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Obesity and metabolic syndrome alter serum lipid profiles. They also increase vulnerability to viral infections and worsen the survival rate and symptoms after infection. How serum lipids affect influenza virus proliferation is unclear. Here, we investigated the effects of lysophosphatidylcholines on influenza A virus (IAV) proliferation. IAV particles in the culture medium were titrated using extraction-free quantitative PCR, and viral RNA and protein levels were assessed using real-time PCR and Western blot, respectively. RNA sequencing data were analyzed using PCA and heatmap analysis, and pathway analysis was performed using the KEGG mapper and PathIN tools. Statistical analysis was conducted using SPSS21.0. LPC treatment of THP-1 cells significantly increased IAV proliferation and IAV RNA and protein levels, and saturated LPC was more active in IAV RNA expression than unsaturated LPC was. The functional analysis of genes affected by LPCs showed that the expression of genes involved in IAV signaling, such as suppressor of cytokine signaling 3 (SOCS3), phosphoinositide-3-kinase regulatory subunit 3 (PI3K) and AKT serine/threonine kinase 3 (AKT3), Toll-like receptor 7 (TKR7), and interferon gamma receptor 1 (IFNGR1), was changed by LPC. Altered influenza A pathways were linked with MAPK and PI3K/AKT signaling. Treatment with inhibitors of MAPK or PI3K attenuated viral gene expression changes induced by LPCs. The present study shows that LPCs stimulated virus reproduction by modifying the cellular environment to one in which viruses proliferated better. This was mediated by the MAPK, JNK, and PI3K/AKT pathways. Further animal studies are needed to confirm the link between LPCs from serum or the respiratory system and IAV proliferation.

Panax ginseng Meyer and Inula japonica Thunb. are well established in traditional medicine and are known for their therapeutic properties in managing a range of ailments such as diabetes, asthma, and cancer. Although P. ginseng and I. japonica can alleviate pulmonary fibrosis (PF), the anti-fibrosis effect on PF by the combination of two herbal medicines remains unexplored. Therefore, this study explores this combined effect. In conditions that were not cytotoxic, MRC-5 cells underwent treatment using the formula combining P. ginseng and I. japonica (ISE081), followed by stimulation with transforming growth factor (TGF)-β1, to explore the fibroblast-to-myofibroblast transition (FMT). After harvesting the cells, mRNA levels and protein expressions associated with inflammation and FMT-related markers were determined to evaluate the antiinflammation activities and antifibrosis effect of ISE081. Additionally, the anti-migratory effects of ISE081 were validated through a wound-healing assay. ISE081 remarkably reduced the mRNA levels of interleukin (IL)-6, IL-8, α-smooth muscle actin (SMA), and TGF-β1 in MRC-5 cells and suppressed the α-SMA and fibronectin expressions, respectively. Furthermore, ISE081 inhibited Smad2/3 phosphorylation and wound migration of MRC-5 cells. Under the same conditions, comparing those of ISE081, P. ginseng did not affect the expression of α-SMA, fibronectin, and Smad2/3 phosphorylation, whereas I. japonica significantly inhibited them but with cytotoxicity. The results indicate that the synergistic application of P. ginseng and I. japonica enhances the anti-fibrotic properties in pulmonary fibroblasts and concurrently diminishes toxicity. Therefore, ISE081 has the potential as a prevention and treatment herbal medicine for PF.

Thuja orientalis Folium (TOF) has been prescribed traditionally as an expectorant for inflammatory airway disease. In this study, we evaluated the anti-influenza A virus (IAV) activity of TOF by detecting GFP expressed by influenza A virus (A/PR/8/34-GFP) infection. The fluorescence microscopy and fluorescence-activated cell sorting analysis showed that TOF potently inhibited IAV infection, dose-dependently. Consistently, immunofluorescence and Q-PCR analysis results confirmed TOF significantly represses IAV protein and RNA expression. TOF inhibited IAV infection at the binding and entry step upon viral infection and interferes with HA protein. Further, TOF exhibited a virucidal effect and inhibited the neuraminidase activity of IAV. Additionally, TOF prevented the cytopathic effect caused by H1N1 and H3N2 IAV infection. Amentoflavone among the constituents in TOF exerted the strongest anti-IAV effect. Myricetin, quercetin, and quercitrin also inhibited IAV infection. However, the potent anti-IAV effect of TOF may be related to the synergistic effect of constituents, not by a single specific compound. Our results suggest TOF exhibits a significant inhibitory effect against IAV infection at multi-stages via the blockage of viral attachment and entry, inhibition of neuraminidase, and induction of virucidal effects., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Pulse-modulated plasma etching of copper masked using SIO₂ films was conducted via a CH₃COOH/Ar. The etch characteristics were examined under pulse-modulated plasma. As the duty ratio of pulse decreased and the frequency of pulse increased, the etch selectivity and etch profile were improved. X-ray photoelectron spectroscopy and indicated that more copper oxides (Cu₂O and CuO) and Cu(CH₃COO)₂ were formed using pulse-modulated plasma than those formed using continuous-wave (CW) plasma. As the concentration of CH3COOH gas in pulse-modulated plasma increased, the formation of these copper compounds increased, which improved the etch profiles. Optical emission spectroscopy confirmed that the active ingredients of the plasma increased with decreasing pulse duty ratio and increasing frequency. Therefore, the optimized pulsed plasma etching of copper via a CH₃COOH/Ar gas provides better etch profile than that by CW plasma etching.

The use of phenicol antibiotics in animals has increased. In recent years, it has been reported that the transferable gene mediates phenicol-oxazolidinone resistance. This study analyzed the prevalence and characteristics of phenicol-oxazolidinone resistance genes in Enterococcus faecalis and Enterococcus faecium isolated from food-producing animals and meat in Korea in 2018. Furthermore, for the first time, we reported the genome sequence of E. faecalis strain, which possesses the phenicol-oxazolidinone resistance gene on both the chromosome and plasmid. Among the 327 isolates, optrA , poxtA , and fexA genes were found in 15 (4.6%), 8 (2.5%), and 17 isolates (5.2%), respectively. Twenty E. faecalis strains carrying resistance genes belonged to eight sequence types (STs), and transferability was found in 17 isolates. The genome sequences revealed that resistant genes were present in the chromosome or plasmid, or both. In strains EFS17 and EFS108, optrA was located downstream of the ermA and ant ( 9 ) -1 genes. The strains EFS36 and EFS108 harboring poxtA -encoding plasmid cocarried fexA and cfr ( D ). These islands also contained IS1216E or the transposon Tn554, enabling the horizontal transfer of the phenicol-oxazolidinone resistance with other antimicrobial-resistant genes. Our results suggest that it is necessary to promote the prudent use of antibiotics through continuous monitoring and reevaluation.

The risk factors for stroke, a fatal disease, include type two diabetes, hypertension, and genetic influences. Small vessel occlusion (SVO) can be affected by epigenetic alterations, but an association between SVO and the methylation of cytochrome P450 family 26 subfamily C member 1 (CYP26C1) has not been identified. In this study, we measured the level of DNA methylation in the CYP26C1 promoter and the 5' untranslated region of 115 normal subjects and 56 patients with SVO in Korea. The DNA methylation level of each subject was measured by bisulfite amplicon sequencing, and statistical analysis was performed using the general linear model or Pearson's correlation. The average level of DNA methylation was markedly lower in patients with SVO than in normal subjects (20.4% vs. 17.5%). We found that the methylation of CYP26C1 has a significant positive correlation with blood parameters including white blood cells, hematocrit, lactate dehydrogenase, and Na+ in subjects with SVO. We predicted that binding of RXR-α and RAR-β might be affected by CYP26C1 methylation at CpG sites -246-237 and -294-285. These findings suggest that CYP26C1 methylation in the promoter region may be a predictor of SVO.

Although cisplatin is an effective platinum-based anticancer drug against solid cancer, its availability is limited owing to its adverse side effects. Our study aimed to identify the potential relationship within cisplatin-induced multi-organ physiological changes and genetic factors associated with sex differences in nephrotoxicity susceptibility. To investigate this, mice received a single intraperitoneal injection of cisplatin. Cisplatin administration resulted in renal dysfunction, as evidenced by the elevation in serum biomarkers of renal damage (blood urea nitrogen and creatinine) and the degree of histopathological alterations. In particular, along with testicular damage and low testosterone levels, we also observed a decrease in male-specific (CYP3A2) or male-dominant (CYP2B1 and CYP3A1) CYP isoforms in the livers of rats with hepatotoxicity following cisplatin treatment, which may be associated with an imbalance in male hormone regulation caused by renal and testicular injury. Notably, we found that male rats were more susceptible to cisplatin-induced nephrotoxicity, as characterized by histopathological and biochemical analyses. Therefore, RNA sequencing was performed at baseline (pre-treatment) and at 48 h following cisplatin administration (post-treatment) to identify the genes associated with sex differences in nephrotoxicity susceptibility. Gap junctions, which play a role in replenishing damaged cells to maintain tissue homeostasis, and mismatch repair associated with a pathological apoptotic mechanism against cisplatin nephrotoxicity were significantly enriched only in males following cisplatin treatment. Moreover, among the 322 DEGs showing different basal expression patterns between males and females before cisplatin treatment, the male expressed high levels of genes, which are responsible for transmembrane transport and regulation of apoptotic process, pre-cisplatin treatment; additionally, genes involved in the PI3K-Akt signaling pathway and the oxidation-reduction process were significantly lower in males before cisplatin treatment. Collectively, our comprehensive findings provided valuable insight into the potential mechanisms of sex differences in cisplatin-induced nephrotoxicity susceptibility., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Blood stasis syndrome (BSS) is considered as the cause of several chronic disease including metabolic diseases in traditional East Asian medicine. In this study, we investigated the levels of serum resistin and other proteins related to metabolic syndrome (MS) and several other diseases categories to identify the association with BSS., Methods: This was a cross-sectional, multicenter study of patients recruited from seven traditional Korean Medicine (TKM) hospitals. To identify whether there was an association with BSS in specific disease conditions, including MS, serum protein levels were evaluated using the multiplex method., Results: A total of 885 patients (419 patients with BSS, 376 patients without BSS, and 90 healthy controls) participated in the study, and 139 patients had MS. The resistin and insulin levels were significantly higher in patients with BSS than in patients without BSS and normal subjects ( P  = 0.002 and P  = 0.046, respectively). Patients with BSS who had MS exhibited significantly higher resistin levels than those in patients without BSS and normal subjects ( P  = 0.049). In addition, the levels of serum resistin were significantly correlated with symptoms of the BSS, especially dark red gums, dark facial complexion, and nocturnal pain., Conclusions: Despite several limitations, these results demonstrated that resistin levels are potentially associated with the pathogenesis of BSS in MS., Trial Registration Number: Clinical Research Information Service (CRIS): KCT0000916., Competing Interests: The authors declare that they have no conflicts of interest., (© 2021 Published by Elsevier B.V. on behalf of Korea Institute of Oriental Medicine.)

Acinetobacter strains are widely present in the environment. Some antimicrobial-resistant strains of this genus have been implicated in infections acquired in hospitals. Genetic similarities have been reported between Acinetobacter strains in nosocomial infections and those isolated from foods. However, the antimicrobial resistance of Acinetobacter strains in foods, such as meat, remains unclear. This study initially aimed to isolate Campylobacter strains; instead, strains of the genus Acinetobacter were isolated from meat products, and their antimicrobial resistance was investigated. In total, 58 Acinetobacter strains were isolated from 381 meat samples. Of these, 32 strains (38.6%) were from beef, 22 (26.5%) from pork, and 4 (4.8%) from duck meat. Antimicrobial susceptibility tests revealed that 12 strains were resistant to more than one antimicrobial agent, whereas two strains were multidrug-resistant; both strains were resistant to colistin. Cephalosporin antimicrobials showed high minimal inhibitory concentration against Acinetobacter strains. Resfinder analysis showed that one colistin-resistant strain carried mcr-4.3 ; this plasmid type was not confirmed, even when analyzed with PlasmidFinder. Analysis of the contig harboring mcr-4.3 using BLAST confirmed that this contig was related to mcr-4.3 of Acinetobacter baumannii . The increase in antimicrobial resistance in food production environments increases the resistance rate of Acinetobacter strains present in meat, inhibits the isolation of Campylobacter strains, and acts as a medium for the transmission of antimicrobial resistance in the environment. Therefore, further investigations are warranted to prevent the spread of antimicrobial resistance in food products.

Objectives: To investigate the distribution and genetic characteristics of linezolid-resistant enterococci., Methods: Enterococcus faecalis and Enterococcus faecium strains were isolated from pigs, equipment, grounds, and employees of 19 Korean swine farms in 2017. Antimicrobial susceptibility testing was then performed and linezolid resistance genes were detected via PCR. For genetic epidemiological characterization, multilocus sequence typing and whole-genome sequencing data were analysed., Results: Twenty-eightE. faecalis and five E. faecium strains were isolated from 1026 samples obtained from the 19 farms. Ten sequence types were identified among the E. faecalis strains, of which ST256 (42.9%) and ST86 (25%) were the most abundant. The oxazolidinone and phenicol resistance genes poxtA, optrA, and fexA were detected in isolates of E. faecalis (100%, 85.7%, and 67.9%, respectively) and E. faecium (100%, 60%, and 80%, respectively). The minimum inhibitory concentrations of linezolid in these isolates ranged from 2 mg/L to 12 mg/L. The whole-genome sequencing data indicated that fexA was located upstream of poxtA., Conclusions: This is the first study to report the detection of poxtA in isolates that were both susceptible and resistant to linezolid in Korea. These results demonstrate the importance of antimicrobial resistance monitoring programmes, including regular antimicrobial susceptibility testing and resistance gene expression analysis, to facilitate the control of the spread of antibiotic resistance in non-clinical settings in Korea., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Foreign object ingestion (FOI) and food bolus impaction (FBI) are common causes of emergent endoscopic intervention. The choice of sedation used is often dictated by physician experience. Many endoscopists frequently prefer to use monitored anesthesia care (MAC) and general anesthesia (GA) as opposed to conscious sedation (CS) due to the concern for inadequate airway protection. However, there is insufficient data examining the safety of different sedation modalities in emergent endoscopic management of FOI and FBI., Aim: To investigate the complication rates of emergent endoscopic extraction performed under different sedation modalities., Methods: We conducted a retrospective chart review of patients presenting with acute FBI and FOI between 2010 and 2018 in two hospitals. A standardized questionnaire was utilized to collect data on demographics, endoscopic details, sedation practices, hospital stay and adverse events. Complications recognized during and within 24 h of the procedure were considered early, whereas patients presenting with a procedure-related adverse event within two weeks of the index event were considered delayed complications. Complication rates of patients who underwent emergent endoscopic retrieval were compared based on sedation types, namely CS, MAC and GA. Chi-square analysis and multiple logistic regression were used to compare complication rate based on sedation type., Results: Among the 929 procedures analyzed, 353 procedures (38.0%) were performed under CS, 278 procedures (29.9%) under MAC and the rest (32.1%) under GA. The median age of the subjects was 52 years old, with 57.4% being male. The majority of the procedures (64.3%) were FBI with the rest being FOI (35.7%). A total of 132 subjects (14.2%) had chronic comorbidities while 29.0% had psychiatric disorders. The most commonly observed early complications were mucosal laceration (3.8%) and bleeding (2.6%). The most common delayed complication was aspiration pneumonia (1.8%). A total of 20 patients (5.6%) could not adequately be sedated with CS and had to be converted to MAC or GA. Patient sedated with MAC and GA were more likely to require hospitalization, P < 0.0001. Analysis revealed no statistically significant difference in the complication rate between patients sedated under CS (14.7%), MAC (14.7%) and GA (19.5%), P = 0.19., Conclusion: For patients who present with FOI or FBI and undergo emergent endoscopic treatment, there is no significant difference in adverse event rates between CS, MAC and GA., Competing Interests: Conflict-of-interest statement: There are no conflict of interest pertaining to this manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Uterine leiomyomas are the most common benign gynecologic tumors. This study was aimed to identify single nucleotide polymorphism of Fanconi anemia complementation group A (FANCA), associated with the rate of proliferation in uterine leiomyomas. In vitro study of patient-derived primary-cultured leiomyoma cells and direct sequencing of fresh frozen leiomyoma from each subject was conducted. Leiomyomas obtained from 44 patients who had underwent surgery were both primary-cultured and freshly frozen. Primary-cultured leiomyoma cells were divided into, according to the rate of proliferation, fast and slow groups. Single nucleotide polymorphism (SNP) of FANCA were determined from fresh frozen tissues of each patient using direct sequencing. Direct sequencing revealed a yet unidentified role of FANCA, a caretaker in the DNA damage-response pathway, as a possible biomarker molecule for the prediction of uterine leiomyoma proliferation. We identified that rs2239359 polymorphism, which causes a missense mutation in FANCA, is associated with the rate of proliferation in uterine leiomyomas. The frequency of C allele in the fast group was 35.29% while that in slow group was 11.11% (odds ratio (OR) 4.036 (1.176-13.855), p = 0.0266). We also found that the TC + CC genotype was more frequently observed in the fast group compared with that in the slow group (OR 6.44 (1.90-31.96), p = 0.0227). Taken together, the results in the current study suggested that a FANCA missense mutation may play an important regulatory role in the proliferation of uterine leiomyoma and thus may serve as a prognostic marker.

Colistin is an important antibiotic currently used to manage infections caused by multidrug-resistant pathogens in both humans and livestock animals. A new mobile colistin-resistance ( mcr-9 ) gene was recently discovered; this discovery highlighted the need for rigorous monitoring of bacterial resistance against colistin. Salmonella is one of the major pathogens responsible for foodborne illnesses; however, there is minimal information regarding the presence of mcr genes in foodborne Salmonella strains. The aim of this study was to investigate the presence of mcr genes among 178 Salmonella strains isolated from chicken meat in Korea. Antimicrobial susceptibility was measured using the broth microdilution method. Bioinformatics characterization of colistin-resistant strains and genetic environment of the mcr-9 gene were analyzed using next-generation sequencing. Transferability of the mcr-9 carrying colistin-resistant Salmonella strain was tested using broth-mating conjugation. Thirteen of the 178 Salmonella isolates showed colistin resistance, but only one strain, Salmonella Dessau ST14 (KUFSE-SAL043) from a traditional chicken market in Korea, carried an mcr family gene, mcr-9 . This strain also carried other acquired antimicrobial resistance genes such as bla TEM-1B , qnrS1 , and aac(6')-Iaa . Only the IncX1 plasmid replicon type was detected in this strain. In the strain KUFSE-SAL043, the mcr-9 gene was located between two insertion sequences, IS 903B and IS 26 , followed by the downstream regulatory genes qseB -like and qseC -like, which were located between IS 1R and Δ IS 1R . Conjugation tests revealed that the mcr-9 gene was successfully transferred to Escherichia coli J53 at a mean frequency of 2.03 × 10 -7 . This is the first report of a transferable mcr-9 gene in Salmonella isolated from chicken meat in Korea, highlighting the possibility of transfer of colistin resistance. Therefore, the wide use of colistin should be reconsidered, and a One Health perspective should be adopted to monitor the antimicrobial resistance of Enterobacteriaceae strains in humans, livestock, and the environment.

The effect of inhomogeneous quantum dot (QD) size distribution on the electronic transport of one-dimensional (1D) QD chains (QDCs) is theoretically investigated. The non-equilibrium Green function method is employed to compute the electron transmission probabilities of QDCs. The ensemble averaged transmission probability shows a close agreement with the conductivity equation predicted by Anderson et al. for a disordered electronic system. The fidelity of quantum transport is defined as the transmission performance of an ensemble of QDCs of length N (N-QDCs) to assess the robustness of QDCs as a practical electronic device. We found that the fidelity of inhomogeneous N-QDCs with the standard deviation of energy level distribution σ ε is a Lorentzian function of variable Nσ ε 2 . With these analytical expressions, we can predict the conductance and fidelity of any QDC characterized by (N, σ ε ). Our results can provide a guideline for combining the chain length and QD size distributions for high-mobility electron transport in 1D QDCs.

Abstract: This study was conducted to characterize Escherichia coli strains and evaluate the spread of antimicrobial resistance among these strains from fresh produce and farm environments in Korea. We then conducted phenotypic and genetic studies on antimicrobial-resistant isolates. We determined the genetic epidemiological characteristics of isolates that produced extended-spectrum β-lactamase (ESBL) and confirmed plasmid transfer in isolates that carried blaCTX-M-type genes. E. coli strains were isolated from 8 samples of fresh produce and 152 samples from the farm environment collected from May 2014 to June 2016. Cephalosporin resistance was the most prevalent (61.8%) type of resistance among the isolates. Five ESBL-producing strains with high genetic homology with E. coli of human or livestock origin were identified. Lateral transfer of plasmids harboring blaCTX-M-type genes to transconjugants was successful. Two isolates from Chinese cabbage and from water samples collected from a nearby stream harbored the ISEcp1-blaCTX-M-55-orf477 operon and were confirmed as sequence type 1196 and the same type of plasmid replicon, suggesting that cross-contamination was highly likely. A high-risk clone of sequence type 69 (clonal complex 69) isolates was also recovered from the farm environment. This study provides genetic evidence that antimicrobial resistance factors in E. coli from farm environments originate in the clinic or in livestock, highlighting the fact that good agricultural practices in farming are important to inhibit the spread of antimicrobial resistance to bacteria on fresh produce., (Copyright ©, International Association for Food Protection.)

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that causes coronavirus disease-2019 (COVID-19) is a global pandemic, manifested by an infectious pneumonia. Although patients primarily present with fever, cough and dyspnea, some patients also develop gastrointestinal (GI) and hepatic manifestations. The most common GI symptoms reported are diarrhea, nausea, vomiting, and abdominal discomfort. Liver chemistry abnormalities are common and include elevation of aspartate transferase, alanine transferase, and total bilirubin. Studies have shown that SARS-CoV-2 infects the GI tract via its viral receptor angiotensin converting enzyme II, which is expressed on enterocytes of the ileum and colon. Viral RNA has also been isolated from stool specimens of COVID-19 patients, which raised the concern for fecal-oral transmission in addition to droplet transmission. Although indirect evidence has suggested possible fecal-oral transmission of SARS-CoV-2, more effort is needed to establish the role of the fecal-oral transmission route. Further research will help elucidate the association between patients with underlying GI diseases, such as chronic liver disease and inflammatory bowel disease, and severity of COVID-19. In this review, we summarize the data on GI involvement to date, as well as the impact of COVID-19 on underlying GI diseases., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest pertaining to this manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Obesity is a major chronic disease associated with the risk of serious cardiovascular or endocrinal diseases, such as hypertension, diabetes, atherosclerosis and stroke. Considerable interest has been directed towards the potential effects of epigenetic variations in obesity. In this study, we evaluated DNA methylation level at the promoter region of the gene encoding TSPO-associated protein 1 antisense RNA 1 (TSPOAP1-AS1) in 80 overweight/obese subjects (body mass index (BMI) > 25) and 104 non-obese subjects who participated in the SOPI-Stroke study in Korea. DNA methylation was measured using bisulfite amplicon sequencing (BSAS). A general linear model or relative correlation was used to determine the effects of DNA methylation on obesity and obese phenotypes. Notably, the mean level of DNA methylation was significantly higher in the overweight/obese group than in the non-obese group (18.62% vs. 17.18%). Further analyses revealed significant positive correlations of the BMI, the serum total cholesterol and low-density lipoprotein cholesterol levels with the DNA methylation level ( p = 0.0493, p = 0.003, and p = 0.0094, respectively). The study findings suggest an association between DNA methylation at the TSPOAP1-AS1 promoter and overweight/obesity. Accordingly, methylation in this promoter region might be a potential predictor of obesity.

An ideal adjuvant should increase vaccine efficacy through balanced Th1/Th2 responses and be safe to use. Recombinant protein-based vaccines are usually formulated with aluminum (alum)-based adjuvants to ensure an adequate immune response. However, use of alum triggers a Th2-biased immune induction, and hence is not optimal. Although the adjuvanticity of RNA has been reported, a systematic and overall investigation on its efficacy is lacking. We found that single strand RNA (termed RNA adjuvant) derived from cricket paralysis virus intergenic region internal ribosome entry site induced the expression of various adjuvant-function-related genes, such as type 1 and 2 interferon (IFN) and toll-like receptor (TLR), T cell activation, and leukocyte chemotaxis in human peripheral blood mononuclear cells; furthermore, its innate and IFN transcriptome profile patterns were similar to those of a live-attenuated yellow fever vaccine. This suggests that protein-based vaccines formulated using RNA adjuvant function as live-attenuated vaccines. Application of the RNA adjuvant in mouse enhanced the efficacy of Middle East respiratory syndrome spike protein, a protein-subunit vaccine and human papillomavirus L1 protein, a virus-like particle vaccine, by activating innate immune response through TLR7 and enhancing pAPC chemotaxis, leading to a balanced Th1/Th2 responses. Moreover, the combination of alum and the RNA adjuvant synergistically induced humoral and cellular immune responses and endowed long-term immunity. Therefore, RNA adjuvants have broad applicability and can be used with all conventional vaccines to improve vaccine efficacy qualitatively and quantitively., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

As a sequel of part I (Kothari et al. 2018 Proc. R. Soc. A 474 , 20180054), we present a general thermodynamic framework of flexoelectric constitutive laws for multi-layered graphene (MLG), and apply these laws to explain the role of crinkles in peculiar molecular adsorption characteristics of highly oriented pyrolytic graphite (HOPG) surfaces. The thermodynamically consistent constitutive laws lead to a non-local interaction model of polarization induced by electromechanical deformation with flexoelectricity-dielectricity coupling. The non-local model predicts curvature and polarization localization along crinkle valleys and ridges very close to those calculated by density functional theory (DFT). Our analysis reveals that the non-local model can be reduced to a simplified uc-local or e-local model (Kothari et al. 2018 Proc. R. Soc. A 474 , 20180054) only when the curvature distribution is uniform or highly localized. For the non-local model, we calibrated and formulated the layer-number-dependent dielectric and intrinsic flexoelectric coefficients of MLGs. In addition, we also obtained layer-number dependent flexoelectric coefficients for uc-local and e-local models. Our DFT analysis shows that polarization-induced adsorption of neutral molecules at crinkle ridges depends on the molecular weight of the molecule. Furthermore, our detailed study of polarization localization in graphene crinkles enables us to understand previously unexplained self-organized adsorption of C 60 buckyballs in a linear array on an HOPG surface., Competing Interests: We declare we have no competing interests.

Lysophosphatidylcholine (LPC), a major component of oxidized low-density lipoprotein, is associated with atherosclerosis, obesity, stroke, and cancer. However, the direction and mechanism of this relationship remains unclear. In this study, we conducted RNA profiling in THP-1 derived macrophages treated with LPC and uncovered a relationship between LPC and the cholesterol biosynthesis pathway. Principal component analysis (PCA) of RNA profiling showed that untreated THP-1 cells and those treated with 10, 20, or 40 µM LPC were distinctly distributed. Functional annotation revealed that LPC affected the expression of genes involved in cytokine-cytokine receptor interaction, TNF signaling, and MAPK signaling. Interestingly, LPC also altered the expression of 11 genes involved in cholesterol synthesis such as those in terpenoid backbone biosynthesis and steroid biosynthesis pathways. This increased gene expression occurred in a dose-dependent manner in response to LPC treatment. Especially, LPC with saturated acyl groups enhanced the expression of these genes compared to LPC with unsaturated acyl groups, and similar results were shown in response to saturated and unsaturated free fatty acids. Our findings demonstrate that LPCs with saturated acyl groups induce the expression of genes involved in cholesterol biosynthesis and may have implications for cholesterol related diseases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Yijin-Tang (YJT) is a traditional prescription for the treatment of hyperlipidaemia, atherosclerosis and other ailments related to dampness phlegm, a typical pathological symptom of abnormal body fluid metabolism in Traditional Korean Medicine. However, a holistic network pharmacology approach to understanding the therapeutic mechanisms underlying hyperlipidaemia and atherosclerosis has not been pursued., Aim of the Study: To examine the network pharmacological potential effects of YJT on hyperlipidaemia and atherosclerosis, we analysed components, performed target prediction and network analysis, and investigated interacting pathways using a network pharmacology approach., Materials and Methods: Information on compounds in herbal medicines was obtained from public databases, and oral bioavailability and drug-likeness was screened using absorption, distribution, metabolism, and excretion (ADME) criteria. Correlations between compounds and genes were linked using the STITCH database, and genes related to hyperlipidaemia and atherosclerosis were gathered using the GeneCards database. Human genes were identified and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis., Results: Network analysis identified 447 compounds in five herbal medicines that were subjected to ADME screening, and 21 compounds and 57 genes formed the main pathways linked to hyperlipidaemia and atherosclerosis. Among them, 10 compounds (naringenin, nobiletin, hesperidin, galangin, glycyrrhizin, homogentisic acid, stigmasterol, 6-gingerol, quercetin and glabridin) were linked to more than four genes, and are bioactive compounds and key chemicals. Core genes in this network were CASP3, CYP1A1, CYP1A2, MMP2 and MMP9. The compound-target gene network revealed close interactions between multiple components and multiple targets, and facilitates a better understanding of the potential therapeutic effects of YJT., Conclusions: Pharmacological network analysis can help to explain the potential effects of YJT for treating dampness phlegm-related diseases such as hyperlipidaemia and atherosclerosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Here, we report the discovery of a new, curvature-localizing, subcritical buckling mode that produces shallow-kink corrugation in multi-layer graphene. Our density functional theory (DFT) analysis reveals the mode configuration-an approximately 2 nm wide boundary layer of highly localized curvature that connects two regions of uniformly but oppositely sheared stacks of flat atomic sheets. The kink angle between the two regions is limited to a few degrees, ensuring elastic deformation. By contrast, a purely mechanical model of sandwich structures shows progressive supercritical curvature localization spread over a 50-100 nm wide boundary layer. Our effective-locality model of electromechanics reveals that coupling between atomic-layer curvature and electric-charge polarization, i.e. quantum flexoelectricity, leads to emergence of a boundary layer in which curvature is focused primarily within a 0.86 nm fixed band width. Both DFT and the model analyses show focused distributions of curvature and polarization exhibiting oscillating decay within the approximately 2 nm wide boundary layer. The results show that dipole-dipole interaction lowers the potential energy with such a distribution. Furthermore, this model predicts peak-polarization density approximately 0.12 e -  nm -1 for 3° tilt angle. This high polarization concentration can be controlled by macroscopic deformation and is expected to be useful in studies of selective graphene-surface functionalization for various applications., Competing Interests: We have no competing interests.

Increased enterococcal infections in hospitals and multidrug-resistant and vancomycin-resistant enterococci (VRE) isolated from humans, animals, and food sources raised public health concern on the presence of VRE in multiple sources. We performed a comparative analysis of the antimicrobial resistance and genetics of VRE isolates derived from fresh produce and human fecal samples. Of 389 Enterococcus isolates, 8 fecal and 3 produce isolates were resistant to vancomycin and teicoplanin; all harbored vanA gene. The VRE isolates showed multidrug-resistant properties. The isolates from fresh produce in this study showed to have the common shared characteristics with the isolates from humans by the results of antimicrobial resistance, multilocus sequence typing, and Tn 1546 transposon analysis. Therefore, VRE isolates from fresh produce are likely related to VRE derived from humans. The results suggested that VRE may contaminate vegetables through the environment, and the contaminated vegetables could then act as a vehicle for human infections. Ongoing nationwide surveillance of antibiotic resistance and the promotion of the proper use of antibiotics are necessary.

In Korea, patients with stroke are commonly treated using traditional Korean medicine (TKM). The aim of this study was to provide information on the clinical characteristics of the pattern identification (PI) of stroke used in TKM. Stroke patients admitted to 15 TKM university hospitals from April 2005 through December 2013 were evaluated. The measured variables included the following factors as they related to the PI: (a) stroke etiology; (b) distribution of symptoms/signs; (c) physical characteristics and lifestyle parameters; (d) medical history; and (e) stroke-related laboratory results. Among 4912 stroke patients, 3466 patients received the same PI by two experts with the following distribution: Qi-Deficiency pattern (n = 810), Fire-Heat (FH) pattern (n = 1031), Dampness-Phlegm (DP) pattern (n = 1127), and Yin-Deficiency pattern (n = 498). Approximately 89.9% of subjects enrolled in this study had cerebral infarction. Some of specific symptoms were related to each type of PI, and obese phenotypes and blood lipids were significantly related to DP and FH. These results showed the characteristics of each type of PI and should lead to the standardization of diagnosis for stroke in TKM.

Obesity is a disease threatening health and is known one of risk factors causing chronic disease. In Traditional Korean Medicine, bi-sup is casus of obesity. Wnt10b has been indicated as a potential regulator of adipogenesis in vivo and in vitro models of obesity. To analyze the distribution of wnt10b polymorphism between bi-sup group and non-bi-sup group in Korean elder subjects with cerebral infarction (CI). The study group was composed of patients with CIwho were admitted to one of the thirteen Korean oriental medical hospitals participating in this study from 2009 to 2010. A total of 670 CI patients, including 416 with bi-sup group and 254 with non-bi-sup group, participated in this study. Genotype of G-607C was conducted by primer extension using TaqManprobe and five percent of subjects were re-genotyped by direct sequencing to confirm the accuracy of the genotyping. The association of the SNP with the bi-sup group versus non-bi-sup group was performed by multiple logistic regression. Frequency of C allele in bi-sup was 45.75% which was significantly lower than 56.69% in non-bi-sup (P=0.0043, OR=0.628 [0.453-0.864]). Subjects with GC or CC type in bi-sup was also 72.36%, that was also small compared with 78.35% in non-bi-sup (P=0.0467, OR=0.675 [0.458-0.994]). These results suggest that G-607C might be used as a diagnostic genetic marker for bi-sup in stroke patients and in the development of personalized medical care.

Blood stasis (BS) is characterized as a disorder of blood circulation. In traditional Korean medicine (TKM), it is viewed as a cause factor of diseases such as multiple sclerosis and stroke. This study investigated differences in the plasma metabolites profiles of subjects displaying BS or non-BS patterns. Thirty-one patients with cerebral infarction diagnosed with BS and an equal number of sex- and age-matched non-BS patients were enrolled. Metabolic profiling was performed using UPLC-MS. The ratio of subjects with a rough pulse and purple coloration of the tongue was higher in patients presenting with BS pattern. Through metabolomics analysis, 82 metabolites that differed significantly between the BS and non-BS pattern were identified, and the two groups were significantly separated using an orthogonal partial least square-discriminant analysis model (P < 0.001). Of these 82 metabolites, acetyl carnitine, leucine, kynurenine, phosphocholine, hexanoyl carnitine, and decanoyl carnitine were present in significantly higher levels in patients with a BS pattern than those with a non-BS pattern. Our results also demonstrated that seven plasma metabolites, including acyl-carnitines and kynurenine, were associated with a BS pattern, suggesting that variant plasma metabolic profiles may serve as a biomarker for diagnosis of BS in patients with cerebral infarction.

Dedifferentiated human chondrocytes severely limit successful hyaline cartilage repair in clinical practice. The primary interest of this study is to evaluate the naturally obtained cell-derived matrix (CDM) as a physical microenvironment for chondrocyte re-differentiation. Once different cell types were cultured for 6 days and decellularized using detergents and enzymes, the fibroblast-derived matrix (FDM), preosteoblast-derived matrix (PDM), and chondrocyte-derived matrix (CHDM) were obtained. From scanning electron microscope observation, each CDM was found to resemble a fibrous mesh with self-assembled fibrils. Both the FDM and PDM showed a more compact matrix structure compared to the CHDM. For compositional analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis displayed numerous matrix proteins, which were quite different from each CDM in quantity and type. Specific matrix components, such as fibronectin, type I collagen (Col I), and laminin, were detected using immunofluorescent staining. In addition, the water contact angle suggests that the FDM is more hydrophilic than the PDM or CHDM. The proliferation of rat primary chondrocytes growing on CDMs was better than those growing on a plastic coverslip (control) or gelatin. Meanwhile, synthesis of glycosaminoglycan (GAG) was more effective for passaged chondrocytes (P4) cultivated on CDMs, and the difference was significant compared to cells grown on the control or on gelatin. As for the gene expression of cartilage-specific markers, CDMs exhibited good chondrocyte re-differentiation with time: the dedifferentiating marker, Col I was restrained, whereas the ratio between Col II and Col I, and between aggrecan and Col I, as an indicator of re-differentiation, was greatly improved. In addition, immunofluorescence of Col II showed a very positive signal in chondrocytes cultivated for 2 weeks on the CDMs. In an additional study, when three-dimensional cell pellets made from either plate-grown or matrix-grown dedifferentiated chondrocytes (P5) were cultured for 4 weeks, the results of Safranin-O staining, immunohistochemistry of Col II, and total GAG assay suggested that matrix-grown cells were significantly better in the induction of chondrocyte re-differentiation, than those grown on the plate. This work suggests that the naturally occurring matrix, CDM, can provide a favorable surface texture for cell attachment, proliferation, and more importantly, a chondroinductive microenvironment for the re-differentiation of dedifferentiated chondrocytes.

TRADITIONAL KOREAN MEDICINE CLASSIFIES STROKE INTO FOUR SUBTYPE PATTERNS ACCORDING TO SYMPTOMATIC PATTERN IDENTIFICATION: Qi deficiency (QD), Yin deficiency (YD), Dampness-phlegm (DP), and Fire and Heat (FH). This study investigated the difference in metabolic profiles of plasma comparing subjects displaying non-DP and DP patterns. A total of 141 patients with cerebral infarction enrolled in this study were distributed as non-DP (N = 68) and DP (N = 73). Anthropometric parameters and symptom/sign index were measured. Metabolic profiling was performed using ultrahigh-performance liquid chromatography-mass spectrometry. The Ratio of subjects with slippery pulse was higher in DP pattern, but fine pulse was lower than that in non-DP pattern. As a result of metabolomics analysis, twenty-one metabolites displayed different levels between non-DP and DP patterns. Two were identified as lysophosphatidylcholines (LPCs), LPC(18:2), and LPC(20:3) having an unsaturated acyl chain and showed lower levels in DP pattern than in non-DP pattern (P = 0.015, 0.034, resp.). However, the saturated LPCs, LPC(18:0) and LPC(16:0), exhibited slight but statistically insignificant elevation in DP pattern. Our results demonstrated that plasma LPCs with polyunsaturated fatty acid groups were associated with DP pattern and suggest that variation of plasma lipid profiles may serve as potential biomarker for diagnosis of DP pattern.

Background: Patients with stroke have various syndromes and symptoms. Through pattern identification (PI), traditional Korean medicine (TKM) classifies the several syndromes and symptoms of stroke patients into five categories: Fire-heat (FH), Dampness-phlegm (DP), Yin-deficiency (YD), Qi-deficiency (QD) and Blood-stasis (BS). DP has been associated with obesity and hyperlipidemia. Uncoupling protein-1 (UCP-1), which plays a major role in thermogenesis and energy expenditure can increase the risk of obesity and can be related metabolic disorders. In this study, we elucidated the association of three polymorphisms located in the UCP-1 promoter and coding region with DP among Korean stroke patients., Methods: 1,593 patients with cerebral infarction (583/DP, 1,010/non-DP) and 587 normal subjects were enrolled. The genotypes A-3826G, G-1766A and Ala64Thr (G+1068A) for each subject were determined by polymerase chain reaction with TaqMan probes and five percent of subjects were re-genotyped by sequencing method to confirm the accuracy of genotyping. The results were analyzed using a multiple logistic regression model to evaluate the genetic associations: the UCP-1polymorphisms of normal versus those of DP subjects and those of normal versus those of non-DP subjects., Results: A significantly higher percentage of subjects in the DP group possessed the A-3826G G allele than the A allele (OR=1.508, p=0.006). Furthermore, the number of subjects with the GG type of A-1766G was significantly lower in the non-DP group than the normal group in the recessive model (OR=0.606, p=0.042). In addition, an analysis of the relationship among 2 SNPs of UCP-1 and lipid serum concentration showed that the serum level of HDL cholesterol was significantly higher in subjects with the A-3826G G allele in the normal group (p=0.032). Serum triglyceride and HDL cholesterol were also associated with the A-1766G variant in the recessive model (p=0.002, p=0.046)., Conclusions: These results suggest that that the A-3826G and A-1766G UCP-1 polymorphisms, which are related to obesity, might be candidate genetic markers for the DP pattern in the TKM diagnosis system.

Background: To investigate if single nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 would be associated with earlier-onset (vs. late-onset) first-ever ischemic stroke and increase silent cerebrovascular lesions prior to the manifestation of the stroke., Methods: We prospectively enrolled 164 patients (67.6 ± 12.9 years, 92 men) admitted with first-ever ischemic strokes. All patients underwent genotyping of rs11833579 and rs12425791 as well as systemic investigations including magnetic resonance (MR) imaging and other vascular workup. Stroke-related MR lesions were registered on a brain-template-set using a custom-built software package 'Image&#95;QNA': high-signal-intensity ischemic lesions on diffusion, T2-weighted, or fluid attenuation inversion recovery (FLAIR) MR images, and low signal intensity hemorrhagic lesions on gradient-echo MR images., Results: The rs11833579 A/A or G/A genotype was independently associated with the first-ever ischemic stroke before the age 59 vs. 59 or over, after adjusting for cardiovascular risk factors and prior medication of antiplatelet or anticoagulant drugs, increasing the risk by about 2.5 fold. In the quantitative MR lesion maps from age-sex matched subgroups (n = 124 or 126), there was no difference between the patients with the rs11833579 A/A or G/A genotype and those with the G/G genotype. Unexpectedly, the extent of leukoaraiosis on FLAIR-MR images tended to be smaller in the corona radiata and centrum semiovale of the patients with the rs12425791 A/A or G/A genotype than in those with the G/G genotype (P = 0.052). Neither the rs11833579 nor the rs12425791 genotype significantly affected initial stroke severity; however the latter was associated with relatively low modified Rankin scale scores at 1 year after stroke., Conclusions: The rs11833579 A/A or G/A genotype may bring forward the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions prior to the stroke. Further studies are required to confirm our preliminary findings.

Purpose: The aim of this prospective, double-blind, randomized study was to investigate the analgesic effects of low-dose ketamine on intravenous patient-controlled analgesia (IV-PCA) with fentanyl for pain control in pediatric patients following the Nuss procedure for pectus excavatum., Materials and Methods: Sixty pediatric patients undergoing the Nuss procedure were randomly assigned to receive fentanyl (Group F, n=30) or fentanyl plus ketamine (Group FK, n=30). Ten minutes before the end of surgery, following the loading dose of each solution, 0.5 μg/kg/hr of fentanyl or 0.5 μg/kg/hr of fentanyl plus 0.15 mg/kg/hr of ketamine was infused via an IV-PCA pump (basal rate, 1 mL/hr; bolus, 0.5 mL; lock out interval, 30 min). Fentanyl consumption, pain score, ketorolac use, nausea/vomiting, ondansetron use, pruritus, respiratory depression, hallucination, dreaming, and parent satisfaction with pain control were measured throughout the 48 hours following surgery., Results: The pain scores, ketorolac use, and fentanyl consumption of Group FK were significantly lower than in Group F (p<0.05). The incidence of nausea/vomiting and ondansetron use in Group FK was significantly lower than in Group F (p<0.05). There were no reports of respiratory depression, hallucination or dreaming. Parent satisfaction with pain control was similar between the two groups., Conclusion: We concluded that low-dose ketamine added to IV-PCA with fentanyl after the Nuss procedure in pediatric patients can reduce pain scores, consumption of fentanyl, and incidence of nausea/vomiting without increasing side effects.

Neuropeptide Y (NPY), which is widely expressed in both the central and peripheral nervous systems, has an important role in a variety of biological fields. In this study, we analyzed the distribution of NPY polymorphisms in dampness-phlegm pattern and non-dampness-phlegm pattern in elderly Korean subjects with cerebral infarction (CI). A total of 1.097 subjects (498 normal subjects and 599 CI patients, including 198 with dampness-phlegm pattern and 401 with non-dampness-phlegm pattern) participated in this study. Genotyping for five SNPs (G-1484A, C-1471T, C-399T, A1201G, and C5325T) was conducted by primer extension. The results were statistically analyzed for genetic association of NPY-polymorphisms with normal versus dampness-phlegm pattern or non-dampness-phlegm pattern subjects. Among the five SNPs tested, the T allele of C-399T has a negative association with the dampness-phlegm pattern and is marked by a decrease in serum cholesterol levels. Furthermore, serum cholesterol levels were significantly higher in dampness-phlegm pattern patients than in non-dampness-phlegm pattern patients.In this study, for the first time, the association of NPY polymorphisms with pattern identification (PI) of traditional Korean medicine (TKM) was analyzed in a large CI patient population.

The production of proinflammatory cytokines including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) plays a key role in chronic pain such as neuropathic pain. We investigated changes in cytokine expression in injured peripheral nerves and dorsal root ganglia (DRG) following electroacupuncture (EA) treatment. Neuropathic pain was induced by peripheral nerve injury to the left hind limb of Sprague-Dawley rats under pentobarbital anesthesia. Two weeks later, the nerve-injured rats were treated by EA for 10 minutes. The expression levels of IL-1β, IL-6, and TNF-α in peripheral nerves and DRG of neuropathic rats were significantly increased in nerve-injured rats. However, after EA, the cytokine expression levels were noticeably decreased in peripheral nerves and DRG. These results suggest that EA stimulation can reduce the levels of proinflamtory cytokines elevated after nerve injury.

Uncoupling protein 2 (UCP2), a mitochondrial protein present in many organs and cell types, is known to dissipate the proton gradient formed by the electron transport chain. Its function is correlated with predictive parameters, such as obesity, diabetes, and metabolic syndromes. We analyzed the distribution of UCP2 polymorphisms in stroke patients diagnosed with one of the following four stroke subtypes based on the TKM standard pattern identification (PI): Qi-deficiency (QD), Dampness and Phlegm (D&P), Yin-deficiency (YD), and Fire and Heat (F&D). We studied a total of 1,786 stroke patients (397/QD, 645/D&P, 223/YD, and 522/F&D, 586/normal). Genotyping for the G-1957A, G-866A and A55V UCP2 polymorphisms was performed using the TaqMan. G-866A and A55V were significantly associated with the D&P and H&F subtypes. The frequency of subjects with the A allele of G-866A was significantly lower than the frequency of subjects with the GG type. The A55V polymorphism was also shown similar effect with G-866A in the dominant model. In contrast, no SNPs were shown to be associated with the QD or YD subtypes in this study. These results showed that the G-866A and A55V UCP2 polymorphisms may be genetic factors for specific PI types among Korean stroke patients.

WNT10B has been indicated as a potential regulator of adipogenesis in vivo and in vitro models of obesity. In this study, we analyzed the distribution of WNT10B polymorphism in elderly Korean subjects with cerebral infarction (CI) and Yin Deficiency pattern and Non-Yin Deficiency pattern. A total of 630 CI patients, including 75 with Yin Deficiency pattern and 555 with Non-Yin Deficiency pattern, participated in this study. SNP (G-607C) genotyping was conducted by primer extension using TaqMan probe; five percent of subjects were regenotyped by direct sequencing to confirm the accuracy of the genotyping. The results were analyzed using a multiple logistic regression model to evaluate the genetic association between the G-607C variant and Yin Deficiency pattern. The frequency of the CC genotype of G-607C in the Yin Deficiency pattern group (29.33%) was significantly higher than that in the Non-Yin Deficiency pattern group (23.96%) (P = 0.0339 , OR = 2.005 (1.054-3.814)) in a recessive model. This is the first study to demonstrate an association between a WNT10B polymorphism and the Yin Deficiency pattern of traditional Korean medicine (TKM) in a CI patient population. These results suggest that G-607C might be used as a diagnostic genetic marker for Yin Deficiency pattern in stroke patients and in the development of personalized medical care.

Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., has many beneficial biological activities. However, there are relatively few reports of the effects of curcumin on pathogen infections. This study examined the effect of curcumin on a Vibrio vulnificus infection. The cytotoxicity of V. vulnificus to HeLa cells was significantly inhibited by curcumin (at 10 or 30 μM). To further examine the inhibitory mechanism of curcumin against V. vulnificus-mediated cytotoxicity, the level of bacterial growth, bacterial motility, cell adhesion, RTX toxin expression and host cell reactions were evaluated. Curcumin inhibited V. vulnificus growth in HI broth. Curcumin inhibited both bacterial adhesion and RTX toxin binding to the host cells, which can be considered the major protective mechanisms for the decrease in V. vulnificus cytotoxicity. Curcumin also inhibited host cell rounding and actin aggregation, which are the early features of cell death caused by V. vulnificus. In addition, curcumin decreased the V. vulnificus-induced NF-κB translocation in HeLa cells. Finally, curcumin protected mice from V. vulnificus-induced septicemia. In conclusion, curcumin may be an alternative antimicrobial agent against fatal bacterial infections., (© 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

Thermosensitive poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer, Pluronic F68, containing a hydrophobic unit, oligo-(lactic acid)(oligo-LA) or oligo-caprolactone (oligo-CL), 2-META and RGD as side groups was successfully synthesized and characterized by (1)H NMR, FTIR, and elemental analysis. Their aqueous solution displayed special gel-sol-gel phase transition behavior with increasing temperature from 10 to 70°C, when the polymer concentration was above critical micelle concentration (CMC). The gel-sol phase diagram was investigated using tube inversion method, rheological measurement, and dynamic light scattering. Based on these results, the gelation properties of modified F68 were affected by several factors such as the composition of the substituents, chain length of oligo L-LA or oligo ε-CL, and the concentration of the polymer solutions. The unique phase transition behavior with temperature was observed by modified F68 triblock copolymer, composed of the PPO blocks core and the PEO blocks shell in aqueous solution. This phenomenon was elucidated using (1)H NMR data; the alteration of hydrophobic interaction and chain mobility led to the formation of transparent gel, coexistence of gel-sol, and opaque gel. These hydrogels may be useful in drug delivery and tissue engineering., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Stroke is the second leading cause of death and a major cause of morbidity and mortality worldwide. Evidence of variations in adiponectin (AdipoQ) genes that are associated with ischemic stroke has not been consistent, and it is unclear whether the same loci contribute to these associations in the Korean population. Using a Korean population, we tested ischemic stroke-associated AdipoQ markers., Materials and Methods: In a preliminary genome-wide association study using 320 250 k Affymetrix NSP chips, AdipoQ was found to be associated with ischemic stroke in Koreans. To study of AdipoQ, a further 673 ischemic stroke patients and 267 unrelated individuals without a history of stroke or transient ischemic attack were examined in a case-control study., Results: Six polymorphisms (rs182052G > A, rs16861205G > A, rs822391T > C, rs822396A > G, rs12495941G > T and rs3774261A > G) that had a minor allele frequency of over 1% were strongly associated with stroke (p < 0.05). Two of these, rs822391T > C and rs822396A > G showed this association on both dominant and additive logistic regression analysis after adjusting for age and sex. The haplotypes ht 1 (AGGCGG and AAGTAG) were significantly associated with susceptibility to stroke., Conclusion: Our findings show that polymorphisms in AdipoQ are associated with risk for ischemic stroke in the Korean population. This study lends further support to the putative role of AdipoQ in stroke.

Background: To understand how stroke risk factors mechanistically contribute to stroke, the genetic components regulating each risk factor need to be integrated and evaluated with respect to biological function and through pathway-based algorithms. This resource will provide information to researchers studying the molecular and genetic causes of stroke in terms of genomic variants, genes, and pathways., Methods: Reported genetic variants, gene structure, phenotypes, and literature information regarding stroke were collected and extracted from publicly available databases describing variants, genome, proteome, functional annotation, and disease subtypes. Stroke related candidate pathways and etiologic genes that participate significantly in risk were analyzed in terms of canonical pathways in public biological pathway databases. These efforts resulted in a relational database of genetic signals of cerebral stroke, SigCS base, which implements an effective web retrieval system., Results: The current version of SigCS base documents 1943 non-redundant genes with 11472 genetic variants and 165 non-redundant pathways. The web retrieval system of SigCS base consists of two principal search flows, including: 1) a gene-based variant search using gene table browsing or a keyword search, and, 2) a pathway-based variant search using pathway table browsing. SigCS base is freely accessible at http://sysbio.kribb.re.kr/sigcs., Conclusions: SigCS base is an effective tool that can assist researchers in the identification of the genetic factors associated with stroke by utilizing existing literature information, selecting candidate genes and variants for experimental studies, and examining the pathways that contribute to the pathophysiological mechanisms of stroke.

A series of pyrimidine derivatives as acid pump antagonists (APAs) was synthesized and the inhibitory activities against H(+)/K(+) ATPase isolated from hog gastric mucosa were determined. After elaborating on substituents at C2 and C4 position of the pyrimidine scaffold, we have observed that the compound 7h is a potent APA with H(+)/K(+) ATPase, IC(50) = 52 nM., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Host-parasite contact is a prerequisite for the acute cytotoxicity of Vibrio vulnificus, which is mediated primarily by RtxA1, a repeat in toxin (RTX) toxin. We found that resveratrol (at 10 or 30 microM), a natural polyphenol, protected HeLa cells from V. vulnificus cytotoxicity. To further characterize the underlying mechanism, the effect of resveratrol was investigated at the level of the host-microbe interactions. We studied the effects of resveratrol on adhesion, motility, cytotoxicity, and RtxA1 toxin expression of V. vulnificus. In addition, the effect of resveratrol on mouse mortality caused by V. vulnificus was investigated. Resveratrol inhibited V. vulnificus motility and the microbe adhesion to host cells, critical virulence traits for many bacteria. Resveratrol also down-regulated the expression of RtxA1 toxin at the transcriptional level and thereby protected the host cells from becoming rounded and damaged. In addition, resveratrol (20mg/kg) protected CD-1 mice from V. vulnificus infection. Taken together, these results suggest that resveratrol, a modulator of host-microbe interactions, has potential for development as a new paradigm drug to treat infectious diseases., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Background: In our previous study, the neuropeptide Y (NPY) C-399T promoter polymorphism (rs16147C>T) was identified as a risk factor for ischemic stroke in Koreans. In this study, we investigated whether age and sex modify the genetic effect of C-399T on susceptibility to ischemic stroke., Methods: A total of 1,350 subjects (802 ischemic stroke patients, 548 healthy controls) were genotyped for C-399T using a primer extension method. The results were statistically analyzed for the genetic association of C-399T with ischemic stroke and clinical parameters., Results: The TT genotype for C-399T was observed at a significantly lower frequency in stroke patients relative to control (CC+CT vs. TT, odds ratio [OR]=0.578, 95% confidence interval [95% CI]=0.360-0.927, P<0.05). This trend was also observed in female (OR=0.495, 95% CI=0.240-1.022) and older subjects (y>60, OR=0.556, 95% CI=0.304-1.018) with borderline statistical significance (P=0.0571 and P=0.0574, respectively). However, C-399T allele frequency was not different between controls and stroke patients in any groups. The C-399T polymorphism was found to be associated with body mass index and levels of some blood lipids., Conclusions: The C-399T NPY promoter polymorphism should be considered a genetic risk factor for ischemic stroke in the older adult and female Korean populations., (Copyright 2010 Elsevier B.V. All rights reserved.)

A series of 1H-pyrrolo[2,3-c]pyridines as acid pump antagonists (APAs) was synthesized and the inhibitory activities against H(+)/K(+) ATPase isolated from hog gastric mucosa were determined. After elaborating on substituents at N1, C5, and C7 position of 1H-pyrrolo[2,3-c]pyridine scaffold, we have observed that compounds 14f and 14g are potent APAs with H(+)/K(+) ATPase IC(50)=28 and 29 nM, respectively., (Copyright 2010 Elsevier Ltd. All rights reserved.)

This study explored the conceptual framework of dieticians' intentions to recommend functional food and the mediating role of consumption frequency. A web-based survey was designed using a self-administered questionnaire. A sample of Korean dieticians (N=233) responded to the questionnaire that included response efficacy, risk perception, consumption frequency, and recommendation intention for functional foods. A structural equation model was constructed to analyze the data. We found that response efficacy was positively related to frequency of consumption of functional foods and to recommendation intention. Consumption frequency also positively influenced recommendation intention. Risk perception had no direct influence on recommendation intention; however, the relationship was mediated completely by consumption frequency. Dieticians' consumption frequency and response efficacy were the crucial factors in recommending functional foods. Dieticians may perceive risks arising from the use of functional foods in general, but the perceived risks do not affect ratings describing dieticians' intentions to recommend them. The results also indicated that when dieticians more frequently consume functional foods, the expression of an intention to recommend functional foods may be controlled by the salience of past behaviors rather than by attitudes.

Objectives: To examine the effects of electroacupuncture stimulation on behavioral changes and neuronal nitric oxide synthase expression in the rat spinal cord after nerve injury., Methods: Under pentobarbital anesthesia, male Sprague-Dawley rats were subjected to neuropathic surgery by tightly ligating and cutting the left tibial and sural nerves. Behavioral responses to mechanical stimulation were tested for 2 weeks post-operatively. At the end of behavioral testing, electroacupuncture stimulation was applied to ST36 (Choksamni) and SP9 (Eumleungcheon) acupoints. Immunocytochemical staining was performed to investigate changes in the expression of neuronal nitric oxide synthase-immunoreactive neurons in the L4-5 spinal cord., Results: Mechanical allodynia was observed by nerve injury. The mechanical allodynia was decreased after electroacupuncture stimulation. Neuronal nitric oxide synthase expression was also decreased in L4-5 spinal cord by electroacupuncture treatment., Discussion: These results suggest that electroacupuncture relieves mechanical allodynia in the neuropathic rats possibly by the inhibition of neuronal nitric oxide synthase expression in the spinal cord.

We investigate the mechanism of dihydrogen adsorption onto Ca cation centers, which has been the significant focus of recent research for hydrogen storage. We particularly concentrate on reliability of commonly used density-functional theories, in comparison with correlated wave function theories. It is shown that, irrespective of the chosen exchange-correlation potentials, density-functional theories result in unphysical binding of H2 molecules onto Ca1+ system. This suggests that several previous publications could contain a serious overestimation of storage capacity at least in part of their results.