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1.
Int J Mol Sci ; 25(17)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39273699

RESUMO

Inflammatory Bowel Diseases (IBD), which encompass ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic inflammation and tissue damage of the gastrointestinal tract. This study aimed to uncover novel disease-gene signatures, dysregulated pathways, and the immune cell infiltration landscape of inflamed tissues. Eight publicly available transcriptomic datasets, including inflamed and non-inflamed tissues from CD and UC patients were analyzed. Common differentially expressed genes (DEGs) were identified through meta-analysis, revealing 180 DEGs. DEGs were implicated in leukocyte transendothelial migration, PI3K-Akt, chemokine, NOD-like receptors, TNF signaling pathways, and pathways in cancer. Protein-protein interaction network and cluster analysis identified 14 central IBD players, which were validated using eight external datasets. Disease module construction using the NeDRex platform identified nine out of 14 disease-associated genes (CYBB, RAC2, GNAI2, ITGA4, CYBA, NCF4, CPT1A, NCF2, and PCK1). Immune infiltration profile assessment revealed a significantly higher degree of infiltration of neutrophils, activated dendritic cells, plasma cells, mast cells (resting/activated), B cells (memory/naïve), regulatory T cells, and M0 and M1 macrophages in inflamed IBD tissue. Collectively, this study identified the immune infiltration profile and nine disease-associated genes as potential modulators of IBD pathogenesis, offering insights into disease molecular mechanisms, and highlighting potential disease modulators and immune cell dynamics.


Assuntos
Biologia Computacional , Mapas de Interação de Proteínas , Humanos , Biologia Computacional/métodos , Mapas de Interação de Proteínas/genética , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Transcriptoma , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Perfilação da Expressão Gênica , Doença de Crohn/genética , Doença de Crohn/imunologia , Doença de Crohn/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Mastócitos/imunologia , Mastócitos/metabolismo , Redes Reguladoras de Genes , Neutrófilos/imunologia , Neutrófilos/metabolismo , Transdução de Sinais/genética , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , NADPH Oxidases
2.
Biomed Pharmacother ; 164: 114967, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37290189

RESUMO

Lactoferrin (LF) is a protein found in several bodily fluids, such as milk. This protein has a diverse range of functions and is evolutionarily conserved. Lactoferrin is a multifunction protein with distinct biological abilities affecting mammals' immune structures. Reports indicated that the daily uptake of LF from dairy products is unsatisfactory in detecting further health-promoting abilities. Research has shown that it protects against infection, mitigates cellular senescence, and improves nutritional quality. Additionally, LF is being studied as a potential treatment for various diseases and conditions, including gastrointestinal issues and infections. Studies have also demonstrated its effectiveness against various viruses and bacteria. In this article, we'll look closer at the structure of LF and its various biological activities, including its antimicrobial, anti-viral, anti-cancer, anti-osteoporotic, detoxifying, and immunomodulatory properties. More specifically, the protective effect of LF against oxidative DNA damage was also clarified through its ability to abolish DNA damaging issues without interfacing with host genetic material. Fortification with LF protects mitochondria dysfunction syndromes via sustaining redox status and biogenesis and suppressing apoptosis and autophagy singling. Additionally, we'll examine the potential benefits of lactoferrin and provide an overview of recent clinical trials conducted to examine its use in laboratory and living models.


Assuntos
Anti-Infecciosos , Lactoferrina , Humanos , Animais , Lactoferrina/farmacologia , Lactoferrina/uso terapêutico , Relevância Clínica , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Leite/metabolismo , Mamíferos , Genômica
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