Project description:Opioid abuse poses significant risk to individuals in the United States and epigenetic changes are a leading potential biomarker of opioid abuse. Current evidence, however, is mostly limited to candidate gene analysis in whole blood. Here, we provide Illumina HumanMethylationEPIC array data generated in dorsolateral prefrontal cortex tissue from 153 deceased invidiuals: 72 who died of acute opioid intoxication, 53 psychiatric controls, and 28 normal controls. Using these data, we conducted an epigenome-wide association study and identified one CpG site within a gene (NTN1) that may be related to opioid use. We also detected accelerated PhenoAge in opioid samples compared to control samples.
Project description:To identify possible target molecules for acute alcohol intoxication therapy, we used microarray analysis to compare cerebella gene expression profiles of control and acute alcohol-intoxicated rats. We first established a model of acute alcohol intoxication in SD rats, and then used rat cDNA microarray to profile mRNA expression in the cerebella of alcohol-intoxicated rats (experimental group) and saline-treated rats (control group).
Project description:To identify possible target molecules for acute alcohol intoxication therapy, we used microarray analysis to compare cerebella gene expression profiles of control and acute alcohol-intoxicated rats. We first established a model of acute alcohol intoxication in SD rats, and then used rat cDNA microarray to profile mRNA expression in the cerebella of alcohol-intoxicated rats (experimental group) and saline-treated rats (control group). A six chip study using total RNA recovered from three separate experimental groups and three separate control groups. We first established a model of acute alcohol intoxication in SD rats, and then used rat cDNA microarray to profile mRNA expression in the cerebella of alcohol-intoxicated rats (experimental group) and saline-treated rats (control group). Cerebellar tissues from three rats were ground to a mixed sample,so we use 3 rats in one group.
Project description:Cholera toxin (CT) is the etiological agent of cholera. Here we report that multiple classes of fucosylated glycoconjugates function in CT binding and intoxication of intestinal epithelial cells. In Colo205 cells, knockout of B3GNT5, the enzyme required for synthesis of lacto- and neolacto-series glycosphingolipids (GSLs), reduces CT binding but sensitizes cells to intoxication. Overexpressing B3GNT5 to generate more fucosylated GSLs confers protection against intoxication, indicating that fucosylated GSLs act as decoy receptors for CT. Knockout (KO) of B3GALT5 causes increased production of fucosylated O-linked and N-linked glycoproteins, and leads to increased CT binding and intoxication. Knockout of B3GNT5 in B3GALT5 KO cells eliminates production of fucosylated GSLs but increases intoxication, identifying fucosylated glycoproteins as functional receptors for CT. These findings provide insight into molecular determinants regulating CT sensitivity of host cells.
Project description:Opioids analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit their use. It has been recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. Further study indicated distinct alterations in the gut microbiome and metabolome following morphine treatment, contributing to the negative consequences associated with opioid use. However, it is unclear how opioids modulate gut homeostasis in the context of a hospital acquired bacterial infection. In the current study, a mouse model of C. rodentium infection was used to investigate the role of morphine in the modulation of gut homeostasis in the context of a hospital acquired bacterial infection. Citrobacter rodentium is a natural mouse pathogen that models intestinal infection by enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) and causes attaching and effacing lesions and colonic hyperplasia. Morphine treatment resulted in 1) the promotion of C. rodentium systemic dissemination, 2) increase in virulence factors expression with C. rodentium colonization in intestinal contents, 3) altered gut microbiome, 4) damaged integrity of gut epithelial barrier function, 5) inhibition of C. rodentium-induced increase in goblet cells, and 6) dysregulated IL-17A immune response. This is the first study to demonstrate that morphine promotes pathogen dissemination in the context of intestinal C. rodentium infection, indicating morphine modulates virulence factor-mediated adhesion of pathogenic bacteria and induces disruption of mucosal host defense during C. rodentium intestinal infection in mice. This study demonstrates and further validates a positive correlation between opioid drug use/abuse and increased risk of infections, suggesting over-prescription of opioids may increase the risk in the emergence of pathogenic strains and should be used cautiously. Therapeutics directed at maintaining gut homeostasis during opioid use may reduce the comorbidities associated with opioid use for pain management.
Project description:This study profiles targeted mRNA expression in neonatal saliva to investigate the sex-specific effects of prenatal opioid exposure. Saliva samples collected within 48 hours of birth from opioid-exposed and non-exposed neonates were analyzed using the NanoString nCounter Analysis System with a custom CodeSet targeting 72 genes, including housekeeping genes. Raw RCC files are provided for all assay instances, and processed data are provided as normalized, log2-transformed expression values for the QC-passed samples included in the final analysis.