• Journal of Microbiology and Biotechnology
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• v.29 no.10
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• pp.1665-1674
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• 2019

Zika virus (ZIKV) is a mosquito-transmitted, emerging Flavivirus that causes Guillain-$Barr{\acute{e}}$ syndrome and microcephaly in adults and fetuses, respectively. Since ZIKV was first isolated in 1947, severe outbreaks have occurred at various places worldwide, including Yap Island in 2007, French Polynesia in 2013, and Brazil in 2015. Although incidences of ZIKV infection and dissemination have drastically increased, the mechanisms underlying the pathogenesis of ZIKV have not been sufficiently studied. In addition, despite extensive research, the exact roles of individual ZIKV genes in the viral evasion of the host innate immune responses remain elusive. Besides, it is still possible that more than one ZIKV-encoded protein may negatively affect type I interferon (IFN) induction. Hence, in this study, we aimed to determine the modulations of the IFN promoter activity, induced by the MDA5/RIG-I signaling pathway, by over-expressing individual ZIKV genes. Our results show that two nonstructural proteins, NS2A and NS4A, significantly down-regulated the promoter activity of IFN-${\beta}$ by inhibiting multiple signaling molecules involved in the activation of IFN-${\beta}$. Interestingly, while NS2A suppressed both full-length and constitutively active RIG-I, NS4A had inhibitory activity only on full-length RIG-I. In addition, while NS2A inhibited all forms of IRF3 (full-length, regulatory domain-deficient, and constitutively active), NS4A could not inhibit constitutively active IRF3-5D. Taken together, our results showed that NS2A and NS4A play major roles as antagonists of MDA5/RIG-I-mediated IFN-${\beta}$ induction and more importantly, these two viral proteins seem to inhibit induction of the type I IFN responses in differential mechanisms. We believe this study expands our understanding regarding the mechanisms via which ZIKV controls the innate immune responses in cells and may pave the way to development of ZIKV-specific therapeutics.

• BMB Reports
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• v.55 no.2
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• pp.98-103
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• 2022

Increased mRNA levels of cancer upregulated gene (CUG)2 have been detected in many different tumor tissues using Affymetrix microarray. Oncogenic capability of the CUG2 gene has been further reported. However, the mechanism by which CUG2 overexpression promotes cancer stem cell (CSC)-like phenotypes remains unknown. With recent studies showing that pyruvate kinase muscle 2 (PKM2) is overexpressed in clinical tissues from gastric, lung, and cervical cancer patients, we hypothesized that PKM2 might play an important role in CSC-like phenotypes caused by CUG2 overexpression. The present study revealed that PKM2 protein levels and translocation of PKM2 into the nucleus were enhanced in CUG2-overexpressing lung carcinoma A549 and immortalized bronchial BEAS-2B cells than in control cells. Expression levels of c-Myc, CyclinD1, and PKM2 were increased in CUG2-overexpressing cells than in control cells. Furthermore, EGFR and ERK inhibitors as well as suppression of Yap1 and NEK2 expression reduced PKM2 protein levels. Interestingly, knockdown of β-catenin expression failed to reduce PKM2 protein levels. Furthermore, reduction of PKM2 expression with its siRNA hindered CSC-like phenotypes such as faster wound healing, aggressive transwell migration, and increased size/number of sphere formation. The introduction of mutant S37A PKM2-green fluorescence protein (GFP) into cells without ability to move to the nucleus did not confer CSC-like phenotypes, whereas forced expression of wild-type PKM2 promoted such phenotypes. Overall, CUG2-induced increase in the expression of nuclear PKM2 contributes to CSC-like phenotypes by upregulating c-Myc and CyclinD1 as a co-activator.

• Archives of Plastic Surgery
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• v.49 no.2
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• pp.195-199
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• 2022

Nasolacrimal duct (NLD) damage is associated in the majority of type II and III naso-orbito-ethmoid (NOE) fractures. Our study aims to investigate the efficacy and safety of prophylactic NLD intubation in the setting of facial fractures, by comparing incidence of postoperative epiphora and wound infection. A retrospective matched control study was conducted on all patients with surgically treated facial fractures from 2008 to 2013 (n=280) (IRB ref number: DSRB 2013/01198). Patients with the following fracture types were included: NOE (n=16), frontal sinus (n=2), Le Fort II/III (n=8), and > 1 type (n=48). All patients in this study were included with the intention to treat. The study group comprised patients who were intubated, while the control group patients were not intubated. Each group had 37 patients matched for age, gender, fracture type, and injury type. A single oculoplastic surgeon skilled in lacrimal surgery performed the procedure for all intubated patients. Patients with more severe and complex facial fractures were intubated with bicanalicular Crawford stents. Postoperative epiphora and infective complications (both facial wound and dacryocystitis) were assessed at 1, 3, 6, and 12 months. There was no significant difference in incidence of either postoperative epiphora (p=0.152) or wound infection (p=0.556) comparing both groups. Reduced incidence of postoperative epiphora in the study group is statistically not significant and does not support the need for prophylactic intubation. If radiographic evidence of NLD disruption or regurgitation seen on syringing on the NLD intraoperatively is present, intubation is safe and efficacious only if performed by an expert.

• Archives of Plastic Surgery
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• v.50 no.4
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• pp.370-376
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• 2023

Background The posterior ledge (PL) is a vital structure that supports the implant posteriorly during orbital floor reconstruction. This study describes a technique for mapping the PL in relation to the infraorbital margin (IM) in patients with orbital floor blowout fractures. This study establishes the location of the optic foramen in relation to the PL. Methods Facial computed tomography (FCT) scans of 67 consecutive patients with isolated orbital floor blowout fractures were analyzed using Osirix. Planes of reference for orbital fractures, a standardized technique for performing measurements on FCT, was used. Viewed coronally, the orbit was divided into seven equal sagittal slices (L1 laterally to L7 medially) with reference to the midorbital plane. The distances of PL from IM and location of optic foramen were determined. Results The greatest distance to PL is found at L5 (median: 30.1 mm, range: 13.5-37.1 mm). The median and ranges for each slice are as follows: L1 (median: 0.0 mm, range: 0.0-19.9 mm), L2 (median: 0.0 mm, range: 0.0-21.5 mm), L3 (median: 15.8 mm, range: 0.0-31.7 mm), L4 (median: 26.1 mm, range: 0.0-34.0 mm), L5 (median: 30.1 mm, range: 13.5-37.1 mm), L6 (median: 29.0 mm, range: 0.0-36.3 mm), L7 (median: 20.8 mm, range: 0.0-39.2 mm). The median distance of the optic foramen from IM is 43.7 mm (range: 37.0- 49.1) at L7.

• Journal of Preventive Medicine and Public Health
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• v.57 no.3
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• pp.288-297
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• 2024

Objectives: This study explored the prevalence and predictors of alcohol and cannabis co-use among 9263 Filipino adolescents, using data from the 2019 Global School-based Student Health Survey (GSHS). Methods: We conducted a cross-sectional secondary analysis of the GSHS, targeting adolescents aged 13-17 years and excluding cases with incomplete data on alcohol and cannabis use. Our analysis employed the bivariate chi-square test of independence and multivariable logistic regression using Stata version 18 to identify significant predictors of co-use, with a p-value threshold set at 0.05. Results: The weighted prevalence of co-users was 4.2% (95% confidence interval [CI], 3.4 to 5.3). Significant predictors included male sex (adjusted odds ratio [aOR], 4.50; 95% CI, 3.31 to 6.10; p<0.001) and being in a lower academic year, specifically grade 7 (aOR, 4.08; 95% CI, 2.39 to 6.99; p<0.001) and grade 8 (aOR, 2.20; 95% CI, 1.30 to 3.72; p=0.003). Poor sleep quality was also a significant predictor (aOR, 1.77; 95% CI, 1.29 to 2.44; p<0.001), as was a history of attempted suicide (aOR, 5.31; 95% CI, 4.00 to 7.06; p<0.001). Physical inactivity was associated with lower odds of co-use (aOR, 0.45; 95% CI, 0.33 to 0.62; p<0.001). Additionally, non-attendance of physical education classes (aOR, 1.48; 95% CI, 1.06 to 2.05; p=0.021), infrequent unapproved parental checks (aOR, 1.37; 95% CI, 1.04 to 1.80; p=0.024), and lower parental awareness of free-time activities (aOR, 0.63; 95% CI, 0.45 to 0.87; p=0.005) were associated with higher odds of co-use. Factors not significantly linked to co-use included age group, being in grade 9, always feeling lonely, having no close friends, being bullied outside school, and whether a parent or guardian understood the adolescent's worries. Conclusions: The findings highlight the critical need for comprehensive interventions in the Philippines, addressing not only physical inactivity and parental monitoring but also focusing on sex, academic grade, participation in physical education classes, sleep quality, and suicide attempt history, to effectively reduce alcohol and cannabis co-use among adolescents.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.191-201
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• 2023

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.

• Journal of Pharmacopuncture
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• v.7 no.3
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• pp.5-25
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• 2004

Objectives : To observe changes in the serum proteins before and after intravenous injection of wild ginseng herbal acupuncture. Methods : Blood was collected before and after the administration of wild ginseng herbal acupuncture and only the serum was centrifuged. Then differences in the spots on the scanned image after running 2-Dimensionl electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of wild ginseng herbal acupuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 803, 1505, 2205, 3105, 7104, 9001 spots, with more than one-time increase were 1101, 1302, 2013, 3009, 3010, 4002, 4009, 6706, 7103, 8006, 8101, and spots with decrease were 205, 801, 3205, 5202, 6105. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1101 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAP1 protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein L1, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as Transferrin, 9001 as(Alpha-Oxy, Beta-(C112g)deoxy) T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d, which acts against microbes and pathogenic organisms, and Antitrypsin(803), which is secreted with inflammatory response in the lungs, were increased by more than 200% after the administration of herbal acupuncture. 5. Immunoglobulin lambda chain(3105), Alpha-Oxy, Beta-(C112g)deoxy T-State Human Hemoglobin(9001), and human hemoglobin(9003) were increased by more than two-times after the administration of herbal acupuncture. 6. Proapolipoprotein(2013, 3010) and apolipoprotein(7104), key components of the HDL-cholesterol which plays an important role in preventing arteriosclerosis, were increased after the administration of herbal acupuncture. 7. Vitamin D binding protein(DBP, 2403), protecting the lung at the time of inflammatory response, was increased after the administration of herbal acupuncture. 8. Transthyretin(TTR, 3205), which is the main protein causing familial aimyloid polyneuropathy(FAP), was decreased after the administration of herbal acupuncture. 9. Ras-related protein Ral-A(4002) that controls phospholipid metabolism, cytoskeletal formation, and membrane traffic, was increased after the administration of herbal acupuncture. 10. Testis-specific protein Y(8006), which takes part in determination of the gender, was increased by more than two-times after the administration of herbal acupuncture. 11. Transferrin(8101), T-State Human Hemoblobin(9001), and Human Hemoblobin(9003) which balances the iron level in the body, were increased after the administration of herbal acupuncture. Conousion : Above results support the notion that intravenous injection of cultivated wild ginseng herbal acupuncture induce changes in serum proteins and this research can be a pioneer work in finding biomarkers.

• Journal of the Korean earth science society
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• v.26 no.5
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• pp.395-403
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• 2005

This study is focused on the relationship between snowfall and the Bowen’s Ratio (sensible heat flux/latent heat flux) through calculation of heat exchange between air and sea for snowfall events in Jeju Island from 1993 to 2003. The four weather stations for this study are located at Jeju, Seoguipo, Seongsanpo and Gosan in Jeju Island. In order to improve the reliability of snowfall forecast, the Bowen’s Ratio for snowfall, which includes influences from the atmosphere such as wind, is compared with the temperature difference between air and sea for snowfall. As a results, in the case for fresh snowfall, the minimum temperature differences between air and sea were 10, 12.3, 11.5, and $14.3^{\circ}C$ at Jeju, Seoguipo, Seongsanpo and Gosan, respectively. The probabilities of fresh snowfall were 26, 29, 13, and $23\%$, respectively, when the temperature differences were higher than the previous values. On the other hand, the minimum Bowen ratios were 0.59, 0.60, 0.65 and 0.65 at Jeju, Seoguipo, Seongsanpo and Gosan, respectively. The probabilities of fresh snowfall were 33, 70, 31 and $58\%$ respectively, when the Bowen ratio is higher than those. The reason for this is because the probability of fresh snowfall with the Bowen ratio was higher than the probability with temperature difference between air and sea. This result occurred because heat exchange by wind increased the probability of snowfall, along with the temperature difference between air and sea, and the Bowen ratio. Therefore, snowfall forecast of Jeju Island is significantly influenced by the sea, whereas forecast with Bowen ratio seems to have higher reliability than that with the temperature difference between air and sea. The data analysis for the ten-year period $(1993\~2002)$ showed that when each fresh snowfall was within 0.0 to 0.9cm, the average Bowen’s ratio was 0.63 to 0.67, and when each fresh snowfall was 1.0 to 4.9 cm, the average Bowen’s ratio was over 0.72. Therefore, fresh snowfall shows a proportional relationship with the Bowen’s ratio during snowfall.