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1.
Curr Rheumatol Rep ; 25(12): 247-258, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37737528

RESUMO

PURPOSE OF REVIEW: The resident gut microbiota serves as a double-edged sword that aids the host in multiple ways to preserve a healthy equilibrium and serve as early companions and boosters for the gradual evolution of our immune defensive layers; nevertheless, the perturbation of the symbiotic resident intestinal communities has a profound impact on autoimmunity induction, particularly in systemic lupus erythematosus (SLE). Herein, we seek to critically evaluate the microbiome research in SLE with a focus on intestinal dysbiosis. RECENT FINDINGS: SLE is a complex and heterogeneous disorder with self-attack due to loss of tolerance, and there is aberrant excessive immune system activation. There is mounting evidence suggesting that intestinal flora disturbances may accelerate the formation and progression of SLE, presumably through a variety of mechanisms, including intestinal barrier dysfunction and leaky gut, molecular mimicry, bystander activation, epitope spreading, gender bias, and biofilms. Gut microbiome plays a critical role in SLE pathogenesis, and additional studies are warranted to properly define the impact of gut microbiome in SLE, which can eventually lead to new and potentially safer management approaches for this debilitating disease.


Assuntos
Microbioma Gastrointestinal , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Masculino , Disbiose/complicações , Sexismo , Autoimunidade
2.
Int J Mol Sci ; 21(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339129

RESUMO

Enzalutamide, an antiandrogen, is approved for therapy of castration resistant prostate cancer. Clinical applications have shown that approximately 30% of patients acquire resistance after a short period of treatment. However, the molecular mechanisms underlying this resistance is not completely understood. To identify transcriptomic signatures associated with acquisition of drug resistance we profiled gene expression of paired enzalutamide sensitive and resistant human prostate cancer LNCaP (lymph node carcinoma of the prostate) and C4-2B cells. Overlapping genes differentially regulated in the enzalutamide resistant cells were ranked by Ingenuity Pathway Analysis and their functional validation was performed using ingenuity knowledge database followed by confirmation to correlate transcript with protein expression. Analysis revealed that genes associated with cancer stem cells, such as POU5F1 (OCT4), SOX2, NANOG, BMI1, BMP2, CD44, SOX9, and ALDH1 were markedly upregulated in enzalutamide resistant cells. Amongst the pathways enriched in the enzalutamide-resistant cells were those associated with RUNX2, hedgehog, integrin signaling, and molecules associated with elastic fibers. Further examination of a patient cohort undergoing ADT and its comparison with no-ADT group demonstrated high expression of POU5F1 (OCT4), ALDH1, and SOX2 in ADT specimens, suggesting that they may be clinically relevant therapeutic targets. Altogether, our approach exhibits the potential of integrative transcriptomic analyses to identify critical genes and pathways of antiandrogen resistance as a promising approach for designing novel therapeutic strategies to circumvent drug resistance.


Assuntos
Androgênios/deficiência , Redes Reguladoras de Genes , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias de Próstata Resistentes à Castração/genética , Transcriptoma , Antagonistas de Receptores de Andrógenos/farmacologia , Benzamidas , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Células-Tronco Neoplásicas/metabolismo , Nitrilas , Feniltioidantoína/análogos & derivados , Feniltioidantoína/farmacologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia
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