Curcumin ameliorates hepatic chronic inflammation induced by bile duct obstruction in mice through the activation of heme oxygenase-1

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Differential effects of interleukin 12 and interleukin 10 on superantigen-induced expression of cutaneous lymphocyte-associated antigen (CLA) and alphaEbeta7 integrin (CD103) by CD8+ T cells

At both cutaneous and mucosal sites, interleukin (IL)-10, IL-12 and transforming growth factor (TGF)-beta are important regulators of chronic inflammatory disease, where cutaneous lymphocyte-associated antigen (CLA) and alphaE integrin (CD103) may be expressed. Stimulation with streptococcal pyrogenic exotoxin C (SpeC) increased the expression of CD103 by CD8+ but not CD4+ T cells. While adding IL-12 augmented the expression of CLA, superantigen-induced expression of CD103 was markedly suppressed by IL-12, which could be reversed by TGF-beta. Antibodies against TGF-beta inhibited, and a combination of anti-TGF-beta and IL-12 completely abrogated the induced CD103 expression. IL-10 strongly decreased the frequency of CLA+ and although not increasing the frequency of CD103+CD8+ T cells, the amount of CD103 expressed per cell was markedly increased. Thus, the expression of CLA and CD103 may be antagonistically regulated by IL-10 and IL-12 and the balance between these cytokines could influence the T cell migration of inflammatory cells into epithelial tissues.     

两例补体第8成份β亚基缺陷家系患者的进一步分子遗传基础研究

目的　在白人群体中 ,导致人类补体第 8成份 β亚基缺陷的分子基础主要是在编码 β亚基基因的第 9外显子上发生碱基 C→ T的突变 ,从而形成终止密码 ,导致 C8β亚基不能完全合成。国外学者在两例 C8β亚基完全缺失的患者家系研究中 ,发现这两例β亚基缺失个体只是第 9外显子上碱基 C→ T突变的杂合子 ,现进一步寻找这两例 C8β亚基完全缺失的分子遗传学机理。方法　对两例 C8β亚基完全缺失患者的 C8β编码基因的全部 11个外显子的 PCR扩增产物进行 DNA测序分析并与正常人 DNA序列进行对比。结果　两例完全性 C8β亚基缺失患者的蛋白质编码基因中 ,分别在第 3外显子的 2 98和 388位置发现了 C→T突变 ,同时对这两个突变位点的家系分析也证实 ,位于第 3外显子上的这两个突变位点是独立于第 9外显子的突变而遗传。结论　所发现的两个突变位点均能形成终止密码而导致 C8β亚基合成提前终止 ,因此这两例患者 C8β亚基完全缺失的分子遗传学机理是由于编码 C8β亚基的基因在第 3和第 9外显子上同时发生了点突变 ,进而形成终止密码造成 C8β亚基合成终止所致。     

TCRVβ基因谱系分析在AIDS疾病T细胞克隆性研究中的应用

对于T淋巴细胞TCRVB基因家族以及T细胞的克隆性的研究是近年的热点问题.通过对艾滋病人(模型)的TCRVβ基因谱系分析,测定特定CDR3长度及序列出现的频率能反映T细胞克隆扩增的程度和功能状态,进而有助于对MDS的临床诊断、免疫机制、药物或疫苗的治疗效果等的理解.     

Type 1 and type 2 tumor infiltrating effector cell subpopulations in progressive breast cancer

Effector T cells fall into two subpopulations based on cytokine-secretion. Type 1 cells secrete IFN-gamma, whereas type 2 cells secrete IL-4, IL-10, and GM-CSF. NKT cells represent a third subpopulation that secretes similar cytokines and have been associated with immunoregulation. Using the TS/A adenocarcinoma, we assessed the phenotype and kinetics of tumor-infiltrating lymphocytes (TIL) in mice challenged subcutaneously in the mammary region. Flow cytometric analysis shows that T cells do not infiltrate the primary tumor site until days 7-14 following tumor challenge. Both CD4 and CD8 TILs were predominantly CD44(High) and expressed CD25, CD69, and CD95 cell surface activation markers. Activated CD4/CD44(High) TIL numbers reached peak levels at day 21 that precipitously decreased by day 28 whereas corresponding CD8 cell numbers progressively increased, however, at lower levels and with later kinetics. Intracellular cytokine staining showed that greater numbers of IL-4-producing Th2 cells were elicited and with earlier kinetics than that of IFN-gamma-producing Th1 cells. T cells co-expressing DX5 (CD3(+)/DX5(+)) emerged (>21 days), suggesting a recruitment of NK-like T cells at later stages of tumor progression. Moreover, tumors selectively up-regulated TGF-beta, MIF, and IP-10 gene expression at times as early as day 4, with peak levels at day 7 in vivo. Such gene expression remained elevated and correlated with a continued progression in tumor growth suggesting that preferential effector cell recruitment and production of select factors during different stages of tumor maturation may aid in regulating effective endogenous antitumor responses in progressive breast cancer.     

P>胰岛素样生长因子-1抑制β淀粉样蛋白25～35诱导的神经干细胞凋亡/P>

目的 观察β-淀粉样蛋白(Aβ)对神经干细胞(NSCs)增殖和凋亡的影响,探讨胰岛素样生长因子-1(IGF-1)对Aβ介导的NSCs毒性作用的保护机制.方法 从E14 SD大鼠大脑中分离神经干细胞,分别用Aβ、IGF-1和Aβ加IGF-1处理,锥虫蓝(trypan blue)染色确定细胞死亡数量和细胞死亡率,BrdU标记并分析细胞增殖能力,免疫细胞化学法鉴定神经干细胞和新生细胞,TUNEL技术检测凋亡细胞.结果 IGF-1处理时细胞死亡率低下,有大量BrdU阳性细胞生成,但无TUNEL阳性细胞.Aβ处理组细胞死亡率在6～48 h快速上升,并形成大量TUNEL阳性细胞.而IGF-1加Aβ处理时,细胞死亡率较Aβ组显著下降.TUNEL阳性细胞显著减少.结论 Aβ促进神经干细胞死亡和凋亡;而IGF-1促进神经干细胞增殖并抑制由Aβ诱导的神经干细胞凋亡.     

日本血吸虫尾蚴cDNA文库的免疫学筛选及EST序列的分析

目的为获得日本血吸虫（Schistosoma japonicura，Sj）转化生长因子β1（TGF—β1）基因的部分或全长cDNA序列。同时验证用针对某一蛋白的抗体筛选表达文库是否可以得到相应蛋白对应的基因序列。方法采用兔抗鼠TGF—β1血清，对Sj尾蚴cDNA表达文库进行免疫学筛选，对阳性克隆进行PCR扩增后，将大于500bp的克隆进行复筛，对复筛阳性的克隆进行测序和生物信息学鉴定。结果对大约10^6个噬菌斑进行了初筛。共获得7个阳性克隆；经过PCR扩增后，其中有4个克隆大于500bp，复筛获得3个持续阳性克隆；对测序后的阳性克隆进行生物信息学鉴定，得到的三个克隆均与日本血吸虫辅酶Q10氧化还原酶（SjCHGC）基因具有高的同源性（Bhata分值都大于200）。结论SjCHGC蛋白与兔抗鼠TGF—β1抗体的反应为交叉反应，用抗某一蛋白的抗体筛选表达文库得到相应蛋白的基因序列的方法不一定可行。     

Clonal composition and persistence of antigen-specific circulating T follicular helper cells

T follicular helper (T_FH) cells play an essential role in promoting B cell responses and antibody affinity maturation in germinal centers (GC). A subset of memory CD4⁺ T cells expressing the chemokine receptor CXCR5 has been described in human blood as phenotypically and clonally related to GC T_FH cells. However, the antigen specificity and relationship of these circulating T_FH (cT_FH) cells with other memory CD4⁺ T cells remain poorly defined. Combining antigenic stimulation and T cell receptor (TCR) Vβ sequencing, we found T cells specific to tetanus toxoid (TT), influenza vaccine (Flu), or Candida albicans (C.alb) in both cT_FH and non-cT_FH subsets, although with different frequencies and effector functions. Interestingly, cT_FH and non-cT_FH cells specific for C.alb or TT had a largely overlapping TCR Vβ repertoire while the repertoire of Flu-specific cT_FH and non-cT_FH cells was distinct. Furthermore, Flu-specific but not C.alb-specific PD-1⁺ cT_FH cells had a “GC T_FH-like” phenotype, with overexpression of IL21, CXCL13, and BCL6. Longitudinal analysis of serial blood donations showed that Flu-specific cT_FH and non-cT_FH cells persisted as stable repertoires for years. Collectively, our study provides insights on the relationship of cT_FH with non-cT_FH cells and on the heterogeneity and persistence of antigen-specific human cT_FH cells.     

β-内酰胺酶抑制剂研究进展

报道了4种β-内酰胺酶抑制剂(包括克拉维酸、舒巴坦、他唑巴坦以及BRL-42715)的特性、各抑制剂的复方制剂、作用 机制,以及这些酶抑制剂与不耐酶的β-内酰胺类抗生素联合应用后的协同作用,并对酶抑制剂抑酶作用进行了比较。