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Molecular Cloning and In Silico Analysis of hIL-6 Gene from Pakistani Dengue Hemorrhagic Fever Patients 巴基斯坦登革热患者hIL-6基因的分子克隆及原位杂交分析
Pub Date : 2017-06-14 DOI: 10.15406/moji.2017.05.00170
Fariha Kanwal, A. Simair, Ting Chen, Yunlon Zhang, I. Qadri, Changrui Lu
Interleukin 6 (IL-6) is an important player against infections and tissue damage in mammalian host defense. Its biological functions are evidently spacious including hematopoiesis, modulation of immune response, regulation of endocrine and nervous systems, protective plasma proteins, acute-phase proteins by the liver and control of body temperature [1-3]. IL-6 works in an expansive manner on cells of the immune and nonimmune system and most often behave like a hormone affecting homeostatic processes. Its prompt induction starts with the onset of any tissue damage or inflammation, activating the host defense and terminates upon tissue homeostasis restoration [4,5]. However, the deregulated persistent synthesis of IL-6 has been seen in the development of various autoimmune, chronic inflammatory diseases and cancers [6]. Clinical trials using the humanized anti-IL-6 receptor monoclonal antibody have verified the efficacy of IL-6 blockade for the treatment of unmanageable inflammatory diseases, such as systemic juvenile idiopathic arthritis, rheumatoid arthritis, and Castleman’s disease. Its situation-dependent pro and anti-inflammatory nature makes cytokine as a top intention for clinical intervention [7-10]. However, IL-6 have several alternative molecular forms with multi-pattern post-translational modifications but its diverse cellular response is unclear and the recombinant IL-6 from bacteria without modifications reproducing all known functions left these post-translational modifications as non-causative for diverse actions of IL-6 [11,12].
白细胞介素6 (IL-6)在哺乳动物宿主防御中具有重要的抗感染和组织损伤作用。其生物学功能明显丰富,包括造血、调节免疫反应、调节内分泌和神经系统、保护血浆蛋白、肝脏急性期蛋白和控制体温[1-3]。IL-6以广泛的方式作用于免疫和非免疫系统的细胞,通常表现得像一种影响体内平衡过程的激素。它的迅速诱导始于任何组织损伤或炎症的发生,激活宿主防御,并在组织稳态恢复时终止[4,5]。然而,在各种自身免疫性疾病、慢性炎症性疾病和癌症的发展中,IL-6的持续合成已被发现。使用人源化抗IL-6受体单克隆抗体的临床试验证实了IL-6阻断治疗难以控制的炎症性疾病的疗效,如全身性青少年特发性关节炎、类风湿性关节炎和Castleman病。细胞因子的情境依赖性和抗炎性使其成为临床干预的首选[7-10]。然而,IL-6有多种可选择的分子形式,具有多种模式的翻译后修饰,但其不同的细胞反应尚不清楚,来自细菌的重组IL-6没有修饰,复制了所有已知的功能,使得这些翻译后修饰对IL-6的不同作用没有导致作用[11,12]。
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引用次数: 0
Tumor Lysis Syndrome Caused by Therapeutic Monoclonal Antibodies Approved by FDA 美国食品药品监督管理局批准的治疗性单克隆抗体引起的肿瘤溶解综合征
Pub Date : 2017-06-06 DOI: 10.15406/MOJI.2017.05.00169
H. Cai
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引用次数: 8
Immunopathological Effects Of Aquaporin-4 Ig G In Neuromyelitis Optica Spectrum Disorders 水通道蛋白- 4ig在视神经脊髓炎中的免疫病理作用
Pub Date : 2017-05-29 DOI: 10.15406/moji.2017.05.00168
K. Chan, Cl Ng, L. Yick
Neuromyelitis optica spectrum disorders (NMOSD) are central nervous system inflammatory disorders. Recently, autoimmunity against aquaporin-4 (AQP4) water channel is identified to be the underlying immunopathogenetic mechanism of the majority of NMOSD patients. This is evidenced by the detection of IgG autoantibodies against aquaporin-4 (AQP4-IgG) in the serum of ~75%-80% of typical neuromyelitis optica patients. Detection of AQP4-IgG is highly specific for NMOSD, facilitates diagnosis of NMOSD and their distinction from classical multiple sclerosis. Besides its diagnostic value, AQP4-IgG is likely directly pathogenic in NMOSD. This review focuses on the immunopathological effects of AQP4-IgG in NMOSD.
视神经脊髓炎谱系障碍(NMOSD)是中枢神经系统炎症性疾病。近年来,针对水通道蛋白-4 (aquaporin-4, AQP4)的自身免疫被认为是大多数NMOSD患者潜在的免疫发病机制。75% ~ 80%典型视神经脊髓炎患者血清中检测到抗水通道蛋白-4 (AQP4-IgG)的IgG自身抗体,证明了这一点。检测AQP4-IgG对NMOSD具有高度特异性,有助于NMOSD的诊断和与经典多发性硬化的区分。除了诊断价值外,AQP4-IgG可能是NMOSD的直接致病因子。本文就AQP4-IgG在NMOSD中的免疫病理作用作一综述。
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引用次数: 0
Linear Immunoglobulin A Dermatosis-A Less Reported Clinicopathologic Entity 线性免疫球蛋白A皮肤病-一个较少报道的临床病理实体
Pub Date : 2017-05-17 DOI: 10.15406/MOJI.2017.05.00166
C. Bg, Sridhar, P. Giri, R. Rao
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引用次数: 0
Comparing Vitamin D and Uterine Leiomyoma Association to VDR Knock-Out Mouse 比较维生素D与VDR敲除小鼠子宫平滑肌瘤的关系
Pub Date : 2017-05-09 DOI: 10.15406/MOJI.2017.05.00165
A. Andaloussi
Uterine leiomyoma is common women health issue at reproductive age. The vitamin D and it’s receptor deficiency are associated with UL in African-American patients at reproductive age. This association are not strong enough to be supported by VDR knock-out animal model phenotype, due to lack of spontaneous UL development. Here, we are trying to emphasize on the fact that VDR KO mice phenotype reveal predisposition to malignancy diet dependent to lead to tumor mass induction.
子宫平滑肌瘤是育龄妇女常见的健康问题。维生素D及其受体缺乏与育龄非裔美国人的UL有关。由于缺乏自发的UL发展,这种关联不足以得到VDR敲除动物模型表型的支持。在这里,我们试图强调这样一个事实,即VDR-KO小鼠的表型揭示了恶性饮食依赖性的倾向,从而导致肿瘤质量诱导。
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引用次数: 0
CEACAM Gene Family: A Circuitous Journey towards Metastasis in Breast Cancer CEACAM基因家族:癌症转移的迂回之旅
Pub Date : 2017-05-04 DOI: 10.15406/MOJI.2017.05.00164
Waqas Iqbal, Saleh Al-karim, H. M. Ali, K. Saini
The ubiquitous up-regulation of CEACAM6 in colon, pancreatic, breast and lung cancer is well established. This protein is known for its invasive and metastatic properties in pancreatic adenocarcinoma as well as in breast cancer. We propose that the overexpression of CEACAM5 and CEACAM6 are a pre-requisite for invasive and metastatic behavior of breast cancer. We have conducted bioinformatics studies to compare the expression profiles of CEA gene family members in sets of RNA-seq data for MCF10A (non-tumorigenic epithelial cell line) and MCF7 (human breast cancer cell line) obtained from European Nucleotide Archives. RNA-seq data was mapped using HISAT2 followed by alignment and abundance analysis using Stringtie and visualized using ballgown package in R software environment. Specifically, we observed a 4.5-fold upregulation in CEACAM5 expression while 7-fold increase was recorded for CEACAM6 expression. We propose that the up-regulation of both these proteins in MCF7 cell line compared to MCF10A implicates their inconspicuous role in tumorigenesis, enhanced invasiveness and thus, leading to increased propensity towards breast cancer metastasis. Further studies are required in breast cancer cell lines and appropriate animal models to validate these in silico observations.
CEACAM6在结肠癌、胰腺癌、乳腺癌和肺癌中的普遍上调已得到充分证实。这种蛋白在胰腺癌和癌症中具有侵袭性和转移性。我们认为CEACAM5和CEACAM6的过度表达是癌症侵袭和转移行为的先决条件。我们进行了生物信息学研究,以比较从欧洲核苷酸档案馆获得的MCF10A(非致瘤上皮细胞系)和MCF7(人类癌症细胞系)的RNA-seq数据集中CEA基因家族成员的表达谱。使用HISAT2绘制RNA-seq数据,然后使用Stringtie进行比对和丰度分析,并在R软件环境中使用ballroath包进行可视化。具体而言,我们观察到CEACAM5表达上调4.5倍,而CEACAM6表达上调7倍。我们认为,与MCF10A相比,MCF7细胞系中这两种蛋白的上调表明,它们在肿瘤发生中的作用不明显,增强了侵袭性,从而增加了乳腺癌症转移的倾向。需要对乳腺癌症细胞系和适当的动物模型进行进一步研究,以验证这些计算机观测结果。
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引用次数: 2
Extracellular Traps and Co-Stimulatory Molecules in Leukocytes of Patients with Positive Serology for Chagas Disease Chagas病血清学阳性患者白细胞中的细胞外陷阱和共刺激分子
Pub Date : 2017-04-21 DOI: 10.15406/moji.2017.05.00163
Fern, O. MarcosRodriguez, A. Vargas, C. Miotti, Natalio Emilio González Silva, S. Frattari, Ivon Teresa ClaraNovak
Extracellular traps (ETs) are structures composed of chromatin, histones and granular proteins, first described on 2004 in neutrophils by Brinkmann, et al. [1], constitute a new mechanism of defense of the immune system in response to diverse microorganisms and other varied stimuli. In stimulated cells, the development of this phenomenon begins with the decondensation of the chromatin simultaneously with the loss of the nuclear structure. As the nuclear sheaths are separated, cytoplasm and granules are shown unchanged. At a later time the nuclear membrane disintegrates into vesicles and the granules disintegrate, resulting in the mixing of the contents of the nuclear, cytoplasmic and granular compartments. Finally, the combination of all these components is thrown into the extracellular space [2]. The most studied costimulatory pathway in T lymphocyte activation is the B7-1 (CD80)/B7-2 (CD86): CD28/CTLA4 pathway. Regulatory T lymphocytes are dependent for their generation and maintenance of costimulation by this B7: CD28 pathway [3]. The co-stimulatory molecules CD80 and CD86 are constitutively expressed in some cell types and are classically described as molecules of professional antigen-presenting cells such as dendritic cells, macrophages and B lymphocytes. These molecules are expressed at low intensity in resting cells but can be induced by inflammatory cytokines and by stimulation of Toll-like receptors with microbial products such as lipopolysaccharide (LPS) [3]. In neutrophils, it has been observed that such costimulatory molecules can be stored in their cytoplasmic granules and under certain stimuli expressed on the cell surface [4]. In a previous work, we have described the Colocalization of CD80 and CD86 costimulatory molecules in neutrophil extracellular traps (NETs) in cultures of total autologous leukocytes in healthy human blood samples [5].
细胞外陷阱(Extracellular traps, ETs)是由染色质、组蛋白和颗粒蛋白组成的结构,由Brinkmann等人于2004年首次在中性粒细胞中描述,构成了免疫系统应对多种微生物和其他各种刺激的一种新的防御机制。在受刺激的细胞中,这种现象的发展始于染色质的去浓缩,同时细胞核结构的丧失。随着核鞘的分离,细胞质和颗粒不变。稍后,核膜分解成囊泡,颗粒分解,导致细胞核、细胞质和颗粒室的内容物混合。最后,所有这些成分的组合被抛入细胞外空间[2]。目前研究最多的T淋巴细胞激活共刺激通路是B7-1 (CD80)/B7-2 (CD86): CD28/CTLA4通路。调节性T淋巴细胞依赖于B7: CD28通路产生和维持共刺激[3]。共刺激分子CD80和CD86在某些细胞类型中组成性表达,通常被描述为专业抗原呈递细胞(如树突状细胞、巨噬细胞和B淋巴细胞)的分子。这些分子在静息细胞中以低强度表达,但可被炎症细胞因子和微生物产物如脂多糖(LPS)[3]刺激toll样受体诱导。在中性粒细胞中,已经观察到这种共刺激分子可以储存在它们的细胞质颗粒中,并在某些刺激下在细胞表面表达[4]。在之前的工作中,我们描述了CD80和CD86共刺激分子在健康人类血液样本中培养的总自体白细胞的中性粒细胞胞外陷阱(NETs)中的共定位。
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引用次数: 2
Chronic Urticaria in Children: An Update about Etiology 儿童慢性荨麻疹病因研究进展
Pub Date : 2017-04-17 DOI: 10.15406/MOJI.2017.05.00162
H. Meena, P. Dara, B. Sharma, R. Choudhary, Prity Sharma
Urticaria, one of the most common dermatological disorders across the globe is characterized by itchy wheels with or without angioedema. The incidence of Urticaria in children is about 0.1% to 6% Chronic Urticaria is defined as a daily occurrence of spontaneous wheals, angioedema, or both for >6 weeks. The etiology of chronic Urticaria is multifactorial in children and it can be explored in 20% to 50% children. In most of children the cause of chronic Urticaria are either idiopathic or autoimmune.
荨麻疹是全球最常见的皮肤病之一,其特征是伴有或不伴有血管性水肿的车轮发痒。儿童荨麻疹的发病率约为0.1%至6%。慢性荨麻疹被定义为每天发生自发性风团、血管性水肿,或持续6周以上。慢性荨麻疹的病因在儿童中是多因素的,可以在20%至50%的儿童中进行探索。在大多数儿童中,慢性荨麻疹的病因要么是特发性的,要么是自身免疫性的。
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引用次数: 1
The Sea Star Igkappa Gene and its Applications in Cancerology 海星Igkappa基因及其在肿瘤学中的应用
Pub Date : 2017-04-11 DOI: 10.15406/moji.2017.05.00161
M. Leclerc
It was shown 32 years ago that the sea star axial organ cells (AO cells) produced a spontaneous cytotoxicity against mouse cancerous cells. Recently, we discovered a sea star Igkappa gene with immune properties. This gene was inserted in a CMV (cytomegalovirus) and finally in a plasmid called « young » plasmid. The induced« young » protein exerted a spontaneous cytotoxicity against osteosarcom cells (U2oS cells) and recently against Hela cells (cervix carcinoma cells).
32年前,海星轴状器官细胞(AO细胞)对小鼠癌细胞产生了自发的细胞毒性。最近,我们发现了一种具有免疫特性的海星Igkappa基因。该基因被插入CMV(巨细胞病毒)中,最后被插入一个名为“年轻”质粒的质粒中。诱导的“年轻”蛋白对骨肉瘤细胞(U2oS细胞)和最近对Hela细胞(宫颈癌细胞)产生自发的细胞毒性。
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引用次数: 0
Presence of Co-Morbidities in Patients Suffering from Diabetes Mellitus Type-2 Attending Two Clinics in Delhi 在德里两家诊所就诊的2型糖尿病患者的合并症
Pub Date : 2017-04-10 DOI: 10.15406/MOJI.2017.05.00160
A. Rathi, Ritesh Bansal, Kakalee K. Saha
India is a hotbed of diabetes with the highest number of diabetics in the world (62 million) and it is predicted that by 2030 the disease might afflict as high as 79.4 million individuals. Often the individuals with diabetes mellitus type-2 have other metabolic abnormalities-the clustering of which contributes to the overall morbidity and mortality profile. Comorbidity, defined as the occurrence of one or more chronic conditions in the same person with an index-disease, occurs frequently among patients with diabetes. Multiple health conditions lead to a faster deterioration of health and poses a great burden on the healthcare delivery system and patient’s pocket as well. It is a cross sectional study involving the data obtained from 144 patients with diabetes mellitus type-2 attending 2 diabetes clinics in Delhi between July-Sept 2016. Out of the total patients, 37 (25.7%) were females. The average age of the patients was 52.4 years, their average BMI was 27.3 kg/m2 and their average HbA1c was 8.9. Hypertension and dyslipidemia are the most common co-existing conditions with diabetes, followed by neuropathy and sleep apnea. Diabetes care program should also focus on rigorously treating co-morbidities, as these are often associated with patient’s discomfort and dismay.
印度是糖尿病的温床,拥有世界上最多的糖尿病患者(6200万),据预测,到2030年,糖尿病患者可能高达7940万人。2型糖尿病患者通常还有其他代谢异常,这些异常的聚集导致了总体发病率和死亡率。合并症,定义为同一患者同时出现一种或多种慢性疾病,常见于糖尿病患者。多种健康状况导致健康恶化的速度更快,给医疗保健服务系统和患者的口袋带来了巨大的负担。这是一项横断面研究,涉及2016年7月至9月期间在德里2家糖尿病诊所就诊的144名2型糖尿病患者的数据。其中女性37例(25.7%)。患者平均年龄52.4岁,平均BMI为27.3 kg/m2,平均HbA1c为8.9。高血压和血脂异常是最常见的与糖尿病共存的疾病,其次是神经病变和睡眠呼吸暂停。糖尿病护理计划还应注重严格治疗合并症,因为这些合并症通常与患者的不适和沮丧有关。
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引用次数: 0
期刊
MOJ immunology
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