Endothelial cells (ECs) regulate vascular homeostasis, and their dysfunction is a key driver of many cardiovascular and cerebrovascular diseases. Human-induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) provide access to patient-specific vascular cells that can be directed toward arterial, venous, or organotypic phenotypes, enabling personalized in vitro modeling of endothelial pathology. In this review, we discuss how patient-specific iPSC-ECs are used as predictive and personalized two- and three-dimensional models to dissect disease mechanisms and prioritize targeted therapies. We highlight some limitations of this methodology and outline future directions for integrating iPSC-EC-based assays into individualized treatment algorithms.
The relevance of formal hypnotic induction to the experience of trance and its neural correlates is not clear, in that hypnotizability, beliefs and expectation of hypnosis may play a major role. The aim of the study was assessing the EEG brain activity of participants with high (highs) or low hypnotizability scores (lows), aware of their hypnotizability level and informed that the session will include simple relaxation, formal hypnotic induction and neutral hypnosis. A total of 16 highs and 15 lows (according to the Stanford Hypnotic Susceptibility Scale, form A) were enrolled. Their EEGs were recorded during consecutive conditions of open/closed-eyes relaxation, hypnotic induction, neutral hypnosis and post hypnosis not interrupted by interviews. The studied variables were theta, alpha and gamma power spectral density (PSD), and the Determinism (DET) and Entropy (ENT) of the EEG signal Multidimensional Recurrence Plot (mRP). Highs reported significantly greater changes in their state of consciousness than lows across the session. The theta, alpha and gamma PSD did not exhibit condition-related changes in both groups. The Alpha PSD was larger in highs than in lows on midline sites, and the different sides/regions’ theta and gamma PSD were observed in the two groups independently from conditions. ENT showed no correlation with hypnotizability, while DET positively correlated with hypnotizability during hypnosis. In conclusion, the relevance of formal hypnotic induction to the experience of trance may be scarce in highs, as they are aware of their hypnotizability scores and expecting hypnosis. Cognitive processing varies throughout the session depending on the hypnotizability level.
The inherent technical difficulties, ethical/regulatory issues and costs of experimental studies in animal models is prompting investigators to replace as much as possible living organisms with in vitro physiological models named organoids and assembloids. Generated from induced pluripotent stem cells, these three-dimensional structures approximate the complexity of tissues and their interactions, enabling personalized disease modelling and drug testing. The integration of multiple components in assembloids further enhances their predictive value for multi-system interactions and toxicities. This review describes how neuromuscular organoids, incorporating functional neuromuscular junctions and contractile muscle tissue, have been used to replicate, in vitro, complex neuromuscular morpho-functional structures, offering very valuable platforms to study molecular mechanisms and drug effects in models of incurable diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis. In the cardiological field, cardiac organoids and assembloids are proving reliable models for testing drug effects at molecular, morphological, electrophysiological and mechanical level. Recently, the integration of neuronal components into cardiac organoids has provided a potential approach to investigate autonomic function, a fundamental aspect of many neurological, neuromuscular and cardiac diseases. Challenges and limitations still remain, including the non-uniform differentiation protocols across studies, the incomplete maturation of cell phenotypes, and the lack of integrated pharmacokinetic modelling. We discussed some future developments aimed at overcoming such hurdles. Despite their current limitations, organoids and assembloids clearly hold great promises and will help advancing many fields of biomedicine.
Studies conducted in healthy subjects have clearly shown that different hypnotic susceptibility, which is measured by scales, is associated with different functional equivalence between imagery and perception/action (FE), cortical excitability, and information processing. Of note, physiological differences among individuals with high (highs), medium (mediums), and low hypnotizability scores (lows) have been observed in the ordinary state of consciousness, thus independently from the induction of the hypnotic state, and in the absence of specific suggestions. The potential role of hypnotic assessment and its relevance to neurological diseases have not been fully explored. While current knowledge and therapies allow a better survival rate, there is a constant need to optimize rehabilitation treatments and quality of life. The aim of this paper is to provide an overview of hypnotizability-related features and, specifically, to discuss the hypothesis that the stronger FE, the different mode of information processing, and the greater proneness to control pain and the activity of the immune system observed in individuals with medium-to-high hypnotizability scores have potential applications to neurology. Current evidence of the outcome of treatments based on hypnotic induction and suggestions administration is not consistent, mainly owing to the small sample size in clinical trials and inadequate control groups. We propose that hypnotic assessment may be feasible in clinical routine and give additional cues into the treatment and rehabilitation of neurological diseases.