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Bioelectronic Medicines-A Novel Approach of Therapeutics in Current Epoch. 生物电子药物--当代治疗的新方法。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-20 DOI: 10.2174/0113816128326489240827100537
Ajay Kumar, Mahendra Singh Ashawat, Vinay Pandit, Pravin Kumar

Background: Bioelectronic medicines aim to diagnose and treat a wide range of illnesses and ailments, including cancer, rheumatoid arthritis, inflammatory bowel disease, obesity, diabetes, asthma, paralysis, blindness, bleeding, ischemia, organ transplantation, cardiovascular disease, and neurodegenerative diseases. The focus of bioelectronic medicine is on electrical signaling of the nervous system. Understanding the nervous system's regulatory roles and developing technologies that record, activate, or inhibit neural signaling to influence particular biological pathways.

Objective: Bioelectronic medicine is an emerging therapeutic option with the interconnection between molecular medicine, neuroscience, and bioengineering. The creation of nerve stimulating devices that communicate with both the central and peripheral nervous systems has the potential to completely transform how we treat disorders. Although early clinical applications have been largely effective across entire nerves, the ultimate goal is to create implantable, miniature closed-loop systems that can precisely identify and modulate individual nerve fibers to treat a wide range of disorders.

Methodology: The data bases such as PubMed, and Clinicaltrial.gov.in were searched for scientific research, review and clinical trials on bioelectronic medicine.

Conclusion: The field of bioelectronic medicine is trending at present. In recent years, researchers have extended the field's applications, undertaken promising clinical trials, and begun delivering therapies to patients, thus creating the groundwork for significant future advancements. Countries and organizations must collaborate across industries and regions to establish an atmosphere and guidelines that foster the advancement of the field and the fulfillment of its prospective advantages.

背景:生物电子药物旨在诊断和治疗多种疾病,包括癌症、类风湿性关节炎、炎症性肠病、肥胖症、糖尿病、哮喘、瘫痪、失明、出血、缺血、器官移植、心血管疾病和神经退行性疾病。生物电子医学的重点是神经系统的电信号。了解神经系统的调节作用,开发记录、激活或抑制神经信号的技术,从而影响特定的生物通路:生物电子医学是分子医学、神经科学和生物工程相互联系的一种新兴治疗方法。能够与中枢神经系统和外周神经系统进行沟通的神经刺激装置的问世,有可能彻底改变我们治疗疾病的方式。虽然早期的临床应用在很大程度上对整个神经有效,但我们的最终目标是建立可植入的微型闭环系统,精确识别和调节单个神经纤维,治疗各种疾病:方法:在 PubMed 和 Clinicaltrial.gov.in 等数据库中搜索有关生物电子医学的科学研究、综述和临床试验:结论:生物电子医学领域是当前的发展趋势。近年来,研究人员扩大了该领域的应用范围,开展了前景广阔的临床试验,并开始向患者提供疗法,从而为未来的重大进展奠定了基础。各国和各组织必须开展跨行业、跨地区的合作,营造促进该领域发展的氛围,制定相关准则,发挥该领域的预期优势。
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引用次数: 0
A Captivating Potential of Schiff Bases Derivatives for Antidiabetic Activity. 希夫碱衍生物抗糖尿病的迷人潜力
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-20 DOI: 10.2174/0113816128339161240913055034
Rakesh Sahu, Kamal Shah

A double bond between the nitrogen and carbon atoms characterizes a wide class of compounds known as Schiff bases. The flexibility of Schiff bases is formed from several methods and may be combined with alkyl or aryl substituents. The group is a part of organic compounds, either synthetic or natural, and it serves as a precursor and an intermediate in drugs that have therapeutic action. The review focuses on molecular docking and structure-activity relationship (SAR) analysisfor antidiabetic effects of the different non-metal Schiff bases. Many studies have found that Schiff bases are used as linkers in an extensive range of synthesized compounds and other activities. Thus, this current study aims to give the scientific community a thoughtful look at the principal ideas put forward by investigators regarding antidiabetic actions exhibited by certain Schiff-based derivatives, as this review covered many aspects, including docking and SAR analysis. For individuals who intend to create novel antidiabetic compounds with Schiff bases as pharmacophores or physiologically active moieties, it will be an invaluable informational resource.

氮原子和碳原子之间的双键是希夫碱一类化合物的特征。希夫碱的柔韧性由多种方法形成,可与烷基或芳基取代基结合。该基团是合成或天然有机化合物的一部分,也是具有治疗作用的药物的前体和中间体。这篇综述重点分析了不同非金属席夫碱的分子对接和结构-活性关系(SAR)分析,以了解它们的抗糖尿病作用。许多研究发现,希夫碱在大量合成化合物和其他活动中被用作连接剂。因此,本研究旨在让科学界深入了解研究人员就某些席夫碱衍生物的抗糖尿病作用提出的主要观点,因为本综述涵盖了许多方面,包括对接和 SAR 分析。对于打算用希夫碱作为药源或生理活性分子来开发新型抗糖尿病化合物的人来说,这将是一个宝贵的信息资源。
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引用次数: 0
An Integrated Approach of Network Pharmacology, Bioinformatics, Molecular Docking, and Experimental Verification Uncovers Prunellae Spica as the potential Medicine of Prognosis Improvement for Oral Squamous Cell Carcinoma 网络药理学、生物信息学、分子对接和实验验证的综合方法揭示了刺五加是改善口腔鳞状细胞癌预后的潜在药物
IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-18 DOI: 10.2174/0113816128328547240827045955
Jiahui Chen, Xinyan Zhang
Background: Prunellae Spica (PS), the spike from Prunella vulgaris L., is a traditional Chinese medicine that can treat Oral Squamous Cell Carcinoma (OSCC), whereas its molecular mechanisms and effects on the prognosis of patients remain unclear. Methods: Our study aimed to identify potential anti-OSCC targets of PS and explore its mechanisms and effects on prognosis through network pharmacology, bioinformatics analysis, molecular docking, and in vitro cell assays. Results: Sixty-two potential targets of 11 active anti-OSCC ingredients of PS were identified, with Quercetin, the core ingredient of PS, exhibiting the most significant number of OSCC-related targets. GO analysis indicated that the primary biological processes involved in OSCC treatment by PS were the cellular response to nitrogen compound, response to xenobiotic stimulus, and cellular response to organonitrogen compound. KEGG analysis revealed that Pathways in cancer were the top highly enriched signaling pathway in the treatment of OSCC by PS. DisGeNET analysis is mainly about Lip and Oral Cavity Carcinoma. More importantly, 6 of the 62 targets were markedly related to prognosis. Molecular docking revealed high affinities between the key component and the prognosis-related target proteins. Treatment of OSCC cell line SCC-25 with Quercetin could inhibit malignant biological behaviors, such as cell proliferation, colony formation, invasion, and migration, as well as affect the targets related to prognosis and promote autophagy. Conclusion: Overall, these results suggest that PS plays a significant role in treating and improving the prognosis of OSCC by directly influencing various processes in OSCC.
背景:刺五加(Prunellae Spica,PS)是一种传统中药,可治疗口腔鳞状细胞癌(OSCC),但其分子机制及其对患者预后的影响仍不清楚。研究方法我们的研究旨在通过网络药理学、生物信息学分析、分子对接和体外细胞实验,确定 PS 的潜在抗 OSCC 靶点,并探讨其机制及其对预后的影响。研究结果发现了 PS 中 11 种抗 OSCC 活性成分的 62 个潜在靶点,其中 PS 的核心成分槲皮素与 OSCC 相关的靶点数量最多。GO分析表明,PS治疗OSCC的主要生物学过程是细胞对氮化合物的反应、对异生物刺激的反应和细胞对有机氮化合物的反应。KEGG分析表明,在PS治疗OSCC的过程中,癌症中的通路是首要的高富集信号通路。DisGeNET 分析主要涉及唇癌和口腔癌。更重要的是,62个靶点中有6个与预后明显相关。分子对接显示,关键成分与预后相关的靶蛋白之间具有很高的亲和力。用槲皮素治疗OSCC细胞株SCC-25可抑制细胞增殖、集落形成、侵袭和迁移等恶性生物学行为,并影响与预后相关的靶标和促进自噬。结论总之,这些结果表明,PS通过直接影响OSCC的各种过程,在治疗和改善OSCC预后方面发挥着重要作用。
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引用次数: 0
Recent Developments and Applications of 3D-Printing Technology in Pharmaceutical Drug Delivery Systems: A New Research Direction and Future Trends 三维打印技术在药物输送系统中的最新发展和应用:新的研究方向和未来趋势
IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-18 DOI: 10.2174/0113816128309717240826101647
Suryakanta Swain, Bikash Ranjan Jena, Rabinarayan Parhi
The advent of 3D printing technology has emerged as a key technical revolution in recent years, enabling the development and production of innovative medication delivery methods in the pharmaceutical sector. The designs, concepts, techniques, key challenges, and potential benefits during 3D-printing technology are the key points discussed in this review. This technology primarily enables rapid, safe, and low-cost development of pharmaceutical formulations during the conventional and additive manufacturing processes. This phenomenon has wide-ranging implications in current as well as future medicinal developments. Advanced technologies such as Ink-Jet printing, drop-on-demand printing, Zip dose, Electrohydrodynamic Printing (Ejet) etc., are the current focus of the drug delivery systems for enhancing patient convenience and improving medication compliance. The current and future applications of various software, such as CAD software, and regulatory aspects in 3D and 4D printing technology are discussed briefly in this article. With respect to the prospective trajectory of 3D and 4D printing, it is probable that the newly developed methods will be predominantly utilized in pharmacies and hospitals to accommodate the unique requirements of individuals or niche groups. As a result, it is imperative that these technologies continue to advance and be improved in comparison to 2D printing in order to surmount the aforementioned regulatory and technical obstacles, render them applicable to a vast array of drug delivery systems, and increase their acceptability among patients of every generation.
近年来,3D 打印技术的出现已成为一场关键的技术革命,使制药行业能够开发和生产创新的给药方法。本综述将重点讨论 3D 打印技术的设计、概念、技术、主要挑战和潜在优势。这项技术主要是在传统和增材制造过程中实现快速、安全和低成本的药物制剂开发。这一现象对当前和未来的医药发展有着广泛的影响。喷墨打印、按需滴注打印、Zip dose、电流体动力打印(Ejet)等先进技术是当前给药系统的重点,可为患者提供更多便利,提高用药依从性。本文简要讨论了 CAD 软件等各种软件的当前和未来应用,以及 3D 和 4D 打印技术的监管问题。关于三维和四维打印技术的发展前景,新开发的方法很可能主要用于药房和医院,以满足个人或特殊群体的独特需求。因此,与二维打印相比,当务之急是继续推进和改进这些技术,以克服上述监管和技术障碍,使其适用于各种给药系统,并提高每一代患者的接受程度。
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引用次数: 0
Inhibition of Colorectal Cancer Metastasis by Total Flavones of Abelmoschus Manihot via Lncrna AL137782-mediated STAT3/EMT Pathway Regulation 通过 Lncrna AL137782 介导的 STAT3/EMT 通路调节,马齿苋总黄酮抑制结直肠癌转移
IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-18 DOI: 10.2174/0113816128298998240828060306
Qian Li, Hui Zhang, Yongshan He, Hao Zhang, Conghui Han
Background: Colorectal cancer (CRC) ranks among the most lethal malignancies globally, particularly following metastasis which results in poor prognosis. In recent years, CRC incidence in China has persistently increased. Total flavonoids (TFA) from Abelmoschus manihot, a natural compound, are recognized for their anti-inflammatory, analgesic, and antioxidant properties. However, despite extensive research into the therapeutic potential of TFA, coverage of its role in cancer treatment is notably lacking. To address this research void, our study aims to unveil the role and potential mechanisms of TFA in treating CRC. Methods: We conducted a series of experiments to assess the impact of TFA on CRC cells. Two specific CRC cell lines, DLD-1 and HCT116, were employed in cell proliferation, colony formation, flow cytometry, and cell migration assays. Additionally, to test the in vivo effects of TFA, we developed a nude mouse xenograft tumor model to assess TFA's impact on tumor growth and liver metastasis. Furthermore, we meticulously analyzed the gene expression differences between CRC cells pretreated with TGF-β and those treated with TFA using RNA-seq technology. We also examined the molecular mechanisms of TFA and assessed the expression of proteins related to the STAT3/EMT signaling pathway through Western blotting and siRNA technology. Results: Our research findings reveal for the first time the effect of TFA on CRC cells. Result shows that TFA could suppress cell proliferation, migration, and induce apoptosis. In vivo results showed that TFA inhibited tumor growth and liver metastasis. Molecular mechanism studies have shown that TFA exerts these effects by upregulating the expression of non-coding RNA AL137782, inhibiting the EMT/STAT3 signaling pathway. These results suggest that TFA is a potential candidate for mitigating CRC metastasis. Conclusion: However, further research is needed to comprehensively evaluate the efficacy and safety of TFA in animal models and clinical settings. These findings bring great hope for the development of innovative CRC treatment methods.
背景:结直肠癌(CRC)是全球致死率最高的恶性肿瘤之一,尤其是转移后预后较差。近年来,中国的 CRC 发病率持续上升。从天然化合物马齿苋中提取的总黄酮(TFA)具有抗炎、镇痛和抗氧化作用。然而,尽管对反式脂肪酸的治疗潜力进行了广泛的研究,但有关其在癌症治疗中的作用的报道却明显不足。为了填补这一研究空白,我们的研究旨在揭示反式脂肪酸在治疗 CRC 中的作用和潜在机制。研究方法我们进行了一系列实验来评估反式脂肪酸对 CRC 细胞的影响。在细胞增殖、集落形成、流式细胞术和细胞迁移实验中使用了两种特定的 CRC 细胞系 DLD-1 和 HCT116。此外,为了测试反式脂肪酸的体内效应,我们建立了裸鼠异种移植肿瘤模型,以评估反式脂肪酸对肿瘤生长和肝转移的影响。此外,我们还利用 RNA-seq 技术仔细分析了经 TGF-β 预处理的 CRC 细胞与经 TFA 处理的 CRC 细胞之间的基因表达差异。我们还研究了TFA的分子机制,并通过Western印迹和siRNA技术评估了STAT3/EMT信号通路相关蛋白的表达。研究结果我们的研究结果首次揭示了反式脂肪酸对 CRC 细胞的影响。结果表明,反式脂肪酸能抑制细胞增殖、迁移并诱导细胞凋亡。体内研究结果表明,反式脂肪酸可抑制肿瘤生长和肝转移。分子机制研究表明,反式脂肪酸通过上调非编码 RNA AL137782 的表达、抑制 EMT/STAT3 信号通路来发挥上述作用。这些结果表明,反式脂肪酸是减轻 CRC 转移的潜在候选药物。结论然而,要全面评估 TFA 在动物模型和临床环境中的有效性和安全性,还需要进一步的研究。这些发现为开发创新的 CRC 治疗方法带来了巨大希望。
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引用次数: 0
Exploring Hepatocellular Carcinoma Pathogenesis: The Influence of Genetic Polymorphisms. 探索肝细胞癌的发病机制:基因多态性的影响。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-18 DOI: 10.2174/0113816128327773240827062719
Samaneh Mollazadeh, Nikoo Saeedi, Abdulridha Mohammed Al-Asady, Elnaz Ghorbani, Majid Khazaei, Mikhail Ryzhikov, Amir Avan, Seyed Mahdi Hasanian

Hepatocellular carcinoma (HCC) is influenced by several factors, among which genetic polymorphisms play a key role. Polymorphisms in various genes affect key pathways involved in HCC development, including metabolism, expression of inflammatory cytokines, cell proliferation, and apoptosis regulation. These polymorphisms induce differential effects on susceptibility to HCC, disease progression, and treatment outcomes. Understanding the effect of genetic variations on HCC pathogenesis is essential to elucidate underlying mechanisms and identify potential therapeutic targets. This review explores the diverse roles of genetic polymorphisms in HCC, providing insights into the complex interplay between genetic factors and disease development.

肝细胞癌(HCC)受多种因素影响,其中基因多态性起着关键作用。各种基因的多态性会影响参与 HCC 发展的关键通路,包括代谢、炎症细胞因子的表达、细胞增殖和凋亡调节。这些多态性会对 HCC 易感性、疾病进展和治疗效果产生不同的影响。了解基因变异对 HCC 发病机制的影响对于阐明潜在机制和确定潜在治疗靶点至关重要。本综述探讨了遗传多态性在 HCC 中的不同作用,为了解遗传因素与疾病发展之间复杂的相互作用提供了见解。
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引用次数: 0
Health Benefits and Safety of Postbiotics Derived from Different Probiotic Species. 从不同益生菌种提取的益生菌后的健康益处和安全性。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-18 DOI: 10.2174/0113816128335414240828105229
Siyavash Ghadiri Harat, Hadi Pourjafar

Nowadays, the usage of probiotics in the food industry has become common. It has been proven that probiotics have many health benefits, such as adjusting the intestinal microbiome, boosting the immune system, and enhancing anti-inflammatory and anti-cancer activities. However, in recent years, some concerns have arisen about the consumption of probiotics, especially in vulnerable populations such as elderly, infants, and people with underlying diseases. As a result, finding a new alternative to probiotics that has the same function as probiotics and is safer has been prioritized. In recent years, postbiotics have been introduced as a great replacement for probiotics. However, the safety of these compounds is not exactly confirmed due to the limited in vivo research. In this review, the definition, classification, activities, limitations, and some advantages of postbiotics over probiotics are discussed. Finally, the limited published data about the safety of postbiotics is summarized.

如今,益生菌在食品工业中的应用已十分普遍。事实证明,益生菌对健康有很多益处,如调整肠道微生物群、增强免疫系统、提高抗炎和抗癌活性等。然而,近年来,人们对食用益生菌产生了一些担忧,尤其是老年人、婴儿和患有基础疾病的人等弱势群体。因此,寻找一种与益生菌功能相同且更安全的新的益生菌替代品已成为当务之急。近年来,后益生菌作为益生菌的最佳替代品问世。然而,由于体内研究有限,这些化合物的安全性尚未得到确切证实。本综述讨论了益生菌的定义、分类、活性、局限性以及益生菌的一些优势。最后,总结了已发表的有关益生菌安全性的有限数据。
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引用次数: 0
A Revolutionary Approach for Combating Efflux Transporter-mediated Resistant Epilepsy: Advanced Drug Delivery Systems. 对抗外排转运体介导的抗药性癫痫的革命性方法:先进的给药系统。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-13 DOI: 10.2174/0113816128332345240823111524
Megha Tonk, Indu Singh, Ram Jee Sharma, Shikha Baghel Chauhan

Epilepsy is a persistent neurological condition that affects 60 million individuals globally, with recurrent spontaneous seizures affecting 80% of patients. Antiepileptic drugs (AEDs) are the main course of therapy for approximately 65% of epileptic patients, and the remaining 35% develop resistance to medication, which leads to Drug-Resistant Epilepsy (DRE). DRE continues to be an important challenge in clinical epileptology. There are several theories that attempt to explain the neurological causes of pharmacoresistance in epilepsy. The theory that has been studied the most is the transporter hypothesis. Therefore, it is believed that upregulation of multidrug efflux transporters at the blood-brain barrier (BBB), such as P-glycoprotein (P-gp), which extrudes AEDs from their target location, is the major cause, leading to pharmacoresistance in epilepsy. The most effective strategies for managing this DRE are peripheral and central inhibition of P-gp and maintaining an effective concentration of the drug in the brain parenchyma. Presently, no medicinal product that inhibits P-gp is being used in clinical practice. In this review, several innovative and promising treatment methods, including gene therapy, intracranial injections, Pgp inhibitors, nanocarriers, and precision medicine, are discussed. The primary goal of this work is to review the P-gp transporter, its substrates, and the latest novel treatment methods for the management of DRE.

癫痫是一种神经系统顽疾,影响着全球 6000 万患者,其中 80% 的患者会反复出现自发性癫痫发作。抗癫痫药物(AED)是约 65% 癫痫患者的主要治疗方法,其余 35% 的患者会产生耐药性,从而导致耐药性癫痫(DRE)。耐药性癫痫仍然是临床癫痫学的一个重要挑战。有几种理论试图解释癫痫耐药性的神经学原因。研究最多的理论是转运体假说。因此,人们认为血脑屏障(BBB)多药流出转运体(如P-糖蛋白(P-gp))的上调是导致癫痫药理耐药性的主要原因。控制 DRE 的最有效策略是外周和中枢抑制 P-gp,并保持药物在脑实质中的有效浓度。目前,还没有抑制 P-gp 的药物被用于临床实践。本综述讨论了几种创新且有前景的治疗方法,包括基因治疗、颅内注射、Pgp 抑制剂、纳米载体和精准医疗。这项工作的主要目的是回顾 P-gp 转运体、其底物以及治疗 DRE 的最新新型治疗方法。
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引用次数: 0
Recent Advancement in Drug Development for Treating Malaria using Herbal Medicine and Nanotechnological Approach. 利用草药和纳米技术方法治疗疟疾的药物开发最新进展。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-13 DOI: 10.2174/0113816128321468240828103439
Sarvesh Bhargava, Rohitas Deshmukh, Hitesh Kumar Dewangan

More than two hundred million people around the world are infected with malaria, a blood-borne disease that poses a significant risk to human life. Single medications, such as lumefantrine, primaquine, and chloroquine, as well as combinations of these medications with artemisinin or its derivatives, are currently being used as therapies. In addition, due to rising antimalarial drug resistance, other therapeutic options are needed immediately. Furthermore, due to anti-malarial medication failures, a new drug is required. Medication discovery and development are costly and time-consuming. Many malaria treatments have been developed however, most treatments have low water solubility and bioavailability. They may also cause drug-resistant parasites, which would increase malaria cases and fatalities. Nanotechnology may offer a safer, more effective malaria therapy and control option. Nanoparticles' high loading capacity, concentrated drug delivery, biocompatibility, and low toxicity make them an attractive alternative to traditional therapy. Nanotechnology-based anti-malarial chemotherapeutic medications outperform conventional therapies in therapeutic benefits, safety, and cost. This improves patient treatment compliance. The limitations of malaria treatments and the importance of nanotechnological approaches to the treatment of malaria were also topics that were covered in this review. The most recent advancements in nanomaterials and the advantages they offer in terms of medication delivery are discussed in this article. The prospective therapy for malaria is also discussed. Additionally, the limitations of malaria therapies and the importance of nanotechnology-based approaches to the treatment of malaria were explored.

全世界有两亿多人感染疟疾,这是一种血液传播疾病,对人类生命构成重大威胁。目前使用的治疗方法包括单一药物,如鲁班亭、伯氨喹和氯喹,以及这些药物与青蒿素或其衍生物的复方制剂。此外,由于抗疟药物的抗药性不断增加,需要立即采取其他治疗方案。此外,由于抗疟疾药物治疗失败,需要一种新的药物。药物的发现和开发既昂贵又耗时。目前已开发出许多疟疾治疗药物,但大多数治疗药物的水溶性和生物利用度较低。它们还可能导致寄生虫产生抗药性,从而增加疟疾病例和死亡人数。纳米技术可以提供一种更安全、更有效的疟疾治疗和控制方法。纳米颗粒的高负载能力、集中给药、生物相容性和低毒性使其成为传统疗法的一种有吸引力的替代品。基于纳米技术的抗疟疾化疗药物在治疗效果、安全性和成本方面都优于传统疗法。这提高了患者治疗的依从性。疟疾治疗的局限性和纳米技术方法对疟疾治疗的重要性也是本综述涉及的主题。本文讨论了纳米材料的最新进展及其在给药方面的优势。文章还讨论了疟疾的未来疗法。此外,还探讨了疟疾疗法的局限性以及基于纳米技术的疟疾治疗方法的重要性。
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引用次数: 0
Oligoprotective Activity of Levetiracetam Against Glutamate Toxicity: An in vitro Study. 左乙拉西坦对谷氨酸盐毒性的寡保护活性:体外研究
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-13 DOI: 10.2174/0113816128327215240827071257
Mohaddeseh Sadat Alavi, Abdulridha Mohammed Al-Asady, Farzaneh Abbasinezhad- Moud, Arezoo Rajabian, Zahra Rastegartizabi, Hamid R Sadeghnia

Introduction: The role of glutamate in the development of some brain pathological conditions, such as multiple sclerosis, has been well described. Levetiracetam (LEV), a new broad-spectrum antiseizure medicine, is widely used to control certain types of seizures.

Method: Apart from its anti-seizure activity, LEV exerts neuroprotection via anti-inflammatory, antioxidant, and antiapoptotic effects. The current study was designed to evaluate the protective potential of LEV against glutamate-induced injury in OLN-93 oligodendrocytes.

Method: At first, the potential negative impact of LEV on OLN-93 viability was evaluated. After that, the cells were concurrently treated with LEV (0-100 μM) and glutamate (8 mM) for 24 h. The viability, redox status, and the rate of apoptosis of OLN-93 cells were then assessed using 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT), 2',7' dichlorodihydrofluorescein diacetate (H2DCFDA), 2-thiobarbituric acid reactive substances (TBARS) and annexin V/propidium iodide (PI) assays, respectively. Moreover, caspase-3 expression, as a marker of cell apoptosis, was evaluated by western blotting.

Results: LEV at 1-800 μM did not have any negative effect on cell survival. Treatment with LEV (50 and 100 μM) substantially enhanced the cell viability following glutamate insult. The cytoprotective activity of LEV (50 and 100 μM) against glutamate toxicity was accompanied by reduced Reactive Oxygen Species (ROS) accumulation and Malondialdehyde (MDA) level. Moreover, 100 μM of LEV inhibited apoptosis and decreased the expression level of cleaved caspase-3 following glutamate exposure.

Conclusion: Taken together, the results suggested that LEV has protective effects against glutamate-mediated cytotoxicity in OLN-93 cells. The oligoprotective action of LEV was shown to be exerted via inhibition of oxidative stress and cellular apoptosis.

简介谷氨酸在多发性硬化症等一些脑部病变的发展过程中的作用已被充分描述。左乙拉西坦(LEV)是一种新型广谱抗癫痫药物,被广泛用于控制某些类型的癫痫发作:方法:除抗癫痫活性外,左乙拉西坦还通过抗炎、抗氧化和抗细胞凋亡作用发挥神经保护作用。本研究旨在评估 LEV 对谷氨酸诱导的 OLN-93 少突胶质细胞损伤的保护潜力:方法:首先,评估 LEV 对 OLN-93 活力的潜在负面影响。然后,用 LEV(0-100 μM)和谷氨酸(8 mM)同时处理细胞 24 小时。然后分别使用 3-[4,5-二甲基噻唑- 2-基]-2,5-二苯基-2H-溴化四唑鎓(MTT)、2',7'二氯二氢荧光素二乙酸酯(H2DCFDA)、2-硫代巴比妥酸活性物质(TBARS)和附件素 V/碘化丙啶(PI)检测法评估 OLN-93 细胞的活力、氧化还原状态和凋亡率。此外,细胞凋亡标志物 Caspase-3 的表达也通过 Western 印迹法进行了评估:结果:1-800 μM的LEV对细胞存活没有任何负面影响。LEV(50 μM和100 μM)可显著提高谷氨酸损伤后的细胞存活率。LEV(50 和 100 μM)对谷氨酸毒性的细胞保护活性伴随着活性氧(ROS)积累和丙二醛(MDA)水平的降低。此外,谷氨酸暴露后,100 μM 的 LEV 可抑制细胞凋亡并降低裂解的 Caspase-3 的表达水平:综上所述,研究结果表明,LEV 对 OLN-93 细胞谷氨酸介导的细胞毒性具有保护作用。结果表明,LEV 的寡保护作用是通过抑制氧化应激和细胞凋亡来实现的。
{"title":"Oligoprotective Activity of Levetiracetam Against Glutamate Toxicity: An in vitro Study.","authors":"Mohaddeseh Sadat Alavi, Abdulridha Mohammed Al-Asady, Farzaneh Abbasinezhad- Moud, Arezoo Rajabian, Zahra Rastegartizabi, Hamid R Sadeghnia","doi":"10.2174/0113816128327215240827071257","DOIUrl":"https://doi.org/10.2174/0113816128327215240827071257","url":null,"abstract":"<p><strong>Introduction: </strong>The role of glutamate in the development of some brain pathological conditions, such as multiple sclerosis, has been well described. Levetiracetam (LEV), a new broad-spectrum antiseizure medicine, is widely used to control certain types of seizures.</p><p><strong>Method: </strong>Apart from its anti-seizure activity, LEV exerts neuroprotection via anti-inflammatory, antioxidant, and antiapoptotic effects. The current study was designed to evaluate the protective potential of LEV against glutamate-induced injury in OLN-93 oligodendrocytes.</p><p><strong>Method: </strong>At first, the potential negative impact of LEV on OLN-93 viability was evaluated. After that, the cells were concurrently treated with LEV (0-100 μM) and glutamate (8 mM) for 24 h. The viability, redox status, and the rate of apoptosis of OLN-93 cells were then assessed using 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT), 2',7' dichlorodihydrofluorescein diacetate (H2DCFDA), 2-thiobarbituric acid reactive substances (TBARS) and annexin V/propidium iodide (PI) assays, respectively. Moreover, caspase-3 expression, as a marker of cell apoptosis, was evaluated by western blotting.</p><p><strong>Results: </strong>LEV at 1-800 μM did not have any negative effect on cell survival. Treatment with LEV (50 and 100 μM) substantially enhanced the cell viability following glutamate insult. The cytoprotective activity of LEV (50 and 100 μM) against glutamate toxicity was accompanied by reduced Reactive Oxygen Species (ROS) accumulation and Malondialdehyde (MDA) level. Moreover, 100 μM of LEV inhibited apoptosis and decreased the expression level of cleaved caspase-3 following glutamate exposure.</p><p><strong>Conclusion: </strong>Taken together, the results suggested that LEV has protective effects against glutamate-mediated cytotoxicity in OLN-93 cells. The oligoprotective action of LEV was shown to be exerted via inhibition of oxidative stress and cellular apoptosis.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281605","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}
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Current pharmaceutical design
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