更新于：2024-05-01

PAX6

paired box 6

更新于：2024-05-01

基本信息

别名

AN、AN1、AN2

+ [7]

简介

Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas. Required for the differentiation of pancreatic islet alpha cells (By similarity). Competes with PAX4 in binding to a common element in the glucagon, insulin and somatostatin promoters. Regulates specification of the ventral neuron subtypes by establishing the correct progenitor domains (By similarity). Acts as a transcriptional repressor of NFATC1-mediated gene expression (By similarity).

关联

100 项与 PAX6 相关的临床结果

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100 项与 PAX6 相关的转化医学

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0 项与 PAX6 相关的专利（医药）

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3,910

项与 PAX6 相关的文献（医药）

2024-02-21·Experimental eye research

Isolation and characterization of rabbit limbal niche cells.

Article

作者: Guanyu Su ; Xiaojie Guo ; Lingjuan Xu ; Bihui Jin ; Yongyao Tan ; Xiao Zhou ; Wei Wang ; Xinyu Li ; Shusheng Wang ; Guigang Li

Limbal niche cells (LNCs) are one of the most important supporting cells for corneal epithelial stem cells (CES), however, research on LNCs has been mostly limited to humans and rats previously. To expand the research work into the rabbit animal model, one of the most often used animals in stem cell study, this study was carried out for the in vitro isolation and identification of rabbit LNCs. Rabbit LNCs were isolated by collagenase A digestion method and single cells were obtained, the cells were then seeded on 5% Matrigel-coated plastic surface and cultured in modified embryonic stem cell medium (MESCM). Three biological replicates of the isolating and characterization were recorded from New Zealand White rabbits aged from 2.5 months to 5 months. LNC markers (VIM/CD90/CD105/SCF/PDGFRβ) were analyzed using tyramide signal amplification (TSA) staining, immunohistochemical staining (IHC), western blotting (WB), and real-time reverse transcription polymerase chain reaction (qPCR). TSA staining suggested that VIM was highly expressed in rabbit limbus stroma, which was confirmed by WB, and P63α was expressed in the basal limbus epithelium. Pan-CK and CK12 were highly expressed in the central corneal epithelium but lightly expressed in the limbal epithelium. The WB result indicated that PDGFRβ and VIM expressions in rabbit-LNCs P4 were higher than in P1 and P7. In addition, rabbit corneal epithelium highly expressed Paired Box 6 (PAX6) and Epidermal growth factor-like domain 6(EGFL6). For the three repeat experiments, the cell expansion activity of rabbit-LNC was highest at P4. Rabbit-LNCs were passaged from P0 to P7, and the number of cell doublings (NCD) of P4 for the three repeat experiments was 2.816, 2.737, and 2.849. qPCR showed that high mRNA expression levels of VIM, CD90, CD105, SCF, and PDGFRβ in rabbit-LNCs P4. In conclusion, rabbit-LNCs could be successfully isolated by the collagenase A digestion method as used in human tissue. There were similar characteristics between rabbit and human LNCs (VIM+/CD90+/CD105+/SCF+/PAX6+/PDGFRβ+).

2024-02-17·Molecular plant

OcBSA: an NGS-based Bulk Segregant Analysis Tool for Outcross Populations.

Article

作者: Lingkui Zhang ; Yanfeng Duan ; Zewei Zhang ; Lei Zhang ; Shumin Chen ; Chengcheng Cai ; Shaoguang Duan ; Kang Zhang ; Guangcun Li ; Feng Cheng

Constructing inbred lines for self-incompatible species and species with long generation times is challenging, making the use of F₁ outcross/segregating populations the main strategy for genetic studies of such species. However, there is a lack of dedicated algorithms/tools for rapid QTL mapping using the F₁ populations. To this end, we have designed and developed an algorithm/tool called OcBSA specifically for QTL mapping of F₁ populations. OcBSA transforms the four-haplotype inheritance problem from the two heterozygous diploid parents of the F₁ population into the two-haplotype inheritance problem common in current genetic studies by removing the two haplotypes from the heterozygous parent that do not contribute to phenotype segregation in the F₁ population. Testing of OcBSA on 1,800 simulated F₁ populations demonstrated its advantages over other currently available tools in terms of sensitivity and accuracy. In addition, the broad applicability of OcBSA was validated by QTL mapping using seven reported F₁ populations of apple, pear, peach, citrus, grape, tea, and rice. We also used OcBSA to map the QTL for flower color in a newly constructed F₁ population of potato generated for this study. The OcBSA mapping result was verified by the InDel markers and was consistent with a previously reported locus harboring the AN2 gene, which regulates potato flower color. Taken together, these results highlight the power and broad utility of OcBSA for QTL mapping using F₁ populations, and thus its promise for functional gene mining in species that primarily reproduce by outcrossing. For ease of use, we have developed both Windows and Linux versions of OcBSA, which are freely available at https://gitee.com/Bioinformaticslab/OcBSA.

2024-02-15·The British journal of radiology

Differentiation of acute coronary syndrome with radiomics of pericoronary adipose tissue.

Article

作者: Mengyuan Jing ; Huaze Xi ; Jianqing Sun ; Hao Zhu ; Liangna Deng ; Tao Han ; Bin Zhang ; Yuting Zhang ; Junlin Zhou

OBJECTIVE:

To assess the potential values of radiomics signatures of pericoronary adipose tissue (PCAT) in identifying patients with acute coronary syndrome (ACS).

METHODS:

In total, 149, 227, and 244 patients were clinically diagnosed with ACS, chronic coronary syndrome (CCS), and without coronary artery disease (CAD), respectively, and were retrospectively analyzed and randomly divided into training and testing cohorts at a 2:1 ratio. From the PCATs of the proximal left anterior descending branch, left circumflex branch, and right coronary artery (RCA), the pericoronary fat attenuation index (FAI) value and radiomics signatures were calculated, among which features closely related to ACS were screened out. The ACS differentiation models AC1, AC2, AC3, AN1, AN2, and AN3 were constructed based on the FAI value of RCA and the final screened out first-order and texture features, respectively.

RESULTS:

The FAI values were all higher in patients with ACS than in those with CCS and no CAD (all <P i > < 0.05). For the identification of ACS and CCS, the area-under-the-curve (AUC) values of AC1, AC2, and AC3 were 0.92, 0.94, and 0.91 and 0.91, 0.86, and 0.88 in the training and testing cohorts, respectively. For the identification of ACS and no CAD, the AUC values of AN1, AN2, and AN3 were 0.95, 0.94, and 0.94 and 0.93, 0.87, and 0.89 in the training and testing cohorts, respectively.

CONCLUSIONS:

Identification models constructed based on the radiomics signatures of PCAT are expected to be an effective tool for identifying patients with ACS.

ADVANCES IN KNOWLEDGE:

The radiomics signatures of PCAT and FAI values are expected to differentiate between patients with ACS, CCS and those without CAD on imaging.

项与 PAX6 相关的新闻（医药）

2024-03-12

·药精通Bio

Cell Reports:脑类器官揭示罕见病机制

点击图片查看OTC2023类器官前沿应用与3D培养论坛会后报告，OTC2024论坛征集投稿做报告，详询：王晨 180 1628 8769 近年来，一种名为磷酸甘露糖转移酶2先天性糖基化缺陷（PMM2-CDG）的罕见遗传性代谢障碍引起了科学界的关注。PMM2-CDG主要表现为神经系统症状，但具体的大脑相关变化尚不完全清楚。最新研究通过利用人类诱导多能干细胞（hiPSC）衍生的神经细胞和大脑皮层类器官，揭示了PMM2缺乏症患者在大脑特定机制方面的异常。研究发现，PMM2-CDG患者的2D神经网络活动异常，3D人类皮层类器官（hCOs）显示出蛋白质糖基化减少、线粒体结构受损和异常的葡萄糖代谢，揭示了能量代谢中的干扰。这些发现提高了我们对PMM2-CDG与大脑相关扰动之间关系的理解，并为未来的治疗干预提供了新的方向。文章利用PMM2缺陷的人诱导多能干细胞（hiPSCs）生成了三维人脑皮层类器官（hCOs），以研究PMM2缺陷对神经成熟的影响。这种三维类器官模型与传统的iNeurons（即直接从hiPSCs分化得到的神经元）相比，具有几个显著的优势：它们不绕过早期的神经祖细胞阶段，可以长期培养，允许研究多种细胞类型，并且可以容易地接受不同的组学技术检测。研究首先评估了PMM2缺陷hCOs中PMM2酶活性，并与对照组（CTR）进行了比较。结果显示PMM2缺陷hCOs中的PMM2酶活性显著降低。此外，还检查了hCOs的PMM2酶活性与源自这些类器官的个体的神经系统评分之间的关系，发现PMM2酶活性的提高与较低的神经系统评分相关。此外，研究还探讨了PMM2缺陷hCOs的整体分化或成熟是否受到影响，通过免疫组织化学（IHC）评估了一系列神经分化和成熟标记物。结果没有观察到任何显著的大小或结构缺陷，或者神经干细胞（NESTIN、PAX6和SOX2）、神经元（doublecortin [DCX]、TBR1、CTIP2和TUJ1）或增殖（Ki67）标记物的丰度或分布的差异。最后，通过对保持不同时间点（DIV95、DIV120、DIV170）培养的类器官进行RNA测序，研究确定了PMM2缺陷在hCOs中的转录组后果。这些时间点旨在包括胶质发生开关前后的发展阶段。在转录组水平上，不同基因型的hCOs（如PMM2-CDG hCOs与CTR类器官）在所有时间点上呈现明显的聚类，表明PMM2缺陷的影响不是短暂的，并且会持续存在于发展过程中。点击图片查看OTC2023类器官前沿应用与3D培养论坛会后报告，OTC2024论坛征集投稿做报告，详询：王晨 180 1628 8769

临床研究

2024-02-13

·医药魔方

MAC肺病新药疗效不达预期，AN2股价暴跌72%

2月12日，AN2 Therapeutics宣布自愿暂停无缝II/III期临床试验（EBO-301）中III期研究部分的患者入组，该试验旨在评估口服小分子细菌leucyl-tRNA合成酶抑制剂epetraborole治疗由鸟分枝杆菌复合体（MAC）引起的难治性肺病的疗效与安全性。这项双盲、安慰剂对照的临床试验共分为两个队列，比较了epetraborole+优化背景方案（OBR）与安慰剂+OBR的疗效。II期研究部分已于2023年9月完成了80例患者的入组，III期研究部分迄今为止招募了近100例患者，已入组患者将被允许继续参与研究。该公司表示，做出该决定并非出于安全考虑，而是由于正在进行的II期研究盲法分析数据显示其疗效可能不及预期，暂停招募后将进一步评估数据，未来或将改变III期研究方案。Epetraborole是AN2 Therapeutics目前进度最快的核心产品，因此该消息一出，公司股价暴跌72%。此前，腾盛博药已与AN2 Therapeutics达成战略合作协议，获得了中国大陆、香港、台湾和澳门授权开发、制造和商业化epetraborole的权利。Copyright © 2024 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

临床2期临床3期微生物疗法临床失败

2023-11-25

·药明康德

治疗智力障碍！何川教授团队发现潜在治疗靶点

▎药明康德内容团队编辑（来源：中国科学院上海药物研究所）脆性X综合征（Fragile X syndrome, FXS）是最常见的遗传性智力障碍疾病，其病因主要是编码脆性X染色体智力低下蛋白（FMRP）的FMR1基因5’端非翻译区CGG重复片段的增多，最终导致FMR1基因沉默。FXS的一个重要特征是大脑中非正常活跃的mRNA翻译。FMRP通常被认为是mRNA翻译的抑制因子；也有研究报道FMRP可能在FMRP缺陷神经元中通过结合mRNA的编码序列（CDS）并且阻碍核糖体在mRNA上的移动从而增强其靶mRNA的翻译。FMRP对其靶mRNA翻译相互矛盾的调控提示其在mRNA翻译调控中作用可能涉及多条调控途径，其中一些途径可能在FXS的病理中起到更为决定性的作用，仍需进一步探索。针对这些问题，中国科学院上海药物研究所罗成研究员与芝加哥大学何川教授基于前期合作基础，与美国埃默里大学金鹏教授组成联合团队，在Molecular Cell上发表研究成果，阐明了一条在神经元细胞内YTHDF1翻译功能受FMRP磷酸化调控的路径，发现了YTHDF1可作为治疗FXS的潜在药物靶标，并发现中药丹参重要成分丹酚酸C（Salvianolic acid C，SAC）可通过抑制YTHDF1，进而缓解FXS疾病症状的新策略。研究人员利用Fmr1敲除以及磷酸化位点突变（S499A）的小鼠神经细胞发现未被磷酸化的FMRP抑制YTHDF1介导的mRNA翻译，而磷酸化FMRP会消除这种抑制作用，从而激活YTHDF1。之后，研究人员通过降低HEK293T细胞中FMRP的表达量同样观测到了YTHDF1的激活。因此，研究人员猜想FMRP蛋白表达水平以及它的磷酸化对YTHDF1的翻译相关功能有重要的调控作用。进一步，研究人员利用RNA酶（RNase）处理帮助相分离蛋白沉淀的功能，对YTHDF1相分离液滴中的YTHDF1相互作用蛋白进行研究，发现了未被磷酸化的FMRP会与YTHDF1结合并且抑制YTHDF1的相分离。为了进一步证明YTHDF1相分离与其调控mRNA翻译的关系，研究人员构建了一系列YTHDF1突变体，并且发现失去相分离能力的YTHDF1无法再促进靶向mRNA的翻译过程。这一结果解释了在FXS这个缺陷系统中由于FMRP蛋白缺失导致YTHDF1的非正常激活最终表现出的高翻译活性，同时也表明抑制YTHDF1有望成为治疗FXS的新策略。▲FMRP磷酸化通过YTHDF1调节神经元内靶mRNA翻译（图片来源：原始论文[1]）为了进一步证明YTHDF1是潜在的缓解FXS的靶点，研究人员通过靶向YTHDF1开展化学干预研究。基于建立高通量筛选方法，开展了小分子抑制剂的筛选，获得YTHDF1活性化合物SAC。SAC可以在神经细胞中抑制YTHDF1的相分离以及基于YTHDF1的翻译活性，并且可以特异性地在有FXS特征的类器官（从FXS病人中重编程的诱导多能干细胞分化获得）中抑制YTHDF1靶向转录组的翻译，以及将FXS类器官中的神经前体细胞（neural progenitor cell）的增殖和大脑皮层组织结构（PAX6+和CTIP+细胞）回复至正常水平。同时，在类器官中敲低YTHDF1亦可以达到同样的效果。▲SAC是选择性底物竞争性YTHDF1小分子抑制剂（图片来源：原始论文[1]）综上所述，该研究揭示了m6A“阅读子”YTHDF1的抑制在改善脆性X综合征的调控机制和潜在干预效果，为相关临床治疗提供了新的潜在靶标。获得的YTHDF1小分子抑制剂，不仅为YTHDF1的功能研究提供工具，也为靶向YTHDF1的药物开发提供先导结构。同时，该研究也为中药丹参重要成分在复杂性疾病的潜在治疗作用提供了线索。美国芝加哥大学的何川教授、上海药物所罗成研究员及美国埃默里大学的金鹏教授为FXS论文的共同通讯作者，美国芝加哥大学Zhongyu Zou、Jiangbo Wei、原上海药物所陈彦韬博士（现哈佛大学博士后）和美国埃默里大学Yunhee Kang为该论文的共同第一作者。该研究还得到上海药物所蒋华良院士的支持，研究也得到国家科技创新2030“脑科学与类脑研究”、国家重点研发计划、基金委和国家中医药管理局国家中医药多学科创新团队项目的资助。封面图来源：123RF参考资料：[1] Mol Cell | 上海药物所合作发现抑制YTHDF1可缓解脆性X染色体综合征. Retrieved- November 14, 2023 from http://www.simm.cas.cn/web/xwzx/kydt/202311/t20231114_6932939.html原始论文：[1] Zhongyu Zou et al., FMRP phosphorylation modulates neuronal translation through YTHDF1. Molecular Cell (2023). https://doi.org/10.1016/j.molcel.2023.10.028▼细胞和基因疗法科学讲座点击图片立即观看本文来自药明康德内容微信团队，欢迎转发到朋友圈，谢绝转载到其他平台。如有开设白名单需求，请在“学术经纬”公众号主页回复“转载”获取转载须知。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。更多推荐点个“在看”再走吧~

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