therapeutic applications

治疗应用
  • 文章类型: Journal Article
    近年来,噬菌体展示技术在临床研究中已变得至关重要。它有助于产生可以特异性结合复杂抗原的抗体,这对于识别生物标志物和改善诊断和治疗至关重要。然而,现有的综述往往忽视了它在癌症研究以外领域的重要性。这篇综述旨在通过解释噬菌体展示的基础知识及其在检测和治疗各种非癌性疾病中的应用来填补这一空白。我们特别关注它在退行性疾病中的作用,炎症和自身免疫性疾病,慢性非传染性疾病,显示它如何改变我们诊断和治疗疾病的方式。通过强调重要的发现和未来的可能性,我们希望强调噬菌体展示在现代医疗保健中的重要性。
    In recent years, phage display technology has become vital in clinical research. It helps create antibodies that can specifically bind to complex antigens, which is crucial for identifying biomarkers and improving diagnostics and treatments. However, existing reviews often overlook its importance in areas outside cancer research. This review aims to fill that gap by explaining the basics of phage display and its applications in detecting and treating various non-cancerous diseases. We focus especially on its role in degenerative diseases, inflammatory and autoimmune diseases, and chronic non-communicable diseases, showing how it is changing the way we diagnose and treat illnesses. By highlighting important discoveries and future possibilities, we hope to emphasize the significance of phage display in modern healthcare.
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  • 文章类型: Case Reports
    这篇综述全面概述了神经外科荧光成像的治疗和诊断意义。荧光成像已成为一种有价值的术中可视化和指导工具,促进精确的手术干预。检查了荧光的治疗作用,包括其在光动力治疗和肿瘤靶向治疗中的应用。它还探索了其在肿瘤检测中的诊断能力,保证金评估,和血脑屏障评估。根据临床和临床前研究,这篇综述强调了越来越多的证据支持荧光成像在神经外科实践中的有效性.此外,它讨论了当前的局限性和未来的方向,强调新兴技术增强荧光成像的实用性和可及性的潜力,最终改善神经外科患者的预后。
    This review provides a comprehensive overview of the therapeutic and diagnostic implications of fluorescence imaging in neurosurgery. Fluorescence imaging has become a valuable intraoperative visualization and guidance tool, facilitating precise surgical interventions. The therapeutic role of fluorescence is examined, including its application in photodynamic therapy and tumor-targeted therapy. It also explores its diagnostic capabilities in tumor detection, margin assessment, and blood-brain barrier evaluation. Drawing from clinical and preclinical studies, the review underscores the growing evidence supporting the efficacy of fluorescence imaging in neurosurgical practice. Furthermore, it discusses current limitations and future directions, emphasizing the potential for emerging technologies to enhance the utility and accessibility of fluorescence imaging, ultimately improving patient outcomes in neurosurgery.
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  • 文章类型: Journal Article
    单克隆抗体(mAb)已成为有效的治疗剂,彻底改变了现代医学的格局。这篇全面的综述追溯了单克隆抗体从成立到目前的突出地位的演变,突出其发展的关键里程碑,并探索其多样化的治疗应用。首先概述了它们的分子结构和作用机理,我们深入研究单克隆抗体的生产和工程,包括杂交瘤技术和重组DNA技术。各种医学学科的治疗应用,包括癌症治疗,自身免疫性疾病,和传染病,进行了详细的检查,展示了单克隆抗体的显著临床成功。此外,这篇综述讨论了制造可扩展性方面的挑战和机遇,成本效益,并获得治疗。展望未来,探讨了单克隆抗体在未来研究和临床实践中的意义,强调下一代单克隆抗体的潜力,个性化医疗,以及与免疫疗法和基因治疗等新兴模式的整合。总之,单克隆抗体的发展突显了它们对医疗保健的变革性影响,以及它们对推进医学前沿的持续承诺。
    Monoclonal antibodies (mAbs) have emerged as potent therapeutic agents, revolutionizing the landscape of modern medicine. This comprehensive review traces the evolution of mAbs from their inception to their current prominence, highlighting key milestones in their development and exploring their diverse therapeutic applications. Beginning with an overview of their molecular structure and mechanisms of action, we delve into the production and engineering of mAbs, including hybridoma technology and recombinant DNA techniques. Therapeutic applications across various medical disciplines, including cancer treatment, autoimmune diseases, and infectious diseases, are examined in detail, showcasing the significant clinical successes of mAbs. Furthermore, this review discusses the challenges and opportunities in manufacturing scalability, cost-effectiveness, and access to therapies. Looking ahead, the implications of mAbs in future research and clinical practice are explored, emphasizing the potential for next-generation mAbs, personalized medicine, and integration with emerging modalities such as immunotherapy and gene therapy. In conclusion, the evolution of monoclonal antibodies underscores their transformative impact on healthcare and their continued promise to advance the frontiers of medicine.
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  • 文章类型: Journal Article
    尽管在理解和应用基因沉默机制以及人类疾病的治疗方面取得了重大进展,在治疗应用中仍然存在一些障碍。第一次,ONPATTRO,2018年发明了第一种基于小干扰RNA(siRNA)的药物,用于治疗多发性神经病的hTTR。此外,另外四种基于siRNA的药物命名为吉沃西兰,Inclisiran,Lumasiran,迄今为止,Vutrisiran和Vutrisiran已被美国食品和药物管理局和欧洲药品管理局批准用于临床使用。在这次审查中,我们已经讨论了基于siRNA的药物在临床前和临床阶段的关键和有希望的进展,这些分子在细菌和病毒感染疾病中的影响,交付系统问题,管理方法的影响,siRNA应用的局限性以及如何克服它们以及对未来发展的一瞥。
    While significant progress has been made in understanding and applying gene silencing mechanisms and the treatment of human diseases, there have been still several obstacles in therapeutic use. For the first time, ONPATTRO, as the first small interfering RNA (siRNA) based drug was invented in 2018 for treatment of hTTR with polyneuropathy. Additionally, four other siRNA based drugs naming Givosiran, Inclisiran, Lumasiran, and Vutrisiran have been approved by the US Food and Drug Administration and the European Medicines Agency for clinical use by hitherto. In this review, we have discussed the key and promising advances in the development of siRNA-based drugs in preclinical and clinical stages, the impact of these molecules in bacterial and viral infection diseases, delivery system issues, the impact of administration methods, limitations of siRNA application and how to overcome them and a glimpse into future developments.
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  • 文章类型: Journal Article
    血细胞来源的细胞外囊泡(BCEV)和脂蛋白是血液中主要的循环纳米颗粒,在细胞间通讯中起重要作用。它们在临床应用中引起了极大的兴趣,鉴于它们的内生特性使它们稳定,生物相容性良好的耐受性,并且能够有效地渗透生物屏障。在这次审查中,我们描述了BCEVs和脂蛋白的基本特征,并总结了它们在生理和病理过程中的意义。我们还概述了这些循环纳米颗粒的分离和表征的公认工作流程。重要的是,我们重点介绍了循环纳米颗粒作为多种疾病诊断生物标志物和治疗干预措施的最新进展和挑战.我们聚焦新的工程方法和设计,通过增强它们的稳定性来促进这些纳米粒子的发展,瞄准能力,和交付效率。因此,本工作提供了组成的全面概述,生物发生,功能,以及循环纳米颗粒从工作台到床边的临床翻译。
    Blood cell-derived extracellular vesicles (BCEVs) and lipoproteins are the major circulating nanoparticles in blood that play an important role in intercellular communication. They have attracted significant interest for clinical applications, given their endogenous characteristics which make them stable, biocompatible, well tolerated, and capable of permeating biological barriers efficiently. In this review, we describe the basic characteristics of BCEVs and lipoproteins and summarize their implications in both physiological and pathological processes. We also outline well accepted workflows for the isolation and characterization of these circulating nanoparticles. Importantly, we highlight the latest progress and challenges associated with the use of circulating nanoparticles as diagnostic biomarkers and therapeutic interventions in multiple diseases. We spotlight novel engineering approaches and designs to facilitate the development of these nanoparticles by enhancing their stability, targeting capability, and delivery efficiency. Therefore, the present work provides a comprehensive overview of composition, biogenesis, functions, and clinical translation of circulating nanoparticles from the bench to the bedside.
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  • 文章类型: Journal Article
    使用siRNA靶向基因显示出有望作为缓解糖尿病性神经病变症状的方法。它专注于神经病和远端对称性多发性神经病(DSPN),以探索小干扰RNA(siRNA)作为糖尿病性神经病的治疗的潜在用途。及时识别和治疗神经病变在减轻潜在的并发症中起着至关重要的作用。RNAi的成功取决于理解影响小干扰RNA(siRNA)功能性和特异性的因素。这些包括序列空间限制,结构和序列特征,非特异性基因调节的机制,和化学修饰。解决这些因素增强了siRNA在RNAi介导的基因组研究中的有效基因沉默和信心的性能。糖尿病视网膜病变,特别是在南亚,非洲,拉丁美洲,和土著居民,是一个重要的问题,因为它与糖尿病有关。种族在其发展和进步中起着至关重要的作用。尽管美国的利率下降,全球趋势仍然令人担忧,需要进一步的研究来了解地区差异并加强基于种族的筛查和治疗方案。在这方面,siRNA成为早期干预策略的有价值的工具。在提出有希望的治疗应用的同时,siRNA的利用在昆虫害虫控制环境中遇到挑战,从而为神经病治疗目的提供增强其递送机制的见解。交付方式的最新进展,比如纳米粒子,允许控制释放的siRNA。要充分掌握siRNA技术的安全性和有效性,还需要更多的研究。通过磨练特定基因并解决炎症和氧化应激等问题,它有望改变糖尿病神经病变的治疗方法。递送技术的不断进步具有显著提高患者结果的潜力。SiRNA靶向糖尿病神经病变的基因,抑制神经损伤和疼痛,并有可能预防或延迟病情。基于遗传变异的定制治疗有望为症状管理和提高生活质量提供希望。
    Targeting genes using siRNA shows promise as an approach to alleviate symptoms of diabetic neuropathy. It focuses on neuropathies and distal symmetric polyneuropathy (DSPN) to explore the potential use of small interfering RNA (siRNA) as a treatment for diabetic neuropathy. Timely identification and management of neuropathy play a critical role in mitigating potential complications. RNAi success depends on understanding factors affecting small interfering RNA (siRNA) functionality and specificity. These include sequence space restrictions, structural and sequence features, mechanisms for nonspecific gene modulation, and chemical modifications. Addressing these factors enhances siRNA performance for efficient gene silencing and confidence in RNAi-mediated genomic studies. Diabetic retinopathy, particularly in South Asian, African, Latin American, and indigenous populations, is a significant concern due to its association with diabetes. Ethnicity plays a crucial role in its development and progression. Despite declining rates in the US, global trends remain concerning, and further research is needed to understand regional differences and reinforce ethnicity-based screening and treatment protocols. In this regard, siRNA emerges as a valuable instrument for early intervention strategies. While presenting promising therapeutic applications, siRNA utilization encounters challenges within insect pest control contexts, thereby providing insights into enhancing its delivery mechanisms for neuropathy treatment purposes. Recent advancements in delivery modalities, such as nanoparticles, allow for the controlled release of siRNA. More investigation is necessary to grasp the safety and efficacy of siRNA technology fully. It holds promise in transforming the treatment of diabetic neuropathy by honing in on particular genes and tackling issues such as inflammation and oxidative stress. Continuous advancements in delivery techniques have the potential to enhance patient results significantly. SiRNA targets genes in diabetic neuropathy, curbing nerve damage and pain and potentially preventing or delaying the condition. Customized treatments based on genetic variations hold promise for symptom management and enhancing quality of life.
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  • 文章类型: Journal Article
    本文对AchrasSapotaLinn的当代应用进行了全面分析,或者人心果,在传统医学中。热带水果AchrasSapotaLinn长期以来一直用于许多传统医疗系统。该研究考察了AchrasSapotaLinn的植物化学组成和药理学特征,重点是该植物在治疗一系列疾病中可能的医学用途。此外,它强调了AchrasSapotaLinn的安全性和有效性特征,并讨论了支持其传统应用的新研究和临床试验。本研究还讨论了AchrasSapotaLinn在当代医学中进一步研究和应用的障碍和潜在途径。考虑到所有的事情,它强调了AchrasSapotaLinn作为治疗资源对传统医学的重要性。
    This article offers a thorough analysis of the contemporary application of Achras Sapota Linn, or sapodilla, in conventional medicine. Tropical fruit-bearing Achras Sapota Linn has long been used in many traditional medical systems. The study examines Achras Sapota Linn\'s phytochemical makeup and pharmacological characteristics with an emphasis on the plant\'s possible medical uses in the treatment of a range of illnesses. Moreover, it highlights the safety and efficacy characteristics of Achras Sapota Linn and talks about new research and clinical trials that back up its traditional applications. This study also discusses obstacles and potential avenues for further research and application of Achras Sapota Linn in contemporary medicine. All things considered, it emphasizes how important Achras Sapota Linn is to traditional medicine as a therapeutic resource.
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  • 文章类型: Journal Article
    组蛋白脱乙酰酶(HDAC)是一类锌依赖性酶。它们维持乙酰化稳态,具有许多生物学功能,并与许多疾病有关。HDAC3严格需要多亚基复合物形成以获得活性。它与许多非传染性疾病的进展有关。它在疾病中的广泛参与使其成为表观遗传药物靶标。先前存在的HDAC3抑制剂有许多用途,强调需要继续研究发现HDAC3选择性抑制剂。
    这篇综述概述了2010-2023年发布的24项专利,重点是抑制HDAC3同工酶的化合物。
    HDAC3选择性抑制剂-作为单一或联合疗法的药物应用至关重要-作为摆脱充满并发症的泛HDAC抑制剂的策略,正在获得牵引力。此外,对于具有替代锌结合基团(ZBG)的HDAC3抑制剂存在未满足的需求,因为一些先前存在的ZBG具有与毒性和副作用相关的局限性.实现HDAC3选择性的困难可能是由于同种型选择性。然而,计算机辅助药物设计和HDAC33D共结晶模型的实验数据的进步可能导致发现新型HDAC3选择性抑制剂。具有对HDAC3的选择性和效力平衡的替代ZBG。
    UNASSIGNED: Histone deacetylases (HDACs) are a class of zinc-dependent enzymes. They maintain acetylation homeostasis, with numerous biological functions and are associated with many diseases. HDAC3 strictly requires multi-subunit complex formation for activity. It is associated with the progression of numerous non-communicable diseases. Its widespread involvement in diseases makes it an epigenetic drug target. Preexisting HDAC3 inhibitors have many uses, highlighting the need for continued research in the discovery of HDAC3-selective inhibitors.
    UNASSIGNED: This review provides an overview of 24 patents published from 2010 to 2023, focusing on compounds that inhibit the HDAC3 isoenzyme.
    UNASSIGNED: HDAC3-selective inhibitors - pivotal for pharmacological applications, as single or combination therapies - are gaining traction as a strategy to move away from complications laden pan-HDAC inhibitors. Moreover, there is an unmet need for HDAC3 inhibitors with alternative zinc-binding groups (ZBGs) because some preexisting ZBGs have limitations related to toxicity and side effects. Difficulties in achieving HDAC3 selectivity may be due to isoform selectivity. However, advancements in computer-aided drug design and experimental data of HDAC3 3D co-crystallized models could lead to the discovery of novel HDAC3-selective inhibitors, which bear alternative ZBGs with balanced selectivity for HDAC3 and potency.
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  • 文章类型: Journal Article
    结核病(TB),由细菌病原体结核分枝杆菌(MTB)引起,仍然是世界上最流行和致命的传染病之一。目前,结核病中宿主细胞与病原体之间存在复杂的相互作用。发作时,programming,结核病的消退不仅与MTB的毒力有关,而且与结核病患者的免疫力有关。外泌体是细胞分泌的膜结合纳米囊泡,具有包含多种生物分子的脂质双层,如代谢物,脂质,蛋白质,和核酸。外泌体介导的细胞-细胞通讯和与微环境的相互作用代表了外泌体发挥其功能作用的关键机制。外泌体在生理和病理条件下具有广泛的调节作用,包括MTB感染。外泌体可以调节免疫反应,新陈代谢,和细胞死亡重塑MTB感染的进展。在MTB感染期间,外泌体显示独特的概况和数量,可以作为诊断生物标志物,这表明外泌体提供了对MTB感染不断发展的景观的揭示。此外,来自MTB和间充质干细胞的外泌体可以用作疫苗平台和药物递送载体,用于精确靶向和治疗结核病。在这次审查中,我们重点介绍了外泌体影响结核病进展的功能和机制.此外,我们揭示了外泌体成分在结核病诊断和治疗应用中的重要意义,旨在为抗击结核病提供新的观点和策略。
    Tuberculosis (TB), caused by the bacterial pathogen Mycobacterium tuberculosis (MTB), remains one of the most prevalent and deadly infectious diseases worldwide. Currently, there are complex interactions between host cells and pathogens in TB. The onset, progression, and regression of TB are correlated not only with the virulence of MTB but also with the immunity of TB patients. Exosomes are cell-secreted membrane-bound nanovesicles with lipid bilayers that contain a variety of biomolecules, such as metabolites, lipids, proteins, and nucleic acids. Exosome-mediated cell-cell communication and interactions with the microenvironment represent crucial mechanisms through which exosomes exert their functional effects. Exosomes harbor a wide range of regulatory roles in physiological and pathological conditions, including MTB infection. Exosomes can regulate the immune response, metabolism, and cellular death to remodel the progression of MTB infection. During MTB infection, exosomes display distinctive profiles and quantities that may act as diagnostic biomarkers, suggesting that exosomes provide a revealing glimpse into the evolving landscape of MTB infections. Furthermore, exosomes derived from MTB and mesenchymal stem cells can be harnessed as vaccine platforms and drug delivery vehicles for the precise targeting and treatment of TB. In this review, we highlight the functions and mechanisms through which exosomes influence the progression of TB. Additionally, we unravel the critical significance of exosomal constituents in the diagnosis and therapeutic applications of TB, aiming to offer novel perspectives and strategies for combating TB.
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  • 文章类型: Journal Article
    背景:传统上对疑似遗传性癌症综合征的患者进行生殖系基因检测,以加强癌症监测和/或预防策略,但越来越多地用于治疗适应症。
    方法:我们对在我们中心接受种系基因检测的患者进行了回顾性研究,以确定可操作致病性种系变异(PGV)的患病率及其临床应用。
    结果:从2000年到2022年,1154名癌症患者接受了种系测试,大多数(945/1154)使用多基因面板进行了测试。41111名(35.6%)患者患有PGV,334名(81%)具有临床可行性。BRCA1/2占可操作突变的62.3%,其次是错配修复(18%),和其他同源重组修复(HRR)基因(19.7%)。一百五十二名种系阳性患者患有晚期癌症,79例接受了种系定向治疗(聚ADP核糖聚合酶抑制剂=75;免疫疗法=4).免疫治疗和多聚ADP核糖聚合酶的中位持续时间为20.5个月(范围5-40个月)和8个月(范围1-76个月),分别。在接受铂类化疗的BRCA/HRR突变携带者中,新辅助治疗组的病理完全缓解率为53%(n=17例乳腺癌),晚期治疗组的客观缓解率>80%(n=71).
    结论:接受测试的癌症患者中有三分之一携带PGV,约80%具有临床可行性。在现实世界中,四分之三的种系阳性晚期癌症患者接受了种系指导的治疗,强调种系测试在指导癌症治疗方面的实用性。
    BACKGROUND: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications.
    METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility.
    RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71).
    CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.
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