October 2022 Member Publications
Book Chapter: Alexandra N. Nail, Ana P. Ferragut Cardoso, Lakyn K. Montero, and J. Christopher States. “miRNAs and Arsenic-induced Carcinogenesis.” Advances in Pharmacology 96
- Xie W, Tackett AP, Berlowitz JB, Harlow AF, Kathuria H, Galiatsatos P, Fetterman JL, Cho J, Blaha MJ, Hamburg NM, Robertson RM, DeFilippis AP, Hall ME, Bhatnagar A, Benjamin EJ, Stokes AC. Association of Electronic Cigarette Use with Respiratory Symptom Development among U.S. Young Adults. Am J Respir Crit Care Med. 2022 Jun 1;205(11):1320-1329. doi: 10.1164/rccm.202107-1718OC. PMID: 35089853.
Impact Statement: Electronic cigarette (e-cigarette) use is highly prevalent among young adults. However, longitudinal data assessing the association between e-cigarette use and respiratory symptoms are lacking. In this nationally representative cohort of young adults, we found former and current e-cigarette use was associated with higher odds of developing wheezing-related respiratory symptoms, after accounting for cigarette smoking and other combustible tobacco product use.
- Boakye E, Dzaye O, Erhabor J, Osuji N, Obisesan O, Osei AD, Bhatnagar A, Robertson RM, Blaha MJ. Impact of the Food and Drug Administration enforcement policy on flavored e-cigarettes on the online popularity of disposable e-cigarettes: analyses of Google search query data. BMC Public Health. 2022 Oct 19;22(1):1937. doi: 10.1186/s12889-022-14367-3. PMID: 36258175; PMCID: PMC9580152.
Impact Statement: The impact of the U.S. Food and Drug Administration's (FDA) initial enforcement policy on flavored cartridge-based e-cigarettes and subsequent notice for the removal of flavored disposable electronic cigarettes (e-cigarettes) such as Puff Bar from the market has not been well evaluated. We, therefore, sought to examine the impact of the e-cigarette flavor-related policy changes on the online popularity of Puff Bar, a prototypic disposable e-cigarette. The tracking of online search data demonstrates rapid public recognition of the FDA's announcements of tobacco regulatory actions.
- Adhikari S, Kumar R, Driver EM, Bowes DA, Ng KT, Sosa-Hernandez JE, Oyervides-Muñoz MA, Melchor-Martínez EM, Martínez-Ruiz M, Coronado-Apodaca KG, Smith T, Bhatnagar A, Piper BJ, McCall KL, Parra-Saldivar R, Barron LP, Halden RU. Occurrence of Z-drugs, benzodiazepines, and ketamine in wastewater in the United States and Mexico during the Covid-19 pandemic. Sci Total Environ. 2022 Oct 12;857(Pt 2):159351. doi: 10.1016/j.scitotenv.2022.159351. Epub ahead of print. PMID: 36243065; PMCID: PMC9595400.
Impact Statement: This study measured ketamine concentration in wastewater in the United States, which reflected some of the highest ketamine consumption rates presented in the literature in the United States using Wastewater-based epidemiology (WBE). The present study highlights the need for monitoring substance use during high-stress events, such as the COVID-19 pandemic, and illustrates the utility of WBE to provide data that cannot be obtained by other means to determine actual drug use, which is the sum of both licit and illicit drug sourcing and consumption.
Carll AP, Arab C, Salatini R, Miles MD, Nystoriak MA, Fulghum KL, Riggs DW, Shirk GA, Theis WS, Talebi N, Bhatnagar A, Conklin DJ. E-cigarettes and their lone constituents induce cardiac arrhythmia and conduction defects in mice. Nat Commun. 2022 Oct 25;13(1):6088. doi: 10.1038/s41467-022-33203-1. PMID: 36284091; PMCID: PMC9596490.
Impact Statement: Our findings in mice indicate e-cigarette aerosols can rapidly disrupt cardiac conduction and cause cardiac arrhythmias. Similar effects in humans could precipitate severe cardiac events, including atrial or ventricular fibrillation, and cardiac arrest. The findings provide new insight to the public, clinicians, and regulatory agencies about the potential health impacts of e-cigarettes and their individual ingredients. The findings of the paper were reported worldwide by over 320 news outlets.
- Sagaram M, Royer AJ, Hu H, Rajhans A, Parthasarathy R, Krishnasamy SS, Mokshagundam SP, Kong M, Schwandt ML, Parajuli D, Cave MC, Vatsalya V. Illustration of Gut-Thyroid Axis in Alcohol Use Disorder: Interplay of Gut Dysfunction, Pro-Inflammatory Responses, and Thyroid Function. Cells. 2022 Oct 1;11(19):3100. doi: 10.3390/cells11193100. PMID: 36231061; PMCID: PMC9563601.
Impact Statement: This research investigated mechanisms for the thyroid dysfunction associated with alcohol use. Mechanistic biomarkers were measured in human subjects.
Conklin DJ. How Irritating! Electronic Cigarettes Not "95% Safer" Than Combustible Cigarettes: Recent Mechanistic Insights Into Endothelial Dysfunction. Arterioscler Thromb Vasc Biol. 2022 Nov;42(11):1351-1354. doi: 10.1161/ATVBAHA.122.318468. Epub 2022 Oct 26. PMID: 36288291.
Impact Statement: This invited Editorial highlights findings of human and animal studies that demonstrate the negative vascular consequences of exposure to electronic cigarette aerosols or their constituents, i.e., vaping. Moreover, the animal study demonstrates a novel mechanism whereby irritating constituents in aerosols can harm blood vessels. This Editorial encourages FDA to regulate the level of irritants in tobacco product aerosols to lower levels in order to protect human health.
- Furmanek S, Salunkhe V, Pahwa S, Samanapally H, Nathala P, Xu Q, Ali T, Deepti F, Glynn A, McGuffin T, Titus D, Farah I, Jones CM, Ramirez JA, Clifford SP, Arnold FW, Kong M, Roser L, Huang J; Center of Excellence for Research in Infectious Diseases Coronavirus Study Group on behalf of the COVID-19 CardioVascular Research Group. Correlations of Before and After Event Echocardiographic Parameters with Troponin and BNP in Hospitalized COVID-19 Patients With Cardiovascular Events. J Cardiothorac Vasc Anesth. 2022 Sep 2:S1053-0770(22)00593-6. doi: 10.1053/j.jvca.2022.08.024. Epub ahead of print. PMID: 36184474; PMCID: PMC9436869.
Impact Statement: Left heart systolic and diastolic dysfunction before a cardiovascular event were correlated with initial myocardial injury levels and increase in right heart size on after-event echocardiography was correlated with maximal myocardial injury in COVID-19 patients.
- Mehra S, Srinivasan S, Singh S, Zhou Z, Garrido V, Silva IC, Totiger TM, Dosch AR, Dai X, Dawra RK, Jala VR, Shi C, Datta J, VanSaun M, Merchant N, Nagathihalli N. Urolithin A attenuates severity of chronic pancreatitis associated with continued alcohol intake by inhibiting PI3K/AKT/mTOR signaling. Am J Physiol Gastrointest Liver Physiol. 2022 Oct 1;323(4):G375-G386. doi: 10.1152/ajpgi.00159.2022. Epub 2022 Sep 13. PMID: 36098401.
Impact Statement: Heavy alcohol consumption is the dominant risk factor for chronic pancreatitis (CP); however, treatment and prevention strategies for alcoholic chronic pancreatitis (ACP) remains limited. The present study demonstrates that ACP induction in C57BL/6 mice causes significant acinar cell injury, pancreatic stellate cell (PSC) activation, exocrine function insufficiency, and an increased fibroinflammatory response when compared with alcohol or CP alone. Our novel findings presented here demonstrate the utility of Uro A as an effective therapeutic agent in attenuating alcoholic chronic pancreatitis (ACP) severity with alcohol continuation after established disease, through suppression of the PI3K/AKT/mTOR signaling pathway.
Kouokam JC ,Meaza I, Wise JP Sr. Inflammatory effects of hexavalent chromium in the lung: A comprehensive review. Toxicol Appl Pharmacol. 2022 Nov 15;455:116265. doi: 10.1016/j.taap.2022.116265. Epub 2022 Oct 5. PMID: 36208701.
Impact Statement: Besides smoking, lung cancer can be caused by other factors, including heavy metals such as cadmium, nickel, arsenic, beryllium and hexavalent chromium [Cr(VI)], which is used in multiple settings, resulting in widespread environmental and occupational exposures as well as heavy use. This work provides insights into the mechanisms by which Cr(VI) induces lung inflammation.
- SenthilKumar G, Gutierrez Huerta CA, Freed JK, Beyer AM, Fancher IS, LeBlanc AJ. New Developments in Translational Microcirculatory Research. Am J Physiol Heart Circ Physiol. 2022 Oct 28. doi: 10.1152/ajpheart.00566.2022. Epub ahead of print. PMID: 36306213.
Impact Statement:This is a mini-review highlighting the original research papers and review articles that were submitted to the American Journal of Physiology- Heart and Circulatory Physiology Call for Papers collection: New Developments in Translational Microcirculatory Research. In addition to putting disease- and location-dependent original research articles into context of the existing literature, we discuss the state-of-the-art reviews on both coronary endothelial function and assessing microvascular health in different organ systems, as well as how to establish rigor in clinical trial design.
- Warner JB, Guenthner SC, Hardesty JE, McClain CJ, Warner DR, Kirpich IA. Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease. World J Gastroenterol. 2022 Sep 28;28(36):5280-5299. doi: 10.3748/wjg.v28.i36.5280. PMID: 36185629; PMCID: PMC9521517.
Impact Statement: This review provides basic information on liver-targeting drug delivery platforms, including their benefits and limitations, and summarizes the current research efforts to apply them to the treatment of ALD in rodent models. We also discuss gaps in knowledge in the field, which when addressed, may help to increase the efficacy of novel therapies and better translate them to humans.
- Cummins TD, Powell DW, Wilkey DW, Brady M, Benz FW, Barati MT, Caster DJ, Klein JB, Merchant ML. Quantitative Mass Spectrometry Normalization in Urine Biomarker Analysis in Nephrotic Syndrome. Glomerular Dis. 2022 Jul;2(3):121-131. doi: 10.1159/000522217. Epub 2022 Jan 27. PMID: 36199623; PMCID: PMC9529004.
Impact Statement:For this report, we analyzed urine samples from patients with focal segmental glomerulosclerosis (FSGS) as proof of principle of development of an innovative method for identifying novel diagnostic markers for chronic kidney disease (CKD). We present a mass spectrometry-based method utilizing multiplex tandem mass tag (TMT) quantification and improved protein quantification using reporter ion normalization to urinary creatinine to analyze urinary proteins from patients with a form of nephrotic syndrome (FSGS). Our findings provide support for the utility of this method for identification of novel diagnostic markers of CKD and identify SERPINA1 and ORM1 as promising candidate diagnostic markers for FSGS.
- Peart NJ, Hwang JY, Quesnel-Vallières M, Sears MJ, Yang Y, Stoilov P, Barash Y, Park JW, Lynch KW, Carstens RP. The global Protein-RNA interaction map of ESRP1 defines a post-transcriptional program that is essential for epithelial cell function. iScience. 2022 Sep 23;25(10):105205. doi: 10.1016/j.isci.2022.105205. PMID: 36238894; PMCID: PMC9550651.
Impact Statement:The genome-wide binding sites of the epithelial splicing regulators, ESRP 1/2, were thoroughly examined with high-throughput sequencing (RNA-seq and eCLIP-seq) in epithelial cells of mouse epidermis. This study provides a transcriptome-wide map of ESRP1 binding and regulation in epithelial cells which is essential to understand disease-related splicing regulation.
- Shi H, Prough RA, McClain CJ, Song M. Different Types of Dietary Fat and Fructose Interactions Result in Distinct Metabolic Phenotypes in Male Mice. J Nutr Biochem. 2022 Oct 19:109189. doi: 10.1016/j.jnutbio.2022.109189. Epub ahead of print. PMID: 36272691.
Impact Statement:Fat and fructose are the two major components over-represented in the Western diet. The aim of this study was to determine the combined effects of different types of dietary fat and fructose on the development of nonalcoholic fatty liver disease (NAFLD) in a murine model. Our study shed light on the role of different types of dietary fat and fructose interaction on the development of metabolic disorders and provides preclinical evidence that would be helpful for future clinical studies on the prevention and treatment of NAFLD.
- Shuck B, Hart JL, Walker KL, Rai J, Srivastava S, Srivastava S, Rai S, Bhatnagar A, Keith RJ. Workplace Culture and Biomarkers of Health Risk. Int J Environ Res Public Health. 2022 Sep 21;19(19):11920. doi: 10.3390/ijerph191911920. PMID: 36231223; PMCID: PMC9565767.
Impact Statement:Workplace culture has been studied for impact on health risk; however, connections with robust biologic markers of health remain to be established. We examined associations between the work environment and urinary levels of catecholamines and their metabolites as biomarkers of sympathetic nervous system activity, indicative of stress. Our finding were consistent with an important relationship between workplace environment and sympathetic nervous system activity.
Wise JP Jr. The intersection between toxicology and aging research: A toxic aging coin perspective. Front Aging. 2022 Sep 21;3:1014675. doi: 10.3389/fragi.2022.1014675. PMID: 36213344; PMCID: PMC9532842.
Impact Statement:This perspective paper serves as a call for expanding research at the intersection of toxicology and aging, taking a dual view of this intersection as (1) how age impacts toxic effects, and (2) how chemicals accelerate aging and act as 'gerontogens.' We are entering a new world paradigm where a significant portion (~20%) of our population will reach a geriatric age and continue living as geriatrics for multiple decades, but there is a detrimental lack of data considering how geriatrics may be distinctly affected by chemicals from other age groups. Similarly, the term 'gerontogen' was coined in 1987, but since its introduction there has been little research into how chemicals act as gerontogens. In this paper I introduce the concept of a "toxic aging coin" to emphasize this dual intersection, and discuss the relevance of both sides in the context of the brain (my area of expertise), though it could be applied to any organ system.
Wise SS, Lu H, Speer RM, Wise JP, Young J, Toyoda JH, Meaza I, Croom-Perez TJ, Kouokam JC, Specht A, Liu KJ, Hoyle GW, Wise JP. Chromium distribution in an oropharyngeal aspiration model for hexavalent chromium in rats. Toxicol Appl Pharmacol. 2022 Oct 22:116294. doi: 10.1016/j.taap.2022.116294. Epub ahead of print. PMID: 36283442.
Impact Statement:Particulate Cr(VI) is a well-known lung carcinogen but the early and initiating carcinogenic mechanisms are still poorly understood. Establishing an accurate and relevant exposure regimen is crucial to further our understanding for environmentally relevant exposures. We evaluated an oropharyngeal aspiration exposure route for zinc chromate particles in Wistar rats and found that oropharyngeal aspiration provides a practicable exposure route for chronic and sub-chronic exposures of Cr(VI) particles.
Young JL, Xin Y, Rajesh M, Cai L. Editorial: Cardiovascular diseases related to diabetes and obesity - volume II. Front Endocrinol (Lausanne). 2022 Oct 5;13:1044326. doi: 10.3389/fendo.2022.1044326. PMID: 36277685; PMCID: PMC9583653.
Impact Statement:Despite our advances at the bench and in the clinic, approximately 17.9 million people die each year from CVDs, accounting for 32% of all deaths globally . Therefore, it is imperative to better understand the underlying mechanisms involved in the pathogenesis of obesity- and diabetes-related cardiovascular events to develop more effective, targeted therapies aimed at prevention and attenuation of disease progression. This editorial introduces the second volume of a special issue on Cardiovascular diseases related to diabetes and obesity, compiling recent clinical, pre-clinical and basic research studies as well as review articles aimed at filling the knowledge gaps and expanding our understanding of the complicated and intertwined relationship between obesity, diabetes, and CVDs.
- Zhang Y, Du L, Yan J, Bai Q, Niu Q, Mo Y, Zhang Q, Nie J. Prenatal benzo[a]pyrene exposure impairs hippocampal synaptic plasticity and cognitive function in SD rat offspring during adolescence and adulthood via HDAC2-mediated histone deacetylation. Ecotoxicol Environ Saf. 2022 Nov;246:114180. doi: 10.1016/j.ecoenv.2022.114180. Epub 2022 Oct 17. PMID: 36265406.
Impact Statement: Benzo[a]pyrene (B[a]P) is a widespread carcinogenic pollutant in the environment. Although previous studies have demonstrated the neurodevelopmental toxicity of B[a]P, the precise mechanisms underlying the neurotoxic effects induced by prenatal B[a]P exposure remain largely unknown. Our results suggest that prenatal B[a]P exposure impairs cognitive function and hippocampal synaptic plasticity of offspring in adolescence and adulthood, and HDAC2-mediated histone deacetylation plays a crucial role in these deficits.
- Feng S, Xu Z, Zhang Z, Mo Y, Deng Y, Li L, Fei S, Wu J, Wang K, Zhang Q, Song J, Zhou R. RNA-Seq approach to investigate the effects of melatonin on bone marrow-derived dendritic cells from dextran sodium sulfate-induced colitis mice. Toxicology. 2022 Nov;481:153354. doi: 10.1016/j.tox.2022.153354. Epub 2022 Oct 17. PMID: 36265525.
Impact Statement: Melatonin (MLT) was reported to have therapeutic effects on inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) due to its anti-inflammatory and immunomodulatory properties. However, whether the beneficial effects of melatonin on colitis are through altering the immune response of bone marrow-derived dendritic cells (BMDCs) has not been well characterized. Our findings may provide some clues for understanding MLT inhibiting inflammatory response in DSS-induced colitis, which may be through alteration of BMDCs function.