOS、D-17 和 DH-82)研究了从褐藻和微藻中制备的不同提取物的细胞毒性。使用 MTS 细胞活力测定法研究了斜管草和微藻提取物的细胞毒性,并使用协同矩阵效应研究了提取物的综合效应。应用等全息图分析和最高单剂协同作用模型研究并验证了斜管圆叶藻和微藻提取物之间的协同作用。与水提取物相比,乙醇提取物和超临界水提取物能显著抑制多种哺乳动物癌细胞的生长。骨肉瘤细胞更容易受到欧鼠李超临界萃取物以及微藻无叶绿素和无糖乙醇萃取物的影响。将乙醇提取物和不含叶绿素的微藻提取物结合使用,可与各种受测癌细胞产生协同作用。这项研究提供了实验证据,支持将具有协同效应的斜管圆叶藻和微藻类提取物用于潜在的治疗,以抑制各种哺乳动物癌细胞的生长。还需要进行更多的体内研究,以充分探索这些独特混合物在治疗癌症方面可能的治疗应用。
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引用次数: 0
Retracted: Rhodiola Rosea Extract Counteracts Stress in an Adaptogenic Response Curve Manner via Elimination of ROS and Induction of Neurite Outgrowth 撤回:红景天提取物通过消除 ROS 和诱导神经元生长以适应性反应曲线的方式对抗压力
2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-09 DOI: 10.1155/2024/9782834
Oxidative Medicine and Cellular Longevity
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引用次数: 0
Retracted: Pinosylvin Extract Retinari™ Sustains Electrophysiological Function, Prevents Thinning of Retina, and Enhances Cellular Response to Oxidative Stress in NFE2L2 Knockout Mice 撤回:Pinosylvin 提取物 Retinari™ 可维持 NFE2L2 基因敲除小鼠的电生理功能、防止视网膜变薄并增强细胞对氧化应激的反应
2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-09 DOI: 10.1155/2024/9835864
Oxidative Medicine and Cellular Longevity
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引用次数: 0
Retracted: Pharmacological Properties of Bergapten: Mechanistic and Therapeutic Aspects 撤回:Bergapten 的药理特性:机制和治疗方面
2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-09 DOI: 10.1155/2024/9849584
Oxidative Medicine and Cellular Longevity
{"title":"Retracted: Pharmacological Properties of Bergapten: Mechanistic and Therapeutic Aspects","authors":"Oxidative Medicine and Cellular Longevity","doi":"10.1155/2024/9849584","DOIUrl":"https://doi.org/10.1155/2024/9849584","url":null,"abstract":"<jats:p />","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"42 46","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139442229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Retracted: Progress of Statin Therapy in the Treatment of Idiopathic Pulmonary Fibrosis 撤稿:他汀类药物治疗特发性肺纤维化的进展
2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-09 DOI: 10.1155/2024/9830469
Oxidative Medicine and Cellular Longevity
{"title":"Retracted: Progress of Statin Therapy in the Treatment of Idiopathic Pulmonary Fibrosis","authors":"Oxidative Medicine and Cellular Longevity","doi":"10.1155/2024/9830469","DOIUrl":"https://doi.org/10.1155/2024/9830469","url":null,"abstract":"<jats:p />","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"40 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139442494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Retracted: Black Truffle Extract Exerts Antidiabetic Effects through Inhibition of Inflammation and Lipid Metabolism Regulation 撤稿:黑松露提取物通过抑制炎症和调节脂质代谢发挥抗糖尿病作用
2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-09 DOI: 10.1155/2024/9765609
Oxidative Medicine and Cellular Longevity
{"title":"Retracted: Black Truffle Extract Exerts Antidiabetic Effects through Inhibition of Inflammation and Lipid Metabolism Regulation","authors":"Oxidative Medicine and Cellular Longevity","doi":"10.1155/2024/9765609","DOIUrl":"https://doi.org/10.1155/2024/9765609","url":null,"abstract":"<jats:p />","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"35 42","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139442839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Retracted: Theaflavin Chemistry and Its Health Benefits 撤回:茶黄素的化学性质及其对健康的益处
2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-09 DOI: 10.1155/2024/9893267
Oxidative Medicine and Cellular Longevity
{"title":"Retracted: Theaflavin Chemistry and Its Health Benefits","authors":"Oxidative Medicine and Cellular Longevity","doi":"10.1155/2024/9893267","DOIUrl":"https://doi.org/10.1155/2024/9893267","url":null,"abstract":"<jats:p />","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"35 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139442904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
期刊
Oxidative Medicine and Cellular Longevity
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