Site-specific recombination of T2 phage using IP008 long tail fiber genes provides a targeted method for expanding host range while retaining lytic activity

The application of bacteriophages (phages) in therapy urgently requires the production of wide-host-range recombinant phages that possess strong lytic activity. The wide-host-range IP008 phage was classified by transmission electron microscopy analysis as an A2 morphotype member of the Myoviridae family of the order Caudovirales . IP008 showed a high homology (99.4% similarity in the amino acid alignment of the major capsid protein Gp 23) with KEP10, another wide-host-range phage. The long tail fiber genes (genes 37 and 38 ) from the genome of T2 were replaced with those of the IP008 phage by homologous recombination. The host range of the recombinant phages was identical to that of IP008. Furthermore, the recombinant phage bacterial lytic activity was restored. Future analyses of host-range mutants of the closely related phages T2 and IP008 could lead to a more precise localization of the genetic factors responsible for receptor specificity.     

Circulating visfatin levels and cancers risk: A systematic review and meta-analysis

Visfatin levels have been reported to be abnormal in many types of cancers. However, epidemiological studies yielded inconsistent results. Therefore, a meta-analysis was performed to assess the association between circulating visfatin levels and cancer risk. A systematic search was conducted for relevant studies in health-related electronic databases up to March 2018. Data related to standard mean difference (SMD) and overall odds ratio (ORS) were collected and analyzed. Summary SMD and pooled OR with 95% CIs were calculated using a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. A total of 27 studies with 2,693 cases and 3,040 healthy controls were included in meta-analysis for pooling SMD analysis. The results of the meta-analysis showed a significant higher visfatin levels in patients with various cancers than in controls, with a pooled SMD of 0.88, 95% CI = 0.56–1.20, p = 0.000. In subgroup, metaregression, Galbraith plot, and sensitivity analysis showed no substantial difference among all the analyzed factors. Data from 14 studies were also used for pooling ORs analysis. Metaresults revealed that high visfatin levels were associated with cancer risk (OR = 1.24, 95% CI: 1.14–1.34, p = 0.000). No evidence of publication bias was observed for pooling ORs and SMD analysis. This meta-analysis indicated a significant association between high circulating visfatin levels and increased risk of various cancers. Visfatin may represent a potential biomarker for early detection of cancers who may benefit from preventive treatment.Note.     

Oncogenic Kras expression in postmitotic neurons leads to S100A8-S100A9 protein overexpression and gliosis

Previous studies suggest that up-regulation of Ras signaling in neurons promotes gliosis and astrocytoma formation in a cell nonautonomous manner. However, the underlying mechanisms remain unknown. To address this question, we generated compound mice (LSL Kras G12D/+;CamKII-Cre) that express oncogenic Kras from its endogenous locus in postmitotic neurons after birth. These mice developed progressive gliosis, which is associated with hyperactivation of Ras signaling pathways. Microarray analysis identified S100A8 and S100A9 as two secreted molecules that are significantly overexpressed in mutant cortices. In contrast to their usual predominant expression in myeloid cells, we found that overexpression of S100A8 and S100A9 in the mutant cortex is primarily in neurons. This neuronal expression pattern is associated with increased infiltration of microglia in mutant cortex. Moreover, purified S100A8-S100A9 but not S100A8 or S100A9 alone promotes growth of primary astrocytes in vitro through both TLR4 and receptor of advanced glycation end product receptors. In summary, our results identify overexpression of S100A8-S100A9 in neurons as an early step in oncogenic Kras-induced gliosis. These molecules expressed in nonhematopoietic cells may be involved in tumorigenesis at a stage much earlier than what has been reported previously.     

Ultrastructural localization of lectin-binding sites in different basement membranes

Summary In the present work we localized binding sites for the lectins WGA, RCA I, con A and SBA at the ultrastructural levels in morphologically different basement membranes. These different basement membranes included (a) thin ones, for example, tubular basement membrane of the mouse kidney which separates epithelial cell layers from mesenchymal cells and glomerular basement membrane which separates epithelial cells from other epithelial cells, (b) thick multilayered ones, for example, Reichert's membrane which is built up during the embryonic development of rodents and as an example of a pathologically thickened basement membrane, the basement membrane of the Engelbreth-Holm-Swarm (EHS) sarcoma. We were able to show that, in contrast to the thick multilayered basement membranes, the thin ones showed a strong positive SBA-binding pattern. Thick basement membranes otherwise revealed very strong labelling with the lectins WGA and RCA I. Our findings lead us to conclude that thin and thick basement membranes differ markedly in the quality and quantity of the carbohydrates which they contain.     

Circulating microRNA-133, microRNA-17 and microRNA-25 in serum and its potential diagnostic value in gastric cancer

Gastric cancer is one of the most common malignancies in the world and is considered as the most lethal gastrointestinal cancer. microRNAs (miRNAs) can be very important in detecting a disease at an early stage. The aim of this study was to investigate the microRNA-17 (miR-17), miR-25, and miR-133b in the serum of gastric cancer subjects. Serum samples were obtained from 120 gastric cancers and 102 healthy subjects. We evaluated expression levels of miR-17, miR-25 and miR-133b by quantitative real-time polymerase chain reaction. Our results showed that in the patients with gastric cancer, the expression level of miR-17 and miR-25 were significantly increased compared with the control group (P < 0.5), while the expression level of miR-133b was significantly decreased in patient groups compared with control cases (P < 0.5). It seems that expression of miRNAs in Iranian patients with gastric cancer is similar to other patients in other populations. These findings suggested that miR-17, miR-25 and miR-133b could be introduced as potential diagnostic candidates for the detection in gastric cancer patients in the early stage.