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1.
Carbohydr Polym ; 330: 121740, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38368119

RESUMO

Cellulose cryogels are promising eco-friendly materials that exhibit low density, high porosity, and renewability. However, the applications of these materials are limited by their lower mechanical and water resistance compared to petrochemical-based lightweight materials. In this work, nanocelluloses were functionalized with cationic and anionic groups, and these nanomaterials were combined to obtain strong and water-resilient cryogels. To prepare the cryogels, anionic and cationic micro- and nanofibrils (CNFs) were produced at three different sizes and combined in various weight ratios, forming electrostatic complexes. The complex phase was concentrated by centrifugation and freeze-dried. Porous and open cellular structures were assembled in all compositions tested (porosity >90 %). Compressive testing revealed that the most resistant cryogels (1.7 MPa) were obtained with equivalent amounts of negatively and positively charged CNFs with lengths between 100 and 1200 nm. The strength at this condition was achieved as CNF electrostatic complexes assembled in thick cells, as observed by synchrotron X-ray tomography. In addition to mechanical strength, electrostatic complexation provided remarkable structural stability in water for the CNF cryogels, without compromising their biodegradability. This route by electrostatic complexation is a practical strategy to combine and concentrate nanocelluloses to tailor biodegradable lightweight materials with high strength and wet stability.

2.
Arch Biochem Biophys ; 746: 109741, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37689256

RESUMO

Intercellular communication plays a crucial role in cancer, as well as other diseases, such as inflammation, tissue degeneration, and neurological disorders. One of the proteins responsible for this, are connexins (Cxs), which come together to form a hemichannel. When two hemichannels of opposite cells interact with each other, they form a gap junction (GJ) channel, connecting the intracellular space of these cells. They allow the passage of ions, reactive oxygen and nitrogen species (RONS), and signaling molecules from the interior of one cell to another cell, thus playing an essential role in cell growth, differentiation, and homeostasis. The importance of GJs for disease induction and therapy development is becoming more appreciated, especially in the context of oncology. Studies have shown that one of the mechanisms to control the formation and disruption of GJs is mediated by lipid oxidation pathways, but the underlying mechanisms are not well understood. In this study, we performed atomistic molecular dynamics simulations to evaluate how lipid oxidation influences the channel properties of Cx26 hemichannels, such as channel gating and permeability. Our results demonstrate that the Cx26 hemichannel is more compact in the presence of oxidized lipids, decreasing its pore diameter at the extracellular side and increasing it at the amino terminus domains, respectively. The permeability of the Cx26 hemichannel for water and RONS molecules is higher in the presence of oxidized lipids. The latter may facilitate the intracellular accumulation of RONS, possibly increasing oxidative stress in cells. A better understanding of this process will help to enhance the efficacy of oxidative stress-based cancer treatments.


Assuntos
Metabolismo dos Lipídeos , Simulação de Dinâmica Molecular , Comunicação Celular , Ciclo Celular , Diferenciação Celular
3.
Biomolecules ; 13(7)2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37509079

RESUMO

The potential of cold atmospheric plasma (CAP) in biomedical applications has received significant interest, due to its ability to generate reactive oxygen and nitrogen species (RONS). Upon exposure to living cells, CAP triggers alterations in various cellular components, such as the cell membrane. However, the permeation of RONS across nitrated and oxidized membranes remains understudied. To address this gap, we conducted molecular dynamics simulations, to investigate the permeation capabilities of RONS across modified cell membranes. This computational study investigated the translocation processes of less hydrophilic and hydrophilic RONS across the phospholipid bilayer (PLB), with various degrees of oxidation and nitration, and elucidated the impact of RONS on PLB permeability. The simulation results showed that less hydrophilic species, i.e., NO, NO2, N2O4, and O3, have a higher penetration ability through nitro-oxidized PLB compared to hydrophilic RONS, i.e., HNO3, s-cis-HONO, s-trans-HONO, H2O2, HO2, and OH. In particular, nitro-oxidation of PLB, induced by, e.g., cold atmospheric plasma, has minimal impact on the penetration of free energy barriers of less hydrophilic species, while it lowers these barriers for hydrophilic RONS, thereby enhancing their translocation across nitro-oxidized PLB. This research contributes to a better understanding of the translocation abilities of RONS in the field of plasma biomedical applications and highlights the need for further analysis of their role in intracellular signaling pathways.


Assuntos
Peróxido de Hidrogênio , Oxigênio , Peróxido de Hidrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Membrana Celular/metabolismo , Oxigênio/metabolismo , Simulação de Dinâmica Molecular , Espécies Reativas de Nitrogênio/metabolismo , Fosfolipídeos/metabolismo
4.
Pediatr Pulmonol ; 58(3): 727-737, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36382503

RESUMO

OBJECTIVE: There have been conflicting reports on the relationship between asthma and COVID-19 severity. This study aimed to compare the risk of death among children with asthma and healthy peers hospitalized due to COVID-19. METHODS: We carried out an analysis of all pediatric patients 2-19 years of age with asthma and COVID-19 registered in Influenza Epidemiological Surveillance Information System-Gripe, a Brazilian nationwide surveillance database, between February 2020 and March 2022. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk using the cumulative incidence function. RESULTS: Among 30,405 hospitalized children with COVID-19, 21,340 (70.2%) had no comorbidities, 6444 (21.2%) had comorbidities other than asthma, 2165 (7.1%) had asthma, and 465 (1.5%) had asthma with other comorbidities. The estimated probability of a fatal outcome for each group was 4.1%, 14.9%, 2.1%, and 10.7%, respectively. After adjustment, children with asthma had a 60% reduction in the hazard of death than healthy peers (hazard ratio [HR] = 0.39, 95% confidence interval [CI], 0.29-0.53, p < 0.0001). Among children with asthma and no other comorbidities, two covariates were independently associated with in-hospital mortality, age ≥12 years, HR = 4.0, 95% CI, 2.5-6.4), and low oxygen saturation at admission (HR = 2.3, 95% CI, 1.4-3.2). CONCLUSION: Children with asthma and no comorbidities had a lower risk of death compared with healthy peers after controlling for clinical and demographic confounding factors.


Assuntos
Asma , COVID-19 , Humanos , Criança , Adolescente , COVID-19/epidemiologia , Brasil/epidemiologia , SARS-CoV-2 , Asma/epidemiologia , Comorbidade , Hospitalização
5.
Redox Biol ; 57: 102503, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36228438

RESUMO

Gap junctions (GJs), essential structures for cell-cell communication, are made of two hemichannels (commonly called connexons), one on each adjacent cell. Found in almost all cells, GJs play a pivotal role in many physiological and cellular processes, and have even been linked to the progression of diseases, such as cancer. Modulation of GJs is under investigation as a therapeutic strategy to kill tumor cells. Furthermore, GJs have also been studied for their key role in activating anti-cancer immunity and propagating radiation- and oxidative stress-induced cell death to neighboring cells, a process known as the bystander effect. While, gap junction (GJ)-based therapeutic strategies are being developed, one major challenge has been the paradoxical role of GJs in both tumor progression and suppression, based on GJ composition, cancer factors, and tumoral context. Therefore, understanding the mechanisms of action, regulation, and the dual characteristics of GJs in cancer is critical for developing effective therapeutics. In this review, we provide an overview of the current understanding of GJs structure, function, and paradoxical pro- and anti-tumoral role in cancer. We also discuss the treatment strategies to target these GJs properties for anti-cancer responses, via modulation of GJ function.

6.
Arch Biochem Biophys ; 717: 109136, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35085576

RESUMO

It is well established that lipid aldehydes (LAs) are able to increase the permeability of cell membranes and induce their rupture. However, it is not yet clear how LAs are distributed in phase-separated membranes (PSMs), which are responsible for the transport of selected molecules and intracellular signaling. Thus, we investigate here the distribution of LAs in a PSM by coarse-grained molecular dynamics simulations. Our results reveal that LAs derived from mono-unsaturated lipids tend to accumulate at the interface between the liquid-ordered/liquid-disordered domains, whereas those derived from poly-unsaturated lipids remain in the liquid-disordered domain. These results are important for understanding the effects caused by oxidized lipids in membrane structure, properties and organization.


Assuntos
Aldeídos/química , Membrana Celular , Permeabilidade da Membrana Celular , Lipídeos/química , Conformação Molecular , Simulação de Dinâmica Molecular , Transição de Fase
7.
Plant Dis ; 106(5): 1330-1333, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34854758

RESUMO

Maize striate mosaic virus (MSMV; genus Mastrevirus) was recently reported in maize plants in Brazil and also detected by metagenomic analyses in the corn leafhopper, Dalbulus maidis (DeLong & Wolcott). Although these findings suggested that D. maidis is a potential vector, no transmission studies have been performed. Here, we tested the transmission of MSMV by D. maidis from field-collected infected plants and plants infected with MSMV via leafhopper-mediated transmission in the laboratory; all plants were confirmed positive for MSMV by PCR. In each one of three transmission replicates, aviruliferous D. maidis nymphs and adults were confined together on a source plant during a 4-day acquisition access period (AAP) and subsequently transferred to healthy maize seedlings (10 individuals per test plant) in a series of 4-day inoculation access periods (IAPs). We also tested transmission by the corn aphid, Rhopalosiphum maidis (Fitch) and by mechanical inoculation of healthy maize seedlings. Only D. maidis transmitted MSMV, with overall transmission rates of 29.4 and 39.5% on field-collected infected plants and 18.5% on infected plants in laboratory. D. maidis transmitted MSMV until the third (8 to 12 days after the AAP) or fourth successive IAP (12 to 16 days), with gradual loss in transmission efficiency and rate of viruliferous insects over time, suggesting a persistent but nonpropagative mode of transmission. Infected test plants showed mottling symptoms with mild chlorotic streaks and height reduction. This is the first report of transmission of a mastrevirus by D. maidis, facilitating the completion of Koch's postulate for MSMV.


Assuntos
Afídeos , Geminiviridae , Animais , Brasil , Metagenômica , Zea mays
8.
Pharmaceuticals (Basel) ; 16(1)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36678552

RESUMO

Alzheimer's Disease (AD) is characterized by a progressive cholinergic neurotransmission imbalance, with a decrease of acetylcholinesterase (AChE) activity followed by a significant increase of butyrylcholinesterase (BChE) in the later AD stages. BChE activity is also crucial for the development of Aß plaques, the main hallmarks of this pathology. Moreover, systemic copper dyshomeostasis alters neurotransmission leading to AD. In the search for structures targeting both events, a set of novel 6-benzamide purine nucleosides was synthesized, differing in glycone configuration and N7/N9 linkage to the purine. Their AChE/BChE inhibitory activity and metal ion chelating properties were evaluated. Selectivity for human BChE inhibition required N9-linked 6-deoxy-α-d-mannosylpurine structure, while all three tested ß-d-derivatives appeared as non-selective inhibitors. The N9-linked l-nucleosides were cholinesterase inhibitors except the one embodying either the acetylated sugar or the N-benzyl-protected nucleobase. These findings highlight that sugar-enriched molecular entities can tune bioactivity and selectivity against cholinesterases. In addition, selective copper chelating properties over zinc, aluminum, and iron were found for the benzyl and acetyl-protected 6-deoxy-α-l-mannosyl N9-linked purine nucleosides. Computational studies highlight molecular conformations and the chelating molecular site. The first dual target compounds were disclosed with the perspective of generating drug candidates by improving water solubility.

9.
Comput Biol Med ; 136: 104768, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34426173

RESUMO

Reactive oxygen and nitrogen species (RONS) are involved in many biochemical processes, including nitro-oxidative stress that causes cancer cell death, observed in cancer therapies such as photodynamic therapy and cold atmospheric plasma. However, their mechanisms of action and selectivity still remain elusive due to the complexity of biological cells. For example, it is not well known how RONS generated by cancer therapies permeate the cell membrane to cause nitro-oxidative damage. There are many studies dedicated to the permeation of RONS across native and oxidized membranes, but not across nitrated membranes, another lipid product also generated during nitro-oxidative stress. Herein, we performed molecular dynamics (MD) simulations to calculate the free energy barrier of RONS permeation across nitrated membranes. Our results show that hydrophilic RONS, such as hydroperoxyl radical (HO2) and peroxynitrous acid (ONOOH), have relatively low barriers compared to hydrogen peroxide (H2O2) and hydroxyl radical (HO), and are more prone to permeate the membrane than for the native or peroxidized membranes, and similar to aldehyde-oxidized membranes. Hydrophobic RONS like molecular oxygen (O2), nitrogen dioxide (NO2) and nitric oxide (NO) even have insignificant barriers for permeation. Compared to native and peroxidized membranes, nitrated membranes are more permeable, suggesting that we must not only consider oxidized membranes during nitro-oxidative stress, but also nitrated membranes, and their role in cancer therapies.


Assuntos
Peróxido de Hidrogênio , Nitratos , Simulação de Dinâmica Molecular , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio
10.
Medicina (Ribeirão Preto) ; 54(1)jul, 2021. tab
Artigo em Português | LILACS | ID: biblio-1354277

RESUMO

RESUMO: Fundamentos e objetivos: Apesar dos reconhecidos benefícios da prática de atividade física em pacientes com doença cardiovascular, acredita-se que pacientes com insuficiência cardíaca e fração de ejeção reduzida com comportamento não sedentário, mesmo que não pratiquem exercício físico regular, apresentem melhora da função cardiovascular e qualidade de vida em comparação a pacientes sedentários. Objetivo: comparar a capacidade funcional, função ventricular e quali-dade de vida de pacientes com insuficiência cardíaca sedentários e não sedentários. Métodos: Foram avaliados pacientes com Insuficiência Cardíaca e Fração de ejeção <50%, sendo compostos dois grupos, sedentários (n=45) e não sedentários (n=36), de acordo com o Questionário Internacional de Atividade Física. Os grupos foram submetidos à avaliação clínica e de qualidade de vida, teste de caminhada de Cooper, ecocardiograma e comparação pelo teste Qui-Quadrado para variáveis categóricas ou teste T de Student ou Mann-Whitney para variáveis contínuas. Nível de significância de 5%. Resultados: Os grupos foram homogêneos em relação às características basais e etiologia. Os pacientes do Grupo Não Sedentário apre-sentaram menos sintomas limitantes (p<0,01), menor necessidade de digitálicos (p=0,02), melhor fração de encurtamento ventricular (p=0,03) e menor aumento do volume indexado do átrio esquerdo (p=0,004). Não foram encontradas diferen-ças no teste de caminhada entre os grupos. Houve maior prejuízo do quesito capacidade funcional da qualidade de vida do grupo Sedentário. Conclusão: Considerando a limitação da amostra, pacientes com insuficiência cardíaca e comporta-mento não sedentário apresentam maior tolerabilidade ao exercício por apresentarem sintomas menos limitantes, melhor função ventricular e melhor qualidade de vida no quesito capacidade funcional quando comparados a pacientes sedentáriosRESUMOFundamentos e objetivos: Apesar dos reconhecidos benefícios da prática de atividade física em pacientes com doença cardiovascular, acredita-se que pacientes com insuficiência cardíaca e fração de ejeção reduzida com comportamento não sedentário, mesmo que não pratiquem exercício físico regular, apresentem melhora da função cardiovascular e qualidade de vida em comparação a pacientes sedentários. Objetivo: comparar a capacidade funcional, função ventricular e quali-dade de vida de pacientes com insuficiência cardíaca sedentários e não sedentários. Métodos: Foram avaliados pacientes com Insuficiência Cardíaca e Fração de ejeção <50%, sendo compostos dois grupos, sedentários (n=45) e não sedentários (n=36), de acordo com o Questionário Internacional de Atividade Física. Os grupos foram submetidos à avaliação clínica e de qualidade de vida, teste de caminhada de Cooper, ecocardiograma e comparação pelo teste Qui-Quadrado para variáveis categóricas ou teste T de Student ou Mann-Whitney para variáveis contínuas. Nível de significância de 5%. Resultados: Os grupos foram homogêneos em relação às características basais e etiologia. Os pacientes do Grupo Não Sedentário apre-sentaram menos sintomas limitantes (p<0,01), menor necessidade de digitálicos (p=0,02), melhor fração de encurtamento ventricular (p=0,03) e menor aumento do volume indexado do átrio esquerdo (p=0,004). Não foram encontradas diferen-ças no teste de caminhada entre os grupos. Houve maior prejuízo do quesito capacidade funcional da qualidade de vida do grupo Sedentário. Conclusão: Considerando a limitação da amostra, pacientes com insuficiência cardíaca e comporta-mento não sedentário apresentam maior tolerabilidade ao exercício por apresentarem sintomas menos limitantes, melhor função ventricular e melhor qualidade de vida no quesito capacidade funcional quando comparados a pacientes sedentários. (AU)


ABSTRACT: Purpose: Despite the recognized benefits of practicing physical activity in patients with cardiovascular disease, it is believed that patients with heart failure and reduced ejection fraction with non-sedentary behavior may present an improvement in cardiovascular function and quality of life compared to sedentary patients, even if they do not practice regular physical ex-ercise. The aim of the present study was to compare functional capacity, systolic and diastolic cardiac function and quality of life of sedentary and non-sedentary patients with heart failure and reduced ejection fraction. Methods: Patients with heart failure and ejection fraction below 50% were divided into two groups, Sedentary (n = 45) and Non-Sedentary (n = 36), using the IPAQ questionnaire. These two groups were evaluated with clinical evaluation, quality of life SF-36 questionnaire, Cooper walking test and transthoracic echocardiography. They were compared by Chi-Square test for categorical variables or Test T or Man-Whitney for continuous variables; the level of significance adopted in the statistical analysis was 5%. Results: The groups were homogeneous in relation to the baseline characteristics and etiology. The Non-Sedentary Group had fewer patients with severe symptoms (p <0.01), less necessity of digitalis (p = 0.02) and better left ventricle fractional shorten-ing (p = 0.03). There was no apparent difference in the walk-test data between groups. Additionally, there was a greater impairment in the functional capacity of the SF-36 Questionnaire in the Sedentary Group. Conclusion: Considering the sample limitation, patients with heart failure and non-sedentary behavior have greater tolerability to exercise because they have fewer limiting symptoms and better quality of life in the functional capacity domain than sedentary patients.


Assuntos
Humanos , Qualidade de Vida , Ecocardiografia , Doenças Cardiovasculares , Exercício Físico , Inquéritos e Questionários , Caminhada , Comportamento Sedentário , Teste de Caminhada , Insuficiência Cardíaca , Ventrículos do Coração
11.
Environ Sci Pollut Res Int ; 28(40): 57248-57259, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34086172

RESUMO

Due to the public and environmental health impact of cyanotoxins, investigations have been focused on finding environmental friendly algaecides from aquatic plants. The present study had the objective to evaluate the population control and physiological response of Microcystis aeruginosa (Kützing) Kützing (strain BCCUSP232) exposed to Pistia stratiotes L. extracts. Aqueous and ethanolic extracts of P. stratiotes at different concentrations (10, 25, and 50 mg L-1) were submitted to M. aeruginosa and reduced significantly (p<0.05) the cyanobacterium cell density. The ethanolic extract presented the greatest growth inhibition of the strain at the highest concentration. During exposure to P. stratiotes extracts, intracellular hydrogen peroxide levels, malondialdehyde content, and antioxidant enzymes (peroxidase, catalase, and glutathione S-transferase) activities increased in M. aeruginosa, while total protein concentration decreased when compared to the control group. Superoxide dismutase (SOD) activities presented a sharp decline, suggesting superoxide radical and peroxide accumulation. This implied that SOD was a target for bioactive substance(s) from aqueous and ethanolic extracts of P. stratiotes. Phytochemical screening of the extracts revealed that the ethanolic extract presented 93.36 mg gallic acid equivalent (GAE) per gram dry weight (g-1 DW) total polyphenols and 217.33 mg rutin equivalent (RE) per gram dry weight total flavonoids, and for the aqueous extract, 5.19 mg GAE g-1 DW total polyphenols and 11.02 mg RE g-1 DW total flavonoids were detected. Gas chromatography (GC)/mass spectrometry (MS) analyses of the ethanolic and aqueous extracts presented palmitic acid ethyl ester as major allelochemical. In view of these results, it can be concluded that P. stratiotes showed potential in controlling M. aeruginosa populations.


Assuntos
Araceae , Microcystis , Antioxidantes , Malondialdeído , Feromônios
12.
J Chem Inf Model ; 61(6): 2857-2868, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34080860

RESUMO

Lipid oxidation is associated with several inflammatory and neurodegenerative diseases, but many questions to unravel its effects on biomembranes are still open due to the complexity of the topic. For instance, recent studies indicated that phase-separated domains can have a significant effect on membrane function. It is reported that domain interfaces are "hot spots" for pore formation, but the underlying mechanisms and the effect of oxidation-induced phase separation on membranes remain elusive. Thus, to evaluate the permeability of the membrane coexisting of liquid-ordered (Lo) and liquid-disordered (Ld) domains, we performed atomistic molecular dynamics simulations. Specifically, we studied the membrane permeability of nonoxidized or oxidized homogeneous membranes (single-phase) and at the Lo/Ld domain interfaces of heterogeneous membranes, where the Ld domain is composed of either oxidized or nonoxidized lipids. Our simulation results reveal that the addition of only 1.5% of lipid aldehyde molecules at the Lo/Ld domain interfaces of heterogeneous membranes increases the membrane permeability, whereas their addition at homogeneous membranes does not have any effect. This study is of interest for a better understanding of cancer treatment methods based on oxidative stress (causing among others lipid oxidation), such as plasma medicine and photodynamic therapy.


Assuntos
Bicamadas Lipídicas , Simulação de Dinâmica Molecular , Membrana Celular , Humanos , Metabolismo dos Lipídeos , Microdomínios da Membrana , Oxirredução
13.
Discov Mater ; 1(1): 12, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33899049

RESUMO

Herein, we review aspects of leading-edge research and innovation in materials science that exploit big data and machine learning (ML), two computer science concepts that combine to yield computational intelligence. ML can accelerate the solution of intricate chemical problems and even solve problems that otherwise would not be tractable. However, the potential benefits of ML come at the cost of big data production; that is, the algorithms demand large volumes of data of various natures and from different sources, from material properties to sensor data. In the survey, we propose a roadmap for future developments with emphasis on computer-aided discovery of new materials and analysis of chemical sensing compounds, both prominent research fields for ML in the context of materials science. In addition to providing an overview of recent advances, we elaborate upon the conceptual and practical limitations of big data and ML applied to materials science, outlining processes, discussing pitfalls, and reviewing cases of success and failure.

14.
J Adv Nurs ; 76(12): 3473-3482, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32989824

RESUMO

AIMS: To identify clinical symptoms and nursing interventions for stem cell therapy in autoimmune diseases. DESIGN: This is a retrospective, cross-sectional study. METHODS: This study was undertaken with patients diagnosed with type 1 diabetes or multiple sclerosis, undergoing autologous haematopoietic stem cell transplantation from January 2004 - December 2018. Data were registered in a questionnaire, taken during the conditioning regimen comprising cyclophosphamide and rabbit anti-thymocyte globulin. Descriptive statistics and Fisher's exact test were used for data analysis. RESULTS: There were 68 and 23 patients in the multiple sclerosis and type 1 diabetes groups respectively. Skin rash, nausea, vomiting and fever were more frequent and diverse in the type 1 diabetes group. Steroids were used as prophylaxis for anti-thymocyte globulin-associated allergic reactions in 97% of multiple sclerosis patients. Most of the identified symptoms and nursing interventions were more associated with one or other disease group (p < .05) and were more frequent in the type 1 diabetes group. CONCLUSION: Patients with autoimmune diseases who underwent stem cell therapy present differences in their repertoire of adverse events and require disease-specific nursing actions. IMPACT: Our results may enable nurses to establish transplant and disease-specific guidelines to improve prevention and management of adverse events and therefore optimize patient care and therapeutic success.


Assuntos
Doenças Autoimunes , Transplante de Células-Tronco Hematopoéticas , Doenças Autoimunes/terapia , Estudos Transversais , Humanos , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
15.
Bioorg Med Chem Lett ; 30(20): 127469, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32768650

RESUMO

The pentacyclic triterpene 3ß,6ß,16ß-tri-hydroxilup-20(29)-ene is a natural product produced by the Brazilian medicinal plant Combretum leprosum. Its cytotoxicity has been previously reported against breast cancer cell lines. The low water solubility of this natural product, that hampers its bioavailability, motivated the investigation of a new nanoparticle formulation containing the triterpene in order to improve its bioactivity. The triterpene was encapsulated in polycaprolactone (PCL) polymer by nanoprecipitation, producing homogenic nanoparticles with nanometer sizes (122.7 ± 2.06 nm), which were characterized by FT-IR, SEM imaging and DSC. The cytotoxicity (MTT method) of the nanoparticle containing the triterpene 1, besides the free natural product and the nanoparticle control (without 1), was assayed against three human tumor cell lines [human colon carcinoma line (HCT116), prostate (PC3) and glioblastoma (SNB19)] and the normal epithelial embryo kidney human cell line (Hek293T). The nanocarrier produced a significative effect in the cytotoxicity of the natural product in the nanoformulation (IC50 0.11-0.26 µg mL-1) when compared with its free form (IC50 1.07-1.44 µg mL-1). Additionally, higher selectivity of the triterpene to the tumor cells was found when it was encapsulated (SI 1.92-4.54) than in its free form (SI 0.42-0.56). In this case, the nanoencapsulated triterpene was more selective to PC3 (SI 3.33) and SNB19 (SI 4.54) tumor cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Produtos Biológicos/farmacologia , Combretum/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Cápsulas , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Folhas de Planta/química , Relação Estrutura-Atividade
16.
Arch Biochem Biophys ; 695: 108548, 2020 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-32828794

RESUMO

Biological membranes are under constant attack of free radicals, which may lead to lipid nitro-oxidation, producing a complex mixture of nitro-oxidized lipids that are responsible for structural and dynamic changes on the membrane. Despite the latter, nitro-oxidized lipids are also associated with several inflammatory and neurodegenerative diseases, the underlying mechanisms of which remain elusive. We perform atomistic molecular dynamics simulations using several isomers of nitro-oxidized lipids to study their effect on the structure and permeability of the membrane, as well as the interaction between the mixture of these products in the phospholipid membrane environment. Our results show that the stereo- and positional isomers have a stronger effect on the properties of the membrane composed of oxidized lipids compared to that containing nitrated lipids. Nevertheless, nitrated lipids lead to three-fold increase in water permeability compared to oxidized lipids. In addition, we show that in a membrane consisting of combined nitro-oxidized lipid products, the presence of oxidized lipids protects the membrane from transient pores. Is well stablished that plasma application and photodynamic therapy produces a number of oxidative species used to kill cancer cells, through membrane damage induced by nitro-oxidative stress. This study is important to elucidate the mechanisms and the molecular level properties involving the reactive species produced during that cancer therapies.


Assuntos
Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Nitratos/química , Fosfolipídeos/química , Oxirredução
17.
Rev. colomb. cienc. pecu ; 33(2): 110-120, Apr.-June 2020. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1289288

RESUMO

Abstract Background: Residual annatto seed meal (RASM) is a byproduct after extraction of bixin in the cosmetic industry and may be used in animal diets. Objective: Two experiments were carried out to determine the nutritive value and effect of RASM inclusion levels in the diets of Japanese quails. Methods: For the digestibility experiment, 160 Japanese quails were distributed in a randomized study with two treatments and 10 replicates with eight birds each. The treatments consisted of a reference diet and a test diet containing 75% of the reference diet and 25% of RASM. For the performance assay, 192 Japanese quails were used in a randomized study with six treatments and four replicates with eight birds each. Treatments consisted of a control corn-based diet (Contr1) and another diet based on sorghum + canthaxanthin (Contr2), and four diets based on sorghum with increasing inclusion levels of RASM (0, 3, 6, and 9%). Results: Digestibility of dry matter and crude protein, metabolization coefficient of gross energy, and retention of calcium and phosphorus were 41.05, 43.12, 47.97, 25.49, and 30.35%, respectively. RASM inclusion did not influence bird productivity; however, feed conversion worsened in treatments with 0-6% RASM inclusion relative to that in Contr1. Yolk color increased due to RASM treatment. Conclusion: RASM may be included in sorghum-based diets for quails at 9%, with improvement in yolk color and no negative effects on productivity and egg quality.


Resumen Antecedentes: La harina de la semilla de achiote (RASM) es un subproducto de la extracción de bixina por la industria cosmética y puede ser usada en alimentación animal. Objetivo: Se realizaron dos experimentos para determinar el valor nutritivo y los efectos de la inclusión de RASM en dietas para codorniz. Métodos: Para el experimento de digestibilidad, 160 codornices japonesas fueron distribuidas en un estudio al azar con dos tratamientos y 10 repeticiones con ocho aves cada uno. Los tratamientos consistieron en una dieta referencia y una dieta de prueba, la cual estuvo compuesta por 75% de la dieta referencia y 25% de RASM. Para el ensayo de desempeño, 192 codornices japonesas fueron usadas en un estudio al azar con seis tratamientos y cuatro repeticiones con ocho aves cada uno. Los tratamientos consistieron en una dieta control a base de maíz (Contr1) y otra a base de sorgo + cantaxantina (Contr2) y cuatro dietas a base de sorgo con niveles de inclusión de RASM (0, 3, 6 y 9%). Resultados: Los coeficientes de digestibilidad de materia seca y proteína bruta, el coeficiente de metabolización de la energía bruta y la retención de calcio y fósforo fueron 41,05; 43,12; 47,97; 25,49 y 30,35%, respectivamente. La inclusión de RASM no influyó la productividad de las aves; entretanto la conversión alimenticia empeoró debido a los tratamientos con 0-6% RASM comparado con el tratamiento Contr1. El color de la yema aumentó debido a la RASM. Conclusión: RASM puede ser incluido en dietas a base de sorgo para codornices en un 9%, debido a la mejora en el color de la yema, además de no tener ningún efecto negativo en el desempeño productivo y calidad del huevo.


Resumo Antecedentes: O farelo residual da semente de urucum (RASM) é um subproduto da extração da bixina pela indústria cosmética e pode ser usado na alimentação animal. Objetivo: Dois experimentos foram conduzidos para determinar o valor nutritivo e os efeitos de inclusão do FRSU em dietas para codornas Japonesas. Métodos: Para o experimento de digestibilidade, 160 codornas Japonesas foram distribuídas em um estudo casualizado com dois tratamentos e 10 repetições com oito aves cada. Os tratamentos consistiram em uma dieta referência e uma dieta teste, a qual era composta por 75% da dieta referência e 25% de RASM. Para o ensaio de desempenho, 192 codornas Japonesas foram usadas em estudo ao acaso com seis tratamentos e quatro repetições com oito aves cada. Os tratamentos consistiram em uma dieta controle a base de milho (Contr1) e outra à base de sorgo com cantaxantina (Contr2) e quatro dietas a base de sorgo com níveis de inclusão de RASM (0, 3, 6 e 9%). Resultados: Os coeficientes de digestiblidade de matéria seca e proteína bruta, coeficiente de metabolização da energia bruta e retenção de cálcio e fósforo foram 41,05; 43,12; 47,97; 25,49 e 30,35%, respectivamente. A inclusão do FRSU não influenciou a produtividade das aves; entretanto, a conversão alimentar piorou devido aos tratamentos com 0-6% FRSU comparado com o tratamento Contr1. A cor da gema aumentou devido ao FRSU. Conclusão: RASM pode ser incluido em dietas baseadas em sorgo para codornas em 9%, devido a mehoria na cor da gema e nenhum efeito negativo no desempenho produtivo e qualidade de ovo.

19.
Curr Org Synth ; 17(4): 252-270, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32209046

RESUMO

Phthalimide derivatives have been presenting several promising biological activities in the literature, such as anti-inflammatory, analgesic, antitumor, antimicrobial and anticonvulsant. The most well-known and studied phthalimide derivative (isoindoline-1,3-dione) is thalidomide: this compound initially presented important sedative effects, but it is now known that thalidomide has effectiveness against a wide variety of diseases, including inflammation and cancer. This review approaches some of the recent and efficient chemical synthesis pathways to obtain phthalimide analogues and also presents a summary of the main biological activities of these derivatives found in the literature. Therefore, this review describes the chemical and therapeutic aspects of phthalimide derivatives.


Assuntos
Ftalimidas/síntese química , Ftalimidas/uso terapêutico , Animais , Linhagem Celular Tumoral , Humanos , Ftalimidas/farmacologia
20.
Biophys Chem ; 254: 106266, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31629220

RESUMO

Biomembranes are under constant attack of free radicals that may lead to lipid oxidation in conditions of oxidative stress. The products generated during lipid oxidation are responsible for structural and dynamical changes which may jeopardize the membrane function. For instance, the local rearrangements of oxidized lipid molecules may induce membrane rupture. In this study, we investigated the effects of mechanical stress on oxidized phospholipid bilayers (PLBs). Model bilayers were stretched until pore formation (or poration) using non-equilibrium molecular dynamics simulations. We studied single-component homogeneous membranes composed of lipid oxidation products, as well as two-component heterogeneous membranes with coexisting native and oxidized domains. In homogeneous membranes, the oxidation products with -OH and -OOH groups reduced the areal strain required for pore formation, whereas the oxidation product with O group behaved similarly to the native membrane. In heterogeneous membranes composed of oxidized and non-oxidized domains, we tested the hypothesis according to which poration may be facilitated at the domain interface region. However, results were inconclusive due to their large statistical variance and sensitivity to simulation setup parameters. We pointed out important technical issues that need to be considered in future simulations of mechanically-induced poration of heterogeneous membranes. This research is of interest for photodynamic therapy and plasma medicine, because ruptured and intact plasma membranes are experimentally considered hallmarks of necrotic and apoptotic cell death.


Assuntos
Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Oxirredução , Fosfatidilcolinas/química
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