Aveiro Institute of Biomedicine

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Tracking prostate carcinogenesis over time through urine proteome profiling in an animal model: an exploratory approach

Publication . Moreira-Pais, Alexandra; Nogueira-Ferreira, Rita; Reis, Stephanie; Aveiro, Susana; Barros, António; Melo, Tânia; Matos, Bárbara; Duarte, José Alberto; Seixas, Fernanda; Domingues, Pedro; Amado, Francisco; Fardilha, Margarida; Oliveira, Paula A.; Ferreira, Rita; Vitorino, Rui

Prostate cancer (PCa) is one of the most lethal diseases in men, which justifies the search for new diagnostic tools. The aim of the present study was to gain new insights into the progression of prostate carcinogenesis by analyzing the urine proteome. To this end, urine from healthy animals and animals with prostate adenocarcinoma was analyzed at two time points: 27 and 54 weeks. After 54 weeks, the incidence of pre-neoplastic and neoplastic lesions in the PCa animals was 100%. GeLC-MS/MS and subsequent bioinformatics analyses revealed several proteins involved in prostate carcinogenesis. Increased levels of retinol-binding protein 4 and decreased levels of cadherin-2 appear to be characteristic of early stages of the disease, whereas increased levels of enolase-1 and T-kininogen 2 and decreased levels of isocitrate dehydrogenase 2 describe more advanced stages. With increasing age, urinary levels of clusterin and corticosteroid-binding globulin increased and neprilysin levels decreased, all of which appear to play a role in prostate hyperplasia or carcinogenesis. The present exploratory analysis can be considered as a starting point for studies targeting specific human urine proteins for early detection of age-related maladaptive changes in the prostate that may lead to cancer.

2022-07-08Journal article

Open access

Impact of physical exercise programs in breast cancer survivors on health-related quality of life, physical fitness, and body composition: Evidence from systematic reviews and meta-analyses

Publication . Joaquim, Ana; Leão, Inês; Antunes, Pedro; Capela, Andreia; Viamonte, Sofia; Alves, Alberto J.; Helguero, Luísa A.; Macedo, Ana

Background: Breast cancer is the most common cancer worldwide, and despite remarkable progress in its treatment, the survivors' quality of life is hampered by treatment-related side effects that impair psychosocial and physiological outcomes. Several studies have established the benefits of physical exercise in breast cancer survivors in recent years. Physical exercise reduces the impact of treatment-related adverse events to promote a better quality of life and functional outcomes.Aim: This study aims to provide an overview of systematic reviews and meta-analyses on the effect of physical exercise on the health-related quality of life, cardiorespiratory fitness, muscle strength, and body composition of breast cancer survivors.Methods: PubMed and Cochrane databases were searched for systematic reviews and meta-analyses from January 2010 to October 2022. The main focus was ascertaining the effectiveness of physical exercise in breast cancer survivors undergoing curative treatment (surgery and/or radiotherapy and/or chemotherapy). Two reviewers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies.Results: A total of 101 studies were identified, and 12 were yielded for final analysis. The eligible studies included nine systematic reviews/meta-analyses, one meta-analysis/meta-regression, and two systematic reviews. The number of randomised clinical trials included in each review varied from 11 to 63, and the number of participants was from 214 to 5761. A positive and significant effect of different physical exercise interventions on health-related quality of life was reported in 83.3% (10 studies) of the eligible studies. Physical exercise also improved cardiorespiratory fitness (3 studies; 25%) and showed to be effective in reducing body weight (3 studies; 25%) and waist circumference (4 studies; 33.3%).Conclusions: Our results suggest that physical exercise is an effective strategy that positively affects breast cancer survivors' quality of life, cardiorespiratory fitness, and body composition. Healthcare professionals should foster the adoption of physical exercise interventions to achieve better health outcomes following breast cancer treatments.

2022-12Journal article

Open access

Exercise training decreases the load and changes the content of circulating SDS-resistant protein aggregates in patients with heart failure with reduced ejection fraction

Publication . Gouveia, Marisol; Schmidt, Cristine; Basilio, Priscilla Gois; Aveiro, Susana; Domingues, Pedro; Xia, Ke; Colón, Wilfredo; Vitorino, Rui; Ferreira, Rita; Santos, Mário; Vieira, Sandra I.; Ribeiro, Fernando

BackgroundHeart failure (HF) often disrupts the protein quality control (PQC) system leading to protein aggregate accumulation. Evidence from tissue biopsies showed that exercise restores PQC system in HF; however, little is known about its effects on plasma proteostasis.AimTo determine the effects of exercise training on the load and composition of plasma SDS-resistant protein aggregates (SRA) in patients with HF with reduced ejection fraction (HFrEF).MethodsEighteen patients with HFrEF (age: 63.4 +/- 6.5 years; LVEF: 33.4 +/- 11.6%) participated in a 12-week combined (aerobic plus resistance) exercise program (60 min/session, twice per week). The load and content of circulating SRA were assessed using D2D SDS-PAGE and mass spectrometry. Cardiorespiratory fitness, quality of life, and circulating levels of high-sensitive C-reactive protein, N-terminal pro-B-type natriuretic peptide (NT-proBNP), haptoglobin and ficolin-3, were also evaluated at baseline and after the exercise program.ResultsThe exercise program decreased the plasma SRA load (% SRA/total protein: 38.0 +/- 8.9 to 36.1 +/- 9.7%, p = 0.018; % SRA/soluble fraction: 64.3 +/- 27.1 to 59.8 +/- 27.7%, p = 0.003). Plasma SRA of HFrEF patients comprised 31 proteins, with alpha-2-macroglobulin and haptoglobin as the most abundant ones. The exercise training significantly increased haptoglobin plasma levels (1.03 +/- 0.40 to 1.11 +/- 0.46, p = 0.031), while decreasing its abundance in SRA (1.83 +/- 0.54 x 1011 to 1.51 +/- 0.59 x 1011, p = 0.049). Cardiorespiratory fitness [16.4(5.9) to 19.0(5.2) ml/kg/min, p = 0.002], quality of life, and circulating NT-proBNP [720.0(850.0) to 587.0(847.3) pg/mL, p = 0.048] levels, also improved after the exercise program.ConclusionExercise training reduced the plasma SRA load and enhanced PQC, potentially via haptoglobin-mediated action, while improving cardiorespiratory fitness and quality of life of patients with HFrEF.

2023-10Journal article

Open access