Publications by authors named "Jeong-Hun Lee"

60 Publications

Improved tumor-suppressive effect of OZ-001 combined with cisplatin mediated by mTOR/p70S6K and STAT3 inactivation in A549 human lung cancer cells.

Biomed Pharmacother 2021 Oct 28;142:111961. Epub 2021 Jul 28.

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea; Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea. Electronic address:

We previously reported the anticancer activity of 4-(4-fluorobenzylcarbamoylmethyl)-3-(4-cyclohexylphenyl)-2-[3-(N,N-dimethylureido)-N'-methylpropylamino]-3,4-dihydroquinazoline (OZ-001), a T-type calcium channel (TTCC) blocker, against non-small cell lung cancer (NSCLC) in vitro and in vivo. Here, we evaluated the synergistic effect of OZ-001 and cisplatin on A549 human lung cancer cells and A549 xenograft mice. Our study demonstrated that treatment with OZ-001 and cisplatin sensitized A549 cells to cisplatin and significantly inhibited cell growth, increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, and induced poly (ADP-ribose) polymerase (PARP) cleavage in A549 cells and an A549 xenograft tumor mouse model. Moreover, our findings showed that mechanistic target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and signal transducer and activator of transcription (STAT3) inactivation was required for apoptosis induced by the combination of OZ-001 and cisplatin in in vitro and in vivo experiments. Our results suggest that combined treatment with OZ-001 and cisplatin could potentiate antiproliferative effects via suppression of the mTOR/p70S6K and STAT3 pathways and may be considered a potential therapeutic agent for NSCLC.
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http://dx.doi.org/10.1016/j.biopha.2021.111961DOI Listing
October 2021

End-Tidal Carbon Dioxide Monitoring for Spontaneous Pneumothorax.

Emerg Med Int 2021 14;2021:9976543. Epub 2021 Jun 14.

Department of Emergency Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea.

Background: Spontaneous pneumothorax should be classified as primary spontaneous pneumothorax (PSP) or secondary spontaneous pneumothorax (SSP) because treatment strategies may differ depending on underlying lung conditions and clinical course. The pulmonary dysfunction can lead to changes in end-tidal carbon dioxide (ETCO). The aim of this study was to investigate the difference in ETCO between PSP and SSP.

Methods: This retrospective observational study included adult patients diagnosed with spontaneous pneumothorax in the emergency room from April 2019 to September 2020. We divided patients into PSP and SSP groups and compared ETCO variables between the two groups.

Results: There were 33 (66%) patients in the PSP group and 17 (34%) patients in the SSP group. Initial ETCO was lower in the SSP group than in the PSP group (30 (23-33) vs. 35 (33-38) mmHg, =0.002). Multivariate analysis revealed that respiratory gas associated with SSP was initial ETCO (OR: 0.824; 95% CI: 0.697-0.974, =0.023). The optimal cutoff for initial ETCO to detection of SSP was 32 mmHg (area under curve, 0.754), with 76.5% sensitivity and 72.7% specificity.

Conclusion: ETCO monitoring is a reliable noninvasive indicator of differentiating between PSP and SSP. Initial ETCO lower than 32 mmHg is a predictor of SSP.
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http://dx.doi.org/10.1155/2021/9976543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216832PMC
June 2021

Medical X-band linear accelerator for high-precision radiotherapy.

Med Phys 2021 Sep 28;48(9):5327-5342. Epub 2021 Jul 28.

Advanced Institute for Radiation Fusion Medical Technology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Purpose: Recently, high-precision radiotherapy systems have been developed by integrating computerized tomography or magnetic resonance imaging to enhance the precision of radiotherapy. For integration with additional imaging systems in a limited space, miniaturization and weight reduction of the linear accelerator (linac) system have become important. The aim of this work is to develop a compact medical linac based on 9.3 GHz X-band RF technology instead of the S-band RF technology typically used in the radiotherapy field.

Methods: The accelerating tube was designed by 3D finite-difference time-domain and particle-in-cell simulations because the frequency variation resulting from the structural parameters and processing errors is relatively sensitive to the operating performance of the X-band linac. Through the 3D simulation of the electric field distribution and beam dynamics process, we designed an accelerating tube to efficiently accelerate the electron beam and used a magnetron as the RF source to miniaturize the entire linac. In addition, a side-coupled structure was adopted to design a compact linac to reduce the RF power loss. To verify the performance of the linac, we developed a beam diagnostic system to analyze the electron beam characteristics and a quality assurance (QA) experimental environment including 3D lateral water phantoms to analyze the primary performance parameters (energy, dose rate, flatness, symmetry, and penumbra) The QA process was based on the standard protocols AAPM TG-51, 106, 142 and IAEA TRS-398.

Results: The X-band linac has high shunt impedance and electric field strength. Therefore, even though the length of the accelerating tube is 37 cm, the linac could accelerate an electron beam to more than 6 MeV and produce a beam current of more than 90 mA. The transmission ratio is measured to be approximately 30% ~ 40% when the electron gun operates in the constant emission region. The percent depth dose ratio at the measured depths of 10 and 20 cm was approximately 0.572, so we verified that the photon beam energy was matched to approximately 6 MV. The maximum dose rate was measured as 820 cGy/min when the source-to-skin distance was 80 cm. The symmetry was smaller than the QA standard and the flatness had a higher than standard value due to the flattening filter-free beam characteristics. In the case of the penumbra, it was not sufficiently steep compared to commercial equipment, but it could be compensated by improving additional devices such as multileaf collimator and jaw.

Conclusions: A 9.3 GHz X-band medical linac was developed for high-precision radiotherapy. Since a more precise design and machining process are required for X-band RF technology, this linac was developed by performing a 3D simulation and ultraprecision machining. The X-band linac has a short length and a compact volume, but it can generate a validated therapeutic beam. Therefore, it has more flexibility to be coupled with imaging systems such as CT or MRI and can reduce the bore size of the gantry. In addition, the weight reduction can improve the mechanical stiffness of the unit and reduce the mechanical load.
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http://dx.doi.org/10.1002/mp.15077DOI Listing
September 2021

Using RNA-Sequencing Data to Examine Tissue-Specific Garlic Microbiomes.

Int J Mol Sci 2021 Jun 24;22(13). Epub 2021 Jun 24.

Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea.

Garlic () is a perennial bulbous plant. Due to its clonal propagation, various diseases threaten the yield and quality of garlic. In this study, we conducted in silico analysis to identify microorganisms, bacteria, fungi, and viruses in six different tissues using garlic RNA-sequencing data. The number of identified microbial species was the highest in inflorescences, followed by flowers and bulb cloves. With the Kraken2 tool, 57% of identified microbial reads were assigned to bacteria and 41% were assigned to viruses. Fungi only made up 1% of microbial reads. At the species level, was the most dominant bacteria while was the most abundant fungi. Several allexiviruses were identified. Of them, the most abundant virus was garlic virus C followed by shallot virus X. We obtained a total of 14 viral genome sequences for four allexiviruses. As we expected, the microbial community varied depending on the tissue types, although there was a dominant microorganism in each tissue. In addition, we found that Kraken2 was a very powerful and efficient tool for the bacteria using RNA-sequencing data with some limitations for virome study.
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http://dx.doi.org/10.3390/ijms22136791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268838PMC
June 2021

Comparative Study of Metagenomics and Metatranscriptomics to Reveal Microbiomes in Overwintering Pepper Fruits.

Int J Mol Sci 2021 Jun 8;22(12). Epub 2021 Jun 8.

Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea.

Red pepper (, L.), is one of the most important spice plants in Korea. Overwintering pepper fruits are a reservoir of various microbial pepper diseases. Here, we conducted metagenomics (DNA sequencing) and metatranscriptomics (RNA sequencing) using samples collected from three different fields. We compared two different library types and three different analytical methods for the identification of microbiomes in overwintering pepper fruits. Our results demonstrated that DNA sequencing might be useful for the identification of bacteria and DNA viruses such as bacteriophages, while mRNA sequencing might be beneficial for the identification of fungi and RNA viruses. Among three analytical methods, KRAKEN2 with raw data reads (KRAKEN2_R) might be superior for the identification of microbial species to other analytical methods. However, some microbial species with a low number of reads were wrongly assigned at the species level by KRAKEN2_R. Moreover, we found that the databases for bacteria and viruses were better established as compared to the fungal database with limited genome data. In summary, we carefully suggest that different library types and analytical methods with proper databases should be applied for the purpose of microbiome study.
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http://dx.doi.org/10.3390/ijms22126202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227054PMC
June 2021

Microcomputed Tomography and Histological Study of Bone Regeneration Using Tooth Biomaterial with BMP-2 in Rabbit Calvarial Defects.

Scanning 2021 10;2021:6690221. Epub 2021 May 10.

Department of Oral and Maxillofacial Surgery, Graduate School of Clinical Dentistry, Korea University Guro Hospital, Seoul 08308, Republic of Korea.

Our study was aimed to analyze the osteoinductive effect of powdered and block type autogenous bone graft along with bone morphogenetic protein (BMP-2) as compared to synthetic bone graft. Three circular bicortical defects were made in the calvaria of each rabbit and randomly divided into three groups as follows: powdered tooth biomaterial+BMP-2, block tooth biomaterial+BMP-2, and control group: synthetic bone+BMP-2. The samples taken from these defects after 4 and 8 weeks were analyzed histologically along with micro CT analysis. In our study, both powered and block type tooth autogenous bone graft successfully stimulated mesenchymal cells leading to endochondral ossification and bone regeneration. We observed that the powered bone graft material which is acid insoluble especially is preferable as a carrier for BMP-2.
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http://dx.doi.org/10.1155/2021/6690221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131161PMC
May 2021

Development of a compact X-band linear accelerator system mounted on an O-arm rotating gantry for radiation therapy.

Rev Sci Instrum 2021 Feb;92(2):024103

Electro-Medical Device Research Center, Korea Electrotechnology Research Institute, Ansan 15588, South Korea.

A compact X-band linear accelerator (LINAC) system equipped with a small and lightweight magnetron was constructed to develop a high-precision image-guided radiotherapy system. The developed LINAC system was installed in an O-ring gantry where cone-beam computed tomography (CBCT) was embedded. When the O-arm gantry is rotated, an x-ray beam is stably generated, which resulted from the stable transmission of radio frequency power into the X-band LINAC system. Quality assurance (QA) tests, including mechanical and dosimetry checks, were carried out to ensure safety and operation performance according to the American Association of Physicists in Medicine's TG-51, 142, an international standard protocol established by accredited institutions. In addition, delivery QA of the radiotherapy planning system was conducted to verify intensity-modulated radiotherapy techniques. Therefore, it was demonstrated that the developed X-band LINAC system mounted on the O-arm gantry proved to be valid and reliable for potential use in CBCT image-guided radiation therapy.
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http://dx.doi.org/10.1063/5.0030271DOI Listing
February 2021

Transcriptome Profiling of Human Follicle Dermal Papilla Cells in response to Porphyra-334 Treatment by RNA-Seq.

Evid Based Complement Alternat Med 2021 13;2021:6637513. Epub 2021 Jan 13.

Anti-aging Research Institute of BIO-FD&C Co., Ltd., Incheon 21990, Republic of Korea.

Porphyra-334 is a kind of mycosporine-like amino acid absorbing ultraviolet-A. Here, we characterized porphyra-334 as a potential antiaging agent. An assay revealed that porphyra-334 dramatically promoted collagen synthesis in fibroblast cells. The effect of porphyra-334 on cell proliferation was dependent on the cell type, and the increase of cell viability by porphyra-334 was the highest in keratinocyte cells among the three tested cell types. An clinical test with 22 participants demonstrated the possible role of porphyra-334 in the improvement of periorbital wrinkles. RNA-sequencing using human follicle dermal papilla (HFDP) cells upon porphyra-334 treatment identified the upregulation of metallothionein- (MT-) associated genes, confirming the antioxidant role of porphyra-334 with MT. Moreover, the expression of genes involved in nuclear chromosome segregation and the encoding of components of kinetochores was upregulated by porphyra-334 treatment. Furthermore, we found that several genes associated with the hair follicle cycle, the hair follicle structure, the epidermal structure, and stem cells were upregulated by porphyra-334 treatment, suggesting the potential role of porphyra-334 in hair follicle growth and maintenance. In summary, we provided several new pieces of evidence of porphyra-334 as a potential antiaging cosmetic agent and elucidated the expression network in HFDP cells upon porphyra-334.
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http://dx.doi.org/10.1155/2021/6637513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817261PMC
January 2021

Gene expression profile of human follicle dermal papilla cells in response to Camellia japonica phytoplacenta extract.

FEBS Open Bio 2021 03 14;11(3):633-651. Epub 2021 Feb 14.

Anti-aging Research Institute of BIO-FD&C Co., Ltd., Incheon, Korea.

Camellia japonica L. is a flowering tree with several medicinal and cosmetic applications. Here, we investigated the efficacy of C. japonica placenta extract (CJPE) as a potential therapeutic agent for promotion of hair growth and scalp health by using various in vitro and in vivo assays. Moreover, we performed transcriptome analysis to examine the relative expression of human follicle dermal papilla cells (HFDPC) in response to CJPE by RNA-sequencing (RNA-seq). In vitro assays revealed upregulation of the expression of hair growth marker genes in HFDPC after CJPE treatment. Moreover, in vivo clinical tests with 42 adult female participants showed that a solution containing 0.5% CJPE increased the moisture content of the scalp and decreased the scalp's sebum content, dead scalp keratin, and erythema. Furthermore, RNA-seq analysis revealed key genes in HFDPC which are associated with CJPE. Interestingly, genes associated with lipid metabolism and cholesterol efflux were upregulated. Genes upregulated by CJPE are associated with several hormones, including parathyroid, adrenocorticotropic hormone, α-melanocyte-stimulating hormone (alpha-MSH), and norepinephrine, which are involved in hair follicle biology. Furthermore, some upregulated genes are associated with the regulation of axon guidance. In contrast, many genes downregulated by CJPE are associated with structural components of the cytoskeleton. In addition, CJPE suppressed genes associated with muscle structure and development. Taken together, this study provides extensive evidence that CJPE may have potential as a therapeutic agent for scalp treatment and hair growth promotion.
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http://dx.doi.org/10.1002/2211-5463.13076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931240PMC
March 2021

Immunostimulatory Effects of Live K040706 on the CYP-Induced Immunosuppression Mouse Model.

Nutrients 2020 Nov 22;12(11). Epub 2020 Nov 22.

Department of Pharmaceutical Biochemistry, College of Pharmacy Kyung Hee University, Seoul 02447, Korea.

Our previous studies have shown that heat-killed K040706 exerts immunostimulatory and anti-inflammatory activities in macrophages, cyclophosphamide (CYP)-treated mice, and dextran sulfate sodium-induced colitis mice. However, the immunostimulatory effects of live K040706 (live K040706) against CYP-induced immunosuppression and its underlying molecular mechanisms remain unknown. Therefore, we investigated the immunostimulatory effects of live K040706 (10 or 10 colony forming unit (CFU)/day, p.o.) in CYP-induced immunosuppressed mice. Oral administration of live K040706 prevented the CYP-induced decreases in body weight, thymus index, natural killer (NK) cell activity, T and B cell proliferation, and cytokine (interferon (IFN)-γ, interleukin (IL)-2, and IL-12) production. The administration of live K040706 also exerted positive effects on the gut microbiota of CYP-induced mice, resulting in a microbiota composition similar to that of normal mice. Moreover, live K040706 significantly enhanced IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) production in the splenocytes and Peyer's patch (PP) cells of mice and increased bone marrow (BM) cell proliferation. Taken together, our data indicate that live K040706 may effectively accelerate recovery from CYP-induced immunosuppression, leading to activation of the immune system. Therefore, live K040706 may serve as a potential immunomodulatory agent against immunosuppression.
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http://dx.doi.org/10.3390/nu12113573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700367PMC
November 2020

Development and Validation of an LC-MS/MS Assay to Quantitate 2',4',6'-Trihydroxyacetophenone in Rat and Dog Plasma and its Application to a Pharmacokinetic Study.

Molecules 2020 Sep 23;25(19). Epub 2020 Sep 23.

Department of Pharmaceutical Biochemistry, Kyung Hee University, Seoul 02447, Korea.

In the present study, a simple, rapid, and reliable bioanalytical method was developed using liquid chromatography with tandem-mass spectrometry (LC-MS/MS) to quantify 2',4',6'-trihydroxyacetophenone (THAP) in rat and dog plasma with 2',4',6'-trihydroxybenzaldehyde as an internal standard (IS). The LC-MS/MS instrument was operated in the multiple reaction monitoring (MRM) mode to detect THAP at m/z transition 166.89 > 82.8 and IS at 152.89 > 82.8, respectively. A simple, one-step protein precipitation (PP) method was employed with acetonitrile for sample preparation. Utilizing a Gemini C18 column, THAP and IS were separated with an isocratic mobile phase consisting of 10 mM ammonium acetate and methanol (10:90, ) at a flow rate of 0.2 mL/min. Total chromatographic run time was 2.5 min per sample injection. The standard calibration curve for THAP was linear ( 0.9987) over the concentration range of 0.1 to 100 µg/mL with the lower limit of quantitation (LLOQ) of 0.1 µg/mL (S/N ratio > 10). According to the regulatory guidelines from the U.S. Food and Drug Administration (FDA) and the Korea Ministry of Food and Drug Safety (MFDS), our newly developed biomedical analytical method was fully and adequately validated in terms of selectivity, sensitivity, linearity, intra- and inter-day precision and accuracy, recovery, matrix effect, stability, and dilution integrity. Our validated assay was successfully utilized in a nonclinical pharmacokinetic study of THAP in rats and dogs.
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http://dx.doi.org/10.3390/molecules25194373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583961PMC
September 2020

Clinical Difference between Acute Appendicitis and Acute Right-Sided Colonic Diverticulitis.

Emerg Med Int 2020 1;2020:4947192. Epub 2020 Sep 1.

Department of Emergency Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea.

Background: Clinical presentations of acute appendicitis (AA) and acute right-sided colonic diverticulitis (ARCD) are similar. However, the usual treatment for each disease differs between surgical and conservative management. The aim of this study was to identify clinical differences between AA and ARCD.

Method: We performed a single-center retrospective study on adult patients, with uncomplicated AA and ARCD confirmed by computed tomography, who visited an emergency department between March 2018 and August 2019. Clinical variables including past medical history, presented symptoms and signs, and laboratory findings were compared between the two groups. A logistic regression analysis was subsequently performed to differentiate ARCD from AA based on results of univariate analyses.

Results: A total of 212 (79.1%) and 56 (20.9%) patients were enrolled in AA and ARSD groups, respectively. Logistic regression analysis revealed that a past history of diverticulitis [OR: 102.679 (95% CI: 9.964-1058.055), < 0.001] was associated with ARCD, while ketonuria [OR: 2.907 (95% CI: 1.091-7.745), =0.033], anorexia [OR: 21.544 (95% CI: 3.905-118.868), < 0.001], and neutrophilia [OR: 3.406 (95% CI: 1.243-9.336), =0.017] were associated with AA.

Conclusion: Anorexia, neutrophilia, and ketonuria were predictors of AA while a history of diverticulitis was a predictor of ARCD.
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http://dx.doi.org/10.1155/2020/4947192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481953PMC
September 2020

Diarylurea derivatives comprising 2,4-diarylpyrimidines: Discovery of novel potential anticancer agents via combined failed-ligands repurposing and molecular hybridization approaches.

Bioorg Chem 2020 10 22;103:104121. Epub 2020 Jul 22.

Chemical Kinomics Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science &Technology, KIST School, University of Science and Technology, Seoul 02792, Republic of Korea. Electronic address:

A series of diarylurea derivatives comprising 2,4-diarylpyrimidines were synthesized based on a combination of postulated molecular hybridization design and failed-ligands repurposing approaches, which enabled the discovery of novel potential antiproliferative agents. Towards credible biological evaluation, an in vitro anticancer activity assay was conducted employing a library of 60 cancer cell lines constituting nine panels representing blood, lung, colon, CNS, skin, ovary, renal, prostate, and breast cancers. The results revealed high effectiveness and broad-spectrum anticancer activity of compounds 4m and 4g. Five-dose assay of compounds 4m and 4g proved their high potency that surpassed that of four standard kinase inhibitors FDA-approved anticancer drugs against many cancer cells. Towards the identification of their molecular target, screening of kinase inhibitory profile employing a panel of 51 kinases involved in cancer revealed inhibition of several kinases from the platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) kinase family, which might mediate, at least in part, the antiproliferative activity. Molecular docking of 4g into the crystal structure of the Feline McDonough Sarcoma (FMS) kinase predicted that it binds to a pocket formed by the juxtamembrane domain, the catalytic loop, and the αE helix, thus stabilizing the inhibited conformation of the kinase. Flow cytometric study of the cytotoxic effects of compound 4g in A549 cells showed it induces dose- and time-dependent apoptotic events leading to cell death. Collectively, this work presents compound 4g as a potential broad-spectrum anticancer agent against multiple cancer types.
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http://dx.doi.org/10.1016/j.bioorg.2020.104121DOI Listing
October 2020

Effect of percutaneous coronary intervention team prenotification based on real time electrocardiogram transmission in interhospital transfer of ST elevation myocardial infarction patients: pilot trial of Preparing Revascularization Effort before Patients' Arrival via Regionalization Engagement protocol.

Clin Exp Emerg Med 2020 Jun 30;7(2):114-121. Epub 2020 Jun 30.

Department of Emergency Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea.

Objective: Prompt reperfusion is important for patients with ST elevation myocardial infarction (STEMI). However, patients often require interhospital transfer for percutaneous coronary intervention (PCI) because not all hospitals can provide. The purpose of this study is to reduce the PCI delay using a regionalization protocol in patients with STEMI following transfer from another hospital lacking PCI facility.

Methods: We established a revascularization protocol designated as Preparing Revascularization Effort before Patients' Arrival via Regionalization Engagement (PREPARE) for the STEMI patients transferred from an outside regional hospital. The protocol included immediate referral acceptance by an emergency physician, real-time electrocardiogram sharing via mobile phone and early activation of the PCI team. We analyzed the differences between the PREPARE and the non-PREPARE groups.

Results: In the PREPARE group, the median time from the first hospital visit to the ballooning procedure via PCI at the receiving facility (D1-to-B time) was 111.0 (interquartile range 97.0-130.0) minutes, which was significantly shorter than in the non-PREPARE group 134.0 (interquartile range 115.0-182.0) minutes. The proportion of D1-to-B time within 120 minutes was 30.4% in the group and 60.0% in the PREPARE group, which represents a significant difference (P=0.004). Multivariate logistic regression analysis revealed that patient transfer via PREPARE protocol (odds ratio, 3.399; 95% confidence interval, 1.150-10.050, P=0.027) was related to adequate D1-to-B time. No statistically significant differences were found in the hospital length of stay or major adverse cardiac events within 4 weeks.

Conclusion: The PREPARE protocol is an effective strategy to reduce the time to revascularization of the transferred STEMI patients.
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http://dx.doi.org/10.15441/ceem.19.077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348670PMC
June 2020

Perovskite Granular Wire Photodetectors with Ultrahigh Photodetectivity.

Adv Mater 2020 Aug 26;32(32):e2002357. Epub 2020 Jun 26.

School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.

Control over the morphology and crystallinity of metal halide perovskite materials is of key importance to enable high-performance optoelectronics. Here, a simple yet effective template-free self-assembly synthesis of perovskite granular wires with ultrahigh photodetectivity (3.17 × 10 Jones) is reported. The 1D self-assembly of perovskite grains is driven by differences in the surface interaction energies of the granular facets. The superb photodetecting performance originates from extremely low dark current engendered by energetic barriers featuring unique band-edge modulation along the long axis of wire. Flexible photodetector arrays, fabricated by selectively placing perovskite granular wires onto pre-patterned electrode arrays on a transparent polymer substrate, show independently addressable photonic signal mapping with remarkably high detectivity, photoconductive gain, and responsivity. The "self-assembled nanograin engineering" strategy developed in this study provides a viable method for the development of high-performance perovskite photodetectors and can be extended to other integrated optoelectronic systems.
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http://dx.doi.org/10.1002/adma.202002357DOI Listing
August 2020

Alpha-neoendorphin can reduce UVB-induced skin photoaging by activating cellular autophagy.

Arch Biochem Biophys 2020 08 8;689:108437. Epub 2020 Jun 8.

Department of Biomedical Science, BK21-plus Research Team for Bioactive Control Technology, National Research Center for Dementia, College of Natural Sciences, Chosun University, Gwangju, 61452, Republic of Korea. Electronic address:

Skin aging is influenced by several genetic, physiological, and environmental factors. In particular, ultraviolet (UV) exposure is an important factor involved in inducing skin photoaging. Autophagy controlling homeostatic balance between the synthesis, degradation, and recycling of cellular organelles and proteins plays important regulatory roles in several biological processes, including aging. The opioid neuropeptide α-neoendorphin (named NEP) is an endogenous decapeptide (N-YGGFLRKYPK-C) that activates the kappa opioid receptor and exhibits certain anti-aging and anti-wrinkling effects on skin cells; however, its action mechanism has not yet been elucidated. Therefore, the aim of this study was to determine the effects of NEP on anti-skin aging and autophagy activation in human dermal fibroblast cells. Western blot results showed that NEP down-regulates the production of phospho-mammalian target of rapamycin (p-mTOR), whereas increases the expression of key autophagy-related molecules such as Beclin-1, Atg5-Atg12, and LC3-II. The immunocytochemical analysis performed with anti-LC3-II antibody also showed that the autophagic indicators, autophagosomes are formed by NEP. These results suggest that NEP can activate cellular autophagy through mTOR-Beclin-1-mediated signaling pathway. It was also revealed by CM-HDCF-DA assay and Western blottings that NEP can reduce the production of ultraviolet B (UVB)-induced reactive oxygen species (ROS) like with N-acetylcysteine (NAC), resulting in decreasing the expression levels of skin aging-related proteins, such as phospho-ERK (p-ERK), phospho-p38 (p-p38), and phospho-JNK (p-JNK). Furthermore, NEP could increase the type I procollagen production, while decreasing MMP-1, MMP-2, and MMP-9 activities. Taken together, the results demonstrate that NEP can reduce UVB-induced photoaging by activating autophagy.
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http://dx.doi.org/10.1016/j.abb.2020.108437DOI Listing
August 2020

Oral Intake of Hydrangea serrata (Thunb.) Ser. Leaves Extract Improves Wrinkles, Hydration, Elasticity, Texture, and Roughness in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study.

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

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea.

Previously, we reported that the hot water extract of leaves (WHS) and its active component, hydrangenol, possess in vitro and in vivo effects on skin wrinkles and moisturization. We conducted a randomized, double-blind, placebo-controlled trial to clinically evaluate the effect of WHS on human skin. Participants ( = 151) were randomly assigned to receive either WHS 300 mg, WHS 600 mg, or placebo, once daily for 12 weeks. Skin wrinkle, hydration, elasticity, texture, and roughness parameters were assessed at baseline and after 4, 8, and 12 weeks. Compared to the placebo, skin wrinkles were significantly reduced in both WHS groups after 8 and 12 weeks. In both WHS groups, five parameters (R1-R5) of skin wrinkles significantly improved and skin hydration was significantly enhanced when compared to the placebo group after 12 weeks. Compared with the placebo, three parameters of skin elasticity, including overall elasticity (R2), net elasticity (R5), and ratio of elastic recovery to total deformation (R7), improved after 12 weeks of oral WHS (600 mg) administration. Changes in skin texture and roughness were significantly reduced in both WHS groups. No WHS-related adverse reactions were reported. Hence, WHS could be used as a health supplement for skin anti-aging.
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http://dx.doi.org/10.3390/nu12061588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352416PMC
May 2020

Evaluation of IAQ Management Using an IoT-Based Indoor Garden.

Int J Environ Res Public Health 2020 03 13;17(6). Epub 2020 Mar 13.

Life & Industry Environmental R&D Center in Pyeongtaek University, 3825, Seodong-daero, Pyeongtaek-si, Gyeonggi-do 17869, Korea.

This study was designed to verify the effectiveness of smart gardens by improving indoor air quality (IAQ) through the installation of an indoor garden with sensor-based Internet-of-Things (IoT) technology that identifies pollutants such as particulate matter. In addition, the study aims to introduce indoor gardens for customized indoor air cleaning using the data and IoT technology. New apartments completed in 2016 were selected and divided into four households with indoor gardens installed and four households without indoor gardens. Real-time data and data on PM, CO, temperature, and humidity were collected through an IoT-based IAQ monitoring system. In addition, in order to examine the effects on the health of occupants, the results were analyzed based on epidemiological data, prevalence data, current maintenance, and recommendation criteria, and were presented and evaluated as indices. The indices were classified into a comfort index, which reflects the temperature and humidity, an IAQ index, which reflects PM and CO, and an IAQ composite index. The IAQ index was divided into five grades from "good" to "hazardous". Using a scale of 1 to 100 points, it was determined as follows: "good (0-20)", "moderate (21-40)", "unhealthy for sensitive group (41-60)", "bad (61-80)", "hazardous (81-100)". It showed an increase in the "good" section after installing the indoor garden, and the "bad" section decreased. Additionally, the comfort index was classified into five grades from "very comfortable" to "very uncomfortable". In the comfort index, the "uncomfortable" section decreased, and the "comfortable" section increased after the indoor garden was installed.
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http://dx.doi.org/10.3390/ijerph17061867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142759PMC
March 2020

KCP10043F Represses the Proliferation of Human Non-Small Cell Lung Cancer Cells by Caspase-Mediated Apoptosis via STAT3 Inactivation.

J Clin Med 2020 Mar 5;9(3). Epub 2020 Mar 5.

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea.

We previously reported that 4-(4-fluorobenzylcarbamoylmethyl)-3-(4-cyclohexylphenyl)-2-[3-(-dimethylureido)--methylpropylamino]-3,4-dihydroquinazoline (KCP10043F) can induce G-phase arrest and synergistic cell death in combination with etoposide in lung cancer cells. Here, we investigated the underlying mechanism by which KCP10043F induces cell death in non-small cell lung cancer (NSCLC). Propidium iodide (PI) and annexin V staining revealed that KCP10043F-induced cytotoxicity was caused by apoptosis. KCP10043F induced a series of intracellular events: (1) downregulation of Bcl-2 and Bcl-xL and upregulation of Bax and cleaved Bid; (2) loss of mitochondrial membrane potential; (3) increase of cytochrome release; (4) cleavage of procaspase-8, procaspase-9, procaspase-3, and poly (ADP-ribose) polymerase (PARP). In addition, KCP10043F exhibited potent inhibitory effects on constitutive or interleukin-6 (IL-6)-induced signal transducer and activator of transcription (STAT3) phosphorylation and STAT3-regulated genes including survivin, Mcl-1, and cyclin D. Furthermore, STAT3 overexpression attenuated KCP10043F-induced apoptosis and the cleavage of caspase-9, caspase-3, and PARP. Docking analysis disclosed that KCP10043F could bind to a pocket in the SH2 domain of STAT3 and prevent STAT3 phosphorylation. The oral administration of KCP10043F decreased tumor growth in an A549 xenograft mouse model, as associated with the reduced phosphorylated STAT3, survivin, Mcl-1, and Bcl-2 expression and increased TUNEL staining and PARP cleavage in tumor tissues. Collectively, our data suggest that KCP10043F suppresses NSCLC cell growth through apoptosis induction via STAT3 inactivation.
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http://dx.doi.org/10.3390/jcm9030704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141374PMC
March 2020

Acceleration of somatic cell reprogramming into the induced pluripotent stem cell using a mycosporine-like amino acid, Porphyra 334.

Sci Rep 2020 02 28;10(1):3684. Epub 2020 Feb 28.

Anti-aging Research Institute, BIO-FD&C Co., Ltd, Inchon, 21990, Korea.

Porphyra 334 (P334), a mycosporine-like amino acid (MAA), is a secondary metabolite found in diverse marine and terrestrial organisms and has several beneficial effects on fibroblast proliferation, wound healing, and antioxidant activity. Here, we report that P334 accelerates the cell reprogramming process of mouse tail-tip fibroblasts (TTFs) and human dermal papilla (HDP) cells into induced pluripotent stem cells (iPSCs). We found that P334 significantly improved the cell reprogramming efficiency by activating the tri-methylation of histone 3 lysine 4 (H3K4me3), which controls mesenchymal to epithelial transition (MET) during the reprogramming process. Thus, we found that P334 directly regulates epigenetic changes, providing an efficient approach for natural compound-based cell reprogramming.
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http://dx.doi.org/10.1038/s41598-020-60680-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048830PMC
February 2020

Anti-Aging Effects of (Edelweiss) Callus Culture Extract Through Transcriptome Profiling.

Genes (Basel) 2020 02 21;11(2). Epub 2020 Feb 21.

Anti-Aging Research Institute of BIO-FD&C Co., Ltd., Incheon 21990, Korea.

Edelweiss () in the family is a wildflower that grows in rocky limestone places. Here, we investigated the efficacy of edelweiss callus culture extract ( callus culture extract; LACCE) using multiple assays from to as well as transcriptome profiling. Several assay results showed the strong antioxidant activity of LACCE in response to UVB treatment. Moreover, LACCE suppressed inflammation and wrinkling; however, moisturizing activity was increased by LACCE. The clinical test demonstrated that constant application of LACCE on the face and skin tissues improved anti-periorbital wrinkles, skin elasticity, dermal density, and skin thickness compared with the placebo. The RNA-Sequencing results showed at least 16.56% of human genes were expressed in keratinocyte cells. LACCE up-regulated genes encoding several KRT proteins; DDIT4, BNIP3, and IGFBP3 were involved in the positive regulation of the developmental process, programmed cell death, keratinization, and cornification forming skin barriers, which provide many advantages in the human skin. By contrast, down-regulated genes were stress-responsive genes, including metal, oxidation, wounding, hypoxia, and virus infection, suggesting LACCE did not cause any harmful stress on the skin. Our comprehensive study demonstrated LACCE is a promising agent for anti-aging cosmetics.
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http://dx.doi.org/10.3390/genes11020230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074254PMC
February 2020

The Anti-Proliferative Activity of the Hybrid TMS-TMF-4f Compound Against Human Cervical Cancer Involves Apoptosis Mediated by STAT3 Inactivation.

Cancers (Basel) 2019 Dec 3;11(12). Epub 2019 Dec 3.

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Korea.

We previously reported the potential anti-proliferative activity of 3-(5,6,7-trimethoxy-4-oxo-4-chromen-2-yl)--(3,4,5-trimethoxyphenyl) benzamide (TMS-TMF-4f) against human cancer cells; however, the underlying molecular mechanisms have not been investigated. In the present study, TMS-TMF-4f showed the highest cytotoxicity in human cervical cancer cells (HeLa and CaSki) and low cytotoxicity in normal ovarian epithelial cells. Annexin V-FITC and propidium iodide (PI) double staining revealed that TMS-TMF-4f-induced cytotoxicity was caused by the induction of apoptosis in both HeLa and CaSki cervical cancer cells. The compound TMS-TMF-4f enhanced the activation of caspase-3, caspase-8, and caspase-9 and regulated Bcl-2 family proteins, which led to mitochondrial membrane potential (MMP) loss and resulted in the release of cytochrome and Smac/DIABLO into the cytosol. Also, TMS-TMF-4f suppressed both constitutive and IL-6-inducible levels of phosphorylated STAT3 (p-STAT3) and associated proteins such as Mcl-1, cyclin D1, survivin, and c-Myc in both cervical cancer cells. STAT-3 overexpression completely ameliorated TMS-TMF-4f-induced apoptotic cell death and PARP cleavage. Docking analysis revealed that TMS-TMF-4f could bind to unphosphorylated STAT3 and inhibit its interconversion to the activated form. Notably, intraperitoneal administration of TMS-TMF-4f (5, 10, or 20 mg/kg) decreased tumor growth in a xenograft cervical cancer mouse model, demonstrated by the increase in TUNEL staining and PARP cleavage and the reduction in p-STAT3, Mcl-1, cyclin D1, survivin, and c-Myc expression levels in tumor tissues. Taken together, our results suggest that TMS-TMF-4f may potentially inhibit human cervical tumor growth through the induction of apoptosis via STAT3 suppression.
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http://dx.doi.org/10.3390/cancers11121927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966466PMC
December 2019

Parental involvement in the manual reduction of pulled elbow in children.

Eur J Emerg Med 2020 Jun;27(3):193-196

Department of Emergency Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea.

Objective: To investigate the effect of parental involvement in the manual reduction of pulled elbow in children.

Methods: We conducted a prospective case-control study from January to December 2018. The patients were under 6 years old with suspected radial head subluxation and were randomly assigned to two groups (an intervention group with a physician's and a parent's finger placed on the patient's radial head and a control group with the physician's finger only placed on the patient's radial head) according to the method of reduction. The results of a questionnaire given to the parent and physician were analyzed.

Results: A total of 150 patients were included in the study: 75 in the intervention group and 75 in the control group. There were no significant differences between the groups. The average number of attempts at manual reduction was 1.29 ± 0.73 in the intervention group and 1.31 ± 0.72 in the control group (P = 0.91) and the success rate of manual reduction was 96.0 and 94.7% (P = 0.70), respectively. The ease of conducting the procedure by the doctors did not show a significant difference between the two groups. However, the parents' understanding and satisfaction was significantly higher in the intervention group.

Conclusion: Parental involvement did not affect the procedure of physician, but it improved the understanding and satisfaction of the parents.
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http://dx.doi.org/10.1097/MEJ.0000000000000636DOI Listing
June 2020

β-Caryophyllene in the Essential Oil from Induces G Phase Cell Cycle Arrest in Human Lung Cancer Cells.

Molecules 2019 Oct 18;24(20). Epub 2019 Oct 18.

College of Pharmacy, Kyung Hee University, Seoul 02447, Korea.

is a plant widespread in East Asia, used in folk medicine to treat various disorders, such as pneumonia, colitis, stomatitis, and carbuncle. Whether the essential oil from (ECB) and its active constituents have anti-proliferative activities in lung cancer is unknown. Therefore, we investigated the cytotoxic effects of ECB in A549 and NCI-H358 human lung cancer cells. Culture of A549 and NCI-H358 cells with ECB induced apoptotic cell death, as revealed by an increase in annexin V staining. ECB treatment reduced mitochondrial membrane potential (MMP), disrupted the balance between pro-apoptotic and anti-apoptotic Bcl-2 proteins, and activated caspase-8, -9, and -3, as assessed by western blot analysis. Interestingly, pretreatment with a broad-spectrum caspase inhibitor (z-VAD-fmk) significantly attenuated ECB-induced apoptosis. Furthermore, gas chromatography-mass spectrometry (GC/MS) analysis of ECB identified six compounds. Among them, β-caryophyllene exhibited a potent anti-proliferative effect, and thus was identified as the major active compound. β- Caryophyllene induced G cell cycle arrest by downregulating cyclin D1, cyclin E, cyclin-dependent protein kinase (CDK) -2, -4, and -6, and RB phosphorylation, and by upregulating p21 and p27. These results indicate that β-caryophyllene exerts cytotoxic activity in lung cancer cells through induction of cell cycle arrest.
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http://dx.doi.org/10.3390/molecules24203754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832734PMC
October 2019

High-Performance Hybrid Photovoltaics with Efficient Interfacial Contacts between Vertically Aligned ZnO Nanowire Arrays and Organic Semiconductors.

ACS Omega 2019 Jun 7;4(6):9996-10002. Epub 2019 Jun 7.

School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

Hybrid photovoltaics (HPVs) incorporating both organic and inorganic semiconducting materials have attracted much attention as next-generation photovoltaics because of their advantage of combining both materials. The hybridization of ZnO nanowires (NWs) and organic semiconductors is expected to be a suitable approach to overcome the limited exciton diffusion length and low electron mobility associated with current organic photovoltaics. The use of ZnO NWs allows researchers to tune nanoscale dimensions more precisely and to achieve rod-to-rod spacing below 10 nm. However, the perfect incorporation of organic semiconductors into densely packed ZnO NW arrays has yet to be achieved. In this study, we report the fabrication of ZnO NW arrays and various organic heterojunction-based HPVs using the feasible and effective vacuum-assisted double coating (VADC) method, achieving full coverage of the organic semiconductors on the compact ZnO NW arrays. The newly proposed VADC method ensures perfect infiltration and full coverage of the organic semiconductors on the densely packed NW arrays. Compared with the conventional single spin-coating process, the use of the VADC method led to 11 and 14% increases in the power conversion efficiency of P3HT:PCBM- and PBDTTT-C-T:PCBM-based HPVs, respectively. Our studies provide a feasible method for the fabrication of efficient HPVs.
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http://dx.doi.org/10.1021/acsomega.9b00778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648691PMC
June 2019

A novel mPGES-1 inhibitor alleviates inflammatory responses by downregulating PGE in experimental models.

Prostaglandins Other Lipid Mediat 2019 10 20;144:106347. Epub 2019 Jun 20.

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea; Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea. Electronic address:

We previously reported the strong inhibitory potency of N-phenyl-N'-(4- benzyloxyphenoxycarbonyl)-4-chlorophenylsulfonyl hydrazide (PBCH) on lipopolysaccharide (LPS)-induced prostaglandin E (PGE) production in macrophages. Herein, we characterized PBCH as a microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor and evaluated its anti-inflammatory effects using in vivo experimental models. PBCH inhibited PGE production in various activated cells in addition to inhibiting the mPGES-1 activity. In the ear edema and paw edema rat models, PBCH significantly reduced ear thickness and paw swelling, respectively. Besides, in adjuvant-induced arthritis (AIA) rat model, PBCH decreased paw swelling, plasma rheumatoid factor (RF), and receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. Furthermore, while PBCH reduced the plasma prostaglandin E metabolite (PGEM) levels, it did not affect the plasma levels of prostacyclin (PGI) and thromboxane A (TXA). Our data suggest that PBCH downregulates PGE production by interfering with the mPGES-1 activity, thus reducing edema and arthritis in rat models.
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http://dx.doi.org/10.1016/j.prostaglandins.2019.106347DOI Listing
October 2019

Seasonal effects on resting energy expenditure are dependent on age and percent body fat.

Clin Nutr 2020 04 28;39(4):1276-1283. Epub 2019 May 28.

Department of Physiology, University of Ulsan College of Medicine/Asan Medical Center, 88 OlympicRo 43-gil Songpa-gu, Seoul, 05505, Republic of Korea. Electronic address:

Seasonal variation in resting energy expenditure (REE) is still under debate. This study investigated seasonal changes in REE and relevant factors among Korean adults. A total of 867 healthy volunteers (385 men and 482 women) aged 20-69 years were divided into four seasonal groups and subgroups based on age, body mass index (BMI), and percent body fat (PBF) quartiles. REE, body composition, glucose metabolism, thyroid hormones, and catecholamines were measured. The seasonal factor contributed to REE independent of anthropometric indices, with additional variation decreasing from 6% to 2% among younger and older persons, respectively. The adjusted REE in the winter was 5.4-13.9%, 7.8-14.3%, and 8.6-11.9% higher than that in the summer in the age, BMI, and PBF subgroups, respectively. T3 and log-transformed norepinephrine (NE) were higher, whereas log-transformed epinephrine (EPI) was lower in the winter compared to the summer. The magnitude of the winter-summer difference in REE and T3 and of the summer-winter difference in EPI were reduced three-fold between the lowest and highest intervals of age and PBF, whereas the difference in NE was constant across all age and PBF intervals. There was no obvious change in seasonal differences in REE or its relevant biomarkers across BMI intervals. In summary, season is an independent predictor of REE and its effect is attenuated by the increment of age and PBF but not BMI.
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http://dx.doi.org/10.1016/j.clnu.2019.05.021DOI Listing
April 2020

Concentrations of particulate matter, carbon dioxide, VOCs and risk assessment inside Korean taxis and ships.

Environ Sci Pollut Res Int 2019 Apr 7;26(10):9619-9631. Epub 2019 Feb 7.

Life & Industry Environmental R&D center, Pyeongtaek University, Pyeongtaek, 17869, South Korea.

The objective of this study was to investigate the concentration distribution of indoor air pollutants in taxis and ships (passengers) which are frequently used for public transportation and recreational activities in South Korea. In addition, it aimed to assess air quality factors to establish and evaluate the health risks of exposure to polluted indoor air. Particulate matter (PM) concentrations were not affected by the number of passengers, time of day, and driving characteristics because there were only a few passengers (2 to 4 people) and the space was confined. In the ships, indoor air pollutants responded more sensitively to the operation characteristics depending on the time of sailing (i.e., anchoring and departure, movement of vehicles on the ship, movement of passengers, combustion in the shop, and ventilation) than to the number of people boarding and alighting. The carbon dioxide concentrations in different ship rooms did not vary according to season and degree of congestion; however, there were differences between different ships. These differences may result from the size, type, and operating characteristics of the ships. Volatile organic compounds (VOCs) and aldehydes in new taxis exceeded the standard levels during summer. VOC concentrations in ships were particularly high during summer when the outdoor temperature was high. Similar observations were made for other means of transportation. The risk assessment depended on the means of transportation and demonstrated that mortality risks due to PM and excess carcinogenic and non-carcinogenic risks from VOCs and aldehydes were within safety levels.
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http://dx.doi.org/10.1007/s11356-019-04361-5DOI Listing
April 2019

23-Hydroxyursolic Acid Isolated from the Stem Bark of Induces Apoptosis through Fas/Caspase-8-Dependent Pathway in HL-60 Human Promyelocytic Leukemia Cells.

Molecules 2018 Dec 13;23(12). Epub 2018 Dec 13.

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea.

The natural product 23-hydroxyursolic acid (23-HUA) is a derivative of ursolic acid, which is known to induce cancer cell apoptosis. However, apoptotic effects and mechanisms of 23-HUA have not been well characterized yet. Herein, we investigated the molecular mechanisms of 23-HUA-induced apoptosis in HL-60 human promyelocytic leukemia cells. 23-HUA-treated HL-60 cells showed apoptotic features including internucleosomal DNA condensation and fragmentation as well as externalization of phosphatidylserine residues. 23-HUA induced a series of mitochondrial events including disruption of mitochondrial membrane potential (), cytochrome and Smac/DIABLO release and loss of balance between pro-apoptotic and anti-apoptotic Bcl-2 proteins in HL-60 cells. In addition, 23-HUA activated caspase-8, caspase-9 and caspase-3. Pretreatment with a broad caspase inhibitor (z-VAD-fmk), a caspase-3 inhibitor (z-DEVD-fmk), and a caspase-8 inhibitor (z-IETD-fmk) significantly attenuated 23-HUA-induced DNA fragmentation. After 23-HUA-induced apoptosis, proteins expression levels of FasL, Fas and FADD constituting the death-inducing signaling complex (DISC) were upregulated in HL-60 cells. Moreover, transfection with Fas or FADD siRNA significantly blocked 23-HUA-induced DNA fragmentation and caspases activation. Taken together, these findings indicate that 23-HUA induces apoptosis in HL-60 human promyelocytic leukemia cells through formation of DISC and caspase-8 activation leading to loss of and caspase-3 activation.
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http://dx.doi.org/10.3390/molecules23123306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321063PMC
December 2018

Resveratrol analog, N-(4-methoxyphenyl)-3,5-dimethoxybenzamide induces G/M phase cell cycle arrest and apoptosis in HeLa human cervical cancer cells.

Food Chem Toxicol 2019 Feb 30;124:101-111. Epub 2018 Nov 30.

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul, 02447, Republic of Korea; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul, 02447, Republic of Korea. Electronic address:

In this study, several resveratrol analogs were synthesized and evaluated in search of a more effective anti-proliferative resveratrol analog. Among the evaluated resveratrol analogs, we have identified N-(4-methoxyphenyl)-3,5-dimethoxybenamide (MPDB) as a potent anti-proliferative compound. Treatment with MPDB resulted in G/M phase cell cycle arrest, which was accompanied by alteration of G/M-related protein expression and phosphorylation. MPDB-induced G/M arrest was blocked by transfection of ATM/ATR siRNAs, indicating the critical role of ATM/ATR in G/M phase arrest. In addition, treatment with MPDB displayed the activation of caspase and decreased Bcl-xl protein expression after 20 h in HeLa cells. Moreover, MPDB increased cytosolic cytochrome c release and Fas and Fas-L protein expression, indicating intrinsic and extrinsic apoptosis pathway, respectively. These results suggest that MPDB is a new and potent compound that induces ATM/ATR-dependent G/M phase cell cycle arrest and apoptosis, implicating it as a putative candidate in the investment of cervical cancer therapy.
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http://dx.doi.org/10.1016/j.fct.2018.11.062DOI Listing
February 2019
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