Circular RNA hsa_circ_0002938 (circCRIM1) promotes the progression of esophageal squamous cell carcinoma by upregulating transcription factor 12.

Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in the tumorigenesis and progression of diverse malignancies. However, the majority of circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined and the exact functions and underlying mechanisms of circRNAs in ESCC still need further exploration. In this study, we identified a novel onco-circRNA hsa_circ_0002938, derived from the exons of cysteine-rich transmembrane BMP regulator 1 (CRIM1) pre-mRNA, referred to as circCRIM1. We found that the expression of circCRIM1 was higher in ESCC tissues, compared to para-carcinoma tissues. Increased expression of circCRIM1 was positively correlated with clinical parameters of ESCC patients including tumor-node-metastasis (TNM) stage, tumor invasion range, and lymph node metastasis. Functionally, the results from the experiments in vitro showed that the knockdown of circCRIM1 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in ESCC cells. By conducting bioinformatics algorithms analyses and microRNA (miRNA) rescue experiments, we found that circCRIM1 could act as a competing endogenous RNA (ceRNA) to sponge miR-342-3p in ESCC cells, and thereby upregulated the expression of transcription factor 12 (TCF12), a key regulator promoting the EMT process. Taken together, circCRIM1 facilitates the progression of ESCC by sponging miR-342-3p to regulate TCF12 and promote EMT, and the circCRIM1/miR-342-3p/TCF12 axis may be regarded as a potential predictive biomarker and therapeutic target for treating ESCC.

Optical flow estimation of coronary angiography sequences based on semi-supervised learning.

Optical flow is widely used in medical image processing, such as image registration, segmentation, 3D reconstruction, and temporal super-resolution. However, high-precision optical flow training datasets for medical images are challenging to produce. The current optical flow estimation models trained on these non-medical datasets, such as KITTI, Sintel, and FlyingChairs are unsuitable for medical images. In this work, we propose a semi-supervised learning mechanism to estimate the optical flow of coronary angiography. Our proposed method only needs the original medical images, segmentation results of regions of interest, and pre-trained models based on other optical flow datasets to train a new optical flow estimation model suitable for medical images. First, we use the coronary segmentation results to perform image enhancement processing on the coronary vascular region to improve the image contrast between the vascular region and the surrounding tissues. Then, we extract the high-precision optical flow of coronary arteries based on the coronary-enhanced images and the pre-trained optical flow estimation model. After estimating the optical flow, we take it and its corresponding original coronary angiography images as the training dataset to train the optical flow estimation network. Furthermore, we generate a large-scale synthetic Flying-artery dataset based on coronary artery segmentation results and original coronary angiography images, which is used to improve and evaluate the accuracy of optical flow estimation for coronary angiography. The experimental results on the coronary angiography datasets demonstrate that our proposed method can significantly improve the optical flow estimation accuracy of coronary angiography sequences compared with other methods.

Amino-Nogo inhibits optic nerve regeneration and functional recovery via the integrin αv signaling pathway in rats.

BACKGROUND: Nogo-A, a major myelin-associated inhibitor, can inhibit injured optic nerve regeneration. However, whether Amino-Nogo is the most important functional domain of Nogo-A remains unknown. This study aimed to identify the role of Amino-Nogo following optic nerve injury, and the mechanism of the Amino-Nogo-integrin αv signaling pathway in vivo. METHODS: Sprague-Dawley rats with optic nerve crush injury were injected with Nogo-A siRNA (Nogo-A-siRNA), the Nogo-66 functional domain antagonist peptide of Nogo-A (Nep1-40) or a recombinant rat Amino-Nogo-A protein (∆20) into the vitreous cavity to knock down Nogo-A, inhibit Nogo-66 or activate the Amino-Nogo, resparately. Retinal ganglion cell (RGC) density, axon regeneration and the pattern of NPN of visual electrophysiology (flash visual evoked potentials [F-VEP]) at different times post-injury were investigated. RESULTS: Our study revealed a lower RGC survival rate; shorter axonal outgrowth; longer N1, P1 and N2 waves latencies; and lower N1-P1 and P1-N2 amplitudes in the Δ20 group, and Δ20 treatment significantly attenuated integrin αv expression and phosphorylated focal adhesion kinase (p-FAK) levels. In the Nep1-40 and Nogo-A siRNA groups, there were higher RGC survival rates, longer axonal outgrowth, shorter N1 and P1 wave latencies, and higher N1-P1 and P1-N2amplitudes. Nogo-A siRNA treatment significantly increased integrin αv expression and p-FAK levels. Nepl-40 treatment did not alter integrin αv expression. In addition, there was no significant change in integrin α5 in any group. CONCLUSION: These results suggest that the integrin signaling pathway is regulated by Amino-Nogo, which inhibits optic nerve regeneration and functional recovery, and that the integrin subunit involved might be integrin αv but not integrin α5.

Constitutive Gαi coupling activity of very large G protein-coupled receptor 1 (VLGR1) and its regulation by PDZD7 protein.

The very large G protein-coupled receptor 1 (VLGR1) is a core component in inner ear hair cell development. Mutations in the vlgr1 gene cause Usher syndrome, the symptoms of which include congenital hearing loss and progressive retinitis pigmentosa. However, the mechanism of VLGR1-regulated intracellular signaling and its role in Usher syndrome remain elusive. Here, we show that VLGR1 is processed into two fragments after autocleavage at the G protein-coupled receptor proteolytic site. The cleaved VLGR1 ß-subunit constitutively inhibited adenylate cyclase (AC) activity through Gαi coupling. Co-expression of the Gαiq chimera with the VLGR1 ß-subunit changed its activity to the phospholipase C/nuclear factor of activated T cells signaling pathway, which demonstrates the Gαi protein coupling specificity of this subunit. An R6002A mutation in intracellular loop 2 of VLGR1 abolished Gαi coupling, but the pathogenic VLGR1 Y6236fsx1 mutant showed increased AC inhibition. Furthermore, overexpression of another Usher syndrome protein, PDZD7, decreased the AC inhibition of the VLGR1 ß-subunit but showed no effect on the VLGR1 Y6236fsx1 mutant. Taken together, we identified an independent Gαi signaling pathway of the VLGR1 ß-subunit and its regulatory mechanisms that may have a role in the development of Usher syndrome.

Inhibition of retinal ganglion cell axonal outgrowth through the Amino-Nogo-A signaling pathway.

Nogo-A is a myelin-derived inhibitor playing a pivotal role in the prevention of axonal regeneration. A functional domain of Nogo-A, Amino-Nogo, exerts an inhibitory effect on axonal regeneration, although the mechanism is unclear. The present study investigated the role of the Amino-Nogo-integrin signaling pathway in primary retinal ganglion cells (RGCs) with respect to axonal outgrowth, which is required for axonal regeneration. Immunohistochemistry showed that integrin αv, integrin α5 and FAK were widely expressed in the visual system. Thy-1 and GAP-43 immunofluorescence showed that axonal outgrowth of RGCs was promoted by Nogo-A siRNA and a peptide antagonist of the Nogo-66 functional domain of Nogo-A (Nep1-40), and inhibited by a recombinant rat Nogo-A-Fc chimeric protein (Δ20). Western blotting revealed increased integrin αv and p-FAK expression in Nogo-A siRNA group, decreased integrin αv expression in Δ20 group and decreased p-FAK expression in Nep1-40 group. Integrin α5 expression was not changed in any group. RhoA G-LISA showed that RhoA activation was inhibited by Nogo-A siRNA and Δ20, but increased by Nep1-40 treatment. These results suggest that Amino-Nogo inhibits RGC axonal outgrowth primarily through the integrin αv signaling pathway.

Association between MTHFR C677T polymorphism and primary open-angle glaucoma: a meta-analysis.

Epidemiological studies have evaluated the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and primary open-angle glaucoma (POAG) risk. However, the results remain conflicting. The aim of this study was to investigate the association between MTHFRC677T polymorphism and POAG risk. All genetic association studies on MTHFR C677T polymorphism and POAG were systematically searched by the electronic databases PubMed, Embase and Web of Science. Study selection, data abstraction and study quality evaluation were conducted in duplicate independently. The strength of association between MTHFR C677T polymorphism and POAG was measured by odds ratios (ORs) and 95% confidence intervals (CIs). Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 10 studies including 1224 cases and 1105 controls were included in our final meta-analysis. There was no evidence of significant association of the overall population (for allelic model: OR=1.17, 95% CI=0.94-1.46; for additive model: OR=1.15, 95% CI=0.85-1.57; for dominant model: OR=1.19, 95% CI=0.92-1.55 and for recessive model: OR=1.11, 95% CI=0.83-1.49). Significant associations were found between MTHFR C677T polymorphisms and POAG in allelic model (OR=1.39, 95% CI=1.05-1.83) and additive model (OR=1.88, 95% CI=1.04-3.43) for population-based (PB) subgroup. This meta-analysis suggested that there were significant associations between MTHFR C677T polymorphism and POAG in allelic model and additive model for PB subgroup which indicated that the T allele or TT genotype might increase the risk of POAG, whereas no evidence of significant association was shown of the overall studied population. However, this conclusion should be interpreted cautiously. More large sample-size and multi-ethnicity studies with well-defined POAG patients and well-study design are needed in the future study.

Clinical features of ankylosing spondylitis associated with acute anterior uveitis in Chinese patients.

AIM: To characterize the clinical features, diagnosis, treatment and prognosis of uveitis associated with ankylosing spondylitis (AS) in Chinese patients. METHODS: Two hundred and three patients with uveitis associated with AS followed-up in the Third Military Medical University Daping Hospital between 2005 and 2010 were retrospectively evaluated in this study. Complete ophthalmological examinations were evaluated at baseline and during the follow-up period. The gender, age, follow-up time, mean frequency of uveitis onset, and accompanying eye examination findings, history, demographical parameters were reviewed. All the patients presented complete clinical and radiologic (sacroiliac, lumbar, dorsal and cervical spine, knee, ankle, shoulder, hip, elbow) evaluation. HLA-B27 typing was also searched. RESULTS: There were 203 patients diagnosed with AS associated uveitis. All showed sacroiliac X-ray changes indicative of AS. There were 184 male and 19 female patients. The average age of patients was 35±12 (range 18-50). Mean follow-up period was 2.4 years (1-5 years). Acute anterior uveitis was the most common type of uveitis in both genders. 121 eyes presented unilateral involvement (55.2%), and 92 eyes presented bilateral involvement (45.3%) with onset alternately. 22 eyes occurred hypopyon, 16 eyes were found anterior vitreous cells, 7 eyes were noted reactive macular edema or exudation, 29 eyes presented posterior synechiae of iris, and 14 eyes presented cataract, 9 eyes presented secondary glaucoma, 2 eyes presented bend corneal degeneration and 1 eyes presented atrophy of eyeball. At the final visit, uveitis was well controlled in most patients. CONCLUSION: AS associated with uveitis in Chinese patients mainly manifests as acute anterior uveitis. A combination of corticosteroids with other mydriasis agents is effective for most AS associated with uveitis patients. In general, the prognosis is good in these cases.

[Expression of Nogo-A and Nogo receptor in neonatal rats visual system during development].

OBJECTIVE: To study the expression of Nogo-A and Nogo receptor (NgR) in the development of neonatal rats retinal and visual cortex and their effects on the development of central nervous system (CNS). METHODS: Immunohistochemical staining method was used to detect the expression of Nogo-A and NgR in neonatal rats retinal and visual cortex at 1, 3, 7, 14, 28, 56 days after birth. One-way Anova was used to analyze the results of Western blot analysis of Nogo-A and NgR in neonatal rats visual cortex. RESULTS: Nogo-A and NgR was found to express in neonatal rats retinal and visual cortex at the developing stage. In 1, 3, 7, 14, 28, 56 days, the IDV ratio of Nogo-A was 0.852 ± 0.026, 0.917 ± 0.024, 0.810 ± 0.028, 0.417 ± 0.053, 0.258 ± 0.029, 0.298 ± 0.054 respectively and the IDV ratio of NgR was 0.070 ± 0.014, 0.185 ± 0.035, 0.678 ± 0.046, 0.705 ± 0.021, 1.210 ± 0.057, 1.140 ± 0.0420 respectively by Western blot analysis. The expression of Nogo-A was decreased (F = 376.56, P = 0.000) and the expression of NgR was increased (F = 888.26, P = 0.000) during postnatal development. CONCLUSION: Nogo-A and NgR is closely related to the CNS growth and development.

Effect of CD4(+)CD25(+) regulatory T cells in the development of anterior chamber-associated immune deviation.

AIM: To investigate whether CD4(+)CD25(+) regulatory T (Treg) cells play a role in the development of anterior chamber-associated immune deviation (ACAID). METHODS: The dynamic changes in the frequency of CD4(+)CD25(+) T cells, CD4(+)CD25(+) FoxP3(+) T cells and CD4(+)CD25(+) PD-1(+) T cells from spleens of mice with ACAID were analyzed by flow cytometry. Foxp3 mRNA expression in purified CD4(+)CD25(+) T cells was analyzed using real-time PCR. The suppressive effect of purified CD4(+)CD25(+) T cells on the proliferation of CD4(+)CD25(-) T cells was evaluated by [(3)H] thymidine incorporation. A blocking experiment was performed to further address the role of CD4(+)CD25(+) T cells in ACAID. The expression of IL-10 in purified CD4(+)CD25(+) T cells was evaluated by ELISA. RESULTS: Increased frequencies of CD4(+)CD25(+) T cells, CD4(+)CD25(+) FoxP3(+) T cells and CD4(+)CD25(+) PD-1(+) T cells were observed in ACAID. The CD4(+)CD25(+) T cells from mice with ACAID showed enhanced suppressive effect on the proliferation of CD4(+)CD25(-) T cells. Treatment of BALB/c mice with anti-CD25 antibody after injection of OVA into the anterior chamber significantly inhibited the induction of ACAID. Furthermore, purified CD4(+)CD25(+) T cells from ACAID mice secreted IL-10. CONCLUSION: Our results demonstrate that Treg cells are induced in the mice undergoing ACAID. These Treg cells may play a role in the development of ACAID.

A case of circumscribed choroidal hemangioma in Sturge-Weber syndrome in China.

We present a case of circumscribed choroidal hemangioma (CCH) in Sturge-Weber syndrome in a 30-year-old woman with congenital port-wine stains on the left side of face involving the upper eyelid, cheek and the nose, and she had undergone facial hemangioma surgery 3 years ago suggestive of Sturge-Weber syndrome. She presented with a 1-month history of rapidly decreased visual acuity (VA) to counting fingers in the left eye which had no prior history of visual problem. And there was no evidence of glaucoma. At 3 months after the treatment of the standard photodynamic therapy (PDT) the VA was 20/200. For some reasons, we have no idea about the changes of tumor thickness and subretinal fluid. We confirmed the curative effect of PDT treatment for CCH because of the significantly improved VA in the bad eye.

Bietti crystalline dystrophy with bilateral macular holes.

OBJECTIVE: Bietti crystalline dystrophy is a rare form of tapetoretinal degeneration associated with retinal crystalline deposits. However, Bietti crystalline dystrophy is extremely unusually associated with macular hole formation. A 32-year-old man with Bietti crystalline dystrophy and bilateral macular holes is described. DESIGN: Case report and literature review. RESULTS: Clinical and angiographic features, optical coherence tomography results, electroretinographic findings, and visual evoked potentials are reported. CONCLUSION: Bietti crystalline dystrophy can occur with bilateral macular holes, but the cause is unclear.

[Construction of siRNA expression vector of NgR and its inhibition on the expression of NgR].

OBJECTIVE: To construct the expressing vector of siRNA in order to inhibit NgR expression, which provides a new gene therapy approach to the optic nerve impairment. METHODS: It was a experimental study. Specific short chain oligonucleotides was designed by using the siRNA software according to the mRNA sequence provided by genebank, the double chain DNA sequence was gained through annealing after chemosynthesis and was inserted to the pSUPER-EGFP vector linearized with Bgl II and Hind II enzyme, the recombinant expression vector was evaluated by using EcoR I and Hind II enzyme cutting and sequencing. At last, the constructed vectors were transfected into wistar rat retinal ganglion cells and the expression level of NgR was observed. RESULTS: Identification by enzyme cutting and sequencing showed that the expression vector was constructed successfully, and it was proved that the NgR expression level was effectively inhibited. CONCLUSION: The constructed siRNA expression vectors can block the NgR gene expression, it will be the foundation for the research of gene therapy to optic nerve regeneration.