Intestinal dysbiosis causes spatial memory impairment in alcohol-exposed male mice by inducing neuroinflammation.

Alcohol abuse damages the brain and triggers cognitive impairment. Intestinal dysbiosis has recently been shown to be involved in psychiatric disorders, which suggests the possibility of intestine-to-brain interactions in the development of alcohol abuse. In this study, chronic intermittent alcohol exposure (CIAE) model was established in C57BL/6 male mice and the spatial memory were detected by Barnes maze (n = 16/group).

BCI Improves Alcohol-Induced Cognitive and Emotional Impairments by Restoring pERK-BDNF.

Binge drinking causes a range of problems especially damage to the nervous system, and the specific neural mechanism of brain loss and behavioral abnormalities caused by which is still unclear. Extracellular regulated protein kinases (ERK) maintain neuronal survival, growth, and regulation of synaptic plasticity by phosphorylating specific transcription factors to regulate expression of brain-derived neurotrophic factor (BDNF). Dual-specific phosphatase 1 (DUSP1) and DUSP6 dephosphorylate tyrosine and serine/threonine residues in ERK1/2 to inactivate them.

Development and Validation of a Multimodality Model Based on Whole-Slide Imaging and Biparametric MRI for Predicting Postoperative Biochemical Recurrence in Prostate Cancer.

Purpose To develop and validate a machine learning multimodality model based on preoperative MRI, surgical whole-slide imaging (WSI), and clinical variables for predicting prostate cancer (PCa) biochemical recurrence (BCR) following radical prostatectomy (RP). Materials and Methods In this retrospective study (September 2015 to April 2021), 363 male patients with PCa who underwent RP were divided into training ( = 254; median age, 69 years [IQR, 64-74 years]) and testing ( = 109; median age, 70 years [IQR, 65-75 years]) sets at a ratio of 7:3. The primary end point was biochemical recurrence-free survival.

Prediction of clinically significant prostate cancer using radiomics models in real-world clinical practice: a retrospective multicenter study.

Purpose: To develop and evaluate machine learning models based on MRI to predict clinically significant prostate cancer (csPCa) and International Society of Urological Pathology (ISUP) grade group as well as explore the potential value of radiomics models for improving the performance of radiologists for Prostate Imaging Reporting and Data System (PI-RADS) assessment.

Material And Methods: A total of 1616 patients from 4 tertiary care medical centers were retrospectively enrolled. PI-RADS assessments were performed by junior, senior, and expert-level radiologists.

The practical clinical role of machine learning models with different algorithms in predicting prostate cancer local recurrence after radical prostatectomy.

Background: The detection of local recurrence for prostate cancer (PCa) patients following radical prostatectomy (RP) is challenging and can influence the treatment plan. Our aim was to construct and verify machine learning models with three different algorithms based on post-operative mpMRI for predicting local recurrence of PCa after RP and explore their potential clinical value compared with the Prostate Imaging for Recurrence Reporting (PI-RR) score of expert-level radiologists.

Methods: A total of 176 patients were retrospectively enrolled and randomly divided into training (n = 123) and testing (n = 53) sets.

Machine learning-based CT texture analysis in the differentiation of testicular masses.

Purpose: To evaluate the ability of texture features for distinguishing between benign and malignant testicular masses, and furthermore, for identifying primary testicular lymphoma in malignant tumors and identifying seminoma in testicular germ cell tumors, respectively.

Methods: We retrospectively collected 77 patients with an abdominal and pelvic enhanced computed tomography (CT) examination and a histopathologically confirmed testicular mass from a single center. The ROI of each mass was split into two parts by the largest cross-sectional slice and deemed to be two samples.

Epigenetic Regulation of Neuroinflammation in Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease and clinically manifests with cognitive decline and behavioral disabilities. Over the past years, mounting studies have demonstrated that the inflammatory response plays a key role in the onset and development of AD, and neuroinflammation has been proposed as the third major pathological driving factor of AD, ranking after the two well-known core pathologies, amyloid β (Aβ) deposits and neurofibrillary tangles (NFTs). Epigenetic mechanisms, referring to heritable changes in gene expression independent of DNA sequence alterations, are crucial regulators of neuroinflammation which have emerged as potential therapeutic targets for AD.

Alcohol Consumption During Adolescence Alters the Cognitive Function in Adult Male Mice by Persistently Increasing Levels of DUSP6.

Binge alcohol drinking during adolescence has long-term effects on the adult brain that alter brain structure and behaviors, but the underlying mechanisms remain poorly understood. Extracellular signal-regulated kinase (ERK) is involved in the synaptic plasticity and pathological brain injury by regulating the expression of cyclic adenosine monophosphate response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF). Dual-specificity phosphatase 6 (DUSP6) is a critical effector that dephosphorylates ERK1/2 to control the basal tone, amplitude, and duration of ERK signaling.

Value of a combined magnetic resonance imaging-based radiomics-clinical model for predicting extracapsular extension in prostate cancer: a preliminary study.

Background: Extracapsular extension (ECE) of prostate cancer (PCa) is closely related to the treatment and prognosis of patients, and radiomics has been widely used in the study of PCa. This study aimed to evaluate the value of a combined model considering magnetic resonance imaging (MRI)-based radiomics and clinical parameters for predicting ECE in PCa.

Methods: A total of 392 PCa patients enrolled in this retrospective study were randomly divided into the training and validation sets at a ratio of 7:3.

DNA Methylation in Alcohol Use Disorder.

Excessive drinking damages the central nervous system of individuals and can even cause alcohol use disorder (AUD). AUD is regulated by both genetic and environmental factors. Genes determine susceptibility to alcohol, and the dysregulation of epigenome drives the abnormal transcription program and promotes the occurrence and development of AUD.

Decitabine improves MMS-induced retinal photoreceptor cell damage by targeting DNMT3A and DNMT3B.

Introduction: Retinitis pigmentosa (RP) is a group of neurodegenerative retinopathies causing blindness due to progressive and irreversible photoreceptor cell death. The alkylating agent methyl methanesulfonate (MMS) can induce selective photoreceptor cell death, which is used to establish RP animal models. MMS induces DNA base damage by adding alkyl groups to DNA, and epigenetic modifications influence DNA damage response.

and Expression is Regulated by C in CRISPR/Cas9-Edited HepG2 Cells.

Functional (G>A, rs2242480) in cytochrome P450 () regulates the drug-metabolizing enzyme expression. The objective of this study was to investigate whether regulates both basal and rifampicin (RIF)-induced expression and enzyme activity of and in gene-edited human HepG2 cells. GG and AA genotype HepG2 cells were established using the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) single nucleotide polymorphism technology and homology-directed repair in the GA HepG2 cell line.

Dual attention guided multiscale neural network trained with curriculum learning for noninvasive prediction of Gleason Grade Group from MRI.

Background: The Gleason Grade Group (GG) is essential in assessing the malignancy of prostate cancer (PCa) and is typically obtained by invasive biopsy procedures in which sampling errors could lead to inaccurately scored GGs. With the gradually recognized value of bi-parametric magnetic resonance imaging (bpMRI) in PCa, it is beneficial to noninvasively predict GGs from bpMRI for early diagnosis and treatment planning of PCa. However, it is challenging to establish the connection between bpMRI features and GGs.

Predicting clinically significant prostate cancer with a deep learning approach: a multicentre retrospective study.

Purpose: This study aimed to develop deep learning (DL) models based on multicentre biparametric magnetic resonance imaging (bpMRI) for the diagnosis of clinically significant prostate cancer (csPCa) and compare the performance of these models with that of the Prostate Imaging and Reporting and Data System (PI-RADS) assessment by expert radiologists based on multiparametric MRI (mpMRI).

Methods: We included 1861 consecutive male patients who underwent radical prostatectomy or biopsy at seven hospitals with mpMRI. These patients were divided into the training (1216 patients in three hospitals) and external validation cohorts (645 patients in four hospitals).

Utility of Clinical-Radiomic Model to Identify Clinically Significant Prostate Cancer in Biparametric MRI PI-RADS V2.1 Category 3 Lesions.

Purpose: To determine the predictive performance of the integrated model based on clinical factors and radiomic features for the accurate identification of clinically significant prostate cancer (csPCa) among Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions.

Materials And Methods: A retrospective study of 103 patients with PI-RADS 3 lesions who underwent pre-operative 3.0-T MRI was performed.

Modafinil rescues repeated morphine-induced synaptic and behavioural impairments via activation of D1R-ERK-CREB pathway in medial prefrontal cortex.

Long-term opioid abuse causes a variety of long-lasting cognitive impairments such as attention, impulsivity and working memory. These cognitive impairments undermine behavioural treatment for drug abuse and lead to poor treatment retention and outcomes. Modafinil is a wake-promoting drug that shows potential in improving attention and memory in humans and animals.

Ethanol-Induced Neuronal and Cognitive/Emotional Impairments are Accompanied by Down-Regulated NT3-TrkC-ERK in Hippocampus.

Aims: Ethanol ingestion affects cognition and emotion, which have been attributed to the dysfunction of specific brain structures. Studies of alcoholic patients and animal models consistently identify reduced hippocampal mass as a key ethanol-induced brain adaptation. This study evaluated how neuroadaptation in the hippocampus (Hip) produced by ethanol contributed to related behavioral deficits in male and female rats.

Neuroprotective Effects of Grape Seed Procyanidins on Ethanol-Induced Injury and Oxidative Stress in Rat Hippocampal Neurons.

Aims: Ethanol is a small molecule capable of interacting with numerous targets in the brain, the mechanisms of which are complex and still poorly understood. Studies have revealed that ethanol-induced hippocampal neuronal injury is associated with oxidative stress. Grape seed procyanidin (GSP) is a new type of antioxidant that is believed to scavenge free radicals and be anti-inflammatory.

Dual-specificity phosphatase 15 (DUSP15) in the nucleus accumbens is a novel negative regulator of morphine-associated contextual memory.

Drug relapse among addicts often occurs due to the learned association between drug-paired cues and the rewarding effects of these drugs, such as morphine. Contextual memory associated with morphine has a central role in maintenance and relapse. We showed that morphine-conditioned place preference (CPP) activates extracellular-regulated protein kinase (ERK) in the nucleus accumbens (NAc).

PI3K-AKT-GSK3β-CREB signaling pathway regulates anxiety-like behavior in rats following alcohol withdrawal.

Background: Alcohol abuse and anxiety disorders often occur concurrently, but their underlying cellular mechanisms remain unclear. Neuroadaptation within the medial prefrontal cortex (mPFC) have been implicated in the molecular mechanisms underlying alcohol drinking behavior and withdrawal.

Methods: A chronic alcohol exposure rat model (35 consecutive days of 10% alcohol intake and 48 h of withdrawal) was established, then, wortmannin (0.

5-Aza-2'-deoxycytidine in the medial prefrontal cortex regulates alcohol-related behavior and Ntf3-TrkC expression in rats.

Recent studies have indicated that DNA methylation plays an important role in the development of alcohol abuse. 5-Aza-2'-deoxycytidine (5-Aza-dc), an inhibitor of DNA methyltransferases, was FDA approved for myelodysplastic syndrome treatment. However, it is unclear whether 5-Aza-dc is involved in alcohol abuse.

Dopamine D1 and D3 Receptors Modulate Heroin-Induced Cognitive Impairment through Opponent Actions in Mice.

Background: Chronic abuse of heroin leads to long-lasting and complicated cognitive impairment. Dopamine receptors are critically involved in the impulsive drug-driven behavior and the altered attention, processing speed, and mental flexibility that are associated with higher relapse rates. However, the effects of the different dopamine receptors and their possible involvement in heroin-induced cognitive impairment remain unclear.

A Population-Based Study of Four Genes Associated with Heroin Addiction in Han Chinese.

Recent studies have shown that variants in FAT atypical cadherin 3 (FAT3), kinectin 1 (KTN1), discs large homolog2 (DLG2) and deleted in colorectal cancer (DCC) genes influence the structure of the human mesolimbic reward system. We conducted a systematic analysis of the potential functional single nucleotide polymorphisms (SNPs) in these genes associated with heroin addiction. We scanned the functional regions of these genes and identified 20 SNPs for genotyping by using the SNaPshot method.

AUTS2 in the nucleus accumbens is essential for heroin-induced behavioral sensitization.

Autism susceptibility candidate 2 (AUTS2) is a gene associated with autism and mental retardation. Recent studies have suggested an association of the AUTS2 gene with heroin dependence, and reduced AUTS2 gene expression may confer increased susceptibility to heroin dependence. However, the functional role of the AUTS2 protein in regulating enduring neuroadaptations in response to heroin exposure has not been established.