Mesenchymal stromal (stem) cell therapy modulates miR-193b-5p expression to attenuate sepsis-induced acute lung injury.

Although mesenchymal stromal (stem) cell (MSC) administration attenuates sepsis-induced lung injury in pre-clinical models, the mechanism(s) of action and host immune system contributions to its therapeutic effects remain elusive. We show that treatment with MSCs decreased expression of host-derived microRNA (miR)-193b-5p and increased expression of its target gene, the tight junctional protein occludin (Ocln), in lungs from septic mice. Mutating the Ocln 3' untranslated region miR-193b-5p binding sequence impaired binding to Ocln mRNA. Inhibition of miR-193b-5p in human primary pulmonary microvascular endothelial cells prevents tumour necrosis factor (TNF)-induced decrease in Ocln gene and protein expression and loss of barrier function. MSC-conditioned media mitigated TNF-induced miR-193b-5p upregulation and Ocln downregulation in vitro When administered in vivo, MSC-conditioned media recapitulated the effects of MSC administration on pulmonary miR-193b-5p and Ocln expression. MiR-193b-deficient mice were resistant to pulmonary inflammation and injury induced by lipopolysaccharide (LPS) instillation. Silencing of Ocln in miR-193b-deficient mice partially recovered the susceptibility to LPS-induced lung injury. In vivo inhibition of miR-193b-5p protected mice from endotoxin-induced lung injury. Finally, the clinical significance of these results was supported by the finding of increased miR-193b-5p expression levels in lung autopsy samples from acute respiratory distress syndrome patients who died with diffuse alveolar damage.

Immunophenotypic characterization and therapeutics effects of human bone marrow- and umbilical cord-derived mesenchymal stromal cells in an experimental model of sepsis.

Sepsis is a complicated multi-system disorder characterized by a dysregulated host response to infection. Despite substantial progress in the understanding of mechanisms of sepsis, translation of these advances into clinically effective therapies remains challenging. Mesenchymal Stromal Cells (MSCs) possess immunomodulatory properties that have shown therapeutic promise in preclinical models of sepsis. The therapeutic effects of MSCs may vary depending on the source and type of these cells. In this comparative study, the gene expression pattern and surface markers of bone marrow-derived MSCs (BM-MSCs) and umbilical cord-derived MSCs (UC-MSCs) as well as their therapeutic effects in a clinically relevant mouse model of polymicrobial sepsis, cecal ligation and puncture (CLP), were investigated. The results showed remarkable differences in gene expression profile, surface markers and therapeutic potency in terms of enhancing survival and pro/anti-inflammatory responses between the two MSC types. BM-MSCs improved survival concomitant with an enhanced systemic bacterial clearance and improved inflammatory profile post CLP surgery. Despite some improvement in the inflammatory profile of the septic animals, treatment with UC-MSCs did not enhance survival or bacterial clearance. Overall, the beneficial therapeutic effects of BM-MSCs over UC-MSCs may likely be attributed to their pro-inflammatory function, and to some extent anti-inflammatory features, reflected in their gene expression pattern enhancing macrophage polarization to M1/M2 phenotypes resulting in a balanced pro- and anti-inflammatory response against polymicrobial sepsis.

Cathelicidins Mitigate Staphylococcus aureus Mastitis and Reduce Bacterial Invasion in Murine Mammary Epithelium.

Staphylococcus aureus, an important cause of mastitis in mammals, is becoming increasingly problematic due to the development of resistance to conventional antibiotics. The ability of S. aureus to invade host cells is key to its propensity to evade immune defense and antibiotics. This study focuses on the functions of cathelicidins, small cationic peptides secreted by epithelial cells and leukocytes, in the pathogenesis of S. aureus mastitis in mice. We determined that endogenous murine cathelicidin (CRAMP; Camp) was important in controlling S. aureus infection, as cathelicidin knockout mice (Camp-/- ) intramammarily challenged with S. aureus had higher bacterial burdens and more severe mastitis than did wild-type mice. The exogenous administration of both a synthetic human cathelicidin (LL-37) and a synthetic murine cathelicidin (CRAMP) (8 µM) reduced the invasion of S. aureus into the murine mammary epithelium. Additionally, this exogenous LL-37 was internalized into cultured mammary epithelial cells and impaired S. aureus growth in vitro We conclude that cathelicidins may be potential therapeutic agents against mastitis; both endogenous and exogenous cathelicidins conferred protection against S. aureus infection by reducing bacterial internalization and potentially by directly killing this pathogen.

Macrophage migration inhibitory factor (MIF) controls cytokine release during respiratory syncytial virus infection in macrophages.

OBJECTIVE AND DESIGN: Respiratory syncytial virus (RSV) is the major cause of infection in children up to 2 years old and reinfection is very common among patients. Tissue damage in the lung caused by RSV leads to an immune response and infected cells activate multiple signaling pathways and massive production of inflammatory mediators like macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine. Therefore, we sought to investigate the role of MIF during RSV infection in macrophages. METHODS: We evaluated MIF expression in BALB/c mice-derived macrophages stimulated with different concentrations of RSV by Western blot and real-time PCR. Additionally, different inhibitors of signaling pathways and ROS were used to evaluate their importance for MIF expression. Furthermore, we used a specific MIF inhibitor, ISO-1, to evaluate the role of MIF in viral clearance and in RSV-induced TNF-α, MCP-1 and IL-10 release from macrophages. RESULTS: We showed that RSV induces MIF expression dependently of ROS, 5-LOX, COX and PI3K activation. Moreover, viral replication is necessary for RSV-triggered MIF expression. Differently, p38 MAPK in only partially needed for RSV-induced MIF expression. In addition, MIF is important for the release of TNF-α, MCP-1 and IL-10 triggered by RSV in macrophages. CONCLUSIONS: In conclusion, we demonstrate that MIF is expressed during RSV infection and controls the release of pro-inflammatory cytokines from macrophages in an in vitro model.

Nano Silver Vanadate AgVO3 : Synthesis, New Functionalities and Applications.

Silver vanadates have been widely investigated because of their many interesting properties and their potential use in several applications. In addition to this, a large number of groups have investigated silver vanadates in the form of nanostructures. Here, we address first the synthesis and properties of nanosilver vanadate. Different techniques, such as precipitation, thermal decomposition, hydrothermal treatment, and sol-gel, are among the methods that have been employed for the controlled synthesis of silver vanadate. The use of nanosilver vanadate for the development of novel electronic devices, catalysts, and antibacterial agents for industry and biomedical applications will then be discussed. In this sense, the present review highlights the major advances regarding the synthesis, properties and applications of nanostructured silver vanadates.

Protective effect of gedunin on TLR-mediated inflammation by modulation of inflammasome activation and cytokine production: Evidence of a multitarget compound.

Activation of toll-like receptors (TLRs) by pathogen-associated molecular patterns (PAMPs) triggers an innate immune response, via cytokine production and inflammasome activation. Herein, we have investigated the modulatory effect of the natural limonoid gedunin on TLR activation in vitro and in vivo. Intraperitoneal (i.p.) pre- and post-treatments of C57BL/6 mouse with gedunin impaired the influx of mononuclear cells, eosinophils and neutrophils, as well as the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nitric oxide (NO), triggered by lipopolysaccharide (LPS) in mouse pleura. Accordingly, in vitro post-treatment of immortalized murine macrophages with gedunin also impaired LPS-induced production of such mediators. Gedunin diminished LPS-induced expression of the nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) on pleural leukocytes in vivo and in immortalized macrophages in vitro. In line with this, gedunin inhibited LPS-induced caspase-1 activation and the production of IL-1ß in vivo and in vitro. In addition, gedunin treatment triggered the generation of the anti-inflammatory factors IL-10 and heme oxigenase-1 (HO-1) at resting conditions or upon stimulation. We also demonstrate that gedunin effect is not restricted to TLR4-mediated response, since this compound diminished TNF-α, IL-6, NO, NLRP3 and IL-1ß, as well as enhanced IL-10 and HO-1, by macrophages stimulated with the TLR2 and TLR3 agonists, palmitoyl-3-Cys-Ser-(Lys)4 (PAM3) and polyriboinosinic:polyribocytidylic acid (POLY I:C), in vitro. In silico modeling studies revealed that gedunin efficiently docked into caspase-1, TLR2, TLR3 and to the myeloid differentiation protein-2 (MD-2) component of TLR4. Overall, our data demonstrate that gedunin modulates TLR4, TLR3 and TLR2-mediated responses and reveal new molecular targets for this compound.

Short-Term Regulation of FcγR-Mediated Phagocytosis by TLRs in Macrophages: Participation of 5-Lipoxygenase Products.

TLRs recognize a broad spectrum of microorganism molecules, triggering a variety of cellular responses. Among them, phagocytosis is a critical process for host defense. Leukotrienes (LTs), lipid mediators produced from 5-lipoxygenase (5-LO) enzyme, increase FcγR-mediated phagocytosis. Here, we evaluated the participation of TLR2, TLR3, TLR4, and TLR9 in FcγR-mediated phagocytosis and whether this process is modulated by LTs. Rat alveolar macrophages (AMs), murine bone marrow-derived macrophages (BMDMs), and peritoneal macrophages (PMs) treated with TLR2, TLR3, and TLR4 agonists, but not TLR9, enhanced IgG-opsonized sheep red blood cell (IgG-sRBC) phagocytosis. Pretreatment of AMs or BMDMs with drugs that block LT synthesis impaired the phagocytosis promoted by TLR ligands, and TLR potentiation was also abrogated in PMs and BMDMs from 5-LO-/- mice. LTB4 production induced by IgG engagement was amplified by TLR ligands, while cys-LTs were amplified by activation of TLR2 and TLR4, but not by TLR3. We also noted higher ERK1/2 phosphorylation in IgG-RBC-challenged cells when preincubated with TLR agonists. Furthermore, ERK1/2 inhibition by PD98059 reduced the phagocytic activity evoked by TLR agonists. Together, these data indicate that TLR2, TLR3, and TLR4 ligands, but not TLR9, amplify IgG-mediated phagocytosis by a mechanism which requires LT production and ERK-1/2 pathway activation.

Leukotriene B4 modulates P2X7 receptor-mediated Leishmania amazonensis elimination in murine macrophages.

ATP is an important signaling molecule in the immune system, and it is able to bind the P2X7 purinergic receptor. Recently, our group showed that ATP-treated macrophages eliminate Leishmania amazonensis. It has been reported that leukotriene B4 (LTB4) reduces the parasitic load of infected macrophages. Additionally, it has been demonstrated that the P2X7 receptor can induce PLA2 activation and arachidonic acid mobilization. Based on these findings, we investigated whether LTB4 is produced upon P2X7 receptor activation and examined whether LTB4 modulates parasite elimination. Using macrophages lacking the P2X7 receptor, we observed that ATP was not able to reduce L. amazonensis load. This result suggests a role of the P2X7 purinergic receptor in parasite elimination. In addition, ATP was sufficient to induce LTB4 release from infected control macrophages but not from macrophages lacking the P2X7 receptor. Moreover, we found that ATP failed to decrease the parasitic load in 5-lipoxygenase (LO)-deficient macrophages. Treatment with the 5-LO inhibitor AA861 also impairs the ATP effect on parasitic loads. Furthermore, macrophages from 5-LO knockout mice eliminated L. amazonensis in the presence of exogenous LTB4, and macrophages obtained from P2X7 receptor knockout mice eliminated L. amazonensis when incubated with ionomycin. Finally, we demonstrated that in the presence of CP105696, an antagonist for LTB4 high-affinity receptor, ATP was not able to reduce parasitic load. These results indicate that P2X7 receptor activation leads to LTB4 formation, which is required for L. amazonensis elimination.

Cultural competence in mental health nursing: validity and internal consistency of the Portuguese version of the multicultural mental health awareness scale-MMHAS.

BACKGROUND: Cultural competence is an essential component in rendering effective and culturally responsive services to culturally and ethnically diverse clients. Still, great difficulty exists in assessing the cultural competence of mental health nurses. There are no Portuguese validated measurement instruments to assess cultural competence in mental health nurses. This paper reports a study testing the reliability and validity of the Portuguese version of the Multicultural Mental Health Awareness Scale-MMHAS in a sample of Portuguese nurses. METHODS: Following a standard forward/backward translation into Portuguese, the adapted version of MMHAS, along with a sociodemographic questionnaire, were applied to a sample of 306 Portuguese nurses (299 males, 77 females; ages 21-68 years, M = 35.43, SD = 9.85 years). A psychometric research design was used with content and construct validity and reliability. Reliability was assessed using internal consistency and item-total correlations. Construct validity was determined using factor analysis. RESULTS: The factor analysis confirmed that the Portuguese version of MMHAS has a three-factor structure of multicultural competencies (Awareness, Knowledge, and Skills) explaining 59.51% of the total variance. Strong content validity and reliability correlations were demonstrated. The Portuguese version of MMHAS has a strong internal consistency, with a Cronbach's alpha of 0.958 for the total scale. CONCLUSIONS: The results supported the construct validity and reliability of the Portuguese version of MMHAS, proving that is a reliable and valid measure of multicultural counselling competencies in mental health nursing. The MMHAS Portuguese version can be used to evaluate the effectiveness of multicultural competency training programs in Portuguese-speaking mental health nurses. The scale can also be a useful in future studies of multicultural competencies in Portuguese-speaking nurses.

Cyborgs, biotechnologies, and informatics in health care - new paradigms in nursing sciences.

Nursing Sciences are at a moment of paradigmatic transition. The aim of this paper is to reflect on the new epistemological paradigms of nursing science from a critical approach. In this paper, we identified and analysed some new research lines and trends which anticipate the reorganization of nursing sciences and the paradigms emerging from nursing care: biotechnology-centred knowledge; the interface between nursing knowledge and new information technologies; body care centred knowledge; the human body as a cyborg body; and the rediscovery of an aesthetic knowledge in nursing care.

The influence of 5-lipoxygenase on cigarette smoke-induced emphysema in mice.

BACKGROUND: Pulmonary emphysema is characterized by the loss of lung architecture. Our hypothesis is that the inhibition of 5-lipoxygenase (5-LO) production may be an important strategy to reduce inflammation, oxidative stress, and metalloproteinases in lung tissue resulting from cigarette smoke (CS)-induced emphysema. METHODS: 5-LO knockout (129S2-Alox5(tm1Fun)/J) and wild-type (WT) mice (129S2/SvPas) were exposed to CS for 60days. Mice exposed to ambient air were used as Controls. Oxidative, inflammatory, and proteolytic markers were analyzed. RESULTS: The alveolar diameter was decreased in CS 5-LO(-/-) mice when compared with the WT CS group. The CS exposure resulted in less pronounced pulmonary inflammation in the CS 5-LO(-/-) group. The CS 5-LO(-/-) group showed leukotriene B4 values comparable to those of the Control group. The expression of MMP-9 was decreased in the CS 5-LO(-/-) group when compared with the CS WT group. The expression of superoxide dismutase, catalase, and glutathione peroxidase were decreased in the CS 5-LO(-/-) group when compared with the Control group. The protein expression of nuclear factor (erythroid-derived 2)-like 2 was reduced in the CS 5-LO(-/-) group when compared to the CS WT group. CONCLUSION: In conclusion, we show for the first time that 5-LO deficiency protects 129S2 mice against emphysema caused by CS. We suggest that the main mechanism of pathogenesis in this model involves the imbalance between proteases and antiproteases, particularly the association between MMP-9 and TIMP-1. General significance This study demonstrates the influence of 5-LO mediated oxidative stress, inflammation, and proteolytic markers in CS exposed mice.

Inflammasome in platelets: allying coagulation and inflammation in infectious and sterile diseases?

Platelets are crucial effector cells in hemostasis. In addition, platelets are increasingly recognized as major inflammatory cells with key roles in innate and adaptive immune responses. Activated platelets have key thromboinflammatory activities linking coagulation to inflammatory response in a variety of coagulation disorders and vasculopathies. Recently identified inflammatory activities of platelets include the synthesis of IL-1ß from spliced pre-RNA, as well as the presence and assembly of inflammasome which intermediate IL-1ß secretion. Here we review the mechanisms by which platelets activate translation machinery and inflammasome assembly to synthesize and release IL-1ß. The contributions of these processes to protective and pathogenic responses during infectious and inflammatory diseases are discussed.

Pivotal role of the 5-lipoxygenase pathway in lung injury after experimental sepsis.

Postsepsis lung injury is a common clinical problem associated with significant morbidity and mortality. Leukotrienes (LTs) are important lipid mediators of infection and inflammation derived from the 5-lipoxygenase (5-LO) metabolism of arachidonate with the potential to contribute to lung damage after sepsis. To test the hypothesis that LTs are mediators of lung injury after sepsis, we assessed lung structure, inflammatory mediators, and mechanical changes after cecal ligation and puncture surgery in wild-type (WT) and 5-LO knockout (5-LO(-/-)) mice and in WT mice treated with a pharmacologic LT synthesis inhibitor (MK886) and LT receptor antagonists (CP105,696 and montelukast). Sixteen hours after surgery, WT animals exhibited severe lung injury (by histological analysis), substantial mechanical impairment (i.e., an increase in static lung elastance), an increase in neutrophil infiltration, and high levels of LTB4, cysteinyl-LTs (cys-LTs), prostaglandin E2, IL-1ß, IL-6, IL-10, IL-17, KC (CXCL1), and monocyte chemotactic protein-1 (CCL2) in lung tissue and plasma. 5-LO(-/-) mice and WT mice treated with a pharmacologic 5-LO inhibitor were significantly protected from lung inflammation and injury. Selective antagonists for BLT1 or cys-LT1, the high-affinity receptors for LTB4 and cys-LTs, respectively, were insufficient to provide protection when used alone. These results point to an important role for 5-LO products in sepsis-induced lung injury and suggest that the use of 5-LO inhibitors may be of therapeutic benefit clinically.

Pro-environmental behavior, personality and emotional intelligence in adolescents: a systematic review.

Introduction: Human behavior significantly contributes to environmental problems, making the study of pro-environmental behavior an important task for psychology. In this context, it is crucial to understand the pro-environmental behavior of adolescents, as young people play a fundamental role in facilitating long-term changes in environmental consciousness and encouraging decision-makers to take action. However, little is currently known about the pro-environmental behavior of adolescents. Recently, there has been growing interest in examining the influence of personality traits and emotional intelligence on pro-environmental behavior. Methods: We conducted a systematic review to enhance our understanding of adolescent pro-environmental behavior. Thus, this systematic review was designed to enhance understanding of adolescent's pro-environmental behavior by summarizing existing evidence on how it relates to personality and emotional intelligence. Results: Our findings suggest associations between specific personality traits and dimensions of emotional intelligence with adolescent pro-environmental behavior, aligning with similar studies conducted on adults. Discussion: While our findings offer valuable insights, further research is needed to establish causality and deepen our understanding of the interplay between multiple variables influencing pro-environmental behavior among adolescents. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023387836], identifier [CRD42023387836].

Leukotriene B4 mediates neutrophil migration induced by heme.

High concentrations of free heme found during hemolytic events or cell damage leads to inflammation, characterized by neutrophil recruitment and production of reactive oxygen species, through mechanisms not yet elucidated. In this study, we provide evidence that heme-induced neutrophilic inflammation depends on endogenous activity of the macrophage-derived lipid mediator leukotriene B(4) (LTB(4)). In vivo, heme-induced neutrophil recruitment into the peritoneal cavity of mice was attenuated by pretreatment with 5-lipoxygenase (5-LO) inhibitors and leukotriene B(4) receptor 1 (BLT1) receptor antagonists as well as in 5-LO knockout (5-LO(-/-)) mice. Heme administration in vivo increased peritoneal levels of LTB(4) prior to and during neutrophil recruitment. Evidence that LTB(4) was synthesized by resident macrophages, but not mast cells, included the following: 1) immuno-localization of heme-induced LTB(4) was compartmentalized exclusively within lipid bodies of resident macrophages; 2) an increase in the macrophage population enhanced heme-induced neutrophil migration; 3) depletion of resident mast cells did not affect heme-induced LTB(4) production or neutrophil influx; 4) increased levels of LTB(4) were found in heme-stimulated peritoneal cavities displaying increased macrophage numbers; and 5) in vitro, heme was able to activate directly macrophages to synthesize LTB(4). Our findings uncover a crucial role of LTB(4) in neutrophil migration induced by heme and suggest that beneficial therapeutic outcomes could be achieved by targeting the 5-LO pathway in the treatment of inflammation associated with hemolytic processes.

Dark Personality Traits and Online Behaviors: Portuguese Versions of Cyberstalking, Online Harassment, Flaming and Trolling Scales.

The main objective of this study is to assess moderation effects of online behaviors between personality traits and addiction to Internet. To this end, four instruments were validated for Portuguese version through confirmatory factor analysis and exploratory factor analysis (Study 1) Multiple regression analysis was applied to examine the personality predictors of specific online behaviors while controlling for gender and age; and moderation effects were assessed (Study 2). Results showed good psychometric properties for the four validated scales. Machiavellianism is positively associated with all the dimensions of this study. Psychopathy is positively associated with total Cyberstalking, Cyberstalking Control, Flaming and Trolling. Narcissism is positively associated with all the dimensions, except Online Harassment and Flaming. Machiavellianism is positively associated with Addiction to Internet through Cyberstalking, Flaming and Trolling. Psychopathy is positively associated with Addiction to Internet through Cyberstalking Control and Flaming. Narcissism is also positively associated with Addiction to Internet through Cyberstalking and Trolling. This study demonstrates that dimensions of the dark triad of personality play an important role in Internet addiction through online behaviors. The results of this study have theoretical and practical implications: on the one hand, they reinforces the findings of other studies showing that dimensions of the dark personality triad play an important role in Internet and social network addition, contributing to the literature; and, on the other hand, on a practical level, they allow to conduct awareness campaigns in communities, schools, and work to understand that one can be exposed to unpleasant situations due to behaviors that some people with personality traits of Machiavellianism, narcissism and/or psychopathy that may cause problems affecting the mental, emotional and psychological health of others.

DJ-1 Deficiency Protects against Sepsis-Induced Myocardial Depression.

Oxidative stress is considered one of the early underlying contributors of sepsis-induced myocardial depression. DJ-1, also known as PARK7, has a well-established role as an antioxidant. We have previously shown, in a clinically relevant model of polymicrobial sepsis, DJ-1 deficiency improved survival and bacterial clearance by decreasing ROS production. In the present study, we investigated the role of DJ-1 in sepsis-induced myocardial depression. Here we compared wildtype (WT) with DJ-1 deficient mice at 24 and 48 h after cecal ligation and puncture (CLP). In WT mice, DJ-1 was increased in the myocardium post-CLP. DJ-1 deficient mice, despite enhanced inflammatory and oxidative responses, had an attenuated hypertrophic phenotype, less apoptosis, improved mitochondrial function, and autophagy, that was associated with preservation of myocardial function and improved survival compared to WT mice post-CLP. Collectively, these results identify DJ-1 as a regulator of myocardial function and as such, makes it an attractive therapeutic target in the treatment of early sepsis-induced myocardial depression.

Liver morphologic analysis in perinatal autopsies with intrauterine stress liver morphology in perinatal autopsies.

Quantify steatosis, fibrosis, and focuses of extramedullary erythropoiesis (ER) in the liver and report it to the causes of death in the perinatal. Morphologic analysis of steatosis', percentage of fibrosis, and ER of 467 perinatal autopsies. Cases with hypoxia/perinatal anoxia and ascending infection showed higher percentage of fibrosis. The number of ER was significantly higher among premature infants and in cases with infection. Our results contribute to a better quality of perinatal care through clinical demonstration of which injuries are associated with them, what may help in early diagnosis of these alterations in children who survive.

Multicultural competencies training programs for health care staff and health students in academic and professional settings: a scoping review protocol.

OBJECTIVE: The aim of the proposed scoping review is to identify training programs in multicultural competencies for health care staff and health students in professional and academic settings. INTRODUCTION: Cultural competence training for health care professionals is an imperative challenge in today's culturally diverse societies to ensure that all people receive equitable and effective health care, particularly those from culturally diverse backgrounds. INCLUSION CRITERIA: This scoping review will consider literature with adult participants aged ≥ 18 years, health care staff, and health students who may have received or are receiving multicultural competencies training. Literature published since 1960 in English, Portuguese, Spanish, and French will be considered for inclusion. Literature will be excluded if it reports on multicultural competencies training programs for students outside the health domain or for non-professional high school programs. METHODS: The search strategy, designed according to the inclusion and exclusion criteria, will aim to find both published and unpublished literature. The following electronic databases will be searched: MEDLINE, CINAHL, Psychology and Behavioral Sciences Collection, Web of Science, Open Access Scientific Repository of Portugal (RCAAP), and Open Grey. Other sites to be searched include ClinicalTrials.gov; United Nations High Commissioner for Refugees (UNHCR); International Organization for Migration (IOM); and International Migration, Integration and Social Cohesion in Europe (IMISCOE). The screening process will consist of two steps carried out by two independent reviewers: firstly, screening by title and abstract; and secondly, by full text. Data will be charted to describe the body of literature according to the review research questions, which were defined following the Population, Concept, Context (PCC) mnemonic. Data will be presented graphically when possible, and accompanied by a narrative that describes the characteristics of the training programs.

DJ-1 binds to Rubicon to Impair LC-3 Associated Phagocytosis.

The ability to effectively clear infection is fundamental to host survival. Sepsis, defined as dysregulated host response to infection, is a heterogenous clinical syndrome that does not uniformly clear intact bacterial or sterile infection (i.e., lipopolysaccharide). These findings were further associated with increased survival in DJ-1 deficient animals exposed to intact bacteria relative to DJ-1 deficient challenged with lipopolysaccharide. We analyzed bacterial and lipopolysaccharide clearance in bone marrow macrophages (BMM) cultured ex vivo from wild-type and DJ-1 deficient mice. Importantly, we demonstrated that DJ-1 deficiency in BMM promotes Rubicon-dependent increase in L3C-associated phagocytosis, non-canonical autophagy pathway used for xenophagy, during bacterial but not lipopolysaccharide infection. In contrast to DJ-1 deficient BMM challenged with lipopolysaccharide, DJ-1 deficient BMM exposed to intact bacteria showed enhanced Rubicon complexing with Beclin-1 and UVRAG and consistently facilitated the assembly of complete autophagolysosomes that were decorated with LC3 molecules. Our data shows DJ-1 impairs or/and delays bacterial clearance and late autophagolysosome formation by binding to Rubicon resulting in Rubicon degradation, decreased L3C-associated phagocytosis, and decreased bacterial clearance in vitro and in vivo - implicating Rubicon and DJ-1 as critical regulators of bacterial clearance in experimental sepsis.