盘点：2017年11月Nature Medicine研究精选

2017-11-13 zhangfan MedSci原创

2017年11月Nature Medicine研究精选

【1】封面文章--N6-甲基腺嘌呤酶METTL3控制正常造血细胞和白血病细胞的髓系分化

N6-甲基腺苷(m6A)是常见的mRNA核苷酸修饰方法，在小鼠胚胎干细胞的分化过程中是必需的，但m6A调控正常和/或恶性骨髓造血细胞分化的机制尚不明确。近日研究人员发现，在人类造血干/祖细胞中，shRNA介导的m6A形成的关键酶METTL3 可推动细胞的分化，减少细胞增殖，而野生型METTL3的过表达可抑制细胞分化，增加细胞增殖。在急性髓细胞样白血病中，METTL3 mRNA和蛋白的表达量增加。小鼠模型中敲除METTL3可延缓AML疾病进展。m6A核糖体结合分析显示，m6A在人类AML细胞系中可促进c-MYC， BCL2和PTEN mRNA的翻译，METTL3缺失可增加AKT磷酸化。

【2】108 vDNA+细胞淋巴残留导致HIV感染复发

doi：10.1038/nm.4411

HIV的治疗中断后极容易造成感染反弹。近日研究人员对SIV感染的非人灵长类和HIV感染者进行淋巴组织（LT）活检，以定量组织中的病毒负担。研究发现，在抗病毒治疗前，淋巴包含了>98%的SIV RNA+和 DNA+ 细胞；治疗后，病毒RNA+细胞个数下降，但仍可以检出，且淋巴中的病毒阳性细胞对药物治疗的敏感性高于外周血。持续的治疗可降低阳性细胞数，但组织中残余的108 vDNA+细胞仍含有复制能力的原病毒。这种组织残留导致HIV治愈十分困难。

【3】ω-3脂肪酸环氧化物通过IgE介导调控肥大细胞活化

doi：10.1038/nm.4417

肥大细胞在免疫应答及过敏反应中发挥了重要作用，目前仅ω-6花生四烯酸途径得到了充分的研究。近日研究人员采用综合脂类组学的方法，考察了ω-3环氧脂肪酸对肥大细胞的影响。研究发现，ω-3环氧脂肪酸由氧化磷脂选择性磷脂酶A2（PAF-AH2）生成，导致肥大细胞活性和过敏性降低。机制上，ω-3环氧化物可痛过下调Srcin1推动IgE介导的肥大细胞活化。研究认为PAF-AH2-ω-3 环氧-Srcin1轴是潜在的过敏性疾病治疗靶点。

【4】肥胖人群肠内缺氧诱导因子2α激活导致脂肪肝发生

doi：10.1038/nm.4412

非酒精性脂肪肝是西方最常见的肝病，目前治疗手段有限。近日研究发现肠道缺氧诱导因子（HIF）在肝细胞脂肪变性过程中发挥了重要作用。研究人员比较肥胖者和体重正常人群的肠活检结果后发现，肠HIF-2α与体重指数和肝毒性相关。小鼠模型中，特异性活化的Hif2a小鼠对高脂饮食造成的肥胖更为敏感。HIF-2α特异性抑制剂PT2385对代谢紊乱有预防和治疗作用，可降低肠道和血清神经酰胺水平。机制而言，肠道HIF-2α主要从挽救途径调节神经酰胺代谢，通过积极调控神经氨酶编码基因Neu3的表达发挥作用，有望成为潜在的脂肪肝治疗表达。

【5】染色体1q21 0.3扩增与乳腺癌复发和治疗

doi：10.1038/nm.4405

肿瘤复发是导致乳腺癌相关死亡的主要原因，发现新的生物标记物和治疗方案对于临床乳腺癌复发患者十分重要。近日研究发现1q21.3染色体拷贝数扩增乳腺细胞具有肿瘤起始细胞特征，与乳腺癌复发密切相关。约10-30%的原发瘤以及70%的乳腺癌复发患者存在1q21.3扩增，且与乳腺癌亚型无关。游离DNA清除可实现患者的早期缓解，提高化疗敏感性。1q21.3编码S100钙结合蛋白(S100A)家族，包括

S100A7，S100A8， S100A9(S100A7/8/9)和IL-1受体相关激酶1，形成完整的功能网络。小分子抑制剂Pacritinib可抑制1q21.3- S100A7/8/9-IRAK1反馈回路。

【6】EZH2 联合BMI1抑制治疗胶质母细胞瘤

doi：10.1038/nm.4415

胶质母细胞瘤是一种致命的癌症。近日研究发现胶质母细胞瘤的组织特征与不同的转录程序相关，血管区域呈现出神经分布而缺氧区域呈现出间充质，但二种区域中都含有胶质瘤干细胞(GSCs)。研究发现血管周的GSCs可激活EZH2而缺氧区间叶细胞周边GSCs 则表达BMI1蛋白以适应缺氧条件。血管周围的GSCs细胞对EZH2抑制敏感，而缺氧区间GSCs细胞对BMI1抑制剂敏感。EZH2 联合BMI1治疗对胶质母细胞瘤的效果显著优于单一治疗，该研究为胶质母细胞瘤的治疗提供了全新的思路。

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2018-09-08 jeanqiuqiu

#DIC#

75 0
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2017-12-13 kalseyzl

#CIN#

51 0
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2018-01-16 一叶知秋

#Nat#

64 0
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2017-11-26 虈亣靌

学习一下谢谢分享

92 0
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2017-11-15 虈亣靌

好好看下.内容丰富

94 0
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2017-11-15 ms1692212821629096

#Medicine#

58 0
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2017-11-15 ms3994565386320060

#Med#

49 0
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2017-11-13 huizi3382

是很好的文章

75 0
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2017-11-13 131****1460

学习了受益匪浅

84 0
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GetPortalCommentsPageByObjectIdResponse(id=261062, encodeId=83ee261062a9, content=是很好的文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/iatia2cT76F0wiceqgFicEXqwC1iaC4mwmVOR9onEYJ9mHKVUHx8tqoPbJiakAIzgut3SdoQspXkbPY9FiabzE14IusDA/132, createdBy=60641826220, createdName=huizi3382, createdTime=Mon Nov 13 21:14:26 CST 2017, time=2017-11-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261043, encodeId=aa8426104393, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Mon Nov 13 18:59:18 CST 2017, time=2017-11-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261030, encodeId=c39026103016, content=前沿文章.学习了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/10/22/baa107716840a3dbb76fe88b0f8a4b05.jpg, createdBy=9f161580808, createdName=jennyli5986, createdTime=Mon Nov 13 17:43:38 CST 2017, time=2017-11-13, status=1, ipAttribution=)]
2017-11-13 jennyli5986

前沿文章.学习了!

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