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1.
J Cell Biol ; 222(11)2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37851005

RESUMO

The c-Jun N-terminal kinase (JNK) regulates various important physiological processes. Although the JNK pathway has been under intense investigation for over 20 yr, its complexity is still perplexing, with multiple protein partners underlying the diversity of its activity. We show that JNK is associated with the basal bodies in both primary and motile cilia. Loss of JNK disrupts basal body migration and docking and leads to severe ciliogenesis defects. JNK's involvement in ciliogenesis stems from a dual role in the regulation of the actin networks of multiciliated cells (MCCs) and the establishment of the intraflagellar transport-B core complex. JNK signaling is also critical for the maintenance of the actin networks and ciliary function in mature MCCs. JNK is implicated in the development of diabetes, neurodegeneration, and liver disease, all of which have been linked to ciliary dysfunction. Our work uncovers a novel role of JNK in ciliogenesis and ciliary function that could have important implications for JNK's role in the disease.


Assuntos
Actinas , Proteínas Quinases JNK Ativadas por Mitógeno , Sistema de Sinalização das MAP Quinases , Actinas/genética , Actinas/metabolismo , Cílios/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional
2.
Mol Psychiatry ; 28(5): 2008-2017, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37147389

RESUMO

Using machine learning, we recently decomposed the neuroanatomical heterogeneity of established schizophrenia to discover two volumetric subgroups-a 'lower brain volume' subgroup (SG1) and an 'higher striatal volume' subgroup (SG2) with otherwise normal brain structure. In this study, we investigated whether the MRI signatures of these subgroups were also already present at the time of the first-episode of psychosis (FEP) and whether they were related to clinical presentation and clinical remission over 1-, 3-, and 5-years. We included 572 FEP and 424 healthy controls (HC) from 4 sites (Sao Paulo, Santander, London, Melbourne) of the PHENOM consortium. Our prior MRI subgrouping models (671 participants; USA, Germany, and China) were applied to both FEP and HC. Participants were assigned into 1 of 4 categories: subgroup 1 (SG1), subgroup 2 (SG2), no subgroup membership ('None'), and mixed SG1 + SG2 subgroups ('Mixed'). Voxel-wise analyses characterized SG1 and SG2 subgroups. Supervised machine learning analyses characterized baseline and remission signatures related to SG1 and SG2 membership. The two dominant patterns of 'lower brain volume' in SG1 and 'higher striatal volume' (with otherwise normal neuromorphology) in SG2 were identified already at the first episode of psychosis. SG1 had a significantly higher proportion of FEP (32%) vs. HC (19%) than SG2 (FEP, 21%; HC, 23%). Clinical multivariate signatures separated the SG1 and SG2 subgroups (balanced accuracy = 64%; p < 0.0001), with SG2 showing higher education but also greater positive psychosis symptoms at first presentation, and an association with symptom remission at 1-year, 5-year, and when timepoints were combined. Neuromorphological subtypes of schizophrenia are already evident at illness onset, separated by distinct clinical presentations, and differentially associated with subsequent remission. These results suggest that the subgroups may be underlying risk phenotypes that could be targeted in future treatment trials and are critical to consider when interpreting neuroimaging literature.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Brasil , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética
3.
Sci Rep ; 12(1): 19028, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347932

RESUMO

The Ciliary Adhesion (CA) complex forms in close association with the basal bodies of cilia during the early stages of ciliogenesis and is responsible for mediating complex interactions with the actin networks of multiciliated cells (MCCs). However, its precise localization with respect to basal body accessory structures and the interactions that lead to its establishment in MCCs are not well understood. Here, we studied the distribution of the CA proteins using super-resolution imaging and possible interactions with the microtubule network. The results of this study reveal that the apical CA complex forms at the distal end of the basal foot and depends on microtubules. Our data also raise the possibility that CAs may have additional roles in the regulation of the organization of the microtubule network of MCCs.


Assuntos
Corpos Basais , Cílios , Cílios/metabolismo , Corpos Basais/metabolismo , Microtúbulos/metabolismo , Actinas/metabolismo
4.
Exp Eye Res ; 225: 109282, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36265576

RESUMO

Aging is a multifactorial process that affects the entire organism by cumulative alterations. Visual function impairments that go along with aging are commonly observed, causing lower visual acuity, lower contrast sensitivity, and impaired dark adaptation. Electroretinogram analysis revealed that the amplitudes of rod- and cone-mediated responses are reduced in aged mice and humans. Reports suggested that age-related changes observed in both rod and cone photoreceptor functionality were linked to oxidative stress regulation or free radical production homeostasis. Interestingly, several recent reports linked the fragile X mental retardation protein (FMRP) cellular activity with oxidative stress regulation in several tissue including brain tissue where FMRP participates to the response to stress via protein translation in neurite or is involved in free radical production and abnormal glutathione homeostasis. Based on these recent literatures, we raised the question about the effect of FMRP absence in the aging retina of Fmr1-/y compared to their WT littermates. Indeed, up to now, only young or adult mice (<6 months) were investigated and have shown a specific retinal phenotype. Herein, we demonstrated that Fmr1-/y mice do not present the aging effect on retinal function observed in WT littermates since ERG a- and b-waves amplitudes as well as oscillatory potentials amplitudes were not collapsed with age (12/18 months old). Absence of FMRP and its consequences seem to protect the retina against aging effect, rising a pivotal role of FMRP in retinal aging process.


Assuntos
Eletrorretinografia , Proteína do X Frágil de Retardo Mental , Retina , Animais , Camundongos , Envelhecimento/fisiologia , Sensibilidades de Contraste , Proteína do X Frágil de Retardo Mental/genética , Retina/patologia , Células Fotorreceptoras Retinianas Cones/metabolismo
5.
Cell Rep ; 40(3): 111091, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858563

RESUMO

Cadherins and integrins are intrinsically linked through the actin cytoskeleton and are largely responsible for the mechanical integrity and organization of tissues. We show that cadherin clustering stimulates and spatially guides integrin activation. Adherens junction (AJ)-associated integrin activation depends on locally generated tension and does not require extracellular matrix ligands. It leads to the creation of primed integrin clusters, which spatially determine where focal adhesions will form if ligands are present and where ligands will be deposited. AJs that display integrin activation are targeted by microtubules facilitating their disassembly via caveolin-based endocytosis, showing that integrin activation impacts the stability of the core cadherin complex. Thus, the interplay between cadherins and integrins is more intimate than what was once believed and is rooted in the capacity of active integrins to be stabilized via AJ-generated tension. Altogether, our data establish a mechanism of cross-regulation between cadherins and integrins.


Assuntos
Junções Aderentes , Caderinas , Adesão Celular/fisiologia , Matriz Extracelular , Adesões Focais , Integrinas , Ligantes
6.
Development ; 149(13)2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35662330

RESUMO

Neural tube closure (NTC) is a fundamental process during vertebrate development and is indispensable for the formation of the central nervous system. Here, using Xenopus laevis embryos, live imaging, single-cell tracking, optogenetics and loss-of-function experiments, we examine the roles of convergent extension and apical constriction, and define the role of the surface ectoderm during NTC. We show that NTC is a two-stage process with distinct spatiotemporal contributions of convergent extension and apical constriction at each stage. Convergent extension takes place during the first stage and is spatially restricted at the posterior tissue, whereas apical constriction occurs during the second stage throughout the neural plate. We also show that the surface ectoderm is mechanically coupled with the neural plate and its movement during NTC is driven by neural plate morphogenesis. Finally, we show that an increase in surface ectoderm resistive forces is detrimental for neural plate morphogenesis.


Assuntos
Tubo Neural , Neurulação , Animais , Morfogênese/fisiologia , Placa Neural , Neurulação/fisiologia , Xenopus laevis
7.
J Intellect Disabil Res ; 66(7): 577-616, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35698311

RESUMO

BACKGROUND: Little is known about how to evaluate relationships and sex education (RSE) delivered to students with intellectual disability and what stakeholders perceive are important outcomes. The present study aimed to systematically review existing studies on outcomes of RSE, as the first step in the development of a core outcome set (COS) for students with intellectual disability. METHOD: A systematic literature process included two stages: (1) searching for studies reporting on RSE outcomes for students with intellectual disability and (2) studies reporting on measurement properties (e.g. validity, reliability and responsiveness) of standardised instruments identified in stage 1. RESULTS: A total of 135 RSE outcomes were extracted from 42 studies: 43 outcomes for students in secondary education and 92 outcomes for students in further education. No RSE outcomes were reported for primary education. Outcomes referred to the human body, hygiene, relationships, sexuality, sex and its consequences, inappropriate and appropriate social and sexual behaviour, keeping safe, emotional vocabulary and positive self-esteem. Outcomes were predominantly knowledge-based, rather than relating to skills and attitudes development. Students with intellectual disability, parents and teachers perceive different RSE outcomes meaningful. Five instruments were used to measure the outcomes, but none have established psychometric properties with this population. CONCLUSIONS: The comprehensive list of RSE outcomes for students with intellectual disability will be used to inform the next steps of a Core Outcome Set needed for RSE evaluations in research and education settings. There is an urgent need to develop standardised instruments validated for students with intellectual disability.


Assuntos
Deficiência Intelectual , Educação Sexual , Humanos , Deficiência Intelectual/psicologia , Reprodutibilidade dos Testes , Sexualidade , Estudantes/psicologia
8.
Intern Emerg Med ; 17(7): 2093-2101, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35733074

RESUMO

To test the prognostic performance of different scores, both specifically designed for patients with COVID-19 and generic, in predicting in-hospital mortality and the need for mechanical ventilation (MV). We retrospectively collected clinical data of patients admitted to the Emergency Department of the University Hospital AOU Careggi, Florence, Italy, between February 2020 and January 2021, with a confirmed infection by SARS-CoV2. We calculated the following scores: Sequential Organ Failure Assessment (SOFA) score, CALL score, 4C Mortality score, QUICK score, CURB-65 and MuLBSTA score. The end-points were in-hospital mortality and the need for MV. We included 1208 patients, mean age 60 ± 17 years, 57% male sex. Compared to survivors, non-survivors showed significantly higher values of all the prognostic scores (4C: 13 [10-15] vs 8 [4-10]; CALL: 11 [10-12] vs 9 [7-11]; QUICK: 4 [1-6] vs 0 [0-3]; SOFA: 5 [4-6] vs 4 [4-5]; CURB: 2 [1-3] vs 1 [0-1]; MuLBSTA: 11 [9-13] vs 9 [7-11], all p < 0.001). Discriminative ability evaluated by the Receiver Operating Curve analysis showed the following values of the Area under the Curve: 0.83 for 4C, 0.74 for CALL, 0.70 for QUICK, 0.68 for SOFA, 0.76 for CURB and 0.64 for MuLBSTA. The mortality rate significantly increased in increasing quartiles of 4C and CALL score (respectively, 2, 8, 24 and 54% for the 4C score and 1, 17, 33 and 68% for the CALL score, both p < 0.001). 4C and CALL score allowed an early and good prognostic stratification of patients admitted for pneumonia induced by SARS-CoV2.


Assuntos
COVID-19 , Pandemias , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Viral , Curva ROC , Estudos Retrospectivos , SARS-CoV-2
9.
IEEE Trans Image Process ; 31: 4011-4022, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35588408

RESUMO

Functional magnetic resonance imaging (fMRI) is one of the most popular methods for studying the human brain. Task-related fMRI data processing aims to determine which brain areas are activated when a specific task is performed and is usually based on the Blood Oxygen Level Dependent (BOLD) signal. The background BOLD signal also reflects systematic fluctuations in regional brain activity which are attributed to the existence of resting-state brain networks. We propose a new fMRI data generating model which takes into consideration the existence of common task-related and resting-state components. We first estimate the common task-related temporal component, via two successive stages of generalized canonical correlation analysis and, then, we estimate the common task-related spatial component, leading to a task-related activation map. The experimental tests of our method with synthetic data reveal that we are able to obtain very accurate temporal and spatial estimates even at very low Signal to Noise Ratio (SNR), which is usually the case in fMRI data processing. The tests with real-world fMRI data show significant advantages over standard procedures based on General Linear Models (GLMs).


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Análise de Correlação Canônica , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Razão Sinal-Ruído
10.
Front Cell Dev Biol ; 10: 1091629, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36699010

RESUMO

Neural tube closure is a fundamental process during vertebrate embryogenesis, which leads to the formation of the central nervous system. Defective neural tube closure leads to neural tube defects which are some of the most common human birth defects. While the intrinsic morphogenetic events shaping the neuroepithelium have been studied extensively, how tissues mechanically coupled with the neural plate influence neural tube closure remains poorly understood. Here, using Xenopus laevis embryos, live imaging in combination with loss of function experiments and morphometric analysis of fixed samples we explore the reciprocal mechanical communication between the neural plate and the somitic mesoderm and its impact on tissue morphogenesis. We show that although somitic mesoderm convergent extension occurs independently from neural plate morphogenesis neural tube closure depends on somitic mesoderm morphogenesis. Specifically, impaired somitic mesoderm remodelling results in defective apical constriction within the neuroepithelium and failure of neural tube closure. Last, our data reveal that mild abnormalities in somitic mesoderm and neural plate morphogenesis have a synergistic effect during neurulation, leading to severe neural tube closure defects. Overall, our data reveal that defective morphogenesis of tissues mechanically coupled with the neural plate can not only drastically exacerbate mild neural tube defects that may arise from abnormalities within the neural tissue but can also elicit neural tube defects even when the neural plate is itself free of inherent defects.

11.
Front Hum Neurosci ; 15: 771668, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970129

RESUMO

General Linear Modeling (GLM) is the most commonly used method for signal detection in Functional Magnetic Resonance Imaging (fMRI) experiments, despite its main limitation of not taking into consideration common spatial dependencies between voxels. Multivariate analysis methods, such as Generalized Canonical Correlation Analysis (gCCA), have been increasingly employed in fMRI data analysis, due to their ability to overcome this limitation. This study, evaluates the improvement of sensitivity of the GLM, by applying gCCA to fMRI data after standard preprocessing steps. Data from a block-design fMRI experiment was used, where 25 healthy volunteers completed two action observation tasks at 1.5T. Whole brain analysis results indicated that the application of gCCA resulted in significantly higher intensity of activation in several regions in both tasks and helped reveal activation in the primary somatosensory and ventral premotor area, theoretically known to become engaged during action observation. In subject-level ROI analyses, gCCA improved the signal to noise ratio in the averaged timeseries in each preselected ROI, and resulted in increased extent of activation, although peak intensity was considerably higher in just two of them. In conclusion, gCCA is a promising method for improving the sensitivity of conventional statistical modeling in task related fMRI experiments.

12.
Data Brief ; 39: 107470, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34712748

RESUMO

This dataset presents the thermal performance of building-integrated flat solar collectors with a uniform and multiple riser structure. The input data of the numerical model were obtained with the use of the PVGIS tool. Solar radiation and ambient temperature values at slopes 0°, 45°, and 90° were extracted and used as boundary conditions. Numerical calculations were carried using Finite Element (FE) analysis. Three-dimensional transient models were developed to calculate the investigated configurations' thermal performance based on the environmental temperature, the solar radiation, and the inclination angle. The numerical model was validated with the use of an experimental data set showing a good agreement between the two models with RMSE of 5%. Data of hourly heat flux through the building masonry with the building-integrated solar collector and the average fluid temperature of each system is presented.

13.
Pharmaceutics ; 13(7)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34371692

RESUMO

Silver nanoparticles (AgNPs) not only have shown remarkable results as antimicrobial and antiviral agents but also as antitumor agents. This work reports the complete characterization of five polyvinylpyrrolidone-coated AgNP (PVP-AgNP) formulations, their cytotoxic activity against human colon tumor cells (HCT-15), their cytotoxic effect on primary mouse cultures, and their lethal dose on BALB/c mice. The evaluated AgNP formulations have a composition within the ranges Ag: 1.14-1.32% w/w, PVP: 19.6-24.5% and H2O: 74.2-79.2% with predominant spherical shape within an average size range of 16-30 nm according to transmission electron microscopy (TEM). All formulations assessed increase mitochondrial ROS concentration and induce apoptosis as the leading death pathway on HCT-15 cells. Except for AgNP1, the growth inhibition potency of AgNP formulations of human colon tumor cancer cells (HCT-15) is 34.5 times higher than carboplatin, one of the first-line chemotherapy agents. Nevertheless, 5-10% of necrotic events, even at the lower concentration evaluated, were observed. The cytotoxic selectivity was confirmed by evaluating the cytotoxic effect on aorta, spleen, heart, liver, and kidney primary cultures from BALB/c mice. Despite the cytotoxic effects observed in vitro, the lethal dose and histopathological analysis showed the low toxicity of these formulations (all of them on Category 4 of the Globally Harmonized System of Classification and Labelling of Chemicals) and minor damage observed on analyzed organs. The results provide an additional example of the rational design of safety nanomaterials with antitumor potency and urge further experiments to complete the preclinical studies for these AgNP formulations.

14.
Data Brief ; 36: 107034, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34307799

RESUMO

Hourly heat flux for variant boundary conditions of a novel controlled-temperature double skin façade (DSF) building element in a two- dimensional time- dependent study was determined. The building element is subjected to boundary conditions, characterizing different orientations (azimuth 0°, 90°, 180°, 270°) and climatic conditions of the four seasons. This data article provides detailed numerical data on the hourly heat flux, temperatures attained at the exterior and within the building element for six different geometries and for the variant boundary conditions under study. The external boundary conditions were determined with the use of the PVGIS tool, corrected in accordance to the sol-air temperature equation. The numerical simulation studies were performed with the use of the computational fluid dynamics (CFD) tool Comsol Multiphysics [2].

15.
J Environ Manage ; 295: 113146, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34186317

RESUMO

In Europe, regions in the Mediterranean area share common characteristics in terms of high sensitivity to climate change impacts. Does this translate into specificities regarding climate action that could arise from these Mediterranean characteristics? This paper sheds light on regional and local climate mitigation actions of the Mediterranean Europe, focusing on the plans to reduce greenhouse gases emissions in a representative sample of 51 regions and 73 cities across 9 Mediterranean countries (Croatia, Cyprus, France, Greece, Italy, Malta, Portugal, Slovenia, Spain). The study investigates: (i) the availability of local and regional mitigation plans, (ii) their goals in term of greenhouse gas emissions reduction targets on the short and medium-long term, and (iii) the impact of transnational climate networks on such local and regional climate mitigation planning. Results of this study indicate an uneven and fragmented planning, that shows a Mediterranean West-East divide, and a link with population size. However, overall, both regional and city action seem insufficiently ambitious with regards to meeting the Paris Agreement, at least at city level. While national frameworks are currently weak in influencing regional and local actions, transnational networks seem to be engaging factors for commitment (at city level) and ambitiousness (at regional level). The uneven and fragmented progress revealed by this study, does not align with the characteristics shared by investigated regions and cities in terms of environmental, socio-political, climatic and economic conditions. The results support the call of a common green deal at the Mediterranean level to further address specific Mediterranean challenges and related needs. This will allow to capitalise on available resources, generate local-specific knowledge, build capacities, and support Mediterranean regions and cities in preparing the next generation of more ambitious mitigation plans.


Assuntos
Mudança Climática , Cidades , Croácia , Chipre , Europa (Continente) , França , Grécia , Itália , Região do Mediterrâneo , Paris , Portugal , Eslovênia , Espanha
16.
J Control Release ; 332: 553-562, 2021 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-33737202

RESUMO

Most infectious agents use mucosal tissues as entry portals, thus, mucosae are frequently defined as a first line of defense against pathogens. Mucosal protection generally operates through antibody-mediated and cytotoxic T-cell responses which can be triggered by mucosal vaccines. Sublingual vaccination provides many advantages such as systemic and mucosal responses (both locally and at remote mucosal sites), besides being a needle-free administration route with high patient compliance and limited adverse effects. Buccal mucosa complexity nonetheless represents a challenge for vaccine administration, hence, many efforts were recently deployed to improve vaccine components, mucoadhesion and/or penetration. Several innovative approaches indeed confirmed that a robust and protective immunity can be achieved by sublingual vaccines. This review will then specify the most recent delivery systems and improvements developed to increase sublingual vaccines efficiency. We will focus our description on the immune mechanisms involved and the requirements for optimal sublingual immunization and mucosal protection.


Assuntos
Imunidade nas Mucosas , Vacinas , Administração Sublingual , Humanos , Imunização , Vacinação
17.
Cell Commun Signal ; 19(1): 3, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413438

RESUMO

BACKGROUND: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is overexpressed or activated in several advanced-stage solid cancers. It is known to play both kinase-dependent and -independent roles in promoting tumor progression and metastasis. Numerous inhibitors, targeting either the enzymatic or scaffolding activities of FAK have been generated, with varying degree of success. Here, we describe a novel approach to site-specifically target both kinase-dependent and -independent FAK functions at focal adhesions (FAs), the primary sites at which the kinase exerts its activity. METHODS: We took advantage of the well-characterized interactions between the paxillin LD motifs and the FAK FAT domain and generated a polypeptide (LD2-LD3-LD4) expected to compete with interactions with paxillin. Co-immunoprecipitation experiments were performed to examine the interaction between the LD2-LD3-LD4 polypeptide and FAK. The effects of LD2-LD3-LD4 in the localization and functions of FAK, as well as FA composition, were evaluated using quantitative immunofluorescence, cell fractionation, FA isolation and Western Blot analysis. Live cell imaging, as well as 2-D migration and cell invasion assays were used to examine the effects on FA turnover and tumor cell migration and invasion. RESULTS: Expression of the LD2-LD3-LD4 polypeptide prevents FAK localization at FAs, in a controlled and dose-dependent manner, by competing with endogenous paxillin for FAK binding. Importantly, the LD2-LD3-LD4 peptide did not otherwise affect FA composition or integrin activation. LD2-LD3-LD4 inhibited FAK-dependent downstream integrin signaling and, unlike existing inhibitors, also blocked FAK's scaffolding functions. We further show that LD2-LD3-LD4 expression markedly reduces FA turnover and inhibits tumor cell migration and invasion. Finally, we show that dimers of a single motif, linked through a flexible linker of the proper size, are sufficient for the displacement of FAK from FAs and for inhibition of tumor cell migration. This work raises the possibility of using a synthetic peptide as an antimetastatic agent, given that effective displacement of FAK from FAs only requires dimers of a single LD motif linked by a short flexible linker. CONCLUSION: In conclusion, these results suggest that FAK displacement from FAs is a promising new strategy to target critical processes implicated in cancer progression and metastasis. Video abstract.


Assuntos
Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Adesões Focais/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Paxilina/metabolismo , Linhagem Celular , Movimento Celular , Progressão da Doença , Humanos , Paxilina/genética , Domínios Proteicos
18.
Pharmaceutics ; 13(1)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430184

RESUMO

Nanomaterials quickly evolve to produce safe and effective biomedical alternatives, mainly silver nanoparticles (AgNPs). The AgNPs' antibacterial, antiviral, and antitumor properties convert them into a recurrent scaffold to produce new treatment options. This work reported the full characterization of a highly biocompatible protein-coated AgNPs formulation and their selective antitumor and amoebicidal activity. The protein-coated AgNPs formulation exhibits a half-inhibitory concentration (IC50) = 19.7 µM (2.3 µg/mL) that is almost 10 times more potent than carboplatin (first-line chemotherapeutic agent) to inhibit the proliferation of the highly aggressive human adenocarcinoma HCT-15. The main death pathway elicited by AgNPs on HCT-15 is apoptosis, which is probably stimulated by reactive oxygen species (ROS) overproduction on mitochondria. A concentration of 111 µM (600 µg/mL) of metallic silver contained in AgNPs produces neither cytotoxic nor genotoxic damage on human peripheral blood lymphocytes. Thus, the AgNPs formulation evaluated in this work improves both the antiproliferative potency on HCT-15 cultures and cytotoxic selectivity ten times more than carboplatin. A similar mechanism is suggested for the antiproliferative activity observed on HM1-IMSS trophozoites (IC50 = 69.2 µM; 7.4 µg/mL). There is no change in cell viability on mice primary cultures of brain, liver, spleen, and kidney exposed to an AgNPs concentration range from 5.5 µM to 5.5 mM (0.6 to 600 µg/mL). The lethal dose was determined following the OECD guideline 420 for Acute Oral Toxicity Assay, obtaining an LD50 = 2618 mg of Ag/Kg body weight. All mice survived the observational period; the histopathology and biochemical analysis show no differences compared with the negative control group. In summary, all results from toxicological evaluation suggest a Category 5 (practically nontoxic) of the Globally Harmonized System of Classification and Labelling of Chemicals for that protein-coated AgNPs after oral administration for a short period and urge the completion of its preclinical toxicological profile. These findings open new opportunities in the development of selective, safe, and effective AgNPs formulations for the treatment of cancer and parasitic diseases with a significant reduction of side effects.

19.
Data Brief ; 34: 106622, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33354603

RESUMO

Agricultural waste mapping is an indispensable tool for the development and adoption of sustainable waste management practises in the agricultural sector. Current practices of agricultural plastic waste (APW) management in countries with large agricultural areas and thus high generation volumes of APW include uncontrollable disposal in fields or near water sources, or uncontrolled burning of the waste. These practices lead to irreversible deterioration of the natural environment through land and soil contamination, contamination of freshwater resources, air pollution and also pose public health issues. Given these negative effects on the environment, spatial prediction of APW generation becomes significant in sustainable agriculture. This dataset consists of the coordinates of the agricultural plots identified in the Republic of Cyprus and the area in square meters covered by agricultural greenhouses. The dataset has been used to perform APW generation mapping and predict the national generation quantities of waste low- density polyethylene (LDPE). The collection of the data is included in sixteen tables separated per geographical area-cluster. The agricultural plastic waste (APW) generation mapping was conducted with the use of up-to-date statistics from Cyprus Agricultural Payments Organization (CAPO), geographic information system (GIS) and satellite imagery.

20.
Data Brief ; 33: 106599, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33318983

RESUMO

This dataset consists of the hourly heat flux for four seasons and orientations of 15 different construction configurations of brick and stone masonry combined with insulation system solutions. The analysis was conducted with the use of Finite Element Modelling (FEM). The development of the models and the investigation of their thermal performance was conducted with the use of thermal modelling and numerical simulation analysis with COMSOL Multiphysics. For this purpose, a transient 2D multi- dimensional, time- dependent simulation model on finite elements was developed. The governing equations of heat transfer were considered as well as the convection and radiation heat transfer coefficients in accordance to the ISO 6946:2017 [1].

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