YCa_2Cu_3O_(ya)的合成、结构和半导电性

合成了化合物YCa_2Cu_3Oy,这个化合物结构属正交晶系a=6.528A, b=5.421(?),c=10.404(?)。氧含量y=6.55。Yca_2Cu_3Oy是黑色n型半导体材料,室温电阻率1.2×10~5Ω·cm。测量了该化合物的R—T关系,并把它的组成、结构和性质与超导化合物YBa_2Cu_3Oy进行了对比和分析。

中国明对虾核转录因子NF-κB家族基因的克隆与表达分析

对虾流行病爆发以来，我国乃至世界的对虾产业一直受到各种虾病的困扰，对虾养殖业严重受阻。解决这一问题的关键是加强对虾免疫机制的研究，并在此基础上寻找对虾疾病防治的有效方法。Rel/NF-κB是一类核转录因子，在无脊椎动物的先天性免疫中，起着极为重要的作用。 本论文根据其他无脊椎动物中NF-κB家族基因Relish和Dorsal的保守氨基酸序列分别设计简并引物，从中国明对虾血细胞cDNA中先后克隆到了Relish和Dorsal基因的部分片段，并结合SMART-RACE技术分别获得了中国明对虾Relish基因（FcRelish）和Dorsal基因（FcDorsal）的cDNA 全长。 FcRelish的cDNA 全长为2157个碱基，其中开放阅读框为1512个碱基，编码504个氨基酸；FcRelish蛋白的推导分子量为57373.5 Da，理论等电点为7.00。FcDorsal基因的cDNA 全长为1627个碱基，其中开放阅读框为1071个碱基，编码357个氨基酸；FcDorsal蛋白的推导分子量为39780.7 Da，理论等电点为8.85。 分析了FcRelish基因和FcDorsal基因的在血细胞、淋巴器官、肠和肌肉等12个组织中的表达水平。组织表达结果表明FcRelish和FcDorsal在淋巴器官和血细胞中表达水平明显高于其他组织，而淋巴器官和血细胞是对虾免疫系统中最重要的两个组织，由此可以推测中国明对虾中的Relish和Dorsal可能与免疫关系密切。 本论文还利用实时荧光定量PCR技术，对灭活鳗弧菌刺激，以及WSSV病毒刺激后，对虾血细胞和淋巴器官中FcRelish基因和FcDorsal基因的转录水平进行了研究。FcRelish基因在WSSV病毒刺激后，在血细胞和淋巴器官中都出现了波浪形变化，说明FcRelish对WSSV病毒刺激产生了应答。在灭活鳗弧菌刺激后，FcRelish在血细胞中变化不明显，而在淋巴器官中出现了两次明显的下调上调交替，出现这种现象的具体原因有待探究。在WSSV病毒刺激后，血细胞和淋巴器官中FcDorsal的转录表达呈波浪形变化。而在鳗弧菌刺激后，FcDorsal在血细胞和淋巴器官中的转录均在短时间内出现明显的上调表达，说明FcDorsal对鳗弧菌非常敏感。 作为核转录因子的NF-κB蛋白的转录激活作用需要在细胞质中通过蛋白水解作用来激活，为了进一步阐明NF-κB对病菌感染的应答机制，需要进一步研究这两种转录因子在蛋白水平的变化，以便从分子水平阐明NF-κB在对虾天然免疫中的作用。

Proteasome and NF-kappa B inhibiting phaeophytins from the green alga Cladophora fascicularis

Chemical examination of the green alga Cladophora fascicularis resulted in the isolation and characterization of a new porphyrin derivative, porphyrinolactone (1), along with five known phaeophytins 2-6 and fourteen sterols and cycloartanes. The structure of 1 was determined on the basis of spectroscopic analyses and by comparison of its NMR data with those of known phaeophytins. Compounds 1-6 displayed moderate inhibition of tumor necrosis factor alpha (TNF-alpha) induced nuclear factor-kappa B (NF-kappa B) activation, while 2 and 4 displayed potential inhibitory activity toward proteasome chymotripsin-like activation. The primary structure-activity relationship was also discussed.

In vivo luminescence imaging of NF-κB activity and serum cytokine levels predict pain sensitivities in a rodent model of osteoarthritis.

OBJECTIVE: To investigate the relationship between NF-κB activity, cytokine levels, and pain sensitivities in a rodent model of osteoarthritis (OA). METHODS: OA was induced in transgenic NF-κB-luciferase reporter mice via intraarticular injection of monosodium iodoacetate (MIA). Using luminescence imaging we evaluated the temporal kinetics of NF-κB activity and its relationship to the development of pain sensitivities and serum cytokine levels in this model. RESULTS: MIA induced a transient increase in joint-related NF-κB activity at early time points (day 3 after injection) and an associated biphasic pain response (mechanical allodynia). NF-κB activity, serum interleukin-6 (IL-6), IL-1β, and IL-10 levels accounted for ∼75% of the variability in pain-related mechanical sensitivities in this model. Specifically, NF-κB activity was strongly correlated with mechanical allodynia and serum IL-6 levels in the inflammatory pain phase of this model (day 3), while serum IL-1β was strongly correlated with pain sensitivities in the chronic pain phase of the model (day 28). CONCLUSION: Our findings suggest that NF-κB activity, IL-6, and IL-1β may play distinct roles in pain sensitivity development in this model of arthritis and may distinguish the acute pain phase from the chronic pain phase. This study establishes luminescence imaging of NF-κB activity as a novel imaging biomarker of pain sensitivities in this model of OA.

Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity.

Immune responses must be well restrained in a steady state to avoid excessive inflammation. However, such restraints are quickly removed to exert antimicrobial responses. Here we report a role of autophagy in an early host antifungal response by enhancing NFκB activity through A20 sequestration. Enhancement of NFκB activation is achieved by autophagic depletion of A20, an NFκB inhibitor, in F4/80(hi) macrophages in the spleen, peritoneum and kidney. We show that p62, an autophagic adaptor protein, captures A20 to sequester it in the autophagosome. This allows the macrophages to release chemokines to recruit neutrophils. Indeed, mice lacking autophagy in myeloid cells show higher susceptibility to Candida albicans infection due to impairment in neutrophil recruitment. Thus, at least in the specific aforementioned tissues, autophagy appears to break A20-dependent suppression in F4/80(hi) macrophages, which express abundant A20 and contribute to the initiation of efficient innate immune responses.

NF-KB Activation and Severity of Gastritis in Helicobacter pylori-Infected Children and Adults.

In contrast to adults, Helicobacter pylori gastritis in children is reported as milder and ulcer disease as uncommon, but unequivocal data are lacking.

HIF-1 and NF-kappaB-mediated upregulation of CXCR1 and CXCR2 expression promotes cell survival in hypoxic prostate cancer cells

Hypoxic cancer cells are resistant to treatment, leading to the selection of cells with a more malignant phenotype. The expression of interleukin-8 (IL-8) plays an important role in the tumorigenesis and metastasis of solid tumors including prostate cancer. Recently, we detected elevated expression of IL-8 and IL-8 receptors in human prostate cancer tissue. The objective of the current study was to determine whether hypoxia increases IL-8 and IL-8 receptor expression in prostate cancer cells and whether this contributes to a survival advantage in hypoxic cells. IL-8, CXCR1 and CXCR2 messenger RNA (mRNA) expression in PC3 cells was upregulated in response to hypoxia in a time-dependent manner. Elevated IL-8 secretion following hypoxia was detected by enzyme-linked immunosorbent assay, while immunoblotting confirmed elevated receptor expression. Attenuation of hypoxia-inducible factor (HIF-1) and nuclear factor-kappaB (NF-kappaB) transcriptional activity using small interfering RNA (siRNA), a HIF-1 dominant-negative and pharmacological inhibitors, abrogated hypoxia-induced transcription of CXCR1 and CXCR2 in PC3 cells. Furthermore, chromatin-IP analysis demonstrated binding of HIF-1 and NF-kappaB to CXCR1. Finally, inhibition of IL-8 signaling potentiated etoposide-induced cell death in hypoxic PC3 cells. These results suggest that IL-8 signaling confers a survival advantage to hypoxic prostate cancer cells, and therefore, strategies to inhibit IL-8 signaling may sensitize hypoxic tumor cells to conventional treatments.

Elafin prevents lipopolysaccharide-induced AP-1 and NF-kB activation via an effect on the ubiquitin-proteasome pathway

In this paper we follow on from our research into SLPI by assessing the immunomodulatory activity of elafin - an antiprotease related to SLPI and also present on the respiratory tract. We demonstrate for the first time that exogenously applied elafin inhibits lipopolysaccharide-induced activation of the NF-kappaB and AP-1 pathways in monocytes. I designed this project and supervised Marcus Butler during his MD thesis.