MCE 產(chǎn)品發(fā)表的高分應用文章錦集
Combination of ERK and autophagyinhibition as a treatment approach for pancreatic cancer.
ARS-1620 purchased from MCE.
胰腺導管腺癌(PDAC)的特征是 KRAS 和自噬依賴的致瘤生長，但 KRAS 在自噬中的作用尚未確定。令人驚訝的是，研究人員發(fā)現(xiàn) KRAS 的抑制增加了自噬通量，其效應物 ERK MAPK 的藥理抑制也增加了自噬通量。此外，研究人員還證明 KRAS 抑制或 ERK 抑制都會降低糖酵解和線粒體功能。因此推測， ERK 抑制可能因此增強PDAC 對自噬的依賴，部分破壞其他 KRAS 或 ERK 驅(qū)動的代謝過程。研究人員發(fā)現(xiàn)自噬抑制劑氯喹與特異性自噬調(diào)節(jié)因子的遺傳或藥理抑制協(xié)同增強了 ERK 抑制劑介導 kras 驅(qū)動的 PDAC 抗腫瘤活性的能力。進而得出結論，同時阻斷 ERK MAPK 和自噬過程的藥物抑制劑組合可能是治療 PDAC 的有效方法。
Researchers show that either KRAS suppression or ERK inhibition decreased both glycolytic and mitochondrial functions. Therefore,researchers speculated that ERK inhibition might enhance PDAC dependence onautophagy, in part by impairing other KRAS- or ERK-driven metabolic processes. Autophagy inhibitor chloroquine and genetic or pharmacologic inhibition of specificautophagy regulators synergistically enhanced the ability of ERK inhibitors tomediate antitumor activity in KRAS-driven PDAC. Accordingly, combinations of pharmacologic inhibitors that concurrently block both ERK MAPK and autophagic processes that are upregulated in response to ERK inhibition maybe effective treatments for PDAC.
Cryo-EM Structure and Assembly of anExtracellular Contractile Injection System.
Protease Inhibitor Cocktail purchased from MCE.
收縮注射系統(tǒng)(CISs)是一種細胞穿刺納米器件，它與收縮尾噬菌體具有同源性。發(fā)光毒力盒(PVC)是細菌和古生菌中都存在的一組細胞外 CISs。研究人員報告了來自P. asymbiotica 的完整 PVC 的低溫電子顯微鏡結構。這個超過 10-MDa 的裝置類似于一個簡化的 T4 噬菌體尾，包含一個六角形的基板復合體，其中有 6 根纖維和一個 117 納米管的覆蓋體。PVC 的一個顯著特征是管狀蛋白和鞘狀蛋白都存在三種變異，這表明它們在進化過程中具有功能專門化。末端的六美冠與內(nèi)管狀物的最上層對接，用六個伸縮臂將外鞘鎖在預收縮狀態(tài)。研究人員在 PVC 上的研究結果為廣泛理解 CISs 一般機制使用，提供了一個框架，并為將它們用作生物或治療應用中的傳遞工具鋪平了道路。Researchers report the cryo-EM structure of an intact PVC from P. asymbiotica. This over10-MDa device resembles a simplified T4 phage tail, containing a hexagonalbaseplate complex with six fibers and a capped 117-nanometer sheath-tube trunk.The terminal hexameric cap docks onto the topmost layer of the inner tube andlocks the outer sheath in pre-contraction state with six stretching arms. Researchers result on the PVC provide a framework for understanding the general mechanism of widespread CISs and pave the way for using them as delivery tools inbiological or therapeutic applications.
Entinostat purchased from MCE.
細胞質(zhì)中出現(xiàn) DNA，通常是微生物感染的一種跡象，可通過循環(huán) GMP-AMP 合成酶(cGAS)快速檢測到，從而引發(fā)抗感染免疫反應。然而，自我 DNA 對 cGAS 的慢性激活會導致嚴重的自身免疫性疾病，目前尚無有效的治療方法。重要的是，證明阿司匹林可以直接乙酰化 cGAS，并有效抑制 cGAS 介導的免疫反應。最后，研究人員證明阿司匹林可以有效抑制 aicardii - goutieres 綜合征(AGS)患者細胞和 AGS 小鼠模型中自我 DNA 誘導的自身免疫。因此，研究表明乙酰化有助于 cGAS 的活性調(diào)節(jié)，并為治療 DNA 介導的自身免疫性疾病提供了一種潛在的治療方法。
Researchers report that acetylation inhibits cGAS activation and that the enforced acetylation of cGAS by aspirin robustly suppresses self-DNA-induced autoimmunity. cGAS isdeacetylated in response to DNA challenges. Importantly, we show that aspirincan directly acetylate cGAS and efficiently inhibit cGAS-mediated immune responses. Finally, researchers demonstrate that aspirin can effectivelysuppress self-DNA-induced autoimmunity in Aicardi-Goutières syndrome (AGS) patient cells and in an AGS mouse model. Consequently, the study reveals that acetylation contributes to cGAS activity regulation and provides a potentialtherapy for treating DNA-mediated autoimmune diseases.
