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Myopia is a refractive error of the eye that is prevalent worldwide. The most extreme form, high myopia, is usually associated with other ocular disorders such as retinal detachment, macular degeneration, cataract, and glaucoma, and is one of leading causes of blindness. The etiology is complex and has not been fully elucidated. In this study, we identified a novel missense variant of the CCDC111 gene (NM_152683.2: c.265T > G; p.Y89D) in a high myopia family by exome sequencing. The variant was identified in 4 patients from an additional 270 sporadic high myopia patients, but not found in 270 controls. The amino acid is highly conserved across species, and variants giving rise to amino acid substitutions are predicted to be functionally damaging. The CCDC111 gene was ubiquitously expressed in primary cell cultures from human eye tissue, including corneal epithelial cells, choroidal melanoma cells, scleral fibroblasts, retinal epithelial cells, retinal Müller cells, and lens capsule epithelial cells. In summary, our results suggested that the CCDC111 may be a susceptibility gene for high myopia.  相似文献   
104.

Purpose

To assess the activity and safety of postoperative adjuvant immunotherapy with transfusion of cytokine-induced killer (CIK) cells combined with chemotherapy in patients with colorectal cancer.

Methods

We retrospectively studied 96 consecutive patients with colorectal cancer who were treated with resection between January 2010 and December 2012 as well as adjuvant chemotherapy. Twenty-one of these patients accepted at least 1 cycle of CIK cell transfusion for immunotherapy (CIK group). Disease free survival (DFS), immune cells and treatment related side effects were assessed. The patients were followed up until May 2013.

Results

By the end of follow-up, 10 patients (10.42 %) had died. Eighteen patients (18.75 %) had withdrawn. All the patients in the CIK group are still alive, and only 1 patient had withdrawn. Patients in the CIK group had significantly longer DFS than those in the control group [HR = 0.28, 95 % CI (0.09, 0.91), p = 0.034]. The 2-year DFS rates of patients in the CIK group and the control group were 59.65 ± 24.80 % and 29.35 ± 6.39 %, respectively. The CD4+/CD8+ ratios were significantly lower during the period of chemotherapy than those before chemotherapy (p = 0.0038), while the ratios were significantly higher during the period of CIK cell transfusion than those before CIK therapy (p = 0.0484). There were no immediate adverse reactions to the CIK cell transfusions.

Conclusion

Adjuvant transfusion of CIK cells prolongs DFS in patients with colorectal cancer.  相似文献   
105.
The proliferation of neonatal Schwann cells (SCs) in response to mitogenic agents has been well analyzed in vitro (mono-layer-culture method, 2D environment), but not in vivo (3D environment). To assess the mitogenic effect of platelet-derived growth factors-BB (PDGF-BB), Fibroblast Growth Factors-base (bFGF), and their combinations for SCs in collagen gel (three-dimensional, 3D environment), we have developed an integrated microfluidic device on which can reproducibly measure the proliferation from small number of cells (1–100). The rat SCs were cultured for 4 week at the different concentrations of growth factors generated by concentration gradient generator. In the collagen gel culture, almost all of the cells in colonies presented a round cell morphology and maintained their round morphology by the 4th week. The results showed that PDGF-BB and bFGF are all capable of moderately stimulating SCs growth and every group reached the peak in the growth curve at 3 weeks. Moreover, the proliferation test using the conventional method was performed simultaneously and revealed similar results. The biggest difference between 2D and 3D was that cells decrease more remarkable in 3D than that in 2D at 4 weeks. And at 2 and 3 weeks, the growth rate in the collagen gel with 7.14/2.86 and 8.57/1.43 ng/mL groups was higher than that in the mono-layer culture. Our results showed that PDGF-BB and bFGF are capable of moderately stimulating neonatal SCs growth, respectively and synergistically, and the microfluidic technique is highly controllable, contamination free, fully automatic, and inexpensive.  相似文献   
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Chronic obstructive pulmonary disease (COPD) is associated with chronic severe airway inflammation and causes increasing global health problems. New biological markers for COPD prediction and prognosis are urgently necessary. Previous studies indicate that histone deacetylases (HDACs) play essential roles in COPD. This study is to investigate if HDAC2 levels can be used as a promising, easily detected biomarker of COPD. In this paper, 49 COPD patients were enrolled and 42 healthy individuals (smokers or non-smokers) were used as healthy controls. Human bronchial epithelial cells derived from non-smokers, smokers, or COPD patients were grown in primary cultures. Total proteins were harvested from lung tissues or bronchial epithelial cells and then subjected to immunoblot analyses of HDAC2, HDAC3, and HDAC5. Quantitative RT-PCR analysis of HDAC2, HDAC3, and HDAC5 mRNA levels in tissues or cells were also preformed. We found that among the three HDAC proteins, the mRNA and protein levels of HDAC2, but not HDAC3 and HDAC5, in the tissues or cultured cells from patients have a significant correlation with development and prognosis of COPD. These results suggested that HDAC2 levels may serve as a promising, easily detected biomarker of COPD.  相似文献   
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Molecular docking and pharmacophore model approaches were used to characterise the binding features of four different series of Rho kinase (ROCK) inhibitors. Docking simulation of 20 inhibitors with ROCK was performed. The binding conformations and binding affinities of these inhibitors were obtained using AutoDock 4.0 software. The predicted binding affinities correlate well with the activities of these inhibitors (R 2 = 0.904). 3D pharmacophore models were generated for ROCK based on highly active inhibitors implemented in Catalyst 4.11 program. The best pharmacophore model consists of one hydrogen bond acceptor feature and two hydrophobic features, and they all seemed to be essential for inhibitors in terms of their binding activities. It is anticipated that the findings reported in this paper may provide very useful information for designing new ROCK inhibitors.  相似文献   
110.

Key message

Efficient Agrobacterium -mediated genetic transformation for investigation of genetic and molecular mechanisms involved in inflorescence architectures in Cornus species.

Abstract

Cornus canadensis is a subshrub species in Cornus, Cornaceae. It has recently become a favored non-model plant species to study genes involved in development and evolution of inflorescence architectures in Cornaceae. Here, we report an effective protocol of plant regeneration and genetic transformation of C. canadensis. We use young inflorescence buds as explants to efficiently induce calli and multiple adventitious shoots on an optimized induction medium consisting of basal MS medium supplemented with 1 mg/l of 6-benzylaminopurine and 0.1 mg/l of 1-naphthaleneacetic acid. On the same medium, primary adventitious shoots can produce a large number of secondary adventitious shoots. Using leaves of 8-week-old secondary shoots as explants, GFP as a reporter gene controlled by 35S promoter and hygromycin B as the selection antibiotic, a standard procedure including pre-culture of explants, infection, co-cultivation, resting and selection has been developed to transform C. canadensis via Agrobacterium strain EHA105-mediated transformation. Under a strict selection condition using 14 mg/l hygromycin B, approximately 5 % explants infected by Agrobacterium produce resistant calli, from which clusters of adventitious shoots are induced. On an optimized rooting medium consisting of basal MS medium supplemented with 0.1 mg/l of indole-3-butyric acid and 7 mg/l hygromycin B, most of the resistant shoots develop adventitious roots to form complete transgenic plantlets, which can grow normally in soil. RT-PCR analysis demonstrates the expression of GFP transgene. Green fluorescence emitted by GFP is observed in transgenic calli, roots and cells of transgenic leaves under both stereo fluorescence microscope and confocal microscope. The success of genetic transformation provides an appropriate platform to investigate the molecular mechanisms by which the various inflorescence forms are developed in Cornus plants.  相似文献   
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