Publications by authors named "Wei-Lun Chen"

38 Publications

Comparing the effectiveness of negative-pressure barrier devices in providing air clearance to prevent aerosol transmission.

PLoS One 2021 21;16(4):e0250213. Epub 2021 Apr 21.

Department of Energy and Refrigerating Air-conditioning Engineering, National Taipei University of Technology, Taipei, Taiwan.

Purpose: To investigate the effectiveness of aerosol clearance using an aerosol box, aerosol bag, wall suction, and a high-efficiency particulate air (HEPA) filter evacuator to prevent aerosol transmission.

Methods: The flow field was visualized using three protective device settings (an aerosol box, and an aerosol bag with and without sealed working channels) and four suction settings (no suction, wall suction, and a HEPA filter evacuator at flow rates of 415 liters per minute [LPM] and 530 LPM). All 12 subgroups were compared with a no intervention group. The primary outcome, aerosol concentration, was measured at the head, trunk, and foot of a mannequin.

Results: The mean aerosol concentration was reduced at the head (p < 0.001) but increased at the feet (p = 0.005) with an aerosol box compared with no intervention. Non-sealed aerosol bags increased exposure at the head and trunk (both, p < 0.001). Sealed aerosol bags reduced aerosol concentration at the head, trunk, and foot of the mannequin (p < 0.001). A sealed aerosol bag alone, with wall suction, or with a HEPA filter evacuator reduced the aerosol concentration at the head by 7.15%, 36.61%, and 84.70%, respectively (99.9% confidence interval [CI]: -4.51-18.81, 27.48-45.73, and 78.99-90.40); trunk by 70.95%, 73.99%, and 91.59%, respectively (99.9% CI: 59.83-82.07, 52.64-95.33, and 87.51-95.66); and feet by 69.16%, 75.57%, and 92.30%, respectively (99.9% CI: 63.18-75.15, 69.76-81.37, and 88.18-96.42), compared with an aerosol box alone.

Conclusions: As aerosols spread, an airtight container with sealed working channels is effective when combined with suction devices.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250213PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059829PMC
April 2021

Review of Emergency Response Management of 33 Major Burn Victims of the Formosa Fun Coast Dust Explosion Disaster in a Regional Hospital Without Burn Units.

J Acute Med 2019 Sep;9(3):110-117

Taipei City Hospital, Zhong-Xing branch Department of Emergency Medicine Taipei Taiwan.

Background: The Formosa Fun Coast Dust Explosion is one of the major national disasters in Taiwan. The Taipei City Hospital (TCH), a regional hospital without a burn unit, received 33 patients out of 499 casualties in the initial response period. This retrospective study aimed to review the primary response of TCH and the outcome and mortality of the patients who were initially managed at TCH.

Methods: Basic profi les, total body surface area (TBSA) with burn injury, facial burn injury, vital signs, laboratory data, intubation rate and clinical outcomes, such as urine output and mortality, were analyzed. Moreover, the emergency department (ED) response faculties, who were involved in the initial response, were interviewed about the critical decision-making processes during the patient surge in the ED.

Results: The average initial estimated TBSA with burn injury in ED was 34.2%, and the average final TBSA assessed in the intensive care unit was 41.0%. The patients with facial burn injury were 38.7%, and the intubation rate was 22.6%. When comparing the result of TCH to the patient group transferred directly to Chang Gung Memorial Hospital (CGMH), and the group received by CGMH from other hospital, the mortality rate was 0.0, 5.7, 9.1%; and the delayed intubation rate was 3.0, 14.3, 27.3%, respectively. The key elements for effi cient initial response were the multidisciplinary response team cooperated as a production line, using the clipboards for orders recordings, and the plastic surgeons ED-operating room (OR) direct transferring.

Conclusions: Regarding airway complications, and mortality, patients who were initially managed in TCH had comparable results with patients directly sent to the burn centers. This study supports the notion that immediate resuscitation in multiple level of hospitals, even without burn units but with adequate recruited response personnel, provided the best chance for the survival of casualties during such national disasters.
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http://dx.doi.org/10.6705/j.jacme.201909_9(3).0003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440376PMC
September 2019

Lifting of epiglottis superior to preloaded bougie technique when only the epiglottis is visible: a randomized, cross-over simulated mannequin study.

Eur J Emerg Med 2020 04;27(2):147-148

Department of Biomedical Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu City.

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http://dx.doi.org/10.1097/MEJ.0000000000000656DOI Listing
April 2020

Bioactivity-Guided Isolation of Totarane-Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3-Deoxy-2α-hydroxynagilactone E.

Nat Prod Bioprospect 2019 Apr 19;9(2):157-163. Epub 2019 Feb 19.

Division of Medicinal Chemistry and Pharmacognosy, The Ohio State University, College of Pharmacy, Columbus, OH, USA.

Bioactivity-guided phytochemical investigation of Podocarpus neriifolius D. Don. (Podocarpaceae) has led to the isolation of one new (2) and three known (1, 3, and 4) B-type podolactones, along with three totarane-type diterpenes (5-7). Their structures were determined by interpretation of High Resolution ElectroSpray Ionization Mass Spectrometry (HRESIMS) and 1D and 2D NMR data, and comparison with the values reported in the literature. The structure of compound 1, previously identified as 3-deoxy-2α-hydroxynagilactone E (8), was revised as its 2β-epimer, which has been reported recently as a new compound. All of the isolates were evaluated for their antiproliferative activity against a panel of four human cancer cell lines, namely, ovarian (OVCAR3), breast (MDA-MB-231), colon (HT-29), and melanoma (MDA-MB-435), and compounds 1 and 3 were found to be cytotoxic with IC values in the low micromolar range for most of the cell lines used. The major compound, inumakilactone A (3), was further tested in vivo using the HT-29, MDA-MB-435, and OVCAR3 cells in a murine hollow fiber model, for the first time.
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http://dx.doi.org/10.1007/s13659-019-0198-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426912PMC
April 2019

Biochemical and Anti-Triple Negative Metastatic Breast Tumor Cell Properties of Psammaplins.

Mar Drugs 2018 Nov 10;16(11). Epub 2018 Nov 10.

Institute of Interdisciplinary Integrative Medical Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China.

Breast tumors reprogram their cellular metabolism, nutrient uptake, and utilization-associated biochemical processes. These processes become further transformed as genetically predisposed metastatic breast tumor cells colonize specific organs. Breast tumor cells often metastasize to the brain, bone, lung and liver. Massagué and colleagues isolated organotropic subclones and established organ-specific gene signatures associated with lung-, bone-, and brain-specific metastatic triple-negative breast cancer (TNBC) MDA-MB-231 cells. Using these genetically characterized metastatic subclones specific to lung (LM4175), bone (BoM1833), and brain (BrM-2a), we evaluated marine natural products for the ability to differentially suppress metastatic breast cancer cells in a target organ-dependent manner. Psammaplin-based histone deacetylase (HDAC) inhibitors were found to differentially inhibit HDAC activity, induce activation of hypoxia-inducible factor-1 (HIF-1), and disrupt organotropic metastatic TNBC subclone growth. Further, psammaplins distinctly suppressed the outgrowth of BoM1833 tumor spheroids in 3D-culture systems. Similar results were observed with the prototypical HDAC inhibitor trichostatin A (TSA). These organotropic tumor cell-based studies suggest the potential application of HDAC inhibitors that may yield new directions for anti-metastatic breast tumor research and drug discovery.
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http://dx.doi.org/10.3390/md16110442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265740PMC
November 2018

Revisiting the linkage between ethnomedical use and development of new medicines: A novel plant collection strategy towards the discovery of anticancer agents.

J Med Plant Res 2017 Oct 25;11(40):621-634. Epub 2017 Oct 25.

Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 S. Wood St., Chicago, Illinois 60612, USA.

The Vietnam-Laos International Cooperative Biodiversity Group (ICBG) based at the University of Illinois at Chicago (UIC) catalyzed a country-wide network of medicinal plant preserves (MPP) and medicinal biodiversity preserves (MBP) now established in ten provinces of the Lao People's Democratic Republic (Lao PDR), which are relied upon as protected sources of ethnomedicines for local villagers and traditional healers. In collaboration with the Lao PDR's Institute of Traditional Medicine (ITM), our ongoing P01 Program Project (Ohio State University) examined the anticancer bioprospecting potential for two of the most exhaustively inventoried of these sites: the Bolikhamxay MPP and the Xiengkhouang MBP. Guided by prior voucher specimens sourced from these preserves with an overwhelming emphasis on plants employed in traditional medicine, 201 distinct samples from 96 species were collected along with proper herbarium documentation. Aliquots of these plant samples were extracted in azeotropic ethanol and evaporated to dryness for initial biological evaluation. In six samples from six different species (2.99% of the collected samples, 6.25% of taxa) it was observed that extracts exhibited notable cytotoxicity against HT-29 colon adenocarcinoma cells. The wisdom behind the utilization of HT-29 cells in this preliminary biological screen is discussed. Furthermore, comparison of screening results based on longstanding considerations and ideological underpinnings of ethnobotanical vs. "random" biodiversity-based collection approaches is detailed herein. The results of this interdisciplinary study support the hypothesis that, by privileging the initial sample set in terms of human safety and pharmacological activity, ethnobotanically driven collection for biological screening efforts can produce leads unprecedented by the strict traditional usages of plants.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686776PMC
http://dx.doi.org/10.5897/jmpr2017.6485DOI Listing
October 2017

Phenologic variation of major triterpenoids in regular and white Antrodia cinnamomea.

Bot Stud 2016 Dec 25;57(1):33. Epub 2016 Oct 25.

Department of Natural Resources and Environmental Studies, National Dong Hwa University, Shou-feng, Hualien, 97401, Taiwan.

Background: Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea.

Results: The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The TLC and HPLC profiles indicated that specific triterpenoids varied between white and regular strains. Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain.

Conclusions: Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture.
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http://dx.doi.org/10.1186/s40529-016-0148-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432900PMC
December 2016

Merocyclophanes C and D from the Cultured Freshwater Cyanobacterium Nostoc sp. (UIC 10110).

J Nat Prod 2017 04 2;80(4):1073-1080. Epub 2017 Mar 2.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago , Chicago, Illinois 60612, United States.

Merocyclophanes C and D (1 and 2) were isolated from the cell extract of the cultured cyanobacterium UIC 10110. The structures were determined by one-dimensional nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry and confirmed by 2D NMR techniques. The absolute configurations were determined using electronic circular dichroism spectroscopy. Merocyclophanes C and D represent the first known analogues of the merocyclophane core structure, a recently discovered scaffold of [7,7] paracyclophanes characterized by an α-branched methyl at C-1/C-14; 1 and 2 showed antiproliferative activity against the MDA-MB-435 cell line with IC values of 1.6 and 0.9 μM, respectively. Partial 16S analysis determined UIC 10110 to be a Nostoc sp., and it was found to clade with UIC 10062 Nostoc sp., the only other strain known to produce merocyclophanes. The genome of UIC 10110 was sequenced, and a biosynthetic gene cluster was identified that is proposed to encode type I and type III polyketide synthases that are potentially responsible for production of the merocyclophanes; however, further experiments will be required to verify the true function of the gene cluster. The gene cluster provides a genetic basis for the observed structural differences of the [7,7] paracyclophane core structures.
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http://dx.doi.org/10.1021/acs.jnatprod.6b01175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898374PMC
April 2017

(+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks.

J Nat Prod 2017 03 24;80(3):659-669. Epub 2017 Feb 24.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago , Chicago, Illinois 60612, United States.

(+)-Strebloside, a cardiac glycoside isolated from the stem bark of Streblus asper collected in Vietnam, has shown some potential for further investigation as an antineoplastic agent. A mechanistic study using an in vitro assay and molecular docking analysis indicated that (+)-strebloside binds and inhibits Na/K-ATPase in a similar manner to digitoxin. Inhibition of growth of different high-grade serous ovarian cancer cells including OVCAR3, OVSAHO, Kuramochi, OVCAR4, OVCAR5, and OVCAR8 resulted from treatment with (+)-strebloside. Furthermore, this compound blocked cell cycle progression at the G2 phase and induced PARP cleavage, indicating apoptosis activation in OVCAR3 cells. (+)-Strebloside potently inhibited mutant p53 expression through the induction of ERK pathways and inhibited NF-κB activity in human ovarian cancer cells. However, in spite of its antitumor potential, the overall biological activity of (+)-strebloside must be regarded as being typical of better-known cardiac glycosides such as digoxin and ouabain. Further chemical alteration of cardiac glycosides might help to reduce negative side effects while increasing cancer cell cytotoxicity.
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http://dx.doi.org/10.1021/acs.jnatprod.6b01150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768141PMC
March 2017

Cardiac Glycoside Constituents of Streblus asper with Potential Antineoplastic Activity.

J Nat Prod 2017 03 16;80(3):648-658. Epub 2016 Dec 16.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago , Chicago, Illinois 60612, United States.

Three new (1-3) and two known (4 and 5) cytotoxic cardiac glycosides were isolated and characterized from a medicinal plant, Streblus asper Lour. (Moraceae), collected in Vietnam, with six new analogues and one known derivative (5a-g) synthesized from (+)-strebloside (5). A preliminary structure-activity relationship study indicated that the C-10 formyl and C-5 and C-14 hydroxy groups and C-3 sugar unit play important roles in the mediation of the cytotoxicity of (+)-strebloside (5) against HT-29 human colon cancer cells. When evaluated in NCr nu/nu mice implanted intraperitoneally with hollow fibers facilitated with either MDA-MB-231 human breast or OVCAR3 human ovarian cancer cells, (+)-strebloside (5) showed significant cell growth inhibitory activity in both cases, in the dose range 5-30 mg/kg.
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http://dx.doi.org/10.1021/acs.jnatprod.6b00924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365359PMC
March 2017

A probabilistic bridge safety evaluation against floods.

Springerplus 2016 18;5(1):783. Epub 2016 Jun 18.

Department of Civil and Construction Engineering, National Taiwan University of Science and Technology, No. 43, Sec. 4, Keelung Rd., Taipei, 106 Taiwan.

To further capture the influences of uncertain factors on river bridge safety evaluation, a probabilistic approach is adopted. Because this is a systematic and nonlinear problem, MPP-based reliability analyses are not suitable. A sampling approach such as a Monte Carlo simulation (MCS) or importance sampling is often adopted. To enhance the efficiency of the sampling approach, this study utilizes Bayesian least squares support vector machines to construct a response surface followed by an MCS, providing a more precise safety index. Although there are several factors impacting the flood-resistant reliability of a bridge, previous experiences and studies show that the reliability of the bridge itself plays a key role. Thus, the goal of this study is to analyze the system reliability of a selected bridge that includes five limit states. The random variables considered here include the water surface elevation, water velocity, local scour depth, soil property and wind load. Because the first three variables are deeply affected by river hydraulics, a probabilistic HEC-RAS-based simulation is performed to capture the uncertainties in those random variables. The accuracy and variation of our solutions are confirmed by a direct MCS to ensure the applicability of the proposed approach. The results of a numerical example indicate that the proposed approach can efficiently provide an accurate bridge safety evaluation and maintain satisfactory variation.
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http://dx.doi.org/10.1186/s40064-016-2366-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912552PMC
July 2016

Di-nor- and 17-nor-pimaranes from Icacina trichantha.

J Nat Prod 2016 07 24;79(7):1815-21. Epub 2016 Jun 24.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago , Chicago, Illinois 60612, United States.

Six new pimarane derivatives, including two di-nor-pimaranes (1, 2), two 17-nor-pimaranes (3, 4), and two 17-nor-(9β-H)-pimaranes (5, 6), were isolated from the tuber of Icacina trichantha. Their structures were elucidated based on spectroscopic and HRMS data. The absolute configurations of 1 and 5 were determined by single-crystal X-ray diffraction, and that of 2 was established by electronic circular dichroism data analysis. Compound 3 possesses a unique C-20 acetal moiety. This is the first report of the isolation of di-nor-(9β-H)-pimarane derivatives from Icacina plants. Compounds 5 and 6 showed moderate cytotoxicity against MDA-MB-435, MDA-MB-231, and OVCAR3 cell lines, with IC50 values of 2.91-7.60 and 1.48-3.23 μM, respectively.
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http://dx.doi.org/10.1021/acs.jnatprod.6b00289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096845PMC
July 2016

miR-144 suppresses the growth and metastasis of laryngeal squamous cell carcinoma by targeting IRS1.

Am J Transl Res 2016 15;8(1):1-11. Epub 2016 Jan 15.

Department of Hand Surgery, The First Hospital of Jilin University 3302 Jilin Main Road, Changchun 130021, China.

Increasing evidence has been suggested that microRNA-144 (miR-144) involved in tumor initiation, development and metastasis in various cancers. However, the biological roles and potential mechanisms of miR-144 in laryngeal squamous cell carcinoma (LSCC) remain unclear. In the present study, we discovered that miR-144 expression levels in LSCC tissues were significantly lower than those of adjacent normal tissues. Furthermore, overexpression of miR-144 in LSCC cells inhibited cell proliferation, colony formation, migration, and invasion in vitro. Consistently, stable overexpression of miR-144 suppressed the growth of LSCC cell xenografts in vivo. Bioinformatic algorithms and luciferase reporter assays confirmed that insulin receptor substrate 1 (IRS1) is a direct target of miR-144. Overexpreesion of miR-144 obviously decreased IRS1 expression thereby suppressing phosphatidylinositol 3-kinase (PI3K)/AKT pathway activation. Further functional studies suggested that downregulation of IRS1 had similar effects as that of miR-144 overexpression, and upregulation of IRS1 partially reversed the inhibitory effects of miR-144. These findings suggested that miR-144 functioned as a tumor suppressor in LSCC by targeting IRS1, and that miR-144 might serve as a potential target for LSCC treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759411PMC
April 2016

Silvestrol induces early autophagy and apoptosis in human melanoma cells.

BMC Cancer 2016 Jan 13;16:17. Epub 2016 Jan 13.

Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL, 60607, USA.

Background: Silvestrol is a cyclopenta[b]benzofuran that was isolated from the fruits and twigs of Aglaia foveolata, a plant indigenous to Borneo in Southeast Asia. The purpose of the current study was to determine if inhibition of protein synthesis caused by silvestrol triggers autophagy and apoptosis in cultured human cancer cells derived from solid tumors.

Methods: In vitro cell viability, flow cytometry, fluorescence microscopy, qPCR and immunoblot was used to study the mechanism of action of silvestrol in MDA-MB-435 melanoma cells.

Results: By 24 h, a decrease in cyclin B and cyclin D expression was observed in silvestrol-treated cells relative to control. In addition, silvestrol blocked progression through the cell cycle at the G2-phase. In silvestrol-treated cells, DAPI staining of nuclear chromatin displayed nucleosomal fragments. Annexin V staining demonstrated an increase in apoptotic cells after silvestrol treatment. Silvestrol induced caspase-3 activation and apoptotic cell death in a time- and dose-dependent manner. Furthermore, both silvestrol and SAHA enhanced autophagosome formation in MDA-MB-435 cells. MDA-MB-435 cells responded to silvestrol treatment with accumulation of LC3-II and time-dependent p62 degradation. Bafilomycin A, an autophagy inhibitor, resulted in the accumulation of LC3 in cells treated with silvestrol. Silvestrol-mediated cell death was attenuated in ATG7-null mouse embryonic fibroblasts (MEFs) lacking a functional autophagy protein.

Conclusions: Silvestrol potently inhibits cell growth and induces cell death in human melanoma cells through induction of early autophagy and caspase-mediated apoptosis. Silvestrol represents a natural product scaffold that exhibits potent cytotoxic activity and could be used for the further study of autophagy and its relationship to apoptosis in cancer cells.
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http://dx.doi.org/10.1186/s12885-015-1988-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712514PMC
January 2016

Diaza-anthracene Antibiotics from a Freshwater-Derived Actinomycete with Selective Antibacterial Activity toward .

ACS Infect Dis 2015 Apr 11;1(4):168-174. Epub 2015 Mar 11.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street (MC 781), Room 539, Chicago, Illinois 60612-7231, United States ; Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago, Molecular Biology Research Building, 900 South Ashland Avenue (MC 870), Room 3150, Chicago, Illinois 60607-7173, United States.

Multidrug- and extensively drug-resistant strains of are resistant to first- and second-line drug regimens and resulted in 210,000 fatalities in 2013. In the current study, we screened a library of aquatic bacterial natural product fractions for their ability to inhibit this pathogen. A fraction from a Lake Michigan bacterium exhibited significant inhibitory activity, from which we characterized novel diazaquinomycins H and J. This antibiotic class displayed an in vitro activity profile similar or superior to clinically used anti-tuberculosis agents and maintained this potency against a panel of drug-resistant strains. Importantly, these are among the only freshwater-derived actinomycete bacterial metabolites described to date. Further in vitro profiling against a broad panel of bacteria indicated that this antibiotic class selectively targets . Additionally, in the case of this pathogen we present evidence counter to previous reports that claim the diazaquinomycins target thymidylate synthase in Gram-positive bacteria. Thus, we establish freshwater environments as potential sources for novel antibiotic leads and present the diazaquinomycins as potent and selective inhibitors of .
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http://dx.doi.org/10.1021/acsinfecdis.5b00005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648258PMC
April 2015

(9βH)-Pimaranes and Derivatives from the Tuber of Icacina trichantha.

J Nat Prod 2015 Nov 2;78(11):2731-7. Epub 2015 Nov 2.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago , Chicago, Illinois 60612, United States.

New 17-nor-pimaranes (1, 2), (9βH)-pimaranes (3, 4), and 17-nor-(9βH)-pimarane (5) were isolated from the tuber of Icacina trichantha. The structures were elucidated based on spectroscopic and HRMS data. The absolute configurations of 3 and 5 were determined by single-crystal X-ray diffraction. Compound 5 possesses a unique 19,20-δ-lactone moiety. Compound 3 showed cytotoxicity against MDA-MB-435 (human melanoma cancer) cells with an IC50 value of 7.04 μM. A plausible biogenetic pathway for compounds 1-5 is proposed.
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http://dx.doi.org/10.1021/acs.jnatprod.5b00688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703074PMC
November 2015

Cytotoxic Homoisoflavones from the Bulbs of Bellevalia eigii.

J Nat Prod 2015 Jul 6;78(7):1708-15. Epub 2015 Jul 6.

#Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina 27402, United States.

Eight new and 10 known compounds were isolated from an organic extract of the bulbs of Bellevalia eigii as part of a search for anticancer leads from native plants of Jordan. Of these, the series of 16 homoisoflavonoids (1-16) comprise the seven new analogues 7-O-methyl-3'-hydroxy-3,9-dihydropunctatin (3), 6-hydroxy-7-O-methyl-3,9-dihydropunctatin (6), 7,4'-di-O-methyl-3'-hydroxy-3,9-dihydropunctatin (9), 7-O-methylpunctatin (10), 7-O-methyl-3'-hydroxypunctatin (13), 5-hydroxy-7,8-dimethoxychroman-4-one (14), and 7-O-methyl-8-demethoxy-3-hydroxy-3,9-dihydropunctatin (15). The known ferulic acid-derived acrylamide (17) and the new methylthioacrylate bellegimycin (18) are also reported. The structures were elucidated using a set of spectroscopic and spectrometric techniques; the absolute configurations of compounds 1-9, 15, and 16 were determined using ECD spectroscopy, while a modified Mosher's ester method was used for compound 18. Optical rotation data for the known compounds 1, 2, and 8 are reported here for the first time. The cytotoxic activities of all compounds were evaluated using the MDA-MB-435 (melanoma) and HT-29 (colon) cancer cell lines. Compounds 4 and 9 were the most potent on the latter cell line, with IC50 values of 1.0 and 1.1 μM, respectively. Compounds 1-18 were assessed for antimicrobial activity using a collection of bacteria and fungi; compounds 4 and 12 showed promising activity against the bacterium Mycobacterium smegmatis with MIC values of 17 and 24 μg/mL, respectively.
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http://dx.doi.org/10.1021/acs.jnatprod.5b00357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615712PMC
July 2015

New diketopiperazine dimer from a filamentous fungal isolate of Aspergillus sydowii.

Magn Reson Chem 2015 Aug 3;53(8):616-9. Epub 2015 Jun 3.

Department of Chemistry Biochemistry, University of North Carolina at Greensboro, P.O. Box 26170, Greensboro, NC, 27402, United States.

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http://dx.doi.org/10.1002/mrc.4254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692248PMC
August 2015

Nasolacrimal Duct Probing under Topical Anesthesia for Congenital Nasolacrimal Duct Obstruction in Taiwan.

Pediatr Neonatol 2015 Dec 23;56(6):402-7. Epub 2015 Apr 23.

Department of Ophthalmology, Cathay General Hospital, Taipei, Taiwan.

Background: To report the success rates of office probing for congenital nasolacrimal duct obstruction (NLDO) among children of different age groups in Taiwan.

Methods: In this single-center, retrospective study, 564 eyes of 477 patients under the age of 5 years diagnosed with congenital NLDO were treated in a stepwise manner between 2001 and 2013. For infants aged < 6 months, treatment with massage and observation was suggested, followed by deferred probing under topical anesthesia if symptoms persisted. However, in cases of severe infection, immediate probing was suggested. In children aged > 6 months, office probing was usually highly recommended. Those with probing failures received either a second probing or silicone intubation. Treatment success was defined as anatomic patency by immediate irrigation after probing and absence of epiphora or mucous discharge at the follow-up visit.

Results: Primary probing was successful in 457 of 564 eyes (success rate: 81%). The success rate of primary probing was negatively correlated with increasing age: 90.1% (163/181), 79.6% (164/206), 76.8% (73/95), 73.5% (36/49), 75% (18/24), and 33% (3/9) for the age groups of 0 to <6 months, 6 to <12 months, 12 to <18 months, 18 to <24 months, 24 to <36 months, and 36-60 months, respectively (p < 0.001, Fisher's exact test). The second probing was successful in 52 of 81 eyes. In total, probing was successful in 509 of 564 eyes (success rate: 90.2%).

Conclusion: Office probing is safe and effective for treating congenital NLDO. The success rate of primary probing decreases significantly with age.
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http://dx.doi.org/10.1016/j.pedneo.2015.04.001DOI Listing
December 2015

Trichormamides C and D, antiproliferative cyclic lipopeptides from the cultured freshwater cyanobacterium cf. Oscillatoria sp. UIC 10045.

Bioorg Med Chem 2015 Jul 1;23(13):3153-62. Epub 2015 May 1.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, IL 60612, United States. Electronic address:

Extract from the cultured freshwater cf. Oscillatoria sp. UIC 10045 showed antiproliferative activity against HT-29 cell line. Bioassay-guided fractionation led to the isolation of two new cyclic lipopeptides, named trichormamides C (1) and D (2). The planar structures were determined by combined analyses of HRESIMS, Q-TOF ESIMS/MS, and 1D and 2D NMR spectra. The absolute configurations of the amino acid residues were assigned by advanced Marfey's analysis after partial and complete acid hydrolysis. Trichormamides C (1) is a cyclic undecapeptide and D (2) is a cyclic dodecapeptide, both containing a lipophilic β-aminodecanoic acid residue. Trichormamide C (1) displayed antiproliferative activities against HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 1.7 and 1.0μM, respectively, as well as anti-Mycobacterium tuberculosis activity with MIC value of 23.8μg/mL (17.3μM). Trichormamide D (2) was found to be less potent against both HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 11.5 and 11.7μM, respectively.
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http://dx.doi.org/10.1016/j.bmc.2015.04.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469202PMC
July 2015

17-Norpimaranes and (9βH)-17-Norpimaranes from the Tuber of Icacina trichantha.

J Nat Prod 2015 Apr 17;78(4):789-96. Epub 2015 Mar 17.

†Department of Medicinal Chemistry and Pharmacognosy and WHO Collaborating Center for Traditional Medicine, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.

Seven new 17-norpimarane and (9βH)-17-norpimarane diterpenoids, icacinlactones A-G (1-7), were isolated from the tuber of Icacina trichantha. The structures were elucidated by spectroscopic and HRMS techniques, and the absolute configuration of 2 was determined by means of X-ray crystallographic analysis. Compounds 1-7, as well as four known related structures, were evaluated for cytotoxic activity against MDA-MB-435 (human melanoma cancer), MDA-MB-231 (human breast cancer), and OVCAR3 (human ovarian cancer) cell lines. Several of these natural products displayed significant cytotoxic activity, with humirianthenolide C being the most active.
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http://dx.doi.org/10.1021/np5010328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703125PMC
April 2015

Cytotoxic (9βH)-pimarane and (9βH)-17-norpimarane diterpenes from the tuber of Icacina trichantha.

Chem Biodivers 2014 Dec;11(12):1914-22

Department of Medicinal Chemistry and Pharmacognosy, WHO Collaborating Center for Traditional Medicine, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA, (phone: +1-312-996-1557; fax: +1-312-996-7107); Department of Veterinary Physiology and Pharmacology, Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Nigeria; Department of Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Abuja, PMB 117, Abuja, Nigeria.

Three (9βH)-pimaranes, 1, 2, and 3, and two (9βH)-17-norpimaranes, 4 and 5, belonging to a rare compound class in nature, were obtained from the tubers of Icacina trichantha for the first time. Compound 1 is a new natural product, and 2-5 have been previously reported. The structures were elucidated based on NMR and MS data, and optical rotation values. The absolute configurations of (9βH)-pimaranes were unambiguously established based on X-ray crystallographic analysis. Full NMR signal assignments for the known compounds 2, 4, and 5, which were not available in previous publications, are also reported. All five isolates displayed cytotoxic activities on MDA-MB-435 cells (IC50 0.66-6.44 μM), while 2, 3, and 4 also exhibited cytotoxicities on HT-29 cells (IC50 3.00-4.94 μM).
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http://dx.doi.org/10.1002/cbdv.201400151DOI Listing
December 2014

Carbamidocyclophanes F and G with Anti- Activity from the Cultured Freshwater Cyanobacterium sp.

Tetrahedron Lett 2014 Jan;55(3):686-689

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612.

Two new ( and ) and three known () carbamidocyclophanes were isolated from a cultured freshwater cyanobacterium sp. (UIC 10274) obtained from a sample collected at Des Plaines, Illinois. Their planar structures and stereoconfigurations were determined by extensive spectroscopic analysis including 1D/2D NMR experiments, HRESIMS as well as CD spectroscopy. Carbamidocyclophane F () showed potent anti- activity in the microplate Alamar blue assay and low-oxygen-recovery assay with MIC values of 0.8 and 5.4 µM, respectively. Carbamidocyclophane F () also displayed antimicrobial activities against the gram positive bacteria and with MIC values of 0.1 and 0.2 µM, respectively. Carbamidocyclophane F () and Carbamidocyclophane G () both showed antiproliferative activity against MDA-MB-435 and HT-29 human cancer cell lines with IC values in the range from 0.5 to 0.7 µM.
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http://dx.doi.org/10.1016/j.tetlet.2013.11.112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161986PMC
January 2014

Greensporones: resorcylic acid lactones from an aquatic Halenospora sp.

J Nat Prod 2014 Sep 5;77(9):2088-98. Epub 2014 Aug 5.

Department of Chemistry and Biochemistry, University of North Carolina at Greensboro , Greensboro, North Carolina 27402, United States.

Fourteen new resorcylic acid lactones (1-14) were isolated from an organic extract of a culture of a freshwater aquatic fungus Halenospora sp. originating from a stream in North Carolina. The structures were elucidated using a set of spectroscopic and spectrometric techniques. The absolute configuration of one representative member of the compounds (7) was assigned using X-ray crystallography of an analogue that incorporated a heavy atom, whereas for compounds 8-11, a modified Mosher's ester method was utilized. The relative configurations of compounds 12-14 were determined on the basis of NOE data. Compounds 12-14 were proposed as artifacts produced by intramolecular cycloetherification of the ε-hydroxy-α,β-unsaturated ketone moieties of the parent compounds during the purification processes. The isolated compounds, except for 8 and 12, were tested against the MDA-MB-435 (melanoma) and HT-29 (colon) cancer cell lines. Compound 5 was the most potent, with IC50 values of 2.9 and 7.5 μM, respectively. The compounds were evaluated as TAK1-TAB1 inhibitors but were found to be inactive.
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http://dx.doi.org/10.1021/np500497rDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176394PMC
September 2014

Trichormamides A and B with Antiproliferative Activity from the Cultured Freshwater Cyanobacterium Trichormus sp. UIC 10339.

J Nat Prod 2014 Aug 4;77(8):1871-80. Epub 2014 Aug 4.

†Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, Illinois 60612, United States.

Two new cyclic lipopeptides, trichormamides A (1) and B (2), were isolated from the cultured freshwater cyanobacterium Trichormus sp. UIC 10339. The strain was obtained from a sample collected in Raven Lake in Northern Wisconsin. The planar structures of trichormamides A (1) and B (2) were determined using a combination of spectroscopic analyses including HRESIMS and 1D and 2D NMR experiments. The absolute configurations of the amino acid residues were assigned by the advanced Marfey's method after acid hydrolysis. Trichormamide A (1) is a cyclic undecapeptide containing two D-amino acid residues (D-Tyr and D-Leu) and one β-amino acid residue (β-aminodecanoic acid). Trichormamide B (2) is a cyclic dodecapeptide characterized by the presence of four nonstandard α-amino acid residues (homoserine, N-methylisoleucine, and two 3-hydroxyleucines) and one β-amino acid residue (β-aminodecanoic acid). Trichormamide B (2) was cytotoxic against MDA-MB-435 and HT-29 cancer cell lines with IC50 values of 0.8 and 1.5 μM, respectively.
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http://dx.doi.org/10.1021/np5003548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143178PMC
August 2014

Epigenetic Manipulation of a Filamentous Fungus by the Proteasome-Inhibitor Bortezomib Induces the Production of an Additional Secondary Metabolite.

RSC Adv 2014 Jan;4(35):18329-18335

Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, P.O. Box 26170, Greensboro, North Carolina 27402, United States.

The use of epigenetic modifiers, such as histone deacetylase inhibitors and DNA methyltransferase inhibitors, has been explored increasingly as a technique to induce the production of additional microbial secondary metabolites. The application of such molecules to microbial cultures has been shown to upregulate otherwise suppressed genes, and in several cases has led to the production of new molecular structures. In this study, the proteasome inhibitor bortezomib was used to induce the production of an additional metabolite from a filamentous fungus (Pleosporales). The induced metabolite was previously isolated from a plant, but the configuration was not assigned until now; in addition, an analogue was isolated from a degraded sample, yielding a new compound. Proteasome inhibitors have not previously been used in this application and offer an additional tool for microbial genome mining.
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http://dx.doi.org/10.1039/C4RA00274ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061710PMC
January 2014

Papillary thyroid carcinoma and laryngeal squamous cell carcinoma manifesting as a collision tumor of the neck: A case report.

Oncol Lett 2013 Dec 15;6(6):1616-1618. Epub 2013 Oct 15.

Department of Otolaryngology Head-Neck Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

A 55-year-old male presented with a rapidly expanding mass on the right side of the neck and progressive hoarseness. An electronic laryngoscopy and a computed tomography scan were performed, and the patient was subsequently diagnosed with tumors of the larynx and the thyroid gland. An en bloc near-total thyroidectomy combined with a total laryngectomy was performed. The final pathological analysis revealed a collision tumor that was derived from a laryngeal squamous cell carcinoma and a papillary thyroid carcinoma. Collision tumors of the head and neck are rare. The therapy for a collision tumor should consist of a combination of the treatments that are normally used for each focus.
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http://dx.doi.org/10.3892/ol.2013.1628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834194PMC
December 2013

Profile measurement of transparent inclined surface with transmitted differential interference contrast shearing interferometer.

Opt Express 2012 Aug;20(18):19868-81

Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan.

A quantitative phase shifting differential interference contrast (PS-DIC) shearing interferometer is adopted to measure the profile of transparent specimen with inclined surface. The effects of the incline angle on DIC measurement accuracy were studied. The optical model of the test system was constructed and the measurement of surface with various incline angles ranging from 5° to 60° was simulated. The experiments validate the simulation model and show the feasibility of profile reconstruction of inclined structure. It is interested to find that even with an inclined angle of 15°, unwrapping technique is required to make the measurement more accurate. In addition, the measurement can be further improved by taking into account the effects of the change in shear distance on the optical path difference. This study provides useful information that should be considered for complex geometry measurement with quantitative DIC technique.
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http://dx.doi.org/10.1364/OE.20.019868DOI Listing
August 2012

[Report of a case with neurilemmoma under torus tubarius].

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2010 Aug;45(8):693-4

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August 2010