Normalization of non-canonical Wnt signalings does not compromise blood-brain barrier protection conferred by upregulating endothelial Wnt/ß-catenin signaling following ischemic stroke.

BACKGROUND: Endothelial canonical (Wnt/ß-catenin) and non-canonical Wnt signalings (Wnt/PCP and Wnt/Ca2+ ) promote blood-brain barrier (BBB) development and antagonize each other. However, the effects of ischemic stroke on endothelial canonical and non-canonical Wnt signalings are unclear. Further, how non-canonical Wnt signalings are influenced by upregulation of endothelial Wnt/ß-catenin signaling and subsequently affect BBB function following ischemic stroke have not been studied. METHODS: First, we determined the levels of Wnt signaling markers including TCF/LEF1 transcription activity, Axin2 mRNA, phospho-JNKThr183/Tyr185 , and NFAT in brain endothelial cells (ECs) with the deletion of Wnt receptor Frizzled (Fzd)4 or Fzd6, the two most abundant Fzds in brain ECs. Next, we observed the effect of ischemia/reperfusion injury on Wnt signalings in brain ECs and adult mice. Last, we assessed the changes of non-canonical Wnt signalings and BBB injury in the early stage of ischemic stroke in mice with endothelial ß-catenin activation (ß-cat mice). RESULTS: Fzd4 or Fzd6 deletion dampened both Wnt/ß-catenin and Wnt/PCP signalings but enhanced Wnt/Ca2+ signaling in brain ECs. Both canonical and non-canonical Wnt signalings in brain ECs were downregulated after ischemia/reperfusion injury in vitro and in vivo. Upregulating endothelial Wnt/ß-catenin signaling in ß-cat mice normalized the downregulated non-canonical Wnt signalings, which did not compromise its protective effects on BBB integrity and endothelial tight junction following ischemic stroke. CONCLUSIONS: The BBB protection induced by upregulation of endothelial Wnt/ß-catenin signaling may be not interfered by the normalization of non-canonical Wnt signalings in the early stage of ischemic stroke.

Identification of Potential Hub Genes of Atherosclerosis Through Bioinformatic Analysis.

Cardiovascular and cerebrovascular diseases, which mainly consist of atherosclerosis (AS), are major causes of death. A great deal of research has been carried out to clarify the molecular mechanisms of AS. However, the etiology of AS remains poorly understood. To screen the potential genes of AS occurrence and development, GSE43292 and GSE57691 were obtained from the Gene Expression Omnibus (GEO) database in this study for bioinformatic analysis. First, GEO2R was used to identify differentially expressed genes (DEGs) and the functional annotation of DEGs was performed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The Search Tool for the Retrieval of Interacting Genes (STRING) tool was used to construct the protein-protein interaction network and the most important modules and core genes were mined. The results show that a total of 211 DEGs are identified. The functional changes of DEGs are mainly associated with the cellular process, catalytic activity, and protein binding. Eighteen genes were identified as core genes. Bioinformatic analysis showed that the core genes are mainly enriched in numerous processes related to actin. In conclusion, the DEGs and hub genes identified in this study may help us understand the potential etiology of the occurrence and development of AS.

Expression and clinical significance of PTPN12 in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common urological disease. Expression of the protein tyrosine phosphatase 12 gene (PTPN12) is decreased in many cancers; however, the relationship between PTPN12 gene function and renal cancer remains unclear. METHODS: We detected PTPN12 protein expression in ccRCC and corresponding normal tissues from 64 patients with ccRCC by immunohistochemistry, and relative PTPN12 mRNA levels by real-time quantitative polymerase chain reaction. The relationships between the relative expression levels of PTPN12 mRNA and the patients' clinical data were analyzed. RESULTS: PTPN12 protein and mRNA expression levels were significantly lower in ccRCC compared with the corresponding normal tissues. The mRNA expression levels in the ccRCC and corresponding normal tissues from the 64 patients with ccRCC were 0.459±0.445 and 1.001±0.128, respectively, compared with the control (glyceraldehyde 3-phosphate dehydrogenase). There was a significant correlation between relative expression of PTPN12 mRNA in ccRCC tissues and tumor diameter and clinical stage. CONCLUSION: The expression levels of PTPN12 protein and mRNA were significantly lower in ccRCC tissues compared with normal tissues. The role of PTPN12 may provide new insights and evidence to aid the diagnosis and targeted therapy of ccRCC.

Identification of biomarkers for the diagnosis and treatment of primary colorectal cancer based on microarray technology.

BACKGROUND: Primary colorectal cancer (PCRC) is one of the most common malignant tumors in clinic, and is characterized by high heterogeneity occurring between tumors and intracellularly. Therefore, this study aimed to explore potential gene targets for the diagnosis and treatment of PCRC via bioinformatic technology. METHODS: Gene Expression Omnibus (GEO) was used to download the data used in this study. Differently expressed genes (DEGs) were identified with GEO2R, and the gene set enrichment analysis (GSEA) was implemented for enrichment analysis. Then, the researchers constructed a protein-protein interaction (PPI) network, a significant module, and a hub genes network. RESULTS: The GSE81558 dataset was downloaded, and a total of 97 DEGs were found. There were 23 up-regulated DEGs and 74 down-regulated DEGs in the PCRC samples, compared with the control group. The PPI network included a total of 42 nodes and 63 edges. One module network consisted of 11 nodes and 25 edges. Another module network consisted of 4 nodes and 6 edges. The hub genes network was created by cytoHubba using GCG, GUCA2B, CLCA4, ZG16, TMIGD1, GUCA2A, CHGA, PYY, SST, and MS4A12. CONCLUSIONS: Ten hub genes were found from the genomic samples of patients with PCRC and normal controls by bioinformatics analysis. The hub genes might provide novel ideas and evidence for the diagnosis and targeted therapy of PCRC.

Efficacy of Therapeutic Endoscopy for Gastrointestinal Lesion (GI): A network meta-analysis.

OBJECTIVE: Endoscopic therapy can reduce the risks of rebleeding, continued bleeding, need for surgery, and mortality. The objective of this systematic review was to compare the different modalities of endoscopic therapy for GI bleeding. METHODS: Studies were identified by searching electronic databases MEDLINE. We selected all available clinical studies published after 2000 that assessed efficacy and/or safety of different endoscopic hemostatic techniques in treating GI bleeding. The outcomes evaluated included initial hemostasis, rebleeding rate, and 30-day all-cause mortality. Network meta-analyses were performed to summarize the treatment effects. RESULTS: Total 20 studies involving 1845 patients were evaluated. Ten different treatment categories including mechanic, ablative, injection, and combined therapy were compared in our analysis in terms of their efficacy in stopping bleeding and complications. Band ligation [rate: 0.757; 95% Credible Interval (0.565, 0.887)] and injection therapy [rate: 0.891; 95% CI (0.791, 0.944)] had inferior efficacy in attaining initial hemostasis compared to others. Combined therapy of band ligation and HPC and hemoclip may represent the best options for preventing rebleeding and mortality respectively. No significant difference was found among other treatments in terms of complications. CONCLUSIONS: We recommend the application of hemoclips in treating GI bleeding due to its high hemostasis efficacy and low risk of 30-day mortality.

catena-Poly[[(2,2'-bipyridyl)oxidovanadium]-di-mu2-oxido-[(2,2'-bipyridyl)oxidovanadium]-mu3-selenito-bis[(2,2'-bipyridyl)dioxidovanadium]-mu3-selenito].

In the title compound, [V(4)O(8)(SeO(3))(2)(C(10)H(8)N(2))(4)], there are two distinct vanadium coordination environments. Alternating corner-shared VO(4)N(2) octahedra and SeO(3) pyramids result in eight-membered centrosymmetric V(2)Se(2)O(4) rings. In addition, pairs of V centres form centrosymmetric V(2)O(6)N(4) clusters via edge-sharing. These two kinds of secondary building units are linked in an ABABAB fashion to give an infinite chain whose nature is unprecedented in Se-V-O systems.