Relationship and significance between anti-b2-glycoproteinⅠantibodies and platelet activation state in patients with ulcerative colitis

AIM： To study the relationship between anti-β2- glycoprotein Ⅰ （aβ2GPⅠ） antibodies and platelet activation state in patients with ulcerative colitis （UC） and its significance. METHODS： Peripheral blood samples were collected from 56 UC patients （34 males and 22 females, aged 43.5 years, range 21-66 years）, including 36 at active stage and 20 at remission stage, and 25 sex-and age-matched controls. The level of aβ2GP Ⅰ was measured by ELISA. The platelet activation markers, platelet activation complex- Ⅰ （PAC- Ⅰ ） and P-selectin （CD62P） were detected by flow cytometry. RESULTS： The A value for IgG aβ2GP Ⅰ in the active UC group was 0.61 ± 0.13, significantly higher than that in the remittent UC and control groups （0.50 ± 0.13 and 0.22 ± 0.14, P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. The A value for IgM aβ2GP Ⅰ in the active and remittent UC groups was 0.43 ± 0.13 and 0.38 ± 0.12, significantly higher than that in the control group （0.20 ± 0.12, P 〈 0.01）. However, there was no significant difference between the two groups （P 〉 0.05）. The PAC- Ⅰ positive rate for the active and remittent UC groups was 30.6% ± 7.6% and 19.6% ± 7.8% respectively, significantly higher than that for the control group （6.3% ± 1.7%,P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. The CD62P positive rate for the active and remittent UC groups was 45.0% ± 8.8% and 31.9% ± 7.8% respectively, significantly higher than that for the control group （9.2% ± 2.7%, P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. In the active UC group, the more severe the state of illness was, the higher the A value for IgG aβ2GP Ⅰ was, and the positive rate for PAC-Ⅰ and CD62P was positively correlated with the state of illness （Faβ2GP Ⅰ = 3.679, P 〈 0.05; FPAC-Ⅰ （%） = 5.346, P 〈 0.01; and FCD62P （%） = 5. 418, P 〈 0.01）. Meanwhile, in the same state of illness, the A value for IgG aβ2GP Ⅰ was positively correlated to the positive rates for PAC-Ⅰ and CD62P. CONCLUSION： aβ2GP Ⅰ level, platelet activation state and their relationship of them are closely correlated with the pathogenesis and development of UC.

Comparison ofβ-Amyloid Plaque Labeling Methods:Antibody Staining,Gallyas Silver Staining,and Thioflavin-S Staining

Objective To evaluate senile plaque formation and compare the sensitivity of three differentβ-amyloid(Aβ)labeling methods(antibody staining,Gallyas silver staining,and thioflavin-S staining)to detect Aβdeposition.Methods APPswe/PSEN1dE9 transgenic mice(APP/PS1)of different ages were used to examine spatiotemporal changes in Aβplaque deposition.Antibody staining,Gallyas silver staining,and thioflavin-S staining were used to detect Aβplaque deposition in the same brain region of adjacent slices from model mice,and the results were compared.Results With aging,Aβplaques first appeared in the cortex and then the deposition increased throughout the whole brain.Significantly greater plaque deposition was detected by 6E10 antibody than that analyzed with Gallyas silver staining or thioflavin-S staining(P<0.05).Plaque deposition did not show significant difference between the APP/PS1 mice brains assayed with Gallyas silver staining and ones with thioflavin-S staining(P=0.0033).Conclusions The APP/PS1 mouse model of Alzheimer’s disease could mimick the progress of Aβplaques occurred in patients with Alzheimer’s disease.Antibody detection of Aβdeposition may be more sensitive than chemical staining methods.

Anti-amyloid beta single-chain Fv ameliorates behavioral impairment in Alzheimer's disease mice via adeno-associated virus delivery

Intracranial delivery of human Fc-deleted antibody specific to amyloid-β peptide （Aβ, anti-Aβ single-chain Fv, scFv） via adeno-associated virus （AAV） inhibits amyloid deposition in transgenic mice. However, the effects of AAV-mediated Fc-deleted antibody on animal behavior remain unclear. In this study, the anti-Aβ scFv antibody gone, isolated from phage display, was fused to the 5＇ end of the scFv antibody gone for antibody secretion by 2 rounds of polymerase chain reaction amplification. The fused antibody cDNA was cloned into a pSNAV2 plasmid under the control of the cytomegalovirus promoter. The sequence verified expression vector pSNAV2/scFv was transferred to BHK-21 ceils, and stable transfected BHK-21/scFv cells were established by G418 selection and infected with the recombinant herpes simplex virus rHSV/repcap for AAV production. Recombinant AAV was injected into the left quadriceps femoris of PDAPP transgenic mice. After 3 months, Morris water-maze results confirmed significantly improved cognitive function in a mouse model of Alzheimer＇s disease. Key Words： Alzheimer＇s disease; adeno-associated virus; amyloid-β peptide; single-chain antibody; neurodegenerative diseases; neural regeneration

Expression of secreted human single-chain fragment variable antibody against human amyloid beta peptide in Pichia pastoris

BACKGROUND：Studies have shown that monoclonal or polyclonal antibody injections of amyloid β peptide are effective in removing amyloid β peptide overload in the brain. OBJECTIVE： Based on successful screening of a human single-chain fragment variable antibody specific to amyloidβpeptide, this paper aimed to express recombinant human single-chain variable antibody against amyloid β peptide. DESIGN, TIME AND SETTING： A single sample experiment was performed at the Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Hospital （Beijing, China） from January to July 2006. MATERIALS： Human single-chain fragment variable antibody gene against amyloid β peptide was screened from a human phage-display antibody library. METHODS： Human single-chain fragment variable antibody gene was mutated to eliminate a BamHI restriction site and cloned into a T easy plasmid for pT-scFvAβ construction, which was identified by PCR amplification and endonuclease digestion. Plasmid pT-scFvAβ was cut by EcoRI and NotI endonucleases, and the antibody gene was cloned into pPIC9K plasmid to construct pPIC9K-scFvAβ expression vector, which was confirmed by gene sequencing. Linearized pPIC9K-scFvAβ was used to transform a Pichia pastoris GS115 cell line, and the recombinant was induced by 0.5% methanol to express human single-chain fragment variable antibody specific to amyloid β peptide. MAIN OUTCOME MEASURES： Protein electrophoresis was used to identify PCR products, gene sequencing was used to verify the pPIC9K-scFvA sequence, and SDS-PAGE was used to detect recombinant expression of human single-chain fragment variable antibody specific to amyloid β peptide in Pichia pastoris. RESULTS： Gene sequencing confirmed pPIC9K-scFvAβ orientation. Recombinants were obtained by linearized pPIC9K-scFvAβ transformation. After induction with 0.5% methanol, the recombinant yeast cells secreted proteins of 33-ku size. CONCLUSION： The expression vector pPIC9K-scFvAβ was successfully constructed. Human single-chain fragment variable antibody specific to amyloid β peptide was recombinantly expressed in Pichia pastoris.

Prevalence of Anti-Cardiolipin and Anti-β2 Glycoprotein Antibodies in Indian Systemic Lupus Erythematosus Patients

Anti-phospholipid antibodies (APA) like anti-cardiolipin antibodies (ACA) and anti-β2glycoprotien (anti-β2GP) are important cause of venous and arterial thrombosis and other occlusive vascular diseases. The prevalence of these antibodies in SLE patients at the time of diagnosis is not known in Indian SLE patients. This study was conducted to evaluate the prevalence of ACA and anti-β2GP autoantibodies in SLE patients and to correlate them with disease activity and immune parameters such as C3, C4 and CRP levels. where 85 SLE patients referred from Rheumatology Department, KEM hospital, Mumbai were studied. SLE disease activity was evaluated by SLE Disease Activity Index (SLEDAI) score at the time of evaluation. All patients studied were in an active stage of disease of which 37.6% patients had renal disorders, which were categorized as Lupus Nephritis (LN) and 62.3% patients did not show any renal manifestations (non-LN). ACA and anti-β2GP autoantibodies, to IgG and IgM subclasses were tested by ELISA. C3, C4 and CRP levels were detected by nephelometer. It was observed that 12.9% patients were IgG-ACA and IgM-ACA positive and ACA positivity was noted more among LN group Anti-β2GP autoantibody positivity was 27.1% for IgG and 31.8% for IgM., IgG-anti-β2GP antibodies were slightly higher in non-LN patients, whereas a higher incidence of IgM-anti-β2GP antibodies were detected in LN patients. Hence detection both ACA and anti-β2GP antibodies along with associated immune parameters were helpful to evaluate their possible association with disease severity in SLE patients. A long term follow up of patients having ACA and anti-β2GP antibodies without thrombotic event is also needed to detect their possible thrombotic event in future along with their clinical presentation.

Construction of human Fab library and screening of a single-domain antibody of amyloid-beta 42 oligomers

Screening humanized antibodies from a human Fab phage display library is an effective and quick method to obtain beta-amyloid oligomers. Thus, the present study prepared amyloid-beta 42 oli- gomers and constructed a have human Fab phage display library based on blood samples from six healthy people. After three rounds of biopanning in vitro, a human single-domain antibody that spe- cifically recognized amyloid-beta 42 oligomers was identified. Western blot and enzyme-linked im- munosorbent assay demonstrated this antibody bound specifically to human amyloid-beta 42 tetramer and nonamer, but not the monomer or high molecular weight oligomers. This study suc- cessfully constructed a human phage display library and screened a single-domain antibody that specifically recognized amyloid-beta 42 oligomers.

Periodontitis and Inflammation: Plasma High Titer Naturally Occurring Anti-Glucan Antibodies Form Immune Complex with Streptococcus mutans Antigen

Atheromatous plaques usually contain antigens of the periodontitis-causing bacteria Streptococcus mutans though molecular mechanism of this incorporation remains unknown. Since vascular adhesion and inflammatory potential of Immune Complexes (IC) are known we investigated the naturally occurring plasma antibodies that recognize major antigens from S. mutans. S. mutans-binding plasma proteins (SMBP) prepared by affinity chromatography on a column of heat-killed S. mutans could recognize α- and β-linked glucose in dextran and yeast respectively but not galactose in glycoproteins. SMBP contained only three proteins, each corresponding in electrophoretic mobility to standard plasma IgG, IgA or IgM. The major positively and negatively charged protein antigens (PSMAg and NSMAg) isolated from S. mutans by electrophoresis and ion exchange chromatography respectively were recognized sugar-reversibly by the anti-β-glucan antibody (ABG) and though less avidly, by the dextran-binding immunoglobulin (DIg) in normal plasma. NSMAg addition resulted in near doubling of IC-bound immunoglobulins in immunoglobulin-rich fraction of plasma. IC isolated from above fraction after NSMAg addition had substantially more IgA and IgM content than total plasma immunoglobulins. IC formation by NSMAg was significantly inhibited by ABG- and DIg-specific sugars or by selective withdrawal of ABG or DIg from plasma. ABG and DIg being relatively high titer plasma antibodies IC formation with them suggested a possible route for vascular adhesion and damage by S. mutans and its antigens. Further, high IgA content of these ICs indicated their susceptibility to tissue uptake through cell surface galectin-1 for which IgA is the lone immunoglobulin ligand.

关于抗Aβ单克隆抗体的临床应用建议(2024版)

最新研发的抗Aβ单克隆抗体陆续在国内外获批上市,并逐渐应用于我国临床实践。为促进抗Aβ单克隆抗体在我国阿尔茨海默病治疗中更合理、安全的应用,本文结合抗Aβ单克隆抗体现有临床试验证据及阿杜卡单抗在上海交通大学医学院附属瑞金医院海南医院的临床应用经验,总结抗Aβ单克隆抗体的临床应用建议,包括临床用药指征、用药前评估及准备、用药时医嘱及注意事项、用药后临床监测,旨在为临床医师提供翔实的用药指导和建议。

阿尔茨海默病的药物治疗新进展

近年来,随着以β淀粉样蛋白(β-Amyloid,Aβ)单抗为代表的疾病修饰治疗(disease-modifying therapies,DMT)药物的出现,阿尔茨海默病(Alzheimer's disease,AD)的药物治疗进入了一个全新的阶段,目前已经有2种靶向淀粉样蛋白的抗体-阿杜卡单抗和伦卡纳单抗相继上市,在全世界引起了广泛关注;同时非Aβ非tau蛋白治疗靶点的药物研发也取得明显进展。本文拟对AD新型药物的研发和应用,包括临床试验阶段和已获批上市的药物治疗进展进行一全面分析和阐述。

抗CCL20单克隆抗体对血清淀粉样蛋白A相关的结节病中促炎性细胞因子的抑制作用

目的探讨抗CCL20单克隆抗体是否可抑制高水平血清淀粉样蛋白A(SAA)相关的结节病外周血单个核细胞(PBMC)中促炎性细胞因子的表达。方法提取健康人和结节病患者的PBMC,并进行分组。除空白对照组(正常人PBMC)和结节病PBMC对照组(患者PBMC)外,另将结节病组PBMC中分别加入SAA、SAA+抗CCL20单克隆抗体、SAA+NF-κB抑制剂BAY11-7082或地塞米松,经培养48 h后收集各组细胞,分别作为PBMC+SAA刺激组、PBMC+SAA+NF-κB抑制剂BAY11-7082组、PBMC+SAA+抗CCL20单抗组、PBMC+地塞米松干预组,使用ELISA分别测定各组细胞上清液中细胞因子IL-17A、IL-23、IL-6、CCL20和TGF-β1的表达,使用RT-PCR测定各组细胞中CCR6、IL-17、ROR-γt和Foxp3的mRNA表达水平,使用Western blot检测各组细胞中p-NF-κB和NF-κB蛋白的表达水平。结果PBMC+SAA+抗CCL20单抗组与PBMC+SAA组相比,细胞上清液中的IL-17A、IL-23和IL-6的水平显著降低(P<0.01),而TGF-β1的含量显著升高(P<0.01)。PBMC+SAA+抗CCL20单抗组相较于PBMC+SAA组,细胞中CCR6、IL-17A、ROR-γtmRNA水平显著降低(P<0.01),而Foxp3 mRNA差异无统计学意义(P>0.05)。PBMC+SAA+抗CCL20单抗组中p-NF-κB蛋白表达水平较PBMC+SAA组明显降低(P<0.01)。结论抗CCL20单克隆抗体可抑制高水平SAA相关的结节病PBMC中促炎性细胞因子的表达。

小儿肺炎支原体免疫球蛋白M抗体与超敏C反应蛋白和血清淀粉样蛋白A检验的诊断价值分析

目的 分析小儿肺炎支原体免疫球蛋白M(immunoglobulin M, IgM)与超敏C反应蛋白(hypersensitive Creactive protein, hs-CRP)和血清淀粉样蛋白A(serum amyloid A, SAA)联合检测的诊断价值。方法 非随机选取2022年1月-2023年6月兖州区人民医院收治的肺炎支原体肺炎患儿及同期健康体检儿童各110例,肺炎支原体肺炎患儿为观察组,健康体检儿童作为参照组。对比两组肺炎支原体IgM抗体、hs-CRP、SAA水平检验结果,绘制ROC曲线,分析支原体IgM抗体+hs-CRP与SAA+hs-CRP及联合检验的诊断效能。结果 观察组小儿肺炎支原体IgM抗体水平、hs-CRP水平以及SAA水平比参照组高,差异有统计学意义(P均<0.05);在ROC曲线图中,三者联合检测的AUC值为0.930,高于IgM抗体+hs-CRP与SAA+hs-CRP检测的0.885、0.835,三者联合检测小儿肺炎支原体的灵敏度及特异度高于IgM抗体+hs-CRP与SAA+hs-CRP检测,差异有统计学意义(P均<0.05)。结论 对小儿肺炎支原体肺炎患儿应用肺炎支原体IgM抗体+hs-CRP与SAA三项指标联合检测具有一定价值,具有较高灵敏度、特异度。

Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease

AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.

Aβ28-Induced Specific and Effective Serum Antibodies Against Aβ42

Though phase I clinical trial of immunotherapy for Alzheimer＇s disease（AD） with inoculated Aβ42 in humans had been proven to be effective,phase II immunotherapy trial was discontinued in 2002 because a few patients developed significant inflammatory reactions caused by C-terminal domain of Aβ42.The aim of the study was to investigate the levels and the abilities of antibodies induced by C-terminal truncated Aβ species to inhibit Aβ42 aggregation and cytotoxity in vitro.46-week-old male BALB/c mice,Aβ42 and Aβ28/Aβ35/Aβ42 with a C-terminal eight-histidine tag（Aβ28H8,Aβ35H8,and Aβ42H8） were applied in the present study.The mice were randomly divided into 5 groups（n=8）,control mice immunized with the normal saline,Aβ42-immunized mice and Aβ42H-/Aβ35H-/Aβ28H-immunized mice.All the serum antibodies were evaluated by measuring their abilities to inhibit Aβ42 aggregation and cytotoxity in vitro.Each mouse was vaccinated with purified Aβ peptide emulsified with Freund＇s adjuvant（volume ratio 1：1）.Titers,concentrations and isotypes of serum antibodies against Aβ42 were measured by indirect ELISA.Effects of serum antibodies on Aβ42 aggregation and disassembly of Aβ42 fibrils in vitro were observed by electron microscopy.Effects of serum antibodies on Aβ42 cytotoxicity were determined by MTT assay.Aβ42 or Aβ28 could induce higher anti-Aβ42 antibody titer（1：6400） than Aβ35（1：3200）.Significantly,Aβ28 induced more IgG1 and IgG2b isotype antibodies and less IgG2b isotype antibody than other Aβ species though all the induced serum antibodies could inhibit Aβ42 aggregation or fibrillogenesis,could induce the disassembly of Aβ42 aggregates,and neutralized or inhibited the cytotoxicity of Aβ42 in vitro.C-Terminal truncated Aβ28 could induce the same effective but safer serum antibodies against Aβ42 than full length Aβ42 by eliciting more Th2-type immune responses.

PGE₂Generation in Myocardium from Isolated Rat Atrium under Hypoxia and Reoxygenation Conditions. Effect of Anti-<i>β</i>₁IgG from Patients with Chronic Severe Periodontitis

Background: Hypoxia is one of the most frequently encountered stresses in health and disease. Methods: We compared the effects of an anti-β1 periodontal IgG (pIgG) and an authentic β1 adrenergic agonist, xamoterol, on isolated myocardium from rat atria contractility. We used an ELISA assay to measure the generation of PGE2 in vitro after the addition of either the antibody or the adrenergic agonist. We analyzed the myocardium histopathologically in the presence of both the antibody and/or the adrenergic agonist drug during normoxia, hypoxia and reperfusion conditions. Results: PGE2 generation increased during the hypoxia and was unchanged during reoxygenation period compared with the production of this prostanoid in atria during normoxia condition. A β1 specific adrenoceptor antagonist atenolol and the β1 synthetic peptide abrogated the increment of the prostanoid in the presence of pIgG but only atenolol due to it in the presence of xamoterol. The increment of PGE2 was dependent on the activation of cox-1 and cox-2 isoforms. Moreover, cox-2 was more active and produced more increments in the production of PGE2 in the presence of the pIgG than cox-1 activation. Histopathologically, studies of myocardium specimens during these different periods of the experimental protocol: basal (B), hypoxia (H) and reoxygenation (R), were also performed and showed tissue necrosis and edematization at the myocardium level. Conclusion: The phenomenon studied here supports the notion that PGE2 may be responsible for tissue edematization. PGE2 maybe acts as a beneficial modulator in the myocardium and prevents a major injury of it. The inflammation damage to the heart organ and cardiomyocytes caused by the actions of the antibodies in the course of heart lesions provoked by cardiovascular autoimmune disease, explains some of these results obtained in the present experiments. Further studies will be needed to establish the real role of PGE2 during hypoxia injury of the heart in the course of autoimmune diseases.

Copper Ions Enhance Signal Intensity of Sandwich ELISA for Amorphous Aggregates of Amyloid-β42

Amyloid-β42 (Aβ42) accumulates within senileplaque, a pathological hall mark of Alzheimer’s disease (AD). Our previous reports showed that the monoclonal antibodies 37-11 and 77-3 react with conformational epitopes on the surface of the soluble aggregates of Aβ42 and that sandwich ELISA using these two monoclonal antibodies yields high reactivity to detect soluble aggregates of Aβ42. Here, the reactivity of the sandwich ELISA was shown to increase in the presence of 50 μM Cu2+. However, the addition of Cu2+ had only a small effect on the reactivity of a direct ELISA using antibody 37-11 or 77-3, suggesting that Cu2+ has a small effect on the number of epitopes on the surface of the aggregates. Atomic force microscopy images showed that larger aggregates were formed in the presence of Cu2+, as shown in the other reports. Cu2+ may gather the aggregates with distinct epitopes recognized by antibodies 37-11 and 77-3, leading to increased signal intensity of the sandwich ELISA.

Aβ寡聚体与阿尔茨海默病研究进展

阿尔茨海默病(Alzheimer's disease,AD)是一种以记忆损害为主要表现渐进性发展的神经退行性疾病,随着老龄化社会发展发病率呈上升趋势,带来巨大的社会经济负担。近年来的研究使AD经典发病机制淀粉样蛋白级联假说受到了挑战,Aβ寡聚体(Aβoligomers,AβOs)的毒性作用得到了一致性的认可,可能是AD发病的触发因素。关于Aβ寡聚体具体来源、结构和致病机制的认识还不充分,可能不同类型寡聚体致病毒性不一致,作用机制有差别。本文综述了对Aβ寡聚体的新近认知,以及它们的结构特点和致病作用,以求更好的理解Aβ寡聚体和AD的关系,为之后的研究提供可能的方向。

Inducing prion protein shedding as a neuroprotective and regenerative approach in pathological conditions of the brain:from theory to facts

In the last decades,the role of the prion protein(PrP) in neurodegenerative diseases has been intensively investigated,initially in prion diseases of humans(e.g., Creutzfeldt-J akob disease) and animals(e.g.,scrapie in sheep,chronic wasting disease in deer and elk,or "mad cow disease" in cattle).Templated misfolding of physiological cellular prion protein(PrPC) into an aggregation-prone isoform(termed PrP "Scrapie"(PrPSc)),self-re plication and spreading of the latter inside the brain and to peripheral tissues,and the associated formation of infectious proteopathic seeds(termed "prions")are among the essential pathogenic mechanisms underlying this group of fatal and transmissible spongiform encephalopathies.Late r,key roles of the correctly folded PrPCwere identified in more common human brain diseases(such as Alzheimer s disease or Parkinson’s disease) associated with the misfolding and/or accumulation of other proteins(such as amyloid-β,tau or α-synuclein,respectively).PrPChas also been linked with n euro protective and regenerative functions,for instance in hypoxic/ischemic conditions such as stroke.However,despite a mixed "bouquet" of suggested functions,our understanding of pathological and,especially,physiological roles played by PrPCin the brain and beyond is ce rtainly incomplete.Interactions with various other proteins at the cell surfa ce or within intracellular compartments may account for the functional diversity linked with PrPC.Moreover,conserved endogenous proteolytic processing of PrPCgenerates seve ral defined PrPCfragments,possibly holding intrinsic functions in physiological and pathological conditions,thus making the "true and complete biology" of this protein more complicated to be elucidated.Here,we focus on one of those released PrPCfragments,namely shed PrP(sPrP),generated by a membrane-proximate ADAM10-mediated cleavage event at the cell surfa ce.Similar to other soluble PrP fragments(such as the N1 fragment representing PrP’s released N-terminal tail upon the major α-cleavage event)or expe rimentally employed recombinant PrP,sPrP is being suggested to act n euro protective in Alzheimer’s disease and other protein misfolding diseases.Seve ral lines of evidence on extracellular PrPC(fragments) suggest that induction of PrPCrelease co uld be a future therapeutic option in various brain disorders.Our recent identification of a substrate-specific approach to stimulate the shedding by ADAM 10,based on ligands binding to cell surface PrPC,may further set the stage for research into this direction.

Immune-mediated necrotizing myopathy:Report of two cases

BACKGROUND Immune-mediated necrotizing myopathy is a rare autoimmune myopathy characterized by muscle weakness and elevated serum creatine kinase,with unique skeletal muscle pathology and magnetic resonance imaging features.CASE SUMMARY In this paper,two patients are reported:One was positive for anti-signal recognition particle antibody,and the other was positive for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibody.CONCLUSION The clinical characteristics and treatment of the two patients were analysed,and the literature was reviewed to improve the recognition,diagnosis,and treatment of this disease.

针对淀粉样蛋白不同靶点的抗体研究进展

阿尔茨海默病(Alzheimer's disease,AD)是一种起病隐匿的进行性发展的神经系统变性疾病。AD发病机理十分复杂,可能是多因素相互作用的结果。β-淀粉样蛋白(Aβ)级联假说是既往针对其发病机制中的经典学说,在此学说的指导下投入了大量的药物研发,大多研发将Aβ作为研究靶点试图预防或延缓AD的发生发展。该文就目前国外针对淀粉样蛋白不同形式的抗体研究进行阐述,希望可以帮助研究人员了解淀粉样蛋白相关抗体药物的研发现状,为以后研制AD新药提供思路。