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Abstract The relation between the improvement of mechanical quality factor (Qm) and internal electric field (Ei) generated during the aging process in lead‐free piezoelectric BiFeO3‐BaTiO3 ceramics is investigated for hard piezoelectric application of power transducers. The change of built‐in Ei depends on the ferroelectric polarization (P) direction during the aging process. For the aging process with P parallel to Ei, Qm and Ei increases but Qm and Ei decreases with P antiparallel to Ei. These results are attributed to the migration of defects by depolarization fields and domain‐wall pinning. This work provides the systematic guidance to develop high‐power piezoelectric transducers with lead‐free ceramics.

Subscription to multiple subscription video-on-demand (SVOD) services, known as multi-homing, is increasingly prevalent. This research explores the relationship between multi-homing and traditional media consumption and identifies the key factors that predict multi-homing tendencies among SVOD users. We analyzed data from 2019 to 2021 across the U.S., Canada, China, Japan, Germany, and France to investigate the impact of SVOD usage on legacy media viewing time, and then explored the predictors of multi-homing behaviors. Our findings indicate that multi-homing users are more inclined to consume content on legacy media platforms, such as terrestrial or cable television, compared with single-homing users. Critical differentiators between multi-homing and single-homing users include demographic profiles, lifestyle preferences, content expectations, and usage habits, particularly in terms of account sharing and primary devices for content consumption. These results are crucial for both SVOD and traditional media providers, as they offer strategic guidance for companies to effectively operate in various international markets. Such a comprehensive analysis of multi-homing behavior also offers a new perspective on the dynamics of global media consumption.

Abstract Recently, HfO2‐based ferroelectric thin films have attracted widespread interest in developing next‐generation nonvolatile memories. To form a metastable ferroelectric orthorhombic phase in HfO2, a post‐annealing process is typically necessary. However, the microscopic mechanism underlying the effect of annealing temperature on ferroelectric domain nucleation and growth is still obscure, despite its importance in optimizing the operation speed of HfO2‐based devices. In this study, the ferroelectric properties and polarization switching of Hf0.5Zr0.5O2 thin films annealed at different temperatures (550–700 °C) are systematically investigated. Evidently, the crystal structure, remnant polarization, and dielectric constant monotonically change with annealing temperature. However, microscopic piezoresponse force microscopy images as well as macroscopic switching current measurements reveal non‐monotonic changes in the polarization switching speed with annealing temperature. This intriguing behavior is ascribed to the difference in the ferroelectric‐domain nucleation process induced by the amount of oxygen vacancies in the Hf0.5Zr0.5O2 thin films annealed at different temperatures. This work demonstrates that controlling the defect concentration of ferroelectric HfO2 by tuning the post‐annealing process is critical for optimizing device performance, particularly polarization switching speed.

Background/Aims: H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA. However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis. Methods: A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared. Results: According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different. Conclusions: DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).

Human iPSC-derived cardiac organoids (hiPSC-COs) for cardiotoxicity drug testing via the variety of cell lines and unestablished protocols may lead to differences in response results due to a lack of criteria for generation period and size. To ensure reliable drug testing, it is important for researchers to set optimal generation period and size of COs according to the cell line and protocol applied in their studies. Hence, we sought to propose a process to establish minimum criteria for the generation duration and size of hiPSC-COs for cardiotoxic drug testing. We generated hiPSC-COs of different sizes based on our protocol and continuously monitored organoids until they indicated a minimal beating rate change as a control that could lead to more accurate beating rate changes on drug testing. Calcium transients and physiological tests to assess the functionality of hiPSC-COs on selected generation period, which showed regular cardiac beating, and immunostaining assays to compare characteristics were performed. We explained the generation period and size that exhibited and maintained regular beating rate changes on hiPSC-COs, and lead to reliable response results to cardiotoxicity drugs. We anticipate that this study will offer valuable insights into considering the appropriate generation period and size of hiPSC-COs ensuring reliable outcomes in cardiotoxicity drug testing.

Background/Aims: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the stomach. We evaluated the clinical outcomes of endoscopic treatment for gastric GISTs. Methods: This is a single center, retrospective study that enrolled 135 cases of gastric subepithelial tumors (SETs) resected by endoscopic procedures and confirmed as GISTs by histopathology from March 2005 to July 2019. The immediate and long-term clinical outcomes were analyzed retrospectively. Results: The mean patient age was 57.9 years, and the mean tumor size was 2.1 cm. Of the tumors, 43.0% were located in the body, followed by the fundus (26.7%) and cardia (17.0%). Most tumors (85.2%) were resected by endoscopic submucosal dissection, followed by endoscopic mucosal resection (6.7%), submucosal tunneling endoscopic resection (5.9%), and endoscopic full-thickness resection (2.2%). Macroperforation occurred in 4.4% and microperforation in 6.7% of the cases. The R0 resection rate was 15.6%. However, the rate of complete resection by the endoscopic view was 90.4%, of which 54.8% of cases were in the very-low-risk group, followed by the low-risk group (28.1%), intermediate-risk group (11.9%), and high-risk group (5.2%). During 36.5 months of follow-up, recurrence was found in four (3.4%) of the 118 patients who were monitored for more than 6 months (low-risk group, 1/37 [2.7%]; intermediate-risk group, 2/11 [18.2%]; high-risk group, 1/6 [16.7%]). Conclusions: Endoscopic treatment of a GIST appears to be a feasible procedure in selected cases. However, additional surgery should be considered if the pathologic results correspond to intermediate- or high-risk groups.

Electroporation is pivotal in bioelectrochemistry for cellular manipulation, with prominent applications in drug delivery and cell membrane studies. A comprehensive understanding of pore generation requires an in-depth analysis of the critical pore size and the corresponding energy barrier at the onset of cell rupture. However, many studies have been limited to basic models such as artificial membranes or theoretical simulations. Challenging this paradigm, our study pioneers using a microfluidic electroporation chip array. This tool subjects live breast cancer cell species to a diverse spectrum of alternating current electric field conditions, driving electroporation-induced cell rupture. We conclusively determined the rupture voltages across varying applied voltage loading rates, enabling an unprecedented characterization of electric cell rupture dynamics encompassing critical pore radius and energy barrier. Further bolstering our investigation, we probed cells subjected to cholesterol depletion via methyl-β-cyclodextrin and revealed a strong correlation with electroporation. This work not only elucidates the dynamics of electric rupture in live cell membranes but also sets a robust foundation for future explorations into the mechanisms and energetics of live cell electroporation.

Vapours from origanum oil (O) and thyme oil (T) were applied to the four soil-borne strawberry pathogens Fusarium oxysporum f. sp. fragariae, Colletotrichum fructicola, Lasiodiplodia theobromae, and Phytophthora cactorum, causing Fusarium wilt, anthracnose, dieback, and Phytophthora rot, respectively. Increasing T vapour doses in the presence of O vapour strongly inhibited mycelial growths of the four pathogens and vice versa. When mycelia of F. oxysporum f. sp. fragariae and P. cactorum exposed to the combined O + T vapours were transferred to the fresh media, mycelial growth was restored, indicating fungistasis by vapours. However, the mycelial growth of C. fructicola and L. theobromae exposed to the combined O + T vapours have been slightly retarded in the fresh media. Prolonged exposure of strawberry pathogens to O + T vapours in soil environments may be suggested as an alternative method for eco-friendly disease management.

Background/Aims: Endoscopic submucosal dissection (ESD) of gastric neoplasm involving the pyloric channel (GNPC) is technically challenging due to difficulty in precise assessment of resection margin and inadequate visualization. The aim of this study was to evaluate the effectiveness and long-term outcome of ESD for GNPC and introduce a noble technique for resection of GNPC. Methods: A total of 97 patients with GNPC underwent ESD from January 2007 to October 2017. We divided them into a conventional anterograde resection group and a retrograde resection group according to the method of procedure. We compared their clinical outcomes and investigated risk factors for postprocedural complications. Results: The en bloc resection rate was 87.6%, and complete resection rate was 83.5%. Postprocedure stenosis occurred in 16 cases (16.5%). GNPCs of the retrograde resection group were more frequently located from antrum to bulb, were significantly larger, were related to ≥75% resection of the circumference, and involved significantly longer procedure times than those in the anterograde resection group. Multivariate analysis showed that resection ≥75% of the circumference was the only significant risk factor for postprocedure stenosis. Conclusions: ESD by retrograde resection method is a novel technique to make the procedure easier, depending on the size, location, and circumference of resection.

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from the bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, a higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to the reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating the acquisition of a rapid supply of ATP for proliferation in AML. Therefore, the targeting of mesothelin presents a potentially promising approach to mitigating the progression of AML through the inhibition of glycolysis and mitochondrial respiration in myeloid cells.

Merremia umbellata Hallier f. (MU) has been used as an anti-inflammatory agent to treat burns and scales. However, the potential anti-inflammatory mechanisms of action of this plant have not been elucidated. This study aimed to assess the antioxidant and anti-inflammatory effects of the leaf and shoot of MU grown in Bangladesh. The MU extract exhibited antioxidant activities as demonstrated by DPPH and ABTS free-radical-scavenging activities and the total polyphenol and total flavonoid contents. MU extract significantly reduced the lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW264.7 macrophage. Accordingly, the gene levels of inducible NO synthase and cyclooxygenase-2 were suppressed. The MU extract alleviated the LPS-induced expression of TLR4, NF-κB, and inflammatory cytokines (TNF-α, IL-6, and IL-1β). The constituents of a MU extract were tentatively identified using UHPLC-PDA-QTOF/MS techniques. The main compounds were identified as 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, quercitrin, and 4,5-dicaffeoylquinic acid. Molecular docking analysis revealed that these compounds interact with TLR4 protein, with quercitrin showing the highest binding affinity among them. Overall, our findings demonstrate the antioxidant and in vitro anti-inflammatory activities of MU and its potential compounds to target the TLR4-NF-κB signaling pathway. These findings are potentially used to further explore promising natural food ingredients that are effective in regulating inflammation.

Polycomb group proteins (PcG) play a crucial role in developmental programs in eukaryotic organisms, including plants. PcG-mediated gene repression is achieved by epigenetic histone modification on target chromatins. Loss of PcG components leads to severe developmental defects. CURLY LEAF (CLF), a PcG component in Arabidopsis, catalyzes the trimethylation of histone H3 on lysine 27 (H3K27me3), a repressive histone mark in numerous genes in Arabidopsis. In this study, we isolated a single homolog of Arabidopsis CLF, namely, BrCLF, in Brassica rapa ssp. trilocularis. Transcriptomic analysis revealed that BrCLF participated in B. rapa developmental processes, such as seed dormancy, leaf and flower organ development, and floral transition. BrCLF was also involved in stress signaling and stress-responsive metabolism, such as aliphatic and indolic glucosinolate metabolism in B. rapa. Epigenome analysis showed that H3K27me3 was substantially enriched in genes related to these developmental and stress-responsive processes. Thus, this study provided a basis for elucidating the molecular mechanism of the PcG-mediated regulation of development and stress responses in B. rapa.

Glucosinolates (GSLs) are secondary metabolites providing defense against pathogens and herbivores in plants, and anti-carcinogenic activity against human cancer cells. Profiles of GSLs vary greatly among members of genus Brassica. In this study, we found that a reference line of Chinese cabbage (B. rapa ssp. pekinensis), ‘Chiifu’ contains significantly lower amounts of total GSLs than the oilseed-type B. rapa (B. rapa ssp. trilocularis) line ‘LP08’. This study aimed to identify the key regulators of the high accumulation of GSLs in Brassica rapa plants using transcriptomic and linkage mapping approaches. Comparative transcriptome analysis showed that, in total, 8,276 and 9,878 genes were differentially expressed between ‘Chiifu’ and ‘LP08’ under light and dark conditions, respectively. Among 162 B. rapa GSL pathway genes, 79 were related to GSL metabolism under light conditions. We also performed QTL analysis using a single nucleotide polymorphism-based linkage map constructed using 151 F5 individuals derived from a cross between the ‘Chiifu’ and ‘LP08’ inbred lines. Two major QTL peaks were successfully identified on chromosome 3 using high-performance liquid chromatography to obtain GSL profiles from 97 F5 recombinant inbred lines. The MYB-domain transcription factor gene BrMYB28.1 (Bra012961) was found in the highest QTL peak region. The second highest peak was located near the 2-oxoacid-dependent dioxygenase gene BrGSL-OH.1 (Bra022920). This study identified major genes responsible for differing profiles of GSLs between ‘Chiifu’ and ‘LP08’. Thus, our study provides molecular insights into differences in GSL profiles between vegetative- and oilseed-type B. rapa plants.

Abstract Vernalization is the process by which long-term cold like winter triggers transition to flowering in plants. Many biennial and perennial plants including Brassicaceae family plants require vernalization for floral transition. Not only floral transition, but dynamic physiological and metabolic changes might also take place during vernalization. However, vernalization-mediated metabolic change is merely investigated so far. One of secondary metabolites found in Brassiceceae family plants is glucosinolates (GSLs). GSLs provides defense against pathogens and herbivores attack in plants and also exhibits inhibitory activity against human cancer cell. Profiles of GSLs are highly modulated by different environmental stresses in Brassciaceae family plants. To grasp the effect of vernalization on GSLs metabolic dynamics in radish (Raphanus sativus L.), we performed transcriptomic and metabolic analysis during vernalization in radish. Through transcriptome analysis, we found many GSLs metabolic genes were significantly down-regulated by vernalization in radish plants. Ultra-High Performance Liquid Chromatography analysis also revealed that GSLs compounds were substantially reduced in vernalized radish samples compared to non-vernalized radish samples. Furthermore, we found that repressive histone modification (i.e. H3K27me3) is involved in the modulation of GSLs metabolism via epigenetic suppression of Glucoraphasatin Synthase 1 (GRS1) during vernalization in radish. This study revealed that GSLs metabolism is modulated by vernalization, suggestive of a newly identified target of vernalization in radish.

Constipation is a common disease that reduces life quality. Drugs of various mechanisms are being developed to resolve this affliction. Intestinal motility can be easily monitored in zebrafish, and so we selected this organism to develop a constipation model to measure drug-induced prokinetic effects. In this study, intestinal motility was monitored in zebrafish by tracking intestinal transit using fluorescence, after which an opioid-induced constipation model was established using loperamide. We then evaluated the prokinetic effect of diatrizoate meglumine (Gastrografin®), which has been empirically used to treat post-operative ileus or adhesive small bowel obstructions. Diatrizoate meglumine was effective in promoting bowel movements in an opioid-induced zebrafish constipation model and its prokinetic effect was associated with an increased expression of interstitial cells of Cajal (ICC) markers. Therefore, the loperamide-induced zebrafish constipation model developed herein is a promising tool to evaluate novel constipation therapies.

PURPOSENeck ultrasonography (US), computed tomography (CT), and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are all known to be useful imaging modalities for detecting supraclavicular lymph node (SCN) metastasis in breast cancer. The authors compared the diagnostic values of neck US, CT, and PET/CT in the detection of SCN metastasis in breast cancer.METHODSSCN metastases identified in neck US, CT, or PET/CT during follow-up visits of patients with breast cancer were pathologically confirmed with the use of US-guided fine-needle aspiration cytology. The clinicopathological factors of the patients were analyzed, and the statistical parameters including sensitivity, specificity, positive and negative predictive values, false-positive and false-negative rates, and accuracy of neck US, CT, and PET/CT were compared.RESULTSAmong 32 cases of suspicious SCNs, 24 were pathologically confirmed as metastasis of breast cancer. The sensitivity of US + CT was 91.7%, which was the same as that of PET/CT, while the sensitivity rates of US alone and CT alone were 87.5% and 83.3%, respectively. Accuracy was 99.8% in PET/CT alone and 98.1% in US + CT. The false-negative rate was 0.1% in US + PET/CT, while it was 0.2% in PET/CT and US + CT, 0.3% in US alone and 0.4% in CT alone.CONCLUSIONPET/CT can be the first choice for detecting SCN metastases in breast cancer. However, if PET/CT is unavailable for any reason, US + CT could be a good second option to avoid false-negative results.

Purpose: This study evaluated the efficiency of preoperative ultrasound (US)-guided tattooing of the axillary lymph nodes with activated charcoal and the correlation between sonographically suspicious nodes and final histologic results by node-to-node analysis. The concordance rate between the tattooed nodes and sentinel nodes was also determined. Methods : : US-guided tattooing of sonographically suspicious axillary nodes was performed preoperatively by an injection of activated charcoal. The identification of black pigment and the concordance between the sentinel and tattooed nodes was evaluated. Results : : Regarding node-to-node analysis, the false-negative rate of US-fine needle aspiration (FNA) was 43.3%. The sensitivity and negative predictive values were 56.7% and 81.7%, respectively. The specificity and positive predictive values were 100%. The accuracy of US-FNA was 85.2%. In the final pathology, 45/125 patients (36.0%) had positive nodes, including two micrometastases. The false-negative rate of sentinel lymph node biopsy (SLNB) was 4.0%, but there were no skip metastases. The sensitivity and specificity of SLNB were 95.6% and 100%, respectively. The negative predictive value was 97.6%, and the positive predictive value was 100%. The accuracy of SLNB was 98.4%. In 117 of 125 patients (93.6%), there was concordance between the charcoal tattooed axillary lymph nodes and SLNs. Conclusion : : SLNB, in conjunction with US-guided tattooing of sonographically suspicious axillary lymph nodes, is a useful procedure to reduce the false-negative rate of SLNB and improve the accuracy of an intraoperative evaluation of axillary nodes in breast cancer patients. This paper proposes the concept of targeted axillary node biopsy with preoperative US-guided tattooing for the most accurate axillary staging in patients with breast cancer.

Selaginellaceae plants are used in cosmetics to limit skin aging. This study is the first to investigate the anti-aging effects of Selaginella rossii (SR) on ultraviolet B (UVB)- and oxidative stress-induced skin cells. The 95% ethanol extract of Selaginella rossii (SR95E) contained much higher amounts of amentoflavone (AMF), an active compound, than other Selaginellaceae plants and was more effective in inhibiting matrix metalloproteinase (MMP)-1 expression in CCD-986sk fibroblasts. SR95E significantly decreased UVB-induced MMP-1, MMP-2, MMP-3 and MMP-9 expression and enhanced procollagen type I C-peptide content and mRNA expression of collagen type I alpha (COL1A)1 and COL1A2 in CCD-986sk fibroblasts. In HaCaT keratinocytes, SR95E treatment also dose-dependently decreased UVB-induced MMP-1 concentration and MMP-1, MMP-2, MMP-3 and MMP-9 mRNA expression. Moreover, SR95E treatment markedly inhibited UVB-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinase signaling and nuclear factor kappa-B signaling in HaCaT cells. Furthermore, SR95E and AMF markedly regulated the 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced expression of cellular senescence-related markers, including p16, p21 and LMNB1, in HaCaT cells. Overall, this study indicates that SR may have potential as a functional material on preventing UVB- and AAPH-induced skin aging and wrinkles.

In the last two decades, methods to incorporate non-canonical amino acids (ncAAs) into specific positions of a protein have advanced significantly; these methods have become general tools for engineering proteins. However, almost all these methods depend on the translation elongation process, and strategies leveraging the initiation process have rarely been reported. The incorporation of a ncAA specifically at the translation initiation site enables the installation of reactive groups for modification at the N-termini of proteins, which are attractive positions for introducing abiological groups with minimal structural perturbations. In this study, we attempted to engineer an orthogonal protein translation initiation system. Introduction of the identity elements of Escherichia coli initiator tRNA converted an engineered Methanococcus jannaschii tRNATyr into an initiator tRNA. The engineered tRNA enabled the site-specific incorporation of O-propargyl-l-tyrosine (OpgY) into the amber (TAG) codon at the translation initiation position but was inactive toward the elongational TAG codon. Misincorporation of Gln was detected, and the engineered system was demonstrated only with OpgY. We expect further engineering of the initiator tRNA for improved activity and specificity to generate an orthogonal translation initiation system.

Protons may have contributed to the evolution of plants as a major component of cosmic-rays and also have been used for mutagenesis in plants. Although the mutagenic effect of protons has been well-characterized in animals, no comprehensive phenotypic and genomic analyses has been reported in plants. Here, we investigated the phenotypes and whole genome sequences of Arabidopsis M2 lines derived by irradiation with proton beams and gamma-rays, to determine unique characteristics of proton beams in mutagenesis. We found that mutation frequency was dependent on the irradiation doses of both proton beams and gamma-rays. On the basis of the relationship between survival and mutation rates, we hypothesized that there may be a mutation rate threshold for survived individuals after irradiation. There were no significant differences between the total mutation rates in groups derived using proton beam or gamma-ray irradiation at doses that had similar impacts on survival rate. However, proton beam irradiation resulted in a broader mutant phenotype spectrum than gamma-ray irradiation, and proton beams generated more DNA structural variations (SVs) than gamma-rays. The most frequent SV was inversion. Most of the inversion junctions contained sequences with microhomology and were associated with the deletion of only a few nucleotides, which implies that preferential use of microhomology in non-homologous end joining was likely to be responsible for the SVs. These results show that protons, as particles with low linear energy transfer (LET), have unique characteristics in mutagenesis that partially overlap with those of low-LET gamma-rays and high-LET heavy ions in different respects.

In recent years, an interesting biomarker called membrane breakdown voltage has been examined using artificial planar lipid bilayers. Even though they have great potential to identify cell electrical phenotyping for distinguishing similar cell lines or cells under different physiological conditions, the biomarker has not been evaluated in the context of living cell electrical phenotyping. Herein, we present a single-cell analysis platform to continuously measure the electric response in a large number of cells in parallel using electric frequency and voltage variables. Using this platform, we measured the direction of cell displacement and transparent cell image alteration as electric polarization of the cell responds to signal modulation, extracting the dielectrophoretic crossover frequency and membrane breakdown voltage for each cell, and utilizing the measurement results in the same spatiotemporal environment. We developed paired parameters using the dielectrophoretic crossover frequency and membrane breakdown voltage for each cell and evaluated the paired parameter efficiency concerning the identification of two different breast cancer cells and cell drug response. Moreover, we showed that the platform was able to identify cell electrical phenotyping, which was generated by subtle changes in cholesterol depletion-induced cell membrane integrity disruption when the paired parameter was used. Our platform introduced in this paper is extremely useful for facilitating more accurate and efficient evaluation of cell electrical phenotyping in a variety of applications, such as cell biology and drug discovery.

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic has affected medical practice in diverse ways. We aimed to investigate the change in trends of lower gastrointestinal (LGI) endoscopy conducted in children and adolescents after the COVID-19 outbreak in Korea. Material and Methods: This was a multicenter, retrospective study conducted in Korea. We included children and adolescents aged Results: We included 1307 patients in this study. Colonoscopies, instead of sigmoidoscopies, were conducted in most patients in the postCOVID-19 era compared to those in the preCOVID-19 era (86.9% vs. 78.5%, p = 0.007). The diagnosis of inflammatory bowel disease (IBD) was also significantly higher in the postCOVID-19 era compared to the preCOVID-19 era (47.2% vs. 28.5%, p < 0.001). According to multivariate logistic regression analysis, age at LGI endoscopy, LGI bleeding indication, and IBD diagnosis were independently associated with the use of a colonoscopy over a sigmoidoscopy (odds ratio (OR) 1.19, 95% confidence interval (CI) 1.12–1.27, p < 0.001; OR 0.56, 95% CI 0.37–0.83, p = 0.005; OR 1.80, 95% CI 1.20–2.77, p = 0.006, respectively). Conclusions: The COVID-19 pandemic has changed LGI endoscopy practice trends of pediatric gastroenterologists in Korea, who tended to perform lesser LGI endoscopies compared to previous years while conducting significantly more colonoscopies than sigmoidoscopies in the postCOVID-19 era. Furthermore, these colonoscopies were significantly associated with the diagnosis of IBD, as well as a significant increase in IBD diagnosis in the postCOVID-19 era.

439L stainless steel composites blended with fifteen micron SiC particles were prepared by uniaxial pressing of raw powders at 100 MPa and conventional sintering at 1350oC for 2 h. Based on the results of X-ray diffraction analysis, dissolution of SiC particles were apparent. The 5 vol% SiC specimen demonstrated maximal densification (91.5%) among prepared specimens ­(0-10 vol% SiC); the relative density was higher than the specimens in the literature (80-84%) prepared by a similar process but at a higher forming pressure (700 MPa). The stress-strain curve and yield strength were also maximal at the 5 vol% of SiC, indicating that densification is the most important parameter determining the mechanical property. The added SiC particles in this study did not serve as the reinforcement phase for the 439L steel matrix but as a liquid-phase-sintering agent for facilitating densification, which eventually improved the mechanical property of the sintered product.

Chemicals related to hydrogen peroxide (H2O2) and nitric oxide (NO) generations were exogenously applied to Fusarium oxysporum f. sp. fragariae (Fof) causing Fusarium wilt disease in strawberry plants, and regulations of In vitro conidial germination and mycelial growth of the fungus by the chemical treatments were evaluated. H2O2 drastically reduced the conidial germination of Fof in a dose-dependent manner, and treatment with 3-amino-1,2,4-triazole (3-AT) catalase inhibitor also led to dose-dependent inhibition of conidial germination but relatively moderately. Gradual decreases in mycelial growth of Fof were found by high concentrations of H2O2, whilst exogenous 3-AT slightly increased the mycelial growth. Increasing sodium nitroprusside (SNP) NO donor, NG-nitro-l-arginine methyl ester (L-NAME) NO synthase (NOS)-inhibitor and tungstate nitrate reductase (NR) inhibitor led to dose-dependent reductions in conidial germination of Fof in quite different levels. SNP conversely increased the mycelial growth but increasing L-NAME moderately decreased the mycelial growth. Tungstate strongly enhanced mycelial growth. Differentially regulated In vitro mycelial growths of Fof were demonstrated by SNP, L-NAME and tungstate with or without H2O2 supplement. Superoxide anion production was also regulated during the mycelial growth of Fof by nitric oxide. These results show that H2O2 and NO-associated enzymes can be suggested as fungal growth regulators of Fof as well as eco-friendly disease-managing agents in strawberry production fields.

Antioxidants are an important strategy for treating photoaging because excessive reactive oxygen species (ROS) are produced during UV irradiation. The therapeutic effects of methanol extracts of Hygrophila erecta (Brum. F.) Hochr. (MEH) against UV-induced photoaging were examined by monitoring the changes in the antioxidant defense system, apoptosis, extracellular matrix (ECM) modulation, inflammatory response, and melanin synthesis in normal human dermal fibroblast (NHDF) cells and melanoma B16F1 cells. Four bioactive compounds, including 4-methoxycinnamic acid, 4-methoxybenzoic acid, methyl linoleate, and asterriquinone C-1, were detected in MEH, while the DPPH free radical scavenging activity was IC50 = 7.6769 µg/mL. UV-induced an increase in the intracellular ROS generation, NO concentration, SOD activity and expression, and Nrf2 expression were prevented with the MEH treatment. Significant decreases in the number of apoptotic cells, the ratio of Bax/Bcl-2, and cleaved Cas-3/Cas-3 were observed in MEH-treated NHDF cells. The MEH treatment induced the significant prevention of ECM disruption and suppressed the COX-2-induced iNOS mediated pathway, expression of inflammatory cytokines, and inflammasome activation. Finally, the expression of the melanin synthesis-involved genes and tyrosinase activity decreased significantly in the α-melanocyte-stimulating hormone (MSH)-stimulated B16F1 cells after the MEH treatment. MEH may have an antioxidative role against UV-induced photoaging by suppressing ROS-induced cellular damage.

Melanoma is visible unlike other types of cancer, but it is still challenging to diagnose correctly because of the difficulty in distinguishing between benign nevus and melanoma. We conducted a robust investigation of melanoma, identifying considerable differences in local elastic properties between nevus and melanoma tissues by using atomic force microscopy (AFM) indentation of histological specimens. Specifically, the histograms of the elastic modulus of melanoma displayed multimodal Gaussian distributions, exhibiting heterogeneous mechanical properties, in contrast with the unimodal distributions of elastic modulus in the benign nevus. We identified this notable signature was consistent regardless of blotch incidence by sex, age, anatomical site (e.g., thigh, calf, arm, eyelid, and cheek), or cancer stage (I, IV, and V). In addition, we found that the non-linearity of the force-distance curves for melanoma is increased compared to benign nevus. We believe that AFM indentation of histological specimens may technically complement conventional histopathological analysis for earlier and more precise melanoma detection.

Many Selaginellaceae species are used as traditional medicines in Asia. This study is the first to investigate the anti-obesity and anti-diabetic effects of Selaginella rossii (SR) in high-fat diet (HFD)–fed C57BL/6J mice. Seven-day oral administration of ethanol extract (100 mg/kg/day) or ethyl acetate (EtOAc) extract (50 mg/kg/day) from SR improved oral fat tolerance by inhibiting intestinal lipid absorption; 10-week long-term administration of the EtOAc extract markedly reduced HFD-induced body weight gain and hyperglycemia by reducing adipocyte hypertrophy, glucose levels, HbA1c, and plasma insulin levels. Treatment with SR extracts reduced the expression of intestinal lipid absorption-related genes, including Cd36, fatty acid-binding protein 6, ATP-binding cassette subfamily G member 8, NPC1 like intracellular cholesterol transporter 1, and ATP-binding cassette subfamily A member 1. In addition, the EtOAc extract increased the expression of protein absorption–related solute carrier family genes, including Slc15a1, Slc8a2, and Slc6a9. SR extracts reduced HFD-induced hepatic steatosis by suppressing fatty acid transport to hepatocytes and hepatic lipid accumulation. Furthermore, amentoflavone (AMF), the primary compound in SR extracts, reduced intestinal lipid absorption by inhibiting fatty acid transport in HFD-fed mice. AMF-enriched SR extracts effectively protected against HFD-induced body weight gain and hyperglycemia by inhibiting intestinal lipid absorption.

As a new class of cancer therapeutic agents, oncolytic viruses (OVs) have gained much attention not only due to their ability to selectively replicate in and lyse tumor cells, but also for their potential to stimulate antitumor immune responses. As a result, there is an increasing need for in vitro modeling systems capable of recapitulating the 3D physiological tumor microenvironment. Here, we investigated the potential of our recently developed microphysiological system (MPS), featuring a vessel-like channel to reflect the in vivo tumor microenvironment and serving as culture spaces for 3D multicellular tumor spheroids (MCTSs). The MCTSs consist of cancer A549 cells, stromal MRC5 cells, endothelial HUVECs, as well as the extracellular matrix. 3D MCTSs residing in the MPS were infected with oncolytic VSV expressing GFP (oVSV-GFP). Post-infection, GFP signal intensity increased only in A549 cells of the MPS. On the other hand, HUVECs were susceptible to virus infection under 2D culture and IFN-β secretion was quite delayed in HUVECs. These results thus demonstrate that OV antitumoral characteristics can be readily monitored in the MPS and that its behavior therein somewhat differs compared to its activity in 2D system. In conclusion, we present the first application of the MPS, an in vitro model that was developed to better reflect in vivo conditions. Its various advantages suggest the 3D MCTS-integrated MPS can serve as a first line monitoring system to validate oncolytic virus efficacy.

Background/Aims Ulcerative colitis undergoes periods of exacerbation and remission. Fecal calprotectin levels increase with gut inflammation and correlate with endoscopic disease activity in ulcerative colitis. Intestinal blood loss and fecal immunochemical test levels also correlate with endoscopic disease activity. This study statistically evaluated the usefulness of fecal calprotectin, fecal immunochemical test, and C-reactive protein (CRP) as markers of disease activity. Methods A total 106 ulcerative colitis patients who underwent endoscopy and fecal calprotectin, fecal immunochemical test, and CRP testing, from March 2015 to August 2016, were retrospectively reviewed. Disease activity was assessed using a partial Mayo score and Mayo endoscopic score. The ability of fecal and serologic tests to reflect endoscopic disease severity was statistically evaluated. Results Among 106 patients, 68 underwent endoscopy and stool study within 2 weeks. In patients with mild to severe activity, fecal immunochemical test and fecal calprotectin were superior to CRP at Mayo endoscopic score detection rate. The area under the curves of fecal immunochemical test and fecal calprotectin for the detection of Mayo endoscopic score ≥1 were 0.956 and 0.942, respectively, and were superior to that of CRP (0.756). At Mayo endoscopic score, the effects of combination of fecal immunochemical test and CRP or fecal calprotectin and CRP were found to be higher than those of the independent fecal immunochemical test or fecal calprotectin. Conclusions Fecal immunochemical test and fecal calprotectin can effectively detect active ulcerative colitis better than remission. As these markers reflect the status of mucosal inflammation, they may reduce the requirement for invasive endoscopic examination.

Abstract Background We investigated the inhibitory effect of pantoprazole on signal transducer and activator of transcription 3 (STAT3) activity and invasiveness of gastric adenocarcinoma cells, and the role of SH2-containing protein tyrosine phosphatase 1 (SHP-1) in mediating role. Methods We used AGS and MKN-28 cells because of reduced SHP-1 and preserved p-STAT3 expression. Western blot, wound closure assay, Matrigel invasion assay and 3-D culture invasion assay were performed. Pharmacologic inhibitor of SHP-1 and siRNA were used for validation of the role of SHP-1. Results We observed that pantoprazole at 40, 80, and 160 μg/ml upregulated SHP-1 and downregulated p-STAT3 expression in a dose-dependent manner in AGS and MKN-28 cells. Furthermore, pantoprazole significantly downregulated mesenchymal markers (Snail1 and vimentin), upregulated epithelial marker (E-cadherin), and inhibited migration and invasion of AGS and MKN-28 cells. To validate the role of SHP-1 in inhibition of STAT3 activity by pantoprazole in gastric cancer cells, we performed pharmacologic inhibition (pervanadate) or knockdown of SHP-1 before pantoprazole treatment, which significantly attenuated the suppression of p-STAT3 and anti-migration and invasion effect by pantoprazole in AGS cells. In xenograft tumor model, tumor volume was significantly reduced by intraperitoneal injection of pantoprazole, with upregulation of SHP-1 and downregulation of p-STAT3, which were attenuated by concomitant injection of pervanadate. Conclusion Our data suggest that the inhibitory effect of pantoprazole on cellular migration and invasion might be through inducing SHP-1 in gastric cancer cells.

Background/Aims: Several previous studies suggest that eradication of Helicobacter pylori (H. pylori) leads to the disappearance of gastric hyperplastic polyps. However, little is known about the effect of H. pylori status and eradication on the recurrence of gastric polyps after endoscopic removal. Here, we investigated the recurrence of gastric polyps according to the final H. pylori status in patients who underwent endoscopic removal of gastric hyperplastic polyps. Methods: Between January 2011 and December 2016, patients who underwent endoscopic removal of gastric hyperplastic polyps and were followed-up for more than two months were enrolled. The success of H. pylori eradication was assessed by histology and rapid urease test or urea breath test, at least 4 weeks after the completion of eradication treatment. At follow-up, the recurrence of gastric polyp was evaluated via esophagogastroduodenoscopy. Results: Seventy-nine patients were enrolled. During the mean follow-up period of 16.4 months, the recurrence rate of gastric polyp was 25.3%. Among those who received H. pylori eradication therapy, the H. pylori persistent group showed a higher recurrence of polyp than the H. pylori eradicated group; but there was no statistical significance (42.9% vs. 21.7%, p=0.269). Regarding the final H. pylori infection status, the recurrence rate of gastric polyps was significantly higher in the H. pylori positive group than in the H. pylori negative group (42.9% vs. 18.9%, p=0.031). In multivariate analysis, the final H. pylori infection status was a significant risk factor for gastric polyp recurrence after endoscopic removal. Conclusions: The final positive H. pylori infection status is significantly associated with higher recurrence of gastric hyperplastic polyps after endoscopic removal.

Abstract Background We investigated the effect of arsenic trioxide (ATO) for inhibition of signal transducer and activator of transcription 3 (STAT3) and epithelial-mesenchymal transition (EMT) in gastric cancer cells, and the role of SH2 domain-containing phosphatase-1 (SHP-1) during this process. Methods We used AGS cells, which showed minimal SHP-1 expression and constitutive STAT3 expression. After treatment of ATO, cellular migration and invasion were assessed by using wound closure assay, Matrigel invasion assay and 3-D culture invasion assay. To validate the role of SHP-1, pervanadate, a pharmacologic phosphatase inhibitor, and SHP-1 siRNA were used. Xenograft tumors were produced, and ATO or pervanadate were administered via intraperitoneal (IP) route. Results Treatment of ATO 5 and 10 μM significantly decreased cellular migration and invasion in a dose-dependent manner. Western blot showed that ATO upregulated SHP-1 expression and downregulated STAT3 expression, and immunofluorescence showed upregulation with E-cadherin (epithelial marker) and downregulation of Snail1 (mesenchymal marker) expression by ATO treatment. Anti-migration and invasion effect and modulation of SHP-1/STAT3 axis by ATO were attenuated by pervanadate or SHP-1 siRNA. IP injection of ATO significantly decreased the xenograft tumor volume and upregulated SHP-1 expression, which were attenuated by co-IP injection of pervanadate. Conclusion Our data suggest that ATO inhibits STAT3 activity and EMT process by upregulation of SHP-1 in gastric cancer cells.

Background/Aims Patients may feel embarrassed during colonoscopy. Our study aimed to assess changes in patient preference, over the past decade, for the sex of their colonoscopist. Methods Prospective studies were performed at a single health center from July to September 2008, and from July to September 2016. Subjects included colonoscopy patients (2008: 354, 2016: 304) who were asked to complete a questionnaire before colonoscopy. Results In 2016, 69 patients (24.9%) expressed a sex preference, compared with 46 patients (14.6%) in 2008. By 2016, female patient preference for a female colonoscopist had significantly increased to 95% (odds ratio [OR], 2.678; 95% confidence interval [CI], 1.418– 5.057; P=0.002). In multivariate analysis, patient sex (OR, 4.404; P=0.000), patient age (OR, 0.977; 95% CI, 0.961–0.992; P=0.004), and year of procedure (OR, 1.674; 95% CI, 1.028–2.752) were statistically significant factors in sex preference. Between 2008 and 2016, female patients preferred a female colonoscopist because of embarrassment. Male patients also preferred a male colonoscopist, and the primary reason shifted from expertise to patient embarrassment (2008: 29%, 2016: 63%). Conclusions Patients have an increased gender preference for the colonoscopist because of embarrassment. Taking this into account can increase patient satisfaction during colonoscopy.

The objective of this study was to determine inhibitory activities of four volatile plant essential oils (cinnamon oil, fennel oil, origanum oil and thyme oil) on in vitro growth of Fusarium oxysporum f. sp. fragariae causing Fusarium wilt of strawberry plants. Results showed that these essential oils inhibited in vitro conidial germination and mycelial growth of F. oxysporum f. sp. fragariae in a dose-dependent manner. Cinnamon oil was found to be most effective one in suppressing conidial germination while fennel oil, origanum oil and thyme oil showed moderate inhibition of conidial germination at similar levels. Cinnamon oil, origanum oil and thyme oil showed moderate antifungal activities against mycelial growth at similar levels while fennel oil had relatively lower antifungal activity against mycelial growth. Antifungal effects of these four plant essential oils in different combinations on in vitro fungal growth were also evaluated. These essential oils demonstrated synergistic antifungal activities against conidial germination and mycelial growth of F. oxysporum f. sp. fragariae in vitro. Simultaneous application of origanum oil and thyme oil enhanced their antimicrobial activities against conidial germination and fungal mycelial growth. These results underpin that volatile plant essential oils could be used in eco-friendly integrated disease management of Fusarium wilt in strawberry fields.

Background/AimsVarious clinical scoring systems, including the Glasgow-Blatchford score (GBS), Rockall risk score (RS), and AIMS65 score (AIMS65), have been validated to predict the clinical outcomes in patients with upper gastrointestinal bleeding (UGIB). We compared the performance of these three scoring systems in predicting clinical outcomes in patients with UGIB in Korea.Methods : We retrospectively evaluated 286 patients with UGIB who visited emergency department. The primary outcome was the need for clinical intervention (endoscopic, radiologic, or surgical) and blood transfusion.Results : The causes of UGIB were esophageal/gastric varices in 64 patients, peptic ulcer in 168, Mallory-Weiss tear in 32, malignancy of UGI tract in eight, and unknown in 14. One hundred seventy-four (61%) patients required blood transfusion, 166 (58%) required endoscopic intervention, and 10 (3.5%) required surgical intervention. The GBS outperformed the RS and AIMS65 in predicting the need for endoscopic intervention.Conclusion : sThe GBS and RS were more accurate than AIMS65 in predicting the need for clinical interventions and transfusion patients with UGIB, regardless of variceal or nonvariceal bleeding. The AIMS65 may not be optimal for predicting clinical outcomes of UGIB in Korea.

Heterotopic gastric mucosa (HGM) is a rare anomaly in the small bowel and may be the cause of intussusception when it gets a lead point in the jejunum. All cases of intussusception due to intestinal HGM have been treated with surgical resection. A 5-year-old girl presented with chief complaints of vomiting and abdominal pain for 2 weeks. A computed tomography scan of the abdomen showed intussusception at the proximal jejunal loops. Three air reductions and one saline reduction were attempted without success. She continued to be symptomatic, and endoscopic evaluation was performed. Enteroscopy revealed some variable-sized polypoid mucosal lesions with erosions on the proximal jejunum. Endoscopic mucosal resection was performed using a snare. The resected tissues histologically showed a hyperplastic polyp arising from the HGM. Her symptoms did not recur within 1 year after the treatment. Our case showed that enteroscopy could be useful for the diagnosis and management of jejunal intussusception caused by HGM.

Background/Aims: Percutaneous endoscopic gastrostomy (PEG) is performed to provide enteral nutrition to patients who require tube-feeding support due to impaired oral intake. As life expectancy increases, the need for, and use of PEG also tend to increase. We aimed to evaluate the indications and complications of PEG insertion, and to investigate any differences in the complication group. Materials and Methods: We conducted a retrospective analysis of 109 patients who received a PEG procedure between April 2011 and April 2016 in the Korea University Ansan Hospital. We reviewed the indications and complications related to PEG insertion and time interval of tube change. Results: Among 109 patients who underwent a PEG procedure, 71.6% were male, and the mean age was 68.2 years. The most common indications for PEG were central nervous system diseases, including stroke (33.9%), cerebral hemorrhage (29.4%), and hypoxic brain damage (8.3%). The overall complication rate was 14.7%, and the most common complication was peristomal infection (7.3%). Most of the complications occurred within 10 days in 14 of 16 patients (87.5%). The patients with complications were older than those without complications (74.6±11.1 vs. 67.1±14.0 years, P=0.043). The mean time interval for gastrostomy tube change was 7.3 months. Conclusions: The most common indication of PEG was brain disease, and the complication rate cannot be ignored. Careful attention is needed after a PEG procedure especially in elderly patients.

Abstract Prion fibrils, which are a hallmark for neurodegenerative diseases, have recently been found to exhibit the structural diversity that governs disease pathology. Despite our recent finding concerning the role of the disease-specific structure of prion fibrils in determining their elastic properties, the mechanical deformation mechanisms and fracture properties of prion fibrils depending on their structures have not been fully characterized. In this work, we have studied the tensile deformation mechanisms of prion and non-prion amyloid fibrils by using steered molecular dynamics simulations. Our simulation results show that the elastic modulus of prion fibril, which is formed based on left-handed β-helical structure, is larger than that of non-prion fibril constructed based on right-handed β-helix. However, the mechanical toughness of prion fibril is found to be less than that of non-prion fibril, which indicates that infectious prion fibril is more fragile than non-infectious (non-prion) fibril. Our study sheds light on the role of the helical structure of amyloid fibrils, which is related to prion infectivity, in determining their mechanical deformation mechanisms and properties.

The 3D multi-cellular tumoroid (MCT) model is an in vivo-like, avascular tumor model that has received much attention as a refined screening platform for drug therapies. Several types of research have been efforted to improve the physiological characteristics of the tumor microenvironment (TME) of the in vivo-like MCTs. Size-controlled MCTs have received much attention for obtaining highly reproducible results in drug screening assays and achieving a homogeneous and meaningful level of biological activities. Here, we describe an effective method for fabricating the size-controlled in vivo-like MCTs using a cell-loss-free (CLF) microwell arrays. The CLF microwell arrays was fabricated by using the simple operation of laser carving of a poly (methyl methacrylate) (PMMA) master mold. We also demonstrated the biophysicochemical effect of tumor microenvironment (TME) resident fibroblasts through the expression of TGFβ, αSMA, Type I-, IV collagen, angiogenesis related markers on tumorigenesis, and confirmed the drug response of MCTs with anti-cancer agents. This technology for the fabrication of CLF microwell arrays could be used as an effective method to produce an in vitro tumor model for cancer research and drug discovery.

Previous studies reported substantial differences between proximal and distal gastric cancer, however, most of the cases included in these studies were advanced gastric cancers (AGCs). The aim of this study was to investigate the unique characteristics of proximal early gastric cancer (EGC) by comparing with distal EGC. From March 2007 to March 2016, proximal and distal EGC patients who underwent endoscopic or surgical resection at our institution were matched 1:3 according to age and sex. We retrospectively analyzed the clinical and histopathological information. A total of 368 patients were enrolled including 92 (25%) in the proximal and 276 (75%) in the distal group. The proportion of patients who underwent surgery (56.5 vs. 20.3%, p

Until now, the physiological effects of Soroseris hirsuta were primarily unknown. Here we have evaluated the anti-inflammatory and antioxidant effects of Soroseris hirsuta extract (SHE) on lipopolysaccharide (LPS)-activated murine macrophages RAW 264.7 cells. SHE inhibited nitric oxide expression and inducible nitric oxide synthase expression in RAW 264.7 cells treated with LPS. Moreover, SHE suppressed LPS-induced phosphorylation of IκB kinase, inhibitor of kappa B, p65, p38, and c-JUN N-terminal kinase. Western blot and immunofluorescence analyses showed that SHE suppressed p65 nuclear translocation induced by LPS. Furthermore, SHE inhibited the reactive oxygen species in LPS-treated RAW 264.7 cells. SHE significantly increased heme oxygenase-1 expression and the nuclear translocation of nuclear factor erythroid 2-related factor 2. SHE suppressed LPS-induced interleukin-1β mRNA expression in RAW 264.7 cells. Thus, SHE is a promising nutraceutical as it displays anti-inflammatory and antioxidant properties.

Background/AimsTo investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis.Methods : A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score.Results : The mean decreases in the total symptom score at 4 weeks were estimated to be −18.1±13.8 in the combination therapy group and −15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were −8.4±6.6 in the combination therapy group and −6.8±5.9 in the monotherapy group (p=0.009).Conclusion : sOver a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy.

Background/AimsAstaxanthin is a carotenoid pigment that has antioxidant, antitumoral, and anti-inflammatory properties. In this in vitro study, we investigated the mechanism of anticancer effects of astaxanthin in gastric carcinoma cell lines.Methods : The human gastric adenocarcinoma cell lines AGS, KATO-III, MKN-45, and SNU-1 were treated with various concentrations of astaxanthin. A cell viability test, cell cycle analysis, and immunoblotting were performed.Results : The viability of each cancer cell line was suppressed by astaxanthin in a dose-dependent manner with significantly decreased proliferation in KATO-III and SNU-1 cells. Astaxanthin increased the number of cells in the G0/G1 phase but reduced the proportion of S phase KATO-III and SNU-1 cells. Phosphorylated extracellular signal-regulated kinase (ERK) was decreased in an inverse dose-dependent correlation with astaxanthin concentration, and the expression of p27kip-1 increased the KATO-III and SNU-1 cell lines in an astaxanthin dose-dependent manner.Conclusion : sAstaxanthin inhibits proliferation by interrupting cell cycle progression in KATO-III and SNU-1 gastric cancer cells. This may be caused by the inhibition of the phosphorylation of ERK and the enhanced expression of p27kip-1.

We sought to visualize the migration of tumor-associated macrophages (TAMs) to tumor lesions and to evaluate the effects of anti-inflammatory drugs on TAM-modulated tumor progression in mice with colon cancer using a multimodal optical reporter gene system. Murine macrophage Raw264.7 cells expressing an enhanced firefly luciferase (Raw/effluc) and murine colon cancer CT26 cells coexpressing Rluc and mCherry (CT26/Rluc-mCherry, CT26/RM) were established. CT26/RM tumor-bearing mice received Raw/effluc via their tail veins, and combination of bioluminescence imaging (BLI) and fluorescence imaging (FLI) was conducted for in vivo imaging of TAMs migration and tumor progression. Dexamethasone (DEX), a potent anti-inflammatory drug, was administered intraperitoneally to tumor-bearing mice following the intravenous transfer of Raw/effluc cells. The migration of TAMs and tumor growth was monitored by serial FLI and BLI. The migration of Raw/effluc cells to tumor lesions was observed at day 1, and BLI signals were still distinct at tumor lesions on day 4. Localization of BLI signals from migrated Raw/effluc cells corresponded to that of FLI signals from CT26/RM tumors. In vivo FLI of tumors demonstrated enhanced tumor growth associated with macrophage migration to tumor lesions. Treatment with DEX inhibited the influx of Raw/effluc cells to tumor lesions and abolished the enhanced tumor growth associated with macrophage migration. These findings suggest that molecular imaging approach for TAM tracking is a valuable tool for evaluating the role of TAMs in the tumor microenvironment as well as for the development of new drugs to control TAM involvement in the modulation of tumor progression.

To understand the dynamics of a living system, the analysis of particular and/or cellular dynamics has been performed based on shape-based center point detection. After collecting sequential time-lapse images of cellular dynamics, the trajectory of a moving object is determined from the set of center points of the cell analyzed from each image. The accuracy of trajectory is significant in understanding the stochastic nature of the dynamics of biological objects. In this study, to localize a cellular object in time-lapse images, three different localization methods, namely radial symmetry, circular Hough transform, and modified active contour, were considered. To analyze the accuracy of cellular dynamics, several statistical parameters such as mean square displacement and velocity autocorrelation function were employed, and localization error derived from these was reported for each localization method. In particular, through denoising using a Poisson noise filter, improved localization characteristics could be achieved. The modified active contour with denoising reduced localization error significantly, and thus allowed for accurate estimation of the statistical parameters of cellular dynamics.

V Live is a live-streaming service made by South Korean IT company in August 2015. The service provides diverse video contents specific to entertainment content. Most of V Live users are K-pop fans, and they actively express emotions on V Live content by writing comments, pressing “hearts”, and sharing video content. Based on Uses and Gratifications theory, this study investigated why people use live streaming service, and the factors influencing users’ viewing behavior in live streaming. We conducted an in-depth interview with V Live users. Based on the results of the interview, an online survey was conducted. As a result, six factors—“Interpersonal relationship motivation”, “Social presence motivation”, “Celebrity support motivation”, “Celebrity presence motivation”, “Social interaction motivation”, and “Differentiation motivation”—were derived as motivations to use V Live. While “Social presence motivation” and “Differentiation motivation” among V Live use motivations that have been shown to mediate the relationship between fans’ fanship and V Live viewing time, all motivations using V Live have been shown to mediate the relationship between fans’ fanship and V Live viewing participation.

Inflammation is a fundamental process for defending against foreign antigens that involves various transcriptional regulatory processes as well as molecular signaling pathways. Despite its protective roles in the human body, the activation of inflammation may also convey various diseases including autoimmune disease and cancer. Sorbaria kirilowii is a plant originating from Asia, with no anti-inflammatory activity reported. In this paper, we discovered an anti-inflammatory effect of S. kirilowii ethanol extract (Sk-EE) both in vivo and in vitro. In vitro effects of Sk-EE were determined with lipopolysaccharide (LPS)-stimulated RAW264.7 cells, while ex vivo analysis was performed using peritoneal macrophages of thioglycollate (TG)-induced mice. Sk-EE significantly reduced the nitric oxide (NO) production of induced macrophages and inhibited the expression of inflammation-related cytokines and the activation of transcription factors. Moreover, treatment with Sk-EE also decreased the activation of proteins involved in nuclear factor (NF)-κB signaling cascade; among them, Src was a prime target of Sk-EE. For in vivo assessment of the anti-inflammatory effect of Sk-EE, HCl/EtOH was given by the oral route to mice for gastritis induction. Sk-EE injection dose-dependently reduced the inflammatory lesion area of the stomach in gastritis-induced mice. Taking these results together, Sk-EE exerts its anti-inflammatory activity by regulating intracellular NF-κB signaling pathways and also shows an authentic effect on reducing gastric inflammation.

Inflammation is a complex protective response of body tissues to harmful stimuli. Acute inflammation can progress to chronic inflammation, which can lead to severe disease. Therefore, this research focuses on the development of anti-inflammatory drugs, and natural extracts have been explored as potential agents. No study has yet examined the inflammation-associated pharmacological activity of Potentilla glabra Var. mandshurica (Maxim.) Hand.-Mazz ethanol extract (Pg-EE). To examine the mechanisms by which Pg-EE exerts anti-inflammatory effects, we studied its activities in lipopolysaccharide (LPS)-treated murine macrophage RAW264.7 cells and an HCl/EtOH-induced gastritis model. LPS-triggered nitric oxide (NO) release and mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in RAW264.7 cells were suppressed by Pg-EE in a dose-dependent manner. Using a luciferase assay and western blot assay, we found that the NF-κB pathway was inhibited by Pg-EE, particularly by the decreased level of phosphorylated proteins of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunits (p65 and p50), inhibitor of kappa B alpha (IκBα), p85, and Src. Using an overexpression strategy, cellular thermal shift assay, and immunoprecipitation analysis, we determined that the anti-inflammatory effect of Pg-EE was mediated by the inhibition of Src. Pg-EE further showed anti-inflammatory effects in vivo in the HCl/EtOH-induced gastritis mouse model. In conclusion, Pg-EE exerts anti-inflammatory activities by targeting Src in the NF-κB pathway, and these results suggest that Pg-EE could be used as an anti-inflammatory herbal medicine.

Wikstroemia indica (L.) C.A. Mey. is used in traditional Chinese medicine to treat inflammatory diseases such as arthritis and bronchitis. In this study, we aimed to investigate the effects of an ethanolic extract of W. indica on cutaneous inflammation in mice with 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD). Dermal administration of W. indica ethanolic extract to DNCB-sensitized hairless mice with dermatitis, for two weeks, reduced erythema, scaling, and edema. Skin hydration was improved and transepidermal water loss was reduced at a W. indica concentration of 1%. Furthermore, W. indica also significantly reduced serum IgE and IL-4 concentrations in our mouse model. These results suggest that W. indica has potential as a topical treatment for AD and as an adjunctive agent to control AD.