immune responses

免疫应答
  • 文章类型: Journal Article
    海洋软体动物的产量在全球范围内不断增加,这种趋势在南美国家得到了证明,在那里生产了几种双壳类动物,利用,和交易。这项活动为生态系统带来了好处,因为它比其他水产养殖方式影响小,污染小,和沿海人类社区,因为它提供食物和收入。然而,病原体爆发是一个主要问题,可能会使整个发展中部门面临风险。Perkinsosis是一种由Perkinsusspp引起的疾病。影响全球软体动物的原生动物。在这篇综述中,我们提供了有关Perkinsusspp的信息。在南美的双壳类动物中。迄今为止,这些寄生虫的感染仅在阿根廷沿海的大西洋双壳类动物中报告,乌拉圭,和巴西。绝大多数病例和研究报告来自巴西。我们在这里全面回顾这些结果。最后,我们建议对未来的研究进行一些考虑,这可能会扩大我们对这些寄生虫的认识。
    Marine mollusk production is increasing worldwide, and this trend is being evidenced in South American countries, where several species of bivalves are produced, exploited, and traded. This activity brings benefits either for the ecosystem, as it is a less impactful and polluting than other aquaculture practices, and to coastal human communities, as it provides food and income. However, emergence of outbreaks by pathogens is a major concern and can put an entire developing sector at risk. Perkinsosis is a disease caused by Perkinsus spp. protozoans that affect mollusks worldwide. In this review we provide information on Perkinsus spp. among bivalves from South America. Infections by these parasites were only reported to date among coastal Atlantic bivalves of Argentina, Uruguay, and Brazil. The vast majority of cases and studies are reported from Brazil. We comprehensively review those results here. Finally, we suggest some considerations for future investigations that may expand our knowledge of these parasites.
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  • 文章类型: Journal Article
    腺相关病毒(AAV)载体在基因治疗中的应用已显示出治疗遗传疾病的巨大潜力。然而,输注相关反应(IAR)对基于AAV的基因治疗的安全性和有效性提出了重大挑战.这篇综述提供了当前对IAR对AAV治疗的理解的全面总结。包括它们的潜在机制,临床表现,和治疗选择。Toll样受体激活和随后产生的促炎细胞因子与IAR相关,刺激中和抗体(Nab)和干扰基因治疗的T细胞反应。IAR的风险因素包括高滴度的预先存在的Nabs,以前接触过AAV,和特定的合并症。临床表现范围从轻度流感样症状到严重过敏反应,并且可在AAV施用期间或之后发生。对于AAV疗法的给药前后测试,没有既定的指南,和常规实验室要求不标准化。治疗方案包括皮质类固醇,血浆置换,以及抗组胺药和对乙酰氨基酚等支持性药物,但是在管理路线上没有共识,剂量,和持续时间。这篇综述强调了目前IAR治疗方案的不足,以及需要进一步研究以提高基于AAV的基因治疗的安全性和有效性。
    The use of adeno-associated virus (AAV) vectors in gene therapy has demonstrated great potential in treating genetic disorders. However, infusion-associated reactions (IARs) pose a significant challenge to the safety and efficacy of AAV-based gene therapy. This review provides a comprehensive summary of the current understanding of IARs to AAV therapy, including their underlying mechanisms, clinical presentation, and treatment options. Toll-like receptor activation and subsequent production of pro-inflammatory cytokines are associated with IARs, stimulating neutralizing antibodies (Nabs) and T-cell responses that interfere with gene therapy. Risk factors for IARs include high titers of pre-existing Nabs, previous exposure to AAV, and specific comorbidities. Clinical presentation ranges from mild flu-like symptoms to severe anaphylaxis and can occur during or after AAV administration. There are no established guidelines for pre- and postadministration tests for AAV therapies, and routine laboratory requests are not standardized. Treatment options include corticosteroids, plasmapheresis, and supportive medications such as antihistamines and acetaminophen, but there is no consensus on the route of administration, dosage, and duration. This review highlights the inadequacy of current treatment regimens for IARs and the need for further research to improve the safety and efficacy of AAV-based gene therapy.
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  • 文章类型: Journal Article
    背景与目的:炎症性肠病(IBD),包括克罗恩病和溃疡性结肠炎,是一种慢性炎性疾病,其特征在于胃肠道中异常的免疫应答和受损的屏障功能。IBD与结肠中肠道微生物群及其代谢产物的改变有关。丁酸,肠道微生物代谢产物,在调节免疫功能中起着至关重要的作用,上皮屏障功能,和肠道稳态。在这次审查中,我们旨在概述丁酸盐的合成和代谢以及丁酸盐在维持肠道稳态中的作用机制,并讨论丁酸盐在IBD中的治疗意义。方法:我们通过PubMed搜索了截至2023年3月的文献,WebofScience,以及其他使用诸如丁酸盐之类的搜索词的来源,炎症,IBD,克罗恩病,和溃疡性结肠炎.患者的临床研究和IBD啮齿动物模型的临床前研究包括在丁酸盐的治疗意义的总结中。结果:近二十年的研究表明丁酸对肠道免疫功能和上皮屏障功能的有益作用。大多数临床前和临床研究表明,丁酸盐口服补充剂在减轻结肠炎动物模型和IBD患者的炎症和维持缓解方面具有积极作用。然而,丁酸灌肠显示混合效应。产丁酸饮食,包括发芽的大麦食品和燕麦麸,在动物模型和IBD患者中发现增加粪便丁酸盐浓度并降低疾病活动指数。结论:目前的文献表明丁酸盐是减少炎症和维持IBD缓解的潜在附加疗法。需要进一步的临床研究来确定单独施用丁酸盐是否是IBD的有效治疗性治疗。
    Background and objective: Inflammatory bowel disease (IBD), including Crohn\'s disease and ulcerative colitis, is a chronic inflammatory disorder characterized by aberrant immune responses and compromised barrier function in the gastrointestinal tract. IBD is associated with altered gut microbiota and their metabolites in the colon. Butyrate, a gut microbial metabolite, plays a crucial role in regulating immune function, epithelial barrier function, and intestinal homeostasis. In this review, we aim to present an overview of butyrate synthesis and metabolism and the mechanism of action of butyrate in maintaining intestinal homeostasis and to discuss the therapeutic implications of butyrate in IBD. Methods: We searched the literature up to March 2023 through PubMed, Web of Science, and other sources using search terms such as butyrate, inflammation, IBD, Crohn\'s disease, and ulcerative colitis. Clinical studies in patients and preclinical studies in rodent models of IBD were included in the summary of the therapeutic implications of butyrate. Results: Research in the last two decades has shown the beneficial effects of butyrate on gut immune function and epithelial barrier function. Most of the preclinical and clinical studies have shown the positive effect of butyrate oral supplements in reducing inflammation and maintaining remission in colitis animal models and IBD patients. However, butyrate enema showed mixed effects. Butyrogenic diets, including germinated barley foodstuff and oat bran, are found to increase fecal butyrate concentrations and reduce the disease activity index in both animal models and IBD patients. Conclusions: The current literature suggests that butyrate is a potential add-on therapy to reduce inflammation and maintain IBD remission. Further clinical studies are needed to determine if butyrate administration alone is an effective therapeutic treatment for IBD.
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  • 文章类型: Journal Article
    冠状病毒在自然界中广泛存在,可以感染哺乳动物和家禽,让他们成为公众健康问题。全球范围内,预防和控制新出现和重新出现的动物冠状病毒是一个巨大的挑战。病毒介导的免疫应答机制对病毒防控研究具有重要意义。抗原表位是能够刺激抗体或致敏淋巴细胞产生的化学基团。在抗病毒免疫反应中发挥重要作用。因此,它可以揭示诊断方法和新型疫苗的发展。这里,我们回顾了动物冠状病毒抗原表位研究的进展,旨在为动物和人冠状病毒的防控提供参考。
    在线版本包含10.1186/s44149-023-00080-0提供的补充材料。
    Coronaviruses are widespread in nature and can infect mammals and poultry, making them a public health concern. Globally, prevention and control of emerging and re-emerging animal coronaviruses is a great challenge. The mechanisms of virus-mediated immune responses have important implications for research on virus prevention and control. The antigenic epitope is a chemical group capable of stimulating the production of antibodies or sensitized lymphocytes, playing an important role in antiviral immune responses. Thus, it can shed light on the development of diagnostic methods and novel vaccines. Here, we have reviewed advances in animal coronavirus antigenic epitope research, aiming to provide a reference for the prevention and control of animal and human coronaviruses.
    UNASSIGNED: The online version contains supplementary material available at 10.1186/s44149-023-00080-0.
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  • 文章类型: Systematic Review
    霍乱是由霍乱弧菌引起的肠道疾病,一种水媒病原体,以严重腹泻为特征。世卫组织已建议在资源有限的环境中使用疫苗。目前获得许可的霍乱疫苗在地方性环境中的效果并不理想,在五岁以下的儿童中效果较低,最容易感染这种疾病的一部分人口。开发下一代霍乱疫苗需要详细了解所需的保护性免疫反应。
    在这篇评论中,我们回顾了临床试验,这些试验的重点是在霍乱弧菌感染期间和疫苗接种后引起的早期转录粘膜反应,同时总结了针对霍乱弧菌的效应免疫反应的各种成分.
    目前获得许可的灭活疫苗无法在局部引发关键的炎症途径,这可能是它们在地方性环境中功效受限的原因。需要更多的研究来了解这些地区霍乱减毒活疫苗的免疫原性。各种外在和内在因素影响抗霍乱免疫,需要考虑开发区域特异性下一代疫苗。
    Cholera is an enteric disease caused by Vibrio cholerae, a water-borne pathogen, and characterized by severe diarrhea. Vaccines have been recommended for use by the WHO in resource-limited settings. Efficacies of the currently licensed cholera vaccines are not optimal in endemic settings and low in children below the age of five, a section of the population most susceptible to the disease. Development of next generation of cholera vaccines would require a detailed understanding of the required protective immune responses.
    In this review, we revisit clinical trials which are focused on the early transcriptional mucosal responses elicited during Vibrio cholerae infection and upon vaccination along with summarizing various components of the effector immune response against Vibrio cholerae.
    The inability of currently licensed killed/inactivated vaccines to elicit key inflammatory pathways locally may explain their restricted efficacy in endemic settings. More studies are required to understand the immunogenicity of the live attenuated cholera vaccine in these regions. Various extrinsic and intrinsic factors influence anti-cholera immunity and need to be considered to develop region-specific next generation vaccines.
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  • 文章类型: Journal Article
    2019年冠状病毒病(COVID-19),由SARS-CoV-2引起的,已经影响了数百万人,具有各种影响。与微生物组在决定人类健康和疾病方面的关键作用一致,各种研究调查了肠道和呼吸道微生物组对COVID-19的影响。微生物菌群失调可能支持进入,复制,并通过调节各种机制建立SARS-CoV-2感染。COVID-19感染期间呼吸道微生物组成的调节影响疾病程度的主要机制之一是先天和获得性免疫反应的变化,包括炎症标志物和细胞因子以及B细胞和T细胞。COVID-19患者呼吸道微生物群的多样性存在争议;一些研究报告称微生物多样性较低,而其他人发现了高度的多样性,提示呼吸道微生物在这种疾病中的作用。通过补充和营养素调节微生物群的多样性和分布可用于预防和治疗COVID-19。这里,我们讨论了各种肺部疾病期间的肺部微生物群失调及其与免疫细胞的相互作用,专注于COVID-19。
    Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has affected millions of individuals with various implications. Consistent with the crucial role of the microbiome in determining health and disease in humans, various studies have investigated the gut and respiratory microbiome effect on the COVID-19. Microbiota dysbiosis might support the entry, replication, and establishment of SARS-CoV-2 infection by modulating various mechanisms. One of the main mechanisms that the modulation of respiratory microbiota composition during the COVID-19 infection affects the magnitude of the disease is changes in innate and acquired immune responses, including inflammatory markers and cytokines and B- and T-cells. The diversity of respiratory microbiota in COVID-19 patients is controversial; some studies reported low microbial diversity, while others found high diversity, suggesting the role of respiratory microbiota in this disease. Modulating microbiota diversity and profile by supplementations and nutrients can be applied prophylactic and therapeutic in combating COVID-19. Here, we discussed the lung microbiome dysbiosis during various lung diseases and its interaction with immune cells, focusing on COVID-19.
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  • 文章类型: Journal Article
    在围产期,脂肪组织(AT)中的脂解动员脂肪酸储备以满足奶牛的高能量需求。这种生理反应伴随着调节代谢功能的过多蛋白质(脂肪因子)和脂质产物的合成和分泌。在AT,脂肪分解产生自由基(FR),包括活性氧,并导致以炎症反应为特征的重塑过程。在具有足够脂肪分解反应的健康奶牛的AT中,抗氧化剂防御中和FR,与重塑相关的炎症迅速解决。这些过程的控制是通过最近的转录组和蛋白质组分析鉴定的许多炎症和氧化应激(OS)相关途径协调的。例如,分娩和泌乳开始增强补体和急性期蛋白的转录和翻译,同时,丰富的抗氧化剂防御,中和FR,包括Nrf2。然而,在脂肪分解加剧和延长的奶牛中,FR的生产迅速耗尽抗氧化系统,和操作系统的发展。OS在AT中的有害作用包括激活炎症反应和抑制AT内的胰岛素信号传导。通过加强AT炎症,OS损害脂肪细胞对胰岛素的反应。这导致了一个恶性循环,OS加剧了AT脂解和炎症,这进一步促进了OS。这篇综述总结了当前有关奶牛围产期AT炎症反应和OS调节机制的知识。
    During the periparturient period, lipolysis in adipose tissue (AT) mobilizes fatty acid reserves to meet high energy needs of dairy cows. This physiological response is accompanied by the synthesis and secretion of a plethora of proteins (adipokines) and lipid products that modulate metabolic functions. In the AT, lipolysis generates free radicals (FR), including reactive oxygen species, and leads to a remodeling process characterized by an inflammatory response. In the AT of healthy cows with adequate lipolytic responses, antioxidant defenses neutralize FR, and the inflammation associated with remodeling is rapidly resolved. The control of these processes is orchestrated by numerous inflammatory and oxidative stress (OS)-related pathways identified by recent transcriptomic and proteomic analyses. For example, parturition and the onset of lactation enhance the transcription and translation of complement and acute-phase proteins and, at the same time, enrich antioxidant defenses that neutralize FR, including Nrf2. However, in cows with exacerbated and protracted lipolysis, the production of FR rapidly depletes antioxidant systems, and OS develops. The harmful effects of OS in AT include activating inflammatory responses and inhibiting insulin signaling within AT. By intensifying AT inflammation, OS impairs adipocyte response to insulin. This leads to a vicious circle where OS exacerbates AT lipolysis and inflammation, which further promotes OS. This review summarizes current knowledge on the mechanisms that modulate AT inflammatory responses and OS during the periparturient period of dairy cows.
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  • 文章类型: Journal Article
    尽管潜在的疾病与成人的严重病程有关,并且已经广泛报道了实验室异常,关于已有共患疾病的儿童2019年冠状病毒病(COVID-19)的临床病程和实验室检查结果,没有足够的数据.我们旨在描述评估儿童COVID-19严重程度的独立危险因素。在2020年3月11日至12月31日期间因COVID-19住院的所有1个月至18岁儿童均纳入研究。根据标准将患者分为轻度(组1)和中度+重度/危重(组2)严重程度。人口特征,合并症,比较两组间的实验室变量。共有292名确认感染COVID-19的儿童被纳入研究。最常见的相关疾病是肥胖(5.1%)和支气管哮喘(4.1%)。我们观察到患有基础疾病的患者疾病进展更严重,尤其是肥胖和支气管哮喘(肥胖比值比[OR]9.1,95%置信区间[CI]1.92-43.28,p=0.005,支气管哮喘患者OR4.1,95%CI1.04-16.80,p=0.044).在第2组患者中,存在淋巴细胞减少和低蛋白血症,以及血清C反应蛋白水平的升高,降钙素原,和尿酸检测,这些结果具有统计学意义(p值;p<0.001,p=0.046,p=0.006,p=0.045,p<0.001)。儿童中重度COVID-19感染的最强预测因子是尿酸,比值比为1.6(95%CI1.14-2.13,p=0.005),淋巴细胞比值比为0.7(95%CI0.55-0.88,p=0.003)。尽管儿童不太容易感染COVID-19,但预先存在的合并症可能易患严重疾病。此外,淋巴细胞减少和高尿酸是COVID-19感染可能进展更严重的指标。
    Although the underlying disease is associated with a severe course in adults and laboratory abnormalities have been widely reported, there are not sufficient data on the clinical course of coronavirus disease 2019 (COVID-19) in children with pre-existing comorbid conditions and on laboratory findings. We aimed to describe the independent risk factors for estimating the severity of the COVID-19 in children. All children between 1 month and 18 years old who were hospitalized during the period of March 11-December 31, 2020, resulting from COVID-19 were included in the study. Patients were categorized into mild (group 1) and moderate + severe/critically (group 2) severity based on the criteria. Demographic characteristics, comorbidities, and laboratory variables between the two groups were compared. A total of 292 children confirmed to have COVID-19 infection were included in the study. The most common associated diseases were obesity (5.1%) and asthma bronchiale (4.1%). We observed that disease progressed more severely in patients with underlying diseases, especially obesity and asthma bronchiale (for patients with obesity odds ratio [OR] 9.1, 95% confidence interval [CI] 1.92-43.28, p = 0.005 and for patients with asthma bronchiale OR 4.1, 95% CI 1.04-16.80, p = 0.044). In group 2 patients, presence of lymphopenia and hypoalbuminemia, and also an elevation in serum levels of C-reactive protein, procalcitonin, and uric acid were detected and these results were statistically significant (p values; p < 0.001, p = 0.046, p = 0.006, p = 0.045, p < 0.001, respectively). The strongest predictor of moderate-severe COVID-19 infections in the children was uric acid, with an odds ratio of 1.6 (95% CI 1.14-2.13, p = 0.005) and lymphocytes with an odds ratio of 0.7 (95% CI 0.55-0.88, p = 0.003). Although children are less susceptible to COVID-19, the pre-existing comorbid condition can predispose to severe disease. In addition, lymphopenia and high uric acid are indicators that COVID-19 infection may progress more severely.
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  • 文章类型: Journal Article
    Therapeutic manipulation of the immune system in cancer has been an extensive area of research in the field of oncoimmunology. Immunosuppression regulates antitumour immune responses. An immunosuppressive enzyme, indoleamine 2,3-dioxygenase (IDO) mediates tumour immune escape in various malignancies including breast cancer. IDO upregulation in breast cancer cells may lead to the recruitment of regulatory T (T-regs) cells into the tumour microenvironment, thus inhibiting local immune responses and promoting metastasis. Immunosuppression induced by myeloid derived suppressor cells activated in an IDO-dependent manner may enhance the possibility of immune evasion in breast cancer. IDO overexpression has independent prognostic significance in a subtype of breast cancer of emerging interest, basal-like breast carcinoma. IDO inhibitors as adjuvant therapeutic agents may have clinical implications in breast cancer. This review proposes future prospects of IDO not only as a therapeutic target but also as a valuable prognostic marker for breast cancer.
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  • 文章类型: Journal Article
    The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted an urgent need to identify effective medicines for the prevention and treatment of the disease. A comparative analysis between SARS-CoV-2 and Hepatitis C Virus (HCV) can expand the available knowledge regarding the virology and potential drug targets against these viruses. Interestingly, comparing HCV with SARS-CoV-2 reveals major similarities between them, ranging from the ion channels that are utilized, to the symptoms that are exhibited by patients. Via this comparative analysis, and from what is known about HCV, the most promising treatments for COVID-19 can focus on the reduction of viral load, treatment of pulmonary system damages, and reduction of inflammation. In particular, the drugs that show most potential in this regard include ritonavir, a combination of peg-IFN, and lumacaftor-ivacaftor. This review anaylses SARS-CoV-2 from the perspective of the role of ion homeostasis and channels in viral pathomechanism. We also highlight other novel treatment approaches that can be used for both treatment and prevention of COVID-19. The relevance of this review is to offer high-quality evidence that can be used as the basis for the identification of potential solutions to the COVID-19 pandemic.
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