基于肿瘤免疫微环境鉴定IDH突变型弥漫性胶质瘤的预后标志物

异柠檬酸脱氢酶(IDH)突变存在于大多数低级别胶质细胞瘤中,免疫逃逸是肿瘤标志性特征之一,免疫治疗在胶质瘤的治疗中的作用越来越重要。利用生信手段分析TCGA、CGGA、GEO数据集中IDH突变胶质瘤的770个免疫相关基因及其临床相关数据,从而获得每个患者的免疫风险评分(IMRS);结合IMRS和临床信息,筛选出6个差异表达基因(TRAF3、ATG10、BID、TAB1、MAP3K1、RPS6)组成IMRS模型并生成诺莫图对患者预后进行评估,发现低风险组患者的总生存期(OS)较高风险组均明显延长。此外,签名相关免疫细胞浸润分析发现肿瘤相关巨噬细胞浸润评分(TAM)与肿瘤相关T细胞浸润评分(TIS)呈明显的负相关,表明高IMRS富集了促肿瘤免疫浸润,而低IMRS则富集了相对较多的抗肿瘤免疫浸润。     

微生态制剂辅助普米克令舒提高过敏性哮喘患儿免疫功能

目的探讨微生态制剂辅助普米克令舒是否能提高过敏性哮喘患儿免疫功能。方法选择2018年1月至2019年12月在我院确诊并进行治疗的过敏性哮喘患儿150例,根据数字表法随机分为观察组与对照组,每组各75例。对照组患儿给予普米克令舒雾化吸入及常规综合治疗,观察组在对照组基础上辅助微生态制剂双歧四联活菌片进行治疗。对两组患儿治疗效果、治疗前后肠道菌群变化、免疫功能和用药期间不良反应发生率等指标进行比较分析。结果两组患儿治疗后观察组有效率为92.0%,显著高于对照组的77.3%(P<0.05)。两组患儿治疗前肠道菌群差异无统计学意义(P>0.05)。与治疗前比较,观察组患儿治疗后乳酸菌、双歧杆菌数量明显增多,肠球菌、肠杆菌数量明显减少(P<0.05),组间比较,观察组乳酸菌、双歧杆菌数量显著多于对照组,肠球菌、肠杆菌数量显著低于对照组(P<0.05)。与治疗前比较,治疗后两组患儿CD3⁺、CD4⁺水平、CD4⁺/CD8⁺比值均升高,CD8⁺水平下降(P<0....     

肠内营养联合微生态制剂对重症胰腺炎患者的疗效

目的 观察肠内营养联合微生态制剂对重症胰腺炎患者细菌移位、免疫功能、炎症反应的影响.方法 选择我院2017年1月至2019年7月收治的200例重症胰腺炎患者为研究对象,根据治疗方法不同分为A组、B组、C组.A组患者采用肠外营养治疗,B组患者采用肠内营养治疗,C组患者采用肠内营养联合微生态制剂治疗.比较3组患者的治疗效果...     

Growth performance,haematological assessment and chemical composition of Nile tilapia,Oreochromis niloticus (Linnaeus, 1758) fed different levels of Aloe vera extract as feed additives in a closed aquaculture system

A 105-day experimental trial was conducted to assess different levels of dietary Aleo vera extract supplementation on water quality parameters, proximate composition, growth performance and haematological parameters of fry Oreochromis niloticus. Four different percentages of dietary leaf extract powder of Aleo vera (ALE) with a basal feed, designated as, i.e., T0 (Control group; without ALE), T1 (1% ALE), T2 (2% ALE), and T3 (3% ALE). Fish fry was reared in concrete tanks (7.0 m, 1.6 m, 1.0: L, W, H; water volume 11.2 m3/tank), with an average initial weight 4.04 ± 0.03 g/ fry, and each treatment was triplicated. Fry was randomly distributed at a stocking rate of 450 individuals/ tanks. The water quality parameters revealed that temperature, pH, salinity, dissolved oxygen (DO) and nitrates were found in a promising range as given by FAO/WHO limits. However, the record values obtained for Electric Conductivity (EC), Total dissolved solids (TDS), and alkalinities were not found in all tanks' suitable range according to FAO/WHO limits. The results revealed a significant impact of different percentages of dietary ALE supplementation on fry's body composition and haematological parameters. Moreover, the final body weight, final body length, average daily weight gain (g), net weight gain (g) and specific growth rate (%) were significantly higher (p < 0.05) in T1 and T2 compared with T0 and T3 treatments. The poorest feed conversion ratio was recorded in the T2 group compared with other treatments. Thus, the current study provides information about the nutritional quality of Nile tilapia culturing in Pakistan.     

l-Arginine Effects on Na+ Transport in M-1 Mouse Cortical Collecting Duct Cells—A Cationic Amino Acid Absorbing Epithelium

The effect of l-arginine on transepithelial ion transport was examined in cultured M-1 mouse renal cortical collecting duct (CCD) cells using continuous short circuit current (I _SC ) measurements in HCO₃ ⁻/CO₂ buffered solution. Steady state I _SC averaged 73.8 ± 3.2 μA/cm² (n= 126) and was reduced by 94 ± 0.6% (n= 16) by the apical addition of 100 μm amiloride. This confirms that the predominant electrogenic ion transport in M-1 cells is Na⁺ absorption via the epithelial sodium channel (ENaC). Experiments using the cationic amino acid l-lysine (radiolabeled) as a stable arginine analogue show that the combined activity of an apical system y⁺ and a basal amino acid transport system y⁺L are responsible for most cationic amino acid transport across M-1 cells. Together they generate net absorptive cationic amino acid flux. Application of l-arginine (10 mm) either apically or basolaterally induced a transient peak increase in I _SC averaging 36.6 ± 5.4 μA/cm² (n= 19) and 32.0 ± 7.2 μA/cm² (n= 8), respectively. The response was preserved in the absence of bath Cl⁻ (n= 4), but was abolished either in the absence of apical Na⁺ (n= 4) or by apical addition of 100 μm amiloride (n= 6). l-lysine, which cannot serve as a precursor of NO, caused a response similar to that of l-arginine (n= 4); neither L-NMMA (100 μm; n= 3) nor L-NAME (1 mm; n= 4) (both NO-synthase inhibitors) affected the I _SC response to l-arginine. The effects of arginine or lysine were replicated by alkalinization that mimicked the transient alkalinization of the bath solution upon addition of these amino acids. We conclude that in M-1 cells l-arginine stimulates Na⁺ absorption via a pH-dependent, but NO-independent mechanism. The observed net cationic amino acid absorption will counteract passive cationic amino acid leak into the CCD in the presence of electrogenic Na⁺ transport, consistent with reports of stimulated expression of Na⁺ and cationic amino acid transporters by aldosterone. Received: 11 September 2000/Revised: 6 December 2000     

Immune dysfunction in patients with diabetes mellitus (DM)

Patients with diabetes mellitus (DM) have infections more often than those without DM. The course of the infections is also more complicated in this patient group. One of the possible causes of this increased prevalence of infections is defects in immunity. Besides some decreased cellular responses in vitro, no disturbances in adaptive immunity in diabetic patients have been described. Different disturbances (low complement factor 4, decreased cytokine response after stimulation) in humoral innate immunity have been described in diabetic patients. However, the clinical relevance of these findings is not clear. Concerning cellular innate immunity most studies show decreased functions (chemotaxis, phagocytosis, killing) of diabetic polymorphonuclear cells and diabetic monocytes/macrophages compared to cells of controls. In general, a better regulation of the DM leads to an improvement of these cellular functions. Furthermore, some microorganisms become more virulent in a high glucose environment. Another mechanism which can lead to the increased prevalence of infections in diabetic patients is an increased adherence of microorganisms to diabetic compared to nondiabetic cells. This has been described for Candida albicans. Possibly the carbohydrate composition of the receptor plays a role in this phenomenon.     

Macrophage response to <Emphasis Type="Italic">Mycobacteriumtuberculosis</Emphasis> infection

The immune response to Mycobacterium tuberculosis (Mtb) infection is the formation of multicellular lesions, or granolomas, in the lung of the individual. However, the structure of the granulomas and the spatial distribution of the immune cells within is not well understood. In this paper we develop a mathematical model investigating the early and initial immune response to Mtb. The model consists of coupled reaction-diffusion-advection partial differential equations governing the dynamics of the relevant macrophage and bacteria populations and a bacteria-produced chemokine. Our novel application of mathematical concepts of internal states and internal velocity allows us to begin to study this unique immunological structure. Volume changes resulting from proliferation and death terms generate a velocity field by which all cells are transported within the forming granuloma. We present numerical results for two distinct infection outcomes: controlled and uncontrolled granuloma growth. Using a simplified model we are able to analytically determine conditions under which the bacteria population decreases, representing early clearance of infection, or grows, representing the initial stages of granuloma formation.     

Optimal HIV treatment by maximising immune response

We present an optimal control model of drug treatment of the human immunodeficiency virus (HIV). Our model is based upon ordinary differential equations that describe the interaction between HIV and the specific immune response as measured by levels of natural killer cells. We establish stability results for the model. We approach the treatment problem by posing it as an optimal control problem in which we maximise the benefit based on levels of healthy CD4+ T cells and immune response cells, less the systemic cost of chemotherapy. We completely characterise the optimal control and compute a numerical solution of the optimality system via analytic continuation.Research supported by the Natural Science and Engineering Research Council (NSERC) and the Mathematics of Information Technology and Complex Systems (MITACS) of Canada     

Tetraspanins connect several types of Ig proteins: IgM is a novel component of the tetraspanin web on B-lymphoid cells

The tetraspanins form a family of about 30 molecules mainly expressed on the cell surface. They have been reported to be involved in many physiological or pathological processes, such as fertilization, immune response, development of the nervous system, and metastasis, as well as in infectious diseases (HCV, malaria, etc.). The tetraspanins may play a role as organizers of multimolecular complexes on the cell surface associating numerous proteins, the tetraspanin web. To better define the composition of the tetraspanin web, its characterization has been recently performed using mass spectrometry and proteomics. We report the proteomic analysis of tetraspanin complexes on B-lymphoid cells. Immunoprecipitation experiments were performed using mAbs directed against the tetraspanin CD9, and associated molecules were identified by MALDI-TOF (matrix assisted laser desorption ionization time of flight) mass spectrometry. This led to the identification of IgM as a novel component of the complexes. Thus, tetraspanins may connect several types of proteins with Ig domains, including HLA-DR, EWI-2, and IgM, that may play a role in immune responses.This work was presented at the first Cancer Immunology and Immunotherapy Summer School, 8–13 September 2003, Ionian Village, Bartholomeio, Peloponnese, Greece.     

Targeting the immune system: novel therapeutic approaches in squamous cell carcinoma of the head and neck

Despite advances in surgery, radiotherapy, and chemotherapy, the overall survival rates for patients with squamous cell carcinoma of the head and neck (SCCHN) have not changed over the last decades. Clearly, novel therapeutic strategies are needed for this cancer, which is highly immunosuppressive. Therefore, biologic therapies able to induce and/or up-regulate antitumor immune responses could represent a complementary approach to conventional treatments. Because patients with SCCHN are frequently immunocompromised due to the elimination or dysfunction of critical effector cells of the immune system, it might be necessary to restore these immune functions to allow for the generation of more effective antitumor host responses. Simultaneously, to prevent tumor escape, it might be necessary to alter attributes of the malignant cells. The present review summarizes recent advances in the field of immunotherapy of SCCHN, including techniques of nonspecific immune stimulation, the use of monoclonal antibodies, advances in adoptive immunotherapy and genetic engineering, as well as anticancer vaccines. These biologic therapies, alone or in combination with conventional treatment, are likely to develop into useful future treatment options for patients with SCCHN.