Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that ...exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer's disease and depression. Lipids are a major constituent of the brain and specifically signaling lipids have been shown to regulate brain function. Here, we used a mass spectrometry-based lipidomic approach to evaluate the impact of a chronic unpredictable stress (CUS) paradigm on the rat brain in a region-specific manner. We found that the prefrontal cortex (PFC) was the area with the highest degree of changes induced by chronic stress. Although the hippocampus presented relevant lipidomic changes, the amygdala and, to a greater extent, the cerebellum presented few lipid changes upon chronic stress exposure. The sphingolipid and phospholipid metabolism were profoundly affected, showing an increase in ceramide (Cer) and a decrease in sphingomyelin (SM) and dihydrosphingomyelin (dhSM) levels, and a decrease in phosphatidylethanolamine (PE) and ether phosphatidylcholine (PCe) and increase in lysophosphatidylethanolamine (LPE) levels, respectively. Furthermore, the fatty-acyl profile of phospholipids and diacylglycerol revealed that chronic stressed rats had higher 38 carbon(38C)-lipid levels in the hippocampus and reduced 36C-lipid levels in the PFC. Finally, lysophosphatidylcholine (LPC) levels in the PFC were found to be correlated with blood corticosterone (CORT) levels. In summary, lipidomic profiling of the effect of chronic stress allowed the identification of dysregulated lipid pathways, revealing putative targets for pharmacological intervention that may potentially be used to modulate stress-induced deficits.
Broiler embryonic development depends on the nutrients that are available in the egg, which includes mostly water, lipids, and proteins. Carbohydrates represent less than 1%, and free glucose only ...0.3%, of the total nutrients. Considering that energy requirements increase during incubation and metabolism is shifted toward the use of glycogen stores and gluconeogenesis from amino acids, extensive muscle protein degradation in the end of incubation can compromise chick development in the initial days after hatch. Significant prehatch changes occur in embryonic metabolism to parallel the rapid embryonic development. Oral consumption of the amniotic fluid begins around 17 d of incubation and promotes rapid development of the intestinal mucosa, which is characterized by morphological changes and increased expression and activity of enzymes and transporters. Furthermore, ingested substrates are stored as nutritional reserves to be used during hatching and in the first week after hatch. At hatch, this limited-nutrient store is directed to the functional development of the gastrointestinal tract to enable assimilation of exogenous nutrients. In ovo feeding is an alternative to deliver essential nutrients to chick embryos at this critical and challenging phase. The improved nutritional status and physiological changes triggered by in ovo feeding can resonate throughout the entire rearing period with significant health and economic gains. The present review addresses the main changes in metabolism and intestinal development throughout incubation, and also addresses scientific advances, limitations and future perspectives associated with the use of in ovo feeding that has been regarded as an important technology by the poultry industry.
Background/Aim
A link between an impaired intestinal barrier, endotoxemia, and the pathogenesis of metabolic diseases, such as type 2 diabetes mellitus (T2DM), has been proposed. In previous work, we ...have demonstrated that the tight junction (TJ)-mediated intestinal barrier in ileum/colon was marginally changed in prediabetic mice; therefore, it does not seem to mainly contribute to the T2DM onset. In this study, the TJ-mediated epithelial barrier in the duodenum and jejunum was evaluated in mice during the development of type 2 prediabetes.
Methods/Results
HF diet induced prediabetes after 60 days associated with a significant rise in intestinal permeability to the small-sized marker Lucifer yellow in these mice, with no histological signs of mucosal inflammation or rupture of the proximal intestine epithelium. As revealed by immunofluorescence, TJ proteins, such as claudins-1, -2, -3, and ZO-1, showed a significant decrease in junctional content in duodenum and jejunum epithelia, already after 15 days of treatment, suggesting a rearrangement of the TJ structure. However, no significant change in total cell content of these proteins was observed in intestinal epithelium homogenates, as assessed by immunoblotting. Despite the changes in intestinal permeability and TJ structure, the prediabetic mice showed similar LPS, zonulin, and TNF-α levels in plasma or adipose tissue, and in intestinal segments as compared to the controls.
Conclusion
Disruption of the TJ-mediated paracellular barrier in the duodenum and jejunum is an early event in prediabetes development, which occurs in the absence of detectable endotoxemia/inflammation and may contribute to the HF diet-induced increase in intestinal permeability.
The
genus comprises opportunistic fungi that can become pathogenic when the immune system of the host fails.
is the most important and prevalent species. Polyenes, fluoropyrimidines, echinocandins, ...and azoles are used as commercial antifungal agents to treat candidiasis. However, the presence of intrinsic and developed resistance against azole antifungals has been extensively documented among several
species. The advent of original and re-emergence of classical fungal diseases have occurred as a consequence of the development of the antifungal resistance phenomenon. In this way, the development of new satisfactory therapy for fungal diseases persists as a major challenge of present-day medicine. The design of original drugs from traditional medicines provides new promises in the modern clinic. The urgent need includes the development of alternative drugs that are more efficient and tolerant than those traditional already in use. The identification of new substances with potential antifungal effect at low concentrations or in combination is also a possibility. The present review briefly examines the infections caused by
species and focuses on the mechanisms of action associated with the traditional agents used to treat those infections, as well as the current understanding of the molecular basis of resistance development in these fungal species. In addition, this review describes some of the promising alternative molecules and/or substances that could be used as anticandidal agents, their mechanisms of action, and their use in combination with traditional drugs.
Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance ...of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclonal antibodies, such as Infliximab, has brought improvements in the treatment of patients with chronic inflammatory diseases, but this treatment also increases the risk of reactivation of latent tuberculosis. Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guérin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients. We evaluated 76 individuals, with tuberculosis active, treated and subjects with positive PPD. Granuloma formation was induced in the presence or absence of Infliximab for up to 10 days. The use of Infliximab in cultures significantly blocked TNF-α production (p <0.05), and led to significant changes in granuloma structure, in vitro, only in the treated TB group. On the other hand, there was a significant reduction in the levels of IFN-γ, IL-12p40, IL-10 and IL-17 after TNF-α blockade in the three experimental groups (p <0.05). Taken together, our results demonstrate that TNF-α blockade by Infliximab directly influenced the structure of granuloma only in the treated TB group, but negatively modulated the production of Th1, Th17 and regulatory T cytokines in the three groups analyzed.
Lipase from
Rhizomucor miehei
(RML) was immobilized onto chitosan support in the presence of some surfactants added at low levels using two different strategies. In the first approach, the enzyme was ...immobilized in the presence of surfactants on chitosan supports previously functionalized with glutaraldehyde. In the second one, after prior enzyme adsorption on chitosan beads in the presence of surfactants, the complex chitosan beads-enzyme was then cross-linked with glutaraldehyde. The effects of surfactant concentrations on the activities of free and immobilized RML were evaluated. Hexadecyltrimethylammonium bromide (CTAB) promoted an inhibition of enzyme activity while the nonionic surfactant Triton X-100 caused a slight increase in the catalytic activity of the free enzyme and the derivatives produced in both methods of immobilization. The best derivatives were achieved when the lipase was firstly adsorbed on chitosan beads at 4 °C for 1 h, 220 rpm followed by cross-link the complex chitosan beads-enzyme with glutaraldehyde 0.6% v.v
−1
at pH 7. The derivatives obtained under these conditions showed high catalytic activity and excellent thermal stability at 60° and 37 °C. The best derivative was also evaluated in the synthesis of two flavor esters namely methyl and ethyl butyrate. At non-optimized conditions, the maximum conversion yield for methyl butyrate was 89%, and for ethyl butyrate, the esterification yield was 92%. The results for both esterifications were similar to those obtained when the commercial enzyme Lipozyme® and free enzyme were used in the same reaction conditions and higher than the one achieved in the absence of the selected surfactant.
Abstract We evaluated a modified HBV regimen in a cohort of HIV-infected subjects in Rio de Janeiro, Brazil. HIV-infected subjects with no serologic evidences of previous hepatitis B infection were ...immunized with 4 doses (40 μg each) of recombinant hepatitis B vaccine given at 0, 1, 2 and 6 months. Blood samples were collected 1 month after the last dose and anti-HBs titers were measured. A protective antibody response was defined as an anti-HBs titer ≥10 mIU/mL. Forty-seven subjects (30 women, 17 men; mean age was 36 years, ranging from 21 to 58 years) were included in the final analysis. Median baseline CD4+ lymphocyte count was 402 cells/mm3 and 33 subjects (70%) had an HIV viral load below 80 copies/mL. A protective antibody response was observed in 42 (89%) subjects. Thirty-seven (78%) and 28 (60%) patients developed anti-HBs titers higher than 100 mIU/mL and 1000 mIU/mL, respectively. 1 out of 5 non-responders (20%) had an HIV viral load below the detection limit, in contrast with 32 (76%) of those with an adequate serologic response ( p = 0.02). These findings suggest that 4-double dose alternative schedule may be considered to overcome the lower seroconversion rates observed with the standard regimens in HIV-infected subjects.
This study investigated the associations of occupational physical activity and active transport with depressive symptoms, stratified by income range, among Brazilian working adults.
This ...cross-sectional study drew on data from the 2019 Brazilian National Health Survey.
We used the Patient Health Questionnaire (PHQ-9) to assess depressive symptoms in working adults aged 18–65 years, with physical activities (occupational physical activity and active transport) self-reported through a specially developed questionnaire. Crude and adjusted logistic regression models were fitted.
Individuals at the highest level of occupational physical activity (odds ratio OR 1.35; 95% confidence interval 95% CI 1.19–1.53) and at the moderate level of active transport to work (OR 1.66; 95% CI 1.24–2.22) returned increased odds of depressive symptoms as compared with those who were inactive in these domains. Stratified by income group, light active transport to work (OR 0.57; 95% CI 0.34–0.95) in the lower income group (Range 1) was associated with lower odds of depressive symptoms. On the other hand, individuals at the highest level of active transport to work returned higher odds of depressive symptoms in the low- and intermediate-income groups, Ranges 3 and 4 (OR 1.92; 95% CI 1.22–3.00 and OR 2.91; 95% CI 1.71–4.95, respectively).
Our results suggest that occupational physical activity and active transport may be a risk factor for depressive symptoms. They also point to differences in this relationship by income range. Further studies are needed to pursue the analysis of how specific domains of physical activity contribute to depressive symptoms.
Abstract Sulfated polysaccharides from 11 species of tropical marine algae (one edible specie of Rhodophyta, six species of Phaeophyta and four species of Chlorophyta) collected from Natal city coast ...(Northeast of Brazil) were evaluated for their anticoagulant, antioxidant and antiproliverative in vitro activities. In the activated partial thromboplastin time (APTT) test, which evaluates the intrinsic coagulation pathway, seven seaweeds presented anticoagulant activity. Dictyota cervicornis showed the highest activity, prolonging the coagulation time to double the baseline value in the APTT with only 0.01 mg/100 μl of plasma, 1.4-fold lesser than Clexane® , a low molecular weight heparin. In the protrombin time (PT) test, which evaluates the extrinsic coagulation pathway, only Caulerpa cupresoides showed anticoagulant activity. All species collected showed antioxidant activities. This screening emphasized the great antioxidant potential (total capacity antioxidant, power reducing and ferrous chelating) of four species: C. sertularioide ; Dictyota cervicornis; Sargassum filipendula and Dictyopteris delicatula . After 72 h incubation, HeLa cell proliferation was inhibited ( p < 0.05) between 33.0 and 67.5% by S. filipendula ; 31.4 and 65.7% by D. delicatula ; 36.3 and 58.4% by Caulerpa prolifera and 40.2 and 61.0% by Dictyota menstrualis at 0.01–2 mg/mL algal polysaccharides. The antiproliferative efficacy of these algal polysaccharides were positively correlated with the sulfate content ( r = 0.934). Several polysaccharides demonstrated promising antioxidant, antiproliferative an/or anticoagulant potential and have been selected for further studies on bioguided fractionation, isolation and characterization of pure polysaccharides from these species as well as in vivo experiments are needed and are already in progress.
Skeletal muscle plays major roles in metabolism and overall health across the lifecycle. Emerging evidence indicates that prenatal (maternal diet during pregnancy and genetic defects) and postnatal ...factors (physical activity, hormones, dietary protein, and obesity) influence muscle mass acquisition and strength early in life. As a consequence, low muscle mass and strength contributes to several adverse health outcomes during childhood. Specifically, studies demonstrated inverse associations of muscle mass and strength to single and clustered metabolic risk factors. The literature also consistently reports that low muscle mass and strength are associated with reduced bone parameters during growth, increasing the risk of osteoporosis in old age. Furthermore, muscle mass gains are associated with improved neurodevelopment in the first years of life. Given these negative implications of low muscle mass and strength on health, it is crucial to track muscle mass and strength development from childhood to adolescence. Several body composition techniques are currently available for estimation of muscle mass, all with unique advantages and disadvantages. The value of ultrasound as a technique to measure muscle mass is emerging in pediatric research with potential for translating the research findings to clinical settings. For the assessment of muscle strength, the handgrip strength test has been widely employed but without a standardized protocol. Although further research is needed to define normative data and cut points for the low muscle mass and strength phenotype, the use of such non-invasive medical monitoring is a promising strategy to identify early abnormalities and prevent low muscle mass in adulthood.
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