Jun 2018, Volume 32 Issue 3

    
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  • Original Article
    Cuiying Li, Haiyan Gong, Lijun Ling, Liwen Du, Tong Su, Shui Wang, Jie Wang
    Journal of Biomedical Research. 2018, 32 (3) : 198-207. https://doi.org/10.7555/JBR.32.20180015

    In the current study, we sought to evaluate the diagnostic efficacies of conventional ultrasound (US), contrast-enhanced US (CEUS), combined US and CEUS and magnetic resonance imaging (MRI) in detecting focal solid breast lesions. Totally 117 patients with 120 BI-RADS category 4A-5 breast lesions were evaluated by conventional US and CEUS, and MRI, respectively. SonoVue was used as contrast agent in CEUS and injected as an intravenous bolus; nodule scan was performed 4 minutes after bolus injection. A specific sonographic quantification software was used to obtain color-coded maps of perfusion parameters for the investigated lesion, namely the time-intensity curve. The pattern of contrast enhancement and related indexes regarding the time-intensity curve were used to describe the lesions, comparatively with pathological results. Histopathologic examination revealed 46 benign and 74 malignant lesions. Sensitivity, specificity, and accuracy of US in detecting malignant breast lesions were 90.14%, 95.92%, and 92.52%, respectively. Meanwhile, CE-MRI showed sensitivity, specificity, and accuracy of 88.73%, 95.92%, and 91.67%, respectively. The area under the ROC curve for combined US and CEUS in discriminating benign from malignant breast lesions was 0.936, while that of MRI was 0.923, with no significant difference between them, as well as among groups. The time-intensity curve of malignant hypervascular fibroadenoma and papillary lesions mostly showed a fast-in/fast-out pattern, with no good correlation between them (kappa<0.20). In conclusion, the combined use of conventional US and CEUS displays good agreement with MRI in differentiating benign from malignant breast lesions.

  • Original Article
    Yu-tuan Wu, Xin Li, Lin-jie Lu, Lu Gan, Wei Dai, Yan-ling Shi, Vishnu Prasad Adhikari, Kai-nan Wu, Ling-quan Kong
    Journal of Biomedical Research. 2018, 32 (3) : 191-197. https://doi.org/10.7555/JBR.32.20170059

    This study was designed to investigate the effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki67 in Chinese female breast cancer patients. The expression of estrogen receptor (ER), progesterone receptor (PR) and Ki67 among 525 neoadjuvant chemotherapy cases was studied by immunohistochemistry. Differences between specimens made through preoperative core needle biopsy and excised tissue biopsy were observed. The positive rates of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy were 65.3% and 63.2%, 51.0% and 42.6%, 65.6% and 43.4%, respectively. The expression of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy had no statistically significant difference. However, after neoadjuvant chemotherapy, the discordance rates of ER, PR and Ki67 were 15.2% (79/521), 26.9% (140/520) and 44.8% (225/502), respectively. The ER, PR and Ki67 status changed from positive to negative in 7.5% (39/521), 13.3% (69/520) and 21.1% (106/502) of the patients, whereas ER, PR and Ki67 status changed from negative to positive in 7.7% (40/521), 13.6% (71/520) and 23.7% (119/502) of the patients, respectively. These results showed that the status of some biomarkers changes after neoadjuvant chemotherapy and biomarker status needs to be reexamined to optimize adjuvant systemic therapy and better prognosis assessment.

  • Original Article
    Andi Li, Lu Zhang, Jiajia Jiang, Nan Yang, Ying Liu, Lingbo Cai, Yugui Cui, Feiyang Diao, Xiao Han, Jiayin Liu, Yujie Sun
    Journal of Biomedical Research. 2018, 32 (3) : 208-214. https://doi.org/10.7555/JBR.32.20170136

    Polycystic ovary syndrome (PCOS) is a common reproductive disease with high heterogeneity. The role of excess androgen in PCOS etiology remains disputed, since around 20%–50% of PCOS women do not display hyperandrogenemia. The microenvironment of the ovary critically influences follicular development. In the present study, we assessed the role of androgen in PCOS by investigating whether excessive follicular fluid androgen was present in PCOS patients with normal serum androgen levels and influenced by follicular fluid insulin resistance (IR). Follicular fluid samples of 105 women with PCOS and 105 controls were collected. Levels of steroid hormones, glucose and insulin in the follicular fluid were examined and compared with data from serum biochemistry tests.? We found that 64.9% (63/97) of PCOS patients with normal serum androgen levels displayed abnormally high follicular fluid androgen level. The follicular fluid androgen level was positively correlated with follicular fluid IR within a certain range and follicular fluid estrogen-to-testosterone (E2/T) ratio was significantly reduced in these patients. These results indicated that there existed a subgroup of PCOS patients who displayed excessive follicular fluid androgen and IR despite their normal circulating testosterone (T) levels. Our study highlights the importance of ovary hyperandrogenism and IR in the etiology of PCOS.

  • Original Article
    Vijayakumar Subramaniyan, Ramesh Venkatachalam, Prabhu Srinivasan, Manogar Palani
    Journal of Biomedical Research. 2018, 32 (3) : 222-236. https://doi.org/10.7555/JBR.31.20160109

    Reverse vaccinology method was used to predict the monovalent peptide vaccine candidate to produce antibodies for therapeutic purpose and to predict tetravalent vaccine candidate to act as a common vaccine to cover all the dengue virus serotypes. Envelope (E)-proteins of DENV-1-4 serotypes were used for vaccine prediction using NCBI, Uniprot/Swissprot, Swiss-prot viewer, VaxiJen V2.0, TMHMM, BCPREDS, Propred-1, Propred and MHC Pred. E-proteins of DENV-1-4 serotypes were identified as antigen from which T cell epitopes, through B cell epitopes, were predicted to act as peptide vaccine candidates. Each selected T cell epitope of E-protein was confirmed to act as vaccine and to induce complementary antibody against particular serotype of dengue virus. Chimeric tetravalent vaccine was formed by the conjugation of four vaccines, each from four dengue serotypes to act as a common vaccine candidate for all the four dengue serotypes. It can be justifiably concluded that the monovalent 9-mer T cell epitope for each DENV serotype can be used to produce specific antibody against dengue virus and a chimeric common tetravalent vaccine candidate to yield a comparative vaccine to cover any of the four dengue virus serotype. This vaccine is expected to be highly immunogenic against dengue fever.

  • Review Article
    Kyriakos E. Kypreos, Eleni A. Karavia, Caterina Constantinou, Aikaterini Hatziri, Christina Kalogeropoulou, Eva Xepapadaki, Evangelia Zvintzou
    Journal of Biomedical Research. 2018, 32 (3) : 183-190. https://doi.org/10.7555/JBR.32.20180007

    Apolipoprotein E (APOE) is a major protein component of peripheral and brain lipoprotein transport systems. APOE in peripheral circulation does not cross the blood brain barrier or blood cerebrospinal fluid barrier. As a result, peripheral APOE expression does not affect brain APOE levels and vice versa. Numerous epidemiological studies suggest a key role of peripherally expressed APOE in the development and progression of coronary heart disease while brain APOE has been associated with dementia and Alzheimer’s disease. More recent studies, mainly in experimental mice, suggested a link between Apoe and morbid obesity. According to the latest findings, expression of human apolipoprotein E3 (APOE3) isoform in the brain of mice is associated with a potent inhibition of visceral white adipose tissue (WAT) mitochondrial oxidative phosphorylation leading to significantly reduced substrate oxidation, increased fat accumulation and obesity. In contrast, hepatically expressed APOE3 is associated with a notable shift of substrate oxidation towards non-shivering thermogenesis in visceral WAT mitochondria, leading to resistance to obesity. These novel findings constitute a major paradigm shift from the widely accepted perception that APOE promotes obesity via receptor-mediated postprandial lipid delivery to WAT. Here, we provide a critical review of the latest facts on the role of APOE in morbid obesity.

  • Original Article
    Qing Cao, Yan Shen, Wei Zheng, Hao Liu, Chen Liu
    Journal of Biomedical Research. 2018, 32 (3) : 215-221. https://doi.org/10.7555/JBR.32.20170056

    Kruppel-like factor 4 (Klf4) is a zinc finger transcription factor and plays crucial roles in Xenopus embryogenesis. However, its regulation during embryogenesis is still unclear. Here, we report that Tcf7l1, a key downstream transducer of the Wnt signaling pathway, could promote Klf4 transcription and stimulate Klf4 promoter activity in early Xenopus embryos. Furthermore, cycloheximide treatment showed a direct effect on Klf4 transcription facilitated by Tcf7l1. Moreover, the dominant negative form of Tcf7l1 (dnTcf7l1), which lacks N-terminus of the β-catenin binding motif, could still activate Klf4 transcription, suggesting that this regulation is Wnt/β-catenin independent. Taken together, our results demonstrate that Tcf7l1 lies upstream of Klf4 to maintain its expression level during Xenopus embryogenesis.

  • Original Article
    Yemisi Olukemi Adesiji, Santhosh Kogaluru Shivakumaraswamy, Vijaya Kumar Deekshit, Girisha Shivani Kallappa, Indrani Karunasagar
    Journal of Biomedical Research. 2018, 32 (3) : 237-244. https://doi.org/10.7555/JBR.31.20160094

    Salmonella enterica has been documented as one of the leading causes of salmonellosis throughout the world and is most commonly associated with the consumption of contaminated food products. Thus, this research was aimed at studying the antimicrobial susceptibility pattern and detection of quinolone resistance in Salmonella spp isolated from food of animal origin. Thirty-six Salmonella isolates comprising 8 from poultry and 28 from seafood (clams) were identified, serotyped and characterized for their antimicrobial susceptibility against 10 different antibiotics. Plasmid DNA was isolated from all the isolates by alkaline lysis, quinolone resistant non-typhoidal S. Weltevreden were examined for mutation in the DNA gyrase coding gene. Among the 36 Salmonella isolates, 20 were S. weltevreden (8 from poultry and 12 from seafood) and 16 were S. Typhimurium (from seafood). All the isolates showed multiple resistance to nalidixic acid, tetracycline, co-trimoxazole and nitrofurantoin, but, interestingly, the isolates were 100% susceptible to ampicillin, chloramphenicol and gentamicin. Resistant isolates from the study carried the genes responsible for resistance to respective antibiotics. The strain S130 isolated in the study showed single point mutation, Asp87Gly, at position 87 in quinolone resistance determining region. It revealed mutation in quinolone resistance determining region as a cause for quinolone resistance in non-typhoidal Salmonellae. The occurrence of genes accountable for plasmid mediated resistance to quinolones (viz., qnrA, qnrB and qnrS) in plasmid of non-typhoidal Salmonellae isolates provides evidence for plasmid mediated quinolone resistance.

  • Perspective
    David Li, Hong Liu
    Journal of Biomedical Research. 2018, 32 (3) : 161-163. https://doi.org/10.7555/JBR.32.20180008
  • Review Article
    Guilaine Boyce, Emily Button, Sonja Soo, Cheryl Wellington
    Journal of Biomedical Research. 2018, 32 (3) : 164-182. https://doi.org/10.7555/JBR.31.20160103

    The pleiotropic functions of circulating high density lipoprotein (HDL) on peripheral vascular health are well established. HDL plays a pivotal role in reverse cholesterol transport and is also known to suppress inflammation, endothelial activation and apoptosis in peripheral vessels. Although not expressed in the central nervous system, HDL has nevertheless emerged as a potential resilience factor for dementia in multiple epidemiological studies. Animal model data specifically support a role for HDL in attenuating the accumulation of β-amyloid within cerebral vessels concomitant with reduced neuroinflammation and improved cognitive performance. As the vascular contributions to dementia are increasingly appreciated, this review seeks to summarize recent literature focused on the vasoprotective properties of HDL that may extend to cerebral vessels, discuss potential roles of HDL in dementia relative to brain-derived lipoproteins, identify gaps in current knowledge, and highlight new opportunities for research and discovery.