Up-regulation of corticotropin releasing hormone is associated with the downregulation of corticotropin releasing hormone binding protein and up-regulation of IL- 33 and IL-8 expression in psoriasis

Purpose: To determine the expression of corticotropin releasing hormone (CRH) in psoriasis and normal skin biopsy samples, and to correlate the expression of CRH with the expression of CRHBP and inflammatory cytokines IL-8 and IL-33.Methods: Psoriasis and normal skin biopsy samples were obtained from three psoriatic and three normal healthy patients. The mRNA expression was examined by quantitative real-time polymerase chain reaction (RT-PCR). Protein expression analysis was carried out by Western blotting and then further validated by immunohistochemistry.Results: The results of the present study revealed that the expression of CRH was highly significant (p < 0.0001) in psoriatic skin, compared to normal skin. Increase of CRH in psoriatic samples ranged from 2.7 to 3.5-fold. Expression of CRH was associated with the concomitant downregulation of CRHBP in all the psoriatic skin biopsy samples, with expression of CRHBP 3.0 to 6.2-fold lower in psoriatic skin than in normal skin. Analysis of mRNA expression of IL-8 and IL-33, revealed that expression of both IL-8 and IL-33 was significantly (p < 0.0001) upregulated in psoriatic skin samples while the expression of IL-8 and IL-33 was approximately 4.1- and 3.2-fold higher in psoriatic skin than in normal skin. The expression of CRHBP, IL-8 and IL-33 was further confirmed by western blotting and immunohistochemistry results.Conclusion: The results confirm that the expression of CRH is associated with the suppression of CRHBP and upregulation of IL-8 and IL-33.Keywords: Psoriasis, Corticotropin releasing hormone, Inflammatory cytokines, Interleukin, Skin biops

ENU-Induced Mutagenesis in Grass Carp (Ctenopharyngodon idellus) by Treating Mature Sperm

N-ethyl-N-nitrosourea (ENU) mutagenesis is a useful approach for genetic improvement of plants, as well as for inducing functional mutants in animal models including mice and zebrafish. In the present study, mature sperm of grass carp (Ctenopharyngodon idellus) were treated with a range of ENU concentrations for 45 min, and then wild-type eggs were fertilized. The results indicated that the proportion of embryos with morphological abnormalities at segmentation stage or dead fry at hatching stage increased with increasing ENU dose up to 10 mM. Choosing a dose that was mutagenic, but provided adequate numbers of viable fry, an F1 population was generated from 1 mM ENU-treated sperm for screening purposes. The ENU-treated F1 population showed large variations in growth during the first year. A few bigger mutants with morphologically normal were generated, as compared to the controls. Analysis of DNA from 15 F1 ENU-treated individuals for mutations in partial coding regions of igf-2a, igf-2b, mstn-1, mstn-2, fst-1and fst-2 loci revealed that most ENU-treated point mutations were GC to AT or AT to GC substitution, which led to nonsense, nonsynonymous and synonymous mutations. The average mutation rate at the examined loci was 0.41%. These results indicate that ENU treatment of mature sperm can efficiently induce point mutations in grass carp, which is a potentially useful approach for genetic improvement of these fish

Equation of motion for multiqubit entanglement in multiple independent noisy channels

We investigate the possibility and conditions to factorize the entanglement evolution of a multiqubit system passing through multi-sided noisy channels. By means of a lower bound of concurrence (LBC) as entanglement measure, we derive an explicit formula of LBC evolution of the N-qubit generalized Greenberger-Horne-Zeilinger (GGHZ) state under some typical noisy channels, based on which two kinds of factorizing conditions for the LBC evolution are presented. In this case, the time-dependent LBC can be determined by a product of initial LBC of the system and the LBC evolution of a maximally entangled GGHZ state under the same multi-sided noisy channels. We analyze the realistic situations where these two kinds of factorizing conditions can be satisfied. In addition, we also discuss the dependence of entanglement robustness on the number of the qubits and that of the noisy channels.Comment: 14 page

Sphingosine kinase 2 activates autophagy and protects neurons against ischemic injury through interaction with Bcl-2 via its putative BH3 domain

Our previous findings suggest that sphingosine kinase 2 (SPK2) mediates ischemic tolerance and autophagy in cerebral preconditioning. The aim of this study was to determine by which mechanism SPK2 activates autophagy in neural cells. In both primary murine cortical neurons and HT22 hippocampal neuronal cells, overexpression of SPK2 increased LC3II and enhanced the autophagy flux. SPK2 overexpression protected cortical neurons against oxygen glucose deprivation (OGD) injury, as evidenced by improvement of neuronal morphology, increased cell viability and reduced lactate dehydrogenase release. The inhibition of autophagy effectively suppressed the neuroprotective effect of SPK2. SPK2 overexpression reduced the co-immunoprecipitation of Beclin-1 and Bcl-2, while Beclin-1 knockdown inhibited SPK2-induced autophagy. Both co-immunoprecipitation and GST pull-down analysis suggest that SPK2 directly interacts with Bcl-2. SPK2 might interact to Bcl-2 in the cytoplasm. Notably, an SPK2 mutant with L219A substitution in its putative BH3 domain was not able to activate autophagy. A Tat peptide fused to an 18-amino acid peptide encompassing the native, but not the L219A mutated BH3 domain of SPK2 activated autophagy in neural cells. The Tat-SPK2 peptide also protected neurons against OGD injury through autophagy activation. These results suggest that SPK2 interacts with Bcl-2 via its BH3 domain, thereby dissociating it from Beclin-1 and activating autophagy. The observation that Tat-SPK2 peptide designed from the BH3 domain of SPK2 activates autophagy and protects neural cells against OGD injury suggest that this structure may provide the basis for a novel class of therapeutic agents against ischemic stroke

A Multi-Inverter Multi-Rectifier Wireless Power Transfer System for Charging Stations With Power Loss Optimized Control

Electric vehicles with different output power levels can use wireless power transfer (WPT) systems. Different vehicle assemblies (VAs) may be charged by different ground assemblies (GAs) in charging stations. However, the overall efficiency of the WPT system may drop significantly when the power class difference between GA and VA is large. To address this issue this article proposes a dc-link parallel ac-link series multi-inverter multirectifier architecture for high-power WPT systems. Modulation, power transfer capability, and power sharing from the design aspects are investigated. A detailed power loss analysis and an easy-to-implemented power loss optimized control method based on mutual inductance identification are presented in this article. Finally, experimental results are obtained from a 20-kW LCC-LCC WPT system to validate the analysis and proposed system operation

High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial

Objectives: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). Methods: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. Results: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. Conclusions: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment