 |
 |
 |
 |
 |
 |
||
 |
 |
 |
 |
 |
| 5 | 1/1 | 返回列表 |
| 查看: 627 | 回復: 2 | |||
| 本帖產生 1 個 翻譯EPI ，點擊這里進行查看 | |||
| 當前只顯示滿足指定條件的回帖，點擊這里查看本話題的所有回帖 | |||
yaoguiyang木蟲 (小有名氣)
|
[求助]
翻譯一段話
|
||
| Inappropriate activation of Toll-like receptors（TLRs）, on the other hand, contributes to development of a variety of human diseases including systemic lupus erythematosus (SLE), bacterial sepsis, inflammatory bowel disease, psoriasis, multiple sclerosis, rheumatoid arthritis, and atherosclerosis. Upon infection or injury of tissue, the infected or damaged tissue releases various intracellular factors that can recruit and activate innate immune cells. Nucleic acids that originate from host cells or intracellular microorganisms can be recognized by nucleic acid-sensing TLRs and can result in the induction of pathological inflammatory responses . In patients with bacterial sepsis, toxic shock, SLE or rheumatoid arthritis, hypomethylated CpG DNAs, or RNAs have been detected in extracellular compartments and these extracellular nucleic acids have been correlated to the pathogenesis of these diseases. Although inhibition of one or two nucleic acid-sensing TLRs using receptor antagonists has been demonstrated to attenuate disease progression in polymicrobial sepsis and autoimmune disease models to some extent, the redundancy of the TLR family of proteins suggests that concurrent inhibition of all nucleic acid-sensing TLRswould be the most effective means to control nucleic acid-induced inflammation in humans. Because all the nucleic acid-sensing TLRs bind to RNA or DNA, albeit each TLR ligand contains a distinguishable molecular pattern, we hypothesized that agents that bind to DNAs and RNAs regardless of their sequence, structure or chemistry might be able to inhibit nucleic acid-mediated activation of all RNA- and DNA-sensing TLRs. Herein we demonstrate that certain cationic polymers can act as molecular scavengers and block the immune stimulatory effects of extracellular ssRNA, dsRNA, and unmethylated DNA. Nucleic Acid-Binding Polymers Inhibit Nucleic Acid-Mediated Activation of TLRs. We initially evaluated six agents known to bind nucleic acids for their ability to attenuate nucleic acid-mediated activation of TLRs on macrophages: polyphosphoramidate polymer (PPA-DPA), polyamidoamine dendrimer, 1,4-diaminobutane core-PAMAM-G3 (PAMAM-G3), poly-L-lysine, β-cyclodextrincontaining polycation (CDP), hexadimethrine bromide (HDMBr), and protamine sulfate. All of the compounds except protamine sulfate inhibit TLR3 activation by synthetic dsRNA, polyinosinic-polycytidylic acid (poly I∶C) as measured by TNFα and IL-6 production and CD80 expression.Moreover three of the cationic polymers, CDP, HDMBr, and PAMAM-G3 inhibit the ability of synthetic CpG DNAs (CpG 1668) to activate TLR9. Similarly these three polymers inhibit the ability of ssRNA-lipid complexes (ssRNA40) to activate TLR7. Such cationic polymers are specific for nucleic acid-mediated activation of the TLRs. They do not inhibit activation of TLRs that recognize nonnucleic acid-based TLR agonists such as bacterial LPS, which activate TLR4, and Pam3CSK4, a synthetic bacterial lipoprotein, which activates the TLR2/1 complex. Furthermore CDP, HDMBr, and PAMAM-G3 neutralize immune stimulatory activity of all types of nucleic acid-based TLR agonists in a variety of primary cells including B cells, fibroblasts and dendritic cells (DCs) |
回復此樓» 猜你喜歡
284求調劑
已經有10人回復
-
一志愿山東大學藥學學碩求調劑
已經有4人回復
-
07化學280分求調劑
已經有4人回復
-
298-一志愿中國農業(yè)大學-求調劑
已經有12人回復
-
求材料，環(huán)境專業(yè)調劑
已經有3人回復
-
335求調劑
已經有5人回復
-
求調劑
已經有7人回復
-
一志愿吉大化學322求調劑
已經有4人回復
-
環(huán)境學碩288求調劑
已經有8人回復
-
341求調劑(一志愿湖南大學070300)
已經有6人回復
reko34
木蟲 (正式寫手)
- 翻譯EPI: 132
- 應助: 117 (高中生)
- 金幣: 4794.2
- 散金: 22
- 紅花: 12
- 帖子: 780
- 在線: 417.4小時
- 蟲號: 3055206
- 注冊: 2014-03-15
- 性別: GG
- 專業(yè): 機械測試理論與技術
【答案】應助回帖
★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ...
yaoguiyang: 金幣+60, 翻譯EPI+1, ★★★★★最佳答案 2014-06-20 12:41:46
yaoguiyang: 金幣+60, 翻譯EPI+1, ★★★★★最佳答案 2014-06-20 12:41:46
| 另一方面，Toll樣受體的不恰當激活有助于各種人體疾病的發(fā)展，包括系統性紅斑狼瘡(SLE)、細菌性敗血癥、炎性腸道疾病、銀屑病、多發(fā)性硬化、類風濕性關節(jié)炎和動脈粥樣硬化。組織感染或受傷時，感染或受損組織釋放出各種能吸引和激活先天性免疫細胞的細胞因子。來自宿主細胞或細胞內微生物的核酸能被核酸感知的TLRs識別，可能導致誘發(fā)病理性炎癥反應。在有細菌性敗血癥、中毒性休克、SLE或類風濕關節(jié)炎的病人的細胞間隔中發(fā)現低甲基化CpGDNA或RNA，這些細胞外核酸與疾病的發(fā)病有關。盡管在多細菌敗血癥和自身免疫性疾病模型中，用受體拮抗劑抑制一兩種核酸感知的TLRs經證明能在一定程度上衰減疾病發(fā)展，TLR蛋白家族的過剩顯示，同時抑制所有核酸感知的TLRs是控制人體中核酸誘發(fā)炎癥的最有效方式。由于所有的核酸感知TLRs都結合RNA或DNA，盡管每種TLR配體含有可分辨的分子模式，我們假設與DNAs和RNAs結合的成分也許能抑制以核酸為媒介的所有RNA和DNA感知TLRs的激活，不論其順序、結構或化學。于是我們證實，特定的陽離子聚合物能充當分子清道夫，阻斷細胞外ssRNA、dsRNA和未甲基化DNA的免疫刺激作用。結合核酸的聚合物抑制以核酸為媒介的TLRs激活。我們最初評價巨噬細胞中6種已知結合核酸并能減弱以核酸為媒介的TLRs激活的成分：聚氨基磷酸酯聚合物(PPA-DPA)、聚酰胺-胺樹狀大分子、1,4-二氨基丁烷芯PAMAM-G3(PAMAM-G3)、聚-L-賴氨酸、β-環(huán)糊精的聚陽離子(CDP)、溴化己二甲（HDMBr）和硫酸魚精蛋白。通過TNFα和IL-6產物的測量及CD80表現度，除硫酸魚精蛋白外的所有成分都阻礙TLR3被合成dsRNA、聚肌胞苷酸(poly I∶C)激活。此外，3種陽離子聚合物，CDP、HDMBr和PAMAM-G3阻礙合成CpG DNAs（CpG 1668）激活TLR9。類似地，這3種聚合物阻礙ssRNA-脂質復合物（ssRNA40）激活TLR7。這類陽離子聚合物在以核酸為媒介的TLRs激活中是特例。它們不抑制識別非基于核酸的TLR激動劑——如細菌LPS、Pam3CSK4、合成細菌脂蛋白、TLR2/1復合物——的TLRs的激活。此外，CDP、HDMBr和PAMAM-G3在各種原代細胞包括B細胞、成纖維細胞和樹突狀細胞（DCs）內中和各類基于核酸的TLR激動劑的免疫刺激活性。 |
3樓2014-06-20 11:30:18
QQ905063299 
新蟲 (初入文壇)
- 應助: 2 (幼兒園)
- 金幣: 69
- 帖子: 12
- 在線: 24.1小時
- 蟲號: 3242116
- 注冊: 2014-05-29
- 性別: GG
- 專業(yè): 高分子組裝與超分子結構
2樓2014-06-20 09:10:25
| 最具人氣熱帖推薦 [查看全部] | 作者 | 回/看 | 最后發(fā)表 | |
|---|---|---|---|---|
|
[考研] 求材料，環(huán)境專業(yè)調劑 +3 | 18567500178 2026-03-18 | 3/150 |
|
|---|---|---|---|---|
|
|
[考研] 341求調劑(一志愿湖南大學070300) +5 | 番茄頭--- 2026-03-22 | 6/300 |
|
|
[考研] 085600材料與化工調劑 +7 | A-哆啦Z夢 2026-03-23 | 12/600 |
|
|
|
[考研] 269求調劑 +4 | 我想讀研11 2026-03-23 | 4/200 |
|
|
|
[考研] 一志愿南航材料專317分求調劑 +3 | 炸呀炸呀炸薯條 2026-03-23 | 3/150 |
|
|
|
[考研] 328求調劑，英語六級551，有科研經歷 +7 | 生物工程調劑 2026-03-17 | 12/600 |
|
|
|
[考研] 一志愿中國石油大學（華東） 本科齊魯工業(yè)大學 +4 | 石能偉 2026-03-17 | 4/200 |
|
|
|
[考研] 287求調劑 +8 | 晨昏線與星海 2026-03-19 | 9/450 |
|
|
|
[考研] 354求調劑 +7 | Tyoumou 2026-03-18 | 10/500 |
|
|
|
[考研] 0856材料專碩353求調劑 +4 | NIFFFfff 2026-03-20 | 4/200 |
|
|
|
[考研] 280求調劑 +11 | 咕嚕曉曉 2026-03-18 | 12/600 |
|
|
|
[考研] 初試 317 +7 | 半拉月丙 2026-03-20 | 7/350 |
|
|
|
[考研] 求調劑 +4 | 要好好無聊 2026-03-21 | 4/200 |
|
|
|
[考研] 【考研調劑】化學專業(yè) 281分，一志愿四川大學，誠心求調劑 +11 | 吃吃吃才有意義 2026-03-19 | 11/550 |
|
|
|
[考研] 302求調劑 +12 | 呼呼呼。。。。 2026-03-17 | 12/600 |
|
|
|
[考研] 336求調劑 +5 | rmc8866 2026-03-21 | 5/250 |
|
|
|
[考研] 材料學學碩080502 337求調劑-一志愿華中科技大學 +4 | 順順順mr 2026-03-18 | 5/250 |
|
|
|
[考研] 考研調劑求學校推薦 +3 | 伯樂29 2026-03-18 | 5/250 |
|
|
|
[考研] 求調劑，一志愿:南京航空航天大學大學 ，080500材料科學與工程學碩，總分289分 +4 | @taotao 2026-03-19 | 4/200 |
|
|
|
[考研] 【同濟軟件】軟件（085405）考研求調劑 +3 | 2026eternal 2026-03-18 | 3/150 |
|