Relevance of obesity and overweight to salivary and plasma proteomes of human young adults from Brazil / Relevância da obesidade e sobrepeso para os proteomas salivares e plasmáticos de adultos jovens humanos do Brasil

Obesity is a chronic condition related to multiple comorbidities such as hypertension, type 2 diabetes, periodontal and cardiovascular diseases. Obesity can lead to a metabolic change, creating a prolonged and low-intensity inflammatory process. This study aims to analyze the plasma and saliva proteomes of young adults with obesity and overweight comparing to normal weight individuals, to reveal if the rise on body mass influences the proteomic profiles. The reported population consisted of 18 students and/or employees of Rio de Janeiro State, Brazil, aged between 18 and 35 years. Individuals were categorized according to their anthropometric measures in the Normal Weight, Overweight and Obese groups. Proteomic characterization was assessed by quantitative Mass Spectrometry (LC-ESI Q/TOF). In addition, cytokines were identified by Multiplex analysis. A total of 118 human proteins from saliva and plasma were identified, including 7 that were common between both fluids. The salivary and plasma proteomes seemed to be related to the body mass index, once the three groups showed distinct proteome profiles. Altogether 49 proteins presented different abundances between the obese, overweight, and normal weight individuals. The main functional category modified in both fluids was the immune response. Most of the modified proteins were previously reported as related to inflammatory diseases, such as cardiovascular diseases and Type 2 Diabetes Mellitus, in particular alpha-1 antitrypsin, C3 complement, alpha-1-antichymotrypsin, zinc-alpha2-glycoprotein, apolipoprotein AI and lysozyme, that could be tested to possible use as early biomarkers of obesity comorbidities

Estratégias nutricionais no tratamento da síndrome da caquexia associada ao câncer

A síndrome da caquexia é considerada uma doença crônica degenerativa inflamatória, profundamente relacionada com o aumento de fatores pró-inflamatórios. O efeito de fatores pró-inflamatórios, é contrabalançado pelo efeito de fatores anti-inflamatórios. A perda de peso é um dos sintomas clínicos mais marcantes, essa diminuição de peso corporal, principalmente de massa gorda de massa magra era atribuída à anorexia e ao aumento do gasto energético. No entanto, a administração de suplementos nutricionais enteral ou paraenteralmente não reverte esses sintomas, refutando, dessa forma, a hipótese de que deficiência de nutrientes é o agente causador da caquexia associada ao câncer. Atualmente, acredita-se que fatores produzidos pelo tumor e fatores produzidos pelo hospedeiro induzem a anorexia e as alterações metabólicas que resultam no quadro de caquexia. A fim de combater a inflamação na doença crônica, nosso grupo tem atualmente adotado estratégias nutrucionais em modelo animal de caquexia associada ao câncer. Os efeitos dos diferentes nutrientes frente aos danos ocasionados pela sindrome da caquexia associada ao câncer são abordados na presente revisão

Estratégias nutricionais no tratamento da síndrome da caquexia associada ao câncer

A síndrome da caquexia é considerada uma doença crônica degenerativa inflamatória, profundamente relacionada com o aumento de fatores pró-inflamatórios. O efeito de fatores pró-inflamatórios, é contrabalançado pelo efeito de fatores anti-inflamatórios. A perda de peso é um dos sintomas clínicos mais marcantes, essa diminuição de peso corporal, principalmente de massa gorda de massa magra era atribuída à anorexia e ao aumento do gasto energético. No entanto, a administração de suplementos nutricionais enteral ou paraenteralmente não reverte esses sintomas, refutando, dessa forma, a hipótese de que deficiência de nutrientes é o agente causador da caquexia associada ao câncer. Atualmente, acredita-se que fatores produzidos pelo tumor e fatores produzidos pelo hospedeiro induzem a anorexia e as alterações metabólicas que resultam no quadro de caquexia. A fim de combater a inflamação na doença crônica, nosso grupo tem atualmente adotado estratégias nutrucionais em modelo animal de caquexia associada ao câncer. Os efeitos dos diferentes nutrientes frente aos danos ocasionados pela sindrome da caquexia associada ao câncer são abordados na presente revisão

Poly-lactic acid nanoparticles (PLA-NP) promote physiological modifications in lung epithelial cells and are internalized by clathrin-coated pits and lipid rafts

BackgroundPoly-lactic acid nanoparticles (PLA-NP) are a type of polymeric NP, frequently used as nanomedicines, which have advantages over metallic NP such as the ability to maintain therapeutic drug levels for sustained periods of time. Despite PLA-NP being considered biocompatible, data concerning alterations in cellular physiology are scarce.MethodsWe conducted an extensive evaluation of PLA-NP biocompatibility in human lung epithelial A549 cells using high throughput screening and more complex methodologies. These included measurements of cytotoxicity, cell viability, immunomodulatory potential, and effects upon the cells’ proteome. We used non- and green-fluorescent PLA-NP with 63 and 66 nm diameters, respectively. Cells were exposed with concentrations of 2, 20, 100 and 200 µg/mL, for 24, 48 and 72 h, in most experiments. Moreover, possible endocytic mechanisms of internalization of PLA-NP were investigated, such as those involving caveolae, lipid rafts, macropinocytosis and clathrin-coated pits.ResultsCell viability and proliferation were not altered in response to PLA-NP. Multiplex analysis of secreted mediators revealed a low-level reduction of IL-12p70 and vascular epidermal growth factor (VEGF) in response to PLA-NP, while all other mediators assessed were unaffected. However, changes to the cells’ proteome were observed in response to PLA-NP, and, additionally, the cellular stress marker miR155 was found to reduce. In dual exposures of staurosporine (STS) with PLA-NP, PLA-NP enhanced susceptibility to STS-induced cell death. Finally, PLA-NP were rapidly internalized in association with clathrin-coated pits, and, to a lesser extent, with lipid rafts.ConclusionsThese data demonstrate that PLA-NP are internalized and, in general, tolerated by A549 cells, with no cytotoxicity and no secretion of pro-inflammatory mediators. However, PLA-NP exposure may induce modification of biological functions of A549 cells, which should be considered when designing drug delivery systems. Moreover, the pathways of PLA-NP internalization we detected could contribute to the improvement of selective uptake strategies

Peptide Prodrugs for the Treatment of CNS Disorders: A Perspective for New Drugs

The treatment of central nervous system (CNS) diseases is a major challenge. The presence of the barrier intended to protect the brain from unwanted molecules also impairs the efficacy of CNS-targeted drugs. The discovery of drug targets for CNS diseases opens a door for the selective treatment of these diseases. However, the physicochemical properties of drugs, including their hydrophilic properties and their peripheral metabolism, as well as the blood-brain barrier, can adversely affect the therapeutic potential of CNS-targeted drugs. Although peptides are often metabolized by enzymes, they are of particular interest for the treatment of CNS diseases or as carriers to deliver drugs to the brain. In this review, we discuss the use of peptides as potential prodrugs for the treatment of CNS diseases

Chronic low frequency/low volume resistance training reduces pro-inflammatory cytokine protein levels and TLR4 mRNA in rat skeletal muscle

Skeletal muscle is the source of pro- and anti-inflammatory cytokines, and recently, it has been recognized as an important source of interleukin 6 (IL-6), a cytokine that exerts inhibitory effects on several pro-inflammatory cytokines. Although dynamic chronic resistance training has been shown to produce the known ""repeated bout effect"", which abolishes the acute muscle damage, performing of high-intensity resistance training has been regarded highly advisable, at least from the hypertrophy perspective. On the other hand, a more therapeutic, ""non-damaging"" resistance training program, mainly composed of concentric forces, low frequency/low volume of training, and the same exercise, could theoretically benefit the muscle when the main issue is to avoid muscle inflammation (as in the treatment of several ""low-grade"" inflammatory diseases) because the acute effect of each resistance exercise session could be diminished/avoided, at the same time that the muscle is still being overloaded in a concentric manner. However, the benefits of such ""less demanding"" resistance training schedule on the muscle inflammatory profile have never been investigated. Therefore, we assessed the protein expression of IL-6, TNF-alpha, IL-10, IL-10/TNF-alpha ratio, and HSP70 levels and mRNA expression of SCF(beta-TrCP), IL-15, and TLR-4 in the skeletal muscle of rats submitted to resistance training. Briefly, animals were randomly assigned to either a control group (S, n = 8) or a resistance-trained group (T, n = 7). Trained rats were exercised over a duration of 12 weeks (two times per day, two times per week). Detection of IL-6, TNF-alpha, IL-10, and HSP70 protein expression was carried out by western blotting and SCF(beta-TrCP) (SKP Cullin F-Box Protein Ligases), a class of enzymes involved in the ubiquitination of protein substrates to proteasomal degradation, IL-15, and TLR-4 by RT-PCR. Our results show a decreased expression of TNF-alpha and TLR4 mRNA (40 and 60%, respectively; p < 0.05) in the plantar muscle from trained, when compared with control rats. In conclusion, exercise training induced decreased TNF-alpha and TLR-4 expressions, resulting in a modified IL-10/TNF-alpha ratio in the skeletal muscle. These data show that, in healthy rats, 12-week resistance training, predominantly composed of concentric stimuli and low frequency/low volume schedule, down regulates skeletal muscle production of cytokines involved in the onset, maintenance, and regulation of inXammation.Brazilian Funding Agency (FAPESP-Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)[08/51090-1]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP