Current Issue : July - September Volume : 2020 Issue Number : 3 Articles : 5 Articles
Determination of the cellular tropism of viral vectors is imperative for designing precise gene\ntherapy. It has been widely accepted that transduction of hepatocytes using adeno-associated virus\nserotype 8 (AAV8) is a promising approach to correct inborn errors in neonates, but the type of neonatal\nhepatic cells transduced by AAV8 has not been thoroughly investigated. To address this question,\nwe used a reporter mouse that carries Cre recombinase (Cre)-inducible yellow fluorescent protein\n(YFP). Our analysis primarily focused on cholangiocytes, given their pivotal roles in normal liver\nfunction and disease. We treated...................
Noncoding RNAs (ncRNAs), especially microRNA (miRNA) and long noncoding RNA (lncRNA), have an impact on a variety of\nimportant biological processes during colon adenocarcinoma (COAD) progression. This includes chromatin organization,\ntranscriptional and posttranscriptional regulation, and cell-cell signaling. The aim of this study is to identify the ncRNAregulated\nmodules that accompany the progression of COAD and to analyze their mechanisms, in order to screen the potential\nprognostic biomarkers for COAD. An integrative molecular analysis was carried out to identify the crosstalks of gene modules\nbetween different COAD stages, as well as the essential ncRNAs in the posttranscriptional regulation of these modules. 31\nncRNA regulatory modules were found to be significantly associated with overall survival in COAD patients. 17 out of the 31\nmodules (in which ncRNAs played essential roles) had improved the predictive ability for COAD patient survival compared to\nonly the mRNAs of those modules, which were enriched in the core cancer hallmark pathways with closer interactions. These\nsuggest that the ncRNAsâ?? regulatory modules not only exhibit close relation to COAD progression but also reflect the dynamic\nsignificant crosstalk of genes in the modules to the different malignant extent of COAD....
Humanartificial chromosomes (HACs), including the de novo synthesized alphoidtetO-HAC,\nare a powerful tool for introducing genes of interest into eukaryotic cells. HACs are mitotically\nstable, non-integrative episomal units that have a large transgene insertion capacity and allow\nefficient and stable transgene expression. Previously, we have shown that the alphoidtetO-HAC\nvector does not interfere with the pluripotent state and provides stable transgene expression in\nhuman induced pluripotent cells (iPSCs) and mouse embryonic stem cells (ESCs). In this study,\nwe have elaborated on a mouse model of ex vivo iPSC- and HAC-based treatment of hemophilia A\nmonogenic disease. iPSCs were developed from.......................
Recombinant measles AIK-C vaccine expressing the hemagglutinin (HA) protein of\ninfluenza A/Sapporo/107/2013(H1N1pdm) (MVAIK/PdmHA) was constructed. Measles particle\nagglutination (PA) and influenza hemagglutinin inhibition (HI) antibodies were induced in cotton\nrats immunized with MVAIK/PdmHA. Cotton rats immunized with two doses of the HA split vaccine\nwere used as positive controls, and higher HI antibodies were detected 3 weeks after the first dose.\nFollowing the challenge of A/California/07/2009(H1N1pdm), higher viral loads (107 TCID50/g) were\ndetected in the lung homogenates of cotton rats immunized with the empty vector (MVAIK) or control\ngroups than those immunized with MVAIK/Pdm HA (103 TCID50/g) or the group immunized with\nHA split vaccine (105 TCID50/g). Histopathologically, destruction of the alveolar structure, swelling\nof broncho-epithelial cells, and thickening of the alveolar wall with infiltration of inflammatory\ncells and HA antigens were detected in lung tissues obtained from non-immunized rats and those\nimmunized with the empty vector after the challenge, but not in those immunized with the HA spilt\nor MVAIK/PdmHA vaccine......................
In order to break tumor resistance towards traditional treatments, we investigate the response of tumor and immune cells to a novel, cytokine-armed oncolytic adenovirus: Ad5/3-d24-E2F-hTNFa-IRES-hIL2 (also known as TILT-123 and OAd.TNFa-IL2). There are several pattern recognition receptors (PRR) that might mediate adenovirus-infection recognition. However, the role and specific effects of each PRR on the tumor microenvironment and treatment outcome remain unclear. Hence, the aim of this study was to investigate the effects of OAd.TNFa-IL2 infection on PRR-mediated danger- and pathogen-associated molecular pattern (DAMP and PAMP, respectively) signaling. In addition, we wanted to see which PRRs mediate an antitumor response and are therefore relevant for optimizing this virotherapy. We determined that OAd.TNFa-IL2 induced DAMP and PAMP release and consequent tumor microenvironment modulation. We show that the AIM2 inflammasome is activated during OAd.TNFa-IL2 virotherapy, thus creating an immunostimulatory antitumor microenvironment....
Loading....