Biomedical Applications of Reactive Oxygen Species Generation by Metal Nanoparticles

The design, synthesis and characterization of new nanomaterials represents one of the most dynamic and transversal aspects of nanotechnology applications in the biomedical field. New synthetic and engineering improvements allow the design of a wide range of biocompatible nanostructured materials (NSMs) and nanoparticles (NPs) which, with or without additional chemical and/or biomolecular surface modifications, are more frequently employed in applications for successful diagnostic, drug delivery and therapeutic procedures. Metal-based nanoparticles (MNPs) including metal NPs, metal oxide NPs, quantum dots (QDs) and magnetic NPs, thanks to their physical and chemical properties have gained much traction for their functional use in biomedicine. In this review it is highlighted how the generation of reactive oxygen species (ROS), which in many respects could be considered a negative aspect of the interaction of MNPs with biological matter, may be a surprising nanotechnology weapon. From the exchange of knowledge between branches such as materials science, nanotechnology, engineering, biochemistry and medicine, researchers and clinicians are setting and standardizing treatments by tuning ROS production to induce cancer or microbial cell death

Cytotoxicity and Thermal Characterization Assessment of Excipients for the Development of Innovative Lyophilized Formulations for Oncological Applications

Freeze-drying, also known as lyophilization, significantly improves the storage, stability, shelf life, and clinical translation of biopharmaceuticals. On the downside, this process faces complex challenges, i.e., the presence of freezing and drying stresses for the active compounds, the uniformity and consistency of the final products, and the efficiency and safety of the reconstituted lyophilized formulations. All these requirements can be addressed by adding specific excipients that can protect and stabilize the active ingredient during lyophilization, assisting in the formation of solid structures without interfering with the biological and/or pharmaceutical action of the reconstituted products. However, these excipients, generally considered safe and inert, could play an active role in the formulation interacting with the biological cellular machinery and promoting toxicity. Any side effects should be carefully identified and characterized to better tune any treatments in terms of concentrations and administration times. In this work, various concentrations in the range of 1 to 100 mg/mL of cellobiose, lactose, sucrose, trehalose, isoleucine, glycine, methionine, dextran, mannitol, and (2-hydroxypropyl)-β-cyclodextrin were evaluated in terms of their ability to create uniform and solid lyophilized structures. The freeze-dried products were then reconstituted in the appropriate cell culture media to assess their in vitro cytotoxicity on both a healthy cell line (B-lymphocytes) and their tumoral lymphoid counterpart (Daudi). Results showed that at 10 mg/mL, all the excipients demonstrated suitable lyophilized solid structures and high tolerability by both cell lines, while dextran was the only excipient well-tolerated also up to 100 mg/mL. An interesting result was shown for methionine, which even at 10 mg/mL, selectively affected the viability of the cancerous cell line only, opening future perspectives for antitumoral applications

Alexandre Eulalio, poeta, diante de Quirino Campofiorito, pintor

The article is focused on analisys of a poem written by AlexandreEulalio, know essayist. This analysis is based on Goethe’s conception of poetry of occasion – word that means, in the specific context, an exhibition of the painter’s screens Quirino Campofiorito.O artigo está centrado na análise de um poema escrito por Alexandre Eulalio, conhecido ensaísta. Essa análise baseia-se na concepção de Goethe de poesia de ocasião – palavra que significa, no contexto específico, uma exposição de telas do pintor Quirino Campofiorito

DEVICE FOR OBTAINING THREE-DIMENSIONAL CELL CULTURES, METHOD FOR THE IMPLEMENTATION THEREOF, AND USE OF SUCH DEVICE

A device for obtaining threedimensional cell cultures comprising: a sub strate (1); a plurality of micro-structures (2) which protrude from the surface of the sub strate (1) and are arranged on such substrate (1) according to a periodical grid so as to make the substrate (1) super hydrophobic. The device is characterised in that the micro-struc tures (2) have side walls at least partially nano-patterned and have projections (14) and recesses (16) alternated with a predetermined distance

In vitro evaluation of the presence of apical deviation with employment of automated handpieces with continuous and alternate motion for root canal preparation

O presente trabalho avaliou, in vitro, a presença de desvio apical no preparo de canais radiculares em raízes mésio-vestibulares de molares superiores humanos utilizando-se de peças automatizadas de giro contínuo, sistema Pow R (Moyco Union Broach) e giro alternado, sistema M4 (Kerr - USA). A análise da presença de desvios apicais foi realizada por meio de radiografias obtidas na plataforma radiográfica confeccionada para o experimento. Os resultados mostraram não haver diferença estatisticamente significante quanto à avaliação da presença de desvio entre os dois sistemas. Não houve correlação entre o grau de curvatura das raízes e o grau de desvio apical, no sistema de giro contínuo. No entanto, o sistema de giro alternado apresentou diferença estatística de correlação direta e grau médio.The present study conducted an in vitro evaluation of the presence of apical deviation on the root canal preparation of the mesiobuccal roots of human maxillary molars employing automated handpieces with continuous motion, the Pow R system (Moyco Union Broach), and alternate motion, the M4 system (Kerr). Analysis of the presence of apical deviation was carried out by means of radiographs obtained on a radiographic desk fabricated for the study. The results demonstrated the lack of statistically significant differences between the two systems as to the evaluation of the presence of apical deviation. There was no correlation between the degree of curvature of the roots and the degree of apical deviation for the continuous motion system. However, there was a statistic difference for the alternate motion system, with a direct correlation of moderate degree

Tailoring dry microparticles for pulmonary drug delivery: ultrasonic spray freeze-drying with mannitol and salbutamol sulphate

Spray freeze-drying has emerged as a valid alternative to traditional spray drying to produce therapeutic dry microparticles. In particular, the spherical shape and high porosity of spray freeze-dried microparticles make them suitable for pulmonary drug delivery through dry powder inhalers. However, an appropriate particle size and fine particle fraction are required to guarantee lung deposition. This study used ultrasonic spray freeze-drying to generate dry microparticles composed of mannitol either alone or added with the bronchodilator salbutamol sulphate. The influence of the solid concentration and the feed flow rate on the particle size, morphology, surface area, porosity, and crystallinity was investigated. Growing particle size was observed, increasing the concentration and feed flow rate. Similarly, the addition of the drug led to a larger particle size and surface area. The in vitro simulation of drug deposition highlighted the dependence of the aerodynamic properties on the solid concentration and feed flow rate. Due to the lower density and particle geometric size, the highest fine particle fraction (26%) and smallest mass median aerodynamic diameter (4.4 μm) were reached at the lowest solid concentration and feed flow rate

Comparative Studies of Different Preservation Methods and Relative Freeze-Drying Formulations for Extracellular Vesicle Pharmaceutical Applications

Extracellular vesicles (EVs) have been studied for years for their role as effectors and mediators of cell-to-cell communication and their potential application to develop new and increasingly performing nanotechnological systems for the diagnosis and/or treatment of many diseases. Given all the EVs applications as just isolated, functionalized, or even engineered cellular-derived pharmaceuticals, the standardization of reliable and reproducible methods for their preservation is urgently needed. In this study, we isolated EVs from a healthy blood cell line, B lymphocytes, and compared the effectiveness of different storage methods and relative freeze-drying formulations to preserve some of the most important EVs’ key features, i.e., concentration, mean size, protein content, and surface antigen’s expression. To develop a preservation method that minimally affects the EVs’ integrity and functionality, we applied the freeze-drying process in combination with different excipients. Since EVs are isolated not only from body fluids but also from culture media conditioned by the cells growing there, we decided to test both the effects of the traditional pharmaceutical excipient and of biological media to develop EVs solidified products with desirable appearance and performance properties. Results showed that some of the tested excipients, i.e., sugars in combination with dextran and glycine, successfully maintained the stability and integrity of EVs upon lyophilization. In addition, to evaluate the preservation of the EVs’ biological activity, we assessed the cytotoxicity and internalization ability of the reconstituted EVs in healthy (B lymphocytes) and tumoral (Burkitt’s lymphoma) cells. Reconstituted EVs demonstrated toxicity only toward the cancerous cells, opening new therapeutic opportunities for the oncological field. Furthermore, our study showed how some biological or cellular-conditioned fluids, commonly used in the field of cell cultures, can act not only as cryoprotectants but also as active pharmaceutical ingredients, significantly tuning the therapeutic effect of EVs, even increasing their cellular internalization

Progressive changes in descriptive discourse in First Episode Schizophrenia: a longitudinal computational semantics study

Computational semantics, a branch of computational linguistics, involves automated meaning analysis that relies on how words occur together in natural language. This offers a promising tool to study schizophrenia. At present, we do not know if these word-level choices in speech are sensitive to the illness stage (i.e., acute untreated vs. stable established state), track cognitive deficits in major domains (e.g., cognitive control, processing speed) or relate to established dimensions of formal thought disorder. In this study, we collected samples of descriptive discourse in patients experiencing an untreated first episode of schizophrenia and healthy control subjects (246 samples of 1-minute speech; n = 82, FES = 46, HC = 36) and used a co-occurrence based vector embedding of words to quantify semantic similarity in speech. We obtained six-month follow-up data in a subsample (99 speech samples, n = 33, FES = 20, HC = 13). At baseline, semantic similarity was evidently higher in patients compared to healthy individuals, especially when social functioning was impaired; but this was not related to the severity of clinically ascertained thought disorder in patients. Across the study sample, higher semantic similarity at baseline was related to poorer Stroop performance and processing speed. Over time, while semantic similarity was stable in healthy subjects, it increased in patients, especially when they had an increasing burden of negative symptoms. Disruptions in word-level choices made by patients with schizophrenia during short 1-min descriptions are sensitive to interindividual differences in cognitive and social functioning at first presentation and persist over the early course of the illness

Deslocamento apical produzido por instrumentos de níquel-titânio acionados a motor e limas de aço inoxidável

The aim of this study was to evaluate the apical displacement produced by different rotary nickel-titanium instruments, testing the hypothesis that rotary systems with nickel-titanium instruments produce lower mean values of apical displacement than stainless steel hand instruments. A total of 100 maxillary permanent first molars were selected for the study. The mesiobuccal roots were sectioned at the top cervical third and embedded in blocks of self-curing resin. The specimens were randomly divided into 5 groups and the root canals were prepared using the following nickel-titanium instruments: Group 1 - Quantec system 2000 (Analytic Endodontics, Mexico); Group 2 - Pro-File T.0.04 (Dentsply/Maillefer, Switzerland); Group 3 - Pro-File Series 29 T.0.04 (Dentsply Tulsa, Switzerland); Group 4 - Pow-R T.0.02 (Moyco-Union Broach, USA). Specimens in Group 5 were prepared using stainless steel hand instruments Flexofile (Dentsply/Maillefer, Switzerland). All root canals were previously submitted to cervical preparation using Orifice Shaper instruments #1, 2, 3 and 4 (Dentsply/Maillefer, Switzerland). After odontometry, the remaining root canal was shaped employing increasingly larger instruments, so that the final instrument corresponded to Quantec #9, Pro-File Series 29 #6, and #35 for the other groups. Specimens in Groups 1 to 4 were prepared using an electric handpiece with 16:1 reduction at 350 rpm. The specimens in Group 5 were manually prepared. Apical displacement was measured and recorded by means of radiographic superimposition on a specific desk. Statistical analysis (ANOVA) of the results revealed that all groups presented apical displacements. Considering only the nickel-titanium instruments, Group 4 showed the lowest mean value while Groups 2 and 3 produced the highest mean apical displacement values (pO objetivo deste trabalho foi avaliar o deslocamento apical produzido por diferentes instrumentos de níquel-titânio acionadas a motor testando a hipótese de que os sistemas rotatórios que usam instrumentos de níquel-titânio produzem valores médios de deslocamento apical menores que as limas manuais de aço inox. Foram utilizados 100 primeiros molares permanentes superiores, cujas raízes mesiovestibulares foram separadas e incluídas em blocos de resina autopolimerizável. Os corpos de prova foram divididos aleatoriamente em 5 grupos e os canais radiculares preparados com instrumentos de níquel-titânio: Grupo 1 - sistema Quantec 2000 (Analytic Endodontics, México); Grupo 2 - Pro-File T.0.04 (Dentsply/Maillefer, Suíça); Grupo 3 - Pro-File Série 29 T.0.04 (Dentsply Tulsa, Suíça); Grupo 4 - Pow-R T.0.02 (Moyco-Union Broach, EUA); e Grupo 5 (limas manuais) - limas manuais de aço inox Flexofile (Dentsply/Maillefer, Suíça). Todos os canais mesiovestibulares foram submetidos a um preparo cervical prévio utilizando-se instrumentos Orifice Shaper números 1, 2, 3 e 4 (Dentsply/Maillefer, Suíça). Realizada a odontometria, o restante do canal radicular foi modelado a partir dos instrumentos do menor para o maior calibre de tal ordem que o instrumento final de preparo correspondeu ao número 9 para o Quantec, número 06 para o Pro-File Série 29 e o número 35 para os demais grupos. Nos grupos de 1 a 4 foi utilizado motor elétrico com contra-ângulo de redução de 16:1 numa velocidade de 350 rpm. No grupo 5 o preparo foi realizado manualmente. A análise dos resultados (ANOVA), obtidos pela sobreposição radiográfica numa plataforma especifica, demonstraram que todos os grupos apresentaram deslocamentos apicais, sendo que o menor valor médio foi verificado no grupo 4 e os maiores valores médios foram observados nos grupos 2 e 3 (