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1.
Medicine (Baltimore) ; 103(18): e37837, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701259

RESUMO

In this study, we aimed to investigate the involvement of PANoptosis, a form of regulated cell death, in the development of steroid-induced osteonecrosis of the femoral head (SONFH). The underlying pathogenesis of PANoptosis in SONFH remains unclear. To address this, we employed bioinformatics approaches to analyze the key genes associated with PANoptosis. Our analysis was based on the GSE123568 dataset, allowing us to investigate both the expression profiles of PANoptosis-related genes (PRGs) and the immune profiles in SONFHallowing us to investigate the expression profiles of PRGs as well as the immune profiles in SONFH. We conducted cluster classification based on PRGs and assessed immune cell infiltration. Additionally, we used the weighted gene co-expression network analysis (WGCNA) algorithm to identify cluster-specific hub genes. Furthermore, we developed an optimal machine learning model to identify the key predictive genes responsible for SONFH progression. We also constructed a nomogram model with high predictive accuracy for assessing risk factors in SONFH patients, and validated the model using external data (area under the curve; AUC = 1.000). Furthermore, we identified potential drug targets for SONFH through the Coremine medical database. Using the optimal machine learning model, we found that 2 PRGs, CASP1 and MLKL, were significantly correlated with the key predictive genes and exhibited higher expression levels in SONFH. Our analysis revealed the existence of 2 distinct PANoptosis molecular subtypes (C1 and C2) within SONFH. Importantly, we observed significant variations in the distribution of immune cells across these subtypes, with C2 displaying higher levels of immune cell infiltration. Gene set variation analysis indicated that C2 was closely associated with multiple immune responses. In conclusion, our study sheds light on the intricate relationship between PANoptosis and SONFH. We successfully developed a risk predictive model for SONFH patients and different SONFH subtypes. These findings enhance our understanding of the pathogenesis of SONFH and offer potential insights into therapeutic strategies.


Assuntos
Biologia Computacional , Necrose da Cabeça do Fêmur , Humanos , Necrose da Cabeça do Fêmur/genética , Necrose da Cabeça do Fêmur/induzido quimicamente , Biologia Computacional/métodos , Aprendizado de Máquina , Esteroides/efeitos adversos , Caspase 1/genética , Nomogramas , Perfilação da Expressão Gênica/métodos , Proteínas Quinases/genética
2.
Chin Med ; 12: 31, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29093746

RESUMO

BACKGROUND: Wound ointment (WO), a kind of Chinese medicine, can significantly promote fracture healing. The study aimed at analyzing the chemical composition and the effects of WO on fracture of rabbits and tried to explore the corresponding molecular mechanism in cytokine. METHODS: The qualitative and quantitative analysis of WO was conducted by liquid chromatography-mass spectrometry (LC-MS). Fifty-four Zealand mature male rabbits were randomly divided into 3 groups: Control group, Yunnan Baiyao (YB) group and WO group. All the rabbits suffered a fracture of right radius and were then stabilized with an external fixator. Treated with different methods, fracture healing was observed. The bone specimens were subjected to radiograph, immunohistochemistry (IHC) analysis, hematoxylin-eosin staining (HE), western blot and enzyme linked immunosorbent assay (ELISA). RESULTS: A total of 12 active compositions were detected by LC-MS. Radiographs showed a considerably better bone healing and remodeling of the fracture in WO group. HE experiments showed that a large number of osteoclasts appeared in the early stage when treated with WO. In immunohistochemistry (IHC), western blot and ELISA test, significant increases in vascular endothelial growth factor (VEGF) expression were observed in WO group compared with other two groups. CONCLUSIONS: Wound ointment contained active compositions which efficiently promoted fracture healing through increasing the expression of VEGF. Trial Registration Not applicable.

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