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1.
Sci Rep ; 14(1): 2767, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307957

RESUMO

Colorectal cancer (CRC) is one of the most prevalent and deadliest illnesses all around the world. Growing proofs demonstrate that tumor-associated macrophages (TAMs) are of critical importance in CRC pathogenesis, but their mechanisms remain yet unknown. The current research was designed to recognize underlying biomarkers associated with TAMs in CRC. We screened macrophage-related gene modules through WGCNA, selected hub genes utilizing the LASSO algorithm and COX regression, and established a model. External validation was performed by expression analysis using datasets GSE14333, GSE74602, and GSE87211. After validating the bioinformatics results using real-time quantitative reverse transcription PCR, we identified SPP1, C5AR1, MMP3, TIMP1, ADAM8 as potential biomarkers associated with macrophages in CRC.


Assuntos
Neoplasias Colorretais , Genes Reguladores , Humanos , Prognóstico , Macrófagos , Biomarcadores , Neoplasias Colorretais/genética , Biomarcadores Tumorais/genética , Proteínas de Membrana , Proteínas ADAM
2.
Aging Cell ; 23(3): e14064, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38100161

RESUMO

Vitamin A (VA) is a micronutrient essential for the physiology of many organisms, but its role in longevity and age-related diseases remains unclear. In this work, we used Caenorhabditis elegans to study the impact of various bioactive compounds on lifespan. We demonstrate that VA extends lifespan and reduces lipofuscin and fat accumulation while increasing resistance to heat and oxidative stress. This resistance can be attributed to high levels of detoxifying enzymes called glutathione S-transferases, induced by the transcription factor skinhead-1 (SKN-1). Notably, VA upregulated the transcript levels of skn-1 or its mammalian ortholog NRF2 in both C. elegans, human cells, and liver tissues of mice. Moreover, the loss-of-function genetic models demonstrated a critical involvement of the SKN-1 pathway in longevity extension by VA. Our study thus provides novel insights into the molecular mechanism of anti-aging and anti-oxidative effects of VA, suggesting that this micronutrient could be used for the prevention and/or treatment of age-related disorders.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Humanos , Camundongos , Caenorhabditis elegans/metabolismo , Longevidade/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Vitamina A/farmacologia , Vitamina A/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Regulação para Cima , Proteínas de Caenorhabditis elegans/metabolismo , Estresse Oxidativo , Mamíferos/metabolismo , Micronutrientes/metabolismo , Micronutrientes/farmacologia
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