Detection of t(9;22), and consequent fusion, is still a marker of worse prognosis for acute lymphoblastic leukemia (ALL), with resistance to tyrosine-kinase inhibitor therapy being a major obstacle in the clinical practice for this subset of patients. In this study, we investigated the effectiveness of targeting poly-ADP-ribose polymerase (PARP) in a model of p190+ ALL, the most common isoform to afflict ALL patients, and demonstrated the use of experimental PARP inhibitor (PARPi), AZD2461, as a therapeutic option with cytotoxic capabilities similar to that of imatinib, the current gold standard in medical care. We characterized cytostatic profiles, induced cell death, and biomarker expression modulation utilizing cell models, also providing a comprehensive genome-wide analysis through an aCGH of the model used, and further validated PARP1 differential expression in samples of ALL p190+ patients from local healthcare institutions, as well as in larger cohorts of online and readily available datasets.
View Article and Find Full Text PDFOur current genetic engineering capacity through synthetic biology and genome editing is the foundation of a revolution in biomedical science: the use of genetically programmed cells as therapeutics. The prime example of this paradigm is the adoptive transfer of genetically engineered T cells to express tumor-specific receptors, such as chimeric antigen receptors (CARs) or engineered T-cell receptors (TCR). This approach has led to unprecedented complete remission rates in patients with otherwise incurable hematological malignancies.
View Article and Find Full Text PDFMicroRNAs (miRNAs) are responsible for regulating gene expression post-transcriptionally. Are involved in several biological processes, such as wound healing. Understanding the miRNAs involved in this process is fundamental for the development of new therapies.
View Article and Find Full Text PDFIntroduction: Studies on maternal microRNA expression have emerged to better understand regulatory mechanisms during the gestational period, since microRNA expression has been associated with pregnancy disorders.
Objectives: This study aims to investigate the association between the expression of the maternal microRNAs miR-let-7d-3p and miR-451a during the second gestational trimester and neuropsychomotor development at 90 days of life of infants.
Methods: This is a case-control study nested within a cohort, with the groups being divided into dyads in which pregnant women presented Major Depressive Episode (MDE) (n = 64), these being the cases, and their respective controls (no MDE; n = 64).
Immune checkpoint (IC) blockade using monoclonal antibodies is currently one of the most successful immunotherapeutic interventions to treat cancer. By reinvigorating antitumor exhausted T cells, this approach can lead to durable clinical responses. However, the majority of patients either do not respond or present a short-lived response to IC blockade, in part due to a scarcity of tumor-specific T cells within the tumor microenvironment.
View Article and Find Full Text PDFThis article analyzes the discourses within Health Promotion (HP) practices in Primary Health Care (PHC) that constitute actions of resistance and counter-conduct to the neoliberal governmentality inscribed in these tools. Drawing upon descriptive and exploratory field research, together with a qualitative approach, we interviewed 23 PHC workers in a municipality in southern Brazil. The results point out possibilities to enhance HP in PHC: strengthening training activities within health units; problematizing Social Determinants of Health (SDH); methods to encourage participation; collectivization of health demands; appreciation and reinforcement of achievements and collective actions; recovery of the local community's culture and habits; and HP advocacy in PHC.
View Article and Find Full Text PDFObjective: To critically evaluate the literature and answer the question, "How effective is photobiomodulation treatment on pain control in patients with TMJ disorder?".
Methods: PRISMA, PubMed, Web of Science, Scopus, and Embase databases were used for the personalized search strategy. For risk of bias, Rob 2.
The field of cell therapy is leading a paradigm shift in drug development. The recent convergence of several fields, including immunology, genetics, and synthetic biology, now allows for the introduction of artificial receptors and the design of entire genetic circuitries to finely program the behavior of injected cells. A prime example of these next-generation living drugs comes in the form of T cells expressing chimeric antigen receptors (CARs), which have already demonstrated definitive evidence of therapeutic efficacy against some hematological malignancies.
View Article and Find Full Text PDFBackground: Post-donation illness can be described as appearance of clinical symptoms in blood donors after donation. The consequent call back of the donor to report these symptoms to the blood collection institution is considered a post-donation illness report (PDIR). The most suitable way to examine whether PDIR is related to infection is to apply next-generation sequencing (NGS) and viral metagenomics.
View Article and Find Full Text PDFThe HIV-1 accessory protein Nef downregulates the cell surface expression of major histocompatibility complex class I (MHC-I) molecules to facilitate virus spreading. The Nef-induced downregulation of MHC-I molecules such as HLA-A requires the clathrin adaptor protein 1 (AP-1) complex. The cooperative interaction of Nef, AP-1, and the cytosolic tail (CT) of HLA-A leads to a redirection of HLA-A targeting from the -Golgi network (TGN) to lysosomes for degradation.
View Article and Find Full Text PDFFood Chem
June 2019
This work has proposed the application of optimized dispersive liquid-liquid microextraction (DLLME) in order to extract acrylamide from brewed coffee samples for its subsequent determination by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). DLLME achieved superior results employing 300 μL of brewed coffee, 100 μL of dichloromethane, 400 μL of acetonitrile and without sodium chloride addition. Quantitative analyses were carried out by the standard addition method, and the limits of detection and quantification were 0.
View Article and Find Full Text PDFTransfus Apher Sci
April 2019
Objective: Human pegivirus (HPgV-1, GBV-C) is classified within the Pegivirus genus of the Flaviviriade family. The natural history of HPgV-1 infection is still unclear, however, the main route of viral transmission seems to be the parenteral one. The detection of HPgV-1 viremia in blood donors without parenteral exposure demonstrates that other routes of HPgV-1 transmission might also exist.
View Article and Find Full Text PDFFood Res Int
December 2017
Fast and innovative methodology to monitors the addition of soybean oil in extra virgin olive oil was developed employing ESI-MS with ionization operating in positive mode. A certified extra virgin olive oil and refined soybean oil samples were analyzed by direct infusion, the identification of a natural lipid marker present only in soybean oil (m/z 886.68 [TAG+NH]) was possible.
View Article and Find Full Text PDFNeosporosis, caused by the apicomplexan protozoan Neospora caninum, is a disease which affects a wide range of mammalian hosts (mainly cattle and dogs). N. caninum infection is considered the major cause of livestock abortions worldwide, and therefore is responsible for great losses in the industry.
View Article and Find Full Text PDFIn this study, the determination of fructose, glucose and sucrose by capillary electrophoresis (CE) was investigated. The tendency of the analyte to undergo electromigration dispersion and the buffer capacity were evaluated using the Peakmaster(®) software and considered in the optimization of the background electrolyte, which was composed of 20 mmol L(-1) sorbic acid, 0.2 mmol L(-1) CTAB and 40 mmol L(-1) NaOH at pH 12.
View Article and Find Full Text PDFActive compounds from Agave sisalana with antiparasitic action against gastrointestinal nematodes (GINs) could be an alternative to diversify the range of parasite management methods in the livestock sector. The objective of this study was to evaluate the in vitro action of A. sisalana extract on the development of sheep and goat GINs.
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