September 2022 Member Publications
Banerjee M, Yaddanapudi K, States JC. Zinc supplementation prevents mitotic accumulation in human keratinocyte cell lines upon environmentally relevant arsenic exposure. Toxicol Appl Pharmacol. 2022 Sep 24;454:116255. doi: 10.1016/j.taap.2022.116255. Epub ahead of print. PMID: 36162444.
Impact Statement: Dysregulated cell cycle is an early event in several chronic arsenic exposure-induced diseases. In this work, we demonstrate that environmentally relevant arsenic exposure leads to accumulation of human skin cell lines exclusively in mitosis as early as 24 hours and this can be prevented by zinc supplementation.
- Smith T, Holm RH, Keith RJ, Amraotkar AR, Alvarado CR, Banecki K, Choi B, Santisteban IC, Bushau-Sprinkle AM, Kitterman KT, Fuqua J, Hamorsky KT, Palmer KE, Brick JM, Rempala GA, Bhatnagar A. Quantifying the relationship between sub-population wastewater samples and community-wide SARS-CoV-2 seroprevalence. Sci Total Environ. 2022 Sep 6;853:158567. doi: 10.1016/j.scitotenv.2022.158567. Epub ahead of print. PMID: 36084773; PMCID: PMC9444845.
Impact Statement: Robust epidemiological models relating wastewater to community disease prevalence are lacking. Assessments of SARS-CoV-2 infection rates have relied primarily on convenience sampling, which does not provide reliable estimates of community disease prevalence due to inherent biases. This study conducted serial stratified randomized samplings to estimate the prevalence of SARS-CoV-2 antibodies and the analysis indicates that wastewater may provide robust estimates of community spread of infection, in line with the modeled prevalence estimates obtained from stratified randomized sampling, and is therefore superior to publicly available health data.
- Adhihetty PK, Halder S, Jasinski JB, Fu XA, Nantz MH. Harnessing the cation-π interactions of metalated gold monolayer-protected clusters to detect aromatic volatile organic compounds. Talanta. 2022 Sep 13;253:123915. doi: 10.1016/j.talanta.2022.123915. Epub ahead of print. PMID: 36155323.
Impact Statement: The paper investigated chemiresistors made from carboxylate-linked alkali metals bound to the surface of gold monolayer- protected clusters formulated on microfabricated interdigitated electrodes. Sensor responses to aromatic and non-aromatic VOCs are consistent with a model for cation-π interactions arising from association of electron-rich aromaticπ-systems to metal ions. The sensors are promising for detection of benzene, toluene, ethylbenzene and xylene.
- Salazar-González RA, Doll MA, Hein DW. N-acetyltransferase 2 genetic polymorphism modifies genotoxic and oxidative damage from new psychoactive substances. Arch Toxicol. 2022 Sep 23. doi: 10.1007/s00204-022-03383-2. Epub ahead of print. PMID: 36138126.
Impact Statement: The use of new psychoactive substances (NPS) as drugs of abuse is common and increasingly popular, particularly among youth. We investigated the gene-environment interaction between N-acetyltransferase 2 (NAT2) genetic polymorphism and toxicity after exposure to these chemicals. We found that exposure to these psychoactive substances results in genotoxic and oxidative damage that is modified by the NAT2 genetic polymorphism.
- Habil MR, Salazar-González RA, Doll MA, Hein DW. N-acetyltransferase 2 acetylator genotype-dependent N-acetylation and toxicity of the arylamine carcinogen β-naphthylamine in cryopreserved human hepatocytes. Arch Toxicol. 2022 Sep 16. doi: 10.1007/s00204-022-03381-4. Epub ahead of print. PMID: 36112171.
Impact Statement: We used cryopreserved human hepatocytes that express rapid, intermediate, and slow acetylator N-acetyltransferase 2 (NAT2) genotypes to measure the N-acetylation of β-naphthylamine (BNA) which is one of the aromatic amines found in cigarette smoke including E-cigarettes. We investigated the role of NAT2 genetic polymorphism in genotoxicity and oxidative stress induced by BNA. We found that the N-acetylation of BNA is NAT2 genotype dependent in cryopreserved human hepatocytes and document an important role for NAT2 genetic polymorphism in modifying BNA-induced genotoxicity and oxidative damage.
Hong KU, Gardner JQ, Doll MA, Stepp MW, Wilkey DW, Benz FW, Cai J, Merchant ML, Hein DW. Proteomic analysis of arylamine N-acetyltransferase 1 knockout breast cancer cells: Implications in immune evasion and mitochondrial biogenesis. Toxicol Rep. 2022 Jul 19;9:1566-1573. doi: 10.1016/j.toxrep.2022.07.010. PMID: 36158865; PMCID: PMC9500399.
Impact Statement: This paper reveals potential and novel mechanisms by which arylamine N-acetyltransferase 1 (NAT1) contributes to breast cancer growth. Delineating these mechanisms will help us not only better-understand breast cancer biology but also identify new therapeutic approaches.
Hong KU, Salazar-González RA, Walls KM, Hein DW. Transcriptional Regulation of Human Arylamine N-Acetyltransferase 2 Gene by Glucose and Insulin in Liver Cancer Cell Lines. Toxicol Sci. 2022 Sep 26:kfac103. doi: 10.1093/toxsci/kfac103. Epub ahead of print. PMID: 36156098.
Impact Statement: This paper reports, for the first time, that a xenobiotic metabolic enzyme, arylamine N-acetyltransferase 2 (NAT2) is induced by glucose and insulin in liver cancer cells. Our findings implicates NAT2 in lipid and cholesterol homeostasis. NAT2 is a potentially important genetic factor that alters the risk of hyperlipidemia which raises the risk of cardiometabolic disorders.
- Liang S, Pang Z, Zhou N, Liu Z, Guo Q, Huang J, Zou W. Development and validation of a prediction model for catheter-related bladder discomfort: a prospective observational study. Br J Anaesth. 2022 Sep 23:S0007-0912(22)00461-5. doi: 10.1016/j.bja.2022.08.018. Epub ahead of print. PMID: 36163078.
Impact Statement: Urinary catheterisation is a routine practice in the perioperative period. However, patients undergoing surgery with an indwelling urinary catheter frequently complain of an urge to void or discomfort in the supra-pubic region after emerging from general anaesthesia in the PACU, known as catheter-related bladder discomfort (CRBD), which could cause major distress. The goal of this observational study was to develop a prediction model that can be used to assess risks of developing CRBD in patients undergoing surgery.
Huang J, El-Kersh K, Mann KK, James KA, Cai L. Overview of the cardiovascular effects of environmental metals: New preclinical and clinical insights. Toxicol Appl Pharmacol. 2022 Sep 17;454:116247. doi: 10.1016/j.taap.2022.116247. Epub ahead of print. PMID: 36122736.
Impact Statement: Environmental causes of cardiovascular diseases (CVDs) are global health issues. In particular, an association between metal exposure and CVDs has become evident but causal evidence still lacks. The symposium at the Society of Toxicology 2022 annual meeting addressed epidemiological, clinical, pre-clinical animal model-derived and mechanism-based evidence by five presentations and the data summarized by the presenters infers a potential causal link between multiple metals and CVDs and defines differences and commonalities. Therefore, summary of these presentations may accelerate the development of efficient preventive and therapeutic strategies by facilitating collaborations among multidisciplinary investigators.
- Ghosh S, Moorthy B, Haribabu B, Jala VR. Cytochrome P450 1A1 is essential for the microbial metabolite, Urolithin A-mediated protection against colitis. Front Immunol. 2022 Sep 8;13:1004603. doi: 10.3389/fimmu.2022.1004603. PMID: 36159798; PMCID: PMC9493474.
Impact Statement: Previously, we showed that treatment with microbial metabolite Urolithin A mitigated ulcerative colitis in mice (Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway | Nature Communications). The current publication described that Urolithin A requires expression of host Cytochrome P450 1A1 to protect against chemical-induced colitis in mouse models and enhancement of gut barrier function.
- Ait-Aissa K, Norwood-Toro LE, Terwoord J, Young M, Paniagua LA, Hader SN, Hughes WE, Hockenberry JC, Beare JE, Linn J, Kohmoto T, Kim J, Betts DH, LeBlanc AJ, Gutterman DD, Beyer AM. Noncanonical Role of Telomerase in Regulation of Microvascular Redox Environment With Implications for Coronary Artery Disease. Function (Oxf). 2022 Sep 3;3(5):zqac043. doi: 10.1093/function/zqac043. PMID: 36168588; PMCID: PMC9508843.
Impact Statement: This study is the first evidence that mitochondrial telomerase reverse transcriptase (TERT), independent of its nuclear functions, plays a critical physiological role in preserving NO-mediated vasodilation in the microcirculation. Additionally, the balance of mitochondrial to nuclear TERT is fundamentally altered in states of human disease, like CVD, that are driven by increased expression of dominant negative splice variants.
- Rowe G, Heng DS, Beare JE, Hodges NA, Tracy EP, Murfee WL, LeBlanc AJ. Stromal Vascular Fraction Reverses the Age-Related Impairment in Revascularization following Injury. J Vasc Res. 2022 Sep 8:1-15. doi: 10.1159/000526002. Epub ahead of print. PMID: 36075199.
Impact Statement: This study reveals the negative effect that advancing age has on stimulating new vessel growth (angiogenesis) in baseline and ischemic injury; however, treatment with stromal vascular fraction therapy from young donors can reverse the impairment.
- Warner JB, Zirnheld KH, Hu H, Floyd A, Kong M, McClain CJ, Kirpich IA. Analysis of alcohol use, consumption of micronutrient and macronutrients, and liver health in the 2017-2018 National Health and Nutrition Examination Survey. Alcohol Clin Exp Res. 2022 Sep 20. doi: 10.1111/acer.14944. Epub ahead of print. PMID: 36124871.
Impact Statement: Alcohol use is a major global healthcare burden that contributes to numerous adverse health outcomes, including liver disease. Many factors influence individual susceptibility to alcohol-associated diseases, including nutritional factors. The objective of the current study was to examine inter-relations among alcohol, dietary micronutrients and macronutrient consumption, and liver health by analyzing data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). Our findings suggest that the category of heavy drinkers in the 2017-2018 NHANES consisted of generally healthy individuals with high-energy intake and no evidence of liver steatosis or fibrosis.
- Lei C, Sun R, Xu G, Tan Y, Feng W, McClain CJ, Deng Z. Enteric VIP-producing neurons maintain gut microbiota homeostasis through regulating epithelium fucosylation. Cell Host Microbe. 2022 Sep 13:S1931-3128(22)00418-8. doi: 10.1016/j.chom.2022.09.001. Epub ahead of print. PMID: 36150396.
Impact Statement: Interactions between the enteric nervous system (ENS) and intestinal epithelium are thought to play a vital role in intestinal homeostasis. How the ENS monitors the frontier with commensal and pathogenic microbes while maintaining epithelial function remains unclear. We further demonstrate that perturbation of enteric neurons leads to gut dysbiosis through α1,2-fucosylation in the steady state and results in increased susceptibility to alcohol-associated liver disease (ALD).
- Anwar MY, Baldassari AR, Polikowsky HG, Sitlani CM, Highland HM, Chami N, Chen HH, Graff M, Howard AG, Jung SY, Petty LE, Wang Z, Zhu W, Buyske S, Cheng I, Kaplan R, Kooperberg C, Loos RJF, Peters U, McCormick JB, Fisher-Hoch SP, Avery CL, Taylor KC, Below JE, North KE. Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations. BMC Med Genomics. 2022 Sep 10;15(1):192. doi: 10.1186/s12920-022-01352-3. PMID: 36088317; PMCID: PMC9464371.
Impact Statement: Concurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Results from this study demonstrate the importance of considering pleiotropy for improving our understanding of the etiology of the various metabolic pathways that regulate cardiovascular disease development.
- Nong Y, Guo Y, Ou Q, Gumpert A, Tomlin A, Zhu X, Bolli R. PU.1 inhibition does not attenuate cardiac function deterioration or fibrosis in a murine model of myocardial infarction. Mol Cell Biochem. 2022 Sep 17. doi: 10.1007/s11010-022-04561-7. Epub ahead of print. PMID: 36114991.
- Dyess RJ, McKay T, Feygin Y, Wintergerst K, Thrasher BJ. Factory-Calibrated Continuous Glucose Monitoring System Accuracy During Exercise in Adolescents With Type 1 Diabetes Mellitus. J Diabetes Sci Technol. 2022 Sep 1:19322968221120433. doi: 10.1177/19322968221120433. Epub ahead of print. PMID: 36047647.