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1.
J Transl Med ; 21(1): 250, 2023 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-37038181

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer with high morbidity and mortality rates. Due to the heterogeneity of LUAD, its characteristics remain poorly understood. Exploring the clinical and molecular characteristics of LUAD is challenging but vital for early diagnosis. METHODS: This observational and validation study enrolled 80 patients and 13 healthy controls. Nuclear and mtDNA-captured sequencings were performed. RESULTS: This study identified a spectrum of nuclear and mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with diagnosis. The correlation coefficient for somatic mutations in cfDNA and patient-matched tumor tissues was high in nuclear and mitochondrial genomes. The mutation number of highly mutated genes was evaluated, and the Least Absolute Shrinkage and Selection Operator (LASSO) established a diagnostic model. Receiver operating characteristic (ROC) curve analysis explored the diagnostic ability of the two panels. All models were verified in the testing cohort, and the mtDNA panel demonstrated excellent performance. This study identified somatic mutations in the nuclear and mitochondrial genomes, and detecting mutations in cfDNA displayed good diagnostic performance for early-stage LUAD. Moreover, detecting somatic mutations in the mitochondria may be a better tool for diagnosing early-stage LUAD. CONCLUSIONS: This study identified specific and sensitive diagnostic biomarkers for early-stage LUAD by focusing on nuclear and mitochondrial genome mutations. This also further developed an early-stage LUAD-specific mutation gene panel for clinical utility. This study established a foundation for further investigation of LUAD molecular pathogenesis.


Assuntos
Adenocarcinoma de Pulmão , Ácidos Nucleicos Livres , Genoma Mitocondrial , Neoplasias Pulmonares , Humanos , Genoma Mitocondrial/genética , Detecção Precoce de Câncer , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , DNA Mitocondrial/genética
3.
Front Microbiol ; 12: 643449, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796091

RESUMO

Psoriasis is a chronic inflammatory skin disease that affects millions of people worldwide. There is still no effective approach for the clinical treatment of psoriasis. This is largely due to the lack of understanding of the pathological mechanism. Here, we comprehensively characterized the skin microbiome and plasma metabolome alterations of psoriasis patients. We observed that some pathogenic bacteria, including Vibrio, were significantly increased in psoriasis patients. The metabolomics results showed alterations in some metabolic pathways, especially pathways for lipid metabolism. In addition, microbiome-specific metabolites, including bile acids and kynurenine, were significantly changed. Correlation analysis revealed the interplay between the skin microbiota and plasma metabolites, especially between Vibrio and several lipids. Our results provide new evidence for the interplay between the skin microbiome and plasma metabolites, which is dramatically disrupted in psoriasis patients. This study also revealed the mechanism underlying the pathogenesis of psoriasis.

4.
Front Immunol ; 11: 1703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849599

RESUMO

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects thousands of people worldwide. Recently, alterations in metabolism and gut microbiome have emerged as key regulators of SLE pathogenesis. However, it is not clear about the coordination of gut commensal bacteria and SLE metabolism. Here, by integrating 16S sequencing and metabolomics data, we characterized the gut microbiome and fecal and serum metabolome alterations in patients with SLE. Microbial diversity sequencing revealed gut microflora dysbiosis in SLE patients with significantly increased beta diversity. The metabolomics profiling identified 43 and 55 significantly changed metabolites in serum and feces samples in SLE patients. Notably, lipids accounted for about 65% altered metabolites in serum, highlighted the disruption of lipid metabolism. Integrated correlation analysis provided a link between the gut microbiome and lipid metabolism in patients with SLE, particularly according to regulate the conversion of primary bile acids to secondary bile acids. Overall, our results illustrate the perturbation of the gut microbiome and metabolome in SLE patients which may facilitate the development of new SLE interventions.


Assuntos
Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/microbiologia , Adulto , Disbiose/metabolismo , Disbiose/microbiologia , Feminino , Humanos , Masculino , Metaboloma
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