Search

Ubiquitin-specific protease 4 (USP4) is pivotal in negatively regulating the Toll-like receptor (TLR) signaling-mediated innate immune response. Although USP4 has been well studied in mammals, its role in TLR signaling pathways in fish remains largely unknown. In this study, we investigated the role of USP4 (OmUSP4) in regulating TLR response in rainbow trout Oncorhynchus mykiss. OmUSP4 contained the characteristic domains conserved in other USP4s: domain in USP (DUSP), ubiquitin-like (UBL), and the bi-part catalytic domain known as USP. OmUSP4 expression was increased in RTH-149 cells by stimulation with fish-pathogenic bacteria and bacterial ligands. Gain- and loss-of-function experiments revealed that OmUSP4 mitigated the activation of MAPKs and NF-κB, as well as the expression of pro-inflammatory cytokines in LPS-stimulated cells. OmUSP4 interacted with TAK1, a critical mediator in TLR-mediated NF-κB signaling pathways. LPS stimulation increased the K63-linked polyubiquitination of TAK1, which was significantly suppressed when OmUSP4 was compelled to be overexpressed. These results imply that OmUSP4 might function like mammals to downregulate LPS-induced inflammation in rainbow trout by removing the K63-linked ubiquitin chain on TAK1.

Deubiquitinase cylindromatosis (CYLD) inhibits MAPK and NF-κB activation pathways by deubiquitinating upstream regulatory factors. Although CYLD has been identified and actively studied in mammals, nothing is known about its putative function in fish. In this study, we identified the gene encoding CYLD (OmCYLD) from rainbow trout, Oncorhynchus mykiss, and examined its role during pathogenic infections. The deduced amino acid sequence of OmCYLD contains conserved CAP-Gly and USP domains. In RTH-149 cells, the expression of OmCYLD was increased by stimulation with Edwardsiella tarda and Streptococcus iniae. Gain-of-function and loss-of-function experiments showed that OmCYLD down-regulates the activation of MAPK and NF-κB and the expression of pro-inflammatory cytokines in E. tarda-stimulated RTH-149 cells. These findings suggest that OmCYLD might function like those of mammals to negatively regulate bacteria-triggered signaling pathway in fish.

This study investigated the suitability of freeze-dried ice plant (Mesembryanthemum crystallinum) as the source of an edible healthy salt alternative by examining the content of NaCl, D-pinitol, total phenols, total flavonoids, and DPPH radical scavenging activity compared with those of natural and purified salts. Our results showed that the NaCl content of freeze-dried ice plant, natural and purified salts was 19, 94 and 99%, respectively. The Dpinitol content of freeze-dried ice plant was 777 mg/100 g, whereas D-pinitol was not detected in either natural or purified salts. The total phenol and flavonoid contents of freeze-dried ice plant were 115 mg GAE/100 g and 985 mg RE/100 g, respectively. The DPPH radical scavenging activity of freeze-dried ice plant was markedly higher than that of natural and purified salts. Altogether, these results show that freeze-dried ice plant contains both NaCl and bioactive compounds and can be used as a source of edible salt with positive health effects.

Bacterial colonization and transmission via surfaces increase the risk of infection. In this study, we design and employ novel adhesive antimicrobial peptides to prevent bacterial contamination of surfaces. Repeats of 3,4-dihydroxy-L-phenylalanine (DOPA) were added to the C-terminus of NKC, a potent synthetic antimicrobial peptide, and the adhesiveness and antibacterial properties of the resulting peptides are evaluated. The peptide is successfully immobilized on polystyrene, titanium, and polydimethylsiloxane surfaces within 10 min in a one-step coating process with no prior surface functionalization. The antibacterial effectiveness of the NKC-DOPA5-coated polystyrene, titanium, and polydimethylsiloxane surfaces is confirmed by complete inhibition of the growth of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus within 2 h. The stability of the peptide coated on the substrate surface is maintained for 84 days, as confirmed by its bactericidal activity. Additionally, the NKC-DOPA5-coated polystyrene, titanium, and polydimethylsiloxane surfaces show no cytotoxicity toward the human keratinocyte cell line HaCaT. The antimicrobial properties of the peptide-coated surfaces are confirmed in a subcutaneous implantation animal model. The adhesive antimicrobial peptide developed in this study exhibits potential as an antimicrobial surface-coating agent for efficiently killing a broad spectrum of bacteria on contact.

The purpose of this study was to enhance the immune-enhancing activity of mushroom strains through fermentation to promote food use of leaf extracts of S. quelpaertensis containing β-glucan. We evaluated the immunomodulatory effect of extracts from fermented S. quelpaertensis leaves (SQGL, SQHE, SQPL). S. quelpaertensis leaves fermentation products were prepared by using mushroom mycelia (Ganoderma lucidum, Hericium erinaceum, Phellinus linteus). The content of β-glucan, a major substance in S. quelpaertensis leaves fermentation products, was 3.73 ± 0.50 mg/mL in the extract (SQ) of S. quelpaertensis leaves. The fermented mushrooms, SQGL, were the highest at 5.57 ± 0.86 mg/100 mL, followed by SQHE and SQPL, and the β-glucan content of all of the glucan was &gt, 75.3%. To test the immune activity, S. quelpaertensis leaf fermentation products were administered to mice at different doses (60, 160, and 360 mg/kg) for two weeks. Th cell and macrophage populations were found to increase significantly at all three doses compared to the negative control after two weeks. SQGL and SQHE were highest at 160 mg/kg, and SQPL showed the highest Th cell proliferation at 60 mg/kg. In addition, the production of IFN-γ, IL-4, IL-10, and nitric oxide was significantly higher than that of the negative control after two weeks. In particular, an increase was seen at a low concentration of 60 mg/kg. Therefore, the S. quelpaertensis leaf fermentation product can be very useful as a functional ingredient for enhancing immunity.

Objective The objective of this study was to identify the relationships among people's perceived financial status to cope with severe disease, levels of anxiety and determinations of life. Study design This is a secondary analysis of population-based cross-sectional surveys. Methods The 2016 Social Integration Survey of 8000 Korean participants aged 19 years or older was used. Data were analysed using correlation, correspondence and covariate analyses. Results Of all the participants, 84.6% responded that they had insufficient perceptions of financial status; decision-making power was found to have a stronger correlation with perceived financial stability than with real income. In addition, the perceived ability, based on financial status, to cope with severe disease was correlated with anxiety. Conclusions The study proposes that when developing health and medical treatment policy and intervention programmes, perceptions of personal financial status and stability should be considered concurrently.

The objective of the present study was to develop a concoction of natural products that could dramatically improve immune function with minimal possible side effects. Sasa quelpaertensis Nakai and Ficus erecta var. sieboldii are plants that are native to Jeju Island, Korea and are known to be rich in physiologically active substances. We prepared a mixture of different proportions and extraction conditions using two natural plants and determined their optimum mixing ratio and extraction method by assessing immune function-related biomarkers in RAW264.7 macrophages. Optimal extract (HR02/04(8:2)-W) was selected from in vitro experiments and its immunity-enhancing efficacy was evaluated in mice. After oral administration of extract to BALB/c mice for 2 weeks, nitric oxide production in the peritoneal exudate cells, natural killer cell cytotoxicity, cytokine expression in splenocytes, and total cell number of immune tissues and phenotype analysis were evaluated. Our results demonstrated that HR02/04(8:2)-W significantly enhanced the immune system by increasing natural killer cell activity, cytokine expression, and total number of cells in immune tissues. In conclusion, our study validates the role of HR02/04(8:2)-W in enhancing immunity and its potential development as a functional food.

The objective of the present study was to develop a concoction of natural products that could dramatically improve immune function with minimal possible side effects. Sasa quelpaertensis Nakai and Ficus erecta var. sieboldii are plants that are native to Jeju Island, Korea and are known to be rich in physiologically active substances. We prepared a mixture of different proportions and extraction conditions using two natural plants and determined their optimum mixing ratio and extraction method by assessing immune function-related biomarkers in RAW264.7 macrophages. Optimal extract (HR02/04(8:2)-W) was selected from in vitro experiments and its immunity-enhancing efficacy was evaluated in mice. After oral administration of extract to BALB/c mice for 2 weeks, nitric oxide production in the peritoneal exudate cells, natural killer cell cytotoxicity, cytokine expression in splenocytes, and total cell number of immune tissues and phenotype analysis were evaluated. Our results demonstrated that HR02/04(8:2)-W significantly enhanced the immune system by increasing natural killer cell activity, cytokine expression, and total number of cells in immune tissues. In conclusion, our study validates the role of HR02/04(8:2)-W in enhancing immunity and its potential development as a functional food.

The purpose of this study was to compare the nutritional components and antioxidant activities of two different cultivars of Brassica juncea (Dolsan, Yeosu, Korea (BJD) and (Jeongseon, Gangwon, Korea (BJJ)). We investigated the proximate composition (moisture, crude ash, crude protein and crude lipid), antioxidant activities (2,2-Diphenyl-2-picrylhydrazil (DPPH) scavenging activity and ferric reducing antioxidant power (FRAP)), total phenol content, total flavonoid content and sinigrin content by high-performance liquid chromatography analysis. Our results show that the proximate compositions of BJD and BJJ were not significantly different. However, both the DPPH radical scavenging and FRAP activities of the BJJ extracts were higher than those of the BJD extracts. The total phenol contents of the BJD and BJJ extracts were 6.56 and 9.80 mg gallic acid equivalent/g, respectively. The total flavonoids content of the BJD and BJJ extracts were 20.92 and 34.81 mg rutin equivalent/g, respectively, whereas the sinigrin contents, one of the major compounds in BJD and BJJ extracts, were 16.16 mg/g and 11.73 mg/g, respectively. In this study, we confirmed that, by comparing BJJ and BJD, the sinigrin content of BJD was higher than that of BJJ, but the antioxidant activity and phenol content of BJD were superior to that of BJJ.

This study evaluated the mutagenicity and acute toxicity of the juice extract of nutricultured Brassica napus containing vanadium (BECV). The BECV was prepared by nutriculture for 7 days in Jeju water containing vanadium. The mutagenic effects of BECV were investigated using the bacterial reverse mutation test, chromosome aberration test, and micronucleus test. Based on the results of the mutagenicity test, we propose that BECV is not a mutagenicity-inducing agent. In the acute oral toxicity study, male and female Sprague-Dawley rats were administered a single limiting dose of 0.014, 0.14, or 1.4 μg BECV/kg body weight; the rats were then observed for 7 days. No acute lethal effect was observed at the maximal dose of 1.4 μg BECV/kg body weight. In the subacute study, male and female rats were administered once daily, by oral gavage, a dose of 0.028, 0.14, and 0.7 μg/kg body weight of BECV for 28 days. No significant toxicity was observed not only hematological, biochemical, and pathological parameters but also the body and organ weights when compared to controls. The level of BECV with no observed adverse effects in male and female rats was 0.7 μg/kg body weight (concentration of vanadium in BECV) in the subacute toxicity study.

The purpose of this study was to determine the antidiabetic effect of an extract of nutricultured Brassica napus containing vanadium (BECV). The BECV was prepared following nutriculture of B. napus with a Jeju water vanadium concentrate for 7 day. The BECV was administered to db/db mice for 8 weeks at different dosages (0.028, 0.14, and 0.7 μg/kg; as vanadium concentration in BECV). After 8 weeks, the BECV results showed mouse blood glucose concentrations to significantly decrease, in a dose-dependent manner, compared with the results for control mice. In addition, the concentrations of triglyceride, total cholesterol, and glycated hemoglobin were significantly lower after 8 weeks of administration of 0.7 μg/kg BECV. Therefore, the BECV may have protective effects against type 2 diabetes.

In the current study investigated the protective effects of citrus based mixture drinks (CBMDs) using oxidative stress in human dermal fibroblast (HDF) cells and restraint-stressed rats. The CBMDs contained citrus bioflavonoids including narirutin and hesperidin. The cell viability of HDF cells treated with H(2)O(2) was observed at 53.9% but treated with CBMD-1 and CBMD-2 (500 μg/mL) on H(2)O(2) exposed HDF cells significantly increased the relative cell viability at 65.0 and 72.2%, respectively. In the treadmill test, the time spent on the electrode plate in the restraint-stressed group was analyzed 24.1 s, but restraint-stressed rats with administered CBMDs (300 mg/kg) had significantly decreased the time at 2.4 (CBMD-1) and 4.7 (CBMD-2) s, respectively. In addition, number of touches the electrode plate in restraint-stressed group was observed at 42.4 ea, but, restraint-stressed rats with administered CBMD-1 and CBMD-2 (300 mg/kg) were significantly decreased at 7.0 and 10.2 ea, respectively.

The objective of this study was to investigate the inhibitory effects of Litsea japonica fruit flesh extract (LJF-HE) on gastritis in an indomethacin-induced SD rat model. Rats were randomly divided into six groups: G1 (normal group), G2 (control group, indomethacin-induced gastritis), G3 (positive group, indomethacin-induced gastritis and ranitidine 50 mg/kg), G4 (LJF-HE-L group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 30 mg/kg), G5 (LJF-HE-M group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 60 mg/kg), G6 (LJF-HE-H group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 120 mg/kg). In the group treated with LJF-HE (G4, G5, and G6), gastric mucosal damage, gastric juice secretion and pepsin activity were significantly decreased compared to the control group. Additionally, there were decreases in the expression of cholecystokinin 2 receptor (CCK-2r), histamine receptor H2 (H2r) and H+/K+ ATPase in the gastric lesions. The plasma levels of TNF-α and IL-1β significantly decreased in LJF-HE (G4, G5, and G6) treated groups compared with control. The plasma level of PGE2 was also significantly increased by LJF-HE (G5 and G6). These results suggest that LJF-HE (G4, G5, and G6) has the ability to inhibit on indomethacin-induced gastritis.

We evaluated the antioxidative activity of extracts of P. lobata root depending on roasting conditions. P. lobata roots were roasted at three different temperature at 150℃, 200℃, and 250℃ and three different time at 10 min, 20 min, and 30 min respectively. Roasted P. lobata root was extracted using water at 85℃ for 6 h and filtered using filter paper, followed by then evaporated (12±0.3 °Brix) and freeze-dried. The concentration of maker compound puerarin was determined using a high performance liquid chromatography system. 2 phenolic compounds, flavonoid contents, and antioxidant activities of the extract powder were evaluated. Puerarin contents, Phenolic compounds, and flavonoid contents of roasted P. lobata root were higher than those of unroasted P. lobata root. The results of DPPH and ABTS showed that roasted P. lobata root possessed higher antioxidant activity than unroasted P. lobata root. This study suggested that roasting process could be applied to P. lobata root in order to achieve its high quality and functionality.

SummaryWhat is known and objective There are a few Korean studies on the economics of statins based on reduction in low-density lipoprotein cholesterol (LDL-C) data from other countries. This study aimed to analyse and compare the cost-effectiveness of statins according to the baseline LDL-C level in Korea. Methods Between January 2009 and December 2015, the data of patients who were prescribed statins for the first time were extracted from electronic medical records. We performed a cost-effectiveness analysis (CEA) based on the LDL-C reduction rate (CEA-RR) and target achievement rate. Results and discussion Among high-intensity statins, the CEA-RR value of rosuvastatin (20 mg) was significantly lower than that of atorvastatin (40 mg) at all baseline LDL-C levels, except levels of 160–189 mg/dL. Additionally, at baseline LDL-C levels of 130–159 mg/dL, the CEA-RR value of rosuvastatin (20 mg) was three times lower than that of atorvastatin (40 mg) (9·1 ± 2·5 $/% vs. 31·7 ± 15·0 $/%, P < 0·001). Among moderate-to-low-intensity statins, rosuvastatin (5 mg) showed the lowest CEA-RR value (4·0 ± 0·6 $/%), and the value significantly increased for pitavastatin (2 mg) (8·0 ± 0·6 $/%), atorvastatin (10 mg) (9·5 ± 0·5 $/%), simvastatin (10·8 ± 1·1 $/%) and pravastatin (40 mg) (11·5 ± 0·9 $/%) in order (P < 0·0001). On changing from atorvastatin (10 mg) to atorvastatin (20 mg), the additional yearly cost was 16·0 and additional CEA-RR value was 2·74 $/%. On the other hand, on changing from atorvastatin (10 mg) to rosuvastatin (10 mg), the additional yearly cost was −16·3 and additional CEA-RR value was −1·8 $/%. What is new and conclusion We successfully compared the cost-effectiveness of statins according to the baseline LDL-C level in Korea. It is expected that our findings will help clinical decision-making with regard to statin prescription, and this will help reduce national medical expenditure.

The antioxidant and anti-adipogenic activities of a mixture of Nelumbo nucifera L., Morus alba L., and Raphanus sativus were investigated and their anti-obesity activities were established in vitro and in vivo. Among the 26 different mixtures of extraction solvent and mixture ratios, ethanol extract mixture no. 1 (EM01) showed the highest antioxidant (α,α-Diphenyl-β-picrylhydrazyl, total phenolic contents) and anti-adipogenic (Oil-Red O staining) activities. EM01 inhibited lipid accumulation in 3T3-L1 adipocytes compared to quercetin-3-O-glucuronide. Furthermore, body, liver, and adipose tissue weights decreased in the high-fat diet (HFD)-EM01 group compared to in the high-fat diet control group (HFD-CTL). EM01 lowered blood glucose levels elevated by the HFD. Lipid profiles were improved following EM01 treatment. Serum adiponectin significantly increased, while leptin, insulin growth factor-1, non-esterified fatty acid, and glucose significantly decreased in the HFD-EM01 group. Adipogenesis and lipogenesis-related genes were suppressed, while fat oxidation-related genes increased following EM01 administration. Thus, EM01 may be a natural anti-obesity agent.

The antioxidant and anti-adipogenic activities of a mixture of Nelumbo nucifera L., Morus alba L., and Raphanus sativus were investigated and their anti-obesity activities were established in vitro and in vivo. Among the 26 different mixtures of extraction solvent and mixture ratios, ethanol extract mixture no. 1 (EM01) showed the highest antioxidant (α,α-Diphenyl-β-picrylhydrazyl, total phenolic contents) and anti-adipogenic (Oil-Red O staining) activities. EM01 inhibited lipid accumulation in 3T3-L1 adipocytes compared to quercetin-3-O-glucuronide. Furthermore, body, liver, and adipose tissue weights decreased in the high-fat diet (HFD)-EM01 group compared to in the high-fat diet control group (HFD-CTL). EM01 lowered blood glucose levels elevated by the HFD. Lipid profiles were improved following EM01 treatment. Serum adiponectin significantly increased, while leptin, insulin growth factor-1, non-esterified fatty acid, and glucose significantly decreased in the HFD-EM01 group. Adipogenesis and lipogenesis-related genes were suppressed, while fat oxidation-related genes increased following EM01 administration. Thus, EM01 may be a natural anti-obesity agent.

We extend the use of the Tsallis statistic to measure the differences in gas dynamics relative to the mean magnetic field present from natural eddy-type motions existing in magnetohydrodynamical (MHD) turbulence. The variation in gas dynamics was estimated using the Tsallis parameters on the incremental probability distribution function of the observables (intensity and velocity centroid) obtained from compressible MHD simulations. We find that the Tsallis statistic is susceptible to the anisotropy produce by the magnetic field, even when anisotropy is percent the Tsallis statistic can be use to determine MHD parameters such as the Sonic Mach number. We quantize the goodness of the Tsallis parameters using the coefficient of determination to measure the differences in the gas dynamics. These parameters also determine the level of magnetization and compressibility of the medium. To further simulate realistic spectroscopic observational data we introduced smoothing, noise, and cloud boundaries to the MHD simulations., Comment: 7 pages, 6 figures, MNRAS publish Bibcode: 2018MNRAS.475.3324G

NOD1 has important roles in innate immunity as sensor of microbial components derived from bacterial peptidoglycan. In this study, we identified genes encoding components of the NOD1 signaling pathway, including NOD1 (OmNOD1) and RIP2 (OmRIP2) from rainbow trout, Oncorhynchus mykiss, and investigated whether OmNOD1 has immunomodulating activity in a rainbow trout hepatoma cell line RTH-149 treated with NOD1-specific ligand (iE-DAP). The deduced amino acid sequence of OmNOD1 contained conserved CARD, NOD and LRR domains. Loss-of-function and gain-of-function experiments indicated that OmNOD1 is involved in the expression of pro-inflammatory cytokines. Silencing of OmNOD1 in RTH-149 cells treated with iE-DAP decreased the expression of IL-1β, IL-6, IL-8 and TNF-α. Conversely, overexpression of OmNOD1 resulted in up-regulation of IL-1β, IL-6, IL-8 and TNF-α expression. In addition, RIP2 inhibitor (gefitinib) significantly decreased the expression of these pro-inflammatory cytokines induced by iE-DAP in RTH-149 cells. These findings highlight the important role of NOD1 signaling pathway in fish in eliciting innate immune response.

The production of excessive reactive oxygen species by exposure to oxidative stress and solar radiation are primary factors in skin damage. We examined the effects of a citrus-based juice mixture and its bioactive compounds on antioxidant and anti-ageing activities in human dermal fibroblasts and hairless mice via the regulation of antioxidant enzymes and the mitogen-activated protein kinase pathway. The citrus-based juice mixture reduced H2O2-induced cell damage and intracellular reactive oxygen species production in human dermal fibroblasts. Citrus-based juice mixture pretreatment suppressed the activation of the H2O2-mediated mitogen-activated protein kinase pathway by activating the expression of activator protein 1 and matrix metalloproteinases. Moreover, it increased the expression levels of antioxidant enzymes such as glutathione reductase, catalase and manganese superoxide dismutase. In addition, oral administration of the citrus-based juice mixture decreased skin thickness and wrinkle formation and increased collagen content on an ultraviolet light B-exposed hairless mouse. These results indicate that the citrus-based juice mixture is a potentially healthy beverage for the prevention of oxidative stress-induced premature skin ageing.

Cirsium setidens Nakai contains bioactive compounds that exert biological activities. Method validation for analysis of the pectolinarin content in Cirsium setidens extracts (CSE) and radical scavenging-linked antiobesity activities using 3T3-L1 cells and C57BL/6 mice were performed. The pectolinarin content of CSE was 2.81±0.01 mg/g with a high degree of linearity in calibration curves (R2=0.9999). CSE exhibited free radical-scavenging activities and a reducing power. CSE and pectolinarin inhibited lipid accumulation during adipogenesis of 3T3-L1 cells via down-regulation of adipogenic transcription factors. CSE supplementation suppressed body weight in C57BL/6 mice fed a high fat diet and reduced plasma total cholesterol, triglyceride, insulin, and glucose levels. Pectolinarin-enriched CSE can be considered as a good source of natural antioxidants and antiobesity ingredients.

The purpose of this study was to compare the nutritional components and antioxidant activities of two different cultivars of Brassica juncea (Dolsan, Yeosu, Korea (BJD) and (Jeongseon, Gangwon, Korea (BJJ)). We investigated the proximate composition (moisture, crude ash, crude protein and crude lipid), antioxidant activities (2,2-Diphenyl-2-picrylhydrazil (DPPH) scavenging activity and ferric reducing antioxidant power (FRAP)), total phenol content, total flavonoid content and sinigrin content by high-performance liquid chromatography analysis. Our results show that the proximate compositions of BJD and BJJ were not significantly different. However, both the DPPH radical scavenging and FRAP activities of the BJJ extracts were higher than those of the BJD extracts. The total phenol contents of the BJD and BJJ extracts were 6.56 and 9.80 mg gallic acid equivalent/g, respectively. The total flavonoids content of the BJD and BJJ extracts were 20.92 and 34.81 mg rutin equivalent/g, respectively, whereas the sinigrin contents, one of the major compounds in BJD and BJJ extracts, were 16.16 mg/g and 11.73 mg/g, respectively. In this study, we confirmed that, by comparing BJJ and BJD, the sinigrin content of BJD was higher than that of BJJ, but the antioxidant activity and phenol content of BJD were superior to that of BJJ.

The emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa, coupled with shrinking antibiotic pipelines, has increased the demand for new antimicrobials with novel mechanisms of action. As the indiscriminate nature of broad-spectrum antimicrobial toxicity may have negative clinical consequences and increase the incidence of resistance, we have developed a P. aeruginosa-selective antimicrobial peptide capable of preferentially killing P. aeruginosa relative to benign microorganisms. A targeting peptide (PA2) that binds specifically to OprF porin on P. aeruginosa was identified by phage display peptide library screening, and a hybrid peptide was constructed by addition of the targeting peptide to GNU7, a potent antimicrobial peptide. The resulting hybrid peptide PA2-GNU7 exhibited potent antimicrobial activity against P. aeruginosa without causing host toxicity. Confocal laser scanning microscopy analysis and time-kill experiments demonstrated that PA2-GNU7 exhibited a high degree of specificity for P. aeruginosa, and rapidly and selectively killed P. aeruginosa cells in mixed cultures. In addition, in vivo treatment efficacy of PA2-GNU7 was significantly greater than that of conventional antibiotics in a mouse model of MDR P. aeruginosa infection. Taken together, the data suggest that PA2-GNU7 may be a promising template for further development as a novel anti-MDR P. aeruginosa therapeutic agent.

TRAF6 and TAK1 are known to play important roles in vertebrate innate immunity as molecular bridge, linking upstream toll-like receptors (TLRs) with the downstream MAPK and NF-κB signalling pathways. However, their roles in TLR signalling pathway have yet to be fully described in fish. Here we identified genes encoding TRAF6 (OmTRAF6) and TAK1 (OmTAK1) from rainbow trout, Oncorhynchus mykiss, and examined their roles during pathogenic infections. The deduced amino acid sequences of OmTRAF6 and OmTAK1 contained the characteristic domains conserved in the TRAF and TAK1 families, respectively (OmTRAF6: RING, two TRAF-type zinc fingers, CCR and MATH domains; OmTAK1: STKc and CCR domains). In RTH-149 cells, the expression of OmTRAF6 and OmTAK1 was increased by stimulation with Edwardsiella tarda and LPS. Silencing of OmTRAF6 and OmTAK1 in RTH-149 cells negatively regulated the LPS-induced phosphorylation of p38 MAPK and JNK. TAK1 inhibitor (5z)-7-Oxozeaenol significantly decreased the LPS-induced activation of NF-κB in RTH-149 cells. In addition, silencing of OmTRAF6 and OmTAK1 significantly decreased the expression of MAPKs and NF-κB downstream target genes induced by LPS in RTH-149 cells. These findings suggest that OmTRAF6 and OmTAK1 might function like those of mammals to regulate bacteria-triggered signalling pathway in fish.

The aim of this study was to investigate the association between chronic laryngitis (CL) and insulin resistance (IR) in South Korea using data from the 2010 Korea National Health and Nutrition Examination Surveys (KNHANES). Cross-sectional data of 4,261 adults who completed KNHANES were analyzed. CL was considered when participants experienced a voice change and demonstrated flexible laryngoscopic findings of diffuse laryngeal inflammation. All participants were assessed for IR using the homeostasis model assessment of insulin resistance (HOMA-IR). Among the Korean population older than 19 years, the prevalence of chronic laryngitis was 3.8±0.7%. Univariate analysis demonstrated that CL was significantly associated with smoking and systolic and diastolic blood pressure in men and with age, diastolic blood pressure, HDL cholesterol, insulin, and HOMA-IR in women. Multiple regression analysis demonstrated that the mean value of HOMA-IR was significantly associated with CL in women only. In addition, CL was more prevalent in the highest compared with the lowest HOMA-IR quartile (OR [95% CI]: 2.268 [1.053-4.884] after adjusting for age, OR [95% CI]: 2.235 [1.040-6.181] after adjusting for confounding factors of age, body mass index, smoking status, alcohol intake, regular exercise, education, and income). These findings indicate that IR characterized by HOMA-IR is significantly associated with CL in Korean women only. Our results suggest that HOMA-IR could be an early predictive factor of increased risk of CL in Korean women.

Buforin IIb, a novel cell-penetrating anticancer peptide derived from histone H2A, has been reported to induce mitochondria-dependent apoptosis in tumor cells. However, increasing evidence suggests that endoplasmic reticulum and mitochondria cooperate to signal cell death. In this study, we investigated the mechanism of buforin IIb-induced apoptosis in human cervical carcinoma HeLa cells by focusing on ER stress-mediated mitochondrial membrane permeabilization. Two-dimensional PAGE coupled with MALDI-TOF and western blot analysis showed that buforin IIb treatment of HeLa cells resulted in upregulation of ER stress proteins. PBA (ER stress inhibitor) and BAPTA/AM (Ca(2+) chelator) pretreatment rescued viability of buforin IIb-treated cells through abolishing phosphorylation of SAPK/JNK and p38 MAPK. SP600125 (SAPK/JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated down-regulation of Bcl-xL/Bcl-2, mitochondrial translocation of Bax, and cytochrome c release from mitochondria. Taken together, our data suggest that the ER stress pathway has an important role in the buforin IIb-induced apoptosis in HeLa cells.