Ling Li

Publications (765)2241.71 Total impact

• Article: Bis(α-furancarboxylato)oxovanadium(IV) Exerts Durable Antidiabetic Effects and Suppresses Matrix Metalloproteinase-2 Activity in Spontaneous Type 2 Diabetic KKAy Mice.

  Linyi Li, Lihui Gao, Shuainan Liu, Quan Liu, Sujuan Sun, Yi Huan, Caina Li, Jun Peng, Guojiang Hou, Ling Li, Weiping Liu, Zhufang Shen
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  ABSTRACT: Vanadium compounds maintain euglycemic effects in diabetic rats long after drug withdrawal and bis(α-furancarboxylato)oxovanadium(IV) (BFOV) possesses potent antidiabetic effects in diabetic rats. Here, we investigated the treatment and posttreatment effects of BFOV in diabetic Kuo Kondo [1, 2] with Ay gene (KKAy) mice, and whether these effects were associated with changes in matrix metalloproteinases (MMPs). KKAy mice received normal saline or BFOV initially at 70 μmol/kg/day for 1 month, which was tapered to 17 μmol/kg/day in the next 2 months and discontinued thereafter. Compared to diabetic controls, fasting plasma glucose (FPG) was reduced by 46 and 19 % in KKAy mice after 70 μmol/kg BFOV for 1 month and 3 months after BFOV withdrawal, respectively. OGTT and ITT showed improved glucose tolerance and a better response of FPG to insulin with a significant decrease in HOMA-IR and a marked rise in the insulin sensitivity index after 70 μmol/kg BFOV for 1 month and 4 months after BFOV withdrawal (P <0.05 in all vs. diabetic controls). BFOV treatment resulted in a moderate but significant reduction in body weight and systolic blood pressure (SBP) at 1 month of treatment and 4 months following BFOV withdrawal (P <0.05 in all vs. diabetic controls). Gelatin zymography showed that serum MMP2 activity was significantly reduced and immunoblotting assays further showed that MMP2 expression was markedly downregulated in the liver after 1 month of treatment with 70 μmol/kg and 4 months after BFOV withdrawal (P <0.05 in all vs. diabetic controls). These results suggested that BFOV possessed potent treatment and posttreatment effects in KKAy mice with improved metabolic profile and reduced body weight and SBP. Furthermore, these effects were associated with decreased MMP2 expression and activity in diabetic KKAy mice.
  Biological trace element research 05/2013; · 1.92 Impact Factor
• Article: Human cytomegalovirus infection modulates thrombospondins 1 and 2 in primary fetal astrocytes.

  Li Zhang, Ling Li, Bin Wang, Dong-Meng Qian, Xu-Mia Song, Ming Hu
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  ABSTRACT: Transmission of human cytomegalovirus (HCMV) to the fetus is the most common type of intrauterine infection; the mechanism of HCMV pathogenesis in the developing central nervous system remains unclear. Thrombospondins 1 and 2 (TSP1, TSP2) produced by immature astrocytes are critical for fetal synaptogenesis. To examine the effect of HCMV on fetal astrocytes, human fetal astrocytes were isolated and cultured with HCMV AD169. Cells were harvested at different time points. Protein and mRNA expressions of TSP1 and TSP2 were determined using RT-qPCR, western blotting analysis, and enzyme-linked immunosorbent assay. The results showed that HCMV infection induced time-dependent decreases in mRNA and protein expressions of both TSP1 and TSP2 in astrocytes. Flow cytometry was used to detect apoptosis of HCMV-infected astrocytes, and the result indicated that there was no linkage between cell apoptosis and the decrease in TSP1 and TSP2 expressions induced by HCMV infection. When ganciclovir treatment was performed on HCMV-infected astrocytes, results showed that ganciclovir treatment inhibited the reduction of TSP1 and TSP2 expression in astrocytes. In the further study, pEGFP-N3-IE1 was transfected into astrocytes to identify that it was not IE1 but active viral replication that was essential in the continuous decrease of TSP1 and TSP2 expressions in HCMV-infected astrocytes.
  Neuroreport 05/2013; · 1.66 Impact Factor
• Article: Oxidative Stress is not Involved in Motion Sickness in Mice.

  Zhi-Bin Wang, Ping Han, Ye Tu, Wei-Ye Liu, Bei-Lei Tao, Li-Chao Zhang, Ling Li
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  ABSTRACT: AIMS: Some indirect evidences indicate a possible correlation between oxidative stress and motion sickness. The aim of this research was to investigate whether oxidative stress contributing to motion sickness in mice or not. METHODS: We examined the mRNA levels of peroxiredoxin 6 (PRDX6), catalase, and enzyme superoxide dismutase 1 (SOD1); reactive oxygen species (ROS); and total antioxidant capacity and SOD activity in different brain regions after rotary stimulation. Mice motion sickness index was recorded after rotation when pretreated with paraquat, vitamin C, or vitamin E. RESULTS: The ROS level and antioxidant capacity were both increased in cerebellum plus brainstem (CB) after rotation, a critical region determines motion sickness. However, manipulation of oxidants or antioxidants using pharmacological method in vivo had no influence on motion sickness index in mice. CONCLUSION: Oxidative stress is not involved in the development of motion sickness in mice.
  CNS Neuroscience & Therapeutics 04/2013; · 4.44 Impact Factor
• Article: The non-coding RNA llme23 drives the malignant property of human melanoma cells.

  Chuan-Fang Wu, Guang-Hong Tan, Cheng-Chuan Ma, Ling Li
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  ABSTRACT: Several lines of evidence support the notion that increased RNA-binding ability of polypyrimidine tract-binding (PTB) protein-associated splicing factor (PSF) and aberrant expression of long non-coding RNAs (lncRNAs) are associated with mouse and human tumors. To identify the PSF-binding lncRNA involved in human oncogenesis, we screened a nuclear RNA repertoire of human melanoma cell line, YUSAC, through RNA-SELEX affinity chromatography. A previously unreported lncRNA, termed as Llme23, was found to bind immobilized PSF resin. The specific binding of Llme23 to both recombinant and native PSF protein was confirmed in vitro and in vivo. The expression of PSF-binding Llme23 is exclusively detected in human melanoma lines. Knocking down Llme23 remarkably suppressed the malignant property of YUSAC cells, accompanied by the repressed expression of proto-oncogene Rab23. These results may indicate that Llme23 can function as an oncogenic RNA and directly associate the PSF-binding lncRNA with human melanoma.
  Journal of Genetics and Genomics 04/2013; 40(4):179-88. · 1.88 Impact Factor
• Article: Comparative roles of moxifloxacin and levofloxacin in the treatment of pulmonary multidrug-resistant tuberculosis: a retrospective study.

  Rui-Hua Jiang, Hong-Bin Xu, Ling Li
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  ABSTRACT: This study compared the efficacy of moxifloxacin and levofloxacin in the treatment of multidrug-resistant tuberculosis (MDR-TB) in Shanghai, China. A retrospective analysis of 158 patients with MDR-TB receiving either moxifloxacin- or levofloxacin-containing regimens was performed. Clinical data from patients were subjected to univariate analysis, stratification and multiple logistic regression to compare the roles of moxifloxacin and levofloxacin in multidrug regimens. In total, 72 patients received 400mg of moxifloxacin once daily and 86 patients received 509.9±79.4mg (mean±standard deviation) of levofloxacin once daily together with similar active agents for similar durations. The times to sputum culture conversion were similar. Adverse reactions occurred at comparable rates. The combined treatment success rate was 60.1%, being higher among ofloxacin-susceptible than ofloxacin-resistant cases (67.5% vs. 52.0%; P<0.05). The success rates for the moxifloxacin group were 65.3% (overall), 77.1% (ofloxacin-susceptible cases) and 54.1% (ofloxacin-resistant cases) in comparison with 55.8%, 60.4% and 50.0%, respectively, for the levofloxacin group. No demographic, clinical, bacteriological or treatment characteristics were independent predictors of favourable outcome. Fourteen patients from the moxifloxacin group and twelve patients from the levofloxacin group had bacteriological relapse after treatment cessation. In conclusion, compared with levofloxacin, moxifloxacin did not show superior efficacy when incorporated into multidrug regimens used for the treatment of MDR-TB.
  International journal of antimicrobial agents 04/2013; · 3.03 Impact Factor
• Article: Validation study of 131I‑RRL: Assessment of biodistribution, SPECT imaging and radiation dosimetry in mice.

  Qian Zhao, Ping Yan, Lei Yin, Ling Li, Xue Qi Chen, Chao Ma, Rong Fu Wang
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  ABSTRACT: Tumor angiogenesis is important in the growth and metastasis of malignant tumors. In our previous study, we demonstrated that an arginine‑arginine‑leucine (RRL) peptide is a tumor endothelial cell‑specific binding sequence that may be used as a molecular probe for the imaging of malignant tumors in vivo. The aim of the present study was to further explore the characteristics of 131I‑RRL by biodistribution tests, and to estimate the radiation dosimetry of 131I‑RRL for humans using mice data. The RRL peptide was radiolabeled with 131I by a chloramine‑T (CH‑T) method. The radiolabeling efficiency and radiochemical purity were then characterized in vitro. 131I‑RRL was injected intravenously into B16 xenograft‑bearing Kunming mice. Biodistribution analysis and in vivo imaging were performed periodically. The radiation dosimetry in humans was calculated according to the organ distribution and the standard medical internal radiation dose (MIRD) method in mice. All data were analyzed by statistical and MIRDOSE 3.1 software. The labeling efficiency of 131I‑RRL reached 70.0±2.91% (n=5), and the radiochemical purity exceeded 95% following purification. In mice bearing B16 xenografts, 131I‑RRL rapidly cleared from the blood and predominantly accumulated in the kidneys, the stomach and the tumor tissue. The specific uptake of 131I‑RRL in the tumor increased over time and was significantly higher than that of the other organs, 24‑72 h following injection (P<0.05). The ratio of tumor‑to‑skeletal muscle (T/SM) tissue exceeded 4.75, and the ratio of the tumor‑to‑blood (T/B) tissue peaked at 3.36. In the single-photon emission computed tomography (SPECT) imaging of Kunming mice bearing B16 xenografts, the tumors were clearly identifiable at 6 h, and significant uptake was evident 24‑72 h following administration of 131I‑RRL. The effective dose for the adult male dosimetric model was estimated to be 0.0293 mSv/MBq. Higher absorbed doses were estimated for the stomach (0.102 mGy/MBq), the small intestines (0.0699 mGy/MBq), the kidneys (0.0611 mGy/MBq) and the liver (0.055 mGy/MBq). These results highlight the potential of 131I‑RRL as a ligand for the SPECT imaging of tumors. Administration of 131I‑RRL led to a reasonable radiation dose burden and was safe for human use.
  Molecular Medicine Reports 04/2013; 7(4):1355-60. · 0.42 Impact Factor
• Article: Interruptions are significantly associated with the frequency and severity of medication administration errors.

  Johanna I Westbrook, Ling Li
  Research in Nursing & Health 04/2013; 36(2):116-9. · 1.71 Impact Factor
• Article: Plaque characteristics and serum pregnancy-associated plasma protein A levels predict the no-reflow phenomenon after percutaneous coronary intervention.

  Xiao-Yan Zhao, Xiao-Fang Wang, Ling Li, Jin-Ying Zhang, You-You Du, Hai-Mu Yao
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  ABSTRACT: OBJECTIVES: To investigate the relationship between serum plasma pregnancy-associated plasma protein A (PAPP-A) and coronary plaque characteristics, and their prognostic value for coronary no-reflow after percutaneous coronary intervention (PCI). METHODS: Patients with unstable angina undergoing PCI were divided into a normal reflow group and a no-reflow group after stent deployment. Coronary blood flow was measured angiographically; plaque components were detected by virtual histology intravascular ultrasound. Serum PAPP-A and high-sensitivity C-reactive protein (hsCRP) were measured before PCI. Cardiac troponin T (cTnT) was measured before and 24 h after PCI. RESULTS: A total of 166 patients with unstable angina undergoing PCI were included: normal reflow group (n = 145) and no-reflow group (n = 21), after stent deployment. Baseline coronary blood flow was similar in the two groups. The no-reflow group had plaques with less-fibrotic tissue and a larger necrotic core, more thin-cap fibroatheromas and plaque ruptures, and higher serum PAPP-A, hsCRP and post-PCI cTnT levels than the normal reflow group. Serum PAPP-A was correlated negatively with plaque fibrotic area and positively with necrotic core area. CONCLUSION: High serum PAPP-A and plaque lesions with a large necrotic core are associated with the no-reflow phenomenon after PCI, in patients with unstable angina.
  The Journal of international medical research 03/2013; · 0.90 Impact Factor
• Article: Identification of Radioresistance-Associated Proteins in Human Nasopharyngeal Carcinoma Cell Lines by Proteomic Analysis.

  Ling Li, Shiting Huang, Xiaodong Zhu, Zhirui Zhou, Yan Liu, Song Qu, Ya Guo
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  ABSTRACT: Abstract Background and Purpose: Radiotherapy is the mainstay of treatment modality for human nasopharyngeal carcinoma (NPC), but in some cases, the disease is radioresistant. This study aimed to identify proteins potentially responsible for radioresistance of NPC by a proteomic approach. Material and Methods: The radioresistant human NPC cell line CNE-2R and its parental cell line CNE-2 were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/time-of-flight mass spectrometry analysis. The candidate proteins were validated by Western blot analysis. Results: In total, 16 differentially expressed proteins were identified; among them, Nm23 H1 was significantly increased, while Annexin A3 was significantly downregulated in CNE-2R cells, compared to CNE-2 cells. Conclusions: Our findings provide a platform for further characterization of the proteins implicated in radioresistance and suggest that these proteins could be exploited as a biomarker for predicting the NPC response to radiotherapy in the clinic.
  Cancer Biotherapy & Radiopharmaceuticals 03/2013; · 1.44 Impact Factor
• Article: Assessment of Cardiac Proteome Dynamics with Heavy Water: Slower Protein Synthesis Rates in Interfibrillar than Subsarcolemmal Mitochondria.

  Takhar Kasumov, Erinne R Dabkowski, Kadambari C Shekar, Ling Li, Rogério Faustino Ribeiro, Kenneth Walsh, Stephen F Previs, Rovshan G Sadygov, Belinda Willard, William C Stanley
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  ABSTRACT: Traditional proteomics provides static assessment of protein content, but not synthetic rates. Recently proteome dynamics with heavy water (2H2O) was introduced, where 2H labels amino acids that are incorporated into proteins, and the synthesis rate of individual proteins is calculated using mass isotopomer distribution analysis. We refine this approach with a novel algorithm and rigorous selection criteria that improve the accuracy and precision of the calculation of synthesis rates, and use it to measure protein kinetics in spatially distinct cardiac mitochondrial subpopulations. Subsarcolemmal and interfibrillar mitochondria (SSM and IFM) were isolated from adult rats were given 2H2O in the drinking water for up to 60 days. Plasma 2H2O and myocardial 2H enrichment of amino acids were stable throughout the experimental protocol. Multiple tryptic peptides were identified from 28 proteins in both SSM and IFM, and showed a time-dependent increase in heavy mass isotopomers that was consistent within a given protein. Mitochondrial protein synthesis was relatively slow (average half-life of 30 days, 2.4%/day). Although the synthesis rates for individual proteins were correlated between IFM and SSM (R2=0.84, p<0.0001), values in IFM were 15% less than SSM (P<0.001). In conclusion: 1) Administration of 2H2O results in stable enrichment of the cardiac precursor amino acid pool, 2) using a refined analytical and computational methods coupled with cell fractionation one can measure synthesis rates for cardiac proteins in subcellular compartments in vivo, and 3) protein synthesis is slower in mitochondria located among the myofibrils than in the subsarcolemmal region.
  AJP Heart and Circulatory Physiology 03/2013; · 3.71 Impact Factor
• Article: Neural Correlates of Covert Face Processing: fMRI Evidence from a Prosopagnosic Patient.

  Jiangang Liu, Meiyun Wang, Xiaohong Shi, Lu Feng, Ling Li, Justine Marie Thacker, Jie Tian, Dapeng Shi, Kang Lee
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  ABSTRACT: Brains can perceive or recognize a face even though we are subjectively unaware of the existence of that face. However, the exact neural correlates of such covert face processing remain unknown. Here, we compared the fMRI activities between a prosopagnosic patient and normal controls when they saw famous and unfamiliar faces. When compared with objects, the patient showed greater activation to famous faces in the fusiform face area (FFA) though he could not overtly recognize those faces. In contrast, the controls showed greater activation to both famous and unfamiliar faces in the FFA. Compared with unfamiliar faces, famous faces activated the controls', but not the patient's lateral prefrontal cortex (LPFC) known to be involved in familiar face recognition. In contrast, the patient showed greater activation in the bilateral medial frontal gyrus (MeFG). Functional connectivity analyses revealed that the patient's right middle fusiform gyrus (FG) showed enhanced connectivity to the MeFG, whereas the controls' middle FG showed enhanced connectivity to the LPFC. These findings suggest that the FFA may be involved in both covert and overt face recognition. The patient's impairment in overt face recognition may be due to the absence of the coupling between the right FG and the LPFC.
  Cerebral Cortex 02/2013; · 6.54 Impact Factor
• Article: Validation of admittance computed left ventricular volumes against real time three-dimensional echocardiography in the porcine heart.

  Shelby Kutty, Anil T Kottam, Asif Padiyath, Keshore R Bidasee, Ling Li, Shunji Gao, Juefei Wu, John Lof, David A Danford, Titus Kuehne
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  ABSTRACT: Background: The admittance and Wei's equation is a new technique for ventricular volumetry to determine pressure-volume relations that addresses traditional conductance related issues of parallel conductance and field correction factor. These issues with conductance have prevented researchers from obtaining real-time absolute ventricular volumes. Moreover, the time consuming steps involved in processing conductance catheter data has warranted the need for a better catheter-based technique for ventricular volumetry. We aimed to compare the accuracy of left ventricular (LV) volumetry between the new admittance catheterization technique and transesophageal real time three-dimensional echocardiography (RT3DE) in a large animal model. Methods: Eight pigs were used in the study. A 7F admittance catheter was positioned in the LV via right carotid artery. The catheter was connected to an admittance control unit (ADVantage, Transonic Scisense Inc.) and data was recorded on a 4-channel acquisition system (FA404, iWorx Systems). Admittance catheterization data and transesophageal RT3DE (X7-2, Philips) data were simultaneously obtained with the animal ventilated, paralyzed and monitored at 2 conditions: baseline, and during dobutamine infusion. LV volumes measured from admittance catheterization (Labscribe, iWorx Systems) and RT3DE (QLab, Philips) were compared. In a subset of 4 animals, admittance volumes were compared with those obtained from traditional conductance catheterization (MPVS Ultra, Millar Instruments). Results: Of 37 sets of measurements compared, admittance and RT3DE derived LV volumes and ejection fractions at baseline and on dobutamine exhibited general agreement, with mean percentage inter-method differences of 10% for end-diastolic volumes, 14% for end systolic volumes and 9% for ejection fraction; the respective inter-method differences between admittance and conductance in 8 datasets compared were 11%, 11% and 12%. Admittance volumes were generally higher than those by RT3DE, especially among the larger ventricles. Conclusion: It is feasible to derive pressure-volume relations using admittance catheterization in large animals. This study demonstrated agreements between admittance and RT3DE to within 10-14% mean inter-method difference in the estimation of LV volumes. Further investigation will be required to examine accuracy of volumes in largest ventricles where inter-method divergence is greatest.
  Experimental physiology 02/2013; · 3.17 Impact Factor
• Article: Systematic review of the effectiveness of hyperbaric oxygenation therapy in the management of chronic diabetic foot ulcers.

  Rui Liu, Ling Li, Mengliu Yang, Guenther Boden, Gangyi Yang
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  ABSTRACT: To assess the efficacy and safety of hyperbaric oxygenation (HBO) therapy as adjunctive treatment for diabetic foot ulcers with a systematic review and meta-analysis of the literature. MEDLINE, EMBASE, and the Cochrane Library were searched to find relevant articles published up to April 20, 2012, without restriction as to language or publication status. All controlled trials that evaluated adjunctive treatment with HBO therapy compared with treatment without HBO for chronic diabetic foot ulcers were selected. A meta-analysis was performed to assess the efficacy and safety of hyperbaric oxygen in managing foot ulcers. Thirteen trials (a total of 624 patients), including 7 prospective randomized trials, performed between January 1, 1966, and April 20, 2012, were identified as eligible for inclusion in the study. Pooling analysis revealed that, compared with treatment without HBO, adjunctive treatment with HBO resulted in a significantly higher proportion of healed diabetic ulcers (relative risk, 2.33; 95% CI, 1.51-3.60). The analysis also revealed that treatment with HBO was associated with a significant reduction in the risk of major amputations (relative risk, 0.29; 95% CI, 0.19-0.44); however, the rate of minor amputations was not affected (P=.30). Adverse events associated with HBO treatment were rare and reversible and not more frequent than those occurring without HBO treatment (P=.37). This meta-analysis reveals that treatment with HBO improved the rate of healing and reduced the risk of major amputations in patients with diabetic foot ulcers. On the basis of these effects, we believe that quality of life could be improved in selected patients treated with HBO.
  Mayo Clinic Proceedings 02/2013; 88(2):166-75. · 5.70 Impact Factor
• Article: Sero-epidemiological survey of human cytomegalovirus-infected children in Weifang (Eastern China) between 2009 and 2012.

  Xiuning Sun, Zhijun Liu, Bin Wang, Lihong Shi, Ruiwen Liang, Ling Li
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  ABSTRACT: BACKGROUND: To understand the prevalence and characteristics of human cytomegalovirus (HCMV) infection in children in the Weifang area, and to provide information for its prevention and treatment. METHODS: A comprehensive survey was performed from 2009 to 2012 in 7582 children from birth to 6 years of age hospitalized in the Maternity and Child Health Hospital of Weifang. ELISA HCMV serology results and survey data were analyzed by age group and socio-economic level. The infection rates were based on IgG and IgM serology.Results and conclusions: The overall infection rate from IgG and IgM in the Weifang area from 2009 to 2012 was 42.5% (3496/7582), among which 34.2% were HCMV-IgG positive, suggesting past infection. Overall, the probability of active HCMV infection showed no gender difference in any age group (P >0.05). Recent infections centered on the first 6 months of life, presumably due to breastfeeding. Among the 607 children hospitalized for active HCMV infection, 357 (57.9%) were from rural areas and 250 (42.1%) from urban areas, showing that active infection in the countryside was higher than that in the city (chi2 = 32.65, p <0.01).
  Virology Journal 02/2013; 10(1):42. · 2.34 Impact Factor
• Article: Anatomic study of the buccal root with furcation groove and associated root canal shape in maxillary first premolars by using micro-computed tomography.

  Jun Li, Ling Li, Yihuai Pan
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  ABSTRACT: The purpose of this study was to investigate the buccal root anatomy of bifurcated maxillary first premolars with furcation grooves and to determine the correlation between the groove depth and the buccal root canal shape by using micro-computed tomography. Thirty-six bifurcated maxillary first premolars with furcation grooves were obtained from native Chinese individuals aged 17-25 years and scanned by micro-computed tomography. Basic parameters including the groove length, depth, and location were recorded. The wall thickness at different portions of the buccal roots was measured by using a customized application framework in MeVisLab software. The root canal shape was quantified by the form factor, and the correlation between the mean form factor and the maximum groove depth was analyzed. The minimum wall thickness was less on the palatal aspect (<1 mm) than on the buccal aspect of the coronal two thirds of the buccal roots. The mean form factor value ranged from 0.72-0.91 and correlated negatively with the maximum groove depth (ρ(2) = -0.641, P < .001). The irregular wall thickness of buccal roots of bifurcated maxillary first premolars with furcation grooves and the related changes in the root canal shape should be considered during endodontic and prosthetic treatment.
  Journal of endodontics 02/2013; 39(2):265-8. · 2.95 Impact Factor
• Article: The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells.

  Ling Li, Bridget Fox, Julie Keeble, Manuel Salto-Tellez, Paul G Winyard, Mark E Wood, Philip K Moore, Matthew Whiteman
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  ABSTRACT: The role of hydrogen sulfide (H(2) S) in inflammation remains unclear with both pro- and anti-inflammatory actions of this gas described. We have now assessed the effect of GYY4137 (a slow-releasing H(2) S donor) on lipopolysaccharide (LPS)-evoked release of inflammatory mediators from human synoviocytes (HFLS) and articular chondrocytes (HAC) in vitro. We have also examined the effect of GYY4137 in a complete Freund's adjuvant (CFA) model of acute joint inflammation in the mouse. GYY4137 (0.1-0.5 mM) decreased LPS-induced production of nitrite (NO(2) (-) ), PGE(2) , TNF-α and IL-6 from HFLS and HAC, reduced the levels and catalytic activity of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and reduced LPS-induced NF-κB activation in vitro. Using recombinant human enzymes, GYY4137 inhibited the activity of COX-2, iNOS and TNF-α converting enzyme (TACE). In the CFA-treated mouse, GYY4137 (50 mg/kg, i.p.) injected 1 hr prior to CFA increased knee joint swelling while an anti-inflammatory effect, as demonstrated by reduced synovial fluid myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) activity and decreased TNF-α, IL-1β, IL-6 and IL-8 concentration, was apparent when GYY4137 was injected 6 hrs after CFA. GYY4137 was also anti-inflammatory when given 18 hrs after CFA. Thus, although GYY4137 consistently reduced the generation of pro-inflammatory mediators from human joint cells in vitro, its effect on acute joint inflammation in vivo depended on the timing of administration.
  Journal of Cellular and Molecular Medicine 01/2013; · 4.13 Impact Factor
• Article: Usefulness of Hemoglobin A1c as a Criterion to Define Metabolic Syndrome in Nondiabetic Chinese Adolescents.

  Ping Li, Ranhua Jiang, Ling Li, Xue Li, Cong Liu, Wanfeng Xu, Duo Xu
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  ABSTRACT: AIMS: To examine whether hemoglobin A1c (HbA1c) can be used instead of fasting plasma glucose (FPG) to identify nondiabetic Chinese adolescents with metabolic syndrome (MS). METHODS: This was a cross-sectional study involving 910 adolescents (11-16 years; 46.8% girls) with an HbA1c less than or equal to 6.4% and an FPG less than or equal to 6.9 mmol/L. All participants underwent anthropometric and biochemical examinations. Metabolic syndrome was defined using the definition proposed by the International Diabetes Federation (IDF) and the American Heart Association (AHA). Replacement of an FPG greater than or equal to 5.6 mmol/L with an HbA1c greater than or equal to 5.7% yielded 2 HbA1c definitions (IDF-HbA1c and AHA-HbA1c). The use of an HbA1c greater than or equal to 5.7% or an FPG greater than or equal to 5.6 mmol/L in the definition of the glycemic component of the MS was compared. RESULTS: The HbA1c definition resulted in an increase in the population prevalence of MS by 2.4% (IDF-HbA1c) and 2.5% (AHA-HbA1c), respectively (P ≥ 0.05). The degree of concordance (κ index) was as high as 0.900 for the concordance between the IDF and IDF-HbA1c definition, and 0.811 between the AHA and AHA-HbA1c definition. Subjects who were diagnosed as normal based on the FPG definition and met the HbA1c definition for MS had more cardiometabolic risk factors (waist circumference, blood pressure, lipid profiles, uric acid, and homeostasis assessment model of insulin resistance; all P < 0.05), indicating that the HbA1c definition identified more subjects with cardiovascular disease-related risk factors. HbA1c greater than or equal to 5.7% was significantly associated with the presence of MS [adjusted odds ratio, 2.61 (1.13-6.01)]. CONCLUSIONS: An HbA1c greater than or equal to 5.7% was associated with the presence of MS and can be considered a surrogate for FPG in the diagnosis of MS in nondiabetic Chinese adolescents.
  Journal of Investigative Medicine 01/2013; · 1.96 Impact Factor
• Article: GLP-1 analogue prevents NAFLD in ApoE KO mice with diet and Acrp30 knockdown by inhibiting c-JNK.

  Lili Zhang, Mengliu Yang, Hong Ren, Huaidong Hu, Guenther Boden, Ling Li, Gangyi Yang
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  ABSTRACT: BACKGROUND & AIMS: Liraglutide, a Glucagon-like peptide-1(GLP-1) analogue with 97% sequence identity to human GLP-1, increases insulin secretion and insulin sensitivity. Its effect on non-alcoholic fatty liver disease (NAFLD) remains poorly understood. In this study, we examined whether liraglutide can protect against inflammatory stress by inhibiting activation of c-Jun N-terminal protein kinase (JNK). METHODS: ApoE KO and adiponectin (Acrp30) knockdown mice fed a high-fat diet (HFD) were treated with liraglutide (1 mg/kg, twice daily) for 8 weeks. Liver tissue was procured for histological examination, real-time RT-PCR and Western blot analysis. RESULTS: The results showed that the combination of HFD, Acrp30 knockdown and ApoE deficiency had additive effects on the development of insulin resistance (IR) and NAFLD. Administration of liraglutide prevented the development of HFD and hypoadiponectinaemia-induced IR and NAFLD in this model. Liraglutide also attenuated the expression of proinflammatory cytokines or transcription factor, including TNF-α and NF-κB(65) , and the expression of two lipogenesis-related genes, Acetyl-CoA Carboxylase (ACC) and fatty acid synthase (FAS). These changes were accompanied by elevated plasma of Acrp30, increased Acrp30 mRNA, AMP Kinase phosphorylation, and decreased mitogen-activated protein kinase 4 (MKK4) mRNA expression and JNK phosphorylation. CONCLUSIONS: Our study also showed potent inhibitory effects of liraglutide on MKK4/JNK signalling which may be a mechanism for the observed improved insulin sensitivity and inflammatory stress induced by HFD and hypoadiponectinaemia.
  Liver international: official journal of the International Association for the Study of the Liver 01/2013; · 3.82 Impact Factor
• Article: Functional Maturation of Left and Right Atrial Systolic and Diastolic Performance in Infants, Children, and Adolescents.

  Shelby Kutty, Asif Padiyath, Ling Li, Qinghai Peng, Sheela Rangamani, Andreas Schuster, David A Danford
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  ABSTRACT: BACKGROUND: Left atrial (LA) function is an important modulator of left ventricular filling and has a prognostic role in adult heart failure, but pediatric data are limited. The aim of this study was to characterize the normal LA and right atrial (RA) strain (ε) and strain rate (SR) in infants and children. METHODS: Atrial ε and SR were prospectively investigated in 153 subjects using two-dimensional speckle-tracking echocardiography. High-frame rate, three-beat captures of LA (15-segment model; two-chamber, three-chamber, and four-chamber views) and RA (six-segment model; four-chamber view) were analyzed (Vivid 7, EchoPAC BT11). LA and RA segmental and global peak positive ε (ε(Pos)) and negative ε (ε(Neg)) and peak positive SR, early negative SR, and late negative SR were measured. Linear and nonlinear regressions of ε and SR were performed with age and heart rate. Relationships of ε and SR with ventricular inflow Doppler and myocardial tissue Doppler indices were explored. RESULTS: The age range was 3 days to 20 years, and body surface area range from 0.17 to 2.3 m(2) for the study cohort. Mean global LA ε(Pos), LA ε(Neg), RA ε(Pos), and RA ε(Neg) were 28 ± 9%, -16 ± 6%, 23 ± 9%, and -15 ± 6%, respectively. Positive correlations were found for global atrial ε(Pos) and ε(Neg) with age (P < .001). A marked rate of changes in ε and SR was seen in the first year of life, reaching normal adult values by adolescence. Peak positive SR had a strong negative correlation with age, and early negative SR had a strong positive correlation with age (P < .001), while late negative SR was correlated nonlinearly. Heart rate and age both influenced all LA and RA ε and SR indices. CONCLUSIONS: Maturational changes in LA and RA ε and SR occur in normal children and are especially profound in infancy. Consequently, LA and RA performance indices must be interpreted in light of heart rate and age. Normal values and percentiles for atrial ε and SR reported here will provide a foundation for the study of pediatric atrial physiology and function in disease states.
  Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 01/2013; · 2.98 Impact Factor
• Article: [Correlation between Apolipoprotein E polymorphism and age at onset of Alzheimer's disease in a Chinese Han population].

  Jing-Tao Wang, Ling Li, Jing Yuan, Zhen-Xin Zhang
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  ABSTRACT: To investigate the correlation between the ApoE genotype and age at onset in a cohort of hospital-based AD patients of Han population in China. All cases were consecutive probable AD patients from the Memory and Cognitive Impairment Clinic of Peking Union Medical Collge Hospital from 1999 to 2010. They were all Han ethnicity. They were divided into two groups according to age at onset (AAO): early onset AD (EOAD, AAO < 65 years) and late onset AD (LOAD, AAO ≥ 65 years). DNA was extracted and ApoE was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. The linkage between ApoE polymorphism and AAO of AD were analyzed by one-way ANOVA. AAO of all cases (n = 495) was (69 ± 10) years, of EOAD (n = 149) was (58 ± 5) years and of LOAD (n = 346) was (74 ± 6) years. ApoEε4(+) genotypes were not associated with AAO of EOAD [ε4-/-: (57 ± 5) years, n = 90; ε4+/-: (59 ± 5) years, n = 50; ε4+/+: (59 ± 5) years, n = 9; F = 0.99, P = 0.38], while they were significantly associated with AAO of LOAD [ε4-/-: ( 75 ± 6) years, n = 189; ε4+/-: (73 ± 6) years, n = 138; ε4+/+: (71 ± 5) years, n = 19; F = 6.51, P = 0.002]. As for all ApoE genotypes, AAO of LOAD reduced gradually in a way as follows: ε2/3 > ε3/3 > ε3/4 > ε2/4 > ε4/4. There was great correlation between AAO and ApoE polymorphism in LOAD without dementia family history, whereas no correlation in LOAD with dementia family history. ApoE genotypes carrying at least one ε4 allele maybe significantly lower AAO of LOAD in a dose-dependent manner whereas no such correlation in LOAD with dementia family history.
  Zhonghua yi xue za zhi 01/2013; 93(3):182-6.