Publications by authors named "Maria Joao Ramalho"

Article Synopsis
  • In Alzheimer's disease, amyloid beta (Aβ) triggers the cleavage of the TrkB-FL receptor, disrupting essential BDNF signaling that is crucial for neuron health and function.
  • Researchers found that TrkB-FL cleavage occurs early in the disease and worsens with increased pathology, using human samples and cerebrospinal fluid for their studies.
  • They developed a TAT-TrkB peptide that successfully prevents TrkB-FL cleavage, showing potential in improving cognitive function and synaptic issues in a mouse model of Alzheimer's, indicating it could be a safe and effective treatment option.
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Glioblastoma (GBM) conventional treatment is not curative, and it is associated with severe toxicity. Thus, natural compounds with anti-cancer properties and lower systemic toxicity, such as gallic acid (GA), have been explored as alternatives. However, GA's therapeutic effects are limited due to its rapid metabolism, low bioavailability, and low permeability across the blood-brain barrier (BBB).

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Glioblastoma (GBM) is a highly deadly brain tumor that does not respond satisfactorily to conventional treatment. The non-alkylating agent gemcitabine (GEM) has been proposed for treating GBM. It can overcome MGMT protein-mediated resistance, a major limitation of conventional therapy with the alkylating agent temozolomide (TMZ).

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Glioblastoma (GBM) represents almost half of primary brain tumors, and its standard treatment with the alkylating agent temozolomide (TMZ) is not curative. Treatment failure is partially related to intrinsic resistance mechanisms mediated by the O6-methylguanine-DNA methyltransferase (MGMT) protein, frequently overexpressed in GBM patients. Clinical trials have shown that the anticancer agent bortezomib (BTZ) can increase TMZ's therapeutic efficacy in GBM patients by downregulating MGMT expression.

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Bortezomib (BTZ) is a potent proteasome inhibitor currently being used to treat multiple myeloma. However, its high toxicity and resistance to therapy severely limit the treatment outcomes. Drug-membrane interactions have a crucial role in drugs' behavior in vivo, affecting their bioavailability and pharmacological activity.

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Introduction: Glioblastoma multiforme (GBM) is the deadliest type of brain cancer with poor response to the available therapies, mainly due to intrinsic resistance mechanisms. Chemotherapy is based on alkylating agents, but DNA-repair mechanisms can revert this cytotoxic effect. O-methylguanine-DNA methyltransferase (MGMT) protein is the primary mechanism for GBM resistance.

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Clinically available medications face several hurdles that limit their therapeutic activity, including restricted access to the target tissues due to biological barriers, low bioavailability, and poor pharmacokinetic properties. Drug delivery systems (DDS), such as nanoparticles (NPs) and hydrogels, have been widely employed to address these issues. Furthermore, the DDS improves drugs' therapeutic efficacy while reducing undesired side effects caused by the unspecific distribution over the different tissues.

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Aims: Glioblastoma (GBM) is the most common and deadliest type of brain cancer, and the current therapeutic options are not curative, imposing the need for novel strategies. Asiatic acid (AA) is a natural compound and has been explored due to its anti-glioma activity and lower toxicity to healthy tissues compared with conventional chemotherapeutic agents. However, its poor water-solubility is an obstacle for clinical application.

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Glioblastoma multiforme (GBM) is the most common and lethal type of brain tumor, and the clinically available approaches for its treatment are not curative. Despite the intensive research, biological barriers such as the blood-brain barrier (BBB) and tumor cell membranes are major obstacles to developing novel effective therapies. Nanoparticles (NPs) have been explored as drug delivery systems (DDS) to improve GBM therapeutic strategies.

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The long lifespan of the world's population has been raising interest in the research for new solutions to delay the aging process. With the aim of skin aging prevention, solid lipid nanoparticles (SLNs) were developed in this work for the encapsulation of three lipophilic natural compounds extracted from vine cane-epigallocatechin gallate (EGCG), resveratrol and myricetin. The developed loaded-SLNs proved to be stable, maintaining their adequate physicochemical characteristics for 30 days.

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Oxidative stress, triggered by UV radiation, is one of the major causes of free radical-associated disorders, such as skin cancer. The application of natural compounds (NCs) with antioxidant effects can attenuate free radicals' accumulation and, therefore, provide a strategy for skin care and cancer prevention. In this work, three natural compounds, naringenin, nordihydroguaiaretic acid (NDGA), and kaempferol, were encapsulated into nanostructured lipid carriers (NLCs) aiming for the development of a formulation for cutaneous application with antioxidant properties.

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Terbutaline sulphate (TS) is a selective short-acting β adrenoceptor agonist used for asthma treatment. The pharmacological activity of TS depends on its binding to the transmembrane protein, β adrenoceptor. Thus, the interactions of this drug with biological membranes are expected, affecting its pharmacological activity.

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Vitamin B12 (VB12) deficiency is one of the most common malnutrition problems worldwide and is related to its poor bioavailability. The lipid composition of cell membranes and molecule-cell membrane lipid interactions are major factors affecting the bioavailability of nutrients. So, the study of these interactions may allow predicting the behavior of VB12 at cellular membranes and the effects on its activity.

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Alzheimer's disease (AD) is a form of dementia with high impact worldwide, accounting with more than 46 million cases. It is estimated that the number of patients will be four times higher in 2050. The initial symptoms of AD are almost imperceptible and typically involve lapses of memory in recent events.

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Poly(d,l-lactic--glycolic) (PLGA) nanoparticles (NPs) have been widely studied for several applications due to their advantageous properties, such as biocompatibility and biodegradability. Therefore, these nanocarriers could be a suitable approach for glioblastoma multiforme (GBM) therapy. The treatment of this type of tumours remains a challenge due to intrinsic resistance mechanisms.

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Alzheimer's Disease (AD) is a neurodegenerative disorder related with the increase of age and it is the main cause of dementia in the world. AD affects cognitive functions, such as memory, with an intensity that leads to several functional losses. The continuous increase of AD incidence demands for an urgent development of effective therapeutic strategies.

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Temozolomide (TMZ) is the first-line treatment for Glioblastoma Multiforme (GBM). After administration, TMZ is rapidly converted into its active metabolite (MTIC). However, its pharmacological activity is reduced due MTIC low bioavailability in the brain.

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Resveratrol (RES) is a natural polyphenolic non-flavonoid compound present in grapes, mulberries, peanuts, rhubarb and in several other plants. Numerous health effects have been related with its intake, such as anti-carcinogenic, anti-inflammatory and brain protective effects. The neuroprotective effects of RES in neurological diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases, are related to the protection of neurons against oxidative damage and toxicity, and to the prevention of apoptotic neuronal death.

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