Recent Innovations in Footwear and the Role of Smart Footwear in Healthcare-A Survey.

Smart shoes have ushered in a new era of personalised health monitoring and assistive technologies. Smart shoes leverage technologies such as Bluetooth for data collection and wireless transmission, and incorporate features such as GPS tracking, obstacle detection, and fitness tracking. As the 2010s unfolded, the smart shoe landscape diversified and advanced rapidly, driven by sensor technology enhancements and smartphones' ubiquity.

Unlocking the epigenetic symphony: histone acetylation's impact on neurobehavioral change in neurodegenerative disorders.

Recent genomics and epigenetic advances have empowered the exploration of DNA/RNA methylation and histone modifications crucial for gene expression in response to stress, aging and disease. Interest in understanding neuronal plasticity's epigenetic mechanisms, influencing brain rewiring amid development, aging and neurodegenerative disorders, continues to grow. Histone acetylation dysregulation, a commonality in diverse brain disorders, has become a therapeutic focus.

Epigenetics in fetal alcohol spectrum disorder.

During pregnancy, alcohol abuse and its detrimental effects on developing offspring are major public health, economic and social challenges. The prominent characteristic attributes of alcohol (ethanol) abuse during pregnancy in humans are neurobehavioral impairments in offspring due to damage to the central nervous system (CNS), causing structural and behavioral impairments that are together named fetal alcohol spectrum disorder (FASD). Development-specific alcohol exposure paradigms were established to recapitulate the human FASD phenotypes and establish the underlying mechanisms.

Molecular Insights into Epigenetics and Cannabinoid Receptors.

The actions of cannabis are mediated by G protein-coupled receptors that are part of an endogenous cannabinoid system (ECS). ECS consists of the naturally occurring ligands N-arachidonylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB and CB cannabinoid receptors. Epigenetics are heritable changes that affect gene expression without changing the DNA sequence, transducing external stimuli in stable alterations of the DNA or chromatin structure.

Preclinical and randomized clinical evaluation of the p38α kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration.

The endosome-associated GTPase Rab5 is a central player in the molecular mechanisms leading to degeneration of basal forebrain cholinergic neurons (BFCN), a long-standing target for drug development. As p38α is a Rab5 activator, we hypothesized that inhibition of this kinase holds potential as an approach to treat diseases associated with BFCN loss. Herein, we report that neflamapimod (oral small molecule p38α inhibitor) reduces Rab5 activity, reverses endosomal pathology, and restores the numbers and morphology of BFCNs in a mouse model that develops BFCN degeneration.

Binge-like Prenatal Ethanol Exposure Causes Impaired Cellular Differentiation in the Embryonic Forebrain and Synaptic and Behavioral Defects in Adult Mice.

An embryo's in-utero exposure to ethanol due to a mother's alcohol drinking results in a range of deficits in the child that are collectively termed fetal alcohol spectrum disorders (FASDs). Prenatal ethanol exposure is one of the leading causes of preventable intellectual disability. Its neurobehavioral underpinnings warrant systematic research.

Histone Methylation Regulation in Neurodegenerative Disorders.

Advances achieved with molecular biology and genomics technologies have permitted investigators to discover epigenetic mechanisms, such as DNA methylation and histone posttranslational modifications, which are critical for gene expression in almost all tissues and in brain health and disease. These advances have influenced much interest in understanding the dysregulation of epigenetic mechanisms in neurodegenerative disorders. Although these disorders diverge in their fundamental causes and pathophysiology, several involve the dysregulation of histone methylation-mediated gene expression.

Endosomal Dysfunction Induced by Directly Overactivating Rab5 Recapitulates Prodromal and Neurodegenerative Features of Alzheimer's Disease.

Neuronal endosomal dysfunction, the earliest known pathobiology specific to Alzheimer's disease (AD), is mediated by the aberrant activation of Rab5 triggered by APP-β secretase cleaved C-terminal fragment (APP-βCTF). To distinguish pathophysiological consequences specific to overactivated Rab5 itself, we activate Rab5 independently from APP-βCTF in the PA-Rab5 mouse model. We report that Rab5 overactivation alone recapitulates diverse prodromal and degenerative features of AD.

Postnatal Ethanol-Induced Neurodegeneration Involves CB1R-Mediated β-Catenin Degradation in Neonatal Mice.

Alcohol consumption by pregnant women may produce neurological abnormalities that affect cognitive processes in children and are together defined as fetal alcohol spectrum disorders (FASDs). However, the molecular underpinnings are still poorly defined. In our earlier studies, we found that ethanol exposure of postnatal day 7 (P7) mice significantly induced widespread neurodegeneration mediated via endocannabinoids (eCBs)/cannabinoid receptor type 1 (CB1R).

Postnatal Ethanol Exposure Activates HDAC-Mediated Histone Deacetylation, Impairs Synaptic Plasticity Gene Expression and Behavior in Mice.

Background: Alcohol consumption during pregnancy is widespread and contributes to pediatric neurological defects, including hippocampal and neocortex dysfunction, causing cognitive deficits termed fetal alcohol spectrum disorders. However, the critical mechanisms underlying these brain abnormalities remain poorly described.

Methods: Using a postnatal ethanol exposure (PEE) animal model and pharmacological, epigenetic, synaptic plasticity-related and behavioral approaches, we discovered a novel persistent epigenetic mechanism of neurodegeneration in neonatal hippocampus and neocortex brain regions and of cognitive decline in adult animals.

Endocannabinoid System and Alcohol Abuse Disorders.

Δ-tetrahydrocannabinol (Δ-THC), the primary active component in Cannabis sativa preparations such as hashish and marijuana, signals by binding to cell surface receptors. Two types of receptors have been cloned and characterized as cannabinoid (CB) receptors. CB1 receptors (CB1R) are ubiquitously present in the central nervous system (CNS) and are present in both inhibitory interneurons and excitatory neurons at the presynaptic terminal.

Distinct functions of endogenous cannabinoid system in alcohol abuse disorders.

Δ -tetrahydrocannabinol, the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signalling by binding to cannabinoid CB and CB receptors on the cell surface. The CB receptors are present in both inhibitory and excitatory presynaptic terminals and the CB receptors are found in neuronal subpopulations in addition to microglial cells and astrocytes and are present in both presynaptic and postsynaptic terminals. Subsequent to the discovery of the endocannabinoid (eCB) system, studies have suggested that alcohol alters the eCB system and that this system plays a major role in the motivation to abuse alcohol.

Potential Mechanisms Underlying the Deleterious Effects of Synthetic Cannabinoids Found in Spice/K2 Products.

The chief psychoactive constituent of many bioactive phytocannabinoids (Δ⁸-tetrahydrocannabinol, Δ⁸-THC) found in hemp, cannabis or marijuana plants are scientifically denoted by the Latin term, , acts on cell surface receptors. These receptors are ubiquitously expressed. To date, two cannabinoid receptors have been cloned and characterized.

CB1R regulates CDK5 signaling and epigenetically controls Rac1 expression contributing to neurobehavioral abnormalities in mice postnatally exposed to ethanol.

Fetal alcohol spectrum disorders (FASD) represent a wide array of defects that arise from ethanol exposure during development. However, the underlying molecular mechanisms are limited. In the current report, we aimed to further evaluate the cannabinoid receptor type 1 (CB1R)-mediated mechanisms in a postnatal ethanol-exposed animal model.

Neurofilament light interaction with GluN1 modulates neurotransmission and schizophrenia-associated behaviors.

Neurofilament (NFL) proteins have recently been found to play unique roles in synapses. NFL is known to interact with the GluN1 subunit of N-methyl-D-aspartic acid (NMDAR) and be reduced in schizophrenia though functional consequences are unknown. Here we investigated whether the interaction of NFL with GluN1 modulates synaptic transmission and schizophrenia-associated behaviors.

Activity-dependent Signaling and Epigenetic Abnormalities in Mice Exposed to Postnatal Ethanol.

Postnatal ethanol exposure has been shown to cause persistent defects in hippocampal synaptic plasticity and disrupt learning and memory processes. However, the mechanisms responsible for these abnormalities are less well studied. We evaluated the influence of postnatal ethanol exposure on several signaling and epigenetic changes and on expression of the activity-regulated cytoskeletal (Arc) protein in the hippocampus of adult offspring under baseline conditions and after a Y-maze spatial memory (SP) behavior (activity).

CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice.

Alcohol exposure can affect brain development, leading to long-lasting behavioral problems, including cognitive impairment, which together is defined as fetal alcohol spectrum disorder (FASD). However, the fundamental mechanisms through which this occurs are largely unknown. In this study, we report that the exposure of postnatal day 7 (P7) mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R) in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2) levels.

Endocannabinoid system in neurodegenerative disorders.

Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well-defined. Several mechanisms have been proposed to contribute to the development of NDDs.

A single day of 5-azacytidine exposure during development induces neurodegeneration in neonatal mice and neurobehavioral deficits in adult mice.

The present study was undertaken to evaluate the immediate and long-term effects of a single-day exposure to 5-Azacytidine (5-AzaC), a DNA methyltransferase inhibitor, on neurobehavioral abnormalities in mice. Our findings suggest that the 5-AzaC treatment significantly inhibited DNA methylation, impaired extracellular signal-regulated kinase (ERK1/2) activation and reduced expression of the activity-regulated cytoskeleton-associated protein (Arc). These events lead to the activation of caspase-3 (a marker for neurodegeneration) in several brain regions, including the hippocampus and cortex, two brain areas that are essential for memory formation and memory storage, respectively.

Epigenetic Mechanisms in Developmental Alcohol-Induced Neurobehavioral Deficits.

Alcohol consumption during pregnancy and its damaging consequences on the developing infant brain are significant public health, social, and economic issues. The major distinctive features of prenatal alcohol exposure in humans are cognitive and behavioral dysfunction due to damage to the central nervous system (CNS), which results in a continuum of disarray that is collectively called fetal alcohol spectrum disorder (FASD). Many rodent models have been developed to understand the mechanisms of and to reproduce the human FASD phenotypes.

Fetal Alcohol Spectrum Disorder: Potential Role of Endocannabinoids Signaling.

One of the unique features of prenatal alcohol exposure in humans is impaired cognitive and behavioral function resulting from damage to the central nervous system (CNS), which leads to a spectrum of impairments referred to as fetal alcohol spectrum disorder (FASD). Human FASD phenotypes can be reproduced in the rodent CNS following prenatal ethanol exposure. Several mechanisms are expected to contribute to the detrimental effects of prenatal alcohol exposure on the developing fetus, particularly in the developing CNS.

Neurofilament subunits are integral components of synapses and modulate neurotransmission and behavior in vivo.

Synaptic roles for neurofilament (NF) proteins have rarely been considered. Here, we establish all four NF subunits as integral resident proteins of synapses. Compared with the population in axons, NF subunits isolated from synapses have distinctive stoichiometry and phosphorylation state, and respond differently to perturbations in vivo.