福氏2a痢疾杆菌膜抗原的免疫电镜定位

本文报告应用抗福氏2a痢疾杆菌膜成份McAb及胶体金探针对细菌膜抗原进行了定位。结果显示4种抗脂多糖McAb(3A6、2E6、4F1、2A3)可不均一的识别位于细菌壁表面的抗原,而另外一种抗LPS的McAb种(1G8)和一种抗膜蛋白McAb(1A1)识别的抗原未暴露于细菌表面。应用细菌膜碎片包埋前染色成功定位了抗膜蛋白McAb(1A1)位于细菌内膜的抗原。与McAb的生物活性比较表明阳性标记细菌表面抗原的McAb的抗原与其阻段志贺氏菌接触性溶血试验和对小鼠的被动保护力密切相关。提示免疫电镜标记技术确定LPS抗原表位在细菌表面的可及性和拷贝数对构建和筛选痢疾工程菌苗具有重要意义。     

Ratio of spontaneous and o-aminoazotoluene-induced hepatocarcinogenesis in mice

No correlation was found between the frequency of spontaneous and o-aminoazotoluene (o-AAT)-induced hepatic tumours in mice. High susceptibility to tumour induction with o-AAT in mice both genetically susceptible (strains CBA and A/He) and resistant (strains DBA/2J and DD) to spontaneous hepatocarcinogenesis was detected. The CC57BR mice predisposed to spontaneous hepatomas were insensitive to their induction with o-AAT. The model described may be helpful in studies of the nature of the initiation and promotion stages of hepatocarcinogenesis.     

The effect of biocarbazine on the indices of humoral and cellular immunity in mice

Biocarbazin (5-3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide) when administered in different doses and schedules depressed the primary immune response of mice to erythrocytes (SE). A dose-dependent effect on the immunosuppression degree is revealed. Both the inductive and productive stages of antibody formation are sensitive to the immunosuppressive action of the agent. Under certain conditions biocarbazin induced a sharp suppression of humoral immune response. At the same time, it enhanced significantly the delayed-type hypersensitivity (DTH) response to SE.     

Modification of repair of X-irradiation damage of hemopoietic system of mice by microwaves.

Microwaves (2450 tmhz, 10e mW/cm2, 300 s) were used to modify X-irradiation damage of the hemopoietic system in the mouse. Compared with X-irradiated controls, microwave-treated mice manifested an increased number of surviving hemopoietic stem cells, heightened erythropoiesis and myelopoiesis and increased rate of survival.     

一阶相关免疫函数的新构造方法与计数

本文研究了一阶相关免疫函数构造、计数问题,提出了一种新的一阶相关免疫函数的构造方法,由此得到了大量的一阶相关免疫函数;并通过这种构造方法给出了一个目前最好的一阶相关免疫函数个数下界,此下界比现有的结果至少改进了(2^2<em>n-1+2n)/(2ⁿ⁺⁸-2¹⁰).     

Effect of androgens on the development of leukemia in AKR-strain mice

A possibility of the androgen's correction of spontaneous and transplanted leukogenesis has been investigated in AKR mice. Prolongation of life was observed in the animals treated with the hormone at early stages of the leukemia development. The obtained results may be related to the stem hemopoietic precursors differentiation change under the testosterone influence manifested by erythropoiesis stimulation and the reduction of granulocytic colonies determined by the growth in the cellulose-acetate membranes (CFUcam).     

Immunity to embryonal stage-specific antigens in viral carcinogenesis

The oncogenesis induced by the monkey SA7(C8) adenovirus in CBA/Ca mice has shown that immune responses to embryonal antigens are formed at early stages of the latent period and are preserved for a long time reaching the maximum by the 30th day of the latent period. The observed immune response to early embryonal antigens is considered as a factor of the tumour growth immunostimulation and also as a condition limiting the antitumour immunity.     

低强度532nm绿激光照射对小鼠腹腔巨噬细胞功能的影响

目的:观察低强度532nm激光对小鼠腹腔巨噬细胞吞噬功能的影响。方法:用不同功率和照射时间的532nm激光辐照小鼠腹腔巨噬细胞,采用中性红吞噬实验测定巨噬细胞的吞噬能力。结果:在适当的激光功率和照射时间下巨噬细胞的吞噬能力有显著性增强。结论:低强度532nm激光照射对小鼠腹腔巨噬细胞有激活作用,可增强其免疫活性。     

癫痫患者血清细胞因子水平与脑电图的相关性探讨

目的：探究癫痫患者血清细胞因子水平同脑电图之间存在的相关性。方法：将2015年4月~2016年4月期间我院收治的56例癫痫患者作为试验组,再选取同期在我院进行体检的56名健康人作为对照组,全部患者都给予常规脑电图检查。结果：试验组人员的血清肿瘤坏死因子、白细胞介素以及脑电图检测结果等都明显的比对照组高,差异具有统计学意义（P＜0.05）;其中癫痫患者的血清肿瘤坏死因子及白细胞介素之间具有显著的正相关（P＜0.05）。结论：癫痫患者一般具有细胞免疫功能紊乱的症状,免疫细胞CD8、CD4及肿瘤坏死因子（TNF）-α与白细胞介素（IL）-2等均为影响癫痫病情的关键介质。其中脑电图改变同免疫细胞CD8、CD4及TNF-α与IL-2水平等紧密相关,距离癫痫发作期越近,有关免疫细胞及细胞因子异常水平则越高,而同期脑电图异常率则越高。     

基于高光谱的砂岩露头孔隙度估算方法

为快速获得宏观、定量的砂岩露头孔隙度,提出了基于高光谱的孔隙度估算新方法.采集野外露头砂岩样品并测得其孔隙度,利用岩石薄片鉴定资料分析砂岩孔隙度的影响因素;对岩样实测光谱预处理,探索砂岩孔隙度的光谱响应机理;考虑到光谱波段高维性和波段间多重相关性,采用偏最小二乘方法构建孔隙度估算模型;通过变量投影重要性分析模型中重要波段.研究结果表明:基于砂岩填隙物与孔隙度的相关性以及填隙物的光谱特征,可间接反演孔隙度;砂岩孔隙度具有良好的光谱响应;反射率能够定量估算砂岩孔隙度(全波段模型R2=0. 72,RMSE=2. 28,RPD=1. 94);重要波段帮助降低自变量维度,发现孔隙度敏感波谱响应.本研究为基于高光谱图像的野外露头孔隙度表征奠定了基础.     

Metformin Mediated PD-L1 Downregulation in Combination with Photodynamic-Immunotherapy for Treatment of Breast Cancer

Intelligent nanomaterials open up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of simple enzymatically cleavable self-delivery nanoparticles (MA-pepA-Ce6 NPs) is developed by conjugating acidic-sensitive small-molecule programmed cell death ligand 1 (PD-L1) inhibitor (Metformin, MET) with photosensitizer (chlorin e6, Ce6) through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGDK, pepA). Noticeably, these self-delivery peptide-based NPs can circumvent the controversial biosafety facing nanomaterials. Moreover, MA-pepA-Ce6 NPs are degraded by overexpressed MMP-2 in tumor microenvironment (TME) and expose the VRGDK-Ce6. The exposed VRGDK-Ce6 shows superior targeting ability towards integrin α_vβ₃ receptor, ensuring sufficient accumulation and laser-activated robust antitumor immune effects. Remarkably, the released MET in tumor microenvironment hampers the PD-L1 expression and augments the antitumor immune response elicited by photodynamics therapy (PDT), thus significantly improving therapeutic outcomes. Overall, this study offers a potential appealing paradigm of synergistic PDT-triggered immunotherapy by revealing MET-mediated PD-L1 downregulation to achieve tumor eradication.     

H布尔函数的相关免疫性与重量的关系

将布尔函数的导数和与导数一起便可直接明确刻画布尔函数的重量而定义的e-导数一起作研究工具,深入到布尔函数取值的内部结构中去,讨论了在H布尔函数存在的一个大重量范围内,所有不同重量的H布尔函数的一阶、任意m阶相关免疫函数存在与否的问题。对存在m阶相关免疫性的H布尔函数,它的相关免疫阶数m与维数n的具体关系,以及m的最大值问题。给出了m阶相关免疫H布尔函数只存在于2种重量的H布尔函数中,其相关免疫阶数m的最大值为n-2,以及其余重量的H布尔函数中不存在二阶以上(包括二阶)相关免疫函数等一系列结果。同时,也给出了一些判断布尔函数相关免疫性的方法。     

Possible zymosan stimulation of the immune response of BALB/c mice to sheep erythrocytes and tumor target cells

Zymosan and its combinations with cyclophosphamide were tested for their effect on various immune responses. Zymosan alone had only minor effect on the cytotoxicity of lymphocytes to allogeneic and syngeneic tumour cells but significantly stimulated delayed-type hypersensitivity response, rosette formation and plaque forming cell response to sheep red blood cells in normal mice. Zymosan diminished immunosuppressive action of cyclophosphamide on the plaque and rosette formations and nonspecific allogeneic lysis of target cells by lymph node lymphocytes. Delayed-type hypersensitivity skin reaction and syngeneic T-killer cell activity increased significantly after the procedure of combination therapy. Lymphocyte stimulation action by the polysaccharide depended on the injection schedule used. Preliminary injection of zymosan was an optimal condition for enhancement of the cellular immune response.     

光动力法制备抗小鼠H22肝癌的肿瘤疫苗

研究了光动力疗法(PDT)制备的抗小鼠H22肝癌肿瘤疫苗的抗瘤效应.将昆明鼠60只,随机分为2组,每组30只.实验组取6~12周龄的昆明鼠背部皮下接种光动力疗法产生的疫苗,每3天注射一次,每次注射50μL(相当于3×105个细胞),连续两周.隔一周于第22天注射H22肿瘤细胞悬液0.1 mL(1×106个细胞);对照组:每周每次注射50μL生理盐水,连续两周.隔一周于第22天注射H22肿瘤细胞悬液0.1 mL(1×106个细胞).比较两组的抑瘤率、生存率以及两组之间免疫学的相关指标.结果表明,实验组小鼠具有显著的抑瘤效果,抑瘤率、生存率较对照组有显著提高.实验组肿瘤抑瘤率最高可达60%且长期有效,100天生存率达56%.说明光动力疗法产生的抗小鼠H22肝癌疫苗可以有效地抑制肿瘤生长,提高荷瘤小鼠的生存率,具有明显的抗瘤效应.该方法可能成为一种辅助性治疗肿瘤的手段而应用于临床.     

Immune Complexes Mimicking Synthetic Vaccine Nanoparticles for Enhanced Migration and Cross‐Presentation of Dendritic Cells

The well‐designed activation of dendritic cells (DCs) by enhancing the delivery of antigens and immunostimulatory adjuvants into DCs is a key strategy for efficient cancer immunotherapy. Antigen‐antibody immune complexes (ICs) are known to directly bind to and cross‐link Fc‐gamma receptors (FcγRs) on DCs, which induce enhanced migration of DCs to draining lymph nodes through the up‐regulation of the chemokine receptor CCR7 and cross‐presentation inducing cytotoxic T lymphocyte (CTL) response against tumor antigen. In this study, ICs mimicking synthetic vaccine nanoparticles (NPs) are designed and synthesized by the coating of poly (lactic‐co‐glycolic acid) (PLGA) NPs containing adjuvant (CpG oligodeoxynuleotides (ODNs) as toll‐like receptor 9 ligands) with ovalbumin (OVA) proteins (as model antigens) and by the formation of OVA–OVA antibody ICs. Through the combination of FcγRs‐mediated efficient antigen uptake and CpG ODNs‐based immunostimulation, the secretion of TNF‐α (12.3‐fold), IL‐6 (7.29‐fold), and IL‐12 (11‐fold), homing ability to lymph nodes (7.5‐fold), and cross‐presentation (83.8‐fold IL‐2 secretion) are dramatically increased in DCs treated with PLGA(IC/CpG) NPs. Furthermore, mice vaccinated with DCs treated with PLGA(IC/CpG) NPs induced significant tumor (EG7‐OVA) growth inhibition as well as prolonged survival through CTL‐mediated enhanced cytotoxicity, antigen‐specific responses, and IFN‐γ secretion.     

Modulation of mammalian immunity by electromagnetic radiation

There have been reports that electromagnetic radiation (EMR) alters the function of the immune system; however, these reports are often contradictory. This review reexamines the literature and attempts to evaluate the data on potential mechanisms of interaction of EMR on mammalian immune function. This report concludes that there is no convincing evidence that EMR effects on the human immune system are a health hazard. It was suggested by some authors that long-term EMR exposure may impair immune surveillance, and hypothetically thus facilitate tumor growth. Additional research is needed to prove or disprove this hypothesis. Available data indicate that EMR exposure does not affect the ability of cells of the immune system to respond to a subsequent challenge. However, the time-course and magnitude of the response may be affected by exposure following stimulation. Research to date provided evidence that at least at some frequencies and/or amplitude and pulse modulations, the site of primary interaction of EMR is at the cell membrane. However, it was shown that one specific response, the increase in B complement-receptor positive lymphocytes (Cr+) in the mouse is under genetic control by a single gene localized on chromosome 5. It is suggested that cells of the immune system are a convenient model for further studies on mechanisms of EMR interaction with living systems. Future research should be directed at exploring beneficial medical applications of EMR modulation of immune responses.     

Characteristics of metastasis and antimetastatic activity of macrophages in mice after postoperative immunomodulation

Results of the treatment of spontaneous pulmonary metastases by immunocorrection after tumour resection in mice and the analysis of antimetastatic activity of spleen macrophages (SM) by the method of adoptive transfer are presented. The injection of cytotoxic SM, NK-cells or the use of the biological response (lipid A and MDP-PE) modifiers cause no decrease in the number of lung metastases. The SM of operated mice, as distinct from the SM of immunocorrected mice causes the metastatic spreading in lungs of recipient mice. This effect is supposed to be mediated by the suppressor macrophages secreting prostaglandin E2 (PgE2). The treatment of mice with indometacin (inhibitor of the PgE2-synthesis) in the drinking water resulted in the 7-8-fold decrease in the number of lung metastases in operated mice.     

Nanotechnology‐Enabled Closed Loop Insulin Delivery Device: In Vitro and In Vivo Evaluation of Glucose‐Regulated Insulin Release for Diabetes Control

Recently, a new multifunctional, bio‐inorganic nanocomposite membrane with the ability to self‐regulate the release of insulin in response to blood glucose (BG) levels was reported. Herein, the application of this material as part of a small, implantable, closed‐loop insulin delivery device designed to continuously monitor BG concentrations and regulate insulin release is proposed. The insulin delivery device consists of a nanocomposite glucose‐responsive plug covalently bound to an insulin reservoir made of surface‐modified silicone. The plug is prepared with crosslinked bovine serum albumin (BSA) and enzymes (glucose oxidase (GOx) and catalase (CAT)), pH‐responsive hydrogel nanoparticles, and multifunctional MnO₂ nanoparticles. The plug functions both as a glucose sensor and controlled delivery unit to release higher rates of insulin from the reservoir in response to hyperglycemic BG levels and basal insulin rates at normal BG concentration. The surfaces of the device are modified by silanization followed by PEGylation to ensure its safety and biocompatibility and the stability of encased insulin. Our results show that insulin release can be modulated in vitro in response to glucose concentrations. In vivo experiments show that the glycemia of diabetic rats can be controlled with implantation of the prototype device. The glucose‐responsiveness of the device is also demonstrated by rapid drop in BG level after challenging diabetic rats with bolus injection of glucose solution. In addition, it is demonstrated that surface PEGylation of the device is necessary for reducing the immune response of the host to the implanted foreign object and maintaining insulin stability and bioactivity. With this molecular architecture and the bio‐inorganic nanocomposite plug, the device has the ability to maintain normal BG levels in diabetic rats.     

Beta3 receptors mediate relaxation in stomach fundus whereas a fourth beta receptor mediates tachycardia in atria from transgenic beta3 receptor knockout mice

Pharmacological studies have revealed a non-beta1, beta2 or beta3 adrenergic receptor that mediates tachycardia in rat and human atria. The present studies utilized transgenic mice that lack the rodent beta3 receptor to explore, in a more definitive fashion, whether a non-beta1, beta2 or beta3 receptor can mediate atrial tachycardia. Insofar as the rat stomach fundus possesses a beta3 receptor mediating relaxation, we examined the stomach fundus from beta3 receptor knockout mice for the presence or absence of the beta3 relaxant receptor. Contractile responses to carbamylcholine were similar in potency and magnitude between mouse stomach fundus from wild type and beta3 receptor knockout animals. However, the classical beta3 receptor agonist CL316243, (10(-8)-10(-6)M) relaxed stomach fundus from wild type mice, but not from the beta3 receptor knockout animals. These data provide functional evidence for the absence of the beta3 receptor in beta3 receptor knockout animals and support the role of beta3 receptors mediating relaxation in mouse stomach fundus. Atria from mice lacking the beta3 receptor responded similarly (in potency and maximal increase in heart rate) to isoproterenol (10(-9)-10(-6)M) as atria from wild type mice. Furthermore, propranolol (3 x 10(-7) M) produced a dextral shift in the concentration response to isoproterenol in atria from both the beta3 receptor knockout and wild type mice with negative log K(B) values of 8.03 and 8.09, respectively. Thus, beta receptors mediating tachycardia to isoproterenol are intact and respond similarly in atria from both knockout and wild type mice. Furthermore, CGP12177, a prototypic 'atypical' beta receptor agonist produced tachycardia with a similar EC50 and maximal response in atria from both the wild type and beta3 receptor knockout mice. Cyanopindolol was a partial agonist relative to CGP12177 in both wild type and beta3 receptor knockout mice. Tachycardia to CGP12177 and cyanopindolol was not blocked by propranolol (3 x 10(-7) M) in atria from either group. These data provide definitive evidence that the receptor mediating tachycardia to CGP12177 and to cyanopindolol in atria from the transgenic beta3 receptor knockout mice is neither the beta1, beta2, nor beta3 adrenergic receptor.     

Microneedle-Based Local Delivery of CCL22 and IL-2 Enriches Treg Homing to the Skin Allograft and Enables Temporal Monitoring of Immunotherapy Efficacy

Skin allografts only serve as temporary dressing for patients suffering major burns due to their high immunogenicity and rejection by the immune system, requiring systemic immunosuppressive therapies that lead to deleterious side effects. Microneedle arrays composed of hyaluronic acid (HA) and placed on skin allografts can locally deliver immunomodulators and simultaneously sample immune cells in interstitial fluid to monitor the response to the therapy. The cells can be retrieved from the microneedles for downstream analysis by degrading the HA using a reducing agent. Using an allogeneic skin transplantation model, it is shown that the microneedle-mediated local delivery of the chemokine CCL22 (to attract T_regs) and the cytokine IL-2 (to promote their expansion) increases the local immune suppression in the allograft. Moreover, immune cell population in the allograft correlates with that seen in the microneedles. The delivery and sampling functions of the microneedle arrays can help regulate the immune system locally, without inducing systemic immune suppression, and facilitate the monitoring of the response to the therapy following skin transplantation.