Xiao Yang

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (218)822.11 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Arsenic, a ubiquitous presence in the biosphere, often occurs from both natural and anthropogenic sources. Bacterial biosensors based on genetically engineered bacteria have promising applications in detecting the chemical compound and its toxicity. However, most of the bactiria biosensor takes advantage of the existing wild-type substrate-induced promoters, which are often low in specificity, affinity and sensitivity, and thus limiting their applications in commercial or field use. In this study, we developed an in vivo evolution procedure with bi-directional selection scheme for improving the sensitivity of arsenite-responsive bacterial biosensor through optimization of the inducible operon. As a proof of concept, we evolved the arsenite-induced arsR operon for both low background and high expression through three successive rounds of fluorescence activated cell sorting (FACS) with bi-directional strategy. An arsR operon variant with 12-fold higher activity over the control was isolated, confirming multiple rounds of construction and screening of mutation library, as described here, can be efficiently applied to bacterial biosensor optimization. The evolved arsenite-responsive biosensor demonstrated an excellent performance in the detection of low trace arsenite in environmental water. These results indicate that the technologies of directed evolution could be used to improve the performance of bacterial biosensors, which will be helpful in promoting the practical application of bacterial biosensors.
    Environmental Science & Technology 04/2015; DOI:10.1021/acs.est.5b00832 · 5.48 Impact Factor
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    ABSTRACT: Zfp57 is a maternal-zygotic effect gene that maintains genomic imprinting. Here we report that Zfp57 mutants exhibited a variety of cardiac defects including atrial septal defect (ASD), ventricular septal defect (VSD), thin myocardium, and reduced trabeculation. Zfp57 maternal-zygotic mutant embryos displayed more severe phenotypes with higher penetrance than the zygotic ones. Cardiac progenitor cells exhibited proliferation and differentiation defects in Zfp57 mutants. ZFP57 is a master regulator of genomic imprinting, so the DNA methylation imprint was lost in embryonic heart without ZFP57. Interestingly, the presence of imprinted DLK1, a target of ZFP57, correlated with NOTCH1 activation in cardiac cells. These results suggest that ZFP57 may modulate NOTCH signaling during cardiac development. Indeed, loss of ZFP57 caused loss of NOTCH1 activation in embryonic heart with more severe loss observed in the maternal-zygotic mutant. Maternal and zygotic functions of Zfp57 appear to play redundant roles in NOTCH1 activation and cardiomyocyte differentiation. This serves as an example of a maternal effect that can influence mammalian organ development. It also links genomic imprinting to NOTCH signaling and particular developmental functions.
    Proceedings of the National Academy of Sciences 04/2015; DOI:10.1073/pnas.1415541112 · 9.81 Impact Factor
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    ABSTRACT: To perform a profiling analysis of changes in intestinal microRNA (miRNA) expression during hypothermic circulatory arrest (HCA). A total of eight piglets were randomly divided into HCA and sham operation (SO) groups. Under general anesthesia, swine in the HCA group were subjected to hypothermic cardiopulmonary bypass at 24 °C followed by 80 min of circulatory arrest, and the reperfusion lasted for 180 min after cross-clamp removal. The counterparts in the SO group were only subjected to median sternotomy. Histopathological analysis was used to detect mucosal injury, and Pick-and-Mix custom miRNA real-time polymerase chain reaction (PCR) panels containing 306 unique primer sets were utilized to assay unpooled intestinal samples harvested from the two groups. The intestinal mucosa of the animals that were subjected to 24 °C HCA exhibited representative ischemic reperfusion injury of grade 2 or 3 according to the Chiu score. Such intestinal mucosal injuries, with the subepithelial space and epithelial layer lifting away from the lamina propria, were accompanied by shortened and irregular villi. On the contrary, the intestinal mucosa remained normal in the sham-operated animals. In total, twenty-five miRNAs were differentially expressed between the two groups (15 upregulated and 10 downregulated in the HCA group). Among these, eight miRNAs (miR-122, miR-221-5p, miR-31, miR-421-5p, miR-4333, miR-499-3p, miR-542 and let-7d-3p) were significantly dysregulated (four higher and four lower). The expression of miR-122 was significantly (5.37-fold) increased in the HCA group vs the SO group, indicating that it may play a key role in HCA-induced mucosal injury. Exposure to HCA caused intestinal miRNA dysregulation and barrier dysfunction in swine. These altered miRNAs might be related to the protection or destruction of the intestinal barrier.
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    ABSTRACT: Protein-energy wasting (PEW) is strongly associated with high mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. However, its clinical assessment has not been well defined. The aim of the present study was to investigate the relationship between combined nutritional indicators and mortality in CAPD patients. In the present retrospective cohort study, a total of 885 incident CAPD patients were enrolled. Nutritional status at the initiation of CAPD was assessed by BMI and biochemical indices (serum albumin, prealbumin, transferrin, creatinine and total cholesterol). The primary outcome was all-cause mortality. Principal components factor analysis was used to identify the combined nutritional parameters. Their association with mortality was examined by multivariable-adjusted Cox models. The mean age was 47·4 (sd 14·8) years, 59·2 % (n 524) were male and 24·6 % (n 218) were diabetic. Of the total patients, 130 (14·7 %) had BMI < 18·5 kg/m2, 439 (49·6 %) had albumin < 38 g/l ( < 3·8 g/dl), 303 (34·2 %) had prealbumin < 300 mg/l ( < 30 mg/dl), 404 (45·6 %) had transferrin < 2 g/l ( < 200 mg/dl), 501 (56·6 %) had total cholesterol < 5·2 mmol/l ( < 200 mg/dl) and 466 (52·7 %) had creatinine < 707 μmol/l ( < 8 mg/dl). Overall, three components such as visceral proteins, muscle-mass surrogate and BMI were extracted, which explained 69·95 % of the total variance of the nutritional parameters. After adjusting for demographic variables, co-morbid conditions, Hb, TAG and high-sensitivity C-reactive protein, the factor score of visceral proteins including albumin, prealbumin and transferrin was independently associated with mortality (hazard ratio 0·73, 95 % CI 0·60, 0·89; P= 0·002). Lower visceral protein concentrations may be independently associated with higher mortality in incident CAPD patients. Simultaneous measurements of serum albumin, prealbumin and transferrin could be helpful to monitor PEW.
    British Journal Of Nutrition 01/2015; 113(04):1-7. DOI:10.1017/S0007114514004061 · 3.34 Impact Factor
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    ABSTRACT: Accumulating evidence indicates that some miRNAs could form feedback loops with their targets to fine-tune tissue homeostasis, while disruption of these loops constitutes an essential step towards human tumorigenesis. In this study, we report the identification of a novel negative feedback loop formed between miR-139 and its oncogenic target Jun. In this loop, miR-139 could inhibit Jun expression by targeting a conserved site on its 3'-UTR, whereas Jun could induce miR-139 expression in a dose dependent manner through a distant upstream regulatory element. Interestingly, aberration in this loop was found in human gastric cancer, where miR-139 was down-regulated and inversely correlated with Jun expression. Further functional analysis showed that restored expression of miR-139 in gastric cancer cells significantly induces apoptosis, and inhibits cell migration and proliferation as well as tumour growth through targeting Jun. Thus, our data strongly suggests a role of aberrant miR-139/Jun negative feedback loop in the development of human gastric cancer and miR-139 as a potential therapeutic target for gastric cancer. Given that miR-139 and Jun are deregulated in many cancers, our findings here might have broader implication in other types of human cancers.
    Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 12/2014; 1853(2). DOI:10.1016/j.bbamcr.2014.12.002 · 5.30 Impact Factor
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    ABSTRACT: In mouse, continuous growth of the postnatal incisor is coordinated by two populations of multipotent progenitor cells, the dental papilla mesenchymal cells and dental epithelial stem cells, residing at the proximal end of the incisor, yet the molecular mechanism underlying the cooperation between mesenchymal and epithelial cells is largely unknown. Here, TGF-β type II receptor (Tgfbr2) was specifically deleted within the postnatal dental papilla mesenchyme. The Tgfbr2-deficient mice displayed malformed incisors with wavy mineralized structures at the labial side as a result of increased differentiation of dental epithelial stem cells. We found that mesenchymal Tgfbr2 disruption led to upregulated expression of Wnt5a and downregulated expression of Fgf3/10 in the mesenchyme, both of which synergistically enhanced Lrp5/6-β-catenin signaling in the cervical loop epithelium. In accord with these findings, mesenchyme-specific depletion of the Wnt transporter gene Wls abolished the aberrant mineralized structures caused by Tgfbr2 deletion. Thus, mesenchymal TGF-β signaling provides a unifying mechanism for the homeostasis of dental epithelial stem cells via a Wnt signaling mediated mesenchymal–epithelial cell interaction. Stem Cells 2014
    Stem Cells 11/2014; 32(11). DOI:10.1002/stem.1772 · 7.70 Impact Factor
  • Xueqing Yu, Xiao Yang
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    ABSTRACT: Due to limited medical and economic resources, particularly in the countryside and remote areas, the proportion of individuals with end-stage kidney disease who are treated with dialysis in China is only about 20%. For the rest, renal replacement therapy currently is not available. Peritoneal dialysis (PD) has been developed and used for more than 30 years in China to treat patients with end-stage kidney disease. Several national PD centers of first-rate scale and quality have sprung up, but the development of PD varies widely among geographic regions across China. The Chinese government has dedicated itself to continually increasing the coverage and level of medical service for patients with end-stage kidney disease. Under the guidance of the government and because of promotion by kidney care professionals, presently there are more than 40,000 prevalent PD patients in China, representing approximately 20% of the total dialysis population. Recently, a National Dialysis Unit Training Program for countywide hospitals has been initiated. Through the efforts of programs like this, we believe that awareness of PD and advances in the underlying technology will benefit more patients with end-stage kidney disease in China. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 11/2014; 65(1). DOI:10.1053/j.ajkd.2014.08.023 · 5.76 Impact Factor
  • Clinical Chemistry and Laboratory Medicine 09/2014; DOI:10.1515/cclm-2014-0770 · 2.96 Impact Factor
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    ABSTRACT: Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine involved in the pathogenesis of spontaneous preterm birth (SPTB). We examined whether the MCP-1 G-2518A polymorphism is associated with the risk of SPTB in a Chinese population. The MCP-1 G-2518A polymorphism was genotyped in 569 preterm singleton neonates and in 673 term neonates using polymerase chain reaction-restriction fragment length polymorphism analysis. The distribution of the MCP-1 G-2518A genotype and the allele frequencies between the SPTB patients and the controls were not significantly different in the overall sample. However, we found that the AA genotype was associated with significantly increased susceptibility to very SPTB (<32 weeks) [odds ratio (OR) 2.07; 95 % confidence interval (CI), 1.27-3.36; P = 0.005) and extremely SPTB (<28 weeks) (OR 2.74; 95 % CI, 1.10-6.72; P = 0.014) compared with -2518G-positive genotypes (GG + GA genotypes). When extremely preterm neonates and very preterm neonates were combined, the AA genotype was also significantly associated with increased susceptibility to SPTB (OR 2.23; 95 % CI, 1.40-3.54; P < 0.001). The MCP-1 G-2518A polymorphism was not associated with increased susceptibility to SPTB in patients with premature rupture of the membranes (PROM) or in those without PROM. Our findings suggest that the MCP-1 G-2518A polymorphism may plays a role in mediating the susceptibility to SPTB in the Chinese population. Knowledge of genetic factors contributing to the pathogenesis of SPTB may have implications for screening and treatment of this disorder.
    Molecular Genetics and Genomics 09/2014; 290(1). DOI:10.1007/s00438-014-0921-6 · 2.83 Impact Factor
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    ABSTRACT: BackgroundThe first episode of peritonitis affects survival of the peritoneal membrane as a medium for dialysis as well as survival of patients. The aim of this study is to investigate risk factors associated with the first episode of peritonitis in Southern Chinese continuous ambulatory peritoneal dialysis (CAPD) patients.MethodsThis is a single-center, retrospective, cohort study. All incident CAPD patients from 1 January 2006 to 31 December 2010 were recruited, and followed up until their first episode of peritonitis or 31 December, 2012. Baseline demographic, socioeconomic, clinical and laboratory data were collected. Cox proportional model was used to determine the factors associated with the first episode of peritonitis.ResultsIn a cumulative 30756.5 patient-months follow-up (the median vintage 26.1 months) of 1117 CAPD patients, 309(27.7%) patients presented the first episodes of peritonitis. The cumulative peritonitis-free survival was 86.2%, 78.1%, 71.4% and 57.8% at 1, 2, 3 and 5 year, respectively. The multivariate analysis showed that factors associated with risk for the first episode of peritonitis were elderly patients (>65 years) [hazard ratio (HR) = 1.427, 95% confidence interval (CI) = 1.051 to 1.938, P = 0.023], male(HR = 1.315, 95% CI = 1.028 to 1.684, P = 0.030), lower education level (HR = 1.446, 95% CI: 1.127 to 1.855, P = 0.004) and albumin <38g/L (HR = 1.425, 95% CI: 1.112 to 1.825, P = 0.005).ConclusionsOlder age, male, lower educational level and hypoalbuminemia at the commencement of PD were the risk factors associated with the first episode of peritonitis in Southern Chinese CAPD patients.
    PLoS ONE 09/2014; 9(9):e107485. DOI:10.1371/journal.pone.0107485 · 3.53 Impact Factor
  • Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 09/2014; DOI:10.3747/pdi.2013.00332 · 2.20 Impact Factor
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    Cell Research 08/2014; 24(10). DOI:10.1038/cr.2014.111 · 11.98 Impact Factor
  • International Journal of Cardiology 08/2014; 176(3). DOI:10.1016/j.ijcard.2014.08.030 · 6.18 Impact Factor
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    ABSTRACT: Cystatin play an important role in parasite immune evasion. It is involved in many immune responses processes regulations such as inhibiting antigen presentation, modifying cytokines production and macrophage polarization. In recent years, more and more cystatins were used in treating some inflammatory diseases such as asthma and inflammation bowel diseases; however, cystatins from Schistosoma japonicum were rarely studied. In the present study, we have cloned a cystatin from the adult stage of Schistosoma japonicum, named as SjCystatin, and its sequence shares conserved domains with other type II family cystatins. It was further verified by enzyme inhibition assays. SjCystatin retained its inhibitory activity under a wide range of pH values and temperatures, can maintain its inhibitory activity at pH 6.5-7.5 and 37 °C, respectively. Then, we investigated the effects of SjCystatin on the lipopolysaccharide (LPS)-induced activated RAW264.7. Results showed that SjCystatin inhibit LPS-induced nitric oxide production in a dose-dependent manner. LPS-induced TNF-α and IL-6 production began to be inhibited at least 6 h after SjCystatin stimulation. SjCystatin significantly increased IL-10 production at 6 h after stimulation and its effect on IL-10 production diminished quickly. These results imply that SjCystatin can induce M2 macrophage polarization and can be expected to serve as a potential drug source for the medication of inflammatory disorders like other cystatins.
    Parasitology Research 08/2014; 113(11). DOI:10.1007/s00436-014-4064-9 · 2.33 Impact Factor
  • Yu Lan, Wenyan He, Bing Liu, Xiao Yang
    Experimental Hematology 08/2014; 42(8S):S44. DOI:10.1016/j.exphem.2014.07.163 · 2.81 Impact Factor
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    ABSTRACT: Retinoic acid-inducible gene I (RIG-I) is an intracellular RNA virus sensor that induces type I interferon-mediated host protective innate immunity against viral infection. Although cylindromatosis (CYLD) has been shown to negatively regulate innate antiviral response by removing K-63-linked polyubiquitin from RIG-I, the regulation of its expression and the underlying regulatory mechanisms are still incompletely understood. Here we show that RIG-I activity is regulated by miR-526a-mediated inhibition of CYLD expression. We found that viral infection specifically upregulates miR-526a expression in macrophages via IRF-dependent mechanisms. In turn, miR-526a positively regulates virus-triggered type I Interferon (IFN-I) production, thus suppressing viral replication, the underlying mechanism of which is the enhancement of RIG-I K63-linked ubiquitination by miR-526a via suppressing the expression of CYLD. Remarkably, viral-induced miR-526a upregulation and CYLD downregulation are blocked by enterovirus 71 (EV71) 3C protein, while ectopic miR-526a expression inhibits the replication of EV71 virus. The collective results of this study suggest a novel mechanism of the regulation of RIG-I activity during RNA virus infection by miR-526a and propose a novel mechanism for the evasion of innate immune response controlled by EV71.
    Journal of Virology 07/2014; 88(19). DOI:10.1128/JVI.01400-14 · 4.65 Impact Factor
  • Xiaoguang Fan, LEI Ming, XIAO Yang
    WCS2014; 07/2014
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    ABSTRACT: We have shown recently that endothelial Grb-2-associated binder 1 (Gab1), an intracellular scaffolding adaptor, has a protective effect against limb ischemia via mediating angiogenic signaling pathways. However, the role of Gab1 in cardiac ischemia/reperfusion (I/R) injury remains unknown. In this study, we show that Gab1 is required for cardioprotection against I/R injury. I/R injury led to remarkable phosphorylation of Gab1 in cardiomyocytes. Compared with controls, the mice with cardiomyocyte-specific deletion of Gab1 gene (CGKO mice) exhibited an increase in infarct size and a decrease in cardiac function after I/R injury. Consistently, in hearts of CGKO mice subjected to I/R, the activation of caspase 3 and myocardial apoptosis was markedly enhanced whereas the activation of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK), which are critical for cardiomyocyte survival, was attenuated. Oxidative stress is regarded as a major contributor to myocardial I/R injury. To examine the role of Gab1 in oxidative stress directly, isolated adult cardiomyocytes were subject to oxidant hydrogen peroxide and the cardioprotective effects of Gab1 were confirmed. Furthermore, we found that the phosphorylation of Gab1 and Gab1-mediated activation of Akt and MAPK by oxidative stress was suppressed by ErbB receptor and Src kinase inhibitors, accompanied by an increase in apoptotic cell death. In conclusion, our results suggest that Gab1 is essential for cardioprotection against I/R oxidative injury via mediating survival signaling.
    Archiv für Kreislaufforschung 07/2014; 109(4):420. DOI:10.1007/s00395-014-0420-2 · 5.96 Impact Factor
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    ABSTRACT: Objectives The study was to investigate the prevalence and associated factors of erectile dysfunction (ED) in peritoneal dialysis (PD) patients. Methods This was a cross-sectional survey. Eligible patients were interviewed by questionnaire: the five-item version of International Index of Erectile Function. Residual renal function (RRF) was assessed by daily urine volume and residual glomerular filtration rate. Results Totally, 176 male prevalent PD patients were interviewed, six of them were not included in analysis for sexually inactive unrelated to ED. The prevalence of ED was 80.6 %. After adjusting for confounding factors, advance age (P = 0.014), less daily urine volume (P = 0.032) and higher high-sensitivity C-reactive protein (hs-CRP) (P = 0.043) were independent risk factors for the development of ED. Conclusion The prevalence of ED was high in Chinese PD patients. Advanced age, poor RRF and higher hs-CRP were independently associated with the prevalence of ED.
    International Urology and Nephrology 06/2014; 47(2). DOI:10.1007/s11255-014-0767-1 · 1.29 Impact Factor
  • Xueqing Yu, Xiao Yang, Naya Huang
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    ABSTRACT: Managing a rapidly growing peritoneal dialysis program with more than 1000 patients involves multiple challenges, labor constraints, logistics, and excessive geographic distance. This paper describes how Sun Yat-sen University, Guangzhou, China, manages those issues, while simultaneously improving quality of the care and, subsequently, clinical outcomes.
    Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 06/2014; 34(Supplement 2):S31-S34. DOI:10.3747/pdi.2013.00122 · 2.20 Impact Factor

Publication Stats

3k Citations
822.11 Total Impact Points


  • 2004–2015
    • Sun Yat-Sen University
      • • Department of Medical Oncology
      • • The First Affiliated Hospital
      Shengcheng, Guangdong, China
  • 2002–2015
    • Sun Yat-Sen University of Medical Sciences
      • • Department of Nephrology
      • • First Affiliated Hospital
      Shengcheng, Guangdong, China
  • 2001–2014
    • Fuerkang Beijing Institute of Biotechnology
      Peping, Beijing, China
  • 2007–2013
    • Shanghai University
      • Department of Automation
      Shanghai, Shanghai Shi, China
    • University of Rochester
      Rochester, New York, United States
  • 2012
    • Xinqiao Hospital
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2010–2012
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China
    • Lanzhou University
      • School of Life Science
      Lanzhou, Gansu Sheng, China
  • 2009–2012
    • Chinese Academy of Sciences
      • Graduate School
      Peping, Beijing, China
    • 307 Hospital of the Chinese People's Liberation Army
      Peping, Beijing, China
  • 2000–2012
    • Academy of Military Medical Sciences
      T’ien-ching-shih, Tianjin Shi, China
  • 2011
    • Hunan University
      Ch’ang-sha-shih, Hunan, China
  • 2003–2009
    • Government of the People's Republic of China
      Peping, Beijing, China
    • Henan Provincial People’s Hospital
      Cheng, Henan Sheng, China
  • 2006
    • Peking Union Medical College Hospital
      Peping, Beijing, China
  • 2005
    • Second Military Medical University, Shanghai
      Shanghai, Shanghai Shi, China
    • Guangzhou First People's Hospital
      Shengcheng, Guangdong, China
  • 1997–2002
    • National Institutes of Health
      • • Branch of Genetics of Development and Disease (GDDB)
      • • Laboratory of Metabolism
      Bethesda, MD, United States