The fabrication of complex and stable vasculature in engineered cardiac tissues represents a significant hurdle towards building physiologically relevant models of the heart. Here, we implemented a 3D model of cardiac vasculogenesis, incorporating endothelial cells (EC), stromal cells, and human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) in a fibrin hydrogel. The presence of CMs disrupted vessel formation in 3D tissues, resulting in the upregulation of endothelial activation markers and altered extracellular vesicle (EV) signaling in engineered tissues as determined by the proteomic analysis of culture supernatant.
View Article and Find Full Text PDFMitochondrial transplantation and transfer are being explored as therapeutic options in acute and chronic diseases to restore cellular function in injured tissues. To limit potential immune responses and rejection of donor mitochondria, current clinical applications have focused on delivery of autologous mitochondria. We recently convened a Mitochondrial Transplant Convergent Working Group (CWG), to explore three key issues that limit clinical translation: (1) storage of mitochondria, (2) biomaterials to enhance mitochondrial uptake, and (3) dynamic models to mimic the complex recipient tissue environment.
View Article and Find Full Text PDFEpicardial cells (EPIs) form the outer layer of the heart and play an important role in development and disease. Current heart-on-a-chip platforms still do not fully mimic the native cardiac environment due to the absence of relevant cell types, such as EPIs. Here, using the Biowire II platform, engineered cardiac tissues with an epicardial outer layer and inner myocardial structure are constructed, and an image analysis approach is developed to track the EPI cell migration in a beating myocardial environment.
View Article and Find Full Text PDFThe Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English.
View Article and Find Full Text PDFOxoguanine glycosylase 1 (OGG1) is widely known to repair the reactive oxygen species (ROS)-initiated DNA lesion 8-oxoguanine (8-oxoG), and more recently was shown to act as an epigenetic modifier. We have previously shown that saline-exposed -/- knockout progeny exhibited learning and memory deficits, which were enhanced by in utero exposure to a single low dose of ethanol (EtOH) in both +/+ and -/- progeny, but more so in -/- progeny. Herein, OGG1-deficient progeny exposed in utero to a single low dose of EtOH or its saline vehicle exhibited OGG1- and/or EtOH-dependent alterations in global histone methylation and acetylation, DNA methylation and gene expression ( (Tet Methylcytosine Dioxygenase 1) (Neuroligin 3) (Histone Deacetylase 2) (Reelin) and (Estrogen Receptor 1)) in fetal brains, and behavioural changes in open field activity, social interaction and ultrasonic vocalization, but not prepulse inhibition.
View Article and Find Full Text PDFBackground: Mitochondrial dysfunction is involved in several diseases ranging from genetic mitochondrial disorders to chronic metabolic diseases. An emerging approach to potentially treat mitochondrial dysfunction is the transplantation of autologous live mitochondria to promote cell regeneration. We tested the differential filtration-based mitochondrial isolation protocol established by the McCully laboratory for use in cellular models but found whole cell contaminants in the mitochondrial isolate.
View Article and Find Full Text PDFLarge-scale microarray studies on post-mortem brain tissues have been utilized to investigate the complex molecular pathology of bipolar disorder. However, a major challenge in characterizing the dysregulation of gene expression in patients with bipolar disorder includes the lack of convergence between different studies, limiting comprehensive understanding from individual results. In this study, we aimed to identify genes that are both validated in published literature and are important classification features of unsupervised machine learning analysis of Stanley Brain Bank microarray database, followed by augmented intelligence method to identify distinct patient molecular subgroups.
View Article and Find Full Text PDFNeurological disorders have been demonstrated to be associated with mitochondrial dysfunction. This impairment may lead to oxidative stress and neuroinflammation, specifically promoted by NLRP3 expression. Açaí (Euterpe oleracea Mart.
View Article and Find Full Text PDFIntroduction: Neuropsychiatric diseases are responsible for one of the highest burden of morbidity and mortality worldwide. These illnesses include schizophrenia, bipolar disorder, and major depression. Individuals affected by these diseases may present mitochondrial dysfunction and oxidative stress.
View Article and Find Full Text PDFThe underlying pathology of bipolar disorder remains unknown, though evidence is accumulating to support a role of mitochondrial dysfunction. In this study, we aim to investigate electron transport chain complex I subunit NDUFS7 protein expression; mtDNA content; common deletion; and oxidation in the Broadmann area 24 (BA24), cerebellum, hippocampus, and prefrontal cortex from patients with bipolar disorder, schizophrenia, and non-psychiatric controls. Here, we demonstrate no changes in NDUFS7 in BA24, cerebellum or hippocampus, increases in mtDNA content in hippocampus of patients with bipolar disorder, and decreases in mtDNA oxidation in patients with bipolar disorder and schizophrenia, respectively.
View Article and Find Full Text PDFA Berlin Team for Documentation in Psychotherapy has developed an extensive documentation system. It provides data of a social, psychological and life-history nature, refering to computerized dataanalysis, which are pertinent in the psychological assessment of patients with neurotic and psychosomatic symptoms. The instrument which serves in collecting the data--a special type of psychoanalytic interview--has been used routinely in the Berlin-Group since 1951 to diagnose neurotic disturbances and to prognostically assess the chances for treatment.
View Article and Find Full Text PDFThe protein, RNA and DNA content of wing discs increase exponentially during the last larval instar. Biosynthesis of protein, RNA and DNA was studied by injecting labelled precursors into larvae or white prepupae and measuring the incorporation in the wing discs dissected out after an appropriate time. Protein synthesis is stimulated by ecdysterone, methoprene has no effect.
View Article and Find Full Text PDFThe development of Drosophila organ discs can be arrested by culturing them in adult male flies. These aged discs lose some of their differentiation competence and form incomplete imaginal structures. The more advanced the aging, the greater the loss of competence.
View Article and Find Full Text PDF