Fourier Transform Infrared Spectroscopy Analysis as a Tool to Address Aβ Impact on Extracellular Vesicles.

Alzheimer's disease is a challenge in modern healthcare due to its complex etiology and increasing prevalence. Despite advances, further understanding of Alzheimer's disease pathophysiology is needed, particularly the role of Aβ neurotoxic peptide. Fourier transform infrared spectroscopy (FTIR) has shown potential as a screening tool for several pathologies, including Alzheimer's disease.

Regional distribution of polymorphisms associated to the disease-causing gene of spinocerebellar ataxia type 3.

Introduction: Knowledge about the distribution and frequency of the respective haplotypes on the wildtype and mutant allele is highly relevant in the context of future gene therapy clinical studies in Spinocerebellar Ataxia Type 3, the most common autosomal dominantly inherited ataxia. Single nucleotide polymorphisms associated to the disease-causing gene, ATXN3, have been determined. We wanted to investigate the frequency and regional distribution of two intragenic single nucleotide polymorphisms (SNPs) in a large European SCA3 cohort and their relation to the clinical phenotype.

Mannose and Lactobionic Acid in Nasal Vaccination: Enhancing Antigen Delivery via C-Type Lectin Receptors.

Background/objectives: Nasal vaccines are a promising strategy for enhancing mucosal immune responses and preventing diseases at mucosal sites by stimulating the secretion of secretory IgA, which is crucial for early pathogen neutralization. However, designing effective nasal vaccines is challenging due to the complex immunological mechanisms in the nasal mucosa, which must balance protection and tolerance against constant exposure to inhaled pathogens. The nasal route also presents unique formulation and delivery hurdles, such as the mucous layer hindering antigen penetration and immune cell access.

Brain-targeted drug delivery - nanovesicles directed to specific brain cells by brain-targeting ligands.

Neurodegenerative diseases are characterized by extensive loss of function or death of brain cells, hampering the life quality of patients. Brain-targeted drug delivery is challenging, with a low success rate this far. Therefore, the application of targeting ligands in drug vehicles, such as lipid-based and polymeric nanoparticles, holds the promise to overcome the blood-brain barrier (BBB) and direct therapies to the brain, in addition to protect their cargo from degradation and metabolization.

Isolation of Adeno-associated Viral Vectors Through a Single-step and Semi-automated Heparin Affinity Chromatography Protocol.

Adeno-associated virus (AAV) has become an increasingly valuable vector for in vivo gene delivery and is currently undergoing human clinical trials. However, the commonly used methods to purify AAVs make use of cesium chloride or iodixanol density gradient ultracentrifugation. Despite their advantages, these methods are time-consuming, have limited scalability, and often result in vectors with low purity.

FTIR Spectroscopy and Blood-Derived Extracellular Vesicles Duo in Alzheimer's Disease.

Background: Alzheimer's disease (AD) diagnosis is difficult, and new accurate tools based on peripheral biofluids are urgently needed. Extracellular vesicles (EVs) emerged as a valuable source of biomarker profiles for AD, since their cargo is disease-specific and these can be easily isolated from easily accessible biofluids, as blood. Fourier Transform Infrared (FTIR) spectroscopy can be employed to analyze EVs and obtain the spectroscopic profiles from different regions of the spectra, simultaneously characterizing carbohydrates, nucleic acids, proteins, and lipids.

Phosphoproteome Microarray Analysis of Extracellular Particles as a Tool to Explore Novel Biomarker Candidates for Alzheimer's Disease.

Phosphorylation plays a key role in Alzheimer's disease (AD) pathogenesis, impacting distinct processes such as amyloid-beta (Aβ) peptide production and tau phosphorylation. Impaired phosphorylation events contribute to senile plaques and neurofibrillary tangles' formation, two major histopathological hallmarks of AD. Blood-derived extracellular particles (bdEP) can represent a disease-related source of phosphobiomarker candidates, and hence, in this pilot study, bdEP of Control and AD cases were analyzed by a targeted phosphoproteomics approach using a high-density microarray that featured at least 1145 pan-specific and 913 phosphosite-specific antibodies.

Graft-derived neurons and bystander effects are maintained for six months after human iPSC-derived NESC transplantation in mice's cerebella.

Machado-Joseph disease (MJD) is a neurodegenerative disorder characterized by widespread neuronal death affecting the cerebellum. Cell therapy can trigger neuronal replacement and neuroprotection through bystander effects providing a therapeutic option for neurodegenerative diseases. Here, human control (CNT) and MJD iPSC-derived neuroepithelial stem cells (NESC) were established and tested for their therapeutic potential.

Stage-Dependent Biomarker Changes in Spinocerebellar Ataxia Type 3.

Spinocerebellar ataxia type 3/Machado-Joseph disease is the most common autosomal dominant ataxia. In view of the development of targeted therapies, knowledge of early biomarker changes is needed. We analyzed cross-sectional data of 292 spinocerebellar ataxia type 3/Machado-Joseph disease mutation carriers.

Selective, broad-spectrum antiviral photodynamic disinfection with dicationic imidazolyl chlorin photosensitizers.

The COVID-19 pandemic exposes our vulnerability to viruses that acquire the ability to infect our cells. Classical disinfection methods are limited by toxicity. Existing medicines performed poorly against SARS-CoV-2 because of their specificity to targets in different organisms.

A Novel Genetic Variant in Associated with Severe Epilepsy and Intellectual Disability: Potential Implications on Neural Primary Cilia.

Disruptions in the gene have been linked with an array of clinical features such as global developmental delay, intellectual disability, autistic-like symptoms, and seizures, through unclear mechanisms. haploinsufficiency has been associated with the disruption of primary cilium-related processes during early cortical development, and this has been reported in many neurodevelopmental disorders. In this study, we describe the clinical history of a 12-year-old child harboring a novel rare variant and presenting psychomotor delay and seizures.

Stage-dependent biomarker changes in spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies for SCA3, precise knowledge of stage-dependent fluid and MRI biomarker changes is needed. We analyzed cross-sectional data of 292 SCA3 mutation carriers including 57 pre-ataxic individuals, and 108 healthy controls from the European Spinocerebellar ataxia type 3/Machado-Joseph Disease Initiative (ESMI) cohort.

Isolation of Extracellular Vesicles from Human Follicular Fluid: Size-Exclusion Chromatography versus Ultracentrifugation.

Follicular fluid (FF) is the microenvironment where a growing oocyte develops. Intrafollicular communication ensures oocyte competence and is carried out through paracrine signaling, the exchange of molecules via gap junctions, and the trafficking of extracellular vesicles (EVs). The study of FF-derived EVs is important for both translational and fundamental research in the female reproductive field.

Extracellular communication between brain cells through functional transfer of Cre mRNA.

In the central nervous system (CNS), the crosstalk between neural cells is mediated by extracellular mechanisms, including brain-derived extracellular vesicles (bdEVs). To study endogenous communication across the brain and periphery, we explored Cre-mediated DNA recombination to permanently record the functional uptake of bdEVs cargo overtime. To elucidate functional cargo transfer within the brain at physiological levels, we promoted the continuous secretion of physiological levels of neural bdEVs containing Cre mRNA from a localized region in the brain by lentiviral transduction of the striatum of Flox-tdTomato Ai9 mice reporter of Cre activity.

A standardised protocol for blood and cerebrospinal fluid collection and processing for biomarker research in ataxia.

The European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative (ESMI) is a consortium established with the ambition to set up the largest European longitudinal trial-ready cohort of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD), the most common autosomal dominantly inherited ataxia worldwide. A major focus of ESMI has been the identification of SCA3/MJD biomarkers to enable future interventional studies. As biosample collection and processing variables significantly impact the outcomes of biomarkers studies, biosampling procedures standardisation was done previously to study visit initiation.

The frequency of non-motor symptoms in SCA3 and their association with disease severity and lifestyle factors.

Background: Non-motor symptoms (NMS) are a substantial burden for patients with SCA3. There are limited data on their frequency, and their relation with disease severity and activities of daily living is not clear. In addition, lifestyle may either influence or be affected by the occurrence of NMS.

Osteosarcoma-Derived Exosomes as Potential PET Imaging Nanocarriers for Lung Metastasis.

Lung metastases represent the most adverse clinical factor and rank as the leading cause of osteosarcoma-related death. Nearly 80% of patients present lung micrometastasis at diagnosis not detected with current clinical tools. Herein, an exosome (EX)-based imaging tool is developed for lung micrometastasis by positron emission tomography (PET) using osteosarcoma-derived EXs as natural nanocarriers of the positron-emitter copper-64 ( Cu).

SIRT1 activation and its circadian clock control: a promising approach against (frailty in) neurodegenerative disorders.

With the increase in life expectancy, the incidence of neurodegenerative disorders and their impact worldwide has been increasing in recent years. Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, have complex and varied mechanisms of pathogenesis. Importantly, they share the common feature of disrupted circadian rhythms.

Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases.

The establishment of robust human brain organoids to model cerebellar diseases is essential to study new therapeutic strategies for cerebellum-associated disorders. Machado-Joseph disease (MJD) is a cerebellar hereditary neurodegenerative disease, without therapeutic options able to prevent the disease progression. In the present work, control and MJD induced-pluripotent stem cells were used to establish human brain organoids.

Exogenous loading of extracellular vesicles, virus-like particles, and lentiviral vectors with supercharged proteins.

Cell membrane-based biovesicles (BVs) are important candidate drug delivery vehicles and comprise extracellular vesicles, virus-like particles, and lentiviral vectors. Here, we introduce a non-enzymatic assembly of purified BVs, supercharged proteins, and plasmid DNA called pDNA-scBVs. This multicomponent vehicle results from the interaction of negative sugar moieties on BVs and supercharged proteins that contain positively charged amino acids on their surface to enhance their affinity for pDNA.

Cerebellar morphometric and spectroscopic biomarkers for Machado-Joseph Disease.

Machado-Joseph disease (MJD) or Spinocerebellar ataxia type 3 (SCA3) is the most common form of dominant SCA worldwide. Magnetic Resonance Imaging (MRI) and Proton Magnetic Resonance Spectroscopy (H-MRS) provide promising non-invasive diagnostic and follow-up tools, also serving to evaluate therapies efficacy. However, pre-clinical studies showing relationship between MRI-MRS based biomarkers and functional performance are missing, which hampers an efficient clinical translation of therapeutics.

Photodynamic disinfection of SARS-CoV-2 clinical samples using a methylene blue formulation.

The amplitude of the coronavirus disease 2019 (COVID-19) pandemic motivated global efforts to find therapeutics that avert severe forms of this illness. The urgency of the medical needs privileged repositioning of approved medicines. Methylene blue (MB) has been in clinical use for a century and proved especially useful as a photosensitizer for photodynamic disinfection (PDI).