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INTRODUCTION: Several studies show an association between obesity, impulsivity, and anger. The condition of obesity has moreover an important correlation with Eating Disorders (EDs), the most frequent of which is Binge Eating Disorder (BED). Obese patients seem to express peculiarities regarding the expression of some emotional processes, including impulsivity, aggression and anger, compared with regular-weight patients and those without an ED. SUBJECT AND METHODS: This is a cross-sectional study carried out on a population of 47 obese patients undergoing bariatric surgery. Patients underwent a psychiatric evaluation at the outpatient clinics of the Section of Psychiatry, Clinical Psychology and Psychiatric Rehabilitation of the University Hospital of Perugia. Levels of anger and impulsivity were characterized using the STAXI-2 and BIS-11 scores. Scores were compared based on sex, the presence/absence of EDs and on the presence/absence of psychiatric disorders attested during the evaluation. RESULTS: No statistically significative difference were detected on STAXI-2 and BIS-11 scores comparing men and women. People diagnosed with EDs had higher scores in the subscores of attention, cognitive complexity, motor impulsivity, non-planning impulsivity, and in the BIS-11 total score. No differences were detected in the STAXI-2 scores. When comparing patients on the presence/absence of psychiatric comorbidities, obese patients with a psychiatric diagnosis had higher scores on the impulsivity measures, but also a higher value on the ER index of the STAXI-2. CONCLUSIONS: Obese subjects undergoing bariatric surgery represent a fragile population that must be carefully evaluated from a psychiatric point of view. Indeed, the co-existence of psychiatric comorbidities may underpin the present of trait-like characteristics, such as impulsivity and anger, that should be carefully considered when proposing treatment strategies.
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Ira , Cirugía Bariátrica , Conducta Impulsiva , Obesidad , Humanos , Femenino , Masculino , Conducta Impulsiva/fisiología , Adulto , Estudios Transversales , Ira/fisiología , Persona de Mediana Edad , Obesidad/cirugía , Obesidad/psicología , Obesidad/epidemiología , Comorbilidad , Obesidad Mórbida/cirugía , Obesidad Mórbida/psicologíaRESUMEN
INTRODUCTION: The characteristics of the working environment significantly influence the mental well-being of workers, and the presence of unfavorable conditions in the workplace can have a negative impact on mental health. Healthcare professionals are particularly exposed to the risk of burnout and the development of psychiatric, and particularly affective, symptoms. This paper aims to describe the activity of a psychological support service dedicated to work-related stress at the General Hospital of Perugia, Italy. SUBJECTS AND METHODS: In June 2022, a free and anonymous psychological service dedicated to healthcare professionals was established at the Perugia General Hospital. The main objectives of the service were to promote overall well-being of workers, to provide psychological support, and to address professionals towards specific pathways to care. RESULTS: The activity of the service consisted of clinical consultations with psychiatrists and psychologists who also administered psychometric tools to better characterize the overall clinical picture. After the clinical evaluation process, healthcare professionals who accessed the service were addressed to specific pathways of care, when needed. The data collection carried out from June 2022 to April 2024 showed a total number of 139 accesses to the Service, with a majority of requests from women (80%) and mainly belonging to nursing staff (53%). CONCLUSIONS: Preliminary data from the psychological service dedicated to healthcare professionals confirms the high prevalence of work-related stress, especially in specific settings. In the near future, psychological support services are expected to identify work-related stress situations as soon possible, possibly contributing to the reduction of stigma and to the built of healthier working environments.
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Hospitales Generales , Estrés Laboral , Humanos , Estrés Laboral/psicología , Estrés Laboral/terapia , Femenino , Italia , Masculino , Adulto , Servicios de Salud Mental/normas , Personal de Salud/psicología , Agotamiento Profesional/psicología , Persona de Mediana EdadRESUMEN
INTRODUCTION: Obese subjects undergoing bariatric surgery often display medical and psychiatric comorbidities, influencing post-operative course and long-term prognosis. Candidates for bariatric surgery are evaluated through a multidisciplinary assessment in the pre-operative phase, including a psychiatric visit. The psychiatric examination aims to screen psychiatric comorbidities, including feeding and eating disorders (FEDs). Indeed, there is evidence of the association between obesity and several psychiatric disorders, such as FEDs, but also anxiety disorders, mood disorders, psychotic disorders, neurodevelopment disorders and personality disorders, particularly B and C cluster personalities. This study aims to evaluate the presence of psychiatric comorbidities among a population of candidates for bariatric surgery, and to underline the clinical correlates of FEDs diagnosis at the pre-operative assessment. SUBJECTS AND METHODS: Patients were recruited at the outpatient service of the Section of Psychiatry, Clinical Psychology and Rehabilitation of the General Hospital/University of Perugia. Psychiatric comorbidities were investigated by a psychiatric interview and hetero-administered scales for the evaluation of DSM-5 psychiatric syndromes (Structured Interview for DSM-5 Disorders - clinical version - SCID-5-CV), psychopathological and personality characteristics (Minnesota Multiphasic Personality Inventory - MMPI-2 and Structured Clinical Interview for DSM-5-Personality Disorders - SCID-5-PD) and specific scales for the evaluation of FEDs (Binge Eating Scale - BES, Obesity Questionnaire - OQ, Bulimia Test-Revised - BULIT-R and Body Shape Questionnaire - BSQ). After performing descriptive statistics, we performed bivariate analyses to assess significant differences between subjects with and without FEDs diagnosis (pË0.05). RESULTS: The sample was composed of 160 subjects (70.6% F versus 29.4% M). The average BMI was 42.90 ±6.258 and 86.8% of subjects had a Class 3 Obesity (BMI ≥40). 41.3% of patients received a psychiatric diagnosis and, specifically, a diagnosis of FEDs was highlighted in 28.7% cases. Individuals with FEDs more frequently had a family history of obesity and FEDs. As for psychopathological characteristics, altered scores on the BES and on the BULIT-R were more frequent in the group with psychiatric disorders excluding FEDs. CONCLUSIONS: Patients evaluated in bariatric surgery pre-operative assessment often display FEDs. Patients with FEDs more frequently suffer from other psychiatric disorders, showing the need for specific support pathways in this group of patients.
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Cirugía Bariátrica , Trastornos de Alimentación y de la Ingestión de Alimentos , Obesidad Mórbida , Humanos , Estudios Retrospectivos , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Cirugía Bariátrica/psicología , ObesidadRESUMEN
BACKGROUND: The aim of this systematic review is to critically summarize current literature concerning ethical and legal issues related compulsory treatment (CT) in patients with anorexia nervosa (AN). SUBJECTS AND METHODS: Relevant articles were identified following the PRISMA guidelines after performing title/abstract screening and full text screening. We built the search string using the following terms: "coercion", "compulsory/involuntary treatment", "eating disorders", "anorexia nervosa", "mental capacity", "ethical/legal issues". Research was conducted on original articles published from any time until June 2023. RESULTS: Out of 302 articles retrieved, seven were included for the analysis, including five studies on mental health practitioners, and two on hospital records. The results show that mental health practitioners a) favor the use of CT, but the support is weaker in AN vs other psychiatric conditions (i.e., schizophrenia or depression); b) support of mental capacity is controversial and some variability was found between different categories of psychiatrists; in particular, both ED-treating and CT experienced mental health practitioners support higher use of CT and lack of capacity of AN patients vs. general psychiatrists; c) use of CT is more supported in the early vs. chronic AN, when chances of success are lower. The analysis of hospital records identified 1) comorbidities, previous admissions and current health risk as CT predictors in 96 Australian patients; 2) family conflicts association with longer hospitalizations in 70 UK patients. CONCLUSION: CT is usually intended for patients with AN at the onset of disease, mainly to prevent risk of death and self-injury. However, there is some variability in the attitude to perform CT among psychiatrists working in different setting, also related to the concept of mental capacity. There are also cross-national variabilities regarding CT. We can conclude that forcing patients to treatment is a conceivable option, but the balance between protection respect for patient's autonomy should be evaluated on individual bases.
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Anorexia Nerviosa , Trastornos de Alimentación y de la Ingestión de Alimentos , Tratamiento Involuntario , Humanos , Anorexia Nerviosa/terapia , Anorexia Nerviosa/psicología , Coerción , AustraliaRESUMEN
A simple procedure to incorporate enzymes (horseradish peroxidase, HRP, and lactate oxidase, LOx) within alginate hydrogels is reported with electrochemiluminescence (ECL) used to detect the enzymatic reactions with the corresponding substrates. First, HRP and LOx were successfully immobilized into CaCO3 microspheres, followed by the electrostatic layer-by-layer deposition of a nanoshell onto the microspheres, and finally by their dispersion into alginate solution. The as-prepared dispersion was drop cast onto the glassy carbon electrodes and cross-linked by the external and internal gelation methods using Ca2+ cations. The enzymes encapsulated within the alginate hydrogels were characterized using cyclic voltammetry and kinetic studies performed using ECL. The results showed that the enzymatic activity was significantly maintained as a result of the immobilization, with values of the apparent Michaelis-Menten constants estimated as 7.71 ± 0.62 and 8.41 ± 0.43 µM, for HRP and LOx, respectively. The proposed biosensors showed good stability and repeatability with an estimated limit of detection of 5.38 ± 0.05 and 0.50 ± 0.03 µM for hydrogen peroxide and lactic acid, respectively. The as-prepared enzymes encapsulated within the alginate hydrogels showed good stability up to 28 days from their preparation. The sensitivity and selectivity of the enzymes encapsulated within the alginate hydrogels were tested in real matrices (HRP, hydrogen peroxide, in contact lens solution; LOx, lactic acid in artificial sweat) showing the sensitivity of the ECL detection methods for the detection of hydrogen peroxide and lactic acid in real samples.
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Alginatos , Técnicas Biosensibles , Alginatos/química , Enzimas Inmovilizadas/química , Peróxido de Hidrógeno/química , Hidrogeles , Cinética , Peroxidasa de Rábano Silvestre/química , Técnicas Biosensibles/métodos , Electrodos , Ácido LácticoRESUMEN
The effect of plasticizers, namely glycerol, sorbitol, and citric acid, on the structural and mechanical properties of biodegradable films obtained from xanthan gum (XG) and starch was studied. The plasticizing effect of glycerol, sorbitol, and citric acid on XG-starch films is justified by the destruction of intermolecular contacts between starch and XG macromolecules and the redistribution of hydrogen bonds in the system as a result of the hydrotropic action of plasticizer molecules. The use of glycerol proved to be the most effective for regulating the deformation of films, while the use of sorbitol to preserve strength. The dependence of the film roughness on the type and concentration of plasticizers was characterized. The smallest values of protrusions on the surface of XG-starch films were found in the presence of sorbitol. Considering the effect of the concentration of plasticizers on the stickiness of the surface of XG-starch films and their structural and mechanical properties, 1.5 % concentration of glycerol, sorbitol and citric acid was determined as optimal.
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Advanced in vitro models of the brain have evolved in recent years from traditional two-dimensional (2D) ones, based on rodent derived cells, to three-dimensional (3D) ones, based on human neurons derived from induced pluripotent stem cells. To address the dynamic changes of the tissue microenvironment, bioreactors are used to control the in vitro microenvironment for viability, repeatability, and standardization. However, in neuronal tissue engineering, bioreactors have primarily been used for cell expansion purposes, while microfluidic systems have mainly been employed for culturing organoids. In this study, we explored the use of a commercial perfusion bioreactor to control the culture microenvironment of neuronal cells in both 2D and 3D cultures. Namely, neurons differentiated from human induced pluripotent stem cells (iNeurons) were cultured in 2D under different constant flow rates for 72 h. The impact of different flow rates on early-stage neuronal development and synaptogenesis was assessed by morphometric characterization and synaptic analysis. Based on these results, two involving variable flow rates were developed and applied again in 2D culture. The most effective protocol, in terms of positive impact on neuronal development, was then used for a preliminary study on the application of dynamic culturing conditions to neuronal cells in 3D. To this purpose, both iNeurons, co-cultured with astrocytes, and the human neuroblastoma cells SH-SY5Y were embedded into a hydrogel and maintained under perfusion for up to 28 days. A qualitative evaluation by immunocytochemistry and confocal microscopy was carried out to assess cell morphology and the formation of a 3D neuronal network.
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Breast cancer is a significant global health concern, with the overexpression of human epidermal growth factor receptor 2 (HER2/ERBB2) being a driver oncogene in 20%-30% of cases. Indeed, HER2/ERBB2 plays a crucial role in regulating cell growth, differentiation, and survival via a complex signaling network. Overexpression of HER2/ERBB2 is associated with more aggressive behavior and increased risk of brain metastases, which remains a significant clinical challenge for treatment. Recent research has highlighted the role of breast cancer secretomes in promoting tumor progression, including excessive proliferation, immune invasion, and resistance to anti-cancer therapy, and their potential as cancer biomarkers. In this study, we investigated the impact of ERBB2+ breast cancer SKBR-3 cell line compared with MCF10-A mammary non-tumorigenic cell conditioned medium on the electrophysiological activity and morphology of neural networks derived from neurons differentiated from human induced pluripotent stem cells. Our findings provide evidence of active modulation of neuronal-glial networks by SKBR-3 and MCF10-A conditioned medium. These results provide insights into the complex interactions between breast cancer cells and the surrounding microenvironment. Further research is necessary to identify the specific factors within breast cancer conditioned medium that mediate these effects and to develop targeted therapies that disrupt this interaction.
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Polylactic acid (PLA), a polymer derived from renewable resources, is gaining increasing attention in the development of biomedical devices due to its cost-effectiveness, low immunogenicity, and biodegradability. However, its inherent hydrophobicity remains a problem, leading to poor cell adhesion features. On this basis, the aim of this work was to develop a method for functionalizing the surface of PLA films with a biopolymer, chitosan (CH), which was proved to be a material with intrinsic cell adhesive properties, but whose mechanical properties are insufficient to be used alone. The combination of the two polymers, PLA as a bulk scaffold and CH as a coating, could be a promising combination to develop a scaffold for cell growth. The modification of PLA films involved several steps: aminolysis followed by bromination to graft amino and then bromide groups, poly(glycidyl methacrylate) (PGMA) grafting by surface-initiated supplemental activator and reducing agent atom transfer radical polymerization (SI-SARA ATRP) and finally the CH grafting. To prove the effective adhesive properties, conjugated and non-conjugated films were tested in vitro as substrates for neuronal cell growth using differentiated neurons from human induced pluripotent stem cells. The results demonstrated enhanced cell growth in the presence of CH.
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Proliferación Celular , Quitosano , Neuronas , Poliésteres , Andamios del Tejido , Quitosano/química , Poliésteres/química , Humanos , Andamios del Tejido/química , Neuronas/citología , Neuronas/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Polimerizacion , Adhesión Celular/efectos de los fármacos , Materiales Biocompatibles/químicaRESUMEN
Vascular tissue engineering endeavors to design, fabricate, and validate biodegradable and bioabsorbable small-diameter vascular scaffolds engineered with bioactive molecules, capable of meeting the challenges imposed by commercial vascular prostheses. A comprehensive investigation of these engineered scaffolds in bioreactor is deemed essential as a prerequisite before any in vivo experimentation in order to get information regarding their behavior under physiological conditions and predict the biological activities they will possess. This study focuses on an innovative electrospun scaffold made of poly(caprolactone) and poly(glycerol sebacate), integrating quercetin, able to modulate inflammation, and gelatin, necessary to reduce permeability. A custom-made bioreactor was used to assess the performances of the scaffolds maintained under different pressure regimes, covering the human physiological pressure range. As results, the 3D microfibrous architecture was notably influenced by the release of bioactives, maintaining the adequate properties needed for the in vivo regeneration and scaffolds showed mechanical properties similar to human native artery. Release of gelatin was adequate to avoid blood leakage and useful to make the material porous during the testing period, whereas the amount of released quercetin was useful to counteract the post-surgery inflammation. This study showcases the successful validation of an engineered scaffold in a bioreactor, enabling to consider it as a promising candidate for vascular substitutes in in vivo applications. Our approach represents a significant leap forward in the field of vascular tissue engineering, offering a multifaceted solution to the complex challenges associated with small-diameter vascular prostheses. .
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In vitro three-dimensional models aim to reduce and replace animal testing and establish new tools for oncology research and the development and testing of new anticancer therapies. Among the various techniques to produce more complex and realistic cancer models is bioprinting, which allows the realization of spatially controlled hydrogel-based scaffolds, easily incorporating different types of cells in order to recreate the crosstalk between cancer and stromal components. Bioprinting exhibits other advantages, such as the production of large constructs, the repeatability and high resolution of the process, as well as the possibility of vascularization of the models through different approaches. Moreover, bioprinting allows the incorporation of multiple biomaterials and the creation of gradient structures to mimic the heterogeneity of the tumor microenvironment. The aim of this review is to report the main strategies and biomaterials used in cancer bioprinting. Moreover, the review discusses several bioprinted models of the most diffused and/or malignant tumors, highlighting the importance of this technique in establishing reliable biomimetic tissues aimed at improving disease biology understanding and high-throughput drug screening.
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Methods for studying brain function and disease heavily rely onin vivoanimal models,ex-vivotissue slices, and 2D cell culture platforms. These methods all have limitations that significantly impact the clinical translatability of results. Consequently, models able to better recapitulate some aspects ofin vivohuman brain are needed as additional preclinical tools. In this context, 3D hydrogel-basedin vitromodels of the brain are considered promising tools. To create a 3D brain-on-a-chip model, a hydrogel capable of sustaining neuronal maturation over extended culture periods is required. Among biopolymeric hydrogels, chitosan-ß-glycerophosphate (CHITO-ß-GP) thermogels have demonstrated their versatility and applicability in the biomedical field over the years. In this study, we investigated the ability of this thermogel to encapsulate neuronal cells and support the functional maturation of a 3D neuronal network in long-term cultures. To the best of our knowledge, we demonstrated for the first time that CHITO-ß-GP thermogel possesses optimal characteristics for promoting neuronal growth and the development of an electrophysiologically functional neuronal network derived from both primary rat neurons and neurons differentiated from human induced pluripotent stem cells (h-iPSCs) co-cultured with astrocytes. Specifically, two different formulations were firstly characterized by rheological, mechanical and injectability tests. Primary nervous cells and neurons differentiated from h-iPSCs were embedded into the two thermogel formulations. The 3D cultures were then deeply characterized by immunocytochemistry, confocal microscopy, and electrophysiological recordings, employing both 2D and 3D micro-electrode arrays. The thermogels supported the long-term culture of neuronal networks for up to 100 d. In conclusion, CHITO-ß-GP thermogels exhibit excellent mechanical properties, stability over time under culture conditions, and bioactivity toward nervous cells. Therefore, they are excellent candidates as artificial extracellular matrices in brain-on-a-chip models, with applications in neurodegenerative disease modeling, drug screening, and neurotoxicity evaluation.
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Quitosano , Células Madre Pluripotentes Inducidas , Enfermedades Neurodegenerativas , Humanos , Ratas , Animales , Quitosano/química , Hidrogeles/química , EncéfaloRESUMEN
Understanding how the spatial organization of a neural network affects its activity represents a leading issue in neuroscience. Thanks to their accessibility and easy handling, in vitro studies remain an essential tool to investigate the relationship between the structure and function of a neuronal network. Among all the patterning techniques, ink-jet printing acquired great interest thanks to its direct-write approach, which allows the patterned substrate realization without mold, leading to a considerable saving of both cost and time. However, the inks commonly used give the possibility to control only the structure of a neuronal network, leaving aside the functional aspect. In this work, we synthesize a photosensitive ink combining the rheological and bioadhesive properties of chitosan with the plasmonic properties of gold nanorods, obtaining an ink able to control both the spatial organization of a two-dimensional neuronal network and its activity through photothermal effect. After the ink characterization, we demonstrate that it is possible to print, with high precision, different geometries on a microelectrode array. In this way, it is possible obtaining a patterned device to control the structure of a neuronal network, to record its activity and to modulate it via photothermal effect. Finally, to our knowledge, we report the first evidence of photothermal inhibition of human neurons activity. STATEMENT OF SIGNIFICANCE: Patterned cell cultures remain the most efficient and simple tool for linking structural and functional studies, especially in the neuronal field. Ink-jet printing is the technique with which it is possible to realize patterned structures in the fastest, simple, versatile and low-cost way. However, the inks currently used permit the control only of the neuronal network structure but do not allow the control-modulation of the network activity. In this study, we realize and characterize a photosensitive bioink with which it is possible to drive both the structure and the activity of a neuronal network. Moreover, we report the first evidence of activity inhibition by the photothermal effect on human neurons as far as we know.
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Nanotubos , Impresión , Humanos , Impresión/métodos , Neuronas , Técnicas de Cultivo de Célula , TintaRESUMEN
With the advent of human-induced pluripotent stem cells (hiPSCs) and differentiation protocols, methods to create in-vitro human-derived neuronal networks have been proposed. Although monolayer cultures represent a valid model, adding three-dimensionality (3D) would make them more representative of an in-vivo environment. Thus, human-derived 3D structures are becoming increasingly used for in-vitro disease modeling. Achieving control over the final cell composition and investigating the exhibited electrophysiological activity is still a challenge. Thence, methodologies to create 3D structures with controlled cellular density and composition and platforms capable of measuring and characterizing the functional aspects of these samples are needed. Here, we propose a method to rapidly generate neurospheroids of human origin with control over cell composition that can be used for functional investigations. We show a characterization of the electrophysiological activity exhibited by the neurospheroids by using micro-electrode arrays (MEAs) with different types (i.e., passive, C-MOS, and 3D) and number of electrodes. Neurospheroids grown in free culture and transferred on MEAs exhibited functional activity that can be chemically and electrically modulated. Our results indicate that this model holds great potential for an in-depth study of signal transmission to drug screening and disease modeling and offers a platform for in-vitro functional testing.
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Most in vitro functional and morphological studies for developing nervous system have been performed using traditional monolayer cultures onto supports modified by extracellular matrix components or synthetic biopolymers. These biomolecules act as adhesion factors essential for neuronal growth and differentiation. In this study, the use of chitosan as adhesion factor was investigated. Primary rat neurons and neurons differentiated from human induced pluripotent stem cells were cultured onto chitosan and standard adhesion factors modified supports. The initiation, elongation and branching of neuritic processes, synaptogenesis and electrophysiological behavior were studied. The biopolymers affected neurites outgrowth in a time dependent manner; in particular, chitosan promoted neuronal polarity in both cell cultures. These results indicate chitosan as a valid adhesion factor alternative to the standard ones, with the advantage that it can be used both in 2D and 3D cultures, acting as a bridge between these in vitro models.
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Quitosano , Células Madre Pluripotentes Inducidas , Animales , Células Cultivadas , Quitosano/metabolismo , Quitosano/farmacología , Humanos , Neuritas/metabolismo , Neuronas/metabolismo , RatasRESUMEN
Cisplatin is a first-choice chemotherapeutic agent used to treat solid tumors even though the onset of multi-drug resistance and the time-dose side-effects impair its mono-therapeutic application. Therefore, new drug-delivery approaches, based on nanomedicine strategies, are needed to enhance its therapeutic potential in favor of a dose-reduction of cisplatin. Polyunsaturated fatty acids and their metabolism-derived intermediates, as well as lipid peroxidation end-products, are used as adjuvants to improve the effectiveness of chemotherapy. Lipid hydroperoxides, derived from the oxidation of edible oils, can contribute to cell death, generating breakdown products (e.g., reactive aldehydes). In this regard, the aim of this present study was to evaluate an invitro combinatory strategy between a lecithin-based nanoemulsion system of K600, a patented mixture of peroxidated oil and peroxidated cholesterol, and cisplatin on DLD1 human adenocarcinoma cells. Our findings showed that nanoemulsions, acting in synergy with cisplatin, improve cisplatin bioactivity, in terms of enhancing its anti-cancer activity, towards DLD1 cells. Indeed, this combination approach, whilst maintaining cisplatin at low concentrations, induces a significant reduction in DLD1 cell viability, an increase in pro-apoptotic markers, and genotoxic damage. Therefore, K600 nanoemulsions as an efficient targeted delivery system of cisplatin allow for the reduction in the chemotherapeutic agent doses.
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The development of heterogeneous drug delivery systems leads to innovative strategies for targeted therapy of common pathologies, such as cancer, immunological and neurological disorders. Nowadays, it is possible to choose among a great variety of nanoparticles on the basis of the needs they have to satisfy. However, a candidate for the treatment of cardiovascular pathologies is still missing. In this context, a targeted therapy implies the conceptualization of nanoparticles that take active part in the treatment of vascular pathologies. The aim of this work was to provide a method to produce multi-layered calcium carbonate (CaCO3) nanoparticles encapsulating a model protein, bovine serum albumin, with model antibodies on their surface. CaCO3 nanoparticles were produced by the combination of complex coacervation and mineralization and were engineered using layer-by-layer technique with a polysaccharide, dextran sulfate, and a homo-poly-amino acid, poly-L-arginine. Morphology, biocompatibility, cellular uptake, influence on cell expression of the inflammatory marker matrix metalloproteinase-9, and hemocompatibility of the nanoparticles were studied. The presence of the dextran/poly-L-arginine layers did not negatively affect the nanoparticle overall characteristics and they did not trigger proinflammatory response in vitro. Taking together all the obtained results, we consider the proposed CaCO3 nanoparticles as a promising tool in cardiovascular field.
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Carbonato de Calcio , Dextranos , Portadores de Fármacos , Células Endoteliales/metabolismo , Nanoestructuras/química , Péptidos , Carbonato de Calcio/química , Carbonato de Calcio/farmacología , Línea Celular , Dextranos/química , Dextranos/farmacología , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Humanos , Péptidos/química , Péptidos/farmacologíaRESUMEN
In this work, novel composite microparticles based on chitosan (CHI) and graphite nanoplatelets (GNP) were developed as 3D scaffolds for neuronal cells. The aim is to improve the scaffold strength while maintaining its ability to sustain cell adhesion and differentiation. An air-assisted jetting technique followed by physical crosslinking is employed to obtain CHI/GNP microparticles. Optical and Field Emission Scanning Electron Microscopy micrographs showed a uniform distribution of GNP within the CHI porous matrix. The presence of GNP turned out to improve the strength of the microparticles while conferring good electrical conductivity and ameliorating their stability in aqueous environment. The morphological and immunocytochemical characterization, combined with a preliminary electrophysiological analysis, evidenced the effectiveness of the developed composite microparticles as a scaffold for neuron growth. These scaffolds could be employed for the development of advanced 3D neuronal in vitro models for networks dynamics analysis and drug screening.
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Quitosano/química , Grafito/química , Hidrogeles/química , Nanoestructuras/química , Neuronas/efectos de los fármacos , Andamios del Tejido/química , Módulo de Elasticidad , Conductividad Eléctrica , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Ingeniería de Tejidos/métodosRESUMEN
This work describes the preparation and characterization of printed biodegradable polymer (polylactic acid) capsules made in two different shapes: pyramid and rectangular capsules about 1 and 11 µm in size. Obtained core-shell capsules are described in terms of their morphology, loading efficiency, cargo release profile, cell cytotoxicity, and cell uptake. Both types of capsules showed monodisperse size and shape distribution and were found to provide sufficient stability to encapsulate small water-soluble molecules and to retain them for several days and ability for intracellular delivery. Capsules of 1 µm size can be internalized by HeLa cells without causing any toxicity effect. Printed capsules show unique characteristics compared with other drug delivery systems such as a wide range of possible cargoes, triggered release mechanism, and highly controllable shape and size.
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Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos , Poliésteres/química , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Cápsulas/química , Línea Celular , Doxiciclina/administración & dosificación , Doxiciclina/farmacocinética , Composición de Medicamentos/instrumentación , Diseño de Equipo , Células HeLa , Humanos , Ratones , Tamaño de la Partícula , Impresión Tridimensional/instrumentaciónRESUMEN
The work investigated the possibility to develop an easy scalable treatment capable of modifying only the surface of chitosan-based materials, limiting the degradation of the bulk and the burst release of a drug, without compromising the properties of the polymeric matrix. To this aim, microparticles of CHI were superficially coated with poly-(styrene-co-maleic anhydride) (PSMA), taking advantage of the potential reactivity of chitosan amino groups and maleic functionalities of PSMA. The specific reactions/interactions occurring between the two polymers were studied by IR measurements, while FE-SEM analysis evidenced the modification of the morphology of the particles contacted with PSMA. Contact angle measurements demonstrated the change of wettability in the modified systems and TGA analysis allowed to estimate the amount of the deposited PSMA. The above treatment turned out to improve the particle stability both in an acidic environment and in an enzymatic system. The release properties of the treated and of the untreated particles, over a period of 10 h, were tested using, as model drug, the protein Bovine Serum Albumin (BSA). Finally, the cytocompatibility of the developed composite microparticles was assessed on MCF-7 human breast cancer cells, which measurements demonstrated the non-toxicity of the treatment.