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Xu Yiyang,Mao Guping,Long Dianbo,Deng Zengfa,Xin Ruobin,Zhang Ziji,Xue Ting,Liao Weiming,Xu Jie,Kang Yan 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Osteoarthritis, characterized by articular cartilage degradation, is the leading cause of chronic disability in older adults. Studies have indicated that circular RNAs are crucial regulators of chondrocyte development and are involved in the progression of osteoarthritis. In this study, we investigated the function and mechanism of a circular RNA and its potential for osteoarthritis therapy. The expression levels of circCREBBP, screened by circular RNA sequencing during chondrogenic differentiation in adipose tissue-derived stem cells, and TGFβ2 were significantly increased in the cartilage of patients with osteoarthritis and IL-1β-induced chondrocytes. circCREBBP knockdown increased anabolism in the extracellular matrix and inhibited chondrocyte degeneration, whereas circCREBBP overexpression led to the opposite effects. Luciferase reporter assays, rescue experiments, RNA immunoprecipitation, and RNA pulldown assays confirmed that circCREBBP upregulated TGFβ2 expression by sponging miR-1208, resulting in significantly enhanced phosphorylation of Smad1/5 in chondrocytes. Moreover, intra-articular injection of adeno-associated virus-sh-circCrebbp alleviated osteoarthritis in a mouse model of destabilization of the medial meniscus. Our findings reveal a critical role for circCREBBP in the progression of osteoarthritis and provide a potential target for osteoarthritis therapy.
Xu, Ting,Xu, Zi-Cheng,Zou, Qin,Yu, Bin,Huang, Xin-En Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5
Objective: Individual studies of the associations between P53 codon 72 polymorphism (rs1042522) and bladder cancer susceptibility have shown inconclusive results. To derive a more precise estimation of the relationship, we performed this systemic review and meta-analysis based on 15 publications. Methods: We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Results: We found that there was no association between P53 codon 72 polymorphism and bladder cancer risk in the comparisons of Pro/Pro vs Arg/Arg; Pro/Arg vs. Arg/Arg; Pro/Pro plus Pro/Arg vs. Arg/Arg; Arg/Arg vs. Pro/Arg plus Arg/Arg (OR=1.06 95%CI 0.81-1.39; OR=1.06 95%CI 0.83-1.36; OR=0.98 95%CI 0.78-1.23; OR=1.06 95%CI 0.84-1.32). However, a significantly increased risk of bladder cancer was found among Asians in the homozygote comparison (Pro/Pro vs. Arg/Arg, OR=1.36 95%CI 1.05-1.75, P=0.790 for heterogeneity) and the dominant model (Arg/Pro plus Pro/Pro vs. Arg/Arg, OR=1.26 95%CI 1.05-1.52, P=0.564 for heterogeneity). In contrast, no evidence of an association between bladder cancer risk and P53 genotype was observed among Caucasian population in any genetic model. When stratifying for the stage of bladder, no statistical association were found (Pro/Pro vs. Arg/Arg, OR=0.45 95%CI 0.17-1.21; Pro/Arg vs. Arg/Arg, OR=0.60 95%CI 0.28-1.27; Dominant model, OR=0.56 95%CI 0.26-1.20; Recessive model, OR=0.62 95%CI0.35-1.08) between P53 codon 72 polymorphism and bladder cancer in all comparisons. Conclusions: Despite the limitations, the results of the present meta-analysis suggest that, in the P53 codon 72, Pro/Pro type and dominant mode might increase the susceptibility to bladder cancer in Asians; and there are no association between genotype distribution and the stage of bladder cancer.
Roles of PTEN (Phosphatase and Tensin Homolog) in Gastric Cancer Development and Progression
Xu, Wen-Ting,Yang, Zhen,Lu, Nong-Hua Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1
Gastric cancer is highly invasive, aggressively malignant, and amongst the most prevalent of all forms of cancer. Despite improved management strategies, early stage diagnosis of gastric cancer and accurate prognostic assessment is still lacking. Several recent reports have indicated that the pathogenesis of gastric cancer involves complex molecular mechanisms and multiple genetic and epigenetic alterations in oncogenes and tumor suppressor genes. Functional inactivation of the tumor suppressor protein PTEN (Phosphatase and Tensin Homolog) has been detected in multiple cases of gastric cancer, and already shown to be closely linked to the development, progression and prognosis of the disease. Inactivation of PTEN can be attributed to gene mutation, loss of heterozygosity, promoter hypermethylation, microRNA- mediated regulation of gene expression, and post-translational phosphorylation. PTEN is also involved in mechanisms regulating tumor resistance to chemotherapy. This review provides a comprehensive analysis of PTEN and its roles in gastric cancer, and emphasizes its potential benefits in early diagnosis and gene therapy-based treatment strategies.
Xu, Ting,Shen, Xiangfeng,Yu, Huali,Sun, Lili,Lin, Weihong,Zhang, Chunxiao The Korean Society of Ginseng 2016 Journal of Ginseng Research Vol.40 No.3
Background: Panax ginseng root is used in traditional oriental medicine for human health. Its main active components such as saponins and polysaccharides have been widely evaluated for treating diseases, but secondary active components such as oligosaccharides have been rarely studied. This study aimed to assess the impact of water-soluble ginseng oligosaccharides (WGOS), which were isolated from the warm-water extract of Panax ginseng root, on scopolamine-induced cognitive impairment in mice and its antineuroinflammatory mechanisms. Methods: We investigated the impact of WGOS on scopolamine-induced cognitive impairment in mice by using Morris water maze and novel object recognition task. We also analyzed the impact of WGOS on scopolamine-induced inflammatory response (e.g., the hyperexpression of proinflammatory cytokines IL-$1{\beta}$ and IL-6 and astrocyte activation) by quantitative real-time polymerase chain reaction and glial fibrillary acid protein (GFAP) immunohistochemical staining. Results: WGOS pretreatment protected against scopolamine-induced learning and memory deficits in the Morris water maze and in the novel object recognition task. Furthermore, WGOS pretreatment downregulated scopolamine-induced hyperexpression of proinflammatory cytokines interleukin (IL)-$1{\beta}$ and IL-6 mRNA and astrocyte activation in the hippocampus. These results indicate that WGOS can protect against scopolamine-induced alterations in learning and memory and inflammatory response. Conclusion: Our data suggest that WGOS may be beneficial as a medicine or functional food supplement to treat disorders with cognitive deficits and increased inflammation.
A Method for Tree Image Segmentation Combined Adaptive Mean Shifting with Image Abstraction
( Ting-ting Yang ),( Su-yin Zhou ),( Ai-jun Xu ),( Jian-xin Yin ) 한국정보처리학회 2020 Journal of information processing systems Vol.16 No.6
Although huge progress has been made in current image segmentation work, there are still no efficient segmentation strategies for tree image which is taken from natural environment and contains complex background. To improve those problems, we propose a method for tree image segmentation combining adaptive mean shifting with image abstraction. Our approach perform better than others because it focuses mainly on the background of image and characteristics of the tree itself. First, we abstract the original tree image using bilateral filtering and image pyramid from multiple perspectives, which can reduce the influence of the background and tree canopy gaps on clustering. Spatial location and gray scale features are obtained by step detection and the insertion rule method, respectively. Bandwidths calculated by spatial location and gray scale features are then used to determine the size of the Gaussian kernel function and in the mean shift clustering. Furthermore, the flood fill method is employed to fill the results of clustering and highlight the region of interest. To prove the effectiveness of tree image abstractions on image clustering, we compared different abstraction levels and achieved the optimal clustering results. For our algorithm, the average segmentation accuracy (SA), over-segmentation rate (OR), and under-segmentation rate (UR) of the crown are 91.21%, 3.54%, and 9.85%, respectively. The average values of the trunk are 92.78%, 8.16%, and 7.93%, respectively. Comparing the results of our method experimentally with other popular tree image segmentation methods, our segmentation method get rid of human interaction and shows higher SA. Meanwhile, this work shows a promising application prospect on visual reconstruction and factors measurement of tree.
Ting Xu,Xicheng Wang,Ying Xin,Zhenghang Wang,Jifang Gong,Xiaotian Zhang,Yanyan Li,Congcong Ji,Yu Sun,Feilong Zhao,Depei Huang,Yuezong Bai,Jian Li,Lin Shen 대한암학회 2023 Cancer Research and Treatment Vol.55 No.2
Purpose The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.
Ting Xu,Fei Yao,Wu-Sheng Liang,Yong-Hong Li,Dian-Rong Li,Hao Wang,Zheng-Yi Wang 한국미생물학회 2012 The journal of microbiology Vol.50 No.4
Sclerotinia sclerotiorum is a cosmopolitan, filamentous, fungal pathogen that can cause serious disease in many kinds of crops. Alternative oxidase is the terminal oxidase of the alternative mitochondrial respiratory pathway in fungi and higher plants. We report the presence of this alternative pathway respiration and demonstrate its expression in two isolates of S. sclerotiorum under unstressed, normal culture conditions. Application of salicylhydroxamic acid, a specific inhibitor of alternative oxidase, severely inhibited the mycelial growth of S. sclerotiorum both on potato dextrose agar plates and in liquid culture media. Inhibition of alternative oxidase could influence the growth pattern of S. sclerotiorum,as salicylhydroxamic acid treatment induced obvious aerial mycelia growing on potato dextrose agar plates. Under the treatment with salicylhydroxamic acid, S. sclerotiorum formed sclerotia much more slowly than the control. Treatment with hydrogen peroxide in millimolar concentrations greatly decreased the growth rate of mycelia and delayed the formation of sclerotia in both tested S. sclerotiorum isolates. As well, this treatment obviously increased their alternative pathway respiration and the levels of both mRNA and protein of the alternative oxidase. These results indicate that alternative oxidase is involved in the regulation of growth, development,and resistance to oxidative stress of S. sclerotiorum.
Xu, Na,Lei, Zhen,Li, Xiao-Long,Zhang, Jun,Li, Chen,Feng, Guo-Quan,Li, Di-Nuo,Liu, Jing-Yi,Wei, Qiang,Bian, Ting-Ting,Zou, Tian-Yu Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1
Objectives: To explore the correlation between multi-slice spiral CT (MSCT) perfusion parameters and the expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-2 (MMP-2) in breast cancer. Methods: Forty five breast cancer patients and 16 patients with benign breast tumor, both confirmed by pathology examination, were enrolled. All underwent MSCT perfusion imaging to obtain perfusion maps and data for parameters including blood flow (BF), blood volume (BV) and permeability surface (PS). Cancer patients did not receive treatment prior to surgery. The expression of VEGF and MMP-2 were examined with both immunohistochemistry and Western blotting. Results: The levels of VEGF and MMP-2 by immunohistochemistry were significantly higher in the breast cancer group (P < 0.01) than the benign tumor group. Relative OD values from Western blotting were also higher in cancer cases (P < 0.05). Similarly, the mean MSCT perfusion parameters (BF, BV, PS) were significantly higher in the breast cancer group (P < 0.01), BF and BV positively correlating with VEGF expression (r = 0.878 and 0.809 respectively, P < 0.01); PS and VEGF and MMP-2 expression were also positively correlated (r= 0.860, 0.786 respectively, P < 0.01). Conclusion: There is a correlation between breast cancer MSCT perfusion parameters and VEGF andMMP-2 expression, which might be useful for detection of breast lesions, qualitative diagnosis of breast cancer, and evaluation of breast cancer treatment.
Ting Xu,Ya-Ting Wang,Wu-Sheng Liang,Fei Yao,Yong-Hong Li,Dian-Rong Li,Hao Wang,Zheng-Yi Wang 한국미생물학회 2013 The journal of microbiology Vol.51 No.3
Sclerotinia sclerotiorum is a filamentous fungal pathogen that can infect many economically important crops and vegetables. Alternative oxidase is the terminal oxidase of the alternative respiratory pathway in fungal mitochondria. The function of alternative oxidase was investigated in the regulation of sensitivity of S. sclerotiorum to two commercial fungicides, azoxystrobin and procymidone which have different fungitoxic mechanisms. Two isolates of S. sclerotiorum were sensitive to both fungicides. Application of salicylhydroxamic acid, a specific inhibitor of alternative oxidase, significantly increased the values of effective concentration causing 50% mycelial growth inhibition (EC50) of azoxystrobin to both S. sclerotiorum isolates, whereas notably decreased the EC50 values of procymidone. In mycelial respiration assay azoxystrobin displayed immediate inhibitory effect on cytochrome pathway capacity, but had no immediate effect on alternative pathway capacity. In contrast, procymidone showed no immediate impact on capacities of both cytochrome and alternative pathways in the mycelia. However, alternative oxidase encoding gene (aox) transcript and protein levels, alternative respiration pathway capacity of the mycelia were obviously increased by pre-treatment for 24 h with both azoxystrobin and procymidone. These results indicate that alternative oxidase was involved in the regulation of sensitivity of S. sclerotiorum to the fungicides azoxystrobin and procymidone, and that both fungicides could affect aox gene expression and the alternative respiration pathway capacity development in mycelia of this fungal pathogen.