Genome-Wide mRNA Expression Analysis of Acute Psychological Stress Responses.

INTRODUCTION: Most previous studies have examined the effects of acute psychological stress in humans based on select gene panels. The genomic approach may help identify novel genes that underline biological mechanisms of acute psychological stress responses. OBJECTIVE: This exploratory study aimed to investigate genome-wide transcriptional activity changes in response to acute psychological stress. METHODS: The sample included 40 healthy women (mean age 31.4 ± 11.6 years). Twenty-two participants had a stress experience induced by the Trier Social Stress Test (experimental group) and 18 did not (control group). Psychological stress levels and hemodynamic changes were assessed before and after the Trier Social Stress Test. Peripheral blood samples obtained before and after the Trier Social Stress Test were processed for mRNA sequencing. RESULTS: Psychological and hemodynamic stress parameters indicated that the Trier Social Stress Test induced moderate levels of stress in the experimental group. Six genes (HCG26, HCP5, HLA-F, HLA-F-AS1, LOC1019287, and SLC22A16) were up-regulated, and fi ve genes (CA1, FBXO9, SNCA, STRADB, and TRMT12) were down-regulated among those who experienced stress induction, compared with the control group. Nine genes of eleven were linked to endocrine system disorders, neurological disease, and organismal injury and abnormalities. CONCLUSIONS: Of the genes identifi ed in this study, HCP5, SLC22A16, and SNCA genes have previously been proposed as therapeutic targets for cancer and Parkinson disease. Further studies are needed to examine pathological mechanisms through which these genes mediate eff ects of psychological stress on adverse health outcomes. Such studies may ultimately identify therapeutic targets that enhance biological resilience to adverse eff ects of psychological stress.

Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping.

Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson's disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents.