Phelpsiqbal6418

At an early age, dKO females displayed lower levels of liver injury and B-cell infiltration, with higher percentage of binuclear hepatocytes. BLU-222 purchase In human samples, H19 expression was higher in females, positively correlated with cirrhosis (in nontumor liver samples) and negatively correlated with CTNNB1 (beta-catenin) mutations and patients' survival (in tumors). Our data demonstrate that the lncRNA H19 is pro-oncogenic during the development of chronic inflammation-mediated HCC in the Mdr2-KO mouse model, mainly by increasing liver injury and decreasing hepatocyte polyploidy in young mice.Sleep abnormalities are often a prominent contributor to withdrawal symptoms following chronic drug use. Notably, rapid eye movement (REM) sleep regulates emotional memory, and persistent REM sleep impairment after cocaine withdrawal negatively impacts relapse-like behaviors in rats. However, it is not understood how cocaine experience may alter REM sleep regulatory machinery, and what may serve to improve REM sleep after withdrawal. Here, we focus on the melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH), which regulate REM sleep initiation and maintenance. Using adult male Sprague-Dawley rats trained to self-administer intravenous cocaine, we did transcriptome profiling of LH MCH neurons after long-term withdrawal using RNA-sequencing, and performed functional assessment using slice electrophysiology. We found that 3 weeks after withdrawal from cocaine, LH MCH neurons exhibit a wide range of gene expression changes tapping into cell membrane signaling, intracellular signaling, and transcriptional regulations. Functionally, they show reduced membrane excitability and decreased glutamatergic receptor activity, consistent with increased expression of voltage-gated potassium channel gene Kcna1 and decreased expression of metabotropic glutamate receptor gene Grm5. Finally, chemogenetic or optogenetic stimulations of LH MCH neural activity increase REM sleep after long-term withdrawal with important differences. Whereas chemogenetic stimulation promotes both wakefulness and REM sleep, optogenetic stimulation of these neurons in sleep selectively promotes REM sleep. In summary, cocaine exposure persistently alters gene expression profiles and electrophysiological properties of LH MCH neurons. Counteracting cocaine-induced hypoactivity of these neurons selectively in sleep enhances REM sleep quality and quantity after long-term withdrawal.Enhancing endocannabinoid signaling produces anxiolytic- and antidepressant-like effects, but the neural circuits involved remain poorly understood. The medial habenula (MHb) is a phylogenetically-conserved epithalamic structure that is a powerful modulator of anxiety- and depressive-like behavior. Here, we show that a robust endocannabinoid signaling system modulates synaptic transmission between the MHb and its sole identified GABA input, the medial septum and nucleus of the diagonal band (MSDB). With RNAscope in situ hybridization, we demonstrate that key enzymes that synthesize or degrade the endocannabinoids 2-arachidonylglycerol (2-AG) or anandamide are expressed in the MHb and MSDB, and that cannabinoid receptor 1 (CB1) is expressed in the MSDB. Electrophysiological recordings in MHb neurons revealed that endogenously-released 2-AG retrogradely depresses GABA input from the MSDB. This endocannabinoid-mediated depolarization-induced suppression of inhibition (DSI) was limited by monoacylglycerol lipase (MAGL) but not by fatty acid amide hydrolase. Anatomic and optogenetic circuit mapping indicated that MSDB GABA neurons monosynaptically project to cholinergic neurons of the ventral MHb. To test the behavioral significance of this MSDB-MHb endocannabinoid signaling, we induced MSDB-specific knockout of CB1 or MAGL via injection of virally-delivered Cre recombinase into the MSDB of Cnr1loxP/loxP or MgllloxP/loxP mice. Relative to control mice, MSDB-specific knockout of CB1 or MAGL bidirectionally modulated 2-AG signaling in the ventral MHb and led to opposing effects on anxiety- and depressive-like behavior. Thus, depression of synaptic GABA release in the MSDB-ventral MHb pathway may represent a potential mechanism whereby endocannabinoids exert anxiolytic and antidepressant-like effects.NF-κB signaling pathway has important roles in the regulation of growth and development of nervous system. This pathway has also been shown to participate in the pathogenesis of schizophrenia. Meanwhile, activity of NF-κB signaling pathway is regulated by several factors including non-coding RNAs (lncRNAs). In the current study, we evaluated expression of nine NF-κB-related lncRNAs namely DILC, ANRIL, PACER, CHAST, ADINR, DICER1-AS1, HNF1A-AS1, H19 and NKILA as well as two mRNA coding genes namely ATG5 and CEBPA in the peripheral blood of patients with schizophrenia compared with matched healthy subjects. Expressions of these genes were assessed by real time PCR technique. Expression of PACER was lower in patients with schizophrenia compared with controls (Posterior beta = - 0.684, P value = 0.049). On the other hand, expressions of CHAST, CEBPA, H19, HNF1A-AS1 and DICER1-AS1 were higher in patients compared with controls (Posterior beta = 0.39, P value = 0.005; Posterior beta = 0.844, P value  less then  0.0001; Posterior beta = 0.467, P value  less then  0.0001; Posterior beta = 1.107, P value = 0.005; Posterior beta = 0.176, P value = 0.044, respectively). We also appraised the diagnostic power of transcript quantities of CHAST, CEBPA, DICER1-AS1, H19 and HNF1A-AS1 in distinguishing between patients with schizophrenia and controls through depicting ROC curves. Based on the area under curve (AUC) values, CEBPA had the best diagnostic power (AUC = 0.948, P  less then  0.0001), followed by H19 (AUC = 0.815, P  less then  0.0001). Taken together, our study demonstrated dysregulation of NF-κB-related lncRNAs and genes in the peripheral blood of patients with schizophrenia and their potential as peripheral markers for this psychiatric condition.