Prognostic implications of the ID1 expression in acute myeloid leukemia patients treated in a resource-constrained setting

Introduction: The aberrant expression of the inhibitor of DNA binding (ID1) gene has been frequently associated with the leukemogenesis and prognostication acute myeloid leukemia (AML), although its clinical importance has never been investigated in patients treated outside well-controlled clinical trials. Methods: Using quantitative real-time polymerase chain reaction, we investigated the role of the ID1 expression in the clinical outcomes of non-selected patients with acute myeloid leukemia treated in a real-life setting. Results: Overall, 128 patients were enrolled. Patients with high ID1 expression had a lower 3-year overall survival (OS) rate of 9%, with the 95% confidence interval (95%CI) at 3 to 20%, compared to patients with a low ID1 expression (22%, 95%CI: 11 - 34%) (p = 0.037), although these findings did not retain significance after adjustment (hazard ratio (HR): 1.5, 95%CI: 0.98 - 2.28; p = 0.057). The ID1 expression had no impact on post-induction outcomes (disease-free survival, p = 0.648; cumulative incidence of relapse, p = 0.584). Conclusions: Although we are aware thar our data are confronted with many variables that cannot be fully controlled, including drug unavailability, risk-adapted treatment, comorbidities and the time from diagnosis to treatment initiation, we are firm believers that such an initiative can provide more realistic data on understudied populations, in particular those from low- and middle-income countries.</p

GAMMA-ORYZANOL HAS AN EQUIVALENT EFFICACY AS A LIPID-LOWERING AGENT COMPARED TO FIBRATE AND STATIN IN TWO DYSLIPIDEMIA MICE MODELS

Objective: A substantial fraction of the population is intolerant or does not respond well to the recommended treatments for dyslipidemia. The purpose of this study was to evaluate the efficacy ofgamma-oryzanol (γ-ORZ) treatment in acute and long-term mouse experimental models of dyslipidemia in comparison toGemfibrozil and Simvastatin. Methods: For the acute dyslipidemia-induced model, dyslipidemia was induced in 40 mice using a single intra-peritoneal administration of Triton WR-1339. For the long-termmodel, dyslipidemia was induced in 24 mice using a hypercholesterolemic diet over 14 days. Thereafter, animals were divided into different groups of treatment,and orally received treatments with gamma-oryzanol (5, 25, 50mg. kg-1), gemfibrozil or simvastatin. For biochemical analysis, glucose, total cholesterol and triacylglycerols were measured. Body weight and net food intake was registered weekly, and urea, creatinine, AST and ALT levels were evaluated. The data were analyzed by analysis of variance (ANOVA), followed by the Student-Newman-Keuls method,and p value of less than 0.05 was considered significant. Results: Only the highest dose of γ-ORZ exhibited significant protective effects. Gamma-oryzanol andGemfibrozil treatments reduced total cholesterol and triacylglycerols levels in a similar manner in the acute model. In the second model, γ-ORZ and simvastatin treatments reduced glucose and total cholesterol levels in the same way. In addition, the administration ofγ-ORZ did not cause any adverse events, or significantly altered hepatic enzymes levels, plasmatic urea or creatinine concentrations. Conclusion: The results of this study suggest that gamma-oryzanol acts as a potential lipid-lowering agent, reducing triglycerides and total cholesterol in dyslipidemia-induced models

Design of Nickel Supported on Water-Tolerant Nb2O5 Catalysts for the Hydrotreating of Lignin Streams Obtained from Lignin-First Biorefining

R.R. acknowledges the financial support provided by the ERC Consolidator Grant LIGNINFIRST (Project Number: 725762). R.R. and A.A.S.C. thank FAPESP for the support provided (Process Number: 2016/50423-3). The authors are grateful to LNLS/CNPEM for the infrastructure (XPD beamline and chemistry laboratory), LNNano for the STEM infrastructure, the GPMMM laboratory (IQ-UNICAMP) for the quantitative FTIR of adsorbed pyridine analysis, CNPq for the PhD scholarship (Process Number: 165106/2014-0), and CAPES for the PDSE scholarship (Process Number: 88881.132245/2016-01). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. Finally, the authors are thankful to CBMM for the ammonium niobium oxalate hydrate samples.Peer reviewedPublisher PD

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets