Genetics, Genomics...

The central nervous system is the last major organ system in the vertebrate body to yield its cellular structure, due to the complexity of its cells and their interactions. The fundamental unit of the nervous system is the neuron, which forms complex circuits that receive and integrate information and generate adaptive responses. Each neuron is composed of an input domain consisting of multiple dendrites along with the cell body, which is also responsible for the majority of macromolecule synthesis for the cell...

RATIONALE AND SCOPE OF THE GUIDELINES Pain is a subjective unpleasant sensory and emotional experience. Acute pain occurs irrespective of age and has a prevalence of about 5% of the general population. Surgical procedures and painful diagnostic procedures are the main causes of this unpleasant and dangerous phenomenon for hospitalized children. It should be remembered that maintaining homeostasis in a child undergoing surgery is also affected by provision of an adequate level of analgesia and sedation as well as nerve conduction block within the surgical site...

Physical exercise is rewarding and protective against drug abuse and addiction. However, the neural mechanisms underlying these actions remain unclear. Here, we report that long-term wheel-running produced a more robust increase in c-fos expression in the red nucleus (RN) than in other brain regions. Anatomic and functional assays demonstrated that most RN magnocellular portion (RNm) neurons are glutamatergic. Wheel-running activates a subset of RNm glutamate neurons that project to ventral tegmental area (VTA) dopamine neurons...

AIMS: Sleep loss at high altitude (HA) play major role in worsening of neuropsychological functions, such as attention, memory and decision making. This study investigates the role of phosphorylated delta sleep inducing peptide (p-DSIP) in improving sleep architecture during chronic hypobaric hypoxia (HH) exposure and restoration of spatial navigational memory. METHODS: Morris water maze (MWM) trained rats were exposed to HH at 7620 m. p-DSIP was injected intra-peritoneally (10 μg/Kg bw) during HH exposure as an intervention against sleep alteration...

This study investigated the recently reported association between alcohol dependence and accelerated ageing and the potential effects of abstinence and relapse on DNA methylation status using Levine's epigenetic clock to estimate DNA methylation age in two independent cohorts. The first sample comprised 88 (15 female) detoxified patients with alcohol use disorder (AUD) and 32 (5 female) healthy control (CON) subjects (NCT02615977), and the second included 69 (10 female) AUD patients that were followed up for 12 months with respect to relapse (n = 38, 4 female) and abstinence (n = 31, 6 female) (NCT01679145)...

The gut microbiota plays a fundamental role in human nutrition and metabolism and may have direct implications for type 2 diabetes and associated preconditions. An improved understanding of relations between human gut microbiota and glucose metabolism could lead to novel opportunities for type 2 diabetes prevention, but human observational studies reporting on such findings have not been extensively reviewed. Here, we review the literature on associations between gut microbiota and markers and stages of glucose dysregulation and insulin resistance in healthy adults and in adults with metabolic disease and risk factors...

BACKGROUND: Ovarian cancer is the world's dreaded disease and its prevalence is expanding globally. The study of integrated molecular networks is crucial for the basic mechanism of cancer cells and their progression. During the present investigation, we have examined different flavonoids that target protein kinases B (AKT1) protein which exerts their anticancer efficiency intriguing the role in cross-talk cell signalling, by metabolic processes through in-silico approaches. METHOD: Molecular dynamics simulation (MDS) was performed to analyze and evaluate the stability of the complexes under physiological conditions and the results were congruent with molecular docking...

BACKGROUND: The current study evaluates the free gallic acid (GA) and GA-loaded mesoporous silica nanoparticles (MSNs) antidepressant efficacy in a rat model of depression caused by reserpine. METHODS: By using a scanning electron microscope (SEM), dynamic light scattering (DLS), and zeta potential, MSNs and GA-loaded MSNs were characterized. The efficiency of encapsulation and the release of GA-loaded MSNs were also investigated. The effect of GA, either in its free form or loaded on (MSNs) on oxidative stress biomarkers and monoamine neurotransmitters levels (serotonin (5-HT), norepinephrine (NEP), and dopamine (DA)), were evaluated in these areas (cortex, hippocampus, striatum, and hypothalamus) of control, a depression model of rat, a depression model of rat treated with either free GA, MSNs or GA loaded MSNs...

OBJECTIVE: Resveratrol (RSV) is a polyphenol compound found in grapes, veratrum and other plants. It has been reported that RSV has anti-inflammatory, anti-oxidant, anti-cancer and other pharmacological effects. However, the impacts of RSV on development of nervous system are not understood well. The study aims to investigate RSV's neuroprotective effect during development and to provide a health care for pregnant women and their fetuses with RSV supplementation. METHODS: In this study, we induced human induced pluripotent stem cells (hiPSCs) to form the embryoid bodies (EBs) and cerebral organoids (COs) with 3 dimensional (3D) culture...

BACKGROUND: Colorectal cancer is among the most common cancers and accounts for nearly 9% of all cancers in the world. Chrysophanol is a naturally occurring anthraquinone exerts a number of pharmacological activities such as anti-inflammation, anti-cancer, anti-bacterial, anti-viral, and anti-oxidant effects. This study aims to produce a novel gemini chrysophanol nanoparticles (Gemini-Chr NPs), and to evaluate its anti-cancer effect on the human colorectal cancer cell lines...

Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are peptide hormones and growth factors. A major pathological feature of both Alzheimer's dis-ease (AD) and Parkinson's disease (PD) is the loss of synaptic transmission in the cortex in AD and the loss of dopaminergic synapses in the nigra-striatal dopaminergic projection. Several studies demonstrate that GLP-1 and GIP receptor agonists protect synapses and synaptic transmission from the toxic events that underlie AD and PD...

BACKGROUND: Long-term amphetamine and methamphetamine dependence has been linked to cerebral blood perfusion, metabolic, and white matter abnormalities. Several studies have linked methamphetamine abuse to cortical grey matter reduction, though with divergent findings. Few publications investigate unmethylated amphetamine's potential effects on cortical grey matter. This work investigated if amphetamine dependent patients showed reduced cortical grey matter thickness. Subjects were 40 amphetamine dependent subjects and 40 healthy controls...

The opioid crisis has reached epidemic proportions in the United States with rising overdose death rates. Identifying the underlying factors that contribute to addiction vulnerability may lead to more effective prevention strategies. Supply side environmental factors are a major contributing component. Psychosocial factors such as stress, trauma, and adverse childhood experiences have been linked to emotional pain leading to self-medication. Genetic and epigenetic factors associated with brain reward pathways and impulsivity are known predictors of addiction vulnerability...

Epigenetic regulation of cellular identity and function is at least partly achieved through changes in covalent modifications on DNA and histones. Much progress has been made in recent years to understand how these covalent modifications affect cell identity and function. Despite the advances, whether and how epigenetic factors contribute to memory formation is still poorly understood. In this review, we discuss recent progress in elucidating epigenetic mechanisms of learning and memory, primarily at the DNA level, and look ahead to discuss their potential implications in reward memory and development of drug addiction...

Objective: Pilot study to assess utility in opioid use disorder (OUD) of a panel of single nucleotide polymorphisms in genes previously related to substance use disorder (SUD) and/or phenotypes that predispose individuals to OUD/SUD. Design: Genetic association study. Setting: West Virginia University's Chestnut Ridge Center Comprehensive Opioid Abuse Treatment (COAT) clinic for individuals diagnosed with OUD. Patients: Sixty patients 18 years of age or older with OUD undergoing medication (buprenorphine/naloxone)-assisted treatment (MAT); all sixty patients recruited contributed samples for genetic analysis...

Mammalian gene expression is inherently stochastic1,2 , and results in discrete bursts of RNA molecules that are synthesized from each allele3-7 . Although transcription is known to be regulated by promoters and enhancers, it is unclear how cis-regulatory sequences encode transcriptional burst kinetics. Characterization of transcriptional bursting, including the burst size and frequency, has mainly relied on live-cell4,6,8 or single-molecule RNA fluorescence in situ hybridization3,5,8,9 recordings of selected loci...

Application of deep learning to genomic datasets is an exciting area that is rapidly developing and is primed to revolutionize genome analysis. We embrace the potential that deep learning holds for understanding genome biology, and we encourage further advances in this area, extending to all aspects of genomics research.