Immunomodulatory effect of water soluble extract separated from mycelium of Phellinus linteus on experimental atopic dermatitis

Background: Complementary and alternative medicine (CAM) is becoming a popular treatment for modulating diverse immune disorders. Phellinus linteus (P. linteus) as one of the CAMs has been used to modulate cancers, inflammation and allergic activities. However, little evidence has been shown about its underlying mechanism of action by which it exerts a beneficial role in dermatological disease in vivo. In this study, we examined the immunomodulatory effects of P. linteus on experimental atopic dermatitis (AD) and elucidated its action mechanism. Methods: The immunomodulatory effect of total extract of P. linteus on IgE production by human myeloma U266B1 cells was measured by ELISA. To further identify the effective components, P. linteus was fractionated into methanol soluble, water soluble and boiling water soluble extracts. Each extract was treated to U266B1 cells and primary B cells to compare their inhibitory effects on IgE secretion. To test the in vivo efficacy, experimental atopic dermatitis (AD) was established by alternative treatment of DNCB and house dust mite extract into BALB/c mice. Water soluble extract of P. linteus (WA) or ceramide as a positive control were topically applied to ears of atopic mouse every day for 2 weeks and progression of the disease was estimated by the following criteria: (a) ear thickness, clinical score, (b) serum total IgE, IgG and mite specific IgE level by ELSIA, (c) histological examination of ear tissue by H&E staining and (d) cytokine profile of total ear cells and CD4+ T cells by real time PCR and ELSIA. Results: Treatment of total extracts of P. linteus to U266B1 inhibited IgE secretion. Among the diverse extracts of P. linteus, water soluble extract of P. linteus (WA) significantly reduced the IgE production in primary B cells and B cell line U266B1. Moreover, treatment of WA reduced AD symptoms such as ear swelling, erythema, and dryness and decreased recruitment of lymphocyte into the inflamed site. Interestingly WA treatment significantly reduced IgE level without affecting IgG levels and also down-regulated the levels of pathogenic cytokines (IL-4, IL-13, IL-12 and IFN-γ) and chemokines (CCL17 and CCL22) involved in AD development. Conclusions: Our study indicates that protective effect of water soluble extract of P. linteus in atopic dermatitis is mediated by inhibiting IgE production and expression of AD associated pathogenic cytokines as well as chemokines, suggesting the beneficial effect of P. linteus to modulate allergic skin disease

The Molecular Mechanism of Transforming Growth Factor-β Signaling for Intestinal Fibrosis: A Mini-Review

Inflammatory bowel disease is known as the most chronic inflammatory disorder in colon, which subsequently progresses to intestinal obstruction and fistula formation. Many studies to date for the treatment of IBD have been focused on inflammation. However, most of the anti-inflammatory agents do not have anti-fibrotic effects and could not relieve intestinal stricture in IBD patients. Because preventing or reversing intestinal fibrosis in IBD is a major therapeutic target, we analyzed the papers focusing on TGF-β signaling in intestinal fibrosis. TGF-β is a good candidate to treat the intestinal fibrosis in IBD which involves TGF-β signaling pathway, EMT, EndMT, ECM, and other regulators. Understanding the mechanism involved in TGF-β signaling will contribute to the treatment and diagnosis of intestinal fibrosis occurring in IBD as well as the understanding of the molecular mechanisms underlying the pathogenesis

Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration.

Mechanistic studies of axon growth during development are beneficial to the search for neuron-intrinsic regulators of axon regeneration. Here, we discovered that, in the developing neuron from rat, Akt signaling regulates axon growth and growth cone formation through phosphorylation of serine 14 (S14) on Inhibitor of DNA binding 2 (Id2). This enhances Id2 protein stability by means of escape from proteasomal degradation, and steers its localization to the growth cone, where Id2 interacts with radixin that is critical for growth cone formation. Knockdown of Id2, or abrogation of Id2 phosphorylation at S14, greatly impairs axon growth and the architecture of growth cone. Intriguingly, reinstatement of Akt/Id2 signaling after injury in mouse hippocampal slices redeemed growth promoting ability, leading to obvious axon regeneration. Our results suggest that Akt/Id2 signaling is a key module for growth cone formation and axon growth, and its augmentation plays a potential role in CNS axonal regeneration

The impact of sagittal balance on clinical results after posterior interbody fusion for patients with degenerative spondylolisthesis: A Pilot study

<p>Abstract</p> <p>Background</p> <p>Comparatively little is known about the relation between the sagittal vertical axis and clinical outcome in cases of degenerative lumbar spondylolisthesis. The objective of this study was to determine whether lumbar sagittal balance affects clinical outcomes after posterior interbody fusion. This series suggests that consideration of sagittal balance during posterior interbody fusion for degenerative spondylolisthesis can yield high levels of patient satisfaction and restore spinal balance</p> <p>Methods</p> <p>A retrospective study of clinical outcomes and a radiological review was performed on 18 patients with one or two level degenerative spondylolisthesis. Patients were divided into two groups: the patients without improvement in pelvic tilt, postoperatively (Group A; n = 10) and the patients with improvement in pelvic tilt postoperatively (Group B; n = 8). Pre- and postoperative clinical outcome surveys were administered to determine Visual Analogue Pain Scores (VAS) and Oswestry disability index (ODI). In addition, we evaluated full spine radiographic films for pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), sacrofemoral distance (SFD), and sacro C7 plumb line distance (SC7D)</p> <p>Results</p> <p>All 18 patients underwent surgery principally for the relief of radicular leg pain and back pain. In groups A and B, mean preoperative VAS were 6.85 and 6.81, respectively, and these improved to 3.20 and 1.63 at last follow-up. Mean preoperative ODI were 43.2 and 50.4, respectively, and these improved to 23.6 and 18.9 at last follow-up. In spinopelvic parameters, no significant difference was found between preoperative and follow up variables except PT in Group A. However, significant difference was found between the preoperative and follows up values of PT, SS, TK, LL, and SFD/SC7D in Group B. Between parameters of group A and B, there is borderline significance on preoperative PT, preoperative LL and last follow up SS.</p> <p>Correlation analysis revealed the VAS improvements in Group A were significantly related to postoperative lumbar lordosis (Pearson's coefficient = -0.829; p = 0.003). Similarly, ODI improvements were also associated with postoperative lumbar lordosis (Pearson's coefficient = -0.700; p = 0.024). However, in Group B, VAS and ODI improvements were not found to be related to postoperative lumbar lordosis and to spinopelvic parameters.</p> <p>Conclusion</p> <p>In the current series, patients improving PT after fusion were found to achieve good clinical outcomes in degenerative spondylolisthesis. Overall, our findings show that it is important to quantify sagittal spinopelvic parameters and promote sagittal balance when performing lumbar fusion for degenerative spondylolisthesis.</p

In-situ fabrication of cobalt-doped SrFe2As2 thin films by using pulsed laser deposition with excimer laser

The remarkably high superconducting transition temperature and upper critical field of iron(Fe)-based layered superconductors, despite ferromagnetic material base, open the prospect for superconducting electronics. However, success in superconducting electronics has been limited because of difficulties in fabricating high-quality thin films. We report the growth of high-quality c-axis-oriented cobalt(Co)-doped SrFe2As2 thin films with bulk superconductivity by using an in-situ pulsed laser deposition technique with a 248-nm-wavelength KrF excimer laser and an arsenic(As)-rich phase target. The temperature and field dependences of the magnetization showing strong diamagnetism and transport critical current density with superior Jc-H performance are reported. These results provide necessary information for practical applications of Fe-based superconductors.Comment: 8 pages, 3figures. to be published at Appl. Phys. Let

Analysis of the predictive role and new proposal for surgical strategies based on the modified Tomita and Tokuhashi scoring systems for spinal metastasis

BACKGROUND: We sought to identify preoperative factors significantly correlated with survival. We also aimed to evaluate the validity of the prognostic scores in the Tomita and Tokuhashi systems and discuss several aspects to improve the predictive accuracy of these systems. Moreover, we suggest modified criteria for selecting treatment strategies. METHODS: In total, the outcomes of 112 patients with spinal metastasis who underwent surgery between January 2006 and June 2011 were retrospectively reviewed. The validity of the prognostic scores was assessed on the basis of their correlation with survival. For various primary malignancies, new scoring criteria were applied in each system according to the survival results obtained in this study. Each revised scoring system was adjusted with a similar principle of scoring as described previously. Patient survival according to each preoperative factor was analyzed by the Kaplan-Meier method. The predictive value of each scoring system was evaluated by the log-rank test and Cox regression analysis. RESULTS: The interval from the diagnosis of the primary malignancy to that of spinal metastasis (p = 0.023) and the interval from the diagnosis of spinal metastasis to surgery (p = 0.039) were significantly correlated with survival. Regarding Tokuhashi scores, the correlation coefficient was 0.790 before adjustment (p = 0.001) and 0.853 after adjustment (p < 0.001). For Tomita scores, the correlation coefficient was -0.994 (p < 0.001) both before and after adjustment. CONCLUSIONS: Tomita scores more accurately predicted survival than Tokuhashi scores. It is helpful to evaluate both scoring systems with adjustment for primary malignancy depending on the clinical setting. Patients with Tomita scores less than or equal to 8 and Tokuhashi scores greater than or equal to 6 are recommended to undergo surgical management

The Role of Sphingosine Kinase 1/Sphingosine-1-Phosphate Pathway in the Myogenic Tone of Posterior Cerebral Arteries

AIMS: The goal of the current study was to determine whether the sphingosine kinase 1 (SK1)/sphingosine-1-phosphate (S1P) pathway is involved in myogenic vasoconstriction under normal physiological conditions. In the present study, we assessed whether endogenous S1P generated by pressure participates in myogenic vasoconstriction and which signaling pathways are involved in SK1/S1P-induced myogenic response under normal physiological conditions. METHODS AND RESULTS: We measured pressure-induced myogenic response, Ca(2+) concentration, and 20 kDa myosin light chain phosphorylation (MLC(20)) in rabbit posterior cerebral arteries (PCAs). SK1 was expressed and activated by elevated transmural pressure in rabbit PCAs. Translocation of SK1 by pressure elevation was blocked in the absence of external Ca(2+) and in the presence of mechanosensitive ion channel and voltage-sensitive Ca(2+) channel blockers. Pressure-induced myogenic tone was inhibited in rabbit PCAs treated with sphingosine kinase inhibitor (SKI), but was augmented by treatment with NaF, which is an inhibitor of sphingosine-1-phosphate phosphohydrolase. Exogenous S1P further augmented pressure-induced myogenic responses. Pressure induced an increase in Ca(2+) concentration leading to the development of myogenic tone, which was inhibited by SKI. Exogenous S1P further increased the pressure-induced increased Ca(2+) concentration and myogenic tone, but SKI had no effect. Pressure- and exogenous S1P-induced myogenic tone was inhibited by pre-treatment with the Rho kinase inhibitor and NADPH oxidase inhibitors. Pressure- and exogenous S1P-induced myogenic tone were inhibited by pre-treatment with S1P receptor blockers, W146 (S1P1), JTE013 (S1P2), and CAY10444 (S1P3). MLC(20) phosphorylation was increased when the transmural pressure was raised from 40 to 80 mmHg and exogenous S1P further increased MLC(20) phosphorylation. The pressure-induced increase of MLC(20) phosphorylation was inhibited by pre-treatment of arteries with SKI. CONCLUSIONS: Our results suggest that the SK1/S1P pathway may play an important role in pressure-induced myogenic responses in rabbit PCAs under normal physiological conditions