详细内容（全部5条）

1. GSE252846 胰腺癌先天免疫调节因子的评估

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、immune
• 📝 描述：Contributors : Bassam F Kashgari ; Brendan J Jenkins ; Linden J GearingSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusPancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic cancer cases, and is among the most aggressive and lethal malignancies worldwide. PDAC is driven by genetic alterations in the pancreatic epithelium (e.g. KRAS, TRP53) coupled with a dysregulated innate immune response, the latter leading to an inflammatory tumor microenvironment enriched in innate immune cells (e.g. macrophages). However, immune-based treatment regimens for PDAC patients have primarily focused on immunotherapy with adaptive immune checkpoint inhibitors (e.g. PD-1) which disappointingly have yielded minimal clinical benefit. Thus, there is an unmet clinical need to identity disease-associated innate immune regulators as therapeutic targets in PDAC. Innate immune responses depend on a series of cell surface, endosomal and cytosolic pattern recognition receptors (PRRs) that are expressed in immune and non-immune cells. PRRs are classified into several structurally and functionally conserved subfamilies, including Toll-like receptors (TLRs), Absent in melanoma 2 (AIM2)-like receptors (ALRs), and Nod-like receptors (NLRs). A subset of NLRs and AIM2 are also well documented for their formation of multiprotein complexes called ‘inflammasomes’ - comprising the adaptor ASC and Caspase-1 - which direct the maturation and release of bioactive pro-inflammatory cytokines, IL-18 and IL-1beta. However, the role of these critical innate immune regulators in PDAC has been underexplored, and is virtually unknown. Here, using the genetically engineered KPC PDAC mouse model, we performed whole transcriptome profiling to identify unique ASC-inflammasome driven downstream molecular networks associated with a range of oncogenic cellular processes in pancreatic tumorigenesis.
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2. GSE314890 RNA-seq 分析四面体 DNA 纳米结构 (TDN) 处理后的大鼠尿道组织

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq
• 📝 描述：Series Type : Expression profiling by high throughput sequencingOrganism : Rattus norvegicusUrethral injury often leads to excessive inflammation and fibrosis, which are major contributors to urethral stricture and impaired tissue repair. Tetrahedral DNA nanostructures (TDN) are emerging nucleic acid nanomaterials with favorable biocompatibility and immunomodulatory properties; however, their transcriptomic effects during urethral injury repair remain poorly understood. In this study, a rat model of urethral injury was established using a mechanical method, and animals were treated with TDN or vehicle control. Urethral tissues were collected at defined time points after injury and treatment for RNA sequencing (RNA-seq) analysis. Transcriptomic profiling was performed to characterize global gene expression changes associated with urethral injury and to explore the molecular responses to TDN treatment. This dataset provides a comprehensive resource for investigating gene expression programs involved in urethral injury, inflammation, and fibrosis, and may facilitate further studies on the molecular mechanisms underlying nucleic acid nanomaterial-based therapeutic strategies for urethral repair.
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3. GSE222333 阿尔茨海默病神经炎症风险基因可作为人小胶质细胞中 RNase-H 活性反义寡核苷酸的靶点

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：Series Type : Expression profiling by arrayOrganism : Homo sapiensThis SuperSeries is composed of the SubSeries listed below.
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4. GSE222332 阿尔茨海默病神经炎症风险基因可作为人类小胶质细胞中 RNase-H 活性反义寡核苷酸的靶点（TREM2 子集_GEO）

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：Contributors : Lina Vandermeulen ; Ivana Geric ; Mohamed Kreir ; Ashley Lu ; Annelies Nonneman ; Leen Wolfs ; Rafaela Policarpo ; Nicola Fattorelli ; An De Bondt ; Ilse Van Den Wyngaert ; Mark Fiers ; Bart De Strooper ; Constantin d’Ydewalle ; Renzo MancusoSeries Type : Expression profiling by arrayOrganism : Homo sapiensMicroglia play important roles in maintaining brain homeostasis. The discovery of genetic variants in the genes encoding Apolipoprotein E (APOE) and triggering receptor expressed on myeloid cells 2 (TREM2) as the strongest risk factors for Alzheimer’s disease (AD) highlights the importance of microglial biology in the brain. The sequence, structure and function of microglial proteins are poorly conserved across species, and this hampered the development of APOE and TREM2 targeting therapeutic strategies. One way to target APOE and TREM2 is to modulate their expression using antisense oligonucleotides (ASOs). In this study, we identified ASOs that selectively and potently reduce human APOE and TREM2 levels in human myeloid cells including iPSC-derived microglia. We demonstrated that a single bolus delivery of the ASOs in the mouse cerebrospinal fluid is sufficient for the ASO to be pharmacologically active and modify the phenotype of xenografted human microglia throughout the rodent brain for at least 4 weeks. This study is the first proof-of-concept that the expression of microglial genes can be modulated using ASOs in a dose-dependent manner in order to manipulate human microglia phenotypes in vivo, and demonstrates the utility of these ASOs both as research and therapeutic tools to modulate neuroinflammation.
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5. GSE222331 阿尔茨海默病神经炎症风险基因可作为人类小胶质细胞中 RNase-H 活性反义寡核苷酸的靶点（APOE 子集_GEO）

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：Contributors : Lina Vandermeulen ; Ivana Geric ; Mohamed Kreir ; Ashley Lu ; Annelies Nonneman ; Leen Wolfs ; Rafaela Policarpo ; Nicola Fattorelli ; An De Bondt ; Ilse Van Den Wyngaert ; Mark Fiers ; Bart De Strooper ; Constantin d’Ydewalle ; Renzo MancusoSeries Type : Expression profiling by arrayOrganism : Homo sapiensMicroglia play important roles in maintaining brain homeostasis. The discovery of genetic variants in the genes encoding Apolipoprotein E (APOE) and triggering receptor expressed on myeloid cells 2 (TREM2) as the strongest risk factors for Alzheimer’s disease (AD) highlights the importance of microglial biology in the brain. The sequence, structure and function of microglial proteins are poorly conserved across species, and this hampered the development of APOE and TREM2 targeting therapeutic strategies. One way to target APOE and TREM2 is to modulate their expression using antisense oligonucleotides (ASOs). In this study, we identified ASOs that selectively and potently reduce human APOE and TREM2 levels in human myeloid cells including iPSC-derived microglia. We demonstrated that a single bolus delivery of the ASOs in the mouse cerebrospinal fluid is sufficient for the ASO to be pharmacologically active and modify the phenotype of xenografted human microglia throughout the rodent brain for at least 4 weeks. This study is the first proof-of-concept that the expression of microglial genes can be modulated using ASOs in a dose-dependent manner in order to manipulate human microglia phenotypes in vivo, and demonstrates the utility of these ASOs both as research and therapeutic tools to modulate neuroinflammation.
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详细内容（全部1条）

1. 非裔美国人脑部研究发现阿尔茨海默病的关键基因

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：Scientists studying Alzheimer’s in African Americans have uncovered a striking genetic clue that may cut across racial lines. In brain tissue from more than 200 donors, the gene ADAMTS2 was significantly more active in people with Alzheimer’s than in those without it. Even more surprising, this same gene topped the list in an independent study of White individuals. The discovery hints at a common biological pathway behind Alzheimer’s and opens the door to new treatment strategies.
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