November 2022 Member Publications
- Habil MR, Doll MA, Hein DW. Acetyl coenzyme A kinetic studies on N-acetylation of environmental carcinogens by human N-acetyltransferase 1 and its NAT1*14B variant. Front Pharmacol. 2022 Oct 28;13:931323. doi: 10.3389/fphar.2022.931323. PMID: 36386142; PMCID: PMC9650386.
Impact Statement: Chinese hamster ovary (CHO) cells stably transfected with human NAT1*4 (reference allele) or NAT1*14B (variant allele) were utilized to determine AcCoA kinetic parameters for N-acetyltransferase activity towards p-aminobenzoic acid and arylamine carcinogens 4-aminobiphenyl, β-naphthylamine, benzidine and 3,4-dimethylaniline. N-acetylation rates for each substrate were greater when catalyzed by NAT1*4 which also exhibited higher affinity for AcCoA compared to NAT1*14B. The results provide further insights into differences in carcinogen metabolism among individuals possessing the NAT1*14B haplotype.
Hong KU, Tagnedji AH, Doll MA, Walls KM, Hein DW. Upregulation of cytidine deaminase in NAT1 knockout breast cancer cells. J Cancer Res Clin Oncol. 2022 Nov 3. doi: 10.1007/s00432-022-04436-w. Epub ahead of print. PMID: 36329350.
Impact Statement: This study presents a novel, potential therapeutic approach for breast cancer that express N-acetyltransferase 1 (NAT1). NAT1 deletion in breast cancer results in upregulation of cytidine deaminase which makes the cells sensitive to certain cytidine analogs.
Hong KU, Gardner JQ, Doll MA, Stepp MW, Wilkey DW, Benz FW, Cai J, Merchant ML, Hein DW. Dataset for proteomic analysis of arylamine N-acetyltransferase 1 knockout MDA-MB-231 breast cancer cells. Data Brief. 2022 Sep 24;45:108634. doi: 10.1016/j.dib.2022.108634. PMID: 36426076; PMCID: PMC9679541.
Impact Statement: This study identifies global changes in proteome in parental vs. NAT1 knockout breast cancer cells and potential mechanisms by which NAT1 contributes to breast cancer cell growth.
- Ali AS, Sheikh D, Chandler TR, Furmanek S, Huang J, Ramirez JA, Arnold F, Cavallazzi R. Cardiovascular complications are the primary drivers of mortality in hospitalized patients with SARS-CoV-2 community-acquired pneumonia. Chest. 2022 Nov 18:S0012-3692(22)04161-7. doi: 10.1016/j.chest.2022.11.013. Epub ahead of print. PMID: 36410493.
Impact statement: In hospitalized patients with COVID-19 pneumonia, once patients develop cardiovascular complications, the risk of death is extremely high. Cardiovascular complications are the primary drivers of mortality.
- Petri BJ, Klinge CM. m6A readers, writers, erasers, and the m6A epitranscriptome in breast cancer. J Mol Endocrinol. 2022 Nov 1:JME-22-0110. doi: 10.1530/JME-22-0110. Epub ahead of print. PMID: 36367225.
Impact Statement: This is a review of the current state of knowledge on the altered levels of the writers, readers, and erasers of the m6A epitranscriptomic modification in RNA in breast cancer.
- McLeish AC, Smith T, Riggs DW, Hart JL, Walker KL, Keith RJ, Anderson L, Sithu I, Pinilla-Baquero J, Srivastava S, Bhatnagar A. Community-Based Evaluation of the Associations Between Well-Being and Cardiovascular Disease Risk. J Am Heart Assoc. 2022 Nov 15;11(22):e027095. doi: 10.1161/JAHA.122.027095. Epub 2022 Nov 12. PMID: 36370026.
Impact Statement:In a community‐based cohort, individuals reporting higher levels of well‐being have lower odds of hypertension and dyslipidemia as well as lower rates of age‐dependent increase in vascular stiffness.
- Cui K, Gao X, Wang B, Wu H, Arulsamy K, Dong Y, Xiao Y, Jiang X, Malovichko MV, Li K, Peng Q, Wei Lu Y, Zhu B, Zheng R, Wong S, Cowan DB, Linton M, Srivastava S, Shi J, Chen K, Chen H. Epsin Nanotherapy Regulates Cholesterol Transport to Fortify Atheroma Regression. Circ Res. 2022 Nov 29. doi: 10.1161/CIRCRESAHA.122.321723. Epub ahead of print. PMID: 36444722.
Impact statement: Our findings suggest that targeting Epsins in lesional macrophages may offer therapeutic benefits for advanced atherosclerosis by reducing CD36-mediated lipid uptake and increasing ABCG1-mediated cholesterol efflux.
- Petri BJ, Piell KM, Wahlang B, Head KZ, Andreeva K, Rouchka EC, Cave MC, Klinge CM. Polychlorinated biphenyls alter hepatic m6A mRNA methylation in a mouse model of environmental liver disease. Environ Res. 2023 Jan 1;216(Pt 3):114686. doi: 10.1016/j.envres.2022.114686. Epub 2022 Oct 28. PMID: 36341798.
Impact Statement: This is first report to demonstrate that PCB exposure in vivo alters the m6A landscape in liver genes in a HFD-fed mouse model of nonalcoholic fatty liver disease (NAFLD). Pathway analysis of differentially expressed genes with altered numbers of m6A peaks includes lipoprotein metabolism. m6A peaks were dependent on the type of PCB (PCB 126 vs. Aroclor 1260 or the combined exposure to PCB 126 + Aroclor 1260) and may be involved in the dysregulation of lipoprotein metabolism genes in this mouse model of NAFLD progression.
- Gripshover TC, Wahlang B, Head KZ, Young JL, Luo J, Mustafa MT, Kirpich IA, Cave MC. The environmental pollutant, polychlorinated biphenyl 126, alters liver function in a rodent model of alcohol-associated liver disease. Alcohol Clin Exp Res. 2022 Nov 14. doi: 10.1111/acer.14976. Epub ahead of print. PMID: 36377258.
Impact Statement: Various environmental toxicants are known to modify or enhance fatty liver disease (FLD) in high-fat diet models. Findings from the present study suggest that they interact with other lifestyle factors such as alcohol consumption to reprogram intermediary metabolism resulting in exacerbated ethanol-associated systemic malnutrition in alcohol-associated liver disease (ALD).
- Tan Y, El-Kersh K, Watson SE, Wintergerst KA, Huang J, Cai L. Cardiovascular effects of environmental metal antimony: Redox dyshomeostasis as the key pathogenic driver. Antioxid Redox Signal. 2022 Nov 24. doi: 10.1089/ars.2022.0185. Epub ahead of print. PMID: 36424825.
Impact Statement: Compared to other heavy metals, antimony has been less addressed. Although exposure to antimony has been potentially linked epidemiologically and even experimentally to cardiovascular diseases (CVDs), whether antimony alone or combined with other metals can contribute to the pathogenesis of CVDs and underlying mechanisms remain unclear. This review addresses this gap in knowledge by presenting the current available evidence that highlights the potential role of antimony in the pathogenesis of CVDs, most likely via antimony-mediated redox dyshomeostasis, and urges more direct evidence from pre-clinical and mechanistic studies.
- Westcott CE, Sokoloski KJ, Rouchka EC, Chariker JH, Holm RH, Yeager RA, Moore JB 4th, Elliott EM, Talley D, Bhatnagar A, Smith T. The Detection of Periodic Reemergence Events of SARS-CoV-2 Delta Strain in Communities Dominated by Omicron. Pathogens. 2022 Oct 28;11(11):1249. doi: 10.3390/pathogens11111249. PMID: 36365000; PMCID: PMC9697103.
Impact statement: This publication will enhance knowledge on the unexpected reemergence of SARS-CoV-2 variants and corresponding infectious disease dynamics. It also contributes additional perspectives on the usefulness of disease surveillance through wastewater.
- Zierold KM, Myers JV, Brock GN, Sears CG, Zhang CH, Sears L. Indoor coal ash and school and social competency among children aged 6-14 years. J Expo Sci Environ Epidemiol. 2022 Nov 17. doi: 10.1038/s41370-022-00500-2. Epub ahead of print. PMID: 36396715.
Impact Statement: Children living near coal burning power plants and coal ash disposal sites may be at increased risk for neurobehavioral problems due to the known neurotoxins in by-products of coal burning. A sample of indoor air and behavior ratings in 280 children living within 10 miles of a coal power plant found that 43% of homes had fly ash, a by product of coal burning, in the home and that the presence of fly ash was associated with increased rates of school learning problems after controlling for possible confounding factors. Results indicated that childhood exposure to pollution may impact school learning possibly through the effects of heavy metals in the coal ash which have been shown to impact learning and behavior.
- Yuan J, Mo Y, Zhang Y, Zhang Y, Zhang Q. Nickel nanoparticles induce epithelial-mesenchymal transition in human bronchial epithelial cells via the HIF-1α/HDAC3 pathway. Nanotoxicology. 2022 Nov 7:1-18. doi: 10.1080/17435390.2022.2142169. Epub ahead of print. PMID: 36345150.
Impact statement: Our findings suggest that exposure to nickel nanoparticles (Nano-Ni) promotes the development of epithelial-mesenchymal transition in human bronchial epithelial cells by decreasing histone acetylation through HIF-1α-mediated HDAC3 upregulation. Our findings may provide information for further understanding of the molecular mechanisms of Nano-Ni-induced fibrosis and carcinogenesis.