BioScience Trends
Online ISSN : 1881-7823
Print ISSN : 1881-7815
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Reviews
  • Xiaojing Lin, Junjun Qiu, Keqin Hua
    2018 Volume 12 Issue 4 Pages 342-353
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 27, 2018
    JOURNALS FREE ACCESS

    Gynecologic cancer is a vital global healthcare issue with high rates of mortality and morbidity. Tumor metastasis attributes to most of the death suffering from solid tumors. The epithelial-mesenchymal transition (EMT) plays a pivotal role in initiating metastasis. Long non-coding RNAs (lncRNAs), a well-known group of non-coding RNAs, and a prominent topic in life science research, are misregulated in many malignancies and some are EMT-associated. In the case of gynecologic cancers, several EMT-associated lncRNAs have been identified and found to be implicated in cancer aggressiveness and progression. Mechanically, these lncRNAs participate in the EMT-related metastatic process in multiple ways including interaction with polycomb repressive complex 2 (PRC2), regulation of EMT signaling networks, mediation of EMT-transcription factors (EMT-TFs) and EMT markers, and cooperation with microRNAs (miRNAs). Further studies on these EMT-associated lncRNAs and identification of more relevant lncRNAs are imperative for the lncRNAs-based clinical management of high rate of metastasis in patients with gynecologic cancers.

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  • Mingshan Lin, Yuan Zhang, Zhaozhuo Niu, Yifan Chi, Qiang Huang
    2018 Volume 12 Issue 4 Pages 354-359
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 26, 2018
    JOURNALS FREE ACCESS

    Transcriptomic response of peripheral blood cells to coronary artery diseases (CAD) is a long recognized phenomenon. Currently, accumulating evidence indicates that such response having significant clinical utility in CAD-associated events determination. In this review, we summarized the existing data of transcriptomic biomarkers at mRNA, microRNA, long non-coding RNA, and circular RNA for the diagnosis, progression and outcome prediction and treatment response of CAD. Furthermore, we also discussed the functional significance on the gene expression patterns caused by CAD, and emphasized the importance of inflammatory pathways in CAD tissues-blood cells interaction. Based on the current knowledge, we proposed a perspective on the future strategies to further improve the robustness and reproducibility of transcriptomic biomarkers in the personalized medicine of CAD patients.

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Original Articles
  • Yingying Wang, Jianfeng Liu, Hongyan Wu, Yunpeng Cai
    2018 Volume 12 Issue 4 Pages 360-368
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 29, 2018
    JOURNALS FREE ACCESS

    It was widely accepted that stroke onset was the result of interactions between environment and genetic factors. However, the combined biomarkers covering environment and genetic factors and their interplay information in stroke were still lacking. In this study, we proposed a framework to identify the targeting or indicating role each factor played in the combined stroke biomarkers. A combined set of 36 biomarkers were identified based on evaluation and importance scores. Validations on three independent microarray data sets justified that the obtained markers were pervasively effective in discriminating stroke patients of different stages from healthy people on genetic levels. 8 and 3 genetic factors were identified as biomarkers in the acute and recovery phases of stroke, respectively. For example, the expression changing of SERPINH1 only appeared in the acute phase of stroke showing its targeting role in the combined biomarker. Compared with this, 11 genetic factors such as MMP9 were found to be differentially expressed in both acute and recovery phases of stroke showing their indicating roles in stroke. Functional analyses further revealed that the biomarkers could be grouped into 4 closely related processes of stroke including prevention, occurrence, processing, and recovery, respectively. These results indicated that the adoption of interactions between environment and genetic factors would be helpful in selecting robust and biologically relevant biomarkers, which cast a new insight for stroke biomarker identification.

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  • Rui Ma, Zhenyu Li, Xiaxia Di, Dongxiao Guo, Jianbo Ji, Shuqi Wang
    2018 Volume 12 Issue 4 Pages 369-374
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 10, 2018
    JOURNALS FREE ACCESS

    Interaction of riociguat with human serum albumin (HSA) is extremely important in understanding the drug's disposition and efficiency. In the current study, the binding of riociguat to HSA was explored using spectroscopic methods and molecular docking. The quenching constant, the binding constant, the number of binding sites, thermodynamic parameters, and the secondary structure of protein were determined. A fluorescence study revealed that riociguat quenched HSA fluorescence via static quenching with a binding constant of 1.55 × 104 L mol-1 at 298 K. The calculated thermodynamic parameters indicated that the binding process was spontaneous and that the main interaction force was hydrophobic interaction. Site marker competitive binding experiments and molecular docking studies suggested that riociguat was inserted into the subdomain IIA (site I) of HSA. Alterations in the protein secondary structure after drug complexation were predicted. Results indicated that the protein a-helix structure increased with an increasing concentration of riociguat. This indicated that a riociguat-HSA complex was formed and that the protein secondary structure was altered by the addition of riociguat.

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  • Miao Wei, Meng Feng, Yue Guan, Ce Guo, Hang Zhou, Yongfeng Fu, Hiroshi ...
    2018 Volume 12 Issue 4 Pages 375-381
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 10, 2018
    JOURNALS FREE ACCESS

    Entamoeba nuttalli infection is prevalent in captive and wild macaques. Recent studies have suggested that genotypes of E. nuttalli isolates are correlated with the geographical distribution of host macaques. Correlation of amoebic genotypes with genetic diversity of host macaques was analyzed in present study. Sixty fresh stool samples were obtained from wild Tibetan macaques living in Mount Huang (HS) of the An-hui Province in China. PCR analysis revealed that the most prevalent Entamoeba species was E. chattoni (E. polecki ST2) (86.7%) followed by E. nuttalli (58.3%) and E. coli (25%). Six E. nuttalli HS isolates were successfully cultured. The tRNA-linked short tandem repeat (STR) loci and serine-rich protein gene of E. nuttalli isolates from four different regions of China (Mount Long-hu, Gui-yang, Mount E-mei, and HS, the former three isolates were obtained in previous studies) were studied and high numbers of polymorphisms were detected. When genetic diversity of different populations of E. nuttalli isolates was compared with geographical distance, an r2 value of 0.919 was assigned by a Mantel test based on the tRNA-STR loci. In host macaques, the mtDNA HVS-I gene was also highly polymorphic in each of the genomes. Multiple regression analysis using E. nuttalli tRNA-STR loci genetic, macaque mtDNA HVS-I gene, and geographic distances showed an r2 value of 0.943, indicating that a higher relevance was demonstrated when geographic and host gene factors were considered. Analysis of genetic factor of host would benefit for better understanding of the evolution of E. nuttalli.

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  • Zen'ichiro Wajima, Toshiya Shiga, Kazuyuki Imanaga
    2018 Volume 12 Issue 4 Pages 382-388
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 10, 2018
    JOURNALS FREE ACCESS

    Hypotension commonly accompanies combined epidural and general anesthesia, and intravenous bolus ephedrine and etilefrine are widely used to correct hypotension. We have noticed that systemic vascular resistance (SVR) transiently decreases just after intravenous bolus administration of these drugs. The goal of the present study was to investigate whether bolus administration of these drugs decrease SVR just after intravenous administration in combined epidural and general anesthesia patients. We investigated 40 patients who were scheduled for elective abdominal surgery. Patients were chosen as subjects if their systolic arterial pressure decreased by 20% or to <100 mmHg at 30 min after the induction of general anesthesia. Baseline hemodynamic values were recorded, and after ephedrine 10 mg injection or etilefrine 2 mg injection (equipotent), the parameters were recorded again at 0.5 min and once each min for the next 5 min thereafter. The 40 patients were enrolled into the ephedrine (n = 20) or etilefrine (n = 20) treatment groups. Patient characteristics were comparable in both groups. After ephedrine injection, SVR decreased significantly at the 1-min time point, whereas after etilefrine injection, SVR decreased significantly at the 0.5- to 2-min time points compared with baseline values. SVR at the 0.5- to 1-min time points was lower in the etilefrine versus the ephedrine group. Both drugs transiently decreased SVR after intravenous injection, but etilefrine decreased SVR much more than ephedrine, indicating that more vasodilation occurred after the injection of etilefrine than after ephedrine. It is thus important to recognize the different characteristics of these drugs.

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  • Xiaoyong Lan, Haiping Ma, Zhiping Zhang, Dong Ye, Jun Min, Feng Cai, J ...
    2018 Volume 12 Issue 4 Pages 389-394
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 27, 2018
    JOURNALS FREE ACCESS

    Long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) promotes osteosarcoma, while its involvement in other bone diseases, such as ankylosing spondylitis (AS) is unknown. Expression of TUG1 in serum and open sacroiliac biopsies of AS patents and healthy controls was detected by real-time quantitative PCR (qRT-PCR). Ankylosing spondylitis disease activity score (ASDAS) system was used to evaluate disease activity. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of lncRNA TUG1 for AS. Chi-square test was performed to analyze the correlations between TUG1 expression and patients' clinicopathological data. Patients were divided into 2 groups (high and low expression groups) according to the median expression level of TUG1 and were followed-up for 5 years after discharge. Treatment courses and rehospitalization rate were compared between two groups. It was observed that TUG1 expression level was significantly lower in AS patients than in healthy controls in both serum and biopsies. Reduced expression level of TUG1 distinguished AS patients from controls. LncRNA TUG1 expression was significantly correlated with patients' smoking habits, disease activity, and course of disease. Patients in high expression group showed longer hospitalization time and higher rehospitalization rate. We therefore conclude that expression of lncRNA TUG1 was inhibited in AS patients and downregulation of lncRNA TUG1 is related to higher disease activity, longer course of treatment and higher rehospitalization rate.

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  • Askin Gulsen
    2018 Volume 12 Issue 4 Pages 395-402
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 28, 2018
    JOURNALS FREE ACCESS

    Bronchoscopic lung volume reduction (BLVR) coil treatment is a alternative and promising treatment modality for selected severe emphysema patients. The main indication of this treatment modality is a forced expiration volume in one second (FEV1) of 15-45% and a residual volume (RV) > 175%. The aim of this study was to investigate the efficacy of BLVR coil therapy in patients with end-stage emphysema who were potential candidates for lung transplantation and had FEV1 values less than 25%. Twenty-one patients who underwent bilateral BLVR coil therapy between September 2013 and May 2015 were retrospectively reviewed. We compared the changes in clinical and laboratory parameters at the baseline and 12 months after the treatment. Twelve months after the bilateral BLVR coil treatment, we observed an average increase in FEV1 (110 mL and 4.6%), a decrease in residual volume (660 mL and 33%), and an increase in 6-minute walk tests (67 m). The most common complications were chronic obstructive pulmonary disease exacerbation (47.6%) and pneumonia (23.8%). All patients tolerated the general anesthesia and procedure very well. BLVR coil therapy is safe and effective in patients with end-stage emphysema, who are potential candidates for lung transplantation within a short to medium period. The complication rates of this treatment were not different from those of the other coil treatments, and the improvements in the clinical parameters after the treatment resulted in gaining time for lung transplantation. Future research for evaluating the long-term efficacy of BLVR coil therapy in these patients is essential.

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  • Duo-Shun Wang, Rui-Xing Yin, Kai-Guang Li, Li Lu, Yuan Su, Rong-Qin Ya ...
    2018 Volume 12 Issue 4 Pages 403-411
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 12, 2018
    JOURNALS FREE ACCESS

    The association between the mevalonate kinase gene (MVK) single nucleotide polymorphism (SNP) and serum lipid levels has been detected in several previous genome-wide association studies, but the results are inconsistent. In addition, it is still unclear whether the loci indentified exert the similar effect on the susceptibility of coronary heart disease (CHD) or ischemic stroke (IS). Therefore, the present study was undertaken to detect the association between the MVK rs2287218 SNP and serum lipid levels, the susceptibility of CHD and IS in a Southern Chinese Han population. The genotypes of the SNP in 1764 unrelated subjects (CHD, 583; IS, 555; and healthy controls, 626) were determined by the Snapshot technology. The genotypic and allelic frequencies were different between CHD and control subjects (P ≤ 0.013 for each), or between IS and control groups (P < 0.01 for each). The T allele carriers had an increased risk of CHD and IS (CHD: OR = 1.674, 95%CI = 1.25-2.25, P = 0.001 for CT/TT vs. CC genotypes; OR = 1.595, 95%CI = 1.23-2.07, P < 0.001 for T vs. C alleles; IS: OR = 1.890, 95%CI = 1.36-2.47, P = 0.001 for CT/TT vs. CC genotypes; OR = 1.829, 95%CI = 1.38-2.42, P < 0.001 for T vs. C alleles). The T allele carriers in healthy controls had lower serum high-density lipoprotein cholesterol (HDL-C) levels than the T allele non-carriers (P = 0.013). These findings suggest that the MVK rs2287218 SNP is likely to increase the risk of CHD and IS by decreasing serum HDL-C levels in our study populations.

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  • Hisako Okuhira, Yuki Yamamoto, Yutaka Inaba, Kayo Kunimoto, Naoya Miki ...
    2018 Volume 12 Issue 4 Pages 412-418
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 29, 2018
    JOURNALS FREE ACCESS

    Biomarkers to distinguish patients with advanced melanoma responsive to nivolumab are of great interest. Therefore, we examined the possibility that laboratory data of daily blood examination become novel biomarkers. Laboratory data of 16 melanoma patients who were treated with nivolumab were retrospectively analyzed. Patients were classified as responder group or non-responder group. Examined were: white blood cell count (WBC), absolute lymphocyte counts (ALC), absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute eosinophil count (AEC), and absolute basophil count (ABC), as well as levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), one hour value of erythrocyte sedimentation rate (ESR), and 5-S-cysteinydopa (5-S-CD). Responder group showed significantly higher baseline levels of ESR or CRP and significantly lower ALC level before nivolumab treatment. Additionally, nivolumab treatment decreased the levels of CRP, ESR, and ANC, while it increased ALC level in the responder group. CRP was the most effective in distinguishing responder group from non-responder group both before and during treatment, according to the receiver operating characteristic (ROC) curve. We firstly showed that ESR is also the baseline biomarker of the efficacy of nivolumab. Furthermore, we confirmed that CRP is useful to predict the efficacy both before and during the treatment, and suggested that CRP is the most effective biomarker among daily blood examination by using ROC curve analysis. There is a possibility that nivolumab treatment may be more effective for malignant melanoma with stronger inflammation.

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  • Xianlei Wang, Lihui Huang, Xuelei Zhao, Xueyao Wang, Xiaohua Cheng, Ya ...
    2018 Volume 12 Issue 4 Pages 419-425
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 27, 2018
    JOURNALS FREE ACCESS

    The current study retrospectively investigated variations in audiological phenotypes in children with GJB2 gene mutations. Subjects were 128 infants and young children who were seen as outpatients by Otology at Beijing Tongren Hospital from 2012 to 2018. Of the 128 subjects, 99 had biallelic truncating (T/T) mutations and 29 had truncating/nontruncating (T/NT) mutations. Genotypes, results of universal newborn hearing screening (UNHS), and the degree and symmetry of hearing loss were examined in the two groups. Twenty-two subjects (20.37%, 22/128) passed UNHS, including 13 children with T/T mutations and 9 with T/NT mutations. Of the 128 subjects, 22 had normal hearing, 2 had unilateral hearing loss, and 115 had bilateral hearing loss. Severe-to-profound hearing loss was the most prevalent phenotype in children with T/T mutations (73.23%), while normal hearing was prevalent in children with T/NT mutations (41.38%). Symmetrical hearing loss was the main phenotype in both groups, and the number of subjects with symmetrical hearing loss did not differ significantly between the two groups. Therefore, children with GJB2 gene mutations have phenotypic variability in terms of their results of UNHS and their degree and symmetry of hearing loss. Subjects with T/NT mutations of the GJB2 gene were more likely to pass UNHS and had milder hearing loss compared to those with T/T mutations. Symmetrical hearing loss was the main phenotype in the two groups, but 36.53% of children had bilateral asymmetric hearing loss. Parents of all subjects with sensorineural hearing loss were informed that their children may have a GJB2 mutation.

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  • Takamune Yamaguchi, Alessandra Cristaudi, Takashi Kokudo, Emilie Uldry ...
    2018 Volume 12 Issue 4 Pages 426-431
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 26, 2018
    JOURNALS FREE ACCESS

    Congenital intrahepatic bile duct dilatation (Caroli's disease) is a rare biliary disease. Although multiple reports exist describing its surgical treatment, relatively few have provided long-term follow-up. Prospective data about 25 cases of monolobular Caroli's disease, with liver resection between 1974 and 2016, were retrospectively analyzed. Patient demographics together with postoperative outcomes and long-term follow-up were assessed. Our 25-patient cohort (average age 53.4 years (range: 27-82)) included 20 cases with disease limited to the left lobe, and 5 to the right. The average time interval between first symptoms and final diagnosis was 5 years (range: 0-34 years). The surgical procedures included left lobectomy in 11 cases, left hepatectomy in 8 cases, right hepatectomy in 3, and sub-segmentectomy in 3 cases. Biliodigestive anastomosis was performed in 7 cases. Complications were observed in 3 patients (25%). Metachronous cholangiocarcinoma was observed in one single case, 10 years after initial operation. In conclusion, surgical treatment for monolobular Caroli's disease is effective, with good short-term results and few complications. Median long-term follow-up was 18 months (range: 3-132), with favorable clinical evolution in 96% of patients.

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  • Rujie Qin, Akira Koike, Osamu Nagayama, Yuta Takayanagi, Longmei Wu, I ...
    2018 Volume 12 Issue 4 Pages 432-437
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 12, 2018
    JOURNALS FREE ACCESS

    Ventilation (VE) increases linearly with the increase of carbon dioxide output (VCO2) during cardiopulmonary exercise testing. VE-VCO2 slope rises in parallel with exercise intensity, reaches a turning point (called the RC point), then steepens because of respiratory compensation for lactic acidosis. While this RC point can be identified universally, it is undetectable in some patients. In this study we evaluated whether the respiratory compensation during exercise testing has clinical significance in cardiac patients. In total, 152 cardiac patients with a respiratory exchange ratio at peak exercise (peak R) of between 1.10 and 1.20 were enrolled. Cardiopulmonary parameters were compared between patients who manifested the RC point (n = 118) and those who did not (n = 34). The peak R did not significantly differ between these two groups. Compared to the patients without the RC point, those with the RC point had a higher oxygen uptake at peak exercise (peak VO2) (20.2 ± 5.3 vs 13.6 ± 3.4 mL/min/kg, p < 0.001), higher anaerobic threshold (AT) (12.4 ± 3.2 vs 9.2 ± 2.3 mL/min/kg, p < 0.001), and lower VE-VCO2 slope (31.7 ± 5.8 vs 37.8 ± 9.6, p = 0.001). Brain natriuretic peptide (BNP) tended to be lower in the patients with the RC point (175.4 ± 364.7 vs 327.9 ± 381.1 pg/mL, p = 0.067). Peak VO2, the marker of cardiopulmonary function, was found to be the independent predictor of the presence of the RC point. The present findings suggest that the phenomenon of respiratory compensation during heavy exercise indicates better cardiopulmonary function in cardiac patients within a prescribed range of effort.

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Brief Report
  • Tomoka Yamashita, Masatoshi Jinnin, Katsunari Makino, Ikko Kajihara, J ...
    2018 Volume 12 Issue 4 Pages 438-441
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 26, 2018
    JOURNALS FREE ACCESS

    Infantile hemangioma sometimes grows rapidly to a significant size around the first 2 months of life, which can be problematic and even destroy normal tissue. However, it is very difficult to predict the tumor growth at the first visit and to decide necessity of treatment. Therefore the identification of the biomarkers that can indicate a tendency to grow is clinically very important. In the present study, we evaluated the possibility that serum cytokine levels are available as the marker of hemangioma growth. Progressive hemangioma was defined as a lesion showing increased tumor size and/or coloration two weeks before and after the serum sampling, and we used membrane array to compare the twenty cytokine profiles between the sera of 3 progressive hemangioma patients and sex-/age-matched non-progressive hemangioma patients. As a result, many of the 20 cytokines were detected in the patients' sera. When a 2-fold difference in the mean levels of each group was considered meaningful, 6 of the 20 cytokines (IGF-1, IL-6, IL-8, PIGF, RANTES, TGF-β1) were down-regulated in the progressive hemangioma group compared to the non- progressive hemangioma group, and there were statistically significant difference (p < 0.05): especially, IGF-1, IL-6, IL-8, PIGF, and TGF-β1 did not expressed in all 3 progressive hemangioma patients. Accordingly, complicated cytokine network by these multiple cytokines may control the pathogenesis, and these cytokine levels may become clinically useful tumor markers. Furthermore, immunotherapy against them will be novel therapeutic approach.

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Letter
  • Chao Han, Maoshui Wang, Yu He
    2018 Volume 12 Issue 4 Pages 442-444
    Published: August 31, 2018
    Released: September 19, 2018
    [Advance publication] Released: August 12, 2018
    JOURNALS FREE ACCESS

    The clinicopathologic characteristics of patients with tuberculosis (TB) and schizophrenia are unclear. In order to facilitate early diagnosis and prompt treatment, a retrospective study was conducted in China. Subjects were 54 consecutive patients who were seen between October 2006 and December 2015. Data on demographic characteristics, underlying diseases, clinical features, and outcomes were collected from medical records using a standardized data collection form. Acid-fast bacilli were detected at a rate of 26.9%, a mycobacterial culture was positive at a rate of 35.4%, and a real-time polymerase chain reaction was positive for TB at a rate of 35%. Of the 54 patients, i) 44 (81.5%) had symptoms for at least 2 weeks; ii) 10 (18.5%) were transferred from a local psychiatric hospital, and 23 (42.6%) were transferred at least twice before arriving at this Hospital. Unfortunately, the outcome was not successful in these patients, 18 patients (33.3%) had to be retreated, 7 patients (13.0%) had their care interrupted because their schizophrenia worsened. The current study found that the management of TB in patients with schizophrenia poses several challenges. These include delays in diagnosis and treatment of TB, inefficient strategies for control of TB transmission in psychiatric hospitals, the need for a psychiatrist to be involved in care, and a high rate of retreatment.

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Erratum
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