Laboratory for Integrative and Translational Research in Population Health

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Publications

Peritoneal protein loss, inflammation, and nutrition: refuting myths

Publication . Malho Guedes, A.; Calças Marques, Roberto; Ribeiro, Brigitte; Fernandes, Mónica T.; Faísca, Marília; Silva, Ana Paula; Bragança, José; Rodrigues, Anabela

Peritoneal protein loss (PPL) has been correlated with mortality, malnutrition and inflammation. More recently overhydration was brought to the equation. This study aims to review classic and recent factors associated with PPL. Prevalent and incident peritoneal dialysis (PD) patients were included. Dialysate and serum IL-6 was obtained during PET. Hydration and nutritional status were assessed by bio-impedance. Linear regression and Cox regression were performed. The 78 included patients presented median values of PPL 4.8 g/24 h, serum IL-6: 5.1 pg/mL, and IL-6 appearance rate 153.5 pg/min. Mean extracellular water excess (EWexc) was 0.88 ± 0.94 L, and lean body mass index (LBMI) 17.3 ± 2.4 kg/m2 . After mean follow-up of 33.9 ± 29.3 months, 12 patients died. Linear univariable analysis showed positive associations between PPL and small solute transport, body composition (LBMI and EWexc), comorbidities and performing CAPD (vs. cycler). PPL correlated positively with dialysate appearance rate of IL-6, but not with serum IL-6. Linear multivariable analysis confirmed positive association between PPL and EWexc (p = 0.012; 95%CI: 4.162–31.854), LBMI (p = 0.008; 95%CI: 1.720–11.219) and performing CAPD (p = 0.023; 95%CI: 4.375–54.190). In survival analysis, no relationship was found between mortality and PPL. Multivariable Cox regression showed Charlson Comorbidity Index (HR: 1.896, 95%CI: 1.235–2.913), overhydration (HR: 10.034, 95%CI: 1.426–70.587) and lower PPL (HR: 0.576, 95%CI: 0.339–0.978) were predictors for mortality. Overhydration, was a strong predictor of PPL, overpowering variables previously reported as determinants of PPL, namely clinical correlates of endothelial dysfunction or local inflammation. PPL were not associated with malnutrition or higher mortality, emphasizing the importance of volume overload control in PD patients.

2022Journal article

Open Access

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

A systematic review of bleomycin-induced gonadotoxicity: Mechanistic implications for male reproductive health and fertility

Publication . Almeida, Ana Lobo de; Fortuna, Ana; Sousa, Mário; Sá, Rosália

Long-term cancer treatment complications in men include testicular dysfunction and infertility. Although various chemotherapies have been studied, there is limited evidence on their effects, especially for bleomycin. Despite its known lung toxicity, bleomycin's impact on male reproductive health is not well-researched. This systematic review aimed to evaluate bleomycin's effects on testicular function and fertility. A search of PubMed and Web of Science identified seven relevant animal studies on bleomycin's gonadotoxicity. The research, limited to animal models, shows that bleomycin significantly disrupts male reproductive health, including DNA damage in sperm, analogous to its effects on cancer cells, and notable histopathological changes in rodent testes. It reduces sperm quality and testosterone levels, correlating with Leydig cell degeneration and inflammatory responses, which further aligns with the drug's known capacity to induce lung inflammation. Due to the inherent limitations in extrapolating results from rodents to humans, further research, particularly in humans, is needed to confirm these findings, assess hormonal impacts, temporal patterns of effects (whether transient or permanent), and their impacts implications for offspring, as well explore potential mitigation strategies. These findings are a first step in raising awareness among clinicians about bleomycin's fertility risks and developing strategies for fertility preservation.

2024-12Journal article

Open Access