Publications

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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, which begins with isolated steatosis and advances to nonalcoholic steatohepatitis (NASH), steatofibrosis, and cirrhosis. The pathways involved in disease progression are not understood. Loss-of-function mutations in Wnt coreceptor LDL receptor-related protein 6 (LRP6) underlie early-onset atherosclerosis, metabolic risk factors, and NAFLD in humans by unknown mechanisms. We generated mice with the human disease-associated LRP6(R611C) mutation and phenotypically characterized their liver. Homozygote LRP6(R611C) (LRP6(mut/mut)) mice exhibited both steatohepatitis and steatofibrosis. These traits were associated with increased activity of the noncanonical Wnt/Ras homolog family member A, Rho-associated protein kinase 2, and PKC-α/-μ pathways. Accordingly, there was increased TGF-β1 activity, coupled with enhanced expression of smooth muscle α-actin and vimentin that colocalized with albumin in LRP6(mut/mut) mouse liver. LRP6 knockdown reprogramed HepG2 cells to express both these markers, linking impaired Wnt signaling with hepatocyte transdifferentiation. The causal link between altered Wnt signaling and NASH was established by normalization of the disease pathways and rescue of the liver traits by Wnt3a administration to LRP6(mut/mut) mice. Thus, this study identifies diverse disease pathways that underlie a spectrum of NASH-related liver diseases and are linked by a single human genetic variant. LRP6 and noncanonical Wnt pathways are important potential therapeutic targets against NASH.-Wang, S., Song, K., Srivastava, R., Dong, C., Go, G.-W., Li, N., Iwakiri, Y., Mani, A. Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a. © FASEB.
    The FASEB Journal 04/2015; DOI:10.1096/fj.15-271171 · 5.48 Impact Factor
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    ABSTRACT: This study was aimed to identify the prognostic risk markers for thyroid papillary carcinoma (TPC) by bioinformatics. The clinical data of TPC and their microRNAs (miRNAs) and genes expression profile data were downloaded from The Cancer Genome Atlas. Elastic net-Cox's proportional regression hazards model (EN-COX) was used to identify the prognostic associated factors. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve were used to screen the significant prognostic risk miRNA and genes. Then, the target genes of the obtained miRNAs were predicted followed by function prediction. Finally, the significant risk genes were performed literature mining and function analysis. Total 1046 miRNAs and 20531 genes in 484 cases samples were identified after data preprocessing. From the EN-COX model, 30 prognostic risk factors were obtained. Based on the 30 risk factors, 3 miRNAs and 11 genes were identified from the ROC and KM curves. The target genes of miRNA-342 such as B-cell CLL/lymphoma 2 (BCL2) were mainly enriched in the biological process related to cellular metabolic process and Disease Ontology terms of lymphoma. The target genes of miRNA-93 were mainly enriched in the pathway of G1 phase. Among the 11 prognostic risk genes, v-maf avian musculoaponeurotic fibrosarcoma oncogene homologue F (MAFF), SRY (sex-determining region Y)-box 4 (SOX4), and retinoic acid receptor, alpha (RARA) encoded transcription factors. Besides, RARA was enriched in four pathways. These prognostic markers such as miRNA-93, miRNA-342, RARA, MAFF, SOX4, and BCL2 may be used as targets for TPC chemoprevention.
    Tumor Biology 04/2015; DOI:10.1007/s13277-015-3410-6 · 2.84 Impact Factor
  • Chao Dong, Li Gong, Wen Ouyang
    International Journal of Surgery (London, England) 03/2015; 99(3):1111. DOI:10.1016/j.athoracsur.2014.11.028 · 1.65 Impact Factor
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    Li Gong, Chao Dong, Wen Ouyang
    European Journal of Anaesthesiology 01/2015; DOI:10.1097/EJA.0000000000000211 · 3.01 Impact Factor
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    ABSTRACT: A high rate of glycolytic flux, even in the presence of oxygen, is a key metabolic hallmark of cancer cells. Lactate, the end product of glycolysis, decreases the extracellular pH and contributes to the proliferation, invasiveness and metastasis of tumor cells. CD147 play a crucial role in tumorigenicity, invasion and metastasis; and CD147 also interacts strongly and specifically with monocarboxylate transporter1 (MCT1) that mediates the transport of lactate. The objective of this study was to determine whether CD147 is involved, via its association with MCT1 to transport lactate, in glycolysis, contributing to the progression of thyroid carcinoma. The expression levels of CD147 in surgical specimens of normal thyroid, nodular goiter (NG), well-differentiated thyroid carcinoma (WDTC), and undifferentiated thyroid carcinoma (UDTC) were determined using immunohistochemical techniques. The effects of CD147 silencing on cell proliferation, invasiveness, metastasis, co-localization with MCT1, glycolysis rate and extracellular pH of thyroid cancer cells (WRO and FRO cell lines) were measured after CD147 was knocked-down using siRNA targeting CD147. Immunohistochemical analysis of thyroid carcinoma (TC) tissues revealed significant increases in signal for CD147 compared with normal tissue or NG, while UDTC expressed remarkably higher levels of CD147 compared with WDTC. Furthermore, silencing of CD147 in TC cells clearly abrogated the expression of MCT1 and its co-localization with CD147 and dramatically decreased both the glycolysis rate and extracellular pH. Thus, cell proliferation, invasiveness, and metastasis were all significantly decreased by siRNA. These results demonstrate in vitro that the expression of CD147 correlates with the degree of dedifferentiation of thyroid cancer, and show that CD147 interacts with MCT1 to regulate tumor cell glycolysis, resulting in the progression of thyroid carcinoma.
  • AASLD; 11/2014
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    Dataset: 174127DQJ
    L Gong, C Dong, W Ouyang, Q Qin
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    ABSTRACT: Objectives. To evaluate the learning curve for endoscopic thyroidectomy by the breast approach (ETBBA) based on the cumulative summation (CUSUM) technique. Methods. The study included 110 consecutive patients who underwent ETBBA by a single surgeon between January 2009 and May 2012 at the Xiangya Hospital of Central South University, Changsha, China. The learning curve was evaluated using the CUSUM technique. The patients were chronologically arranged into 3 phases by the CUSUM analysis for operative time. Demographic data and operative parameters were also analyzed. Results. The mean operative time (OT) was 125.3 minutes. The conversion rate for technical difficulties and the definitive complication rate were 6.4% and 10%, respectively. The learning curve was analyzed mainly by OT using the CUSUM technique. There was a significant improvement in the average OT (P < .05) after the first 27 patients and again after the first 67 patients (P < .05). A downward trend in OT was found up to the last patient. There were similarities in gender, tumor size, extent of surgery, blood loss, histology, hospital stay, conversion rate, and complications among the 3 phases. Comparison of 2 neighboring phases also showed no significant differences in age. Conclusions. ETBBA performed by surgeons has a remarkable learning curve. There were 27 cases in the early stage of the learning curve, whereas mastery level could be achieved with 67 cases.
    Surgical Innovation 08/2013; 21(2). DOI:10.1177/1553350613500722 · 1.34 Impact Factor
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    ABSTRACT: BACKGROUNDAIMS: We aimed to investigate the correlation between a disintegrin and metalloprotease with thrombospondin motif 2 (ADAMTS-2) and transforming growth factor-β1 (TGF-β1) in clinical human cirrhotic tissues. The liver tissues of 24 patients (16 cases with cirrhotic portal hypertension as the cirrhosis group and eight cases with healthy livers as the normal group) were collected. Immunohistochemistry and Western blots were performed to evaluate the protein expression levels of ADAMTS-2 and TGF-β1. Western blots for other key mediators of cirrhotic progression, including SMAD2, SMAD3, TGF-β receptor II (TGFβRII), matrix metalloproteinases 2 (MMP2), and tissue inhibitor of matrix metalloproteinases 2 (TIMP2), were also performed. Cirrhotic tissues showed higher percentages of collagen. The protein expression levels of ADAMTS-2 and TGF-β1 were significantly higher in the cirrhotic group as compared to the matched normal group (p<0.05), and there was a positive correlation between these two proteins (r=0.862, p<0.01). The protein expressions of MMP2, TIMP2, and TGFβRII, as well as the phosphorylated forms of SMAD2 and SMAD3, were significant higher in the cirrhotic group (p<0.01 or p<0.05). These findings suggested that ADAMTS-2 and TGF-β1 may play important roles in the pathogenesis of human cirrhosis; specifically, TGF-β1 may induce the expression of ADAMTS-2 through the TGFβ/SMAD pathway.
    Gut and liver 03/2013; 7(2):213-20. DOI:10.5009/gnl.2013.7.2.213 · 1.49 Impact Factor
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    L Gong, C Dong, W Ouyang, Q Qin
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    ABSTRACT: Cancer recurrence is one of the most important causes of cancer-related deaths. In present, it has been revealed that there exist some factors especially opioids being able to affect the recovery of cancer patients in a long period. As the most commonly used potent analgesics in practice, morphine appears to be of crucial importance in the regulation of neoplastic tissues by modulating immune responses and promoting angiogenesis. Indeed, regulatory T cells have been shown to inhibit the response of the immune system to tumor and thereby to worsen prognoses. Some reliable evidences indicate that morphine acts directly on regulatory T cells through VEGFR 2 and opioid receptors present in, both of which play a vital role in the cancer recurrence. In addition, morphine might have a noticeable effect on regulatory T cells by regulating the function of some other immune cells or cytokines, TGF-β and IL-2 for instance. Thus, this paper speculates that morphine could induce cancer recurrence by disturbing the behavior of the regulatory T cells and provides a logical reasoning.
    Medical Hypotheses 01/2013; DOI:10.1016/j.mehy.2012.12.013 · 1.15 Impact Factor
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    ABSTRACT: Objective: To explore the expression and distribution of a disintegrin and metalloprotease with thrombospondin motif (ADAMTS)-2 and transforming growth factor (TGF) -β1 in patients with or without cirrhosis, and to determine their relation. Methods: The liver tissues from 16 patients with cirrhotic portal hypertensive and 8 patients with liver injury were collected in Wuhan General Hospital from March to June, 2010. Immunohistochemistry and Western blot were applied to detect the protein expression of ADAMTS-2 and TGF-β1. Results: Immunohistochemistry showed that the expression of ADAMTS-2 and TGF-β1 was significantly higher in the cirrhotic tissues than that in normal tissues (P<0.05). Western blot also showed the expression of ADAMTS-2 and TGF-β1 in the cirrhosis tissues was significantly higher than that in normal tissues (P<0.05). There was a positive correlation between ADAMTS-2 and TGF-β1 (r=0.862, P<0.01). Conclusion: ADAMTS-2 and TGF-β1 may have a synergistic reaction in promoting liver cirrhosis.
    Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 10/2012; 37(10):1026-30. DOI:10.3969/j.issn.1672-7347.2012.10.010
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    ABSTRACT: To study the clinical features, diagnosis and therapy of thyroid neoplasm in children. A retrospective study was performed on 32 children with thyroid nodular who were underwent operation in Xiangya Hospital between January 2002 and December 2010. Of the 32 cases, there were 23 girls and 9 boys. Six cases were diagnosed as nodular Goiter adenoma and 26 cases were diagnosed as thyroid papillary carcinoma. B-ultrasonic examination showed a 100% accurate rate for the diagnosis of thyroid carcinoma. Fourteen children (44%) were proven to have concurrent Hashimoto's thyroiditis. Twenty-two (69%) children with thyroid carcinoma were found to have lymph metastasis in the lateral neck. The children younger than 10 years showed a high rate of metastasis than those older one (94% vs 56%, P<0.05). All 32 children received a surgical therapy. Subtotal thyroidectomy was performed on the 6 children with nodular Goiter adenoma. Total thyroidectomy (17 cases) or ipsilateral thyroidectomy (9 cases) was performed according to the stage of thyroid carcinoma. The surgical outcomes were followed up for 3 months to 9 years and no recurrence or death occurred. The development and growth were normal in the children. Childhood thyroid nodular attacks girls more than boys, and the frequency of malignancy is high. Hashimoto's thyroiditis is a common concurrent disease. The incidence of local lymph metastasis is high in those younger than 10 years. The surgical therapy for thyroid neoplasm may lead satisfactory outcomes in children.
    Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 09/2011; 13(9):736-9.

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