therapeutics

治疗学
  • 文章类型: Journal Article
    外泌体是所有细胞类型分泌的最小的细胞外囊泡(30-150nm),包括滑液.然而,因为生物液体很复杂,异质,含有污染物,他们的隔离是困难和耗时的。此外,骨关节炎(OA)的病理生理学涉及携带复杂成分的外泌体,这些成分导致巨噬细胞释放趋化因子和促炎细胞因子。这篇叙述性综述旨在为外泌体生物学提供深入的见解,隔离技术,在OA病理生理学中的作用,以及在未来OA治疗中的潜在作用。
    使用PubMed进行了文献检索,Scopus,和WebofScience数据库,用于使用关键词“外泌体”和“骨关节炎”进行骨关节炎外泌体研究。包括过去15年中涉及人类和动物模型的相关文章。其他炎症性疾病中涉及外泌体的研究被排除。
    尽管取得了一些进展,分离外泌体的常规技术仍然是费力和困难的,需要复杂和耗时的程序在各种体液和样品来源。此外,外泌体参与与OA相关的各种生理过程,像软骨钙化,骨关节炎关节的退化,和炎症。
    实现标准化的过程,一体化,和高吞吐量的外泌体隔离设备是具有挑战性和耗时的。各种方法的整合可以通过利用它们的互补利益来有效地解决具体问题。外泌体具有有效修复受损软骨OA的潜力,减少炎症,维持软骨基质的形成和分解之间的平衡,因此显示出有望作为OA的治疗选择。
    UNASSIGNED: Exosomes are the smallest extracellular vesicles (30-150 nm) secreted by all cell types, including synovial fluid. However, because biological fluids are complex, heterogeneous, and contain contaminants, their isolation is difficult and time-consuming. Furthermore, the pathophysiology of osteoarthritis (OA) involves exosomes carrying complex components that cause macrophages to release chemokines and proinflammatory cytokines. This narrative review aims to provide in-depth insights into exosome biology, isolation techniques, role in OA pathophysiology, and potential role in future OA therapeutics.
    UNASSIGNED: A literature search was conducted using PubMed, Scopus, and Web of Science databases for studies involving exosomes in the osteoarthritis using keywords \"Exosomes\" and \"Osteoarthritis\". Relevant articles in the last 15 years involving both human and animal models were included. Studies involving exosomes in other inflammatory diseases were excluded.
    UNASSIGNED: Despite some progress, conventional techniques for isolating exosomes remain laborious and difficult, requiring intricate and time-consuming procedures across various body fluids and sample origins. Moreover, exosomes are involved in various physiological processes associated with OA, like cartilage calcification, degradation of osteoarthritic joints, and inflammation.
    UNASSIGNED: The process of achieving standardization, integration, and high throughput of exosome isolation equipment is challenging and time-consuming. The integration of various methodologies can be employed to effectively address specific issues by leveraging their complementary benefits. Exosomes have the potential to effectively repair damaged cartilage OA, reduce inflammation, and maintain a balance between the formation and breakdown of cartilage matrix, therefore showing promise as a therapeutic option for OA.
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  • 文章类型: Journal Article
    颞下颌关节紊乱病包括影响咀嚼系统的各种病症,影响它的结构,函数,或生理学。临床医生在治疗这类疾病时面临着一系列复杂的治疗选择,强调评估当前证据以指导患者护理决策的重要性。本文的主要目的是对治疗颞下颌关节紊乱病(TMDs)的可用治疗方法进行范围审查。在Scopus上进行了广泛的文献搜索,Pubmed,Embase,和WebofScience。考虑了过去5年发表的系统评价。在确定的2183种出版物中,109项研究纳入本综述。其中,39篇文章聚焦于非侵入性方法,当120人深入研究微创方法时,15探索了手术方法。非侵入性或保守的方法,如认知行为疗法,物理治疗,和针灸提供有效的疼痛管理和TMD的功能改善。新兴的治疗方法为治疗这些疾病提供了有希望的替代方案。手术应保留用于严重病例,保守疗法与侵入性手术结合使用,以获得最佳患者预后。
    Temporomandibular disorders include various conditions that impact the masticatory system, affecting its structure, function, or physiology. Clinicians face a complex array of therapeutic options when treating this group of diseases, emphasizing the importance of evaluating the current evidence to guide decisions in patient care. The main objective of this article is to conduct a scoping review on the available treatment approaches to manage temporomandibular disorders (TMDs). An extensive search of the literature was performed on Scopus, Pubmed, Embase, and Web of Science. Systematic reviews published in the last 5 years were considered. Out of the 2183 publications identified, 109 studies were included in this review. Among them, 39 articles focused on the non-invasive approach, while 120 delved into the minimally invasive approach, and 15 explored the surgical approach. Non-invasive or conservative approaches like cognitive-behavioral therapy, physical therapy, and acupuncture offer effective pain management and functional improvements in TMDs. Emerging treatments offer promising alternatives for treating these disorders. Surgery should be reserved for severe cases, with conservative therapies used in conjunction with invasive procedures for optimal patient outcomes.
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  • 文章类型: Journal Article
    多形性胶质母细胞瘤(GBM)是一种高度侵袭性和不可治愈的疾病,在美国每年约有10,000例死亡。尽管目前的治疗方法包括化疗和放疗,复发率仍然很高。在同时接受抗高血压药物如肾素血管紧张素抑制剂(RAS)或抗糖尿病药物二甲双胍标准治疗的患者中观察到显著的改善。在体外和体内研究中已经观察到RAS抑制剂和二甲双胍的抗肿瘤作用。尽管临床试验显示结果好坏参半,RAS抑制剂和二甲双胍作为GBM辅助治疗的潜力仍然很有希望.然而,有证据表明,这些药物发挥多模式抗肿瘤作用;特别是针对几种癌症标志。在这次审查中,我们重点介绍了GBM标准治疗中使用含有RAS抑制剂和/或二甲双胍的多药混合物的临床研究结果.此外,我们强调了这些具有优异安全性的再利用药物可能引发抗肿瘤作用的分子机制.RAS抑制引起抗炎,抗血管生成,和GBM中的免疫敏感性效应。然而,二甲双胍促进抗迁徙,抗增殖和促凋亡作用主要通过激活AMP激活的蛋白激酶。此外,我们讨论了二甲双胍靶向GBM细胞和GBM相关干细胞的潜力。最后,我们总结了一些可能引起累加或拮抗作用的药物相互作用,这些作用可能导致不良反应并影响治疗结果.
    Glioblastoma multiforme (GBM) is a highly aggressive and incurable disease accounting for about 10,000 deaths in the USA each year. Despite the current treatment approach which includes surgery with chemotherapy and radiation therapy, there remains a high prevalence of recurrence. Notable improvements have been observed in persons receiving concurrent antihypertensive drugs such as renin angiotensin inhibitors (RAS) or the antidiabetic drug metformin with standard therapy. Anti-tumoral effects of RAS inhibitors and metformin have been observed in in vitro and in vivo studies. Although clinical trials have shown mixed results, the potential for the use of RAS inhibitors and metformin as adjuvant GBM therapy remains promising. Nevertheless, evidence suggest that these drugs exert multimodal antitumor actions; by particularly targeting several cancer hallmarks. In this review, we highlight the results of clinical studies using multidrug cocktails containing RAS inhibitors and or metformin added to standard therapy for GBM. In addition, we highlight the possible molecular mechanisms by which these repurposed drugs with an excellent safety profile might elicit their anti-tumoral effects. RAS inhibition elicits anti-inflammatory, anti-angiogenic, and immune sensitivity effects in GBM. However, metformin promotes anti-migratory, anti-proliferative and pro-apoptotic effects mainly through the activation of AMP-activated protein kinase. Also, we discussed metformin\'s potential in targeting both GBM cells as well as GBM associated-stem cells. Finally, we summarize a few drug interactions that may cause an additive or antagonistic effect that may lead to adverse effects and influence treatment outcome.
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  • 文章类型: Journal Article
    对自然疗法的日益偏好导致药用植物的使用增加。最重要和最多样化的植物之一是水芹(Lepidiumsativum),含有高浓度的蛋白质,脂肪酸,矿物,和维生素。它还含有广泛的生物活性成分,包括山奈酚葡糖苷酸,没食子酸,原儿茶酸,香豆酸,咖啡酸,萜烯,芥子油苷,还有更多。这些物质,其中包括抗氧化剂,产热,去净化,眼科,反蝎子,抗贫血,利尿剂,补品,泻药,半乳糖,壮阳药,rubefacient,和emmengogue品质,增加花园水芹的药用和功能潜力。本综述的主要目标是广泛总结水芹种子的植物化学特征和生物活性。研究表明,水芹是世界上利用最少的作物之一,即使具有营养和功能特征。因此,这篇综述的目的是强调Lepidiumsativum的化学和营养组成,同时特别注意其生物活性特征,各种健康声明,治疗益处,和工业应用。
    The growing preference for natural remedies has resulted in increased use of medicinal plants. One of the most significant and varied plants is garden cress (Lepidium sativum), which has large concentrations of proteins, fatty acids, minerals, and vitamins. It also contains a wide range of bioactive components, including kaempferol glucuronide, gallic acid, protocatechuic acid, coumaric acid, caffeic acid, terpenes, glucosinolates, and many more. These substances, which include antioxidant, thermogenic, depurative, ophthalmic, antiscorbutic, antianemic, diuretic, tonic, laxative, galactogogue, aphrodisiac, rubefacient, and emmengogue qualities, add to the medicinal and functional potential of garden cress. An extensive summary of the phytochemical profile and biological activity of garden cress seeds is the main goal of this review. Research showed that garden cress is one of the world\'s most underutilized crops, even with its nutritional and functional profile. Consequently, the goal of this review is to highlight the chemical and nutritional makeup of Lepidium sativum while paying particular attention to its bioactive profile, various health claims, therapeutic benefits, and industrial applications.
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  • 文章类型: Journal Article
    免疫性血小板减少症(ITP)是一种自身免疫性出血性疾病,其特征是网状内皮血小板过度破坏和代偿性血小板产生不足。然而,ITP的发病机制相对复杂,其确切机制和病因尚未明确确定。肠道微生物组,即居住在胃肠系统中的共生微生物的多样化群落,通过参与人体新陈代谢影响健康,免疫调节,保持生理平衡.新的证据表明,与健康个体相比,ITP患者的肠道微生物组组成不同,这与血小板计数有关,疾病持续时间,以及对治疗的反应。这些发现表明,个体的微生物组和代谢组特征可以揭示一种新的辅助诊断途径,预测预后,评估治疗反应,并制定针对ITP的个性化治疗方法。然而,由于有争议的报道,无法得出明确的结论,需要进一步调查。
    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by excessive reticuloendothelial platelet destruction and inadequate compensatory platelet production. However, the pathogenesis of ITP is relatively complex, and its exact mechanisms and etiology have not been definitively established. The gut microbiome, namely a diverse community of symbiotic microorganisms residing in the gastrointestinal system, affects health through involvement in human metabolism, immune modulation, and maintaining physiological balance. Emerging evidence reveals that the gut microbiome composition differs in patients with ITP compared to healthy individuals, which is related with platelet count, disease duration, and response to treatment. These findings suggest that the microbiome and metabolome profiles of individuals could unveil a new pathway for aiding diagnosis, predicting prognosis, assessing treatment response, and formulating personalized therapeutic approaches for ITP. However, due to controversial reports, definitive conclusions cannot be drawn, and further investigations are needed.
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  • 文章类型: Journal Article
    背景:关于感染危险因素的证据很少,和感染部位的精确定位及其治疗在临床上仍然具有挑战性。
    目的:本研究旨在为接受左心室辅助装置植入的成年患者提供建议。
    方法:这是一个范围审查,在DOI10.17605/OSF下的开放科学框架中注册。IO/Q76B3(https://osf.io/q76b3/)。
    方法:这是一项范围界定审查,仅限于2015年至2022年之间。本范围审查的结果在3篇文章中分别进行了讨论和介绍。第二篇论文综合了风险因素的研究证据,成人左心室辅助装置植入患者感染的诊断方法和治疗。
    结果:最初的搜索确定了771项研究。69名患者符合资格标准,并被纳入范围审查。关于风险因素的43篇文章,包括感染的诊断和治疗以回答本综述的问题。
    结论:肥胖已被证明是左心室辅助装置感染过程中最常见的危险因素。和标记的白细胞或柠檬酸镓-67闪烁显像显示对左心室辅助装置感染的高度特异性;因此,它可以帮助区分感染和炎症,特别是在不明确的氟脱氧葡萄糖正电子发射断层扫描的患者中。此外,这篇综述带来并讨论了诊断测试的局限性和优势,了解左心室辅助装置感染的危险因素,治疗异质性,研究的方法论问题,以及未来左心室辅助装置研究的广阔机会。
    结论:心室辅助装置专业人员应在装置植入前和定期评估危险因素。18F-氟代脱氧葡萄糖正电子发射断层扫描应被视为检测浅层和深层传动系统感染的诊断工具。早期治疗,包括慢性抑制疗法和连续手术清创术,结合传动系外置和延迟的传动系重新定位可能构成了深层传动系感染的潜在治疗策略.
    BACKGROUND: Evidence on infection risk factors is scarce, and precise localization of the site of infection and its treatment remain clinically challenging.
    OBJECTIVE: This study aimed to map the recommendations for adult patients undergoing left ventricular assist device implantation.
    METHODS: This is a scoping review, registered in the Open Science Framework under DOI10.17605/OSF.IO/Q76B3(https://osf.io/q76b3/).
    METHODS: This is a scoping review limited to the period between 2015 and 2022.The results of this scoping review are discussed and presented separately in 3 articles. This second paper synthesizes research evidence on the risk factors, diagnostic methods and treatment of infection in adult patients undergoing left ventricular assist device implantation.
    RESULTS: The initial searches identified 771 studies. Sixty-nine patients met the eligibility criteria and were included in the scoping review. Forty-three articles addressing the risk factors, diagnosis and treatment of infection were included to answer the questions of this review.
    CONCLUSIONS: Obesity has been shown to be the most common risk factor for the described process of infection by left ventricular assist devices.18F-fluorodeoxyglucose positron emission tomography showed high sensitivity in detecting cardiac device infection, and labeled leukocyte or gallium citrate-67 scintigraphy showed high specificity for left ventricular assist device infections; therefore, it can help differentiate infection from inflammation, particularly in patients with equivocal fluorodeoxyglucose positron emission tomography. Also, this review brings and discusses the limitations and strengths of diagnostic tests, the knowledge regarding the risk factors for left ventricular assist device infection, the therapeutic heterogeneity, the methodological issues of the studies, and the vast opportunity for future research on left ventricular assist device.
    CONCLUSIONS: Ventricular assist device professionals should evaluate risk factors prior to device implantation and periodically.18F-fluorodeoxyglucose positron emission tomography should be considered as diagnostic tool in detecting superficial and deep driveline infections. Early treatment, including chronic suppressive therapy and serial surgical debridement, combined with driveline exteriorization and delayed driveline relocation may constitute a potential therapeutic strategy for deep driveline infections.
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  • 文章类型: Journal Article
    受体酪氨酸激酶(RTK)是具有激酶活性的细胞表面受体,在多种细胞过程中起着至关重要的作用。在RTK家族成员中,人表皮生长因子受体2(HER2)和HER3与乳腺癌特别相关。这篇综述深入研究了受体酪氨酸激酶相互作用的复杂性,抵抗机制,以及抗HER3药物的潜力,为这一研究领域的临床意义和未来方向提供有价值的见解。它评估了抗HER3药物的潜力,如帕妥珠单抗,克服在HER2阳性乳腺癌治疗中观察到的耐药性。该综述还探讨了与各种药物相关的耐药机制,包括曲妥珠单抗,拉帕替尼,和PI3K抑制剂,提供有关抗性发展的复杂分子过程的见解。该综述最后强调了进一步临床试验的必要性,以评估HER3抑制剂的疗效,以及开发安全有效的抗HER3治疗以改善HER2阳性乳腺癌患者治疗结果的潜力。
    Receptor tyrosine kinases (RTKs) are cell surface receptors with kinase activity that play a crucial role in diverse cellular processes. Among the RTK family members, Human epidermal growth factor receptor 2 (HER2) and HER3 are particularly relevant to breast cancer. The review delves into the complexities of receptor tyrosine kinase interactions, resistance mechanisms, and the potential of anti-HER3 drugs, offering valuable insights into the clinical implications and future directions in this field of study. It assesses the potential of anti-HER3 drugs, such as pertuzumab, in overcoming resistance observed in HER2-positive breast cancer therapies. The review also explores the resistance mechanisms associated with various drugs, including trastuzumab, lapatinib, and PI3K inhibitors, providing insights into the intricate molecular processes underlying resistance development. The review concludes by emphasizing the necessity for further clinical trials to assess the efficacy of HER3 inhibitors and the potential of developing safe and effective anti-HER3 treatments to improve treatment outcomes for patients with HER2-positive breast cancer.
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  • 文章类型: Journal Article
    神经科学界基本上接受了这样的观点,即成人大脑中的神经干细胞可以产生功能性神经元,尤其是在两个大脑区域:侧脑室的脑室下区和海马齿状回的颗粒下区。然而,在一些神经退行性疾病中观察到受损的神经发生,特别是在阿尔茨海默氏症中,帕金森,和亨廷顿病,还有路易体痴呆症。因此,神经退行性疾病中神经源性功能的恢复是一种潜在的治疗策略,或者至少是延迟,疾病进展。考虑到这一点,本研究总结了不同的神经元生态位,在临床前和临床研究中提供了不同的前神经源策略的治疗潜力的集合,提供他们可能的行动方式的细节,指导未来的研究和临床实践。
    The neuroscience community has largely accepted the notion that functional neurons can be generated from neural stem cells in the adult brain, especially in two brain regions: the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus. However, impaired neurogenesis has been observed in some neurodegenerative diseases, particularly in Alzheimer\'s, Parkinson\'s, and Huntington\'s diseases, and also in Lewy Body dementia. Therefore, restoration of neurogenic function in neurodegenerative diseases emerges as a potential therapeutic strategy to counteract, or at least delay, disease progression. Considering this, the present study summarizes the different neuronal niches, provides a collection of the therapeutic potential of different pro-neurogenic strategies in pre-clinical and clinical research, providing details about their possible modes of action, to guide future research and clinical practice.
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  • 文章类型: Journal Article
    口腔癌(OC)是世界上最常见的恶性肿瘤之一。尽管治疗取得了进展,OC的最坏情况仍然是转移,有50%的存活率。因此,了解该病的病理生理学并制定OC的诊断和治疗计划至关重要。高通量基因组测序的发展表明,超过90%的人类基因组编码非编码转录本,或不编码任何蛋白质的转录本。本文描述了这些不同类型的非编码RNA(ncRNA)在OC中的功能以及它们有趣的治疗潜力。OC的产生和发展,以及治疗抗性,与ncRNA表达失调相关。这些ncRNAs在诊断和预后中的潜在重要作用已经通过它们在血液或唾液中的不同表达来提示。在这项研究中,我们概述了ncRNAs在治疗OC中的每一个有希望的特征。
    Oral cancer (OC) is among the most common malignancies in the world. Despite advances in therapy, the worst-case scenario for OC remains metastasis, with a 50% survival rate. Therefore, it is critical to comprehend the pathophysiology of the condition and to create diagnostic and treatment plans for OC. The development of high-throughput genome sequencing has revealed that over 90% of the human genome encodes non-coding transcripts, or transcripts that do not code for any proteins. This paper describes the function of these different kinds of non-coding RNAs (ncRNAs) in OC as well as their intriguing therapeutic potential. The onset and development of OC, as well as treatment resistance, are linked to dysregulated ncRNA expression. These ncRNAs\' potentially significant roles in diagnosis and prognosis have been suggested by their differing expression in blood or saliva. We have outlined every promising feature of ncRNAs in the treatment of OC in this study.
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  • 文章类型: Journal Article
    目的:前列腺癌(PCa)的主要确定性治疗后生化复发(BCR)是一种异质性疾病状态。虽然BCR与更糟糕的肿瘤学结果相关,影响结果的风险因素可能差异很大,风险分层的必要途径。我们试图确定原发性前列腺癌根治术或放疗后复发时的预后危险因素。在抢救治疗之前,与不良肿瘤学结果相关。
    方法:我们对EMBASE的前瞻性研究进行了系统评价,MEDLINE,和ClinicalTrials.gov(从2000年1月1日至2023年10月16日)根据系统审查和荟萃分析指南(CRD42023466330)的首选报告项目。我们回顾了主要确定性治疗后BCR患者与肿瘤预后相关的因素。
    共纳入37项研究(总n=10.632),前列腺切除术后25例(总n=9010)和放疗后12例(总n=1622)。前列腺切除术后复发,与不良结局相关的因素包括较高的病理T分期和分级组,阴性手术切缘,更短的前列腺特异性抗原倍增时间(PSADT),抢救治疗前前列腺特异性抗原(PSA)较高,复发时间更短,22个基因的肿瘤RNA签名,和分子成像上的复发位置。放疗后复发,与不良结局相关的因素包括较短的复发时间,和较短的PSADT或较高的PSA速度。年级组,T级,先前的短期激素治疗(4-6个月)与不良结局无明显关联,尽管与前列腺切除术后数据相比,样本量和随访通常有限。
    结论:这项工作强调了对PCa复发患者进行风险分层的建议和证据水平,并可作为基于预测的个性化救助处理的基准。
    结果:我们总结了先前报道的临床试验的数据,主题是哪些因素预测前列腺癌患者在初次治疗后复发的癌症预后较差。
    OBJECTIVE: Biochemical recurrence (BCR) after primary definitive treatment for prostate cancer (PCa) is a heterogeneous disease state. While BCR is associated with worse oncologic outcomes, risk factors that impact outcomes can vary significantly, necessitating avenues for risk stratification. We sought to identify prognostic risk factors at the time of recurrence after primary radical prostatectomy or radiotherapy, and prior to salvage treatment(s), associated with adverse oncologic outcomes.
    METHODS: We performed a systematic review of prospective studies in EMBASE, MEDLINE, and ClinicalTrials.gov (from January 1, 2000 to October 16, 2023) according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (CRD42023466330). We reviewed the factors associated with oncologic outcomes among patients with BCR after primary definitive treatment.
    UNASSIGNED: A total of 37 studies were included (total n = 10 632), 25 after prostatectomy (total n = 9010) and 12 after radiotherapy (total n = 1622). Following recurrence after prostatectomy, factors associated with adverse outcomes include higher pathologic T stage and grade group, negative surgical margins, shorter prostate-specific antigen doubling time (PSADT), higher prostate-specific antigen (PSA) prior to salvage treatment, shorter time to recurrence, the 22-gene tumor RNA signature, and recurrence location on molecular imaging. After recurrence following radiotherapy, factors associated with adverse outcomes include a shorter time to recurrence, and shorter PSADT or higher PSA velocity. Grade group, T stage, and prior short-term hormone therapy (4-6 mo) were not clearly associated with adverse outcomes, although sample size and follow-up were generally limited compared with postprostatectomy data.
    CONCLUSIONS: This work highlights the recommendations and level of evidence for risk stratifying patients with PCa recurrence, and can be used as a benchmark for personalizing salvage treatment based on prognostics.
    RESULTS: We summarize the data from previously reported clinical trials on the topic of which factors predict worse cancer outcomes for patients who recur with prostate cancer after their initial treatment.
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