The colony-forming ability of cervical cancer is affected by many factors. Oct4, an important transcription factor, is highly expressed in several tumors and promotes the colony-forming ability of cancer cells. Thus, it is considered a potential target for the treatment of cancer. However, we know little about the expression level of Oct4 and its epigenetic regulatory mechanism in cervical cancer cells. In this study, we are the first to observe that human papillomavirus (HPV)-positive cervical cancer cell lines (HeLa, Caski) have a stronger colony-forming ability than HPV-negative cervical cancer cell lines (C-33A). Moreover, the expression level of Oct4 in both HeLa and Caski cells was also higher than that in C-33A cells. We then confirmed that there was a negative correlation between the expression of Oct4 and DNMT3A in these three types of cervical cancer cells, whereas DNA methyltransferase 1 and 3B had no differences among the cell lines. However, after DNA methylation in both key regulatory regions of the Oct4 gene and the genomic levels were analyzed, we found that DNA methyltransferase 3A could neither regulate the expression of Oct4 nor affect the whole level of genomic DNA methylation. These results suggest three points: (1) Oct4 might be treated as a new target for the treatment of cervical cancer, (2) we could not inhibit the expression of Oct4 by DNA demethylation, and (3) HPV virus might initiate cervical carcinogenesis by upregulation of Oct4 expression.
Objective To screen oligopeptides interacted with DNA binding domain of NF-κB p65 saubunit and explore the inhibiting effect of these oligopeptides on DNA binding activity of NF-κB. Methods By means of primer dimer building bridge,the gene fragment of(NF-κB) p65 subunit DNA binding domain was amplified,and then inserted into pGBKT_7 DNA-BD vector to construct pGBKT_7 DNA-BD/p65BD.The oligopeptides interacted with p65BD were screened from a random peptides library having an open reading frame for 16 amino acids by yeast two-hybrid system method.The positive oligopeptides were synthesized and purified.The inhibitory effect of the oligopeptides on DNA binding(activity) of NFκB was identified by EMSA.Results The cDNA of NF-κB p65 subunit DNA binding domain was obtained,and inserted into pGBKT_7 DNA-BD vector to construct pGBKT7 DNA-BD/p65BD.Five positive oligopeptides possessed capability of specific interaction with DNA binding domain of NF-κB p65 subunit were obtained from 1.28×10~7 yeast transformants.The DNA and protein sequences of the five oligopeptides were different with each other,but four of them contained a common motif.EMSA results showed that two of the five peptides could inhibit DNA probe from binding to NF-κB in a concentration-dependent manner.Conclusion Five novel oligopeptides specially interacted with DNA binding domain of NF-κB p65 subunit are found,and two of them possess the inhibiting effect on DNA binding activity of NF-κB.
Objective To investigate the expression of C-C motif chemokine ligand 23 (CCL23) in hepatocellular carcinoma (HCC) and its clinical significance for survival and prognosis. Methods GEPIA, HCCDB, MetaScape, TIMER, TISIDB, Kaplan-Meier Plotter and other online databases were used to analyze the expression level of CCL23 in HCC, the functional notes of co-expression gene and its gene ontology (GO), the enrichment of Kyoto gene and genome encyclopedia (KEGG), the correlation between tumor cell purity, the expression of CCL23 in immune cells and its significance for survival and prognosis of patients. Results The expression of CCL23 in all stages of HCC was negatively correlated with the purity of HCC tumor cells. The short prognosis of HCC patients with low expression of CCL23 was poor. The GO function and KEGG pathway of CCL23 co-expressed gene in HCC were mainly enriched in immune cell activation and complement system activation. CCL23 was the strongest chemokine factor in HCC, and it could bind to multiple receptors including CC chemokine receptor 1 (CCR1), CCR2, CCR7 and CXC chemokine receptor 6 (CXCR6) to exert chemokine effect on immune cells, among which CD8+ T cells and macrophages have the most obvious chemokine effect. Conclusion The low expression of CCL23 in HCC tissue is not conducive to the development of anti-tumor immune defense in HCC patients and significantly shortens the survival of HCC patients.
Sporocytophaga is a kind of bacteria that can glide on the solid medium surface. It can decompose the cotton and filter paper after 6 days cultured. The sporocytophaga can only produce a low extracellular carboxymethylcellulase activity and no other cellulase activities. In this work, the process about degradation of filter paper fibre by a strain of Sporocytophaga was studied using scan electronmicroscopy. The morphological changes that Sporocytophaga sp. JI-01 grew on filter paper were observed. The study revealed the JL-01 adhered tightly to the surface of filter paper fibre or penetrated into interior of the fibre through its 2.5 microm - 4.0 microm bacilliform cells in the process of degrading. The bacilliform cells degrade the cellulose strongly and produced a mass of sticky polysaccharides. At the anaphase of cultured, the bacteria existed as a cycloidal dormancy body-sporocyst.
Organosulfur compounds (OSCs) are the bioactive components of garlic. Some OSCs have apoptotic or autophagy-inducing effects. Autophagy plays roles in both cytoprotection and apoptosis-related cell death, and the interaction between autophagy and apoptosis is important in the modulation of immune responses. The mechanism of an OSC-mediated effect via the interaction of autophagy and apoptosis is unknown. In this study, the effects of five OSC compounds on autophagy in the macrophage cell line RAW264.7 and primary macrophages were investigated. We found that S-allylcysteine (SAC), diallyl disulde (DADS) and diallyl tetrasulfide (DTS) treatment increased the number of autophagosomes of RAW264.7 cells, inhibited the phosphorylation of ribosomal protein S6 kinase beta-1 (p70S6K/S6K1) which is a substrate of mammalian target of rapamycin (mTOR), and significantly enhanced autophagy flux. The induction of autophagy by SAC, DADS and DTS was inhibited by stably knocking down the expression of autophagy-related gene 5 (ATG5) with short hairpin RNA (shRNA). Further experiments confirmed that SAC, DADS and DTS also induced apoptosis in RAW264.7 cells. The induction of apoptosis and Caspase 3 activity by SAC, DADS and DTS were increased by stably knocking down of ATG5 expression with shRNA in RAW264.7 cells or treating with 5 mM 3-MA in primary macrophages. Our results suggest that SAC, DADS and DTS induce both autophagy and apoptosis. The autophagy induction protects macrophages from apoptosis by inhibiting mTOR phosphorylation activity to maintain the mass of immune cells.
Kidney renal papillary cell carcinoma (KIRP) has a high mortality rate and a poor prognosis. Cu concentrations differed significantly between renal cancer tissues and adjacent normal tissues. Cuproptosis is a newly identified cell death. Long non-coding RNAs (lncRNAs) play a crucial role in the progression of KIRP. In this study, we focused on constructing and validating cuproptosis-related lncRNA signatures to predict the prognosis of KIRP patients and their immune correlation. We created prognosis models using Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. We found that patients in the high-risk group had poorer overall survival (OS) and progression-free survival (PFS) and higher mortality. Risk score and stage are prognosis factors independent of other clinical features. Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and C-index curves showed that cuproptosis-related lncRNA signatures could more accurately predict the prognosis of patients. Functional enrichment analysis suggests that the function of differentially expressed genes (DEGs) is associated with KIRP development and immunity. In immune-related function analysis, we found a significant difference in parainflammation responses between high-risk and low-risk groups. The mutation frequencies of TTN, MET, KMT2C, PKHD1, SETD2, and KMT2D genes in the high-risk group were higher than those in the low-risk group, but the mutation frequencies of MUC16, KIAA109, CUBN, USH2A, DNAH8 and HERC2 genes were significantly lower than those in the low-risk group. Survival analysis of tumor mutation burden (TMB) and combined TMB-risk showed better OS in patients with high TMB. Immune infiltration and immune checkpoint analysis assessed the immune association of six high mutation frequency genes (TTN, MET, KMT2C, PKHD1, SETD2, and KMT2D) with KIRP. Finally, we performed a drug sensitivity analysis and screened 15 potential drugs that differed between high-risk and low-risk patients. In this study, we constructed and validated cuproptosis-related lncRNA signatures that can more accurately predict the prognosis of KIRP patients and provide new potential therapeutic targets and prognosis markers for KIRP patients.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)