Smithwinters2227

Finally, inhibition of aerobic glycolysis can further increase the cytotoxicity induced by IC261. Collectively, our results revealed that IC261 could inhibit the growth of colon cancer cells and increase the level of aerobic glycolysis, which is regulated by p53-dependent manner. This result suggested that targeting CK1δ/ε and glycolysis might be a valuable strategy treatment and combination therapies for colon cancer. © The author(s).Cholangiocarcinoma (CCA) is an epithelial cancer and has high death and recurrence rates, current methods cannot satisfy the need for predicting cancer relapse effectively. So, we aimed at conducting a multi-mRNA signature to improve the relapse prediction of CCA. We analyzed mRNA expression profiling in large CCA cohorts from the Gene Expression Omnibus (GEO) database (GSE76297, GSE32879, GSE26566, GSE31370, and GSE45001) and The Cancer Genome Atlas (TCGA) database. The Least absolute shrinkage and selection operator (LASSO) regression model was used to establish a 7-mRNA-based signature that was significantly related to the recurrence-free survival (RFS) in two test series. Based on the 7-mRNA signature, the cohort TCGA patients could be divided into high-risk or low-risk subgroups with significantly different RFS [p less then 0.001, hazard ratio (HR) 48.886, 95% confidence interval (CI) 6.226-3.837E+02]. Simultaneously, the prognostic value of the 7-mRNA signature was confirmed in clinical samples of Ren Ji hospital (p less then 0.001, HR 4.558, 95% CI 1.829-11.357). selleck chemical Further analysis including multivariable and sub-group analyses revealed that the 7-mRNA signature was an independent prognostic value for recurrence of patients with CCA. In conclusion, our results might provide an efficient tool for relapse prediction and were beneficial to individualized management for CCA patients. © The author(s).COL2A1-related disorders represent a heterogeneous group of skeletal dysplasias with a wide phenotypic spectrum. Our aim is to characterize the clinical and molecular phenotypes of Chinese patients with COL2A1-related dysplasia and to explore their phenotype-genotype relations. Clinical data were collected, physical examinations were conducted, and X-ray radiography and genetic analyses were performed in ten families involving 29 patients with COL2A1-related dysplasia. Nine mutations were identified in COL2A1, including five novel (c.816+6C>T, p.Gly246Arg, p.Gly678Glu, p.Gly1014Val and p.Ter1488Gln) and four reported previously (p.Gly204Val, p.Arg275Cys, p.Gly504Ser and p.Arg719Cys). Based on clinical features and molecular mutations, the ten families were classified into five definite COL2A1-related disorders four families with spondyloepiphyseal dysplasia congenita (SEDC), three with osteoarthritis with mild chondrodysplasia (OSCPD), one with Czech dysplasia, one with Kniest dysplasia, and one with epiphyseal dysplasia, multiple, with myopia and deafness (EDMMD). Based on genetic testing results, prenatal diagnosis and genetic counseling were accomplished for one female proband with OSCDP. Chinese patients with OSCDP, Czech dysplasia and EDMMD caused by COL2A1 mutations were first reported, expanding the spectrum of COL2A1 mutations and the phenotype of COL2A1-related disorders and providing further evidence for the phenotype-genotype relations, which may help improve procreative management of COL2A1-related disorders. © The author(s).Changes in mitochondrial structure and function are mostly responsible for aging and age-related features. Whether healthy mitochondria could prevent aging is, however, unclear. Here we intravenously injected the mitochondria isolated from young mice into aged mice and investigated the mitotherapy on biochemistry metabolism and animal behaviors. The results showed that heterozygous mitochondrial DNA (mtDNA) of both aged and young mouse coexisted in tissues of aged mice after mitochondrial administration, and meanwhile, ATP content in tissues increased while reactive oxygen species (ROS) level reduced. Besides, the mitotherapy significantly improved cognitive and motor performance of aged mice. link2 Our study, at the first report in aged animals, not only provides a useful approach to study mitochondrial function associated with aging, but also a new insight into anti-aging through mitotherapy. © The author(s).Many bacterial-related databases are developed to meet the researchers' needs of analysis and search for a number of bacterial information. However, these databases have different data resources, construction methods, data formats, and analysis tools. It's difficult for researchers to select appropriate databases and analysis tools to promote their researches. In the paper, we compared the contents, construction methods, data sources, update frequency, scope and scale of data, analysis tools, and features of nine famous bacterial databases CARD, EffectiveDB, MBGD, MPD, PATRCI, PHI-base, VFDB, gcMeta and SILVA, and help researchers to better make better use of these databases. In addition, we also hope this review can help researchers develop a more comprehensive database and better tools to meet the needs of researchers. © The author(s).We investigated the role of microRNA (miR)-9 in modulating chemoresistance in hepatocellular carcinoma (HCC) cells. MiR-9 was overexpressed or knocked down in HCC cell lines. Cell viability, cell proliferation, the expression of EIF5A2 and the epithelial-mesenchymal transition (EMT)-related proteins were examined. HCC cells overexpressing miR-9 were more sensitive to cisplatin; miR-9 knockdown yielded the opposite result. The in vivo nude mouse HCC xenograft tumors yielded the same results. EIF5A2 was identified as a potential target of miR-9, where miR-9 regulated EIF5A2 expression at mRNA and protein level. EIF5A2 knockdown reversed miR-9 inhibition-mediated cisplatin resistance. Altering miR-9 and EIF5A2 expression changed E-cadherin and vimentin expression. Furthermore, EIF5A2 mediated miR-9 EMT pathway regulation, indicating that miR-9 can enhance cisplatin sensitivity by targeting EIF5A2 and inhibiting the EMT pathway. Targeting miR-9 may be useful for overcoming drug resistance in HCC. © The author(s).Colorectal cancer (CRC) is the second leading cause of death globally. Integrin α1 (ITGA1) belongs to integrin family and involves in regulating cell adhesion, invasion, proliferation and tumorigenicity, its expression is up-regulated in various cancers, including CRC. However, the molecular understanding and clinical relevance of ITGA1 in the development and progression of CRC remain unclear. In the present study, we detected ITGA1 in 50 CRC tissues and adjacent non-cancerous tissues, sera from 100 CRC patients and 50 healthy subjects, and four CRC cell lines using immunohistochemistry staining, enzyme-linked immunosorbent assay and Western blotting. We found that the ITGA1 protein was significantly higher in human CRC tissues and cell lines than both paired non-tumor tissues and normal cells, respectively. In addition, the serum concentration of ITGA1 was also higher in CRC patients compared to the healthy subjects (p less then 0.01) and was significantly associated with metastatic TNM stages (p less then 0.0001) and circulating carbohydrate antigen 199 (CA199) (p less then 0.022). Furthermore, down-regulation of ITGA1 with transfecting LV-shITGA1 inhibited the progressive capacity of cell migration and invasion in CRC SW480 cell line and the tumorgenicity in nude mice. In functional studies, ITGA1 knockdown also inhibited Ras/ERK signaling pathway by decreasing the expression of Ras, p-Erk1/2 and c-Myc in SW480. Contrastly, when evelated expression of ITGA1 in NCM460 coincided with the increased expression of Ras, p-Erk1/2 and c-Myc. Taken together, our findings suggest that ITGA1 is an oncogene with a capability to promote CRC cell migration, invasion and tumorigenicity by activating the Ras/Erk signaling, implying that it may be a novel target for the diagnosis and treatment of CRC, and warrants further investigation. © The author(s).Lung cancer is one of the most common and deadly malignancies worldwide, in spite of advances in targeted therapy in recent years. An effective strategy for lung cancer prevention remains a major problem. Advances in next-generation sequencing have helped in understanding the RNA and identifying novel circular RNAs (circRNAs) that may have a broad impact on the early diagnosis and treatment of lung cancer. The circRNAs, exhibiting spatiotemporal-specific expression, are stable and conserved and present diverse biological functions in the normal and diseased states, including cancer. In this review, we summarize the recent advances in elucidating the functional role of circRNAs in lung cancer pathogenesis and discuss their potential mechanisms. © The author(s).Trimethylamine N-oxide (TMAO) leads to the development of cardiovascular and chronic kidney diseases, but there are currently no potent drugs that inhibit the production or toxicity of TMAO. In this study, high-fat diet-fed ApoE-/- mice were treated with finasteride, ranitidine, and andrioe. Subsequently, the distribution and quantity of gut microbiota in the faeces of the mice in each group were analysed using 16S rRNA sequencing of the V3+V4 regions. Pathological examination confirmed that both ranitidine and finasteride reduced atherosclerosis and renal damage in mice. HPLC analysis also indicated that ranitidine and finasteride significantly reduced the synthesis of TMAO and the TMAO precursor delta-Valerobetaine in their livers. The 16S rRNA sequencing showed that all 3 drugs significantly increased the richness and diversity of gut microbiota in the model mice. Bioinformatic analysis revealed that the faeces of mice treated with ranitidine and finasteride, had significant increases in the number of microbes in the families g_Helicobacter, f_Desulfovibrionaceae, Mucispirillum_schaedleri_ASF457, and g_Blautia, whereas the relative abundances of microbes in the families Enterobacter_sp._IPC1-8 and g_Bacteroides were significantly reduced. The microbiota metabolic pathways, such as nucleotide and cofactor and vitamin metabolism were also significantly increased, whereas the activities of metabolic signalling pathways related to glycan biosynthesis and metabolism and cardiovascular diseases were significantly reduced. Therefore, our study indicates that in addition to their known pharmacological effects, ranitidine and finasteride also exhibit potential cardiovascular and renal protective effects. They inhibit the synthesis and metabolism of TMAO and delay the deposition of lipids and endotoxins through improving the composition of the gut microbiota. © The author(s).Loco-regional recurrence of nasopharyngeal carcinoma (NPC) after radiation therapy is one of the main types of treatment failure. This study is aimed to explore the possible causes of inside-field recurrence of NPC patients in order to develop effective treatment methods. Our study indicated that CD44 and autophagy proteins in tumor tissues of patients with recurrent NPC are higher than that of the relapse free patients. The in vitro experiments further confirmed that cancer stem cells (CSCs) were more radioresistant with enhanced autophagy activity. Treatment with clioquinol (CQ) combined with zinc could obviously enhance the radiosensitivity of CNE-2s cells through autophagy inhibition, activation of the caspase system and impairment of DNA damage repair. link3 The in vivo experiments have further consolidated our findings. Our results suggest that CSCs and enhanced autophagy activity may be involved in the inside-field recurrence of NPC, and CQ combined with zinc could be an important therapeutic approach for recurrent NPC.