Inhibition of c-Jun NH(2)-terminal kinase or extracellular signal-regulated kinase improves lung injury

BACKGROUND: Although in vitro studies have determined that the activation of mitogen-activated protein (MAP) kinases is crucial to the activation of transcription factors and regulation of the production of proinflammatory mediators, the roles of c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in acute lung injury have not been elucidated. METHODS: Saline or lipopolysaccharide (LPS, 6 mg/kg of body weight) was administered intratracheally with a 1-hour pretreatment with SP600125 (a JNK inhibitor; 30 mg/kg, IO), or PD98059 (an MEK/ERK inhibitor; 30 mg/kg, IO). Rats were sacrificed 4 hours after LPS treatment. RESULTS: SP600125 or PD98059 inhibited LPS-induced phosphorylation of JNK and ERK, total protein and LDH activity in BAL fluid, and neutrophil influx into the lungs. In addition, these MAP kinase inhibitors substantially reduced LPS-induced production of inflammatory mediators, such as CINC, MMP-9, and nitric oxide. Inhibition of JNK correlated with suppression of NF-κB activation through downregulation of phosphorylation and degradation of IκB-α, while ERK inhibition only slightly influenced the NF-κB pathway. CONCLUSION: JNK and ERK play pivotal roles in LPS-induced acute lung injury. Therefore, inhibition of JNK or ERK activity has potential as an effective therapeutic strategy in interventions of inflammatory cascade-associated lung injury

Associations among Organochlorine Pesticides, Methanobacteriales, and Obesity in Korean Women

BACKGROUND: Although Methanobacteriales in the gut has recently been linked to obesity, no study has examined the hypothesis that waist circumference, a marker of visceral obesity, are positively associated with Methanobacteriales in the general population. Since Methanobacteriales increase in a petroleum-contaminated environment to biodegrade petroleum as one way of autopurification, we also hypothesized that high body burden of highly lipophilic petroleum-based chemicals like organochlorine pesticides (OCPs) is associated with higher levels of Methanobacteriales in the gut. METHODOLOGY/PRINCIPAL FINDINGS: Among 83 Korean women who visited a community health service center for a routine health checkup, quantitative real-time PCR (qPCR) based on 16S rDNA was used to quantify Methanobacteriales in feces. Nine OCPs were measured in both serum and feces of 16 subjects. Methanobacteriales were detected in 32.5% (27/83 women). Both BMI and waist circumference among women with Methanobacteriales were significantly higher than in women without Methanobacteriales (P = 0.04 and P = 0.01, respectively). Also, Methanobacteriales levels in feces were positively associated with BMI and waist circumference (r = +0.23 and P = 0.03 for both). Furthermore, there were significant correlations between feces Methanobacteriales levels and serum concentrations of most OCPs, including with cis-nonachlor (r = +0.53, P<0.05), oxychlordane (r = +0.46, P<0.1), and trans-nonachlor (r = +0.43, P<0.1). Despite high correlations of serum and feces concentrations of most OCPs, feces OCP concentrations were not clearly associated with feces Methanobacteriales levels. CONCLUSION/SIGNIFICANCE: In this cross-sectional study, the levels of Methanobacteriales in the human gut were associated with higher body weight and waist circumference. In addition, serum OCP concentrations were positively correlated with levels of Methanobacteriales. There may be a meaningful link among body burden of OCP, Methanobacteriales in the gut, and obesity in the general population

Computed tomography-based assessment of radiographic progression in spine and sacroiliac joints after pregnancy in women with radiographic axial spondyloarthritis

BackgroundMechanical stress are one of the pathogenesis of axial spondyloarthritis (axSpA). During pregnancy, the mechanical overload on the spine and pelvis increases due to gravid uterus. We aimed to investigate whether pregnancy affects radiographic progression in patients with radiographic axSpA (r-axSpA) based on computed tomography (CT) evaluations.Materials and methodsThis retrospective study included women with r-axSpA aged 19–49 years who underwent at least two CT evaluations of the whole spine and/or sacroiliac joints (SIJs) at intervals of 2–4 years. To compare radiographic progression after delivery, we classified the patients into two groups: delivery group and controls. The delivery group was restricted to women who had the first CT ∼2 years before delivery and the second CT ∼2 years after delivery. The CT Syndesmophyte Score (CTSS) (0–522) and SIJ scores (0–40) were used to evaluate spinal syndesmophytes and erosion, joint space narrowing, and sclerosis of the SIJs.ResultsA total of 21 women in the delivery group and 38 women in the control group were included. The median (Q1–Q3) CTSS at baseline in the delivery group and controls was 19 (16–23) and 20 (13.25–27.75), and the median progression was 1 (0–3) and 0 (0–1) during the median 2.9-year follow-up, respectively. The median (Q1–Q3) SIJ score at baseline in the delivery group and controls was 13 (8–22) and 11 (6–22), and the median progression was 1.5 (0–3) and 1 (0–2), respectively. Using cut-off 0.5, 52.9, and 61.9% of r-axSpA patients and 39.3 and 44.4% of controls showed progression of whole spine and SIJs, respectively. However, no difference in proportion of spinal and SIJ progression and absolute score changes per time point was observed between two groups. Moreover, the SIJ score changes were comparable according to the delivery method.ConclusionPregnancy and delivery do not affect the radiographic progression of the spine and SIJs in women with r-axSpA assessed by CT

Practical Application of Iterative Decomposition of Water and Fat with Echo Asymmetry and Least-Squares Estimation (IDEAL) Imaging in Minimizing Metallic Artifacts

Iterative decomposition of water and fat with echo asymmetry and the least-squares estimation (IDEAL) is a recently developed method for robust separation of fat and water with very high signal-to-noise-ratio (SNR) efficiency. In contrast to conventional fat-saturation methods, IDEAL is insensitive to magnetic field (B0 and B1) inhomogeneity. The aim of this study was to illustrate the practical application of the IDEAL technique in reducing metallic artifacts in postoperative patients with metallic hardware. The IDEAL technique can help musculoskeletal radiologists make an accurate diagnosis particularly in musculoskeletal imaging by reducing metallic artifacts, enabling the use of contrast enhancement, improving SNR performance, and providing various modes of MR images with one scan parameter

Novel Antidepressant-Like Activity of Caffeic Acid Phenethyl Ester Is Mediated by Enhanced Glucocorticoid Receptor Function in the Hippocampus

Caffeic acid phenethyl ester (CAPE) is an active component of propolis that has a variety of potential pharmacological effects. Although we previously demonstrated that propolis has antidepressant-like activity, the effect of CAPE on this activity remains unknown. The present study assessed whether treatment with CAPE (5, 10, and 20 µmol/kg for 21 days) has an antidepressant-like effect in mice subjected to chronic unpredictable stress via tail suspension (TST) and forced swim (FST) tests. CAPE administration induced behaviors consistent with an antidepressant effect, evidenced by decreased immobility in the TST and FST independent of any effect on serum corticosterone secretion. Western blots, conducted subsequent to behavioral assessment, revealed that CAPE significantly decreased glucocorticoid receptor phosphorylation at S234 (pGR(S234)), resulting in an increased pGR(S220/S234) ratio. We also observed negative correlations between pGR(S220)/(S234) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation, which was decreased by CAPE treatment. These findings suggest that CAPE treatment exerts an antidepressant-like effect via downregulation of p38MAPK phosphorylation, thereby contributing to enhanced GR function