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Nucleotide oligomerization domain (NOD)-like receptor-12 (NLRP12) has emerged as a negative regulator of inflammation. It is well described that the Th17 cell population increases in patients with early Rheumatoid Arthritis (RA), which correlates with the disease activity. Here, we investigated the role of NLRP12 in the differentiation of Th17 cells and the development of experimental arthritis, using the antigen-induced arthritis (AIA) murine model. We found that Nlrp12-/ - mice develop severe arthritis characterized by an exacerbated Th17-mediated inflammatory response with increases in the articular hyperalgesia, knee joint swelling, and neutrophil infiltration. Adoptive transfer of Nlrp12-/ - cells into WT mice recapitulated the hyperinflammatory response seen in Nlrp12-/ - mice and the treatment with anti-IL-17A neutralizing antibody abrogated arthritis development in Nlrp12-/ - mice, suggesting that NLRP12 works as an inhibitor of Th17 cell differentiation. Indeed, Th17 cell differentiation markedly increases in Nlrp12-/- T cells cultured under the Th17-skewing condition. Mechanistically, we found that NLRP12 negatively regulates IL-6-induced phosphorylation of STAT3 in T cells. Finally, pharmacological inhibition of STAT3 reduced Th17 cell differentiation and abrogated hyperinflammatory arthritis observed in Nlrp12-/ - mice. Thus, we described a novel role for NLRP12 as a checkpoint inhibitor of Th17 cell differentiation, which controls the severity of experimental arthritis.

As larvas de Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae) ocasionam injúrias em diferentes plantas do gênero Citrus (Rutaceae), reduzindo taxa fotossintética e desenvolvimento de novas brotações, ocasionando seca e queda das folhas afetadas, além de facilitar a penetração de Xanthomonas citri subsp. citri, bactéria causadora do cancro cítrico. Diante disto, conhecer a variação sazonal da praga pode otimizar seu manejo. O objetivo do trabalho foi caracterizar a dinâmica populacional das larvas em plantas de laranja De Russas [Citrus sinensis (L.) Osbeck] ao longo de 12 meses. Realizaram-se amostragens quinzenalmente, registrando-se o total de brotações contendo minas ou larvas, número de folhas com larvas por brotação, além do número de larvas, minas e pupas por folha. O desenvolvimento das laranjeiras foi registrado por avaliações biométricas, enquanto dados meteorológicos foram utilizados para gerar um gráfico da incidência em função da condição climática. Constatou-se que a oferta de alimento (novas brotações) ao longo do ano, apesar de influenciar na ocorrência do minador, não foi o fator mais significativo, verificando-se que a densidade populacional variou principalmente devido a temperatura e umidade. Os maiores índices de larvas e pupas foram registrados nos primeiros meses, resultando em 43% de brotações atacadas e até 3 minas por folha. As condições que propiciaram maiores densidades populacionais foram temperaturas próximas à 26 °C, precipitações de 60 mm e umidade relativa de 60%. O que na prática pode otimizar o manejo integrado de pragas, permitindo a adoção de técnicas preventivas para manter as populações de minador dos citros abaixo do nível de controle. Made available in DSpace on 2021-02-12T04:14:38Z (GMT). No. of bitstreams: 1 Dinamica-populacional-de-minador-dos-citros-em-pomares-de-laranja-2020.pdf: 2118887 bytes, checksum: ef8a3fbf1f8b106e1bccf84f2baef6eb (MD5) Previous issue date: 2020

Sepsis results in elevated adenosine in circulation. Extracellular adenosine triggers immunosuppressive signaling via the A2a receptor (A2aR). Sepsis survivors develop persistent immunosuppression with increased risk of recurrent infections. We utilized the cecal ligation and puncture (CLP) model of sepsis and subsequent infection to assess the role of adenosine in post-sepsis immune suppression. A2aR-deficient mice showed improved resistance to post-sepsis infections. Sepsis expanded a subset of CD39hi B cells and elevated extracellular adenosine, which was absent in mice lacking CD39-expressing B cells. Sepsis-surviving B cell-deficient mice were more resistant to secondary infections. Mechanistically, metabolic reprogramming of septic B cells increased production of ATP, which was converted into adenosine by CD39 on plasmablasts. Adenosine signaling via A2aR impaired macrophage bactericidal activity and enhanced interleukin-10 production. Septic individuals exhibited expanded CD39hi plasmablasts and adenosine accumulation. Our study reveals CD39hi plasmablasts and adenosine as important drivers of sepsis-induced immunosuppression with relevance in human disease.

The objective of this work is to show the role of the pharmaceutical professional and Searching for the integrality of health actions and services provided in a health unit also means thinking about the actions and services of Pharmaceutical Assistance, since the pharmacist also participates in the multidisciplinary team from hospital. Considering that the majority of health interventions involve the use of medications and that this use can be decisive for obtaining less or greater results, it is imperative that Pharmaceutical Assistance be seen from a comprehensive perspective, that is, in a much broader way (Duranes, 2017). The methodology used in this study was a literature review on reputable websites. The search for data was carried out in the Literature database, such as the Ministry of Health, SciELO, PubMed, which aimed at gaining knowledge on the subject, including the concept and practices relevant to the exercise of Pharmaceutical Assistance, in addition to verifying the importance of the pharmaceutical professional in promoting of health. The Microsoft Office Word® 2013 program was used to create the flowchart. 33 publications were searched, all publications are in article format, and were found in scientific journals in the areas of public health. In which 18 articles were included, as these were related to the research title and 5 were not included because it was not related to the proposed title. El objetivo de este trabajo es mostrar el rol del profesional farmacéutico y Buscar la integralidad de las acciones y servicios de salud que se brindan en una unidad de salud significa también pensar en las acciones y servicios de Asistencia Farmacéutica, ya que el farmacéutico también participa en el equipo multidisciplinario. del hospital. Considerando que la mayoría de las intervenciones en salud involucran el uso de medicamentos y que este uso puede ser determinante para obtener menores o mayores resultados, es imperativo que la Asistencia Farmacéutica sea vista desde una perspectiva integral, es decir, de una manera mucho más amplia (Duranes, 2017). La metodología utilizada en este estudio fue una revisión de la literatura en sitios web de renombre. La búsqueda de datos se realizó en la base de datos de Literatura, tales como el Ministerio de Salud, SciELO, PubMed, lo que tuvo como objetivo conocer el tema, incluyendo el concepto y prácticas relevantes para el ejercicio de la Asistencia Farmacéutica, además de verificar la importancia del profesional farmacéutico en la promoción de salud. Se utilizó el programa Microsoft Office Word® 2013 para crear el diagrama de flujo. Se buscaron 33 publicaciones, todas las publicaciones están en formato de artículo y fueron encontradas en revistas científicas en las áreas de salud pública. En el cual se incluyeron 18 artículos por estar relacionados con el título de la investigación y 5 no fueron incluidos por no estar relacionado con el título propuesto. O objetivo desse trabalho é mostrar o papel do profissional farmacêutico e buscar sobre a integralidade das ações e serviços de saúde prestados em uma unidade de saúde também significa pensar sobre as ações e serviços de Assistência Farmacêutica, já que o farmacêutico também participa da equipe de multidisciplinar do hospital. Considerando que a maioria das intervenções em saúde envolve o uso de medicamentos e que este uso pode ser determinante para a obtenção de menor ou maior resultado, é imperativo que a Assistência Farmacêutica seja vista sob ótica integral, ou seja, de forma bem mais ampla (Duranes, 2017). A metodologia utilizada neste estudo foi uma revisão de literatura em site conceituados. A busca dos dados foi realizada na base de dados da Literatura, como Ministério da Saúde, SciELO, PubMed que visou um conhecimento sobre o assunto, incluindo conceito e práticas pertinentes ao exercício da Assistência Farmacêutica, além de verificar a importância do profissional farmacêutico na promoção da saúde. O programa Microsoft Office Word® 2013 foi utilizado para a criação do fuxograma. Foram pesquisadas 33 publicações, todas as publicações estão no formato de artigo, e que foram encontradas em revistas científicas das áreas de saúde pública. Na qual 18 artigos foram incluídos, pois esses tinham relação com o título da pesquisa e 5 não foram incluídos pois não tinha relação com o título proposto.

Sepsis results in elevated adenosine in circulation. Extracellular adenosine triggers immunosuppressive signaling via the A2a receptor (A2aR). Sepsis survivors develop persistent immunosuppression with increased risk of recurrent infections. We utilized the cecal ligation and puncture (CLP) model of sepsis and subsequent infection to assess the role of adenosine in post-sepsis immune suppression. A2aR-deficient mice showed improved resistance to post-sepsis infections. Sepsis expanded a subset of CD39

Sepsis is an overwhelming systemic inflammation resulting from an uncontrolled infection that causes extensive tissue damage, organ dysfunction and eventually death. A growing body of evidence indicates that impaired neutrophil migration to the site of infection is associated with poor outcome in sepsis. Here we show that galectin-3 (Gal-3), an endogenous glycan-binding protein, plays a critical role in sepsis outcome. We found that serum Gal-3 concentration increased in patients with septic shock and mice undergoing sepsis induced by cecal ligation and puncture (CLP). Mice deficient in Gal-3 (Gal-3 KO) are more resistant to sepsis induced by CLP, showing lower levels of biochemical markers and neutrophil infiltration for organ injury/dysfunction than those observed in wild-type mice (WT). Furthermore, Gal-3 KO mice show an increased number of neutrophils in the primary focus of infection and reduced bacterial loads in the peritoneal cavity, blood, and lungs. Mechanistically, blood neutrophils from septic mice show higher levels of surface-bound Gal-3 than neutrophils from naive mice. The deficiency of Gal-3 was associated with increased rolling and adhesion of these cells in mesenteric venules. Our results indicate that Gal-3, secreted during sepsis, inhibits neutrophil migration into the infectious focus, which promotes the bacterial spread and worsens the outcome of sepsis.

O objetivo desse trabalho é mostrar o papel do profissional farmacêutico e buscar sobre a integralidade das ações e serviços de saúde prestados em uma unidade de saúde também significa pensar sobre as ações e serviços de Assistência Farmacêutica, já que o farmacêutico também participa da equipe de multidisciplinar do hospital. Considerando que a maioria das intervenções em saúde envolve o uso de medicamentos e que este uso pode ser determinante para a obtenção de menor ou maior resultado, é imperativo que a Assistência Farmacêutica seja vista sob ótica integral, ou seja, de forma bem mais ampla (Duranes, 2017). A metodologia utilizada neste estudo foi uma revisão de literatura em site conceituados. A busca dos dados foi realizada na base de dados da Literatura, como Ministério da Saúde, SciELO, PubMed que visou um conhecimento sobre o assunto, incluindo conceito e práticas pertinentes ao exercício da Assistência Farmacêutica, além de verificar a importância do profissional farmacêutico na promoção da saúde. O programa Microsoft Office Word® 2013 foi utilizado para a criação do fuxograma. Foram pesquisadas 33 publicações, todas as publicações estão no formato de artigo, e que foram encontradas em revistas científicas das áreas de saúde pública. Na qual 18 artigos foram incluídos, pois esses tinham relação com o título da pesquisa e 5 não foram incluídos pois não tinha relação com o título proposto.

Sepsis is associated with a hyper inflammatory state and switch of metabolic profile of immune cells leading to organ damage and lethality. MiR-21 is one of the most abundant microRNAs in phagocytes and plays important roles in both increasing and dampening inflammation. Here, we aim to investigate the role of miR-21 in inflammatory and metabolic state of phagocytes during acute sepsis. Sepsis induced by CLP (Cecal ligation and puncture) enhanced miR-21 expression in neutrophils and macrophages from peritoneal cavity and lung. MiR-21 deficient myeloid cells mice (miR21Δmyel) show increased sepsis survival, which was correlated with increased bacterial clearance and decreased production of IL6 and IL1β, and reduced of heart and liver damage markers (CK-MB and AST, respectively). Next, we sought to test whether decreased inflammation in miR21Δmyel is dependent on the aerobic glycolysis. Both peritoneal and BALF cells from miR21Δmyel septic mice showed decreased expression of genes encoding glycolytic molecules. Also, decreased HK1 was associated with lower lactate release than septic miR21fl/fl mice. Corroborating the in vivo data, LPS-challenged BMDM and peritoneal neutrophils from miR21Δmyel also exhibited lower expression of glycolytic genes and inflammatory cytokines than miR21fl/fl cells. Both, macrophages and neutrophils were submitted to glycolytic stress assay after LPS stimulation in order to confirm the functional impact of miR-21 over glycolysis. Similarity in both cells the lack of miR-21 leads to decrease of ECAR (extracellular acidification rate). In conclusion, higher expression of miR-21 after sepsis and LPS stimulation leads to assembly of inflammatory and glycolytic metabolic program in myeloid cells.

Patients who survive sepsis can develop long-term immune dysfunction, with expansion of the regulatory T (Treg) cell population. However, how Treg cells proliferate in these patients is not clear. Here we show that IL-33 has a major function in the induction of this immunosuppression. Mice deficient in ST2 (IL-33R) develop attenuated immunosuppression in cases that survive sepsis, whereas treatment of naive wild-type mice with IL-33 induces immunosuppression. IL-33, released during tissue injury in sepsis, activates type 2 innate lymphoid cells, which promote polarization of M2 macrophages, thereby enhancing expansion of the Treg cell population via IL-10. Moreover, sepsis-surviving patients have more Treg cells, IL-33 and IL-10 in their peripheral blood. Our study suggests that targeting IL-33 may be an effective treatment for sepsis-induced immunosuppression., Patients who survive sepsis are at increased risk of infection owing to long-term immunosuppression that is associated with an increase in Treg cell numbers. Here the authors show expansion of the Treg cell population in sepsis mice is driven by IL-33-induced ILC2 activation of IL-10 production by macrophages.

Organ dysfunction is a major concern in sepsis pathophysiology and contributes to its high mortality rate. Neutrophil extracellular traps (NETs) have been implicated in endothelial damage and take part in the pathogenesis of organ dysfunction in several conditions. NETs also have an important role in counteracting invading microorganisms during infection. The aim of this study was to evaluate systemic NETs formation, their participation in host bacterial clearance and their contribution to organ dysfunction in sepsis. C57Bl/6 mice were subjected to endotoxic shock or a polymicrobial sepsis model induced by cecal ligation and puncture (CLP). The involvement of cf-DNA/NETs in the physiopathology of sepsis was evaluated through NETs degradation by rhDNase. This treatment was also associated with a broad-spectrum antibiotic treatment (ertapenem) in mice after CLP. CLP or endotoxin administration induced a significant increase in the serum concentrations of NETs. The increase in CLP-induced NETs was sustained over a period of 3 to 24 h after surgery in mice and was not inhibited by the antibiotic treatment. Systemic rhDNase treatment reduced serum NETs and increased the bacterial load in non-antibiotic-treated septic mice. rhDNase plus antibiotics attenuated sepsis-induced organ damage and improved the survival rate. The correlation between the presence of NETs in peripheral blood and organ dysfunction was evaluated in 31 septic patients. Higher cf-DNA concentrations were detected in septic patients in comparison with healthy controls, and levels were correlated with sepsis severity and organ dysfunction. In conclusion, cf-DNA/NETs are formed during sepsis and are associated with sepsis severity. In the experimental setting, the degradation of NETs by rhDNase attenuates organ damage only when combined with antibiotics, confirming that NETs take part in sepsis pathogenesis. Altogether, our results suggest that NETs are important for host bacterial control and are relevant actors in the pathogenesis of sepsis.

Survivors from sepsis are in an immunosuppressed state that is associated with higher long-term mortality and risk of opportunistic infections. Whether these factors contribute to neoplastic proliferation, however, remains unclear. Tumor-associated macrophages (TAM) can support malignant cell proliferation, survival, and angiogenesis. We addressed the relationship between the post-sepsis state, tumor progression and TAM accumulation, and phenotypic and genetic profile, using a mouse model of sepsis resolution and then B16 melanoma in mice. In addition, we measured the serum concentrations of TNFα, TGFβ, CCL2, and CXCL12 and determined the effect of in vivo CXCR4/CXCL12 inhibition in this context. Mice that survived sepsis showed increased tumor progression both in the short and long term, and survival times were shorter. TAM accumulation, TAM local proliferation, and serum concentrations of TGFβ, CXCL12, and TNFα were increased. Naïve mice inoculated with B16 together with macrophages from post-sepsis mice also had faster tumor progression and shorter survival. Post-sepsis TAMs had less expression of MHC-II and leukocyte activation-related genes. Inhibition of CXCR4/CXCL12 prevented the post-sepsis–induced tumor progression, TAM accumulation, and TAM in situ proliferation. Collectively, our data show that the post-sepsis state was associated with TAM accumulation through CXCR4/CXCL12, which contributed to B16 melanoma progression. Cancer Immunol Res; 4(4); 312–22. ©2016 AACR.

Hemorrhagic cystitis is an important dose limiting side effect of ifosfamide based cancer chemotherapy. Despite chemoprophylaxis inflammation can still be found in cystoscopy guided biopsies. Previous studies confirmed the role of TNF-α and IL-1β. We evaluated the protective effect of the IL-1R antagonist anakinra and the anti-TNF-α antibody infliximab in experimental ifosfamide induced hemorrhagic cystitis.Hemorrhagic cystitis was induced by an injection of ifosfamide (400 mg/kg intraperitoneally) in Swiss wild-type C57Bl/6, IL-1R-/-, TNFR1-/- or TNFR1/R2-/- mice. Mice were treated 30 minutes before ifosfamide with anakinra (100 mg/kg intraperitoneally), infliximab (5 mg/kg intraperitoneally) or vehicle. Visceral nociception was evaluated after hemorrhagic cystitis induction. At 12 hours the animals were sacrificed. Bladders were harvested to assess bladder wet weight, vascular permeability, macroscopic and microscopic findings, muscle contractility, and for cystometrography. Inflammatory cell infiltration was assessed by myeloperoxidase assay and flow cytometry.Anakinra attenuated hemorrhage, edema, neutrophil infiltration, visceral hyperalgesia and bladder dysfunction. IL-1R-/- mice also showed milder hemorrhagic cystitis. Infliximab inhibited bladder edema and visceral hyperalgesia without preventing hemorrhage, bladder dysfunction, neutrophils or accumulation. Additionally, the lack of TNFR1 decreased bladder edema but not cell infiltration whereas concomitant deficiency of TNFR1 and TNFR2 resulted in worse hemorrhagic cystitis.Anakinra is effective for preventing experimentally ifosfamide induced hemorrhagic cystitis. It seems that neutrophil and macrophage infiltration in this circumstance depends on IL-1 signaling through IL1R. Possibly TNFR2 has a protective role in hemorrhagic cystitis.