RESUMO
Diet habits and nutrition quality significantly impact health and disease. Here is delve into the intricate relationship between diet habits, nutrition quality, and their direct impact on health and homeostasis. Focusing on (-)-Epicatechin, a natural flavanol found in various foods like green tea and cocoa, known for its positive effects on cardiovascular health and diabetes prevention. The investigation encompasses the absorption, metabolism, and distribution of (-)-Epicatechin in the human body, revealing a diverse array of metabolites in the circulatory system. Notably, (-)-Epicatechin demonstrates an ability to activate nitric oxide synthase (eNOS) through the G protein-coupled estrogen receptor (GPER). While the precise role of GPER and its interaction with classical estrogen receptors (ERs) remains under scrutiny, the study employs computational methods, including density functional theory, molecular docking, and molecular dynamics simulations, to assess the physicochemical properties and binding affinities of key (-)-Epicatechin metabolites with GPER. DFT analysis revealed distinct physicochemical properties among metabolites, influencing their reactivity and stability. Rigid and flexible molecular docking demonstrated varying binding affinities, with some metabolites surpassing (-)-Epicatechin. Molecular dynamics simulations highlighted potential binding pose variations, while MMGBSA analysis provided insights into the energetics of GPER-metabolite interactions. The outcomes elucidate distinct interactions, providing insights into potential molecular mechanisms underlying the effects of (-)-Epicatechin across varied biological contexts.
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Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by cerebellar ataxia and retinopathy. SCA7 is caused by a CAG expansion in the ATXN7 gene, which results in an extended polyglutamine (polyQ) tract in the encoded protein, the ataxin-7. PolyQ expanded ataxin-7 elicits neurodegeneration in cerebellar Purkinje cells, however, its impact on the SCA7-associated retinopathy remains to be addressed. Since Müller glial cells play an essential role in retinal homeostasis, we generate an inducible model for SCA7, based on the glial Müller MIO-M1 cell line. The SCA7 pathogenesis has been explained by a protein gain-of-function mechanism, however, the contribution of the mutant RNA to the disease cannot be excluded. In this direction, we found nuclear and cytoplasmic foci containing mutant RNA accompanied by subtle alternative splicing defects in MIO-M1 cells. RNA foci were also observed in cells from different lineages, including peripheral mononuclear leukocytes derived from SCA7 patient, suggesting that this molecular mark could be used as a blood biomarker for SCA7. Collectively, our data showed that our glial cell model exhibits the molecular features of SCA7, which makes it a suitable model to study the RNA toxicity mechanisms, as well as to explore therapeutic strategies aiming to alleviate glial dysfunction.
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La Parálisis Facial (PF) es una condición infrecuente en pacientes pediátricos, representa un problema clínico relevante y conlleva diversas implicaciones. Tanto el curso natural como el tratamiento y pronóstico no se encuentran bien documentados en la literatura, más aún en sujetos sometidos a cirugía. Se presentan 2 casos de PF sometidos a cirugía reconstructiva, niño de 9 años y niña de 8, ambos casos revisados de forma retrospectiva. Se planteó un bordaje y evaluación kinésica estructurado como tratamiento para estos pacientes. El sistema de graduación facial Sunnybrook (SGFS) fue usado para evaluar resultados funcionales. Durante el seguimiento los sujetos mostraron mejoras continuas con una ganancia promedio de 30 puntos en el SGFS. En nuestra experiencia, la rehabilitación kinésica estructurada con el enfoque presentado, parece ser un coadyuvante efectivo en potenciar el proceso de recuperación de la función muscular y simetría facial en sujetos con PF sometidos a cirugía reconstructiva.
Facial Palsy (FP) is an uncommon condition in pediatric patients, it represents a serious linical problem and carries various implications. Both the natural course, as well as the treatment and prognosis are not well documented in the literature especially in subjects undergoing surgery. Two cases of FP undergoing reconstructive surgery are presented, a 9-year-old boy and an 8-year-old girl, both cases reviewed retrospectively. A structured kinesic approach and valuation was proposed as a treatment for these patients. The Sunnybrook Facial Grading System (SGFS) was applied to evaluate functional outcomes. During follow-up the subjects showed continuous improvement with an average increment of 30 points in the SGFS. In our experience, structured kinesic rehabilitation with the approach presented, seems to be an effective adjunct in enhancing the process of recovery of muscle function and facial symmetry in subjects with FP undergoing reconstructive surgery.
Assuntos
Humanos , Masculino , Feminino , Criança , Período Pós-Operatório , Paralisia Facial/reabilitação , Modalidades de Fisioterapia , Procedimentos de Cirurgia Plástica , Recuperação de Função FisiológicaRESUMO
Cellular commitment and differentiation involve highly coordinated mechanisms by which tissue-specific genes are activated while others are repressed. These mechanisms rely on the activity of specific transcription factors, chromatin remodeling enzymes, and higher-order chromatin organization in order to modulate transcriptional regulation on multiple cellular contexts. Tissue-specific transcription factors are key mediators of cell fate specification with the ability to reprogram cell types into different lineages. A classic example of a master transcription factor is the muscle specific factor MyoD, which belongs to the family of myogenic regulatory factors (MRFs). MRFs regulate cell fate determination and terminal differentiation of the myogenic precursors in a multistep process that eventually culminate with formation of muscle fibers. This developmental progression involves the activation and proliferation of muscle stem cells, commitment, and cell cycle exit and fusion of mononucleated myoblast to generate myotubes and myofibers. Although the epigenetics of muscle regeneration has been extensively addressed and discussed over the recent years, the influence of higher-order chromatin organization in skeletal muscle regeneration is still a field of development. In this review, we will focus on the epigenetic mechanisms modulating muscle gene expression and on the incipient work that addresses three-dimensional genome architecture and its influence in cell fate determination and differentiation to achieve skeletal myogenesis. We will visit known alterations of genome organization mediated by chromosomal fusions giving rise to novel regulatory landscapes, enhancing oncogenic activation in muscle, such as alveolar rhabdomyosarcomas (ARMS).
RESUMO
OBJECTIVE: This study was undertaken to describe demographics and contraceptive familiarity and use among postpartum adolescents in El Salvador. STUDY DESIGN: Questionnaire-guided interviews were conducted in Spanish with 50 postpartum adolescents at an urban, public hospital in El Salvador. Open-ended questions included assessments of education, partnership status, and contraceptive knowledge and use patterns. RESULTS: The median age of subjects was 17 years, 84% were nulliparous, 80% had partners, and 6% were married. Eighty-four percent of the women reported contraception knowledge and 18% reported contraception use. Educational experience and literacy predicted contraceptive knowledge (P = .008 and .001, respectively), but not use. After delivery and postpartum contraception education, 58% of the subjects stated intention to use contraception. Having a partner and living with him were predictors of intent to use contraception (P = .001 and .002, respectively). Being single negatively predicted intention to use contraception (P = .001). CONCLUSION: Education and literacy predicted contraceptive knowledge; however, contraceptive knowledge did not predict contraceptive use. Adolescent contraception use depends on more than just contraceptive knowledge.