NR3C2 affects the proliferation and invasiveness of colon cancer cells through the Wnt/ß-Catenin signaling pathway.

PURPOSE: The aim of this study was to explore the potential correlation between the nuclear receptor subfamily 3 group C member 2 (NR3C2) and outcomes of colon cancer, along with the mechanisms underlying this association. METHOD: mRNA (messenger RNA) data and clinical records pertaining to colon cancer were retrieved from The Cancer Genome Atlas (TCGA) database. The analysis of NR3C2 expression discrepancies between normal colon and tumor tissues was conducted using R software. In addition, we also studied the relationship between NR3C2 expression and prognosis, pathological parameters. The relative role of NR3C2 were further predicted through bioinformatics methods and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of NR3C2 in colon cancer. Single-cell data from colon cancer samples in the GEO (Gene Expression Omnibus) database further investigated the mechanism of the lower survival associated with NR3C2 dysregulation. NR3C2 expression in three fresh colon cancer samples and their respective paracancer samples was determined. Furthermore, colon cancer cell models overexpressing NR3C2 and with knockdown NR3C2 were constructed by lentiviral vector transfection. Cell Counting Kit-8 assay, transplantation of tumors in nude mice and transwell assays were used to examine the proliferation, migration and invasion of colon cancer cells. The effect on the Wnt/ß-catenin pathway, activities of cellular autophagy and cell apoptosis were examined by assessing the expression levels of several key proteins, including Bcl-2, Bax, and LC3. RESULTS: We found that NR3C2 was found a significantly lower level in colon cancer tissues than in adjacent tissues, which was associated with distant and lymphatic metastases, clinical stage, and poor clinical outcome, and it was an independent prognostic factor and potential marker of colon cancer. Single-cell transcriptome data identified the subset of circulating T and B cells with high expression of NR3C2, which is involved in TNF signaling pathway. Functional experiments show that downregulation of NR3C2 resultsed in the activation of the Wnt/ß-catenin signaling pathway, and promotesd the proliferation and invasion of colon cancer cells while suppressing cell autophagy and apoptosis. CONCLUSION: NR3C2 may regulate Wnt/ß-catenin to affect the proliferation, invasion apoptosis and autophagy of colon cancer, and this axis is a potential target for the treatment of colon cancer.

[The mechanisms of microenvironments influence on vasculogenic mimicry between intraocular and subcutaneous melanoma].

OBJECTIVE: To investigate the influence of different microenvironments on melanoma vasculogenic mimicry, invasiveness and metastasis behavior. METHODS: It was an experimental study. Sixty C57BL/6J mice were randomly divided into two groups with 30 mice per group. Melanoma B16 cells were injected into the subretinal space and groin area of mice synchronously. The number of each type of microcirculation pattern was counted. The invasion and metastasis were observed. EphA2, MMP-2 and MMP-9 expression and their mRNA levels were detected by immunohistochemical staining and real time RT-PCR and compared between two groups. RESULTS: Five invasions and six lung metastases were found in the subretinal group while no invasion and metastasis were found in the groin group. The number of VM channels was significantly higher in subretinal group (t = 4. 188, P = 0.000). However, no significant difference of mosaic vessel and endothelium-dependent vessel was observed between two groups (t = 1.473, 1.805; P = 0.146, 0.076, respectively). EphA2, MMP-2 and MMP-9 expression was significantly higher in the subretinal group (data not shown). The mRNA levels of EphA2, MMP-2 and MMP-9 were rather higher in the subretinal tumor (t = 3.642, 8.109, 9.357; P = 0.002, 0.001 and 0.001, respectively). There was a positive association in melanoma cells of the VM between expression of EphA2 (r = 0.412, P = 0.021) but no statistically significant correlation between VM and MMP-2 (P > 0.05), nor between VM and MMP-9. CONCLUSIONS: Different microenvironments affect invasiveness and blood supply patterns of melanoma. Melanoma cells in intraocular microenvironment increased EphA2 expression which induced the formation of VM channels. Moreover, the expression of MMP-2 and MMP-9 in tumor tissue increased to enhance the invasiveness and metastasis behavior.

Research strategies and applications of functional metabolomics in anti-depressive mechanisms of traditional Chinese medicine / 药学学报

Depression is a common emotional disorder that seriously affects people's life and health all over the world. The pathogenesis of depression is complex, and traditional Chinese medicine (TCM) for antidepressants has a good therapeutic effect because of its multi-component, multi-pathway, and multi-target action mode. At present, the anti-depressive mechanism of TCM has not been fully clarified, but it is clear that depression is closely related to metabolic health. Therefore, in order to further explore the anti-depressive mechanism of TCM, this paper proposes research strategies on the anti-depressive mechanism of TCM based on functional metabolomics from the perspective of metabolism, the potential biomarkers of depression are analyzed with the help of multi-omics combined analysis technology, and the functional molecules of TCM for antidepressant are studied. Molecular biology techniques are used to accurately capture the molecular interactions between biomarkers of depression and functional compounds, which identify effective drug targets and further elucidate the biochemical functions and related mechanisms involved in depression metabolic disorders. This paper systematically reviews the research strategies and applications of functional metabolomics in the anti-depressive mechanisms of TCM, expounds on the core value of functional metabolomics, and summarizes the current research status and hot issues of TCM for antidepressants in recent years, providing new methods and new ideas for the study of mechanisms of TCM with the help of functional metabolomics.

[Experimental study a new device of scleral flap stent on filtration surgery in normal sheep].

OBJECTIVE: To test the effectiveness and safety of a filtering drainage device, a scleral flap stent (SFS) made of poly methyl methacrylate (PMMA) in trabeculectomy (or filtering drainage-plasty) in sheep. METHODS: 32 of normal sheep were used. Trabeculectomy was performed in both eyes and the filtering drainage device, a SFS was randomly implanted under the scleral flap in one eye. After the surgery, the intraocular pressure (IOP) was measured by Schiotz tonometer; The filtering blebs and its histopathology was examined by a slit lamp, an ultrasound biomicroscope (UBM), and electronmicroscopy. RESULTS: The IOP in eyes with trabeculectomy plus SFS was statistically significant (P < 0.001) lower than that in eyes with trabeculectomy along at one month (11.38 +/- 1.20) mm Hg vs (14.05 +/- 0.93) mm Hg and at three months (11.95 +/- 1.18) mm Hg vs (15.2 +/- 1.09 mm Hg). Compared to the pre-operation, no difference in IOP was found at one month in eyes with trabeculectomy along (16.04 +/- 1.02) mm Hg vs (14.05 +/- 0.93) mm Hg. The filtering bleb was lasted more than 3 months in eyes with trabeculectomy plus SFS while existed only one month in eyes with trabeculectomy along by both slit lamp and UBM examination. The fibroblastic proliferation of filtering pathway and scar formation was found at one months post-operation in eyes with trabeculectomy along, however, the fibroblastic proliferation and the scar formation were found at three months and at six months after surgery in eyes with trabeculectomy plus SFS, respectively, by a light and electronmicroscopy examination. Tissue compliance was good and no elimination occurred. No toxic or adverse effects were observed in the following year post-operatively. CONCLUSION: SFS is a safe and effective newly designed filtering drainage device in lowering IOP when performed together with trabeculectomy.