Nov 2017, Volume 31 Issue 6

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  • Original Article
    Bing Zhang, Ling Ni, Fangfang Wang, Weiping Li, Xin Zhang, Xiaohua Gu, Zuzana Nedelska, Fei Chen, Kun Wang, Bin Zhu, Renyuan Liu, Jun Xu, Jinfan Wang
    Journal of Biomedical Research. 2017, 31 (6) : 486-493.

    We studied the influence of doctor-patient communication skills training on brain functional architecture using resting-state functional MRI (rs-fMRI) with a regional homogeneity (ReHo) method. Ten medical students participated in the study. A 1-year long doctor-patient communication skills training program was conducted. Rs-fMRI data were collected at baseline, one month and one year after training. There was a significant increase in the communication skills test average scores between baseline and 1-month duration of training (P<0.001). After one month of communication skills training, medical students had decreased ReHo in the right superior temporal gyrus compared with the baseline. After one year of communication skills training, students had increased ReHo in multiple regions and decreased ReHo in several regions (P<0.05, Alphasim corrected). The change of ReHo values in the superior temporal gyrus negatively correlated with the change of communication skills scale score between one month after communication skills training and baseline (r=0.734, P= 0.036). The training program we used can be an effective approach of improving doctor-patient communication skills, and the training resulted in functional plasticity of the brain's architecture toward optimizing locally functional organization.

  • Original Article
    Jieun Choi, Eun Suk An, Young-Hwan Ban, Da Woom Seo, Tae-Su Kim, Sung-Pyo Lee, You Lin, Ehn-Kyoung Choi, Yun-Bae Kim
    Journal of Biomedical Research. 2017, 31 (6) : 503-511.

    Particulate matters (PM) are one of the major body burdens leading to diseases. We investigated the capacities of a hydrogen-enriched water (HW) eliminating carbon nanoparticles (CNP) and carbon microparticles (CMP) from the lungs and blood, respectively. In CNP-elimination test, rats were orally administered with purified water (PW) or HW (10 or 30 mL/kg/day) for 10 weeks. At the time point of 4 weeks, the rats were challenged with intratracheal instillation of CNP (4 mg). CNP accumulated in the airways and alveoli, and induced inflammatory lesions. Such pneumoconiosis was markedly improved by feeding HW, while PW was ineffective. CNP-induced pneumoconiosis caused systemic hematological alterations, decreasing major inflammatory cells, but markedly increasing eosinophils, indicative of an allergic reaction, which were attenuated by treatment with HW. Such PM-eliminating and anti-allergic effects of HW reduced body burden as confirmed from the facilitated recovery of body and lung weights. In CMP-clearance test, mice were orally administered with PW or HW for 7 days, and intravenously injected with CMP (300 mg/kg). CMP was rapidly eliminated from the blood in HW-fed mice. Indeed, the phagocytic indices increased to 3.5 and 6.7 folds at 10 and 30 mL/kg of HW, in comparison with a negligible effect of PW. As a mechanism study, only HW significantly inhibited lipid peroxidationin vitro Fenton reaction-mediated ·OH-generating system. Collectively, the results indicate that HW not only effectively eliminated PM from the lungs and blood by enhancing phagocytic activity, but also attenuated the lung injuries by inhibiting lipid peroxidation.

  • Original Article
    Li Xin, Tian Han, Jiao Tang, Xiaoyu Wang, Hao Zhang, Hongyan Dong, Kaijin Guo, Zhongming Zhang
    Journal of Biomedical Research. 2017, 31 (6) : 512-520.

    Acrylic bone cements are currently the most frequently and extensively used materials in orthopedic implant treatment. However, adverse effects have been described of acrylic bone cement on the cardiovascular system. In the present study, we examined the cytotoxicity of bone cement ingredient methyl methacrylate (MMA) to cardiomyocytes and the potential detoxifying effect of pigment epithelium-derived factor (PEDF) in H9c2 cells. We found that high concentration of MMA (>120 mmol/L) led to necrotic cell death in H9c2 cells. However, MMA at low concentrations (30-90 mmol/L) caused apoptosis. Pretreatment of PEDF prevented MMA-induced cytotoxicity. In addition, PEDF enhanced total superoxide dismutase activities, and decreased MMA-induced production of malonaldehyde. Furthermore, MMA-induced downregulation of Akt activity was suppressed by PEDF. PEDF also increased the levels of peroxisome proliferator activated receptor gamma (PPAR g) and lysophosphatidic acids (LPA) through PEDF receptor. These results indicated that PEDF inhibited MMA-induced cytotoxicity through attenuating oxidative stress, activating the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and/or PEDF receptor-LPA-PPAR g pathways in H9c2 cells. PEDF may be explored as a candidate therapeutic agent for alleviating bone cement implantation syndrome during orthopedic surgery.

  • Review Article
    Vassilis I. Zannis, Shi Su, Panagiotis Fotakis
    Journal of Biomedical Research. 2017, 31 (6) : 471-485.

    In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1 (ABCA1), and lecithin: cholesterol acyltransferase (LCAT) in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I (and to a lesser extent with apoE and apoA-IV) and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant preβ HDL subpopulations that cannot be converted efficiently to α subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size α4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL. The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL.

  • Original Article
    Leijian Guan, Kaixuan Xu, Shuyang Xu, Ningning Li, Xinru Wang, Yankai Xia, Di Wu
    Journal of Biomedical Research. 2017, 31 (6) : 528-540.

    Leptin deficiency is principally linked to metabolic disorders. Leptin knockout (LepΔI14/ΔI14) Sprague Dawley rats created by CRISPR/Cas9 is a new model to study metabolic disorders. We used a whole rat genome oligonucleotide microarray to obtain tissue-specific gene expression profiles of the white adipose tissue, liver and hypothalamus inLepΔI14/ΔI14 and wild-type (WT) rats. We found 1,651 differentially expressed (enriched) genes in white adipose tissue, 916 in the liver, and 306 in the hypothalamus in theLepΔI14/ΔI14 rats compared to WT. Gene ontology category and KEGG pathway analysis of the relationships among differentially expressed genes showed that these genes were represented in a variety of functional categories, including fatty acid metabolism, molecular transducers and cellular processes. The reliability of the data obtained from microarray was verified by quantitative real-time PCR on 14 representative genes. These data will contribute to a greater understanding of different metabolic disorders, such as obesity and diabetes.

  • Original Article
    Hamid Reza Hemmati, Mahdi Alizadeh, Alireza Kamali-Asl, Shapour Shirani
    Journal of Biomedical Research. 2017, 31 (6) : 548-558.

    Carotid artery stenosis causes narrowing of carotid lumens and may lead to brain infarction. The purpose of this study was to develop a semi-automated method of segmenting vessel walls, surrounding tissues, and more importantly, the carotid artery lumen by contrast computed tomography angiography (CTA) images and to define the severity of stenosis and present a three-dimensional model of the carotid for visual inspection.In vivo contrast CTA images of 14 patients (7 normal subjects and 7 patients undergoing endarterectomy) were analyzed using a multi-step segmentation algorithm. This method uses graph cut followed by watershed and Hessian based shortest path method in order to extract lumen boundary correctly without being corrupted in the presence of surrounding tissues. Quantitative measurements of the proposed method were compared with those of manual delineation by independent board-certified radiologists. The results were quantitatively evaluated using spatial overlap surface distance indices. A slightly strong match was shown in terms of dice similarity coefficient (DSC) = 0.87±0.08; mean surface distance (Dmsd) = 0.32±0.32; root mean squared surface distance (Drmssd) = 0.49±0.54 and maximum surface distance (Dmax) = 2.14±2.08 between manual and automated segmentation of common, internal and external carotid arteries, carotid bifurcation and stenotic artery, respectively. Quantitative measurements showed that the proposed method has high potential to segment the carotid lumen and is robust to the changes of the lumen diameter and the shape of the stenosis area at the bifurcation site. The proposed method for CTA images provides a fast and reliable tool to quantify the severity of carotid artery stenosis.

  • Original Article
    Eun-sung Park, Jung-mo Ahn, Sang-min Jeon, Hee-jung Cho, Ki-myung Chung, Je-yoel Cho, Dong-ho Youn
    Journal of Biomedical Research. 2017, 31 (6) : 494-502.

    Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice. In this study, whole proteins were extracted from the ipsilateral dorsal half of the 4th–6th lumbar spinal cord in a mouse model of spared nerve injury (SNI)-induced neuropathic pain. In-gel digests of the proteins size-separated on a polyacrylamide gel were subjected to reverse-phase liquid-chromatography coupled with electrospray ionization ion trap tandem mass spectrometry (MS/MS). After identifying proteins, the data were analyzed with subtractive proteomics usingProtAn, an in-house analytic program. Consequently, 15 downregulated and 35 upregulated proteins were identified in SNI mice. The identified proteins may contribute to the maintenance of neuropathic pain, and may provide new or valuable information in the discovery of new therapeutic targets for neuropathic pain.

  • Original Article
    Xiaoyang Liu, Chunlin Zheng, Cheng Xu, Qian Liu, Jin Wang, Yongzhi Hong, Peng Zhao
    Journal of Biomedical Research. 2017, 31 (6) : 541-547.

    Relationship between nighttime snack and human health conditions remains unclear. In this paper, we analyzed the association of frequency of nighttime snacking with obesity, hyperlipidemia and hyperglycemia using a Chinese teacher cohort. The Chinese teacher study contains 22,176 of the general adult population operated on in 2015. Information of nighttime snacking frequency was acquired by questionnaire. Overweight and obesity outcome were assessed by body mass index (BMI), and hypertension; hyperlipidemia and hyperglycemia were self-reported. Associations between nighttime snacking consumption and outcomes were performed with multivariat regression and further stratification analyses. We found a significant association (OR 2.11, 95% CI 1.24, 3.62;P for trend<0.001) between most frequent nighttime snacking and hyperglycemia. A remarkable association was also observed between most frequent consumption of nighttime snack and obesity (OR 3.10, 95% CI 1.63, 5.89;Pfor trend<0.001). The present results provide epidemiological evidence that consumption of nighttime snack was associated with obesity and hyperglycemia in Chinese adult teachers. However, the underlying mechanisms still need further investigation.

  • Original Article
    Alireza Shirpoor, Farzaneh Hosseini Gharalari, Yousef Rasmi, Elaheh Heshmati
    Journal of Biomedical Research. 2017, 31 (6) : 521-527.

    Chronic ethanol consumption is associated with changes in the function and structure of the lungs. The aim of this study was to investigate the effect of chronic ethanol exposure on the lungs and whether ginger extract mitigated pulmonary abnormalities induced by ethanol in rats. Male Wistar rats were divided into the control group, the ethanol group, and the ethanol plus ginger extract group. Six weeks of ethanol treatment increased the proliferation of lung cells, and induced fibrosis, inflammation and leukocyte infiltration. A significant rise in the level of 8-hydroxydeoxyguanosine, NADPH oxidase, and oxidized low-density lipoprotein was also observed. Ginger extract significantly ameliorated the above changes. These findings indicate that ethanol induces abnormalities in the lungs by oxidative DNA damage and oxidative stress, and that these effects can be alleviated by ginger, which may function as an antioxidant and anti-inflammatory agent.

  • Case Report
    Natalia Liapounova, Kamran H. Azar, J. Max Findlay, Jian-Qiang Lu
    Journal of Biomedical Research. 2017, 31 (6) : 559-562.

    Immune-mediated mechanisms are involved in the pathogenesis of both cerebral vasculitis and Parkinson's disease (PD, brainstem-predominant Lewy pathology), but the presentation of cerebral vasculitis with comorbid Lewy pathology has not yet been reported. Here we present a case of pathologically confirmed vasculitis in a 73-year-old male patient whose postmortem examination revealed Lewy pathology diagnostic of PD. This case study suggests a comorbidity of cerebral vasculitis and Lewy pathology, as well as potential pathogenic interactions between these two disorders with immune-mediated mechanisms.