January 2025 Member Publications

  1. Yao Z, Tasdighi E, Dardari ZA, Jha KK, Osuji N, Rajan T, Boakye E, Rodriguez CJ, Matsushita K, Simonsick EM, Lima JAC, Widome R, Cohen DL, Appel LJ, Khera A, Hall ME, Judd S, Cole SA, Vasan RS, Benjamin EJ, Bhatnagar A, DeFilippis AP, Blaha MJ. Differential Associations of Cigar, Pipe, and Smokeless Tobacco Use Versus Combustible Cigarette Use With Subclinical Markers of Inflammation, Thrombosis, and Atherosclerosis: The Cross-Cohort Collaboration-Tobacco Working Group. Circulation. 2025 Jan 27. doi: 10.1161/CIRCULATIONAHA.124.070852. Epub ahead of print. PMID: 39866105.
    Impact Statement: This study highlights that noncigarette tobacco products, including cigars, pipes, and smokeless tobacco, are associated with subclinical markers of cardiovascular harm, such as elevated inflammatory biomarkers and carotid plaque. These findings emphasize the need for regulatory policies that consider the cardiovascular risks of all tobacco products, not just cigarettes. 
  2. Srivastava S, Krivokhizhina T, Keith R, Bhatnagar A, Srivastava S, Xie Z, Lorkiewicz P. High-throughput UPLC-ESI/MSMS method for simultaneous measurement of the urinary metabolites of volatile organic compounds and tobacco alkaloids. J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Feb 1;1252:124463. doi: 10.1016/j.jchromb.2025.124463. Epub 2025 Jan 10. PMID: 39826161.
    Impact Statement: This study introduces a high-throughput UPLC-MS/MS method that enables simultaneous measurement of 35 urinary VOC metabolites and tobacco alkaloids with enhanced sensitivity and efficiency. By improving analyte coverage and accounting for tobacco use as a confounder, this method advances accurate VOC exposure assessment in population-based studies. 
  3. Tasdighi E, Yao Z, Jha KK, Dardari ZA, Osuji N, Rajan T, Boakye E, Rodriguez CJ, Matsushita K, Simonsick EM, Lima JAC, Widome R, Cohen D, Appel LJ, Khera A, Hall ME, Judd S, Cole SA, Ramachandran VS, Benjamin EJ, Bhatnagar A, DeFilippis AP, Blaha MJ. Cigar, Pipe, and Smokeless Tobacco Use and Cardiovascular Outcomes From Cross Cohort Collaboration. JAMA Netw Open. 2025 Jan 2;8(1):e2453987. doi: 10.1001/jamanetworkopen.2024.53987. PMID: 39804647; PMCID: PMC11731180.
    Impact Statement: This study demonstrates that noncigarette tobacco products, including cigars, pipes, and smokeless tobacco, are associated with increased risks of cardiovascular disease, heart failure, stroke, and mortality. These findings highlight the need for evidence-based regulatory policies to address the cardiovascular risks of all tobacco products, not just cigarettes. 
  4. Habil MR, Salazar-González RA, Doll MA, Hein DW. Bioactivation, Mutagenicity, DNA Damage, and Oxidative Stress Induced by 3,4-Dimethylaniline. Biomolecules. 2024 Dec 7;14(12):1562. doi: 10.3390/biom14121562. PMID: 39766269; PMCID: PMC11674834.
    Impact Statement:3,4-dimethylaniline (3,4-DMA) is an alkylaniline found in pharmaceuticals and personal care products, pesticides, tobacco smoke, and the dye industry. A DNA repair-deficient CHO cell model transfected with human CYP1A2 and N-acetyltransferase 1 (NAT1). We investigated how NAT1 genetic variants affect acetylation and kinetic constants (Km and Vmax) and investigated DNA damage, mutagenesis and oxidative stress induced by 3,4-DMA. 
  5. Walls KM, Joh JY, Martinez MM, Hong KU, Hein DW. Metabolic effects of heterocyclic amines on insulin induced AKT phosphorylation and gluconeogenic gene expression are modified by N-acetyltransferase 2 genetic polymorphism. Pharmacogenet Genomics. 2025 Jan 29. doi: 10.1097/FPC.0000000000000559. Epub ahead of print. PMID: 39878101.
    Impact Statement:Recent epidemiological studies reported significant associations between dietary heterocyclic amine (HCA) exposure and insulin resistance and type II diabetes. We investigated the role of N-acetyltransferase 2 (NAT2) genetic polymorphism in HCA-induced metabolic dysregulation. HCA treatment significantly reduced insulin-induced AKT phosphorylation and significantly increased expression of genes involved in gluconeogenesis (G6PC, PCK1, FOXO1, PPARA) in cryopreserved human hepatocytes from rapid but not from slow acetylators. The findings suggest that NAT2 genetic polymorphism modifies HCA-induced insulin resistance and gluconeogenic gene expression, implying that individuals with rapid acetylator phenotype may be at greater risk of dysregulated glucose homeostasis following exposure to HCAs. 
  6. Sheneman KR, Cummins TD, Merchant ML, Hood JL, Uriarte SM, Lawrenz MB. Yersinia pestis actively inhibits the production of extracellular vesicles by human neutrophils. bioRxiv [Preprint]. 2024 Dec 21:2024.12.20.629761. doi: 10.1101/2024.12.20.629761. PMID: 39763979; PMCID: PMC11702605.
    Impact Statement: Yersinia pestis, the bacteria causing the plague, disrupts the host immune response by interfering with signaling pathways required for inflammation, creating a non-inflammatory environment that supports bacterial colonization. This research focused on Y. pestis significantly affects neutrophil extracellular vesicles (EVs) produced during infection as a function of Y. pestis effector proteins. EVs from cells infected with the mutant strain were rich in antimicrobial and cytotoxic proteins, which were not present in EVs from Y. pestis-infected cells. Furthermore, EVs from Y. pestis-infected neutrophils lacked the inflammatory properties seen in those from mutant-infected cells. These findings suggest that Y. pestis actively inhibits the production of antimicrobial EVs, likely aiding in immune evasion. 
  7. Zheng J, Dhakal H, Qing E, Shrestha R, Geller AE, Morrissey SM, Saxena D, Hu X, Li H, Li H, Wilhelmsen K, Wendt LH, Klumpp K, Hume PS, Janssen WJ, Brody R, Palmer KE, Uriarte SM, Ten Eyck PP, Meyerholz DK, Merchant ML, McLeish K, Gallagher T, Huang J, Yan J, Perlman S. CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection. J Clin Invest. 2025 Jan 7:e188222. doi: 10.1172/JCI188222. Epub ahead of print. PMID: 39773555.
    Impact Statement: CXC motif chemokine 12 CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection. 
  8. Ghare S, Warner D, Warner J, Chilton PM, Lee J, Zhang J, Wang M, Hardesty J, Treves R, Gabbard J, Anderson C, Batra L, Sreenivasan C, Kraenzle J, McCulley M, McCoy S, Zhang L, Feng W, Gondim DD, Barve S, Zheng J, Palmer K, McClain C, Kirpich I. Impact of chronic ethanol consumption and SARS-COV-2 on the liver and intestine: A pilot dose-response study in mice. Alcohol Clin Exp Res (Hoboken). 2025 Jan 5. doi: 10.1111/acer.15528. Epub ahead of print. PMID: 39757351.
    Impact Statement: This study demonstrates that SARS-CoV-2 infection exacerbates alcohol-induced liver inflammation and increases early mortality in a dose-dependent manner in an experimental model of alcohol-associated liver disease. These findings highlight the potential for worsened liver dysfunction in individuals with chronic alcohol use during COVID-19 infection, underscoring the need for targeted health interventions. 
  9. Williams PG, Sears L, Watson WH, Gunaratnam B, Feygin Y, Wright SP, Sullivan JE. Glutathione, Vitamin C, and Cysteine Use in Autistic Children With Disruptive Behavior: A Double-Blind, Placebo-Controlled Crossover Pilot Study. J Dev Behav Pediatr. 2025 Jan 9. doi: 10.1097/DBP.0000000000001334. Epub ahead of print. PMID: 39823357.
    Impact Statement: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication differences and restricted interests. One proposed biologic mechanism underlying ASD is oxidative stress, leading to the clinical use of glutathione based on anecdotal reports of improved behavior in autistic children. In this pilot study, we tested this observation using a randomized clinical trial format to collect preliminary data on glutathione safety and efficacy. Treatment with glutathione or glutathione in combination with vitamin C and N-acetylcysteine did not result in improvements in behavior or biologic measures. The positive trends over the course of the study were likely due to the placebo effect or decreased anxiety associated with the study routine. 
  10. Schubert M, Logsdon MC, Sears C, Miller E, Alobaydullah AA, Lain KL. Integrating Community-Based Doulas into the Maternity Health Care System in an Urban Hospital. MCN Am J Matern Child Nurs. 2024 Sep-Oct 01;49(5):261-267. doi: 10.1097/NMC.0000000000001032. Epub 2024 Aug 13. PMID: 39784695.
    Impact Statement: This study demonstrates that integrating culturally congruent doulas into the health care system improved postpartum visit attendance and received positive feedback from both patients and providers. These findings highlight the potential of doula programs to address health disparities and improve maternal health outcomes for Black childbearing women. 
  11. Ritzenthaler JD, Ekuban A, Horsman B, Roman J, Watson WH. Alcohol-induced liver injury is mediated via α4-containing nicotinic acetylcholine receptors expressed in hepatocytes. Alcohol Clin Exp Res (Hoboken). 2025 Jan 23. doi: 10.1111/acer.15533. Epub ahead of print. PMID: 39853711.
    Impact Statement: This study demonstrates that hepatocyte-specific α4 nicotinic acetylcholine receptors (nAChRs) play a critical role in alcohol-induced liver damage, including steatosis, inflammation, and injury. Targeting hepatocyte α4-containing nAChRs could serve as a potential therapeutic strategy for mitigating alcohol-associated liver disease (ALD).