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330 result(s) for "Silva-Santos, Bruno"
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Working in “NK Mode”: Natural Killer Group 2 Member D and Natural Cytotoxicity Receptors in Stress-Surveillance by γδ T Cells
Natural killer cell receptors (NKRs) are germline-encoded transmembrane proteins that regulate the activation and homeostasis of NK cells as well as other lymphocytes. For γδ T cells, NKRs play critical roles in discriminating stressed (transformed or infected) cells from their healthy counterparts, as proposed in the \"lymphoid stress-surveillance\" theory. Whereas the main physiologic role is seemingly fulfilled by natural killer group 2 member D, constitutively expressed by γδ T cells, enhancement of their therapeutic potential may rely on natural cytotoxicity receptors (NCRs), like NKp30 or NKp44, that can be induced selectively on human Vδ1 T cells. Here, we review the contributions of NCRs, NKG2D, and their multiple ligands, to γδ T cell biology in mouse and human.
Tribological Investigations on Tool Surfaces for Temperature-Supported Forming of Magnesium AZ31 Sheets
Aiming to decrease friction coefficient ( μ ) during the forming of magnesium alloy sheets, nine (9) tools with different hole geometries in their surface (flat, elliptical, and circular) were manufactured from steel Boehler W400 VMR (as known as DIN 1.2343). Tribological investigations were accomplished on a strip drawing machine at 288 °C without lubricants. When compared with a standard tool (surface flat), on average, tools with circular geometries in their surface showed the smallest friction coefficient, while tools with elliptical geometries shown higher. The friction coefficient also was confronted with the ratio between area occupied by holes in the surface of the tool and the total tool surface (i.e., factor f (%)), hole diameter (Ø), and the distance between circle centers (d(c,c)). Principal Component Analysis (PCA) complemented the experimental approach. In summary, both approaches (experimental and theoretical) indicated that the manufactured tool with circular geometries on its surface presented lower friction coefficient values on the forming processes of the magnesium AZ31 sheets.
DABCO-promoted photocatalytic C–H functionalization of aldehydes
Herein we present a direct application of DABCO, an inexpensive and broadly accessible organic base, as a hydrogen atom transfer (HAT) abstractor in a photocatalytic strategy for aldehyde C–H activation. The acyl radicals generated in this step were arylated with aryl bromides through a well stablished nickel cross-coupling methodology, leading to a variety of interesting aryl ketones in good yields. We also performed computational calculations to shine light in the HAT step energetics and determined an optimized geometry for the transition state, showing that the hydrogen atom transfer between aldehydes and DABCO is a mildly endergonic, yet sufficiently fast step. The same calculations were performed with quinuclidine, for comparison of both catalysts and the differences are discussed.
Tumor-associated neutrophils suppress pro-tumoral IL-17+ γδ T cells through induction of oxidative stress
Interleukin 17 (IL-17)-producing γδ T cells (γδ17 T cells) have been recently found to promote tumor growth and metastasis formation. How such γδ17 T-cell responses may be regulated in the tumor microenvironment remains, however, largely unknown. Here, we report that tumor-associated neutrophils can display an overt antitumor role by strongly suppressing γδ17 T cells. Tumor-associated neutrophils inhibited the proliferation of murine CD27- Vγ6+ γδ17 T cells via induction of oxidative stress, thereby preventing them from constituting the major source of pro-tumoral IL-17 in the tumor microenvironment. Mechanistically, we found that low expression of the antioxidant glutathione in CD27- γδ17 T cells renders them particularly susceptible to neutrophil-derived reactive oxygen species (ROS). Consistently, superoxide deficiency, or the administration of a glutathione precursor, rescued CD27- Vγ6+ γδ17 T-cell proliferation in vivo. Moreover, human Vδ1+ γδ T cells, which contain most γδ17 T cells found in cancer patients, also displayed low glutathione levels and were potently inhibited by ROS. This work thus identifies an unanticipated, immunosuppressive yet antitumoral, neutrophil/ROS/γδ17 T-cell axis in the tumor microenvironment.
Molecular Determinants of Target Cell Recognition by Human γδ T Cells
The unique capabilities of gamma-delta (γδ) T cells to recognize cells under stressed conditions, particularly infected or transformed cells, and killing them or regulating the immune response against them, paved the way to the development of promising therapeutic strategies for cancer and infectious diseases. From a mechanistic standpoint, numerous studies have unveiled a remarkable flexibility of γδ T cells in employing their T cell receptor and/or NK cell receptors for target cell recognition, even if the relevant ligands often remain uncertain. Here, we review the accumulated knowledge on the diverse mechanisms of target cell recognition by γδ T cells, focusing on human γδ T cells, to provide an integrated perspective of their therapeutic potential in cancer and infectious diseases.
Murine CD27⁽⁻⁾ Vγ6⁽⁺⁾ γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages
Cancer-associated inflammation mobilizes a variety of leukocyte populations that can inhibit or enhance tumor cell growth in situ. These subsets include γδ T cells, which can infiltrate tumors and typically provide large amounts of antitumor cytokines, such as IFN-γ. By contrast, we report here that in a well-established transplantable (ID8 cell line) model of peritoneal/ovarian cancer, γδ T cells promote tumor cell growth. γδ T cells accumulated in the peritoneal cavity in response to tumor challenge and could be visualized within solid tumor foci. Functional characterization of tumor-associated γδ T cells revealed preferential production of interleukin-17A (IL-17), rather than IFN-γ. Consistent with this finding, both T cell receptor (TCR)δ-deficient and IL-17–deficient mice displayed reduced ID8 tumor growth compared with wild-type animals. IL-17 production by γδ T cells in the tumor environment was essentially restricted to a highly proliferative CD27 ⁽⁻⁾ subset that expressed Vγ6 instead of the more common Vγ1 and Vγ4 TCR chains. The preferential expansion of IL-17–secreting CD27 ⁽⁻⁾ Vγ6 ⁽⁺⁾ γδ T cells associated with the selective mobilization of unconventional small peritoneal macrophages (SPMs) that, in comparison with large peritoneal macrophages, were enriched for IL-17 receptor A, and for protumor and proangiogenic molecular mediators, which were up-regulated by IL-17. Importantly, SPMs were uniquely and directly capable of promoting ovarian cancer cell proliferation. Collectively, this work identifies an IL-17–dependent lymphoid/myeloid cross-talk involving γδ T cells and SPMs that promotes tumor cell growth and thus counteracts cancer immunosurveillance.
Corn Oil Supplementation Enhances Locomotor Performance and Mitochondrial Function in Drosophila melanogaster
Polyunsaturated fatty acids are vital for brain health, supporting cognitive development and helping to prevent neurodegenerative diseases. Since the body cannot produce them, they must be obtained through food. This study aimed to assess the effects of corn oil on the behavior and biochemical parameters of Drosophila melanogaster. The flies were fed a diet supplemented with different concentrations of corn oil from the larval stage until the fifth day of adulthood. A diet containing corn oil (37.8 mg/mL of linoleic acid) reduced mortality under starvation conditions and enhanced locomotor performance (p < 0.01). Biochemical analyses revealed increased levels of glutathione (p < 0.001), citrate synthase activity (p < 0.05), and mitochondrial phosphorylation (p < 0.05), indicating a potential boost in energy metabolism. Conversely, a decrease in acetylcholinesterase activity (p < 0.05) was observed, suggesting cholinergic modulation. These results demonstrate that corn oil supplementation supports neural health in this animal model, opening pathways for further research into non-pharmacological treatments for neurodegenerative diseases such as Alzheimer’s disease.
Natural Cytotoxicity Receptors: Broader Expression Patterns and Functions in Innate and Adaptive Immune Cells
Natural cytotoxicity receptors (NCRs) have been classically defined as activating receptors delivering potent signals to Natural Killer (NK) cells in order to lyze harmful cells and to produce inflammatory cytokines. Indeed, the elicitation of NK cell effector functions after engagement of NCRs with their ligands on tumor or virus infected cells without the need for prior antigen recognition is one of the main mechanisms that allow a rapid clearance of target cells. The three known NCRs, NKp46, NKp44, and NKp30, comprise a family of germ-line encoded Ig-like trans-membrane (TM) receptors. Until recently, NCRs were thought to be NK cell specific surface molecules, thus making it possible to easily distinguish NK cells from phenotypically similar cell types. Moreover, it has also been found that the surface expression of NKp46 is conserved on NK cells across mammalian species. This discovery allowed for the use of NKp46 as a reliable marker to identify NK cells in different animal models, a comparison that was not possible before due to the lack of a common and comprehensive receptor repertoire between different species. However, several studies over the recent few years indicated that NCR expression is not exclusively confined to NK cells, but is also present on populations of T as well as of NK-like lymphocytes. These insights raised the hypothesis that the induced expression of NCRs on certain T cell subsets is governed by defined mechanisms involving the engagement of the T cell receptor (TCR) and the action of pro-inflammatory cytokines. In turn, the acquisition of NCRs by T cell subsets is also associated with a functional independence of these Ig-like TM receptors from TCR signaling. Here, we review these novel findings with respect to NCR-mediated functions of NK cells and we also discuss the functional consequences of NCR expression on non-NK cells, with a particular focus on the T cell compartment.
Adherence to standard precautions by nursing professionals in a public university hospital: a cross-sectional study
Introduction: The aim of this study was to analyze the adherence to standard precautions by nursing professionals in a public university hospital, and to identify associated factors. Methodology: This was a cross-sectional study with the nursing staff of a public university hospital. The participants provided sociodemographic and immunization data, training data on standard precautions and occupational accident history, and responded to the questionnaire on adherence to standard precautions (QASP). Descriptive data analysis and Pearson’s Chi-square test (χ²) were performed, followed by Fisher’s exact test to verify the association between the adherence to standard precautions (total score ≥ 76 points) and the sample characterization variables. Additionally, binary logistic regression indicated the odds ratio (OR) of the sample characterization variables for adherence to standard precautions. A p value ≤ 0.05 was considered statistically significant. Results: The average score for adherence to standard precautions, through QASP, by nursing professionals evaluated was 70.5 points. Association between the adherence to standard precautions and the professionals’ sample characterization variables was not identified. However, it was observed that experienced professionals (≥15 years of experience in the institution) were more likely to adhere to standard precautions (OR 0.062; IC95% [0.006-0.663]; p = 0.021). Conclusions: In general, the adherence to standard precautions by nursing professionals working in health service in this study can be considered inadequate, highlighting major weaknesses in hand hygiene practices, use of personal protective equipment (PPE), recapping of used needles, and conduct after suffering occupational accidents. Experienced professionals were more likely to adhere to standard precautions.
Therapeutic avenues for γδ T cells in cancer
γδ T cells are regarded as promising effector lymphocytes for next-generation cancer immunotherapies. In spite of being relatively rare in human peripheral blood, γδ T cells are more abundant in epithelial tissues where many tumors develop, and have been shown to actively participate in anticancer immunity as cytotoxic cells or as “type 1” immune orchestrators. A major asset of γδ T cells for tackling advanced cancers is their independence from antigen presentation via the major histocompatibility complex, which clearly sets them apart from conventional αβ T cells. Here we discuss the main therapeutic strategies based on human γδ T cells. These include antibody-based bispecific engagers and adoptive cell therapies, either focused on the Vδ1+ or Vδ2+ γδ T-cell subsets, which can be expanded selectively and differentiated or engineered to maximize their antitumor functions. We review the preclinical data that supports each of the therapeutic strategies under development; and summarize the clinical trials being pursued towards establishing γδ T cell-based treatments for solid and hematological malignancies.