Enhancing Biocompatibility and Antibacterial Activity of Ti6Al4V by Entrapping Ag and Hydroxyapatite Inside Alginate Filled Pores of TiO 2 Layer Grown by Spark Anodizing

A three-step electrochemical process is developed to grow a coating on Ti6Al4V alloy for biomedical applications aimed to enhance its bioactivity. The coating is composed by a porous titanium oxide filled with Ag, alginic acid, and hydroxyapatite to provide antibacterial properties and, at the same time, osteointegration capability. Anodized and treated with the electrochemical process samples are characterized by Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray Spectroscopy (EDX), X-Ray Diffraction, and Raman Spectroscopy to have information about morphology and composition soon after the fabrication and after immersion in Hanks' solution. Bioactivity of the samples is also prov…

Lipid nanocarriers containing esters prodrugs of Flurbiprofen. Preparation, physical-chemical characterization and biological studies.

In this paper, the preparation, chemical-physical, technological and in vitro characterization of nanostructured lipid carriers (NLC) carrying R-flurbiprofen ester prodrugs, were analyzed for a potential pharmaceutical application. R-flurbiprofen was chosen as a model drug because it has been found to play an effective role in counteracting secretases involved in neurodegenerative diseases, although it does not cross the Blood Brain Barrier (BBB). In this study, two R-flurbiprofen ester prodrugs (ethyl and hexyl) were successfully synthesized and entrapped into non-pegylated and pegylated NLC. The obtained systems showed average diameters in the colloidal size range, negative zeta potential…

Biofortification: Effect of Iodine Fortified Food in the Healthy Population, Double-Arm Nutritional Study

It is estimated that one-third of the world’s population lives in areas where iodine (I) is scarce and its deficiency is responsible for many related disorders, such as goiter, reproductive failure, hearing loss, growth impairment, congenital I deficiency syndrome, and numerous kinds of brain injury. Mineral deficiencies can be overcomeviadietary diversification and mineral supplementation. An alternative or even complementary way is represented by the intake of biofortified foods, which can tackle this lack of micronutrients. In this short-term double-arm nutritional intervention study, a cohort of ten people was supplemented with curly endive leaf biofortified with I and ten people with c…

Fluorinated and pegylated polyaspartamide derivatives to increase solubility and efficacy of Flutamide

New fluorinated amphiphilic copolymers based on a biocompatible polyaspartamide have been prepared in order to obtain polymeric micelles useful for delivering anticancer drugs. In particular, α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) has been derivatized with polyethylene glycol (PEG(2000)) and ethylendiamine (EDA). Both these portions form the hydrophilic part of the copolymer, while the hydrophobic moiety is given by 1,2,4-oxadiazoles: 5-pentafluorophenyl-3-perfluoroheptyl-1,2,4-oxadiazole (PPOX) or 3-carboxyethyl-5-pentadecafluoroheptyl-1,2,4-oxadiazole (CPOX). Copolymers named PHEA-PEG(2000)-EDA-PPOX and PHEA-PEG(2000)-EDA-CPOX have been prepared with various degrees of derivati…

Data concerning the proteolytic resistance and oxidative stress in LAN5 cells after treatment with BSA hydrogels

AbstractProteolytic resistance is a relevant aspect to be tested in the formulation of new nanoscale biomaterials. The action of proteolytic enzymes is a very fast process occurring in the range of few minutes. Here, we report data concerning the proteolytic resistance of a heat-set BSA hydrogel obtained after 20-hour incubation at 60°C prepared at the pH value of 3.9, pH at which the hydrogel presents the highest elastic character with respect to gel formed at pH 5.9 and 7.4 “Heat-and pH-induced BSA conformational changes, hydrogel formation and application as 3D cell scaffold” (G. Navarra, C. Peres, M. Contardi, P. Picone, P.L. San Biagio, M. Di Carlo, D. Giacomazza, V. Militello, 2016) […

Nose-to-brain delivery of insulin enhanced by radiation-engineered nanogels

Recent evidences suggest thet insulin delivery to the brain can be an important pharmacological therapy for some neurodegenerative pathologies, including Alzheimer disease (AD)

Systemic Immune Responses in Alzheimer's Disease: In Vitro Mononuclear Cell Activation and Cytokine Production

To investigate the systemic signs of immune-inflammatory responses in Alzheimer's disease (AD), in the present study we have analyzed blood lymphocyte subsets and the expression of activation markers on peripheral blood mononuclear cells (PBMCs) from AD patients and age-matched healthy controls (HC) activated in vitro by recombinant amyloid-beta peptide (rAbeta42). Our study of AD lymphocyte subpopulations confirms the already described decrease of the absolute number and percentage of B cells when compared to HC lymphocytes, whereas the other subsets are not significantly different in patients and controls. We report the increased expression of the activation marker CD69 and of the chemoki…

CONCANAVALIN A AGGREGATION AND TOXICITY ON NEUROBLASTOMA LAN5 CELL CULTURES

Data concerning the protein absorption and retention properties of xyloglucan-based hydrogel film

In wound dressing applications, exudate absorption and retention are important properties. The data presented here assess the ability of the crosslinked xyloglucan-poly(vinyl alcohol) hydrogel films (XG-PVA), described in "Xyloglucan-based hydrogel films for wound dressing: Structure-property relationships" (Ajovalasit et al., 2018) [1] and "Biocompatibility, hemocompatibility and antimicrobial properties of xyloglucan-based hydrogel film for wound healing application" (Picone et al., 2019), to absorb and retain proteins. These properties were investigated by Comassie blue staining and electrophoresis of Fetal Serum Proteins. (C) 2018 The Authors. Published by Elsevier Inc. This is an open …

Concanavalin A toxicity on Neuroblastoma LAN5 cell cultures

Recovery from Food Waste-Biscuit Doughs Enriched with Pomegranate Peel Powder as a Model of Fortified Aliment

This research was funded by the "IEV Programme de Cooperation Italie-Tunisie 2014-2020, Re-lancer une nouvelle economie (Re-Ne)". EU project code C-5-3.1-39.

Insulin resistance as common molecular denominator linking obesity to Alzheimer’s disease

Alzheimer’s disease (AD) is an aging-related multi-factorial disorder to which metabolic factors contribute at what has canonically been considered a centrally mediated process. Although the exact underlying mechanisms are still unknown, obesity is recognized as a risk factor for AD and the condition of insulin resistance seems to be the link between the two pathologies. Using mice with high fat diet (HFD) obesity we dissected the molecular mechanisms shared by the two disorders. Brains of HFD fed mice showed elevated levels of APP and Aβ 40 /Aβ 42 together with BACE, GSK3β and Tau proteins involved in APP processing and Aβ accumulation. Immunofluorescence, Thioflavin T staining experiments…

Xyloglucan-based hydrogel film for wound dressing: Structure and biological properties relationships

Crosslinked xyloglucan-poly(vinyl alcohol) based hydrogel films have been synthetized and characterized for wound healing applications. Polyvinyl alcohol (PVA) and glycerol (Gro) were added to have an optimal combination of softness, conformability and resilience. Physical hydrogel have been transformed into permanent covalent hydrogels by reaction with glutaraldehyde (GA). Chemical and physical properties of the films have been analyzed by different technique. Moreover, biocompatibility of a selected formulation was assessed in vitro by investigating different aspects, such as cell viability, oxidative stress, mitochondrial dysfunction and specific stress biomarkers. Partial adhesiveness w…

Aβ Oligomers and Fibrillar Aggregates Induce Different Apoptotic Pathways in LAN5 Neuroblastoma Cell Cultures

Fibril deposit formation of amyloid beta-protein (Abeta) in the brain is a hallmark of Alzheimer's disease (AD). Increasing evidence suggests that toxicity is linked to diffusible Abeta oligomers, which have been found in soluble brain extracts of AD patients, rather than to insoluble fibers. Here we report a study of the toxicity of two distinct forms of recombinant Abeta small oligomers and fibrillar aggregates to simulate the action of diffusible Abeta oligomers and amyloid plaques on neuronal cells. Different techniques, including dynamic light scattering, fluorescence, and scanning electron microscopy, have been used to characterize the two forms of Abeta. Under similar conditions and …

Post-acute COVID-19 neurological syndrome: a new medical 2 challenge

In December 2019, inWuhan (China), a highly pathogenic coronavirus, named SARS-CoV-2, dramatically emerged. This new virus, which causes severe pneumonia, is rapidly spreading around the world, hence it provoked the COVID-19 pandemic. This emergency launched by SARS-CoV-2 also had, and still has, devastating socio-economic aspects. Assessing the impact of COVID-19 on vulnerable groups of people is crucial for the adaptation of governments' responses. Growing scientific evidence suggests that it is essential to keep the attention on people after acute SARSCoV- 2 infection; indeed, some clinical manifestations are frequently present even after recovery. There is consensus on the need to defin…

NAFLD and Atherosclerosis Are Prevented by a Natural Dietary Supplement Containing Curcumin, Silymarin, Guggul, Chlorogenic Acid and Inulin in Mice Fed a High-Fat Diet

Non-alcoholic fatty liver disease (NAFLD) confers an increased risk of cardiovascular diseases. NAFDL is associated with atherogenic dyslipidemia, inflammation and renin-angiotensin system (RAS) imbalance, which in turn lead to atherosclerotic lesions. In the present study, the impact of a natural dietary supplement (NDS) containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin on NAFLD and atherosclerosis was evaluated, and the mechanism of action was examined. C57BL/6 mice were fed an HFD for 16 weeks; half of the mice were simultaneously treated with a daily oral administration (os) of the NDS. NAFLD and atherogenic lesions in aorta and carotid artery (histological analys…

Xyloglucan-based hydrogel films for the design of "smart" bandages

A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do. Chronic wounds mostly affect people over the age of 60, but a significant proportion is becoming radiation induced chronic wounds caused by cancer radiotherapy. Hydrogels are often used as dressings in the management of a variety of wounds. These materials can help to maintain a moist wound environment, promote natural debridement, hydrate necrotic tissue, absorb slough and exudates.We are developing hydrogel dressings that can enable constant monitoring of selected key parameters through embedded radio-sensors, providing information on the progress of the re…

A Natural Dietary Supplement with a Combination of Nutrients Prevents Neurodegeneration Induced by a High Fat Diet in Mice

Obesity and metabolic disorders can be risk factors for the onset and development of neurodegenerative diseases. The aim of the present study was to investigate the protective effects of a natural dietary supplement (NDS), containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin, on dysmetabolism and neurodegeneration in the brains of high fat diet (HFD)-fed mice. Decrease in the expression of FACL-4, CerS-1, CerS-4, cholesterol concentration and increase in the insulin receptor expression and insulin signaling activation, were found in brains of NDS-treated HFD brains in comparison with HFD untreated-mice, suggesting that NDS is able to prevent brain lipid accumulation and …

Toxic effects induced by recombinant Ab 42 Peptide

The sea urchin embryo: a model to study Alzheimer's beta amyloid induced toxicity.

Abstract Alzheimer’s disease (AD) is the most common form of dementia. The cause of AD is closely related to the accumulation of amyloid beta peptide in the neuritic plaques. The use of animal model systems represents a good strategy to elucidate the molecular mechanism behind the development of this pathology. Here we use the Paracentrotus lividus embryo to identify molecules and pathways that can be involved in the degenerative process. As a first step, we identified the presence of an antigen related to the human APP, called Pl APP. This antigen, after gastrula stage, is processed producing a polypeptide of about 10 kDa. By immunohistochemistry we localized the Pl APP antigen in some ser…

Obesità e resistenza all'insulina: due fattori di rischio per l'insorgenza della malattia di Alzheimer

Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate metformin's effect

AbstractClinical and experimental biomedical studies have shown Type 2 diabetes mellitus (T2DM) to be a risk factor for the development of Alzheimer's disease (AD). This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on β-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models. Furthermore, the protective role of insulin against metformin is also demonstrated. In LAN5 neuroblastoma cells, metformin increases APP and presenilin levels, proteins involved in AD. Overexpression of APP and presenilin 1 (Pres 1) increases APP cleavage and intracellular accumulation of β-amyloid peptide (Aβ), which, in turn, promotes ag…

The sea urchin embryo: a model to study Alzheimer's Disease

Nose-to-brain delivery of insulin enhanced by a nanogel carrier.

Recent evidences suggest that insulin delivery to the brain can be an important pharmacological therapy for some neurodegenerative pathologies, including Alzheimer disease (AD). Due to the presence of the Blood Brain Barrier, a suitable carrier and an appropriate route of administration are required to increase the efficacy and safety of the treatment. Here, poly(N-vinyl pyrrolidone)-based nanogels (NG), synthetized by e-beam irradiation, alone and with covalently attached insulin (NG-In) were characterized for biocompatibility and brain delivery features in a mouse model. Preliminarily, the biodistribution of the "empty" nanocarrier after intraperitoneal (i.p.) injection was investigated b…

Biological and biophysics aspects of metformin-induced effects: cortex mitochondrial dysfunction and promotion of toxic amyloid pre-fibrillar aggregates

The onset of Alzheimer disease (AD) is influenced by several risk factors comprising diabetes. Within this context, antidiabetic drugs, including metformin, are investigated for their effect on AD. We report that in the C57B6/J mice, metformin is delivered to the brain where activates AMP-activated kinase (AMPK), its molecular target. This drug affects the levels of β- secretase (BACE1) and β-amyloid precursor protein (APP), promoting processing and aggregation of β-amyloid (Aβ), mainly in the cortex region. Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-sel…

The sea urchin embryos: a model system to study Alzheimer’s disease

Concanavalin A aggregation and toxicity on cell cultures

A number of neurodegenerative diseases are known to involve protein aggregation. Common mechanisms and structural properties of amyloids are thought to be involved in aggregation-related cytotoxicity. In this context we propose an experimental study on Concanavalin A (Con A) aggregation and use it as a model to study the relationship between cell toxicity and aggregation processes. Depending on solution conditions, Con A aggregation has been monitored by static and dynamic light scattering, Thioflavin T emission, and FTIR absorption. The morphology of different aggregate species was verified by means of Atomic Force Microscopy and Confocal Microscopy. During the aggregation pathway the nati…

Toxic effects of recombinant b-amyloid prefibrillar oligomers on different model systems

Heat- and pH-induced BSA conformational changes, hydrogel formation and application as 3D cell scaffold

Aggregation and gelation of globular proteins can be an advantage to generate new forms of nanoscale biomaterials based on the fibrillar architecture. Here, we report results obtained by exploiting the proteins' natural tendency to self-organize in 3D network, for the production of new material based on BSA for medical application. In particular, at five different pH values the conformational and structural changes of the BSA during all the steps of the thermal aggregation and gelation have been analyzed by FTIR spectroscopy. The macroscopic mechanical properties of these hydrogels have been obtained by rheological measurements. The microscopic structure of the gels have been studied by AFM…

NANOSTRUCTURED LIPID CARRIER (NLC) CONTAINING FERULIC ACID: PREPARATION, CARACTERIZATION AND CYTOTOXICITY STUDIES

Cationic solid-lipid nanoparticles as vector for RNA delivery

SOLID LIPID NANOPARTICLES CONTAINING AN ANTIOXIDANT COMPOUND IN ALZHEIMER’S DISEASE

Ionizing radiation-engineered nanogels as insulin nanocarriers for the development of a new strategy for the treatment of Alzheimer's disease

A growing body of evidence shows the protective role of insulin in Alzheimer's disease (AD). A nanogel system (NG) to deliver insulin to the brain, as a tool for the development of a new therapy for Alzheimer's Disease (AD), is designed and synthetized. A carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system produced by ionizing radiation is chosen as substrate for the covalent attachment of insulin or fluorescent molecules relevant for its characterization. Biocompatibility and hemocompatibility of the naked carrier is demonstrated. The insulin conjugated to the NG (NG-In) is protected by protease degradation and able to bind to insulin receptor (IR), as demonstrated by immunofl…

Preparation and characterization of lipid nanoparticles as potential carriers for ester prodrugs of flurbiprofen

EMPLOYMENT OF CATIONIC SOLID-LIPID NANOPARTICLES AS RNA CARRIERS

Gene transfer represents an important advance in the treatment of both genetic and acquired diseases. In this article, the suitability of cationically modified solid-lipid nanoparticles (SLN) as a nonviral vector for gene delivery was investigated, in order to obtain stable materials able to condense RNA. Cationic SLN were produced by microemulsion using Compritol ATO 888 as matrix lipid, Pluronic F68 as tenside, and dimethyldioctadecylammonium bromide (DDAB) as cationic lipid. The resulting particles were approximately 100 nm in size and showed a highly positive surface charge (+41 mV) in water. Size and shape were further characterized by scanning electron microscopy (SEM) measurements. M…

SOLID LIPID NANOPARTICLES (SLNs) CONTAINING FERULIC ACID AGAINST OXIDATIVE STRESS IN NEURODEGENERATIVE DISEASES

Glucagon-like peptide-2 reduces the obesity-associated inflammation in the brain.

Growing evidence suggests a link between obesity and neurodegeneration. The purpose of the present study was to explore the neuroprotective potential of glucagon-like peptide-2 (GLP-2) in the brain of high fat diet (HFD)-fed mice. Markers of inflammation and oxidative stress were analysed in the brains of obese mice chronically treated with [Gly2]-GLP-2 (teduglutide), the stable analogue of the GLP-2, and they were compared to age-matched untreated obese and lean animals. Neurodegeneration was examined by TUNEL assay. HFD feeding increased the expression of pro-inflammatory mediators (NF-kB, IL-8, TNF-α, IL-1β and IL-6), glial fibrillary acidic protein (GFAP), index of gliosis and neurodege…

Inflammatory mediators as biomarkers in brain disorders.

Neurodegenerative diseases such as Alzheimer, Parkinson, amyotrophic lateral sclerosis, and Huntington are incurable and debilitating conditions that result in progressive death of the neurons. The definite diagnosis of a neurodegenerative disorder is disadvantaged by the difficulty in obtaining biopsies and thereby to validate the clinical diagnosis with pathological results. Biomarkers are valuable indicators for detecting different phases of a disease such as prevention, early onset, treatment, progression, and monitoring the effect of pharmacological responses to a therapeutic intervention. Inflammation occurs in neurodegenerative diseases, and identification and validation of molecules…

Ferulic Acid-Loaded Lipid Nanostructures as Drug Delivery Systems for Alzheimers Disease: Preparation, Characterization and Cytotoxicity Studies

Idrogeli a base di xyloglucano per la produzione di medicazioni avanzate nel trattamento delle ferite

In questo lavoro sono stati preparati film sottili di idrogelo (reticolati fisicamente o chimicamente) a base di xyloglucano (XG) e XG/polivinilalcol (PVA), a cui si è aggiunto glicerolo come plasticizzante. Lo xyloglucano è un polisaccaride di origine vegetale, caratterizzato da una catena principale di (1,4)--Dglucosio con ramificazioni laterali di (1-6)-α-xilosio, parzialmente sostituite con (1-2)–β galattosio. E’ stata indagata la possibilità di modulare la densità di reticolazione dell’idrogelo per ottenere il miglior compromesso tra resistenza meccanica e flessibilità, l’integrità strutturale nel tempo e la capacità di assorbire fluidi biologici o trattenere l’umidità. Inoltre, ne è …

Curcumin entrapped into lipid nanosystems inhibits neuroblastoma cancer cell growth and activates Hsp70 protein

Curcumin is a natural anti-cancer compound utilized on a wide variety of human cancer cell lines and animal carcinogenesis models. However, its clinical application has been limited for its minimal systemic bioavailability. Nanoparticle-based drug delivery approaches have the potential for rendering hydrophobic molecules such as curcumin dispersible in aqueous media, thus overtaking the limits of its poor solubility. In this paper, we reported the preparation and chemical-physical characterization of Nanostructured Lipid Carriers (NLC) containing curcumin, based on Imwitor, Compritol or Precirol as lipid matrix. By in vitro experiments, we have demonstrated that these nano-systems are able …

Insulin-activated Akt rescues Aβ oxidative stress-induced cell death by orchestrating molecular trafficking

Increasing evidence indicates that Alzheimer's disease, one of the most diffused aging pathologies, and diabetes may be related. Here, we demonstrate that insulin signalling protects LAN5 cells by amyloid-β42 (Aβ)-induced toxicity. Aβ affects both activation of insulin receptors and the levels of phospho-Akt, a critical signalling molecule in this pathway. In contrast, oxidative stress induced by Aβ can be antagonized by active Akt that, in turn, inhibits Foxo3a, a pro-apoptotic transcription factor activated by reactive oxygen species generation. Insulin cascade protects against mitochondrial damage caused by Aβ treatment, restoring the mitochondrial membrane potential. Moreover, we show t…

From Small Peptides to Large Proteins against Alzheimer'sDisease.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly. The two cardinal neuropathological hallmarks of AD are the senile plaques, which are extracellular deposits mainly constituted by beta-amyloids, and neurofibrillary tangles formed by abnormally phosphorylated Tau (p-Tau) located in the cytoplasm of neurons. Although the research has made relevant progress in the management of the disease, the treatment is still lacking. Only symptomatic medications exist for the disease, and, in the meantime, laboratories worldwide are investigating disease-modifying treatments for AD. In the present review, results centered on the use of peptides of different sizes invol…

Biocompatibility, hemocompatibility and antimicrobial properties of xyloglucan-based hydrogel film for wound healing application.

Crosslinked xyloglucan-poly(vinyl alcohol) based hydrogel films are interesting materials for wound healing applications. This work focuses on the hydrolytic degradation and consequent morphological modification of a XG-PVA film and on its interaction with cells, blood, bacteria. Biocompatibility of the film was assessed in vitro by investigating different aspects, such as cell viability, oxidative stress level, mitochondrial dysfunction and specific stress biomarkers. Partial adhesiveness was demonstrated by performing different attaching assays and phalloidin staining. Hemocompatibility of XG-PVA film after interaction with blood was evaluated by using a multi-parametric approach, includi…

A potential host and virus targeting tool against COVID-19: Chemical characterization, antiviral, cytoprotective, antioxidant, respiratory smooth muscle relaxant effects of Paulownia tomentosa Steud

COronaVIrus Disease 2019 (COVID-19) is a newly emerging infectious disease that spread across the world, caused by the novel coronavirus Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Despite the advancements in science that led to the creation of the vaccine, there is still an urgent need for new antiviral drugs effective against SARS-CoV-2. This study aimed to investigate the antiviral effect of Paulownia tomentosa Steud extract against SARS-CoV-2 and to evaluate its antioxidant properties, including respiratory smooth muscle relaxant effects. Our results showed that P. tomentosa extract can inhibit viral replication by directly interacting with both the 3-chymotrypsin-like…

Neurological Consequences, Mental Health, Physical Care, and Appropriate Nutrition in Long-COVID-19.

SARS-CoV-2 pandemic has caused a collapse of the world health systems. Now, vaccines and more effective therapies have reversed this crisis but the scenario is further aggravated by the appearance of a new pathology, occurring as SARS-CoV-2 infection consequence: the long-COVID-19. This term is commonly used to describe signs and symptoms that continue or develop after acute infection of COVID-19 up to several months. In this review, the consequences of the disease on mental health and the neurological implications due to the long-COVID are described. Furthermore, the appropriate nutritional approach and some recommendations to relieve the symptoms of the pathology are presented. Data colle…

CURCUMIN-LOADED LIPID NANOSTRUCTURES AS DRUG DELIVERY SYSTEMS.

Toxicity of recombinant β-amyloid prefibrillar oligomers on morphogenesis of Sea Urchin Paracentrotus lividus.

Nutritional epigenomic and DNA-damage modulation effect of natural stilbenoids

The aim of the present work is the evaluation of biological effects of natural stilbenoids found in Vitis vinifera, with a focus on their activity as epigenetic modulators. In the present study, resveratrol, pterostilbene and for the first time their dimers (±)-trans-δ-viniferin, (±)-trans-pterostilbene dehydrodimer were evaluated in Caco-2 and HepG-2 cell lines as potential epigenetic modulators. Stilbenoids were added in a Caco-2 cell culture as a model of the intestinal epithelial barrier and in the HepG-2 as a model of hepatic environment, to verify their dose-dependent toxicity, ability to interact with DNA, and epigenomic action. Resveratrol, pterostilbene, and (±)-trans-pterostilbene…

Biocompatible micelles based on squalene portions linked to pegylated polyaspartamide as potential colloidal drug carriers

FERULIC ACID LOADED SOLID LIPID NANOPARTICLES PROTECTS LAN5 NEUROBLASTOMA CELL LINE BY Ab-AMYLOID OXIDATIVE STRESS

Insulin-nanogels: preliminary study in mouse for the treatment of Alzheimer's disease

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signalling are involved in brain cognitive functions and their dysfunction is implicated in Alzheimer’s disease (AD). Thus, administration of insulin could be a strategy for AD treatment. For this aim we have designed, synthesized and characterized a nanogel system (NG) that has been conjugated to insulin molecules (NG-In) (1) as new therapeutic approach against AD. In our preclinical studies in mice, intraperitoneal injection of fluorescent-labeled NG has allowed to determine the biodistribution of NG vs time in the whole body and its clearance through the kidneys and bladder. Furthermore, we have observed that mic…

Xyloglucan-based hydrogel films for wound dressing: Structure-property relationships

Thin xyloglucan-based hydrogel films have been synthetized and characterized in the prospect of producing wound dressings. Polyvinyl alcohol (PVA) and glycerol (Gro) were added to have an optimal combination of softness, conformability and resilience. Physical hydrogels have been transformed into permanent covalent hydrogels by reaction with glutaraldehyde (GA). Network structure-process-property relationships are discussed on the account of the results of several complementary characterizations: FTIR, rheology, thermal analysis, morphological analysis, moisture retention and swelling measurements. Selected formulations were also subjected to preliminary in vitro cytotoxicity tests. The phy…

In vitro reactivity of peripheral blood mononuclear cells from subjects with different genetic background to amyloid b (Ab42) peptide: implication for cancer an immunotherapy.

FERULIC ACID INHIBITS OXIDATE STRESS AND CELL DEATH INDUCED BY Ab OLIGOMERS: IMPROVED DELIVERY BY SOLID LIPID NANOPARTICLES.

Oxidative stress and dysfunctional mitochondria are among the earliest events in AD, triggering neurodegeneration. The use of natural antioxidants could be a neuroprotective strategy for blocking cell death. Here, the antioxidant action of ferulic acid (FA) on different paths leading to degeneration of recombinant beta-amyloid peptide (rAbeta42) treated cells was investigated. Further, to improve its delivery, a novel drug delivery system (DDS) was used. Solid lipid nanoparticles (SLNs), empty or containing ferulic acid (FA-SNL), were developed as DDS. The resulting particles had small colloidal size and highly negative surface charge in water. Using neuroblastoma cells and rAbeta42 oligome…

SELF-ASSEMBLED AMPHIPHILIC HYALURONIC ACID GRAFT COPOLYMERS FOR TARGETED RELEASE OF ANTITUMORAL DRUG

Polymeric micelles obtained by self-assembling of amphiphilic hyaluronic acid (HA) graft copolymers have been prepared and characterized. In particular, hyaluronic acid (HA) has been grafted to polylactic acid (PLA) and polyethylenglycol chains (PEG), then the copolymers able to form micelles in aqueous medium have been chosen to entrap the antitumoral drug Doxorubicin. The critical aggregation concentration of HA-g-PLA or HA-g-PLA-g-PEG micelles has been determined by using pyrene as a fluorescent probe, whereas their shape and size have been evaluated by light scattering measurements, scanning and transmission electron microscopies. The selective cytotoxicity of drug loaded micelles towar…

Ab42 toxicity on Paracentrotus lividus development

Temporal control of xyloglucan self-assembly into layered structures by radiation-induced degradation

Partially degalactosylated xyloglucan from tamarind seeds (Deg-XG) is a very appealing biopolymer for the production of in situ gelling systems at physiological temperature. In this work, we observe that the morphology of hydrogels evolves towards high degrees of structural organization with time, yielding to dense stacks of thin membranes within 24 h of incubation at 37 °C. We also explore the possibility offered by gamma irradiation of controlling the time scale of this phenomenon, the final morphology and mechanical properties of the system. Structural and molecular modifications of Deg-XG with dose are investigated by FTIR, dynamic light scattering (DLS) and rotational viscosimetry. The…

CURCUMIN ENTRAPPED INTO LIPID NANOSYSTEMS IMPROVES INHIBITION OF NEUROBLASTOMA CANCER CELL GROWTH ACTIVATING HSP70 PROTEIN

Additional file 1 of Synaptosomes: new vesicles for neuronal mitochondrial transplantation

Additional file 1: Figure S1. A) Morphological analysis of LAN5 cells incubated with different doses (5-10 and 20 µl, which correspond to concentration of 2.5 × 107; 5.1 × 107; 10.2 × 107 particles/100µl respectively) of synaptosomes (Synap). B) Nuclear staining by fluorescence probe Hoechst 3341 of LAN5 cells incubated with different doses (5-10 and 20 µl) of synaptosomes (Synap).