Public Health and Medicine's Need to Respond to Cannabis Commercialization in the United States: A Commentary.

Cannabis legalization has resulted in rapid commercialization, making this new market increasingly attractive to tobacco, alcohol and beverage, agricultural, and pharmaceutical multinational corporations, who are well positioned to capitalize on the synergy between cannabis and their products. The fact that cannabis remains a Schedule I drug under the Controlled Substances Act is inhibiting research, which consequently prevents evidence-based regulation of modern, more potent, engineered cannabis products and their use. Without a research exemption for legitimate studies of commercially available products, cannabis' Schedule I classification makes it very difficult to conduct medical and scientific research to inform policymaking and regulation. As corporate commercialization looms large, public health organizations need to engage the issue of rapid commercialization of cannabis products and press for evidence-based policies based on public health best practices.

Uneven Access to Smoke-Free Laws and Policies and Its Effect on Health Equity in the United States: 2000-2019.

Tobacco control measures have played an important role in the reduction of the cigarette smoking prevalence among US adults.However, although overall smoking prevalence has declined, it remains high among many subpopulations that are disproportionately burdened by tobacco use, resulting in tobacco-related health disparities. Slow diffusion of smoke-free laws to rural regions, particularly in the South and Southeast, and uneven adoption of voluntary policies in single-family homes and multiunit housing are key policy variables associated with the disproportionate burden of tobacco-related health disparities in these subpopulations.Developing policies that expand the reach of comprehensive smoke-free laws not only will facilitate the decline in smoking prevalence among subpopulations disproportionately burdened by tobacco use but will also decrease exposure to secondhand smoke and further reduce tobacco-caused health disparities in the United States.

Characterization of the EBV-Induced Persistent DNA Damage Response.

Epstein-Barr virus (EBV) is an oncogenic herpesvirus that is ubiquitous in the human population. Early after EBV infection in vitro, primary human B cells undergo a transient period of hyper-proliferation, which results in replicative stress and DNA damage, activation of the DNA damage response (DDR) pathway and, ultimately, senescence. In this study, we investigated DDR-mediated senescence in early arrested EBV-infected B cells and characterized the establishment of persistent DNA damage foci. We found that arrested EBV-infected B cells exhibited an increase in promyelocytic leukemia nuclear bodies (PML NBs), which predominantly localized to markers of DNA damage, as well as telomeric DNA. Furthermore, arrested EBV-infected B cells exhibited an increase in the presence of telomere dysfunction-induced foci. Importantly, we found that increasing human telomerase reverse transcriptase (hTERT) expression with danazol, a drug used to treat telomere diseases, permitted early EBV-infected B cells to overcome cellular senescence and enhanced transformation. Finally, we report that EBV-infected B cells undergoing hyper-proliferation are more sensitive than lymphoblastoid cell lines (LCLs) to inhibition of Bloom syndrome-associated helicase, which facilitates telomere replication. Together, our results describe the composition of persistent DNA damage foci in the early stages of EBV infection and define key regulators of this barrier to long-term outgrowth.

Metabolic stress is a barrier to Epstein-Barr virus-mediated B-cell immortalization.

Epstein-Barr virus (EBV) is an oncogenic herpesvirus that has been causally linked to the development of B-cell and epithelial malignancies. Early after infection, EBV induces a transient period of hyperproliferation that is suppressed by the activation of the DNA damage response and a G1/S-phase growth arrest. This growth arrest prevents long-term outgrowth of the majority of infected cells. We developed a method to isolate and characterize infected cells that arrest after this early burst of proliferation and integrated gene expression and metabolic profiling to gain a better understanding of the pathways that attenuate immortalization. We found that the arrested cells have a reduced level of mitochondrial respiration and a decrease in the expression of genes involved in the TCA cycle and oxidative phosphorylation. Indeed, the growth arrest in early infected cells could be rescued by supplementing the TCA cycle. Arrested cells were characterized by an increase in the expression of p53 pathway gene targets, including sestrins leading to activation of AMPK, a reduction in mTOR signaling, and, consequently, elevated autophagy that was important for cell survival. Autophagy was also critical to maintain early hyperproliferation during metabolic stress. Finally, in assessing the metabolic changes from early infection to long-term outgrowth, we found concomitant increases in glucose import and surface glucose transporter 1 (GLUT1) levels, leading to elevated glycolysis, oxidative phosphorylation, and suppression of basal autophagy. Our study demonstrates that oncogene-induced senescence triggered by a combination of metabolic and genotoxic stress acts as an intrinsic barrier to EBV-mediated transformation.