Construction of HBV-HCC prognostic model and immune characteristics based on potential genes mining through protein interaction networks.

OBJECTIVE: To search for human protein-coding genes related to hepatocellular carcinoma (HCC) in the context of hepatitis B virus (HBV) infection, and perform prognosis risk assessment. METHODS: Genes related to HBV-HCC were selected through literature screening and protein-protein interaction (PPI) network database analysis. Prognosis potential genes (PPGs) were identified using Cox regression analysis. Patients were divided into high-risk and low-risk groups based on PPGs, and risk scores were calculated. Kaplan-Meier plots were used to analyze overall survival rates, and the results were predicted based on clinicopathological variables. Association analysis was also conducted with immune infiltration, immune therapy, and drug sensitivity. Experimental verification of the expression of PPGs was done in patient liver cancer tissue and normal liver tissue adjacent to tumors. RESULTS: The use of a prognosis potential genes risk assessment model can reliably predict the prognosis risk of patients, demonstrating strong predictive ability. Kaplan-Meier analysis showed that the overall survival rate of the low-risk group was significantly higher than that of the high-risk group. There were significant differences between the two subgroups in terms of immune infiltration and IC50 association analysis. Experimental verification revealed that CYP2C19, FLNC, and HNRNPC were highly expressed in liver cancer tissue, while UBE3A was expressed at a lower level. CONCLUSION: PPGs can be used to predict the prognosis risk of HBV-HCC patients and play an important role in the diagnosis and treatment of liver cancer. They also reveal their potential role in the tumor immune microenvironment, clinical-pathological characteristics, and prognosis.

UHRF2 promotes the malignancy of hepatocellular carcinoma by PARP1 mediated autophagy.

Autophagy have critical implications in the proliferation and metastasis of HCC. In the current study, we aimed to explore the underlying mechanisms of UHRF2 regulates HCC cells autophagy and HCC progression. We initially determined the relationship between UHRF2 and HCC autophagy, oncogenicity and patient survival through GSEA database and TCGA database. We mainly investigated the effect of UHRF2 on HCC development and autophagy through western blot, electron microscopy, and immunofluorescence. Functionally, UHRF2 was positively involved in the autophagy activation. Overexpression of UHRF2 reduced apoptosis in HCC cells, and promoted the malignancy phenotype of HCC both in vitro and in vivo. Mechanistically, PRDX1 bound to UHRF2 and upregulated its protein expression to facilitate the biological function of UHRF2 in HCC. Meanwhile, UHRF2 bound to autophagy-related protein PARP1 and upregulated PARP1 protein level. The results showed that UHRF2 promoted autophagy and contributed to the malignant phenotype of HCC by regulating PARP1 protein level. In summary, a novel interaction between PRDX1, UHRF2, and PARP1 was revealed, suggesting that UHRF2 could inspire a potential biomarker and potential therapeutic target for HCC.

Proteomic Analysis of Plasma in Adult Active Pulmonary Tuberculosis Patients with Diabetes Mellitus.

BACKGROUND: There is a high burden of both diabetes and tuberculosis in China. Diabetes depresses the immunologic response that facilitates the development of infectious diseases, including infection by Mycobacterium tuberculosis, the agent of tuberculosis. Tuberculosis is the third cause of death among subjects with non-communicable diseases, and among the non-communicable diseases, diabetes is one of the most important. The relationship between diabetes and tuberculosis has already been object of many investigations but the association between these two diseases is not fully understood. The aim of this study was to determine whether relative qualitative and quantitative differences in protein expression of plasma could be related to active pulmonary tuberculosis complicated with diabetes. METHODS: Biological parameters are useful tools for understanding and monitoring complicated disease processes. Our study employed two-dimensional gel electrophoresis and mass spectrometry to analyze the proteins associated with active pulmonary tuberculosis complicated with diabetes. RESULTS: Under the baseline condition, we found that the levels of α-1 antitrypsin precursor, vitamin D-binding protein precursor, CD5 antigen like precursor, clusterin precursor, apolipoprotein A-I precursor, haptoglobin, and fibrinogen γ-chain differed between patients with active pulmonary tuberculosis and active pulmonary tuberculosis complicated with diabetes subjects. Western blotting results confirmed differential expression of clusterin. CONCLUSIONS: We identified active pulmonary tuberculosis complicated with diabetes-associated proteins in plasma. C-terminal haptoglobin is a possible candidate protein of interest, which might be a link between active pulmonary tuberculosis and diabetes. The dynamics of protein expression during disease progression may improve our understanding of the pathogenesis of active pulmonary tuberculosis complicated with diabetes.

[Proteomic differential display analysis of high glucose load human U937 cell line stimulated by vitamin D3].

OBJECTIVE: The purpose of this study was to analysis on the affection of key protein expression by vitamin D3, and to investigate the mechanism of vitamin D3 on contributing to diabetes. METHOD: Good status U937 cells were cultured by high glucose medium which contained 45 mmol/L D-Glucose, and treated by 1, 25-(OH)(2)-D3. The control groups were U937 cells cultured by high glucose. The whole cell proteins were extracted and separated by 2-dimentional gel electrophoresis (2-DE), differential expression proteins were identified by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). RESULT: There were 30 protein spots whose expression was significantly different between vitamin D-treated and untreated high glucose loaded cells. Six protein spots were identified by MALDI-TOF-MS, three of which, prohibitin, heat shock 70 kD protein 8, and catalase were protection of cell stress proteins, one of which, electron transport flavoprotein, was respiratory chain related proteins, two of which, fumarylacetoacetate hydrolase and triosephosphate isomerase, were cell metabolism related proteins. CONCLUSION: The differentially expressed proteins of high glucose load human U937 cell line stimulated by vitamin D3 were found. These differential proteins were mainly related to oxidative stress and energy metabolism. These data suggested that 1, 25-(OH)(2)-D3 might regulate cell high glucose load by reduction oxidative stress injury and affection energy metabolism.