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Novel Strategies for the Treatment of Lung Cancer: An In-depth Analysis of the Use of Immunotherapy, Precision Medicine, and Artificial Intelligence to Improve Prognoses. 肺癌治疗的新策略:免疫疗法、精准医学和人工智能改善预后的深入分析。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-14 DOI: 10.2174/0109298673347323241119184648
Pawan Kedar, Sankha Bhattacharya, Abhishek Kanugo, Bhupendra G Prajapati
<p><p>Therapeutic hurdles persist in the fight against lung cancer, although it is a leading cause of cancer-related deaths worldwide. Results are still not up to par, even with the best efforts of conventional medicine, thus new avenues of investigation are required. Examining how immunotherapy, precision medicine, and AI are being used to manage lung cancer, this review shows how these tools can change the game for patients and increase their chances of survival. In the fight against cancer, immunotherapy has demonstrated encouraging results, especially in cases of small cell lung cancer [SCLC] and non-small cell lung cancer [NSCLC]. A key component in improving T cell responses against tumours is the use of immune checkpoint inhibitors, which include PD-1/PD-L1 and CTLA-4 blockers. Cancer vaccines and CAR T-cell therapy are two examples of adoptive cell therapies that might be used to boost the immune system's ability to eliminate tumours. In order to improve surgical results and decrease recurrence, neoadjuvant immunotherapy is being investigated for its ability to preoperatively reduce tumours. Precision medicine tailors treatment based on individual genetic profiles and tumour features, boosting therapeutic efficacy and avoiding unwanted effects. For certain types of non-small cell lung cancer [NSCLC], targeted treatments based on mutations in genes including EGFR, ALK, and ROS1 have shown excellent results. When it comes to optimizing treatment regimens, biomarker-driven approaches guarantee that the patients most likely to benefit from particular medicines are selected. Artificial intelligence [AI] is revolutionizing lung cancer care through increased diagnostic accuracy, prognostic assessments, and therapy planning. Machine learning algorithms examine enormous information to detect trends and forecast outcomes, permitting individualized treatment techniques. AI-driven imaging tools enable early diagnosis and monitoring of disease progression, while predictive models assist in evaluating therapy responses and potential toxicity. The convergence of these advanced technologies holds promise for overcoming the constraints of conventional therapy. Combining immunotherapy with targeted treatments and utilizing AI for precision medicine delivers a multimodal approach that tackles the heterogeneous and dynamic nature of lung cancer. The incorporation of these new tactics into clinical practice demands cross-disciplinary collaboration and continuing study to develop and confirm their effectiveness. The synergistic application of immunotherapy, precision medicine, and AI constitutes a paradigm shift in lung cancer management. These discoveries provide a robust basis for individualized and adaptable therapy, potentially altering the prognosis for lung cancer patients. Ongoing research and clinical studies are vital to unlocking the full potential of these technologies, paving the way for enhanced therapeutic outcomes and improved quality of life fo
尽管肺癌是全球癌症相关死亡的主要原因,但在与肺癌的斗争中,治疗障碍仍然存在。即使在传统医学的最大努力下,结果仍未达到标准,因此需要新的研究途径。研究了免疫疗法、精准医学和人工智能如何用于治疗肺癌,这篇综述展示了这些工具如何改变患者的游戏规则并增加他们的生存机会。在与癌症的斗争中,免疫疗法已经显示出令人鼓舞的结果,特别是在小细胞肺癌(SCLC)和非小细胞肺癌(NSCLC)的病例中。改善T细胞对肿瘤反应的一个关键组成部分是使用免疫检查点抑制剂,包括PD-1/PD-L1和CTLA-4阻滞剂。癌症疫苗和CAR - t细胞疗法是过继细胞疗法的两个例子,它们可能被用来增强免疫系统消除肿瘤的能力。为了提高手术效果和减少复发,新辅助免疫疗法正在研究其术前减少肿瘤的能力。精准医疗根据个体基因图谱和肿瘤特征定制治疗方案,提高治疗效果,避免不必要的影响。对于某些类型的非小细胞肺癌(NSCLC),基于EGFR、ALK和ROS1等基因突变的靶向治疗已经显示出良好的效果。当涉及到优化治疗方案时,生物标志物驱动的方法保证了最有可能从特定药物中受益的患者被选中。人工智能(AI)通过提高诊断准确性、预后评估和治疗计划,正在彻底改变肺癌治疗。机器学习算法检查大量信息以检测趋势和预测结果,从而实现个性化治疗技术。人工智能驱动的成像工具能够早期诊断和监测疾病进展,而预测模型有助于评估治疗反应和潜在毒性。这些先进技术的融合有望克服传统疗法的限制。将免疫治疗与靶向治疗相结合,并利用人工智能进行精准医疗,提供了一种多模式的方法,可以解决肺癌的异质性和动态性。将这些新策略纳入临床实践需要跨学科合作和持续研究,以发展和确认其有效性。免疫疗法、精准医学和人工智能的协同应用构成了肺癌管理的范式转变。这些发现为个性化和适应性治疗提供了坚实的基础,可能会改变肺癌患者的预后。正在进行的研究和临床研究对于释放这些技术的全部潜力,为增强治疗结果和改善与这一棘手疾病作斗争的人们的生活质量铺平道路至关重要。
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引用次数: 0
Theoretical Modeling of the Interactions of CoFe2O4-BaTiO3 Magnetoelectric Nanoparticles with Cancer and Healthy Cells. CoFe2O4-BaTiO3磁电纳米粒子与癌症和健康细胞相互作用的理论建模。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-14 DOI: 10.2174/0109298673348662241210111400
Gençay Sevim, Gizem Değer, Gülay Büyükköroğlu

Introduction: The effectiveness of pharmaceutical treatment methods is vital in cancer treatment. In this context, various targeted drug delivery systems are being developed to minimize or eliminate existing deficiencies and harms. This study aimed to model the interaction of MEN-based drug-targeting systems with cancer cells and determine the properties of interacting MENs.

Methods: Magnetoelectric Nanostructures (MENs) have both targeting and nano-electroporation effects due to their ferroic properties. Among these structures, the most used nanoparticles as targeting mechanisms are CoFe2O4-BaTiO3 structures. For this purpose, the electrical field produced by MENs was modeled using MATLAB R2023b, and a theoretical data pool of appropriate physical properties was created. Testing and applying other magnetoelectric materials defined in the literature may be costly and time-consuming.

Results: The problems with MENs can be eliminated by performing theoretical simulations of each material before proceeding with laboratory tests.

Conclusion: By simulating the interaction of CoFe2O4-BaTiO3 MENs with cancer cells, physical properties affecting drug targeting were theoretically identified and a data pool of MENs with these properties was created.

药物治疗方法的有效性在癌症治疗中至关重要。在这种情况下,正在开发各种靶向给药系统,以尽量减少或消除现有的缺陷和危害。本研究旨在模拟基于MENs的药物靶向系统与癌细胞的相互作用,并确定相互作用MENs的特性。方法:磁电纳米结构(MENs)由于其铁性质而具有靶向效应和纳米电穿孔效应。在这些结构中,最常用的靶向机制是CoFe2O4-BaTiO3结构。为此,利用MATLAB R2023b对MENs产生的电场进行建模,并建立相应物理性质的理论数据池。测试和应用文献中定义的其他磁电材料可能是昂贵和耗时的。结果:在进行实验室测试之前,可以通过对每种材料进行理论模拟来消除MENs的问题。结论:通过模拟CoFe2O4-BaTiO3 MENs与癌细胞的相互作用,从理论上确定了影响药物靶向的物理性质,并建立了具有这些性质的MENs数据池。
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引用次数: 0
A Promising Druggable Target for Translational Therapy of Ovarian Cancer: A Molecular Profiling of Therapeutic Innovations, Extracellular Vesicle Acquired Resistance, and Signaling Pathways. 卵巢癌转化治疗的一个有希望的药物靶点:治疗创新、细胞外囊泡获得性耐药和信号通路的分子分析。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-14 DOI: 10.2174/0109298673331849240930140120
Mohd Mustafa, Kashif Abbas, Waleem Ahmad, Rizwan Ahmad, Sidra Islam, Hamda Khan, Moinuddin, Md Imtaiyaz Hassan, Shazia Parveen, Safia Habib

Ovarian cancer (OC) ranks as the fifth leading cause of cancer-related deaths in the United States, posing a significant threat to female health. Late-stage diagnoses, driven by elusive symptoms often masquerading as gastrointestinal issues, contribute to a concerning 70% of cases being identified in advanced stages. While early-stage OC brags a 90% cure rate, progression involving pelvic organs or extending beyond the peritoneal cavity drastically diminishes it. Overcoming chemoresistance and metastasis requires a deep understanding of the associated progression mechanisms for innovative therapies. Extracellular vesicles (EVs), containing proteins, RNAs, DNAs, and metabolites, have surged in recent years, significantly impacting tumor progression, recurrence, immune evasion, and metastasis associated with the ovarian tumor microenvironment. Recent research unveils organ-specific metastatic patterns in OC, providing insights into tumor cell interactions and signaling crosstalk with stromal cells. The review explores the role of EVs behind OC cell metastasis and chemoresistance. Furthermore, the article delves into the role of EVs in the tumor microenvironment, immune evasion, and as biomarkers in context to OC, offering promising therapeutic strategies to enhance survival rates for OC patients. Lastly, the article focuses on an overview of PI3K/AKT/mTOR, MAPK/ERK, and VEGFR signaling pathways in the pathophysiology of ovarian cancer.

卵巢癌(OC)是美国癌症相关死亡的第五大原因,对女性健康构成重大威胁。由于难以捉摸的症状常常被伪装成胃肠道问题,晚期诊断导致70%的病例在晚期被确诊。虽然早期卵巢癌有90%的治愈率,但如果进展到盆腔器官或扩展到腹膜腔以外,则会大大减少其治愈率。克服化疗耐药和转移需要深入了解创新疗法的相关进展机制。近年来,含有蛋白质、rna、dna和代谢物的细胞外囊泡(Extracellular vesicles, ev)数量激增,显著影响着与卵巢肿瘤微环境相关的肿瘤进展、复发、免疫逃逸和转移。最近的研究揭示了OC中器官特异性转移模式,为肿瘤细胞相互作用和与基质细胞的信号串扰提供了见解。本文综述了ev在卵巢癌细胞转移和化疗耐药中的作用。此外,本文还深入探讨了ev在肿瘤微环境、免疫逃避以及作为OC背景下的生物标志物中的作用,为提高OC患者的生存率提供了有希望的治疗策略。最后,本文重点综述了PI3K/AKT/mTOR、MAPK/ERK和VEGFR信号通路在卵巢癌病理生理中的作用。
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引用次数: 0
Experimental Research Progress of mPGES-1 Inhibitor 2,5-Dimethylcelecoxib in Various Diseases. mPGES-1抑制剂2,5-二甲基塞来昔布在多种疾病中的实验研究进展
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-14 DOI: 10.2174/0109298673327820241004042817
Zhanfei Chen, Rong Chen, Laiping Wang, Zihao Yu, Weitong Chen, Hua Lin, Liumin Yu, Jinqiu Li, Zhonghui Chen, Jianlin Shen, Nanhong Tang

Prostaglandin E2 (PGE2) plays a crucial role in inflammation. Non-steroidal anti-inflammatory medications are commonly utilized to alleviate pain and address inflammation by blocking the production of PGE2 and cyclooxygenase (COX). However, selective inhibition of COX can easily lead to a series of risks for cardiovascular diseases. Hence, it is imperative to discover safer and more efficient targets for reducing inflammation. Research has demonstrated that mPGES-1 serves as the final enzyme that controls the rate of prostaglandin E2 synthesis. Moreover, it is only triggered by inflammation and could serve as a possible treatment target instead of COX in cases of inflammation. 2,5-dimethylcelecoxib (DMC) can effectively inhibit mPGES-1 expression, maintain the overall balance of prostaglandins, reduce the secretion of PGE2, and, most importantly, avoid the side effects of COX inhibitors. DMC has the ability to address illnesses through the stimulation of autophagy and apoptosis, as well as the regulation of the immune microenvironment and intestinal flora. This study provides a comprehensive overview of the advancements in DMC within experimental research and offers suggestions for potential avenues of future investigation.

前列腺素E2 (PGE2)在炎症中起着关键作用。非甾体类抗炎药物通常通过阻断PGE2和环氧合酶(COX)的产生来缓解疼痛和解决炎症。然而,COX的选择性抑制容易导致一系列心血管疾病的风险。因此,发现更安全、更有效的消炎靶点势在必行。研究表明,mPGES-1是控制前列腺素E2合成速率的最终酶。此外,它仅由炎症触发,在炎症情况下可以代替COX作为可能的治疗靶点。2,5-二甲基塞来昔布(DMC)可以有效抑制mPGES-1的表达,维持前列腺素的整体平衡,减少PGE2的分泌,最重要的是避免COX抑制剂的副作用。DMC具有通过刺激自噬和细胞凋亡,以及调节免疫微环境和肠道菌群来治疗疾病的能力。本研究综述了DMC在实验研究中的进展,并对未来的研究方向提出了建议。
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引用次数: 0
Computational Model to Predict Potential Therapeutic Targets Employing Generative Adversarial Networks for Analysis of Proteins Involved in Mycobacterium fortuitum Biofilm Formation. 利用生成对抗网络预测潜在治疗靶点的计算模型,用于分析与偶然性分枝杆菌生物膜形成有关的蛋白质。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-14 DOI: 10.2174/0109298673345515241122024326
Shan Ghai, Rahul Shrivastava, Shruti Jain

A planktonic population of bacteria can form a biofilm by adhesion and colonization. Proteins known as "adhesins" can bind to certain environmental structures, such as sugars, which will cause the bacteria to attach to the substrate. Quorum sensing is used to establish the population is dense enough to form a biofilm. This paper presents a comprehensive overview of our investigation into these processes, specifically focusing on Mycobacterium fortuitum, an emerging pathogen of increasing clinical relevance. In our study, we detailed the methodology employed for the proteomic analysis of M. fortuitum, as well as our innovative application of Generative Adversarial Networks (GANs). These advanced computational tools allow us to analyze complex data sets and identify patterns that might otherwise remain obscured. With a particular focus on the effectiveness of GAN, the identified proteins and their potential roles in the context of M. fortuitum's pathogenesis were discussed. The insights gained from this study can significantly contribute to our understanding of this emerging pathogen and pave the way for developing targeted interventions, potentially leading to improved diagnostic tools and more effective therapeutic strategies against M. fortuitum infection. The authors can achieve 95.43% accuracy for the generator and 87.89% for the discriminator. The model was validated by considering different Machine learning algorithms, reinforcing that integrating computational techniques with microbiological investigations can significantly enhance our understanding of emerging pathogens. Overall, this study emphasizes the importance of exploring the molecular mechanisms behind biofilm formation and pathogenicity, providing a foundation for future research that could lead to innovative solutions in combating infections caused by M. fortuitum and other similar pathogens.

浮游菌群可以通过粘附和定植形成生物膜。被称为“粘附素”的蛋白质可以与特定的环境结构结合,比如糖,这将导致细菌附着在底物上。群体感应用于确定种群是否足够密集以形成生物膜。本文介绍了我们对这些过程的调查的全面概述,特别侧重于偶发分枝杆菌,一种日益临床相关性的新兴病原体。在我们的研究中,我们详细介绍了用于M. fortuitum蛋白质组学分析的方法,以及我们对生成对抗网络(gan)的创新应用。这些先进的计算工具使我们能够分析复杂的数据集,并识别出可能仍然模糊不清的模式。特别关注GAN的有效性,讨论了鉴定的蛋白质及其在福氏分枝杆菌发病机制中的潜在作用。从这项研究中获得的见解可以显著有助于我们对这种新兴病原体的理解,并为开发有针对性的干预措施铺平道路,可能导致改进诊断工具和更有效的治疗策略,以对抗幸运分枝杆菌感染。生成器和鉴别器的准确率分别达到95.43%和87.89%。该模型通过考虑不同的机器学习算法进行了验证,强调了将计算技术与微生物研究相结合可以显著提高我们对新兴病原体的理解。总之,本研究强调了探索生物膜形成和致病性背后的分子机制的重要性,为未来的研究提供了创新的解决方案,以对抗幸运分枝杆菌和其他类似病原体引起的感染奠定了基础。
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引用次数: 0
Cordycepin and Its Structural Derivatives Effectively Suppress the High Expression of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase in Breast Carcinomas: A Computational Drug Development Approach. 虫草素及其结构衍生物有效抑制乳腺癌中表皮生长因子受体酪氨酸激酶的高表达:一种计算药物开发方法。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-14 DOI: 10.2174/0109298673333884241119063458
Shabana Bibi, Partha Biswas, Md Mohaimenul Islam Tareq, Md Imtiaz, Md Hasan Jafre Shovon, Md Ridoy Hossain, Nasim Ahmed, Norah A Albekairi, Abdulrahman Alshammari, Md Nazmul Hasan

Background: Breast cancer is a frequently diagnosed malignant disease and the primary cause of mortality among women with cancer worldwide. The therapy options are influenced by the molecular subtype due to the intricate nature of the condition, which consists of various subtypes. By focusing on the activation of receptors, Epidermal Growth Factor Receptor (EGFR) tyrosine kinase can be utilized as an effective drug target for therapeutic purposes of breast cancer.

Objectives: The objective of this study is to compare the underlying pharmacological properties of several modified agents to the parental Cordycepin to target and inhibit the EGFR tyrosine kinase high expression, and to discover the inhibitor with the highest affinity for this drug target to treat the breast cancer patients.

Methods: The Maestro Application of Schrödinger Suite Paid Software was initially employed for conducting extra precision (XP) structure-based virtual screening to evaluate the binding affinity of the Cordycepin and its 500 structural derivatives with the EGFR tyrosine kinase protein structure. In addition, the anti-breast cancer activity of the chosen compounds was assessed by looking at their drug-likeness and ADMET characteristics using Lipinski's rule of five along with Quantitative structure- activity relationship (QSAR) validation, the prediction of cell line anti-cancer, as well as anti- breast cancer activity of top docked scored compounds. Subsequently, the Desmond paid software- based molecular dynamics simulations (MDS) were conducted for a duration of 100 nanoseconds on the promising candidates followed by the binding free energy estimation was performed utilizing MM-GBSA analysis. To determine the stability of the protein-ligand complex, root-meansquare deviation (RMSD), root-mean-square fluctuation (RMSF), protein-ligand interactions, and other necessary parameters were evaluated from the 100 ns MDS Trajectory.

Results: Based on the overall analysis of our study, N (6)-octylamine adenosine (CID-194932) reported the optimum inhibitory potential against the EGFR tyrosine kinase protein, followed by Adenosine 5-monophosphate (CID-83862) and Cordycepin (CID-6303), which compared favorably to the control drug Vandetanib (CID-3081361).

Conclusion: Consequently, these derivative compounds Cordycepin have the potential to be utilized as lead molecules in the development of highly effective and potent EGFR tyrosine kinase inhibitors for the treatment of breast cancer patients.

背景:乳腺癌是一种常见的恶性疾病,也是全世界女性癌症患者死亡的主要原因。治疗方案受到分子亚型的影响,因为病情的复杂性,它由各种亚型组成。通过关注受体的激活,表皮生长因子受体酪氨酸激酶可以作为治疗乳腺癌的有效药物靶点。目的:本研究的目的是比较几种修饰药物与亲本虫草素靶向和抑制EGFR酪氨酸激酶高表达的潜在药理学性质,并发现对该药物靶点亲和力最高的抑制剂来治疗乳腺癌患者。方法:初步采用Schrödinger Suite付费软件Maestro Application进行基于extra precision (XP)结构的虚拟筛选,评价虫草素及其500个结构衍生物与EGFR酪氨酸激酶蛋白结构的结合亲和力。此外,采用Lipinski的五法则,通过药物相似性和ADMET特征,定量构效关系(QSAR)验证,细胞系抗癌预测以及得分最高的化合物的抗乳腺癌活性来评估所选化合物的抗乳腺癌活性。随后,利用Desmond软件对候选分子进行了持续100纳秒的分子动力学模拟(MDS),并利用MM-GBSA分析进行了结合自由能估算。为了确定蛋白质-配体复合物的稳定性,从100 ns MDS轨迹中评估了均方根偏差(RMSD)、均方根波动(RMSF)、蛋白质-配体相互作用和其他必要参数。结果:综合本研究结果,N(6)-辛胺腺苷(CID-194932)对EGFR酪氨酸激酶蛋白的抑制潜力最佳,其次为5-单磷酸腺苷(CID-83862)和虫草素(CID-6303),且优于对照药万德替尼(CID-3081361)。结论:虫草素衍生物有潜力作为先导分子开发高效的EGFR酪氨酸激酶抑制剂,用于治疗乳腺癌患者。
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引用次数: 0
Poly Lactic Co-glycolic Acid d-α-tocopheryl Polyethylene Glycol 1000 Succinate Fabricated Polyethylene Glycol Hybrid Nanoparticles of Imatinib Mesylate for the Treatment of Glioblastoma Multiforme. 聚乳酸共乙醇酸d-α-生育酚聚乙二醇1000琥珀酸制备甲磺酸伊马替尼聚乙二醇杂化纳米颗粒治疗多形胶质母细胞瘤。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-14 DOI: 10.2174/0109298673323270241118103546
Sankha Bhattacharya, Prafull Shinde, Amit Page, Bhupendra G Prajapati
<p><strong>Aims: </strong>This study aimed to develop Imatinib Mesylate (IMT)-loaded Poly Lactic-co-Glycolic Acid (PLGA)-D-α-tocopheryl polyethylene glycol succinate (TPGS)- Polyethylene glycol (PEG) hybrid nanoparticles (CSLHNPs) with optimized physicochemical properties for targeted delivery to glioblastoma multiforme.</p><p><strong>Background: </strong>Glioblastoma multiforme (GBM) is the most destructive type of brain tumor with several complications. Currently, most treatments for drug delivery for this disease face challenges due to the poor blood-brain barrier (BBB) and lack of site-specific delivery. Imatinib Mesylate (IMT) is one of the most effective drugs for GBM, but its primary issue is low bioavailability. Therefore, nanotechnology presents a promising solution for targeted IMT delivery to GBM. This article primarily explores the fabrication of IMT-loaded core-shell lipid-polymer hybrid nanoparticles (CSLHNPs) to achieve enhanced brain delivery with therapeutic efficacy.</p><p><strong>Objective: </strong>The primary objective of this study is to develop optimized, stable IMT-loaded hybrid nanoparticles with an encapsulated polymer matrix and to evaluate these nanoparticles using sophisticated instruments such as SEM and TEM to achieve smooth, spherical nanoparticles in a monodispersed phase.</p><p><strong>Method: </strong>The enhanced stable formulation yielded a notable increase in entrapment efficiency, reaching 58.89 ± 0.5%. The physical stability analysis of nanoparticles was assessed over 30 days under conditions of 25 ± 2°C and 60 ± 5% relative humidity. Hemolytic assays affirmed the biocompatibility and safety profile of the nanoparticles. in vitro drug release kinetics revealed a sustained IMT release over 48 hours.</p><p><strong>Results: </strong>The formulated CSLHNPs achieved a narrow size distribution with a mean vesicle diameter of 155.03 ± 2.41 nm and a low polydispersity index (PDI) of 0.23 ± 0.4, indicating monodispersity. A high negative zeta potential of -23.89 ± 3.47 mV ensured excellent colloidal stability in physiological conditions. XRD analysis confirmed the successful encapsulation of IMT within the nanoparticle matrix, with the drug transitioning to an amorphous state for enhanced dissolution. During Cell-Cell viability assays on LN229, glioblastoma cells were treated with IMT-loaded nanoparticles and showed a significantly enhanced inhibitory effect compared to free IMT. These hybrid nanoparticles demonstrated potential in reducing oxidative stress-induced cellular damage by mitigating reactive oxygen species (ROS). Thus, the prepared IMT hybrid nanoparticles showed higher cellular uptake and superior cytotoxicity compared to the plain drug.</p><p><strong>Conclusion: </strong>This study posits the IMT-PLGA-TPGS-DSPE PEG 2000-CSPLHNPs as a formidable and innovative drug delivery system for Glioblastoma Multiforme (GBM) treatment, warranting further exploration into their clinical application potential. Futur
目的:本研究旨在开发负载甲磺酸伊马替尼(IMT)的聚乳酸-羟基乙酸(PLGA)- d -α-生育酚基聚乙二醇丁二酸酯(TPGS)-聚乙二醇(PEG)混合纳米颗粒(CSLHNPs),该纳米颗粒具有优化的物理化学性质,可用于靶向递送多形性胶质母细胞瘤。背景:多形性胶质母细胞瘤(GBM)是最具破坏性的脑肿瘤类型,有多种并发症。目前,由于血脑屏障(BBB)差和缺乏部位特异性给药,大多数治疗这种疾病的药物递送面临挑战。甲磺酸伊马替尼(IMT)是治疗GBM最有效的药物之一,但其主要问题是生物利用度低。因此,纳米技术为靶向IMT递送GBM提供了一个很有前途的解决方案。本文主要探讨了负载imt的核-壳-脂质-聚合物混合纳米颗粒(CSLHNPs)的制备,以实现具有治疗效果的增强脑递送。目的:本研究的主要目的是开发具有封装聚合物基质的优化、稳定的负载imt的混合纳米粒子,并使用复杂的仪器(如扫描电镜和透射电镜)对这些纳米粒子进行评估,以获得单分散相中光滑的球形纳米粒子。方法:经强化稳定配方后,包封效率显著提高,达58.89±0.5%。在25±2°C和60±5%相对湿度条件下,对纳米颗粒进行30天的物理稳定性分析。溶血试验证实了纳米颗粒的生物相容性和安全性。体外药物释放动力学显示IMT在48小时内持续释放。结果:制备的CSLHNPs粒径分布较窄,平均囊泡直径为155.03±2.41 nm,多分散性指数(PDI)较低,为0.23±0.4,具有单分散性。-23.89±3.47 mV的高负zeta电位确保了生理条件下良好的胶体稳定性。XRD分析证实了IMT在纳米颗粒基质内的成功包封,药物转变为无定形状态以增强溶解。在LN229的细胞活力测试中,装载了IMT的纳米颗粒处理胶质母细胞瘤细胞,与游离IMT相比,显示出显著增强的抑制作用。这些混合纳米颗粒通过减少活性氧(ROS),显示出减少氧化应激诱导的细胞损伤的潜力。因此,与普通药物相比,制备的IMT杂交纳米颗粒具有更高的细胞摄取和优越的细胞毒性。结论:本研究认为IMT-PLGA-TPGS-DSPE PEG 2000-CSPLHNPs是治疗多形性胶质母细胞瘤(GBM)的一种强大的创新药物传递系统,值得进一步探索其临床应用潜力。未来的工作可能包括进行体内研究,以评估IMT-PLGA-TPGS-DSPE PEG 2000-CSPLHNPs在多形性胶质母细胞瘤(GBM)动物模型中的药代动力学、生物分布和治疗效果。此外,进一步的研究可能集中在优化纳米颗粒配方以增强靶向能力,研究不同储存条件下的长期稳定性,探索与纳米颗粒协同作用的潜在联合疗法,以及评估开发的药物传递系统的可扩展性和可制造性,以实现潜在的临床转化。整合先进的成像技术,实时跟踪和可视化肿瘤内的纳米颗粒分布,也可能是未来研究的一个有希望的方向。
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引用次数: 0
Current Perspectives of Diabetic Dyslipidemia and Treatment Modalities. 糖尿病性血脂异常的研究现状及治疗方法。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-13 DOI: 10.2174/0109298673336501241001093417
Gamze Akkus

Introduction: Diabetes mellitus is associated with an increased risk of atherosclerosis related to dyslipidemia. Although the terms hyperlipidemia and Diabetes Mellitus [DM] or diabetic dyslipidemia are interrelated to each other, these two conditions have some differences.

Aim: This study aimed to highlight possible mechanisms of hyperlipidemia and/or dyslipidemia in diabetic patients, which can be treated with available and newer hypolipidemic drugs. We also re-checked current specific guidelines and their recommendations on the management of patients with diabetic dyslipidemia.

Method: Comprehensive search of peer-reviewed journals was performed based on a wide range of keywords, including diabetes mellitus, dyslipidemia, hyperlipidemia, insulin resistance, free-fatty acids, cardiovascular disease, SCORE-2 calculation, statins, PCSK-9 inhibitors, and fibrates.

Discussion: Diabetic patients with dyslipidemia, including decreased HDL cholesterol, a predominance of small dense LDL particles, and increased triglyceride levels, are more prone to suffering from micro and macrovascular complications regardless of plasma fasting glucose levels. Recent guidelines suggested using the validated scoring system called SCORE2-Diabetes. Moderate to high dosages of statins, aiming for LDL cholesterol reduction, is still the cornerstone in the management of diabetic patients with dyslipidemia. Nowadays, other recommended non-statin drugs, including proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors or other novel therapeutic agents [bempedoic acid, inclisiran], are particularly important and given place in recently published guidelines.

Conclusion: The risk of developing atherosclerotic cardiovascular diseases in people with DM is relatively higher than in patients' without DM. Optimal management of lipid parameters and achieving desired target values in lipid parameters are still a challenging issue for clinicians.

导读:糖尿病与血脂异常相关的动脉粥样硬化风险增加相关。虽然高脂血症和糖尿病(DM)或糖尿病性血脂异常是相互关联的,但这两种情况也有一些区别。目的:本研究旨在揭示糖尿病患者高脂血症和/或血脂异常的可能机制,并可通过现有的和较新的降血脂药物进行治疗。我们还重新检查了当前的特定指南及其对糖尿病性血脂异常患者管理的建议。方法:根据糖尿病、血脂异常、高脂血症、胰岛素抵抗、游离脂肪酸、心血管疾病、SCORE-2计算、他汀类药物、PCSK-9抑制剂、贝特类药物等广泛的关键词,对同行评审期刊进行综合检索。讨论:无论空腹血糖水平如何,伴有血脂异常的糖尿病患者更容易出现微血管和大血管并发症,包括HDL胆固醇降低,小密度LDL颗粒占优势,甘油三酯水平升高。最近的指南建议使用经过验证的评分系统SCORE2-Diabetes。以降低低密度脂蛋白胆固醇为目标的中至高剂量他汀类药物仍然是糖尿病合并血脂异常患者管理的基石。如今,其他推荐的非他汀类药物,包括蛋白转化酶枯草杆菌素/kexin 9型[PCSK9]抑制剂或其他新型治疗药物[苯戊酸,inclisiran],在最近出版的指南中尤为重要。结论:糖尿病患者发生动脉粥样硬化性心血管疾病的风险相对高于非糖尿病患者。脂质参数的优化管理和脂质参数的理想目标值仍然是临床医生面临的一个挑战。
{"title":"Current Perspectives of Diabetic Dyslipidemia and Treatment Modalities.","authors":"Gamze Akkus","doi":"10.2174/0109298673336501241001093417","DOIUrl":"https://doi.org/10.2174/0109298673336501241001093417","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes mellitus is associated with an increased risk of atherosclerosis related to dyslipidemia. Although the terms hyperlipidemia and Diabetes Mellitus [DM] or diabetic dyslipidemia are interrelated to each other, these two conditions have some differences.</p><p><strong>Aim: </strong>This study aimed to highlight possible mechanisms of hyperlipidemia and/or dyslipidemia in diabetic patients, which can be treated with available and newer hypolipidemic drugs. We also re-checked current specific guidelines and their recommendations on the management of patients with diabetic dyslipidemia.</p><p><strong>Method: </strong>Comprehensive search of peer-reviewed journals was performed based on a wide range of keywords, including diabetes mellitus, dyslipidemia, hyperlipidemia, insulin resistance, free-fatty acids, cardiovascular disease, SCORE-2 calculation, statins, PCSK-9 inhibitors, and fibrates.</p><p><strong>Discussion: </strong>Diabetic patients with dyslipidemia, including decreased HDL cholesterol, a predominance of small dense LDL particles, and increased triglyceride levels, are more prone to suffering from micro and macrovascular complications regardless of plasma fasting glucose levels. Recent guidelines suggested using the validated scoring system called SCORE2-Diabetes. Moderate to high dosages of statins, aiming for LDL cholesterol reduction, is still the cornerstone in the management of diabetic patients with dyslipidemia. Nowadays, other recommended non-statin drugs, including proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors or other novel therapeutic agents [bempedoic acid, inclisiran], are particularly important and given place in recently published guidelines.</p><p><strong>Conclusion: </strong>The risk of developing atherosclerotic cardiovascular diseases in people with DM is relatively higher than in patients' without DM. Optimal management of lipid parameters and achieving desired target values in lipid parameters are still a challenging issue for clinicians.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Aptamers as a Potential Therapeutic and Screening Molecule for Oral Cancer. 适配体作为口腔癌潜在的治疗和筛选分子。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-10 DOI: 10.2174/0109298673356297241208155602
Thangavel Lakshmipriya, Subash C B Gopinath, Dhamodharan Prabhu, Evan T Salim, Makram A Fakhri
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引用次数: 0
Design, Synthesis, Biological Evaluation and Docking Studies of 2-hydroxy-4-benzyloxy Chalcone Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease. 2-羟基-4-苄基查尔酮衍生物治疗阿尔茨海默病多功能药物的设计、合成、生物学评价及对接研究
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-09 DOI: 10.2174/0109298673328877241113091539
Wei Li, Jing Huang, Zhixin Chen, Dan Zhang, Lin He, Yan Guo, Lei Zhong, Chenwu Yang, Chunyan Yang, Mei Zeng, Jiang Zhu, Zhongcheng Cao

Objectives: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, but no drugs can cure this disease. Chalcones possess good antioxidant activity, anti-neuroinflammatory activity, neuroprotective effects, inhibitory effects on Aβ aggregation, and Aβ disaggregation ability. Therefore, chalcones are ideal lead compounds, and the discovery of novel anti-AD agent-based chalcones is necessary.

Methods: Hydroxy groups and aryl benzyl ether groups were introduced into chalcone scaffolds to obtain a series of 2-hydroxyl-4-benzyloxy chalcone derivatives. These derivatives were further synthesized, biologically evaluated, and docked.

Results: Most target derivatives exhibited good anti-AD activities. In particular, compound 11d had excellent inhibitory effects on self-induced Aβ1-42 aggregation (90.8% inhibition rate at 25 μM) and Cu2+ induced Aβ1-42 aggregation (93.4% inhibition rate at 25 μM). In addition, it also exhibited good Aβ1-42 fibril disaggregation ability (64.7% at 25 μM), significant antioxidative activity (ORAC = 2.03 Trolox equivalent), moderate MAO-B inhibition (IC50 = 4.81 μM), selective metal chelation, appropriate BBB permeation, and dramatic anti-neuroinflammatory ability. In addition, compound 11d relieved AD symptoms and protected hippocampal neurons in vivo.

Conclusion: Compound 11d is a promising multifunctional anti-Aβ agent.

目标:阿尔茨海默病(AD)是最常见的神经退行性疾病,但目前尚无药物能够治愈这种疾病。查耳酮具有良好的抗氧化活性、抗神经炎症活性、神经保护作用、抑制 Aβ 聚集作用和 Aβ 分解能力。方法:在查尔酮支架中引入羟基和芳基苄基醚基,得到一系列 2-羟基-4-苄氧基查尔酮衍生物。对这些衍生物进行了进一步合成、生物学评价和对接:结果:大多数目标衍生物都表现出了良好的抗厌氧菌活性。结果:大多数目标衍生物都表现出了良好的抗逆转录酶活性,尤其是化合物 11d 对自身诱导的 Aβ1-42 聚集(25 μM 时抑制率为 90.8%)和 Cu2+ 诱导的 Aβ1-42 聚集(25 μM 时抑制率为 93.4%)有很好的抑制作用。此外,它还表现出良好的 Aβ1-42 纤维分解能力(25 μM 时为 64.7%)、显著的抗氧化活性(ORAC = 2.03 Trolox 当量)、中等程度的 MAO-B 抑制能力(IC50 = 4.81 μM)、选择性金属螯合能力、适当的 BBB 渗透能力和显著的抗神经炎能力。此外,化合物 11d 还能缓解 AD 症状,保护体内海马神经元:结论:化合物 11d 是一种很有前景的多功能抗 Aβ 剂。
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引用次数: 0
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Current medicinal chemistry
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