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Mitochondrial dysfunction at the cornerstone of inflammatory exacerbation in aged macrophages 线粒体功能障碍是老年巨噬细胞炎症加重的基础
Pub Date : 2023-10-11 DOI: 10.37349/ei.2023.00112
Rafael Moura Maurmann, Brenda Landvoigt Schmitt, Negin Mosalmanzadeh, Brandt D. Pence
Immunosenescence encompasses multiple age-related adaptations that result in increased susceptibility to infections, chronic inflammatory disorders, and higher mortality risk. Macrophages are key innate cells implicated in inflammatory responses and tissue homeostasis, functions progressively compromised by aging. This process coincides with declining mitochondrial physiology, whose integrity is required to sustain and orchestrate immune responses. Indeed, multiple insults observed in aged macrophages have been implied as drivers of mitochondrial dysfunction, but how this translates into impaired immune function remains sparsely explored. This review provides a perspective on recent studies elucidating the underlying mechanisms linking dysregulated mitochondria homeostasis to immune function in aged macrophages. Genomic stress alongside defective mitochondrial turnover accounted for the progressive accumulation of damaged mitochondria in aged macrophages, thus resulting in a higher susceptibility to excessive mitochondrial DNA (mtDNA) leakage and reactive oxygen species (ROS) production. Increased levels of these mitochondrial products following infection were demonstrated to contribute to exacerbated inflammatory responses mediated by overstimulation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and cyclic GMP-ATP synthase (cGAS)-stimulator of interferon genes (STING) pathways. While these mechanisms are not fully elucidated, the present evidence provides a promising area to be explored and a renewed perspective of potential therapeutic targets for immunological dysfunction.
免疫衰老包括多种与年龄相关的适应,导致对感染、慢性炎症性疾病的易感性增加和死亡风险增加。巨噬细胞是参与炎症反应和组织稳态的关键先天细胞,其功能随着年龄的增长而逐渐受损。这一过程与线粒体生理机能的衰退相吻合,线粒体的完整性是维持和协调免疫反应所必需的。事实上,在衰老巨噬细胞中观察到的多重损伤已被暗示为线粒体功能障碍的驱动因素,但这如何转化为免疫功能受损仍未得到充分探讨。本文综述了近年来有关衰老巨噬细胞线粒体稳态失调与免疫功能联系机制的研究进展。基因组应激和线粒体转换缺陷导致衰老巨噬细胞中受损线粒体的逐渐积累,从而导致线粒体DNA (mtDNA)过度泄漏和活性氧(ROS)产生的易感性更高。研究表明,感染后这些线粒体产物水平的升高有助于炎症反应的加剧,炎症反应是由含有3 (NLRP3)炎症小体的nod样受体家族pyrin结构域和环GMP-ATP合成酶(cGAS)-干扰素基因刺激因子(STING)途径的过度刺激介导的。虽然这些机制尚未完全阐明,但目前的证据提供了一个有希望的探索领域,并为免疫功能障碍的潜在治疗靶点提供了新的视角。
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引用次数: 0
Effect of coronavirus disease 2019 on the vaccine development paradigm 2019冠状病毒病对疫苗开发模式的影响
Pub Date : 2023-10-10 DOI: 10.37349/ei.2023.00111
Sezer Okay
Vaccines are prophylactic medical products effectively used against infectious diseases. Although a high amount of vaccine studies are conducted at the preclinical stage, the number of approved vaccines is less than 10%. Development of vaccines from the research stage to the approval of administrative institutions takes about 5 years to 10 years conventionally. However, this period of time for vaccine development is not convenient during public health emergencies because an effective vaccine is required in a short time to restrict the speed of high mortality and morbidity. The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had its catastrophic effects worldwide quickly. Therefore, an atypical process was followed for the development of COVID-19 vaccines. Great effort was spent in terms of cooperation among the governmental institutions, academia, and medical companies as well as a high amount of budget was allocated to develop effective vaccines against COVID-19. As of March 2023, the numbers of COVID-19 vaccines in clinical and preclinical development were 183 and 199, respectively. An emergency use authorization (EUA) process was applied to accelerate the approval of the vaccines. Consequently, vaccinations could be started in less than a year, which decelerated the speed of the pandemic. Although EUA caused hesitancy among some people questioning the safety and efficacy of the vaccines, the vast majority of the population was vaccinated. Currently, more than 5.5 billion people (about 70% of the world population) have received 13.38 billion doses of 11 different COVID-19 vaccines, and 73% of the doses were Comirnaty manufactured by Pfizer/BioNTech.
疫苗是有效预防传染病的预防性医疗产品。虽然在临床前阶段进行了大量的疫苗研究,但批准的疫苗数量不到10%。疫苗的开发从研究阶段到行政机构的批准通常需要5到10年的时间。然而,在突发公共卫生事件期间,这段疫苗开发时间并不方便,因为需要在短时间内开发出有效的疫苗,以限制高死亡率和发病率的速度。由严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起的2019冠状病毒病(COVID-19)大流行迅速在全球造成了灾难性影响。因此,COVID-19疫苗的开发遵循了一个非典型过程。为了开发有效的疫苗,政府机构、学术界、医疗企业之间的合作付出了巨大的努力,并投入了大量预算。截至2023年3月,临床和临床前开发的COVID-19疫苗数量分别为183个和199个。实施了紧急使用授权(EUA)程序,以加快疫苗的批准。因此,疫苗接种可以在不到一年的时间内开始,从而减缓了大流行的速度。虽然EUA引起了一些人对疫苗的安全性和有效性的质疑,但绝大多数人都接种了疫苗。目前,超过55亿人(约占世界人口的70%)接种了11种不同的COVID-19疫苗133.8亿剂,其中73%的剂量是辉瑞/BioNTech公司生产的Comirnaty疫苗。
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引用次数: 0
Update on laboratory practice for the diagnosis of lupus anticoagulant and the antiphospholipid syndrome 狼疮抗凝血剂和抗磷脂综合征诊断的实验室实践进展
Pub Date : 2023-10-08 DOI: 10.37349/ei.2023.00110
Osamu Kumano, Marie Peyrafitte, Jean Amiral
Antiphospholipid syndrome (APS) is defined as an autoimmune and prothrombotic disorder in patients with the persistent presence of antiphospholipid antibodies (aPLs). In the classification criteria, aPL expresses lupus anticoagulant (LA) activity, which is detected by prolongation of coagulation assays. The LA detection algorithm is a sequential flow including screening tests, mixing tests, and confirmatory tests to differentiate between LA-positive and other anticoagulant abnormalities. Two types of assays are used, like dilute Russell’s viper venom time (dRVVT) and activated partial thromboplastin time (APTT) because no single test is sensitive to all LAs. The anticoagulant drugs prescribed for the prevention and treatment of thrombosis disorders can interfere with the assays, and it is important to know the effects of these drugs in the assays. Especially, new generation anticoagulant drugs, called direct oral anticoagulants (DOACs), affect the results. In this review, the following points are discussed: i) LA detection flow and data interpretation, ii) the principles of coagulation assays proposed and their characteristics, and iii) the effects of anticoagulant drugs in LA detection.
抗磷脂综合征(APS)被定义为抗磷脂抗体(APS)持续存在的患者的自身免疫和血栓形成前疾病。在分类标准中,aPL表达狼疮抗凝血剂(LA)活性,通过延长凝血试验来检测。LA检测算法是一个连续的流程,包括筛选试验、混合试验和确认试验,以区分LA阳性和其他抗凝异常。使用两种类型的测定,如稀释罗素毒蛇毒液时间(dRVVT)和活化部分凝血活素时间(APTT),因为没有单一的测试是敏感的所有LAs。用于预防和治疗血栓障碍的抗凝药物会干扰检测,了解这些药物在检测中的作用是很重要的。特别是新一代抗凝药物,称为直接口服抗凝剂(DOACs),影响结果。本文就以下几点进行综述:1)LA检测流程和数据解释;2)提出的凝血试验原理及其特点;3)抗凝药物在LA检测中的作用。
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引用次数: 0
Immune evasion by cancer stem cells ensures tumor initiation and failure of immunotherapy 癌症干细胞的免疫逃避导致了肿瘤的发生和免疫治疗的失败
Pub Date : 2023-08-31 DOI: 10.37349/ei.2023.00108
S. Chakraborty, S. Mukherjee, Udit Basak, Subhadip Pati, A. Dutta, Saikat Dutta, Subhanki Dhar, Tania Sarkar, A. Guin, G. Sa, T. Das
Cancer stem cells (CSCs) are a small subpopulation of cells that drive the formation and progression of tumors. However, during tumor initiation, how CSCs communicate with neighbouring immune cells to overcome the powerful immune surveillance barrier in order to form, spread, and maintain the tumor, remains poorly understood. It is, therefore, absolutely necessary to understand how a small number of tumor-initiating cells (TICs) survive immune attack during (a) the “elimination phase” of “tumor immune-editing”, (b) the establishment of regional or distant tumor after metastasis, and (c) recurrence after therapy. Mounting evidence suggests that CSCs suppress the immune system through a variety of distinct mechanisms that ensure the survival of not only CSCs but also non-stem cancer cells (NSCCs), which eventually form the tumor mass. In this review article, the mechanisms via which CSCs change the immune landscape of the tissue of origin, which contains macrophages, dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, and tumor-infiltrating lymphocytes, in favour of tumorigenesis were discussed. The failure of cancer immunotherapy might also be explained by such interaction between CSCs and immune cells. This review will shed light on the critical role of CSCs in tumor immune evasion and emphasize the importance of CSC-targeted immunotherapy as a cutting-edge technique for battling cancer by restricting communication between immune cells and CSCs.
癌症干细胞(CSCs)是驱动肿瘤形成和发展的一个小的细胞亚群。然而,在肿瘤发生过程中,CSC如何与邻近的免疫细胞通信,以克服强大的免疫监视屏障,从而形成、传播和维持肿瘤,目前尚不清楚。因此,绝对有必要了解在(a)“肿瘤免疫编辑”的“消除阶段”,(b)转移后建立区域或远处肿瘤,以及(c)治疗后复发期间,少数肿瘤起始细胞(TIC)是如何在免疫攻击中存活的。越来越多的证据表明,CSC通过多种不同的机制抑制免疫系统,这些机制不仅确保CSC的存活,而且确保最终形成肿瘤团的非系统癌症细胞(NSCCs)的存活,讨论了骨髓来源的抑制细胞(MDSCs)、自然杀伤细胞(NK)和肿瘤浸润淋巴细胞有利于肿瘤发生。癌症免疫疗法的失败也可以通过CSC和免疫细胞之间的这种相互作用来解释。这篇综述将阐明CSC在肿瘤免疫逃避中的关键作用,并强调CSC靶向免疫疗法作为通过限制免疫细胞和CSC之间的交流来对抗癌症的尖端技术的重要性。
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引用次数: 1
Inflammatory immune mediators and Plasmodium falciparum infection: a cross-sectional study among Sudanese patients with severe and uncomplicated malaria 炎症免疫介质和恶性疟原虫感染:苏丹严重和无并发症疟疾患者的横断面研究
Pub Date : 2023-08-31 DOI: 10.37349/ei.2023.00109
Dia Aldeen Alfaki, M. Hussein, Mustafa Hassan, Amanda G. Eloraish, M. M. Elbasheir
Aim: A number of questions remain unanswered concerning how infected individuals regulate their immune response to Plasmodium falciparum (P. falciparum) parasites at varying levels of exposure. Due to the interactions of inflammatory mediators and cytokines with the P. falciparum parasite complex density, several mediators influence parasitaemia and may give some indications of disease severity and represent effective signs in clinical manifestations of malaria disease.Methods: In this study, various levels of immune response mediators of interleukin 8 (IL-8), tumor necrosis factor-beta (TNF-β, also known as lymphotoxin-α), interferon-gamma (IFN-γ), IL-6, and IL-10 were investigated to the different phases of infection with P. falciparum in hyperendemic states in Sudan (White Nile, Blue Nile). This study vetted the association between certain inflammatory mediators during malaria infection and parasite density. This study was based on a total of 108 cases, in which 86 patients (62.0%) were uncomplicated and (17.6%) were severe, all met the diagnostic criteria and were clinically admitted for malaria infections. Commercial enzyme-linked immunosorbent assay (ELISA) kits were employed to determine the inflammatory mediator’s serum concentration.Results: The analysis of data indicated that older infected children had substantially raised levels of IFN-γ (P < 0.05), among study groups, levels of IFN-γ, TNF-β, and IL-8 were strongly linked with the severity of malaria, in severe and uncomplicated cases (P < 0.001), IL-6 and IL-10 were significantly associated with severe malaria cases uniquely (P < 0.001). Furthermore, we reported a positive correlation between IL-8 and TNF-β during all infection cases (r = 0.760, P < 0.001), Additionally, in severe malaria cases IL-6 was positively correlated with IL-10 (r = 0.575, P = 0.010).Conclusions: Eliminating P. falciparum blood-stage infection needs effective, specific, and tuned immune response strategies. which may present in the mediator’s correlations and depend on the density of the infection. Besides the effective levels contribution of certain cytokines that play protective roles during different stages of an infection.
目的:关于感染个体如何在不同暴露水平下调节其对恶性疟原虫(恶性疟原虫)寄生虫的免疫反应,许多问题仍未得到解答。由于炎症介质和细胞因子与恶性疟原虫寄生虫复合体密度的相互作用,几种介质影响寄生虫血症,可能给出疾病严重程度的一些指示,并代表疟疾疾病临床表现的有效迹象。方法:在本研究中,研究了不同水平的免疫反应介质白细胞介素8 (IL-8)、肿瘤坏死因子-β (TNF-β,也称为淋巴素-α)、干扰素-γ (IFN-γ)、IL-6和IL-10在苏丹(白尼罗河、青尼罗河)高流行州恶性疟原虫感染不同阶段的免疫反应。本研究审查了疟疾感染过程中某些炎症介质与寄生虫密度之间的关系。本研究共纳入108例病例,其中86例(62.0%)无并发症,重症(17.6%)符合诊断标准,均因疟疾感染住院。采用商用酶联免疫吸附试验(ELISA)试剂盒测定炎症介质的血清浓度。结果:数据分析表明,年龄较大的感染儿童的IFN-γ水平显著升高(P < 0.05),在研究组中,IFN-γ、TNF-β和IL-8水平与疟疾的严重程度密切相关(P < 0.001),在严重和无并发症的病例中,IL-6和IL-10仅与严重疟疾病例显著相关(P < 0.001)。此外,在所有感染病例中,IL-8与TNF-β呈正相关(r = 0.760, P < 0.001),在重症疟疾病例中,IL-6与IL-10呈正相关(r = 0.575, P = 0.010)。结论:消除恶性疟原虫血期感染需要有效、特异性和调整的免疫反应策略。这可能存在于介质的相关性中,并取决于感染的密度。除了在感染的不同阶段发挥保护作用的某些细胞因子的有效水平贡献外。
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引用次数: 0
Immune system rejuvenation—approaches and real achievements 免疫系统恢复活力的方法和真正的成就
Pub Date : 2023-08-31 DOI: 10.37349/ei.2023.00105
I. Pishel
Interest in the mechanisms of aging of the immune system has not faded over the past 100 years, and it is caused by the immune-mediated development of age-related pathology, including autoimmune organ damage, reduced vaccination efficiency, atherosclerosis, the development of cardiovascular pathology, etc. In contrast to many other organs and systems, the immune system aging begins at an early age and has more pronounced changes that lead to the development of secondary pathology, which significantly affects life expectancy. But an effective strategy to restore immune function has not been developed yet. During this time, the mechanisms of age-related dysfunction of organs and cells of both the adaptive and innate immune systems were studied in detail—thymus involution, a decrease in the potential of hematopoietic stem cells, impaired differentiation and functions of immunocompetent cells, as well as the ways of their interaction. Numerous potential therapeutic targets have been identified and various approaches have been used to implement such therapeutic interventions. The review is devoted to replacement therapy using transplantation of hematopoietic stem cells (HSCs) and young lymphoid cells and tissues, cellular and systemic factor exchange in heterochronic parabiosis, and some other widely used life extension approaches. It has been proven that cell therapy using young cells to rejuvenate the old immune system, unfortunately, often turns out to be ineffective because it does not eliminate the root cause of age-related changes. The phenomenon of inflamm-aging that develops with age can significantly affect both the aging of the organism in general and the functioning of immunocompetent cells in particular. Therefore, the most promising direction in the restoration of immune functions during aging is systemic approaches that have a complex effect on the organism as a whole and can slow down the aging process.
在过去的100年里,人们对免疫系统衰老机制的兴趣并没有消退,它是由免疫介导的年龄相关病理学的发展引起的,包括自身免疫器官损伤、疫苗接种效率降低、动脉粥样硬化、心血管病理学的发展等。与许多其他器官和系统相比,免疫系统的衰老在很小的时候就开始了,并且有更明显的变化,导致继发性病理的发展,从而显著影响预期寿命。但是,恢复免疫功能的有效策略尚未开发出来。在此期间,我们详细研究了适应性免疫系统和先天免疫系统的器官和细胞与年龄相关的功能障碍的机制——胸腺退化、造血干细胞潜力降低、免疫活性细胞的分化和功能受损,以及它们之间的相互作用方式。已经确定了许多潜在的治疗靶点,并使用了各种方法来实施这种治疗干预。综述了造血干细胞(HSC)和年轻淋巴细胞和组织移植的替代疗法、异时共生中的细胞和系统因子交换,以及其他一些广泛使用的延长寿命的方法。不幸的是,已经证明,使用年轻细胞来恢复旧免疫系统的细胞疗法往往无效,因为它不能消除与年龄相关的变化的根本原因。随着年龄的增长而发展的炎症性衰老现象会显著影响机体的衰老,尤其是免疫活性细胞的功能。因此,在衰老过程中恢复免疫功能最有希望的方向是系统性方法,这种方法对整个生物体有复杂的影响,可以减缓衰老过程。
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引用次数: 0
Analytical dilemmas in lupus anticoagulant detection 狼疮抗凝检测中的分析困境
Pub Date : 2023-08-31 DOI: 10.37349/ei.2023.00104
G. Moore
Accurate lupus anticoagulant (LA) detection is crucial to antiphospholipid syndrome (APS) diagnosis. Detection is based on LA functional behavior in coagulation assays irrespective of epitope specificity. LA screening tests employ dilute phospholipids to accentuate in vitro inhibition by LAs, although they are not LA-specific and can be elevated by other coagulation abnormalities. Elevated screening tests are reflexed to mixing tests to distinguish between factor deficiency and inhibition. Confirmatory tests with high phospholipid concentration swamp LA to generate shorter clotting times than screening tests, whilst prolongation persists with non-phospholipid-dependent inhibitors. LA heterogeneity means that no single screening test detects every LA and the screen/mix/confirm medley must be applied to at least two assay types, usually dilute Russell’s viper venom time (dRVVT) and an LA-sensitive activated partial thromboplastin time (aPTT). Most laboratories restrict LA testing to these two assays, yet others, such as dilute prothrombin time (dPT), can perform with equal diagnostic efficacy, and additionally detect LA unreactive with dRVVT and aPTT. Converting clotting times to normalized ratios improves assay performance, and practitioners must choose between normal pooled plasma (NPP) clotting time denominators to reflect on-the-day assay performance, or reference interval (RI) mean clotting times to negate the effects of NPP variation. Cut-offs can be generated parametrically from normally distributed data, or different percentiles applied depending on the preferred balance between sensitivity and specificity. Sourcing sufficient donors for accurate cut-off estimations is problematic and transference exercises can be undertaken on low donor numbers. Analytical limitations of mixing tests have led to the adoption of alternative algorithms to the screen/mix/confirm test order, whilst some continue to rigidly apply the latter despite those limitations. Strategies to reduce or eliminate the effects of therapeutic anticoagulation have limitations, whilst the Taipan snake venom time (TSVT) screening test with an ecarin time (ET) confirmatory test is insensitive to vitamin K antagonist (VKA) and direct activated factor X anticoagulation.
准确的狼疮抗凝血剂(LA)检测对抗磷脂综合征(APS)的诊断至关重要。检测基于凝血测定中LA的功能行为,而不考虑表位特异性。LA筛选试验使用稀释的磷脂来增强LA的体外抑制作用,尽管它们不是LA特异性的,并且可以通过其他凝血异常而升高。强化筛选测试被反射为混合测试,以区分因子缺乏和抑制。高磷脂浓度的验证性试验使LA比筛选试验产生更短的凝血时间,而非磷脂依赖性抑制剂则能持续延长凝血时间。LA的异质性意味着没有单一的筛选测试能检测到每个LA,筛选/混合/确认混合物必须应用于至少两种检测类型,通常是稀释Russell毒蛇毒液时间(dRVVT)和LA敏感的活化部分凝血活酶时间(aPTT)。大多数实验室将LA检测限制在这两种检测,而其他检测,如稀释凝血酶原时间(dPT),可以以同等的诊断效果进行,并额外检测dRVVT和aPTT不反应的LA。将凝血时间转换为标准化比率可以提高测定性能,从业者必须在反映当天测定性能的正常合并血浆(NPP)凝血时间分母和抵消NPP变化影响的参考间隔(RI)平均凝血时间之间做出选择。截止值可以根据正态分布数据参数化生成,也可以根据敏感性和特异性之间的首选平衡应用不同的百分位数。为准确的截止估计寻找足够的捐助者是有问题的,可以在捐助者人数较少的情况下进行转移工作。混合测试的分析局限性导致了对筛选/混合/确认测试顺序采用替代算法,而尽管存在这些局限性,一些人仍继续严格应用后者。减少或消除治疗性抗凝作用的策略有局限性,而用ecarin时间(ET)验证试验进行的Taipan蛇毒时间(TSVT)筛选试验对维生素K拮抗剂(VKA)和直接激活因子X抗凝不敏感。
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引用次数: 0
Vitamin D, ageing, and the immune system 维生素D,衰老和免疫系统
Pub Date : 2023-08-31 DOI: 10.37349/ei.2023.00106
V. Bueno
Changes occurring in the immune system along the ageing process increase the risk of infection, susceptibility to tumor development, and autoimmunity. Interventions such as physical exercise, supplements, and probiotics have been proposed in order to circumvent these conditions. Vitamin D supplementation could contribute to the immune system homeostasis in older adults since a large proportion of this population has low levels of circulating vitamin D. Additionally, observational studies have shown the association between vitamin D status and infections, chronic diseases such as cancer, diabetes, and cardiovascular disease. Recently it was observed that old patients with COVID-19 and vitamin D deficiency had enhanced severity of lung damage, longer stay at the hospital, and increased risk of death, suggesting that vitamin D plays an important role in the patient outcome from COVID-19. A high dose of vitamin D supplementation improved clinical recovery in a case-series report but in another study, no evident link between levels of vitamin D and risk of COVID-19 infection was found. Results also remain debatable for vitamin D supplements and improvement of immune response after vaccination, tuberculosis, pneumonia, and sepsis. It has been hypothesized that vitamin D could modulate the immune system and thus provide both efficacies in the immune response to pathogens/vaccinations and reduction of the inflammatory phenotype. This review will discuss vitamin D and homeostasis of the immune system; the literature-based clinical data on vitamin D and infections; and the possible link between vitamin D and immune response after vaccination.
免疫系统在衰老过程中发生的变化会增加感染风险、对肿瘤发展的易感性和自身免疫。为了避免这些情况,人们提出了体育锻炼、补充剂和益生菌等干预措施。补充维生素D可能有助于老年人的免疫系统稳态,因为大部分老年人的循环维生素D水平较低。此外,观察性研究表明,维生素D状态与感染、癌症、糖尿病和心血管疾病等慢性病之间存在关联。最近观察到,患有新冠肺炎和维生素D缺乏症的老年患者肺损伤严重程度加重,住院时间延长,死亡风险增加,这表明维生素D在新冠肺炎患者的预后中起着重要作用。在一份病例系列报告中,高剂量补充维生素D改善了临床恢复,但在另一项研究中,未发现维生素D水平与新冠肺炎感染风险之间存在明显联系。维生素D补充剂和疫苗接种后免疫反应的改善、结核病、肺炎和败血症的结果也存在争议。据推测,维生素D可以调节免疫系统,从而在对病原体/疫苗的免疫反应中提供效力,并减少炎症表型。这篇综述将讨论维生素D和免疫系统的稳态;基于文献的维生素D和感染的临床数据;以及维生素D与疫苗接种后免疫反应之间的可能联系。
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引用次数: 0
The emergence of nanovaccines as a new paradigm in virological vaccinology: a review 纳米疫苗作为病毒学疫苗学新范式的出现:综述
Pub Date : 2023-08-31 DOI: 10.37349/ei.2023.00107
C. Baruah, Pankaj Das, P. Devi, Palash M. Saikia, B. Deka
Vaccination has made an enormous contribution to global health. Treatment resistance for infectious diseases is growing quickly, and chemotherapeutic toxicity in cancer means that vaccines must be made right away to save humanity. But subunit vaccinations alone don’t give enough strong and long-lasting protection against infections that can kill. Nanoparticle (NP)-based delivery vehicles, such as dendrimers, liposomes, micelles, virosomes, nanogels, and microemulsions, offer interesting ways to get around the problems with traditional vaccine adjuvants. The nanovaccines (50–250 nm in size) are most efficient in terms of tissue targeting, staying in the bloodstream for a long time. Nanovaccines can improve antigen presentation, targeted delivery, stimulation of the body’s innate immune system, and a strong T-cell response without putting people at risk. This can help fight infectious diseases and cancers. Also, nanovaccines can be very helpful for making cancer treatments that use immunotherapy. So, this review highlights the various types of NPs used in the techniques that have worked in the new paradigm in viral vaccinology for infectious diseases. It gives a full rundown of the current NP-based vaccines, their potential as adjuvants, and the ways they can be delivered to cells. In the future, the best nanovaccines will try to be more logically designed, have more antigens in them, be fully functionalized, and be given to the right people.
疫苗接种对全球健康做出了巨大贡献。传染病的治疗耐药性正在迅速增长,癌症的化疗毒性意味着必须立即生产疫苗来拯救人类。但单凭亚单位疫苗并不能对可能致命的感染提供足够强大和持久的保护。基于纳米粒子(NP)的递送载体,如树状大分子、脂质体、胶束、病毒体、纳米凝胶和微乳,为解决传统疫苗佐剂的问题提供了有趣的方法。纳米疫苗(尺寸为50-250纳米)在组织靶向方面最有效,可以在血液中停留很长时间。纳米疫苗可以改善抗原呈递、靶向递送、刺激人体先天免疫系统和强大的T细胞反应,而不会使人处于危险之中。这可以帮助对抗传染病和癌症。此外,纳米疫苗可以非常有助于制造使用免疫疗法的癌症治疗方法。因此,这篇综述强调了在传染病病毒疫苗学的新范式中使用的各种类型的NP。它全面概述了目前基于NP的疫苗,它们作为佐剂的潜力,以及它们可以输送到细胞中的方式。未来,最好的纳米疫苗将尝试进行更合理的设计,其中含有更多的抗原,完全功能化,并提供给合适的人。
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引用次数: 0
Considerations for simultaneous detection of autoantibodies to coagulation factor and lupus anticoagulant 凝血因子和狼疮抗凝剂自身抗体同时检测的考虑
Pub Date : 2023-08-30 DOI: 10.37349/ei.2023.00103
M. Ieko, K. Ohmura, S. Naito, Mika Yoshida, Hisaomi Sasaki, Tsuyoshi Sato, Norifumi Sugawara, N. Takahashi, A. Ichinose
In patients with autoimmune coagulation factor deficiency (AiCFD), the production of autoantibodies that inhibit coagulation factors in the blood reduces the activity of those relevant coagulation factors, resulting in severe bleeding symptoms. Recently, reports of patients with AiCFD have noted the concomitant detection of lupus anticoagulant (LA), a risk factor for thrombosis. LA-positive patients may show bleeding symptoms due to decreased activity of coagulation factor II (FII) caused by autoantibodies against FII, in addition to thrombotic symptoms, a condition termed LA-hypoprothrombinemia syndrome (LAHPS). Anti-FII antibodies in LAHPS cases are frequently cleared antibodies that can be detected using immunological techniques, such as enzyme-linked immunosorbent assay (ELISA). Recently, several cases of coagulation FV inhibitors, known as autoimmune FV deficiency, have been reported. Some of these cases may be complicated by LA, which can cause thrombosis. False-positive results for anticoagulant inhibitors are known to occur in LA cases; therefore, immunological confirmation of antibodies against coagulation factors is recommended. Additionally, acquired hemophilia A (AHA), caused by autoantibodies against FVIII, is a typical acquired hemorrhagic diathesis, although affected patients may present with thrombosis associated with LA. Thus, it is important to remember that hemorrhagic diathesis due to autoantibodies against clotting factors can also result in thrombosis, as demonstrated by the co-detection of LA. When clotting factor inhibitors are detected in LA-positive individuals, it is important to confirm the presence of autoantibodies against coagulation factors using immunological methods, such as ELISA, to avoid false-positive results.
在自身免疫性凝血因子缺乏症(AiCFD)患者中,血液中抑制凝血因子的自身抗体的产生会降低这些相关凝血因子的活性,从而导致严重的出血症状。最近,关于AiCFD患者的报告指出,同时检测到狼疮抗凝剂(LA),这是血栓形成的一个危险因素。LA阳性患者可能表现出出血症状,这是由于抗FII自身抗体引起的凝血因子II(FII)活性降低,此外还有血栓症状,这种情况被称为LA低凝血酶原综合征(LAHPS)。LAHPS病例中的抗FII抗体是经常被清除的抗体,可以使用免疫技术检测,如酶联免疫吸附试验(ELISA)。最近,已经报道了几种凝血FV抑制剂的病例,称为自身免疫性FV缺乏症。其中一些病例可能因左心房而变得复杂,从而导致血栓形成。已知抗凝抑制剂的假阳性结果发生在LA病例中;因此,建议对凝血因子抗体进行免疫学确认。此外,由抗FVIII自身抗体引起的获得性血友病A(AHA)是一种典型的获得性出血素质,尽管受影响的患者可能会出现与LA相关的血栓形成。因此,重要的是要记住,抗凝血因子自身抗体导致的出血素质也会导致血栓形成,正如LA的共同检测所证明的那样。当在LA阳性个体中检测到凝血因子抑制剂时,重要的是使用免疫方法(如ELISA)确认抗凝血因子自身抗体的存在,以避免假阳性结果。
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引用次数: 0
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Exploration of immunology
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