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An Acute Inflammation with Special Expression of CD11 & CD4 Produces Abscopal Effect by Intramoral Injection Chemotherapy Drug with Hapten in Animal Model 动物模型内注射含半抗原化疗药物引起CD11和CD4特异表达急性炎症的体外效应
Pub Date : 2022-07-11 DOI: 10.29245/2578-3009/2022/3.1236
Baofa Yu, Q. Fu, Yan Han, Jian Zhang, Dong Chen
Aim: To study the immunity reaction in tumor by intratumoral injection with a drug PYM and DNP, where it produces abscopal effect by the expression of immunological genes of tumor on home side (left side) while it brings a similar expression of same genes in tumor on opposite side (right side) of mice. Method: Prepare each tumor on left side of 6 mice and injected intratumoral with a PYM+DNP and PYM control on day 1 and 7. Two day later of day 1, one of groups mice were inoculated with 0.2ml of H22 cells (105/ml) again on the right underarms as opposite side for controls. On day15, the tumor on bilateral sides were excised for qPCR measurement. Result:It showed that inflammation with the expression of the CoL1a1, CD4, IL12aÂ, TGFb1Â, Elastin, Elastin, Cox2, CD11b/c, CD8, TNFa in different groups; The inflammation in both side of tumor but these is not only a increasing expression of Collal, CD4, IL12aÂ, TGFb1Â, Elastin, NFKB, Cox2, CD11c, CD8 and TNFa in tumor on home side of mice treated with PYM+DNP but also a similar an increasing expression of same genes in tumor on opposite side of mice which not treated at all. In the control group, it showed that inflammation without an expression of all factors related above immunity genes in both tumor on home treated with PYM only and opposite side of mice which not treated at all. Conclusion: It indicated that PYM and hapten of DNP can induce an inflammation with stimulation of immunity reaction with the expression of the CoL1a1, CD4, IL12aÂ, TGFb1Â, Elastin, Elastin, Cox2, CD11b/c, CD8, TNFaÂ, which resulted in an abscopale effect. PYM can induce an inflammation but without expression of immuno genes, therefore, hapten is playing an important role with PYM in the special immunity reaction.
目的:研究肿瘤内注射药物PYM和DNP对肿瘤的免疫反应,通过本侧(左侧)肿瘤免疫基因的表达产生体外作用,同时在对侧(右侧)肿瘤中引起相同基因的类似表达。方法:6只小鼠左侧各制备肿瘤,分别于第1天、第7天瘤内注射PYM+DNP和PYM对照。第1天第2天后,其中一组小鼠在右侧腋下再次接种0.2ml H22细胞(105/ml),作为对照。第15天,切除双侧肿瘤进行qPCR检测。Resultï¼´结果表明,不同组的炎症反应与CoL1a1、CD4、IL12aÂ、TGFb1Â、Elastin、Elastin、Cox2、CD11b/c、CD8、TNFaÂ的表达有关;在肿瘤两侧的炎症,但这些不仅增加了Collal, CD4, IL12aÂ, TGFb1Â, Elastin, NFKB, Cox2, CD11c, CD8和TNFaÂ的表达在PYM+DNP治疗的小鼠的一侧肿瘤中,同样的基因表达在未治疗的小鼠的另一侧肿瘤中也增加了。在对照组中,仅用PYM治疗的小鼠的肿瘤和未用PYM治疗的小鼠的另一侧肿瘤均未表达上述免疫基因相关的所有因素。结论:PYM和DNP半抗原可通过CoL1a1、CD4、IL12aÂ、TGFb1Â、Elastin、Elastin、Cox2、CD11b/c、CD8、TNFaÂ的表达诱导炎症,刺激免疫反应,并具有一定的体外效应。PYM可诱导炎症但不表达免疫基因,因此半抗原与PYM在特殊的免疫反应中起着重要作用。
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引用次数: 2
Protective and Susceptibility Effects of Human Leukocyte Antigen on Melanoma Prevalence and their Implications for Predicting Checkpoint Blockade Immunotherapy Outcomes 人白细胞抗原对黑色素瘤患病率的保护和易感性作用及其对预测检查点阻断免疫治疗结果的影响
Pub Date : 2022-06-29 DOI: 10.29245/2578-3009/2022/2.1238
Lisa M. James, A. Georgopoulos
The association of Human Leukocyte Antigen (HLA) with melanoma has been well documented. Similarly, the outcome of checkpoint blockade immunotherapy (CBI) in melanoma depends, to some extent, on the HLA genotype of the patient. Although specific favorable (or unfavorable) HLA alleles for CBI outcome for melanoma have been identified, there is currently no reliable way to predict a positive, neutral or negative melanoma CBI outcome for other alleles. Here we used an immunogenetic epidemiological approach to identify HLA alleles whose frequency is negatively (or positively) associated with melanoma prevalence (protective or susceptibility alleles, respectively). The findings demonstrated that, indeed, HLA alleles that are negatively associated with melanoma prevalence in the population have been associated with good CBI outcome at the individual level and, conversely, HLA alleles that are positively associated with melanoma prevalence have been associated with poor CBI outcome in individuals. Given this good prediction of CBI cancer immunotherapy by specific immunogenetically discovered HLA alleles, we used this epidemiologic immunogenetic approach to identify more HLA Class I and II alleles protective (or susceptibility) for melanoma which would thus be good predictors of CBI outcomes in those cancers. This is a new approach to successfully (a) identify HLA protective or susceptibility alleles for melanoma, and (b) use that information in anticipating outcomes in CBI cancer immunotherapy.
人类白细胞抗原(HLA)与黑色素瘤的关系已被充分证实。同样,检查点阻断免疫疗法(CBI)治疗黑色素瘤的结果在一定程度上取决于患者的HLA基因型。虽然已经确定了黑色素瘤CBI结果的特定有利(或不利)HLA等位基因,但目前还没有可靠的方法来预测其他等位基因的黑色素瘤CBI结果为阳性、中性或阴性。本研究采用免疫遗传学流行病学方法鉴定HLA等位基因的频率与黑色素瘤患病率呈负(或正)相关(分别为保护性或易感性等位基因)。研究结果表明,在个体水平上,与人群中黑色素瘤患病率呈负相关的HLA等位基因确实与良好的CBI结果相关,相反,与黑色素瘤患病率呈正相关的HLA等位基因与个体中不良的CBI结果相关。鉴于通过特异性免疫遗传学发现的HLA等位基因可以很好地预测CBI癌症免疫治疗,我们使用这种流行病学免疫遗传学方法来鉴定更多的HLA I类和II类等位基因对黑色素瘤有保护作用(或易感性),从而可以很好地预测这些癌症的CBI结果。这是一种新的方法,可以成功地(a)识别黑色素瘤的HLA保护或易感等位基因,(b)利用这些信息预测CBI癌症免疫治疗的结果。
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引用次数: 4
Immunogenetic Association of 127 Human Leukocyte Antigen (HLA) Alleles with 30 Cancers in Continental Western European Countries 127个人类白细胞抗原(HLA)等位基因与西欧大陆国家30种癌症的免疫遗传学关联
Pub Date : 2022-05-05 DOI: 10.29245/2578-3009/2022/2.1227
A. Georgopoulos, Lisa M. James
Human leukocyte antigen (HLA) genes have been associated with susceptibility and protection against a number of cancers. Here we used an immunogenetic epidemiological approach to evaluate the overall influence of 127 HLA Class I and II alleles on 30 types of cancer. We found a preponderance of protective alleles (negatively correlated with cancer prevalences), especially for HLA Class I. Of the 30 cancers investigated, 13 were associated with mostly protective HLA effects whereas only 2 were associated with mostly susceptibility HLA alleles. Taken together, these findings highlight the broad influence of HLA on cancer and the complexity of HLA-cancer associations.­­
人类白细胞抗原(HLA)基因与许多癌症的易感性和保护作用有关。本研究采用免疫遗传学流行病学方法评估了127个HLA I类和II类等位基因对30种癌症的总体影响。我们发现保护性等位基因的优势(与癌症患病率呈负相关),特别是在HLA i类中。在研究的30种癌症中,13种与大部分保护性HLA效应相关,而只有2种与大部分易感性HLA等位基因相关。综上所述,这些发现强调了HLA对癌症的广泛影响以及HLA-癌症关联的复杂性
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引用次数: 5
Controlling the cGAS-STING Pathway: The Signature of ASFV Virulence 控制cGAS-STING通路:ASFV毒力的特征
Pub Date : 2022-04-06 DOI: 10.29245/2578-3009/2022/2.1233
Raquel García-Belmonte, Daniel Pérez-Núñez, Y. Revilla
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引用次数: 1
Experimental Autoimmune Encephalomyelitis Animal Models Induced by Different Myelin Antigens Exhibit Differential Pharmacologic Responses to Anti-Inflammatory Drugs 不同髓磷脂抗原诱导的实验性自身免疫性脑脊髓炎动物模型对抗炎药物表现出不同的药理学反应
Pub Date : 2022-03-31 DOI: 10.29245/2578-3009/2022/1.1231
Yuxi Yan, Quan Zhao, Ya Huang, Janine Yang, J. Zou, Chunxia Ao, Xiaojuan Chai, R. Tang, Wen-qing Yang
Background and objective Experimental autoimmune encephalomyelitis (EAE) is the most commonly used model for studying autoimmune-mediated myelin degradation in multiple sclerosis (MS). Here, we evaluated the pharmacologic responses of several anti-inflammatory drugs with varying mechanisms of actions (MOAs) using EAE models induced by different MOG immunogens to reveal differential pharmacologic characteristics of the disease models and provide a general guidance in animal model selection for MS research. Methods The pharmacologic responses of anti-inflammatory drugs with different mechanisms of actions (MOAs) were evaluated using EAE models induced by either myelin oligodendrocyte glycoprotein p35-55 (MOG35-55)or p1-128 (MOG1-128). EAE animal models were developed in mice with C57BL/6 background. The animals were treated with different anti-MS medications, including 3 B cell-mediated agents and 2 T cell-mediated agents, respectively. Clinical symptoms were monitored and scored, and pharmacodynamic markers including cytokine secretion, inflammatory cell infiltration, and demyelination in spinal cord were analyzed. Results In MOG35-55 peptide-induced EAE model, T cell modulating agents Secukinumab and Fingolimod significantly alleviated clinical symptoms, while B cell-depleting agents, BTK inhibitors PRN2246 and Telitacicept, displayed minimal therapeutic effects or even exacerbated disease progression. In contrast, both T cell-modulating agents and B cell-depleting agents ameliorated disease severity in MOG1-128-induced EAE model. T cell and B cell infiltration in spinal cord increased with disease progression in MOG1-128-induced EAE model. Conclusions Our results demonstrated that induction of EAE by different myelin antigens resulted in differential pharmacologic responses to drugs with specific MOAs. The MOG35-55 peptide-induced EAE model only responded to T cell-modulating drugs, whereas the MOG1-128 protein-induced EAE model exhibited therapeutic sensitivity to both T cell- and B cell-modulating agents. These data suggest the MOG35-55 peptide-induced EAE model is suitable for assessing T cell-modulating agents while MOG1-128 protein-induced model can be employed to evaluate both T cell- and B cell-modulating agents.
背景与目的实验性自身免疫性脑脊髓炎(EAE)是研究多发性硬化症(MS)中自身免疫介导的髓磷脂降解最常用的模型。本研究利用不同MOG免疫原诱导的EAE模型,评价几种不同作用机制(MOAs)抗炎药的药理学反应,揭示疾病模型的差异药理学特征,为MS研究动物模型的选择提供一般性指导。方法采用髓鞘少突胶质细胞糖蛋白p35-55 ï¼MOG35-55ï¼μ或p1-128 (MOG1-128)诱导的EAE模型,评价不同作用机制的抗炎药物(MOAs)的药理作用。采用C57BL/6背景小鼠建立EAE动物模型。这些动物分别用不同的抗ms药物治疗,包括3种B细胞介导的药物和2种T细胞介导的药物。监测临床症状并评分,分析细胞因子分泌、炎症细胞浸润、脊髓脱髓鞘等药效学指标。结果在MOG35-55肽诱导的EAE模型中,T细胞调节剂Secukinumab和Fingolimod显著缓解了临床症状,而B细胞消耗剂、BTK抑制剂PRN2246和Telitacicept的治疗效果微乎其微,甚至加重了疾病进展。相比之下,T细胞调节剂和B细胞消耗剂均可改善mog1 -128诱导的EAE模型的疾病严重程度。在mog1 -128诱导的EAE模型中,随着疾病的进展,脊髓内T细胞和B细胞的浸润增加。结论不同髓鞘抗原诱导EAE对特定MOAs药物产生不同的药理反应。MOG35-55肽诱导的EAE模型仅对T细胞调节药物有反应,而MOG1-128蛋白诱导的EAE模型对T细胞和B细胞调节药物均表现出治疗敏感性。这些数据表明,MOG35-55肽诱导的EAE模型适用于评估T细胞调节剂,而MOG1-128蛋白诱导的EAE模型适用于评估T细胞和B细胞调节剂。
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引用次数: 0
Commentary: Decellularized Versus Conventional Cryopreserved Pulmonary Allografts for Right Ventricular Outflow Tract Reconstruction During the Ross Procedure 评论:在Ross手术中,脱细胞与传统冷冻保存的肺同种异体移植物用于右室流出道重建
Pub Date : 2022-03-23 DOI: 10.29245/2578-3009/2022/1.1229
Dave M. Mathew, Kathryn S. Varghese, S. Mathew, Roshan Pandey, Sarah Ahmed, Stephanie A. Salazar, Dillon O. Rogando, Peter J. Fusco, Kenneth H Levy, Adham Ahmed
the use of and the
和The的用法
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引用次数: 0
HBsAg and Immune Competency; is HBsAg a Mere Biomarker or a Therapeutic Target for Chronic Hepatitis B? 乙肝表面抗原与免疫能力;HBsAg是单纯的生物标志物还是慢性乙型肝炎的治疗靶点?
Pub Date : 2022-02-14 DOI: 10.29245/2578-3009/2022/1.1226
Jin Hyang Kim, Grace Park, Bhavna S. Paratala, R. Rijnbrand, M. Sofia, H. Hann
Hepatitis B virus (HBV) is a main cause of hepatocellular carcinoma (HCC) development. Although controversial, it is increasingly recognized that the immune responses directed against infected hepatocytes drive hepatic inflammation and tissue injury. Here we extended our previous findings to report that serum surface antigen (HBsAg) levels are a biomarker not only for HBV-specific immunity, but also for ongoing non-specific immune activation. We found that the HBV-specific T cell responses in patients with HBsAg < 500 IU/mL, while significantly higher than those in patients with HBsAg > 50,000 IU/mL, had already reached levels comparable to patients with seroclearance. In addition, lower HBsAg levels were associated with reduced non-specific immune activation, while no further reduction was observed with HBsAg < 500 IU/mL. We propose HBsAg is a therapeutic target for reducing inflammation.
乙型肝炎病毒(HBV)是肝细胞癌(HCC)发展的主要原因。尽管存在争议,但越来越多的人认识到,针对受感染肝细胞的免疫反应会导致肝脏炎症和组织损伤。在这里,我们扩展了之前的研究结果,报道血清表面抗原(HBsAg)水平不仅是hbv特异性免疫的生物标志物,也是正在进行的非特异性免疫激活的生物标志物。我们发现,在HBsAg < 500 IU/mL的患者中,hbv特异性T细胞反应虽然显著高于HBsAg > 50,000 IU/mL的患者,但已经达到与血清清除率相当的水平。此外,较低的HBsAg水平与非特异性免疫激活降低相关,而HBsAg < 500 IU/mL时未观察到进一步降低。我们认为HBsAg是一种减少炎症的治疗靶点。
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引用次数: 0
Plasmacyte Heterogeneity of Lame Ducklings 跛脚鸭的浆细胞异质性
Pub Date : 2022-02-10 DOI: 10.29245/2578-3009/2022/1.1225
P. Cotter
The aim is to describe the array of plasmacytes (PC), cells known as the source of antibody, occurring in the bone marrow (BM) of lame ducklings. The method is by a light microscopic examination of touch preparation slides made from femur samples and stained with Wright-Giemsa. Samples were obtained on site at commercial farms where slide preparations were made; reducing the possibility that observations are technical artifacts. The results: indicate that PC occur in a multitude of sizes, shapes, nuclear/cytoplasmic (N/C) ratios, ploidy, and nuclear and cytoplasmic conditions. Normal PC are illustrated first, followed by atypical forms. Some PC are presented in the context of neighboring BM cells of the granulocyte, erythrocyte, and reticulum cell (histiocyte) series. More than 100 Mott-type PC were measured in a single sample from a 13-day lame duck; and several distinct forms were identified. Size, as measured by their longest axis, varied from 6.1 to 28 μm and it appears to be normally distributed. Moreover, N/C ratios were distributed across a three-fold range (0.3 – 0.9) indicating Mott phenotypes can occur at multiple developmental stages. Motts differed in Russell Body (RB) size, and nuclear condition. A novel Mott type, “orb” form, with partially lysed nuclei is also described. PC were often found in association with giant granulated histiocytes (ggh) and non-granulated giant histiocytes (gh). Other atypical forms are “hand-mirror” PC, trinucleate and binucleate PC resembling cells seen in multiple myeloma (MM) and lymphomas. Collectively these PC variants constitute “reactive plasmatosis” (RP) likely arising as a consequence of the presence of various bacteria including Streptococcus and E. coli. The conclusions: It is demonstrated that RP as occurs in lame ducklings suffering from bacterial infections, provides a unique theater for the study of PC variability. Atypical PC, some resembling neoplastic types, were common in RP BM. The significance of the study relates to the importance of PC in disease and immunity; therefore, these observations should interest those who specialize in these areas. They expand the knowledge of avian plasmacyte morphology.
目的是描述一组浆细胞(PC),一种被称为抗体来源的细胞,发生在跛脚鸭的骨髓(BM)中。该方法是通过光镜检查由股骨样品制成的触摸制备载玻片,并用Wright-Giemsa染色。样品是在商业农场现场获得的,在那里制作了滑梯制剂;减少观察是技术工件的可能性。结果表明,PC以多种大小、形状、核/细胞质(N/C)比、倍性以及核和细胞质条件发生。首先是正常PC,其次是非典型PC。一些PC是在粒细胞、红细胞和网状细胞(组织细胞)系列的邻近BM细胞的背景下出现的。在一个13天的跛脚鸭的单一样本中测量了100多个莫特型PC;并确定了几种不同的形式。长轴测量的晶粒尺寸在6.1 ~ 28 μm之间,呈正态分布。此外,N/C比分布在3倍范围内(0.3 - 0.9),表明莫特表型可以发生在多个发育阶段。马茨在罗素体(RB)大小和核状态上存在差异。一个新的莫特类型,“球”形式,与部分裂解的核也被描述。PC常与大颗粒组织细胞(ggh)和非颗粒组织细胞(gh)相关。其他不典型的形式是“手镜”型PC,类似于多发性骨髓瘤(MM)和淋巴瘤的三核和双核PC。总的来说,这些PC变体构成了“反应性浆体病”(RP),可能是由于包括链球菌和大肠杆菌在内的各种细菌的存在而引起的。结论:这表明,RP发生在患有细菌感染的跛脚鸭,为研究PC变异性提供了一个独特的舞台。非典型PC,一些类似肿瘤类型,在RP BM中很常见。本研究的意义涉及到PC在疾病和免疫中的重要性;因此,这些观察结果应该引起那些专门研究这些领域的人的兴趣。它们扩展了鸟类浆细胞形态学的知识。
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引用次数: 0
Vagaries of the Host Response to Chronic Hepatitis B Virus Infection: What is the Ultimate Outcome of So-called “Asymptomatic HBV Carriers” Observed Over Several Decades? 宿主对慢性乙型肝炎病毒感染反应的变幻莫测:几十年来观察到的所谓“无症状HBV携带者”的最终结果是什么?
Pub Date : 2021-12-30 DOI: 10.29245/2578-3009/2021/4.1224
Nicholas Noverati, Daniel Garrido, D. Halegoua-DeMarzio, H. Hann
Introduction: Chronic hepatitis B virus (HBV) infection is prevalent worldwide and up to 40% is known to progress to serious complications including cirrhosis and hepatocellular carcinoma (HCC). The outcome of the remaining infected individuals is not well documented. Our case series describes a longer cohort of chronic HBV infections that have remained asymptomatic with no progression of liver disease. Case Series: Thirty-three patients (ages 31-84) with chronic HBV infection were identified. All patients had no significant elevations in transaminase levels and were followed over 32 years, collectively. 18/33 had a fluctuating greater magnitude of HBV viral load with no elevations in tumor marker or significant radiographic changes to their liver. Discussion/Conclusion: Chronic HBV infection can lead to serious complications over time, the mechanism of which are not well understood. The variation in patients that do and do not develop these complications stresses the importance of the individual response to the virus and may highlight host immune response differences.
慢性乙型肝炎病毒(HBV)感染在世界范围内普遍存在,高达40%的人已知会发展成严重的并发症,包括肝硬化和肝细胞癌(HCC)。其余感染者的结局没有很好的记录。我们的病例系列描述了一个较长的慢性HBV感染队列,这些队列仍然无症状,没有肝脏疾病的进展。病例系列:33例(31-84岁)慢性HBV感染。所有患者转氨酶水平均无显著升高,随访32年。18/33患者的HBV病毒载量波动较大,但肿瘤标志物没有升高,肝脏放射学也没有明显变化。讨论/结论:慢性HBV感染可导致严重的并发症,其机制尚不清楚。有和没有出现这些并发症的患者的差异强调了个体对病毒反应的重要性,并可能突出宿主免疫反应的差异。
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引用次数: 2
Epitope-based Multi-variant SARS-Cov-2 Vaccine Design: Shared Epitopes Among the Natural SARS-Cov-2 Spike Glycoprotein and 5 of its Variants (D614G, α, β, γ, δ) with High in Silico Binding Affinity to Human Leukocyte Antigen (HLA) Class II Molecules 基于表位的多变体SARS-Cov-2疫苗设计:与人白细胞抗原(HLA)ⅱ类分子高硅结合亲和力的天然SARS-Cov-2刺突糖蛋白及其5种变体(D614G、α、β、γ、δ)共享表位
Pub Date : 2021-10-29 DOI: 10.29245/2578-3009/2021/4.1223
Spyros A. Charonis, A. Georgopoulos
Page 9 of 14 Epitope-based Multi-variant SARS-Cov-2 Vaccine Design: Shared Epitopes Among the Natural SARS-Cov-2 Spike Glycoprotein and 5 of its Variants (D614G, α, β, γ, δ) with High in Silico Binding Affinity to Human Leukocyte Antigen (HLA) Class II Molecules Spyros A. Charonis1,2, Apostolos P. Georgopoulos1,2* 1The HLA SARS-CoV-2 Research Group, Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA 2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA
基于表位的SARS-Cov-2多变体疫苗设计天然SARS-Cov-2长链糖蛋白及其变体(D614G、α、β、γ、δ)与人类白细胞抗原(HLA)ⅱ类分子高硅基结合亲和力的共同表位Spyros A. charonis1,2, Apostolos P. Georgopoulos1,2* 1 HLA - cov -2研究组,退伍军人事务部卫生保健系统脑科学中心,明尼阿波利斯,MN 55417,美国2明尼苏达大学医学院神经学系,明尼阿波利斯,MN 55455,美国
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引用次数: 1
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Journal of immunological sciences
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