Jining Medical College Affiliated Hospital

Jining, China

Jining Medical College Affiliated Hospital

Jining, China
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Pang S.,Jining Medical College Affiliated Hospital | Chen D.,Jining Medical College Affiliated Hospital | Zhang A.,Jining Medical College Affiliated Hospital | Qin X.,Jining Medical College Affiliated Hospital | Yan B.,Jining Medical College Affiliated Hospital
Neuroscience Letters | Year: 2012

Parkinson's disease (PD) is a common neurodegenerative disease in the people of over 65. Majority of PD is sporadic, which is caused by interaction of genetic and environmental factors. To date, genetic causes and underlying molecular mechanisms for sporadic PD remain largely unknown. Autophagy is a conserved cellular degradative process, consisting of macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). Macroautophagy (hereafter referred to as autophagy) and CMA are involved in the degradation of alpha-synuclein, a critical protein in the PD pathogenesis. Previous studies with brain tissues and leukocytes have shown that the expression levels of lysosome-associated membrane-2 (LAMP-2) gene are significantly decreased in PD patients. In this study, we genetically and functionally analyze the promoter region of LAMP-2 gene in sporadic PD patients. Two novel sequence variants and two single nucleotide polymorphisms (SNPs) were identified. The heterozygous variant, g.4127A > C, which was only found in one female PD patient, significantly reduced the transcriptional activities of LAMP-2 gene promoter. The hemizygous variant, g.5038G > A, which was only found in one male control, enhanced the transcriptional activities of LAMP-2 gene promoter. No significant difference in frequencies of the SNPs, rs42900 (g.4569A > C) and rs28603270 (g.4760T > G), was observed between PD patients and controls. Collectively, the sequence variants within the LAMP-2 gene promoter may be linked to the PD onset by changing LAMP-2 protein levels and impairing autophagy and CMA activities. © 2012 Elsevier Ireland Ltd.


Yan B.,George Washington University | Yan B.,Jining Medical College Affiliated Hospital | Neilson K.M.,George Washington University | Ranganathan R.,King's 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.


PubMed | The University of Oklahoma Health Sciences Center, Xiangyang Central Hospital, Suizhou Central Hospital, University of Pennsylvania and 4 more.
Type: | Journal: Scientific reports | Year: 2016

Interleukin-27 (IL-27) is an important cytokine in inflammatory diseases, including coronary artery disease (CAD). To explore the precise role of IL-27 in CAD, we investigated the genetic association between IL27 and CAD in the GeneID Chinese Han population. A two-stage case control association analysis was performed for 3075 CAD cases and 2802 controls. Logistic regression analysis was used to adjust the traditional risk factors for CAD. Results showed that a promoter variant, rs153109, tended to be marginally associated with CAD in the discovery population (Padj=0.028, OR=1.27, 95%CI: 1.03-1.58). However, this association was not replicated in the validation stage (Padj=0.559, OR=1.04, 95%CI: 0.90-1.21). In addition, when we classified the combined population into two subgroups according to the age at disease onset or disease state, we again obtained no significant associations. Finally, we estimated the severity of coronary stenosis using the Gensini Scoring system and determined that the rs153109 genotypes were still not associated with the Gensini scores of the CAD patients. In conclusion, our study failed to find an association between common variants in the functional region of IL27 and CAD in a Chinese Han population, which indicated that IL-27 might only be an inflammatory marker during the development of CAD.


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.


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..


Huang J.,Jining Medical College Affiliated Hospital | Xu J.,Jining Medical College Affiliated Hospital | Pang S.,Jining Medical College Affiliated Hospital | Bai B.,Jining Medical College | Yan B.,Jining Medical College Affiliated Hospital
Clinical Biochemistry | Year: 2012

ObjectiveAutophagy is a highly conserved degradation pathway in cells, which has been involved in many physiological processes and implicated in human age-related diseases. However, autophagy activities have not been systemically investigated with human tissues and cells. MethodsLysosomal associated membrane protein-2 (LAMP-2) protein is critical for autophagy and chaperone-mediated autophagy. We examined LAMP-2 gene expression and protein levels in the peripheral leukocytes from healthy subjects over 40 years old. Result s: Compared to those in group of 40-44 years, the LAMP-2 transcript and protein levels in groups of 65-69 (P<0.01) and over 70 years (P<0.001) were significantly decreased. No significant difference in LAMP-2 transcript and protein levels were observed between male and female groups. ConclusionsOur data revealed that there was a progressive and age-related decrease of the LAMP-2 gene expression in the peripheral leukocytes of healthy subjects, indicating a trend of decreasing autophagy activities with aging. © 2012 The Canadian Society of Clinical Chemists.


Sun Z.-P.,Shandong University | Gong L.,Jining Medical College Affiliated Hospital | Huang S.-H.,Shandong University | Geng Z.,Shandong University | And 2 more authors.
Journal of Neurochemistry | Year: 2011

Cerebral dopamine neurotrophic factor (CDNF) is a novel evolutionary conserved protein which can protect and restore the function of dopaminergic neurons in the rat model of Parkinson's disease, suggesting that CDNF might be beneficial for the treatment of Parkinson's disease. CDNF is widely expressed in neurons in several brain regions including cerebral cortex, hippocampus, substantia nigra, striatum and cerebellum. Human CDNF is glycosylated and secreted from transiently transfected cells; however, the mechanism underlying CDNF secretion is currently unclear. In this study, we found that CDNF could be secreted primarily via the regulated secretion pathway in PC12 cells. The glycosylation of CDNF is not required for its secretion. Moreover, we identified two key subdomains in CDNF which are important for its intracellular localization and secretion. Disrupting helix-1 of CDNF significantly reduces its constitutive and regulated secretion and the helix-1 mutant is retained in the endoplasmic reticulum. Although helix-7 mutation only decreases CDNF regulated secretion and has no effect on its constitutive secretion, which is further supported by the reduction in co-localization of helix-7 mutant with secretory granules. In all, these findings will advance our understanding of the molecular mechanism of CDNF trafficking and secretion. © 2011 The Authors Journal of Neurochemistry © 2011 International Society for Neurochemistry.


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.


Wu G.,Jining Medical College Affiliated Hospital | Shan J.,Jining Medical College Affiliated Hospital | Pang S.,Jining Medical College Affiliated Hospital | Wei X.,Jining Medical College Affiliated Hospital | And 2 more authors.
Translational Research | Year: 2012

Ventricular septal defects (VSDs) are the most common type of congenital heart diseases (CHDs). To date, the genetic causes for sporadic VSDs remain largely unknown. GATA transcription factor 4 (GATA4) is a zinc-finger transcription factor that is expressed in developing heart and adult cardiomyocytes. Mutations in the coding region of the GATA4 gene have been identified in CHD patients, including VSD. As the GATA4 factor is a dosage-sensitive regulator, we hypothesized that the promoter region variants of the GATA4 gene may be genetic causes of VSD. In this study, we analyzed the promoter region of the GATA4 gene by bidirectional sequencing in 172 VSD patients and 171 healthy controls. The results showed that 5 heterozygous sequence variants (NG-008177:g.4071T>C, NG-008177:g.4148C>A, NG-008177:g.4566C>T, NG-008177:g.4653G>T, and NG-008177:g. 4690G>deletion) within the promoter region of the GATA gene were identified in 5 VSD patients, but in none of controls. One heterozygous sequence variant (g.4762C>A) was found only in one control, which may have no functional significance. A functional analysis revealed that the transcriptional activity of variant NG-008177:g.4566C>T was reduced significantly, whereas the transcriptional activities of the variants (NG-008177:g.4071T>C, NG-008177:g.4148C>A, NG-008177:g.4653G>T, and NG-008177:g. 4690G>deletion) were increased significantly compared with the wild-type GATA4 gene promoter. As GATA4 is a dosage-sensitive regulator during development, our data suggest that these sequence variants within the promoter region of the GATA4 gene may contribute to the VSD etiology by altering its gene expression. Additional studies in experimental animals will deepen our understanding of the genetic basis of VSD and shed light on designing novel molecular therapies for adult VSD patients carrying these variants. © 2012 Mosby, Inc. All rights reserved.


Wu G.,Jining Medical College Affiliated Hospital | Huang J.,Jining Medical College Affiliated Hospital | Wei G.,Jining Medical College Affiliated Hospital | Liu L.,Jining Medical College Affiliated Hospital | And 2 more authors.
Clinical Cardiology | Year: 2011

Background: Coronary artery disease (CAD) is a commoncomplex disease that is caused by interaction between genetic and environmental factors. Accumulating evidence indicates that foam cells in the atherosclerotic plaques exhibit the characteristics of lysosomal storagediseases,namely lysosomal accumulation of indigested materials. In patients with lysosomal storage diseases, lysosomal accumulation of lipids and cholesterols in atherosclerotic plaque cells has been observed. However, the roles of lysosomal hydrolases and proteins in the pathogenesis of atherosclerosis and CAD remain unclear. Hypothesis: Lysosomal hydrolases and proteins may be involved in the pathogenesis of atherosclerosis and CAD by affecting lipid and cholesterol metabolism. Methods: Expression levels of LAMP-2, a lysosomal membrane marker gene, in the peripheral leukocytes of CAD patients (n=134) and age- and sex-matched healthy controls (n=80) were examined at transcription and protein levels with reverse transcriptase- polymerase chain reaction and Western blot analyses, respectively. The results were compared between CAD patients and healthy controls. Results: LAMP-2 gene expression and LAMp-2 protein levels were significantly increased in the peripheral leukocytes of CAD patients, compared with healthy controls. Furthermore, multivariate logistic regression analyses revealed that CAD is significantly associated with LAMP-2 gene expression levels (odds ratio [OR] 8.84, 95% confidence interval [CI]: 2.15-36.40, P = 0.003) or LAMP-2 protein levels (OR 2.03, 95% CI: 1.15-3.59, P = 0.015). Conclusions: In CAD patients, LAMP-2 gene expression in the peripheral leukocytes was significantly increased than were controls, which indicates lysosomal accumulation. These data suggest that insufficient lysosomal hydrolases and proteins may lead to abnormal lipid and cholesterol metabolism, which cause initiation and progression of atherosclerosis and CAD. © 2011 Wiley Periodicals, Inc.

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