Key Laboratory Of Environment And Genes Related To Diseases Xian Jiaotong University

Xi’an, China

Key Laboratory Of Environment And Genes Related To Diseases Xian Jiaotong University

Xi’an, China

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Li R.,The First Affiliated Hospital Of Xian Medical University | Yang L.,University College West | Yang L.,Key Laboratory Of Environment And Genes Related To Diseases Xian Jiaotong University | Yang L.,Precision for Medicine | Ma L.,University College West
International Journal of Clinical and Experimental Medicine | Year: 2016

Chemerin is a novel adipokine associated with obesity and metabolic syndrome and previous studies indicate that chemerin may also function as a stimulator of angiogenesis. However, the underlying mechanism of its regulatory role in angiogenesis remains unclear. In this study, we determined the role of autophagy in chemerininduced angiogenesis of RF/6A cells. Proliferation, migration and angiogenesis of RF/6A cells can be promoted by treating with different concentrations of chemerin. The expression of LC3II was increased and the autophagyrelated gene beclin-1 was upregulated by chemerin. Treatment with 3-MA, a common autophagy inhibitor, can significantly inhibit chemerin-induced proliferation, migration and tube formation by inhibiting the autophagy level of RF/6A cells. These studies show that autophagy play an important role in chemerin-induced angiogenesis and that targeting at autophagy may provide a new tool for treating retinal neovascularization. © 2016, E-Century Publishing Corporation. All rights reserved.


Zhang Q.-Y.,Health Science University | Wu S.-S.,Capital Medical University | Lv P.-L.,University of Science and Technology of China | Huang H.-W.,Health Science University | And 4 more authors.
Investigative Ophthalmology and Visual Science | Year: 2016

PURPOSE. The aim of this study was to quantify the relationship between categories of body mass index (BMI) and age-related macular degeneration (AMD) risk in different stages. METHODS. MEDLINE, EMBASE, and ISI Web of Science were searched for all eligible studies on the relationship between BMI and incident early or late AMD. The analyses were based on data extracted from study reports. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of this association, and dose-response relationship was assessed by restricted cubic spline. RESULTS. Seven prospective cohort studies with 1613 cases identified among 31,151 subjects were included. For overweight, the relationship remained insignificant for its association with both early AMD (RR = 0.92, 95% CI: 0.68-1.15; P = 0.54) and late AMD (RR = 1.09, 95% CI: 0.93-1.25; P = 0.18). A marked 32% increase in the risk of developing late AMD was noted among obese individuals (RR = 1.32, 95% CI: 1.11-1.53, P < 0.01), while obesity showed no significant association with early AMD (RR = 0.91, 95% CI: 0.74-1.08; P = 0.67). Furthermore, elevated BMI showed a linear dose-response relation with AMD risk (Pnonlinearity = 0.17), and the AMD risk increased by 2% (RR = 1.02, 95% CI: 1.01-1.04) for each 1 kg/m2 increase in BMI within the overweight and obese BMI ranges. CONCLUSIONS. Excess body weight was weakly associated with increase in the risk of AMD in a dose-dependent fashion, especially for its late stage, indicating that keeping normal body weight and avoiding further weight gain may confer potential protection against this disease. © 2016, Association for Research in Vision and Ophthalmology Inc. All Rights Reserved.


Ning F.,First Affiliated Hospital Of Xian Jiaotong University | Luo L.,First Affiliated Hospital Of Xian Jiaotong University | Ahmad S.,University of Cambridge | Valli H.,University of Cambridge | And 14 more authors.
Pflugers Archiv European Journal of Physiology | Year: 2016

Catecholaminergic polymorphic ventricular tachycardia (CPVT) predisposes to ventricular arrhythmia due to altered Ca2+ homeostasis and can arise from ryanodine receptor (RyR2) mutations including RyR2-P2328S. Previous reports established that homozygotic murine RyR2-P2328S (RyR2S/S) hearts show an atrial arrhythmic phenotype associated with reduced action potential (AP) conduction velocity and sodium channel (Nav1.5) expression. We now relate ventricular arrhythmogenicity and slowed AP conduction in RyR2S/S hearts to connexin-43 (Cx43) and Nav1.5 expression and Na+ current (INa). Stimulation protocols applying extrasystolic S2 stimulation following 8 Hz S1 pacing at progressively decremented S1S2 intervals confirmed an arrhythmic tendency despite unchanged ventricular effective refractory periods (VERPs) in Langendorff-perfused RyR2S/S hearts. Dynamic pacing imposing S1 stimuli then demonstrated that progressive reductions of basic cycle lengths (BCLs) produced greater reductions in conduction velocity at equivalent BCLs and diastolic intervals in RyR2S/S than WT, but comparable changes in AP durations (APD90) and their alternans. Western blot analyses demonstrated that Cx43 protein expression in whole ventricles was similar, but Nav1.5 expression in both whole tissue and membrane fractions were significantly reduced in RyR2S/S compared to wild-type (WT). Loose patch-clamp studies similarly demonstrated reduced INa in RyR2S/S ventricles. We thus attribute arrhythmogenesis in RyR2S/S ventricles resulting from arrhythmic substrate produced by reduced conduction velocity to downregulated Nav1.5 reducing INa, despite normal determinants of repolarization and passive conduction. The measured changes were quantitatively compatible with earlier predictions of linear relationships between conduction velocity and the peak INa of the AP but nonlinear relationships between peak INa and maximum Na+ permeability. © 2015, The Author(s).


Wang H.-L.,Key Laboratory Of Environment And Genes Related To Diseases Xian Jiaotong University | Lu X.,Xi'an Jiaotong University | Yang X.,Key Laboratory Of Environment And Genes Related To Diseases Xian Jiaotong University
Archives of Gynecology and Obstetrics | Year: 2016

Purpose: High-risk human papillomavirus (HR-HPV) infection is the main known cause of cervical cancer. Mannose-binding lectin (MBL) is a recognition molecule that mediates phagocytosis and activates complement. Methods: We performed a meta-analysis to investigate the association of MBL-2 functional polymorphisms with HPV infection and cervical cancer (CC). Results: The meta-analyses indicated an association between the MBL2 exon 1 polymorphisms and susceptibility to HPV infection in the recessive model (OO vs. AA + AO, p = 0.042, 95 % CI 1.02–3.15), and O/O vs. A/A mode (P = 0.023, 95 % CI 1.10–3.40) in Caucasian. Meanwhile, there was a significant association between MBL2 exon 1 polymorphisms and cervical cancer risk in AO vs. AA model (p = 0.035, 95 % CI 1.03–2.26), and Allelic model (O vs. A, p = 0.022, 95 % CI 1.05–1.96) as compared to HR-HPV-infected patients with CC vs. healthy controls in Caucasian. In addition, no an association was observed between MBL2 -550 H/L and -221 X/Y polymorphisms and HPV infection among Caucasians, but we found an association between the MBL2 -550 H/L polymorphism and susceptibility to HR-HPV infection in recessive model (HH vs. LL + LH, p = 0.003, 95 % CI 1.18–2.23), HH vs. LL model (p = 0.021, 95 % CI 1.07–2.19), and allelic model(H vs. L, p = 0.042, 95 % CI 1.01–1.40) in Asians. Conclusions: Collectively, we suggest that the MBL2 gene exon1 polymorphisms are associated with increased risk of high-risk HPV infection and cervical cancer development among Caucasians. Additionally, no significant association was found between the MBL2 -550 H/L or -221 X/Y polymorphisms and HPV infection in Caucasians, but there may be potential links in Asians. © 2016 Springer-Verlag Berlin Heidelberg


du Y.,First Affiliated Hospital Of Xian Jiaotong University | Zhang J.,First Affiliated Hospital Of Xian Jiaotong University | Xi Y.,Texas Heart Institute | Wu G.,First Affiliated Hospital Of Xian Jiaotong University | And 8 more authors.
Journal of Physiology and Biochemistry | Year: 2016

Bisoprolol, an antagonist of β1-adrenergic receptors, is effective in reducing the morbidity and mortality in patients with heart failure (HF). It has been found that HF is accompanied with dysfunction of the sinoatrial node (SAN). However, whether bisoprolol reverses the decreased SAN function in HF and how the relevant ion channels in SAN change were relatively less studied. SAN function and messenger RNA (mRNA) expression of sodium channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits were assessed in sham-operated rats, abdominal arterio-venous shunt (volume overload)-induced HF rats, and bisoprolol- treated HF rats. SAN cells of rats were isolated by laser capture microdissection. Quantitative real-time PCR analysis was used to quantify mRNA expression of sodium channels and HCN channel subunits in SAN. Intrinsic heart rate declined and sinus node recovery time prolonged in HF rats, indicating the suppressed SAN function, which could be improved by bisoprolol treatment. Nav1.1, Nav1.6, and HCN4 mRNA expressions were reduced in SAN in HF rats compared with that in control rats. Treatment with bisoprolol could reverse both the SAN function and the Nav1.1, Nav1.6, and HCN4 mRNA expression partially. These data indicated that bisoprolol is effective in HF treatment partially due to improved SAN function by reversing the down-regulation of sodium channels (Nav1.1 and Nav1.6) and HCN channel (HCN4) subunits in SAN in failing hearts. © 2016 University of Navarra


Wang H.,Xi'an Jiaotong University | Wang H.,Key Laboratory Of Environment And Genes Related To Diseases Xian Jiaotong University | Lu X.,Xi'an Jiaotong University | Yang X.,Xi'an Jiaotong University | And 3 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015

Background: Chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Tenofovir monotherapy or tenofovir-based combination therapy have achieved promising results in the treatment of chronic hepatitis B patients who failed adefovir therapy. Objective: The goal of this study was to assess the efficacy of tenofovir monotherapy compared with tenofovir-based combination therapy for treatment of adefovir-experienced chronic hepatitis B (CHB) patients. Methods: randomized and non-randomized control trials directly comparing tenofovir monotherapy and tenofovir-based combination therapy were searched in PUBMED, MEDLINE, EMBASE database up to April 30, 2015. The data were analyzed with Review Manager (v.5.3). Results: Seven articles (total of 478 patients) met entry criteria. The results found that the rates of undetectable hepatitis B virus DNA levels (64.7% vs. 68.5%, P = 0.58 for 24 weeks; 71.4% vs. 71.7%, P = 0.76 for 48 weeks; 71.6% vs. 73.0%, P = 0.92 for 96 weeks), alanine aminotransferase (ALT) normalization (72.6% vs. 69.2%, P = 0.46 for 48 weeks; 72.8% vs. 75.0%, P = 0.74 for 96 weeks) and hepatitis Be antigen loss (5.0% vs. 0, P = 0.43 for 48 weeks; 16.5% vs. 12.5%, P = 0.43 for 96 weeks) were not significantly different between the TDF alone and the TDF-based group. Moreover, the rate of adverse reactions was also not significantly different between the 2 groups (P = 0.06 for 96 weeks). Conclusions: TDF monotherapy and TDF-based combination therapy are similarly effective and safe in adefovir-experienced CHB patients after 48 weeks and 96 weeks of antiviral therapy. Nevertheless, large scale randomized control trials should be carried out to elucidate the long-term outcome of TDF treatment. © 2015 E-Century Publishing Corporation. All rights reserved.


Liu C.,Health Science University | Liu C.,Key Laboratory Of Environment And Genes Related To Diseases Xian Jiaotong University | Hu M.,Xianning University | Ma D.,Xianning University | And 3 more authors.
Lasers in Medical Science | Year: 2016

The worldwide increase in bacterial antibiotic resistance has led to a search for alternative antibacterial therapies. A promising approach to killing antibiotic-resistant bacteria is photodynamic antimicrobial chemotherapy, which uses light in combination with a photosensitizer to induce a phototoxic reaction. We evaluated the photodynamic inactivation (PDI) efficiency of hematoporphyrin monomethyl ether (HMME) on antibiotic-resistant bacteria and biofilms. HMME exhibited no significant dark toxicity and provided dose-dependent inactivation of antibiotic-resistant bacteria and biofilms. After incubation with 100-μM HMME and irradiation with 72-J cm−2 white light, 4.19–7.59 log10 reductions in survival were achieved in planktonic suspension. Antibiotic-resistant strains were as susceptible to PDI in biofilms as in planktonic suspensions, but the inactivation of bacterial cells in biofilms was attenuated. In addition, gram-positive bacterial strains and biofilms were more susceptible than gram-negative strains and biofilms to the PDI effect of HMME. Thus, HMME is a promising photosensitizer for the treatment of infectious diseases caused by antibiotic-resistant bacteria, especially gram-positive bacteria. © 2015, Springer-Verlag London.


Ding C.-P.,Health Science University | Ding C.-P.,Key Laboratory Of Environment And Genes Related To Diseases Xian Jiaotong University | Xue Y.-S.,Shaanxi Provincial Peoples Hospital | Yu J.,Health Science University | And 6 more authors.
Neurochemical Research | Year: 2016

Previous studies have demonstrated that the red nucleus (RN) is involved in the regulation of neuropathic pain and plays both facilitated and inhibitory roles through different cytokines. Here, we aim to investigate the expression changes and roles of interleukin-6 (IL-6), a pleiotropic cytokine, as well as its receptor (IL-6R) in the RN of rats with neuropathic pain induced by spared nerve injury (SNI). Immunohistochemistry indicated that IL-6 and IL-6R were weakly expressed in the RN of normal rats, and were mainly co-localized with neurons and oligodendrocytes. Following SNI, the expression levels of IL-6 and IL-6R in the RN did not show obvious changes at 1 week and 2 weeks postinjury. However, both of them were significantly increased in the RN contralateral (but not ipsilateral) to the nerve ligation side at 3 weeks postinjury, and co-localized not only with neurons and oligodendrocytes, but also with numerous astrocytes. Injection of different doses of anti-IL-6 antibody (100, 250, 500 ng) into the RN contralateral to the nerve ligation side at 3 weeks postinjury dose-dependently increased the paw withdrawal threshold (PWT) of rats and alleviated SNI-induced mechanical allodynia. Conversely, injection of different doses of recombinant rat IL-6 (5.0, 10, 20 ng) into the unilateral RN of normal rats dose-dependently decreased the PWT of contralateral (but not ipsilateral) hind paw and evoked significant mechanical allodynia, which was similar to SNI-induced neuropathic allodynia. These results further support the conclusion that the RN is involved in the modulation of neuropathic pain, and suggest that IL-6 and IL-6R in the RN play a facilitated role in the later maintenance of SNI-induced neuropathic pain. © 2016 Springer Science+Business Media New York


Jiang C.,Health Science University | Jiang C.,Key Laboratory Of Environment And Genes Related To Diseases Xian Jiaotong University | Meng L.,Health Science University | Meng L.,Key Laboratory Of Environment And Genes Related To Diseases Xian Jiaotong University | And 9 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2016

Introduction: Extracellular miRNAs in the blood plasma/serum of patients as novel promising diagnostic markers for various diseases has aroused huge attention. Among various major platforms for extracellular miRNA detection, extensively used RT-qPCR is considered practical and cost-efficient in experimental investigation. However, there are also many technical challenges, hence the development of robust methodology for extracellular miRNA detection is in good need. Methods: Focused on the controversial procedures present in recent studies, we intend to solving these technical problems and seeking for optimal procedures for extracellular miRNA profiling using the RT-qPCR method. Results: We addressed our concerns during the whole detection such as various key points during blood handling, choice making during RNA isolation and miRNA RT process, practical management in global miRNAs profiling using PCR as well as data normalization and processing. Meanwhile, we described and evaluated our profiling method in detail, intended to optimize the procedures that might lead to variable results from independent experiments, and further recommend this standardized optimal procedure. Conclusion: Our work might provide a potent technical optimization for extracellular miRNA detection. © 2016, E-Century Publishing Corporation. All rights reserved.


Yang D.,First Affiliated Hospital Of Xian Jiaotong University | Wang T.,First Affiliated Hospital Of Xian Jiaotong University | Wang T.,Shaanxi Key Laboratory Of Molecular Cardiology Xian Jiaotong University | Wang T.,Key Laboratory Of Environment And Genes Related To Diseases Xian Jiaotong University | And 9 more authors.
Journal of Membrane Biology | Year: 2015

Recent studies have shown that the sensitivity of apamin-sensitive K+ current (IKAS, mediated by apamin-sensitive small conductance calcium-activated potassium channels subunits) to intracellular Ca2+ is increased in heart failure (HF), leading to IKAS upregulation, action potential duration shortening, early after depolarization, and recurrent spontaneous ventricular fibrillation. We hypothesized that casein kinase 2 (CK2) interacted with small conductance calcium-activated potassium channels (SK) is decreased in HF, and protein phosphatase 2A (PP2A) is increased on the opposite, upregulating the sensitivity of IKAS to intracellular Ca2+ in HF. Rat model of volume-overload HF was established by an abdominal arteriovenous fistula procedure. The expression of SK channels, PP2A and CK2 was detected by Western blot analysis. Interaction and colocalization of CK2 with SK channel were detected by co-immunoprecipitation analysis and double immunofluorescence staining. In HF rat left ventricle, SK3 was increased by 100 % (P < 0.05), and SK2 was not significantly changed. PP2A protein was increased by 94.7 % in HF rats (P < 0.05), whereas the level of CK2 was almost unchanged. We found that CK2 colocalized with SK2 and SK3 in rat left ventricle. With anti-CK2α antibody, SK2 and SK3 were immunoprecipitated, the level of precipitated SK2 decreased by half, whereas precipitated SK3 was almost unchanged. In conclusion, the increased expression of total PP2A and decreased interaction of CK2 with SK2 may underlie enhanced sensitivity of IKAS to intracellular Ca2+ in volume-overload HF rat. © 2015, Springer Science+Business Media New York.

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