The Born Bonded program an antenatal services assessment

The administration of NSC1892 in mice also significantly inhibited tumor growth through degrading DDB1 and accumulating ST7. Interestingly, NSC1892 also showed promising cytotoxicity to decrease the growth of other CUL4A- or CUL4B-overexpressing tumor cells such as SKOV3 ovarian cells and Saos2 osteosarcoma cells. Our results provide a new avenue for the development of a therapeutic compound targeting tumors through disrupting the CUL4-DDB1 interaction. © The author(s).Exosome-mediated microRNAs (miRNAs) are closely related to the occurrence, development, invasion, metastasis, therapeutic resistance, diagnosis and treatment of malignant tumors. Guide-strand miRNA and passenger-strand miRNA (miRNA*) exist in miRNA processing, but the function of passenger-strand miRNA is often overlooked. In this study, we attempted to identify functional miRNA*s in exosomes derived from human colon cancer SW620 cells. miRNA expression profiles of human normal colonic epithelial cells NCM460 and colon cancer cells SW620 were compared by high-throughput sequencing. According to the sequencing results, we defined two sets of differentially expressed miRNAs "high in exosome and high in cell" (HEHC) and "high in exosome but low in cell" (HELC). As passenger-strand miRNAs, miR-2277-3p and miR-26b-3p, which belong to different sets, have diametrically opposite functions. MiR-2277-3p promotes proliferation, migration, and invasion of SW620 cells by targeting NUPR1L, while miR-26b-3p exerts an inhib cells of the same kind, thus regulating the paracrine effect of exosomes. © The author(s).Oropharyngeal squamous cell carcinoma (OPSCC) is an important type of head and neck squamous cell carcinoma (HNSCC). The traditional risk factors for OPSCC include carcinogen intake, smoking, alcohol consumption, and lifestyle. In recent years, cases of human papillomavirus (HPV)-related OPSCC have gradually increased. At present, HPV-related OPSCC in developed Western countries comprise up to 90% of all OPSCC cases, while in other developing countries, the proportion of HPV-related OPSCC cases is also gradually increasing. Compared with HPV-negative OPSCC, HPV-positive OPSCC patients have better overall survival rates and local control rates and this improved prognosis may be related to the increased radiosensitivity of HPV-positive tumors. Due to this more favorable prognosis, many downgraded treatment schemes are gradually emerging, including simple radiotherapy instead of concurrent radiotherapy or reduced radiotherapy dose. However, there is insufficient theoretical basis for such schemes. Some studies have shown that delayed repair of DNA damage after radiation, G2/M arrest, increased hypoxia, and decreased proliferation capacity are the main reasons for the increased radiosensitivity of HPV-positive tumor cells. In this review, we discuss the four principles of tumor cell damage caused by radiation, including repair, reoxygenation, redistribution, and regeneration in order to reveal the mechanism whereby HPV increases the radiosensitivity of tumor cells. An attempt was made to provide sufficient information to facilitate more individualized treatment for HPV-positive OPSCC patients, under the premise of good tumor control. © The author(s).Tumor-associated macrophages (TAMs) are closely correlated with tumor occurrence, invasion, and metastasis. However, factors affecting the biological functions of TAMs in colorectal cancer (CRC) are incompletely understood. Here, we found that Wnt5a was mainly expressed on TAMs of tumor stroma but not on CRC cells. Subsequently, we found that Wnt5a+ TAMs facilitated tumor cell proliferation and migration, and recruited macrophages infiltration. Furthermore, Wnt5a knockdown impaired the pro-tumor roles of TAMs in vivo and in vitro. Mechanistically, the cancer-promoting roles of Wnt5a in TAMs depended on CaMKII-ERK pathway-mediated CCL2 secretion. Our data reveal the crucial role played by TAM-expressed Wnt5a in CRC tumorigenesis through paracrine secretion of CCL2. We first report the connection between Wnt5a/CaMKII/ERK/CCL2 axis and biological functions of TAMs in tumor microenvironment, indicating that Wnt5a may be a novel therapeutic target for CRC. © The author(s).Radiotherapy is an effective approach for the treatment of lung adenocarcinoma. However, evidence suggests that lung adenocarcinoma can easily develop tolerance to radiotherapy. The purpose of this study was to investigate the effect and mechanism of SMAD3 on the radiosensitivity of lung adenocarcinoma in vitro and in vivo. We found that knockdown of SMAD3 using two short hairpin RNAs in lentivirus vectors significantly inhibited cell growth and increased radiosensitivity of the lung adenocarcinoma cell lines A549, H1299, and H1975. Using RNA sequencing and bioinformatics analyses, we found that the significantly differentially expressed genes in SMAD3 knockdown cells were mainly enriched in the cell cycle process. We then showed that knockdown of SMAD3 significantly reduced expression of cyclin-dependent kinase inhibitor 1 (p21) and increased the proportion of G2/M phase cells and the radiosensitivity of lung adenocarcinoma. Chromatin immunoprecipitation results in the Gene Expression Omnibus (GEO) database and our luciferase assay verified that SMAD3 directly bound the p21 promoter. A series of rescue experiments showed that overexpression of p21 partly reversed the effect of SMAD3 on proliferation and radioresistance in vitro and in vivo. Moreover, we found that the expression levels of SMAD3 and p21 were highly correlated, and both correlated with the patients' survival in online databases and clinical specimens. Expression of SMAD3 and p21 was also significantly different between radioresistant and radiosensitive patients in our hospital. Our results indicate that SMAD3 is a potential prognosis and radiosensitivity indicator as well as a target for radiotherapy and other treatments of patients with lung adenocarcinoma. find more © The author(s).Osteoarthritis (OA) is a common type of arthritis. Chronic inflammation is an important contributor to the pathogenesis of OA. The maturation and secretion of proinflammatory cytokines are controlled by inflammasomes, especially NLRP1 (NLR Family Pyrin Domain Containing 1) and NLRP3. In this study, we identified a transactivation mechanism of NLRP3 mediated by CtBPs (C-terminal-binding proteins). We found that both the mRNA and protein levels of CtBPs were significantly increased in OA biopsies. Analyzing the profiles of differentially expressed genes in CtBP-knockdown and overexpression cells, we found that the expression of NLRP3 was dependent on CtBP levels. By the knockdown or overexpression of transcription factors that potentially bind to the promoter of NLRP3, we found that only AP1 could specifically regulate the expression of NLRP3. Using immunoprecipitation (IP) and Co-IP assays, we found that AP1 formed a transcriptional complex with a histone acetyltransferase p300 and CtBPs. The knockdown of any member of this transcriptional complex resulted in a decrease in the expression of NLRP3.