NMS: iNOVA4Health - Artigos em revista nacional com arbitragem científica
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- The Hidden Link Between Gut Microbiota and Vascular Dysfunction in DiabetesPublication . Macedo, Luana Rodrigues; de Oliveira, Rita M; iNOVA4Health - pólo NMS; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Recent diabetes research has unveiled novel pathways offering potential therapeutic interventions to slow the disease’s progression and alleviate associated health complications. Particularly, advancements in high-throughput multi-omics technologies over the past two decades have spotlighted the gut microbiota, a rich ecosystem of microorganisms in the digestive tract, as a pivotal area of study. This body of research has established a link between dysbiosis, an imbalance in these microbial communities, and various diseases, including metabolic disorders. This review focuses on the crucial role of the gut microbiota in obesity and diabetes, highlighting its emergence as a promising target for treatment strategies. By detailing the alterations in gut microbiota and associated metabolites in obesity and diabetes, along with the therapeutic potential of fecal microbiota transplantation in these diseases, we underscore the complexity and potential of targeting these microbial communities for health benefits. As we look to the future, the importance of translating this knowledge into clinical applications becomes paramount, setting the stage for innovative treatments that harness the power of the gut microbiota to combat diabetes and other metabolic diseases.
- Cold-Induced Skin Perfusion Adaptive ResponsesPublication . Caetano, Joana; Caetano, Joana; de la Villa Polo, Pedro; DE LA VILLA, PEDRO; Alves, José Delgado; Delgado Alves, José; Rodrigues, Luís Monteiro; L, Monteiro Rodrigues; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); iNOVA4Health - pólo NMS; ALIESIce cooling exposure (ICE) is an interesting, but little explored, technique used to examine human peripheral microcirculatory adaptive mechanisms. In this study, we compare in vivo perfusion changes assessed by laser Doppler flowmetry (LDF) during post-occlusive reactive hyperemia (POHR) and ICE procedures. Eleven healthy women, 29.3±7.3 years old, were selected and sequentially submitted to PORH and ICE procedures in one randomly selected upper limb. Blood perfusion and skin temperature were continuously measured in both hands during baseline (phase I) challenge (phase II) and recovery (phase III). Procedures respected all clinical research principles and were previously submitted to the institutional ethics committee. PORH and ICE evoked significant decreases in skin perfusion in phase II followed by reperfusion in the intervention limb, although with different velocities. Similar significant responses were obtained in the contralateral limbs. Correlation among variables could not be found, except between LDF and temperature signals across phases. Results suggest that ICE is better tolerated than POHR when used with the same objective. More studies are needed to confirm if reflexes elicited by these approaches are equivalent and equally suitable for application in vascular medicine.
- Metabolic profiling and combined therapeutic strategies unveil the cytotoxic potential of selenium-chrysin (SeChry) in NSCLC cellsPublication . Mendes, Cindy; Lemos, Isabel; Hipólito, Ana; Abreu, Bruna; Freitas-Dias, Catarina; Martins, Filipa; Pires, Rita F.; Barros, Hélio; Bonifácio, Vasco D.B.; Gonçalves, Luís G.; Serpa, Jacinta; Serpa, Jacinta; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); iNOVA4Health - pólo NMS; Instituto de Tecnologia Química e Biológica António Xavier (ITQB); Portland PressLung cancer ranks as the predominant cause of cancer-related mortalities on a global scale. Despite progress in therapeutic interventions, encompassing surgical procedures, radiation, chemotherapy, targeted therapies and immunotherapy, the overall prognosis remains unfavorable. Imbalances in redox equilibrium and disrupted redox signaling, common traits in tumors, play crucial roles in malignant progression and treatment resistance. Cancer cells, often characterized by persistent high levels of reactive oxygen species (ROS) resulting from genetic, metabolic, and microenvironmental alterations, counterbalance this by enhancing their antioxidant capacity. Cysteine availability emerges as a critical factor in chemoresistance, shaping the survival dynamics of non-small cell lung cancer (NSCLC) cells. Selenium-chrysin (SeChry) was disclosed as a modulator of cysteine intracellular availability. This study comprehensively characterizes the metabolism of SeChry and investigates its cytotoxic effects in NSCLC. SeChry treatment induces notable metabolic shifts, particularly in selenocompound metabolism, impacting crucial pathways such as glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. Additionally, SeChry affects the levels of key metabolites such as acetate, lactate, glucose, and amino acids, contributing to disruptions in redox homeostasis and cellular biosynthesis. The combination of SeChry with other treatments, such as glycolysis inhibition and chemotherapy, results in greater efficacy. Furthermore, by exploiting NSCLC’s capacity to consume lactate, the use of lactic acid-conjugated dendrimer nanoparticles for SeChry delivery is investigated, showing specificity to cancer cells expressing monocarboxylate transporters.
- Cathepsin DPublication . Gallwitz, Lisa; Schmidt, Lina; Marques, André R.A.; Tholey, Andreas; Cassidy, Liam; Ulku, Irem; Multhaup, Gerhard; Di Spiezio, Alessandro; Saftig, Paul; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); iNOVA4Health - pólo NMS; ElsevierProteolysis catalyzed by the major lysosomal aspartyl protease cathepsin-D (CTSD) appears to be of pivotal importance for proteostasis within the central nervous system and in neurodegeneration. Neuronal Ceroid Lipofuscinosis (NCL) type 10 is caused by a lack of CTSD leading to a defective autophagic flow and pathological accumulation of proteins. We previously demonstrated a therapeutic-relevant clearance of protein aggregates after dosing a NCL10 mouse model with recombinant human pro-cathepsin-D (proCTSD). Similar results could be achieved in cells and mice accumulating α-synuclein. Prompted by these positive effects and our in vitro findings showing that cathepsin-D can cleave the Alzheimer's Disease (AD)-causing amyloid beta peptides (Aβ), we envisaged that such a treatment with proCTSD could similarly be effective in clearance of potentially toxic Aβ species. We demonstrated that CTSD is able to cleave human Aβ1–42 by using liquid chromatography-mass spectrometry. Intracerebral dosing of proCTSD in a NCL10 (CTSD knockout) mouse model revealed uptake and processing of CTSD to its mature and active form. However, the re-addition of CTSD did not obviously affect intracellular APP processing or the generation of soluble APP and Aβ-species. ProCTSD treated HEK cells in comparison with untreated cells were found to contain comparable levels of soluble and membrane bound APP and Aβ-species. Also, the early intracranial application (P1 and P20) of proCTSD in the 5xFAD mouse model did not change Aβ pathology, plaque number and plaque composition and neuroinflammation, however we observed an increased level of Aβ1–42 in the CSF. Our data confirm proteolytic cleavage of human Aβ1–42 by CTSD but exclude a prominent role of CTSD in APP processing and Aβ degradation in our in vitro and in vivo models.