Mitochondria are important regulators of macrophage polarisation. Here, we show that arginase-2 (Arg2) is a microRNA-155 (miR-155) and interleukin-10 (IL-10) regulated protein localized at the mitochondria in inflammatory macrophages, and is critical for IL-10-induced modulation of mitochondrial dynamics and oxidative respiration. Mechanistically, the catalytic activity and presence of Arg2 at the mitochondria is crucial for oxidative phosphorylation. We further show that Arg2 mediates this process by increasing the activity of complex II (succinate dehydrogenase). Moreover, Arg2 is essential for IL-10-mediated downregulation of the inflammatory mediators succinate, hypoxia inducible factor 1α (HIF-1α) and IL-1β in vitro. Accordingly, HIF-1α and IL-1β are highly expressed in an LPS-induced in vivo model of acute inflammation using Arg2−/− mice. These findings shed light on a new arm of IL-10-mediated metabolic regulation, working to resolve the inflammatory status of the cell.
The effectiveness of many vaccines licensed for clinical use relates to the induction of neutralising antibodies, facilitated by the inclusion of vaccine adjuvants, particularly alum. However, the ability of alum to preferentially promote humoral rather than cellular, particularly Th1-type responses, is not well understood. We demonstrate that alum activates immunosuppressive mechanisms following vaccination, which limit its capacity to induce Th1 responses. One of the key cytokines limiting excessive immune responses is IL-10. Injection of alum primed draining lymph node cells for enhanced IL-10 secretion ex vivo. Moreover, at the site of injection, macrophages and dendritic cells were key sources of IL-10 expression. Alum strongly enhanced the transcription and secretion of IL-10 by macrophages and dendritic cells. The absence of IL-10 signalling did not compromise alum-induced cell infiltration into the site of injection, but resulted in enhanced antigen-specific Th1 responses after vaccination. In contrast to its decisive regulatory role in regulating Th1 responses, there was no significant change in antigen-specific IgG1 antibody production following vaccination with alum in IL-10-deficient mice. Overall, these findings indicate that injection of alum promotes IL-10, which can block Th1 responses and may explain the poor efficacy of alum as an adjuvant for inducing protective Th1 immunity.
ObjectiveCognitive impairment is a pervasive outcome of stroke, reported in over half of patients 6 months post-stroke and is associated with increased disability and a poorer quality of life. Despite the prevalence of post-stroke cognitive impairment, the efficacy of existing psychological interventions for the rehabilitation of cognitive impairment following stroke has yet to be established. The aim of this study is to identify psychological interventions from non-randomised studies that intended to improve post-stroke cognitive function and establish their efficacy.DesignSystematic review and meta-analysis of non-randomised studies of psychological interventions addressing post-stroke cognitive impairment.Data sourcesElectronic searches were performed in the Pubmed, EMBASE and PsycINFO databases, the search dating from inception to February 2017.Eligibility criteriaAll non-randomised controlled studies and quasi-randomised controlled trials examining psychological interventions to improve cognitive function following stroke were included, such as feasibility studies, pilot studies, experimental studies, and quasi-experimental studies. The primary outcome was cognitive function. The prespecified secondary outcomes were functional abilities in daily life and quality of life.MethodsThe current meta-analyses combined the findings of seven controlled studies, examining the efficacy of psychological interventions compared with treatment-as-usual controls or active controls, and 13 one-group pre–post studies.ResultsResults indicated an overall small effect on cognition across the controlled studies (Hedges' g=0.38, 95% CI=0.06 to 0.7) and a moderate effect on cognition across the one-group pre–post studies (Hedges' g=0.51, 95% CI=0.3 to 0.73). Specific cognitive domains, such as memory and attention also demonstrated a benefit of psychological interventions.ConclusionsThis review provides support for the potential of psychological interventions to improve overall cognitive function post-stroke. Limitations of the study, in terms of risk of bias and quality of included studies, and future research directions are explored.PROSPERO registration numberCRD42017069714.
Endotoxin-free pristine graphene is capable of inducing innate training and that this effect can be modulated by incorporation in a matrix.
Inconsistent findings on the efficacy of psychosocial interventions in cancer may be due to their lack of specificity. The aim of this study was to identify priorities of psychosocial need among cancer patients currently receiving treatment in Western Sydney (NSW) as a prelude to targeted intervention. A sample of 188 patients (129 female, median age 52 years, median time since diagnosis 12 months), with various solid tumours, completed a self-report ranking questionnaire listing eight major areas of psychosocial need based on a literature search of relevant studies. The resulting ranking of priorities was: family (1), dealing with emotional stress (2), getting information (3), money (4), work (5), social life (6), sex life (7), and dealing with hospital staff (8). These priorities were independent of demographic characteristics, including time since diagnosis, suggesting that support in the areas of major need may be just as important during follow-up as it is at diagnosis. Males reported less distress than females, and patients with cancer of the head/neck or breast reported most distress. To be maximally effective, psychosocial intervention for cancer patients should focus on the principal areas of family interaction, effective stress management, and access to information.
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