Boruplanier7341
Extracellular vesicles (EVs) are membrane-encapsulated particles released by eukaryotic and prokaryotic cells into the extracellular environment. Depending on their origin, size, and composition, EVs are grouped in several classes, with one of them being exosomes, which are small EVs (SEVs) generated within the endosomal compartment of eukaryotic cells via the unique multivesicular body pathway. Being able to deliver their content (proteins, lipids, small molecules, and nucleic acids) to other cells, exosomes/SEVs are considered as bioactive vesicles with multiple biological functions. Importantly, the composition of exosomes/SEVs depends on the cell and tissue of origin including a set of specific proteins. However, the pathological conditions may lead to the appearance of diseases-specific exosomes/SEVs containing pathology-specific cargoes utilized in the malicious cell-cell communication and spread of malady. Viruses demonstrate complex 'dancing' around the exosome biogenesis system, being able to hijack the host systems responsible for the exosome biogenesis. They use the exosome biogenesis system to promote packaging of their capsids, regulate virion production, and virus secretion. They also utilize a Trojan horse stratagem to place virions inside the SEVs and thereby to spread beyond their normal range of cell hosts using the normal EV uptake process. Another illustration of the virus-based utilization of Trojan horse strategy is given by the ability of human viruses to use exosomes/SEVs as carriers of their exogenous miRNA or viral proteins to the non-infected cells. Taken together, these strategies of dancing with Trojan horses can help viruses to fight with the host defense and to spread the infection.Communicated by Ramaswamy H. Sarma.Previous studies suggest an association of cardiac microvascular endothelial cells (CMECs) hyperpermeability with sepsis-related cardiac injury. Our results showed that CMECs permeability was dependent upon concentration and time of lipopolysaccharides (LPS) stimulation. see more Integrin ανβ3 expression decreased after LPS stimulation. Pretreatment with anti-integrin ανβ3 antibody enhanced LPS-induced hyperpermeability. Upregulation of integrin ανβ3 decreased LPS-induced hyperpermeability. F-actin remodeling was enhanced after LPS stimulation and was inhibited by up-regulation of integrin ανβ3. Inhibition of Src or Rac1 reduced CMECs permeability after LPS stimulation, but there were no differences in the phosphorylation of Src and Rac1 when over-expressing or blocking integrin β3. After pretreatment with Src or Rac1 inhibitor, no significant difference was found in the expression of integrin ανβ3 in LPS-induced CMECs. These finding suggested that integrin ανβ3 overexpression decreased LPS-stimulated CMECS permeability by inhibition of cytoskeletal remodeling, but the mechanism might not be mediated via Src/Rac1 signaling.Objective To determine, in a cohort of patients with early rheumatoid arthritis (RA), factors associated with fatigue at baseline, describe its evolution over 5 years of follow-up, and determine baseline predictors of persistent fatigue.Method We selected patients fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA included in the ESPOIR cohort. Using bivariable and multivariable logistic regression models, we examined baseline variables associated with baseline fatigue (defined by visual analogue scale fatigue > 20) and baseline predictors of persistent fatigue (if the patient experienced fatigue at all visits during the 5 year follow-up period).Results We analysed 673 patients; 80.7% reported fatigue at baseline. At baseline, fatigue was associated with female gender, younger age, greater severity of morning stiffness, sleep problems, higher Health Assessment Questionnaire levels, presence of sicca symptoms, history of thyroid problems, and presence of psychological distress (depressive or anxiety symptoms). At 5 years of follow-up, the percentage of fatigued patients who reported fatigue at all time-points since baseline was 24.6% (referred to as 'persistent fatigue'). Independent baseline predictors were presence of sicca symptoms, greater severity of morning stiffness, and psychological distress.Conclusions Fatigue is a frequent symptom in RA. The presence of sicca symptoms, greater severity of morning stiffness, and presence of psychological distress at baseline were associated with baseline fatigue and persistent fatigue at 5 years. We did not observe any association between baseline fatigue or persistent fatigue and the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate.Iron (Fe) is a mineral nutrient and a metal cofactor essential for plants. Iron limitation can have detrimental effects on plant growth and development, while excess iron inside plant cells leads to oxidative damage. As a result, plants have evolved complex regulatory networks to respond to fluctuations in cellular iron concentrations. The mechanisms that regulate these responses however, are not fully understood. Heterologous expression of an Arabidopsis thaliana monothiol glutaredoxin S17 (GRXS17) suppresses the over-accumulation of iron in the Saccharomyces cerevisiae Grx3/Grx4 mutant and disruption of GRXS17 causes plant sensitivity to exogenous oxidants and iron deficiency stress. GRXS17 may act as an important regulator in the plant's ability to respond to iron deficiency stress and maintain redox homeostasis. Here, we extend this investigation by analyzing iron-responsive gene expression of the Fer-like iron deficiency-induced transcription factor (FIT) network (FIT, IRT1, FRO1, and FRO2) and the bHLH transcription factor POPEYE (PYE) network (PYE, ZIF1, FRO3, NAS4, and BTS) in GRXS17 KO plants and wildtype controls grown under iron sufficiency and deficiency conditions. Our findings suggest that GRXS17 is required for tolerance to iron deficiency, and plays a negative regulatory role under conditions of iron sufficiency.Hot water extraction of D-arabinofuranosylvitexin from the raw leaves of commercially available Basella alba "Tsurumurasaki" and subsequent acidic hydrolysis was improved to be a procedure using a high-pressure steam sterilizer to afford vitexin. The amount was estimated to be 14.1 mg from 1 g of dry weight of the raw leaves, whose recovery was calculated to be 95% based on the estimated content of D-arabinofuranosylvitexin in B. alba raw leaves. The product was dehydratively cyclized between hydroxy groups on the carbohydrate and flavone skeletons under modified Mitsunobu reaction conditions in N,N-dimethylformamide to give chafuroside B, which is known to be a bioactive Oolong tea polyphenol. Through these transformations, 10.2 mg of chafuroside B could be semisynthesized from 1 g of dry weight of the raw leaves, and the efficiency was improved compared to that from the extraction from Oolong tea (3.4 μg from 1 g of dry weight).