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Abstract Aspergillus fumigatus represents a public health problem due to the high mortality rate in immunosuppressed patients and the emergence of antifungal-resistant isolates. Protein acetylation is a crucial post-translational modification that controls gene expression and biological processes. The strategic manipulation of enzymes involved in protein acetylation has emerged as a promising therapeutic approach for addressing fungal infections. Sirtuins, NAD+-dependent lysine deacetylases, regulate protein acetylation and gene expression in eukaryotes. However, their role in the human pathogenic fungus A. fumigatus remains unclear. This study constructs six single knockout strains of A. fumigatus and a strain lacking all predicted sirtuins (SIRTKO). The mutant strains are viable under laboratory conditions, indicating that sirtuins are not essential genes. Phenotypic assays suggest sirtuins’ involvement in cell wall integrity, secondary metabolite production, thermotolerance, and virulence. Deletion of sirE attenuates virulence in murine and Galleria mellonella infection models. The absence of SirE alters the acetylation status of proteins, including histones and non-histones, and triggers significant changes in the expression of genes associated with secondary metabolism, cell wall biosynthesis, and virulence factors. These findings encourage testing sirtuin inhibitors as potential therapeutic strategies to combat A. fumigatus infections or in combination therapy with available antifungals.

IntroductionBreast cancer is a significant public health problem around the world, ranking first in deaths due to cancer in females. The therapy to fight breast cancer involves different methods, including conventional chemotherapy. However, the acquired resistance that tumors develop during the treatment is still a central cause of cancer-associated deaths. One mechanism that induces drug resistance is cell communication via extracellular vesicles (EVs), which can carry efflux transporters and miRNA that increase sensitive cells’ survivability to chemotherapy.MethodsOur study investigates the transcription changes modulated by EVs from tamoxifen- and doxorubicin-resistant breast cancer cells in sensitive cells and how these changes may induce acquired drug resistance, inhibit apoptosis, and increase survivability in the sensitive cells. Additionally, we exposed human macrophages to resistant EVs to understand the influence of EVs on immune responses.ResultsOur results suggest that the acquired drug resistance is associated with the ability of resistant EVs to upregulate several transporter classes, which are directly related to the increase of cell viability and survival of sensitive cells exposed to EVs before a low-dose drug treatment. In addition, we show evidence that resistant EVs may downregulate immune system factors to evade detection and block cell death by apoptosis in sensitive breast cancer cells. Our data also reveals that human macrophages in contact with resistant EVs trigger a pro-inflammatory cytokine secretion profile, an effect that may be helpful for future immunotherapy studies.DiscussionThese findings are the first transcriptome-wide analysis of cells exposed to resistant EVs, supporting that resistant EVs are associated with the acquired drug resistance process during chemotherapy by modulating different aspects of sensitive cancer cells that coffer the chemoresistance.

Galectin-3 (Gal-3) is the most studied member of the animal galectin family, which comprises β-galactoside-binding lectins and participates in several cellular events. Its expression in cells involved in innate and adaptive immunity is related to anti- and proinflammatory functions, signaling an important role in inflammatory, infectious, and tumorigenesis processes. Mice deficient in Gal-3 exhibit important phenotypes, but it is unclear whether these phenotypes reflect an impairment of the functions of this protein. Gal-3 plays an important role in modulating the immune response to different pathogenic microorganisms. However, the role of Gal-3 in immunity to infection is still poorly understood. Therefore, we investigated the effects of Gal-3 deletion on the expression of genes involved in the innate immune response in the lungs, spleens, and brains of Gal-3 KO mice. Gene profiling expression analysis suggested that Gal-3 deletion resulted in differentially modulated expression of the genes encoding beta-glucan, mannose and chitin-responsive pattern recognition receptors, signal transduction, inflammation, and phagocytosis. Our data thus suggest the importance of Gal-3 expression in the host innate immune system.

Fungal extracellular vesicles (EVs) mediate intra- and interspecies communication and are critical in host–fungus interaction, modulating inflammation and immune responses. In this study, we evaluated the in vitro pro- and anti-inflammatory properties of Aspergillus fumigatus EVs over innate leukocytes. A. fumigatus EVs induced a partial proinflammatory response by macrophages, characterized by increased tumor necrosis factor-alpha production, and increased gene expression of induced nitric oxide synthase and adhesion molecules. EVs induce neither NETosis in human neutrophils nor cytokine secretion by peripheral mononuclear cells. However, prior inoculation of A. fumigatus EVs in Galleria mellonella larvae resulted in increased survival after the fungal challenge. Taken together, these findings show that A. fumigatus EVs play a role in protection against fungal infection, although they induce a partial pro-inflammatory response.

Fungal infections are a serious global concern because of their ability to spread and colonize host tissues in immunocompromised individuals. Such infections have been frequently reported worldwide and are currently gaining clinical research relevance owing to their resistant character, representing a bottleneck in treating affected people. Resistant fungi are an emergent public health threat. The upsurge of such pathogens has led to new research toward unraveling the destructive potential evoked by these species. Some fungi—grouped into Candida, Aspergillus, and Cryptococcus—are causative agents of severe and systemic infections. They are associated with high mortality rates and have recently been described as sources of coinfection in COVID-hospitalized patients. Despite the efforts to elucidate the challenges of colonization, dissemination, and infection severity, the immunopathogenesis of fungal diseases remains a pivotal characteristic in fungal burden elimination. The struggle between the host immune system and the physiological strategies of the fungi to maintain cellular viability is complex. In this brief review, we highlight the relevance of drug resistance phenotypes in fungi of clinical significance, taking into consideration their physiopathology and how the scientific community could orchestrate their efforts to avoid fungal infection dissemination and deaths.

Introduction: Abdominoplasty, which aims to improve body contour, has been upgraded by its association with limited dissection of the cutaneous flap and quilting sutures in the same surgery to avoid the formation of postabdominoplasty seroma, a complication that troubles both patient and surgeon. Therefore, this study aimed to assess whether the use of quilting sutures is associated with a lower incidence of seroma after abdominoplasty than the use of drains. Methods: A systematic review of the literature and a meta-analysis were performed of the Science Direct, Scielo, Pubmed, Lilacs, CINAHL, and Scopus databases. The data analysis was performed using the Stata 12.0 program and the I2 statistic proposed by Higgins, with a 95% confidence interval for the relative risk for seroma by intervention type (drain, quilting sutures, drain with quilting sutures). The study was registered in PROSPERO (CRD42019120399). Results: Five studies met the inclusion criteria and were included in the meta-analysis. Quilting sutures showed a protective effect (versus use of drain with quilting sutures) in the prevention of seroma (relative risk, 0.13; 95% confidence interval, 0.02-0.66). Conclusion: These findings suggest that the use of quilting sutures instead of drains in abdominoplasty can effectively prevent seroma formation.

Inhalation of Cryptococcus gattii yeasts (causing cryptococcosis) triggers an anti-cryptococcal immune response initiated by macrophages, neutrophils or dendritic cells, and the iNOS expressed by various cells may regulate the function and differentiation of innate and adaptive immune cells. Here, we evaluated the effect of progression of C. gattii infection on the host innate immune response. C. gattii infection in BALB/c mice spreads to several organs by 21 d post infection. The numbers of neutrophils and lymphocytes in the peripheral blood of C. gattii –infected mice were remarkably altered on that day. The frequency of CD11b + cells and cell concentrations of CD4 + and CD8 + T cells was significantly altered in the pulmonary tissue of infected mice. We found a higher frequency of CD11b + /iNOS + cells in the lungs of infected mice, accompanied by an increase in frequency of CD11b + /Arginase-1 + cells over time. Moreover, the iNOS/Arginase-1 expression ratio in CD11b + cells reached its lowest value at 21 d post infection. In addition, the cytokine micro-environment in infected lungs did not show a pro-inflammatory profile. Surprisingly, iNOS knock-out prolonged the survival of infected mice, while their pulmonary fungal burden was higher than that of infected WT mice. Thus, C. gattii infection alters the immune response in the pulmonary tissue, and iNOS expression may play a key role in infection progression.

The protein Galectin-3 modulates host immunity and plays roles during infections. Here, Almeida et al. show that this protein contributes to host defence against infection with the fungal pathogen Cryptococcus neoformans by inhibiting fungal growth and inducing lysis of fungal extracellular vesicles.

Cryptococcus neoformans, the causative agent of cryptococcosis, is the primary fungal pathogen that affects the immunocompromised individuals. Galectin-3 (Gal-3) is an animal lectin involved in both innate and adaptive immune responses. The present study aimed to evaluate the influence of Gal-3 on the C. neoformans infection. We performed histopathological and gene profile analysis of the innate antifungal immunity markers in the lungs, spleen, and brain of the wild-type (WT) and Gal-3 knockout (KO) mice during cryptococcosis. These findings suggest that Gal-3 absence does not cause significant histopathological alterations in the analyzed tissues. The expression profile of the genes related to innate antifungal immunity showed that the presence of cryptococcosis in the WT and Gal-3 KO animals, compared to their respective controls, promoted the upregulation of the pattern recognition receptor (PRR) responsive to mannose/chitin (mrc1) and a gene involved in inflammation (ccr5), as well as the downregulation of the genes related to signal transduction (card9, fos, ikbkb, jun) and PRRs (cd209a, colec12, nptx1). The absence of Gal-3, in fungal infection, a positively modulated gene involved in phagocytosis (sftpd) and negatively genes involved in signal transduction (syk and myd88), proinflammatory cytokines il-1β and il-12b and cd209a receptor. Therefore, our results suggest that Gal-3 may play an essential role in the development of antifungal immune responses against cryptococcosis.

ABSTRACT The thermodimorphic pathogenic fungi Paracoccidioides brasiliensis and Paracoccidioides lutzii are the etiologic causes of paracoccidioidomycosis (PCM), the most prevalent systemic mycosis in Latin America. Galectin-3 (Gal-3), an animal β-galactoside-binding protein, modulates important roles during microbial infections, such as triggering a Th2-polarized immune response in PCM. Herein, we demonstrate that Gal-3 also plays other important roles in P. brasiliensis infection. We verified that Gal-3 levels are upregulated in human and mice infections and established that Gal-3 inhibited P. brasiliensis growth by inhibiting budding. Furthermore, Gal-3 affected disruption and internalization of extracellular vesicles (EVs) from P. brasiliensis by macrophages. Our results suggest important protective roles for Gal-3 in P. brasiliensis infection, indicating that increased Gal-3 production during P. brasiliensis infection may affect fungal growth and EV stability, thus promoting beneficial effects that could influence the course of PCM. The finding that Gal-3 has effects against P. brasiliensis together with previously reported effects against Cryptococcus neoformans suggests that molecule has a general antifungal role in innate defenses against fungal pathogens. IMPORTANCE Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America. Although the immune mechanisms to control PCM are still not fully understood, several events of the host innate and adaptive immunity are crucial to determine the progress of the infection. Mammalian β-galactoside-binding protein galectin-3 (Gal-3) plays significant roles during microbial infections and has been studied for its immunomodulatory roles, but it can also have direct antimicrobial effects. We asked whether this protein plays a role in Paracoccidioides brasiliensis. We report herein that Gal-3 indeed has direct effects on the fungal pathogen, inhibiting fungal growth and reducing extracellular vesicle stability. Our results suggest a direct role for Gal-3 in P. brasiliensis infection, with beneficial effects for the mammalian host.

This article presents the reality of the “Small Claim ́s Courts” of Rio de Janeiro with regarding the need to keep the plea of confidential clause in answer to the complaint, in Courts which is applied the electronic system, until the start of the hearing and trial. The foundation of such need is based on the constitutional principle of equality, considering also the existence of procedures that are still physical, in that the plaintiff only has views of the arguments of the defendant in the aforementioned procedural step in accordance with the Law n. 9.099/1995.

The release of biomolecules critically affects all pathogens and their establishment of diseases. For the export of several biomolecules in diverse species, the use of extracellular vesicles (EVs) is considered to represent an alternative transport mechanism, but no study to date has investigated EVs from dermatophytes. Here, we describe biologically active EVs from the dermatophyte Trichophyton interdigitale, a causative agent of mycoses worldwide. EV preparations from T. interdigitale were examined using nanoparticle-tracking analysis, which revealed vesicular structures 20–380 nm in diameter. These vesicles induced the production of proinflammatory mediators by bone marrow-derived macrophages (BMDMs) and keratinocytes in a dose-dependent manner, and an addition of the EVs to BMDMs also stimulated the transcription of the M1-polarization marker iNOS (inducible nitric oxide synthase) and diminished the expression of the M2 markers arginase-1 and Ym-1. The observed M1 macrophages' polarization triggered by EVs was abolished in cells obtained from knockout Toll-like receptor-2 mice. Also, the EVs-induced productions of pro-inflammatory mediators were blocked too. Furthermore, the EVs from T. interdigitale enhanced the fungicidal activity of BMDMs. These results suggest that EVs from T. interdigitale can modulate the innate immune response of the host and influence the interaction between T. interdigitale and host immune cells. Our findings thus open new areas of investigation into the host-parasite relationship in dermatophytosis.

A intensificação da agricultura e os monocultivos no Cerrado brasileiro têm demonstrado perdas significativas ao meio ambiente, despertando a preocupação da sociedade na busca de uma agricultura sustentável. Voltando-se para o discurso e a prática dos princípios agroecológicos, este trabalho tem o objetivo de espacializar, analisar e definir, por meio de Sistema de Informação Geográfica (SIG), áreas agrícolas que compõe o terço superior do córrego Bebedouro (Frutal/MG) usando como critério de seleção uma Escala de Necessidade de Intervenção Agroecológica (ENIA). Associando os aspectos identificados in loco ao processamento de dados por meio do software QGIS, que permitiu compreender a dinâmica de ocupação da área em estudo, foi possível gerar o mapa de uso e ocupação do solo. A escala ENIA, elaborada neste estudo e usada como uma ferramenta de avaliação e diagnóstico foi sobreposta a este mapa por meio do somatório de indicadores, classificando quais as áreas têm maiores necessidade de intervenção agroecológica, levando em consideração, sobretudo, o tipo de cobertura, o manejo e a conservação do solo, e o uso dos insumos. Os resultados da aplicação da escala ENIA mostraram que 43,1% das áreas necessitam de média intervenção agroecológica, 34,9% necessitam de alta intervenção agroecológica e 2,5% necessitam de baixa intervenção agroecológica. A vegetação nativa presente entre fragmentos florestais e áreas de APP correspondente a 18,6% da unidade territorial do terço superior da bacia, apresentando-se deficitária considerando suas funções ambientais e sua importância para a manutenção da biodiversidade, cobertura do solo e recarga hídrica.

PURPOSE: To investigate whether there are differences between the phagocytic function of the remaining lower spleen pole after subtotal splenectomy and autogenous splenic implants. METHODS: Thirty-six male Wistar rats, weighting 364 ± 60g were used. They were subjected to subtotal splenectomy preserving the lower spleen pole and to autogenous splenic implant in the greater omentum. Its viability was assessed microscopically. Phagocytic function was assessed by splenic uptake of the radioisotope-labeled colloid and by macrophages counting. RESULTS: The viability of the autogenous splenic implant and of the lower spleen pole was found in 33 animals, with no difference between them. The weight of the implants was higher than the lower pole of animals from groups G1, G7, G30, G60 and G120. The implants phagocytic function by radioisotope uptake was higher than the lower pole in G7 and G120 groups and it did not differ from the other groups. The number of macrophages was higher in G1, G60, G90 and G120 and did not differ from the other groups. CONCLUSION: Until the 16th week, the phagocytic function was more pronounced in autogenous splenic implants when compared with the lower spleen pole, but it became similar thereafter.

Fungal diseases have been underestimated worldwide but constitute a substantial threat to several plant and animal species as well as to public health. The increase in the global population has entailed an increase in the demand for agriculture in recent decades. Accordingly, there has been worldwide pressure to find means to improve the quality and productivity of agricultural crops. Antifungal agents have been widely used as an alternative for managing fungal diseases affecting several crops. However, the unregulated use of antifungals can jeopardize public health. Application of fungicides in agriculture should be under strict regulation to ensure the toxicological safety of commercialized foods. This review discusses the use of antifungals in agriculture worldwide, the need to develop new antifungals, and improvement of regulations regarding antifungal use.

To describe patients and multidisciplinary teams demands for pharmaceutical care in a basic health unit. This is a descriptive and cross-sectional study which was conducted in a health unit of São Paulo, from January 2011 to July 2012. All referral patients to pharmaceutical care were accounted. Referrals were classified according to the source, the main rational and patients demand. A total of 1,164 patients were referred to pharmaceutical care, 88% of which were referred by pharmacy technicians. The most frequent reason (25.9%) was the request to participate in health education groups and rational use of medicines. Among them, 79.9% of patients were referred for noncompliance to treatment of chronic diseases. Health professionals demand the pharmacist assistance beyond the access to medication issues such as drug conciliation, non-adherence issues.

The aim of the present study was to quantify drug interactions in prescriptions for women undergoing supportive therapy in an oncology setting at a women’s hospital in Brazil and compare the information provided by different databases regarding these drug interactions. A convenience sample was selected of prescriptions for patients diagnosed with breast or gynecological tumors hospitalized in the clinical oncology and surgery wards from April to June 2009. DRUGDEX/Micromedex (Thomson Micromedex) was the main database used for the identification of drug interactions and was compared with two other databases: Drugs.com and Lexicomp. The search was performed by inputting all drug combinations found in the prescriptions in Micromedex and Drugs.com. All interactions identified and classified by Micromedex and/or Drugs.com as of major severity were then checked in Lexicomp. A total of 152 interactions were identified by Micromedex (61 major, 69 moderate and 22 minor). In Drugs.com, 614 interactions were identified (85 major, 464 moderate and 65 minor). Forty-four were classified as major drug interactions in at least one of the databases: 30 in Micromedex, 26 in Drugs. com and 14 in Lexicomp. The present findings reveal discrepancies among the three databases analyzed. Thus, standardization should be proposed. Moreover, both the pharmacist and multidisciplinary team should perform a critical analysis of prescriptions to promote safe practices in the use of medications and minimize potential complications caused by drug interactions.

ABSTRACT OBJECTIVE: To determine whether the use of autograft associated with platelet-rich plasma (PRP) increases bone healing in patients undergoing lumbar fusion. METHOD: This was a prospective, descriptive, and comparative study, which included 40 patients undergoing lumbar fusion, who were divided into two groups: group I, autograft only, and group II, autograft associated with PRP. After surgery, patients were followed-up on the first, third, and sixth month. The Molinari radiographic classification and Glassman tomographic classification were used as criteria to analyze the bone consolidation. RESULT: Comparing the group I with group II, according to the criteria of Molinari, bilateral fusion was observed in 27.5% of the patients in group I in the first month after surgery. In group II, the rate of bilateral fusion was 25.0% and 20% in the third and sixth months, respectively. The results of computed tomography scans performed at six months after surgery indicated, according to the criteria of Glassman, a rate of bilateral solid fusion of 15.0% and 10.0% in groups I and II, respectively. CONCLUSION: The use of PRP showed no significant difference in bone healing in cases of lumbar arthrodesis.

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