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1.
Cell ; 185(5): 759-761, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35245478

RESUMO

Neutrophil recruitment from blood into tissues is a hallmark of inflammation and anti-microbial host defense. In this issue, De Giovanni et al. describe an unanticipated role for a serotonin metabolite, 5-HIAA, which is produced by activated platelets and mast cells and engages the orphan receptor, GPR35, to recruit neutrophils to inflamed tissues.


Assuntos
Plaquetas , Neutrófilos , Plaquetas/metabolismo , Humanos , Inflamação/metabolismo , Mastócitos/metabolismo , Infiltração de Neutrófilos , Neutrófilos/metabolismo
2.
Proc Natl Acad Sci U S A ; 120(21): e2221967120, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37186857

RESUMO

The structure-based design of small-molecule inhibitors targeting protein-protein interactions (PPIs) remains a huge challenge as the drug must bind typically wide and shallow protein sites. A PPI target of high interest for hematological cancer therapy is myeloid cell leukemia 1 (Mcl-1), a prosurvival guardian protein from the Bcl-2 family. Despite being previously considered undruggable, seven small-molecule Mcl-1 inhibitors have recently entered clinical trials. Here, we report the crystal structure of the clinical-stage inhibitor AMG-176 bound to Mcl-1 and analyze its interaction along with clinical inhibitors AZD5991 and S64315. Our X-ray data reveal high plasticity of Mcl-1 and a remarkable ligand-induced pocket deepening. Nuclear Magnetic Resonance (NMR)-based free ligand conformer analysis demonstrates that such unprecedented induced fit is uniquely achieved by designing highly rigid inhibitors, preorganized in their bioactive conformation. By elucidating key chemistry design principles, this work provides a roadmap for targeting the largely untapped PPI class more successfully.


Assuntos
Apoptose , Naftalenos , Modelos Moleculares , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Ligantes
3.
Mol Biol Evol ; 41(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306290

RESUMO

Orthology information has been used for searching patterns in high-dimensional data, allowing transferring functional information between species. The key concept behind this strategy is that orthologous genes share ancestry to some extent. While reconstructing the history of a single gene is feasible with the existing computational resources, the reconstruction of entire biological systems remains challenging. In this study, we present Bridge, a new algorithm designed to infer the evolutionary root of orthologous genes in large-scale evolutionary analyses. The Bridge algorithm infers the evolutionary root of a given gene based on the distribution of its orthologs in a species tree. The Bridge algorithm is implemented in R and can be used either to assess genetic changes across the evolutionary history of orthologous groups or to infer the onset of specific traits in a biological system.


Assuntos
Evolução Biológica , Evolução Molecular , Algoritmos , Filogenia
4.
J Am Acad Dermatol ; 90(3): 537-544, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37898340

RESUMO

BACKGROUND: No international recommendations exist for a minimum imaging requirement per lesion using reflectance confocal microscopy (RCM). This may be beneficial given the increasing use of remote RCM interpretation internationally. OBJECTIVE: To develop international expert recommendations for image acquisition using tissue-coupled RCM for diagnosis of cutaneous tumors. METHODS: Using a modified Delphi approach, a core group developed the scope and drafted initial recommendations before circulation to a larger group, the Cutaneous Imaging Expert Resource Group of the American Academy of Dermatology. Each review round consisted of a period of open comment, followed by revisions. RESULTS: The recommendations were developed after 5 alternating rounds of review among the core group and the Cutaneous Imaging Expert Resource Group. These were divided into subsections of imaging personnel, recommended lesion criteria, clinical and lesion information to be provided, lesion preparation, image acquisition, mosaic cube settings, and additional captures based on lesion characteristics and suspected diagnosis. LIMITATIONS: The current recommendations are limited to tissue-coupled RCM for diagnosis of cutaneous tumors. It is one component of the larger picture of quality assurance and will require ongoing review. CONCLUSIONS: These recommendations serve as a resource to facilitate quality assurance, economical use of time, accurate diagnosis, and international collaboration.


Assuntos
Dermoscopia , Neoplasias Cutâneas , Humanos , Dermoscopia/métodos , Neoplasias Cutâneas/patologia , Pele/diagnóstico por imagem , Pele/patologia , Microscopia Intravital , Microscopia Confocal/métodos
5.
Rheumatol Int ; 44(5): 831-837, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37610651

RESUMO

Grading the quality of care in patients with systemic lupus erythematosus and determining its relationship with care satisfaction may recognize gaps that could lead to better clinical practice. Eighteen quality indicators (QIs) were recently developed and validated for patients with SLE based on the 2019 EULAR management recommendations. Few studies have analyzed the relationship between quality of care and care satisfaction in patients with lupus. This was a cross-sectional study. We included patients at least 18 years old who met the EULAR/ACR 2019 classification criteria for SLE. We interviewed patients and retrieved data from medical records to assess their compliance with a set of 18 EULAR-based QIs. We calculated each QI fulfillment as the proportion of fulfilled QI divided by the number of eligible patients for each indicator. Care satisfaction was evaluated with the satisfaction domain of LupusPRO version 1.7. Spearman correlation coefficient was used to determine the relationship between quality of care and care satisfaction. Seventy patients with a median age of 33 (IQR 23-48) were included, 90% were women. Overall adherence was 62.29%. The median care satisfaction was 100. Global adherence to the 18-QIs and the care satisfaction score revealed no correlation (r = 0.064, p = 0.599). Higher QI fulfillment was found in the group with remission versus the moderate-high activity group (p = 0.008). In our study, SLE patients in remission had higher fulfillment of quality indicators. We found no correlation between the quality of care and satisfaction with care.


Assuntos
Lúpus Eritematoso Sistêmico , Indicadores de Qualidade em Assistência à Saúde , Humanos , Feminino , Adolescente , Masculino , Estudos Transversais , Satisfação do Paciente , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia
6.
Artigo em Inglês | MEDLINE | ID: mdl-38936832

RESUMO

D-xylose is a metabolizable carbon source for several non-Saccharomyces species, but not for native strains of S. cerevisiae. For the potential application of xylose-assimilating yeasts in biotechnological processes, a deeper understanding of pentose catabolism is needed. This work aimed to investigate the traits behind xylose utilization in diverse yeast species.The performance of nine selected xylose-metabolizing yeast strains was evaluated and compared across three oxygenation conditions. Oxygenation diversely impacted growth, xylose consumption and product accumulation. Xylose utilization by ethanol-producing species such as Spathaspora passalidarum and Scheffersomyces stipitis was less affected by oxygen restriction than other xylitol-accumulating species such as Meyerozyma guilliermondii, Naganishia liquefaciens and Yamadazyma sp., for which increased aeration stimulated xylose assimilation considerably. S. passalidarum exhibited superior conversion of xylose to ethanol and showed the fastest growth and xylose consumption in all three conditions. By performing assays under identical conditions for all selected yeasts, we minimize bias in comparisons, providing valuable insight into xylose metabolism and facilitating the development of robust bioprocesses.

7.
BMC Health Serv Res ; 24(1): 6, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172824

RESUMO

BACKGROUND: This scoping review aims to systematically and critically describe the numerous legal challenges brought about by the utilization of digital oral health in the delivery of oral healthcare. METHODS: A systematic search was conducted. The following electronic databases were reviewed from inception up to March 2023: MEDLINE, Embase, Scopus, and LILACS. The search included any scientific document and paper in English, Spanish, or Portuguese on legal issues raised using digital health in oral healthcare delivery. Two reviewers conducted the selection process and data extraction. Legal issues raised concerning the adoption of digital health technology were analysed using the modified Mars' framework. RESULTS: Seventeen studies were included. Most of the documents identified and covered generic aspects of delivering digital oral healthcare (n = 11) without explicitly referring to any dental specialty. The most mentioned legal issues were data security (n = 15); liability and malpractice (n = 14); consent (n = 12); and confidentiality (n = 12). To a lower extent, patient-practitioner relationship (n = 11); and license and jurisdiction (n = 11) were also covered. These were followed by privacy of information (n = 10); adequacy of records (n = 9); and e-referrals (n = 8). On the other hand, fewer studies commented on social media use (n = 3), authentication (n = 2); or e-prescriptions (n = 2). Before implementing any digital health solution, practitioners need to be aware of the many legal issues that the introduction of these technologies involves, be clear where the responsibility lies, and apply extreme caution in following national guidelines. Current literature concentrates on a few well-known legal issues. Issues around authentication, use of social media, and e-prescriptions received less attention.


Assuntos
Confidencialidade , Saúde Bucal , Humanos , Atenção à Saúde , Privacidade , Saúde Digital
8.
Paediatr Anaesth ; 34(2): 160-166, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37962837

RESUMO

BACKGROUND: Propofol-based total intravenous anesthesia is gaining popularity in pediatric anesthesia. Electroencephalogram can be used to guide propofol dosing to the individual patient to mitigate against overdosing and adverse events. However, electroencephalogram interpretation and propofol pharmacokinetics are not sufficiently taught in training programs to confidently deploy electroencephalogram-guided total intravenous anesthesia. AIMS: We conducted a quality improvement project with the smart aim of increasing the percentage of electroencephalogram-guided total intravenous anesthesia cases in our main operating room from 0% to 80% over 18 months. Balancing measures were number of total intravenous anesthesia cases, emergence times, and perioperative emergency activations. METHODS: The project key drivers were education, equipment, and electronic health record modifications. Plan-Do-Study-Act cycles included: (1) providing journal articles, didactic lectures, intraoperative training, and teaching documents; (2) scheduling electroencephalogram-guided total intravenous anesthesia teachers to train faculty, staff, and fellows for specific cases and to assess case-based knowledge; (3) adding age-based propofol dosing tables and electroencephalogram parameters to the electronic health record (EPIC co, Verona, WI); (4) procuring electroencephalogram monitors (Sedline, Masimo Inc). Electroencephalogram-guided total intravenous anesthesia cases and balancing measures were identified from the electronic health record. The smart aim was evaluated by statistical process control chart. RESULTS: After the four Plan-Do-Study-Act cycles, electroencephalogram-guided total intravenous anesthesia increased from 5% to 75% and was sustained at 72% 9 months after project completion. Total intravenous anesthesia cases/mo and number of perioperative emergency activations did not change significantly from start to end of the project, while emergence time for electroencephalogram-guided total intravenous anesthesia was greater statistically but not clinically (total intravenous anesthesia without electroencephalogram [16 ± 10 min], total intravenous anesthesia with electroencephalogram [18 ± 9 min], sevoflurane [17 ± 9 min] p < .001). CONCLUSION: Quality improvement methods may be deployed to adopt electroencephalogram-guided total intravenous anesthesia in a large academic pediatric anesthesia practice. Keys to success include education, in operating room case training, scheduling teachers with learners, electronic health record modifications, and electroencephalogram devices and supplies.


Assuntos
Propofol , Criança , Humanos , Anestésicos Intravenosos , Hospitais Pediátricos , Melhoria de Qualidade , Anestesia Geral/métodos , Eletroencefalografia , Anestesia Intravenosa/métodos
9.
Eur Arch Otorhinolaryngol ; 281(2): 945-951, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37898592

RESUMO

PURPOSE: Salvage surgery is mandatory when regional persistence/recurrence after chemoradiation. The aim of this study is to describe the outcomes of salvage surgery. METHODS: A retrospective study was conducted in patients with locally advanced head and neck squamous cell carcinoma that were primarily treated with chemorradiation and underwent salvage neck dissection (ND) with suspected recurrent/persistent nodal disease. All patients had a response evaluation at 12 weeks through clinical examination and computed tomography-positron emission tomography. Decision for ND was taken in case of suspected persistence or if there was suspicion of recurrence, histologically confirmed. RESULTS: There were 40 patients included. 32/40 (80%) ND were done because of confirmed/suspected persistence and 8/40 (20%) were done because of recurrences. Persistence was confirmed histologically in 14/32 (43.8%) cases and recurrence in 6/8 (75%) cases. Median survival from diagnosis was 39 months (95% CI 28.162-49.838). Significant differences were observed between patients who had viable tumour cells in the sample and those who did not, but the differences were only significant when only deaths due to tumour progression were considered (p = 0.014). 14/32 (43.8%) patients with suspected or confirmed persistence developed a recurrence after the ND and 3/8 (37.5%) patients with suspected or confirmed recurrence developed a new recurrence. New recurrences were more frequent in cases that had viable tumor in the specimen. CONCLUSIONS: Patients with nodal persistence/recurrence have a poor prognosis, even after salvage surgery. However, in a substantial number of patients the disease is controlled after ND, so it should be offer to these patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Esvaziamento Cervical , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Estudos Retrospectivos , Terapia de Salvação , Recidiva Local de Neoplasia/patologia
10.
Wilderness Environ Med ; : 10806032241249128, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720618

RESUMO

At the Plaza de Mulas medical tent, located at 4300 m (14,100 ft) along the Normal Route to the 6960 m (22,837 ft) summit of Aconcagua in Argentina, a Korean male in his 50s with no known medical conditions presented with lightheadedness and shortness of breath. He had taken sildenafil and acetazolamide that morning without improvement. Vital signs on arrival were notable for oxygen saturations in the high 60s with basilar crackles on lung auscultation, concerning for high altitude pulmonary edema. The patient was started on oxygen via nasal cannula and given dexamethasone. History was limited secondary to language barriers, but on review of systems the patient noted mild chest pressure. Bedside cardiac echocardiogram was performed, which revealed a septal wall motion abnormality. The patient was therefore given aspirin and clopidogrel and was flown to a lower trailhead, where he was met by local Emergency Medical Services. A 12-lead electrocardiogram revealed an anterior ST-elevation myocardial infarction, and the patient was taken emergently to the catheterization lab in Mendoza and underwent stent placement with a full recovery.

11.
BMC Oral Health ; 24(1): 280, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419003

RESUMO

OBJECTIVE: Authors reported multiple definitions of e-oral health and related terms, and used several definitions interchangeably, like mhealth, teledentistry, teleoral medicine and telehealth. The International Association of Dental Research e-Oral Health Network (e-OHN) aimed to establish a consensus on terminology related to digital technologies used in oral healthcare. METHOD: The Crowdsourcing Delphi method used in this study comprised of four main stages. In the first stage, the task force created a list of terms and definitions around digital health technologies based on the literature and established a panel of experts. Inclusion criteria for the panellists were: to be actively involved in either research and/or working in e-oral health fields; and willing to participate in the consensus process. In the second stage, an email-based consultation was organized with the panel of experts to confirm an initial set of terms. In the third stage, consisted of: a) an online meeting where the list of terms was presented and refined; and b) a presentation at the 2022-IADR annual meeting. The fourth stage consisted of two rounds of feedback to solicit experts' opinion about the terminology and group discussion to reach consensus. A Delphi-questionnaire was sent online to all experts to independently assess a) the appropriateness of the terms, and b) the accompanying definitions, and vote on whether they agreed with them. In a second round, each expert received an individualised questionnaire, which presented the expert's own responses from the first round and the panellists' overall response (% agreement/disagreement) to each term. It was decided that 70% or higher agreement among experts on the terms and definitions would represent consensus. RESULTS: The study led to the identification of an initial set of 43 terms. The list of initial terms was refined to a core set of 37 terms. Initially, 34 experts took part in the consensus process about terms and definitions. From them, 27 experts completed the first rounds of consultations, and 15 the final round of consultations. All terms and definitions were confirmed via online voting (i.e., achieving above the agreed 70% threshold), which indicate their agreed recommendation for use in e-oral health research, dental public health, and clinical practice. CONCLUSION: This is the first study in oral health organised to achieve consensus in e-oral health terminology. This terminology is presented as a resource for interested parties. These terms were also conceptualised to suit with the new healthcare ecosystem and the place of e-oral health within it. The universal use of this terminology to label interventions in future research will increase the homogeneity of future studies including systematic reviews.


Assuntos
Ecossistema , Saúde Bucal , Humanos , Consenso
12.
Curr Opin Anaesthesiol ; 37(3): 266-270, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38573191

RESUMO

PURPOSE OF REVIEW: Simulation is a well established practice in medicine. This review reflects upon the role of simulation in pediatric anesthesiology in three parts: training anesthesiologists to care for pediatric patients safely and effectively; evaluating and improving systems of care for children; and visions for the future. RECENT FINDINGS: Simulation continues to prove a useful modality to educate both novice and experienced clinicians in the perioperative care of infants and children. It is also a powerful tool to help analyze and improve upon how care is provided to infants and children. Advances in technology and computational power now allow for a greater than ever degree of innovation, accessibility, and focused reflection and debriefing, with an exciting outlook for promising advances in the near future. SUMMARY: Simulation plays a key role in developing and achieving peak performance in the perioperative care of infants and children. Although simulation already has a great impact, its full potential is yet to be harnessed.


Assuntos
Anestesiologia , Pediatria , Treinamento por Simulação , Humanos , Anestesiologia/educação , Anestesiologia/tendências , Anestesiologia/métodos , Criança , Pediatria/tendências , Pediatria/métodos , Treinamento por Simulação/métodos , Treinamento por Simulação/tendências , Competência Clínica , Lactente , Assistência Perioperatória/métodos , Assistência Perioperatória/tendências , Anestesiologistas/educação , Anestesiologistas/tendências , Simulação por Computador/tendências
13.
Bioinformatics ; 38(5): 1463-1464, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-34864914

RESUMO

MOTIVATION: Dendrogram is a classical diagram for visualizing binary trees. Although efficient to represent hierarchical relations, it provides limited space for displaying information on the leaf elements, especially for large trees. RESULTS: Here, we present TreeAndLeaf, an R/Bioconductor package that implements a hybrid layout strategy to represent tree diagrams with focus on the leaves. The TreeAndLeaf package combines force-directed graph and tree layout algorithms using a single visualization system, allowing projection of multiple layers of information onto a graph-tree diagram. The Supplementary Information provides two case studies that use breast cancer data from epidemiological and experimental studies. AVAILABILITY AND IMPLEMENTATION: TreeAndLeaf is written in the R language, and is available from the Bioconductor project at http://bioconductor.org/packages/TreeAndLeaf/ (version≥1.4.2). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Neoplasias da Mama , Software , Humanos , Feminino , Algoritmos , Idioma
14.
Calcif Tissue Int ; 113(6): 581-590, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37650930

RESUMO

In this study, we aimed to evaluate the association of innate and adaptive immune cell subsets in peripheral blood mononuclear cells (PBMCs) with hip fracture. To conduct this study, we used data from the Cardiovascular Health Study (CHS), a U.S. multicenter observational cohort of community-dwelling men and women aged ≥ 65 years. Twenty-five immune cell phenotypes were measured by flow cytometry from cryopreserved PBMCs of CHS participants collected in 1998-1999. The natural killer (NK), γδ T, T helper 17 (Th17), and differentiated/senescent CD4+CD28- T cell subsets were pre-specified as primary subsets of interest. Hip fracture incidence was assessed prospectively by review of hospitalization records. Multivariable Cox hazard models evaluated associations of immune cell phenotypes with incident hip fracture in sex-stratified and combined analyses. Among 1928 persons, 259 hip fractures occurred over a median 9.7 years of follow-up. In women, NK cells were inversely associated with hip fracture [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.60-0.99 per one standard deviation higher value] and Th17 cells were positively associated with hip fracture [HR 1.18, 95% CI 1.01-1.39]. In men, γδ T cells were inversely associated with hip fracture [HR 0.60, 95% CI 0.37-0.98]. None of the measured immune cell phenotypes were significantly associated with hip fracture incidence in combined analyses. In this large prospective cohort of older adults, potentially important sex differences in the associations of immune cell phenotypes and hip fracture were identified. However, immune cell phenotypes had no association with hip fracture in analyses combining men and women.


Assuntos
Fraturas do Quadril , Leucócitos Mononucleares , Idoso , Feminino , Humanos , Masculino , Fraturas do Quadril/epidemiologia , Incidência , Estudos Prospectivos , Fatores de Risco
15.
J Dairy Res ; : 1-4, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36799037

RESUMO

Health-conscious consumers are increasingly paying attention to healthy diets and focusing on natural bioactive compounds in foods and their effects on mental health. This opens new opportunities for the study of artisanal cheeses as biofunctional foods. In the work described in this Research Communication, the gamma-aminobutyric acid (GABA) content of seven different Portuguese cheeses produced from unpasteurized cow, sheep, and goat milk and granted with protected designation of origin (PDO) status was analysed. The PDO cheeses made from cow milk analysed in this study were São Jorge (3, 4, 7, 12 and 24 months of maturation) and Pico cheeses. PDO cheeses made from sheep milk were Serra da Estrela, Serpa, Nisa and Azeitão. Cheeses made from sheep and goat milk included Beira Baixa yellow cheese. The GABA content in the Azorean PDO cheeses (made from cow milk) ranged from 1.23 to 2.64 g/kg of cheese. Higher variations in GABA content were observed in cheeses made from sheep and goat milk (0.73-2.31 g/kg). This study provides information on the GABA content in different Portuguese PDO cheeses and shows that hard or semi-hard ripened cheeses are a suitable matrix for GABA production by lactic acid bacteria.

16.
Molecules ; 28(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38067603

RESUMO

Nanoencapsulation of native potato bioactive compounds by spray-drying improves their stability and bioavailability. The joint effect of the inlet temperature and the ratio of the encapsulant (quinoa starch/gum arabic) on the properties of the nanocapsules is unknown. The purpose of this study was to determine the best conditions for the nanoencapsulation of these compounds. The effects of two inlet temperatures (96 and 116 °C) and two ratios of the encapsulant (15 and 25% w/v) were evaluated using a factorial design during the spray-drying of native potato phenolic extracts. During the study, measurements of phenolic compounds, flavonoids, anthocyanins, antioxidant capacity, and various physical and structural properties were carried out. Higher inlet temperatures increased bioactive compounds and antioxidant capacity. However, a higher concentration of the encapsulant caused the dilution of polyphenols and anthocyanins. Instrumental analyses confirmed the effective encapsulation of the nuclei in the wall materials. Both factors, inlet temperature, and the encapsulant ratio, reduced the nanocapsules' humidity and water activity. Finally, the ideal conditions for the nanoencapsulation of native potato bioactive compounds were determined to be an inlet temperature of 116 °C and an encapsulant ratio of 15% w/v. The nanocapsules obtained show potential for application in the food industry.


Assuntos
Chenopodium quinoa , Nanocápsulas , Solanum tuberosum , Amido , Antioxidantes/química , Goma Arábica/química , Antocianinas/análise , Temperatura , Baías , Fenóis/análise
17.
Molecules ; 28(13)2023 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-37446623

RESUMO

Native potato clones grown in Peru contain bioactive compounds beneficial to human health. This study aimed to optimize the spray-drying nanoencapsulation of native potato phenolic extracts utilizing a central composite design and response surface methodology, obtaining the optimal treatment to an inlet temperature of 120 °C and an airflow of 141 L/h in the nano spray dryer B-90, which allowed maximizing the yield of encapsulation, antioxidant capacity (DPPH), encapsulation efficiency (EE), total phenolic compounds, and total flavonoids; on the other hand, it allowed minimizing hygroscopicity, water activity (Aw), and moisture. Instrumental characterization of the nanocapsules was also carried out, observing a gain in lightness, reddening of the color, and spherical nanoparticles of heterogeneous size (133.09-165.13 nm) with a negative ζ potential. Thermal, infrared, and morphological analyses confirmed the encapsulation of the core in the wall materials. Furthermore, an in vitro release study of phenolic compounds in an aqueous solution achieved a maximum value of 9.86 mg GAE/g after 12 h. Finally, the obtained nanocapsules could be used in the food and pharmaceutical industry.


Assuntos
Nanocápsulas , Nanopartículas , Solanum tuberosum , Humanos , Secagem por Atomização , Antioxidantes/química , Nanopartículas/química , Água/química
18.
J Chem Inf Model ; 62(2): 340-349, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35018781

RESUMO

The conformational behavior of a small molecule free in solution is important to understand the free energy of binding to its target. This could be of special interest for proteolysis-targeting chimeras (PROTACs) due to their often flexible and lengthy linkers and the need to induce a ternary complex. Here, we report on the molecular dynamics (MD) simulations of two PROTACs, MZ1 and dBET6, revealing different linker conformational behaviors. The simulation of MZ1 in dimethyl sulfoxide (DMSO) agrees well with the nuclear magnetic resonance study, providing strong support for the relevance of our simulations. To further understand the role of linker plasticity in the formation of a ternary complex, the dissociation of the complex von Hippel-Lindau-MZ1-BRD4 is investigated in detail by steered simulations and is shown to follow a two-step pathway. Interestingly, both MZ1 and dBET6 display in water, a tendency toward an intramolecular lipophilic interaction between the two warheads. The hydrophobic contact of the two warheads would prevent them from binding to their respective proteins and might have an effect on the efficacy of induced cellular protein degradation. However, conformations featuring this hydrophobic contact of the two warheads are calculated to be marginally more favorable.


Assuntos
Proteínas Nucleares , Ubiquitina-Proteína Ligases , Proteínas Nucleares/metabolismo , Proteólise , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismo
19.
Environ Res ; 206: 112598, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-34953887

RESUMO

The toxicity of microplastic particles (MPs) on aquatic environments has been widely reported; however, their effects on protists are still contradictory. For example, it is unclear if cell size and cell wall have a role in shaping the response of flagellates to MPs. In this study, seven marine flagellated microalgae (six Dinoflagellates and one Raphidophyceae) were incubated with 10 mg L-1 MPs (polystyrene plastic micro-spheres, 1 µm diameter) to address the above question by measuring different response variables, i.e., growth, optimal photochemical efficiency (Fv/Fm), chlorophyll-a (Chl-a) content, superoxide dismutase (SOD) activity, and cell morphology. The effect of MPs on growth and Fv/Fm showed species-specificity effects. Maximum and minimum MPs-induced inhibitions were detected in Karenia mikimotoi (76.43%) and Akashiwo sanguinea (10.16%), respectively, while the rest of the species showed intermediate responses. The presence of MPs was associated with an average reduction of Chl-a content in most cases and with a higher superoxide dismutase activity in all cases. Seven species were classified into two groups by the variation of Chl-a under MPs treatment. One group (Prorocentrum minimum and Karenia mikimotoi) showed increased Chl-a, while the other (P. donghaiense, P. micans, Alexandrium tamarense, Akashiwo sanguinea, Heterosigma akashiwo) showed decreased Chl-a content. The MPs-induced growth inhibition was negatively correlated with cell size in the latter group. SEM images further indicated that MPs-induced malformation in the smaller cells (e.g., P. donghaiense and K. mikimotoi) was more severe than the bigger cells (e.g., A. sanguinea and P. micans), probably due to a relatively higher ratio of the cell surface to cell volume in the former. These results implicate that the effect of MPs on marine flagellated microalgae was related to the cell size among most species but not cell wall. Thus plastic pollution may have size-dependent effects on phytoplankton in future scenarios.


Assuntos
Microalgas , Poluentes Químicos da Água , Parede Celular/química , Dinoflagellida , Microplásticos , Plásticos/toxicidade , Poluentes Químicos da Água/análise
20.
Arch Insect Biochem Physiol ; 110(2): e21881, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35263470

RESUMO

Rhynchophorus palmarum Linnaeus is an agricultural pest that affects various palm crops, including coconut (Cocos nucifera) plantations which are prominent in the economy of Northeastern Brazil. Characterization of the intestinal microbiota of R. palmarum, as well as elucidation of aspects related to the biochemistry and physiology of the insect's digestion, is essential for intervention in specific metabolic processes as a form of pest control. Thus, this study aimed to characterize the intestinal microbiota of R. palmarum and investigate its ability to degrade cellulosic substrates, to explore new biological control measures. Intestinal dissection of eight adult R. palmarum insects was performed in a laminar flow chamber, and the intestines were homogenized in sterile phosphate-buffered saline solution. Subsequently, serial dilution aliquots of these solutions were spread on nutritive agar plates for the isolation of bacteria and fungi. The microorganisms were identified by matrix-assisted laser desorption/ionization with a time-of-flight mass spectrometry and evaluated for their ability to degrade cellulose. Fourteen bacterial genera (Acinetobacter, Alcaligenes, Arthrobacter, Bacillus, Citrobacter, Enterococcus, Kerstersia, Lactococcus, Micrococcus, Proteus, Providencia, Pseudomonas, Serratia, and Staphylococcus) and two fungal genera (Candida and Saccharomyces)-assigned to the Firmicutes, Actinobacteria, Proteobacteria, and Ascomycota phyla-were identified. The cellulolytic activity was exhibited by six bacterial and one fungal species; of these, Bacillus cereus demonstrated the highest enzyme synthesis (enzymatic index = 4.6). This is the first study characterizing the R. palmarum intestinal microbiota, opening new perspectives for the development of strategies for the biological control of this insect.


Assuntos
Besouros , Microbioma Gastrointestinal , Gorgulhos , Animais , Brasil , Candida
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