Entity

Time filter

Source Type


Yan B.,George Washington University | Yan B.,Jining Medical College Affiliated Hospital | Neilson K.M.,George Washington University | Ranganathan R.,Kings College London | And 3 more authors.
Developmental Dynamics | Year: 2015

Background: Six1 plays an important role in the development of several vertebrate organs, including cranial sensory placodes, somites, and kidney. Although Six1 mutations cause one form of branchio-otic syndrome (BOS), the responsible gene in many patients has not been identified; genes that act downstream of Six1 are potential BOS candidates. Results: We sought to identify novel genes expressed during placode, somite and kidney development by comparing gene expression between control and Six1-expressing ectodermal explants. The expression patterns of 19 of the significantly up-regulated and 11 of the significantly down-regulated genes were assayed from cleavage to larval stages. A total of 28/30 genes are expressed in the otocyst, a structure that is functionally disrupted in BOS, and 26/30 genes are expressed in the nephric mesoderm, a structure that is functionally disrupted in the related branchio-otic-renal (BOR) syndrome. We also identified the chick homologues of five genes and show that they have conserved expression patterns. Conclusions: Of the 30 genes selected for expression analyses, all are expressed at many of the developmental times and appropriate tissues to be regulated by Six1. Many have the potential to play a role in the disruption of hearing and kidney function seen in BOS/BOR patients. © 2014 Wiley Periodicals, Inc. Source


Wu G.,Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis | Wei G.,Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis | Wei G.,Jining Medical College Affiliated Hospital | Huang J.,Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis | And 4 more authors.
European Journal of Clinical Investigation | Year: 2011

Background Coronary artery disease (CAD) is a common and multifactorial arterial disease that is mainly caused by atherosclerosis. Macrophages, lymphocytes and neutrophils have been implicated in atherosclerotic plaque development. Autophagy, a highly conserved cellular process for the removal of long-lived protein and organelles, plays a variety of pathophysiological roles. However, the roles of autophagy in peripheral leucocytes in atherosclerosis and CAD have not been explored. Materials and methods LC3 is a marker gene for autophagy, and LC3-II, a conjugated form of LC3 protein, is a membrane marker for autophagosome and autophagolysosomes. In this study, LC3 gene expression levels and LC3-II protein levels in peripheral leucocytes were measured in patients with CAD (n=146) and healthy controls (n=87). Results In patients with CAD, LC3 gene expression levels in the peripheral leucocytes were significantly decreased compared with age- and sex-matched healthy controls (P<0·01). LC3-II protein levels were also significantly decreased in patients with CAD (P<0·01). Multivariate logistic analyses showed that decreased LC3 gene expression levels were strongly associated with CAD. There were no differences in LC3 transcripts and LC3-II protein levels between subgroups of patients with CAD. Conclusions LC3 gene expression in the peripheral leucocytes was significantly decreased in patients with CAD, indicating that autophagosome formation is decreased. These data suggest that autophagy in circulating leucocytes may be involved in the pathogenesis of atherosclerosis and CAD. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation. Source


Li Q.-X.,Huazhong University of Science and Technology | Li Q.-X.,Jining Medical College Affiliated Hospital | Fu Q.-Q.,Huazhong University of Science and Technology | Shi S.-W.,Huazhong University of Science and Technology | And 7 more authors.
Heart | Year: 2010

Objective: The purpose of this study was to evaluate the relationship between human plaque fibrous cap thickness detected by intravascular optical coherence tomography (OCT) and the plasma levels of inflammatory factors in patients with coronary artery disease (CAD). Methods and Results: OCT was used to measure the fibrous cap thickness of coronary artery atherosclerotic plaques in patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP) and stable angina pectoris (SAP). Plasma levels of inflammatory factors including highly sensitive C-reactive protein (hs-CRP), IL-18 and tumour necrosis factor alpha (TNFα) were detected by ELISA, and peripheral white blood cell (WBC) counts were performed. The results demonstrated that the plasma levels of inflammatory factors and WBC count were correlated inversely with fibrous cap thickness (r = -0.775 for hs-CRP, r = -0.593 for IL-18, r = -0.60 for TNFα and r = -0.356 for WBC count). Patients with cap thickness less than 65 mm (defined to be thin cap fibroatheromas; TCFA) had higher plasma levels of inflammatory factors as well as WBC counts than those with thicker fibrous caps. Receiver operator characteristic (ROC) curves for hs-CRP, IL-18, TNFα and WBC count, which displayed the capability of prediction about TCFA, showed the area under the curves were 0.95, 0.86, 0.79 and 0.70 (p<0.05), respectively. ROC curve analysis confirmed that an hs-CRP cut-off at 1.66 mg/l would detect TCFA with a sensitivity of 96% and a specificity of 90%, and was the strongest independent predictor of TCFA. Conclusion: There is an inverse linear correlation between fibrous cap thickness and plasma levels of inflammatory markers. The plasma hs-CRP concentration is the strongest independent predictor of TCFA. Source


Wu G.,Jining Medical College Affiliated Hospital | Wang X.,Jining Medical College Affiliated Hospital | Feng X.,Jining Medical College Affiliated Hospital | Zhang A.,Jining Medical College Affiliated Hospital | And 7 more authors.
Brain Research | Year: 2011

Parkinson's disease (PD) is a progressive neurodegenerative disease caused by interaction of genetic and environmental factors. To date, genetic genes and variants causing PD remain largely unknown. Autophagy is a conserved cellular process including three subtypes, macroautophagy (hereafter referred to as autophagy), microautophagy and chaperone-mediated autophagy (CMA). Although reduced CMA and induced autophagy are observed in human PD brain samples, cell and animal PD models, CMA and autophagy have not been systemically studied in sporadic PD patients. In the peripheral leukocytes of sporadic PD patients, we examined gene expression levels of lysosome-associated membrane 2 (LAMP-2), a CMA receptor and a limiting step, and microtubule-associated protein 1 light chain 3 (LC3), product of which is sequentially cleaved and lipidated to form LC3-II as an autophagosome marker. Compared to age- and sex-matched healthy controls, LAMP-2 gene expression and protein levels in sporadic PD patients were significantly decreased, which may lead to reduced CMA activity and impaired fusion of autophagosome and lysosome. LC3 gene expression and LC3-II protein levels were significantly increased in sporadic PD patients, suggesting that autophagosomes are accumulated. Our findings, decreased LAMP-2 gene expression and increased LC3 gene expression, are consistent to the previous studies with dopaminergic neuronal cells in vitro and in vivo, which may contribute to the pathogenesis of sporadic PD by altering CMA and autophagy activities. The genetic causes leading to decreased LAMP-2 gene expression need further investigation and genetic or pharmacological restoration of LAMP-2 might be a novel strategy for treating PD patients. Source


Zhang A.,Jining Medical College Affiliated Hospital | Wang H.,Jining Medical College | Qin X.,Jining Medical College Affiliated Hospital | Pang S.,Jining Medical College Affiliated Hospital | Yan B.,Jining Medical College Affiliated Hospital
Biochemical and Biophysical Research Communications | Year: 2012

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. To date, genetic causes and underlying molecular mechanisms for sporadic PD remain largely unknown. Sirtuis are highly conserved NAD-dependent class III deacetylases. SIRT1, the closest to yeast Sir2, has deacetylase activity and ADP-ribosyltransferase activity. SIRT1 gene has been connected to many cellular processes and implicated in human diseases, such as obesity, type 2 diabetes, cancer and neurodegenerative diseases. Studies in animal model have also associated SIRT1 with aggregation of alpha-synuclein, a critical protein in the PD pathogenesis. We hypothesized that the genetic variants within the regulatory regions of SIRT1 gene that repress its gene expression, rather than mutations in its coding region that abolish SIRT1 function, may contribute to PD as a risk factor. In this study, we genetically analyzed the promoter region of SIRT1 gene in sporadic PD patients and ethic-matched healthy controls. Three novel heterozygous sequence variants, g.69644133C>G, g.69644213G>A and g.69644351G>A, were identified in PD patients, but in none of controls, which may alter the transcriptional activities of SIRT1 gene promoter, resulting in reduced SIRT1 levels. One novel heterozygous variant, g.69644219G>A, linked with single-nucleotide polymorphism - g.69644217A>C (rs932658), was only found in one control, which may have no functional activity. Therefore, our results suggested that genetic variants within the SIRT1 gene promoter may repress SIRT1 gene expression, contributing to PD as a risk factor. © 2012 Elsevier Inc.. Source

Discover hidden collaborations