March 2023 Member Publication
- Ferragut Cardoso AP, Nail AN, Banerjee M, Wise SS, States JC. miR-186 induces tetraploidy in arsenic exposed human keratinocytes. Ecotoxicol Environ Saf. 2023 Mar 27;256:114823. doi: 10.1016/j.ecoenv.2023.114823. Epub ahead of print. PMID: 36989553.
Impact Statement: Hsa-miR-186 is overexpressed in skin cancers induced by chronic arsenic exposure as well as other advanced cancers. This study shows that hsa-miR-186 overexpression in human keratinocytes induces a doubling of chromosome number and dysregulated chromosome segregation to daughter cells. These chromosomal abnormalities are characteristic of cancerous cells and support the hypothesis that hsa-miR-186 overexpression contributes to carcinogenesis.
- Pavuk M, Rosenbaum PF, Lewin MD, Serio TC, Rago P, Cave MC, Birnbaum LS. Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, pesticides, and diabetes in the Anniston Community Health Survey follow-up (ACHS II): single exposure and mixture analysis approaches. Sci Total Environ. 2023 Mar 17;877:162920. doi: 10.1016/j.scitotenv.2023.162920. Epub ahead of print. PMID: 36934946.
Impact Statement: Our follow-up study results add to the body of literature that has researched associations between exposure to PCBs, other POPs, and diabetes. We found elevate odds ratios for, p,p’-DDE, trans-Nonachlor, some PCBs, and PCDDs TEQ for prevalent diabetes, but those were attenuated for incident diabetes in single exposure logistic regression models.
- Ge Y, Bruno M, Nash MS, Haykal Coates N, Chorley BN, Cave MC, Beier JI. Vinyl Chloride Enhances High Fat Diet-Induced Proteome Alterations in the Mouse Pancreas Related to Metabolic Dysfunction. Toxicol Sci. 2023 Mar 9:kfad024. doi: 10.1093/toxsci/kfad024. Epub ahead of print. PMID: 36892438.
Impact Statement: Alterations in physiological processes in pancreas have been associated with various metabolic dysfunctions and can result from environmental exposures, such as chemicals and diet. We found that the protein alterations may indicate diet-mediated susceptibility in mouse pancreas induced by HFD to concurrent exposure of low levels of inhaled VC. These proteome biomarkers may lead to a better understanding of pancreas-mediated adaptive or adverse response and susceptibility to metabolic disease.
- Ribble A, Hellmann J, Conklin DJ, Bhatnagar A, Haberzettl P. Fine particulate matter (PM2.5)-induced pulmonary oxidative stress contributes to increases in glucose intolerance and insulin resistance in a mouse model of circadian dyssynchrony. Sci Total Environ. 2023 Mar 18;877:162934. doi: 10.1016/j.scitotenv.2023.162934. Epub ahead of print. PMID: 36934930.
Impact Statement:Results of human and animal studies independently suggest that either ambient fine particulate matter (PM2.5) air pollution exposure or a disturbed circadian rhythm (circadian dyssynchrony) are important contributing factors to the rapidly evolving type-2-diabetes (T2D) epidemic. Our results demonstrate that circadian dyssynchrony is a novel susceptibility state for PM2.5 and suggest that PM2.5 by inducing pulmonary oxidative stress increases glucose intolerance and insulin resistance in circadian dyssynchrony.
- Agbonlahor O, DeJarnett N, Hart JL, Bhatnagar A, McLeish AC, Walker KL. Racial/Ethnic Discrimination and Cardiometabolic Diseases: A Systematic Review. J Racial Ethn Health Disparities. 2023 Mar 28:1–25. doi: 10.1007/s40615-023-01561-1. Epub ahead of print. PMID: 36976513; PMCID: PMC10044132.
Impact Statement:Racial/ethnic discrimination is positively associated with increased risk of cardiometabolic disease and higher levels of cardiometabolic biomarkers. Identifying racial/ethnic discrimination as a potential key contributor to the health inequities associated with cardiometabolic diseases is important for addressing the significant burden borne by racial/ethnic minorities.
- Kurlawala Z, Singh P, Hill BG, Haberzettl P. Fine Particulate Matter (PM2.5)-Induced Pulmonary Oxidative Stress Contributes to Changes in the Plasma Lipidome and Liver Transcriptome in Mice. Toxicol Sci. 2023 Mar 1:kfad020. doi: 10.1093/toxsci/kfad020. Epub ahead of print. PMID: 36857595
Impact Statement:Fine Particulate Matter (PM2.5)-Induced Pulmonary Oxidative Stress Contributes to Changes in the Plasma Lipidome and Liver Transcriptome in Mice” Our findings indicate that exposure of mice to fine particulate matter (PM2.5) induces unique changes in the plasma lipidome, which are accompanied by alterations in the liver transcriptome. These plasmatic and hepatic changes seem to depend, at least in part, on pulmonary oxidative stress.
Huang J, Mazer CD, Boisen ML, Tibi P, Baker RA, Chu D, Moffatt-Bruce S, Shore-Lesserson L. Safety of Andexanet Alfa Use in Cardiac Surgery. J Cardiothorac Vasc Anesth. 2023 Mar 5:S1053-0770(23)00128-3. doi: 10.1053/j.jvca.2023.02.039. Epub ahead of print. PMID: 36997371.
Impact Statement:There are currently no prospective clinical trials or retrospective studies describing andexanet alfa use in cardiac surgery. For the patient who has received andexanet alfa and demonstrates heparin resistance, administration of antithrombin III may be an alternative approach.
- Golebiowska AA, Jala VR, Nukavarapu SP. Decellularized Tissue-Induced Cellular Recruitment for Tissue Engineering and Regenerative Medicine. Ann Biomed Eng. 2023 Mar 23. doi: 10.1007/s10439-023-03182-5. Epub ahead of print. PMID: 36952144.
In this article, in collaboration with Dr. Syam P Nukavarapu, Univ of Connecticut, we explored decellularized human cartilage as a biomaterial/ graft for tissue repair and regeneration. Our 2D and 3D chemotactic assays show that the tissue-derived biomaterials retain biochemical cues of native tissue and stimulate chemotactic migration of stem/ progenitor cells. Together, this study developed a new paradigm in tissue engineering and regenerative medicine.
- Lindsey ML, Kleinbongard P, Kassiri Z, Carter JR, Hansell Keehan K, Ripplinger CM, LeBlanc AJ, Brunt KR, Kirk JA. We Asked and You Answered. Am J Physiol Heart Circ Physiol. 2023 Mar 17. doi: 10.1152/ajpheart.00084.2023. Epub ahead of print. PMID: 36930658.
Impact Statement:This purpose of this editorial was to give an update on the success that American Journal of Physiology – Heart and Circulatory Physiology has had incorporating sex as a biological variable in cardiovascular research manuscripts submitted to the journal. Unless scientifically justified, our journal now requires that research manuscripts incorporate both sexes starting in January of 2023. To summarize briefly, the scientific community has successfully embraced this requirement and we have implemented a new Table of Contents category titled, “Sex as a Biological Variable”.
- Del Rosario O, Suresh K, Kallem M, Singh G, Shah A, Zheng L, Yun X, Philip NM, Putcha N, McClure MB, Jiang H, D'Alessio F, Srivastava M, Bera A, Shimoda LA, Merchant M, Rane MJ, Machamer CE, Mock J, Hagan R, Koch AL, Punjabi NM, Kolb TM, Damarla M. MK2 non-enzymatically promotes nuclear translocation of caspase-3 and resultant apoptosis. Am J Physiol Lung Cell Mol Physiol. 2023 Mar 28. doi: 10.1152/ajplung.00340.2022. Epub ahead of print. PMID: 36976920.
Impact Statement:Taken together, our results demonstrate a non-enzymatic role for MK2 in the nuclear translocation of caspase-3. Furthermore, MK2 may function as a molecular switch in regulating the transition between the cytosolic and nuclear functions of caspase-3.
- Suresh K, Del Rosario O, Kallem M, Singh G, Shah A, Zheng L, Yun X, Philip NM, Putcha N, McClure MB, Jiang H, D'Alessio F, Srivastava M, Bera A, Shimoda LA, Merchant M, Rane MJ, Machamer CE, Mock J, Hagan R, Koch AL, Punjabi NM, Kolb TM, Damarla M. Tumor MK2 transcript levels are associated with improved response to chemotherapy and patient survival in non-small cell lung cancer. Physiol Genomics. 2023 Apr 1;55(4):168-178. doi: 10.1152/physiolgenomics.00155.2022. Epub 2023 Mar 6. PMID: 36878491; PMCID: PMC10042611.
Impact Statement: This study implicates MK2 in apoptosis resistance in NSCLC and suggests prognostic value of MK2 transcript levels in patients with lung adenocarcinoma.
- Anderson LB, Kanneganti D, Houk MB, Holm RH, Smith T. Generative AI as a Tool for Environmental Health Research Translation. medRxiv [Preprint]. 2023 Feb 22:2023.02.14.23285938. doi: 10.1101/2023.02.14.23285938. PMID: 36865187; PMCID: PMC9980240
Impact Statement:This research has the potential to significantly impact society and public health by making scientific information more accessible to non-academic, and specifically environmental justice audiences, thereby empowering communities and promoting informed policy-making. Additionally, the widespread adoption of AI-generated plain language summaries could lead to better public understanding of health research, ultimately resulting in improved public health policies and practices.
- Nail AN, Ferragut Cardoso AP, Montero LK, States JC. miRNAs and arsenic-induced carcinogenesis. Adv Pharmacol. 2023;96:203-240. doi: 10.1016/bs.apha.2022.10.002. Epub 2023 Feb 6. PMID: 36858773.
Impact Statement: Our publication provides a comprehensive resource for researchers to easily determine which miRNAs are dysregulated both in cell models for arsenic-induced cancer and in arsenic-induced human cancers.
- Vielee ST, Wise JP Jr. Among Gerontogens, Heavy Metals Are a Class of Their Own: A Review of the Evidence for Cellular Senescence. Brain Sci. 2023 Mar 16;13(3):500. doi: 10.3390/brainsci13030500. PMID: 36979310; PMCID: PMC10046019.
Impact Statement: As we approach a new era of human history with the largest geriatric population in history, we imminently need to better understand the intersection between toxicology and aging. The term 'gerontogen' was coined in 1987 by Dr. George Martin to describe chemicals that accelerate biological aging, since then this term has received little attention. This review serves to broaden the discussion of gerontogens and considers heavy metals as a distinct class of gerontogen.
- Prathibha P, Yeager R, Bhatnagar A, Turner J. Green Heart Louisville: intra-urban, hyperlocal land-use regression modeling of nitrogen oxides and ozone. medRxiv [Preprint]. 2023 Mar 9:2023.03.03.23286765. doi: 10.1101/2023.03.03.23286765. PMID: 36945554; PMCID: PMC10029020.
Impact Statement: This work evaluates a low-cost, fixed-site approach to characterizing long-term, hyperlocal exposure to oxides of nitrogen (including NO 2, a common surrogate for TRAP) as part of Green Heart Louisville, a prospective cohort study examining linkages between urban vegetation, local air quality, and cardiovascular health.