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Research Interests: Treatment, Adolescent, Portugal, Pregnancy, Humans, and 14 moreFemale, High Performance Liquid Chromatography, High Pressure Liquid Chromatography, Newborn Infant, Adult, Alanine Aminotransferase, Pregnant Women, Study design, Seasons, Neonatal Intrahepatic Cholestasis, Reference Values, Early Diagnosis, Pregnancy Outcome, and Liver function tests
Research Interests: Cognitive Science, Calcium, Oxidative Stress, Western blotting, Free Radical, and 24 moreBrain, ATPase, Reactive Oxygen Species, Animals, Male, Cell Death, Glutathione, Membrane Lipids, Bilirubin, Lipid Oxidation, Lipid peroxidation, Calcium Homeostasis, Fluorescent probes, Neocortex, SYNAPTOSOMES, Membrane Protein, Neurosciences, Oxidation-Reduction, Intracellular Space, Intracellular Calcium, Protein Oxidation, Hyperbilirubinemia, Brain injuries, and Cell Membrane
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Multidrug resistance (MDR), whereby cancer cells become resistant to the cytotoxic effects of various structurally and mechanistically unrelated chemotherapeutic agents, is a major problem in the clinical treatment of cancer.... more
Multidrug resistance (MDR), whereby cancer cells become resistant to the cytotoxic effects of various structurally and mechanistically unrelated chemotherapeutic agents, is a major problem in the clinical treatment of cancer. P-glycoprotein (P-gp) is a transmembrane protein responsible for drug efflux, which decreases drug intracellular bioavailability, consequently decreasing their efficacy against cancer. Solid Lipid Nanoparticles (SLNs) have not only the ability to protect the entrapped drug against proteolytic degradation, but also allow a selective intracellular targeting. Hypothetically, the entrapped drug enter the target cells by different uptake mechanisms, "nanocitose", as compared to the free drug and may evade efflux-transporters, like P-gp. The functional role of P-gp in limiting the permeability of the anticancer drug paclitaxel (Ptx) was assessed in MDA-MB-436 cells. The observed increase in the pharmacologic efficacy of drug entrapped in SLN relatively to t...
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This article brings the choroid plexus into the context of health and disease. It is remarkable that the choroid plexus, composed by the monolayer of epithelial cells that lie in a highly vascularized stroma, floating within the brain... more
This article brings the choroid plexus into the context of health and disease. It is remarkable that the choroid plexus, composed by the monolayer of epithelial cells that lie in a highly vascularized stroma, floating within the brain ventricles, gets so little attention in major physiology and medicine text books and in the scientific literature in general. Consider that it is responsible for producing most of the about 150mL of cerebrospinal fluid that fills the brain ventricles and the subarachnoid space and surrounds the spinal cord in the adult human brain, which is renewed approximately 2-3 times daily. As such, its activity influences brain metabolism and function, which will be addressed. Reflect that it contains an impressive number of receptors and transporters, both in the apical and basolateral sides of the epithelial cells, and as such is a key structure for the communication between the brain and the periphery. This will be highlighted in the context of neonatal jaundi...
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Research Interests:
The expression of CD44 tags cells with stemness-associated properties (cancer initiating cells or cancer stem cells - CSC). This membrane glycoprotein with a cytoplasmic domain indirectly associated with the cellular cytoskeleton, has a... more
The expression of CD44 tags cells with stemness-associated properties (cancer initiating cells or cancer stem cells - CSC). This membrane glycoprotein with a cytoplasmic domain indirectly associated with the cellular cytoskeleton, has a crucial role in tumorigenesis. The CD44 receptor enables the cell to respond to changes in tumor microenvironment, promoting several signaling events related to tumor initiation, progression and fixation in distant host tissues. Although the contribution of this transmembrane protein in gene regulation remains unclear, its overexpression in adenocarcinomas, mostly supported by microRNA (miR)-mediated upregulation of target mRNA, is widely accepted. Herein, we gather the evidence that CD44 is one of the most predominant markers of malignant cells and may be found in diverse phenotypes associated with tumor progression. Additionally, CD44 tumor receptors were found to have different roles at a transcriptional level. Thus, innovative therapeutic strategies should rely heavily on its metastasis-promoting ability. Furthermore, the concept of selectively targeting cell sub-populations may be used to develop specific therapeutic and/or diagnostic systems. An approach based on targeting CD44(+) cells might provide a strategy to design guided-therapeutic systems against multiple malignant cells including putative CSC.
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Research Interests:
Research Interests: Engineering, Physics, Chemistry, Biology, Membrane Proteins, and 20 moreTransmission Electron Microscopy, Mitochondria, Apoptosis, Medicine, Multidisciplinary, Brain, Endothelial Cells, Blood brain barrier, Animals, P-glycoprotein, Beta-Catenin, Bilirubin, Astrocytes, PLoS one, Lipopolysaccharides, Rats, Claudin, Microvessels, Claudins, and Cell membrane permeability
The blood-brain barrier (BBB) is a complex and dynamic structure that plays a key role in central nervous system (CNS) homeostasis. It strictly regulates the entrance of molecules into the brain parenchyma and prevents the access of... more
The blood-brain barrier (BBB) is a complex and dynamic structure that plays a key role in central nervous system (CNS) homeostasis. It strictly regulates the entrance of molecules into the brain parenchyma and prevents the access of neurotoxins and pathogens while promoting the efflux of several molecules. The brain microvascular endothelial cells are the anatomical basis of the BBB, which has unique characteristics such as the elaborate junctional complexes that nearly obliterate the intercellular space as well as the presence of influx and efflux transporters. Endothelial cells establish important interactions with glial cells, neurons, and perivascular pericytes as well as with the acellular components of the basement membrane, which together constitute the neurovascular unit. BBB disruption has been reported in a wide range of CNS pathologies, with an emerging role in the onset and disease progression. Accordingly, recent studies revealed vascular dysfunction in neonatal jaundice, a common pathology in the early neonatal period affecting 1/10 children presenting values of total bilirubin>17 mg/dL (291 μM). Here we summarize the clinical aspects of moderate to severe neonatal jaundice and provide a comprehensive review of the literature regarding bilirubin-induced neurotoxicity from a vascular-centered approach. The collected evidence place endothelial dysfunction and pericyte demise as key players in the disruption of CNS homeostasis, mainly in cases of lasting hyperbilirubinemia, thus pointing to novel targets to prevent neurological dysfunction due to severe neonatal jaundice.
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Research Interests: Pediatric Neurology, Brain, Humans, Female, Male, and 3 moreKernicterus, Neurosciences, and Premature Birth
The expression of CD44 tags cells with stemness-associated properties (cancer initiating cells or cancer stem cells - CSC). This membrane glycoprotein with a cytoplasmic domain indirectly associated with the cellular cytoskeleton, has a... more
The expression of CD44 tags cells with stemness-associated properties (cancer initiating cells or cancer stem cells - CSC). This membrane glycoprotein with a cytoplasmic domain indirectly associated with the cellular cytoskeleton, has a crucial role in tumorigenesis. The CD44 receptor enables the cell to respond to changes in tumor microenvironment, promoting several signaling events related to tumor initiation, progression and fixation in distant host tissues. Although the contribution of this transmembrane protein in gene regulation remains unclear, its overexpression in adenocarcinomas, mostly supported by microRNA (miR)-mediated upregulation of target mRNA, is widely accepted. Herein, we gather the evidence that CD44 is one of the most predominant markers of malignant cells and may be found in diverse phenotypes associated with tumor progression. Additionally, CD44 tumor receptors were found to have different roles at a transcriptional level. Thus, innovative therapeutic strategies should rely heavily on its metastasis-promoting ability. Furthermore, the concept of selectively targeting cell sub-populations may be used to develop specific therapeutic and/or diagnostic systems. An approach based on targeting CD44(+) cells might provide a strategy to design guided-therapeutic systems against multiple malignant cells including putative CSC.
Research Interests:
Research Interests: Neurobiology Of Disease, Cytokines, Inflammation, Neurobiology, Gene expression, and 28 moreWestern blotting, Neuronal cell death, Inflammatory Immune Response, NO, Animals, Microglia, NF-kappa B, Bilirubin, Brain injury, Mitogen Activated Protein Kinase, Pi, Clinical Sciences, NMDA, IL, Rats, Phagocytosis, PBS, MMP, Matrix Metalloproteinases, Wistar Rats, MAPK, Primary Culture, Kernicterus, SDS PAGE, Neurosciences, Matrix Metalloproteinase, Inflammatory response, and Pro-Inflammatory Cytokine
Research Interests: Neurobiology Of Disease, Drug interactions, Neurobiology, Antioxidants, Pregnancy, and 20 moreCerebral Cortex, Reactive Oxygen Species, Female, Animals, Cell Death, Glutathione, Astrocyte, Bilirubin, Neurons, Astrocytes, Lipid peroxidation, Clinical Sciences, Rats, Neuronal Death, Oxidative Damage, Wistar Rats, N-Acetylcysteine, Neurosciences, Oxidation-Reduction, and Protein Oxidation
Research Interests: Electrophysiology, Neurochemistry, Enzyme Inhibitors, Mitochondria, Apoptosis, and 20 moreCrisis, In Vitro, Cell Differentiation, Pregnancy, Humans, Cerebral Cortex, Female, Animals, Cell Death, Cytochrome c oxidase, Mitochondrial Respiratory Chain, Glycolysis, Bilirubin, Neurons, Apoptose, Rats, Rat, Wistar Rats, Neurosciences, and Neuroprotective Agents
Jaundice and sepsis are common neonatal conditions that can lead to neurodevelopment sequelae, namely if present at the same time. We have reported that tumor necrosis factor (TNF)-α and interleukin (IL)-1β are produced by cultured... more
Jaundice and sepsis are common neonatal conditions that can lead to neurodevelopment sequelae, namely if present at the same time. We have reported that tumor necrosis factor (TNF)-α and interleukin (IL)-1β are produced by cultured neurons and mainly by glial cells exposed to unconjugated bilirubin (UCB). The effects of these cytokines are mediated by cell surface receptors through a nuclear factor (NF)-κB-dependent pathway that we have showed to be activated by UCB. The present study was designed to evaluate the role of TNF-α and IL-1β signaling on astrocyte reactivity to UCB in rat cortical astrocytes. Exposure of astrocytes to UCB increased the expression of both TNF-α receptor (TNFR)1 and IL-1β receptor (IL-1R)1, but not TNFR2, as well as their activation, observed by augmented binding of receptors' molecular adaptors, TRAF2 and TRAF6, respectively. Silencing of TNFR1, using siRNA technology, or blockade of IL-1β cascade, using its endogenous antagonist, IL-1 receptor antagonist (IL-1ra), prevented UCB-induced cytokine release and NF-κB activation. Interestingly, lack of TNF-α signal transduction reduced UCB-induced cell death for short periods of incubation, although an increase was observed after extended exposure; in contrast, inhibition of IL-1β cascade produced a sustained blockade of astrocyte injury by UCB. Together, our data show that inflammatory pathways are activated during in vitro exposure of rat cortical astrocytes to UCB and that this activation is prolonged in time. This supports the concept that inflammatory pathways play a role in brain damage by UCB, and that they may represent important pharmacological targets.