RESUMO
Mesenchymal stem cells (MSCs) are used in cell therapy; nonetheless, their application is limited by their poor survival after transplantation in a proinflammatory microenvironment. Macroautophagy/autophagy activation in MSCs constitutes a stress adaptation pathway, promoting cellular homeostasis. Our proteomics data indicate that RUBCNL/PACER (RUN and cysteine rich domain containing beclin 1 interacting protein like), a positive regulator of autophagy, is also involved in cell death. Hence, we screened MSC survival upon various cell death stimuli under loss or gain of function of RUBCNL. MSCs were protected from TNF (tumor necrosis factor)-induced regulated cell death when RUBCNL was expressed. TNF promotes inflammation by inducing RIPK1 kinase-dependent apoptosis or necroptosis. We determine that MSCs succumb to RIPK1 kinase-dependent apoptosis upon TNF sensing and necroptosis when caspases are inactivated. We show that RUBCNL is a negative regulator of both RIPK1-dependent apoptosis and necroptosis. Furthermore, RUBCNL mutants that lose the ability to regulate autophagy, retain their function in negatively regulating cell death. We also found that RUBCNL forms a complex with RIPK1, which disassembles in response to TNF. In line with this finding, RUBCNL expression limits assembly of RIPK1-TNFRSF1A/TNFR1 complex I, suggesting that complex formation between RUBCNL and RIPK1 represses TNF signaling. These results provide new insights into the crosstalk between the RIPK1-mediated cell death and autophagy machineries and suggest that RUBCNL, due to its functional duality in autophagy and apoptosis/necroptosis, could be targeted to improve the therapeutic efficacy of MSCs. Abbreviations: BAF: bafilomycin A1; CASP3: caspase 3; Caspases: cysteine-aspartic proteases; cCASP3: cleaved CASP3; CQ: chloroquine; CHX: cycloheximide; cPARP: cleaved poly (ADP-ribose) polymerase; DEPs: differential expressed proteins; ETO: etoposide; MEF: mouse embryonic fibroblast; MLKL: mixed lineage kinase domain-like; MSC: mesenchymal stem cell; MTORC1: mechanistic target of rapamycin kinase complex 1; Nec1s: necrostatin 1s; NFKB/NF-kB: nuclear factor of kappa light polypeptide gene enhancer in B cells; PLA: proximity ligation assay; RCD: regulated cell death; RIPK1: receptor (TNFRSF)-interacting serine-threonine kinase 1; RIPK3: receptor-interacting serine-threonine kinase 3; RUBCNL/PACER: RUN and cysteine rich domain containing beclin 1 interacting protein like; siCtrl: small interfering RNA nonsense; siRNA: small interfering RNA; TdT: terminal deoxynucleotidyl transferase; Tm: tunicamycin; TNF: tumor necrosis factor; TNFRSF1A/TNFR1: tumor necrosis factor receptor superfamily, member 1a.
RESUMO
Objective: To classify the bibliometric indicators of online scientific research on placentophagy. Methods: A bibliometric study was conducted to quantify the scientific production of authors and institutions with the aim of highlighting the growth and impact of these publications nationally and internationally. The Bradford Law, network maps, and textual statistics were used, with searches conducted in libraries and databases in October 2021. Results: The sample consisted of 64 articles, whose primary authors were associated with 49 institutions, and mostly with degrees in anthropology. The United States of America was the country that published the most papers on the theme, and most studies were reviews with individual production. Through the term analysis, it was found that the predominant themes regarding placentophagy were the following: Alternative therapy for women's health, methodologies used for research in this area, period of placenta ingestion (postpartum period), and its benefits. Conclusion: The bibliometric indicators found are essential for the development of future research.
Assuntos
Bibliometria , Placenta , Feminino , Humanos , Gravidez , Pesquisa BiomédicaRESUMO
Abstract Objective: To classify the bibliometric indicators of online scientific research on placentophagy. Methods: A bibliometric study was conducted to quantify the scientific production of authors and institutions with the aim of highlighting the growth and impact of these publications nationally and internationally. The Bradford Law, network maps, and textual statistics were used, with searches conducted in libraries and databases in October 2021. Results: The sample consisted of 64 articles, whose primary authors were associated with 49 institutions, and mostly with degrees in anthropology. The United States of America was the country that published the most papers on the theme, and most studies were reviews with individual production. Through the term analysis, it was found that the predominant themes regarding placentophagy were the following: Alternative therapy for women's health, methodologies used for research in this area, period of placenta ingestion (postpartum period), and its benefits. Conclusion: The bibliometric indicators found are essential for the development of future research.
Assuntos
Humanos , Feminino , Gravidez , Placenta , Terapias Complementares , Bibliometria , Período Pós-PartoRESUMO
Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by protein accumulation in the brain as a main neuropathological hallmark. Among them, Aß42 peptides tend to aggregate and create oligomers and plaques. Macroautophagy, a form of autophagy characterized by a double-membrane vesicle, plays a crucial role in maintaining neuronal homeostasis by degrading protein aggregates and dysfunctional organelles as a quality control process. Recently, DEF8, a relatively uncharacterized protein, has been proposed as a participant in vesicular traffic and autophagy pathways. We have reported increased DEF8 levels in lymphocytes from mild cognitive impairment (MCI) and early-stage AD patients and a neuronal profile in a murine transgenic AD model. Here, we analyzed DEF8 localization and levels in the postmortem frontal cortex of AD patients, finding increased levels compared to healthy controls. To evaluate the potential function of DEF8 in the nervous system, we performed an in silico assessment of its expression and network profiles, followed by an in vivo evaluation of a neuronal Def8 deficient model using a Drosophila melanogaster model of AD based on Aß42 expression. Our findings show that DEF8 is an essential protein for maintaining cellular homeostasis in the nervous system, and it is upregulated under stress conditions generated by Aß42 aggregation. This study suggests DEF8 as a novel actor in the physiopathology of AD, and its exploration may lead to new treatment avenues.
Assuntos
Doença de Alzheimer , Animais , Humanos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Autofagia/genética , Encéfalo/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Fragmentos de Peptídeos/metabolismoRESUMO
OBJECTIVE: to synthesize the evidence available in the literature on the effects of integrative and complementary practices in nausea and vomiting treatment in pregnant women. METHOD: a systematic review, reported according to PRISMA and registered in PROSPERO. The search for studies was carried out in 11 databases. To assess risk of bias in randomized clinical trials, the Cochrane Collaboration Risk of Bias Tool (RoB 2) was used. RESULTS: the final sample consisted of 31 articles, divided into three categories: aromatherapy, phytotherapy and acupuncture. It was observed that aromatherapy with lemon essential oil, ginger capsules, pericardial 6 point acupressure were the interventions that proved to be effective. Less than half of studies reported adverse effects, with mild and transient symptoms predominating. Most articles were classified as "some concern" in risk of bias assessment. CONCLUSION: the three most effective interventions to control gestational nausea and vomiting were aromatherapy, herbal medicine and acupuncture, with significant results in the assessment of individual studies.
Assuntos
Antieméticos , Óleos Voláteis , Feminino , Gravidez , Humanos , Antieméticos/uso terapêutico , Gestantes , Cápsulas/uso terapêutico , Náusea/prevenção & controle , Vômito/prevenção & controleRESUMO
Alzheimer's disease (AD) is the most prevalent age-associated neurodegenerative disease. A decrease in autophagy during aging contributes to brain disorders by accumulating potentially toxic substrates in neurons. Rubicon is a well-established inhibitor of autophagy in all cells. However, Rubicon participates in different pathways depending on cell type, and little information is currently available on neuronal Rubicon's role in the AD context. Here, we investigated the cell-specific expression of Rubicon in postmortem brain samples from AD patients and 5xFAD mice and its impact on amyloid ß burden in vivo and neuroblastoma cells. Further, we assessed Rubicon levels in human-induced pluripotent stem cells (hiPSCs), derived from early-to-moderate AD and in postmortem samples from severe AD patients. We found increased Rubicon levels in AD-hiPSCs and postmortem samples and a notable Rubicon localization in neurons. In AD transgenic mice lacking Rubicon, we observed intensified amyloid ß burden in the hippocampus and decreased Pacer and p62 levels. In APP-expressing neuroblastoma cells, increased APP/amyloid ß secretion in the medium was found when Rubicon was absent, which was not observed in cells depleted of Atg5, essential for autophagy, or Rab27a, required for exosome secretion. Our results propose an uncharacterized role of Rubicon on APP/amyloid ß homeostasis, in which neuronal Rubicon is a repressor of APP/amyloid ß secretion, defining a new way to target AD and other similar diseases therapeutically.
Assuntos
Doença de Alzheimer , Proteínas Relacionadas à Autofagia , Neuroblastoma , Doenças Neurodegenerativas , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Proteínas Relacionadas à Autofagia/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Camundongos Transgênicos , Neuroblastoma/metabolismo , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismoRESUMO
RESUMO Objetivo: analisar a contribuição do cuidado de enfermagem, com ênfase na comunicação, para o paciente sob cuidados paliativos na fase terminal e seus familiares. Método: estudo qualitativo, realizado em um Hospital Filantrópico da cidade de João Pessoa-PB, Brasil, em 2019, desenvolvido com 15 familiares de pacientes em cuidados paliativos, por meio de entrevistas semiestruturadas. Os dados foram submetidos à análise de conteúdo, proposta por Bardin, à luz da Teoria do Final de Vida Pacífico. Resultados: emergiram duas categorias: 'A comunicação dos profissionais de enfermagem como estratégia para promover conforto, paz, dignidade e respeito para pacientes e familiares em cuidados paliativos'; 'A presença e o diálogo de pessoas importantes para o paciente sob cuidados paliativos são fundamentais para um final de vida pacífico.' Conclusão: espera-se que, através desse estudo, seja possível aprimorar a assistência à família acerca da comunicação nos cuidados paliativos.
ABSTRACT Objective: to analyze the contribution of nursing care, with emphasis on communication, for the patient under palliative care in the terminal phase and their families. Method: qualitative study, conducted in a Philanthropic Hospital in the city of João Pessoa-PB, Brazil, in 2019, developed with 15 family members of patients in palliative care, through semi-structured interviews. The data were submitted to content analysis, proposed by Bardin, in the light of the Pacific End of Life Theory. Results: two categories emerged: 'Communication by nursing professionals as a strategy to promote comfort, peace, dignity and respect for patients and families in palliative care'; 'The presence and dialogue of people important to the patient under palliative care are fundamental for a peaceful end of life.' Conclusion: it is hoped that, through this study, it will be possible to improve assistance to the family about communication in palliative care.
RESUMEN Objetivo: analizar la contribución de los cuidados de enfermería, con énfasis en la comunicación, para el paciente en cuidados paliativos en fase terminal y sus familias. Método: estudio cualitativo, realizado en un Hospital Filantrópico de la ciudad de João Pessoa-PB, Brasil, en 2019, desarrollado con 15 familiares de pacientes en cuidados paliativos, a través de entrevistas semiestructuradas. Los datos fueron sometidos a un análisis de contenido, propuesto por Bardin, a la luz de la Teoría del Final Tranquilo de la Vida. Resultados: surgieron dos categorías: "La comunicación de los profesionales de enfermería como estrategia para promover el confort, la paz, la dignidad y el respeto a los pacientes y familiares en los cuidados paliativos"; "La presencia y el diálogo de las personas importantes para el paciente en los cuidados paliativos son fundamentales para un final de vida tranquilo". Conclusión: se espera que, a través de este estudio, sea posible mejorar la asistencia a la familia sobre la comunicación en los cuidados paliativos.
Assuntos
Cuidados PaliativosRESUMO
Parkinson's disease (PD) is caused by the degeneration of dopaminergic neurons due to an accumulation of intraneuronal abnormal alpha-synuclein (α-syn) protein aggregates. It has been reported that the levels of exosomal α-syn of neuronal origin in plasma correlate significantly with motor dysfunction, highlighting the exosomes containing α-syn as a potential biomarker of PD. In addition, it has been found that the selective autophagy-lysosomal pathway (ALP) contributes to the secretion of misfolded proteins involved in neurodegenerative diseases. In this review, we describe the evidence that supports the relationship between the ALP and α-syn exosomal secretion on the PD progression and its implications in the diagnosis and progression of this pathology.