Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 537
Filtrar
Mais filtros

Intervalo de ano de publicação
1.
PLoS Pathog ; 18(10): e1010499, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36240261

RESUMO

Severe dengue virus (DENV) infection is characterized by exacerbated inflammatory responses that lead to endothelial dysfunction and plasma leakage. We have recently demonstrated that Toll-like receptor 2 (TLR2) on blood monocytes senses DENV infection leading to endothelial activation. Here, we report that non-infectious immature DENV particles, which are released in large numbers by DENV-infected cells, drive endothelial activation via the TLR2 axis. We show that fully immature DENV particles induce a rapid, within 6 hours post-infection, inflammatory response in PBMCs. Furthermore, pharmacological blocking of TLR2/TLR6/CD14 and/or NF-kB prior to exposure of PBMCs to immature DENV reduces the initial production of inter alia TNF-α and IL-1ß by monocytes and prevents endothelial activation. However, prolonged TLR2 block induces TNF-α production and leads to exacerbated endothelial activation, indicating that TLR2-mediated responses play an important role not only in the initiation but also the resolution of inflammation. Altogether, these data indicate that the maturation status of the virus has the potential to influence the kinetics and extent of inflammatory responses during DENV infection.


Assuntos
Vírus da Dengue , Dengue , Humanos , Receptor 2 Toll-Like , Leucócitos Mononucleares , Receptor 6 Toll-Like , Fator de Necrose Tumoral alfa , NF-kappa B , Inflamação , Vírion
2.
J Med Virol ; 96(2): e29416, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38285457

RESUMO

The raising of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to the use of COVID-19 bivalent vaccines, which include antigens of the wild-type (WT) virus, and of the Omicron strain. In this study, we aimed to evaluate the impact of bivalent vaccination on the neutralizing antibody (NAb) response. We enrolled 93 volunteers who had received three or four doses of monovalent vaccines based on the original virus (n = 61), or a booster shot with the bivalent vaccine (n = 32). Serum samples collected from volunteers were subjected to neutralization assays using the WT SARS-CoV-2, and Omicron subvariants. In addition, immunoinformatics to quantify and localize highly conserved NAb epitopes were performed. As main result, we observed that the neutralization titers of samples from individuals vaccinated with the bivalent vaccine were higher for the original virus, in comparison to their capacity of neutralizing the Omicron variant and its subvariants. NAb that recognize epitopes mostly conserved in the WT SARS-CoV-2 were boosted, while those that recognize epitopes mostly present in the Omicron variant, and subvariants were primed. These results indicate that formulation of future vaccines shall consider to target present viruses, and not viruses that no longer circulate.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2/genética , Vacinação , Imunização Secundária , Anticorpos Neutralizantes , Epitopos/genética , Vacinas Combinadas
3.
Ann Vasc Surg ; 106: 80-89, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38579908

RESUMO

BACKGROUND: The study aims to describe midterm outcomes following treatment of infrarenal abdominal aortic aneurysms (AAAs) with short necks by endosutured aneurysm repair using the Heli-FX EndoAnchor system. METHODS: This is a retrospective study of prospectively collected data from 9 vascular surgery departments between June 2010 and December 2019, including treated AAAs with neck lengths ≤10 mm. The decision for the use of EndoAnchors was made by the treating surgeon or multidisciplinary aortic committee according to each center's practice. There were 2 Groups further assessed according to neck length, A (≥4 and <7 mm) and B (≥7 and ≤10 mm). The main outcomes analyzed were technical success, freedom from type Ia endoleaks (TIaELs), sac size increase, all-cause and aneurysm-related mortality. RESULTS: Seventy-six patients were included in the study, 17 fell into Group A and 59 into Group B. Median follow-up for the cohort was 40.5 (interquartile range 12-61) months. A median of 6 (interquartile range 3) EndoAnchors were deployed in each subject. Technical success was 86.8% for the total group, 82.4% and 88.1% (P = 0.534) for Groups A and B respectively. Six out of 10 (60%) of TIaELs at the completion angiographies showed spontaneous resolution. Cumulative freedom from TIaEL at 3 and 5 years for the total group was 89% and 84% respectively; this was 93% and 74% for Group A and 88% at both intervals in Group B (P = 0.545). In total, there were 7 (9.2%) patients presenting with TIaELs over the entire study period. Two (11.8%) in Group A and 5 (8.5%) in Group B (P = 0.679). There were more patients with sac regression in Group B (Group A = 6-35.3% vs. Group B = 34-57.6%, P = 0.230) with no statistical significance. All-cause mortality was 19 (25%) patients, with no difference (4-23.5% vs. 15-25.4%, P = 0.874) between groups; whereas aneurysm-related mortality occurred in 1 patient from Group A and 3 from Group B. CONCLUSIONS: This study demonstrates reasonable outcomes for patients with short-necked AAAs treated by endosutured aneurysm repair in terms of TIaELs up to 5-year follow-up. EndoAnchor use should be judiciously evaluated in short necks and may be a reasonable option when anatomical constraints are encountered, mainly for those with 7-10 mm neck lengths. Shorter neck length aspects, as indicated by the results from Group A, may be an alternative when no other options are available or feasible.

4.
Int J Sport Nutr Exerc Metab ; 34(1): 48-53, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37917959

RESUMO

The purpose of this study was to determine the effect of exercise intensity on the proportion and rate of carbohydrate oxidation and glucoregulatory hormone responses during recovery from exercise. Six physically active participants completed 1 hr of low-intensity (LI; 50% lactate threshold) or moderate-intensity (MI; 100% lactate threshold) exercise on separate days following a randomized counterbalanced design. During exercise and for 6 hr of recovery, samples of expired air were collected to determine oxygen consumption, respiratory exchange ratio, energy expenditure, and substrate oxidation rates. Blood samples were also collected to measure glucoregulatory hormones (catecholamines, GH) and metabolites (glucose, free fatty acids, lactate, pH, and bicarbonate). During exercise, respiratory exchange ratio, energy expenditure, and the proportion and rate of carbohydrate (CHO) oxidation were higher during MI compared with LI. However, during recovery from MI, respiratory exchange ratio and the proportion and rate of CHO oxidation were lower than preexercise levels and corresponding LI. During exercise and early recovery, catecholamines and growth hormone were higher in MI than LI, and there was a trend for higher levels of free fatty acids in the early recovery from MI compared with LI. In summary, CHO oxidation during exercise increases with exercise intensity but there is a preference for CHO sparing (and fat oxidation) during recovery from MI exercise compared with LI exercise. This exercise intensity-dependent shift in substrate oxidation during recovery is explained, in part, by the pattern of change of key glucoregulatory hormones including catecholamines and growth hormone and plasma fatty acid concentrations.


Assuntos
Ácidos Graxos não Esterificados , Hipoglicemia , Humanos , Ácidos Graxos não Esterificados/metabolismo , Oxirredução , Metabolismo Energético/fisiologia , Glucose , Consumo de Oxigênio/fisiologia , Catecolaminas , Ácido Láctico , Hormônio do Crescimento/metabolismo , Glicemia/metabolismo
5.
J Med Virol ; 95(2): e28481, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36609686

RESUMO

The main coronavirus disease 2019 (COVID-19) vaccine formulations used today are mainly based on the wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein as an antigen. However, new virus variants capable of escaping neutralization activity of serum antibodies elicited in vaccinated individuals have emerged. The Omicron (B.1.1.529) variant caused epidemics in regions of the world in which most of the population has been vaccinated. In this study, we aimed to understand what determines individual's susceptibility to Omicron in a scenario of extensive vaccination. For that purpose, we collected nasopharynx swab (n = 286) and blood samples (n = 239) from flu-like symptomatic patients, as well as their vaccination history against COVID-19. We computed the data regarding vaccine history, COVID-19 diagnosis, COVID-19 serology, and viral genome sequencing to evaluate their impact on the number of infections. As main results, we showed that vaccination in general did not reduce the number of individuals infected by Omicron, even with an increased immune response found among vaccinated, noninfected individuals. Nonetheless, we found that individuals who received the third vaccine dose showed significantly reduced susceptibility to Omicron infections. A relevant evidence that support this finding was the higher virus neutralization capacity of serum samples of most patients who received the third vaccine dose. In summary, this study shows that boosting immune responses after a third vaccine dose reduces susceptibility to COVID-19 caused by the Omicron variant. Results presented in this study are useful for future formulations of COVID-19 vaccination policies.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Teste para COVID-19 , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
6.
Chem Biodivers ; 20(5): e202300043, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37066849

RESUMO

n-Alkane and long-chain alcohol (LCOH) profiles of needle cuticular waxes of nine provenances of three Pinus species (P. taeda. P. pinaster and P. pinea) were determined and their chemotaxonomic importance was studied. n-Alkanes concentrations were very low in all Pinus spp. A lack of ability of these compounds to differentiate Pinus spp. and their provenances was observed. LCOH concentrations were much higher, being nonacosan-10-ol (10-C29 -OH) the most abundant one in all Pinus spp. Total LCOH concentrations varied (P<0.001) between Pinus spp. with P. taeda presenting the highest (P<0.05) value and P. pinea the lowest one. Differences in LCOH profiles were large (P<0.001) and allowed separation of Pinus spp. in the Principal Component Analysis (PCA). Although a noticeable separation of individuals was not observed. cluster analysis on LCOH concentrations allowed a clear distinction between species, indicating their potential to be used as chemotaxonomic markers to differentiate provenances of different Pinus spp.


Assuntos
Alcanos , Pinus , Alcanos/análise , Cromatografia Gasosa-Espectrometria de Massas , Ceras , Etanol
7.
Sensors (Basel) ; 23(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36850436

RESUMO

Breast cancer is the most prevalent cancer in the world and the fifth-leading cause of cancer-related death. Treatment is effective in the early stages. Thus, a need to screen considerable portions of the population is crucial. When the screening procedure uncovers a suspect lesion, a biopsy is performed to assess its potential for malignancy. This procedure is usually performed using real-time Ultrasound (US) imaging. This work proposes a visualization system for US breast biopsy. It consists of an application running on AR glasses that interact with a computer application. The AR glasses track the position of QR codes mounted on an US probe and a biopsy needle. US images are shown in the user's field of view with enhanced lesion visualization and needle trajectory. To validate the system, latency of the transmission of US images was evaluated. Usability assessment compared our proposed prototype with a traditional approach with different users. It showed that needle alignment was more precise, with 92.67 ± 2.32° in our prototype versus 89.99 ± 37.49° in a traditional system. The users also reached the lesion more accurately. Overall, the proposed solution presents promising results, and the use of AR glasses as a tracking and visualization device exhibited good performance.


Assuntos
Realidade Aumentada , Feminino , Humanos , Interface Usuário-Computador , Ultrassonografia Mamária , Ultrassonografia , Biópsia
8.
J Aging Phys Act ; 31(4): 693-704, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36623512

RESUMO

OBJECTIVE: Individual unsupervised home-based exercise programs can enhance muscle strength, physical function, gait, and balance in older adults. However, the effectiveness of such programs may be limited by the lack of supervision. This study aims to verify the effectiveness of individual unsupervised home-based programs, compare the effects of individual unsupervised home-based to supervised programs, and verify the influence of supervision over individual unsupervised home-based programs on the physical function of older adults. METHODS: A systematic literature search was performed in four electronic databases, and the trials involved randomized controlled comparing the home-based programs to supervised, control groups, or home-based + supervised evaluating the muscle strength, physical function, gait, and balance in older adults. RESULTS: Eleven studies met the inclusion criteria. The meta-analysis revealed no differences between home-based program versus supervised program in gait, mobility, and balance, revealing a trend of significance to supervised program on strength (standardized mean difference [SMD] = 0.27, p = .05). The analysis revealed effects in mobility (SMD = 0.40, p = .003), balance (SMD = 0.58, p = .0002), and muscle strength (SMD = 0.36, p = .02) favoring home-based program versus control group. Significant effects between home-based program versus home-based + supervised program were observed in balance (SMD = 0.74, p = .002) and muscle strength (SMD = 0.58, p = .01) in favor of home-based + supervised program. CONCLUSION: Home-based programs effectively improve older adults' physical function compared with control groups. However, supervised programs were more effective for muscle strength.


Assuntos
Exercício Físico , Vida Independente , Humanos , Idoso , Terapia por Exercício , Marcha , Força Muscular
9.
Molecules ; 28(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36677889

RESUMO

The effects of mineral fertilizers on the physicochemical properties of olives and oil under rainfed conditions is scarce. In this three-year study, the results of a nitrogen (N), phosphorus (P), potassium (K) and boron (B) fertilization trial carried out in a young rainfed olive grove and arranged as a nutrient omission trial are reported. The control consisted of the application of N, P, K and B (NPKB) and four other treatments corresponded to the removal of one of them (N0, P0, K0 and B0). Olive yield and several variables associated with the physicochemical properties of olives and oil were evaluated. The NPKB treatment increased olive yield compared to the treatment that did not receive N (N0). Although dependent on the climate conditions of the crop season, the NPKB treatment increased fruit weight and the pulp/pit ratio and its fruits tended to accumulate more oil than K0. However, the phenolics concentrations on fruits and oil tended to be lower. All olive oil samples were classified in the "extra virgin" category and all showed a decrease in its stability between 3 and 15 months of storage, regardless of treatment, especially in N0, P0 and B0 treatments. The results of the sensorial analysis indicate that all the oils fell into the medium fruitiness and greenly-fruity category. Only in P0 and B0 were defects detected, namely muddy sediment. Thus, this study seems to indicate the importance of N application, but also a balanced nutrient application and that further studies are needed, given the difficulty in finding clear trends in the response of measured variables to fertilizer treatments.


Assuntos
Olea , Olea/química , Azeite de Oliva/química , Frutas/química , Fenóis/análise , Nutrientes/análise , Óleos de Plantas/química
10.
Molecules ; 28(3)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36770816

RESUMO

Despite specialists' efforts to find the best solutions for cancer diagnosis and therapy, this pathology remains the biggest health threat in the world. Global statistics concerning deaths associated with cancer are alarming; therefore, it is necessary to intensify interdisciplinary research in order to identify efficient strategies for cancer diagnosis and therapy, by using new molecules with optimal therapeutic potential and minimal adverse effects. This review focuses on studies of porphyrin macrocycles with regard to their structural and spectral profiles relevant to their applicability in efficient cancer diagnosis and therapy. Furthermore, we present a critical overview of the main commercial formulations, followed by short descriptions of some strategies approached in the development of third-generation photosensitizers.


Assuntos
Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Medicina de Precisão , Porfirinas/química , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico
11.
Molecules ; 28(8)2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37110775

RESUMO

Brewer's spent yeast (BSY) mannoproteins have been reported to possess thickening and emulsifying properties. The commercial interest in yeast mannoproteins might be boosted considering the consolidation of their properties supported by structure/function relationships. This work aimed to attest the use of extracted BSY mannoproteins as a clean label and vegan source of ingredients for the replacement of food additives and protein from animal sources. To achieve this, structure/function relationships were performed by isolating polysaccharides with distinct structural features from BSY, either by using alkaline extraction (mild treatment) or subcritical water extraction (SWE) using microwave technology (hard treatment), and assessment of their emulsifying properties. Alkaline extractions solubilized mostly highly branched mannoproteins (N-linked type; 75%) and glycogen (25%), while SWE solubilized mannoproteins with short mannan chains (O-linked type; 55%) and (1→4)- and (ß1→3)-linked glucans, 33 and 12%, respectively. Extracts with high protein content yielded the most stable emulsions obtained by hand shaking, while the extracts composed of short chain mannans and ß-glucans yielded the best emulsions by using ultraturrax stirring. ß-Glucans and O-linked mannoproteins were found to contribute to emulsion stability by preventing Ostwald ripening. When applied in mayonnaise model emulsions, BSY extracts presented higher stability and yet similar texture properties as the reference emulsifiers. When used in a mayonnaise formulation, the BSY extracts were also able to replace egg yolk and modified starch (E1422) at 1/3 of their concentration. This shows that BSY alkali soluble mannoproteins and subcritical water extracted ß-glucans can be used as replacers of animal protein and additives in sauces.


Assuntos
Saccharomyces cerevisiae , beta-Glucanas , Animais , Humanos , Saccharomyces cerevisiae/metabolismo , Emulsões/metabolismo , Veganos , Polissacarídeos/química , Mananas/metabolismo , Água/análise , Parede Celular/química , beta-Glucanas/metabolismo , Extratos Vegetais/análise
12.
Socioecon Plann Sci ; 87: 101511, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36687379

RESUMO

Food waste is a worldwide problem. One third of the food produced in the world is lost or wasted every year. Most of this waste takes place downstream of the supply chain due to consumer behavior. This issue is expected to increase in both developed and emerging economies. With the beginning of the COVID-19 pandemic, a range of challenges led to changes in consumer behavior. This study explores household food waste behavior during the COVID-19 pandemic through the lens of the Theory of Planned Behavior. The risk perception regarding the pandemic was integrated into a broader framework, which was analyzed by Structural Equation Modeling. The sample comprises the participation of 452 Brazilian individuals. The results show that all the predictors incorporated in the model were statistically significant. The intention of reducing household food waste during the pandemic was found to be the strongest predictor of food waste behavior. Additionally, the pandemic apparently influenced consumers' perceptions about the control they think they have over food waste. This research has theoretical and managerial implications. From a theoretical perspective, this study identifies key predictors of household food waste by considering a period of health crisis in an emerging country. From a managerial standpoint, this research may provide a learning experience for future similar scenarios. Results may also motivate consumers to look for ways to reduce, reuse and recycle food waste.

13.
J Biol Chem ; 296: 100552, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33744293

RESUMO

The Cellulosome is an intricate macromolecular protein complex that centralizes the cellulolytic efforts of many anaerobic microorganisms through the promotion of enzyme synergy and protein stability. The assembly of numerous carbohydrate processing enzymes into a macromolecular multiprotein structure results from the interaction of enzyme-borne dockerin modules with repeated cohesin modules present in noncatalytic scaffold proteins, termed scaffoldins. Cohesin-dockerin (Coh-Doc) modules are typically classified into different types, depending on structural conformation and cellulosome role. Thus, type I Coh-Doc complexes are usually responsible for enzyme integration into the cellulosome, while type II Coh-Doc complexes tether the cellulosome to the bacterial wall. In contrast to other known cellulosomes, cohesin types from Bacteroides cellulosolvens, a cellulosome-producing bacterium capable of utilizing cellulose and cellobiose as carbon sources, are reversed for all scaffoldins, i.e., the type II cohesins are located on the enzyme-integrating primary scaffoldin, whereas the type I cohesins are located on the anchoring scaffoldins. It has been previously shown that type I B. cellulosolvens interactions possess a dual-binding mode that adds flexibility to scaffoldin assembly. Herein, we report the structural mechanism of enzyme recruitment into B. cellulosolvens cellulosome and the identification of the molecular determinants of its type II cohesin-dockerin interactions. The results indicate that, unlike other type II complexes, these possess a dual-binding mode of interaction, akin to type I complexes. Therefore, the plasticity of dual-binding mode interactions seems to play a pivotal role in the assembly of B. cellulosolvens cellulosome, which is consistent with its unmatched complexity and size.


Assuntos
Proteínas de Bactérias/metabolismo , Bacteroides/metabolismo , Proteínas de Ciclo Celular/metabolismo , Celulossomas/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Clostridiales/metabolismo , Proteínas de Bactérias/genética , Bacteroides/genética , Bacteroides/crescimento & desenvolvimento , Proteínas de Ciclo Celular/genética , Celobiose/metabolismo , Celulose/metabolismo , Proteínas Cromossômicas não Histona/genética , Clostridiales/genética , Clostridiales/crescimento & desenvolvimento , Coesinas
14.
J Vasc Surg ; 76(2): 344-351.e1, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35276266

RESUMO

OBJECTIVE: Endovascular aortic aneurysm repair (EVAR) has become the standard of care for abdominal aortic aneurysms (AAAs) in the modern era. Although numerous devices exist for standard infrarenal AAA repair, fenestrated EVAR (fEVAR) offers a minimally invasive alternative to traditional open repair for patients with a short infrarenal neck. Over time, aortic neck dilation can occur, leading to loss of the proximal seal, endoleaks, and AAA sac growth. In the present study, we analyzed aortic remodeling after EVAR vs fEVAR and further evaluated whether fEVAR confers a benefit in terms of sac shrinkage. METHODS: A retrospective review of prospectively collected data from 120 patients who had undergone EVAR was performed. Of these 120 patients, 30 had been treated with fEVAR (Zenith fenestrated; Cook Medical Inc, Bloomington, IN) and 90 patients were treated with EVAR devices (30 each with Endurant [Medtronic, Dublin, Ireland], Excluder [W.L. Gore & Associates, Flagstaff, AZ], and Zenith [Cook Medical Inc]). The demographic data were recorded. Also, anatomic measurements were performed for each patient preoperatively, at 30 days postoperatively, and at the longest follow-up point using three-dimensional reconstruction software. RESULTS: No significant differences were found in demographic data between the four groups. fEVAR had been used more often in aortas with large necks and irregular morphology (P = .004). At the longest follow-up, the suprarenal aorta encompassing 5, 10, and 15 mm above the lowest renal artery had dilated the most for the fEVAR group vs all EVAR groups. However, the infrarenal segment had tended to increase the least, or to even have regressed, for fEVAR compared with all three EVAR groups and was associated with the overall greatest proportion of sac shrinkage for the fEVAR group compared with the Medtronic, Gore, and Cook devices (-13.90% vs -5.75% vs -2.31% vs -4.68%, respectively; P = .025). CONCLUSIONS: Compared with EVAR, the patients treated with fEVAR had experienced greater suprarenal dilation over time, consistent with an overall greater burden of disease in the proximal native aorta. However, the infrarenal segment had dilated significantly less over time in the fEVAR group compared with all three EVAR groups, suggesting that fEVAR might stabilize the infrarenal neck, promoting positive sac remodeling, which was evidenced by the greatest degree of decrease in the largest AAA diameter in the fEVAR group.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/etiologia , Aneurisma da Aorta Abdominal/cirurgia , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Dilatação Patológica , Procedimentos Endovasculares/efeitos adversos , Humanos , Cavidade Peritoneal/cirurgia , Desenho de Prótese , Estudos Retrospectivos , Stents , Fatores de Tempo , Resultado do Tratamento
15.
Nanomedicine ; 45: 102595, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36031045

RESUMO

The development of safe and effective vaccine formulations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a hallmark in the history of vaccines. Here we report a COVID-19 subunit vaccine based on a SARS-CoV-2 Spike protein receptor binding domain (RBD) incorporated into nano-multilamellar vesicles (NMV) associated with monophosphoryl lipid A (MPLA). The results based on immunization of C57BL/6 mice demonstrated that recombinant antigen incorporation into NMVs improved antibody and T-cell responses without inducing toxic effects under both in vitro and in vivo conditions. Administration of RBD-NMV-MPLA formulations modulated antigen avidity and IgG subclass responses, whereas MPLA incorporation improved the activation of CD4+/CD8+ T-cell responses. In addition, immunization with the complete vaccine formulation reduced the number of doses required to achieve enhanced serum virus-neutralizing antibody titers. Overall, this study highlights NMV/MPLA technology, displaying the performance improvement of subunit vaccines against SARS-CoV-2, as well as other infectious diseases.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunidade , Imunoglobulina G , Lipídeos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Glicoproteína da Espícula de Coronavírus , Vacinas de Subunidades Antigênicas
16.
Int J Mol Sci ; 23(7)2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35409382

RESUMO

In nature, the deconstruction of plant carbohydrates is carried out by carbohydrate-active enzymes (CAZymes). A high-throughput (HTP) strategy was used to isolate and clone 1476 genes obtained from a diverse library of recombinant CAZymes covering a variety of sequence-based families, enzyme classes, and source organisms. All genes were successfully isolated by either PCR (61%) or gene synthesis (GS) (39%) and were subsequently cloned into Escherichia coli expression vectors. Most proteins (79%) were obtained at a good yield during recombinant expression. A significantly lower number (p < 0.01) of proteins from eukaryotic (57.7%) and archaeal (53.3%) origin were soluble compared to bacteria (79.7%). Genes obtained by GS gave a significantly lower number (p = 0.04) of soluble proteins while the green fluorescent protein tag improved protein solubility (p = 0.05). Finally, a relationship between the amino acid composition and protein solubility was observed. Thus, a lower percentage of non-polar and higher percentage of negatively charged amino acids in a protein may be a good predictor for higher protein solubility in E. coli. The HTP approach presented here is a powerful tool for producing recombinant CAZymes that can be used for future studies of plant cell wall degradation. Successful production and expression of soluble recombinant proteins at a high rate opens new possibilities for the high-throughput production of targets from limitless sources.


Assuntos
Escherichia coli , Plantas , Biomassa , Carboidratos , Escherichia coli/genética , Escherichia coli/metabolismo , Biblioteca Gênica , Humanos , Plantas/genética , Plantas/metabolismo
17.
J Strength Cond Res ; 36(6): 1636-1642, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32833890

RESUMO

ABSTRACT: Zandona, BA, Ramos, RA, de Oliveira, CdS, McAnulty, SR, Ferreira, LHB, Smolarek, AC, Enes, AAN, Urbinati, KMdSS, Aragon, AA, Schoenfeld, BJ, and de Souza Junior, TP. Reduced Dose of Beta-Alanine Is Sufficient to Maintain Performance in Repeated Sprints. J Strength Cond Res 36(6): 1636-1642, 2022-Beta-alanine (BA) supplementation has been shown to be effective in improving physical performance by increasing carnosine concentration. However, it is still necessary to know the effect of a maintenance dose on performance. Thus, this study aimed to investigate the effects of a maintenance dose of BA supplementation on performance. Forty-four anaerobically trained men with 23.9 ± 3.8 years of age, 176.0 ± 0.05 cm height, 81.2 ± 7.5 kg body mass, and 15.5 ± 2.9% of body fat performed a cycle ergometer test consisting of 4 sprints of 30 s with 4 minutes of active recovery. The study comprised 3 phases: (a) presupplementation, (b) supplementation with 6.4 g·d-1 BA or placebo, and (c) postsupplementation with a maintenance dose of 1.2 g·d-1 of BA or interruption of supplementation. Data were analyzed using generalized estimated equations with a priori 0.05 level of significance. The placebo group and interruption group presented a lower power (7.28 ± 0.66 and 7.71 ± 0.42 W·kg-1 vs. 8.04 ± 0.84 and 9.25 ± 1.18 W·kg-1, respectively; p < 0.05) during the third sprint in postsupplementation, whereas the maintenance group maintained the required power (7.47 ± 1.03 vs. 8.74 ± 1.07 W·kg-1; p > 0.05). The placebo group also presented higher percentage of fatigue (44.5% ± 12.3 and 44.8% ± 7.7 vs. 37.6 ± 7.2%; p = 0.021) and higher subjective perception of exertion (8.92 ± 0.90 vs. 8.00 ± 1.60; p = 0.028). Therefore, the maintenance dose of 1.2 g·d-1 BA was effective in maintaining performance, whereas a reduction in performance was observed after supplementation interruption.


Assuntos
Desempenho Atlético , Carnosina , Suplementos Nutricionais , Fadiga , Humanos , Masculino , beta-Alanina/farmacologia
18.
Molecules ; 27(19)2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36235306

RESUMO

Carbon nanomaterials endowed with significant luminescence have been synthesized for the first time from an abundant, highly localized waste, the wet pomace (WP), a semi-solid by-product of industrial olive oil production. Synthetic efforts were undertaken to outshine the photoluminescence (PL) of carbon nanoparticles through a systematic search of the best reaction conditions to convert the waste biomass, mainly consisting in holocellulose, lignin and proteins, into carbon dots (CDs) by hydrothermal carbonization processes. Blue-emitting CDs with high fluorescence quantum yields were obtained. Using a comprehensive set of spectroscopic tools (FTIR, Raman, XPS, and 1H/13C NMR) in combination with steady-state and time-resolved fluorescence spectroscopy, a rational depiction of WP-CDs structures and their PL properties was reached. WP-CDs show the up-conversion of PL capabilities and negligible cytotoxicity against two mammalian cell lines (L929 and HeLa). Both properties are excellent indicators for their prospective application in biological imaging, biosensing, and dynamic therapies driven by light.


Assuntos
Olea , Pontos Quânticos , Animais , Carbono/química , Lignina , Luminescência , Mamíferos , Azeite de Oliva , Pontos Quânticos/química
19.
Soft Matter ; 17(48): 10926-10934, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34811564

RESUMO

The formation of hydrogels by photosensitized oxidation and crosslinking of histidine-derived polymers is demonstrated for the first time. The photooxidation of pendant His mediated by singlet oxygen was used to promote covalent coupling by its dimerization. As a proof-of-concept, two systems were studied: (i) chondroitin sulfate (CS) functionalized with His, and (ii) an elastin-like peptide (ELP) containing His produced by recombinant techniques. Both materials were crosslinked by irradiation at 425 nm in the presence of Zn-porphyrin derivatives yielding His-based hydrogels. The molecular structure and physicochemical properties of ELP-His and other 5 ELPs with photooxidizable amino acids were studied in silica by computer simulation. A correlation between the protein conformation and its elastic properties is discussed. CS-His hydrogels demonstrate larger storage moduli than ELPs with other amino acids. The obtained results show the potential use of photooxidation to create a new type of His-based hydrogels.


Assuntos
Histidina , Hidrogéis , Simulação por Computador , Elastina , Oxigênio , Oxigênio Singlete
20.
BMC Infect Dis ; 21(1): 876, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34445956

RESUMO

BACKGROUND: The irregular use of antiretroviral therapy (ART) and late diagnosis still account for a large part of HIV-associated mortality in people living with HIV (PLHIV). Herein, we describe HIV-associated morbidity among hospitalised HIV/AIDS patients with advanced immunosuppression and assess the comorbidities, laboratory parameters, and immunological markers associated with mortality. METHODS: The cross-sectional study was conducted at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) in Manaus, Brazil. In all, 83 participants aged between 12 and 70 years were enrolled by convenience within 72 h of their hospitalisation. Clinical and laboratory data were obtained from electronic medical records. We prospectively measured the cytokines Th1/Th2/Th17 and inflammatory cytokines IL-8, IL-1ß, and IL-12 using cytometric bead array, and the soluble CD14 using in-house enzyme-linked immunosorbent assay. RESULTS: The HIV/AIDS inpatients presented a scenario of respiratory syndromes as the most prevalent comorbidity. Almost all patients had CD4 T counts below 350 cells/mL and the mortality rate was 20.5%. Pulmonary tuberculosis, neurotoxoplasmosis and oropharyngeal-esophageal candidiasis were the most prevalent opportunistic infections. TB and weight loss were more prevalent in HIV/AIDS inpatients who died. The Mann Whitney analysis showed that those who died had higher platelet distribution width (PDW) on admission, which is suggestive for platelet activation. The Poisson multivariate analysis showed the prevalence of TB, digestive syndrome and increases in IL-8 and lactate dehydrogenase (LDH) associated to death. CONCLUSIONS: The advanced immunosuppression characterized by the opportunistic infections presented in these HIV/AIDS inpatients was the major factor of mortality. The role of platelet activation in worse outcomes of hospitalisation and the IL-8 associated with the context of advanced immunosuppression may be promising markers in the prediction of mortality in HIV/AIDS patients.


Assuntos
Infecções por HIV , Adolescente , Adulto , Idoso , Biomarcadores , Brasil/epidemiologia , Contagem de Linfócito CD4 , Criança , Estudos Transversais , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Pessoa de Meia-Idade , Morbidade , Centros de Atenção Terciária , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA