• Journal of Gastric Cancer
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• v.19 no.1
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• pp.121-131
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• 2019

Purpose: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. Materials and Methods: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED ($P_{NED}$) and demographic and clinicopathological parameters. Results: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. $P_{NED}$, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff $P_{NED}$ was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher $P_{NED}$. Tumors with ${\geq}10%$ NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. Conclusions: GC with ${\geq}10%$ NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.1
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• pp.26-33
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• 2019

Recently, the rapid growth of the companion animal market has led to the development of animal disease diagnosis kits. Therefore, the utility of the introduction of biomarkers for the development of animal molecular diagnostics is being reevaluated. A good biomarker should be precise and reliable, distinguish between normal and diseased states, and differentiate between different diseases. Recently reported genetic markers, tumor markers (cell free DNA, circulating tumor cells, granzyme, and skin tumors), and others (brucellosis, programmed death recovery-1, symmetric dimethylarginine, periostin, and cysteinyl leukotrien) have been developed. The biomarkers are used for risk prediction or for the screening, diagnosis, and monitoring of disease progression. The most important criteria for related biomarkers are disease specificity. Many potential biomarkers have emerged from laboratory and test studies, but they have not been validated in independent or large-scale clinical studies. Candidate biomarkers evaluate disease associations, verify the effectiveness of biomarkers for early detection and disease progression, and incorporate them into humans and animals. In the future, it will be necessary to reevaluate the utility of well-structured biomarker-based research and study the development of kits that can be used in on-site tests in accordance with the trends introduced in the diagnosis of animal diseases.

• Journal of the Korean Applied Science and Technology
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• v.36 no.1
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• pp.208-216
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• 2019

The purpose of this study was to investigated the biological activities such as cytotoxic, anti-oxidant and anti-inflammatory using Mentha arvensis L. extracts. Mentha arvensis L. was prepared by extracting with DW and 80% ethanol, after cell viability was assessed by MTT assay using RAW 264.7 cells. Antioxidant activities, and Anti-inflammatory activities measured through changes in the levels of reactive oxygen species (ROS), nitric oxide (NO), leukotrien B4 (LTB4), and anti- or in-flammatory cytokines($IL-1{\beta}$, IL-6, tumor necrosis factor $(TNF)-{\alpha}$, and IL-10) on LPS-induced RAW 264.7 cells. All test measured by ELISA reader and Luminex. Mentha arvensis L. was no cytotoxic in water and 80% ethanol extracts, and Concentration of 100 ug/ml of 80% ethanol extract was suppressed the productions of ROS in LPS-induced RAW 264.7 cells. Also, Productions of NO, LTB4, inflammatory or anti-inflammatory cytokines showed efficacy change that dose-independent of all extracts. In other words, Mentha arvensis L. showed significant biological activities showing anti-inflammatory, and anti-oxidant. These results may be developed as a raw material for new health food and therapeutics to ease the symptoms mentioned above.

• Bulletin of the Korean Chemical Society
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• v.10 no.3
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• pp.243-247
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• 1989

Two crystal structures of dehydrated $Ag^+\;and\;Ca^{2+}$ exchanged zeolite A, $Ag_2Ca_$5-A, reacting with 0.01 Torr of Cs vapor at $200^{\circ}C$ for 2 hours and 0.1 Torr of Cs vapor at $250^{\circ}C$ for 48 hours, respectively, have been determined by single crystal X-ray diffraction techniques. Their structures were solved and refined in the cubic space group Pm3m at $21(1)^{\circ}C$. The stoichiometry of first crystal was $Ag_2Ca_5$-A (a = 12.294(1)${\AA}$), indicating that Cs vapor did not react with cations in zeolite A and that of second crystal was $Ag_2Cs_{10}$-A (a = 12.166(1)${\AA}$), indicating that all $Ca^{2+}$ ions were reduced by Cs vapor and replaced by $Cs^+$ ions. Full-matrix least-squares refinements of $Ag_2Ca_5-A\;and\;Ag_2Cs_{10}$-A has converged to the final error indices, $R_1\;=\;0.041\;and\;R_2$ = 0.048 with 227 reflections, and $R_1\;=\;0.117\;an\;n\;fdd\;R_2$ = 0.120 with 167 reflections, respectively, for which I > $3{\sigma}$(I). In the structure of $Ag_2Ca_5$-A, both $Ag^+$ ions and $Ca^{2+}$ ions lie on two crystal symmetrically independent threefold axis sites on the 6-rings; $2\;Ag^+$ ions are recessed 0.33 ${\;AA}$ from the (111) planes of three O(3) oxygens and 5 $Ca^{2+}$ ions lie on the nearly center of each 6-oxygen planes. In the structure of $Ag_2Cs_{10}-A,\;Cs^+$ ions lie on the 5 different crystallographic sites. 3 $Cs^+$ ions lie at the centers of the 8-rings at sites of D4h symmetry. 6 $Cs^+$ ions lie on the threefold axes of unit cell: $4\;Cs^+$ ions are found deep in the large cavity and 2 $Cs^+$ ions are found in the sodalite cavity. One $Cs^+$ ion is found in the large cavity near a 4-ring.

• Proceedings of the KSAR Conference
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• 2001.03a
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• pp.52-52
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• 2001

Many nucleoside diphosphate (NDP) kinases are ubiquitous enzymes responsible for the exchange of ${\gamma}$-phosphates between tri- and diphosphonucleosides. The catalytic Many nucleoside diphosphate (NDP) kinases are ubiquitous enzymes responsible for the exchange of ${\gamma}$-phosphates between tri- and diphosphonucleosides. The catalytic reaction follows a ping-pong mechanism in which the enzyme is transiently phosphorylated on a histidine residue conserved in all nucleoside diphosphate kinases. Beside their role in nucleotide synthesis, these enzymes present additional functions, possibly independent of catalysis, in processes such as differentiation, cell growth, tumor progression, metastasis and development. To clone murine nm23-M5, several expressed sequence tags (ESTs) of the GenBank data base, selected according to their homology to nm23-H5 cDNA, reconstituted a complete open reading frame (GenBank AF222750). To test whether murine NDPKs (1, 2, 3, 4, 5, and 6) can inhibit Bax-mediated toxicity in yeast, co-transformation was performed respectively. The yeast S.cerevisiae was transformed with a copy expression plasmid containing the histidine selection marker and expressing murine Bax under the control of a galactose-inducible promoter. Several clones were selected and found to be growth inhibited when Bax expression was induced with galactose. A representative clone was transformed again with a copy expression plasmid containing the tryptophane selection marker and expressing either murine Bcl-xL or NDPK under the control of a galactose-inducible promoter. Several subclones of the double-transformants were selected and characterized. The ability of Bcl-xL and NDPKs to suppress Bax-mediated toxicity was determined by growing yeast cells overnight in galactose media and spot-testing on galactose plates starting with an equal number of yeast cells as determined by taking the OD$_{600}$. Ten-fold serial dilutions were used in the spot-test. Plates were grown at 3$0^{\circ}C$ for 2-3 days. All murine NDPKs suppressed Bax dependent apoptosis. Futher study will be peformed whether Bax-toxicity inhibition was caused by NDP kinase activity or additional function.n.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.83-83
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• 2003

The lutropin/choriogonadotropin receptor (LHR) is a member of the rhodopsin-like subfamily of G protein coupled receptor (GPCRs), that has been shown to mediate the internalization of its two naturally occurring agonist, lutropin and choriogonadotropin (CG). The clustered agonist-receptor complex is internalized by a dynamin-dependent pathway and traverses the endosomal compartment without agonist dissociation Dissociation of the agonist-receptor complex occurs in the lysosomes, where both the agonist and receptor are degrade. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty (FMPP). A FMPP is a form of sexual precocious puberty in boys in which testosterone levels are elevated independent of changes in luteinizing hormone-releasing hormone and serum luteinizing hormone levels, We have now analyzed two naturally occurring, constitutively active mutants of the human LHR. These mutations were introduced into the rat LHR (rLHR) and are designated L435R and D556Y. Cells expressing rLHR-D556Y bind human choriogonadotropin (hCG) with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. Cells expressing rLHR-L435R also bind hCG with normal affinity, exhibit a 47-fold increase in basal cAMP, and do not respond to hCG with a further increase in cAMP accumulation. This mutation enhances the internalization of the free and agonist-occupied receptors ~2- and ~17- fold, respectively We conclude that the state of activation of the rLHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing rLHR-L435R is due to the fast rate of internalization of the bound hCG. The finding that membranes expressing rLHR-L435R respond to hCG with an increase in adenylyl cyclase activity supports this suggestion. Autonomous Leydig cell activity in FMPP is caused by a constitutively activating LH/CGR.

• Fisheries and Aquatic Sciences
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• v.26 no.3
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• pp.204-215
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• 2023

The thermolabile haemolysin (tlh) of Vibrio parahaemolyticus (Vptlh) from V. parahaemolyticus is a multiple-function enzyme, initially describes as a haemolytic factor activated by lecithin and phospholipase A2 enzymatic activity (Shinoda, 1991; Vazquez-Morado, 2021; Yanagase et al., 1970). Until now, the tlh structure has hypothesized including N-terminal and C-terminal domain, but what domain of the Vptlh structure does the haemolytic activity has not been refined yet. In this study, a 450-bp VpTLH nucleotide sequence of the entire Vptlh gene encoded the C-terminal domain cloned firstly to examine its responsibility in the activity of the Vptlh. The C-terminal domain fused with a 6-His-tag named the His-tag-VpC-terminal domain was expressed successfully in soluble form in the BL21 (DE3) PlysS cell. Remarkably, both expression and purification results confirmed a high agreement in the molecular weight of the His-tag-VpC-terminal domain was 47 kDa. This work showed the His-tag-VpC-terminal domain lysed the erythrocyte membranes in the blood agar and the phosphate buffered saline (0.9%) media without adding the lecithin substrate of the phospholipase enzyme. Haemolysis occurred at all tested diluted concentrations of His-tag-VpC-terminal domain (p < 0.05), providing evidence for the independent haemolytic activity of the His-tag-VpC-terminal domain. The content of 100 ㎍ of the His-tag-VpC-terminal domain brought the highest haemolytic activity of 80% compared to that in the three remaining contents. Significantly, the His-tag-VpC-terminal domain demonstrated not to involve the phospholipase activity in Luria-Bertani agar supplemented with 1% (vol/vol) egg yolk emulsion. All results proved the vital responsibility of the His-tag-VpC-terminal domain in causing the haemolytic activity without the required activation by the phospholipase enzyme. Raw extracts of Phellinus igniarus and Phellinus pipi at 10^-1 mg/mL inhibited the haemolytic activity of the His-tag-VpC-terminal domain from 67.7% to 87.42%, respectively. Hence applying the His-tag-VpC-terminal domain as a simple biological material to evaluate quickly potential derivatives against the Vptlh in vivo conditions will accessible and more advantageous than using the whole of the Vptlh.

• Journal of Life Science
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• v.32 no.3
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• pp.210-221
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• 2022

This study investigated the mechanisms underlying the anti-cancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) in human cancer cells in combination with either N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, or MHY2245, a new synthetic sirtuin 1 inhibitor. The results showed both DAPT and MHY2245 as novel chemosensitizers of human colon cancer KM12 and human hepatocellular carcinoma SNU475 cells to NSAIDs involving celecoxib and 2, 5-dimethyl celecoxib. The NSAID-induced cytotoxicity of these cells was significantly increased by DAPT and MHY2245 in a cyclooxygenase-2 independent manner. In addition, DAPT and MHY2245 reduced levels of p62, Notch1 intracellular domain, and multiple cancer stemness (CS)-related markers including Notch1, CD44, CD133, octamer-binding transcription factor 4, mutated p53 and c-Myc. However, the level of activating transcription factor 4 (ATF4) was enhanced, probably indicating the down-regulation of multiple CS-related markers by DAPT or MHY2245-mediated autophagy induction. Moreover, the NSAID-mediated reduction of p62/nuclear factor erythroid-derived 2-like 2 and CS-related marker proteins and the up-regulation of C/EBP homologous protein (CHOP)/ATF4 were accelerated by DAPT and MHY2245. As such, the combination of NSAID and either DAPT or MHY2245 resulted in higher cytotoxicity than NSAID alone by accelerating the down-regulation of multiple CS-related markers and PARP activation, indicating that both inhibitors promote NSAID-mediated autophagic cell death, possibly through the CHOP/ATF4 pathway. In conclusion, either combination strategy may be useful for the effective treatment of human cancer cells expressing CS-related markers.

• Korean Journal of Radiology
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• v.22 no.6
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• pp.994-1004
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• 2021

Objective: To extract pulmonary and cardiovascular metrics from chest CTs of patients with coronavirus disease 2019 (COVID-19) using a fully automated deep learning-based approach and assess their potential to predict patient management. Materials and Methods: All initial chest CTs of patients who tested positive for severe acute respiratory syndrome coronavirus 2 at our emergency department between March 25 and April 25, 2020, were identified (n = 120). Three patient management groups were defined: group 1 (outpatient), group 2 (general ward), and group 3 (intensive care unit [ICU]). Multiple pulmonary and cardiovascular metrics were extracted from the chest CT images using deep learning. Additionally, six laboratory findings indicating inflammation and cellular damage were considered. Differences in CT metrics, laboratory findings, and demographics between the patient management groups were assessed. The potential of these parameters to predict patients' needs for intensive care (yes/no) was analyzed using logistic regression and receiver operating characteristic curves. Internal and external validity were assessed using 109 independent chest CT scans. Results: While demographic parameters alone (sex and age) were not sufficient to predict ICU management status, both CT metrics alone (including both pulmonary and cardiovascular metrics; area under the curve [AUC] = 0.88; 95% confidence interval [CI] = 0.79-0.97) and laboratory findings alone (C-reactive protein, lactate dehydrogenase, white blood cell count, and albumin; AUC = 0.86; 95% CI = 0.77-0.94) were good classifiers. Excellent performance was achieved by a combination of demographic parameters, CT metrics, and laboratory findings (AUC = 0.91; 95% CI = 0.85-0.98). Application of a model that combined both pulmonary CT metrics and demographic parameters on a dataset from another hospital indicated its external validity (AUC = 0.77; 95% CI = 0.66-0.88). Conclusion: Chest CT of patients with COVID-19 contains valuable information that can be accessed using automated image analysis. These metrics are useful for the prediction of patient management.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.1
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• pp.40-46
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• 2022

Backgrounds/Aims: The role of inflammation in malignant cell proliferation has been well described. High values of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers of systemic inflammation have shown associations with unfavorable long-term outcomes. The purpose of this study was to determine values of NLR and PLR evaluated prior to and after surgery and their associations with mortality and recurrence rates of liver transplant patients with hepatocellular carcinoma (HCC). Methods: A total of 105 patients with HCC who underwent orthotopic liver transplantation (OLT) were retrospectively reviewed. NLR and PLR values were obtained from complete blood counts prior to and after surgery. Overall survival (OS) and recurrence-free survival (RFS) in relation with delta NLR and PLR were estimated. Results: Serum alpha-fetoprotein levels > 100 ng/mL (p = 0.014) and lymphovascular emboli in the specimen (p = 0.048) were identified to be significant predictors of RFS. Child-Pugh score (p = 0.016) was found to be an independent factor associated with poorer OS. An increasing delta PLR was associated with worse RFS, although it showed no significant association with OS. Conclusions: The analysis of PLR as a continuous variable may predict recurrence outcomes in patients undergoing OLT for HCC. It is more representative than isolated values.