Alcohol: Epigenome alteration and inter/transgenerational effect.

While DNA serves as the fundamental genetic blueprint for an organism, it is not a static entity. Gene expression, the process by which genetic information is utilized to create functional products like proteins, can be modulated by a diverse range of environmental factors. Epigenetic mechanisms, including DNA methylation, histone modification, and microRNAs, play a pivotal role in mediating the intricate interplay between the environment and gene expression. Intriguingly, alterations in the epigenome have the potential to be inherited across generations. Alcohol use disorder (AUD) poses significant health issues worldwide. Alcohol has the capability to induce changes in the epigenome, which can be inherited by offspring, thus impacting them even in the absence of direct alcohol exposure. This review delves into the impact of alcohol on the epigenome, examining how its effects vary based on factors such as the age of exposure (adolescence or adulthood), the duration of exposure (chronic or acute), and the specific sample collected (brain, blood, or sperm). The literature underscores that alcohol exposure can elicit diverse effects on the epigenome during different life stages. Furthermore, compelling evidence from human and animal studies demonstrates that alcohol induces alterations in epigenome content, affecting both the brain and blood. Notably, rodent studies suggest that these epigenetic changes can result in lasting phenotype alterations that extend across at least two generations. In conclusion, the comprehensive literature analysis supports the notion that alcohol exposure induces lasting epigenetic alterations, influencing the behavior and health of future generations. This knowledge emphasizes the significance of addressing the potential transgenerational effects of alcohol and highlights the importance of preventive measures to minimize the adverse impact on offspring.

A systematic review of interleukin-31 inhibitors in the treatment of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a neuroimmunological skin disease. Severe itching is the most challenging symptom which affects patients' quality of life. T helper 2-derived cytokines, such as interleukin-31 and oncostatin M (OSM), play a crucial role in PN pathogenesis. Nemolizumab and vixarelimab are two biologics acting as IL-31 inhibitors. Vixarelimab also suppresses the OSM activity. This systematic review evaluates the efficacy and safety of nemolizumab and vixarelimab in PN management. METHODS: A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science up to September 17th, 2023. Clinical trials and cohort studies published in English were included. RESULTS: Among a total of 96 relevant records, five were included. The results of four studies with 452 patients using nemolizumab showed that a significantly higher percentage of patients treated with nemolizumab demonstrated a reduction in peak pruritus numerical rating scale (PP-NRS) and investigator's global assessment along with improved sleep disturbance (SD) and quality of life than the placebo group. Moreover, one study administered vixarelimab to 49 PN patients, and their finding illustrated a higher rate of subjects who received vixarelimab experienced ≥ 4-point diminution in worst itch NRS, visual analog scale, healing of representative lesions, and SD quality compared to the placebo group. CONCLUSIONS: IL-31 inhibitors suggest distinct advantages in improving pruritus, sleep quality, and overall quality of life in subjects with moderate-to-severe PN. Further clinical studies are recommended to compare the effectiveness of these biologics to other therapeutic choices.

The role of lateral habenula NMDA receptors in tramadol-induced conditioning.

The role of the lateral habenula (LHb) as a hub for receiving and relaying signals from the limbic system to serotonergic, dopaminergic, and norepinephrinergic regions in the brainstem makes this area a critical region in the control of reward and addiction. Behavioral evidence reveals the vital role of the LHb in negative symptoms during withdrawal. In this investigation, we study the role of the LHb N-Methyl D-Aspartate receptor (NMDAR) in the modulation of tramadol reward. Male adult Wistar rats were used in this study. The effect of intra-LHb micro-injection of NMDAR agonist (NMDA, 0.1, 0.5, 2 µg/rat) and antagonist (D-AP5, 0.1, 0.5, 1 µg/rat) was evaluated in conditioned place preference (CPP) paradigm. The obtained results showed that intra-LHb administration of NMDA induced place aversion dose-dependently, while blockade of NMDAR in the LHb using D-AP5 micro-injection led to an increased preference score in the CPP task. Co-administration of NMDA (0.5 µg/rat) with tramadol (4 mg/kg) reduced preference score, while co-administration of D-AP5 (0.5 µg/rat) with a non-effective dose of tramadol (1 mg/kg) potentiate the rewarding effect of tramadol. LHb receives inputs from the limbic system and projects to the monoaminergic nuclei in the brainstem. It has been declared that NMDAR is expressed in LHb, and as obtained data revealed, these receptors could modulate the rewarding effect of tramadol. Therefore, NMDA receptors in the LHb might be a new target for modulating tramadol abuse.

Microfluidic Synthesis of Ultrasmall Chitosan/Graphene Quantum Dots Particles for Intranasal Delivery in Alzheimer's Disease Treatment.

Nanoparticles (NPs) based therapies for Alzheimer's disease (AD) attract interest due to their ability to pass across or bypass the blood-brain barrier. Chitosan (CS) NPs or graphene quantum dots (GQDs) are promising drug carriers with excellent physicochemical and electrical properties. The current study proposes the combination of CS and GQDs in ultrasmall NP form not as drug carriers but as theranostic agents for AD. The microfluidic-based synthesis of the CS/GQD NPs with optimized characteristics makes them ideal for transcellular transfer and brain targeting after intranasal (IN) delivery. The NPs have the ability to enter the cytoplasm of C6 glioma cells in vitro and show dose and time-dependent effects on the viability of the cells. IN administration of the NPs to streptozotocin (STZ) induced AD-like models lead to a significant number of entrances of the treated rats to the target arm in the radial arm water maze (RAWM) test. It shows the positive effect of the NPs on the memory recovery of the treated rats. The NPs are detectable in the brain via in vivo bioimaging due to GQDs as diagnostic markers. The noncytotoxic NPs localize in the myelinated axons of hippocampal neurons. They do not affect the clearance of amyloid ß (Aß) plaques at intercellular space. Moreover, they showed no positive impact on the enhancement of MAP2 and NeuN expression as markers of neural regeneration. The memory improvement in treated AD rats may be due to neuroprotection via the anti-inflammation effect and regulation of the brain tissue microenvironment that needs to be studied.

Camouflage and masking behavior in adult autism.

Introduction: Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and social interaction across multiple contexts. Social camouflaging was first shown to be a characteristic of autistic persons, who actively try to disguise and compensate for their autism features in social contexts in an effort to socially blend in better. Recently, an increasing, though still insufficient, number of studies has been conducted on the concept of camouflage; however, different aspect of it, from psychopathology and etiology to its complications and consequences, are not clearly defined. We aimed to systematically review the existing literature on camouflage in autistic adults to describe the correlates of camouflage, motivations for exhibiting camouflage behavior, and the potential impacts of camouflage on the mental health of autistic individuals. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist guidelines to conduct a systematic review. The databases of PubMed and Scopus, and PsycInfo were searched for eligible studies. Studies were published between January 1st, 1980, to April 1st, 2022. Results: We included 16 articles, of which four studies were qualitative and 11 were quantitative. One study used a mix method. The assessment tools used for camouflage, the correlates of camouflage including autism severity, gender, age, cognitive profile and neuroanatomical correlates, reasons for camouflage and the impacts of camouflaging behavior on mental health are discussed in this review. Discussion: In synthesizing the literature, we conclude that camouflage seems to be more common among females who report more autistic symptoms themselves. There may also be some differences between men and women in reasons of exhibiting it and its neuroanatomical correlates. Further research is needed as to why this phenomenon is more prevalent in females with implications for gender related cognitive and neuroanatomical differences. Effects of camouflage on mental health and daily life measures of individuals such as employment, university graduation, relationship, financial status, and quality of life should be studied with more details in future studies.

Brain Homogenate of a Rat Model of Alzheimer's Disease Modifies the Secretome of 3D Cultured Periodontal Ligament Stem Cells: A Potential Neuroregenerative Therapy.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to neuronal cell death and manifested by cognitive disorders and behavioral impairment. Mesenchymal stem cells (MSCs) are one of the most promising candidates to stimulate neuroregeneration and prevent disease progression. Optimization of MSC culturing protocols is a key strategy to increase the therapeutic potential of the secretome. Objectives: Here, we investigated the effect of brain homogenate of a rat model of AD (BH-AD) on the enhancement of protein secretion in the secretome of periodontal ligament stem cells (PDLSCs) when cultured in a 3D environment. Moreover, the effect of this modified secretome was examined on neural cells to study the impact of the conditioned medium (CM) on stimulation of regeneration or immunomodulation in AD. Methods: PDLSCs were isolated and characterized. Then, the spheroids of PDLSCs were generated in a modified 3D culture plate. PDLSCs-derived CM was prepared in the presence of BH-AD (PDLSCs-HCM) and the absence of it (PDLSCs-CM). The viability of C6 glioma cells was assessed after exposure to different concentrations of both CMs. Then, a proteomic analysis was performed on the CMs. Results: Differentiation into adipocytes and high expression of MSCs markers verified the precise isolation of PDLSCs. The PDLSC spheroids were formed after 7 days of 3D culturing, and their viability was confirmed. The effect of CMs on C6 glioma cell viability showed that both CMs at low concentrations (> 20 mg/mL) had no cytotoxic effect on C6 neural cells. The results showed that PDLSCs-HCM contains higher concentrations of proteins compared to PDLSCs-CM, including Src-homology 2 domain (SH2)-containing PTPs (SHP-1) and muscle glycogen phosphorylase (PYGM) proteins. SHP-1 has a role in nerve regeneration, and PYGM is involved in glycogen metabolism. Conclusions: The modified secretome derived from 3D cultured spheroids of PDLSCs treated by BH-AD as a reservoir of regenerating neural factors can serve as a potential source for AD treatment.