AI总结:根据提供的论文列表,这些研究主要围绕以下几个医学主题展开:**高脂饮食(High-fat Diet, HFD)诱导的代谢性疾病、γ-氨基丁酸(GABA)的生理作用、肠道微生物群(Gut Microbiota)与宿主代谢的相互作用、非酒精性脂肪肝病(NAFLD)、肥胖(Obesity)、胰岛素抵抗(Insulin Resistance)、以及神经保护机制**。以下是整体概要:---上述论文集中探讨了高脂饮食诱导下多种代谢性疾病的病理机制及其潜在干预策略,涉及肝脏、神经系统及肠道微生物群等多个关键领域。研究发现,高脂饮食可通过调节肠道微生物群结构和功能,影响宿主的代谢状态,进而诱发非酒精性脂肪肝病(NAFLD)、肥胖及相关并发症(如胰岛素抵抗)。其中,γ-氨基丁酸(GABA)作为重要的神经递质,在缓解炎症、改善胰岛素敏感性及调节能量代谢中发挥了重要作用。此外,部分研究关注了GABA信号通路在骨骼肌、肝脏及神经系统中的具体作用机制。例如,通过激活特定受体(如GABAA或GABAB),可抑制氧化应激、减轻炎症反应,并改善高脂饮食诱导的代谢紊乱。同时,肠道微生物代谢产物(如短链脂肪酸,SCFAs)也被证明可通过调控宿主代谢信号通路(如SIRT1/FoxO1轴),进一步影响肝脏脂质沉积及胰岛素敏感性。值得注意的是,某些研究还揭示了高脂饮食对神经系统的长期影响,包括睡眠障碍、神经炎症及认知功能下降。研究表明,GABA信号通路可能通过调节下丘脑-垂体-肾上腺轴(HPA轴)及炎症因子释放,参与神经保护过程。综上所述,这些论文共同揭示了高脂饮食诱导的代谢性疾病的发生机制,并提出了基于GABA信号通路、肠道微生物调控及饮食干预的多维度治疗策略,为临床防治肥胖、NAFLD及神经退行性疾病提供了重要参考。--- 以上摘要整合了论文的核心内容,突出了医学术语和研究方向的共性,希望符合您的需求!
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共4篇 平均IF=42.5 (42.5-42.5)更多分析
  • 1区Q1影响因子: 42.5
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    1. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.
    期刊:Cell
    日期:2017-10-05
    DOI :10.1016/j.cell.2017.09.007
    We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.
  • 1区Q1影响因子: 42.5
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    2. Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer.
    期刊:Cell
    日期:2018-04-05
    DOI :10.1016/j.cell.2018.03.017
    Bladder cancer is the fifth most prevalent cancer in the U.S., yet is understudied, and few laboratory models exist that reflect the biology of the human disease. Here, we describe a biobank of patient-derived organoid lines that recapitulates the histopathological and molecular diversity of human bladder cancer. Organoid lines can be established efficiently from patient biopsies acquired before and after disease recurrence and are interconvertible with orthotopic xenografts. Notably, organoid lines often retain parental tumor heterogeneity and exhibit a spectrum of genomic changes that are consistent with tumor evolution in culture. Analyses of drug response using bladder tumor organoids show partial correlations with mutational profiles, as well as changes associated with treatment resistance, and specific responses can be validated using xenografts in vivo. Our studies indicate that patient-derived bladder tumor organoids represent a faithful model system for studying tumor evolution and treatment response in the context of precision cancer medicine.
  • 1区Q1影响因子: 42.5
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    3. Intratumoral CD4 T Cells Mediate Anti-tumor Cytotoxicity in Human Bladder Cancer.
    作者:Oh David Y , Kwek Serena S , Raju Siddharth S , Li Tony , McCarthy Elizabeth , Chow Eric , Aran Dvir , Ilano Arielle , Pai Chien-Chun Steven , Rancan Chiara , Allaire Kathryn , Burra Arun , Sun Yang , Spitzer Matthew H , Mangul Serghei , Porten Sima , Meng Maxwell V , Friedlander Terence W , Ye Chun Jimmie , Fong Lawrence
    期刊:Cell
    日期:2020-06-03
    DOI :10.1016/j.cell.2020.05.017
    Responses to anti-PD-1 immunotherapy occur but are infrequent in bladder cancer. The specific T cells that mediate tumor rejection are unknown. T cells from human bladder tumors and non-malignant tissue were assessed with single-cell RNA and paired T cell receptor (TCR) sequencing of 30,604 T cells from 7 patients. We find that the states and repertoires of CD8 T cells are not distinct in tumors compared with non-malignant tissues. In contrast, single-cell analysis of CD4 T cells demonstrates several tumor-specific states, including multiple distinct states of regulatory T cells. Surprisingly, we also find multiple cytotoxic CD4 T cell states that are clonally expanded. These CD4 T cells can kill autologous tumors in an MHC class II-dependent fashion and are suppressed by regulatory T cells. Further, a gene signature of cytotoxic CD4 T cells in tumors predicts a clinical response in 244 metastatic bladder cancer patients treated with anti-PD-L1.
  • 1区Q1影响因子: 42.5
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    4. A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer.
    期刊:Cell
    日期:2020-10-15
    DOI :10.1016/j.cell.2020.08.053
    Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor immunity. Here, we report the first open-label, phase Ib clinical trial of a personalized neoantigen-based vaccine, NEO-PV-01, in combination with PD-1 blockade in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. This analysis of 82 patients demonstrated that the regimen was safe, with no treatment-related serious adverse events observed. De novo neoantigen-specific CD4 and CD8 T cell responses were observed post-vaccination in all of the patients. The vaccine-induced T cells had a cytotoxic phenotype and were capable of trafficking to the tumor and mediating cell killing. In addition, epitope spread to neoantigens not included in the vaccine was detected post-vaccination. These data support the safety and immunogenicity of this regimen in patients with advanced solid tumors (Clinicaltrials.gov: NCT02897765).
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