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By using a unique animal model of type 2 diabetes mellitus, Psammomys obesus induced by a high-calorie diet (HCD) for nine months, we showed for the first time, in the liver, the impact of inflammation on the remodeling of intercellular junction molecules E-cadherins during the progression of steatohepatitis. Under the effect of HCD, the expressions of immunohistochemical markers, Tumor Necrosis Factor alpha (TNFα) and E-cadherins were inversely correlated. Ultrastructural examination revealed the involvement of destabilization and loss of E-cadherins in the process of hepatic pathogenesis. This mechanical maintenance stress was favored by the recruitment of immune cells which contributed to the triggering and progression of fibrosis by the enlargement of the intercellular space and the invasion of collagen fibers. Furthermore to escape cell death, loss of E-cadherins played a major role in mediating fibrosis. Psammomys obesus is a promising model for experimental research, enabling the extrapolation of observed structural and functional alterations in humans, the objective to find new therapeutic targets. The physiological resemblance between Psammomys obesus and humans enhances the precision and relevance of biomedical research efforts.
Assuntos
Caderinas , Diabetes Mellitus Tipo 2 , Modelos Animais de Doenças , Gerbillinae , Fígado , Fator de Necrose Tumoral alfa , Animais , Fator de Necrose Tumoral alfa/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Caderinas/metabolismo , Fígado/metabolismo , Fígado/patologia , Fígado/ultraestrutura , Doenças Metabólicas/patologia , Doenças Metabólicas/metabolismo , MasculinoRESUMO
HuR (ElavL1) is one of the main post-transcriptional regulators that determines cell fate. Although the role of HuR in apoptosis is well established, the post-translational modifications that govern this function remain elusive. In this study, we show that PARP1/2-mediated poly(ADP)-ribosylation (PARylation) is instrumental in the pro-apoptotic function of HuR. During apoptosis, a substantial reduction in HuR PARylation is observed. This results in the cytoplasmic accumulation and the cleavage of HuR, both of which are essential events for apoptosis. These effects are mediated by a pADP-ribose-binding motif within the HuR-HNS region (HuR PAR-binding site). Under normal conditions, the association of the HuR PAR-binding site with pADP-ribose is responsible for the nuclear retention of HuR. Mutations within this motif prevent the binding of HuR to its import factor TRN2, leading to its cytoplasmic accumulation and cleavage. Collectively, our findings underscore the role of PARylation in controlling the pro-apoptotic function of HuR, offering insight into the mechanism by which PARP1/2 enzymes regulate cell fate and adaptation to various assaults.
Assuntos
Processamento de Proteína Pós-Traducional , Ribose , Mutação , Diferenciação Celular , Domínios ProteicosRESUMO
Poly(ADP-ribosylation) (PARylation) is a post-translational modification mediated by a subset of ADP-ribosyl transferases (ARTs). Although PARylation-inhibition based therapies are considered as an avenue to combat debilitating diseases such as cancer and myopathies, the role of this modification in physiological processes such as cell differentiation remains unclear. Here, we show that Tankyrase1 (TNKS1), a PARylating ART, plays a major role in myogenesis, a vital process known to drive muscle fiber formation and regeneration. Although all bona fide PARPs are expressed in muscle cells, experiments using siRNA-mediated knockdown or pharmacological inhibition show that TNKS1 is the enzyme responsible of catalyzing PARylation during myogenesis. Via this activity, TNKS1 controls the turnover of mRNAs encoding myogenic regulatory factors such as nucleophosmin (NPM) and myogenin. TNKS1 mediates these effects by targeting RNA-binding proteins such as Human Antigen R (HuR). HuR harbors a conserved TNKS-binding motif (TBM), the mutation of which not only prevents the association of HuR with TNKS1 and its PARylation, but also precludes HuR from regulating the turnover of NPM and myogenin mRNAs as well as from promoting myogenesis. Therefore, our data uncover a new role for TNKS1 as a key modulator of RBP-mediated post-transcriptional events required for vital processes such as myogenesis.
Assuntos
Desenvolvimento Muscular , Fibras Musculares Esqueléticas , Miogenina , RNA Mensageiro , Tanquirases , Tanquirases/metabolismo , Tanquirases/genética , Humanos , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Desenvolvimento Muscular/genética , Animais , Fibras Musculares Esqueléticas/metabolismo , Camundongos , Miogenina/genética , Miogenina/metabolismo , Nucleofosmina , Proteína Semelhante a ELAV 1/metabolismo , Proteína Semelhante a ELAV 1/genética , Estabilidade de RNA/genética , Poli ADP Ribosilação/genética , Linhagem Celular , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Diferenciação Celular/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Células HEK293RESUMO
Since its inception in the 1930s, transmission electron microscopy (TEM) has been a powerful method to explore the cellular structure of parasites. TEM usually requires samples of <100 nm thick and with protozoans being larger than 1 µm, their study requires resin embedding and ultrathin sectioning. During the past decade, several new methods have been developed to improve, facilitate, and speed up the structural characterisation of biological samples, offering new imaging modalities for the study of protozoans. In particular, scanning transmission electron microscopy (STEM) can be used to observe sample sections as thick as 1 µm thus becoming an alternative to conventional TEM. STEM can also be performed under cryogenic conditions in combination with cryo-electron tomography providing access to the study of thicker samples in their native hydrated states in 3D. This method, called cryo-scanning transmission electron tomography (cryo-STET), was first developed in 2014. This review presents the basic concepts and benefits of STEM methods and provides examples to illustrate the potential for new insights into the structure and ultrastructure of protozoans.
Assuntos
Tomografia com Microscopia Eletrônica , Microscopia Eletrônica de Transmissão e Varredura/métodos , Tomografia com Microscopia Eletrônica/métodos , Microscopia Crioeletrônica/métodos , Microscopia Eletrônica de VarreduraRESUMO
Objetivo: Conocer la relación entre el clima organizacional del personal de salud y la satisfacción de los usuarios atendidos por el Servicio de Atención Móvil de Urgencias (SAMU) en el contexto COVID-19, Piura. Materiales y métodos: Se aplicó una encuesta a 80 trabajadores de salud para evaluar el clima organizacional y a 110 usuarios del SAMU para evaluar su nivel de satisfacción y si cumplían con los criterios de selección. La encuesta tuvo dos secciones: una dirigida a los trabajadores del SAMU y otra, al usuario. Se evaluaron con escala tipo Likert. Resultados: El 51,3 % del personal de salud fueron hombres, de una edad promedio de 32,65 ± 6,8 % años y hubo más licenciados en enfermería (32,50 %), seguido de médicos (31,30 %). El 54,5 % de usuarios fueron hombres, de una edad promedio de 58,78 ± 20,97 años, el 57,3 % no presentaron ninguna comorbilidad y el 84,5 % utilizaron el servicio una vez. El clima organizacional del personal y sus dimensiones fueron saludables (96,58 ± 3,21). La mayoría (51,60 %) de los usuarios del SAMU se encontraron satisfechos (57/110), mientras que el 38,2 % (42/110) manifestaron estar medianamente satisfechos y el 10,20 % (11/110) mostraron su insatisfacción. Se comprueba la hipótesis principal que existe asociación entre el clima organizacional y la satisfacción de los usuarios atendidos por el SAMU (p < 0,005) y existe asociación entre las cinco dimensiones con la satisfacción de los usuarios. Conclusiones: Existe relación entre el clima organizacional de los trabajadores de salud del Servicio de Atención Móvil de Urgencias y la satisfacción de usuarios atendidos por este servicio en Piura. El clima organizacional y sus dimensiones, comparados con el instrumento elaborado por el Minsa, se encuentran saludables, la mayoría de los pacientes atendidos se mostraron satisfechos con la atención recibida y las comorbilidades más frecuentes fueron la hipertensión y la diabetes mellitus tipo 2.
Objective: To determine the relationship between the organizational climate among healthcare personnel and the satisfaction of users assisted by the Mobile Emergency Care Service (SAMU) in the context of COVID-19, Piura. Materials and methods: A Likert-scale survey was administered to 80 healthcare workers to assess the organizational climate and 110 SAMU users to assess their satisfaction level and whether they met the selection criteria. The survey had one section addressed to SAMU workers and another one to SAMU users. Results: Out of all healthcare personnel, 51.3 % were men with an average age of 32.65 ± 6.8 % years, and there were more registered nurses (32.50 %) than doctors (31.30 %). Out of all users, 54.5 % were men with an average age of 58.78 ± 20.97 years, 57.3 % had no comorbidities and 84.5 % used the service once. The organizational climate and its dimensions showed healthy outcomes (96.58 ± 3.21). Most SAMU users (51.60 %) were satisfied (57/110) while 38.20 % (42/110) were moderately satisfied and 10.20 % (11/110) showed dissatisfaction. The main hypothesis concerning the relationship between the organizational climate and the satisfaction of SAMU users (p < 0.005) was confirmed. Moreover, there was a relationship between the five dimensions and the satisfaction of users. Conclusions: There is a relationship between the organizational climate among SAMU healthcare workers and the satisfaction of SAMU users in Piura. The organizational climate and its dimensions, compared to the instrument developed by MINSA, showed healthy outcomes. Most patients were satisfied with the care received and the most frequent comorbidities were hypertension and type 2 diabetes mellitus.
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If the ocular media are clear, indirect binocular ophthalmoscopy allows retinal detachment and retinal tear identification and treatment under direct visualization. However, if opacities are present preventing direct fundus examination, ultrasonography becomes the most important tool for evaluating the posterior segment. In addition, ultrasonography can be useful in retinal tear treatment by guiding cryotherapy. In this article we describe a rhegmatogenous retinal detachment treatment technique applied to a patient with corneal opacity. Cryopexy and circumferential and radial buckle positioning were guided by ultrasonography, resulting in retinal attachment during the 6-month follow-up period.
Quando os meios oculares são transparentes, oftalmoscopia binocular indireta permite a identificação de descolamento de retina e roturas, bem como seu tratamento sob visibilização direta. Porém, em olhos que apresentam opacidades de meios impedindo o exame oftalmoscópico, a ultrassonografia constitui o exame mais importante do segmento posterior do olho. Além disso, o tratamento de roturas retinianas também pode ser auxiliado pelo uso desse equipamento, orientando a crioterapia. Neste trabalho será apresentada técnica de tratamento de descolamento de retina regmatogênico, no qual a criopexia e o posicionamento dos "buckles" episclerais circunferencial e radial foram guiados pelo ultrassom em paciente com leucoma corneano. O tratamento resultou em aplicação retiniana durante o seguimento em seis meses.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Opacidade da Córnea/cirurgia , Descolamento Retiniano/cirurgia , Ultrassonografia de Intervenção , Opacidade da Córnea/complicações , Opacidade da Córnea , Criocirurgia/métodos , Seguimentos , Descolamento Retiniano/complicações , Descolamento Retiniano , Recurvamento da Esclera/métodos , Resultado do TratamentoRESUMO
Relato de caso de paciente jovem com doenca pulmonar infiltrativa difusa com discussao de diagnosticos diferenciais e elucidacao diagnostica
Assuntos
Humanos , Masculino , Adulto , Fibrose Pulmonar/diagnósticoRESUMO
Nove pacientes consecutivos com diagnóstico de abscesso hepático foram estudados num período de nove anos. Dois apresentavam abscessos amebianos e seis bacterianos; um caso tinha etiologia mista. Sete pacientes apresentavam quadro com duraçäo inferior a 15 dias. O tempo médio para estabelecer-se o diagnóstico foi de cinco dias e meio. Dois casos foram submetidos à drenagem cirúrgica aberta e sete receberam tratamento apenas clínico. Houve um óbito näo relacionado ao abscesso. Concluímos que o tratamento clínico evidencia-se como nova modalidade terapêutica para o abscesso hepático piogênico, reservando-se a cirurgia apenas às complicaçöes