B-cell

B 细胞
  • 文章类型: Journal Article
    B细胞表位作图是一种可以鉴定和表征B细胞受体和分泌抗体的特异性抗原结合位点的方法。确定由B细胞克隆结合的氨基酸的抗原性簇的能力提供了前所未有的细节,这将有助于开发针对各种疾病的新颖且有效的疫苗靶标和治疗性抗体。在这里,我们讨论用于映射B细胞表位的常规方法和新兴技术。
    B-cell epitope mapping is an approach that can identify and characterise specific antigen binding sites of B-cell receptors and secreted antibodies. The ability to determine the antigenic clusters of amino acids bound by B-cell clones provides unprecedented detail that will aid in developing novel and effective vaccine targets and therapeutic antibodies for various diseases. Here, we discuss conventional approaches and emerging techniques that are used to map B-cell epitopes.
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  • 文章类型: Case Reports
    背景:胃淋巴瘤是儿童中极为罕见的疾病;通常表现为非特异性症状,这使得大多数病例的诊断相对较晚。在这里,我们介绍了一例儿童胃原发性淋巴母细胞B细胞淋巴瘤。
    方法:一名14岁女性出现腹部不适3个月。在检查中,她有一个活动的上腹部肿块。CT腹部显示肿块占据胃的较小曲率,内窥镜检查证实了这一点。进行了胃大部切除术。标本的组织病理学和流式细胞术,骨髓检查证实了原发性B细胞淋巴母细胞胃淋巴瘤的诊断。
    结论:原发性胃淋巴瘤,特别是,是一种非常罕见的胃肿瘤。此外,报道的大多数病例是成熟的B细胞淋巴瘤亚型.儿童的临床表现与其他类型的原发性胃恶性肿瘤相同。此外,对于儿科年龄组的此类病症的管理,目前尚无指南.在我们的案例中,进行了手术切除;由于最初的内窥镜活检怀疑腺癌,进一步的检查证实了胃原发性淋巴母细胞B细胞淋巴瘤的诊断。
    结论:儿童胃恶性肿瘤的早期发现是预后的关键因素。此外,最佳的手术切除显示出非常好的结果。
    BACKGROUND: Gastric lymphoma is an extremely rare disease in children; it is usually presented with non-specific symptoms, which makes the diagnosis relatively late in most cases. Here we present a case of a primary lymphoblastic B-cell lymphoma of the stomach in a child.
    METHODS: A 14 -year- old female presented with abdominal discomfort for three months. On examination, she had a mobile epigastric mass. The CT abdomen showed a mass occupying the lesser curvature of the stomach, which was confirmed by the endoscopy. A subtotal gastrectomy was carried out. Histopathology and flow cytometry for the specimen, along with bone marrow examination confirmed the diagnosis of primary B-cell lymphoblastic gastric lymphoma.
    CONCLUSIONS: Primary gastric lymphoma, in particular, is a very rare gastric neoplasm. Furthermore, most of the reported cases are mature B-cell lymphoma subtypes. The clinical presentation in children is the same as for other types of primary gastric malignancies. Moreover, no guidelines are available for the management of such conditions in the paediatric age group. In our case, a surgical resection was carried out; as the initial endoscopic biopsy was suspicious for adenocarcinoma, further workup confirmed the diagnosis of primary lymphoblastic B-cell lymphoma of the stomach.
    CONCLUSIONS: Early detection of gastric malignancies in children is a key element in the prognosis. In addition, optimal surgical resection showed a very good outcome.
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  • 文章类型: Journal Article
    ETS原癌基因1(ETS1)是与淋巴细胞发育和功能密切相关的转录因子(TF)。ETS1表达在T细胞的分化和活化过程中受到严格调控,自然杀伤(NK)细胞,B细胞。它也被描述为一系列实体和血液癌症类型中的癌基因。在血液系统恶性肿瘤中,它的作用在T细胞急性淋巴细胞白血病(T-ALL)中得到了最好的研究,成人T细胞白血病/淋巴瘤(ATLL),和弥漫性大B细胞淋巴瘤(DLBCL)。这些恶性肿瘤中ETS1的异常表达主要由染色体扩增和增强子驱动的转录调控驱动。促进ETS1转录程序。ETS1还促进异常表达或激活的转录复合物以驱动致癌途径。总的来说,ETS1的功能是调节细胞生长,分化,信令,对刺激的反应,和病毒在这些恶性肿瘤中的相互作用。在某些淋巴瘤类型中,ETS1也具有肿瘤抑制作用,强调细胞环境在ETS1功能中的重要性。正在进行研究,以进一步描述血液系统恶性肿瘤中ETS1失调的临床意义。进一步解析结合复合物和转录靶标,并确定有效的治疗靶向方法。
    ETS proto-oncogene 1 (ETS1) is a transcription factor (TF) critically involved in lymphoid cell development and function. ETS1 expression is tightly regulated throughout differentiation and activation in T-cells, natural killer (NK) cells, and B-cells. It has also been described as an oncogene in a range of solid and hematologic cancer types. Among hematologic malignancies, its role has been best studied in T-cell acute lymphoblastic leukemia (T-ALL), adult T-cell leukemia/lymphoma (ATLL), and diffuse large B-cell lymphoma (DLBCL). Aberrant expression of ETS1 in these malignancies is driven primarily by chromosomal amplification and enhancer-driven transcriptional regulation, promoting the ETS1 transcriptional program. ETS1 also facilitates aberrantly expressed or activated transcriptional complexes to drive oncogenic pathways. Collectively, ETS1 functions to regulate cell growth, differentiation, signaling, response to stimuli, and viral interactions in these malignancies. A tumor suppressor role has also been indicated for ETS1 in select lymphoma types, emphasizing the importance of cellular context in ETS1 function. Research is ongoing to further characterize the clinical implications of ETS1 dysregulation in hematologic malignancies, to further resolve binding complexes and transcriptional targets, and to identify effective therapeutic targeting approaches.
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  • 文章类型: Letter
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    背景:已知精神分裂症的免疫系统失调,有类似于慢性神经炎症的状态。这个过程的起源是未知的,但众所周知,T和B淋巴细胞,它们是适应性免疫系统的组成部分,在精神分裂症的致病机制中起着重要作用。
    方法:我们通过蛋白质组学分析(n=5精神分裂症和n=5对照)分析了精神分裂症患者的PBMC膜。我们发现存在Kv1.3电压门控钾通道及其辅助亚基β1(KCNAB1)和β2(KCNAB2)。从90名参与者的样本中,我们用全细胞膜片钳实验对淋巴细胞进行了研究(n=7精神分裂症和n=5对照),westernblot(n=40精神分裂症和n=40对照)和共聚焦显微镜来评估不同通道的存在和功能。Kv在两个细胞。
    结果:我们证明了精神分裂症患者PBMC中Kv1.1,Kv1.2,Kv1.3,Kv1.6,Kv4.2,Kv4.3和Kv7.2通道的过表达。这项研究代表了一个开创性的探索,因为它涉及对精神分裂症患者与健康参与者相比的T和B淋巴细胞进行的电生理分析。我们观察到,与健康对照组相比,精神分裂症患者的B淋巴细胞输出电流增加,峰值电流幅度和电压电导曲线更大。
    结论:本研究显示了B淋巴细胞在精神分裂症中的重要性。我们知道精神分裂症患者的免疫系统会发生改变,但是这个系统的生理机制还不是很清楚。我们建议,B淋巴细胞可能与精神分裂症的病理生理学有关,并且应该对其进行更深入的研究。为结合抗精神病药和免疫调节剂的新疗法开辟了一个新的知识和可能性领域。局限性在于所有参与者都接受了抗精神病药物治疗,这可能影响了患者和对照组之间观察到的差异。这意味着需要进行更多的研究,这些研究可以根据抗精神病药物进行分组。
    BACKGROUND: It is known that the immune system is dysregulated in schizophrenia, having a state similar to chronic neuroinflammation. The origin of this process is unknown, but it is known that T and B lymphocytes, which are components of the adaptive immune system, play an important role in the pathogenic mechanisms of schizophrenia.
    METHODS: We analysed the membrane of PBMCs from patients diagnosed with schizophrenia through proteomic analysis (n = 5 schizophrenia and n = 5 control). We found the presence of the Kv1.3 voltage-gated potassium channel and its auxiliary subunit β1 (KCNAB1) and β2 (KCNAB2). From a sample of 90 participants, we carried out a study on lymphocytes with whole-cell patch-clamp experiments (n = 7 schizophrenia and n = 5 control), western blot (n = 40 schizophrenia and n = 40 control) and confocal microscopy to evaluate the presence and function of different channels. Kv in both cells.
    RESULTS: We demonstrated the overexpression of Kv1.1, Kv1.2, Kv1.3, Kv1.6, Kv4.2, Kv4.3 and Kv7.2 channels in PBMCs from patients with schizophrenia. This study represents a groundbreaking exploration, as it involves an electrophysiological analysis performed on T and B lymphocytes from patients diagnosed of schizophrenia compared to healthy participants. We observed that B lymphocytes exhibited an increase in output current along with greater peak current amplitude and voltage conductance curves among patients with schizophrenia compared with healthy controls.
    CONCLUSIONS: This study showed the importance of the B lymphocyte in schizophrenia. We know that the immune system is altered in schizophrenia, but the physiological mechanisms of this system are not very well known. We suggest that the B lymphocyte may be relevant in the pathophysiology of schizophrenia and that it should be investigated in more depth, opening a new field of knowledge and possibilities for new treatments combining antipsychotics and immunomodulators. The limitation is that all participants received antipsychotic medication, which may have influenced the differences observed between patients and controls. This implies that more studies need to be done where the groups can be separated according to the antipsychotic drug.
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  • 文章类型: Journal Article
    儿童急性淋巴细胞白血病(ALL)亚型的基因组分析,特别是T细胞和B细胞谱系,在确定潜在的治疗靶点方面至关重要。典型的基因组分析已经将注意力转向最常见的突变基因。然而,评估突变对癌症表型的贡献至关重要.因此,我们估计了T细胞和B细胞队列中体细胞替代的癌症效应(缩放选择系数),揭示突变贡献的关键见解。众所周知,癌症的影响,B-ALL中NRAS和KRAS等频繁突变的基因高,这强调了它们作为治疗靶点的重要性。然而,突变基因IL7R的频率较低,XBP1和TOX也显示出高癌症效应,提示存在时在白血病发展中的关键作用。在T-ALL中,KRAS和NRAS的突变频率低于B-ALL。然而,它们的癌症效应在两种亚型中都很高。PIK3R1和RPL10突变的患病率不高,但在个别T细胞ALL患者中表现出一些最高的癌症效应。甚至CDKN2A,患病率低,癌症效应相对适中,可能与其突变形式对其他突变的上位效应高度相关。对这些中等频率但潜在高影响的目标进行优先研究不仅提供了新颖的个性化治疗机会,而且还增强了对疾病机制的理解,并促进了儿科ALL的精准治疗。
    The genomic analyses of pediatric acute lymphoblastic leukemia (ALL) subtypes, particularly T-cell and B-cell lineages, have been pivotal in identifying potential therapeutic targets. Typical genomic analyses have directed attention toward the most commonly mutated genes. However, assessing the contribution of mutations to cancer phenotypes is crucial. Therefore, we estimated the cancer effects (scaled selection coefficients) for somatic substitutions in T-cell and B-cell cohorts, revealing key insights into mutation contributions. Cancer effects for well-known, frequently mutated genes like NRAS and KRAS in B-ALL were high, which underscores their importance as therapeutic targets. However, less frequently mutated genes IL7R, XBP1, and TOX also demonstrated high cancer effects, suggesting pivotal roles in the development of leukemia when present. In T-ALL, KRAS and NRAS are less frequently mutated than in B-ALL. However, their cancer effects when present are high in both subtypes. Mutations in PIK3R1 and RPL10 were not at high prevalence, yet exhibited some of the highest cancer effects in individual T-cell ALL patients. Even CDKN2A, with a low prevalence and relatively modest cancer effect, is potentially highly relevant for the epistatic effects that its mutated form exerts on other mutations. Prioritizing investigation into these moderately frequent but potentially high-impact targets not only presents novel personalized therapeutic opportunities but also enhances the understanding of disease mechanisms and advances precision therapeutics for pediatric ALL.
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  • 文章类型: Journal Article
    目的:现代质谱成像(MSI)可以探索单细胞的代谢。这项研究的目的是开发人类CD19淋巴细胞的单细胞MSI和慢性淋巴细胞白血病(CLL)的代谢谱。
    方法:献血者(BD)样本用于优化CD19淋巴细胞分离和单细胞基质辅助激光解吸/电离飞行时间(MALDITOF)MSI。来自5名CLL患者和5名BD的200个CD19+淋巴细胞的独立集合用于CD19+淋巴细胞分类评估和非靶向代谢谱分析。使用偏最小二乘判别分析(PLS-DA)进行CLLvsBD淋巴细胞分类,使用在300-600和600-950Da范围内记录的归一化单细胞质谱。
    结果:通过CD19+淋巴细胞PLS-DA分类的10倍交叉验证评估的准确性达到>90.0%。火山图显示CLL中106个m/z信号发生了显着变化,其中9个被初步注释。在初步注释的m/z信号中,甲醛和谷胱甘肽代谢物以及四氢叶酸盐脱颖而出。
    结论:成功开发了CD19+淋巴细胞的单细胞MALDITOFMSI方法。该方法证实了氧化应激和单碳代谢的重要性,CLL中的丙酮酸和脂肪酸代谢以及细胞凋亡,它为诊断应用提供了代谢候选物。
    OBJECTIVE: Modern mass spectrometry imaging (MSI) enables single cells\' metabolism exploration. Aims of this study were development of the single-cell MSI of human CD19+ lymphocytes and metabolic profiling of chronic lymphocytic leukemia (CLL).
    METHODS: Blood donor (BD) samples were used for the optimization of CD19+ lymphocyte isolation and single-cell matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) MSI. Independent set of 200 CD19+ lymphocytes coming from 5 CLL patients and 5 BD was used for the CD19+ lymphocytes classification assessment and the untargeted metabolic profiling. CLL vs BD lymphocyte classification was performed using partial least squares-discriminant analysis (PLS-DA) using normalized single-cell mass spectra recorded in 300-600 and 600-950 Da ranges was applied.
    RESULTS: Accuracy assessed by 10-fold cross-validation of CD19+ lymphocyte PLS-DA classification reached >90.0 %. Volcano plots showed 106 significantly altered m/z signals in CLL of which 9 were tentatively annotated. Among tentatively annotated m/z signals formaldehyde and glutathione metabolites and tetrahydrofolate stand out.
    CONCLUSIONS: A method for single-cell MALDI TOF MSI of CD19+ lymphocytes was successfully developed. The method confirmed the significance of oxidative stress and single-carbon metabolism, pyruvate and fatty acid metabolism and apoptosis in CLL and it provided metabolic candidates for diagnostic applications.
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  • 文章类型: Journal Article
    目的:我们设计了一种基于病毒刺突蛋白受体结合域(RBD)的SARS-CoV-2表位疫苗。方法:对COVID-19患者的鼻咽拭子进行RT-PCR。在GenBank中注册RBD区域后,物理化学参数,二级结构,同源建模,使用ProtParamExPASy确定RBD区域的3D结构和抗原性,PSIPRED,善解人意,IEDB和Vaxijen在线工具,分别。结果:在非变应原性和抗原性方面预测了B和T细胞表位。MolProbity分析为RBD提供了一个定性模型。同源性模型表明,大多数残基处于最佳能量区域。结论:表位的高免疫原性评分指示用于开发多表位疫苗的有希望的候选物。它可能有助于开发有效的疫苗。
    为了鉴定SARS-CoV-2中S蛋白的RBD区序列,对4例转诊至Ardabil伊玛目霍梅尼医院的COVID-19患者的鼻咽拭子样本进行了RT-PCR检测。在GenBank数据库中注册RBD区域的序列后,物理化学参数,二级结构,同源建模,使用ProtParamExPASy确定RBD区域的3D结构和抗原性,PSIPRED,善解人意,IEDB和Vaxijen在线工具,分别。
    Aim: We designed a SARS-CoV-2 epitope vaccine based on the receptor-binding domain (RBD) in virus spike protein. Methods: RT-PCR performed on nasopharyngeal swab COVID-19 patients. After registering RBD region in the GenBank, physicochemical parameters, secondary structure, homology modeling, 3D structure of RBD region and antigenicity were determined using ProtParam ExPASy, PSIPRED, MolProbity, IEDB and Vaxijen online tools, respectively. Results: B and T cell epitopes were predicted in terms of non-allergenicity and antigenicity. MolProbity analysis provided a qualitative model for RBD. The homology model showed that most of the residues are in optimal district of energy. Conclusion: High immunogenicity score of epitopes indicates promising candidates for the development of multi-epitope vaccines. It may help to develop an effective vaccine.
    In order to identify the sequence of RBD region of S protein in SARS-CoV-2, RT-PCR test was performed on nasopharyngeal swab samples of four COVID-19 patients referred to Imam Khomeini Hospital in Ardabil. After registering the sequence of the RBD region in the GenBank database, the physicochemical parameters, secondary structure, homology modeling, 3D structure of the RBD region and antigenicity were determined using ProtParam ExPASy, PSIPRED, MolProbity, IEDB and Vaxijen online tools, respectively.
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  • 文章类型: Journal Article
    痘病毒科的猴痘病毒(MPXV)引起一种称为猴痘(Mpox)的人畜共患疾病。MPXV病例在全球范围内的死亡率为0%至11%,并且在儿童中更为普遍。有三代天花疫苗可以预防MPXV。第一代和第二代牛痘病毒(VACV)疫苗保护MPXV。然而,各种不良副作用与第一代和第二代疫苗有关。相比之下,改良的Ankara-Bavarian北欧痘苗(MVA-BN)无复制能力疫苗在哺乳动物细胞中显示较少的不良反应和显著量的中和抗体.第三代改良的安卡拉-巴伐利亚北欧牛痘(MVA-BN)在2019年被批准用于预防水痘。最近,基于MVA-BN的Imvanex,Imvamune,和JYNNEOS疫苗也被用于对抗MPXV。全球范围内,由于MPXV病例增加,世界卫生组织(WHO)于2022年5月宣布全球卫生紧急情况。各种计算研究还设计了针对MPXV的基于多表位的疫苗。在基于多表位的疫苗中,不同的表位,如B细胞,细胞毒性T淋巴细胞(CTL),CD8+,和CD4+表位来源于MPXV蛋白。Further,这些表位在各种接头的帮助下连接,以设计针对MPXV的多表位疫苗.总之,我们概述了MPXV疫苗的现状.
    Monkeypox virus (MPXV) of poxviridae family causes a zoonotic disease called monkeypox (Mpox). MPXV cases have a fatality ratio ranging from 0 to 11% globally and have been more prevalent in children. There are three generations of smallpox vaccines that protect against MPXV. First and second generation of the vaccinia virus (VACV) vaccine protects MPXV. However, various adverse side effects were associated with the first and second generations of vaccines. In contrast, the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) replication-incompetent vaccine shows fewer adverse effects and a significant amount of neutralizing antibodies in mammalian cells. A third-generation Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) was approved to prevent Mpox in 2019. Recently, MVA-BN-based Imvanex, Imvamune, and JYNNEOS vaccines have also been administered against MPXV. Globally, the World Health Organization (WHO) declared a global health emergency in May 2022 due to increased MPXV cases. Various computational studies have also designed a multi-epitope-based vaccine against the MPXV. In the multi-epitope-based vaccine, different epitopes like B-cell, Cytotoxic T Lymphocyte (CTL), CD8+, and CD4+ epitopes were derived from MPXV proteins. Further, these epitopes were linked with the help of various linkers to design a multi-epitope vaccine against MPXV. In summary, we have provided an overview of the current status of the vaccine against MPXV.
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