To evaluate the influence of curcumin supplementation on the glycemic profile, inflammatory markers, and oxidative stress in HIV‐infected individuals under antiretroviral therapy. This double‐blind, ...crossover, randomized clinical trial was composed of 20 subjects arranged initially into experimental group (n = 10) and placebo group (n = 10) groups, receiving 1,000 mg curcumin/day or microcrystalline cellulose/day, respectively, during a 30‐day period and 12‐day washout. Subsequently, the groups were switched to follow the crossover design. Fasting glucose and insulin, IL‐10, tumor necrosis factor alpha, malonialdehyde, and reduced glutathione were measured. Food consumption was evaluated as a control variable. Descriptive statistics are presented as mean and standard deviation, and inferential analyses were performed from two‐way analysis of variance and the magnitude of the effect. No significant improvements were observed in the glycemic, inflammatory, or oxidative stress profiles. Although the mean serum fasting glucose levels and the homeostatic model assessment index presented qualitative improvement in the CG, this result should be interpreted with caution since the observed variation may represent acceptable fluctuation, in addition to the small difference between the means, added to the large variation observed in the standard deviation. Supplementation with curcumin in HIV‐infected individuals undergoing antiretroviral therapy and training did not improve the glycemic, inflammatory, or oxidative stress profiles.
Midostaurin, an oral multitargeted kinase inhibitor, is active in patients with a
FLT3
mutation. Among patients with acute myeloid leukemia and this mutation, the addition of midostaurin to standard ...chemotherapy appeared to improve long-term outcomes.
Vanillin (vanH) is the major component of vanilla and one of the most widely used flavoring agents. In this work the complex Cu(phen)(van)
was prepared and characterized by structural (X-ray), ...spectroscopic (IR, UV-Vis, EPR) and electrochemical techniques. This compound showed an octahedral geometry with an unusual arrangement of the vanillin ligands, where the methoxy groups of the vanillinate ions are coordinated opposite to each other. The compound promoted DNA cleavage in the presence of glutathione (GSH) and H
O
. At 40 μmol L
of complex with GSH (10 mmol L
), there is a complete cleavage of DNA to nicked form II, while only at 10 μmol L
of this complex with H
O
(1 mmol L
) an extensive cleavage leading to form III took place. Additionally, we have evidences of superoxide generation upon reaction with GSH. Therefore, DNA fragmentation occurs likely through an oxidative pathway. MTT assays indicated that the complex is highly cytotoxic against three distinct cell lines: B16-F10 (IC
= 3.39 ± 0.61 μmol L
), HUH-7 (IC
= 4.22 ± 0.31 μmol L
) and 786-0 (IC
= 10.38 ± 0.91 μmol L
). Flow cytometry studies conducted with 786-0 cell line indicated cell death might occur by apoptosis. Cell cycle progression evaluated at 5 and 10 μmol L
resulted in a clear increase of 786-0 cells at G1 phase and depletion of G2/M, while higher doses showed an expressive increase of sub-G1 phase. Altogether, these results pointed out to a promising biological activity and potential as an anti-cancer agent.
Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia. Proteins in plant sources that enable the maintenance of the glycemic profile may be of interest in the context of T2DM. However, ...their mechanisms of action are unclear, unlike other bioactive compounds. This systematic review identified and described the mechanisms of action of isolated and purified proteins and peptides extracted from vegetables on the reduction of blood glucose in T2DM in experimental studies. The research was done in PubMed, ScienceDirect, Scopus, Web of Science, Embase and Virtual Health Library (VHL) databases in March 2019. The initial search retrieved 916 articles, and, after reading the title, abstract and keywords, 24 articles were eligible for full reading. Then, five articles were eligible to build this systematic review. The evaluation of the evidence and the strength of the recommendations of the studies was evaluated with the SYstematic Review Center for Laboratory animal Experimentation - SYRCLE. Studies with proteins or peptides extracted from soybean (Glycine max), corn (Zea mays), peas (Pisum sativum), costus (Costus igneus) and ginseng (Panax ginseng) were found, and all of them decreased glycemia but not by the same mechanisms. The mechanism of action of proteins extracted from Glycine max, Pisum sativum, Costus igneus were similar, acting in the insulin-mediated pathways. The peptide derived from Zea mays increased GLP-1 expression, and the peptide from Panax ginseng reduced NF-kappaB signaling, both resulting in stimulating the release of insulin. Therefore, bioactive proteins and peptides of plant sources act through biochemical pathways, in the modulation of insulin resistance and the hyperglycemic state. These compounds are promising in scientific research on T2DM, because there is a probable similarity of these proteins with insulin, which enables them to act as insulin-like molecules. Keywords: hyperglycemia, hyperinsulinemia, bioactive proteins, plant proteins, plant peptides, hypoglycemic agent
Alterations to genes involved in cellular metabolism and epigenetic regulation are implicated in the pathogenesis of myeloid malignancies. Recurring mutations in isocitrate dehydrogenase (IDH) genes ...are detected in approximately 20% of adult patients with acute myeloid leukemia (AML) and 5% of adults with myelodysplastic syndromes (MDS). IDH proteins are homodimeric enzymes involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation and DNA modification. The IDH2 protein is localized in the mitochondria and is a critical component of the tricarboxylic acid (also called the 'citric acid' or Krebs) cycle. Both IDH2 and IDH1 (localized in the cytoplasm) proteins catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). Mutant IDH enzymes have neomorphic activity and catalyze reduction of α-KG to the (R) enantiomer of 2-hydroxyglutarate, which is associated with DNA and histone hypermethylation, altered gene expression and blocked differentiation of hematopoietic progenitor cells. The prognostic significance of mutant IDH (mIDH) is controversial but appears to be influenced by co-mutational status and the specific location of the mutation (IDH1-R132, IDH2-R140, IDH2-R172). Treatments specifically or indirectly targeted to mIDH are currently under clinical investigation; these therapies have been generally well tolerated and, when used as single agents, have shown promise for inducing responses in some mIDH patients when used as first-line treatment or in relapsed or refractory AML or MDS. Use of mIDH inhibitors in combination with drugs with non-overlapping mechanisms of action is especially promising, as such regimens may address the clonal heterogeneity and the multifactorial pathogenic processes involved in mIDH myeloid malignancies. Advances in mutational analysis have made testing more rapid and convenient, and less expensive; such testing should become part of routine diagnostic workup and repeated at relapse to identify patients who may benefit from treatments that target mIDH.
Abstract Aims We examined the efficacy of exercise training for improving physical functioning and cardiopulmonary fitness in survivors of paediatric brain tumours (BTs) treated with cranial ...irradiation. Methods We conducted a controlled clinical trial with crossover of exercise training versus no training in the community in either a group or combined group/home setting. A volunteer sample of 28 children treated with cranial irradiation for brain tumours completed training (mean age = 11.53 years; mean time since diagnosis = 5.25 years). end-points were physical functioning assessed by four subtests from the Bruininks–Oseretsky Test of motor performance (BOT-2) and pro-rated work rate from a cycle ergometer. Linear mixed modelling was used to evaluate time, training, training setting, and carryover effects. Results Adherence to training was 84%. Performance on the BOT-2 was below average for all assessments. However, training resulted in improvement in bilateral coordination (F (1, 30) = 6.59, p = 0.02), irrespective of training setting and improved performance was maintained even approximately 12°weeks after training had ended (F (1, 24) = 9.60, p = 0.005). Training resulted in increased pro-rated work rate for participants in the group training setting only (F (1, 25) = 4.57, p = 0.04) and these participants maintained their improved work rate approximately 12°weeks after training had ended (F (1, 20) = 8.38, p = 0.01). Conclusion Exercise training improves physical functioning and fitness in paediatric BT survivors. Exercise interventions that ameliorate adverse physical effects and promote health in long-term survivors are highly recommended in this vulnerable population. ( ClinicalTrials.gov , NCT01944761 ).
Docosahexaenoic acid (DHA) is an n-3 polyunsaturated fatty acid that is highly enriched in the brain, and the oxidation products of DHA are present or increased during neurodegenerative disease ...progression. The characterization of the oxidation products of DHA is critical to understanding the roles that these products play in the development of such diseases. In this study, we developed a sensitive and specific analytical tool for the detection and quantification of twelve major DHA hydroperoxide (HpDoHE) and hydroxide (HDoHE) isomers (isomers at positions 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, 19 and 20) in biological systems. In this study, HpDoHE were synthesized by photooxidation, and the corresponding hydroxides were obtained by reduction with NaBH4. The isolated isomers were characterized by LC-MS/MS, and unique and specific fragment ions were chosen to construct a selected reaction monitoring (SRM) method for the targeted quantitative analysis of each HpDoHE and HDoHE isomer. The detection limits for the LC-MS/MS-SRM assay were 1-670 pg for HpDoHE and 0.5-8.5 pg for HDoHE injected onto a column. Using this method, it was possible to detect the basal levels of HDoHE isomers in both rat plasma and brain samples. Therefore, the developed LC-MS/MS-SRM can be used as an important tool to identify and quantify the hydro(pero)xy derivatives of DHA in biological system and may be helpful for the oxidative lipidomic studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Two experiments were designed to evaluate the effect of mineral-amino acid complexes (AACM) as a partial replacement of inorganic mineral (IM) in layer-type chicks' diets. Both studies had the same ...dietary treatments, where in experiment 1 (Exp. 1) was conducted under thermoneutral conditions from 0 to 35 D and chicks in experiment 2 (Exp. 2) were exposed to cold stress conditions at nighttime during the first 15 D and to thermoneutral condition from 16 to 35 D. For each trial, 1,200 one-day-old Lohmann Brown chicks were used, with 20 cage replicates with 30 chicks per cage. Treatments consisted of the control diet (IM; with 70, 70, and 8 mg/kg of zinc Zn, manganese Mn, and copper Cu, respectively) and the treatment diet (AACM, with 40, 40, and 2.75 mg/kg of Zn, Mn, and Cu, respectively, from IM sources, along with 30, 30, and 5.25 mg/kg of Zn, Mn, and Cu, respectively). Data were submitted to analysis of variance, and means were compared using the t-test (P < 0.05). In Exp. 1, there were no significant differences between treatments on chick performance. However, AACM-fed chicks had higher thymus (P = 0.03) and cecum weight (P < 0.01), superior micromineral deposition in the tibias (P < 0.01), and reduced phosphorus excretion (P = 0.03). In Exp. 2, chicks fed with AACM had higher body weight gain (P = 0.04), better average daily feed intake (P = 0.03), lower phosphorus excretion (P = 0.02), and higher liver and pancreas weight (P < 0.01) in the last week of the study. In conclusion, chicks fed with AACM under thermoneutral conditions had higher bone mineralization and reduced excretion of phosphorus, and in adverse conditions, AACM improves performance and liver and pancreas weight, also reducing phosphorus excretion.
High levels of microRNA-155 (miR-155) are associated with poor outcome in acute myeloid leukemia (AML). In AML, miR-155 is regulated by NF-κB, the activity of which is, in part, controlled by the ...NEDD8-dependent ubiquitin ligases. We demonstrate that MLN4924, an inhibitor of NEDD8-activating enzyme presently being evaluated in clinical trials, decreases binding of NF-κB to the miR-155 promoter and downregulates miR-155 in AML cells. This results in the upregulation of the miR-155 targets SHIP1, an inhibitor of the PI3K/Akt pathway, and PU.1, a transcription factor important for myeloid differentiation, leading to monocytic differentiation and apoptosis. Consistent with these results, overexpression of miR-155 diminishes MLN4924-induced antileukemic effects. In vivo, MLN4924 reduces miR-155 expression and prolongs the survival of mice engrafted with leukemic cells. Our study demonstrates the potential of miR-155 as a novel therapeutic target in AML via pharmacologic interference with NF-κB-dependent regulatory mechanisms. We show the targeting of this oncogenic microRNA with MLN4924, a compound presently being evaluated in clinical trials in AML. As high miR-155 levels have been consistently associated with aggressive clinical phenotypes, our work opens new avenues for microRNA-targeting therapeutic approaches to leukemia and cancer patients.
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