Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior to in vivo testing. However, the vast majority of promising ...preclinical drugs have no or weak efficacy in real patients with tumors, thereby delaying the discovery of successful therapeutics. This is because 2D culture lacks cell-cell contacts and natural tumor microenvironment, important in tumor signaling and drug response, thereby resulting in a reduced malignant phenotype compared to the real tumor. In this sense, three-dimensional (3D) cultures of cancer cells that better recapitulate in vivo cell environments emerged as scientifically accurate and low cost cancer models for preclinical screening and testing of new drug candidates before moving to expensive and time-consuming animal models. Here, we provide a comprehensive overview of 3D tumor systems and highlight the strategies for spheroid construction and evaluation tools of targeted therapies, focusing on their applicability in cancer research. Examples of the applicability of 3D culture for the evaluation of the therapeutic efficacy of nanomedicines are discussed.
Variability in snake venom composition is well-documented and crucial for understanding snake ecology and predicting snakebites. In this study, we characterize the venom composition and biological ...activities of newborn female and male Bothrops moojeni and their mother. Our results reveal significant differences between the venom of newborn females and males, demonstrating a broad and diverse range of proteins. The venoms of newborn females showed higher serine protease effects, increased hemorrhagic activity, and greater lethality compared to the venom of newborn males. However, no differences were observed in phospholipase A2 and coagulant activity. The differences in protein composition and toxic activities between maternal and neonatal venom, as well as between the venoms of newborn females and males, contribute to understanding the diverse outcomes of snakebites. These results underscore the importance of considering sex and ontogeny in understanding venom composition in snakes.
The Observations and Modeling of the Green Ocean Amazon (GoAmazon2014/5) Experiment was carried out in the environs of Manaus, Brazil, in the central region of the Amazon basin for 2 years from ...1 January 2014 through 31 December 2015. The experiment focused on the complex interactions among vegetation, atmospheric chemistry, and aerosol production on the one hand and their connections to aerosols, clouds, and precipitation on the other. The objective was to understand and quantify these linked processes, first under natural conditions to obtain a baseline and second when altered by the effects of human activities. To this end, the pollution plume from the Manaus metropolis, superimposed on the background conditions of the central Amazon basin, served as a natural laboratory. The present paper, as the introduction to the special issue of GoAmazon2014/5, presents the context and motivation of the GoAmazon2014/5 Experiment. The nine research sites, including the characteristics and instrumentation of each site, are presented. The sites range from time point zero (T0) upwind of the pollution, to T1 in the midst of the pollution, to T2 just downwind of the pollution, to T3 furthest downwind of the pollution (70 km). In addition to the ground sites, a low-altitude G-159 Gulfstream I (G-1) observed the atmospheric boundary layer and low clouds, and a high-altitude Gulfstream G550 (HALO) operated in the free troposphere. During the 2-year experiment, two Intensive Operating Periods (IOP1 and IOP2) also took place that included additional specialized research instrumentation at the ground sites as well as flights of the two aircraft. GoAmazon2014/5 IOP1 was carried out from 1 February to 31 March 2014 in the wet season. GoAmazon2014/5 IOP2 was conducted from 15 August to 15 October 2014 in the dry season. The G-1 aircraft flew during both IOP1 and IOP2, and the HALO aircraft flew during IOP2. In the context of the Amazon basin, the two IOPs also correspond to the clean and biomass burning seasons, respectively. The Manaus plume is present year-round, and it is transported by prevailing northeasterly and easterly winds in the wet and dry seasons, respectively. This introduction also organizes information relevant to many papers in the special issue. Information is provided on the vehicle fleet, power plants, and industrial activities of Manaus. The mesoscale and synoptic meteorologies relevant to the two IOPs are presented. Regional and long-range transport of emissions during the two IOPs is discussed based on satellite observations across South America and Africa. Fire locations throughout the airshed are detailed. In conjunction with the context and motivation of GoAmazon2014/5 as presented in this introduction, research articles including thematic overview articles are anticipated in this special issue to describe the detailed results and findings of the GoAmazon2014/5 Experiment.
In 2019, the Coronavirus (SARS-CoV-2) virus was identified, also defined as novel coronavirus or severe acute respiratory syndrome coronavirus 2. The Corona VIrus Disease (COVID-19) pandemic ...generated several changes in society in 2020 as a result of its rapid spread in humans. The main symptoms are high fever (greater than or equal to 37.8 degreesC), dry cough, dyspnea, upper respiratory symptoms, myalgia, fatigue and diarrhea in the most uncommon cases. Considering the emergency situation caused by the COVID-19 pandemic and the effects attributed to it, rehabilitation professionals have a fundamental role in the functional recovery of patients, independence and improvement of quality of life. This is a systematic review of the literature, with the aim of discussing the main findings on physical therapy management in functional changes in post-COVID-19 patients. Pubmed, Scielo, Sciencedirect, BVS and PEDro databases were used. The terms MESH/DECs used for the searches were: Rehabilitation, Physical Therapy Modalities, Covid-19, Post-acute Syndromes COVID-19 and Physical Fitness, the keywords were also used: rehabilitation, physiotherapy, Covid-19, post- acute syndrome COVID-19 and functional capacity. To cross the terms, Boolean operators (AND and OR) were used. Randomized trials, recommendations, quasi-randomized or prospective controlled trials, reports, guidelines, and field updates were included. As for the selected population, studies were included in individuals of both sexes, with no age restriction, that evaluated physiotherapeutic interventions in patients who had COVID-19. Literature reviews, case studies, conferences, abstracts of articles published in conference proceedings and letters to the editor were excluded from the research. To measure methodological quality, the PEDro scale was used.Searches for articles were performed restricting the period of publication between the years 2019 to 2022. The electronic search strategy identified a total of 364 records from the selected databases. After screening for duplicates, 14 articles were excluded, followed by screening by titles and abstracts, another 298 articles were excluded, of these 47 potentially relevant records were submitted to full text review and of these 5 randomized clinical trials were included in this review. In view of the findings of this study, it can be concluded that physical therapy rehabilitation should continue after hospital discharge, with the aim of improving physical performance and activities of daily living (ADL) in post-COVID-19 patients.
The Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2), updates NASA’s previous satellite-era (1980 onward) reanalysis system to include additional observations and ...improvements to the Goddard Earth Observing System, version 5 (GEOS-5), Earth system model. As a major step toward a full Integrated Earth Systems Analysis (IESA), in addition to meteorological observations, MERRA-2 now includes assimilation of aerosol optical depth (AOD) from various ground-and space-based remote sensing platforms. Here, in the first of a pair of studies, the MERRA-2 aerosol assimilation is documented, including a description of the prognostic model (GEOS-5 coupled to the GOCART aerosol module), aerosol emissions, and the quality control of ingested observations. Initial validation and evaluation of the analyzed AOD fields are provided using independent observations from ground, aircraft, and shipborne instruments. The positive impact of the AOD assimilation on simulated aerosols is demonstrated by comparing MERRA-2 aerosol fields to an identical control simulation that does not include AOD assimilation. After showing the AOD evaluation, this paper takes a first look at aerosol–climate interactions by examining the shortwave, clear-sky aerosol direct radiative effect. The companion paper (Part II) evaluates and validates available MERRA-2 aerosol properties not directly impacted by the AOD assimilation (e.g., aerosol vertical distribution and absorption). Importantly, while highlighting the skill of the MERRA-2 aerosol assimilation products, both studies point out caveats that must be considered when using this new reanalysis product for future studies of aerosols and their interactions with weather and climate.
Gonadal sex differentiation in teleost fish shows greater plasticity as compared to other vertebrates, as it can be influenced by a variety of factors such as exogenous sex steroids. Exogenous ...estrogens, such as 17β-estradiol (E2), can induce feminization when administered during early embryonic development. However, the mechanisms underlying the E2-induced feminization are not fully understood, especially in Neotropical species. Therefore, the aim of this study was to evaluate the effects of E2 administration on the phenotypic sex characteristics, histological assessment of the gonads, and the expression of selected genes in Astyanax altiparanae exposed to dietary E2 prior to gonadal differentiation. At 4 days post-hatch (dph), groups of 30–40 undifferentiated larvae were fed with a diet containing varying amounts of E2 for 28 days, and fish were sampled at 90 dph. Previous studies revealed that ovary formation in A. altiparanae occurred at 58 dph, whereas the first sign of testis formation was found at 73 dph. In relation to the control, E2 exposure increased the proportion of phenotypic females in 120% and 148.4% for 4 and 6 mg E2/Kg, respectively. However, histological analysis revealed that treatments did not affect gonadal sex ratio between males and females, but induced intersex (testis-ova) in the group treated with 6 mg E2/Kg food. Treatment with E2 also altered gonadal transcript levels of a selected number of genes implicated in sexual differentiation. Males overexpressed dmrt1, sox9 and amh following E2 treatment as compared to control. Females showed increased mRNA levels of dmrt1 and sox9, which might be related to the down-regulation of cyp19a1a after E2 exposure. In summary, E2 exposure during early gonadal development affected male secondary characteristics without changing the gonadal sex ratio, and altered expression of genes implicated in sexual differentiation.
Display omitted
•17β-estradiol (E2) exposure during early gonadal development affected male secondary characteristics of A. altiparanae;•E2 treatment did not change gonadal sex ratio, induced testis-ova and altered genes related to sex differentiation;•Altered expression could be considered a compensatory mechanism, or a mechanism of gonadal resilience;
Abstract Tramadol hydrochloride (TrHC) is a synthetic analgesic drug exhibiting opioid and non-opioid properties, acting mainly on the central nervous system. It has been mostly used to treat pain, ...although its use to treat anxiety and depression has also been documented. These properties arise from the fact that they inhibit serotonin (5-HT) reuptake augmenting 5-HT concentration on the synaptic cleft. Despite this, TrHC has also been described to have several side effects which are mainly due to its fast metabolization and excretion which in turn requires multiple doses per day. To surpass this limitation, new pharmaceutical formulations are being developed intending the protection, target and sustained delivery as well as a reduction on daily dose aiming a reduction on the side effects. In the present work we have revised the efficacy, safety, biological and adverse effects of TrHC, and the added value of developing a novel drug delivery system for topical administration.
Display omitted
•Divaricatic acid exhibits toxicity against B. glabrata embryos and adult snails.•Malformations and delay in embryonic development were observed.•Divaricatic acid showed lethal ...effects against cercariae of Schistosoma mansoni.•Divaticatic acid was not toxic to Artemia salina.
In this study, the molluscicidal and antiparasitic activities of divaricatic acid was evaluated, targeting the mollusc Biomphalaria glabrata and cercariae of the helminth Schistosoma mansoni. In addition, the environmental toxicity of divaricatic acid was assessed by bioassay using the microcrustacean Artemia salina. Divaricatic acid showed high toxicity against both adult snails (5μg/mL) and embryos (20μg/mL after 6h of exposure). Similar activity was observed in Schistosoma mansoni cercariae after only a short exposure time (10μg/mL after 30min of exposure). The divaricatic acid did not show toxicity in the acute test using Artemia salina at concentrations equal to or below 200μg/mL. The divaricatic acid proved to be a promising substance for the elimination of the snail Biomphalaria glabrata, an intermediate host of schistosomiasis, as well as the cercariae of the pathogen, while being non-toxic to the Artemia salina at the same concentrations. This is the first experimental observation of the molluscicidal and cercaricide activity of divaricatic acid.
Polyoxovanadates (POV) are a subgroup of polyoxometalates (POM), which are nanosized clusters with reported biological activities. This manuscript describes the first toxicity evaluation of a ...mixed-valence polyoxovanadate, pentadecavanadate, (Me4N)6V15O36Cl, abbreviated as V15. Cytotoxicity experiments using peripheral blood mononuclear cells (PBMC), larvae of Artemia salina Leach, and in vivo oral acute and repeated 28-day doses in mice was carried out. The LC50 values in PBMC cells and A. salina were 17.5 ± 5.8 μmol L−1, and 17.9 µg L−1, respectively, which indicates high cytotoxic activity. The toxicity in mice was not observed upon acute exposure in a single dose, however, the V15 repeated 28-day oral administration demonstrated high toxicity using 25 mg/kg, 50 mg/kg and, 300 mg/kg doses. The biochemical and hematological analyses during the 28-day administration of V15 showed significant alteration of the metabolic parameters related to the kidney and liver, suggesting moderate toxicity. The V15 toxicity was attributed to the oxidative stress and lipid peroxidation, once thiobarbituric acid (TBAR) levels significantly increased in both males and females treated with high doses of the POV and also in males treated with a lower dose of the POV. This is the first study reporting a treatment-related mortality in animals acutely administrated with a mixed-valence POV, contrasting with the well-known, less toxic decavanadate. These results document the toxicity of this mixed-valence POV, which may not be suitable for biomedical applications.
Advances in the understanding of leishmaniasis progression indicate that cellular interactions more complex than the Th1/Th2 paradigm define the course of infection. Th17 cells are a crucial ...modulator of adaptive immunity against
parasites acting mainly on neutrophil recruitment and playing a dual role at the site of infection. This review describes the roles of both these cell types in linking innate defense responses to the establishment of specific immunity. We focus on the Th17-neutrophil interaction as a crucial component of anti-
immunity, and the clinical evolution of cutaneous or visceral leishmaniasis. To date, information obtained through experimental models and patient evaluations suggests that the influence of the presence of interleukin (IL)-17 (the main cytokine produced by Th17 cells) and neutrophils during
infections is strictly dependent on the tissue (skin or liver/spleen) and parasite species. Also, the time at which neutrophils are recruited, and the persistence of IL-17 in the infection microenvironment, may also be significant. A clearer understanding of these interactions will enable better measurement of the influence of IL-17 and its regulators, and contribute to the identification of disease/resistance biomarkers.
PDF
