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A leucemia mielóide crônica é uma doença proliferativa do sistema hematopoiético, caracterizada pela expansão clonal de uma célula tronco primitiva e pluripotente denominada "stem cell", que tem a capacidade de se diferenciar em células mielóides, monocíticas, megacariocíticas e células B e T. Em homeostase, existe um equilíbrio entre proliferação, diferenciação e renovação das células tronco, equilíbrio este que se encontra alterado em pacientes com Leucemia mielóide crônica, devido a uma proliferação e diferenciação aumentada e anormal relacionada à atividade de tirosino quinase do produto do gene quimérico BCR/ABL resultante da translocação t(9;22), que se apresenta como marcador da doença. Vários transcritos quiméricos têm sido descritos e acredita-se que a gravidade do quadro clínico dependa do tipo de mRNA gerado. No presente trabalho analisamos 28 amostras de 27 pacientes diagnosticados com Leucemia mielóide crônica. Todos possuíam a translocação t(9;22) e foram analisados para a presença dos transcritos resultantes das fusões b3a2 ou b2a2 por RT-PCR e Nested-PCR, técnicas que se mostraram mais sensíveis para a identificação dos transcritos. Entre os pacientes, 12% apresentaram fusão b3a2, 18% possuíam fusão b2a2 e 32% possuíam os dois tipos de transcritos. A presença de um dos tipos de transcritos, b3a2, parece estar relacionada com contagem de plaquetas acima de 1 milhão/mm³ , reconhecida como característica de mau prognóstico em pacientes com Leucemia mielóide crônica.

Pseudomonas aeruginosa is a frequent cause of antimicrobial-resistant hospital-acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro-resolving actions of angiotensin-(1-7) [Ang-(1-7)] signaling through the G protein-coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang-(1-7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor-deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas-infected mice with Ang-(1-7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro-inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang-(1-7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang-(1-7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang-(1-7) pathway during infection is a potential strategy for the development of host-directed therapies to promote mechanisms of resistance and resilience to pneumonia., (© 2024 Federation of American Societies for Experimental Biology.)

Investigation of the endophytic fungi Nigrospora sphaerica , Nigrospora oryzae , and Pseudofusicoccum stromaticum MeOH fractions isolated from the leaves of Vochysia divergens , a medicinal species from the Brazilian Pantanal, led to the identification of five compounds, namely a new compound (1 E ,8 Z )-10,11-dihydroxy-5,5,8-trimethyl-4-oxocycloundeca-1,8-diene-1-carbaldehyde ( 1 ) and four known compounds: 5-methylmellein ( 2 ), sclerone ( 3 ), daldinone A ( 4 ), and lasiodiplodin ( 5 ). All compounds were identified using spectroscopic methods, and 1 was corroborated with mass spectrometry, while the known compounds were compared with data in the literature. The relative configuration of compound 1 was determined based on theoretical conformational studies as well as the J experimental values between the hydroxymethyne hydrogens. The antimicrobial activity of the compounds was evaluated. Promising results were obtained for compounds 2 , 4 , and 5 since they inhibited the bacterium Pseudomonas aeruginosa , an opportunistic pathogen, suggesting the potential of these microorganisms as a source of new antibacterial agents.

Cotton crop yields are largely affected by infestations of Anthonomus grandis, which is its main pest. Although Bacillus thuringiensis (Bt) derived proteins can limit insect pest infestations, the diverse use of control methods becomes a viable alternative in order to prolong the use of technology in the field. One of the alternative methods to Bt technology has been the utilization of certain Pseudomonas species highly efficient in controlling coleopteran insects have been used to produce highly toxic insecticidal proteins. This study aimed to evaluate the toxicity of IPD072Aa and PIP-47Aa proteins, isolated from Pseudomonas spp., in interaction with Cry1Ia10, Cry3Aa, and Cry8B proteins isolated from B. thuringiensis, to control A. grandis in cotton crops. The genes IPD072Aa and PIP-47Aa were synthesized and cloned into a pET-SUMO expression vector. Moreover, Cry1Ia10, Cry3Aa, and Cry8B proteins were obtained by inducing recombinant E. coli clones, which were previously acquired by our research group from the Laboratory of Bacteria Genetics and Applied Biotechnology (LGBBA). These proteins were visualized in SDS-PAGE, quantified, and incorporated into an artificial diet to estimate their lethal concentrations (LC) through individual or combined bioassays. The results of individual toxicity revealed that IPD072Aa, PIP-47Aa, Cry1Ia10, Cry3Aa, and Cry8B were efficient in controlling A. grandis, with the latter being the most toxic. Regarding interaction assays, a high synergistic interaction was observed between Cry1Ia10 and Cry3Aa. All interactions involving Cry3Aa and PIP-47Aa, when combined with other proteins, showed a clear synergistic effect. Our findings highlighted that the tested proteins in combination, for the most part, increase toxicity against A. grandis neonate larvae, suggesting possible constructions for pyramiding cotton plants to the manage and the control boll weevils., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Barbosa Rodrigues et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ethanol abuse is a risk factor for the development of pneumonia caused by Streptococcus pneumoniae , a critical pathogen for public health. The aim of this article was to investigate the inflammatory mechanisms involved in pneumococcal pneumonia that may be associated with chronic ethanol exposure. Male C57BL6/J-Unib mice were exposed to 20% (v/v) ethanol for twelve weeks and intranasally infected with 5x10 4 CFU of S. pneumoniae. Twenty-four hours after infection, lungs, bronchoalveolar lavage and blood samples were obtained to assess the consequences of chronic ethanol exposure during infection. Alcohol-fed mice showed increased production of nitric oxide and CXCL1 in alveoli and plasma during pneumococcal pneumonia. Beside this, ethanol-treated mice exhibited a decrease in leukocyte infiltration into the alveoli and reduced frequency of severe lung inflammation, which was associated with an increase in bacterial load. Curiously, no changes were observed in survival after infection. Taken together, these results demonstrate that chronic ethanol exposure alters the inflammatory response during S. pneumoniae lung infection in mice with a reduction in the inflammatory infiltrate even in the presence of higher levels of the chemoattractant CXCL1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Martins, de Oliveira, Souza, Queiroz-Junior, Lobo, Teixeira, Malacco and Soriani.)

Macrophages are important effectors of inflammation resolution that contribute to the elimination of pathogens and apoptotic cells and restoration of homeostasis. Pre-clinical studies have evidenced the anti-inflammatory and pro-resolving actions of GILZ (glucocorticoid-induced leucine zipper). Here, we evaluated the role of GILZ on the migration of mononuclear cells under nonphlogistic conditions and Escherichia coli- evoked peritonitis. TAT-GILZ (a cell-permeable GILZ-fusion protein) injection into the pleural cavity of mice induced monocyte/macrophage influx alongside increased CCL2, IL-10 and TGF-β levels. TAT-GILZ-recruited macrophages showed a regulatory phenotype, exhibiting increased expression of CD206 and YM1. During the resolving phase of E. coli -induced peritonitis, marked by an increased recruitment of mononuclear cells, lower numbers of these cells and CCL2 levels were found in the peritoneal cavity of GILZ-deficient mice (GILZ -/- ) when compared to WT. In addition, GILZ -/- showed higher bacterial loads, lower apoptosis/efferocytosis counts and a lower number of macrophages with pro-resolving phenotypes. TAT-GILZ accelerated resolution of E. coli- evoked neutrophilic inflammation, which was associated with increased peritoneal numbers of monocytes/macrophages, enhanced apoptosis/efferocytosis counts and bacterial clearance through phagocytosis. Taken together, we provided evidence that GILZ modulates macrophage migration with a regulatory phenotype, inducing bacterial clearance and accelerating the resolution of peritonitis induced by E. coli .

Aspergillus fumigatus is a ubiquitous and saprophytic filamentous fungus and the main etiologic agent of aspergillosis. Infections caused by A. fumigatus culminate in a strong inflammatory response that can evolve into respiratory failure and may be lethal in immunocompromised individuals. In the last decades, it has been demonstrated that extracellular vesicles (EVs) elicit a notable biological response in immune cells. EVs carry a variety of biomolecules, therefore are considered potential antigen delivery vehicles. The role of EVs as a strategy for modulating an effective response against infections caused by A. fumigatus remains unexplored. Here we investigate the use of EVs derived from A. fumigatus as an immunization tool to induce a more robust immune response to A. fumigatus pulmonary infection. In order to investigate that, male C57BL/6 mice were immunized with two doses of EVs and infected with A. fumigatus . Pre-exposure of mice to EVs was able to induce the production of specific IgG serum for fungal antigens. Besides that, the immunization with EVs reduced the neutrophilic infiltrate into the alveoli, as well as the extravasation of total proteins and the production of proinflammatory mediators IL-1β, IL-6, and CXCL-1. In addition, immunization prevented extensive lung tissue damage and also improved phagocytosis and fungus clearance. Noteworthy, immunization with EVs, associated with subclinical doses of Amphotericin B (AmB) treatment, rescued 50% of mice infected with A. fumigatus from lethal fungal pneumonia. Therefore, the present study shows a new role for A. fumigatus EVs as host inflammatory response modulators, suggesting their use as immunizing agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Souza, Gurgel, Malacco, Martins, Queiroz-Junior, Teixeira and Soriani.)

The aim was to verify the association of individual factors and healthcare system characteristics with time to initiate treatment of lung cancer by the Brazilian National Health System, in Minas Gerais state. A retrospective cohort study, with patients who initiated treatment for lung cancer by the SUS, from 2008 to 2015. Sociodemographic and clinical characteristics of patients, besides organizational variables of the healthcare system were selected. The logistic regression model evaluated the association of selected explanatory variables with the outcome of initiating treatment within 60 days after diagnosis. Odds ratio (OR) and respective 95% confidence interval were used to measure the power of association. Most treatments for lung cancer in the state of Minas Gerais initiated within 60 days after diagnosis. However, being male and diagnosed as stage IV increased the likelihood of starting treatment within 60 days. On the other hand, the patient's age, radiation therapy as first treatment, and the place of residence decreased such chance. Time to initiate treatment is associated with individual characteristics and provision of services in macroregions, and the observed inequalities possibly raised from the better or worse access of the population to the services provided by SUS.

Pneumonia is a leading cause of morbidity and mortality. While inflammation is a host protective response that ensures bacterial clearance, a finely regulated response is necessary to prevent bystander tissue damage. Glucocorticoid (GC)-induced leucine zipper (GILZ) is a GC-induced protein with anti-inflammatory and proresolving bioactions, yet the therapeutical role of GILZ in infectious diseases remains unexplored. Herein, we investigate the role and effects of GILZ during acute lung injury (ALI) induced by LPS and Streptococcus pneumoniae infection. GILZ deficient mice (GILZ -/- ) presented more severe ALI, characterized by increased inflammation, decreased macrophage efferocytosis and pronounced lung damage. In contrast, pulmonary inflammation, and damage were attenuated in WT mice treated with TAT-GILZ fusion protein. During pneumococcal pneumonia, TAT-GILZ reduced neutrophilic inflammation and prevented the associated lung damage. There was also enhanced macrophage efferocytosis and bacterial clearance in TAT-GILZ-treated mice. Mechanistically, TAT-GILZ enhanced macrophage phagocytosis of pneumococcus, which was lower in GILZ -/- macrophages. Noteworthy, early treatment with TAT-GILZ rescued 30% of S. pneumoniae -infected mice from lethal pneumonia. Altogether, we present evidence that TAT-GILZ enhances host resilience and resistance to pneumococcal pneumonia by controlling pulmonary inflammation and bacterial loads leading to decreased lethality. Exploiting GILZ pathways holds promise for the treatment of severe respiratory infections.

Chronic ethanol consumption is a leading cause of mortality worldwide, with higher risks to develop pulmonary infections, including Aspergillus infections. Mechanisms underlying increased susceptibility to infections are poorly understood. Chronic ethanol consumption induced increased mortality rates, higher Aspergillus fumigatus burden and reduced neutrophil recruitment into the airways. Intravital microscopy showed decrease in leukocyte adhesion and rolling after ethanol consumption. Moreover, downregulated neutrophil activation and increased levels of serum CXCL1 in ethanol-fed mice induced internalization of CXCR2 receptor in circulating neutrophils. Bone marrow-derived neutrophils from ethanol-fed mice showed lower fungal clearance and defective reactive oxygen species production. Taken together, results showed that ethanol affects activation, recruitment, phagocytosis and killing functions of neutrophils, causing susceptibility to pulmonary A. fumigatus infection. This study establishes a new paradigm in innate immune response in chronic ethanol consumers., Competing Interests: NM, JS, FM, MR, JS, CT, AS, CQ, GG, LV, DS, VP, MT, FS No competing interests declared, (© 2020, Malacco et al.)

Introduction: Cutaneous leishmaniasis is caused by protozoa of the genus Leishmania and transmission occurs through the bite of sandflies. It is an infectious disease, which affects skin and mucosa. The aim was to quantify the macrophages M1 and M2 and the annexin A1 expression in the skin lesions of patients with cutaneous leishmaniasis., Methods: Skin biopsies from patients (n = 50) were analyzed and classified according to the lesion type as: exudative cellular reaction, exudative granulomatous reaction, exudative necrotic reaction, exudative necrotic-granulomatous reaction. Using the immunofluorescence technique, macrophages were identified by CD163 marker, differentiated by anti-MHCII and anti-CD206 antibodies, and annexin A1 expression was determined by arbitrary unit (a.u.) densitometry., Results: In M1 macrophages, a greater expression of this protein was observed in the exudative cellular reaction type lesions (136.3 ± 2.6 a.u., assuming mean and standard derivation) when compared to the expression in the lesions of exudative granulomatous reaction, exudative necrotic reaction and exudative necrotic-granulomatous reaction patients (108.0 ± 2.3, 121.6 ± 3.2 and 124.7 ± 2.4 a.u., respectively). Regarding M2 macrophages, it was observed that patients with exudative cellular reaction lesion also had a higher expression of this protein (128.8 ± 2.6 a.u.), when compared to the expression in the lesions of exudative granulomatous reaction, exudative necrotic reaction and exudative necrotic-granulomatous reaction patients (105.6 ± 2, 113.9 ± 2.8, 114.3 ± 2.1 a.u., respectively)., Conclusions: These data suggest that annexin A1 is assisting macrophages in the phagocytosis process of patients with exudative cellular reaction lesion type.

[This corrects the article DOI: 10.3389/fmicb.2019.02008.]., (Copyright © 2019 Souza, Baltazar, Carregal, Gouveia-Eufrasio, Oliveira, Dias, Rocha, Miranda, Malavazi, Santos, Frézard, Souza, Teixeira and Soriani.)

Extracellular vesicles (EVs) has been considered an alternative process for intercellular communication. EVs release by filamentous fungi and the role of vesicular secretion during fungus-host cells interaction remain unknown. Here, we identified the secretion of EVs from the pathogenic filamentous fungus, Aspergillus fumigatus . Analysis of the structure of EVs demonstrated that A. fumigatus produces round shaped bilayer structures ranging from 100 to 200 nm size, containing ergosterol and a myriad of proteins involved in REDOX, cell wall remodeling and metabolic functions of the fungus. We demonstrated that macrophages can phagocytose A. fumigatus EVs. Phagocytic cells, stimulated with EVs, increased fungal clearance after A. fumigatus conidia challenge. EVs were also able to induce the production of TNF-α and CCL2 by macrophages and a synergistic effect was observed in the production of these mediators when the cells were challenged with the conidia. In bone marrow-derived neutrophils (BMDN) treated with EVs, there was enhancement of the production of TNF-α and IL-1β in response to conidia. Together, our results demonstrate, for the first time, that A. fumigatus produces EVs containing a diverse set of proteins involved in fungal physiology and virulence. Moreover, EVs are biologically active and stimulate production of inflammatory mediators and fungal clearance.

Aspergillus fumigatus is a filamentous fungus which causes invasive pulmonary aspergillosis in immunocompromised individuals. In fungi, cell signaling and cell wall plasticity are crucial for maintaining physiologic processes. In this context, Msb2 is an important signaling mucin responsible for activation of a variety of mitogen-activated protein kinase (MAPK)-dependent signaling pathways that regulate cell growth in several organisms, such as the cell wall integrity (CWI) pathway. Here, we aimed to characterize the MSB2 homologue in A. fumigatus Our results showed that MsbA plays a role in the vegetative and reproductive development of the fungus, in stress adaptation, and in resistance to antifungal drugs by modulating the CWI pathway gene expression. Importantly, cell wall composition is also responsible for activation of diverse receptors of the host immune system, thus leading to a proper immune response. In a model of acute Aspergillus pulmonary infection, results demonstrate that the Δ msbA mutant strain induced less inflammation with diminished cell influx into the lungs and lower cytokine production, culminating in increased lethality rate. These results characterize for the first time the role of the signaling mucin MsbA in the pathogen A. fumigatus , as a core sensor for cell wall morphogenesis and an important regulator of virulence. IMPORTANCE Aspergillus fumigatus is an opportunistic fungus with great medical importance. During infection, Aspergillus grows, forming hyphae that colonize the lung tissue and invade and spread over the mammal host, resulting in high mortality rates. The knowledge of the mechanisms responsible for regulation of fungal growth and virulence comprises an important point to better understand fungal physiology and host-pathogen interactions. Msb2 is a mucin that acts as a sensor and an upstream regulator of the MAPK pathway responsible for fungal development in Candida albicans and Aspergillus nidulans Here, we show the role of the signaling mucin MsbA in the pathogen A. fumigatus , as a core sensor for cell wall morphogenesis, fungal growth, and virulence. Moreover, we show that cell wall composition, controlled by MsbA, is detrimental for fungal recognition and clearance by immune cells. Our findings are important for the understanding of how fungal sensors modulate cell physiology., (Copyright © 2019 Gurgel et al.)

The filter cake from sugar cane processing is rich in organic matter and nutrients, which favors the proliferation of microorganisms with potential to deconstruct plant biomass. From the metagenomic data of this material, we assembled a draft genome that was phylogenetically related to Thermomonospora curvata DSM 43183, which shows the functional and ecological importance of this bacterium in the filter cake. Thermomonospora is a gram-positive bacterium that produces cellulases in compost, and it can survive temperatures of 60 ºC. We identified a complete set of biomass depolymerizing enzymes in the draft genome of Thermomonospora sp. CIT 1, such as α-amylase, catalase-peroxidases, β-mannanase, and arabinanase, demonstrating the potential of this bacterium to deconstruct the components of starch, lignin, and hemicellulose. In addition, the draft genome of Thermomonospora sp. CIT 1 contains 18 genes that do not share identity with five other species of Thermomonospora, suggesting that this bacterium has different genetic characteristics than those present in genomes reported so far for this genus. These findings add a new dimension to the current understanding of the functional profile of this microorganism that inhabits agro-industrial waste, which may boost new gene discoveries and be of importance for application in the production of bioethanol.

Human activities on the Earth's surface change the landscape of natural ecosystems. Mining practices are one of the most severe human activities, drastically altering the chemical, physical and biological properties of the soil environment. Bacterial communities in soil play an important role in the maintenance of ecological relationships. This work shows bacterial diversity, metabolic repertoire and physiological behavior in five ecosystems samples with different levels of impact. These ecosystems belong to a historical area in Iron Quadrangle, Minas Gerais, Brazil, which suffered mining activities until its total depletion without recovery since today. The results revealed Proteobacteria as the most predominant phylum followed by Acidobacteria, Verrucomicrobia, Planctomycetes, and Bacteroidetes. Soils that have not undergone anthropological actions exhibit an increase ability to degrade carbon sources. The richest soil with the high diversity was found in ecosystems that have suffered anthropogenic action. Our study shows profile of diversity inferring metabolic profile, which may elucidate the mechanisms underlying changes in community structure in situ mining sites in Brazil. Our data comes from contributing to know the bacterial diversity, relationship between these bacteria and can explore strategies for natural bioremediation in mining areas or adjacent areas under regeneration process in iron mining areas., (Copyright © 2018 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Objectives: Reoperative procedure for the treatment of a failed mitral bioprosthesis is associated with considerable risk. In some cases, mortality is high and might contraindicate the benefit of the procedure. The minimally invasive valve-in-valve (ViV) transcatheter mitral valve implant offers an alternative less-invasive approach, reducing morbidity and mortality. The objective of this paper was to evaluate the mitral ViV approach using the Braile Inovare prosthesis., Methods: The transcatheter balloon-expandable Braile Inovare prosthesis was used in 12 cases. Procedures were performed in a hybrid operating room, under fluoroscopic and echocardiographic control. Through left minithoracotomy, the prostheses were implanted through the cardiac apex. Serial echocardiographic and clinical examinations were performed. Follow-up varied from 1 to 30 months., Results: A total of 12 transapical mitral ViV procedures were performed. Patients had a mean age of 61.6 ± 9.9 years and 92% were women. Mean logistic EuroSCORE was 20.1%. Successful valve implantation was possible in all cases. In one case, a right lateral thoracotomy was performed for the removal of an embolized prosthesis. There was no operative mortality. Thirty-day mortality was 8.3%. Ejection fraction was preserved after the implant (66.7%; 64.8%; P  = 0.3). The mitral gradient showed a significant reduction (11 mmHg; 6 mmHg; P  < 0.001). Residual mitral regurgitation was not present. There was no left ventricular outflow tract obstruction., Conclusions: The mitral ViV implant in a failed bioprosthesis is an effective procedure. This possibility might alter prosthesis selection in the future initial surgical prosthesis selection, favouring bioprostheses. Further large trials should explore its safety., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective:: To evaluate the prevalence of anemia, mean hemoglobin levels, and the main nutritional, demographic, and socioeconomic factors among Xavante children in Mato Grosso State, Brazil., Methods:: A survey was conducted with children under 10 years of age in two indigenous Xavante communities within the Pimentel Barbosa Indigenous Reserve. Hemoglobin concentration levels, anthropometric measurements, and socioeconomic/demographic data were collected by means of clinical measurements and structured interviews. The cut-off points recommended by the World Health Organization were used for anemia classification. Linear regression analyses with hemoglobin as the outcome and Poisson regression with robust variance and with the presence or absence of anemia as outcomes were performed (95%CI)., Results:: Lower mean hemoglobin values were observed in children under 2 years of age, without a significant difference between sexes. Anemia was observed among 50.8% of children overall, with the highest prevalence among children under 2 years of age (77.8%). Age of the child was inversely associated with the occurrence of anemia (adjusted PR = 0.60; 95%CI 0.38-0.95) and mean hemoglobin values increased significantly with age. Greater height-for-age z-score values reduced the probability of having anemia by 1.8 times (adjusted PR = 0.59; 95%CI 0.34-1.00). Presence of another child with anemia within the household increased the probability of the occurrence of anemia by 52.9% (adjusted PR = 1.89; 95%CI 1.16-3.09)., Conclusion:: Elevated levels of anemia among Xavante children reveal a disparity between this Indigenous population and the national Brazilian population. Results suggest that anemia is determined by complex and variable relationships between socioeconomic, sociodemographic, and biological factors.