COMPARISON STUDY OF EXPERIMENTS AND PREDICTIONS OF WAVE KINEMATICS FOR ROGUE WAVE

To investigate the wave kinematics under the rogue wave crest, a series of experiments were performed in 2-D wave tank with the application of PIV technique to measure the velocities under the free surface. Three different prediction methods of linear extrapolation, Wheeler stretching, and modified stretching were applied to estimate water wave kinematics and compared with PIV experimental results under the highest wave crest of irregular wave trains satisfying with rogue wave criteria. Also, the cut-off frequency dependence for three prediction methods was investigated with varying spectral peak frequencies to estimate wave kinematics including velocities and accelerations in horizontal and vertical directions. It was suggested that the cut-off frequency for the reasonable prediction of the wave kinematics under the rogue wave crest could be chosen three times of spectral peak wave frequency for the linear extrapolation and higher frequency than four times of spectral peak wave frequency for Wheeler stretching and modified stretching method

YAF2 promotes TP53-mediated genotoxic stress response via stabilization of PDCD5

AbstractProgrammed cell death 5 (PDCD5) plays a crucial role in TP53-mediated apoptosis, but the regulatory mechanism of PDCD5 itself during apoptosis remains obscure. We identified YY1-associated factor 2 (YAF2) as a novel PDCD5-interacting protein in a yeast two-hybrid screen for PDCD5-interacting proteins. We found that YY1-associated factor 2 (YAF2) binds to and increases PDCD5 stability by inhibiting the ubiquitin-dependent proteosomal degradation pathway. However, knocking-down of YAF2 diminishes the levels of PDCD5 protein but not the levels of PDCD5 mRNA. Upon genotoxic stress response, YAF2 promotes TP53 activation via association with PDCD5. Strikingly, YAF2 failed to promote TP53 activation in the deletion of PDCD5, whereas restoration of wild-type PDCD5WT efficiently reversed the ineffectiveness of YAF2 on TP53 activation. Conversely, PDCD5 efficiently overcame the knockdown effect of YAF2 on ET-induced TP53 activation. Finally, impaired apoptosis upon PDCD5 ablation was substantially rescued by restoration of PDCD5WT but not YAF2-interacting defective PDCD5E4D nor TP53-interacting defective PDCD5E16D mutant. Our findings uncovered an apoptotic signaling cascade linking YAF2, PDCD5, and TP53 during genotoxic stress responses

Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines

BACKGROUND: MitoQ is a mitochondria-targeted derivative of the antioxidant ubiquinone, with antioxidant and anti-apoptotic functions. Reactive oxygen species are involved in many inflammatory diseases including inflammatory bowel disease. In this study, we assessed the therapeutic effects of MitoQ in a mouse model of experimental colitis and investigated the possible mechanisms underlying its effects on intestinal inflammation. METHODS: Reactive oxygen species levels and mitochondrial function were measured in blood mononuclear cells of patients with inflammatory bowel disease. The effects of MitoQ were evaluated in a dextran sulfate sodium-induced colitis mouse model. Clinical and pathological markers of disease severity and oxidative injury, and levels of inflammatory cytokines in mouse colonic tissue were measured. The effect of MitoQ on inflammatory cytokines released in the human macrophage-like cell line THP-1 was also analyzed. RESULTS: Cellular and mitochondrial reactive oxygen species levels in mononuclear cells were significantly higher in patients with inflammatory bowel disease (P <0.003, cellular reactive oxygen species; P <0.001, mitochondrial reactive oxygen species). MitoQ significantly ameliorated colitis in the dextran sulfate sodium-induced mouse model in vivo, reduced the increased oxidative stress response (malondialdehyde and 3-nitrotyrosine formation), and suppressed mitochondrial and histopathological injury by decreasing levels of inflammatory cytokines IL-1 beta and IL-18 (P <0.001 and P <0.01 respectively). By decreasing mitochondrial reactive oxygen species, MitoQ also suppressed activation of the NLRP3 inflammasome that was responsible for maturation of IL-1 beta and IL-18. In vitro studies demonstrated that MitoQ decreases IL-1 beta and IL-18 production in human THP-1 cells. CONCLUSION: Taken together, our results suggest that MitoQ may have potential as a novel therapeutic agent for the treatment of acute phases of inflammatory bowel disease

Evaluation of barley to replace milk by-product in weaning pig’s diet

The supplementation level of barley was limited because of high contents of fiber in monogastric animals. Barley contained high soluble fiber, thus it could prevent to diarrhea of weaning pigs. Moreover, as the barley break down by enzymes, free sugars come out from the barley, which could be used as an energy source in weaning pigs and replace milk by-products in weaning pig’s diet. Therefore, present study was conducted to investigate the influence of barley to replace milk by-product in weaning pig’s diet on growth performance, blood profile, nutrient digestibility, diarrhea incidence, and economic analysis in weaning pigs. A total of 112 crossbred ([York-shire × Landrace] × Duroc, weaned at 28 days of age) piglets were allotted to 4 treatments in a randomized complete block (RCB) design. Each treatment has 7 replications with 4 pigs per pen. Pigs were fed each treatment diet which containing different levels of barley (0%, 10%, 20%, and 30%) at the expense of whey powder and lactose. Three phase feeding programs were used for 6 weeks of growth trial (phase 1: 0–2 weeks; phase 2: 3–4 weeks; phase 3: 5–6 weeks). During 0–2 week, body weight (BW), average daily gain (ADG) and G:F ratio were decreased as barley level increased in the diet (linear response, p < 0.01). In blood profile, blood urea nitrogen was decreased as the barley level increased in the diet (linear, p < 0.01). However, no significant differences were observed in blood glucose level. In nutrient digestibility, crude fat digestibility was linearly increased as barley increased (linear, p < 0.01). The incidence of diarrhea was improved as increasing barley contents in all phases (linear, p < 0.01). These results demonstrated that supplementation of barley to replace milk by-product influenced negatively on growth performance during 0–2 week. However, the incidence of diarrhea and later growth performance from 3 week postweaning were improved as dietary barley level increased

Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Angiogenesis is a multistep process in which many growth factors and cytokines have an essential role. Vascular endothelial growth factor (VEGF) is a potent angiogenic agent that acts as a specific mitogen for vascular endothelial cells through specific cell surface receptors. The interleukin-6 (IL-6) pathway is another mechanism linking angiogenesis to malignancy. C-reactive protein (CRP), a representative marker for inflammation, is known for its association with disease progression in many cancer types. The aim of this study was to determine preoperative serum levels of VEGF, IL-6, and CRP in colorectal carcinoma, and to correlate them with disease status and prognosis.</p> <p>Methods</p> <p>A 132 of 143 patients who underwent curative resection for colorectal cancer were enrolled in this study. 11 patients with resection margin positive were excluded. Factors considered in analysis of the relationship between VEGF, IL-6, and CRP and histological findings. Patient prognosis was investigated. Serum levels of VEGF and IL-6 were assessed using Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured using immunoturbidimetry.</p> <p>Results</p> <p>Median follow-up duration was 18.53 months (range 0.73-43.17 months) and median age of the patients was 62 years (range, 26-83 years). Mean and median levels of VEGF and CRP in colorectal cancer were significantly higher than in the normal control group; 608 vs. 334 pg/mL and 528 (range 122-3242) vs. 312 (range 16-1121) (<it>p </it>< 0.001); 1.05 mg/dL vs. 0.43 mg/dL and 0.22 (range 0.00-18.40) vs. 0.07 (range 0.02-6.94) (<it>p </it>= 0.002), respectively. However mean and median level of IL-6 in patients were not significantly higher than in control; 14.33 pg/mL vs. 5.65 pg/mL and 6.00 (range 1.02-139.17) vs. 5.30 (4.50-13.78) (<it>p </it>= 0.327). Although IL-6 and CRP levels were not correlated with other pathological findings, VEGF level was significantly correlated with tumor size (<it>p </it>= 0.012) and CEA (<it>p </it>= 0.038). When we established the cutoff value for VEGF (825 pg/mL), IL-6 (8.09 pg/mL), and CRP (0.51 mg/dL) by Receiver Operating Characteristic (ROC) curve, we noted that high VEGF levels tended to reduce overall survival (<it>p </it>= 0.053), but not significantly. However, IL-6 and CRP demonstrated no significance with regard to disease free survival (<it>p </it>= 0.531, <it>p </it>= 0.701, respectively) and overall survival (<it>p </it>= 0.563, <it>p </it>= 0.572, respectively). Multivariate analysis showed that VEGF (<it>p </it>= 0.032), CEA (<it>p </it>= 0.012), lymph node metastasis (<it>p </it>= 0.002), and TNM stage (<it>p </it>= 0.025) were independently associated with overall survival.</p> <p>Conclusions</p> <p>Preoperative serum VEGF and CRP level increased in colorectal cancer patients. High VEGF level has been proposed as a poor prognostic factor for overall survival in patients with colorectal cancer.</p

Renal Toxicity Evaluation and Comparison Between Visipaque (Iodixanol) and Hexabrix (Ioxaglate) in Patients With Renal Insufficiency Undergoing Coronary Angiography The RECOVER Study: A Randomized Controlled Trial

ObjectivesThis study sought to compare the nephrotoxicity of iodixanol and ioxaglate in patients with renal impairment undergoing coronary angiography.BackgroundIodixanol, a nonionic, dimeric, iso-osmolar contrast medium (IOCM), may be less nephrotoxic than low-osmolar contrast media (LOCM) in high-risk patients.MethodsIn a prospective, randomized trial in 300 adults with creatinine clearance (CrCl) ≤60 ml/min, patients received either iodixanol or ioxaglate and underwent coronary angiography with or without percutaneous coronary intervention. The primary end point was the incidence of contrast-induced nephropathy (CIN) (an increase in serum creatinine [SCr] ≥25% or ≥0.5 mg/dl [≥44.2 μmol/l]). The incidence of CIN in patients with severe renal impairment at baseline (CrCl <30 ml/min) or diabetes and in those receiving large doses (≥140 ml) of contrast medium was also determined.ResultsThe incidence of CIN was significantly lower with iodixanol (7.9%) than with ioxaglate (17.0%; p = 0.021), corresponding to an odds ratio (OR) of CIN of 0.415 (95% confidence interval [CI] 0.194 to 0.889) for iodixanol. The incidence of CIN was also significantly lower with iodixanol in patients with severe renal impairment (p = 0.023) or concomitant diabetes (p = 0.041), or in patients given ≥140 ml of contrast media (p = 0.038). Multivariate analysis identified use of ioxaglate (OR 2.65, 95% CI 1.11 to 6.33, p = 0.028), baseline SCr, mg/dl (OR 2.0, 95% CI 1.04 to 3.85, p = 0.038), and left ventricular ejection fraction, % (OR 0.97, 95% CI 0.94 to 0.99, p = 0.019) as independent risk factors for CIN.ConclusionsThe IOCM iodixanol was significantly less nephrotoxic than ioxaglate, an ionic, dimeric LOCM. (The RECOVER Trial; http://clinicaltrials.gov; NCT00247325

Change in the diagnosis of inflammatory bowel disease: a hospital-based cohort study from Korea

Background/AimsAccurately diagnosing inflammatory bowel disease (IBD) remains a challenge, but is crucial for providing proper management for affected patients. The aim of the present study was to evaluate the frequency of change in diagnosis in Korean patients who were referred to our institution with a diagnosis of IBD.MethodsWe enrolled 1,444 patients diagnosed with ulcerative colitis (UC) and 1,452 diagnosed with Crohn's disease (CD), who had been referred to the Asan Medical Center between January 2010 and December 2014. These patients were assessed and subsequently classified as having UC, CD, indeterminate colitis, possible IBD, or non-IBD.ResultsDuring a median follow-up of 15.9 months, 400 of the 2,896 patients (13.8%) analyzed in this study experienced a change in diagnosis. A change in diagnosis from UC to CD, or vice-versa, was made in 24 of 1,444 patients (1.7%) and 23 of 1,452 patients (1.6%), respectively. A change to a non-IBD diagnosis was the most common modification; 7.5% (108 of 1444) and 12.7% (184 of 1452) of the patients with a referral diagnosis of UC and CD, respectively, were reclassified as having non-IBD. Among the 292 patients who were ultimately determined not to have IBD, 135 (55 UC and 80 CD cases) had received IBD-related medication.ConclusionsThere are diagnostic uncertainties and difficulties in relation to IBD. Therefore, precise assessment and systematic follow-up are essential in the management of this condition

Mycobacterium tuberculosis Eis Regulates Autophagy, Inflammation, and Cell Death through Redox-dependent Signaling

The “enhanced intracellular survival” (eis) gene of Mycobacterium tuberculosis (Mtb) is involved in the intracellular survival of M. smegmatis. However, its exact effects on host cell function remain elusive. We herein report that Mtb Eis plays essential roles in modulating macrophage autophagy, inflammatory responses, and cell death via a reactive oxygen species (ROS)-dependent pathway. Macrophages infected with an Mtb eis-deletion mutant H37Rv (Mtb-Δeis) displayed markedly increased accumulation of massive autophagic vacuoles and formation of autophagosomes in vitro and in vivo. Infection of macrophages with Mtb-Δeis increased the production of tumor necrosis factor-α and interleukin-6 over the levels produced by infection with wild-type or complemented strains. Elevated ROS generation in macrophages infected with Mtb-Δeis (for which NADPH oxidase and mitochondria were largely responsible) rendered the cells highly sensitive to autophagy activation and cytokine production. Despite considerable activation of autophagy and proinflammatory responses, macrophages infected with Mtb-Δeis underwent caspase-independent cell death. This cell death was significantly inhibited by blockade of autophagy and c-Jun N-terminal kinase-ROS signaling, suggesting that excessive autophagy and oxidative stress are detrimental to cell survival. Finally, artificial over-expression of Eis or pretreatment with recombinant Eis abrogated production of both ROS and proinflammatory cytokines, which depends on the N-acetyltransferase domain of the Eis protein. Collectively, these data indicate that Mtb Eis suppresses host innate immune defenses by modulating autophagy, inflammation, and cell death in a redox-dependent manner