Circ-EIF3I facilitates proliferation, migration, and invasion of lung cancer via regulating the activity of Wnt/ß-catenin pathway through the miR-1253/NOVA2 axis.

Many studies have shown that circular RNA (circRNA) is an important regulator mediating the malignant progression of cancer. However, the role and mechanism of circ-EIF3I in lung cancer (LC) development are still unclear. A total 36 paired LC tumor tissues and adjacent normal tissues were enrolled. The expression of circ-EIF3I, microRNA (miR)-1253, and neuro-oncological ventral antigen 2 (NOVA2) was measured by quantitative real-time PCR. The proliferation, apoptosis, migration, and invasion of LC cells were determined by MTT assay, colony formation assay, flow cytometry, and transwell assay. Dual-luciferase reporter assay was performed to verify the interaction between miR-1253 and circ-EIF3I or NOVA2. The protein levels of NOVA2 and Wnt/ß-catenin pathway-related markers were detected by western blot analysis. Xenograft tumor was constructed to explore the function of circ-EIF3I on LC tumor growth. Circ-EIF3I was upregulated in LC tumor tissues and cells. Silenced circ-EIF3I could suppress the proliferation, migration, invasion, and enhance the apoptosis of LC cells in vitro, as well as reduce LC tumor growth in vivo. Circ-EIF3I could sponge miR-1253, and miR-1253 inhibitor overturned the regulation of circ-EIF3I knockdown on LC cell progression. NOVA2 was confirmed to be a target of miR-1253, which could reverse the inhibitory effects of miR-1253 on LC cell progression. Further experiments showed that circ-EIF3I regulated NOVA2 expression by sponging miR-1253. In addition, circ-EIF3I silencing could inhibit the activity of Wnt/ß-catenin pathway via regulating the miR-1253/NOVA2 axis. Circ-EIF3I might function as an oncogene in LC, which promoted LC progression by the miR-1253/NOVA2/Wnt/ß-catenin network.

Bioinformatics analysis of CYP1B1 mutation hotspots in Chinese primary congenital glaucoma patients.

Primary congenital glaucoma (PCG) is an inherited blinding eye disease. The CYP1B1 gene was identified as a causal gene for PCG, and many mutations have been found, but no studies have focussed on the molecular epidemiology of CYP1B1 in Chinese populations. We aimed to explore the CYP1B1 mutation hotspots in Chinese PCG patients and the possible impact of these mutations on the protein structure and function. First, we performed a meta-analysis on seven datasets of Chinese populations and found L107V and R390H to be the most common CYP1B1 mutations with allele frequencies of 3.19% and 3.09%, respectively. Then, a series of bioinformatics tools were applied to determine the sequence conservative properties, model the 3D structures, and study the dynamics changes. L107 and R390 are highly conserved residues in close proximity to the hemoglobin-binding region and the active site cavity (ASC), respectively. The mutations changed the distribution of hydrogen bonds and the local electrostatic potential. Long-term molecular dynamics (MD) simulations demonstrated the destabilization of the mutant proteins, especially at the ASC, whose solvent-accessible surface areas (SASAs) were significantly decreased. Compared with the wild-type (WT) protein, the overall structures of the mutants are associated with subtle but significant changes, and the ASC seems to adopt such structures that are not able to perform the WT-like functionality. Therefore, L107V and R390H might be the most important pathogenic mutations in Chinese PCG patients.

Meta analysis of XRCC3 Thr241Met polymorphism and lung cancer susceptibility of populations in East Asia.

OBJECTIVE: To assess the relation between XRCC3 Thr241Met polymorphism and lung cancer susceptibility of populations in East Asia. METHODS: Related studies of XRCC3 Thr241Met polymorphism and lung cancer susceptibility of populations in East Asia were collected through searching the Pubmed, Embase Library, SPRINGER, CNKI and CSSCI. RESULTS: According to the entry criteria, there were 8 case-control studies in the assessing system and there were 6 321 study cases, including 3 215 patients with lung cancer and 3 106 cases without cancers. Meta analysis results showed the combined OR value of the ratio of genotype Thr/Met+Met/Met and Thr/Thr was 1.03 (95%CI: 0.89-1.20) (P>0.05). CONCLUSIONS: XRCC3 Thr241Met polymorphism may not related to lung cancer susceptibility of populations in East Asia. Allele 241Met did not increase the risk of lung cancer.

Clinical and experimental research of corneal lymphangiogenesis after keratoplasty.

The objective of this study is to provide further evidence that corneal lymphangiogenesis occurs after keratoplasty, and to explore the association of corneal hemangiogenesis, corneal inflammation and transplantation history with corneal lymphangiogenesis. Rat corneal lymphangiogenesis was examined by electron microscopy, lymphatic vessel endothelial receptor (LYVE-1) immunohistochemistry, and whole-mount immunofluorescence at 1, 3, 7, 10 and 14 days after corneal transplantation. Blood and lymphatic vessels in human transplanted corneas were identified by LYVE-1 and CD(31) immunohistochemistry, then the association between corneal blood vessel counting, inflammatory index and transplantation history with the lymphatic vessel counting was examined. The results showed that corneal lymphangiogenesis was present in all rat corneas and 26% of human transplanted corneas. Lymphatic vessel counting was significantly associated with blood vessel counting, inflammatory index and transplantation history (all p values <0.0001). We conclude that corneal lymphangiogenesis develops after keratoplasty, and is strongly associated with hemangiogenesis, inflammation and the history of transplantation.

[The experimental histopathologic changes of applying perfluoropropane to filtering surgery in rabbits].

OBJECTIVE: To study the histopathologic changes of filtering blebs by subconjunctival application of perfluoropropane (C(3)F(8)) after trabeculectomy in rabbit eyes. METHODS: Twenty rabbits were randomly divided into two groups, each group consisting of 10 rabbits. Trabeculectomy with topical application of C(3)F(8) was performed on one eye and trabeculectomy alone on the other eye in first group. Whereas, trabeculectomy with topical application of mitomycine (MMC) was performed on one eye and trabeculectomy with topical application of C(3)F(8) on the other eye in second group. Histopathologic changes in filter bleb were investigated by immunostaining at 3 days, and at week 1, 2, 3, and 4 after surgery. RESULTS: Fibroblasts: The numbers of fibroblasts in eyes after trabeculectomy with C(3)F(8) gas as well as trabeculectomy with MMC were significantly reduced (P < 0.05) compared to eyes with trabeculectomy alone. There was no significant statistical difference in the numbers of fibroblasts between trabeculectomy with C(3)F(8) gas group and trabeculectomy with MMC group. Newly formed collagen fiber: Immunostaining of collagen fibers showed that the numbers of newly formed collagen fibers in trabeculectomy with C(3)F(8) gas group and trabeculectomy with MMC group were significantly decreased compared to trabeculectomy alone group. However, there was no significant statistical difference between numbers of fibers in trabeculectomy with C(3)F(8) gas group and trabeculectomy with MMC group. Neovascularization and inflammation of filtering blebs: The differences were not statistically significant among trabeculectomy with C(3)F(8) gas, trabeculectomy with MMC group and trabeculectomy alone group. CONCLUSION: Trabeculectomy with subconjunctival retention of C(3)F(8) gas can enhance the success rates of surgery by suppressing the growth of fibroblasts and synthesis of newly formed collagen fibers, and by inhibiting scar formation.