State Key Laboratory Cultivation Base

Wenzhou, China

State Key Laboratory Cultivation Base

Wenzhou, China

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Wang L.,Wenzhou University | Wang L.,State Key Laboratory Cultivation Base | Chen X.,Wenzhou University | Du Z.,Wenzhou University | And 4 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2017

Background: Curcumin, as a pro-apoptotic agent, is extensively studied to inhibit tumor cell growth of various tumor types. Previous work has demonstrated that curcumin inhibits cancer cell growth by targeting multiple signaling transduction and cellular processes. However, the role of curcumin in regulating cellular bioenergetic processes remains largely unknown. Methods: Western blotting and qRT-PCR were performed to analyze the protein and mRNA level of indicated molecules, respectively. RTCA, CCK-8 assay, nude mice xenograft assay, and in vivo bioluminescence imaging were used to visualize the effects of curcmin on gastric cancer cell growth in vitro and in vivo. Seahorse bioenergetics analyzer was used to investigate the alteration of oxygen consumption and aerobic glycolysis rate. Results: Curcumin significantly inhibited gastric tumor cell growth, proliferation and colony formation. We further investigated the role of curcumin in regulating cellular redox homeostasis and demonstrated that curcumin initiated severe cellular apoptosis via disrupting mitochondrial homeostasis, thereby enhancing cellular oxidative stress in gastric cancer cells. Furthermore, curcumin dramatically decreased mtDNA content and DNA polymerase γ (POLG) which contributed to reduced mitochondrial oxygen consumption and aerobic glycolysis. We found that curcumin induced POLG depletion via ROS generation, and POLG knockdown also reduced oxidative phosphorylation (OXPHOS) activity and cellular glycolytic rate which was partially rescued by ROS scavenger NAC, indiating POLG plays an important role in the treatment of gastric cancer. Data in the nude mice model verified that curcumin treatment significantly attenuated tumor growth in vivo. Finally, POLG was up-regulated in human gastric cancer tissues and primary gastric cancer cell growth was notably suppressed due to POLG deficiency. Conclusions: Together, our data suggest a novel mechanism by which curcumin inhibited gastric tumor growth through excessive ROS generation, resulting in depletion of POLG and mtDNA, and the subsequent disruption of cellular bioenergetics. © 2017 The Author(s).


Xing D.-J.,Wenzhou University | Xing D.-J.,State Key Laboratory Cultivation Base | Zhang H.-X.,Jinan Eye Hospital | Huang N.,State Key Laboratory Cultivation Base | And 11 more authors.
PLoS ONE | Year: 2014

Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder with significant genetic heterogeneity. BBS is linked to mutations in 17 genes, which contain more than 200 coding exons. Currently, BBS is diagnosed by direct DNA sequencing for mutations in these genes, which because of the large genomic screening region is both time-consuming and expensive. In order to develop a practical method for the clinic diagnosis of BBS, we have developed a high-throughput targeted exome sequencing (TES) for genetic diagnosis. Five typical BBS patients were recruited and screened for mutations in a total of 144 known genes responsible for inherited retinal diseases, a hallmark symptom of BBS. The genomic DNA of these patients and their families were subjected to high-throughput DNA re-sequencing. Deep bioinformatics analysis was carried out to filter the massive sequencing data, which were further confirmed through co-segregation analysis. TES successfully revealed mutations in BBS genes in each patient and family member. Six pathological mutations, including five novel mutations, were revealed in the genes BBS2, MKKS, ARL6, MKS1. This study represents the first report of targeted exome sequencing in BBS patients and demonstrates that high-throughput TES is an accurate and rapid method for the genetic diagnosis of BBS. © 2014 Xing et al.


An J.,Wenzhou Medical College | An J.,State Key Laboratory Cultivation Base | Hsi E.,Kaohsiung Medical University | Zhou X.,Wenzhou Medical College | And 4 more authors.
Molecular Vision | Year: 2012

Purpose: Fibroblast growth factor-2 (FGF2) has been implied in the development of myopia according to previous studies investigating FGF2 in the sclera and retinal pigment epithelium. This study measured retinal FGF2 gene expression in an animal model and also tested for the association between single nucleotide polymorphisms (SNPs) in FGF2 and high myopia. Methods: The guinea pigs were assigned to 2 groups: form deprivation myopia (FDM) for two weeks and normal control (free of form deprivation). Biometric measurement was performed and FGF2 expression levels were compared among the FDM eyes, the fellow eyes of the FDM group and the normal eyes in retina. We also enrolled 1,064 cases (≤-6.0 D) and 1,001 controls (≥-1.5 D) from a Chinese population residing in Taiwan. Six tagging SNPs were genotyped to test for an association between genotypes and high myopia. Results: The FDM eyes had the most prominent changes of refraction and axial length. Compared with the mRNA levels of FGF2 in the normal eyes, the FDM eyes had the highest levels of mRNA (p=0.0004) followed by the fellow eyes (p=0.002). The FDM and normal eyes became more myopic compared with the fellow eyes, but the fellow eyes became more hyperopic (p=0.004) in the end of the experiment which may be due to its relatively short axial length when compared with normal eyes (p=0.05). The SNP genotypes were all in Hardy-Weinberg equilibrium. However, none of the SNPs were significantly associated with high myopia (all p values >0.1). Conclusions: We identified a significant change of FGF2 expression in the FDM eyes but FGF2 genetic variants are unlikely to influence susceptibility to myopia. There may be a systemic effect to influence gene expression and refraction on the fellow eyes, which may perturb emmetropization in the fellow eyes. Our data also suggest using normal eyes rather than the fellow eyes as the control eyes when study the form deprivation myopia. © 2012 Molecular Vision.


Jiang L.,Wenzhou Medical College | Jiang L.,State Key Laboratory Cultivation Base | Zhang S.,Wenzhou Medical College | Zhang S.,State Key Laboratory Cultivation Base | And 11 more authors.
Vision Research | Year: 2014

It was recently demonstrated that chromaticity could affect eye growth and refractive development in guinea pigs but it remained unclear whether correction with spectacle lenses could balance these effects and how retinal responses change with different spectral compositions of light. Three illumination conditions were tested: blue, red and white light. Animals were raised without or with monocular spectacle lenses from three to seven weeks of age. Luminance electroretinograms (ERGs) were recorded to explore retinal responses with the different spectral compositions. In our special colony of pigmented guinea pigs, characterized by residual hyperopia, spontaneous myopia and poor emmetropization, red light induced early thinning of the choroid and relative myopia, compared to white light. Effects of red light could not be suppressed if positive spectacle lenses were worn. ERGs showed that red light failed to elicit robust retinal responses. Blue light inhibited axial eye growth, even when animals were reared with negative lenses. Intensity-matched blue and white light elicited similar a-waves but different b-waves, suggesting that the wavelength of light affects visual control of eye growth through different processing in the inner retina. We hypothesize that blue light might stimulate preferentially the ON pathway to inhibit myopia induced by negative lenses, at least in guinea pigs. © 2013 .


Hao T.X.,State Key Laboratory Cultivation Base | Hao T.X.,Henan Polytechnic University | Niu H.,Henan Polytechnic University
Applied Mechanics and Materials | Year: 2014

The mathematic principles and numerical arithmetic of quantification theory I are studied of gas content prediction model and actually measured data during geological prospecting and producing of Jincheng Hebi No.6 coal seam are collected. Thus, twenty-nine reliable data of gas content are gained. Then, the gas content prediction model is founded based on quantification theory by selecting bedrock thickness, coal seam thickness as quantitative values and lithological character of coal roof as qualitative value. By results of calculation and estimation, the model precision can meet the desire of engineering precision, showing that using quantification theory to predict gas content is feasible. © (2014) Trans Tech Publications, Switzerland.


Hao T.-X.,State Key Laboratory Cultivation Base | Hao T.-X.,Henan Polytechnic University | Jin Z.-C.,Henan Polytechnic University | Li F.,Henan Polytechnic University
Procedia Engineering | Year: 2012

Underground coal seam mining can redistribute the stress of the coal and rock, in which gas distribution and migration occurred. In order to draw out the gas in the goaf effectively, reduce the goaf gas emission and avoid the over ranging, the high level drilling site is employed for goaf gas drainage, and rock crack development situation and gas enrichment area are simulated by RFPA2D-Integrated to locate the position of drilling hole. The result indicated that the caving-in zones and fracturing zones of the coal cave mined out area are 0-13m and 13-42m to the roof of the coal, respectively. The optimal position of drilling hole is 14-35m. The practice survey revealed that the overall quantity of gas extraction is 8.47m3/min, and it solves the problem of goaf gas emission better. The result of simulation is accord with the field. © 2012 Published by Elsevier Ltd.


Gao J.-L.,Henan Polytechnic University | Gao J.-L.,State Key Laboratory Cultivation Base | Wang Y.,Henan Polytechnic University
Applied Mechanics and Materials | Year: 2011

The drilling cutting gas desorption index △h 2 is one of the most important indexes for the prediction of coal and gas outburst. Based on the mathematical and physical model of the gas diffusion of coal particles, the analytical solution of △h 2 was deduced. The relationship between the drilling cutting gas desorption index △h 2 and parameters of gas occurrence such as the gas diffusion coefficient, adsorption constants (a and b), gas pressure, and gas content were studied. The results show that △h 2 increases and gas diffusion resistance decreases with the gas diffusion coefficient. The drilling cutting gas desorption index △h 2 increases with the adsorption constant a, and the two meet the linear relationship. △h 2 increases with the adsorption constant b and the raising rate gets lower gradually. And, △h 2 increases with the gas pressure, and the two meet the power relationship with very high correlation coefficient. △h 2 and gas content are in linear relationship. © (2011) Trans Tech Publications.


Hao T.X.,State Key Laboratory Cultivation Base | Hao T.X.,Henan Polytechnic University | Liu M.,Henan Polytechnic University
Advanced Materials Research | Year: 2014

The gas concentration field in goaf of Huangling No.1 Mine 304 fully-mechanized face was simulated numerically by FLUENT software with high fracture drilling or not. The results of numerical simulation were confirmed by fixed sampling method of immersed tube in goaf. Thus, the law of gas concentration field was gained, which provides the important basis for gas control of working face. © (2014) Trans Tech Publications, Switzerland.


Zhao F.,Wenzhou Medical College | Zhao F.,State Key Laboratory Cultivation Base | Wu J.,Wenzhou Medical College | Xue A.,Wenzhou Medical College | And 13 more authors.
Human Genetics | Year: 2013

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. © 2013 Springer-Verlag Berlin Heidelberg.


Ma X.,Wenzhou Medical College | Pan L.,Wenzhou Medical College | Jin X.,Wenzhou Medical College | Jin X.,State Key Laboratory Cultivation Base | And 13 more authors.
Experimental Cell Research | Year: 2012

Cells of the retinal pigment epithelium (RPE) play major roles in metabolic functions, maintenance of photoreceptor function, and photoreceptor survival in the retina. They normally form a stable monolayer, but migrate during disease states. Although growth factors produced by the RPE cells primarily control these cellular events, how these factors are regulated in RPE cells remain largely unknown. Here we show that the basic-helix-loop-helix-leucine zipper microphthalmia-associated transcription factor (MITF), which plays central roles in the development and function of a variety of cell types including RPE cells, upregulates the expression of a multifunctional factor PEDF in RPE cells. Consequently, the upregulation of PEDF impairs microtubule assembly and thus inhibits RPE cell migration. Conversely, specific knockdown of PEDF partially rescues the impairment of microtubule assembly and cell migration proceeds in MITF overexpressing stable cells. We conclude that MITF acts through PEDF to inhibit RPE cell migration and to play a significant role in regulating RPE cellular function. We suggest that MITF has a novel and important role in maintaining RPE cells as a stable monolayer and the down-regulation of PEDF that may contribute to retinal degenerative diseases. © 2011 Elsevier Inc..

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