Oct 2016, Volume 31 Issue 1

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  • Original Article
    Wenping Xu, Sheng Zeng, Min Li, Zhiwen Fan, Bisheng Zhou
    Journal of Biomedical Research. 2017, 31 (1) : 1-9. https://doi.org/10.7555/JBR.31.20160046

    Liver injury represents a continuum of pathophysiological processes involving a complex interplay between hepatocytes, macrophages, and hepatic stellate cells. The mechanism whereby these intercellular interactions contribute to liver injury and fibrosis is not completely understood. We report here that angiogenic factor with G patch and FHA domains 1 (Aggf1) was downregulated in the livers of cirrhotic patients compared to healthy controls and in primary hepatocytes in response to carbon tetrachloride (CCl4) stimulation. Overexpression of Aggf1 attenuated macrophage chemotaxis. Aggf1 interacted with NF-κB to block its binding to the Ccl2 gene promoter and repressed Ccl2 transcription in hepatocytes. Macrophages cultured in the conditioned media collected from Aggf1-overexpressing hepatocytes antagonized HSC activation. Taken together, our data illustrate a novel role for Aggf1 in regulating hepatic inflammation and provide insights on the development of interventional strategies against cirrhosis.

  • Perspective
    Xiao-Bing Cui, Shi-You Chen
    Journal of Biomedical Research. 2017, 31 (1) : 1-2. https://doi.org/10.7555/JBR.31.20160101
  • Original Article
    Objoon Trachoo, Paisan Jittorntam, Sarunpong Pibalyart, Saowanee Kajanachumphol, Norasak Suvachittanont, Suthep Patputthipong, Piyatida Chuengsaman, Arkom Nongnuch
    Journal of Biomedical Research. 2017, 31 (1) : 17-24. https://doi.org/10.7555/JBR.31.20160063

    We aimed to explore the prevalence of Fabry disease in Thai patients who were diagnosed with end-stage renal disease (ESRD) of an unknown origin. Venous blood samples were collected from ESRD patients for biochemical and molecular studies. Alpha-galactosidase A (α-GAL A) screening was performed from dried-blood spots using fluorometry. Molecular confirmation was performed using DNA sequencing of the GLA gene. A total of 142 male and female patients were included in this study. Ten patients (7.04%) exhibited a significant decrease in α-GAL A activity. There were no definitive pathogenic mutations observed in the molecular study. However, four patients revealed a novel nucleotide variant at c.1 -10 C>T, which was identified as a benign variant following screening in the normal population. In conclusion, the α-GAL A assay utilizing dried-blood spots revealed a significant false positive rate. There was no definitive Fabry disease confirmed in Thai patients diagnosed with ESRD of unknown etiology.

  • Original Article
    Timothy McAlindon, Eckart Bartnik, Janina S. Ried, Lenore Teichert, Matthias Herrmann, Klaus Flechsenhar
    Journal of Biomedical Research. 2017, 31 (1) : 25-30. https://doi.org/10.7555/JBR.31.20150167

    To evaluate in an interventional trial on knee osteoarthritis (OA) the level and change of two serum biomarkers and their correlation with imaging parameters. The previously reported interventional OA study (ClinicalTrials.gov: NCT00536302) identified a positive effect of collagen hydrolysate (CH) on cartilage morphology in patients with knee OA using delayed gadolinium enhanced magnetic resonance imaging (dGEMRIC). It was the objective in this research project to evaluate in an interventional clinical trial on knee OA the level and change of two serum biomarkers and their correlation with imaging parameters. In blood samples of study participants, we determined the concentration of procollagen type II N-terminal propeptide (PIIANP) and aggrecan chondroitin sulfate 846 epitope (CS846) at baseline (BL) and at the follow-up (FU) visits at 24 and 48 weeks. We measured the level and change of biomarker concentrations in both study groups, and the correlation of those changes with changes in dGEMRIC. For the biomarker PIIANP, we observed a significantly greater increase in the CH group (29.9% vs. 1.2% at week 24, P= 0.001). For CS846, the mean concentration was lower among the CH treated participants at 24 weeks (78% vs. 96%, P= 0.045). Consistent correlations of changes in biomarkers PIIANP and CS846 with changes of the dGEMRIC score could not be observed. In this study, different changes per treatment group, CH and placebo were seen for dGEMRIC and PIIANP BL to 24 weeks FU, but only weak correlations between changes in dGEMRIC and biochemical markers.

  • Original Article
    Wen-Qing Li, John E. McGeary, Eunyoung Cho, Alan Flint, Shaowei Wu, Alberto Ascherio, Eric Rimm, Alison Field, Abrar A. Qureshi
    Journal of Biomedical Research. 2017, 31 (1) : 31-39. https://doi.org/10.7555/JBR.31.20160098

    The popularity of indoor tanning may be partly attributed to the addictive characteristics of tanning for some individuals. We aimed to determine the association between frequent indoor tanning, which we view as a surrogate for tanning addiction, and food addiction. A total of 67,910 women were included from the Nurses’ Health Study II. In 2005, we collected information on indoor tanning during high school/college and age 25-35 years, and calculated the average use of indoor tanning during these periods. Food addiction was defined as ≥3 clinically significant symptoms plus clinically significant impairment or distress, assessed in 2009 using a modified version of the Yale Food Addiction Scale. Totally 23.3% (15,822) of the participants reported indoor tanning at high school/college or age 25-35 years. A total of 5,557 (8.2%) women met the criteria for food addiction. We observed a dose–response relationship between frequency of indoor tanning and the likelihood of food addiction (Ptrend<0.0001), independent of depression, BMI, and other confounders. Compared with never indoor tanners, the odds ratio (95% confidence interval) of food addiction was 1.07 (0.99-1.17) for average indoor tanning 1-2 times/year, 1.25 (1.09-1.43) for 3-5 times/year, 1.34 (1.14-1.56) for 6-11 times/year, 1.61 (1.35-1.91) for 12-23 times/year, and 2.98 (1.95-4.57) for 24 or more times/year. Frequent indoor tanning before or at early adulthood is associated with prevalence of food addiction at middle age. Our data support the addictive property of frequent indoor tanning, which may guide intervention strategies to curb indoor tanning and prevent skin cancer.

  • Original Article
    Celia Aradillas-GarcÍa, Miguel Cruz, Elva Pérez-Luque, MarÍa E. Garay-Sevilla, Juan M. Malacara, Aduna R, Jesús Peralta, Ana Burguete-GarcÍa, Jorge A. AlegrÍa-Torres
    Journal of Biomedical Research. 2017, 31 (1) : 40-46. https://doi.org/10.7555/JBR.30.20150169

    This research was designed to analyze the possible associations of Arg389Gly ADRB1 and Trp64Arg ADRB3 polymorphisms in children with obesity. A cross-sectional study included 1,046 school-age Mexican participants (6-12 years old) from the cities of San Luis Potosí and León. Children were classified as non-obese or obese according to their body mass index (BMI) percentile; obese children had a BMI≥95th percentile for sex and age. Biochemical data were collected. Polymorphisms were detected using TaqMan qPCR assay. A logistic regression analysis was used to calculate the risk of obesity based on genotypes. Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, LDL-cholesterol, triglycerides, and lower HDL-cholesterol compared with the normal weight group (P<0.05). The distribution of allele frequency in the population was Arg= 87.4 and Gly= 12.6 (Hardy Weinberg equilibrium c2 = 3.16 , P = 0.07 ); Trp= 81.5 and Arg= 18.5 (Hardy Weinberg equilibrium c2 = 2.2, P = 0.14 ) for ADRB1 and ADRB3, respectively. Even though no different frequencies of Arg389Gly polymorphism between groups were found (P = 0.08), children carriers of one Gly389 ADRB1 allele had a risk for obesity of OR=1.40 (95%CI, 1.03–1.90, P = 0.03) after adjustment for age and gender. No other association was found for Trp64Arg ADRB3 polymorphism. Only the Arg389Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.

  • Original Article
    Mingming Gao, Guo Xin, Xu Qiu, Yuhui Wang, George Liu
    Journal of Biomedical Research. 2017, 31 (1) : 47-55. https://doi.org/10.7555/JBR.31.20160020

    Coronary atherosclerotic disease is a serious disease in humans, but no suitable animal model is available currently for further studies. We used apolipoprotein E gene knockout (ApoE KO) rats to induce hypercholesterolemia through a special high cholesterol/bile salt diet (Paigen diet), then analyzed aortic and coronary atherosclerosis lesions and the myocardial injury in order to establish a novel small animal model of coronary atherosclerosis. Plasma cholesterol of ApoE KO rats increased 7.6-fold compared with wild-type rats after 8 weeks on the Paigen diet. After 10 to 12 weeks of subsisting on the Paigen diet, ApoE KO rats developed mild aortic atherosclerosis with severe coronary atherosclerosis. Hematoxilyn and eosin staining showed that 11 out of 12 ApoE KO male rats had right coronary artery atherosclerosis, 7 of them were>70% occluded. Oil Red O (Lipid Stain), Mac2 immuno-staining and Masson’s trichrome staining demonstrated substantial amounts of lipid, macrophages and collagen fibers in coronary atherosclerosis plaques. In addition, ApoE KO male rats had severe myocardial focal lesions with cholesterol ester as the main component in the lesions. In conclusion, ApoE KO rats developed severe hypercholesterolemia, coronary atherosclerosis and myocardial cholesterol ester deposition after subsisting on the Paigen diet and can be used as a novel animal model for studies on cholesterol metabolism and coronary atherosclerotic disease.

  • Original Article
    Zeping Xu, Lianbing Gu, Qingming Bian, Pengyi Li, Lijun Wang, Jingyuan Zhang, Yanning Qian
    Journal of Biomedical Research. 2017, 31 (1) : 56-64. https://doi.org/10.7555/JBR.31.20160108

    Maintaining adequate oxygenation during one-lung ventilation (OLV) requires high inspired oxygen fraction (FiO2). However, high FiO2 also causes inflammatory response and lung injury. Therefore, it remains a great interest to clinicians and scientists to optimize the care of patients undergoing OLV. The aim of this study was to determine and compare oxygenation, inflammatory response and lung injury during OLV in rabbits using FiO2 of 0.6 vs. 1.0. After 30 minutes of two-lung ventilation (TLV) as baseline, 30 rabbits were randomly assigned to three groups receiving mechanical ventilation for 3 hours: the sham group, receiving TLV with 0.6 FiO2; the 1.0 FiO2 group, receiving OLV with 1.0 FiO2; the 0.6 FiO2 group, receiving OLV with 0.6 FiO2. Pulse oximetry was continuously monitored and arterial blood gas analysis was intermittently conducted. Histopathologic study of lung tissues was performed and inflammatory cytokines and the mRNA and protein of nuclear factor kappa B (NF-кB) p65 were determined. Three of the 10 rabbits in the 0.6 FiO2 group suffered hypoxemia, defined by pulse oximetric saturation (SpO2) less than 90%. Partial pressure of oxygen (PaO2), acute lung injury (ALI) score, myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), mRNA and protein of NF-кB p65 were lower in the 0.6 FiO2 group than in the 1.0 FiO2 group. In conclusion, during OLV, if FiO2 of 0.6 can be tolerated, lung injury associated with high FiO2 can be minimized. Further study is needed to validate this finding in human subjects.

  • Original Article
    Yoon Seok Roh, Ara Cho, Zixiong Zhou, Hyuneui Jeong, Jeong-Eun Park, Youn-Soo Cha, Suk-Heung Oh, Chae-Woong Lim, Bumseok Kim
    Journal of Biomedical Research. 2017, 31 (1) : 65-73. https://doi.org/10.7555/JBR.31.2016K0007

    Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. G-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects. To test this hypothesis, C57BL/6 mice were fed a methionine–choline-deficient (MCD) diet for 8 weeks. After four weeks into MCD feeding, mice were provided with plain water (control) or water containing 2 mg/mL of GABA for the subsequent 4 weeks. Using this MCD diet-induced NASH model, we found that mice receiving GABA showed more severe steatohepatitis and liver fibrosis than control mice. This increased liver damage was confirmed by higher levels of serum alanine transaminase (ALT) and aspartate aminotransferase (AST) compared to the control group. In accordance with increased liver steatohepatitis, NASH-related and inflammatory gene expression (collagen α1, tissue inhibitor of metalloproteinase-1, TNF-α) in the liver was markedly increased in GABA-treated mice. Furthermore, GABA directly enhanced production of inflammatory cytokines including IL-6 and TNF-α in LPS activated RAW macrophage cells and increased TIB–73 hepatocyte death. Such effects were abolished when GABA was treated with bicuculline, a competitive antagonist of GABA receptors. These results suggest that oral administration of GABA may be involved in changes of the liver immune milieu and conferred detrimental effects on NASH progression.

  • Case Report
    Ye Yuan, Yi Zhao, Mi Zhang, Huijun Lu
    Journal of Biomedical Research. 2017, 31 (1) : 74-78. https://doi.org/10.7555/JBR.31.20160080