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C135. PERITONEAL DIALYSIS EFFLUENT-DERIVED MESOTHELIAL CELLS AS A MODEL TO STUD...

Sequeira, Diogo; Teixeira-Santos, Luísa; Anão, Sofia; Pimpão, António B.; Calça, Rita; Monteiro, Emília; Branco, Patrícia; Sousa, Cátia

Introduction: Peritoneal dialysis (PD) is a home-based renal replacement therapy that relies on the dialytic properties of the peritoneal membrane [1]. However, progressive membrane dysfunction, mesothelial-to-mesenchymal transition events and fibrosis remain major limitations to long-term PD success [2]. The aryl hydrocarbon receptor (AhR) is a ligand activator transcription factor that has been implicated in ...


A THIOL BASED TOOL TO EXPLORE PERITONEAL MEMBRANE PROTECTIVE DRUG CANDIDATES

Anão, Sofia; Teixeira-Santos, Luísa; Sequeira, Diogo; Sousa, Cátia; Gonçalves, Joana; Monteiro, Emília C.; Calça, Rita; Branco, Patrícia

Introduction: Peritoneal dialysis (PD) is a renal replacement therapy that offers several advantages, including greater patient autonomy. However, peritoneal membrane fibrosis and loss of membrane integrity remain the main limiting factors for the long-term success of PD [1]. At SPF 2024, our group reported an association between peritoneal membrane fibrosis and aminothiol levels, namely cysteine, in PD effluen...


The PDE-thiolome as an indicator of Peritoneal Membrane vulnerability

Sequeira, Diogo; Teixeira-Santos, Luísa; Anão, Sofia; Sousa, Cátia; Monteiro, Emília; Calça, Rita Ribeiro; Branco, Patrícia; Pereira, Sofia A.

Background and Aims: Peritoneal membrane health is crucial for peritoneal dialysis effectiveness [1]. Strategies to overcome peritoneal membrane (PM) injury and fibrosis remain an unmet need in PD, due to many factors [2]. Among these is the lack of early indicators to identify patients at higher risk before structural damage becomes irreversible. While oxidative stress is recognized as an early trigger in fibr...


Multi-thiol assessment upon the Peritoneal Equilibration Test (PET) reveals sol...

Anão, Sofia; Sequeira, Diogo; Calça, Rita; Gonçalves, Joana; Sousa, Cátia; Branco, Patrícia; Pereira, Sofia A.; Teixeira-Santos, Luísa

Peritoneal membrane (PM) dysfunction remains a key limitation to the long-term efficacy of peritoneal dialysis (PD) [1]. The Peritoneal Equilibration Test (PET), widely used to clinically assess PM function, primarily evaluates creatinine transport but may overlook distinct membrane response patterns. Aminothiols such as cysteine (Cys), homocysteine (HCys), cysteinylglycine (CysGly), and glutathione (GSH), a th...


Metabolism-targeted therapy in NSCLC – A new theranostics inhalation approach u...

Mendes, Cindy; Martins, Filipa; Granja, Sara; Gonçalves, Joana; Barros, Hélio; Casimiro, Teresa; Ricardo, Ana Aguiar; Silva, Fernanda; Abreu, Bruna

Lung cancer is one of the most lethal cancers globally, primarily due to delayed diagnosis and lack of specific and effective therapy. Increased lactate production and consumption, along with cysteine metabolic reliance, are features identified in NSCLC in our recent studies. Cancer metabolic remodeling leads to excessive ROS production, triggering oxidative stress, promoting angiogenesis, causing cellular and ...


Metabolism-targeted therapy in NSCLC – A new theranostics inhalation approach u...

Mendes, Cindy; Martins, Filipa; Granja, Sara; Gonçalves, Joana; Barros, Hélio; Casimiro, Teresa; Aguiar-Ricardo, Ana; Silva, Fernanda; Abreu, Bruna

Lung cancer is one of the most lethal cancers globally, primarily due to delayed diagnosis and lack of specific and effective therapy. Increased lactate production and consumption, along with cysteine metabolic reliance, are features identified in NSCLC in our recent studies. Cancer metabolic remodeling leads to excessive ROS production, triggering oxidative stress, promoting angiogenesis, causing cellular and ...


Fighting polymicrobial biofilms in bacterial vaginosis

Sousa, Lúcia Filipa Guimarães Vieira; Pereira, Sofia A.; Cerca, Nuno

Bacterial vaginosis (BV) is the most common cause of vaginal discharge and is often associated with other health consequences mainly in pregnant women. BV is described by an imbalance in the vaginal microbiota where strictly and facultative anaerobic bacteria outgrow the lactic acid- and hydrogen peroxide-producing Lactobacillus species. The species involved in BV are capable to grow and form a polymicrobial bi...


Cysteine as a Multifaceted Player in Kidney, the Cysteine-Related Thiolome and ...

Correia, Maria João; Pimpão, António B.; Fernandes, Dalila G.F.; Morello, Judit; Sequeira, Catarina O.; Calado, Joaquim; Antunes, Alexandra M.M.

In this review encouraged by original data, we first provided in vivo evidence that the kidney, comparative to the liver or brain, is an organ particularly rich in cysteine. In the kidney, the total availability of cysteine was higher in cortex tissue than in the medulla and distributed in free reduced, free oxidized and protein-bound fractions (in descending order). Next, we provided a comprehensive integrated...


The 2-hydroxy-nevirapine metabolite as a candidate for boosting apolipoprotein ...

Marinho, Aline T.; Batuca, Joana R.; Miranda, Joana P.; Caixas, Umbelina; Dias, Clara G.; Branco, Teresa; Soto, Karina; Pinheiro, Pedro

The antiretroviral nevirapine (NVP) is associated to a reduction of atherosclerotic lesions and increases in high-density lipoprotein (HDL)-cholesterol. Despite being a hepatotoxic drug, which forbids its re-purposing to other therapeutic areas, not all NVP metabolites have the same potential to induce toxicity. Our aim was to investigate the effects of NVP and its metabolites in an exploratory study, towards t...


Targeting Glutathione and Cystathionine β-Synthase in Ovarian Cancer Treatment ...

Santos, Inês; Ramos, Cristiano; Mendes, Cindy; Sequeira, Catarina O.; Tomé, Catarina S.; Fernandes, Dalila G. H.; Mota, Pedro; Pires, Rita F.

Ovarian cancer is the main cause of death from gynecological cancer, with its poor prognosis mainly related to late diagnosis and chemoresistance (acquired or intrinsic) to conventional alkylating and reactive oxygen species (ROS)-generating drugs. We and others reported that the availability of cysteine and glutathione (GSH) impacts the mechanisms of resistance to carboplatin in ovarian cancer. Different playe...


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