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1. 发明申请

WO2011133692A1 BOOSTING IMMUNE DEFENSE BY UPREGULATING CCAAT/ENHANCER BINDING PROTEIN EPSILON 审中-公开
标题翻译：通过升级CCAAT /增强蛋白结合蛋白EPSILON来增强免疫力
公开(公告)号：WO2011133692A1
公开(公告)日：2011-10-27
申请号：PCT/US2011/033286
申请日：2011-04-20
申请人： CEDARS-SINAI MEDICAL CENTER , KOEFFLER, H., Phillip , LIU, George, Y. , THOENNISSEN, Nils , KYME, Pierre , GOMBART, Adrian, F.
发明人： KOEFFLER, H., Phillip , LIU, George, Y. , THOENNISSEN, Nils , KYME, Pierre , GOMBART, Adrian, F.
IPC分类号： A61K31/435 , A61K47/00
CPC分类号： A61K31/455 , A61K38/217 , Y02A50/47 , Y02A50/473 , Y02A50/481
摘要： The present invention demonstrates the important role of C/EBP ε in innate immune response against pathogens. Specifically, the inventors showed that in the absence of functional C/EBP ε , mice are severely impaired in their ability to clear S. aureus infection. Neutrophils are particularly affected, and susceptibility to S. aureus can be rectified by treatment with interferon-gamma (IFN-γ). Importantly, increased activity of C/EBP ε , either by induced overexpression of C/EBPE or by application of nicotinamide or an analog, derivative or salt thereof, dramatically enhances immune killing of S. aureus and leads to amelioration of infection.
摘要翻译：本发明证实了C / EBPe在针对病原体的先天免疫应答中的重要作用。具体地说，本发明人表明，在没有功能性C / EBPe的情况下，小鼠在清除金黄色葡萄球菌感染的能力方面严重受损。嗜中性粒细胞特别受影响，通过用干扰素-γ（IFN-γ）治疗可以矫正对金黄色葡萄球菌的易感性。重要的是，通过C / EBPE的诱导过表达或通过应用烟酰胺或其类似物衍生物或盐来增加C / EBPe的活性，显着地增强了金黄色葡萄球菌的免疫杀伤并导致了感染的改善。

2. 发明申请

WO2005115403A3 INDUCTION OF INNATE IMMUNITY BY VITAMIN D3 AND ITS ANALOGS 审中-公开
标题翻译：维生素D3及其类似物诱导无效免疫
公开(公告)号：WO2005115403A3
公开(公告)日：2006-11-23
申请号：PCT/US2005018172
申请日：2005-05-23
申请人： CEDARS SINAI MEDICAL CENTER , GOMBART ADRIAN F , KOEFFLER H PHILLIP
发明人： GOMBART ADRIAN F , KOEFFLER H PHILLIP
IPC分类号： A61K38/00 , A01N25/08 , A61K31/593
CPC分类号： A61K31/593
摘要： Cationic antimicrobial peptides (AMPs) are an integral part of the innate immune system. Cathelicidin and defensin homologs from a variety of species exhibit broad-range bactericidal activity. The human cathelicidin analog, hCAP18, is encoded by the CAMP gene. Vitamin D3 and its analogs upregulate transcription of CAMP and defensin ß2 (defB2) genes, leading to increased expression of hCAP18 mRNA and defB2. Induction of CAMP was observed in acute myeloid leukemia (AML), immortalized keratinocyte and colon cancer cell lines, as well as normal human bone marrow (BM)-derived macrophages and fresh BM cells. The present invention provides methods of inducing cathelicidin production by administering Vitamin D3 or Vitamin D3 analogs, as well as methods of treating skin infections and infections of the colon, sepsis and wound healing, preventing bacterial growth on skin grafts, promoting angiogenesis, and promoting chemoattraction by administering Vitamin D3 or Vitamin D3 analogs to upregulate cathelicidin and defensin expression.
摘要翻译：阳离子抗菌肽（AMP）是先天免疫系统的组成部分。来自各种物种的钩藤素和防御素同系物具有广泛的杀菌活性。人类尿嘧啶类似物hCAP18由CAMP基因编码。维生素D3及其类似物上调CAMP和防御素β2（defB2）基因的转录，导致hCAP18 mRNA和defB2的表达增加。在急性骨髓性白血病（AML），永生化角化细胞和结肠癌细胞系以及正常人骨髓（BM）衍生的巨噬细胞和新鲜BM细胞中观察到CAMP的诱导。本发明提供了通过施用维生素D3或维生素D3类似物诱导导管素生产的方法，以及治疗皮肤感染和结肠感染的方法，脓毒症和伤口愈合，防止皮肤移植物上的细菌生长，促进血管发生和促进化学吸引通过维生素D3或维生素D3类似物上调导管素和防御素表达。

3. 发明申请

WO2005115403A2 INDUCTION OF INNATE IMMUNITY BY VITAMIN D3 AND ITS ANALOGS 审中-公开
标题翻译：维生素D3及其类似物诱导无效免疫
公开(公告)号：WO2005115403A2
公开(公告)日：2005-12-08
申请号：PCT/US2005/018172
申请日：2005-05-23
申请人： CEDARS-SINAI MEDICAL CENTER , GOMBART, Adrian, F. , KOEFFLER, H., Phillip
发明人： GOMBART, Adrian, F. , KOEFFLER, H., Phillip
IPC分类号： A61K31/593
CPC分类号： A61K31/593
摘要： Cationic antimicrobial peptides (AMPs) are an integral part of the innate immune system. Cathelicidin and defensin homologs from a variety of species exhibit broad-range bactericidal activity. The human cathelicidin analog, hCAP18, is encoded by the CAMP gene. Vitamin D3 and its analogs upregulate transcription of CAMP and defensin ß2 (defB2) genes, leading to increased expression of hCAP18 mRNA and defB2. Induction of CAMP was observed in acute myeloid leukemia (AML), immortalized keratinocyte and colon cancer cell lines, as well as normal human bone marrow (BM)-derived macrophages and fresh BM cells. The present invention provides methods of inducing cathelicidin production by administering Vitamin D3 or Vitamin D3 analogs, as well as methods of treating skin infections and infections of the colon, sepsis and wound healing, preventing bacterial growth on skin grafts, promoting angiogenesis, and promoting chemoattraction by administering Vitamin D3 or Vitamin D3 analogs to upregulate cathelicidin and defensin expression.
摘要翻译：阳离子抗菌肽（AMP）是先天免疫系统的组成部分。来自各种物种的钩藤素和防御素同系物具有广泛的杀菌活性。人类尿嘧啶类似物hCAP18由CAMP基因编码。维生素D3及其类似物上调CAMP和防御素β2（defB2）基因的转录，导致hCAP18 mRNA和defB2的表达增加。在急性骨髓性白血病（AML），永生化角化细胞和结肠癌细胞系以及正常人骨髓（BM）衍生的巨噬细胞和新鲜BM细胞中观察到CAMP的诱导。本发明提供了通过施用维生素D3或维生素D3类似物诱导针刺素生产的方法，以及治疗皮肤感染和结肠感染的方法，脓毒症和伤口愈合，防止皮肤移植物上的细菌生长，促进血管发生和促进化学吸引通过维生素D3或维生素D3类似物上调导管素和防御素表达。

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