RESUMO
IMPORTANCE: Hepatitis B virus (HBV) spliced variants are associated with viral persistence or pathogenicity. Hepatitis B doubly spliced protein (HBDSP), which has been previously reported as a pleiotropic transactivator protein, can potentially serve as an HBV virulence factor. However, the underlying mechanisms of HBDSP in HBV-associated liver diseases remain to be elucidated. In this study, we revealed that HBDSP promotes cellular apoptosis and induces wt-p53-dependent apoptotic signaling pathway in wt-p53 hepatocellular cells by transactivating p53 transcription, and increases the release of HBV progeny. Therefore, HBDSP may promote the HBV particles release through wt-p53-dependent hepatocellular apoptosis. Our findings suggest that blocking HBDSP-induced wt-p53-dependent apoptosis might have therapeutic values for chronic hepatitis B.
Assuntos
Apoptose , Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/virologia , Fator de Transcrição GATA2/metabolismo , Hepatite B/complicações , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Neoplasias Hepáticas/virologia , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Fator de Transcrição YY1/metabolismoRESUMO
BACKGROUND: This study observed and described the morphological characteristics of the endometrium of the resected uterus using confocal laser endomicroscopy. This included benign endometrium, non-atypical endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma, thereby laying a foundation for finding the precise localization and resection of endometrial lesions, given the feasibility of confocal laser endomicroscopy-assisted hysteroscopy. METHODS: This prospective study included 32 patients who underwent hysterectomy. We used confocal laser endomicroscopy to observe the endometrium of resected uteruses and described the characteristics of endometrium in different states by comparing histopathological findings (primary objects). The secondary objects of observation were the myometrium, endocervical canal, and surface of the external os of the cervix. RESULTS: A total of 32 patients who underwent hysterectomy for different diseases were included: 9 with endometrial carcinoma (5 with endometrioid carcinoma, 1 with endometrial serous carcinoma, 2 with clear cell carcinoma, and 1 with carcinosarcoma), 2 with atypical endometrial hyperplasia, 9 with benign diseases, 7 with cervical cancer, and 5 with ovarian cancer and borderline tumor. The dynamic images of the endometrium were observed and recorded using probe-based confocal laser endomicroscopy (pCLE). Considering histopathology as the gold standard, the diagnostic concordance rate of pCLE was 96.9% in patients with endometrial carcinoma and precancerous lesions and 100% in patients with endometrial carcinoma. CONCLUSION: Confocal laser endomicroscopy provides real-time high-resolution images of the benign endometrium and endometrial lesions. Compared with histopathology, confocal laser endomicroscopy has high diagnostic accuracy and may become an auxiliary examination tool for hysteroscopy, as it is useful for early identification of endometrial lesions, real-time diagnosis of tumor, and detection of tumor boundaries for complete tumor resection. These findings can lay a foundation for the feasible use of fertility-sparing local excision of tumor lesions by hysteroscopy.