May 2022 Member Publications
- Nail AN, McCaffrey LM, Banerjee M, Ferragut Cardoso AP, States JC. Chronic arsenic exposure suppresses ATM pathway activation in human keratinocytes. Toxicol Appl Pharmacol. 2022 Jul 1;446:116042. doi: 10.1016/j.taap.2022.116042. Epub 2022 May 2. PMID: 35513056.
Impact Statement: Our research sheds direct light on the most accepted explanation for the mode of action of arsenic carcinogenicity in arsenic’s major target organ, skin. Arsenic is known to induce DNA breaks without directly interacting with DNA. We have discovered that a major signaling protein for DNA break repair, ataxia telangiectasia-mutated (ATM), has reduced activation in human keratinocytes chronically exposed to inorganic arsenic. ATM plays an important role in DNA repair by activating enzymes that can fix DNA strand breaks in cells, preventing the accumulation of mutations in cells and carcinogenesis. Thus, it could be hypothesized that arsenic-induced tumors may be more sensitive to certain cancer treatments that induce DNA damage or inhibit DNA repair, such as radiotherapy or PARP inhibitors, respectively. Based on these findings, additional studies are needed determine whether arsenic-induced tumors are sensitive to specific chemotherapeutic regimens. Results from these future studies could be used to design new strategies to treat arsenic-induced cancers.
- Berlowitz JB, Xie W, Harlow AF, Hamburg NM, Blaha MJ, Bhatnagar A, Benjamin EJ, Stokes AC. E-Cigarette Use and Risk of Cardiovascular Disease: A Longitudinal Analysis of the PATH Study (2013-2019). Circulation. 2022 May 17;145(20):1557-1559. doi: 10.1161/CIRCULATIONAHA.121.057369. Epub 2022 May 6. PMID: 35514292.
Impact Statement: Despite increasing popularity of electronic cigarettes (e-cigarettes), the long-term health effects of habitual e-cigarette use remain unclear. Our results suggest that combining smoking with e-cigarette use does not reduce cardiovascular disease (CVD) events and that quitting both products is required to ensure a mitigation of risk.
- Gibson JM, Chu T, Zeng W, Wethall AC, Kong M, Mellen N, Devlin Phinney LA, Cai J. Perinatal methadone exposure attenuates myelination and induces oligodendrocyte apoptosis in neonatal rat brain. Exp Biol Med (Maywood). 2022 Apr 27:15353702221090457. doi: 10.1177/15353702221090457. Epub ahead of print. PMID: 35475383.
Impact statement: Methadone (MTD) is a common medication treatment for opioid use disorder (OUD) during pregnancy. In this study, pregnant rats were administrated a dosing approximately equivalent to the OUD treatment and the effects of passive in utero and postnatal MTD exposure on myelin development was investigated in neonatal rat brain. The findings reveal the potential mechanism(s) underlying the association between myelin impairment and antenatal opioid exposure. Our study alongside others concerns for fetal brain development when using MTD to manage the OUD during pregnancy. Improved understanding of the effects of opioid exposure will allow us to design treatments for OUD during pregnancy that minimize effects on the fetal brain or target postnatal treatment to mitigate the effects of antenatal opioid exposure.
- Halder S, Xie Z, Nantz MH, Fu XA. Integration of a micropreconcentrator with solid-phase microextraction for analysis of trace volatile organic compounds by gas chromatography-mass spectrometry. J Chromatogr A. 2022 Apr 22;1673:463083. doi: 10.1016/j.chroma.2022.463083. Epub ahead of print. PMID: 35508097.
Impact statement: This paper reports a simple method of integrating microfabricated preconcentrators with commercial SPME fibers in a two-stage concentration processes to achieve rapid and reliable measurement of trace VOCs in environmental air by GC–MS. This approach has been demonstrated for measurements of toxic VOCs including benzene, toluene, ethylbenzene, xylene (BTEX) and trichloroethene (TCE).
- Monreal G, Koenig SC, Slaughter MS, Morello GF, Prina SR, Tompkins LH, Huang J, Gellman BN, Dasse KA. Feasibility testing of the Inspired Therapeutics NeoMate mechanical circulatory support system for neonates and infants. PLoS One. 2022 May 11;17(5):e0266822. doi: 10.1371/journal.pone.0266822. PMID: 35544516; PMCID: PMC9094552.
Impact statement: In this article, we present the development of the prototype Inspired Therapeutics NeoMate System for pediatric left ventricular assist device (LVAD) support, and feasibility testing in static mock flow loops (H-Q curves), dynamic mock flow loops (hemodynamics), and in an acute healthy ovine model (hemodynamics and clinical applicability).
- Sagaram M, Parthasarathy R, Condon SL, Closson CF, Kong M, Schwandt ML, Jophlin LL, Feng W, Barve AJ, Vatsalya V. Theragnostic Efficacy of K18 Response in Alcohol Use Disorder with Clinically Significant Fibrosis Using Gut-Liver Axis. Int J Mol Sci. 2022 May 23;23(10):5852. doi: 10.3390/ijms23105852. PMID: 35628661; PMCID: PMC9143806.
Impact Statement: Fibrosis in early-stage alcohol-associated liver disease (ALD) is commonly under-diagnosed in routine clinical practice. This study characterized the liver-injury and cell death response in alcohol use disorder (AUD) patients with ALD who also exhibited fibrosis and assessed the efficacy of standard of care (SOC) treatment in the improvement in liver injury.
- Teng Y, Mu J, Xu F, Zhang X, Sriwastva MK, Liu QM, Li X, Lei C, Sundaram K, Hu X, Zhang L, Park JW, Hwang JY, Rouchka EC, Zhang X, Yan J, Merchant ML, Zhang HG. Gut bacterial isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death. Cell Host Microbe. 2022 May 25:S1931-3128(22)00265-7. doi: 10.1016/j.chom.2022.05.005. Epub ahead of print. PMID: 35654045.
Impact Statement: The gut microbiome has recently revealed itself to be a major player in human health and disease. Here, Drs. Huang-Ge Zhang and collaborators including CIEHS members Michael Merchant and Jun Won Park, show that a small metabolite, isoamylamine (IAA) produce by the bacteria Ruminococcaceae is enriched in aged mice and elderly people. Interestingly a bacteriophage belonging to the Myoviridae family that infects Ruminococcaceae are reduced in these settings. IAA induced cognitive declines in young mice is reversed by Myoviridae phage administration. IAA promoted apoptosis of microglial cells through a p53 dependent mechanism. Our results linked microbiome metabolites to direct transcriptional co-regulation of genomic DNA. These findings suggest a molecular mechanism connecting gut metabolism to gene expression in the brain with implications for disease development.
- Bhattacharyya A, Pal S, Mitra R, Rai S. Applications of Bayesian shrinkage prior models in clinical research with categorical responses. BMC Med Res Methodol. 2022 Apr 28;22(1):126. doi: 10.1186/s12874-022-01560-6. PMID: 35484507; PMCID: PMC9046716.
Impact Statement: Developing accurate prediction method benefits personalized medicine, involving patient’s demographic, history, and gene signatures. Bayesian shrinkage models have emerged as popular and flexible methods of variable selection in regression settings. This work discusses variable selection and illustrates its application to multiple clinical studies, such as Pima Indians Diabetes, Colon cancer, ADNI, and OASIS Alzheimer’s data sets. Informative priors can be used for robust and efficient prediction with accuracy of 91.6% (95% CI: 88.5, 94.7). The proposed method is robust to conduct both variable selection and prediction.
- Miller HA, Rai SN, Yin X, Zhang X, Chesney JA, van Berkel VH, Frieboes HB. Lung cancer metabolomic data from tumor core biopsies enables risk-score calculation for progression-free and overall survival. Metabolomics. 2022 May 14;18(5):31. doi: 10.1007/s11306-022-01891-x. PMID: 35567637.
Impact Statement: Metabolomics has emerged as a powerful method to provide insight into cancer progression, including separating patients into low- and high-risk groups for overall (OS) and progression-free survival (PFS). This proof-of-concept study evaluates metabolites as biomarkers obtained directly from tumor core biopsies along with covariates age, sex, pathological stage at diagnosis (I/II vs. III/VI), histological subtype, and treatment vs. no treatment. A prediction model is developed to stratify patients into low- and high-risk groups based on log-transformed intensities of key metabolites. Risk scores based on 10 metabolites for OS and 5 metabolites for PFS were significant predictors of survival. Risk scores were validated with SPLS-DA classification model (AUROC 0.868 for OS and AUROC 0.755 for PFS, when combined with covariates. Thus, metabolomic analysis of lung tumor core biopsies has the potential to differentiate patients into low- and high-risk groups based on OS and PFS events and probability.
- King KM, McKay T, Thrasher BJ, Wintergerst KA. Maximal Oxygen Uptake, VO2 Max, Testing Effect on Blood Glucose Level in Adolescents with Type 1 Diabetes Mellitus. Int J Environ Res Public Health. 2022 May 3;19(9):5543. doi: 10.3390/ijerph19095543. PMID: 35564936; PMCID: PMC9102981.
Impact Statement: Individuals with type 1 diabetes face many challenges when participating in sporting activities and general exercise. This publication offers some glucose control guidance for athletes participating in maximal aerobic exercise. In addition to benefiting individuals with T1D, this article may also be beneficial to coaches, physical educators, and parents of children participating in sporting activities.
- Yuan J, Wang T, Wang L, Li P, Shen H, Mo Y, Zhang Q, Ni C. Transcriptome-wide association study identifies PSMB9 as a susceptibility gene for coal workers' pneumoconiosis. Environ Toxicol. 2022 May 4. doi: 10.1002/tox.23554. Epub ahead of print. PMID: 35506645.
Impact Statement:Coal workers' pneumoconiosis (CWP) is a type of typical occupational lung disease caused by prolonged inhalation of coal mine dust. The individuals' different genetic background may underlie their different susceptibility to develop pneumoconiosis, even under the same exposure level. This study aimed to identify susceptibility genes associated with CWP. We have identified PSMB9 as a novel susceptibility gene for CWP and provided important insights into the further exploration of the CWP pathogenesis.
- Hardesty J, Day L, Warner J, Warner D, Gritsenko M, Asghar A, Stolz A, Morgan T, McClain C, Jacobs J, Kirpich I. Hepatic Protein and Phosphoprotein Signatures of Alcohol-Associated Cirrhosis and Hepatitis. Am J Pathol. 2022 Jul;192(7):1066-1082. doi: 10.1016/j.ajpath.2022.04.004. Epub 2022 Apr 28. PMID: 35490715; PMCID: PMC9253914.
Jophlin L, Singal AK. Liver Biopsy in Patients With Alcohol-Associated Liver Disease With Acute-on-Chronic Liver Failure. J Clin Exp Hepatol. 2022 Mar-Apr;12(2):544-550. doi: 10.1016/j.jceh.2021.08.009. Epub 2021 Aug 14. PMID: 35535109; PMCID: PMC9077173.