The Galactose-Binding Lectin Isolated from Vatairea macrocarpa Seeds Enhances the Effect of Antibiotics Against Staphylococcus aureus–Resistant Strain

Probiotics and Antimicrobial Proteins - The use of natural products together with standard antimicrobial drugs has recently received more attention as a strategy to combat infectious diseases...     

Aerobic training prevents cardiometabolic changes triggered by myocardial infarction in ovariectomized rats

This study aimed to evaluate the impact of aerobic training (AT) on autonomic, cardiometabolic, ubiquitin‐proteasome activity, and inflammatory changes evoked by myocardial infarction (MI) in ovariectomized rats. Female Wistar rats were ovariectomized and divided into four groups: sedentary + sham (SS), sedentary + MI (SI), AT + sham surgery (TS), AT + MI (TI). AT was performed on a treadmill for 8 weeks before MI. Infarcted rats previously subjected to AT presented improved physical capacity, increased interleukin‐10, and decreased pro‐inflammatory cytokines. Metabolomic analysis identified and quantified 62 metabolites, 9 were considered significant by the Vip Score. SS, SI, and TS groups presented distinct metabolic profiles; however, TI could not be distinguished from the SS group. MI dramatically increased levels of dimethylamine, and AT prevented this response. Our findings suggest that AT may be useful in preventing the negative changes in functional, inflammatory, and metabolic parameters related to MI in ovariectomized rats.     

Can the use of zooplankton dormant stages from natural wetlands contribute to restoration of mined wetlands?

Wetlands are among the most diverse environments on the planet and are strongly threatened by human activities. Their restoration and/or mitigation of human impacts, therefore, relies on information that can aid to the management of impacted wetlands so that they return to a (semi-) natural state. We investigate in this study the relationship between dormant stages of zooplankton and clay removal in areas subjected to mining. We evaluate whether a gradual increase in topsoil addition from donor natural wetlands to the sediment of mined wetlands influenced the zooplankton community. Eight wetlands were sampled in the Sinos River floodplain, four natural and four mined. In the laboratory, four field sediment samples were incubated for zooplankton hatching in five treatments comprising sediments from: mined wetlands, natural wetlands, and three treatments containing mined sediments added with low (5%), medium (20%) and high (40%) quantities of sediment from natural wetlands. Hatching consisted of 61 individuals distributed across eight zooplankton taxa. Copepod nauplii were the most abundant (31.1%) followed by Epiphanes sp. (29.5%) and Ovalona glabra (16.4%). While natural wetlands provided 42.6% of the hatched zooplankton, mined wetlands had just 6.5%. Zooplankton richness and abundance were higher in natural wetland sediments compared with mined and added sediment wetlands. To some degree, the sediment soil donation from natural to mined wetlands was considered viable. As long as prior studies are performed to test the size and quality of the dormant banks present in the sediment of candidate donor wetlands, sediment from donor wetlands may aid in the establishment of a more diverse community in disturbed systems.

     

Retinol supplementation induces oxidative stress and modulates antioxidant enzyme activities in rat Sertoli cells

Recent intervention studies revealed that supplementation with retinoids resulted in a higher incidence of lung cancer. Recently the causal mechanism has begun to be clarified. We report here that retinol caused cellular oxidative stress and modulated superoxide dismutase, catalase and glutathione peroxidase activities. Retinol (7 μM) significantly increased TBARS, conjugated dienes, and hydroperoxide-initiated chemiluminescence in cultured Sertoli cells. In response to retinol treatment superoxide dismutase, catalase and glutathione peroxidase activities increased. TBARS content and catalase activities were decreased by a free radical scavenger. These findings suggest that retinol may induce oxidative stress and modulate antioxidant enzyme activities in Sertoli cells.     

A phase Ib multiple ascending dose study evaluating safety,pharmacokinetics, and early clinical response of brodalumab,a human anti-IL-17R antibody,in methotrexate-resistant rheumatoid arthritis

Introduction

The aim of this study was to evaluate the safety, pharmacokinetics, and clinical response of brodalumab (AMG 827), a human, anti-IL-17 receptor A (IL-17RA) monoclonal antibody in subjects with moderate-to-severe rheumatoid arthritis (RA).

Methods

This phase Ib, randomized, placebo-controlled, double-blind multiple ascending dose study enrolled subjects with moderate to severe RA (≥6/66 swollen and ≥8/68 tender joints). Subjects were randomized 3:1 to receive brodalumab (50 mg, 140 mg, or 210 mg subcutaneously every two weeks for 6 doses per group; or 420 mg or 700 mg intravenously every 4 weeks for two doses per group) or placebo. Endpoints included incidence of adverse events (AEs) and pharmacokinetics. Exploratory endpoints included pharmacodynamics, and improvements in RA clinical metrics.

Results

Forty subjects were randomized to investigational product; one subject discontinued due to worsening of RA (placebo). The study was not designed to assess efficacy. AEs were reported by 70% (7/10) of placebo subjects and 77% (22/30) of brodalumab subjects. Three serious AEs were reported in two subjects; there were no opportunistic infections. Brodalumab treatment resulted in inhibition of IL-17 receptor signaling and receptor occupancy on circulating leukocytes. No treatment effects were observed with individual measures of RA disease activity. On day 85 (week 13) 37% (11/30) of brodalumab subjects and 22% (2/9) of placebo subjects achieved ACR20; 7% (2/30) brodalumab subjects and 11% (1/9) of placebo subjects achieved ACR50; and 0% (0/30) brodalumab subjects and 0% (0/9) of placebo subjects achieved ACR70.

Conclusions

Multiple dose administration of brodalumab was tolerated in subjects with active RA. There was no evidence of a clinical response to brodalumab in subjects with RA.

Trial registration

ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT00771030","term_id":"NCT00771030"}}NCT00771030     

The glyceraldehyde-3-phosphate dehydrogenase promoter of the food yeast Candida utilis strain NRRL Y-660 is functional in Agrobacterium tumefaciens

The glyceraldehyde-3-phosphate dehydrogenase promoter of the food yeast Candida utilis strain NRRL Y-660 was cloned to create a novel integrative vector for Agrobacterium tumefaciens-mediated transformation. The new binary vector harbors β-glucuronidase activity as reporter and kanamicin/geneticin resistance as selection marker. Recombinant clones of A. tumefaciens show kanamycin resistance and high β-glucuronidase activity under the control of the C. utilis promoter. This finding can be explained by the presence of a prokaryotic core in the yeast promoter, predicted by in silico analysis of the sequence. This is the first report about functionality of a yeast promoter in A. tumefaciens.