Influence of Physical Exercise on Advanced Glycation End Products Levels in Patients Living With the Human Immunodeficiency Virus

Introduction: Combined antiretroviral therapy (cART) used to treat acquired immunodeficiency virus (HIV) induces a number of adverse effects, such as insulin resistance and dyslipidemia, which ultimately increases the cardiovascular risk. Advanced glycation end products (AGEs) have been implicated in the etiology of cardiovascular diseases, diabetes and other chronic diseases. It is known that physical exercise improves the lipid profile, insulin resistance and reduces the risk of cardiovascular diseases. However, the impact of physical exercise on AGE levels in HIV-infected patients has not been so far investigated. Therefore, this study compared AGEs levels in people with and without HIV and verified the effect of physical training on serum AGE levels.Methods: Participants were initially assigned into three groups: healthy control (CTL, n = 35), physically inactive HIV-infected (In-HIV, n = 33) and physically active HIV-infected (Ac-HIV, n = 19). The In-HIV group underwent physical training for 3 months, consisting of 60-min sessions of multimodal supervised exercise (aerobic, resistance and flexibility) with moderate intensity (50–80% heart rate reserve), performed 3 times/week. AGEs were measured in serum by fluorescence spectrometry.Results: At baseline, serum AGEs fluorescence level was significantly higher in inactive HIV-patients when compared to controls or active HIV-patients (In-HIV: 0.93 ± 0.08 vs. controls: 0.68 ± 0.13 and Ac-HIV: 0.59 ± 0.04 A.U.; P < 0.001). Triglycerides were also higher in In-HIV than CTL (182.8 ± 102 vs. 132.8 ± 52.3 mg/dL; P < 0.05). Waist circumference was lower in Ac-HIV, compared to In-HIV and controls (83.9 ± 10.4 vs. 92.9 ± 13.5 and 98.3 ± 12.4, respectively; P < 0.05). Body mass, fasting blood glucose, LDL, HDL, and total cholesterol were similar between groups. After training, AGE levels decreased (Baseline: 0.93 ± 0.08 vs. 3 months follow-up: 0.59 ± 0.04 AU; P < 0.001), no further difference being detected vs. CTL or Ac-HIV. Conclusion: HIV-infected patients under cART exhibited elevated AGEs levels compared to healthy individuals and physically active patients. Short-term aerobic training of moderate intensity counteracted this condition

Hair cortisol levels are associated with overweight and obesity in the ELSA-Brasil cohort

IntroductionHair cortisol level has recently been identified as a promising marker for detecting long-term cortisol levels and a marker of hypothalamic-pituitary-adrenal cortex (HPA) axis activity. However, research on the association between obesity and an altered cortisol metabolism remains controversial.ObjectiveThis study aimed to investigate the relationship between hair cortisol levels and overweight and obesity in participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)MethodsThis was a cross-sectional study involving 2,499 participants from the second follow-up (visit 3, 2017-2019) attending research centers in Rio de Janeiro and Rio Grande do Sul states. Hair samples were collected, and cortisol levels were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Cortisol levels were classified as low (< 40 pg/mg), medium (40–128 pg/mg), or high (> 128 pg/mg). The participants were classified as eutrophic, overweight, or obese according to their weight (kg) and height (m2). Odds ratios (ORs) with 95% confidence intervals (95%CI) were estimated.ResultsOf the 2499 individuals, 30% had eutrophic weight, 40% were overweight, and 30% were obese. Notably, cortisol levels gradually increased with increasing body weight. Among participants with high hair cortisol levels, 41.2% were classified as overweight and 34.2% as obese. Multinomial logistic regression analysis indicated that participants with high cortisol levels were 43% (OR =1.43; 95%CI: 1.02–2.03) more likely to be overweight and 72% (OR =1.72; 95%CI:1.20–2.47) more likely to be obese than participants with low hair cortisol levels. After adjustment for all covariates, high cortisol levels remained associated with obesity (OR = 1.54; 95%CI:1.02–2.31) and overweight (OR =1.33; 95%CI:0.91–1.94).ConclusionIn the ELSA-Brazil cohort, hair stress were positively associated with overweight and obesity. These results underscore the importance of considering stress and cortisol as potential factors in obesity prevention and intervention efforts, and highlight a novel aspect of the complex relationship between stress and obesity in the Brazilian population

Time to face the proofs: the BCG Moreau vaccine promotes superior inflammatory cytokine profile in vitro when compared with Russia, Pasteur, and Danish strains

Tuberculosis (TB) has been a major public health problem worldwide, and the Bacillus Calmette–Guérin (BCG) vaccine is the only available vaccine against this disease. The BCG vaccine is no longer a single organism; it consists of diverse strains. The early-shared strains of the BCG vaccine are stronger immunostimulators than the late-shared strains. In this study, we have employed a simple in vitro human model to broadly evaluate the differences among four widely used BCG vaccines during the characterization of strain-specific host immune responses. In general, the BCG Moreau vaccine generated a higher inflammatory cytokine profile and lower TGF-β levels compared with the Russia, Pasteur, and Danish strains in the context of early sensitization with TB; however, no changes were observed in the IL-23 levels between infected and noninfected cultures. Unsurprisingly, the BCG vaccines provided different features, and the variances among those strains may influence the activation of infected host cells, which ultimately leads to distinct protective efficacy to tackle TB

Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress

Increased reactive oxidative stress, lipid peroxidation, inflammation, and fibrosis, which contribute to tissue damage and development and progression of nonalcoholic liver disease (NAFLD), play important roles in microcirculatory disorders. We investigated the effect of the modulatory properties of simvastatin (SV) on the liver and adipose tissue microcirculation as well as metabolic and oxidative stress parameters, including the advanced lipoxidation end product–receptors of advanced glycation end products (ALE-RAGE) pathway. SV was administered to an NAFLD model constructed using a high-fat–high-carbohydrate diet (HFHC). HFHC caused metabolic changes indicative of nonalcoholic steatohepatitis; treatment with SV protected the mice from developing NAFLD. SV prevented microcirculatory dysfunction in HFHC-fed mice, as evidenced by decreased leukocyte recruitment to hepatic and fat microcirculation, decreased hepatic stellate cell activation, and improved hepatic capillary network architecture and density. SV restored basal microvascular blood flow in the liver and adipose tissue and restored the endothelium-dependent vasodilatory response of adipose tissue to acetylcholine. SV treatment restored antioxidant enzyme activity and decreased lipid peroxidation, ALE-RAGE pathway activation, steatosis, fibrosis, and inflammatory parameters. Thus, SV may improve microcirculatory function in NAFLD by downregulating oxidative and ALE-RAGE stress and improving steatosis, fibrosis, and inflammatory parameters

Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease

Submitted by Sandra Infurna ([email protected]) on 2017-11-16T13:43:19Z No. of bitstreams: 1 evelyn_pereira_etal_IOC_2017.pdf: 16299047 bytes, checksum: 784f4efe183b1d6189c0f5a1b9e9a610 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-11-16T13:53:46Z (GMT) No. of bitstreams: 1 evelyn_pereira_etal_IOC_2017.pdf: 16299047 bytes, checksum: 784f4efe183b1d6189c0f5a1b9e9a610 (MD5)Made available in DSpace on 2017-11-16T13:53:46Z (GMT). No. of bitstreams: 1 evelyn_pereira_etal_IOC_2017.pdf: 16299047 bytes, checksum: 784f4efe183b1d6189c0f5a1b9e9a610 (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Cardiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro Nacional de Biologia Estrutura. e Bioimagem. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Endocrinologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Endocrinologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ. Brasil.This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD)

Cirrhotic Liver Sustains In Situ Regeneration of Acellular Liver Scaffolds after Transplantation into G-CSF-Treated Animals

Acellular liver scaffolds (ALS) produced by decellularization have been successfully explored for distinct regenerative purposes. To date, it is unknown whether transplanted ALSs are affected by cirrhotic livers, either becoming cirrhotic themselves or instead remaining as a robust template for healthy cell growth after transplantation into cirrhotic rats. Moreover, little is known about the clinical course of recipient cirrhotic livers after ALS transplantation. To address these questions, we transplanted ALSs into cirrhotic rats previously treated with the granulocyte colony-stimulating factor. Here, we report successful cellular engraftment within the transplanted ALSs at 7, 15, and 30 days after transplantation. Recellularization was orchestrated by liver tissue cell activation, resident hepatocytes and bile duct proliferation, and an immune response mediated by the granulocyte components. Furthermore, we showed that transplanted ALSs ensured a pro-regenerative and anti-inflammatory microenvironment, attracted vessels from the host cirrhotic tissue, and promoted progenitor cell recruitment. ALS transplantation induced cirrhotic liver regeneration and extracellular matrix remodeling. Moreover, the transplanted ALS sustained blood circulation and attenuated alterations in the ultrasonographic and biochemical parameters in cirrhotic rats. Taken together, our results confirm that transplanted ALSs are not affected by cirrhotic livers and remain a robust template for healthy cell growth and stimulated cirrhotic liver regeneration

Ultrasonographic analyses of steatotic livers.

<p>Liver area (A), liver horizontal (B) and vertical diameter (C), portal vein diameter (D), liver ultrasonographic representative images of control (CTL)(E) and high-fed diet (HFD)-fed rats (F). *<i>P</i> < .05 versus control; **<i>P</i> < .01 versus control.</p

Participation of advanced glycation end product (AGE) and the receptor for advanced glycation end products (RAGE) in NAFLD.

<p>AGE deposition in the liver (A) and serum of control and HFD-fed rats (HFD)(B). RAGE protein (C) and mRNA (D) levels where compared between the groups. Liver AGE content <i>versus</i> severity of steatosis is shown in E. *<i>P</i> < .05 versus control; **<i>P</i> < .01 versus control.</p

Insulin signalling components in the liver of NAFLD rat model.

<p>Expression of insulin signalling components in the liver of Wistar rats fed a standard chow (CTL) or high-fat diet (HFD) for 20 weeks was assessed by Western blot (A). The histogram represents means ± SEM of the densitometric scans for the protein bands of insulin pathway components, normalised by cyclophilin (B) and the ratio IRβ/p-IRβ (C) and p-AMPK/AMPK (D). *P < .05 versus control; **P < .01 versus control.</p

Evaluation of steatosis, inflammation and lipid deposition in the liver of HFD-fed rats.

<p>Representative images of livers from the control (A) and high fat diet (B, C, D) groups stained with Hematoxilin and Eosin or Oil-Red O staining. A. Control showing no histopathologic alterations. B. Macrovesicles in individual cells, suggesting macroesteatosis, surrounded by some microsteatotic cells. C. Moderate level of steatosis with several microsteatotic cells. D. Severe hepatic steatosis: almost all cells contain microvesicles and some contain macrovesicles. No fibrotic or inflammatory alterations were observed. Arrows indicate macroesteatotic cells and arrowheads microesteatotic cells. Neutral lipid accumulation in liver from control (E) and high fat diet (G) groups. Quantification of oil-red stained sections (G). Magnification is ×20. Insets from the images are magnified five times in order to highlight the steatosis and lipid-staining morphology. a.u., arbitrary units. **<i>P</i> < .01, compared with control rats.</p