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  • Nixon Jakobsen posted an update 4 days, 8 hours ago

    RNA interference (RNAi) is an important tool for gene function studies in insects, especially in non-model insects. This technology is also being developed for pest control. However, variable RNAi efficiency among insects is limiting its use in insects. Systemic RNAi in Caenorhabditis elegans requires systemic RNA interference defective protein 1 (CeSid1). The expression of CeSid1 in insect cell lines was shown to improve RNAi. However, the mechanisms through which this double-stranded RNA (dsRNA) transporter improves RNAi efficiency in insects is not known. We stably expressed CeSid1 in two Spodoptera frugiperda cell lines, Sf9 and Sf17 cells derived from ovary and midgut, respectively. Expression of CeSid1 enhanced RNAi efficiency in ovarian Sf9 cells, but not in midgut Sf17 cells. Reduced accumulation of dsRNA in late endosomes and successful processing dsRNA to siRNA contribute to enhanced RNAi efficiency in Sf9 cells. Transgenic S. frugiperda expressing CeSid1 were produced and tested for RNAi efficiency. RNAi efficiency enhancement due to CeSid1 expression showed tissue specificity. Compared to RNAi efficiency in wild-type S. frugiperda, CeSid1 expressing transgenic S. frugiperda showed a significant improvement of RNAi in tissues such as Verson’s glands. In contrast, no improvement in RNAi was observed in tissues such as midgut. The in vitro cell-type specific and in vivo tissue-specific enhancement of RNAi efficiency by CeSid1 in S. frugiperda provides valuable information for improving RNAi in insects such as those belonging to order Lepidoptera where RNAi is variable and inefficient.The purpose of this study was to identify long noncoding RNAs (lncRNAs) related to prognosis of patients with colorectal cancer (CRC) and develop a prognostic prediction model for CRC. Transcriptome data and survival information of CRC patients were downloaded from The Cancer Genome Atlas. The differentially expressed lncRNAs (DElncRNAs) between CRC and normal colorectal tissues were identified by the edgeR package. The association of DElncRNAs expression with prognosis of CRC patients was analyzed by the survival package. A nomogram predicting 3- and 5- year overall survival of CRC patients was drawn by the rms package. A total of 1046 DElncRNAs were identified, including 271 down-regulated and 775 up-regulated lncRNAs in CRC. Multivariate Cox regression analysis showed 10 lncRNAs related to the prognosis of CRC patients. Thereinto high expression of AC004009.1, LHX1-DT, ELFN1-AS1, AL136307.1, AC087379.2, RBAKDN and AC078820.1 was associated with poorer prognosis of CRC patients. High expression of LINC01055, AL590483.1 and AC008514.1 was associated with better prognosis of CRC patients. Furthermore, the risk score model developed based on the 10 lncRNAs could effectively predict overall survival of CRC patients. In conclusion, 10 prognostic biomarkers for CRC were identified, which would be helpful to understand the role of lncRNAs in CRC progression.Hepatocellular carcinoma (HCC) is the most aggressive type of gastrointestinal tumor, with a high rate of mortality. However, identifying biomarkers for the treatment of HCC remains to be developed. We aimed to determine whether cell division cycle 25C (CDC25C) could be used as a novel diagnostic and therapeutic biomarker in HCC. Expression of CDC25C in HCC was analyzed by using GEPIA (Gene Expression Profiling Interactive Analysis) and UALCAN databases. GEPIA and CBioPortal databases were applied to analyze patients’survival and CDC25C mutations, respectively. PPI (Protein-Protein Interaction) network was further built by STRING (Search Tool for the Retrieval of Interacting Genes) and Metascape Web portals. To the best of our knowledge, the novel observations identified in the present study reveal that the expression of CDC25C in HCC was significantly enhanced when compare to that in normal liver tissues (P less then 0.001). A higher CDC25C expression resulted in a remarkably shorter disease free survival as well as overall survival. Moreover, the expression of CDC25C in HCC was related to HCC patients’grade and race, but not gender. The expression levels of CDC25C elevated gradually from stage 1 to 3 but decreased in stage 4. The specific gene mutations V41A, L87 H, N222 K and X309-splice of CDC25C occurred in HCC samples and these unique mutations were not detected in any other tumor tissues. Finally, PPI networks and GO enrichment analysis suggested that CDC25C might be associated with cell cycle and p53 signaling pathway. Taken together, bioinformatics analysis revealed that CDC25C might be a potential diagnostic predictor for HCC.Selective degradation of the endoplasmic reticulum (ER; reticulophagy) is a type of autophagy involved in the removal of ER fragments. So far, amino acid starvation as well as ER stress have been described as inducers of reticulophagy, which in turn restores cellular energy levels and ER homeostasis. Here, we explored the autophagy-inducing mechanisms that underlie the autophagic cell death (ACD)-triggering compound loperamide (LOP) in glioblastoma cells. Interestingly, LOP triggers upregulation of the transcription factor ATF4, which is accompanied by the induction of additional ER stress markers. Notably, knockout of ATF4 significantly attenuated LOP-induced autophagy and ACD. Functionally, LOP also specifically induces the engulfment of large ER fragments within autophagosomes and lysosomes as determined by electron and fluorescence microscopy. LOP-induced reticulophagy and cell death are predominantly mediated through the reticulophagy receptor RETREG1/FAM134B and, to a lesser extent, TEX264, confirming tP loperamide; MAP1LC3/LC3 microtubule-associated protein 1 light chain 3; RETREG1/FAM134B reticulophagy regulator 1; RTN3L reticulon 3 long; SEC62 SEC62 homolog, protein translocation factor; TEX264 testis-expressed 264, reticulophagy receptor; UPR unfolded protein response.One of the major causes of erectile dysfunction (ED) is an endothelial vascular disorder. This meta-analysis is performed to determine the efficacy of aspirin on erectile function in men with vasculogenic ED. For this purpose, CENTRAL, MEDLINE, and reference lists of articles up to November 2019 were searched. Randomized controlled trials (RCTs) were selected that compared aspirin with placebo in men of any ethnicity with vasculogenic ED. A total of 58 trials were retrieved. find more Finally, two trials of 214 men fulfilled our selection criteria. High selection and detection bias were identified for one trial. The participants showed a significant improvement in erectile function when they took aspirin (mean difference 5.14, 95% CI [3.89, 6.40], and I2 = 0%). Although the present meta-analysis suggested that aspirin has a significant effect on the improvement of erectile function, there were limited RCTs available on this topic and doses of aspirin varied. Additional studies are needed to support findings from this meta-analysis.

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