therapeutic applications

治疗应用
  • 文章类型: Journal Article
    我们对间充质干细胞(MSCs)及其生物学特性的了解正在稳步增长,随着越来越多的研究关注它们在免疫学领域的治疗效果,组织工程和再生医学。MSCs可能来自组织如骨髓,脂肪,脐带,以及来自牙齿组织(例如,牙胚,牙囊,脱落的乳牙和恒牙的牙髓组织,顶端乳头,牙周膜,牙龈,和牙槽骨)。牙龈间充质干细胞(GMSC)是从牙龈固有层分离的非造血成体干细胞。当与从各种牙齿和非牙齿组织纯化的MSC相比时,GMSCs来源更丰富,相对非侵入性获得,基因稳定。近年来,许多研究发现GMSCs具有自我更新的能力,多方向分化,和趋化性到炎症部位进行免疫调节。它们的分子和干细胞特性使它们非常适合临床前和临床研究。由GMSC分泌的细胞外囊泡(EV)由于其模拟GMSC自身的生物学和治疗活性的能力而具有关键兴趣。因此,本文将回顾目前关于GMSC的共识,调查它们的来源和隔离方法,它们的生物学特性,以及它们在炎症和免疫相关疾病中的治疗应用。
    Our understanding of mesenchymal stem cells (MSCs) and their biological properties is steadily increasing, with more studies focusing on their therapeutic effects in the domains of immunology, tissue engineering and regenerative medicine. MSCs may be derived from tissues such as bone marrow, adipose, the umbilical cord, as well as from dental tissues (e.g., tooth germ, dental follicle, pulp tissue of exfoliated deciduous and permanent teeth, apical papilla, periodontal ligament, gingiva, and alveolar bone). Gingival mesenchymal stem cells (GMSCs) are non-hematopoietic adult stem cells isolated from the gingival lamina propria. When compared to MSCs purified from various dental and non-dental tissues, GMSCs are more abundant in source, relatively non-invasive to obtain, and genetically stable. In recent years, many studies have found that GMSCs possess the ability of self-renewal, multi-directional differentiation, and chemotaxis to inflammatory sites for immunity regulation. Their molecular and stem-cell properties make them highly suitable for both preclinical and clinical research. Extracellular vesicles (EVs) secreted by GMSCs are of key interest due to their ability to emulate the biological and therapeutic activity of GMSCs themselves. This paper will therefore review the current consensus on GMSCs, surveying their sources and isolation methods, their biological properties, and their therapeutic applications on inflammatory and immune-related diseases.
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  • 文章类型: Journal Article
    植物正在被研究作为新药的潜在来源,这导致了最近加速发现新的生物活性化合物。植物化合物合成和加工的组织培养技术的研究迅速发展,超越所有的期望。这些植物可以买到原料或提取物,一些化学物质是通过将植物在水中捣碎来提取的,酒精,或另一种溶剂。草药的使用可能为减少感染的发作和治疗包括癌症在内的不同疾病开辟新的机会。一种在冬天开花的多年生植物,仙客来,是许多国家使用最广泛的盆栽花卉之一。生物碱,黄酮类化合物,酚类物质,单宁,皂苷,固醇,和糖苷是仙客来的主要活性成分。镇痛,细胞毒性,抗氧化剂,抗菌,和抗炎特性都已被证明是仙客来块茎的各种提取物的潜在作用。然而,在官方医学中使用这种药用植物将需要在药理学领域进行进一步研究。此外,有必要为原始草药创建标准的操作程序。在这方面,这篇综述旨在强调仙客来植物的关键特性,比如它的各个部分,物种,发展阶段,和地理范围;查明其有趣的生物活动,它的抗氧化剂,抗炎,及其抗癌作用;并确定其潜在的医疗用途和主要的未来前景。
    Plants are being researched as potential sources of novel drugs, which has led to a recent acceleration in the discovery of new bioactive compounds. Research on tissue culture technology for the synthesis and processing of plant compounds has skyrocketed, surpassing all expectations. These plants can be bought either raw or as extracts, where some of the chemicals are extracted by mashing the plant in water, alcohol, or another solvent. The use of herbal medicine may open new chances for reducing the onset of infections and treating different diseases including cancer. A perennial plant that blooms in the winter, Cyclamen, is one of the most widely used potted flowers in many nations. Alkaloids, flavonoids, phenols, tannins, saponins, sterols, and glycosides are the main active components of Cyclamen. Analgesic, cytotoxic, antioxidant, antimicrobial, and anti-inflammatory properties have all been demonstrated as potential effects of various extracts of Cyclamen tubers. However, the use of this medicinal plant in official medicine will require further research in the areas of pharmacology. Furthermore, it is necessary to create standard operating procedures for a crude herbal medication. In this regard, this review aims to highlight the key characteristics of the Cyclamen plant, such as its various parts, species, stages of development, and geographic range; pinpoint its intriguing bioactivities, its antioxidant, anti-inflammatory, and its anti-cancerous effects; and ascertain its potential medicinal uses and the main future perspectives.
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  • 文章类型: Journal Article
    基因组编辑是一种在细胞或生物体的DNA中进行特定改变的技术。它极大地改变了生命科学的格局,促进建立极其定制的遗传修饰。在各种基因组编辑技术中,CRISPR/Cas9系统,特定的核酸内切酶诱导双链DNA断裂,并能够对基因组进行修饰,已经成为一种强大而适应性强的工具。它的重要性怎么强调都不为过,因为它不仅允许在模型生物中操纵基因组,而且在医学上具有革命性进步的巨大潜力,特别是在治疗遗传疾病方面。这篇综述论文探讨了CRISPR/Cas9的非凡旅程,它的自然功能,机制,以及对基因组编辑的变革性影响,最后是人工智能和其他智能制造工具的使用。引言提供了基因组编辑的背景,强调CRISPR/Cas9的出现和意义。随后的章节全面阐述了它的自然功能,疾病建模,农业,和生物技术,解决治疗应用,和正在进行的临床试验,同时还讨论前景和伦理影响。我们总结了主要发现,这表明CRISPR/Cas9增强了疾病特异性动物模型的创建能力。这为致病机制提供了宝贵的见解,并为药物发现开辟了新途径,重申CRISPR/Cas9对基因组编辑的变革性影响。最后,我们讨论了继续研究和合作的重要性,以综合利用这种分子精密工具在塑造即将到来的进步中的固有能力。
    Genome editing is a technology to make specific changes in the DNA of a cell or an organism. It has significantly altered the landscape of life sciences, facilitating the establishment of exceedingly customized genetic modifications. Among various genome editing technologies, the CRISPR/Cas9 system, a specific endonuclease induces a double stranded DNA break and enabling modifications to the genome, has surfaced as a formidable and adaptable instrument. Its significance cannot be overstated, as it not only allows for the manipulation of genomes in model organisms but also holds great potential for revolutionary advances in medicine, particularly in treating genetic diseases. This review paper explores the remarkable journey of CRISPR/Cas9, its natural function, mechanisms, and transformative impact on genome editing and finally the use of artificial intelligence and other intelligent manufacturing tools used. The introduction provides the background on genome editing, emphasizing the emergence and significance of CRISPR/Cas9. Subsequent sections comprehensively elucidate its natural function, disease modeling, agriculture, and biotechnology, address therapeutic applications, and ongoing clinical trials while also discussing prospects and ethical implications. We summarized the key findings, indicating that CRISPR/Cas9 has empowered the creation of disease-specific animal models. This provides invaluable insights into pathogenic mechanisms and opens new avenues for drug discovery, reaffirming the transformative impact of CRISPR/Cas9 on genome editing. Finally we discussed the importance of continued research and collaboration for comprehensive utilization of the inherent capabilities of this molecular precision tool in shaping forthcoming advancements.
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  • 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
    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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