Publications by authors named "Na Hyun Kim"

79 Publications

Stereochemical Determination of Fistularins Isolated from the Marine Sponge and Their Regulatory Effect on Intestinal Inflammation.

Mar Drugs 2021 Mar 22;19(3). Epub 2021 Mar 22.

Department of Oceanography, Kunsan National University, Gunsan 54150, Korea.

By activity-guided fractionation based on inhibition of nitric oxide (NO) and prostaglandin E2 (PGE), six fistularin compounds (-) were isolated from the marine sponge (order Astrophorida). Based on stereochemical structure determination using Mosher's method, fistularin-3 was assigned as a new stereoisomer. On the basis of the stereochemistry of fistularin-3, the stereochemical homogeneity of all six compounds was established by comparing carbon and proton chemical shifts. For fistularin-1 () and -2 (), quantum calculations were performed to confirm their stereochemistry. In a co-culture system of human epithelial Caco-2 cells and THP-1 macrophages, all six isolated compounds showed potent anti-inflammatory activities. These bioactive fistularins inhibited the production of NO, PGE, TNF-α, IL-1β, and IL-6 induced by lipopolysaccharide and interferon gamma. Inducible NO synthase and cyclooxygenase-2 expression and MAPK phosphorylation were downregulated in response to the inhibition of NF-κB nuclear translocation. Among the compounds tested, fistularin-1 () and 19-deoxyfistularin-3 () showed the highest activity. These findings suggest the potential use of the marine sponge and its metabolites as pharmaceuticals for the treatment of inflammation-related diseases including inflammatory bowel disease.
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http://dx.doi.org/10.3390/md19030170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004254PMC
March 2021

Isoquinolinequinone Derivatives from a Marine Sponge ( sp.) Regulate Inflammation in In Vitro System of Intestine.

Mar Drugs 2021 Feb 4;19(2). Epub 2021 Feb 4.

Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju 52725, Korea.

Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (-) were isolated from the marine sponge sp. Among these, methyl -demethylrenierate () is a noble ester, whereas compounds and are new -demethyl derivatives of known isoquinolinequinones. Compound was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. -demethyl renierone () showed the highest activity, while and showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in and , and the N-formyl group in may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.
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http://dx.doi.org/10.3390/md19020090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913985PMC
February 2021

Risk Factors Influencing the Occurrence and Severity of Symptomatic Dry Eye Syndrome: A Cross-sectional Study.

Ophthalmic Epidemiol 2021 Jan 31:1-7. Epub 2021 Jan 31.

Department of Preventive Medicine, Yonsei University College of Medicine , Seoul, Republic of Korea.

: We aimed to investigate the prevalence and risk factors of dry eye syndrome (DES) among a population-based cohort study.: This cross-sectional study was conducted on 475 subjects (184 men and 291 women) enrolled in the Study Group for Environmental Eye Disease at July 2013. Using the ocular surface disease index (OSDI), we measured the DES severity and defined DES as OSDI score ≥13. Current symptoms of DES and possible risk factors such as body mass index, occupations, comorbidities, exercise, smoking and drinking status were assessed by multivariate logistic regression.: Prevalence of DES was significantly higher in women (52.6%) than in men (41.9%) ( < .001). Compared to white-collar workers, blue-collar workers and unemployed persons showed significantly higher DES prevalence and severity. Compared to those with low BMI (<23.0 kg/m), people with extremely high BMI (≥30.0 kg/m) had significantly higher odds ratio (OR) of having DES after fully adjusted for sex, age, hypertension, diabetes, menopausal status, hormone replacement therapy, occupation, and lifestyle factors (OR: 2.83, 95% confidence interval: 1.04-7.71).: We found some novel factors which have been unknown to the relationship with DES through the five years observation of the cohort. The positive associations of unemployment status, blue-collar work, alcohol habit, and obesity with DES suggests a person's comprehensive condition, not individual factors, contribute significantly in developing DES. Further studies will be helpful to understand the underlying mechanisms.
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http://dx.doi.org/10.1080/09286586.2021.1879172DOI Listing
January 2021

Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study.

Prostate Cancer Prostatic Dis 2021 Jan 28. Epub 2021 Jan 28.

Imperial Prostate, Division of Surgery, Department of Surgery and Cancer, Imperial College London, London, UK.

Introduction: Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP).

Methods: Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason 
Results: 335 radical prostatectomy and 501 focal therapy patients were eligible for matching. For focal therapy, 420 had HIFU and 81 cryotherapy. Cryotherapy was used predominantly for anterior cancer. After matching, 246 RP and 246 FT cases were identified. For radical prostatectomy, mean (SD) age was 63.4 (5.6) years, median (IQR) PSA 7.9 g/ml (6-10) and median (IQR) follow-up 64 (30-89) months. For focal therapy, these were 63.3 (6.9) years, 7.9 ng/ml (5.5-10.6) and 49 [34-67] months, respectively. At 3, 5 and 8 years, FFS (95%CI) was 86% (81-91%), 82% (77-88%) and 79% (73-86%) for radical prostatectomy compared to 91% (87-95%), 86% (81-92%) and 83% (76-90%) following focal therapy (p = 0.12).

Conclusions: In patients with non-metastatic low- intermediate prostate cancer, oncological outcomes over 8 years were similar between focal therapy and radical prostatectomy.
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http://dx.doi.org/10.1038/s41391-020-00315-yDOI Listing
January 2021

Alterations of amygdala-prefrontal cortical coupling and attention deficit/hyperactivity disorder-like behaviors induced by neonatal habenula lesion: normalization by Ecklonia stolonifera extract and its active compound fucosterol.

Behav Pharmacol 2021 Jan 21. Epub 2021 Jan 21.

Department of Food Science and Nutrition, Daegu Catholic University, Gyeongsan, Gyeongbuk Department of Food Science and Nutrition, Pukyong National University, Busan, South Korea Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan.

Alterations of monoamine transmission in mesocorticolimbic regions have been suggested in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). The habenula is an important brain area in regulation of monoamine transmission. In this study, we investigated behavioral and electrophysiological alterations induced by neonatal habenula lesion (NHL) in rats. In NHL rats, age-dependent behavioral alterations relevant to the ADHD symptoms, such as hyperlocomotion, impulsivity, and attention deficit, were observed. Local field potentials (LFPs) in mesocorticolimbic regions of anesthetized rats were examined with in vivo electrophysiological recordings. Abnormally enhanced synchronization of slow (delta) and fast (gamma) LFP oscillations between the amygdala (AMY) and prefrontal cortex (PFC) was found in juvenile, but not in adult, NHL rats. We further examined the effects of an extract and the active compound from the perennial large brown algae Ecklonia stolonifera (ES), which have previously been demonstrated to modulate monoamine transmission, on these NHL-induced alterations. One week of ES extract treatments normalized the NHL-induced behavioral alterations, whereas the active compound fucosterol improved attention deficit and impulsivity, but not hyperlocomotion, in NHL rats. Consistent with the behavioral effects, ES extract treatments also normalized augmented AMY-PFC coupling. These results suggest that altered limbic-cortical information processing may be involved in ADHD-like behavioral alterations induced by NHL, which could be ameliorated by the natural substance, such as ES that affects monoamine transmission.
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http://dx.doi.org/10.1097/FBP.0000000000000620DOI Listing
January 2021

Standardized Fraction of Alleviates Dextran Sulfate Sodium-Induced Chronic Colitis in C57BL/6 Mice via Upregulation of FOXP3 Regulatory T Cells.

Biomolecules 2020 10 20;10(10). Epub 2020 Oct 20.

Department of Oceanography, Kunsan National University, Kunsan 54150, Korea.

is a tropical brown algae (seaweed) known to have anti-inflammatory properties. In this study, we analyzed extract (TOE) using liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) and nuclear magnetic resonance (NMR) and evaluated the in vivo efficacy of TOE against dextran sulfate sodium-induced chronic colitis in C57BL/6 mice. The bioactive fraction of TOE was administered orally daily for 6 weeks to mice under different treatments normal, colitis, and colitis + conventional drug (5-aminosalicylic acid, 5-ASA). Regarding clinical manifestation, the disease activity index and colon length of the colitis + TOE group were significantly reduced compared to those of the colitis group. The results of myeloperoxidase activity and histopathological examination showed similar results. Western blot analysis of colon tissues revealed that cyclooxygenase-2, tumor necrosis factor alpha (TNF-α), and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) were significantly decreased in the colitis + 5-ASA group, whereas forkhead box P3 (FOXP3) was increased. qPCR results showed changes in T cell subsets; the administration of TOE upregulated regulatory T cell (Treg) expression, although T helper 17 cell (Th17) expression did not change significantly. Interestingly, the colitis + TOE group showed high levels of both Th1 and Th2 transcription factors, but the secreted cytokine interferon (IFN)-γ and interleukin (IL)-4 remained unchanged and somewhat reduced. Additionally, TNF-α gene expression was significantly reduced in the colitis + TOE group. IL-6 mRNA levels were also decreased, although not significantly. Four compounds were structurally elucidated using 1D- and 2D-NMR spectroscopy, and five compounds were fully identified or tentatively characterized using LC-QTOF-MS. In conclusion, TOE could alleviate chronic colitis via upregulation of Foxp3 Treg cells and production of the anti-inflammatory cytokine IL-10, which directly inhibits macrophages and pro-inflammatory cytokine synthesis, leading to reduced colitis.
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http://dx.doi.org/10.3390/biom10101463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590162PMC
October 2020

Protein-induced B-Z transition of DNA duplex containing a 2'-OMe guanosine.

Biochem Biophys Res Commun 2020 12 21;533(3):417-423. Epub 2020 Sep 21.

Department of Chemistry and RINS, Gyeongsang National University, Gyeongnam, 52828, South Korea. Electronic address:

Structural transformation of the canonical right-handed helix, B-DNA, to the non-canonical left-handed helix, Z-DNA, can be induced by the Zα domain of the human RNA editing enzyme ADAR1 (hZα). To characterize the site-specific preferences of binding and structural changes in DNA containing the 2'-O-methyl guanosine derivative (G), titration of the imino proton spectra and chemical shift perturbations were performed on hZα upon binding to Z-DNA. The structural transition between B-Z conformation as the changing ratio between DNA and protein showed a binding affinity of the modified DNA onto the Z-DNA binding protein similar to wild-type DNA or RNA. The chemical shift perturbation results showed that the overall structure and environment of the modified DNA revealed DNA-like properties rather than RNA-like characteristics. Moreover, we found evidence for two distinct regimes, "Z-DNA Sensing" and "Modification Sensing", based on the site-specific chemical shift perturbation between the DNA (or RNA) binding complex and the modified DNA-hZα complex. Thus, we propose that modification of the sugar backbone of DNA with 2'-O-methyl guanosine promotes the changes in the surrounding α3 helical structural segment as well as the non-perturbed feature of the β-hairpin region.
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http://dx.doi.org/10.1016/j.bbrc.2020.09.017DOI Listing
December 2020

Intervertebral Disc Regeneration Using Stem Cell/Growth Factor-Loaded Porous Particles with a Leaf-Stacked Structure.

Biomacromolecules 2020 12 2;21(12):4795-4805. Epub 2020 Oct 2.

Department of Nanobiomedical Science, Dankook University, Cheonan 31116, Republic of Korea.

Although biological therapies based on growth factors and transplanted cells have demonstrated some positive outcomes for intervertebral disc (IVD) regeneration, repeated injection of growth factors and cell leakage from the injection site remain considerable challenges for human therapeutic use. Herein, we prepare human bone marrow-derived mesenchymal stem cells (BMSCs) and transforming growth factor-β3 (TGF-β3)-loaded porous particles with a unique leaf-stack structural morphology (LSS particles) as a combination bioactive delivery matrix for degenerated IVD. The LSS particles are fabricated with clinically acceptable biomaterials (polycaprolactone and tetraglycol) and procedures (simple heating and cooling). The LSS particles allow sustained release of TGF-β3 for 18 days and stable cell adhesiveness without additional modifications of the particles. On the basis of and studies, it was observed that the BMSCs/TGF-β3-loaded LSS particles can provide a suitable milieu for chondrogenic differentiation of BMSCs and effectively induce IVD regeneration in a beagle dog model. Thus, therapeutically loaded LSS particles offer the promise of an effective bioactive delivery system for regeneration of various tissues including IVD.
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http://dx.doi.org/10.1021/acs.biomac.0c00992DOI Listing
December 2020

MELAS Syndrome and MIDD Unmasked by Metformin Use: A Case Report.

Ann Intern Med 2021 01 25;174(1):124-125. Epub 2020 Aug 25.

Amita Health Saint Joseph Hospital, Chicago, Illinois (N.H.K., M.S., J.V.).

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http://dx.doi.org/10.7326/L20-0292DOI Listing
January 2021

The Effects of Extract on Testosterone-Induced Benign Prostatic Hyperplasia in Rats, and Quantitative Analysis of Major Constituents Depending on Extract Conditions.

Nutrients 2020 May 28;12(6). Epub 2020 May 28.

Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju 52725, Korea.

This study aimed to investigate the beneficial effects of on testosterone propionate (TP)-induced benign prostatic hyperplasia (BPH) in Wistar rats. Moreover, the bioactive constituents in the extract were determined using LC/MS and HPLC analyses. The dried fruits of were extracted using accelerated solvent extraction (ASE) under different extract conditions (temperature, 30 C or 100 C; extract solvent, 60% or 100% ethanol) to yield four extracts (T1~T4). Of the four extracts, T1 extracted under the condition of 100% ethanol/low temperature (30 C) exhibited the greatest inhibitory activity on TP-induced prostatic hyperplasia in rats. The administration of T1 (100 mg/kg body weight, p.o.) for six weeks attenuated TP-induced prostate enlargement and reduced the levels of dihydrotestosterone (DHT) and 5α-reductase in both serum and prostate tissue. The suppression of PCNA mRNA expression in prostate tissue was remarkable in T1-treated rats. In LC/MS analysis, the levels of main anthocyanins and phenolics were significantly higher in T1 than in the other extracts. Furthermore, the quantitative study showed that the contents of cyanidin-3-glucose and cyanidin-3-xylose in T1 exhibited 1.27~1.67 and 1.10~1.26 folds higher compared to those in the other extracts. These findings demonstrated that extract containing anthocyanins as bioactive constituents attenuated the development of testosterone-induced prostatic hyperplasia, and suggested that this extract has therapeutic potential to treat prostate enlargement and BPH.
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http://dx.doi.org/10.3390/nu12061575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352698PMC
May 2020

Cytotoxic 4-Hydroxyprorocentrolide and Prorocentrolide C from Cultured Dinoflagellate Induce Human Cancer Cell Death through Apoptosis and Cell Cycle Arrest.

Toxins (Basel) 2020 05 7;12(5). Epub 2020 May 7.

Department of Oceanography, Kunsan National University, Gunsan 54150, Korea.

Prorocentrolide and its analogs, the novel naturally derived antitumor agents, have recently been identified in the dinoflagellate . In the current study, the underlying inhibitory mechanisms of 4-hydroxyprorocentrolide () and prorocentrolide C () on the proliferation of human carcinoma cells were determined. and arrested the cell cycle at the S phase in A549 cells and G2/M phase in HT-29 cells, leading to apoptotic cell death, as determined using fluorescence-activated cell sorting analysis with Annexin V/PI double staining. Apoptosis induced by these compounds was associated with alterations in the expression of cell cycle-regulating proteins (cyclin D1, cyclin E1, CDK2, and CDK4), as well as alterations in the levels of apoptosis-related proteins (PPAR, Bcl-2, Bcl-xl, and survivin). These findings provide new insights into the antitumor mechanisms of 4-hydroxyprorocentrolide and prorocentrolide C and a basis for future investigations assessing prorocentrolide analogs as prospective therapeutic drugs.
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http://dx.doi.org/10.3390/toxins12050304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290926PMC
May 2020

Cadmium induces cytotoxicity in normal mouse renal MM55.K cells.

Int J Environ Health Res 2020 Mar 19:1-10. Epub 2020 Mar 19.

Biological Resources Research Group, Bioenvironmental Science & Toxicology Division, Gyeongnam Branch Institute, Korea Institute of Toxicology (KIT), Jinju, Republic of Korea.

The toxicity of cadmium (Cd) occurs through accumulation in the environment. The precise mechanism underlying Cd toxicity remains unclear. Therefore, in the present study, we studied the effects of Cd on MM55.K cells and investigated the mechanisms underlying Cd-induced cell death. CdCl2 significantly elevated apoptotic cell death, mitochondrial membrane potential (ΔΨ) loss, and caspase-dependent cell death. Moreover, immunoblotting results revealed that CdCl2 down-regulated the inhibitor of apoptotic protein such as survivin and Bcl-2 which led to the activation of caspase-3 and the cleavage of PARP in MM55.K cells. Besides, CdCl2 caused the up-regulation of ROS-related proteins such as HO-1 and ER stress-related proteins such as GRP78 and CHOP in MM55.K cells. CdCl2 toxicity resulted in the down-regulation of the AKT pathway that leads to the up-regulation of phosphorylated JNK and p38 in MM55.K cells. Thus, CdCl2 induce toxicity by AKT/MAPK regulation and causing ROS production, ER stress, ΔΨ loss, and apoptotic cell death in normal mouse renal cells.
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http://dx.doi.org/10.1080/09603123.2020.1739236DOI Listing
March 2020

Bone regeneration by bone morphogenetic protein-2 from porous beads with leaf-stacked structure for critical-sized femur defect model in dogs.

J Biomater Appl 2020 05 2;34(10):1437-1448. Epub 2020 Mar 2.

Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea.

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http://dx.doi.org/10.1177/0885328220910033DOI Listing
May 2020

Deacetylphylloketal, a New Phylloketal Derivative from a Marine Sponge, Genus , with Potent Anti-Inflammatory Activity in In Vitro Co-Culture Model of Intestine.

Mar Drugs 2019 Nov 8;17(11). Epub 2019 Nov 8.

Department of Oceanography, Kunsan National University, Kunsan 54150, Korea.

The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn's disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the present study, we successfully isolated a new phylloketal derivative, deacetylphylloketal () along with four known compounds from the sponge genus The anti-inflammatory properties of deacetylphylloketal () and phyllohemiketal A () were evaluated using an in vitro co-culture system that resembles the intestinal epithelial environment. A co-culture system was established that consisted of human epithelial Caco-2 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage cells. The treatment of co-cultured THP-1 cells with compounds or significantly suppressed the production and/or gene expression of lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), Interleukin-6 (IL-6), IL-1β and Tumor Necrosis Factor alpha (TNF-α). The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 were down-regulated in response to inhibition of NF-kB translocation into the nucleus in cells. In addition, we observed that and markedly promoted the nuclear translocation of Nrf2 and subsequent increase in the expression of heme oxygernase (HO)-1. These findings suggest the potential use of sponge genus and its metabolites as a pharmaceutical aid in the treatment of inflammation-related diseases including IBD.
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http://dx.doi.org/10.3390/md17110634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891596PMC
November 2019

(10)-Debromohymenialdisine from Marine Sponge sp. Regulates Intestinal Inflammatory Responses in Co-Culture Model of Epithelial Caco-2 Cells and THP-1 Macrophage Cells.

Molecules 2019 Sep 18;24(18). Epub 2019 Sep 18.

Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju 52725, Korea.

Crohn's disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are autoimmune diseases characterized by chronic inflammation within the gastrointestinal tract. Debromohymenialdisine is an active pyrrole alkaloid that is well known to serve as a stable and effective inhibitor of Chk2. In the present study, we attempted to investigate the anti-inflammatory properties of (10)-debromohymenialdisine () isolated from marine sponge species using an intestinal in vitro model with a transwell co-culture system. The treatment with attenuated the production and gene expression of lipopolysaccharide (LPS)-induced Interleukin (IL)-6, IL-1β, prostaglandin E2 (PGE2), and tumor necrosis factor-α in co-cultured THP-1 macrophages at a concentration range of 1-5 μM. The protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were down-regulated in response to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) translocation into the nucleus in cells. In addition, we observed that markedly promoted the nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2) and subsequent increase of heme oxygenase-1 (HO-1) expression. These findings suggest the potential use of as a pharmaceutical lead in the treatment of inflammation-related diseases including IBD.
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http://dx.doi.org/10.3390/molecules24183394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766964PMC
September 2019

The effects of Engelhardtia chrysolepis Hance on long-term memory and potential dopamine involvement in mice.

Behav Pharmacol 2019 10;30(7):596-604

Department of Food Science and Nutrition, Daegu Catholic University, Gyeongsan, Gyeongbuk, South Korea.

Engelhardtia chrysolepis Hance (ECH) is a perennial plant used in traditional medicine. A major active ingredient of ECH is astilbin (ASB), which has recently been shown to have neuroprotective effects as well as to affect catecholamine neurotransmissions in brain areas such as the prefrontal cortex. In this study, we investigated the effects of ECH and ASB on long-term memory in mice using a battery of behavioral tests. Acute ECH treatments dose-dependently facilitated nonspatial, but not spatial, memory. ECH treatments also upregulated expression of tyrosine hydroxylase, the enzyme mediating catecholamine synthesis, in neuroblastoma cell culture. Acute ASB treatments similarly improved nonspatial memory, whereas chronic ASB treatments improved both nonspatial and spatial memory. In accordance with such behavioral effects, the increased ratio of tissue concentrations of dopamine metabolites over dopamine in striatal regions was observed in mice with chronic ASB treatments. These results suggest that ECH and its active ingredient ASB may facilitate long-term memory by modulating catecholamine transmission.
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http://dx.doi.org/10.1097/FBP.0000000000000495DOI Listing
October 2019

Base-pair Opening Dynamics of Nucleic Acids in Relation to Their Biological Function.

Comput Struct Biotechnol J 2019 13;17:797-804. Epub 2019 Jun 13.

Department of Chemistry and RINS, Gyeongsang National University, Gyeongnam 52828, South Korea.

Base-pair opening is a conformational transition that is required for proper biological function of nucleic acids. Hydrogen exchange, observed by NMR spectroscopic experiments, is a widely used method to study the thermodynamics and kinetics of base-pair opening in nucleic acids. The hydrogen exchange data of imino protons are analyzed based on a two-state (open/closed) model for the base-pair, where hydrogen exchange only occurs from the open state. In this review, we discuss examples of how hydrogen exchange data provide insight into several interesting biological processes involving functional interactions of nucleic acids: ) selective recognition of DNA by proteins; ) regulation of RNA cleavage by site-specific mutations; ) intermolecular interaction of proteins with their target DNA or RNA; ) formation of PNA:DNA hybrid duplexes.
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http://dx.doi.org/10.1016/j.csbj.2019.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607312PMC
June 2019

Downregulation of CHIP promotes ovarian cancer metastasis by inducing Snail-mediated epithelial-mesenchymal transition.

Mol Oncol 2019 05 8;13(5):1280-1295. Epub 2019 Apr 8.

Division of Applied Life Science (BK21 Plus), Research Institute of Life Sciences, Gyeongsang National University, Jinju, Korea.

The epithelial-mesenchymal transition (EMT) plays a pivotal role in the conversion of early-stage tumors into invasive malignancies. The transcription factor Snail, an extremely unstable protein whose subcellular levels are regulated by many E3 ubiquitin ligases, promotes EMT as well as associated pathological characteristics including migration, invasion, and metastasis. Through yeast two-hybrid screening, we identified the carboxyl terminus of Hsc70-interacting protein (CHIP) as a novel Snail ubiquitin ligase that interacts with Snail to induce ubiquitin-mediated proteasomal degradation. Inhibition of CHIP expression increases Snail protein levels, induces EMT, and enhances in vitro migration and invasion as well as in vivo metastasis of ovarian cancer cells. In turn, Snail depletion abrogates all phenomena induced by CHIP depletion. Finally, Snail and CHIP expression is inversely correlated in ovarian tumor tissues. These findings establish the CHIP-Snail axis as a post-translational mechanism of EMT and cancer metastasis regulation.
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http://dx.doi.org/10.1002/1878-0261.12485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487736PMC
May 2019

Antiobesity Effect of Fermented Chokeberry Extract in High-Fat Diet-Induced Obese Mice.

J Med Food 2018 Nov;21(11):1113-1119

3 Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology , Jinju, Korea.

Black-fruited chokeberries (Aronia melanocarpa), growing mainly in the Central and Eastern European countries, have health benefits due to the high concentrations of polyphenolic compounds. However, a strong bitter taste of chokeberries limits its usage as functional food. We hypothesized that the fermented A. melanocarpa with a reduced bitter taste would improve insulin sensitivity and/or ameliorate weight gain induced by high-fat diet (HFD) in male C57BL/6J mice. The mice were administered with HFD together with the 100 mg/kg of natural A. melanocarpa (T1) or the fermented A. melanocarpa (T2) for 8 weeks. The treatment with T2 (100 mg/kg body weight, p.o.) markedly attenuated the weight gain and the increase in serum triglyceride level induced by HFD. The T2-treated group had better glucose tolerance and higher insulin sensitivity as measured by oral glucose tolerance test and intraperitoneal insulin tolerance test in comparison to the T1-treated group. Phytochemical analysis revealed that the main constituents of T2 were cyanidin-3-xyloside and 1-(3',4'-dihydroxycinnamoyl)cyclopenta-2,3-diol, and the content of cyanidin glycosides (3-glucoside, 3-xyloside) was significantly reduced during the fermentation process. From the above results, we postulated that antiobesity effect of black chokeberry was not closely correlated with the cyanidin content. Fermented chokeberry might be a viable dietary supplement rich in bioactive compounds useful in preventing obesity.
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http://dx.doi.org/10.1089/jmf.2017.4124DOI Listing
November 2018

Chokeberry Extract and Its Active Polyphenols Suppress Adipogenesis in 3T3-L1 Adipocytes and Modulates Fat Accumulation and Insulin Resistance in Diet-Induced Obese Mice.

Nutrients 2018 Nov 12;10(11). Epub 2018 Nov 12.

Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju 52725, Korea.

Berries of (chokeberry) are known to be a rich source of biologically active polyphenols. In the present study, the effects of seven anti-adipogenic polyphenolic phytochemicals isolated from methanol extract on adipogenic transcription factors were investigated. Amygdalin and prunasin were found to inhibit 3T3-L1 adipocyte differentiation by suppressing the expressions of PPARγ (peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT/enhancer binding protein α), SREBP1c (sterol regulatory element binding protein 1c), FAS (fatty acid synthase), and aP2 (adipocyte fatty-acid⁻binding protein). extract-treated (100 or 200 mg/kg/day on body weight) high fat diet (HFD)-induced obese mice showed significant decreases in body weight, serum triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) levels and improved insulin sensitivity as compared with HFD controls. This research shows extract is potentially beneficial for the suppression of HFD-induced obesity.
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http://dx.doi.org/10.3390/nu10111734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266992PMC
November 2018

Thermodynamic Model for B-Z Transition of DNA Induced by Z-DNA Binding Proteins.

Molecules 2018 Oct 24;23(11). Epub 2018 Oct 24.

Department of Chemistry and RINS, Gyeongsang National University, Gyeongnam 52828, Korea.

Z-DNA is stabilized by various Z-DNA binding proteins (ZBPs) that play important roles in RNA editing, innate immune response, and viral infection. In this review, the structural and dynamics of various ZBPs complexed with Z-DNA are summarized to better understand the mechanisms by which ZBPs selectively recognize d(CG)-repeat DNA sequences in genomic DNA and efficiently convert them to left-handed Z-DNA to achieve their biological function. The intermolecular interaction of ZBPs with Z-DNA strands is mediated through a single continuous recognition surface which consists of an α3 helix and a β-hairpin. In the ZBP-Z-DNA complexes, three identical, conserved residues (N173, Y177, and W195 in the Zα domain of human ADAR1) play central roles in the interaction with Z-DNA. ZBPs convert a 6-base DNA pair to a Z-form helix via the B-Z transition mechanism in which the ZBP first binds to B-DNA and then shifts the equilibrium from B-DNA to Z-DNA, a conformation that is then selectively stabilized by the additional binding of a second ZBP molecule. During B-Z transition, ZBPs selectively recognize the alternating d(CG) sequence and convert it to a Z-form helix in long genomic DNA through multiple sequence discrimination steps. In addition, the intermediate complex formed by ZBPs and B-DNA, which is modulated by varying conditions, determines the degree of B-Z transition.
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http://dx.doi.org/10.3390/molecules23112748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278649PMC
October 2018

Gene Expressions, Hippocampal Volume Loss, and MMSE Scores in Computation of Progression and Pharmacologic Therapy Effects for Alzheimer's Disease.

IEEE/ACM Trans Comput Biol Bioinform 2020 Mar-Apr;17(2):608-622. Epub 2018 Sep 14.

We build personalized relevance parameterization method (prep-ad) based on artificial intelligence (ai) techniques to compute Alzheimer's disease (ad) progression for patients at the mild cognitive impairment (mci) stage. Expressions of ad related genes, mini mental state examination (mmse) scores, and hippocampal volume measurements of mci patients are obtained from the Alzheimer's Disease Neuroimaging Initiative (adni) database. In evaluation of cognitive changes under pharmacological therapies, patients are grouped based on available clinical measurements and the type of therapy administered, namely donepezil monotherapy and polytherapy of donepezil with memantine. Average leave one out cross validation (loocv) error rates are calculated for prep-ad results as less than 8 percent when mmse scores are used to compute disease progression for a 60 month period, and 3 percent with hippocampal volume measurements for 12 months. Statistical significance is calculated as p = 0.003 for using ad related genes in disease progression and as for the results computed by prep-ad. These relatively small average loocv errors and p-values suggest that our prep-ad methods employing gene expressions, mmse scores and hippocampal volume loss measurements can be useful in supporting pharmacologic therapy decisions during early stages of ad.
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http://dx.doi.org/10.1109/TCBB.2018.2870363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241288PMC
March 2021

Gene Expressions, Hippocampal Volume Loss, and MMSE Scores in Computation of Progression and Pharmacologic Therapy Effects for Alzheimer's Disease.

IEEE/ACM Trans Comput Biol Bioinform 2020 Mar-Apr;17(2):608-622. Epub 2018 Sep 14.

We build personalized relevance parameterization method (prep-ad) based on artificial intelligence (ai) techniques to compute Alzheimer's disease (ad) progression for patients at the mild cognitive impairment (mci) stage. Expressions of ad related genes, mini mental state examination (mmse) scores, and hippocampal volume measurements of mci patients are obtained from the Alzheimer's Disease Neuroimaging Initiative (adni) database. In evaluation of cognitive changes under pharmacological therapies, patients are grouped based on available clinical measurements and the type of therapy administered, namely donepezil monotherapy and polytherapy of donepezil with memantine. Average leave one out cross validation (loocv) error rates are calculated for prep-ad results as less than 8 percent when mmse scores are used to compute disease progression for a 60 month period, and 3 percent with hippocampal volume measurements for 12 months. Statistical significance is calculated as p = 0.003 for using ad related genes in disease progression and as for the results computed by prep-ad. These relatively small average loocv errors and p-values suggest that our prep-ad methods employing gene expressions, mmse scores and hippocampal volume loss measurements can be useful in supporting pharmacologic therapy decisions during early stages of ad.
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http://dx.doi.org/10.1109/TCBB.2018.2870363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241288PMC
March 2021

The Standardized Extract of Alleviates Chronic Alcoholic Liver Injury in C57Bl/6J Mice.

Pharmacogn Mag 2018 Jan-Mar;14(53):58-63. Epub 2018 Feb 20.

Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju 52725, Republic of Korea.

Background: In traditional folk medicine, is used in the treatment of uterine hemorrhage, tinnitus, and oligomenorrhea.

Objective: This study aimed to identify the therapeutic effect of EtOAc extract (EALT) on liver of mice with chronic alcohol poisoning.

Materials And Methods: C57BL/6J mice were administered 100 mg/kg of EALT with a single binge ethanol/Lieber-DeCarli liquid diet for 8 weeks.

Results: The chronic-binge ethanol diet induced a significant increase in liver marker enzyme activities. Coadministration of EALT reversed the elevation of serum total cholesterol and triglyceride as well as aspartate aminotransferase and alanine aminotransferase due to chronic alcohol consumption. Histologic findings including markedly attenuated fat accumulation in hepatocytes were observed in EALT-treated mice. EALT supplementation prevented alcoholic liver injury through attenuation of inflammatory mediators such as toll-like receptor-4, cytochrome P4502E1, and cyclooxygenase-2, and inflammatory cytokine interleukin-6.

Conclusion: Results provided direct experimental evidence for the hepatoprotective effect of EALT in the NIAAA mouse model. Therapeutic attempts with the extract might be useful in the management of alcoholic liver disease.

Summary: Halophyte has recently been of interest in Korea for its nutritional value and salty taste which made it an ideal vegetablePhytochemical analysis of EtOAc extract (EALT) resulted in nine compounds including catechins and myricetin glycosides as main componentsAdministration of EALT for 8 weeks showed hepatoprotective effect on Lieber-DeCarli diet-fed mouse modelA significant decrease in liver marker enzymes and inflammatory mediators was also detected. EALT: EtOAc extract; TC: Total cholesterol; TG: Triglyceride; ROS: Reactive oxygen species; CYP2E1: Cytochrome P4502E1; TLR-4: Toll-like receptor-4; COX-2: Cyclooxygenase-2.
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http://dx.doi.org/10.4103/pm.pm_44_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858243PMC
February 2018

Identification of Hepatoprotective Constituents in and Development of Simultaneous Analysis Method using High-performance Liquid Chromatography.

Pharmacogn Mag 2017 Oct-Dec;13(52):535-541. Epub 2017 Nov 13.

Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju 52725, Republic of Korea.

Background: , a naturally salt-tolerant halophyte, has been studied recently and is of much interest to researchers due to its potent antioxidant and hepatoprotective activities.

Objective: In the present study, we attempted to elucidate bioactive compounds from ethyl acetate (EtOAc) soluble fraction of extract. Furthermore, the simultaneous analysis method of bioactive EtOAc fraction of has been developed using high-performance liquid chromatography (HPLC).

Materials And Methods: Thirteen compounds have been successfully isolated from EtOAc fraction of , and the structures of 1-13 were elucidated by extensive one-dimensional and two-dimensional spectroscopic methods including H-NMR, C-NMR, H-H COSY, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, and nuclear Overhauser effect spectroscopy. Hepatoprotection of the isolated compounds against liver fibrosis was evaluated by measuring inhibition on hepatic stellate cells (HSCs) undergoing proliferation.

Results: Compounds 1-13 were identified as gallincin (1), apigenin-3-O-β-D-galactopyranoside (2), quercetin (3), quercetin-3-O-β-D-galactopyranoside (4), (-)-epigallocatechin (5), (-)-epigallocatechin-3-gallate (6), (-)-epigallocatechin-3-(3″-O-methyl) gallate (7), myricetin-3-O-β-D-galactopyranoside (8), myricetin-3-O-(6″-O-galloyl)-β-D-galactopyranoside (9), myricetin-3-O-α-L-rhamnopyranoside (10), myricetin-3-O-(2″-O-galloyl)-α-L-rhamnopyranoside (11), myricetin-3-O-(3″-O-galloyl)-α-L-rhamnopyranoside (12), and myricetin-3-O-α-L-arabinopyranoside (13), respectively. All compounds except for 4, 8, and 10 are reported for the first time from this plant.

Conclusion: Myricetin glycosides which possess galloyl substituent (9, 11, and 12) showed most potent inhibitory effects on the proliferation of HSCs.

Summary: In the present study, we have successfully isolated 13 compounds from bioactive fraction of . The structures of compounds isolated have been fully elucidated, and hepatoprotective activities of compounds against liver fibrosis were evaluated by measuring inhibition on hepatic stellate cells undergoing proliferation. Furthermore, the simultaneous analysis method of bioactive ethyl acetate fraction of has been developed using HPLC. Ten compounds identified herein are reported for the first time from this plant. HSQC: Heteronuclear single quantum coherence; HMBC: Heteronuclear multiple bond correlation; NOESY: Nuclear Overhauser effect spectroscopy; EGCG: Epigallocatechin-3-gallate; EGC: Epigallocatechin; HSC: Hepatic stellate cell; MTT: 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide.
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http://dx.doi.org/10.4103/pm.pm_477_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701388PMC
November 2017

Anti-obesity Effect of Halophyte Crop, Limonium tetragonum in High-Fat Diet-Induced Obese Mice and 3T3-L1 Adipocytes.

Biol Pharm Bull 2017 ;40(11):1856-1865

Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology.

Halophyte Limonium tetragonum has recently been of interest in Korea for its nutritional value and salty taste which made it an ideal vegetable. In this study, the potential of L. tetragonum preventing excess weight gain, obesity and the related health problem has been evaluated in vitro and in vivo. The treatment with 100 mg/kg of L. tetragonum EtOAc soluble fraction (EALT) apparently prevented the body weight gain, adipose tissue weight gain, and the increase of triglyceride and total cholesterol level in mice fed a high-fat diet for 8 weeks. In addition, both glucose tolerance and insulin resistance in dietary obese mice were improved by EALT administration. A marked decrease in adipocyte differentiation was observed in the EALT (50 µg/mL)-treated 3T3-L1 cells, which was mediated by the suppression of adipogenesis-related transcription factors including peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer binding protein (C/EBP)α, and Sterol regulatory element binding protein-1 (SREBP-1) and adipocyte-specific proteins such as fatty acid synthase (FAS), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein (aP2). The major components contained in EALT were identified as (-)-epigallocatechin-3-(3″-O-methyl) gallate, (-)-epigallocatechin-3-gallate, and myricetin-3-O-β-D-galactopyranoside based on its phytochemical analysis. Results suggested that EALT might be available as functional crop and bioactive diet supplement for the prevention and/or treatment of obesity.
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http://dx.doi.org/10.1248/bpb.b17-00296DOI Listing
June 2018

Mediation effects of medication information processing and adherence on association between health literacy and quality of life.

BMC Health Serv Res 2017 Sep 16;17(1):661. Epub 2017 Sep 16.

College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, South Korea.

Background: To examine whether medication related information processing defined as reading of over-the-counter drug labels, understanding prescription instructions, and information seeking-and medication adherence account for the association between health literacy and quality of life, and whether these associations may be moderated by age and gender.

Methods: A sample of 305 adults in South Korea was recruited through a proportional quota sampling to take part in a cross-sectional survey on health literacy, medication-related information processing, medication adherence, and quality of life. Descriptive statistics and structural equation modeling (SEM) were performed.

Results: Two mediation pathways linking health literacy with quality of life were found. First, health literacy was positively associated with reading drug labels, which was subsequently linked to medication adherence and quality of life. Second, health literacy was positively associated with accurate understanding of prescription instructions, which was associated with quality of life. Age moderation was found, as the mediation by reading drug labels was significant only among young adults whereas the mediation by understanding of medication instruction was only among older adults.

Conclusion: Reading drug labels and understanding prescription instructions explained the pathways by which health literacy affects medication adherence and quality of life. The results suggest that training skills for processing medication information can be effective to enhance the health of those with limited health literacy.
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http://dx.doi.org/10.1186/s12913-017-2598-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602864PMC
September 2017

Comparative Evaluation of Sulfur Compounds Contents and Antiobesity Properties of Prepared by Different Drying Methods.

Evid Based Complement Alternat Med 2017 16;2017:2436927. Epub 2017 Mar 16.

Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju 52725, Republic of Korea.

Despite the nutritional and medicinal values of , its unique flavor (onion or garlic taste and smell) coming from sulfur containing compounds limits its usage as functional food. For comparative study, roots were prepared under two different drying conditions, namely, low-temperature drying that minimizes the volatilization of sulfur components and hot-air drying that minimizes the garlic odor and spicy taste of . In GC/MS olfactory system, the odorous chemicals and organosulfur compounds such as diallyl trisulfide, dimethyl trisulfide, and dipropyl trisulfide were significantly decreased in hot-air drying compared to low-temperature drying. The spiciness and saltiness taste were noticeably reduced, while sourness, sweetness, and umami taste were significantly increased in hot-air dried according to electronic tongue. Although the content of volatile sulfur components was present at lower level, the administration of hot-air dried extract (100 mg/kg ) apparently prevented the body weight gain and improved insulin resistance in C57BL/6J obese mice receiving high fat diet. Results suggested that the hot-air dried possessing better taste and odor might be available as functional crop and bioactive diet supplement for the prevention and/or treatment of obesity.
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http://dx.doi.org/10.1155/2017/2436927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376446PMC
March 2017

Bond Strengths of Orthodontic Metal Brackets to Tribochemically Silica-coated Zirconia Surfaces Using Different 10-Methacryloyloxydecyl Dihydrogen Phosphate-containing Primers.

J Adhes Dent 2017;19(1):21-29

Purpose: To evaluate the effects of tribochemical silica coating and different 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing primers on the shear bond strength (SBS) of orthodontic metal brackets to yttrium-stabilized tetragonal zirconia polycrystal (Y-TZP) surfaces.

Materials And Methods: One hundred ninety polished Y-TZP specimens were randomly assigned to 19 groups (n = 10): 30 specimens were used for surface analyses after polishing with 600-grit silicon carbide paper, airborneparticle abrasion with 50-μm alumina (A), or tribochemical silica coating (CoJet [C]); 160 specimens were used in SBS testing of orthodontic metal brackets to Y-TZP after alumina airborne-particle abrasion or tribochemical silica coating and application of either ESPE-Sil (S) (ASn, ASa, CSn, CSa), Alloy Primer (AP) (AAPn, AAPa, CAPn, CAPa), Clearfil Ceramic Primer (CP) (ACPn, ACPa, CCPn, CCPa), or Scotchbond Universal (U) (AUn, AUa, CUn, CUa) and either stored in water for 24 h (non-aged, n) or thermocycled 5000 times (aged, a). The surface analyses and SBSs were statistically analyzed with ANOVA and Tukey's tests.

Results: Both mechanically treated surfaces had significantly greater surface roughness and surface free energy than did the polished surfaces. The type of primer and aging significantly affected the bond strength. Among the thermocycled specimens, the AAPa, AUa, and CCPa groups showed the greatest SBS.

Conclusion: After alumina airborne-particle abrasion, the application of Alloy Primer, Clearfil Ceramic Primer, or Scotchbond Universal provided stable bonding to Y-TZP ceramics. After tribochemical silica coating, however, only Clearfil Ceramic Primer produced a durable bond to Y-TZP ceramics.
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http://dx.doi.org/10.3290/j.jad.a37724DOI Listing
July 2017