Asian Pacific Journal of Tropical Medicine

Volume 9,Issue 2,2016 Table of Contents

  • Display Type:
  • Text List
  • Abstract List
  • 1  Anti-Alzheimer's disease potential of coumarins from Angelica decursiva and Artemisia capillaris and structure-activity analysis
    Md. Yousof Ali Susoma Jannat Hyun Ah Jung Ran Joo Choi Anupom Roy Jae Sue Choi
    2016, 9(2):101-108. DOI: 10.1016/j.apjtm.2016.01.014
    [Abstract](58) [HTML](0) [PDF 385.50 K](251)
    Abstract:
    Objective: To use structure-activity analysis to study the anti-Alzheimer's disease (anti-AD) activity of natural coumarins isolated from Angelica decursiva and Artemisia capillaries, along with one purchased coumarin (daphnetin). Methods: Umbelliferone, umbelliferone 6-carboxylic acid, scopoletin, isoscopoletin, 7-methoxy coumarin, scoparone, scopolin, and esculetin have been previously isolated; however 2'-isopropyl psoralene was isolated from Angelica decursiva for the first time to evaluate their inhibitory effects against acetylcholinesterase (AChE),butyryl cholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) enzyme activity. We scrutinized the potentials of coumarins as cholinesterase and BACE1 inhibitors via enzyme kinetics and molecular docking simulation. Results: Among the test compounds, umbelliferone 6-carboxylic acid, esculetin and daphnetin exhibited potent inhibitory activity against AChE, BChE and BACE1. Both esculetin and daphnetin have a catechol group and exhibit significant anti-AD activity against AChE and BChE. In contrast, presence of a sugar moiety and methoxylation markedly reduced the anti-AD activity of the coumarins investigated in this study. With respect to BACE1 inhibition, umbelliferone 6-carboxylic acid, esculetin and daphnetin contained carboxyl or catechol groups, which significantly contributed to their anti-AD activities. To further investigate these results, we generated a 3D structure of BACE1 using Autodock 4.2 and simulated binding of umbelliferone 6-carboxylic acid, esculetin and daphnetin. Docking simulations showed that different residues of BACE1 interacted with hydroxyl and carboxylic groups, and the binding energies of umbelliferone 6-carboxylic acid, esculetin and daphnetin were negative (-4.58,-6.25 and-6.37 kcal/mol respectively). Conclusions: Taken together, our results suggest that umbelliferone 6-carboxylic acid, esculetin and daphnetin have anti-AD effects by inhibiting AChE, BChE and BACE1, which might be useful against AD.
    2  Dengue virus non-structural 1 protein interacts with heterogeneous nuclear ribonucleoprotein H in human monocytic cells
    Drishya Diwaker Mishra K P Ganju L Singh S B
    2016, 9(2):109-114. DOI: 10.1016/j.apjtm.2016.01.015
    [Abstract](97) [HTML](0) [PDF 372.94 K](237)
    Abstract:
    Objective: To study protein-protein interaction between heterogeneous nuclear ribonucleoprotein H (hnRNP H) and Dengue virus (DENV) proteins. Methods: DENV proteins were screened against the host hnRNP H protein, in order to identify the host-viral protein-protein interactions in DENV infected THP-1 cells by co-immunoprecipitation. The co-localization of the interacting proteins was further confirmed by immunofluorescence microscopy. Results: The host protein hnRNP H was found to interact with DENV non-structural 1 protein and help the virus to multiply in the cell. Conclusions: The non-structural 1 glycoprotein is a key modulator of host immune response and is also involved in viral replication. Therefore, disruption of this key interaction between hnRNP H and DENV non-structural 1 could be an important therapeutic strategy for management of DENV infection.
    3  Effect of roselle calyx extract on in vitro viability and biofilm formation ability of oral pathogenic bacteria
    Herastuti Sulistyani Mari Fujita Hiroshi Miyakawa Futoshi Nakazawa
    2016, 9(2):115-120. DOI: 10.1016/j.apjtm.2016.01.020
    [Abstract](52) [HTML](0) [PDF 325.13 K](248)
    Abstract:
    Objective: To investigate the effect of the roselle calyx extract (RCE) (Hibiscus sabdariffa L.) on the /i>in vitro viability and biofilm formation ability of oral pathogenic bacteria. Methods: RCE was prepared by soaking roselle calyx powder with ethyl alcohol for 24 h at room temperature. After centrifugation, the extract was lyophilized. Then, the extract was dissolved in phosphate-buffered saline, the pH was adjusted, and the extract was aseptically filtered. We used Streptococcus mutans, Streptococcus sanguinis, Lactobacillus casei, Actinomyces naeslundii, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis and Prevotella intermedia in this study. The antibacterial activity of the RCE was determined by treating the cells of these bacteria with the extract for 10 or 20 min at room temperature. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration was determined using the micro dilution method, and the effect of the RCE on the ability to form biofilm was determined using a polystyrene micro plate assay. In addition, we used the WST-1 assay to determine the cytotoxicity of the RCE on HGF, Ca9-22 and KB cells. Results: The RCE had antibacterial activity against oral bacteria used in this study. In particular, mostsignificantantibacterial activity was observed against Fusobacterium nucleatum, Prevotella intermedia and Porphyromonas gingivalis. The MIC and minimum bactericidal concentration were 7.2 mg/mL–28.8 mg/mL and 14.4 to >57.6 mg/mL. The RCE had an inhibitory effect on biofilm formation at the MIC and sub-MIC levels. In addition, the RCE had low cytotoxic effects on HGF, Ca9-22 and KB cells. Conclusions: Thus, our results indicate that the RCE may be used for preventing oral diseases.
    4  Evaluation of anti-tubercular activity of linolenic acid and conjugatedlinoleic acid as effective inhibitors against Mycobacterium tuberculosis
    Won Hyung Choi
    2016, 9(2):121-125. DOI: 10.1016/j.apjtm.2016.01.021
    [Abstract](46) [HTML](0) [PDF 302.58 K](257)
    Abstract:
    Objective: To evaluate a new pharmacological activity/effect of linolenic acid (α- and γ-form) and conjugated-linoleic acid (CLA) causing antibacterial activity against Mycobacterium tuberculosis (Mtb). Methods: The anti-Mtb activity/effect of linolenic acid and CLA were determined using different anti-Mtb indicator methods such as resazurin microtiter assay (REMA) and MGIT 960 system assay. The Mtb was incubated with various concentrations (12.5–200) μg/mL of the compounds and anti-Mtb first-line drugs for 5 d in the REMA, and for 3 wk in MGIT 960 system assay. Results: Linolenic acid and CLA obviously indicated their anti-Mtb activity/effect by strongly inhibiting the growth/proliferation of Mtb in a dose-dependent manner in the REMA and the MGIT 960 system assay. Interestingly, linolenic acid and CLA consistently induced anti-Mtb activity/effect by effectively inhibiting the growth/ proliferation of Mtb in MGIT 960 system for 21 d with a single-treatment, and their minimum inhibitory concentrations were measured as 200 μg/mL respectively. Conclusions: These results demonstrate that linolenic acid and CLA not only have effective anti-Mtb activity/ properties, but also induce the selective-anti-Mtb effects by strongly inhibiting and blocking the growth/proliferation of Mtb through a new pharmacological activity/action. Therefore, this study provides novel perspectives for the effective use of them and the potential that can be used as potent anti-Mtb candidate drugs, as well as suggests the advantage of reducing the cost and/or time for developing a new/substantive drug by effectively repurposing the existing drugs or compounds as one of new strategies for the global challenge of tuberculosis.
    5  Recognition of a multiple antigen peptide containing sequence from mimotope of the dengue type 3 virus NS4B protein by human antibodies
    Nevis Amin Maritza Pupo Alicia Aguilar Susana Vázquez Yamira Caballero Rolando Ochoa María G Guzmán Armando Acosta
    2016, 9(2):126-129. DOI: 10.1016/j.apjtm.2016.01.019
    [Abstract](21) [HTML](0) [PDF 299.78 K](246)
    Abstract:
    (MAP), by dengue antibodies presents in serum samples from patients with different serotype infections. Methods: A MAP containing mimotope sequence was synthesized and used to evaluate the recognition of NS4B mimotope as MAP by a panel of 66 human sera from dengue cases by an indirect ELISA assay. Results: The MAP differentiated between sera from dengue viruses infected patients and sera from healthy individuals and the best reactivity was shown by serum from dengue type 3 virus patients. The recognition was more intense with serum from patients with secondary infection. Conclusions: The findings suggest the potential use of NS4B mimotope on the development of a multi-epitope diagnostic tool. These results are important for further immunogenicity studies.
    6  Concurrent infections of dengue viruses serotype 2 and 3 in patient with severe dengue from Jakarta, Indonesia
    Soroy Lardo Yaldiera Utami Benediktus Yohan Seri MMU Tarigan Widayat Djoko Santoso Leonard Nainggolan R Tedjo Sasmono
    2016, 9(2):130-135. DOI: 10.1016/j.apjtm.2016.01.013
    [Abstract](68) [HTML](0) [PDF 292.03 K](243)
    Abstract:
    Objective: To describe the clinical manifestation of patient with severe dengue, to identify the serotypes and genotypes of dengue viruses (DENV) which concurrently infecting the patient, and to explore the possible relationship of severe dengue with the concurrent infection of DENV. Methods: Dengue diagnosis was performed using NS1 antigen detection and IgG/ IgM ELISA. Standard clinical and laboratory examinations were performed to obtain the clinical and hematological data. DENV concurrent infections were detected and confirmed using RT-PCR and DENV Envelope gene sequencing. Phylogenetic analyses were performed to determine the genotypes of the viruses. Results: The patient was classified as having severe dengue characterized by severe plasma leakage, hemorrhage, and organ damage involving lung, liver, and kidney. Concurrent infection of DENV serotype 2 and 3 was observed. The infecting DENV-2 virus was grouped into Cosmopolitan genotype while DENV-3 virus was classified into Genotype Ⅰ. Both viruses were closely related to isolates that were endemic in Jakarta. Viremia measurement was conducted and revealed a significantly higher virus titer of DENV-3 compared to DENV-2. Conclusions: The occurrence of multi-serotype DENV infections was presented in a patient with severe clinical manifestation in Indonesia. The hyperendemicity of dengue in Indonesia may contribute to the DENV concurrent infections cases and may underlie the severity of the disease.
    7  Immunological evidence of Zika virus transmission in Thailand
    Nitwara Wikan Yupin Suputtamongkol Sutee Yoksan Duncan R. Smith Prasert Auewarakul
    2016, 9(2):136-139. DOI: 10.1016/j.apjtm.2016.01.017
    [Abstract](67) [HTML](0) [PDF 265.90 K](274)
    Abstract:
    Objective: To identify immunological evidence of Zika virus transmission in Thailand. Methods: To undertake a preliminary serosurvey of possible exposure to Zika virus, 21 serum samples from cohort of acute undifferentiated fever patients were examined for immunoreactivity to Zika, Dengue, Japanese encephalitis and Chikungunya envelope antigens by Western blot analysis. Results: Twenty of the 21 serum samples showed immunoreactivity to at least one of the antigens, with seven samples showing immunoreactivity to all antigens. Of particular note, two serum samples showed immunoreactivity only to Zika envelope antigen, with no immunoreactivity to other envelope antigens. Conclusions: This study presents the first evidence of Zika virus transmission in Thailand, although as yet the relationship between transmission and possible cases of Zika fever in Thailand requires further investigation.
    8  First histopathological study in kidneys of rodents naturally infected with Leptospira pathogenic species from Yucatan, Mexico
    Marco Torres-Castro Leonardo Guillermo-Cordero Silvia Hernández-Betancourt Edwin Gutiérrez-Ruíz Piedad Agudelo-Flórez Ronald Peláez-Sánchez Jorge Zavala-Castro Fernando I. Puerto
    2016, 9(2):140-142. DOI: 10.1016/j.apjtm.2016.01.018
    [Abstract](43) [HTML](0) [PDF 258.61 K](242)
    Abstract:
    Objective: To report the renal histological lesions in synanthropic rodents, Mus musculus and Rattus rattus, naturally infected with Leptospira spp., captured in a rural community in Yucatan, Mexico. Methods: Kidney samples of synanthropic rodents were collected from a rural community in Yucatan, Mexico. Polymerase chain reaction was used to detect Leptospira spp. infection. Tissue kidney was fixed in 10% buffered formalin, processed according to the usual techniques for paraffin inclusion, cut and stained with hematoxylin and eosin, and examined using a conventional electronic microscope. Results: A total of 187 rodents were captured. Nine individuals (4.8%) were positive for Leptospira spp. in the molecular analysis. All renal lesionsobserved in the histopa thological study had been reported previously for Leptospira spp. infection. Conclusions: The histopathological lesions are present in the kidneys, plus the results of the polymerase chain reaction confirm that these rodents are true carriers of Leptospira spp.
    9  Effect of tight junction protein of intestinal epithelium and permeability of colonic mucosa in pathogenesis of injured colonic barrier during chronic recovery stage of rats with inflammatory bowel disease
    Chun-Mei Xu Xiu-Mei Li Bing-Zhao Qin Bo Liu
    2016, 9(2):143-147. DOI: 10.1016/j.apjtm.2016.01.001
    [Abstract](55) [HTML](0) [PDF 317.32 K](292)
    Abstract:
    Objective: To discuss the changes in the tight junction protein of intestinal epithelium andpermeability of colonic mucosa and its possible mechanism by building the rat mode of inflammatory bowel disease at the chronic recovery stage. Methods: A total of 36 SD rats were divided into the model group and control one according to the random number table, with 18 rats in each group. Rats in the model group were given the 3% dextran sulfate sodium solution bythe way of drinking for 7 d to build the rat model of inflammatory bowel disease, while rats inthe control group were given free drinking of water. Six rats were executed at day 7, 14 and 21respectively. The colonic tissues were collected from rats to observe the pathological changes of colonic mucosa. The activity of myeloperoxidase was detected and the white blood count wasperformed for rats in each group. The Ussing chamber technique was employed to detect the transepithelial electrical resistance (TER) and short-circuit current (SC) of colonic mucosa of rats in different time intervals; the quantum dots labeling technique was employed to detect the expression level of claudin-1 and claudin-2 in the colonic tissues. Results: After the successful modeling, the weight of rats in the model group was significantly reduced, while the diseaseactivity index score was increased. The weight was at the lowest level at day 14 and then it began to increase afterwards. The disease activity index score was at the highest level at day 12 and then it began to decrease gradually. The activity of myeloperoxidase and WBC for rats in the model group all reached the peak value at day 14 and then decreased gradually. There was no significant difference in the changes of TER and SC in different time intervals for rats in the control group(P>0.05). TER of model group was at the lowest level at day 14 and then increased gradually;SC was at the highest level at day 14 and then decreased gradually. TER of model group at day 7, 14 and 21 was significantly lower than that of control group, while SC of model group wassignificantly higher than that of control group (P<0.05). There was no significant difference in the change of mean fluorescence intensity of claudin-1 and claudin-2 in different time intervals for rats in the control group (P>0.05). The claudin-1 and claudin-2 for rats in the model group reached the highest level at day 14 and then decreased gradually. The claudin-1 and claudin-2 of model group at day 7, 14 and 21 was significantly higher than that of control group (P<0.05). Conclusions: After the acute stage, the inflammatory bowel disease is then in the chronic recovery stage; the increased permeability of colonic mucosa and increased expression of tight junction protein ofintestinal epithelium are closely related to the pathogenesis and development of disease. The tight junction protein plays a key role in the pathogenesis of injured colonic barrier of inflammatorybowel disease.
    10  Correlation between blood circulation grading and angiogenesis using ultrasonic contrast of rabbit VX2 hepatic carcinoma
    Chang-Song Xu Yi-Jin Su Ming Xu Wei Liu Peng Hao Lian-Fang Du
    2016, 9(2):148-153. DOI: 10.1016/j.apjtm.2016.01.002
    [Abstract](35) [HTML](0) [PDF 302.57 K](237)
    Abstract:
    Objective: To build the rabbit model of VX2 hepatic carcinoma, examine the tumor body using the ultrasonic contrast and study the correlation between the blood circulation grading and angiogenesis. Methods: The VX2 tumor strain was prepared in the lateral muscle of the hind legs of 40 male New Zealand rabbits (which were purchased from Nanjing Senbao Biotech Co., Ltd.). The tumor block was embedded in the center of left liver lobe directly to build the rabbit model of VX2 hepatic carcinoma. The ultrasonic contrast was performed 14 d after implanting the tumor body. The semi-quantitative classification (0-Ⅳ level) was taken according to the blood flow of tumor vessel. Animals were executed using the air embolism method. The liver was separated to extract RNA and total protein respectively. The real-time PCR and western blotting method were employed to detect the expression of angiogenesis-related factors of VEGF, bFGF and TNF-α, while the ultrasonic contrast to detect the correlation with blood circulation grading. The Pearson product moment correlation coefficient was used to measure the linear relationship between these two variables and analyze the correlation between the blood circulation grading and angiogenesis using the ultrasonic contrast. Results: Thirty-three rabbits had the successful model of VX2 hepatic carcinoma. The blood circulation grading by ultrasonic contrast was: 2 cases at level 0 (6.60%), 5 cases at level Ⅰ (16.7%), 12 cases at level Ⅱ (40.0%), 6 cases at level Ⅲ (20.0%) (local dense or clustered blood flow) and 5 cases at level Ⅳ (16.7%). The results showed that there was positive correlation between three angiogenesis-related factors and the blood circulation grading. The correlation coefficient between three angiogenesis-related factors and the blood circulation grading was over 0.9, which indicated the relatively high correlation. Conclusions: The ultrasound blood circulation grading for the hepatic carcinoma can clearly reflect the changes of blood vessel, which will be of critical significance for the early diagnosis of hepatic carcinoma and clinical evaluation of angiogenesis indicators.
    11  Immunogenicity and immunizing protection effect of GAMA gene DNA vaccine on Plasmodium berghei
    Feng Du Si Wang Chen Zhao Ya-Ming Cao En-Jie Luo
    2016, 9(2):154-159. DOI: 10.1016/j.apjtm.2016.01.003
    [Abstract](19) [HTML](0) [PDF 300.86 K](236)
    Abstract:
    Objective: To explore the effect of immunogenicity and immunizing protection of GAMA gene DNA vaccine, which was related with merozoite, ookinete and sporozoite invasion. Methods:Gene fragments were obtained using PCR technique and eukaryotic expression vector (containing immunostimulatory sequence) was built. BALB/c mice were divided into PBS control group,empty vector control group and study group and were immunized at week 0, 3 and 6 respectively.Blood was collected 2 weeks after each immunization and serum was separated to detect the IgG,IgG1 and IgG2a levels. Spleen of mice was obtained for preparation of splenic mononuclear cell and the cytokine IL-4 and IFN-γlevels were detected. Indirect immunofluorescence and western blot were employed to verify the specificity of antiserum. Sporozoite and merozoite invasion were used respectively to detect the immune protective effect 2 weeks after the third immunization.Ookinete conversion rate in vitro and oocyst numbers of mosquito stomach were observed to evaluate the transmission-blocking levels. Results: In GAMA DNA vaccine group: antiserum could be combined with recombinant protein specifically and green fluorescence signals of merozoite, ookinete and sporozoite were observable, while specific fragments and fluorescence signals were not observable in empty vector group. Compared with control group, specific IgG in DNA vaccine immunity group significantly increased (P<0.01), and IgG1 and IgG2a all increased(P<0.01). IL-4, IFN-γcontent in study group significantly increased, compared with control group (P<0.01). GAMA DNA vaccine immunity could not obviously block the erythrocyte-stage infection (caused by sporozoite invasion); compared with control group, liver worm load wasslightly reduced (P<0.05), and antiserum ookinete numbers (cultured in vitro) had no significant difference with oocyst numbers of mosquito stomach in DNA vaccine group. Conclusions:GAMA has good antigenicity, which could stimulate the body to produce specific immune responses; while DNA vaccine immunity could not play a good protective effect, the effect of which is only limited to the slight reduction of liver worm load, and has no obvious erythrocytestage protective effect and transmission-blocking effect. Therefore, trying other immunization strategies for further research on the value of GAMA (as multi-stage antigen vaccine and multistage combined vaccine components of the life-cycle of plasmodium) is necessary.
    12  Effect of lentivirus-mediated integrin α V β 3-shRNA on tumor growth of mice with lung cancer xenografts
    Tao Liang Yong-Fu Ma Jian Chu Dao-Xi Wang Yang Liu
    2016, 9(2):160-163. DOI: 10.1016/j.apjtm.2016.01.004
    [Abstract](35) [HTML](0) [PDF 296.09 K](247)
    Abstract:
    Objective: To study the effect of lentivirus-mediated integrin α V β3-shRNA on tumor growth of mice with lung cancer xenograft. Methods: Lung cancer tissue, paracancer tissue and normal tissue were collected and integrin α V β3 expression was detected; BALB/c nude mice were selected, divided into integrin α V β3 knockdown group (KD group) and negative control group (NC group), and inoculated with cells stably infected by integrin α Vβ3-shRNA lentivirus and cells stably infected by negative control-shRNA lentivirus respectively, the growth of tumor tissue was continuously observed, and the number of apoptosis cells as well as the expression of angiogenesis, apoptosis and invasion genes in tumor tissue were detected. Results: mRNA content and protein content of integrin α V β3 in lung cancer tissue were significantly higher than those in paracancer tissue and normal tissue; increasing trend of tumor tissue volume of KD group was weaker than that of NC group, and tumor volume at various points in time of KD group was lower than that of NC group; mRNA contents and protein contents of VEGF, FGF, EGF, Bcl-2, MMP-9, MMP-12 and MMP-13 in tumor tissue of KD group were lower than those of NC group, and apoptosis index as well as mRNA content and protein content of Bax were higher than those of NC group. Conclusions: The expression of integrin α V β3 increases in lung cancer tissue, and lentivirus-mediated integrin α V β3-shRNA can inhibit tumor growth of mice with lung cancer xenografts.
    13  Anti-proliferation effect of zoledronic acid on human colon cancer line SW480
    Fu-Shi Han Mou-Bin Lin Hui-Yuan Zhu Ying-Qun Chen Wei Shui Jin-Ming Xu
    2016, 9(2):164-168. DOI: 10.1016/j.apjtm.2016.01.005
    [Abstract](47) [HTML](0) [PDF 311.96 K](226)
    Abstract:
    Objective: To investigate the anti-proliferation effect and mechanism of zoledronic acid (ZOL) on human colon cancer line SW480. Methods: SW480 cells were treated with 0, 12.5, 25, 50, 100 and 200 μmoL/L of ZOL for 48 h, and CCK-8 assay was employed to obtain the survival rate of SW480 cells. SW480 cells were treated with 25 μmoL/L of ZOL for 0, 12, 24, 48 and 72 h, and then the survival rate was obtained. SW480 cells of the ZOL group were treated with 25 μmoL/L of ZOL for 48 h, while cells of the CsA+ZOL group were pretreated with 10 μmoL/L of CsA for 0.5 h and then treated with 25 μmoL/L of ZOL for 48 h. Then the survival rates of SW480 cells of the control group, ZOL group and CsA+ZOL group were determined. Flow cytometry was employed to detect the apoptosis rate and the mitochondrial transmembrane potential (ψm) of the three groups and Western blot was used to detect the expressions of cyt C in the cytosol of the three groups. Results: ZOL inhibited the proliferation of SW480 cells, and the inhibition rate positively correlated with the concentration of ZOL and the action time (P< 0.01). The cell survival rate and the ψm of the ZOL group were greatly lower than those of the control group, while the apoptosis rate and the expression of cyt C in the cytosol were obviously higher than those of the control group. All the differences showed distinctly statistical significances (P< 0.01). The cell survival rate and the △ψm of the CsA+ZOL group were all lower than those of the control group, but substantially higher than those of the ZOL group; while the apoptosis rate and the expression of cyt C in the cytosol were higher than those of the control group, but distinctly lower than those of the ZOL group. All the differences were statistically significant (P< 0.01). Conclusions: ZOL can induce the apoptosis in human colon cancer line SW480 and then inhibit the proliferation of SW480 cells directly by opening the mitochondrial permeability transition pore abnormally, decreasing ψm, and releasing the cyt C into the cytosol. And the effect enhances with the increases of the concentration of ZOL and the action time.
    14  E670G polymorphism of PCSK9 gene of patients with coronary heart disease among Han population in Hainan and three provinces in the northeast of China
    Xi-Min He Lin Chen Tian-Song Wang Yun-Bo Zhang Jiang-Bin Luo Xu-Xia Feng
    2016, 9(2):169-174. DOI: 10.1016/j.apjtm.2016.01.008
    [Abstract](73) [HTML](0) [PDF 321.34 K](230)
    Abstract:
    Objective: To investigate the correlation between E670G polymorphism of proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and coronary heart disease (CHD), and contrastively study the regional differences of E670G polymorphism of PCSK9 gene between patients with CHD among the Han population in Hainan and three provinces in the northeast of China (TPNC), providing scientific basis for prevention and treatment of patients with CHD in different regions. Methods: A total of 233 cases of patients with CHD were selected from the Han population in Hainan and TPNC as the experimental group (118 cases from Hainan, 115 cases from TPNC), and 239 cases with non-CHD were selected among the Han population also in the two regions as control group (125 cases from Hainan, 114 cases from TPNC). The triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol and low density lipoprotein cholesterol (LDL-C) levels of plasma were tested and PCR-RFLP method was used to test the E670G polymorphism of PCSK9 gene. The statistical software package SPSS 21.0 was used for the statistical analysis and P<0.05 was considered as statistically significant. Results: The levels of systolic pressure, diastolic blood pressure, fasting blood sugar, TC, TG, and LDL-C of patients in CHD group were significantly higher than those in non-CHD group, while the high density lipoprotein cholesterol level was lower than that in non-CHD group (P<0.05). In CHD group, the frequencies of AG, GG genotypes of PCSK9 gene and G allele were higher than those in non-CHD group (P<0.05), and in CHD group, the frequencies of AG, GG genotypes and G allele of patients both in Hainan and TPNC were higher than those in control group (P<0.05). Among the patients with CHD, the frequencies of GG genotype and G allele of patients in Hainan were lower than those in TPNC (P<0.05), and in CHD group, the levels of TG, TC and LDL-C of GG genotype were higher than those of AA genotype (P<0.05). While in non-CHD group, there were no significant differences between the frequencies of GG genotype and G allele of patients in Hainan and TPNC (P>0.05). Conclusions: There was a close correlation between the E670G polymorphism of PCSK9 gene and CHD with serum lipid level. Among Han population in Hainan and TPNC, the E670G polymorphism of PCSK9 gene of patients with CHD exhibited regional differences.
    15  Association of CT perfusion imaging with plasma levels of TGF-β1 and VEGF in patients with NSCLC
    Da-Wei Li Bao-Zhong Wu Yu-Sen Shi Zhi-Qun Li Xu-Dong Liu Xiao-Hua Li
    2016, 9(2):175-177. DOI: 10.1016/j.apjtm.2016.01.009
    [Abstract](52) [HTML](0) [PDF 270.09 K](301)
    Abstract:
    Objective: To study the association of CT perfusion imaging parameters with plasma level oftransforming growth factor-β1 (TGF-β1) and vascular endothelial growth (VEGF) in patients with non small cell cancer (NSCLC). Methods: A total of 67 patients with NSCLC (NSCLC group) and 64 patients with benign lesion (control group) were given with CT perfusion imaging to obtain blood flow, blood volume, mean transit time, time to peal and permeability surface through CT perfusion software. The plasma levels of TGF-β1 and VEGF were tested by ELISA. The relationship between plasma levels of TGF-β1, VEGF and CT perfusion imaging parameters were analyzed. Results: CT perfusion imaging parameters and the plasma levels of TGF-β1 and VEGF of NSCLC group were significantly higher than the control group (P<0.05), while CT perfusion parameters and the levels of TGF-β1 and VEGF in NSCLC group showed significant difference in different tumor node metastasis stages (P<0.05).Correlation analysis showed that the level of plasma TGF-β1 and VEGF were positively correlated with blood flow, blood volume, and mean transit time (P<0.05), and negatively correlated with time to peal (P<0.05). There was no significant correlation between TGF-β1 and VEGF with the permeability surface. Conclusions: CT perfusion imaging parameters in patients with NSCLC is closely associated with plasma TGF-β1, VEGF and its biological characteristics. CT perfusion imaging is a convenient method to detect tumor blood perfusion.
    16  Inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice
    Yun Zhang Qing-Zhan Liu Su-Ping Xing Jin-Ling Zhang
    2016, 9(2):178-181. DOI: 10.1016/j.apjtm.2016.01.010
    [Abstract](53) [HTML](0) [PDF 241.54 K](234)
    Abstract:
    Objective: To study the inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice. Methods: Female mice were selected as experimental animals, and breast cancer tumor-bearing mouse models were established and then divided into group A, B, C and D that respectively received saline, recombinant human endostatin, ginsenosides Rg3 and recombinant human endostatin combined with Rg3 intervention; 7 d, 14 d and 21 d after intervention, tumor tissue volume was measured; 21 d after intervention, mice were killed, tumor tissue was collected, and mRNA contents of angiogenesis molecules, invasion molecules, autophagy marker molecules and autophagy signaling pathway molecules were detected. Results: At 7 d, 14 d and 21 d after intervention, tumor tissue volume of group B, C and D was lower than that of group A, and tumor tissue volume of group D was lower than that of group B and C; mRNA contents of VEGFA, VEGFB, VEGFC, MMP2, MMP9, p62, mTOR, PI3K, Akt, JNK and Beclin-1 in tumor tissue of group B, C and D were significantly lower than those of group A, and LC3-II/LC3-I was significantly higher than that of group A; mRNA contents of VEGFA, VEGFB, VEGFC, MMP2, MMP9, p62, mTOR, PI3K, Akt, JNK and Beclin-1 in tumor tissue of group D were significantly lower than those of group B and C, and LC3-II/LC3-I was higher than that of group B and C. Conclusions: Endostar combined with ginsenoside Rg3 has stronger inhibiting effect on breast cancer tumor growth in tumor-bearing mice than single drug, and it can inhibit angiogenesis and cell invasion, and enhance cell autophagy.
    17  Therapeutic effect of oridonin on mice with prostate cancer
    Ming Ming Feng-Yin Sun Wen-Tong Zhang Ji-Ke Liu
    2016, 9(2):182-185. DOI: 10.1016/j.apjtm.2016.01.007
    [Abstract](17) [HTML](0) [PDF 238.07 K](267)
    Abstract:
    Objective: To investigate the therapeutic effect and the related mechanism of oridonin on mice with prostate cancer. Methods: Sixty BALB/C male nude mice were selected. A model of RM-1 cell transplantation tumor of prostate cancer was built by the subcutaneous inoculation of RM-1 cells. After that, those 60 experimental mice were randomly divided into groups A, B and C. Each group had 20 mice. Mice in group A were treated with 0.2 mL of normal saline (0.9%) by intraperitoneal injection once a day; mice in group B received intraperitoneal injection of 1.875 mg/mL of oridonin once a day; and mice in group C received intraperitoneal injection of 7.5 mg/mL of oridonin once a day. Mice in the three groups were treated uninterruptedly for 5 weeks and were all killed. Then, tumors were excised and weighed to calculate their growth inhibitory rate, volume increment and anti-tumor rate. Thymus and spleen of mice in the three groups were collected to calculate the thymus and spleen index. Immunohistochemical staining was applied to observe the expression of caspase-3 in prostate cancer tissue of mice of the three groups. Results: The qualities and volume increment of tumors in groups B and C were significantly lower than those of group A (P < 0.05); the qualities and volume increment of tumors in groups C were evidently lower than those of group B (P< 0.05); the tumor volume increment and anti-tumor rate in group C were obviously higher than those of group B (P< 0.05); the thymus and spleen indexes of groups B and C were distinctly higher than those of group A (P< 0.05); comparison of the thymus and spleen indexes between group B and group C showed no statistical differences (P> 0.05). Immumohistochemical staining revealed that the caspase-3 protein in prostate cancer tissue of mice of group A expressed negatively with colourless or light-colored karyon; while the caspase-3 protein in prostate cancer tissue of mice of group B expressed positively with dark-colored karyon, centralized distribution and granular sensation; and the caspase-3 in prostate cancer tissue of mice of group C showed strong positive expression with big and darker colored karyon and dense distribution. Conclusions: Oridonin can inhibit the growth of RM-1 prostate cancer cells effectively and have great therapeutic effects on RM-1 cell transplantation tumor of prostate cancer.
    18  Monitoring of renal ischemia reperfusion injury in rabbits by ultrasonic contrast and its relationship with expression of VEGF in renal tissue
    Peng Hao
    2016, 9(2):186-190. DOI: 10.1016/j.apjtm.2016.01.006
    [Abstract](38) [HTML](0) [PDF 297.03 K](205)
    Abstract:
    Objective: To evaluate the renal ischemia reperfusion injury (IRI) in rabbits using the ultrasonic contrast technique and discuss the clinical value of ultrasonic contrast technique in the diagnosis of renal IRI by comparing the time-intensity curve of renal cortex and the expression of vascular endothelial growth factor (VEGF) of renal tissue. Methods: Twenty 3-month-old New Zealand rabbits were randomly divided into 4 groups, namely Ctrl group, IRI-12 h, IRI-24 h and IRI-48 h groups. The two dimensional gray-scale ultrasonography was employed to determine and mark the position of rabbit kidney. Rabbits were given the intraperitoneal anesthesia with 20% urethane with the dosage of 5 mL/kg. The aseptic operation was performed after the local skin disinfection in the area of both kidneys. The right kidney of animals in the control group was excised without any treatment for the left kidney. After excising the right kidney of animals in groups of IRI-12 h, IRI-24 h and IRI-48 h, the aneurysm clip was used to clip the renal pedicle vessel of left kidney, in order to simulate the ischemia. Because of the tissue ischemia, it could be seen that the color of kidney was changed from bright red to dark red, which indicated the successful modeling of ischemia. The aneurysm clip was released after one hour of maintaining the ischemia. Then the kidney turned out to be bright red from dark red, which indicated that the reperfusion was completed. Taking this moment as the time of ischemia reperfusion, the wound was stitched up. A total of 12, 24 and 36 h after the operation, the two-dimensional and color Doppler flow imaging and ultrasonic contrast were employed for the examination. The dynamic changes of ultrasonic contrast were recorded. The quantitative analysis software (QontraXt) was adopted to analyze the time-intensity curve of echo at different positions of renal cortex. After the ultrasonic contrast testing, rabbits were put to death. The renal cortex tissue was isolated and the tissue RNA and total protein were extracted respectively. Real-time PCR and western blotting were used to detect the VEGF and the Pearson product moment correlation coefficient was used to measure the linear relationship between these two variables. Results: The ultrasonic contrast could clearly reflect the process of IRI. The results of testing at mRNA and protein level indicated that the expression of VEGF in IRI groups was significantly increased (P<0.05) and the expression of VEGF was also increased by the time of reperfusion. Conclusions: There is the certain correlation between the expression of VEGF and process of IRI. The correlation coefficient between the ultrasonic contrast parameters of AT and TTP and the relative expression of VEGF is over 0.9, which indicates the relatively high correlation. But there is no significant difference in the change of perfusion peak intensity between groups, which has no correlation with the expression of VEGF.
    19  Influence of lactulose on interventional therapy for HCC patients with hepatocirrhosis and hypersplenism
    Deng-Wei Zong Chen-Yang Guo Hong-Tao Cheng Hong-Tao Hu Jin-Cheng Xiao Hai-Liang Li
    2016, 9(2):191-194. DOI: 10.1016/j.apjtm.2016.01.011
    [Abstract](57) [HTML](0) [PDF 278.75 K](248)
    Abstract:
    Objective: To investigate the influence of lactulose on immunity of hepatocellular carcinoma (HCC) patients with hepatocirrhosis and hypersplenism after double-interventional therapies. Methods: A total of 40 HCC patients with hepatocirrhosis and hypersplenism, hospitalized during January 2013 to June 2014, were enrolled and randomized into control group and observation group. Both groups received partial splenic embolization combined with transcatheter arterial chemoembolization. Besides, observation group orally took lactulose 30 mL/d. Four days before interventional therapies and at day 1, 3, 7 and 14 after therapies, fasting venous blood was collected to detect white blood cell count, red blood cell count (RBC), and platelet count (PLT). Four days before therapies and at day 7 and 14 after therapies, the levels of alanine aminotransferase, aspartate transaminase, total bilirubin, malondialdehyde, super-oxide dismutase (SOD), IFN-γ, and IL-4 as well as the distribution of T cell subsets in peripheral blood were tested. Complications were observed after interventional therapies. Results: Before interventional therapies the levels of white blood cell count, PLT and RBC in both groups showed no difference, while after interventional therapies the levels of PLT and RBC in both groups showed an increasing tendency (P<0.05). At day 14 after interventional therapies, the level of blood cell as well as that of SOD, IFN-γ and IL-4 in serum were significantly higher than that before therapies; meanwhile, the levels of alanine aminotransferase and total bilirubin of observation group after therapies were significantly lower than before and control group (P<0.05), the levels of CD4+/CD8+, SOD and IFN-γ were all higher than before and control group (P<0.05). Conclusions: Oral administration of lactulose could adjust the imbalance of oxidation system/antioxidant system in HCC patients with hepatocirrhosis and hypersplenism after interventional therapies, and improve the antitumor immunity and prognosis.
    20  Preventive and therapeutic effect of N-Acetyl-L-cysteine on infection-associated preterm labor in mice
    Ling Jiang Qian Yan Rong-Hui Liu Lu Zhang
    2016, 9(2):195-198. DOI: 10.1016/j.apjtm.2016.01.012
    [Abstract](51) [HTML](0) [PDF 280.13 K](221)
    Abstract:
    Objective: To study the preventive and therapeutic effect of N-Acetyl-L-cysteine on infectionassociatedpreterm labor in mice. Methods: A total of 66 C57BL/6 inbred strain pregnant mice were selected and randomly divided into groups A, B and C, with 22 cases in each group. GroupA ,B and C were regarded as model group, prevention group and treatment group, respectively. The model of infection-associated preterm labor was built by intraperitoneal injection of Escherichia coli. Ten mice of each group were taken and observed the preterm birth rates and live birth rates,respectively. Three mice of each group were killed at 3 h, 6 h, 12 h and 24 h after building the model. Their uterus tissues were collected and the expressions of the AP-1 and MCP-1 in those tissues were assayed with immunohistochemical method and the expressions of NF-kBp65 and TNF-α protein in the placenta tissues of those mice were also detected with immunohistochemical method. Results: The preterm birth rates of mice in groups B and C were significantly lower than that in group A, while their live birth rates were distinctly higher than that in group A (P<0.05); the expressions of the AP-1 and MCP-1 in the uterus tissues and NF-kBp65 and TNF-α protein in the placenta tissues of mice in groups B and C were evidently lower than those in group A (P<0.05);the comparison of the expressions of the NF-kBp65 and TNF-α between group B and C showed no statistical differences (P>0.05). Conclusions: N-Acetyl-L-cysteine can lower the incidence rate of infection-associated preterm labor by prohibiting the activation of the protein AP-1/MCP-1 and decreasing the expression of NF-kBp65 and TNF-α in the pregnant tissues of premature mice to reduce the inflammatory reactions.
    21  Sharing experiences from a reference laboratory in the public health response for Ebola viral disease, MERS-CoV and H7N9 influenza virus investigations
    T. S. Saraswathy Subramaniam Ravindran Thayan Mohd Apandi Yusof Jeyanthi Suppiah Tengku Rogayah Tg Abd Rashid Zarina Mohd Zawawi Nor Aziyah Mat Rahim Fauziah Kassim Rozainanee Mohd Zain Zainah Saat
    2016, 9(2):199-200. DOI: 10.1016/j.apjtm.2016.01.016
    [Abstract](37) [HTML](0) [PDF 243.91 K](247)
    Abstract:

    Current Issue


    Volume , No.

    Table of Contents

    Archive

    Volume

    Issue

    Most Read

    Most Cited

    Most Downloaded

    Academic misconduct statement

      Peer review

      WeChat

      Mobile website

      Close