Two-layered immune escape in AML is overcome by Fcγ receptor activation and inhibition of PGE2 signaling in NK cells.

Loss of anticancer NK cell function in AML patients is associated with fatal disease progression and remains poorly understood. Here, we demonstrate that AML-blasts isolated from patients rapidly inhibit NK cell function and escape NK cell-mediated killing. Transcriptome analysis of NK cells exposed to AML-blasts revealed increased CREM expression and transcriptional activity, indicating enhanced cAMP signalling, confirmed by uniform production of the cAMP-inducing prostanoid PGE2 by all AML-blast isolates from patients.

Cognitive Profile Discrepancies among Typical University Students and Those with Dyslexia and Mixed-Type Learning Disorder.

Background: Previous studies have identified areas of cognitive weakness in children diagnosed with Specific Learning Disorder (SLD), in the areas of working memory and processing speed in particular. In adulthood, this literature is still scant, and no studies have compared the cognitive profile of university students with dyslexia (DD) with that of students with Mixed-type SLD.

Method: Thus, in this study, the WAIS-IV was used to examine the cognitive functioning of three groups of university students: students with DD, with Mixed-type SLD, and typical students.

Hepatoprotective Effects of Four Brazilian Savanna Species on Acetaminophen-Induced Hepatotoxicity in HepG2 Cells.

We investigated four Cerrado plant species, i.e., (Miers) A.

Evaluation of Functional and Joint Health and Associated Factors in Adults With Hemophilia From a Developing Country With Government-Backed Efforts to Improve Hemophilia Care.

Introduction Hemophilic arthropathy affects people with hemophilia (PwH) and causes joint dysfunction and disability. Brazil has a unique situation and implemented policies to improve health care for PwH. The aim of this study was to evaluate the Functional Independence Score in Hemophilia (FISH), Hemophilia Joint Health Score (HJHS), and associated factors among adult PwH attending a Hemophilia Comprehensive Care Center in Brazil.

Hydroethanolic Extract of Morus nigra L. Leaves: A Dual PPAR-α/γ Agonist with Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated RAW 264.7.

Inhibition of systemic inflammation has been a beneficial strategy in treating several non-communicable diseases, which represent one of the major causes of mortality in the world. The Peroxisome Proliferator-Activated Receptors (PPAR) are interesting pharmacological targets, since they can act both through the metabolic and anti-inflammatory pathways. L.

effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity.

Many medicinal plants species from European -such as - as well as Latin American traditions -such as , and are shortlisted by the Brazilian National Health System for future clinical use. However, they lack many data on their action upon some key ADME targets. In this study, we assess non-toxic concentrations (up to100 μg/ml) of their infusions for ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR).

A Cysteine Residue within the Kinase Domain of Zap70 Regulates Lck Activity and Proximal TCR Signaling.

Alterations in both the expression and function of the non-receptor tyrosine kinase Zap70 are associated with numerous human diseases including immunodeficiency, autoimmunity, and leukemia. Zap70 propagates the TCR signal by phosphorylating two important adaptor molecules, LAT and SLP76, which orchestrate the assembly of the signaling complex, leading to the activation of PLCγ1 and further downstream pathways. These events are crucial to drive T-cell development and T-cell activation.

T cell-specific constitutive active SHP2 enhances T cell memory formation and reduces T cell activation.

Upon antigen recognition by the T cell receptor (TCR), a complex signaling network orchestrated by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) regulates the transmission of the extracellular signal to the nucleus. The role of the PTPs Src-homology 2 (SH2) domain-containing phosphatase 1 (SHP1, ) and Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2, ) have been studied in various cell types including T cells. Whereas SHP1 acts as an essential negative regulator of the proximal steps in T cell signalling, the role of SHP2 in T cell activation is still a matter of debate.

Type of PaperY192 within the SH2 Domain of Lck Regulates TCR Signaling Downstream of PLC-γ1 and Thymic Selection.

Signaling via the TCR, which is initiated by the Src-family tyrosine kinase Lck, is crucial for the determination of cell fates in the thymus. Because of its pivotal role, ablation of Lck results in a profound block of T-cell development. Here, we show that, in addition to its well-known function in the initiation of TCR signaling, Lck also acts at a more downstream level.

Effects of medicinal plants and natural compounds in models of prostate cancer related to sex steroids: A systematic review.

Prostate cancer remains a health problem for men. Targeting androgen (AR) and estrogen (ER) receptors improves the outcomes of the disease, and many medicinal plants exert their effects by modulating these pathways. Therefore, a systematic review was conducted to identify medicinal plants and their natural compounds that may modulate the AR and/or ER pathways in cell and animal models.

Antiproliferative effects of metformin in cellular models of pheochromocytoma.

Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from adrenal medulla chromaffin cells. Malignancy and recurrence are rare but demand effective treatment. Metformin exerts antiproliferative effects in several cancer cell lines.

Judicialization of coagulation factors in severe hemophilia: compliance with the care protocol and associated factors Judicialization and severe hemophilia.

Objective: This study aimed to analyze the compliance with the assistance protocol and factors associated with the judicialization of coagulation factors in severe hemophilia patients.

Methods: A retrospective, cross-sectional study was conducted from June 2015 to May 2016 in adults with severe hemophilia in the Federal District, Brazil using data from their medical records and the Hemovida Web Coagulopathies System.

Results: One-hundred and three patients from Federal District, the capital of Brazil, were included in the study.

Pitavastatin Is a Highly Potent Inhibitor of T-Cell Proliferation.

Repositioning of approved drugs is an alternative time- and cost-saving strategy to classical drug development. Statins are 3-hydroxy-3-methylglutaryl-CoA (HMG CoA) reductase inhibitors that are usually used as cholesterol-lowering medication, and they also exhibit anti-inflammatory effects. In the present study, we observed that the addition of Pitavastatin at nanomolar concentrations inhibits the proliferation of CD3/CD28 antibody-stimulated human T cells of healthy donors in a dose-dependent fashion.

The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37.

Lymphocyte-specific protein tyrosine kinase (Lck) is a pivotal tyrosine kinase involved in T cell receptor (TCR) signaling. Because of its importance, the activity of Lck is regulated at different levels including phosphorylation of tyrosine residues, protein-protein interactions, and localization. It has been proposed that the co-chaperone Cdc37, which assists the chaperone heat shock protein 90 (Hsp90) in the folding of client proteins, is also involved in the regulation of the activity/stability of Lck.

Factors Associated with Compliance with the Treatment Protocol and Mortality in Adults with Hemophilia.

Objective: Hemophilia is associated with a high prevalence of disabilities and mortality. This finding can be influenced by patient compliance with the treatment protocol. This study aims to identify compliance with a treatment protocol in adult patients with hemophilia and to evaluate the factors associated with and the impact on mortality of noncompliance with a hemophilia treatment protocol.

Tyrosine 192 within the SH2 domain of the Src-protein tyrosine kinase p56 regulates T-cell activation independently of Lck/CD45 interactions.

Background: Upon engagement of the T-cell receptor (TCR), the Src-family protein tyrosine kinase p56Lck phosphorylates components of the TCR (e.g. the TCRζ chains), thereby initiating T-cell activation.

Regulatory myeloid cells paralyze T cells through cell-cell transfer of the metabolite methylglyoxal.

Regulatory myeloid immune cells, such as myeloid-derived suppressor cells (MDSCs), populate inflamed or cancerous tissue and block immune cell effector functions. The lack of mechanistic insight into MDSC suppressive activity and a marker for their identification has hampered attempts to overcome T cell inhibition and unleash anti-cancer immunity. Here, we report that human MDSCs were characterized by strongly reduced metabolism and conferred this compromised metabolic state to CD8 T cells, thereby paralyzing their effector functions.

French Red Cross Volunteer Rescue Workers: Psychological Characteristics and Healthcare Support After the January 2015 Terrorist Attacks in Paris.

Few studies have explored the psychological consequences of terrorism on volunteer rescuers. We examined the psychological characteristics of volunteer rescuers after the January 2015 terrorist attacks in France. We analyzed the results of the IMPACTS study regarding the somatic, psychological, and social characteristics of the French Red Cross volunteer rescuers who intervened during these terrorist attacks.

Beyond TCR Signaling: Emerging Functions of Lck in Cancer and Immunotherapy.

In recent years, the lymphocyte-specific protein tyrosine kinase (Lck) has emerged as one of the key molecules regulating T-cell functions. Studies using Lck knock-out mice or Lck-deficient T-cell lines have shown that Lck regulates the initiation of TCR signaling, T-cell development, and T-cell homeostasis. Because of the crucial role of Lck in T-cell responses, strategies have been employed to redirect Lck activity to improve the efficacy of chimeric antigen receptors (CARs) and to potentiate T-cell responses in cancer immunotherapy.

[The health determinants in young children: testing a new surveillance system in Italy].

In recent years, the scientific community has stressed the need to invest in the first 1,000 days of life - the time spanning between conception and the 2nd birthday - because it is during this period that the foundations of health are laid and whose effects will be present throughout the life and may influence the next generation. Taking this into account, in 2013 the National Centre for Disease Prevention and Control (CCM) of the Italian Ministry of Health promoted and financed a project to test a surveillance system of the main determinants of health concerning the child between the conception period and the 2nd years of life which are included in the National Programme "GenitoriPiù": folic acid before and during pregnancy, abstention from tobacco and alcohol during pregnancy and lactation, breastfeeding, infant sleep position, vaccination attitude, and early reading. The Project, started in January 2014 and ended in August 2016, has piloted the design, testing, and evaluation of the surveillance system with the view to national extension and the repeatability over time.

Lactate modulates CD4 T-cell polarization and induces an immunosuppressive environment, which sustains prostate carcinoma progression via TLR8/miR21 axis.

Leukocyte infiltration plays an active role in controlling tumor development. In the early stages of carcinogenesis, T cells counteract tumor growth. However, in advanced stages, cancer cells and infiltrating stromal components interfere with the immune control and instruct immune cells to support, rather than counteract, tumor malignancy, via cell-cell contact or soluble mediators.

NF-κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling.

NF-κB inducing kinase (NIK) is the key protein of the non-canonical NF-κB pathway and is important for the development of lymph nodes and other secondary immune organs. We elucidated the specific role of NIK in T cells using T-cell specific NIK-deficient (NIK) mice. Despite showing normal development of lymphoid organs, NIK mice were resistant to induction of CNS autoimmunity.