Chronic exposure to TiO2 micro- and nano particles: A biochemical and histopathological experimental study.

The aim of this work was to analyze the effects of long-term exposure to titanium dioxide (TiO2) micro- (MPs) and nanoparticles (NPs) (six and 12 months) on the biochemical and histopathological response of target organs using a murine model. Male Wistar rats were intraperitoneally injected with a suspension of TiO2 NPs (5 nm; TiO2-NP5 group) or MPs (45 µm; TiO2-NP5 group); the control group was injected with saline solution. Six and 12 months post-injection, titanium (Ti) concentration in plasma and target organs was determined spectrometrically (ICP-MS). Blood smears and organ tissue samples were evaluated by light microscopy. Liver and kidney function was evaluated using serum biochemical parameters. Oxidative metabolism was assessed 6 months post-injection (determination of superoxide anion by nitroblue tetrazolium (NBT) test, superoxide dismutase (SOD) and catalase (CAT), lipid peroxidation, and paraoxonase 1). Titanium (Ti) concentration in target organs and plasma was significantly higher in the TiO2-exposed groups than in the control group. Histological evaluation showed the presence of titanium-based particles in the target organs, which displayed no structural alterations, and in blood monocytes. Oxidative metabolism analysis showed that TiO2 NPs were more reactive over time than MPs (p < .05) and mobilization of antioxidant enzymes and membrane damage varied among the studied organs. Clearance of TiO2 micro and nanoparticles differed among the target organs, and lung clearance was more rapid than clearance from the lungs and kidneys (p < .05). Conversely, Ti concentration in plasma increased with time (p < .05). In conclusion, neither serum biochemical parameters nor oxidative metabolism markers appear to be useful as biomarkers of tissue damage in response to TiO2 micro- and nanoparticle deposits at chronic time points.

Design of a New Vaccine Prototype against Porcine Circovirus Type 2 (PCV2), M. hyopneumoniae and M. hyorhinis Based on Multiple Antigens Microencapsulation with Sulfated Chitosan.

This work evaluated in vivo an experimental-multivalent-vaccine (EMV) based on three Porcine Respiratory Complex (PRC)-associated antigens: Porcine Circovirus Type 2 (PCV2), M. hyopneumoniae (Mhyop) and M. hyorhinis (Mhyor), microencapsulated with sulfated chitosan (M- ChS + PRC-antigens), postulating chitosan sulphate (ChS) as a mimetic of the heparan sulfate receptor used by these pathogens for cell invasion. The EMV was evaluated physicochemically by SEM (Scanning-Electron-Microscopy), EDS (Energy-Dispersive-Spectroscopy), Pdi (Polydispersity-Index) and zeta potential. Twenty weaned pigs, distributed in four groups, were evaluated for 12 weeks. The groups 1 through 4 were as follows: 1-EMV intramuscular-route (IM), 2-EMV oral-nasal-route (O/N), 3-Placebo O/N (M-ChS without antigens), 4-Commercial-vaccine PCV2-Mhyop. qPCR was used to evaluate viral/bacterial load from serum, nasal and bronchial swab and from inguinal lymphoid samples. Specific humoral immunity was evaluated by ELISA. M-ChS + PRC-antigens measured between 1.3-10 µm and presented low Pdi and negative zeta potential, probably due to S (4.26%). Importantly, the 1-EMV protected 90% of challenged animals against PCV2 and Mhyop and 100% against Mhyor. A significant increase in antibody was observed for Mhyor (1-EMV and 2-EMV) and Mhyop (2-EMV), compared with 4-Commercial-vaccine. No difference in antibody levels between 1-EMV and 4-Commercial-vaccine for PCV2-Mhyop was observed. Conclusion: The results demonstrated the effectiveness of the first EMV with M-ChS + PRC-antigens in pigs, which were challenged with Mhyor, PCV2 and Mhyop, evidencing high protection for Mhyor, which has no commercial vaccine available.

Fish Burgers Fortified with Microencapsulated Sacha Inchi Oil: Effects on Technological and Sensory Properties.

The long-chain omega-3 fatty acids alpha linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have proven health benefits, but it is not common to find them together in a processed food product. This could lead to healthier and more functional food products, which may have positive implications for consumer health and well-being. This work aimed to fortify a model burger manufactured with fillets of an Amazonian fish (boquichico, Prochilodus nigricans) by adding microencapsulated sacha inchi oil (Plukenetia volubilis, rich in ALA) (MSIO) produced by spray-drying. MSIO was incorporated into the burgers at different levels (0, 3, 4, 5, and 6%). The burgers were characterized by their proximal composition, cooking losses, texture profile, lipid oxidation, sensory profile, overall liking, and fatty acid profile. The results showed that adding MSIO up to concentrations of 5% or 6% increased the instrumental hardness, chewiness, and lipid oxidation in the burgers. However, fortifying the burgers with 3% MSIO was possible without affecting the burgers' sensory properties and overall liking. Regarding the fatty acid profile, the burgers with 3% MSIO had a higher content of polyunsaturated fatty acids, with the ALA, EPA, and DHA types of fatty acids. Therefore, we recommend using this fortification concentration, but future studies should be carried out to improve the oxidative stability of MSIO and the burgers.

Interactive effects between water temperature, microparticle compositions, and fiber types on the marine keystone species Americamysis bahia.

Recently, there has been an increasing emphasis on examining the ecotoxicological effects of anthropogenic microparticles (MPs), especially microplastic particles, and related issues. Nevertheless, a notable deficiency exists in our understanding of the consequences on marine organisms, specifically in relation to microfibers and the combined influence of MPs and temperature. In this investigation, mysid shrimp (Americamysis bahia), an important species and prey item in estuarine and marine food webs, were subjected to four separate experimental trials involving fibers (cotton, nylon, polyester, hemp; 3 particles/ml; approximately 200 µm in length) or fragments (low-density Polyethylene: LDPE, polylactic acid: PLA, and their leachates; 5, 50, 200, 500 particles/ml; 1-20 µm). To consider the effects in the context of climate change, three different temperatures (22, 25, and 28 °C) were examined. Organismal growth and swimming behavior were measured following exposure to fragments and microfibers, and reactive oxygen species and particle uptake were investigated after microfiber exposure. To simulate the physical characteristics of MP exposure, such as microfibers obstructing the gills, we also assessed the post-fiber-exposure swimming behavior in an oxygen-depleted environment. Data revealed negligible fragment, but fiber exposure effects on growth. PLA leachate triggered higher activity at 25 °C and 28 °C; LDPE exposures led to decreased activity at 28 °C. Cotton exposures led to fewer behavioral differences compared to controls than other fiber types. The exposure to hemp fibers resulted in significant ROS increases at 28 °C. Microfibers were predominantly located within the gastric and upper gastrointestinal tract, suggesting extended periods of residence and the potential for obstructive phenomena over the longer term. The combination of increasing water temperatures, microplastic influx, and oxidative stress has the potential to pose risks to all components of marine and aquatic food webs.

Adverse effects of microparticles on transfusion of stored red blood cell concentrates.

BACKGROUND: Systemic and pulmonary coagulopathy and inflammation are important characteristics of transfusion-related acute lung injury (TRALI). Whether microparticles that accumulate in transfused red blood cell concentrates (RBCs) have proinflammatory and procoagulant potential and contribute to adverse reactions of RBC transfusions is unclear. AIM: To investigate the ability of microparticles in stored RBCs to promote thrombin generation and induce human pulmonary microvascular endothelial cell (HMVEC) activation and damage. METHODS: The number and size of microparticles were determined by flow cytometric and nanoparticle tracking analyses, respectively. Thrombin generation and the intrinsic coagulation pathway were assayed by a calibrated automated thrombogram and by measuring activated partial thromboplastin time (aPTT), respectively. The expression of ICAM-1 and the release of cytokines by endothelial cells were detected by flow cytometric analyses. HMVEC damage was assessed by incubating lipopolysaccharide-activated endothelial cells with MP-primed polymorphonuclear neutrophils (PMNs). RESULTS: The size of the microparticles in the RBC supernatant was approximately 100-300 nm. Microparticles promoted thrombin generation in a dose-dependent manner and the aPTT was shortened. Depleting microparticles from the supernatant of RBCs stored for 35 days by either filtration or centrifugation significantly decreased the promotion of thrombin generation. The expression of ICAM-1 on HMVECs was increased significantly by incubation with isolated microparticles. Furthermore, microparticles induced the release of interleukin-6 (IL-6) and interleukin-8 (IL-8) from HMVECs. Microparticles induced lipopolysaccharide-activated HMVEC damage by priming PMNs, but this effect was prevented by inhibiting the PMNs respiratory burst with apocynin. CONCLUSION: Microparticles in stored RBCs promote thrombin generation, HMVEC activation and damage which may be involved in TRALI development.

Light, Copper, Action: Visible-Light Illumination Enhances Bactericidal Activity of Copper Particles.

Bacteria are an old concern to human health, as they are responsible for nosocomial infections, and the number of antibiotic-resistant microorganisms keeps growing. Copper is known for its intrinsic biocidal properties, and therefore, it is a promising material to combat infections when added to surfaces. However, its biocidal properties in the presence of light illumination have not been fully explored, especially regarding the use of microsized particles since nanoparticles have taken over all fields of research and subjugated microparticles despite them being abundant and less expensive. Thus, the present work studied the bactericidal properties of metallic copper particles, in microscale (CuMPs) and nanoscale (CuNPs), in the absence of light and under white LED light illumination. The minimum bactericidal concentration (MBC) of CuMPs against Staphylococcus aureus that achieved a 6-log reduction was 5.0 and 2.5 mg mL-1 for assays conducted in the absence of light and under light illumination, respectively. Similar behavior was observed against Escherichia coli. The bactericidal activity under illumination provided a percentage increase in log reduction values of 65.2% for S. aureus and 166.7% for E. coli when compared to the assays under dark. This assay reproduced the testing CuNPs, which showed superior bactericidal activity since the concentration of 2.5 mg mL-1 promoted a 6-log reduction of both bacteria even under dark. Its superior bactericidal activity, which overcame the effect of illumination, was expected once the nanoscale facilitated the interaction of copper within the surface of bacteria. The results from MBC were supported by fluorescence microscopy and atomic absorption spectroscopy. Therefore, CuMPs and CuNPs proved to have size- and dose-dependent biocidal activity. However, we have shown that CuMPs photoactivity is competitive compared to that of CuNPs, allowing their application as a self-cleaning material for disinfection processes assisted by conventional light sources without additives to contain the spread of pathogens.

Complete holography-based system for the identification of microparticles in water samples.

Here, we present a comprehensive holography-based system designed for detecting microparticles through microscopic holographic projections of water samples. This system is designed for researchers who may be unfamiliar with holographic technology but are engaged in microparticle research, particularly in the field of water analysis. Additionally, our innovative system can be deployed for environmental monitoring as a component of an autonomous sailboat robot. Our system's primary application is for large-scale classification of diverse microplastics that are prevalent in water bodies worldwide. This paper provides a step-by-step guide for constructing our system and outlines its entire processing pipeline, including hologram acquisition for image reconstruction.

New approaches for modulation of alginate-chitosan delivery properties.

Alginate is a biopolymer widely used on delivery systems when bioactive protection at acidic pH is required, while chitosan can enhance mucoadhesion and controlled release at alkaline pHs. In this work, alginate ionotropic gelation and electrostatic complexation to chitosan were evaluated concomitantly or in a two-step approach to improve the delivery properties of systems in different pHs. The effect of pH on alginate gelation and chitosan interactions were also evaluated. Alginate microspheres were prepared by ionotropic gelation in CaCl2 at different pH values (2.5 and 6.0) by extrusion. Complexation with chitosan was carried out during alginate ionotropic gelation (one-step approach) or after alginate gel formation (two-step approach). Alginate microparticles without chitosan showed larger pores and lower mechanical strength. Extruded microspheres at pH 6.0 were more stable to pH and showed smaller pores than the formed at pH 2.5. One-step production retained a large amount of bioactive at pH 7.0 and resulted in lower release at the pH of intestinal digestion. The two-step approach retained less amount of bioactive but confer more protection to the pH of the stomach phase and higher release in pH of the intestinal phase than one-step samples. These results indicate that the formation of alginate gels by ionotropic gelation followed by the complexation with chitosan (in two-step) is promising for the transport and delivery of bioactives into intestinal conditions, whereas the ionotropic gelation concomitantly to electrostatic complexation (one-step approach) is indicated to the delivery of bioactives into lower pH environments.

Microparticles and cardiotoxicity secondary to doxorubicin-based chemotherapy in breast cancer patients.

Doxorubicin (DOXO)-cardiotoxicity is a limiting factor for breast cancer chemotherapy. The relationship between microparticles (MPs) and cardiotoxicity remains unclear. MPs can be released under varying pathophysiological conditions. Thereby, this study aimed to assess MPs derived from cardiomyocytes (CardioMPs), platelets (PMPs) and those that expresses tissue factor (TFMPs) in 80 women with breast cancer undergoing DOXO-based chemotherapy, with or without cardiotoxicity in a one-year follow-up. We observed in the cardiotoxicity group higher count of total-MPs at T0 (prior chemotherapy) (p = 0.034), CardioMPs at T0 and T1 (just after chemotherapy) (p = 0.009 and p = 0.0034) and TFMPs at T0 (p = 0.011) compared to non-cardiotoxicity group. The results suggest that MPs could be associated to cardiotoxicity due to DOXO treatment in breast cancer patients.

Enrichment of a fruit-based smoothie beverage with omega-3 fatty acids from microencapsulated chia seed oil.

BACKGROUND: Omega-3 fatty acids are known for their various health benefits. Chia is the richest vegetable source of omega-3 fatty acids. However, its oil is highly susceptible to oxidative deterioration and should be protected for incorporation into food matrices. This work aimed to study the incorporation of different chia oil microcapsules in a powdered beverage, analyzing the effect on the physicochemical characteristics and stability during storage. RESULTS: Different types of microcapsules were obtained: monolayer microcapsules using sodium caseinate and lactose as wall material, and multilayer microcapsules produced through electrostatic deposition using lecithins, chitosan, and chia mucilage as the first, second, and third layers, respectively. The results demonstrated an efficient enrichment of smoothies, with omega-3 fatty acid values ranging from 24.09% to 42.73%, while the original food matrix powder lacked this component. These powder beverages exhibited low moisture content (≤ 2.91%) and low water activity (≤ 0.39). The aerated, packed density and compressibility assays indicated that adding microcapsules made the powders less dense and compressible. The color of the original powdered beverage was not modified. The dispersibility reflected an acceptable instantaneity, reaching the maximum obscuration after 30 s of stirring. The solubility of all the enriched products was higher than 70%, whereas the pH was ~6.8. The contact angle between the powder and liquid indicated an excellent ability to be reconstituted in water. The analysis of the glass transition temperature showed that the storage temperature (25 °C) was adequate. The peroxide value of all the products was low throughout the storage (≤ 1.63 meq peroxide kg-1 of oil at 90 days at 25 ± 2 °C), thus maintaining the quality of the microencapsulated chia oil. CONCLUSIONS: The results suggest that incorporating the monolayer and multilayer chia oil microcapsules that were studied could be a viable strategy for enriching smoothies with the omega-3 fatty acids present in chia seed oil. © 2023 Society of Chemical Industry.

Endothelial Microparticles: Markers of Inflammatory Response After Sutureless Valve Implantation

ABSTRACT Introduction: Systemic inflammatory response syndrome (SIRS) is related to increased circulating endothelial microparticles (EMP). Objective: The aim of this study was to compare the plasma concentration of EMP between patients undergoing aortic valve replacement with conventional bioprosthesis implantation and Perceval™ S (LivaNova) and to evaluate its impact on the inflammatory response in the short-term follow-up. Methods: This is a randomized clinical trial with 24 patients submitted to isolated aortic valve replacement divided into two groups: Perceval™ S (Group P) and conventional bioprostheses (Group C). Incidence of severe SIRS (three or more criteria) in the first 48 hours postoperatively, EMP release profile, interleukins (IL) 6 and 8, C-reactive protein, and procalcitonin were analyzed preand postoperatively at 24 hours and three months. Results: There were 24 patients (12 in each group), mean age was 69.92±5.17 years, 83.33% were female, the incidence of severe SIRS was 66.7% and 50% in groups C and P, respectively (P=0.68), and EMP showed a significant increase in the 24-hour postoperative period (P≤0.001) and subsequent decrease in the three-month postoperative period (P≤0.001), returning to baseline levels. For IL-6 and IL-8, there was a greater increase in group C at 24 hours postoperatively (P=.0.02 and P<0.001). Conclusion: The incidence of severe SIRS was similar in both groups, with significantly higher levels of IL-6 and IL-8, at the 24-hour postoperative period, in group C, however with higher levels of EMP in group P, and subsequent return to baseline levels at the three-month postoperative period in both groups.

Berberine-fluconazole microparticle-based combination therapy to treat candidiasis infections.

AIM: This study aims to incorporate alginate microparticles containing berberine and fluconazole into two different types of pharmaceutical formulations, to subsequently evaluate the antifungal activity against Candida albicans. METHODS AND RESULTS: Alginate microparticles containing BBR (berberine) and FLU (fluconazole) were produced by the spray-drying technique, characterized and incorporated in two pharmaceutical formulations, a vaginal cream and artificial saliva. Broth microdilution, checkerboard, time-kill curve, and scanning electron microscopy were carried out to determine the antifungal effects of BBR and FLU against C. albicans. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of free BBR were 125 µg ml-1. Synergism between BBR and FLU was demonstrated by a fractional inhibitory concentration index (FICI) = 0.0762. The time-kill curve for the combination BBR + FLU showed a more pronounced decrease in fungal growth in comparison to free drugs, and an antibiofilm effect of BBR occurred in the formation and preformed biofilm. CONCLUSION: Alginate microparticles containing BBR and FLU were obtained and incorporated in a vaginal cream and artificial saliva. Both formulations showed good stability, antifungal effects, and organoleptic characteristics, which suggest that BBR-FLU microparticles in formulations have potential as antifungal therapy.

Systemic Inflammatory Patterns in Ovarian Cancer Patients: Analysis of Cytokines, Chemokines, and Microparticles / Padrões inflamatórios sistêmicos em pacientes com câncer de ovário: Análise de citocinas, quimiocinas e micropartículas

Abstract Objective To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. Materials and Methods We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. Results Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. Conclusion The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.

Resumo Objetivo Comparar os padrões de resposta inflamatória sistêmica em mulheres com câncer epitelial de ovário (CEO) ou sem evidência de doença maligna, bem como avaliar o perfil de respostas inflamatórias sistêmicas em tumores dos tipos 1 e 2. Esta é uma forma não invasiva e indireta de avaliar tanto a atividade tumoral quanto o papel do padrão inflamatório durante as respostas pró- e antitumorais. Métodos Ao todo, 56 pacientes foram avaliados prospectivamente: 30 mulheres sem evidência de doença maligna e 26 mulheres com CEO. A quantificação plasmática de citocinas, quimiocinas e micropartículas (MPs) foi realizada por citometria de fluxo. Resultados Os níveis plasmáticos das citocinas pró-inflamatórias interleucina-12 (IL12), interleucina-6 (IL-6), fator de necrose tumoral alfa (tumor necrosis factor alpha, TNF-α, em inglês), interleucina-1 beta (IL-1β), e interleucina-10 (IL-10), e da quimiocina de motivo C-X-C 9 (CXCL-9) e da quimiocina de motivo C-X-C 10 (CXCL-10) foram significativamente maiores em pacientes com EOC do que nos controles. Os níveis plasmáticos da citocina interleucina-17A (IL17A) e MPs derivados de células endoteliais foram menores em pacientes com CEO do que no grupo de controle. A frequência de leucócitos e de MPs derivadas de células endoteliais foi maior nos tumores de tipo 2 do que naqueles sem malignidade. Observou-se um número expressivo de citocinas e quimiocinas inflamatórias/regulatórias nos casos de CEO, além de correlações negativas e positivas entre elas, o que leva a uma maior complexidade dessas redes. Conclusão Este estudo mostrou que, por meio da construção de redes compostas por citocinas, quimiocinas e MPs, há maior resposta inflamatória sistêmica em pacientes com CEO e correlação mais complexa desses biomarcadores em tumores de tipo 2.

Impact of Breaking up of Sitting Time on Anti-inflammatory Response Induced by Extracellular Vesicles.

Physical inactivity and sedentary behaviors (SB) have promoted a dramatic increase in the incidence of a host of chronic disorders over the last century. The breaking up of sitting time (i.e., sitting to standing up transition) has been proposed as a promising solution in several epidemiological and clinical studies. In parallel to the large interest it initially created, there is a growing body of evidence indicating that breaking up prolonged sedentary time (i.e., > 7 h in sitting time) could reduce overall mortality risks by normalizing the inflammatory profile and cardiometabolic functions. Recent advances suggest that the latter health benefits, may be mediated through the immunomodulatory properties of extracellular vesicles. Primarily composed of miRNA, lipids, mRNA and proteins, these vesicles would influence metabolism and immune system functions by promoting M1 to M2 macrophage polarization (i.e., from a pro-inflammatory to anti-inflammatory phenotype) and improving endothelial function. The outcomes of interrupting prolonged sitting time may be attributed to molecular mechanisms induced by circulating angiogenic cells. Functionally, circulating angiogenic cells contribute to repair and remodel the vasculature. This effect is proposed to be mediated through the secretion of paracrine factors. The present review article intends to clarify the beneficial contributions of breaking up sitting time on extracellular vesicles formation and macrophage polarization (M1 and M2 phenotypes). Hence, it will highlight key mechanistic information regarding how breaking up sitting time protocols improves endothelial health by promoting antioxidant and anti-inflammatory responses in human organs and tissues.

Delivery Strategies of Probiotics from Nano- and Microparticles: Trends in the Treatment of Inflammatory Bowel Disease-An Overview.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, most known as ulcerative colitis (UC) and Crohn's disease (CD), that affects the gastrointestinal tract (GIT), causing considerable symptoms to millions of people around the world. Conventional therapeutic strategies have limitations and side effects, prompting the exploration of innovative approaches. Probiotics, known for their potential to restore gut homeostasis, have emerged as promising candidates for IBD management. Probiotics have been shown to minimize disease symptoms, particularly in patients affected by UC, opening important opportunities to better treat this disease. However, they exhibit limitations in terms of stability and targeted delivery. As several studies demonstrate, the encapsulation of the probiotics, as well as the synthetic drug, into micro- and nanoparticles of organic materials offers great potential to solve this problem. They resist the harsh conditions of the upper GIT portions and, thus, protect the probiotic and drug inside, allowing for the delivery of adequate amounts directly into the colon. An overview of UC and CD, the benefits of the use of probiotics, and the potential of micro- and nanoencapsulation technologies to improve IBD treatment are presented. This review sheds light on the remarkable potential of nano- and microparticles loaded with probiotics as a novel and efficient strategy for managing IBD. Nonetheless, further investigations and clinical trials are warranted to validate their long-term safety and efficacy, paving the way for a new era in IBD therapeutics.

Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis.

Intranasal (i.n.) vaccination with adjuvant-free plasmid DNA encoding the leishmanial antigen LACK (LACK DNA) has shown to induce protective immunity against both cutaneous and visceral leishmaniasis in rodents. In the present work, we sought to evaluate the safety and effectiveness of d,l-glyceraldehyde cross-linked chitosan microparticles (CCM) as a LACK DNA non-intumescent mucoadhesive delivery system. CCM with 5 µm of diameter was prepared and adsorbed with a maximum of 2.4 % (w/w) of DNA with no volume alteration. Histological analysis of mouse nostrils instilled with LACK DNA / CCM showed microparticles to be not only mucoadherent but also mucopenetrant, inducing no local inflammation. Systemic safeness was confirmed by the observation that two nasal instillations one week apart did not alter the numbers of bronchoalveolar cells or blood eosinophils; did not alter ALT, AST and creatinine serum levels; and did not induce cutaneous hypersensitivity. When challenged in the footpad with Leishmania amazonensis, mice developed significantly lower parasite loads as compared with animals given naked LACK DNA or CCM alone. That was accompanied by increased stimulation of Th1-biased responses, as seen by the higher T-bet / GATA-3 ratio and IFN-γ levels. Together, these results demonstrate that CCM is a safe and effective mucopenetrating carrier that can increase the efficacy of i.n. LACK DNA vaccination against cutaneous leishmaniasis.

Endothelial Microparticles: Markers of Inflammatory Response After Sutureless Valve Implantation.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is related to increased circulating endothelial microparticles (EMP). OBJECTIVE: The aim of this study was to compare the plasma concentration of EMP between patients undergoing aortic valve replacement with conventional bioprosthesis implantation and Perceval™ S (LivaNova) and to evaluate its impact on the inflammatory response in the short-term follow-up. METHODS: This is a randomized clinical trial with 24 patients submitted to isolated aortic valve replacement divided into two groups: Perceval™ S (Group P) and conventional bioprostheses (Group C). Incidence of severe SIRS (three or more criteria) in the first 48 hours postoperatively, EMP release profile, interleukins (IL) 6 and 8, C-reactive protein, and procalcitonin were analyzed preand postoperatively at 24 hours and three months. RESULTS: There were 24 patients (12 in each group), mean age was 69.92±5.17 years, 83.33% were female, the incidence of severe SIRS was 66.7% and 50% in groups C and P, respectively (P=0.68), and EMP showed a significant increase in the 24-hour postoperative period (P≤0.001) and subsequent decrease in the three-month postoperative period (P≤0.001), returning to baseline levels. For IL-6 and IL-8, there was a greater increase in group C at 24 hours postoperatively (P=.0.02 and P<0.001). CONCLUSION: The incidence of severe SIRS was similar in both groups, with significantly higher levels of IL-6 and IL-8, at the 24-hour postoperative period, in group C, however with higher levels of EMP in group P, and subsequent return to baseline levels at the three-month postoperative period in both groups.

Chitosan Microparticles Enhance the Intestinal Release and Immune Response of an Immune Stimulant Peptide in Oncorhynchus mykiss.

The aquaculture industry is constantly increasing its fish production to provide enough products to maintain fish consumption worldwide. However, the increased production generates susceptibility to infectious diseases that cause losses of millions of dollars to the industry. Conventional treatments are based on antibiotics and antivirals to reduce the incidence of pathogens, but they have disadvantages, such as antibiotic resistance generation, antibiotic residues in fish, and environmental damage. Instead, functional foods with active compounds, especially antimicrobial peptides that allow the generation of prophylaxis against infections, provide an interesting alternative, but protection against gastric degradation is challenging. In this study, we evaluated a new immunomodulatory recombinant peptide, CATH-FLA, which is encapsulated in chitosan microparticles to avoid gastric degradation. The microparticles were prepared using a spray drying method. The peptide release from the microparticles was evaluated at gastric and intestinal pH, both in vitro and in vivo. Finally, the biological activity of the formulation was evaluated by measuring the expression of il-1ß, il-8, ifn-γ, Ifn-α, and mx1 in the head kidney and intestinal tissues of rainbow trout (Oncorhynchus mykiss). The results showed that the chitosan microparticles protect the CATH-FLA recombinant peptide from gastric degradation, allowing its release in the intestinal portion of rainbow trout. The microparticle-protected CATH-FLA recombinant peptide increased the expression of il-1ß, il-8, ifn-γ, ifn-α, and mx1 in the head kidney and intestine and improved the antiprotease activity in rainbow trout. These results suggest that the chitosan microparticle/CATH-FLA recombinant peptide could be a potential prophylactic alternative to conventional antibiotics for the treatment of infectious diseases in aquaculture.

Magnetic and Viscoelastic Response of Magnetorheological Elastomers Based on a Combination of Iron Nano- and Microparticles.

In this paper, we discuss the creation of a hybrid magnetorheological elastomer that combines nano- and microparticles. The mixture contained 45 wt.% fillers, with combinations of either 0% nanoparticles and 100% microparticles or 25% nanoparticles and 75% microparticles. TGA and FTIR testing confirmed the materials' thermal and chemical stability, while an SEM analysis determined the particles' size and morphology. XRD results were used to determine the crystal size of both nano- and microparticles. The addition of reinforcing particles, particularly nanoparticles, enhanced the stiffness of the composite materials studied, but their overall strength was only minimally affected. The computed interaction parameter relative to the volume fraction was consistent with the previous literature. Furthermore, the study observed a magnetic response increment in composite materials reinforced with nanoparticles above 30 Hz. The isotropic material containing only microparticles had a lower storage modulus than the isotropic sample with nanoparticles without a magnetic field. However, when a magnetic field was applied, the material with only microparticles exhibited a higher storage modulus than the samples with nanoparticles.