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Mucoadhesive polymeric nanocapsules have attracted interest of researchers from different fields from natural sciences because of their ability to interact with the mucosa and increase drug permeation. Anesthesia by immersion causes absorption through the skin and gills of fish, so it is important to evaluate the exposure of these organs to drug nanosystems. Benzocaine (BENZ) is one of the most popular anesthetic agents used in fish anesthesia, but it has drawbacks because of its low bioavailability, resulting in weak absorption after immersion. Here we describe method developed for preparing and characterizing chitosan-coated PLGA mucoadhesive nanoparticles containing BENZ (NPMAs) for zebrafish immersion anesthesia. We determined the lowest effective concentration, characterized the interaction of the mucoadhesive system with fish, measured the anesthetic efficacy, and evaluated possible toxic effects in embryos and adults exposed to the nanoformulations. This study opens perspectives for using nanoformulations prepared with BENZ in aquaculture, allowing reduction of dosage as well as promoting more effective anesthesia and improved interaction with the mucoadhesive system of fish.

Blood tissue has been used to assess animal health and the environment in which they live. This tissue is easily acquired and has the ability to respond to various adverse conditions. Several techniques have been employed in the detection of xenobiotic-induced cell damage in blood cells. In general, traditionally used technologies, such as cellular analysis in blood smears, are time-consuming and require great analytical capacity. The present study proposes flow cytometry as a method to detect changes in blood cell populations. Tilapia ( Oreochromis niloticus ) was selected as a model for plotting the profile of fish blood cell populations after exposure to xenobiotics without euthanizing animals or using cell markers. Populations of erythrocytes and lymphocytes were detected only by combining the techniques of FACSAria cell sorting and light microscopy. Systemic deleterious effects were found through blood analysis, such as an increased lymphocyte-rich population at 48 h of exposure followed by a subsequent decrease. Moreover, the time-dependent expression of Nrf2 suggests its participation in increased membrane disruption, indicating it has a central role in erythrocyte lifespan. The present results shed light on the viability of using flow cytometry for blood analysis of living fish.

To investigate the photodynamic therapeutic potential of ferromagnetic iron oxide nanorods (FIONs), using as a reducing agent, against . FIONs were characterized using ultraviolet visible spectroscopy, x-ray diffraction and scanning electron microscopy. FIONs showed excellent activity against promastigotes and amastigotes (IC 0.036 ± 0.003 and 0.072 ± 0.001 μg/ml, respectively) upon 15 min pre-incubation light-emitting diode light (84 lm/W) exposure, resulting in reactive oxygen species generation and induction of cell death via apoptosis. FIONs were found to be highly biocompatible with human erythrocytes (LD 779 ± 21 μg/ml) and significantly selective (selectivity index >1000) against murine peritoneal macrophages (CC 102.7 ± 2.9 μg/ml). Due to their noteworthy antileishmanial properties, FIONs should be further investigated in an model of the disease.

There is a great need for orally active drugs for the treatment of the neglected tropical disease leishmaniasis. Amphiphilic Sb(V) complexes, such as 1:3 Sb-N-octanoyl-N-methylglucamide complex (SbL8), are promising drug candidates. It has been previously reported that SbL8 forms kinetically stabilized nanoassemblies in water and that this simple dispersion exhibits antileishmanial activity when given by oral route to a murine model of visceral leishmaniasis. The main objective of the present work was to interfere in the structural organization of these nanoassemblies so as to investigate their influence on the oral bioavailability of Sb, and ultimately, optimize an oral formulation of SbL8 for the treatment of cutaneous leishmaniasis. The structural organization of SbL8 nanoassemblies was manipulated through addition of propylene glycol (PG) to the aqueous dispersion of SbL8. The presence of 50% (v/v) PG resulted in the loss of hydrophobic microenvironment, as evidenced by fluorescence probing. However, nanostructures were still present, as demonstrated by dynamic light scattering, small-angle X-ray scattering, and atomic force microscopy (AFM). A remarkable property of these nanoassemblies, as revealed by AFM analysis, is the flexibility of their supramolecular organization, which showed changes as a function of the solvent and substrate polarities. The formulation of SbL8 in 1:1 water:PG given orally to mice promoted significantly higher and more sustained serum levels of Sb, when compared to SbL8 in water. The new formulation, when given as repeated doses (200 mg Sb/kg/day) to BALB/c mice infected with Leishmania amazonensis, was significantly more effective in reducing the lesion parasite burden, compared to SbL8 in water, and even, the conventional drug Glucantime(®) given intraperitoneally at the same dose. In conclusion, this work introduces a new concept of polarity-sensitive nanocarrier that was successfully applied to optimize an oral formulation of Sb(V) for treating cutaneous leishmaniasis.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the major cytokines involved in control of haemopoiesis both in bone marrow and in extramedullar sites. Its biological activity depends upon the composition and physicochemical properties of the microenvironment provided by the supporting stroma. GM-CSF activity is modulated and controlled by the stromal heparan-sulphate proteoglycans, but their optimal interaction occurs only at low pH. We questioned whether the microenvironment organisation of the interface between stroma and haemopoietic cells provides such conditions. We studied myeloid progenitor proliferation in contact with bone marrow-derived and extramedullar stromas using electron microscopy and selective labelling of pericellular components. We present evidence that, upon interaction, the two cell types reorganise their interface both in shape and molecular composition. Haemopoietic cells extend projections that considerably increase the area of intercellular contact, and stromal cells form lamellipodia and carry out a redistribution of membrane-associated sialylated glycoconjugates and proteoglycans. Such rearrangements lead to extensive capping of negatively charged molecules at the interface between the supporting stroma and the haemopoietic cells, leading potentially to a local decrease in pH. Our results indicate that the distribution of negative charges at the cellular interface may be responsible for the selectivity of cell response to GM-CSF.

Electron-dense granules (EDGs) are singular structures found in the tissues of several vertebrate and invertebrate organisms. Two types of EDGs were observed in hepatopancreatic cells of the crab Ucides cordatus: (1) a non-mineralized EDG, found mainly inside vacuoles, which reacted positively to acid phosphatase and D-amino acid oxidase, possibly formed by degradation of lipid membranes, and (2) a mineralized EDG surrounded by endoplasmic reticulum membranes that gave a positive reaction for glucose-6-phosphatase. In this study we show the fine structure and composition of the mineralized EDGs using cytochemistry, analytical transmission electron microscopy and field-emission scanning electron microscopy. They are formed of microvesicle-like structures that are arranged in concentric spherical layers in the most mineralized portions of the granule. Analytical microscopy of mineralized EDGs indicated that they are composed of amorphous calcium-magnesium phosphate. Isolated EDGs treated with NaOCl lose several elements, including P, when compared with EDGs treated with deionized water. Removal of the organic matrix by NaOCl induced marked changes in the mineralized EDGs, showing that the organic matrix plays an important role in its elemental composition and structure.

Summary Establishing new experimental animal models to assess the safety and immune response to the antigen used in the development of COVID-19 vaccine is an imperative issue. Based on the advantages of using zebrafish as a model in research, herein we suggest doing this to test the safety of the putative vaccine candidates and to study immune response against the virus. We produced a recombinant N-terminal fraction of the Spike SARS-CoV-2 protein and injected it into adult female zebrafish. The specimens generated humoral immunity and passed the antibodies to the eggs. However, they presented adverse reactions and inflammatory responses similar to severe cases of human COVID-19. The analysis of the structure and function of zebrafish and human Angiotensin-converting enzyme 2, the main human receptor for virus infection, presented remarkable sequence similarities. Moreover, bioinformatic analysis predicted protein-protein interaction of the Spike SARS-CoV-2 fragment and the Toll-like receptor pathway. It might help in the choice of future therapeutic pharmaceutical drugs to be studied. Based on the in vivo and in silico results presented here, we propose the zebrafish as a model for translational research into the safety of the vaccine and the immune response of the vertebrate organism to the SARS-CoV-2 virus. Competing Interest Statement The authors have declared no competing interest.

Functionalized nanostructured systems can be used for imaging and drug delivery for anti-tumor therapy, including breast tumors. This is a more efficient approach that offers reduced systemic side effects compared to conventional diagnostic and chemotherapy methods. Multifunctional nanoparticles are potential tools in the diagnosis, location tracing and kill tumor cells through a less invasive manner. Functionalized phosphate-based nanoparticles are capable of encapsulating, or may be associated, with fluorescent probes. In this study, we synthesize a nanoparticle phosphate-based composite (NPC) and functionalize it with poly-ethylene glycol (PEG), hyaluronic acid (HA), the fluorescent probe rhodamin 6G (R6G) and the antimitotic doxorubicin (DOX). We focused on targeting human breast cancer cells reporting the biological effects of functionalized NPC on them. NPC and NPC formulations containing PEG, HA, and R6G did not cause cell viability reduction on MCF-7 and MDA-MB-231 cell lines. The cellular internalization of NPC was quantified by real-time in vitro observation, and confirmed by electron microscopy techniques. Intracellular NPC distribution is detected in the cytoplasm and nucleus of tumor cells by confocal fluorescent images. The percent association of doxorubicin to NPC matrix was approximately 18% and NPC formulations associated with doxorubicin led to a significant reduction in cell viability in MDA-MB-231 and MCF-7 cells. This data suggest the potential use of NPC as a non-cytotoxic platform for association with functional ligands to selective targeting breast cancer cells. NPC use can be also explored in drug delivery to cancer cells. Competing Interest Statement The authors have declared no competing interest. Footnotes * Functionalized nanostructured systems can be used for imaging and drug delivery for anti-tumor therapy, including breast tumors. This is a more efficient approach that offers reduced systemic side effects compared to conventional diagnostic and chemotherapy methods. Multifunctional nanoparticles are potential tools in the diagnosis, location tracing and kill tumor cells through a less invasive manner. Functionalized phosphate-based nanoparticles are capable of encapsulating, or may be associated, with fluorescent probes. In this study, we synthesize a nanoparticle phosphate-based composite (NPC) and functionalize it with poly-ethylene glycol (PEG), hyaluronic acid (HA), the fluorescent probe rhodamin 6G (R6G) and the antimitotic doxorubicin (DOX). We focused on targeting human breast cancer cells reporting the biological effects of functionalized NPC on them. NPC and NPC formulations containing PEG, HA, and R6G did not cause cell viability reduction on MCF-7 and MDA-MB-231 cell lines. The cellular internalization of NPC was quantified by real-time in vitro observation, and confirmed by electron microscopy techniques. Intracellular NPC distribution is detected in the cytoplasm and nucleus of tumor cells by confocal fluorescent images. The percent association of doxorubicin to NPC matrix was approximately 18% and NPC formulations associated with doxorubicin led to a significant reduction in cell viability in MDA-MB-231 and MCF-7 cells. This data suggest the potential use of NPC as a non-cytotoxic platform for association with functional ligands to selective targeting breast cancer cells. NPC use can be also explored in drug delivery to cancer cells.

COVID-19 pandemic posed major challenges in obstetric health care services. Preparedness, development, and implementation of new protocols were part of the needed response. This study aims to describe the strategies implemented and the perspectives of health managers on the challenges to face the pandemic in 16 different maternity hospitals that comprise a multicenter study in Brazil, called REBRACO (Brazilian network of COVID-19 during pregnancy). Mixed-method study, with quantitative and qualitative approaches. Quantitative data on the infrastructure of the units, maternal and perinatal health indicators, modifications on staff and human resources, from January to July/2020. Also, information on total number of cases, and availability for COVID-19 testing. A qualitative study by purposeful and saturation sampling was undertaken with healthcare managers, to understand perspectives on local challenges in facing the pandemic. Most maternities early implemented their contingency plan. REBRACO centers reported 338 confirmed COVID-19 cases among pregnant and post-partum women up to July 2020. There were 29 maternal deaths and 15 (51.8%) attributed to COVID-19. All maternities performed relocation of beds designated to labor ward, most (75%) acquired mechanical ventilators, only the minority (25%) installed new negative air pressure rooms. Considering human resources, around 40% hired extra health professionals and increased weekly workload and the majority (68.7%) also suspended annual leaves. Only one center implemented universal screening for childbirth and 6 (37.5%) implemented COVID-19 testing for all suspected cases, while around 60% of the centers only tested moderate/severe cases with hospital admission. Qualitative results showed that main challenges experienced were related to the fear of the virus, concerns about reliability of evidence and lack of resources, with a clear need for mental health support among health professionals. Study findings suggest that maternities of the REBRACO initiative underwent major changes in facing the pandemic, with limitations on testing, difficulties in infrastructure and human resources. Leadership, continuous training, implementation of evidence-based protocols and collaborative initiatives are key to transpose the fear of the virus and ascertain adequate healthcare inside maternities, especially in low and middle-income settings. Policy makers need to address the specificities in considering reproductive health and childbirth during the COVID-19 pandemic and prioritize research and timely testing availability.

Brazil presented a very high number of maternal deaths and evident delays in healthcare. We aimed at evaluating the characteristics of SARS-CoV-2 infection and associated outcomes in the obstetric population. We conducted a prospective cohort study in 15 Brazilian centers including symptomatic pregnant or postpartum women with suspected COVID-19 from Feb/2020 to Feb/2021. Women were followed from suspected infection until the end of pregnancy. We analyzed maternal characteristics and pregnancy outcomes associated with confirmed COVID-19 infection and SARS, determining unadjusted risk ratios. In total, 729 symptomatic women with suspected COVID-19 were initially included. Among those investigated for COVID-19, 51.3% (n = 289) were confirmed COVID-19 and 48% (n = 270) were negative. Initially (before May 15th), only 52.9% of the suspected cases were tested and it was the period with the highest proportion of ICU admission and maternal deaths. Non-white ethnicity (RR 1.78 [1.04–3.04]), primary schooling or less (RR 2.16 [1.21–3.87]), being overweight (RR 4.34 [1.04–19.01]) or obese (RR 6.55 [1.57–27.37]), having public prenatal care (RR 2.16 [1.01–4.68]), planned pregnancies (RR 2.09 [1.15–3.78]), onset of infection in postpartum period (RR 6.00 [1.37–26.26]), chronic hypertension (RR 2.15 [1.37–4.10]), pre-existing diabetes (RR 3.20 [1.37–7.46]), asthma (RR 2.22 [1.14–4.34]), and anaemia (RR 3.15 [1.14–8.71]) were associated with higher risk for SARS. The availability of tests and maternal outcomes varied throughout the pandemic period of the study; the beginning was the most challenging period, with worse outcomes. Socially vulnerable, postpartum and previously ill women were more likely to present SARS related to COVID-19.