Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
1.
J Funct Biomater ; 14(11)2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37998114

RESUMO

Periodontitis is a destructive inflammatory disease characterized by microbial infection that damages the tissues supporting the tooth (alveolar bone, gingiva, periodontal ligament, and cementum), ultimately resulting in the loss of teeth. The ultimate goal of periodontal therapy is to achieve the regeneration of all of the periodontal tissues. Thus, tissue engineering approaches have been evolving from simple membranes or grafts to more complex constructs. Hydrogels are highly hydrophilic polymeric networks with the ability to simulate the natural microenvironment of cells. In particular, hydrogels offer several advantages when compared to other forms of scaffolds, such as tissue mimicry and sustained drug delivery. Moreover, hydrogels can maintain a moist environment similar to the oral cavity. Hydrogels allow for precise placement and retention of regenerative materials at the defect site, minimizing the potential for off-target effects and ensuring that the treatment is focused on the specific defect site. As a mechanism of action, the sustained release of drugs presented by hydrogels allows for control of the disease by reducing the inflammation and attracting host cells to the defect site. Several therapeutic agents, such as antibiotics, anti-inflammatory and osteogenic drugs, have been loaded into hydrogels, presenting effective benefits in periodontal health and allowing for sustained drug release. This review discusses the causes and consequences of periodontal disease, as well as the advantages and limitations of current treatments applied in clinics. The main components of hydrogels for periodontal regeneration are discussed focusing on their different characteristics, outcomes, and strategies for drug delivery. Novel methods for the fabrication of hydrogels are highlighted, and clinical studies regarding the periodontal applications of hydrogels are reviewed. Finally, limitations in current research are discussed, and potential future directions are proposed.

2.
Leiria; s.n; 27 Jul 2023.
Tese em Português | BDENF - Enfermagem | ID: biblio-1526170

RESUMO

O relatório apresenta-se como um processo de construção de saberes profissionais baseados na autorreflexão e análise, constituindo-se como um caminho para o desenvolvimento das competências do enfermeiro especialista e do enfermeiro especialista em saúde comunitária e de saúde pública. Numa abordagem inicial, no primeiro campo de estágio, procedeu-se à elaboração do diagnóstico de saúde da comunidade, emergindo como área problemática a Diabetes Mellitus. Partindo de uma necessidade já identificada pelo Agrupamento de Centros de Saúde do Pinhal Litoral, a inexistência de formação dos enfermeiros de saúde escolar, integrou-se o Projeto DARE+ para colmatar essas necessidades. A Diabetes Mellitus tipo 1 é uma doença metabólica e crónica que pode afetar pessoas de qualquer idade, a mesma desenvolve-se mais em crianças e jovens, tornando-se uma das doenças mais prevalentes em contexto escolar. A permanência da criança e jovem na escola abrange um período alargado do dia, neste sentido as recomendações internacionais orientam para que seja garantida a gestão adequada da doença neste contexto. O Projeto de Intervenção Comunitária, Projeto DARE+, segundo a metodologia do Planeamento em Saúde, teve como objetivo melhorar os conhecimentos dos Enfermeiros de saúde escolar através da formação avançada. Recorreu-se ao referencial teórico de enfermagem Modelo Sistémico de Betty Neuman para a tomada de decisão em enfermagem, que nos conduziu à intervenção comunitária. Desenvolveu-se uma Revisão Integrativa da Literatura com a seguinte questão de investigação: Quais são as intervenções de enfermagem dirigidas a enfermeiros de saúde escolar na área da diabete Mellitus tipo 1? Nas evidências obtidas identificou-se a importância da formação avançada aos respetivos enfermeiros. A avaliação da intervenção realizada teve lugar no segundo campo de estágio, que nos permitiu concluir que a formação reforçou as linhas de defesa dos enfermeiros de saúde escolar criando barreira aos stressores, isto é, à falta de conhecimento. Os resultados apontam para um aumento de conhecimentos médio de 86,6%, demonstrando o impacte positivo na formação deste grupo profissional. É essencial continuar a intervir com os Enfermeiros de saúde escolar com vista à uniformização dos conhecimentos e intervenções adequadas às crianças e jovens com as necessidades identificadas.


The report presents itself as a process of building professional knowledge based on self-reflection and analysis, constituting a path for developing the skills of specialist nurses and specialist nurses in community health and public health. In an initial approach, in the first internship field, a community health diagnosis was drawn up, with Diabetes Mellitus emerging as a problem area. Based on a need already identified by the Pinhal Litoral Health Center Group, the lack of training for school health nurses, the DARE+ Project was integrated to meet these needs. Type 1 Diabetes Mellitus is a metabolic and chronic disease that can affect people of any age, it develops more in children and young people, becoming one of the most prevalent diseases in school contexts. The stay of children and young people at school covers an extended period of the day, in this sense, international recommendations provide guidance to ensure adequate management of the disease in this context. The Community Intervention Project, Project DARE+, according to the Health Planning methodology, aimed to improve the knowledge of school health nurses through advanced training. Betty Neuman's theoretical nursing framework was used for decision-making in nursing, which led us to community intervention. An Integrative Literature Review was developed with the following research question: What are the nursing interventions aimed at school health nurses in the area of type 1 diabetes mellitus? The evidence obtained identified the importance of advanced training for respective nurses. The evaluation of the intervention carried out took place in the second internship field, which allowed us to conclude that the training reinforced the lines of defense of school health nurses by creating a barrier to stressors, that is, the lack of knowledge. The results point to an average increase in knowledge of 86.6%, demonstrating the positive impact on the training of this professional group. It is essential to continue to intervene with school health nurses with a view to standardizing knowledge and appropriate interventions for children and young people with identified needs.


Assuntos
Criança , Adolescente , Enfermagem Pediátrica , Serviços de Enfermagem Escolar , Papel do Profissional de Enfermagem , Diabetes Mellitus Tipo 1 , Cuidados de Enfermagem
3.
Int J Mol Sci ; 24(10)2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37240307

RESUMO

Transfer RNA fragments (tRFs) have gene silencing effects similarly to miRNAs, can be sorted into extracellular vesicles (EVs) and are emerging as potential circulating biomarkers for cancer diagnoses. We aimed at analyzing the expression of tRFs in gastric cancer (GC) and understanding their potential as biomarkers. We explored miRNA datasets from gastric tumors and normal adjacent tissues (NATs) from TCGA repository, as well as proprietary 3D-cultured GC cell lines and corresponding EVs, in order to identify differentially represented tRFs using MINTmap and R/Bioconductor packages. Selected tRFs were validated in patient-derived EVs. We found 613 Differentially Expressed (DE)-tRFs in the TCGA dataset, of which 19 were concomitantly upregulated in TCGA gastric tumors and present in 3D cells and EVs, but barely expressed in NATs. Moreover, 20 tRFs were expressed in 3D cells and EVs and downregulated in TCGA gastric tumors. Of these 39 DE-tRFs, 9 tRFs were also detected in patient-derived EVs. Interestingly, the targets of these 9 tRFs affect neutrophil activation and degranulation, cadherin binding, focal adhesion and the cell-substrate junction, highlighting these pathways as major targets of EV-mediated crosstalk with the tumor microenvironment. Furthermore, as they are present in four distinct GC datasets and can be detected even in low quality patient-derived EV samples, they hold promise as GC biomarkers. By repurposing already available NGS data, we could identify and cross-validate a set of tRFs holding potential as GC diagnosis biomarkers.


Assuntos
Vesículas Extracelulares , MicroRNAs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , RNA de Transferência/genética , Microambiente Tumoral
4.
Nanomaterials (Basel) ; 13(8)2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37110894

RESUMO

Periodontitis is an inflammatory infection caused by bacterial plaque accumulation that affects the periodontal tissues. Current treatments lack bioactive signals to induce tissue repair and coordinated regeneration of the periodontium, thus alternative strategies are needed to improve clinical outcomes. Electrospun nanofibers present high porosity and surface area and are able to mimic the natural extracellular matrix, which modulates cell attachment, migration, proliferation, and differentiation. Recently, several electrospun nanofibrous membranes have been fabricated with antibacterial, anti-inflammatory, and osteogenic properties, showing promising results for periodontal regeneration. Thus, this review aims to provide an overview of the current state of the art of these nanofibrous scaffolds in periodontal regeneration strategies. First, we describe the periodontal tissues and periodontitis, as well as the currently available treatments. Next, periodontal tissue engineering (TE) strategies, as promising alternatives to the current treatments, are addressed. Electrospinning is briefly explained, the characteristics of electrospun nanofibrous scaffolds are highlighted, and a detailed overview of electrospun nanofibers applied to periodontal TE is provided. Finally, current limitations and possible future developments of electrospun nanofibrous scaffolds for periodontitis treatment are also discussed.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36759058

RESUMO

INTRODUCTION: With the widespread introduction of conjugate meningococcal and pneumococcal vaccines, the prevalence and etiology of invasive bacterial infections have changed. We aimed to review all cases of bacteremia in a level II pediatric department over a ten-year period in the post-pneumococcal conjugate vaccine era. METHODS: We reviewed all positive blood cultures (BC) obtained in our department between 2007 and 2016. Results were classified as contaminants, potential pathogens or confirmed pathogens, based on species, number of positive BC in the episode and the patients' medical history. Demographic and clinical data were collected for patients with identified pathogens. RESULTS: A total of 638 positive BC were identified (6.6% of total BC); 120 (1.2%) were considered to represent true bacteremia. The most frequently identified microorganism was Streptococcus pneumoniae (29.2%), with a decrease in the number of cases between 2008 and 2015. Staphylococcus aureus was the second most common organism (19.2%) being 21.7% of these methicillin-resistant. Escherichia coli was the most common isolate in children aged less than three months. CONCLUSION: We found a rate of true bacteremia in children similar to recent studies. Although Streptococcus pneumoniae remains the most common microorganism, its prevalence may be declining. Monitoring microbiological data in children has implications in practice, particularly in local antibiotic prescription.


Assuntos
Bacteriemia , Infecções Pneumocócicas , Humanos , Lactente , Antibacterianos , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas , Streptococcus pneumoniae , Pré-Escolar
6.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 41(2): 85-91, Feb. 2023. graf, tab
Artigo em Inglês | IBECS | ID: ibc-215776

RESUMO

Introduction: With the widespread introduction of conjugate meningococcal and pneumococcal vaccines, the prevalence and etiology of invasive bacterial infections have changed. We aimed to review all cases of bacteremia in a level II pediatric department over a ten-year period in the post-pneumococcal conjugate vaccine era. Methods: We reviewed all positive blood cultures (BC) obtained in our department between 2007 and 2016. Results were classified as contaminants, potential pathogens or confirmed pathogens, based on species, number of positive BC in the episode and the patients’ medical history. Demographic and clinical data were collected for patients with identified pathogens. Results: A total of 638 positive BC were identified (6.6% of total BC); 120 (1.2%) were considered to represent true bacteremia. The most frequently identified microorganism was Streptococcus pneumoniae (29.2%), with a decrease in the number of cases between 2008 and 2015. Staphylococcus aureus was the second most common organism (19.2%) being 21.7% of these methicillin-resistant. Escherichia coli was the most common isolate in children aged less than three months. Conclusion: We found a rate of true bacteremia in children similar to recent studies. Although Streptococcus pneumoniae remains the most common microorganism, its prevalence may be declining. Monitoring microbiological data in children has implications in practice, particularly in local antibiotic prescription.(AU)


Introducción: Con la introducción generalizada de las vacunas conjugadas meningocócicas y neumocócicas, la prevalencia y la etiología de las infecciones bacterianas invasivas han cambiado. Nuestro objetivo fue revisar todos los casos de bacteriemia en un departamento de pediatría de nivel II durante un período de 10 años en la era de la vacuna conjugada posneumocócica. Métodos: Revisamos todos los hemocultivos (HC) positivos obtenidos en nuestro departamento entre 2007 y 2016. Los resultados se clasificaron como contaminantes, patógenos potenciales o patógenos confirmados, según la especie, el número de HC positivos en el episodio y la historia clínica de los pacientes. Se recopilaron datos demográficos y clínicos de pacientes con patógenos identificados. Resultados: Se identificaron un total de 638 HC positivos (6,6% del total de HC); se consideró que 120 (1,2%) representaban una bacteriemia verdadera. El microorganismo identificado con mayor frecuencia fue Streptococcus pneumoniae (29,2%), con una disminución en el número de casos entre 2008 y 2015. Staphylococcus aureus fue el segundo aislado más común (19,2%); El 21,7% eran resistentes a la meticilina. Escherichia coli fue el aislado más común en niños menores de 3 meses. Conclusión: Encontramos una tasa de bacteriemia verdadera similar a la de estudios recientes. Aunque el Streptococcus pneumoniae sigue siendo el microorganismo más común, su prevalencia puede estar disminuyendo. El seguimiento de datos microbiológicos como este tiene implicaciones en la práctica, especialmente en la prescripción local de antibióticos.(AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Vacinas Meningocócicas , Vacinas Pneumocócicas , Bacteriemia/epidemiologia , Hemocultura , Sepse , Pediatria , Microbiologia , Doenças Transmissíveis
7.
Biotechnol J ; 18(1): e2200332, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36330557

RESUMO

A major challenge in the transition to continuous biomanufacturing is the lack of process analytical technology (PAT) tools which are able to collect real-time information on the process and elicit a response to facilitate control. One of the critical quality attributes (CQAs) of interest during monoclonal antibodies production is aggregate formation. The development of a real-time PAT tool to monitor aggregate formation is then crucial to have immediate feedback and process control. Miniaturized sensors placed after each unit operation can be a powerful solution to speed up an analytical measurement due to their characteristic short reaction time. In this work, a micromixer structure capable of mixing two streams is presented, to be employed in the detection of mAb aggregates using fluorescent dyes. Computational fluid dynamics (CFD) simulations were used to compare the mixing performance of a series of the proposed designs. A final design of a zigzag microchannel with 45° angle was reached and this structure was subsequently fabricated and experimentally validated with colour dyes and, later, with a FITC-IgG molecule. The designed zigzag micromixer presents a mixing index of around 90%, obtained in less than 30 seconds. Therefore, a micromixer channel capable of a fast and efficient mixing is hereby demonstrated, to be used as a real-time PAT tool for a fluorescence based detection of protein aggregation.


Assuntos
Técnicas Analíticas Microfluídicas , Microfluídica , Corantes Fluorescentes , Anticorpos Monoclonais
8.
Cureus ; 14(9): e29525, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36312684

RESUMO

Lisfranc injury is extremely rare in the pediatric population and little evidence exists to guide the treatment at this age. We present a clinical case of a rare Lisfranc fracture-dislocation at pediatric age. An 11-year-old male was admitted to the emergency department, in October 2020, after a motorcycle incident. He was diagnosed with a Lisfranc fracture-dislocation of the right foot: Myerson type B2. Fourteen days after the injury, he underwent surgical treatment with open reduction and internal fixation with 3.5 mm solid fully threaded screws. At 18 months postoperative, the patient was asymptomatic, didn't present any limitations, presented an American Orthopedic Foot and Ankle Score (AOFAS) midfoot score of 93%, and excellent results of the 12-Item Short Form Survey (SF-12) - PCS-12 (Physical Score): 52.52277 and MCS-12 (Mental Score): 62.12820. The foot maintained a good configuration without significant malalignment, however, a screw breakage occurred before the implant removal, and a premature physeal arrest developed on the base of the first metatarsal bone. Clinical and radiographic evaluation of Lisfranc injuries may be challenging in the pediatric population. Regarding the treatment, anatomical alignment is mandatory, and good or excellent outcomes have been achieved with anatomical reduction and internal fixation. We recommend early implant removal to avoid screw breakage and avoid the use of screws in the first metatarsal physis, due to the risk of premature physeal arrest.

9.
Biology (Basel) ; 11(7)2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-36101425

RESUMO

Transitions between epithelial and mesenchymal cellular states (EMT/MET) contribute to cancer progression. We hypothesize that EMT followed by MET promotes cell population heterogeneity, favouring tumour growth. We developed an EMT model by on and off exposure of epithelial EpH4 cells (E-cells) to TGFß1 that mimics phenotypic EMT (M-cells) and MET. We aimed at understanding whether phenotypic MET is accompanied by molecular and functional reversion back to epithelia by using RNA sequencing, immunofluorescence (IF), proliferation, wound healing, focus formation and mamosphere formation assays as well as cell xenografts in nude mice. Phenotypic reverted epithelial cells (RE-cells) obtained after MET induction presented epithelial morphologies and proliferation rates resembling E cells. However, the RE transcriptomic profile and IF staining of epithelial and mesenchymal markers revealed a uniquely heterogeneous mixture of cell subpopulations with a high self-renewal ability. RE cell heterogeneity was stably maintained for long periods after TGFß1 removal both in vitro and in large tumours derived from the nude mice. Overall, we show that phenotypic reverted epithelial cells (RE cells) do not return to the molecular and functional epithelial state and present mesenchymal features related to aggressiveness and cellular heterogeneity that favour tumour growth in vivo. This work strengthens epithelial cell reprogramming and cellular heterogeneity fostered by inflammatory cues as a tumour growth-promoting factor in vivo.

11.
Front Mol Biosci ; 9: 809985, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35586191

RESUMO

Serine tRNAs (tRNASer) are frequently overexpressed in tumors and associated with poor prognosis and increased risk of recurrence in breast cancer. Impairment of tRNA biogenesis and abundance also impacts proteome homeostasis, and activates protein quality control systems. Herein, we aimed at testing whether increasing tRNASer abundance could foster tumor establishment through activation of the UPR. In order to do so, firstly we confirmed that the expression of tRNA-Ser-AGA-2-1 [hereafter tRNASer(AGA)] was upregulated by 1.79-fold in Stage I NSCLC tumors when compared to normal adjacent tissue. To study the impact of tRNASer(AGA) in early stage tumorigenesis, we induced its upregulation in a non-tumoral bronchial cell line, BEAS-2B. Upregulation of this tRNA increased cellular proliferation and protein synthesis rate, driven by eIF2α dephosphorylation and ATF4 activation downstream of PERK signaling. Futhermore, tRNASer(AGA) enhanced transformation potential in vitro, and promoted the establishment of slow growing tumors with aggressive features in nude mice. Our work highlights the importance of studying tRNA deregulation on early stage tumorigenesis, as they may be potential malignancy and aggressiveness biomarkers.

12.
Antioxidants (Basel) ; 10(7)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34356321

RESUMO

The adult mammalian brain is capable of generating new neurons from existing neural stem cells (NSCs) in a process called adult neurogenesis. This process, which is critical for sustaining cognition and mental health in the mature brain, can be severely hampered with ageing and different neurological disorders. Recently, it is believed that the beneficial effects of NSCs in the injured brain relies not only on their potential to differentiate and integrate into the preexisting network, but also on their secreted molecules. In fact, further insight into adult NSC function is being gained, pointing to these cells as powerful endogenous "factories" that produce and secrete a large range of bioactive molecules with therapeutic properties. Beyond anti-inflammatory, neurogenic and neurotrophic effects, NSC-derived secretome has antioxidant proprieties that prevent mitochondrial dysfunction and rescue recipient cells from oxidative damage. This is particularly important in neurodegenerative contexts, where oxidative stress and mitochondrial dysfunction play a significant role. In this review, we discuss the current knowledge and the therapeutic opportunities of NSC secretome for neurodegenerative diseases with a particular focus on mitochondria and its oxidative state.

13.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34275687

RESUMO

INTRODUCTION: With the widespread introduction of conjugate meningococcal and pneumococcal vaccines, the prevalence and etiology of invasive bacterial infections have changed. We aimed to review all cases of bacteremia in a level II pediatric department over a ten-year period in the post-pneumococcal conjugate vaccine era. METHODS: We reviewed all positive blood cultures (BC) obtained in our department between 2007 and 2016. Results were classified as contaminants, potential pathogens or confirmed pathogens, based on species, number of positive BC in the episode and the patients' medical history. Demographic and clinical data were collected for patients with identified pathogens. RESULTS: A total of 638 positive BC were identified (6.6% of total BC); 120 (1.2%) were considered to represent true bacteremia. The most frequently identified microorganism was Streptococcus pneumoniae (29.2%), with a decrease in the number of cases between 2008 and 2015. Staphylococcus aureus was the second most common organism (19.2%) being 21.7% of these methicillin-resistant. Escherichia coli was the most common isolate in children aged less than three months. CONCLUSION: We found a rate of true bacteremia in children similar to recent studies. Although Streptococcus pneumoniae remains the most common microorganism, its prevalence may be declining. Monitoring microbiological data in children has implications in practice, particularly in local antibiotic prescription.

14.
BMJ Case Rep ; 14(6)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193450

RESUMO

A 3-month-old, full term female infant, adequate for gestational age, and exclusively breastfed, was admitted with a 10 day history of generalised scaling erythematous dermatitis, affecting the face (perinasal, nasolabial folds and periauricular), acral and intertriginous areas, with irritability and failure to thrive. Her mother had been treated with isoniazid since the third trimester because of family contact with tuberculosis. Based on a diagnosis of suspected impetiginised eczema, the infant was treated with flucloxacillin and prednisolone, and maternal isoniazid was suspended, with no improvement. Investigations found low serum zinc levels in the infant (33 µg/dL; normal range (NR) >60 µg/dL), normal plasma zinc levels in the mother (111.3 µg/dL; NR 68-120 µg/dL) and lower than the normal range of zinc levels in breast milk (270µg/L; NR 1000-2500 µg/L), suggesting acrodermatitis caused by zinc deficiency. Oral zinc supplementation (3 mg/kg/day) was started with a marked improvement in skin lesions, as well as good weight gain. At the age of 6 months, after food diversification, supplementation was suspended, without any recurrence of symptoms.


Assuntos
Acrodermatite , Desnutrição , Acrodermatite/diagnóstico , Acrodermatite/tratamento farmacológico , Acrodermatite/etiologia , Aleitamento Materno , Feminino , Humanos , Lactente , Leite Humano/química , Zinco
15.
BMJ Case Rep ; 13(9)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878858

RESUMO

Vaginal bleeding can occur shortly after delivery in 3%-5% of newborns as a consequence of placental hormone withdrawal . Although usually benign, its differential diagnosis includes central precocious puberty, tumours and other pathological conditions. A girl born at 26 weeks of gestation presented with five episodes of vaginal bleeding, each lasting less than a week, initiated at 4 months of age. Luteinising hormone and oestradiol levels were in the pubertal range. Later, she exhibited breast development, with no other pubertal signs. An ultrasonography test revealed an impregnated endometrium and a right ovarian cyst with 43 mm of diameter. A cranioencephalic MRI was unremarkable. Clinicians adopted expectant management and there was clinical, hormonal and radiological resolution in 3 months. The spontaneous resolution suggested mini-puberty of infancy. This is usually an asymptomatic condition, but to date, four cases of an exacerbated form in extremepremature infants have been reported. Long-term follow-up data are missing.A girl born at 26 weeks of gestation presented with five episodes of vaginal bleeding, each lasting less than a week, initiated at 4 months of age. Luteinising hormone and oestradiol levels were in the pubertal range. Later, she exhibited breast development, with no other pubertal signs. An ultrasonography test revealed an impregnated endometrium and a right ovarian cyst with 43 mm of diameter. A cranioencephalic MRI was unremarkable. Clinicians adopted expectant management and there was clinical, hormonal and radiological resolution in 3 months. The spontaneous resolution suggested mini-puberty of infancy. This is usually an asymptomatic condition, but to date, four cases of an exacerbated form in extremepremature infants have been reported. Long-term follow-up data are missing.


Assuntos
Lactente Extremamente Prematuro/fisiologia , Cistos Ovarianos/diagnóstico , Puberdade/fisiologia , Hemorragia Uterina/diagnóstico , Diagnóstico Diferencial , Endométrio/diagnóstico por imagem , Endométrio/fisiopatologia , Estradiol/sangue , Feminino , Humanos , Lactente , Lactente Extremamente Prematuro/sangue , Hormônio Luteinizante/sangue , Cistos Ovarianos/sangue , Cistos Ovarianos/fisiopatologia , Puberdade/sangue , Puberdade Precoce/diagnóstico , Remissão Espontânea , Hemorragia Uterina/sangue , Hemorragia Uterina/fisiopatologia
16.
RNA Biol ; 17(1): 135-149, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570039

RESUMO

Deregulation of tRNAs, aminoacyl-tRNA synthetases (aaRS) or tRNA modifying enzymes, increase the level of protein synthesis errors (PSE) and are associated with several diseases, but the cause-effect mechanisms of these pathologies remain elusive. To clarify the role of PSE in human biology, we have engineered a HEK293 cell line to overexpress a wild type (Wt) tRNASer and two tRNASer mutants that misincorporate serine at non-cognate codon sites. Then, we followed long-term adaptation to PSE of such recombinant cells by analysing cell viability, protein synthesis rate and activation of protein quality control mechanisms (PQC). Engineered cells showed higher level of misfolded and aggregated proteins; activated the ubiquitin-proteasome system (UPS) and the unfolded protein response (UPR), indicative of proteotoxic stress. Adaptation to PSE involved increased protein turnover, UPR up-regulation and altered protein synthesis rate. Gene expression analysis showed that engineered cells presented recurrent alterations in the endoplasmic reticulum, cell adhesion and calcium homeostasis. Herein, we unveil new phenotypic consequences of protein synthesis errors in human cells and identify the protein quality control processes that are necessary for long-term adaptation to PSE and proteotoxic stress. Our data provide important insight on how chronic proteotoxic stress may cause disease and highlight potential biological pathways that support the association of PSE with disease.


Assuntos
Adaptação Biológica , Regulação da Expressão Gênica , Mutação , Biossíntese de Proteínas , Biologia Computacional/métodos , Ontologia Genética , Células HEK293 , Humanos , Chaperonas Moleculares/metabolismo , Complexo de Endopeptidases do Proteassoma , Processamento de Proteína Pós-Traducional , RNA de Transferência/genética , Ubiquitina/metabolismo , Resposta a Proteínas não Dobradas
17.
Trends Mol Med ; 25(10): 853-865, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31248782

RESUMO

The expression of transfer RNAs (tRNAs) is deregulated in cancer cells but the mechanisms and functional meaning of such deregulation are poorly understood. The proteome of cancer cells is not fully encoded by their transcriptome, however, the contribution of mRNA translation to such diversity remains to be elucidated. We review data supporting the hypothesis that tRNA expression deregulation and translational error rate is an important contributor to proteome diversity and cell population heterogeneity, genome instability, and drug resistance in tumors. This hypothesis is aligned with recent data in various model organisms, showing unanticipated adaptive roles of translational errors (adaptive mistranslation), expression control of specific gene subsets by tRNAs, and proteome diversification by elevation of translational error rates in tumors.


Assuntos
Neoplasias/metabolismo , RNA de Transferência/metabolismo , Animais , Humanos , Neoplasias/genética , Biossíntese de Proteínas , Proteoma/genética , Proteoma/metabolismo , Estabilidade de RNA , RNA de Transferência/química , RNA de Transferência/genética
18.
19.
Appetite ; 134: 34-39, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30557589

RESUMO

Body compassion is a fresh construct that incorporates two multidimensional concepts: body image and self-compassion. Although self-compassion has revealed a protective role against body image and eating-related problems (e.g., binge eating), the study of this specific compassionate competence focused on body image is still largely unexplored. The present study aimed to test two moderation models which hypothesized that body compassion moderates the impacts of (i) the cumulative number and (ii) negative appraisal of major life events on binge eating behaviours, in a sample of 458 women from the Portuguese general population. Results showed that body compassion was negatively associated with major life events and binge eating. Moderation analysis results demonstrated the moderator effect of body compassion on the relationship between major life events (both cumulative number and negative appraisal) and binge eating, accounting for 34% and 33% of the variance of binge eating, respectively. The moderator effect of body compassion was confirmed to low to medium levels of body compassion and, overall, results seem to suggest that, for the same levels of major life events (in number or negative appraisal), women who present higher body compassion present less binge eating symptoms. Although these data are preliminary and need support from a longitudinal design research, current findings appear to be promising by suggesting the relevance of promoting body compassion in prevention and treatment programs for disordered eating attitudes and behaviours.


Assuntos
Imagem Corporal , Bulimia/psicologia , Empatia , Acontecimentos que Mudam a Vida , Adulto , Feminino , Humanos , Portugal , Autoimagem , Adulto Jovem
20.
Int J Mol Sci ; 19(12)2018 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-30477220

RESUMO

Transfer RNAs (tRNAs) are key players of protein synthesis, as they decode the genetic information organized in mRNA codons, translating them into the code of 20 amino acids. To be fully active, tRNAs undergo extensive post-transcriptional modifications, catalyzed by different tRNA-modifying enzymes. Lack of these modifications increases the level of missense errors and affects codon decoding rate, contributing to protein aggregation with deleterious consequences to the cell. Recent works show that tRNA hypomodification and tRNA-modifying-enzyme deregulation occur in several diseases where proteostasis is affected, namely, neurodegenerative and metabolic diseases. In this review, we discuss the recent findings that correlate aberrant tRNA modification with proteostasis imbalances, in particular in neurological and metabolic disorders, and highlight the association between tRNAs, their modifying enzymes, translational decoding, and disease onset.


Assuntos
Doenças Metabólicas/genética , Doenças do Sistema Nervoso/genética , Biossíntese de Proteínas , Proteostase , Processamento Pós-Transcricional do RNA , RNA de Transferência/genética , Animais , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Humanos , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/patologia , Conformação de Ácido Nucleico , Agregados Proteicos/genética , RNA de Transferência/química , RNA de Transferência/metabolismo , Ubiquitinas/genética , Ubiquitinas/metabolismo , tRNA Metiltransferases/genética , tRNA Metiltransferases/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...