Synthesis and characterization of chitosan-grafted-dopamine based micelles as multifunctional nanomedicines for Parkinson's disease treatment by intranasal administration.

The main aim of this work was to synthesize new chitosan amphiphilic derivatives able to self-assembly encapsulating substances acting at different target sites implicated in Parkinson disease (PD). For this purpose, O-carboxymethyl-chitosan (O-CMCS) was grafted with dopamine (DA) exploiting a carbodiimide mediated coupling reaction using different polymer/DA weight ratios. The structural characterization of the resulting O-CMCS-g-DA conjugates was carried out by spectral (i.

Indirect evaluation of lung condition by means of LF-NMR following chest physiotherapy or ETI administration in cystic-fibrosis patients.

Background: As most cystic fibrosis (CF) patients progress to respiratory failure, lung functionality assessment is pivotal. We previously developed a test that monitors airways measuring the spin-spin relaxation time (T) of water hydrogens present in sputum using Low Field-Nuclear Magnetic resonance (LF-NMR).

Objectives: To investigate further the significance of T exploring: 1) T correlation with the effects of chest physiotherapy (CP); 2) the influence of sputum contamination by saliva on T; 3) T relation with sputum mesh size; 4) T correlation with the effects of the CFTR-modulator Elexa-caftor/Tezacaftor/Ivacaftor (ETI).

Dopamine and Citicoline-Co-Loaded Solid Lipid Nanoparticles as Multifunctional Nanomedicines for Parkinson's Disease Treatment by Intranasal Administration.

This work aimed to evaluate the potential of the nanosystems constituted by dopamine (DA) and the antioxidant Citicoline (CIT) co-loaded in solid lipid nanoparticles (SLNs) for intranasal administration in the treatment of Parkinson disease (PD). Such nanosystems, denoted as DA-CIT-SLNs, were designed according to the concept of multifunctional nanomedicine where multiple biological roles are combined into a single nanocarrier and prepared by the melt emulsification method employing the self-emulsifying Gelucire 50/13 as lipid matrix. The resulting DA-CIT-SLNs were characterized regarding particle size, surface charge, encapsulation efficiency, morphology, and physical stability.

Slightly viscous dispersions of mucoadhesive polymers as vehicles for nasal administration of dopamine and grape seed extract-loaded solid lipid nanoparticles.

With the aim to find an alternative vehicle to the most used thermosensitive hydrogels for efficient nanotechnology-based nose-to-brain delivery approach for Parkinson's disease (PD) treatment, in this work we evaluated the Dopamine (DA) and the antioxidant grape seed-derived pro-anthocyanidins (Grape Seed Extract, GSE) co-loaded solid lipid nanoparticles (SLNs) put in slight viscous dispersions (SVDs). These SVDs were prepared by dispersion in water at low concentrations of mucoadhesive polymers to which SLN pellets were added. For the purpose, we investigated two polymeric blends, namely Poloxamer/Carbopol (PF-127/Carb) and oxidized alginate/Hydroxypropylmethyl cellulose (AlgOX/HPMC).

(Tomato)-Derived Nanovesicles Accelerate Wound Healing by Eliciting the Migration of Keratinocytes and Fibroblasts.

Plant-derived nanovesicles have been considered interesting in medicine for their breakthrough biological effects, including those relevant to wound healing. However, tomato-derived nanovesicles (TDNVs) have not been studied for their effects on wound closure yet. TDNVs were isolated from (var.

Mucus Structure, Viscoelastic Properties, and Composition in Chronic Respiratory Diseases.

The respiratory mucus, a viscoelastic gel, effectuates a primary line of the airway defense when operated by the mucociliary clearance. In chronic respiratory diseases (CRDs), such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), the mucus is overproduced and its solid content augments, changing its structure and viscoelastic properties and determining a derangement of essential defense mechanisms against opportunistic microbial (virus and bacteria) pathogens. This ensues in damaging of the airways, leading to a vicious cycle of obstruction and infection responsible for the harsh clinical evolution of these CRDs.

A Vaccine against Cancer: Can There Be a Possible Strategy to Face the Challenge? Possible Targets and Paradoxical Effects.

Is it possible to have an available vaccine that eradicates cancer? Starting from this question, this article tries to verify the state of the art, proposing a different approach to the issue. The variety of cancers and different and often unknown causes of cancer impede, except in some cited cases, the creation of a classical vaccine directed at the causative agent. The efforts of the scientific community are oriented toward stimulating the immune systems of patients, thereby preventing immune evasion, and heightening chemotherapeutic agents effects against cancer.

Carboxymethyl chitosan dopamine conjugates: Synthesis and evaluation for intranasal anti Parkinson therapy.

With respect to the Parkinson's disease (PD), herein, we aimed at synthetizing and characterizing two novel macromolecular conjugates where dopamine (DA) was linked to N,O-carboxymethyl chitosan or O-carboxymethyl chitosan, being both conjugates obtained from an organic solvent free synthetic procedure. They were characterized by FT-IR, H NMR spectroscopies, whereas thermal analysis (including Differential Scanning Calorimetry and Thermal Gravimetric Analysis) revealed good stability of the two conjugates after exposure at temperatures close to 300 °C. Release studies in simulated nasal fluid elucidated that a faster release occurred since O-carboxymethyl chitosan-DA conjugate maybe due to the less steric hindrance exerted by the polymeric moiety.

Blood Clotting Dissolution in the Presence of a Magnetic Field and Preliminary Study with MG63 Osteoblast-like Cells-Further Developments for Guided Bone Regeneration?

Background: The influence of a magnetic field on the activation of bone cells and remodelling of alveolar bone is known to incite bone regeneration. Guided Bone Regeneration (GBR) aims to develop biomimetic scaffolds to allow for the functioning of the barrier and the precise succession of wound healing steps, including haemostasis. The effect of a magnetic field on blood clot dissolution has not been studied yet.

Combined Dopamine and Grape Seed Extract-Loaded Solid Lipid Nanoparticles: Nasal Mucosa Permeation, and Uptake by Olfactory Ensheathing Cells and Neuronal SH-SY5Y Cells.

We have already formulated solid lipid nanoparticles (SLNs) in which the combination of the neurotransmitter dopamine (DA) and the antioxidant grape-seed-derived proanthocyanidins (grape seed extract, GSE) was supposed to be favorable for Parkinson's disease (PD) treatment. In fact, GSE supply would reduce the PD-related oxidative stress in a synergic effect with DA. Herein, two different methods of DA/GSE loading were studied, namely, coadministration in the aqueous phase of DA and GSE, and the other approach consisting of a physical adsorption of GSE onto preformed DA containing SLNs.

IGFBP-6 Network in Chronic Inflammatory Airway Diseases and Lung Tumor Progression.

The lung is an accomplished organ for gas exchanges and directly faces the external environment, consequently exposing its large epithelial surface. It is also the putative determinant organ for inducing potent immune responses, holding both innate and adaptive immune cells. The maintenance of lung homeostasis requires a crucial balance between inflammation and anti-inflammation factors, and perturbations of this stability are frequently associated with progressive and fatal respiratory diseases.

The Oncogenic Theory of Preeclampsia: Is Amniotic Mesenchymal Stem Cells-Derived PLAC1 Involved?

The pathomechanisms of preeclampsia (PE), a complication of late pregnancy characterized by hypertension and proteinuria, and due to improper placentation, are not well known. Mesenchymal stem cells derived from the amniotic membrane (AMSCs) may play a role in PE pathogenesis as placental homeostasis regulators. PLACenta-specific protein 1 (PLAC1) is a transmembrane antigen involved in trophoblast proliferation that is found to be associated with cancer progression.

Polymer Encapsulated Liposomes for Oral Co-Delivery of Curcumin and Hydroxytyrosol.

Curcumin (Cur) is a hydrophobic polyphenol from the rhizome of spp., while hydroxytyrosol (HT) is a water-soluble polyphenol from . Both show outstanding antioxidant properties but suffer from scarce bioavailability and low stability in biological fluids.

Extracellular Vesicles' Role in the Pathophysiology and as Biomarkers in Cystic Fibrosis and COPD.

In keeping with the extraordinary interest and advancement of extracellular vesicles (EVs) in pathogenesis and diagnosis fields, we herein present an update to the knowledge about their role in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Although CF and COPD stem from a different origin, one genetic and the other acquired, they share a similar pathophysiology, being the CF transmembrane conductance regulator (CFTR) protein implied in both disorders. Various subsets of EVs, comprised mainly of microvesicles (MVs) and exosomes (EXOs), are secreted by various cell types that are either resident or attracted in the airways during the onset and progression of CF and COPD lung disease, representing a vehicle for metabolites, proteins and RNAs (especially microRNAs), that in turn lead to events as such neutrophil influx, the overwhelming of proteases (elastase, metalloproteases), oxidative stress, myofibroblast activation and collagen deposition.

Elexacaftor/Tezacaftor/Ivacaftor Accelerates Wound Repair in Cystic Fibrosis Airway Epithelium.

Background: Cystic fibrosis (CF) airway epithelium shows alterations in repair following damage. In vitro studies showed that lumacaftor/ivacaftor (Orkambi) may favor airway epithelial integrity in CF patients. Our aim was to evaluate the effect of the novel triple combination elexacaftor/tezacaftor/ivacaftor (ETI) on wound repair in CF airway epithelial cells.

Characterization of anti-proliferative and anti-oxidant effects of nano-sized vesicles from Brassica oleracea L. (Broccoli).

In this in vitro study, we test our hypothesis that Broccoli-derived vesicles (BDVs), combining the anti-oxidant properties of their components and the advantages of their structure, can influence the metabolic activity of different cancer cell lines. BDVs were isolated from homogenized fresh broccoli (Brassica oleracea L.) using a sucrose gradient ultracentrifugation method and were characterized in terms of physical properties, such as particle size, morphology, and surface charge by transmission electron microscopy (TEM) and laser doppler electrophoresis (LDE).

Mucopenetration study of solid lipid nanoparticles containing magneto sensitive iron oxide.

In most chronic respiratory diseases, excessive viscous airway secretions oppose a formidable permeation barrier to drug delivery systems (DDSs), with a limit to their therapeutic efficacy for the targeting epithelium. Since mucopenetration of DDSs with slippery technology (i.e.

Insulin-Like Growth Factor Binding Protein (IGFBP-6) as a Novel Regulator of Inflammatory Response in Cystic Fibrosis Airway Cells.

Cystic Fibrosis (CF) patients are prone to contracting bacterial lung infections with opportunistic pathogens, especially . Prolonged infections have been linked to chronic inflammation in the CF lung, whose hallmarks are increased levels of cytokines (i.e.

Human Amniotic Mesenchymal Stem Cells and Fibroblasts Accelerate Wound Repair of Cystic Fibrosis Epithelium.

Cystic fibrosis (CF) airways are affected by a deranged repair of the damaged epithelium resulting in altered regeneration and differentiation. Previously, we showed that human amniotic mesenchymal stem cells (hAMSCs) corrected base defects of CF airway epithelial cells via connexin (CX)43-intercellular gap junction formation. In this scenario, it is unknown whether hAMSCs, or fibroblasts sharing some common characteristics with MSCs, can operate a faster repair of a damaged airway epithelium.

Downregulation of epithelial sodium channel (ENaC) activity in cystic fibrosis cells by epigenetic targeting.

The pathogenic mechanism of cystic fibrosis (CF) includes the functional interaction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein with the epithelial sodium channel (ENaC). The reduction of ENaC activity may constitute a therapeutic option for CF. This hypothesis was evaluated using drugs that target the protease-dependent activation of the ENaC channel and the transcriptional activity of its coding genes.

Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Use in Central Nervous System Demyelinating Disorders.

Autoimmune demyelinating diseases-including multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein-associated disease, acute disseminated encephalomyelitis, and glial fibrillary acidic protein (GFAP)-associated meningoencephalomyelitis-are a heterogeneous group of diseases even though their common pathology is characterized by neuroinflammation, loss of myelin, and reactive astrogliosis. The lack of safe pharmacological therapies has purported the notion that cell-based treatments could be introduced to cure these patients. Among stem cells, mesenchymal stem cells (MSCs), obtained from various sources, are considered to be the ones with more interesting features in the context of demyelinating disorders, given that their secretome is fully equipped with an array of anti-inflammatory and neuroprotective molecules, such as mRNAs, miRNAs, lipids, and proteins with multiple functions.

Pathophysiology of Lung Disease and Wound Repair in Cystic Fibrosis.

Cystic fibrosis (CF) is an autosomal recessive, life-threatening condition affecting many organs and tissues, the lung disease being the chief cause of morbidity and mortality. Mutations affecting the () gene determine the expression of a dysfunctional protein that, in turn, triggers a pathophysiological cascade, leading to airway epithelium injury and remodeling. In vitro and in vivo studies point to a dysregulated regeneration and wound repair in CF airways, to be traced back to epithelial CFTR lack/dysfunction.