Pancreatic cancer (PC) is notorious for its parallel morbidity and mortality rates. Recently, necroptosis, a form of programmed cell necrosis, has gained popularity for its role in tumorigenesis and metastasis. In this study, we explored the expression of necroptosis-related genes in PC and normal pancreatic tissues and identified 52 differentially expressed genes (DEGs). The Cox regression analysis was applied to construct the prognostic risk model, which divided patients into high- and low-risk groups. PC patients in the low-risk group showed a significantly better overall survival (OS) than those in the high-risk group. We further validated the prognostic role in ICGC cohort. Further, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and tumor microenvironment (TME) analysis were used to explore the underlying mechanisms. Notably, based on the gene signature, we revealed that the risk score was strongly related to the sensitivity of chemotherapy. In conclusion, necroptosis-related genes serve as an important immune mediator, and the risk model could be used to predict the survival and to guide the development of precision drugs for patients with PC.
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http://dx.doi.org/10.1155/2022/9737587 | DOI Listing |
Geroscience
January 2025
Buck Institute for Research On Aging, Novato, CA, 94945, USA.
Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood.
View Article and Find Full Text PDFActa Neuropathol
January 2025
Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.
Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar to early-onset (EOAD) and late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, and LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.
View Article and Find Full Text PDFDev Growth Differ
January 2025
Division of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
The neural tube, the embryonic precursor to the vertebrate central nervous system, comprises distinct progenitor and neuronal domains, each with specific proliferation programs. In this study, we identified TMEM196, a novel transmembrane protein that plays a crucial role in regulating cell proliferation in the floor plate in chick embryos. TMEM196 is expressed in the floor plate, and its overexpression leads to reduced cell proliferation without affecting the pattern formation of the neural tube.
View Article and Find Full Text PDFMol Oncol
January 2025
Department of Medicine A, Hematology, Oncology and Pneumology, University of Münster, Germany.
The transcriptomic classification of primary colorectal cancer (CRC) into distinct consensus molecular subtypes (CMSs) is a well-described strategy for patient stratification. However, the molecular nature of CRC metastases remains poorly investigated. To this end, this study aimed to identify and compare organotropic CMS frequencies in CRC liver and brain metastases.
View Article and Find Full Text PDFMol Ther
January 2025
Academic Unit of Ophthalmology, Translational Health Sciences, University of Bristol, Bristol, BS8 1TD, UK; NIHR Biomedical Research Centre of Ophthalmology, Moorfields Eye Hospital, London, EC1V 2PD, UK. Electronic address:
Progress for ocular AAV gene therapy has been hindered by AAV-induced inflammation, limiting dose escalation and long-term efficacy. Broadly, the extent of inflammatory responses alters with age and sex, yet these factors are poorly represented in pre-clinical development of ocular AAV gene therapies. Here, we combined clinical imaging, flow cytometry and bulk-sequencing of sorted microglia to interrogate the longitudinal inflammatory response following intravitreal delivery of AAV2 in young (3-month), middle aged (9-month) and old (18-month) Cx3cr1-creER:R26tdTomato+/- mice of both sexes.
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