Alleviating psoriatic skin inflammation through augmentation of Treg cells via CTLA-4 signaling peptide

Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia of keratinocytes and immune cell infiltration. The IL-17-producing T cells play a key role in psoriasis pathogenesis, while regulatory T (Treg) cells are diminished during psoriatic inflammation. Current psoriasis treatments largely focus on IL-17 and IL-23, however, few studies have explored therapeutic drugs targeting an increase of Treg cells to control immune homeostasis. In this study, we investigated the effects of a cytotoxic T lymphocyte antigen-4 (CTLA-4) signaling peptide (dNP2-ctCTLA-4) in Th17, Tc17, γδ T cells, Treg cells in vitro and a mouse model of psoriasis. Treatment with dNP2-ctCTLA-4 peptide showed a significant reduction of psoriatic skin inflammation with increased Treg cell proportion and reduced IL-17 production by T cells, indicating a potential role in modulating psoriatic skin disease. We compared dNP2-ctCTLA-4 with CTLA-4-Ig and found that only dNP2-ctCTLA-4 ameliorated the psoriasis progression, with increased Treg cells and inhibited IL-17 production from γδ T cells. In vitro experiments using a T cell-antigen presenting cell co-culture system demonstrated the distinct mechanisms of dNP2-ctCTLA-4 compared to CTLA-4-Ig in the induction of Treg cells. These findings highlight the therapeutic potential of dNP2-ctCTLA-4 peptide in psoriasis by augmenting Treg/Teff ratio, offering a new approach to modulating the disease

Roles of Arrest-Defective Protein 1225 and Hypoxia-Inducible Factor 1α in Tumor Growth and Metastasis

Background Vascular endothelial growth factor A (VEGFA), a critical mediator of tumor angiogenesis, is a well-characterized target of hypoxia-inducible factor 1 (HIF-1). Murine arrest-defective protein 1A (mARD1A225) acetylates HIF-1??, triggering its degradation, and thus may play a role in decreased expression of VEGFA.Methods We generated ApcMin/+/mARD1A225 transgenic mice and quantified growth of intestinal polyps. Human gastric MKN74 and murine melanoma B16F10 cells overexpressing mARD1A225 were injected into mice, and tumor growth and metastasis were measured. VEGFA expression and microvessel density in tumors were assessed using immunohistochemistry. To evaluate the role of mARD1A 225 acetylation of Lys532 in HIF-1??, we injected B16F10-mARD1A225 cell lines stably expressing mutant HIF-1??/K532R into mice and measured metastasis. All statistical tests were two-sided, and P values less than. 05 were considered statistically significant.Results ApcMin/+/mARD1A225 transgenic mice (n = 25) had statistically significantly fewer intestinal polyps than Apc Min/+ mice (n = 21) (number of intestinal polyps per mouse: Apc Min/+ mice vs ApcMin/+/mARD1A225 transgenic mice, mean = 83.4 vs 38.0 polyps, difference = 45.4 polyps, 95% confidence interval [CI] = 41.8 to 48.6; P <. 001). The growth and metastases of transplanted tumors were also statistically significantly reduced in mice injected with mARD1A225-overexpressing cells than in mice injected with control cells (P <. 01). Moreover, overexpression of mARD1A 225 decreased VEGFA expression and microvessel density in tumor xenografts (P <. 04) and ApcMin/+ intestinal polyps (P =. 001). Mutation of lysine 532 of HIF-1?? in B16F10-mARD1A225 cells prevented HIF-1?? degradation and inhibited the antimetastatic effect of mARD1A225 (P <. 001).Conclusion mARD1A225 may be a novel upstream target that blocks VEGFA expression and tumor-related angiogenesis

Hepatoprotective Activity of Herbal Composition SAL, a Standardize Blend Comprised of Schisandra chinensis

Some botanicals have been reported to possess antioxidative activities acting as scavengers of free radicals rendering their usage in herbal medicine. Here we describe the potential use of “SAL,” a standardized blend comprised of three extracts from Schisandra chinensis, Artemisia capillaris, and Aloe barbadensis, in mitigating chemically induced acute liver toxicities. Acetaminophen and carbon tetrachloride induced acute liver toxicity models in mice were utilized. Hepatic functional tests from serum collected at T24 and hepatic glutathione and superoxide dismutases from liver homogenates were evaluated. Histopathology analysis and merit of blending 3 standardized extracts were also confirmed. Statistically significant and dose-correlated inhibitions in serum ALT ranging from 52.5% (p=0.004) to 34.6% (p=0.05) in the APAP and 46.3% (p<0.001) to 29.9% (p=0.02) in the CCl4 models were observed for SAL administered at doses of 400–250 mg/kg. Moreover, SAL resulted in up to 60.6% and 80.2% reductions in serums AST and bile acid, respectively. The composition replenished depleted hepatic glutathione in association with an increase of hepatic superoxide dismutase. Unexpected synergistic protection from liver damage was also observed. Therefore, the composition SAL could be potentially utilized as an effective hepatic-detoxification agent for the protection from liver damage

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs

Labelling nutrition sensitive food chains: a consumer preference analysis of milk products

Copyright © 2020 Wesana, Gellynck, Dora, Muyama, Mutenyo, Elizabeth, Kagambe and De Steur. While nutrition sensitive value chain approaches are strongly advocated, studies on consumer preferences for such interventions are lacking. This study aims to fill this gap by examining a nutrition sensitive chain labelling scheme, using the Ugandan dairy sector as a case. A survey was conducted among 250 consumers, primarily eliciting perceptions of the importance of a nutrition sensitive chain label compared to nutrition claims/facts. In addition, a choice-based conjoint experiment was designed with nutrition label, brand, fat content and price as attributes. Findings show that nutrition sensitive chain labelling was more positively perceived by consumers than nutrition claims/facts. Ordered logistic regression analysis indicated that BMI, nutrition knowledge and label use influenced consumers’ perceived importance of a nutrition sensitive chain label relative to sex, age, children and milk purchase frequency for nutrition claims/facts. This is confirmed by the higher utilities for the nutrition sensitive chain label in our conjoint experiment. Future research should focus on the integration of nutrition sensitive chain labelling with existing labels in a way that promotes candid interpretation by consumers. Industrial and policy actors in the agri-food sector can use these findings to innovate and regulate appropriate labelling schemes in the context of nutrition sensitive value chains.Ghent University Special Research Fund (Grant No. 01W01515)

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio