Recombinant

重组
  • 文章类型: Journal Article
    恰加斯病(CD),由原生动物克氏锥虫引起的,是一个重要的公共卫生问题,主要发生在拉丁美洲。本病具有主要的社会经济效应,对感染者的生活产生负面影响,给公共卫生带来巨大的代价。早期和准确的诊断对于早期治疗的管理至关重要。此外,预后测试可能有助于疾病管理,降低住院费用。然而,CD的血清学诊断方案仍然面临几个挑战,使开发新的诊断试剂盒成为当务之急。面对这种情况,一些研究人员扩大了开发和测试新抗原的努力,如重组蛋白和重组多表位蛋白,有希望的结果。这些重组抗原提供了几个优点,如提高灵敏度和特异性,除了促进缩放。此外,使用ELISA和即时护理平台观察到越来越多的研究是可能的,在过去几年中使用了这些抗原。其中,重组蛋白是应用最多的抗原,表现出很强的区分阳性和阴性样本的能力。虽然数量较少,重组多表位蛋白也表现出改进的诊断性能。的确,大量使用这些抗原的研究显示灵敏度和特异性值超过90%,极大地影响诊断准确性。然而,尽管发现了良好的结果,仍然有可能观察到新抗原开发的一些瓶颈,例如急性期血清检测的稀缺性以及不同地理区域结果的变异性。在这个意义上,旨在为控制和健康计划做出贡献,不断寻找更准确的血清学诊断至关重要,对于疾病的急性和慢性阶段。
    Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is an important public health problem, occurring mainly in Latin America. The disease has a major social and economical effect, negatively impacting the life of the infected individuals, and bringing great costs to public health. An early and accurate diagnosis is essential for administration of early treatment. In addition, prognostic tests may aid disease management, decreasing hospitalization costs. However, the serological diagnostic scenario for CD still faces several challenges, making the development of new diagnostic kits a pressing matter. Facing this scenario, several researchers have expanded efforts in developing and testing new antigens, such as recombinant proteins and recombinant multiepitope proteins, with promising results. These recombinant antigens offer several advantages, such as improved sensitivity and specificity, in addition to facilitated scaling. Also, it has been possible to observe a rising number of studies using ELISA and point-of-care platforms, employing these antigens in the past few years. Among them, recombinant proteins were the most applied antigens, demonstrating great capacity to discriminate between positive and negative samples. Although fewer in number, recombinant multiepitope proteins also demonstrated an improved diagnostic performance. Indeed, a great number of studies employing these antigens showed sensitivity and specificity values above 90%, greatly impacting diagnostic accuracy. Nevertheless, despite the good results found, it is still possible to observe some bottlenecks in the development of new antigens, such as the scarcity of tests with sera from the acute phase and the variability of results in different geographic areas. In this sense, aiming to contribute to control and health programs, the continuous search for a more accurate serological diagnosis is essential, both for the acute and chronic phases of the disease.
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  • 文章类型: Journal Article
    骆驼类仅重链抗体的单可变结构域,被称为纳米抗体,自1989年发现以来,他们经历了漫长的旅程,直到2022年第一种基于纳米抗体的药物进入市场。由于它们独特的属性,纳米抗体已成功用于各种疾病或病症的诊断和治疗。尽管关于重组抗体应用的研究一直集中在人类医学上,纳米抗体的发展为整合重组抗体生产铺平了道路,有利于兽医学。目前,尽管在开发这些具有多样化应用的生物分子方面做出了许多努力,在兽医学中存在利用这些高度通用且具有成本效益的抗体的重要机会。本研究试图通过对在兽医学中具有潜在应用的骆驼纳米抗体进行最新综述,以确定现有的差距并为未来的研究提供思路。
    The single variable domains of camelid heavy-chain only antibodies, known as nanobodies, have taken a long journey since their discovery in 1989 until the first nanobody-based drug\'s entrance to the market in 2022. On account of their unique properties, nanobodies have been successfully used for diagnosis and therapy against various diseases or conditions. Although research on the application of recombinant antibodies has focused on human medicine, the development of nanobodies has paved the way for incorporating recombinant antibody production in favour of veterinary medicine. Currently, despite many efforts in developing these biomolecules with diversified applications, significant opportunities exist for exploiting these highly versatile and cost-effective antibodies in veterinary medicine. The present study attempts to identify existing gaps and shed light on paths for future research by presenting an updated review on camelid nanobodies with potential applications in veterinary medicine.
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  • 文章类型: Journal Article
    由于HIV-1重组体引起的全球HIV感染正在增加,并阻碍了预防和治疗工作。关键人群遭受大多数新的艾滋病毒感染,但它们在HIV-1重组体传播中的作用尚不清楚。我们对关键人群与HIV-1重组体之间的关联进行了全球分析。
    我们搜索了PubMed,EMBASE,CINAHL,以及1990年1月1日至2015年12月31日发表的全球卫生HIV-1亚型研究。未公布的数据是通过一项全球调查收集的。我们纳入了1990-2015年期间收集的关键人群HIV-1亚型数据的研究。评估的主要人群是异性恋者(HET),男男性行为者(MSM),注射毒品的人(PWID),垂直变速器(VERT),商业性工作者(CSW),和输血相关感染(血液)。使用逻辑回归来确定关键群体与HIV-1重组体的关联。对循环重组形式(CRF)进行亚组分析,独特的重组形式(URFs),regions,和时间段。
    包括来自83个国家的77,284名参与者在内的85个数据集被纳入。全球范围内,PWID与重组体和CRF的最大几率相关(OR2.6[95%CI2.46-2.74]和2.99[2.83-3.16]),与HET相比。CSW与重组和URFs的几率增加相关(1.59[1.44-1.75]和3.61[3.15-4.13])。VERT和BLOOD与重组几率降低相关(0.58[0.54-0.63]和0.43[0.33-0.56])。MSM与2010-2015年重组几率增加相关(1.43[1.35-1.51])。亚组分析支持我们的主要发现。
    作为PWID,CSW,MSM与HIV-1重组体相关,在这些关键人群中,增加预防措施和HIV-1分子监测至关重要.
    PROSPERO[CRD42017067164]。
    Global HIV infections due to HIV-1 recombinants are increasing and impede prevention and treatment efforts. Key populations suffer most new HIV infections, but their role in the spread of HIV-1 recombinants is unknown. We conducted a global analysis of the associations between key populations and HIV-1 recombinants.
    We searched PubMed, EMBASE, CINAHL, and Global Health for HIV-1 subtyping studies published from 1/1/1990 to 31/12/2015. Unpublished data was collected through a global survey. We included studies with HIV-1 subtyping data of key populations collected during 1990-2015. Key populations assessed were heterosexual people (HET), men who have sex with men (MSM), people who inject drugs (PWID), vertical transmissions (VERT), commercial sex workers (CSW), and transfusion-associated infections (BLOOD). Logistic regression was used to determine associations of key populations with HIV-1 recombinants. Subgroup analyses were performed for circulating recombinant forms (CRFs), unique recombinant forms (URFs), regions, and time periods.
    Eight hundred and eighty five datasets including 77,284 participants from 83 countries were included. Globally, PWID were associated with the greatest odds of recombinants and CRFs (OR 2.6 [95% CI 2.46-2.74] and 2.99 [2.83-3.16]), compared to HET. CSW were associated with increased odds of recombinants and URFs (1.59 [1.44-1.75] and 3.61 [3.15-4.13]). VERT and BLOOD were associated with decreased odds of recombinants (0.58 [0.54-0.63] and 0.43 [0.33-0.56]). MSM were associated with increased odds of recombinants in 2010-2015 (1.43 [1.35-1.51]). Subgroup analyses supported our main findings.
    As PWID, CSW, and MSM are associated with HIV-1 recombinants, increased preventative measures and HIV-1 molecular surveillance are crucial within these key populations.
    PROSPERO [CRD42017067164].
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  • 文章类型: Journal Article
    杯状病毒是单链RNA病毒,非包络结构,与各种哺乳动物的非细菌性胃肠炎有关。尤其是在猪身上,病毒性胃肠炎是全球的主要问题,对养猪业的重大经济损失负责。在已证实或怀疑是胃肠炎病因的各种病毒中,Caliciviviridae家族成员的致病性尚不清楚。在这种情况下,本综述介绍并讨论了属于该科的两个属的当前知识,即诺如病毒和萨波病毒,关于猪。致病性等方面,临床证据,症状,流行病学和全球流行,基因组多样性,识别工具以及交换主机不仅要审查,而且要严格评估。一般来说,尽管猪经常无症状,这些微生物在养猪场的流行呈现出全球范围内大幅增加的趋势。应该提到的是,然而,影响这些病毒症状学的因素还远远没有确定。有趣的是,这两种病毒的特征还在于高度的遗传多样性。杯状病毒科中这些高水平的分子多样性更可能是重组的结果,而不是通过突变步骤进行进化或选择性适应的结果。因此,用于其检测的分子标记主要基于保守区域,例如RdRp区域。最后,应该强调的是,诺如病毒和萨波病毒也可能感染其他家庭,农场和野生动物,包括人类,因此,它们在腹泻等疾病中的监测和澄清作用也是公共卫生重要性的问题。
    Caliciviruses are single stranded RNA viruses, non-enveloped structurally, that are implicated in the non-bacterial gastroenteritis in various mammal species. Particularly in swine, viral gastroenteritis represents a major problem worldwide, responsible for significant economic losses for the pig industry. Among the wide range of viruses that are the proven or suspected etiological agents of gastroenteritis, the pathogenicity of the members of Caliciviridae family is among the less well understood. In this context, the present review presents and discusses the current knowledge of two genera belonging to this family, namely the Norovirus and the Sapovirus, in relation to swine. Aspects such as pathogenicity, clinical evidence, symptoms, epidemiology and worldwide prevalence, genomic diversity, identification tools as well as interchanging hosts are not only reviewed but also critically evaluated. Generally, although often asymptomatic in pigs, the prevalence of those microbes in pig farms exhibits a worldwide substantial increasing trend. It should be mentioned, however, that the factors influencing the symptomatology of these viruses are still far from well established. Interestingly, both these viruses are also characterized by high genetic diversity. These high levels of molecular diversity in Caliciviridae family are more likely a result of recombination rather than evolutionary or selective adaptation via mutational steps. Thus, molecular markers for their detection are mostly based on conserved regions such as the RdRp region. Finally, it should be emphasized that Norovirus and the Sapovirus may also infect other domestic, farm and wild animals, including humans, and therefore their surveillance and clarification role in diseases such as diarrhea is a matter of public health importance as well.
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  • 文章类型: Journal Article
    The control of poultry diseases has relied heavily on the use of many live and inactivated vaccines. However, over the last 30 yr, recombinant DNA technology has been used to generate many novel poultry vaccines. Fowlpox virus and turkey herpesvirus are the two main vectors currently used to construct recombinant vaccines for poultry. With the use of these two vectors, more than 15 recombinant viral vector vaccines against Newcastle disease, infectious laryngotracheitis, infectious bursal disease, avian influenza, and Mycoplasma gallisepticum have been developed and are commercially available. This review focuses on current knowledge about the safety and efficacy of recombinant viral vectored vaccines and the mechanisms by which they facilitate the control of multiple diseases. Additionally, the development of new recombinant vaccines with novel vectors will be briefly discussed.
    Estudio Recapitulativo- Revisión acerca de las vacunas con vectores recombinantes para la avicultura. El control de las enfermedades en la avicultura se ha basado en gran medida en el uso de varias vacunas vivas e inactivadas. Sin embargo, durante los últimos 30 años, la tecnología de ADN recombinante se ha utilizado para generar nuevas vacunas avícolas. El virus de la viruela aviar y el virus del herpes del pavo son los dos vectores principales que se utilizan actualmente para construir vacunas recombinantes para la avicultura. Con el uso de estos dos vectores, se han desarrollado y están disponibles comercialmente más de 15 vacunas con vectores virales recombinantes contra la enfermedad de Newcastle, la laringotraqueítis infecciosa, enfermedad infecciosa de la bolsa, influenza aviar y Mycoplasma gallisepticum. Esta revisión se enfoca en el conocimiento actual sobre la seguridad y eficacia de las vacunas con vectores virales recombinantes y los mecanismos por los cuales facilitan el control de múltiples enfermedades. Además, se discutirá brevemente el desarrollo de nuevas vacunas recombinantes con nuevos vectores.
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  • 文章类型: Journal Article
    More than 400 million years of natural selection acting throughout the arthropoda has resulted in highly specialized and energetically efficient processes to produce protein-based fibers with properties that are a source of inspiration for all. As a result, for over 80 years researchers have been inspired by natural silk production in their attempts to spin artificial silks. While significant progress has been made, with fibers now regularly outperforming silkworm silks, surpassing the properties of superior silks, such as spider dragline, is still an area of considerable effort. This review provides an overview of the different approaches for artificial silk fiber spinning and compares all published fiber properties to date which has identified future trends and challenges on the road towards replicating high performance silks.
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  • 文章类型: Journal Article
    UNASSIGNED: Long-acting (LA) recombinant FVIII (rFVIII) products with extended dosing intervals have been developed for the treatment of hemophilia A; however, no direct head-to-head trial has been conducted to compare the efficacy of these products.
    UNASSIGNED: A systematic literature search was conducted to identify published Phase III clinical trials of prophylactic LA rFVIII treatment in previously treated patients aged ≥12 years, with moderate-to-severe hemophilia A (endogenous FVIII levels ≤2%). Studies that did not meet these criteria, or did not report the included outcomes, were excluded. Bleeding rates and consumption were extracted and summarized; only data for the dosing frequencies indicated in the US product labels (which are similar to those indicated in the European Medicines Agency labels) were included.
    UNASSIGNED: Five articles met the inclusion criteria; these studies only included patients with severe hemophilia A. Treatment length, reported outcomes and dose (range: 20-65 IU/kg) varied between studies. Median annualized bleeding rate (ABR) (IQR) reported in the relevant studies was 1.14 (0.00-4.30), rVIII-SingleChain 2 or 3 times weekly; 1.6 (0.0-4.7), rFVIIIFc 2 times weekly followed by every 3-5 days; 1.9 (0.0-5.8), BAX855 2 times weekly; 1.18 (0.00-4.25), N8-GP every 4 days; 1.9 (0.0-5.2) and 4.1 (2.0-10.6), BAY 94-9027 2 times weekly for the cohort who experienced >1 or <1 bleed in the study run-in phase, respectively. Median spontaneous ABR was 0.0 across studies reporting relevant data. Reported consumption was comparable among all LA products.
    UNASSIGNED: The primary limitation of this systematic review was the variation in study design and not all studies reported all desired outcomes, which limited the quantity of data available.
    UNASSIGNED: This systematic review identified pivotal trial data for LA rFVIII products. Real-world evidence is needed to understand how these products perform in clinical practice.
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  • 文章类型: Journal Article
    季节性流感的影响在亚洲被低估,大多数其他地区的监测数据滞后。亚洲流感循环模式的多样性——主要是由于气候的范围——也是最近才被认识到的,其对疾病负担的影响还没有完全理解。最近的报道称,临床保护在流感疫苗接种后的几周内减弱,强调了最佳时机接种对当地流行病学的重要性。它还提出了以下问题:流感疫苗的使用频率是否应高于每年,以及在亚洲获得具有增强免疫原性和有效性的新疫苗可能有什么好处。本综述将总结2011-2018年亚洲国家的流感监测数据,并考虑对亚洲不同地区疫苗接种策略的影响。
    The impact of seasonal influenza has been under-appreciated in Asia and surveillance data lags in most other regions. The variety of influenza circulation patterns in Asia - largely due to the range of climates - has also only recently been recognized and its effect on the burden of disease is not fully understood. Recent reports that clinical protection wanes in the weeks after influenza vaccination emphasize the importance of optimally timing vaccination to local epidemiology. It also raises questions as to whether influenza vaccines should be administered more frequently than annually and what may be the benefits in Asia of access to new vaccines with enhanced immunogenicity and effectiveness. This review will summarize influenza surveillance data from Asian countries over 2011-2018, and consider the implications for vaccination strategies in different parts of Asia.
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  • 文章类型: Journal Article
    Aims: Prophylaxis with standard-acting recombinant factor IX (rFIX) in hemophilia B patients requires frequent injections. Extended half-life (EHL) products allow for prolonged dosing intervals, and so reduce this treatment burden. Three technologies are employed to extend the half-life of FIX; glycopegylation, Fc-fusion, and albumin fusion. rIX-FP is a novel albumin fusion protein, which allows for a prolonged dosing interval of up to 14 days. A systematic review and indirect statistical comparison was performed to evaluate the efficacy of both EHL and standard-acting rFIX products compared with rIX-FP in Phase III trials for prophylaxis in adult hemophilia B patients. Materials and methods: A systematic search was conducted in both EMBASE and PubMed to identify Phase III trials of prophylactic rFIX treatment in previously treated hemophilia B patients aged ≥12 years (FIX ≤2%). Annualized bleeding rate (ABR), spontaneous ABR (AsBR), and joint ABR (AjBR) data were extracted from each study. A z-test was performed using the mean of each parameter, and the mean difference in outcome between studies was calculated. Results: Seven articles investigating six rFIX products were identified. Median ABR, AsBR, and AjBR ranged from 0-3.0, 0-1.0, and 0-1.1 (means = 0.8-4.26, 0.13-2.6, and 0.34-2.85), respectively. rIX-FP achieved the lowest median and mean values in all three parameters. Z-tests showed that mean ABR was significantly lower for rIX-FP 7-day prophylaxis compared with the majority of standard-acting and other EHL rFIX products. Limitations: The low number of appropriate trials available for comparison limits the quantity of data available for comparison, and restricts the use of methods of adjustment for variance in study design or patient characteristics. However, these limitations are shared with similar analyses published in this field. Conclusion: This indirect comparison of Phase III trials indicates that rIX-FP efficacy compares favorably vs other rFIX products for prophylaxis in hemophilia B.
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  • 文章类型: Journal Article
    BACKGROUND: Herpes zoster (HZ) incidence is linked to immunosuppression. Patients with psoriasis or psoriatic arthritis (PsA) on systemic therapy might be at an increased risk for HZ.
    OBJECTIVE: To assess HZ risk in patients with psoriasis and PsA by systemic treatment and provide recommendations regarding HZ vaccination.
    METHODS: A systematic literature search was performed for HZ in patients with psoriasis and PsA. HZ vaccination guidelines were reviewed, and the medical board of the National Psoriasis Foundation made consensus recommendations in psoriasis and PsA patients using graded evidence.
    RESULTS: In total, 41 studies met inclusion criteria. Systemic corticosteroids (strong, 1), tofacitinib (strong, 1), and combination therapy with biologic and conventional synthetic disease-modifying antirheumatic drugs (weak, 2a) carry increased HZ risk while monotherapy does not. There is insufficient evidence to determine risk with interleukin 12/23, 17, and 23 inhibitors or apremilast (weak, 2a). Recombinant zoster vaccine is recommended for all psoriasis and PsA patients >50 years old and patients <50 years old on tofacitinib, systemic steroids, or combination systemic treatment. Vaccination of patients <50 years old on other systemic therapies may be considered on a case-by-case basis.
    CONCLUSIONS: There was significant heterogeneity between studies.
    CONCLUSIONS: HZ risk depends on disease severity and treatment class. Recombinant zoster vaccine should be given to all psoriasis and PsA patients >50 years old and younger patients at increased risk.
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