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1.
Sci Rep ; 10(1): 4271, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144299

RESUMO

Kidney renal clear cell carcinoma (KIRC) is the most common renal cell carcinoma (RCC). However, patients with KIRC usually have poor prognosis due to limited biomarkers for early detection and prognosis prediction. In this study, we analysed key genes and pathways involved in KIRC from an array dataset including 26 tumour and 26 adjacent normal tissue samples. Weighted gene co-expression network analysis (WGCNA) was performed with the WGCNA package, and 20 modules were characterized as having the highest correlation with KIRC. The upregulated genes in the tumour samples are involved in the innate immune response, whereas the downregulated genes contribute to the cellular catabolism of glucose, amino acids and fatty acids. Furthermore, the key genes were evaluated through a protein-protein interaction (PPI) network combined with a co-expression network. The comparatively lower expression of AGXT, PTGER3 and SLC12A3 in tumours correlates with worse prognosis in KIRC patients, while higher expression of ALOX5 predicts reduced survival. Our integrated analysis illustrated the hub genes involved in KIRC tumorigenesis, shedding light on the development of prognostic markers. Further understanding of the function of the identified KIRC hub genes could provide deep insights into the molecular mechanisms of KIRC.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Transformação Celular Neoplásica/genética , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Oncogenes , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Estudos de Casos e Controles , Transformação Celular Neoplásica/metabolismo , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Prognóstico , Transdução de Sinais , Análise de Sobrevida
2.
Nat Protoc ; 13(10): 2247-2267, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30218100

RESUMO

Periodontal disease (PD) is a common dental disease associated with the interaction between dysbiotic oral microbiota and host immunity. It is a prevalent disease, resulting in loss of gingival tissue, periodontal ligament, cementum and alveolar bone. PD is a major form of tooth loss in the adult population. Experimental animal models have enabled the study of PD pathogenesis and are used to test new therapeutic approaches for treating the disease. The ligature-induced periodontitis model has several advantages as compared with other models, including rapid disease induction, predictable bone loss and the capacity to study periodontal tissue and alveolar bone regeneration because the model is established within the periodontal apparatus. Although mice are the most convenient and versatile animal models used in research, ligature-induced periodontitis has been more frequently used in large animals. This is mostly due to the technical challenges involved in consistently placing ligatures around murine teeth. To reduce the technical challenge associated with the traditional ligature model, we previously developed a simplified method to easily install a bacterially retentive ligature between two molars for inducing periodontitis. In this protocol, we provide detailed instructions for placement of the ligature and demonstrate how the model can be used to evaluate gingival tissue inflammation and alveolar bone loss over a period of 18 d after ligature placement. This model can also be used on germ-free mice to investigate the role of human oral bacteria in periodontitis in vivo. In conclusion, this protocol enables the mechanistic study of the pathogenesis of periodontitis in vivo.


Assuntos
Modelos Animais de Doenças , Periodontite/patologia , Animais , Técnicas Bacteriológicas/métodos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Periodontite/etiologia , Periodontite/microbiologia
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