Medicine and Health Sciences Commons^™

Traversing The Triangulum: The Intersection Of Tobacco, Legalised Marijuana And Electronic Vaporisers In Denver, Colorado, Emily Anne Mcdonald, Lucy Popova, Pamela M. Ling

Publications and Research

Objective: To explore the intersection of tobacco, legalised marijuana and electronic vaporiser use among young adults in the ‘natural laboratory’ of Colorado, the first state with legalised retail marijuana.

Methods: We conducted semistructured interviews with 32 young adults (18–26 years old) in Denver, Colorado, in 2015 to understand the beliefs and practices related to the use of tobacco, marijuana and vaporisers.

Results: We found ambiguity about whether the phrase ‘to smoke’ refers to the use of tobacco or marijuana products. Smoking marijuana blunts (emptied cigarillo or tobacco wrap filled with marijuana) was common, but few interpreted this as tobacco use. …

Kcnq Channel Openers Reverse Depressive Symptoms Via An Active Resilience Mechanism, Allyson K. Friedman, Barbara Juarez, Stacy M. Ku, Hongxing Zhang, Rhodora C. Calizo, Jessica J. Walsh, Depish Chaudhury, Song Zhang, Angel Hawkins, David M. Dietz, James W. Murrogh, Maria Ribadeneira, Erik H. Wong, Rachael L. Neve, Ming-Hu Han

Publications and Research

Less than half of patients suffering from major depressive disorder, a leading cause of disability worldwide, achieve remission with current antidepressants, making it imperative to develop more effective treatment. A new therapeutic direction is emerging from the increased understanding of natural resilience as an active stress-coping process. It is known that potassium (Kþ) channels in the ventral tegmental area (VTA) are an active mediator of resilience. However, no druggable targets have been identified to potentiate active resilience mechanisms. In the chronic social defeat stress model of depression, we report that KCNQ-type Kþ channel openers, including FDA-approved drug retigabine (ezogabine), show …

Comparative Error-Free And Error-Prone Translesion Synthesis Of N2‑2′-Deoxyguanosine Adducts Formed By Mitomycin C And Its Metabolite, 2,7-Diaminomitosene, In Human Cells, Arindam Bose, Chaitra Surugihalli, Paritosh Pande, Elise Champeil, Ashis K. Basu

Publications and Research

Mitomycin C (MC) is a cytotoxic and mutagenic antitumor agent that alkylates DNA upon reductive activation. 2,7-Diaminomitosene (2,7-DAM) is a major metabolite of MC in tumor cells, which also alkylates DNA. MC forms seven DNA adducts, including monoadducts and inter- and intrastrand cross-links, whereas 2,7-DAM forms two monoadducts. Herein, the biological effects of the dG-N2 adducts formed by MC and 2,7-DAM have been compared by constructing single-stranded plasmids containing these adducts and replicating them in human embryonic kidney 293T cells. Translesion synthesis (TLS) efficiencies of dG-N2-MC and dG-N2-2,7-DAM were 38 ± 3 and 27 …

Titanocene−Gold Complexes Containing N‑Heterocyclic Carbene Ligands Inhibit Growth Of Prostate, Renal, And Colon Cancers In Vitro, Yiu Fung Mui, Jacob FernáNdez-Gallardo, Benelita T. Elie, Ahmed Gubran, Irene Maluenda, Mercedes Sanau, Marıá Contel

Publications and Research

We report on the synthesis, characterization, and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = −OC(O)-p-C6H4-S−) bound to gold(I)−N-heterocyclic carbene fragments through the thiolate group: [(η5-C5H5)2TiMe(μ-mba)Au(NHC)]. The cytotoxicities of the heterometallic compounds along with those of novel monometallic gold−N-heterocyclic carbene precursors [(NHC)Au(mbaH)] have been evaluated against renal, prostate, colon, and breast cancer cell lines. The highest activity and selectivity and a synergistic effect of the resulting heterometallic species was found for the prostate and colon cancer cell lines. The colocalization of both titanium and gold metals (1:1 ratio) in PC3 prostate cancer …

Drug Repurposing To Target Ebola Virus Replication And Virulence Using Structural Systems Pharmacology, Zheng Zhao, Che Martin, Raymond Fan, Philip E. Bourne, Lei Xie

Publications and Research

Background: The recent outbreak of Ebola has been cited as the largest in history. Despite this global health crisis, few drugs are available to efficiently treat Ebola infections. Drug repurposing provides a potentially efficient solution to accelerating the development of therapeutic approaches in response to Ebola outbreak. To identify such candidates, we use an integrated structural systems pharmacology pipeline which combines proteome-scale ligand binding site comparison, protein-ligand docking, and Molecular Dynamics (MD) simulation.

Results: One thousand seven hundred and sixty-six FDA-approved drugs and 259 experimental drugs were screened to identify those with the potential to inhibit the replication and virulence …