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1.
J Biol Chem ; 299(4): 103056, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36822328

RESUMO

Cationic and amphiphilic peptides can be used as homing devices to accumulate conjugated antibiotics to bacteria-enriched sites and promote efficient microbial killing. However, just as important as tackling bacterial infections, is the modulation of the immune response in this complex microenvironment. In the present report, we designed a peptide chimaera called Chim2, formed by a membrane-active module, an enzyme hydrolysis site and a formyl peptide receptor 2 (FPR2) agonist. This molecule was designed to adsorb onto bacterial membranes, promote their lysis, and upon hydrolysis by local enzymes, release the FPR2 agonist sequence for activation and recruitment of immune cells. We synthesized the isolated peptide modules of Chim2 and characterized their biological activities independently and as a single polypeptide chain. We conducted antimicrobial assays, along with other tests aiming at the analyses of the cellular and immunological responses. In addition, assays using vesicles as models of eukaryotic and prokaryotic membranes were conducted and solution structures of Chim2 were generated by 1H NMR. Chim2 is antimicrobial, adsorbs preferentially to negatively charged vesicles while adopting an α-helix structure and exposes its disorganized tail to the solvent, which facilitates hydrolysis by tryptase-like enzymes, allowing the release of the FPR2 agonist fragment. This fragment was shown to induce accumulation of the cellular activation marker, lipid bodies, in mouse macrophages and the release of immunomodulatory interleukins. In conclusion, these data demonstrate that peptides with antimicrobial and immunomodulatory activities can be considered for further development as drugs.


Assuntos
Anti-Infecciosos , Receptores de Formil Peptídeo , Animais , Camundongos , Antibacterianos/farmacologia , Anti-Infecciosos/química , Bactérias , Membranas , Receptores de Formil Peptídeo/antagonistas & inibidores
4.
Artigo em Inglês | MEDLINE | ID: mdl-38791844

RESUMO

In recent years, weight gain and reduced physical activity in the general population have contributed to the development of obesity and other health problems; on the other hand, studies in behavioral sciences have been used to modify behaviors for a healthier life, so the objective of this study was to identify the evidence of interventions in behavioral sciences on adherence to physical activity and weight loss in obese patients. This systematic review study is based on a search of the electronic databases PubMed, Web of Science, Scopus, and Cochrane. Studies assessed the evidence from intervention studies that assessed the influence of intervention studies of behavioral sciences on public health. The articles were published between 2013 and 2023. The systematic search of the databases identified 2951 articles. The review analyzed 10 studies. Behavioral science interventions presented evidence through strategies such as multicomponent interventions, lottery and financial incentives, message framing, message framing with financial incentive and physical activity, and psychological satisfaction, demonstrating results in weight loss and maintenance and increased physical activity. This study presents scientific evidence through healthy behavior change methodologies, and future studies can explore these strategies in conjunction with public health technologies in the search for public-private partnerships to promote physical activity in adults.


Assuntos
Exercício Físico , Obesidade , Sobrepeso , Ensaios Clínicos Controlados Aleatórios como Assunto , Redução de Peso , Humanos , Obesidade/psicologia , Obesidade/terapia , Sobrepeso/psicologia , Sobrepeso/terapia , Ciências do Comportamento
5.
Int J Cardiol Heart Vasc ; 53: 101438, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38912228

RESUMO

Background: Longitudinal changes in gut microbiome and inflammation may be involved in the evolution of atherosclerosis after an acute coronary syndrome (ACS). We aimed to characterize repeated profiles of gut microbiota and peripheral CD4+ T lymphocytes during the first year after an ACS, and to address their relationship with atherosclerotic plaque changes. Methods: Over one year we measured the microbiome, peripheral counts of CD4+ T populations and cytokines in 67 patients shortly after a first ACS. We compared baseline measurements to those of a matched population of 40 chronic patients. A subgroup of 20 ACS patients underwent repeated assessment of fibrous cap thickness (FCT) of a non-culprit lesion. Results: At admission, ACS patients showed gut dysbiosis compared with the chronic group, which was rapidly reduced and remained low at 1-year. Also, their Th1 and Th2 CD4+ T counts were increased but decreased over time. The CD4+ T counts were related to ongoing changes in gut microbiome. Unsupervised clustering of repeated CD4+ Th0, Th1, Th2, Th17 and Treg counts in ACS patients identified two different cell trajectory patterns, related to cytokines. The group of patients following a high-CD4+ T cell trajectory showed a one-year reduction in their FCT [net effect = -24.2 µm; p = 0.016]. Conclusions: Patients suffering an ACS show altered profiles of microbiome and systemic inflammation that tend to mimic values of chronic patients after 1-year. However, in one-third of patients, this inflammatory state remains particularly dysregulated. This persistent inflammation is likely related to plaque vulnerability as evident by fibrous cap thinning (Clinical Trial NCT03434483).

6.
Artigo em Inglês | MEDLINE | ID: mdl-37887689

RESUMO

In recent decades, health literacy has garnered increasing attention alongside a variety of public health topics. This study aims to explore trends in this area through a bibliometric analysis. A Random Forest Model was utilized to identify keywords and other metadata that predict average citations in the field. To supplement this machine learning analysis, we have also implemented a bibliometric review of the corpus. Our findings reveal significant positive coefficients for the keywords "COVID-19" and "Male", underscoring the influence of the pandemic and potential gender-related factors in the literature. On the other hand, the keyword "Female" showed a negative coefficient, hinting at possible disparities that warrant further investigation. Additionally, evolving themes such as COVID-19, mental health, and social media were discovered. A significant change was observed in the main publishing journals, while the major contributing authors remained the same. The results hint at the influence of the COVID-19 pandemic and a significant association between gender-related keywords on citation likelihood, as well as changing publication strategies, despite the fact that the main researchers remain those who have been studying health literacy since its creation.


Assuntos
COVID-19 , Letramento em Saúde , Humanos , Pandemias , Saúde Pública , Bibliometria , COVID-19/epidemiologia , Aprendizado de Máquina
7.
Children (Basel) ; 10(6)2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37371289

RESUMO

(1) Background: The aim of the present study is to analyze subjective happiness in relation to leisure time in 10-year-old boys and girls from Brazil, Chile and Spain and to determine which leisure time activity has a greater effect on their subjective happiness and whether there are differences according to gender. (2) Methods: Data from the third wave of the Children's Worlds Project was used, which was collected by administering self-report measures to representative samples in each country. The sample was composed of 4008 early adolescents from Brazil (22.1%, n = 886), Chile (22.8%, n = 913) and Spain (55.1%, n = 2209). The mean age of the sample was 10.17 years (SD = 0.57), and 51.7% were girls. (3) Results: In terms of subjective happiness, moderate to high means were observed, with higher scores in boys and the Spanish sample. The results showed some differences in leisure time activities among children from Brazil, Chile and Spain. Furthermore, the results highlighted the importance of relaxation time with the family to promote happiness in pre-adolescence across genders and countries. Additionally, playing outdoors and doing homework were also found to be protective factors for subjective happiness. (4) Conclusions: In Brazil, Chile and Spain the most consistent result was the positive effect of spending time relaxing with the family on subjective happiness.

8.
J Exp Med ; 203(13): 2887-93, 2006 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-17145955

RESUMO

HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction to HIV-1 infection, we used a single-round infection assay with HIV-1 pseudotyped with vesicular stomatitis virus G protein (HIV-VSVG). Small interfering RNA-mediated depletion of APOBEC3G/3F (A3G/3F), but not TRIM5alpha, enhanced HIV-1 infection of iDCs, indicating that A3G/3F controls the sensitivity of iDCs to HIV-1 infection. Furthermore, sequences of HIV reverse transcripts revealed G-to-A hypermutation of HIV genomes during iDC infection, demonstrating A3G/3F cytidine deaminase activity in iDCs. When we separated the fraction of iDCs that was susceptible to HIV, we found the cells to be deficient in A3G messenger RNA and protein. We also noted that during DC maturation, which further reduces susceptibility to infection, A3G levels increased. These findings highlight a role for A3G/3F in explaining the resistance of most DCs to HIV-1 infection, as well as the susceptibility of a fraction of iDCs. An increase in the A3G/3F-mediated intrinsic resistance of iDCs could result in a block of HIV infection at its mucosal point of entry.


Assuntos
Citosina Desaminase/fisiologia , Células Dendríticas/virologia , HIV-1/crescimento & desenvolvimento , Monócitos/citologia , Nucleosídeo Desaminases/fisiologia , Proteínas Repressoras/fisiologia , Desaminase APOBEC-3G , Fatores de Restrição Antivirais , Sequência de Bases , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Transporte/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular , Citidina Desaminase , Citosina Desaminase/genética , Citosina Desaminase/metabolismo , DNA Viral/genética , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Citometria de Fluxo , Expressão Gênica , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , HIV-1/genética , Células HeLa , Humanos , Células Jurkat , Lipopolissacarídeos/farmacologia , Glicoproteínas de Membrana/genética , Dados de Sequência Molecular , Nucleosídeo Desaminases/genética , Nucleosídeo Desaminases/metabolismo , Mutação Puntual , RNA Interferente Pequeno/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Homologia de Sequência do Ácido Nucleico , Transfecção , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Proteínas do Envelope Viral/genética , Replicação Viral/genética
9.
Int J Public Health ; 67: 1604677, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090843

RESUMO

Objectives: We measure the impacts of an intersectoral intervention tackling adolescent substance use implemented between 2017 and 2019 in a tri-border region of Brazil, Paraguay, and Argentina. Methods: The intervention involved 23 institutions from different sectors and 880 adolescents, equally split between randomly selected treatment and control classes across institutions. Treatment group students were involved in the co-development of activities to tackle substance use within their institutions. Both treatment and control group students benefited from the activities developed and implemented from the second year of the intervention. We use difference-in-differences models to measure the impacts of participation in the co-development of the activities on alcohol, tobacco, and cannabis consumption. Results: Adolescents involved in the co-development of activities are 8 pp less likely to consume tobacco and cannabis, and 13 pp less likely to consume alcohol (p < 0.01), compared to those who only participate in the activities. Among cannabis users, frequent consumption is also reduced by the intervention. Peer frequency of consumption is strongly associated with individual consumption. Conclusion: Co-development of activities by the subjects themselves can be key to decreasing substance use in this very crucial stage of life, especially if the institutions and the implementers are familiar with the area and subjects of the intervention.


Assuntos
Consumo de Bebidas Alcoólicas , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Consumo de Bebidas Alcoólicas/prevenção & controle , Humanos , Grupo Associado , Estudantes , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Uso de Tabaco
10.
Arch Cardiol Mex ; 91(4): 444-452, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-34852190

RESUMO

OBJECTIVE: Coarctation of the aorta can be treated surgically or with balloon angioplasty. The objective of our study was to describe the results after percutaneous balloon angioplasty with or without stent implantation for coarctation of the aorta and establish the incidence of recovery during follow-up. METHOD: Cohort study. 89 patients of any age where included in a follow up period of nine years. RESULTS: Of the 89 patients included in the study, 69.0% were male. The mean follow-up for all participants was 33.66 months. 32.5% of the patients had a stent implanted during the angioplasty procedure; of which 24.1% suffered recoarctation during follow-up. In the group without stent implantation, 36.6% suffered recoarctation. There was not significant difference in the survival curves of the two groups (p = 0.899). CONCLUSIONS: Stent implantation during balloon angioplasty to treat aortic coarctation did not influence in the incidence of aortic recoarctation; but factors such as preangioplasty arterial hypertension and the final angioplasty gradient > 20 mmHg is associated with aortic recoarctation.


OBJETIVO: La coartación de la aorta puede ser tratada quirúrgicamente o con angioplastia con balón. El objetivo de nuestro estudio fue describir los resultados postangioplastia percutánea con balón con o sin implantación de stent para coartación de la aorta y establecer la incidencia de recoartación en el seguimiento. MÉTODO: Estudio de cohorte, se incluyeron pacientes de cualquier edad en un periodo de seguimiento de nueve años. RESULTADOS: Se incluyeron 89 pacientes, un 69.0% hombres. La media de seguimiento para todos los participantes fue de 33.66 meses. Al 32.5% se les implantó un stent en angioplastia; de los cuales el 24.1% se recoartaron durante el seguimiento. En el grupo sin stent se recoartaron un 36.6%. No hubo diferencia significativa en las curvas de supervivencia de los dos grupos (p = 0.889). CONCLUSIONES: La implantación de stent durante la angioplastia con balón para tratar coartación de aorta no influyó en la incidencia de recoartación de la aorta; pero factores como la hipertensión arterial preangioplastia y el gradiente final de angioplastia > 20 mmHg se asoció con recoartación de la aorta.


Assuntos
Angioplastia com Balão/métodos , Coartação Aórtica/cirurgia , Stents , Angioplastia com Balão/efeitos adversos , Aorta , Coartação Aórtica/epidemiologia , Cateterismo , Criança , Estudos de Coortes , Humanos , Hipertensão , Masculino , Resultado do Tratamento
11.
Sci Rep ; 11(1): 1421, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446825

RESUMO

Gut microbiota composition can modulate neuroendocrine function, inflammation, and cellular and immunological responses against different pathogens, including viruses. Zika virus (ZIKV) can infect adult immunocompetent individuals and trigger brain damage and antiviral responses. However, it is not known whether ZIKV infection could impact the gut microbiome from adult immunocompetent mice. Here, we investigated modifications induced by ZIKV infection in the gut microbiome of immunocompetent C57BL/6J mice. Adult C57BL/6J mice were infected with ZIKV and the gut microbiota composition was analyzed by next-generation sequencing of the V4 hypervariable region present in the bacterial 16S rDNA gene. Our data showed that ZIKV infection triggered a significant decrease in the bacteria belonging to Actinobacteria and Firmicutes phyla, and increased Deferribacteres and Spirochaetes phyla components compared to uninfected mice. Interestingly, ZIKV infection triggered a significant increase in the abundance of bacteria from the Spirochaetaceae family in the gut microbiota. Lastly, we demonstrated that modulation of microbiota induced by ZIKV infection may lead to intestinal epithelium damage and intense leukocyte recruitment to the intestinal mucosa. Taken together, our data demonstrate that ZIKV infection can impact the gut microbiota composition and colon tissue homeostasis in adult immunocompetent mice.


Assuntos
Firmicutes , Microbioma Gastrointestinal , Mucosa Intestinal , Spirochaetaceae , Infecção por Zika virus , Zika virus/metabolismo , Animais , Firmicutes/classificação , Firmicutes/crescimento & desenvolvimento , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/virologia , Camundongos , Spirochaetaceae/classificação , Spirochaetaceae/crescimento & desenvolvimento , Infecção por Zika virus/metabolismo , Infecção por Zika virus/microbiologia
12.
Arch Cardiol Mex ; 90(3): 313-320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32952160

RESUMO

Los pacientes con cardiopatías congénitas que afectan la continuidad del ventrículo derecho con la arteria pulmonar deben someterse con frecuencia a intervenciones debido a la limitada vida útil de los conductos quirúrgicos, lo que lleva al desarrollo de disfunción ventricular derecha por cambios en la geometría ventricular y predisposición a arritmias letales, con el consiguiente riesgo de reintervenciones. El implante valvular percutáneo pulmonar es una nueva alternativa terapéutica, menos invasiva en comparación con la quirúrgica, para pacientes seleccionados. Se realiza una revisión de las publicaciones médicas actuales disponibles y se describe la experiencia inicial del implante valvular pulmonar percutáneo en un centro colombiano de alta complejidad para el tratamiento de enfermedades cardiovasculares, en dos pacientes con disfunción del homoinjerto aórtico en posición pulmonar con doble lesión valvular, en los cuales el implante valvular pulmonar percutáneo fue una conducta exitosa. Se eligió a pacientes con cardiopatías congénitas, conductos quirúrgicos disfuncionales con estenosis o insuficiencia pulmonar significativa, y disfunción y dilatación ventricular derechas. Se empleó la técnica regular para el implante de la válvula pulmonar Melody, sin documentarse complicaciones durante el procedimiento ni al año de seguimiento. El implante percutáneo de la válvula pulmonar es un gran avance en el tratamiento de pacientes con cardiopatías congénitas, con resultados favorables a corto y mediano plazos, lo cual hace posible la restauración de la función ventricular con riesgo mínimo, frente al reemplazo quirúrgico en pacientes seleccionados.Patients with congenital heart disease that involves reconstruction of the right ventricular outflow tract must frequently undergo interventions derived from the limited useful life of the surgical canals, which leads to the development of right ventricular dysfunction due to changes in the ventricular geometry and predisposition to lethal arrhythmias, with the consequent risk of reinterventions. The percutaneous pulmonary valvular implant is a new therapeutic alternative, less invasive, compared to surgery, for selected patients. A review of the available literature is made and the initial experience of percutaneous pulmonary valve implantation in a Colombian center of high complexity for the treatment of cardiovascular diseases is described, in two patients with aortic homograft dysfunction in a pulmonary position with double valvular lesion, in which the percutaneous pulmonary valve implant was a successful strategy. Patients with congenital heart disease were chosen, with dysfunctional surgical conduits with stenosis or significant pulmonary insufficiency, with dysfunction and right ventricular dilatation. The standard technique for the implantation of the Melody pulmonary valve was used, without complications during the procedure or one year of follow-up. Percutaneous implantation of the pulmonary valve is a great advance in the management of patients with congenital heart diseases, with favorable results in the short and medium term, allowing the restoration of ventricular function with minimal risk, compared to surgical replacement in selected patients.


Assuntos
Implante de Prótese de Valva Cardíaca/métodos , Insuficiência da Valva Pulmonar/cirurgia , Estenose da Valva Pulmonar/cirurgia , Adolescente , Colômbia , Humanos , Masculino , Desenho de Prótese , Valva Pulmonar/patologia , Valva Pulmonar/cirurgia , Insuficiência da Valva Pulmonar/congênito , Estenose da Valva Pulmonar/congênito
13.
Methods Mol Biol ; 2142: 81-92, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32367360

RESUMO

Inflammation is part of a defense reaction of live tissues that is triggered by pathogens, chemical reagents, trauma, and radiation. Understanding the inflammatory process triggered by Zika virus (ZIKV) is important to better understand the pathogen-host interaction. The evaluation of this process can be done using tools such as enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription PCR (RT-qPCR). Both techniques have been an indispensable tool not just for immunologists but for all interested in understanding the inflammatory process.


Assuntos
Inflamação/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Zika virus/fisiologia , Animais , Barreira Hematotesticular/imunologia , Barreira Hematotesticular/metabolismo , Barreira Hematotesticular/virologia , Morte Celular , Ensaio de Imunoadsorção Enzimática/métodos , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/virologia , Masculino , Camundongos , Orquite/diagnóstico , Orquite/genética , Orquite/imunologia , Orquite/virologia , Testículo/patologia , Testículo/fisiologia , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/genética , Infecção por Zika virus/imunologia , Infecção por Zika virus/metabolismo
14.
Cells ; 9(4)2020 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-32325652

RESUMO

Zika virus (ZIKV) has been reported by several groups as an important virus causing pathological damage in the male reproductive tract. ZIKV can infect and persist in testicular somatic and germ cells, as well as spermatozoa, leading to cell death and testicular atrophy. ZIKV has also been detected in semen samples from ZIKV-infected patients. This has huge implications for human reproduction. Global scientific efforts are being applied to understand the mechanisms related to arboviruses persistency, pathogenesis, and host cellular response to suggest a potential target to develop robust antiviral therapeutics and vaccines. Here, we discuss the cellular modulation of the immunologic and physiologic properties of the male reproductive tract environment caused by arboviruses infection, focusing on ZIKV. We also present an overview of the current vaccine effects and therapeutic targets against ZIKV infection that may impact the testis and male fertility.


Assuntos
Células Germinativas/virologia , Células de Sertoli/virologia , Testículo/virologia , Infecção por Zika virus , Humanos , Masculino , Células de Sertoli/patologia , Testículo/imunologia , Testículo/patologia , Replicação Viral/imunologia , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologia
15.
Mitochondrial DNA A DNA Mapp Seq Anal ; 30(5): 721-729, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31188041

RESUMO

The utilization of molecular tools for the certification of fishery products has been increasing over the last years. In general, economically important species are replaced by less valuable species, characterizing a commercial fraud. We evaluated the authenticity of 107 frozen fillets tagged as Gurijuba (Sciades parkeri) and Uritinga (Sciades proops) from local markets in northern amazon coast by sequencing two mitochondrial genes: Cytochrome oxidase subunit I and cytochrome b (Cyt b). About 16% of fillets putatively related to S. parkeri were replaced by S. proops. The Gurijuba faces high fishing pressure, being currently listed by the International Union for Conservation of Nature as vulnerable. Forensic analysis with DNA markers, proved to be highly efficient in the discrimination of the processed seafood products, providing unequivocal identification of species, revealing commercial fraud in the fillets of the Gurijuba, and revealing the utility of Cytb sequences as barcode in fishes.


Assuntos
Peixes-Gato/classificação , Peixes-Gato/genética , Código de Barras de DNA Taxonômico , Alimentos Marinhos/análise , Animais , Brasil , Citocromos b/genética , Citocromos b/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Genoma Mitocondrial/genética , Especificidade da Espécie
16.
Heliyon ; 5(6): e01789, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31194010

RESUMO

In this work, 8 samples of carbon aerogels with different ratios of catalyst versus resorcinol (R/C) from 25 to 1500 were used. The textural properties were evaluated from N2 adsorption isotherms in 77 K, as well as the chemical ones, where the surface chemistry was evaluated through the Boehm titrations. The results were analyzed and related to the adsorption of the nickel (II) ion from aqueous solution. The experimental results show that the aerogel samples can be divided into two series with different properties: Series I, mainly microporous (low ratio R/C) and Series II (high ratio R/C) mainly microporous but with a contribution of mesoporosity. The specific surface area varied between 64 and 990 m2 g-1. The experimental results show that prepared aerogels have an adequate adsorption capacity towards nickel (II) ions. The behavior of the kinetics of Ni(II) adsorption on carbon aerogels adjusts in a better way the kinetic model of pseudo-second order since it is the one that presents the value of the highest R2 correlation coefficient. The calorimetric data shows that the greater the area developed in carbons aerogels the enthalpy increases.

17.
Sci Rep ; 9(1): 20119, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882804

RESUMO

Zika virus (ZIKV) has a strong tropism for the nervous system and has been related to post-infection neurological syndromes. Once neuronal cells are infected, the virus is capable of modulating cell metabolism, leading to neurotoxicity and cellular death. The negative effect of ZIKV in neuron cells has been characterized. However, the description of molecules capable of reversing these cytotoxic effects is still under investigation. In this context, it has been largely demonstrated that docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, is highly neuroprotective. Here, we hypothesized that DHA's neuroprotective proprieties could have an influence on ZIKV-induced neurotoxicity in SH-SY5Y cells. Our data showed that pre-treatment of SH-SY5Y cells with DHA increased the cell viability and proliferation in ZIKV-infected cells. Moreover, DHA triggered an anti-inflammatory response in those infected cells. Besides, DHA was capable of restoring mitochondria function and number in ZIKV-infected SH-SY5Y cells. In addition, cells pre-treated with DHA prior to ZIKV infection presented a lower viral load at different times of infection. Taking together, these results demonstrated that DHA has a potential anti-inflammatory and neuroprotective effect against ZIKV infection in these neuron-like cells and could be a useful tool in the treatment against this virus.


Assuntos
Anti-Inflamatórios/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Fármacos Neuroprotetores/farmacologia , Zika virus/efeitos dos fármacos , Zika virus/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Efeito Citopatogênico Viral/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Replicação Viral/efeitos dos fármacos , Infecção por Zika virus/virologia
18.
Front Immunol ; 10: 2926, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31998283

RESUMO

Obesity is a chronic disease with rising worldwide prevalence and largely associated with several other comorbidities, such as cancer, non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome. Hepatic steatosis, a hallmark of NAFLD, is strongly correlated with obesity and has been correlated with changes in the gut microbiota, which can promote its development through the production of short-chain fatty acids (SCFAs) that regulate insulin resistance, bile acid, choline metabolism, and inflammation. Recent studies have suggested a controversial role for the inflammasome/caspase-1 in the development of obesity and non-alcoholic steatohepatitis (NASH). Here, we evaluated the role of inflammasome NLRP3 and caspases 1/11 in the establishment of obesity and hepatic steatosis in diet-induced obese mice, correlating them with the global lipid profile of the liver and gut microbiota diversity. After feeding wild-type, caspases 1/11, and NLRP3 knockout mice with a standard fat diet (SFD) or a high-fat diet (HFD), we found that the caspases 1/11 knockout mice, but not NLRP3 knockout mice, were more susceptible to HFD-induced obesity, and developed enhanced hepatic steatosis even under SFD conditions. Lipidomics analysis of the liver, assessed by MALDI-MS analysis, revealed that the HFD triggered a significant change in global lipid profile in the liver of WT mice compared to those fed an SFD, and this profile was modified by the lack of caspases 1/11 and NLRP3. The absence of caspases 1/11 was also correlated with an increased presence of triacylglycerol in the liver. Gut microbial diversity analysis, using 16S rRNA gene sequencing, showed that there was also an increase of Proteobacteria and a higher Firmicutes/Bacteroidetes ratio in the gut of caspases 1/11 knockout mice fed an HFD. Overall, mice without caspases 1/11 harbored gut bacterial phyla involved with weight gain, obesity, and hepatic steatosis. Taken together, our data suggest an important role for caspases 1/11 in the lipid composition of the liver and in the modulation of the gut microbial community composition. Our results further suggest that HFD-induced obesity and the absence of caspases 1/11 may regulate both lipid metabolism and gut microbial diversity, and therefore may be associated with NAFLD and obesity.


Assuntos
Caspase 1/metabolismo , Caspases Iniciadoras/metabolismo , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Fígado/metabolismo , Obesidade/enzimologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Caspase 1/genética , Caspases Iniciadoras/genética , Dieta Hiperlipídica , Ácidos Graxos Voláteis/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Obesidade/genética , Obesidade/metabolismo , Obesidade/microbiologia
19.
Front Immunol ; 10: 2927, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31998284

RESUMO

Foam cells are specialized lipid-loaded macrophages derived from monocytes and are a key pathological feature of atherosclerotic lesions. Lysophosphatidylcholine (LPC) is a major lipid component of the plasma membrane with a broad spectrum of proinflammatory activities and plays a key role in atherosclerosis. However, the role of LPC in lipid droplet (LD) biogenesis and the modulation of inflammasome activation is still poorly understood. In the present study, we investigated whether LPC can induce foam cell formation through an analysis of LD biogenesis and determined whether the cell signaling involved in this process is mediated by the inflammasome activation pathway in human endothelial cells and monocytes. Our results showed that LPC induced foam cell formation in both types of cells by increasing LD biogenesis via a NLRP3 inflammasome-dependent pathway. Furthermore, LPC induced pyroptosis in both cells and the activation of the inflammasome with IL-1ß secretion, which was dependent on potassium efflux and lysosomal damage in human monocytes. The present study described the IL-1ß secretion and foam cell formation triggered by LPC via an inflammasome-mediated pathway in human monocytes and endothelial cells. Our results will help improve our understanding of the relationships among LPC, LD biogenesis, and NLRP3 inflammasome activation in the pathogenesis of atherosclerosis.


Assuntos
Células Endoteliais/imunologia , Células Espumosas/imunologia , Inflamassomos/imunologia , Lisofosfatidilcolinas/imunologia , Monócitos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Piroptose , Células Endoteliais/citologia , Células Espumosas/citologia , Humanos , Inflamassomos/genética , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Monócitos/citologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética
20.
PLoS One ; 14(8): e0220656, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31386688

RESUMO

Following the treads of our previous works on the unveiling of bioactive peptides encrypted in plant proteins from diverse species, the present manuscript reports the occurrence of four proof-of-concept intragenic antimicrobial peptides in human proteins, named Hs IAPs. These IAPs were prospected using the software Kamal, synthesized by solid phase chemistry, and had their interactions with model phospholipid vesicles investigated by differential scanning calorimetry and circular dichroism. Their antimicrobial activity against bacteria, yeasts and filamentous fungi was determined, along with their cytotoxicity towards erythrocytes. Our data demonstrates that Hs IAPs are capable to bind model membranes while attaining α-helical structure, and to inhibit the growth of microorganisms at concentrations as low as 1µM. Hs02, a novel sixteen residue long internal peptide (KWAVRIIRKFIKGFIS-NH2) derived from the unconventional myosin 1h protein, was further investigated in its capacity to inhibit lipopolysaccharide-induced release of TNF-α in murine macrophages. Hs02 presented potent anti-inflammatory activity, inhibiting the release of TNF-α in LPS-primed cells at the lowest assayed concentration, 0.1 µM. A three-dimensional solution structure of Hs02 bound to DPC micelles was determined by Nuclear Magnetic Resonance. Our work exemplifies how the human genome can be mined for molecules with biotechnological potential in human health and demonstrates that IAPs are actual alternatives to antimicrobial peptides as pharmaceutical agents or in their many other putative applications.


Assuntos
Anti-Infecciosos/síntese química , Anti-Inflamatórios/síntese química , Peptídeos/farmacologia , Animais , Eritrócitos/efeitos dos fármacos , Humanos , Lipossomos/metabolismo , Macrófagos/metabolismo , Camundongos , Micelas , Peptídeos/análise , Peptídeos/síntese química , Peptídeos/metabolismo , Conformação Proteica em alfa-Hélice , Proteínas/química , Técnicas de Síntese em Fase Sólida , Fator de Necrose Tumoral alfa/metabolismo
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