Efficient derivation of functional astrocytes from human induced pluripotent stem cells (hiPSCs).

Astrocytes are specialized glial cell types of the central nervous system (CNS) with remarkably high abundance, morphological and functional diversity. Astrocytes maintain neural metabolic support, synapse regulation, blood-brain barrier integrity and immunological homeostasis through intricate interactions with other cells, including neurons, microglia, pericytes and lymphocytes. Due to their extensive intercellular crosstalks, astrocytes are also implicated in the pathogenesis of CNS disorders, such as ALS (amyotrophic lateral sclerosis), Parkinson's disease and Alzheimer's disease.

Smarter Pregnancy Coaching and Maternal Blood Pressure.

Introduction: Maternal lifestyle behaviors can affect blood pressure with consequences for maternal and offspring health. The aim of this study was to investigate the effectiveness of the Smarter Pregnancy digital lifestyle coaching program on maternal blood pressure during the first trimester.

Methods: The study was conducted on data of the Rotterdam Periconception Cohort from 2010 to 2019, and analysis was completed in 2024.

Establishment of human pluripotent stem cell-derived cortical neurosphere model to study pathomechanisms and chemical toxicity in Kleefstra syndrome.

In the present study, we aimed to establish and characterize a mature cortical spheroid model system for Kleefstra syndrome (KS) using patient-derived iPSC. We identified key differences in the growth behavior of KS spheroids determined by reduced proliferation marked by low Ki67 and high E-cadherin expression. Conversely, in the spheroid-based neurite outgrowth assay KS outperformed the control neurite outgrowth due to higher BDNF expression.

Assessment and Evaluation of Contemporary Approaches for Astrocyte Differentiation from hiPSCs: A Modeling Paradigm for Alzheimer's Disease.

Background: Astrocytes have recently gained attention as key players in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease. Numerous differentiation protocols have been developed to study human astrocytes in vitro. However, the properties of the resulting glia are inconsistent, making it difficult to select an appropriate method for a given research question.

The Current State of Realistic Heart Models for Disease Modelling and Cardiotoxicity.

One of the many unresolved obstacles in the field of cardiovascular research is an uncompromising in vitro cardiac model. While primary cell sources from animal models offer both advantages and disadvantages, efforts over the past half-century have aimed to reduce their use. Additionally, obtaining a sufficient quantity of human primary cardiomyocytes faces ethical and legal challenges.

Placenta-specific CYP11A1 overexpression lead to autism-like symptom in offspring with altered steroid hormone biosynthesis in the placenta-brain axis and rescued by vitamin D intervention.

Alterations in steroid hormone regulation have been implicated in the etiology and progression of autism spectrum disorders (ASD), with the enzyme cytochrome P450 family 11 subfamily A member 1 (CYP11A1)-a key catalyst in cholesterol side-chain cleavage, prominently expressed in the adrenal glands, ovaries, testes, and placenta-standing at the forefront of these investigations. The potential link between aberrations in placental Cyp11a1 expression and the resultant neurodevelopmental disorders, along with the mechanisms underpinning such associations, remains inadequately delineated. In this study, we employed a placental trophoblast-specific Cyp11a1 Hipp11 (H11) knock-in murine model to dissect the phenotypic manifestations within the placenta and progeny, thereby elucidating the underlying mechanistic pathways.

Evaluation of the impact of iPSC differentiation protocols on transcriptomic signatures.

Human induced pluripotent stem cells (iPSC) have the potential to produce desired target cell types in vitro and allow for the high-throughput screening of drugs/chemicals at population level thereby minimising the cost of drug discovery and drug withdrawals after clinical trials. There is a substantial need for the characterisation of the iPSC derived models to better understand and utilise them for toxicological relevant applications. In our study, iPSC (SBAD2 or SBAD3 lines obtained from StemBANCC project) were differentiated towards toxicologically relevant cell types: alveolar macrophages, brain capillary endothelial cells, brain cells, endothelial cells, hepatocytes, lung airway epithelium, monocytes, podocytes and renal proximal tubular cells.

Non-covalent binding of chlorogenic acid to myofibrillar protein improved its bio-functionality properties and metabolic fate.

As natural antioxidants added to meat products, polyphenols can interact with proteins, and the acid-base environment influenced the extent of non-covalent and covalent interactions between them. This study compared the bio-functional characteristics and metabolic outcomes of the myofibrillar protein-chlorogenic acid (MP-CGA) complexes binding in different environments (pH 6.0 and 8.

Proteomics and disease network associations evaluation of environmentally relevant Bisphenol A concentrations in a human 3D neural stem cell model.

Bisphenol A (BPA) exposure is associated with a plethora of neurodevelopmental abnormalities and brain disorders. Previous studies have demonstrated BPA-induced perturbations to critical neural stem cell (NSC) characteristics, such as proliferation and differentiation, although the underlying molecular mechanisms remain under debate. The present study evaluated the effects of a repeated-dose exposure of environmentally relevant BPA concentrations during the 3D neural induction of human induced pluripotent stem cells (hiPSCs), emulating a chronic exposure scenario.

Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model.

Early embryonic development represents a sensitive time-window during which the foetus might be vulnerable to the exposure of environmental contaminants, potentially leading to heart diseases also later in life. Bisphenol A (BPA), a synthetic chemical widely used in plastics manufacturing, has been associated with heart developmental defects, even in low concentrations. This study aims to investigate the effects of environmentally relevant doses of BPA on developing cardiomyocytes using a human induced pluripotent stem cell (hiPSC)-derived model.

A Novel Multicellular Placental Barrier Model to Investigate the Effect of Maternal Aflatoxin B Exposure on Fetal-Side Neural Stem Cells.

Ingestion of food toxins such as aflatoxin B (AFB) during pregnancy may impair fetal neurodevelopment. However, animal model results may not be accurate due to the species' differences, and testing on humans is ethically impermissible. Here, we developed an in vitro human maternal-fetal multicellular model composed of a human hepatic compartment, a bilayer placental barrier, and a human fetal central nervous system compartment using neural stem cells (NSCs) to investigate the effect of AFB on fetal-side NSCs.

The Effect of an eHealth Coaching Program (Smarter Pregnancy) on Attitudes and Practices Toward Periconception Lifestyle Behaviors in Women Attempting Pregnancy: Prospective Study.

Background: Lifestyle behaviors during the periconception period contribute to achievement of a successful pregnancy. Assessment of attitudes and practices toward these modifiable behaviors can aid in identifying gaps in unhealthy lifestyle behaviors with impact on intervention effectiveness.

Objective: This study investigates the effectiveness of coaching by the eHealth program Smarter Pregnancy during the periconception period on improvement of attitudes and practices toward fruit and vegetable intake and smoking in women attempting pregnancy through assisted reproductive technology (ART) or natural conception.

Capturing time-dependent activation of genes and stress-response pathways using transcriptomics in iPSC-derived renal proximal tubule cells.

Transcriptomic analysis is a powerful method in the utilization of New Approach Methods (NAMs) for identifying mechanisms of toxicity and application to hazard characterization. With this regard, mapping toxicological events to time of exposure would be helpful to characterize early events. Here, we investigated time-dependent changes in gene expression levels in iPSC-derived renal proximal tubular-like cells (PTL) treated with five diverse compounds using TempO-Seq transcriptomics with the aims to evaluate the application of PTL for toxicity prediction and to report on temporal effects for the activation of cellular stress response pathways.

Transcriptomic-based evaluation of trichloroethylene glutathione and cysteine conjugates demonstrate phenotype-dependent stress responses in a panel of human in vitro models.

Environmental or occupational exposure of humans to trichloroethylene (TCE) has been associated with different extrahepatic toxic effects, including nephrotoxicity and neurotoxicity. Bioactivation of TCE via the glutathione (GSH) conjugation pathway has been proposed as underlying mechanism, although only few mechanistic studies have used cell models of human origin. In this study, six human derived cell models were evaluated as in vitro models representing potential target tissues of TCE-conjugates: RPTEC/TERT1 (kidney), HepaRG (liver), HUVEC/TERT2 (vascular endothelial), LUHMES (neuronal, dopaminergic), human induced pluripotent stem cells (hiPSC) derived peripheral neurons (UKN5) and hiPSC-derived differentiated brain cortical cultures containing all subtypes of neurons and astrocytes (BCC42).

Myofibrillar protein-chlorogenic acid complexes ameliorate glucose metabolism via modulating gut microbiota in a type 2 diabetic rat model.

Growing evidence suggests that polyphenols could mitigate type 2 diabetes mellitus (T2DM). The glucose-regulatory effects of protein-bound polyphenols, however, have been rarely studied. In this study, macrogenomic and metabolomic analyses were applied to investigate the modulation of myofibrillar protein-chlorogenic acid (MP-CGA) complexes on T2DM rats from the gut microbiota perspective.

Establishment and characterization of a novel human induced pluripotent stem cell line stably expressing the iRFP720 reporter.

Stem cell therapy has great potential for replacing beta-cell loss in diabetic patients. However, a key obstacle to cell therapy's success is to preserve viability and function of the engrafted cells. While several strategies have been developed to improve engrafted beta-cell survival, tools to evaluate the efficacy within the body by imaging are limited.

Drug resistance prediction and resistance genes identification in Mycobacterium tuberculosis based on a hierarchical attentive neural network utilizing genome-wide variants.

Prediction of antimicrobial resistance based on whole-genome sequencing data has attracted greater attention due to its rapidity and convenience. Numerous machine learning-based studies have used genetic variants to predict drug resistance in Mycobacterium tuberculosis (MTB), assuming that variants are homogeneous, and most of these studies, however, have ignored the essential correlation between variants and corresponding genes when encoding variants, and used a limited number of variants as prediction input. In this study, taking advantage of genome-wide variants for drug-resistance prediction and inspired by natural language processing, we summarize drug resistance prediction into document classification, in which variants are considered as words, mutated genes in an isolate as sentences, and an isolate as a document.

Detection and Functional Evaluation of the P2X7 Receptor in hiPSC Derived Neurons and Microglia-Like Cells.

A large body of evidence suggests the involvement of the ATP-gated purinergic receptor P2X7 (P2X7R) in neurodegenerative diseases, including Alzheimer's disease. While it is well-described to be present and functional on microglia cells contributing to inflammatory responses, some reports suggest a neuronal expression of the receptor as well. Here, we present experimental results showing P2X7 receptors to be expressed on human hiPSC-derived microglia-like cells, hiPSC-derived neuronal progenitors and hiPSC-derived matured neuronal cells.

TUBE Project: Transport-Derived Ultrafines and the Brain Effects.

The adverse effects of air pollutants on the respiratory and cardiovascular systems are unquestionable. However, in recent years, indications of effects beyond these organ systems have become more evident. Traffic-related air pollution has been linked with neurological diseases, exacerbated cognitive dysfunction, and Alzheimer's disease.

Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer's Disease.

Neurotrophin receptors such as the tropomyosin receptor kinase A receptor (TrkA) and the low-affinity binding p75 neurotrophin receptor p75 play a critical role in neuronal survival and their functions are altered in Alzheimer's disease (AD). Changes in the dynamics of receptors on the plasma membrane are essential to receptor function. However, whether receptor dynamics are affected in different pathophysiological conditions is unexplored.