Publications by authors named "Nhan T Nguyen"

31 Publications

VinDr-CXR: An open dataset of chest X-rays with radiologist's annotations.

Sci Data 2022 07 20;9(1):429. Epub 2022 Jul 20.

Vingroup Big Data Institute, Hanoi, Vietnam.

Most of the existing chest X-ray datasets include labels from a list of findings without specifying their locations on the radiographs. This limits the development of machine learning algorithms for the detection and localization of chest abnormalities. In this work, we describe a dataset of more than 100,000 chest X-ray scans that were retrospectively collected from two major hospitals in Vietnam. Out of this raw data, we release 18,000 images that were manually annotated by a total of 17 experienced radiologists with 22 local labels of rectangles surrounding abnormalities and 6 global labels of suspected diseases. The released dataset is divided into a training set of 15,000 and a test set of 3,000. Each scan in the training set was independently labeled by 3 radiologists, while each scan in the test set was labeled by the consensus of 5 radiologists. We designed and built a labeling platform for DICOM images to facilitate these annotation procedures. All images are made publicly available in DICOM format along with the labels of both the training set and the test set.
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http://dx.doi.org/10.1038/s41597-022-01498-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300612PMC
July 2022

Severe COVID-19 during pregnancy treated with pulse corticosteroid therapy and mid-trimester termination: A case report.

Case Rep Womens Health 2022 Apr 9;34:e00396. Epub 2022 Feb 9.

Woolcock Institute of Medical Research, Hanoi, Viet Nam.

Background: At the early stage of the pandemic, severe COVID-19 was thought to be rare among pregnant women. However, cumulating data showed that gestational state is a risk factor for severe pneumonia, particularly due to the hyperinflammatory state. Recent reports suggested the efficacy of pulse corticosteroids in stopping the cytokine storm in people infected with SARS-CoV-2, but limited data exists regarding its use in pregnant women. Moreover, pregnancy termination is a treatment option in this population, but it has been reported mainly in the third trimester and rarely in the second trimester.

Case Presentation: A 37-year-old woman infected with SARS-CoV-2 at 23 weeks of gestation presented with fatigue and dyspnea but soon deteriorated to severely acute respiratory failure and cytokine storm requiring mechanical ventilation combined with hemodialysis just one day after hospitalization. Low-dose corticosteroids and antibiotics were initiated, followed by antiviral therapy, anticoagulant and high-dose corticosteroid therapy. On hospital day 3, a decision to terminate her pregnancy was made; termination led to significant improvement in her clinical condition and a gradual decrease in demand for oxygen supplementation as well as the corticosteroid dose. She was discharged two weeks after admission.

Conclusions: Due to the specific immune response, pregnant women with COVID-19 may differ from others in their clinical presentation, especially the probability of classic acute respiratory distress syndrome (ARDS). This report provides evidence related to the efficacy of pulse corticosteroids on this group and the influence of the mid-trimester termination on recovery.
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http://dx.doi.org/10.1016/j.crwh.2022.e00396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8826598PMC
April 2022

A Phase Defect Framework for the Analysis of Cardiac Arrhythmia Patterns.

Front Physiol 2021 22;12:690453. Epub 2021 Sep 22.

KULeuven Campus KULAK, Department of Mathematics, Kortrijk, Belgium.

During cardiac arrhythmias, dynamical patterns of electrical activation form and evolve, which are of interest to understand and cure heart rhythm disorders. The analysis of these patterns is commonly performed by calculating the local activation phase and searching for phase singularities (PSs), i.e., points around which all phases are present. Here we propose an alternative framework, which focuses on phase defect lines (PDLs) and surfaces (PDSs) as more general mechanisms, which include PSs as a specific case. The proposed framework enables two conceptual unifications: between the local activation time and phase description, and between conduction block lines and the central regions of linear-core rotors. A simple PDL detection method is proposed and applied to data from simulations and optical mapping experiments. Our analysis of ventricular tachycardia in rabbit hearts ( = 6) shows that nearly all detected PSs were found on PDLs, but the PDLs had a significantly longer lifespan than the detected PSs. Since the proposed framework revisits basic building blocks of cardiac activation patterns, it can become a useful tool for further theory development and experimental analysis.
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http://dx.doi.org/10.3389/fphys.2021.690453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494009PMC
September 2021

Glypican 4 mediates Wnt transport between germ layers via signaling filopodia.

J Cell Biol 2021 12 30;220(12). Epub 2021 Sep 30.

Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA.

Glypicans influence signaling pathways by regulating morphogen trafficking and reception. However, the underlying mechanisms in vertebrates are poorly understood. In zebrafish, Glypican 4 (Gpc4) is required for convergence and extension (C&E) of both the mesoderm and endoderm. Here, we show that transgenic expression of GFP-Gpc4 in the endoderm of gpc4 mutants rescued C&E defects in all germ layers. The rescue of mesoderm was likely mediated by Wnt5b and Wnt11f2 and depended on signaling filopodia rather than on cleavage of the Gpc4 GPI anchor. Gpc4 bound both Wnt5b and Wnt11f2 and regulated formation of the filopodia that transport Wnt5b and Wnt11f2 to neighboring cells. Moreover, this rescue was suppressed by blocking signaling filopodia that extend from endodermal cells. Thus, GFP-Gpc4-labeled protrusions that emanated from endodermal cells transported Wnt5b and Wnt11f2 to other germ layers, rescuing the C&E defects caused by a gpc4 deficiency. Our study reveals a new mechanism that could explain in vivo morphogen distribution involving Gpc4.
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http://dx.doi.org/10.1083/jcb.202009082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488972PMC
December 2021

Tyrosinase Inhibitors from the Stems of .

Evid Based Complement Alternat Med 2021 1;2021:5561176. Epub 2021 Jul 1.

Faculty of Chemistry, University of Science, 227 Nguyen Van Cu Street, Ward 4, District 5, Ho Chi Minh City, Vietnam.

Two new stilbene derivatives, named strebluses C and D, were isolated from the EtOAc-soluble fraction of the stems of (Moraceae). Its absolute configuration was elucidated based on NMR spectroscopic data interpretation and optical rotation calculation. Streblus C possesses strong tyrosinase inhibitory activity with an IC value of 0.01 M. Docking studies of and with -tyrosinase were carried out to analyze their interactions. The analysis of the docked poses confirmed that showed better binding affinity for -tyrosinase than that of .
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http://dx.doi.org/10.1155/2021/5561176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266447PMC
July 2021

Effects of the DRD2/3 antagonist ONC201 and radiation in glioblastoma.

Radiother Oncol 2021 08 5;161:140-147. Epub 2021 Jun 5.

Department of Radiation Oncology, David Geffen School of Medicine at UCLA, United States; Jonsson Comprehensive Cancer Center at UCLA, United States. Electronic address:

Background: Glioblastoma (GBM) is the deadliest of all brain cancers in adults. The current standard-of-care is surgery followed by radiotherapy and temozolomide, leading to a median survival time of only 15 months. GBM are organized hierarchically with a small number of glioma-initiating cells (GICs), responsible for therapy resistance and tumor recurrence, suggesting that targeting GICs could improve treatment response. ONC201 is a first-in-class anti-tumor agent with clinical efficacy in some forms of high-grade gliomas. Here we test its efficacy against GBM in combination with radiation.

Methods: Using patient-derived GBM lines and mouse models of GBM we test the effects of radiation and ONC201 on GBM self-renewalin vitro and survivalin vivo.A possible resistance mechanism is investigated using RNA-Sequencing.

Results: Treatment of GBM cells with ONC201 reduced self-renewal, clonogenicity and cell viabilityin vitro. ONC201 exhibited anti-tumor effects on radioresistant GBM cells indicated by reduced self-renewal in secondary and tertiary glioma spheres. Combined treatment of ONC201 and radiation prolonged survival in syngeneic and patient-derived orthotopic xenograft mouse models of GBM. Subsequent transcriptome analyses after combined treatment revealed shifts in gene expression signatures related to quiescent GBM populations, GBM plasticity, and GBM stem cells.

Conclusions: Our findings suggest that combined treatment with the DRD2/3 antagonist ONC201 and radiation improves the efficacy of radiation against GBMin vitroandin vivothrough suppression of GICs without increasing toxicity in mouse models of GBM. A clinical assessment of this novel combination therapy against GBM is further warranted.
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http://dx.doi.org/10.1016/j.radonc.2021.05.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480533PMC
August 2021

A new 7',9-epoxylignan from the stems of .

Nat Prod Res 2022 Aug 17;36(15):4026-4030. Epub 2021 Mar 17.

Faculty of Chemistry, University of Science, Ho Chi Minh City, Vietnam.

Bioactivity-guided isolation of the CHCl-soluble fraction of the stems of L. (Celastraceae) was carried out to obtain a new 7',9-epoxylignan () and three 7,9':7',9-diepoxylignans (-). The absolute configuration of was elucidated based on NMR and ECD spectroscopic data interpretation. All isolated lignans showed intermediate -glucosidase inhibitory activity with the IC values ranging from 28.5 to 85.6 M.
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http://dx.doi.org/10.1080/14786419.2021.1900178DOI Listing
August 2022

Deep learning for detection and segmentation of artefact and disease instances in gastrointestinal endoscopy.

Med Image Anal 2021 05 17;70:102002. Epub 2021 Feb 17.

Instituto Onclologico Veneto, IOV-IRCCS, Padova, Italy.

The Endoscopy Computer Vision Challenge (EndoCV) is a crowd-sourcing initiative to address eminent problems in developing reliable computer aided detection and diagnosis endoscopy systems and suggest a pathway for clinical translation of technologies. Whilst endoscopy is a widely used diagnostic and treatment tool for hollow-organs, there are several core challenges often faced by endoscopists, mainly: 1) presence of multi-class artefacts that hinder their visual interpretation, and 2) difficulty in identifying subtle precancerous precursors and cancer abnormalities. Artefacts often affect the robustness of deep learning methods applied to the gastrointestinal tract organs as they can be confused with tissue of interest. EndoCV2020 challenges are designed to address research questions in these remits. In this paper, we present a summary of methods developed by the top 17 teams and provide an objective comparison of state-of-the-art methods and methods designed by the participants for two sub-challenges: i) artefact detection and segmentation (EAD2020), and ii) disease detection and segmentation (EDD2020). Multi-center, multi-organ, multi-class, and multi-modal clinical endoscopy datasets were compiled for both EAD2020 and EDD2020 sub-challenges. The out-of-sample generalization ability of detection algorithms was also evaluated. Whilst most teams focused on accuracy improvements, only a few methods hold credibility for clinical usability. The best performing teams provided solutions to tackle class imbalance, and variabilities in size, origin, modality and occurrences by exploring data augmentation, data fusion, and optimal class thresholding techniques.
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http://dx.doi.org/10.1016/j.media.2021.102002DOI Listing
May 2021

Diarylalkanoids as Potent Tyrosinase Inhibitors from the Stems of .

Evid Based Complement Alternat Med 2021 4;2021:8872920. Epub 2021 Jan 4.

Faculty of Chemistry, University of Science, 227 Nguyen Van Cu Street, Ward 4, District 5, Ho Chi Minh City, Vietnam.

From a CHCl-soluble extract of the stems of (Anacardiaceae), two new diarylalkanoids, semedienone () and semetrienone (), were isolated. Their structures were elucidated based on NMR spectroscopic data interpretation. These compounds possess strong tyrosinase inhibitory activity with the IC values of 0.033 and 0.11 M, respectively. Docking studies of and with -tyrosinase were carried out to analyze their interactions. Accordingly, semedienone () showed good interactions with the peroxide group and amino acid residues. The biosynthesis of the isolated diarylalkanoids was proposed.
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http://dx.doi.org/10.1155/2021/8872920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801053PMC
January 2021

Panduratins Q-Y, dimeric metabolites from Boesenbergia rotunda and their antiausterity activities against the PANC-1 human pancreatic cancer cell line.

Phytochemistry 2021 Mar 6;183:112646. Epub 2021 Jan 6.

Faculty of Chemistry, University of Science, 227 Nguyen Van Cu Street, District 5, Ho Chi Minh City, Viet Nam; Cancer Research Laboratory, University of Science, 227 Nguyen Van Cu Street, District 5, Ho Chi Minh City, Viet Nam; Vietnam National University, Quarter 6, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Viet Nam. Electronic address:

A methanolic extract of the rhizomes of Boesenbergia rotunda showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient deficiency conditions with a PC value of 6.6 μg/mL. Bioactivity-guided phytochemical investigation of the rhizomes of B. rotunda led to the isolation of nine undescribed dimeric metabolites, panduratins Q-Y. Their structures were elucidated based on NMR, MS, and ECD spectroscopic data interpretation. Panduratins Q-S and U-W exhibited potent cytotoxicity towards PANC-1 cell line with the PC values ranging from 0.8 to 6.3 μM. Panduratin W, which possessed a cyclohexenylchalcone-linked flavanone skeleton, showed the most cytotoxicity with a PC value of 0.8 μM under nutrient-deprived medium.
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http://dx.doi.org/10.1016/j.phytochem.2020.112646DOI Listing
March 2021

Tumor necrosis factor receptor signaling modulates carcinogenesis in a mouse model of breast cancer.

Neoplasia 2021 02 28;23(2):197-209. Epub 2020 Dec 28.

Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA. Electronic address:

Pro-inflammatory conditions have long been associated with mammary carcinogenesis and breast cancer progression. The underlying mechanisms are incompletely understood but signaling of pro-inflammatory cytokine TNFα through its receptors TNFR1 and TNFR2 is a major mediator of inflammation in both obesity and in the response of tissues to radiation, 2 known risk factors for the development of breast cancer. Here, we demonstrated the loss of one TNFR2 allele led to ductal hyperplasia in the mammary gland with increased numbers of mammary epithelial stem cell and terminal end buds. Furthermore, loss of one TNFR2 allele increased the incidence of breast cancer in MMTV-Wnt1 mice and resulted in tumors with a more aggressive phenotype and metastatic potential. The underlying mechanisms include a preferential activation of canonical NF-κB signaling pathway and autocrine production of TNFα. Analysis of the TCGA dataset indicated inferior overall survival for patients with down-regulated TNFR2 expression. These findings unravel the imbalances in TNFR signaling promote the development and progression of breast cancer, indicating that selective agonists of TNFR2 could potentially modulate the risk for breast cancer in high-risk populations.
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http://dx.doi.org/10.1016/j.neo.2020.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779542PMC
February 2021

A new cytotoxic cardenolide from the roots of .

Nat Prod Res 2021 Dec 22;35(23):5096-5101. Epub 2020 Jun 22.

Faculty of Chemistry, University of Science, Ho Chi Minh City, Vietnam.

Bioactivity-guided isolation of the CHCl-soluble fraction of the roots of was carried out to obtain a new cardenolide glycoside, caloside G. Its absolute structure was elucidated based on NMR and ECD spectroscopic data interpretation. Caloside G showed noteworthy cytotoxicity against the PANC-1 human pancreatic and HeLa human cervical carcinoma cell lines, with the submicromolar IC values of 0.038 and 0.09 M, respectively.
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http://dx.doi.org/10.1080/14786419.2020.1781114DOI Listing
December 2021

1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine treatment after brain irradiation preserves cognitive function in mice.

Neuro Oncol 2020 10;22(10):1484-1494

Department of Radiation Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.

Background: Normal tissue toxicity is an inevitable consequence of primary or secondary brain tumor radiotherapy. Cranial irradiation commonly leads to neurocognitive deficits that manifest months or years after treatment. Mechanistically, radiation-induced loss of neural stem/progenitor cells, neuroinflammation, and demyelination are contributing factors that lead to progressive cognitive decline.

Methods: The effects of 1-[(4-nitrophenyl)sulfonyl]-4-phenylpiperazine (NSPP) on irradiated murine neurospheres, microglia cells, and patient-derived gliomaspheres were assessed by sphere-formation assays, flow cytometry, and interleukin (IL)-6 enzyme-linked immunosorbent assay. Activation of the hedgehog pathway was studied by quantitative reverse transcription PCR. The in vivo effects of NSPP were analyzed using flow cytometry, sphere-formation assays, immunohistochemistry, behavioral testing, and an intracranial mouse model of glioblastoma.

Results: We report that NSPP mitigates radiation-induced normal tissue toxicity in the brains of mice. NSPP treatment significantly increased the number of neural stem/progenitor cells after brain irradiation in female animals, and inhibited radiation-induced microglia activation and expression of the pro-inflammatory cytokine IL-6. Behavioral testing revealed that treatment with NSPP after radiotherapy was able to successfully mitigate radiation-induced decline in memory function of the brain. In mouse models of glioblastoma, NSPP showed no toxicity and did not interfere with the growth-delaying effects of radiation.

Conclusions: We conclude that NSPP has the potential to mitigate cognitive decline in patients undergoing partial or whole brain irradiation without promoting tumor growth and that the use of this compound as a radiation mitigator of radiation late effects on the central nervous system warrants further investigation.
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http://dx.doi.org/10.1093/neuonc/noaa095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566405PMC
October 2020

Calosides A-F, Cardenolides from and Their Cytotoxic Activity.

J Nat Prod 2020 02 22;83(2):385-391. Epub 2020 Jan 22.

Division of Natural Drug Discovery, Institute of Natural Medicine , University of Toyama , 2630 Sugitani , Toyama 930-0194 , Japan.

Phytochemical analysis of the roots of led to the isolation of six new cardenolide glycosides, calosides A-F (-), and five known cardenolides (-). The structures of - were elucidated based on NMR and ECD spectroscopic data interpretation. Caloside D () is the first naturally occurring example of a cardenolide containing a C-8/C-19 oxygen bridge. In turn, calosides E () and F () represent the first naturally occurring 3--cannogenol diglycosides having potent cytotoxicity against the PANC-1 cell line (IC, 0.081 and 0.070 μM, respectively) and HeLa (IC, both 0.17 μM) cells, under normoglycemic conditions.
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http://dx.doi.org/10.1021/acs.jnatprod.9b00875DOI Listing
February 2020

Effects of Brain Irradiation in Immune-Competent and Immune-Compromised Mouse Models.

Radiat Res 2020 02 27;193(2):186-194. Epub 2019 Nov 27.

Departments of Radiation Oncology, David Geffen School of Medicine.

Patient-derived orthotopic xenografts (PDOXs) closely recapitulate primary human glioblastoma (GBM) tumors in terms of histology and genotype. Compared to other mouse strains, NOD- IL2Rgamma (NSG) mice show excellent tumor take rates, which makes them an ideal host for PDOXs. However, NSG mice harbor a mutation in the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), which renders them relatively radiosensitive. This has been a frequently voiced concern in studies involving ionizing radiation. In this study, we assessed brain toxicity in NSG mice compared to three other different mouse strains frequently used in radiation studies at radiation doses commonly used in experimental combination therapy studies. C3H/Sed/Kam, C57Bl/6, nude and NOD- IL2Rgamma mice received a single dose of 4 Gy to the right brain hemispheres using an image-guided small animal irradiator. Brains were stained using H&E, luxol fast blue, and antibodies against IBA1 and GFAP one, two, four or six months postirradiation. Additional animals of all four strains were exposed to five daily fractions of 2 Gy (5 × 2 Gy), and tissue sections were stained 72 h later against gH2AX, NeuN, GFAP and IBA1. None of the mouse strains displayed radiation-induced toxicity at any of the time points tested. Radiation doses relevant for testing combination therapies can be safely applied to the brains of NSG mice without the occurrence of radiation-induced normal tissue toxicity.
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http://dx.doi.org/10.1667/RR15373.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135898PMC
February 2020

Imaging of Carbon Nanotube Electronic States Polarized by the Field of an Excited Quantum Dot.

ACS Nano 2019 Feb 29;13(2):1012-1018. Epub 2019 Jan 29.

Faculty of Chemistry , VNU-University of Science , Hanoi 10000 , Vietnam.

Efficient heat dissipation and large gate capacitance have made carbon nanotube field-effect transistors (CNT FETs) devices of interest for over 20 years. The mechanism of CNT FETs involves localization of the electronic structure due to a transverse electric field, yet little is known about the localization effect, nor has the electronic polarization been visualized directly. Here, we co-deposit PbS quantum dots (QDs) with CNTs and optically excite the QD so its excited-state dipolar field biases the local environment of a CNT. Using single-molecule absorption scanning tunneling microscopy, we show that the electronic states of the CNT become transversely localized. By nudging QDs to different distances from the CNT, the magnitude of the localization can be controlled. Different bias voltages probe the degree of localization in different CNT excited states. A simple tight-binding model for the CNT in an electrostatic field provides a semiquantitative model for the observed behavior.
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http://dx.doi.org/10.1021/acsnano.8b06806DOI Listing
February 2019

A new dimeric alkylresorcinol from the stem barks of (Anacardiaceae).

Nat Prod Res 2019 Oct 7;33(20):2883-2889. Epub 2018 Oct 7.

a Faculty of Chemistry, VNUHCM-University of Science , Ho Chi Minh City , Vietnam.

From an EtOAc-soluble fraction of the stem barks of (Anacardiaceae), one new dimeric alkylresorcinol named integracin E (), together with 4 known compounds (-) were isolated. Their chemical structures were elucidated based on the spectroscopic data interpretation. The absolute configuration of was determined by the specific rotation analysis of its acid-catalyzed hydrolysis product. Compound showed potent tyrosinase inhibitory activity with an IC value of 48.2 μM.
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http://dx.doi.org/10.1080/14786419.2018.1509329DOI Listing
October 2019

Artocarmins G-M, Prenylated 4-Chromenones from the Stems of Artocarpus rigida and Their Tyrosinase Inhibitory Activities.

J Nat Prod 2017 12 11;80(12):3172-3178. Epub 2017 Dec 11.

Department of Chemistry, Graduate School of Science, Hiroshima University , Higashi-Hiroshima, Hiroshima 739-8526, Japan.

Phytochemical analysis of an EtOAc extract of the stems of Artocarpus rigida led to the identification of seven new prenylated 4-chromenones, artocarmins G-M (1-7), and nine known compounds (8-17). Their structures were identified based on physical data analysis. In the tyrosinase inhibitory activity test, norartocarpetin (8) displayed the strongest effect, with an IC value of 0.023 μM.
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http://dx.doi.org/10.1021/acs.jnatprod.7b00453DOI Listing
December 2017

LPV Modeling of a Flexible Wing Aircraft Using Modal Alignment and Adaptive Gridding Methods.

Aerosp Sci Technol 2017 Jul 10;66:92-102. Epub 2017 Mar 10.

Intelligent Systems Division, NASA Ames Research Center.

One of the earliest approaches in gain-scheduling control is the based approach, in which a set of local linear time-invariant models are obtained at various gridded points corresponding to the varying parameters within the flight envelop. In order to ensure smooth and effective Linear Parameter-Varying control, aligning all the flexible modes within each local model and maintaining small number of representative local models over the gridded parameter space are crucial. In addition, since the flexible structural models tend to have large dimensions, a tractable model reduction process is necessary. In this paper, the notion of -shifted [Formula: see text]- and [Formula: see text]-norm are introduced and used as a metric to measure the model mismatch. A new modal alignment algorithm is developed which utilizes the defined metric for aligning all the local models over the entire gridded parameter space. Furthermore, an Adaptive Grid Step Size Determination algorithm is developed to minimize the number of local models required to represent the gridded parameter space. For model reduction, we propose to utilize the concept of Composite Modal Cost Analysis, through which the collective contribution of each flexible mode is computed and ranked. Therefore, a reduced-order model is constructed by retaining only those modes with significant contribution. The NASA Generic Transport Model operating at various flight speeds is studied for verification purpose, and the analysis and simulation results demonstrate the effectiveness of the proposed modeling approach.
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http://dx.doi.org/10.1016/j.ast.2017.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713486PMC
July 2017

A new bischromanone from the stems of Semecarpus caudata.

Nat Prod Res 2018 Aug 8;32(15):1745-1750. Epub 2017 Nov 8.

a Faculty of Chemistry , VNUHCM-University of Science , Ho Chi Minh City , Vietnam.

From an CHCl-soluble fraction of the stems of Semecarpus caudata, one new bischromanone named semecarpanone (1), together with 5 known flavonoids (2-6) were isolated. Their structures were elucidated based on interpretation of spectroscopic data. The stereo-configuration of 1 was identified based on the calculated and experimental coupling constants. Compounds 4-6 showed potent tyrosinase inhibitory activity with the IC values ranging from 15.0 to 76.3 μM.
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http://dx.doi.org/10.1080/14786419.2017.1399391DOI Listing
August 2018

Changes in estuarine sediment phosphorus fractions during a large-scale Mississippi River diversion.

Sci Total Environ 2017 Dec 5;609:1248-1257. Epub 2017 Aug 5.

Department of Oceanography and Coastal Sciences, College of the Coast and Environment, Louisiana State University, Baton Rouge, LA 70803, United States.

Ongoing deterioration and loss of wetlands in the Mississippi River delta threatens the survival of Louisiana's coastal ecosystems and human settlements. In response, the State of Louisiana has proposed a $50 billion, 50-year restoration program. A central piece of this program is the reintroduction of Mississippi River water into the deltaic plain using managed diversions that mimic natural flood pulses. These diversions would transport critically needed sediment, but also deliver large nutrient loads. Coastal eutrophication is therefore a concern, particularly blooms of toxin-producing cyanobacteria. The Bonnet Carré Spillway (BCS) is an existing large flood diversion that protects New Orleans and provides an opportunity to investigate diversion nutrient transport. Here, we quantify sediment phosphorus (P) deposited by the BCS for the first time, and use a sequential P fractionation scheme to evaluate the likelihood of future sediment P release to the water column of the Lake Pontchartrain Estuary. In 2011, we collected sediment cores in the estuary for determination of P fractions before and after the discharge of 21.9km of river water through the BCS in just under 6weeks. We observed the greatest net increases in sediment total P, inorganic P forms, and more labile organic P in the region near the inflow. We estimate that the diversion deposited ≥5000 metric tons of P in the sediments of the Lake Pontchartrain Estuary. The sum of readily available inorganic P, Fe/Al-bound inorganic P, and more labile organic P equaled approximately 20-30% of post-diversion sediment total P. These fractions are more likely to be released to the water column than the other sediment P forms we quantified. Diversion designs that encourage sedimentation in coastal marshes versus open bays can likely reduce the chances that deposited particulate P creates eutrophication risk.
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http://dx.doi.org/10.1016/j.scitotenv.2017.07.224DOI Listing
December 2017

Chemical Constituents of Propolis from Vietnamese Trigona minor and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line.

J Nat Prod 2017 08 7;80(8):2345-2352. Epub 2017 Aug 7.

Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama , 2630 Sugitani, Toyama 930-0194, Japan.

The ethanol extract of propolis from the Vietnamese stingless bee Trigona minor possessed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells in nutrient-deprived medium, with a PC value of 14.0 μg/mL. Chemical investigation of this extract led to the isolation of 15 cycloartane-type triterpenoids, including five new compounds (1-5), and a lanostane-type triterpenoid. The structures of the new compounds were elucidated on the basis of NMR spectroscopic analysis. Among the isolated compounds, 23-hydroxyisomangiferolic acid B (5) and 27-hydroxyisomangiferolic acid (13) exhibited the most potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions, with PC values of 4.3 and 3.7 μM, respectively.
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http://dx.doi.org/10.1021/acs.jnatprod.7b00375DOI Listing
August 2017

Quinoliniumolate and 2H-1,2,3-Triazole Derivatives from the Stems of Paramignya trimera and Their α-Glucosidase Inhibitory Activities: In Vitro and in Silico Studies.

J Nat Prod 2017 07 20;80(7):2151-2155. Epub 2017 Jul 20.

Faculty of Chemistry, VNUHCM-University of Science , 227 Nguyen Van Cu Street, District 5, Ho Chi Minh City, Vietnam.

From a CHCl-soluble extract of the stems of Paramignya trimera, two new alkaloids, (E)-2-(prop-1-enyl)-N-methylquinolinium-4-olate (1) and (R)-2-ethylhexyl 2H-1,2,3-triazole-4-carboxylate (2), were isolated. Their structures were elucidated based on the spectroscopic data interpretation. Compound 2 possesses α-glucosidase inhibitory activity, with an IC value of 137.9 μM. Molecular docking studies of 1 and 2 with human maltase-glucoamylase (MGAM) were performed for the first time; thus, the 2,3-diH-1H-1,2,3-triazolium cation (2i) showed good interactions with both MGAM-N (2QMJ) and -C (3TOP) terminal subunits.
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http://dx.doi.org/10.1021/acs.jnatprod.7b00289DOI Listing
July 2017

Lignans from the Roots of Taxus wallichiana and Their α-Glucosidase Inhibitory Activities.

J Nat Prod 2017 06 5;80(6):1876-1882. Epub 2017 Jun 5.

Faculty of Chemistry, VNUHCM-University of Science , 227 Nguyen Van Cu Street, District 5, Ho Chi Minh City, Vietnam.

From an EtOAc-soluble extract of the roots of Taxus wallichiana, six new (1-6) and 11 known lignans were isolated. The structures of the new compounds were elucidated based on interpretation of spectroscopic data. (+)-7'-epi-Tsugacetal (1) is a rare aryltetralin-type lignan having a cis-orientation of H-7' and H-8'. Compounds 3-6 were identified as the first naturally occurring tetrahydrofuranoid lignans having a cis-orientation of H-7 and H-8. All tested compounds were found to possess α-glucosidase inhibitory activity, with formosanol (9) showing the most potent effect with an IC value of 35.3 μM.
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http://dx.doi.org/10.1021/acs.jnatprod.7b00171DOI Listing
June 2017

Phytochemical and cytotoxic studies on the leaves of Calotropis gigantea.

Bioorg Med Chem Lett 2017 07 29;27(13):2902-2906. Epub 2017 Apr 29.

Faculty of Chemistry, VNUHCM-University of Science, 227 Nguyen Van Cu Street, District 5, Ho Chi Minh City, Viet Nam; Cancer Research Laboratory, Vietnam National University, Ho Chi Minh City, 227 Nguyen Van Cu Street, District 5, Ho Chi Minh City, Viet Nam. Electronic address:

A new lignan, 9'-methoxypinoresinol (1), and two new glycosylated 5-hydroxymethylfurfurals, calofurfuralside A (2), and calofurfuralside B (3), together with nine known compounds (4-12) have been isolated from the active fractions, CHCl (IC, 0.32μgmL) and EtOAc (IC, 0.55μgmL) fractions of the leaves of Calotropis gigantea. Their structures were elucidated based on NMR and MS data. Among the isolated compounds, compounds 1 and 9 exhibited potent cytotoxicity against PANC-1 human pancreatic cancer cell line under the normoglycemic condition with IC values of 3.7 and 3.3μM, respectively. 9'-Methoxypinoresinol (1) significantly inhibited the colony formation of PANC-1 cells in a concentration-dependent manner.
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http://dx.doi.org/10.1016/j.bmcl.2017.04.087DOI Listing
July 2017

The dark side of ZNF217, a key regulator of tumorigenesis with powerful biomarker value.

Oncotarget 2015 Dec;6(39):41566-81

ISPB, Faculté de Pharmacie, Lyon, France.

The recently described oncogene ZNF217 belongs to a chromosomal region that is frequently amplified in human cancers. Recent findings have revealed that alternative mechanisms such as epigenetic regulation also govern the expression of the encoded ZNF217 protein. Newly discovered molecular functions of ZNF217 indicate that it orchestrates complex intracellular circuits as a new key regulator of tumorigenesis. In this review, we focus on recent research on ZNF217-driven molecular functions in human cancers, revisiting major hallmarks of cancer and highlighting the downstream molecular targets and signaling pathways of ZNF217. We also discuss the exciting translational medicine investigating ZNF217 expression levels as a new powerful biomarker, and ZNF217 as a candidate target for future anti-cancer therapies.
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http://dx.doi.org/10.18632/oncotarget.5893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747174PMC
December 2015

A functional interplay between ZNF217 and estrogen receptor alpha exists in luminal breast cancers.

Mol Oncol 2014 Dec 10;8(8):1441-57. Epub 2014 Jun 10.

ISPB, Faculté de Pharmacie, Lyon, France; Université Lyon 1, Lyon, France; INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France. Electronic address:

We aimed at highlighting the role of ZNF217, a Krüppel-like finger protein, in Estrogen Receptor-α (ERα)-positive (ER+) and luminal breast cancers. Here we report for the first time that ZNF217 and ERα proteins bind to each other in both breast cancer cells and breast tumour samples, via the ERα hinge domain and the ZNF217 C-terminal domain. ZNF217 enhances the recruitment of ERα to its estrogen response elements (ERE) and the ERα-dependent transcription of the GREB1 estrogen-regulated gene. The prognostic power of ZNF217 mRNA expression levels is most discriminatory in breast cancers classified with a "good prognosis", particularly the Luminal-A subclass. A new immunohistochemistry ZNF217 index, based on nuclear and cytoplasmic ZNF217 staining, also allowed the identification of intermediate/poor relapse-free survivors in the Luminal-A subgroup. ZNF217 confers tamoxifen resistance in ER+ breast cancer cells and is a predictor of relapse under endocrine therapy in patients with ER+ breast cancer. ZNF217 thus allows the re-stratification of patients with ER+ breast cancers considered as cancers with good prognosis where no other biomarkers are currently available and widely used. Here we propose a model in ER+ breast cancer where ZNF217-driven aggressiveness incorporates ZNF217 as a positive enhancer of ERα direct genomic activity and where ZNF217 possesses its highest discriminatory prognostic value.
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http://dx.doi.org/10.1016/j.molonc.2014.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528595PMC
December 2014

The evaporation of mercury droplets in indoor spaces.

J Occup Environ Hyg 2012 ;9(12):712-9

U.S. Environmental Protection Agency, Office of Pollution Prevention and Toxics, Chemical Engineering Branch, Washington, D.C. 20460, USA.

Based on experiments conducted by the U.S. Environmental Protection Agency, the evaporation of mercury droplets in air was modeled as an exponential decay, and values for the decay constant, k(d), were estimated; values for k(d)(-1) ranged from 0.7 days to 2.2 days over a temperature range of 302 K to 310 K. Although values of k(d) did not appear to vary significantly as a function of temperature, they did exhibit significant variability for the temperature range studied. These insights can be incorporated into stochastic-based uncertainty analyses when modeling various exposure scenarios for mercury spills in indoor spaces.
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http://dx.doi.org/10.1080/15459624.2012.728925DOI Listing
February 2013

ZNF217 is a marker of poor prognosis in breast cancer that drives epithelial-mesenchymal transition and invasion.

Cancer Res 2012 Jul 16;72(14):3593-606. Epub 2012 May 16.

ISPB, Faculté de Pharmacie, Université Lyon 1, Lyon, France.

The Krüppel-like zinc finger protein ZNF217 is a candidate oncogene in breast cancer. In this study, we showed that high levels of expression of ZNF217 mRNA are associated with poor prognosis and the development of metastases in breast cancer. Overexpression of ZNF217 in breast cancer cells stimulated migration and invasion in vitro and promoted the development of spontaneous lung or node metastases in mice in vivo. ZNF217 also promoted epithelial-mesenchymal transition (EMT) in human mammary epithelial cells, and the TGF-β-activated Smad signaling pathway was identified as a major driver of ZNF217-induced EMT. In addition, a TGF-β autocrine loop sustained activation of the TGF-β pathway in ZNF217-overexpressing mammary epithelial cells, most likely because of ZNF217-mediated direct upregulation of TGFB2 or TGFB3. Inhibition of the TGF-β pathway led to the reversal of ZNF217-mediated EMT. Together, our findings indicate that ZNF217 mRNA expression may represent a novel prognostic biomarker in breast cancer. Therapeutic targeting of ZNF217 of the TGF-β signaling pathway may benefit the subset of patients whose tumors express high levels of ZNF217.
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http://dx.doi.org/10.1158/0008-5472.CAN-11-3095DOI Listing
July 2012

Distinct activities of the alpha-catenin family, alpha-catulin and alpha-catenin, on beta-catenin-mediated signaling.

Mol Cell Biol 2004 Mar;24(6):2410-22

Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Alpha-catenin, an integral part of cadherin-catenin adhesion complexes, is a major binding partner of beta-catenin, a key component of the Wnt pathway, which activates T-cell factor (TCF)/lymphoid enhancer factor (LEF) transcription and is often upregulated in cancers. Recently, we identified an alpha-catenin-related protein, alpha-catulin, whose function is poorly understood, as part of a Rho GTPase signaling complex. Here, based on evidence suggesting that alpha-catulin may associate with a beta-catenin fraction, we investigated the role of alpha-catenin family members in beta-catenin-mediated signals. Expression of the full length or a 103-residue region of alpha-catenin strongly inhibits the induction of the TCF/LEF-responsive TOPFLASH reporter in HEK293T cells expressing activated beta-catenin or in cancer cells with constitutively upregulated Wnt signaling, whereas alpha-catulin expression had no effect. Interestingly, alpha-catulin expression attenuates the activation of the cyclin D1 promoter, a target of Wnt pathway signals. Alpha-catulin appears to inhibit Ras-mediated signals to the cyclin D1 promoter, rather than beta-catenin signals, and the synergy between Ras and beta-catenin required to fully activate this promoter. Data suggesting the involvement of Rho in this response are presented and discussed. These results suggest a novel function for alpha-catulin and imply that alpha-catenin and alpha-catulin have distinct activities that downregulate, respectively, beta-catenin and Ras signals converging on the cyclin D1 promoter.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC355851PMC
http://dx.doi.org/10.1128/MCB.24.6.2410-2422.2004DOI Listing
March 2004
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