Molecular events associated with epithelial to mesenchymal transition of nasopharyngeal carcinoma cells in the absence of Epstein-Barr virus genome

Epithelial-mesenchymal transition (EMT) is an important process in tumor metastasis. The EMT-related events associated with metastasis of NPC in the absence of EBV have not been elucidated. We established an EBV-negative NPC cell line from a bone marrow biopsy of an NPC patient. Using a Matrigel system we isolated an invasive and non-invasive sublines, designated NPC-BM29 and NPC-BM00. NPC-BM29 acquired an invasive-like phenotype characterized by EMT, marked by down-regulation of E-cadherin and β-catenin with concomitant increased expression of Ets1. NPC-BM29 cells expressed ≥ 10-fold higher of MMP-9 than NPC-BM00 cells. NPC-BM29 cells grew better in 2% serum than NPC-BM00 cells, with a population doubling-time of 26.8 h and 30.7 h, respectively. A marked reduction in colony-formation ability of NPC-BM00 cells compared to NPC-BM29 was observed. Wound-healing assay revealed that NPC-BM29 cells displayed higher motility than NPC-BM00 and the motility was further enhanced by cell treatment with TPA, a PKC activator. Cell surface markers and tumor-associated molecules, AE3, MAK6 and sialyl-Tn, were up-regulated in NPC-BM29 cells, whereas the expression of HLA-DR and CD54 was significantly increased in NPC-BM00 cells. NPC-BM29 consistently released higher levels of IL-8 and IL-10 than NPC-BM00, with low levels of IL-1α expression in both cell lines. Higher level of VEGF production was detected in NPC-BM00 than NPC-BM29 cells. These data show that EBV is not required for exhibiting multiple metastatic phenotypes associated with EMT. More studies that target right molecules/signalings associated with the EMT may offer new therapeutic intervention options for NPC invasion and metastasis

Electromagnetic Wave Theory and Applications

Contains table of contents for Section 3, reports on three research projects and a list of publications.California Institute of Technology/Jet Propulsion Laboratory Contract 959548National Aeronautics and Space Administration Grant NAGW-1617National Aeronautics and Space Administration Grant Contract 958461U.S. Navy - Office of Naval Research Grant N00014-92-J-1616U.S. Navy - Office of Naval Research Grant N00014-92-J-4098Digital Equipment Corporation AGMT DTD 11/16/93Joint Services Electronics Program Contract DAAL03-92-C-0001Joint Services Electronics Program Grant DAAH04-95-1-0038MIT Lincoln Laboratory P.O. No. BX-5424U.S. Navy - Office of Naval Research Grant N00014-90-J-1002U.S. Navy - Office of Naval Research Grant N00014-89-J-1019DEMACO Agreement 11/15/93Federal Aviation Administration Grant 94-G-007U.S. Army Cold Regions Research and Engineering Laboratory Contract DACA89-93-K-000

Giant Cell (Temporal) Arteritis With Anterior Ischemic Optic Neuropathy: A Biopsy-proven Case in Taiwan

Giant cell arteritis with arteritic anterior ischemic optic neuropathy has rarely been diagnosed in Taiwan. Recently, we encountered a 76-year-old Taiwanese patient who presented with right visual impairment and marked pale swelling of his right disc. He also suffered body weight loss, general malaise and many typical manifestations of giant cell arteritis, such as jaw claudication, a tender, non-pulsating engorgement of his temporal arteries, and a highly elevated erythrocyte sedimentation rate and C-reactive protein level. Biopsy of his right superficial temporal artery revealed a granulomatous inflammation with multinucleated giant cell infiltration. This was a biopsy-proven case of giant cell arteritis with arteritic anterior ischemic optic neuropathy and indicated that although rare, this disease could occur in patients in Taiwan

Early blastulation (EB) of day 4 embryo is predictive of outcomes in single embryo transfer (SET) cycles

Objective: The aim of this study was to assess whether the early blastulation (EB) of day 4 embryo is a useful predictor for outcomes in fresh elective single embryo transfer (eSET) cycles. Materials and methods: We retrospectively enrolled patients undergoing fresh SET cycles in our hospital from April 2014 to September 2016 and met with the following criteria: 1) age <38 years, 2) first IVF/ICSI cycle, 3) at least two blastocysts with morphological grading better than or equal to 4BB. Results: A total of 81 patients were included. Of whom, 55 patients (68%) had undergone eSET with embryos that had early blastulation on day 4 while the other 26 patients had had no EB. Early blastulation has shown a higher rate of good blastocyst (84.3% vs. 60.5%, p < 0.0001). The clinical pregnancy rate of EB group was significantly higher than that of non-EB group (56.4% vs. 27.0%, p = 0.013). There is also a tendency in EB group to have a lower abortion rate (3.23% vs. 28.6%, p = 0.081). Conclusions: EB on day 4 is a useful predictor of the quality of the following embryos (i.e. day 5 embryo). It is a simple tool in selecting the best embryo to get a higher pregnancy rate in fresh eSET cycles.Trial registration: This study was supplementally registered by the MacKay Memorial Hospital Institutional Review Board on April 18, 2017 (registration No. 17MMHIS039e). Keywords: Early blastulation, Single-embryo transfer, Blastocyst morphology, Clinical pregnanc

Utilizing methylglyoxal and D-lactate in urine to evaluate saikosaponin C treatment in mice with accelerated nephrotoxic serum nephritis.

The relationship between methylglyoxal (MGO) and D-lactate during saikosaponin C (SSC) treatment of mice with accelerated nephrotoxic serum (NTS) nephritis was investigated. NTS nephritis was induced by administration of anti-basement membrane antibodies to C57BL/6 mice and three dosages of SSC were administered for 14 days. Proteinuria, blood urea nitrogen, serum creatinine, renal histology, urinary MGO and d-lactate changes were examined. Compared to the NTS control group, the middle dosage (10 mg/kg/day) of SSC significantly alleviated the development of nephritis based on urine protein measurements (34.40 ± 6.85 vs. 17.33 ± 4.79 mg/day, p<0.05). Pathological observation of the glomerular basement membrane (GBM) revealed monocyte infiltration, hypertrophy, and crescents were alleviated, and injury scoring also showed improved efficacy for the middle dose of SSC during nephritis (7.92 ± 1.37 vs. 3.50 ± 1.14, p<0.05). Moreover, the significant decreases in urinary levels of MGO (24.71 ± 3.46 vs. 16.72 ± 2.36 μg/mg, p<0.05) and D-lactate (0.31 ± 0.04 vs. 0.23 ± 0.02 μmol/mg, p<0.05) were consistent with the biochemical and pathological examinations. This study demonstrates that MGO and D-lactate may reflect the extent of damage and the efficacy of SSC in NTS nephritis; further studies are required to enable clinical application

Quercetin-3-O-β‑d‑glucuronide in the Nuciferine Leaf Polyphenol Extract Promotes Neurogenesis Involving the Upregulation of the Tropomyosin Receptor Kinase (Trk) Receptor and AKT/Phosphoinositide 3‑Kinase Signaling Pathway

Neurogenesis is crucial during the human lifespan for the maintenance of synaptic plasticity and normal function. The impairment of hippocampal neurogenesis in adults may lead to neurodegenerative disease, such as Alzheimer’s disease. Miquelianin (quercetin-3-O-β-d-glucuronide, Q3GA) is a constituent of the nuciferine leaf polyphenol extract (NLPE), and it has protective effects against neurodegeneration. In this study, we examined the effect of the NLPE on neurogenesis and the mechanisms underlying Q3GA on neurogenesis. We fed 24-week-old male C57BL/6 mice with 0.1 or 0.25% NLPE for 2 weeks. NLPE treatment increased small spindle-shaped stem cell numbers in the subgranular zone and the number of doublecortin (DCX)- and neuron-specific nuclear protein (NeuN)-expressing neurons. HT22, a hippocampal cell line, treated with Q3GA revealed significant neurite growth and upregulated TrkR and PI3K/Akt levels. The evidence from a model of retinoic acid-induced SH-SY5Y cell differentiation showed that Q3GA or NLPE increases neurite growth significantly. Taken together, the NLPE containing Q3GA to promote neurogenesis involving the upregulation of TrkR and the PI3K/Akt signaling pathway might be potentiated as an alternative strategy for the treatment of neurodegeneration

Cytotoxicity and transformation of C3H10T1/2 cells induced by areca nut components

Betel quid (BQ) chewing is popular in Taiwan and many other countries. There are about 200–600 million BQ chewers in the world. BQ chewing is one major risk factor of oral cancer and oral submucous fibrosis (OSF). While areca nut (AN), a main component of BQ, exhibits genotoxicity, its transformation capacity and its role in the initiation and promotion stages of carcinogenesis are not fully clear. Methods: Mouse C3H10T1/2 cells were exposed to AN extract (ANE) for 24 hours. Cytotoxicity was evaluated by colony forming efficiency. For the transformation assay, C3H10T1/2 cells were exposed to ANE for 24 hours and then incubated in medium with/without 12-O-tetradecanolylphorbol-13-acetate (TPA; a tumor promoter) for 42 days. Cells were stained with Giemsa and type II and type III transformed foci were counted for analysis of the transformation capacity of ANE. Results: ANE exhibited cytotoxicity to C3H10T/12 cells at concentrations higher than 320 μg/mL as shown by a decrease in colony numbers. ANE (80–640 μg/mL) alone mildly stimulated the transformed foci formation (p > 0.05). In the presence of TPA, ANE (80–640 μg/mL) markedly stimulated the transformed foci formation. The percentage of dishes with foci increased from 0% in controls to 20% in ANE (80 μg/mL and 320 μg/mL)-treated groups and further increased to 65–94% in ANE plus TPA groups. Conclusion: These results indicate that ANE is a weak complete carcinogen. ANE is an effective tumor initiator and can induce malignant transformation of C3H10T1/2 cells in the presence of a tumor promoter. ANE may be involved in multistep chemical carcinogenesis by its malignant transformation capacity