A5089308827- Mesenchymal stem cell research
- Spinal Cord Injury Research
- Genetic Neurodegenerative Diseases
- Neurogenesis and neuroplasticity mechanisms
- Prion Diseases and Protein Misfolding
- Nerve injury and regeneration
- Alzheimer's disease research and treatments
- Carbohydrate Chemistry and Synthesis
- Fungal Infections and Studies
- Tissue Engineering and Regenerative Medicine
- Mycobacterium research and diagnosis
- Dendrimers and Hyperbranched Polymers
- Ubiquitin and proteasome pathways
- Advanced biosensing and bioanalysis techniques
- Electrospun Nanofibers in Biomedical Applications
- RNA Interference and Gene Delivery
- Mitochondrial Function and Pathology
- Biochemical and Molecular Research
- Antifungal resistance and susceptibility
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Glycosylation and Glycoproteins Research
- Hepatitis Viruses Studies and Epidemiology
- Fungal and yeast genetics research
- Cervical and Thoracic Myelopathy
- Autoimmune Neurological Disorders and Treatments
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2015-2025
Universidade do Porto
2013-2019
University of Minho
2009-2015
Instituto de Biologia Molecular e Celular
2014
Universidade de São Paulo
2000
Abstract A novel four-step pathway identified recently in mycobacteria channels trehalose to glycogen synthesis and is also likely involved the biosynthesis of two other crucial polymers: intracellular methylglucose lipopolysaccharides exposed capsular glucan. The structures three intervening enzymes - GlgB, GlgE TreS were reported, providing first templates for rational drug design. Here we describe structural characterization fourth enzyme pathway, mycobacterial maltokinase (Mak),...
Abstract Introduction It is hypothesized that administration of stromal/stem cells isolated from the adipose tissue (ASCs) and umbilical cord (HUCPVCs) can ameliorate injured central nervous system (CNS). still not clear, however, whether they have similar or opposite effects on primary cultures neuronal populations. The objective present work was to determine if ASCs HUCPVCs preferentially act, not, specific cell populations within CNS. Methods Primary hippocampal neurons were exposed...
Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) has been shown to ameliorate the injured central nervous system (CNS). Although these effects were initially attributed putative differentiation MSCs towards neural lineage, it is now known that most them are mediated by secretome. Up in vitro reports have dealt with secretome on and their differentiation. Consequently, there a lack information regarding role viability survival pre-existent matured differentiated cell...
Spinal cord injury (SCI) leads to devastating neurological deficits. Several tissue engineering (TE)‐based approaches have been investigated for repairing this condition. Poly (3‐hydroxybutyrate‐ co ‐3‐hydroxyvalerate) (PHB‐HV) is found be particularly attractive TE applications due its properties, such as biodegradability, biocompatibility, thermoplasticity and piezoelectricity. Hence, report addresses the development characterization of PHB‐HV‐based 3D scaffolds, produced by freeze‐drying,...
Expansion of polyglutamine stretches leads to the formation polyglutamine-containing neuronal aggregates and death in nine diseases for which there currently are no treatments or cures. This is largely due a lack understanding mechanisms by expanded regions contribute aggregation disease. To complicate matters further, several polyglutamine-disease related proteins, including ataxin-3, have multistage mechanism flanking domain self-assembly precedes yet influenced expansion. How expansion...
Spinocerebellar ataxia type 3 (SCA3) is a rare inherited neurodegenerative disease caused by the expansion of polyglutamine repeat in protease ataxin-3 (Atx3). Despite extensive knowledge downstream pathophysiology, no disease-modifying therapies are currently available to halt progression. The accumulation protein inclusions enriched polyQ-expanded Atx3 neurons suggests that inhibiting its self-assembly may yield targeted therapeutic approaches. Here it shown supramolecular tweezer, CLR01,...
It has been recently reported that mesenchymal progenitor/stem cells isolated from the Wharton's Jelly (WJ) of umbilical cords (UC) ameliorate condition animals suffering central nervous system (CNS)-related conditions. However, little is known on mechanisms regulate these actions. Therefore, objective present work was to determine how conditioned media (CM) a population progenitors in UC WJ, as human cord perivascular (HUCPVCs), processes such cell viability, survival, and proliferation...
Abstract The applicability of CMCht/PAMAM dendrimer nanoparticles for CNS applications was investigated. AFM and TEM observations revealed that the possessed a nanosphere‐like shape with size from 22.0 to 30.7 nm. could be bound fluorescent‐probe FITC tracing purposes. Post‐natal hippocampal neurons cortical glial cells were both able internalize FITC‐labeled high efficiency. percentage positive internalizing varied, reaching peak after 48 h incubation. Further experiments periods up 7 d...
Spine stabilization upon spinal cord injury (SCI) is a standard procedure in clinical practice, but rarely employed experimental models. Moreover, the application of biodegradable biomaterials for this would come as an advantage it eliminate presence nondegradable prosthesis within vertebral bone. Therefore, present work, we propose use new device specifically developed spine rat model SCI. A 3D scaffold based on blend starch with polycaprolactone was implanted, replacing delaminated...
Protein degradation is essential for maintaining cellular homeostasis. The proteasome the central enzyme responsible non-lysosomal protein in eukaryotic cells. Although assembly not yet completely understood, a number of cofactors required proper and maturation have been identified. Ump short-lived factor efficient biogenesis 20S proteasome. Upon association two precursor complexes, encased rapidly degraded after proteolytic sites interior nascent are activated. In order to further...
The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2- advanced/metastatic breast cancer (mBC). However, impact CDK4/6i on circulating immune cells and tumor (CTCs) in patients receiving ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 ER+/HER2- mBC treated CDK4/6i+ET either first or second line. Peripheral blood samples...
Carboxymethylchitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles, comprised of a PAMAM core grafted with chains CMCht, have recently been proposed for intracellular drug delivery. In previous reports, these nanoparticles had lower levels cytotoxicity when compared traditional dendrimers. this study, the short-term in vivo biodistribution fluorescein isothiocyanate (FITC)-labeled CMCht/PAMAM after intravenous (IV) injections Wistar Han rats was determined. The brain, liver,...
Abstract Mycobacteria synthesize unique intracellular methylglucose lipopolysaccharides (MGLP) proposed to modulate fatty acid metabolism. In addition the partial esterification of glucose or units with short-chain acids, octanoate was invariably detected on MGLP reducing end. We have identified a novel sugar octanoyltransferase (OctT) that efficiently transfers glucosylglycerate (GG) and diglucosylglycerate (DGG), earliest intermediates in biosynthesis. Enzymatic studies, synthetic...
Abstract Amyloid fibrils and soluble oligomers are two types of protein aggregates associated with neurodegeneration. Classic therapeutic strategies try to prevent the nucleation spread amyloid fibrils, whilst diffusible have emerged as promising drug targets affecting downstream pathogenic processes. We developed a generic aggregation model validate it against measured compositions fibrillar non‐fibrillar assemblies ataxin‐3, implicated in Machado–Joseph disease. The derived analytic...
ABSTRACT The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate concentrate these multiple cellular components, ensuring concerted function. Similarly all other positive-strand viruses, picornaviruses induce rearrangements host intracellular membranes create structures that act as functional scaffolds for genome replication. membrane-targeting proteins 2B 2C, their precursor 2BC, protein 3A appear be primarily involved in...
Spinal cord injury (SCI) leads to drastic alterations on the quality of life afflicted individuals. With advent Tissue Engineering and Regenerative Medicine where approaches combining biomaterials, cells growth factors are used, one can envisage novel strategies that adequately tackle this problem. The objective study was evaluate a blend starch with poly(ε-caprolactone) (SPCL) aimed be used for development scaffolds spinal repair. SPCL linear parallel filaments were deposited polystyrene...
Drug discovery frequently relies on the kinetic analysis of physicochemical reactions that are at origin disease state. Amyloid fibril formation has been extensively investigated in relation to prevalent and rare neurodegenerative diseases, but thus far no therapeutic solution directly arisen from this knowledge. Other aggregation pathways producing smaller, hard-to-detect soluble oligomers increasingly appointed as main reason for cell toxicity cell-to-cell transmissibility. Here we show...
Abstract Amyloid fibrils and soluble oligomers are two types of protein aggregates associated with neurodegeneration. Classic therapeutic strategies try to prevent the nucleation spread amyloid fibrils, whilst diffusible have emerged as promising drug targets affecting downstream pathogenic processes. We developed a generic aggregation model validate it against measured compositions fibrillar non‐fibrillar assemblies ataxin‐3, implicated in Machado–Joseph disease. The derived analytic...
Despite the research efforts of decades, Mycobacterium tuberculosis is still in origin 1.3 million deaths annually (WHO, Tuberculosis, 2013) and estimated to infect 2 billion people worldwide. The currently available antimicrobial therapies are aimed at only a few molecular targets growing number strains resistant multiple drugs drives an urgent need for identification novel pathways new points therapeutic intervention. Although sequence M. genome has been known more than decade, there no...