RNAi-Induced Immunity

RNA interference has a close relationship with the host defense system including adaptive immunity. It is not only involved in regulating immune cells at different stages of the immune response but also directly induces or enhances antigen presentation and subsequent immune responses. We have previously reported that a small hairpin RNA (shRNA) targeted the downstream site of a dominant cytotoxic T lymphocyte (CTL) epitope of human papillomavirus (HPV) type 16 oncogene E7 can stimulate an immune response against E7 expressing tumors in C57BL/6 mice. This results in the elimination of tumor growth in vivo, whereas an shRNA that targets the upstream site does not. Our recent data further confirm the long half-life of the 5\u27-mRNA fragment after shRNA degradation and its involvement in protein synthesis. This chapter summarizes these findings and provides some updated explanations for the findings

An Empirical Analysis of the Impact of Unemployment Rate and Economic Development Level on Income Inequality

This study used linear regression analysis to inspect influence of unemployment rates and economic development levels on income inequality in the United States and Germany. The results indicate that the level of economic development is the main driving factor for inequality of income in America, while in Germany, high unemployment and inflation can exacerbate income inequality. This study emphasizes the importance of labor market policies, social welfare policies, and tax policies in reducing income inequality. While the analysis only covers two countries, the results have significant policy implications for addressing income inequality. Future research can expand on the factors that contribute to income inequality

TNF-α Promotes IFN-γ-Induced CD40 Expression and Antigen Process in Myb-Transformed Hematological Cells

Tumour necrosis factor-α, interferon-γ and interleukin-4 are critical cytokines in regulating the immune responses against infections and tumours. In this study, we investigated the effects of three cytokines on CD40 expression in Myb-transformed hematological cells and their regulatory roles in promoting these cells into dendritic cells. We observed that both interleukin-4 and interferon-γ increased CD40 expression in these hematological cells in a dose-dependent manner, although the concentration required for interleukin-4 was significantly higher than that for interferon-γ. We found that tumour necrosis factor-α promoted CD40 expression induced by interferon-γ, but not by interleukin-4. Our data showed that tumour necrosis factor-α plus interferon-γ-treated Myb-transformed hematological cells had the greatest ability to take up and process the model antigen DQ-Ovalbumin. Tumour necrosis factor-α also increased the ability of interferon-γ to produce the mixed lymphocyte reaction to allogenic T cells. Furthermore, only cotreatment with tumour necrosis factor-α and interferon-γ induced Myb-transformed hematological cells to express interleukin-6. These results suggest that tumour necrosis factor-α plays a key regulatory role in the development of dendritic cells from hematological progenitor cells induced by interferon-γ

ANTIOXIDANTACTIVITYIN VITRO AND HEPATOPROTECTIVE EFFECTS IN VIVO OF COMPOUND LOBELIA

Background: Chinese medicine has its own uniqueness, advantageous in the treatment of hepatic diseases, and they were widely used in the oxidation.At the same time, oxidation is one of the mechanism of protect liver. Materials and Methods: In the present study, the antioxidant activity in vitro of different extracts from Compound Lobelia were estimated respectively by the methods of measuring the [2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulphonic acid] diamonium salt (ABTS) radical scavenging, ferric reducing antioxidant power (FRAP). The protective effects on carbon tetrachloride (CCl4)-induced acute liver injury in mice which was investigated by analyzing the result of biochemical parameters such as glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in serum, superoxide dismutase (SOD) and malondialdehyde (MDA) in liver tissue homogenate. Result: the result showed that ABTS free radical scavenging activity of ethanol extract (IC50=29.26±0.49 µg/mL) was stronger than that of water extract (IC50=42.09±2.44 µg/mL), but they were lower than that of BHT as positive control (IC50=2.47±0.09 µg/mL). The ferric reducing antioxidant power of ethanol extract (FRAP=329.03±46.30 µmol/g) was higher than that of water extract (FRAP=206.03±54.30 µmol/g); they were lower than that of BHT (FRAP=1541.87±9.70 µmol/g). Water extract and ethanol extract could significantly reduce GOT activity (

ANTIOXIDANT ACTIVITIES IN VITRO AND HEPATOPROTECTIVE EFFECTS OF NELUMBO NUCIFERA LEAVES IN VIVO

Background: Herbal medicines played a major role in the treatment of hepatic disorders, and a number of medicinal plants and their compounds were widely used for the treatment of these disorders, and oxidant stress injury was one of the mechanism of liver injury. Materials and Methods: Antioxidant activity of Nelumbo nucifera leaves (NU) extracts was assayed by the methods of scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2´-azino-bis (3-ethylbenzo- thiazoline-6-sulfonicacid) (ABTS) radical and ferric reducing antioxidant power (FRAP) in vitro. By intraperitoneal injection carbon tetrachloride (CCl4) to establish acute liver injury model in mice, the levels of Glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), superoxide dismutase (SOD) and the content of and maleicdialdehyde (MDA) were detected to evaluate hepatoprotective effect of NU using corresponding test kit. Results: EtOAC (NUEA) and n-BuOH extracts (NUBU) of N. nucifera leaves had good scavenging DPPH and ABTS radical activity and ferric reducing antioxidant power in vitro. DPPH radical scavenging activity and ferric reducing antioxidant power of NUEA (IC50= 6.68±0.29 µg/mL, RACT50=1749.82±67.03 µmol/g) and NUBU (IC50= 4.61±0.01 µg/mL, RACT50=1995.27±135.71 µmol/g ) were higher than that of BHT (IC50=8.76±0.20 µg/mL, RACT50=1581.68±97.41 µmol/g) and Dangfeiliganning (IC50=28.06±0.17 µg/mL, RACT50=1028.55±3.28 µmol/g). ABTS radical scavenging activity of NUEA (IC50= 5.32±0.12 µg/mL) and NUBU (IC50= 8.16±0.27 µg/mL) were higher than that of Dangfeiliganning (IC50= 9.76±0.16 µg/mL). Thus, hepatoprotective effect of NUEA and NUBU was evaluated on CCl4-induced acute liver injury mice. The results showed that the levels of GOT and GPT in each treatment group significantly decreased (

tRNASer(CGA) differentially regulates expression of wild-type and codon-modified papillomavirus L1 genes

Exogenous transfer RNAs (tRNAs) favor translation of bovine papillomavirus 1 wild-type (wt) L1 mRNA in in vitro translation systems (Zhou et al. 1999, J. Virol., 73, 4972-4982). We, therefore, investigated whether papillomavirus (PV) wt L1 protein expression could be enhanced in eukaryotic cells following exogenous tRNA supplementation. Both Chinese hamster ovary (CHO) and Cos1 cells, transfected with PV1 wt L1 genes, effectively transcribed the genes but did not translate them. However, L1 protein translation was demonstrated following co-transfection with the L1 gene and a gene expressing tRNA(Ser)(CGA). Cell lines, stably transfected with a bovine papillomavirus 1 (BPV1) wt L1 expression construct, produced L1 protein after the transfection of the tRNA(Ser)(CGA) gene, but not following the transfection with basal vectors, suggesting that tRNA(Ser)(CGA) gene enhanced wt L1 translation as a result of endogenous tRNA alterations and phosphorylation of translation initiation factors elF4E and elF2alpha in the tRNA(Ser)(CGA) transfected L1 cell lines. The tRNA(Ser)(CGA) gene expression significantly reduced translation of L1 proteins expressed from codon-modified (HB) PV L1 genes utilizing mammalian preferred codons, but had variable effects on translation of green fluorescent proteins (GFPs) expressed from six serine GFP variants. The changes of tRNA pools appear to match the codon composition of PV wt and HB L1 genes and serine GFP variants to regulate translation of their mRNAs. These findings demonstrate for the first time in eukaryotic cells that translation of the target genes can be differentially influenced by the provision of a single tRNA expression construct

Generalized substitution of isoencoding codons shortens the duration of papillomavirus L1 protein expression in transiently gene-transfected keratinocytes due to cell differentiation

Recently we reported that gene codon composition determines differentiation-dependent expression of the PV L1 genes in mouse primary keratinocytes (KCs) in vitro and in vivo (Zhao et al. 2005, Mol. Cell Biol. 25:8643–8655). Here, we investigated whether generalized substitution of isoencoding codons affects the duration of expression of PV L1 genes in mouse and human KCs in day 1 culture transiently transfected with native (Nat) and codon modified (Mod) L1 genes. Following transient transfection, KC continuously transcribed both Nat and Mod PV L1 genes for at least 12 days, with the levels of L1 mRNAs from the Mod L1 genes significantly higher than those from the Nat L1 genes. However, continuous L1 protein expression at day 9 post-transfection was observed for both mouse and human KCs transfected with the Nat L1 genes only. Further, aa-tRNAs prepared from D8 KC cultures enhanced translation of two PV Nat L1 DNAs in RRL lysate and PV Nat L1 mRNAs in D0 cell-free lysate, whereas aa-tRNAs from D0 KCs enhanced translation of PV Mod L1 mRNAs in D8 cell-free lysate. It appears that aa-tRNAs in less-differentiated and differentiated KCs differentially match the PV Nat and Mod L1 mRNAs to regulate their translations in vitro