April 2023 - March 2024 Member Publications
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Basner M, Smith MG, Jones CW, Ecker AJ, Howard K, Schneller V, Cordoza M, Kaizi-Lutu M, Park-Chavar S, Stahn AC, Dinges DF, Shou H, Mitchell JA, Bhatnagar A, Smith T, Smith AE, Stopforth CK, Yeager R, Keith RJ. Associations of bedroom PM2.5, CO2, temperature, humidity, and noise with sleep: An observational actigraphy study. Sleep Health. 2023 Apr 10:S2352-7218(23)00043-8. doi: 10.1016/j.sleh.2023.02.010. Epub ahead of print. PMID: 37076419.
Impact Statement: This study demonstrates that factors such as air pollution, temperature, carbon dioxide, and noise in the bedroom environment have a significant impact on sleep quality. Higher levels of these factors were found to decrease sleep efficiency, highlighting the importance of creating a healthy and comfortable bedroom environment, beyond the mattress, for optimal sleep.Siddiqi TJ, Rashid AM, Siddiqi AK, Anwer A, Usman MS, Sakhi H, Bhatnagar A, Hamburg NM, Hirsch GA, Rodriguez CJ, Blaha MJ, DeFilippis AP, Benjamin EJ, Hall ME. Association of Electronic Cigarette Exposure on Cardiovascular Health: A Systematic Review and Meta-Analysis. Curr Probl Cardiol. 2023 Apr 21:101748. doi: 10.1016/j.cpcardiol.2023.101748. Epub ahead of print. PMID: 37088177.
Impact Statement: Electronic cigarette (EC) usage, despite being perceived as safe, has been associated with adverse cardiovascular effects, including increased heart rate, blood pressure, arterial stiffness, and unfavorable changes in platelet biomarkers. These findings emphasize the need for regulation and informed decision-making by policymakers to protect public health.Wu J, Origgi JM, Ranker LR, Bhatnagar A, Robertson RM, Xuan Z, Wijaya D, Hong T, Fetterman JL. Compliance With the US Food and Drug Administration's Guidelines for Health Warning Labels and Engagement in Little Cigar and Cigarillo Content: Computer Vision Analysis of Instagram Posts. JMIR Infodemiology. 2023 Mar 14;3:e41969. doi: 10.2196/41969. PMID: 37113379; PMCID: PMC10132024.
Impact Statement: This study reveals that health warnings are rarely included in influencer promotions of little cigars and cigarillos (LCCs) on Instagram, and posts with health warnings received less engagement. The findings emphasize the importance of extending health warning regulations to social media tobacco promotions and introduce a computer vision algorithm as a novel tool for monitoring compliance.Gourévitch B, Pitts T, Iceman K, Reed M, Cai J, Chu T, Zeng W, Morgado-Valle C, Mellen N. Synchronization of inspiratory burst onset along the ventral respiratory column in the neonate mouse is mediated by electrotonic coupling. BMC Biol. 2023 Apr 15;21(1):83. doi: 10.1186/s12915-023-01575-5. PMID: 37061721; PMCID: PMC10105963.
Impact Statement: The findings of this study contribute to our understanding of the complex mechanism underlying respiratory rhythm generation and synchronization in newborns. This knowledge may lead to the development of new therapeutic strategies for respiratory disorders (e.g. neonatal opioid withdrawal syndrome) that arise due to dysfunctional rhythm generation. Additionally, it may also aid in the development of novel treatments for other conditions that involve neuronal syncytium coupling.Habil MR, Hein DW. Effects of dose and human N-acetyltransferase 1 genetic polymorphism in benzidine metabolism and genotoxicity. Arch Toxicol. 2023 Apr 25. doi: 10.1007/s00204-023-03497-1. Epub ahead of print. PMID: 37097310.
Impact Statement: Benzidine exposure is associated with urinary bladder cancer but the effect of N-acetyltransferase 1 (NAT1) genetic polymorphism on individual risk remains unclear. We used Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and NAT1*4 allele (reference) or NAT1*14B (variant) to investigate the effects of dose and NAT1 polymorphism on benzidine metabolism and genotoxicity. Our findings support human studies associating NAT1*14B with increased incidence or severity of urinary bladder cancer in workers exposed to benzidine.Walls KM, Hong KU, Hein DW. Heterocyclic amines reduce insulin-induced AKT phosphorylation and induce gluconeogenic gene expression in human hepatocytes. Arch Toxicol. 2023 Apr 2. doi: 10.1007/s00204-023-03488-2. Epub ahead of print. PMID: 37005939.
Impact Statement: The effect of three heterocyclic amines (HCAs) commonly found in cooked meat (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline [MeIQ], 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline [MeIQx], and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine [PhIP]) on insulin signaling and glucose production were assessed in human hepatocytes. Our findings show that HCAs induce insulin resistance and promote hepatic glucose production in human hepatocytes. This implicates that exposure to HCAs may lead to the development of type II diabetes or metabolic syndrome.Hong KU, Walls KM, Hein DW. Non-coding and intergenic genetic variants of human arylamine N-acetyltransferase 2 (NAT2) gene are associated with differential plasma lipid and cholesterol levels and cardiometabolic disorders. Front Pharmacol. 2023 Apr 3;14:1091976. doi: 10.3389/fphar.2023.1091976. PMID: 37077812; PMCID: PMC10106703.
Impact Statement: This is the first report of its kind. Our analysis shows that common genetic variations in human N-acetyltransferase 2 (NAT2) gene are linked to dyslipidemia (e.g., high cholesterol) as well as cardiometabolic disorders. This finding implies that individuals carrying certain genetic variants of NAT2 (e.g., rapid acetylator genotypes) are more likely to develop dyslipidemia and cardiometabolic disorders.Xiang F, Huang F, Huang J, Li X, Dong N, Xiao Y, Zhao Q, Xiao L, Zhang H, Zhang C, Cheng Z, Chen L, Chen J, Wang H, Guo Y, Liu N, Luo Z, Hou X, Ji B, Zhao R, Jin Z, Savage R, Zhao Y, Zheng Z, Chen X; Chinese Association of Cardiovascular Surgeons; Chinese Society of Thoracic and Cardiovascular Surgery; Chinese Society of Cardiothoracic and Vascular Anesthesiology. Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery. Chin Med J (Engl). 2023 Apr 22. doi: 10.1097/CM9.0000000000002709. Epub ahead of print. PMID: 37083122.
Impact Statement: This multidisciplinary international expert consensus will serve to guide the decisions regarding the use of human albumin during and after cardiac surgery.Vatsalya V, Feng W, Kong M, Hu H, Szabo G, McCullough A, Dasarathy S, Nagy LE, Radaeva S, Barton B, Mitchell M, McClain CJ. The Beneficial Effects of Lactobacillus GG Therapy on Liver and Drinking Assessments in Patients with Moderate Alcohol-Associated Hepatitis. Am J Gastroenterol. 2023 Apr 11. doi: 10.14309/ajg.0000000000002283. Epub ahead of print. PMID: 37040544.
Impact Statement: Daily oral supplementation of Lactobacillus rhamnosus GG (LGG) was found to reduce liver injury and decrease heavy drinking levels in individuals with alcohol use disorder and alcohol-associated hepatitis. These findings suggest that LGG could be a beneficial intervention for improving liver health and promoting healthier drinking behaviors in this population.Lindsey ML, Kassiri Z, LeBlanc AJ, Ripplinger CM, Kirk JA, Carter JR, Kleinbongard P, Brunt KR. Spring Cleaning: Freshening up the portfolio. Am J Physiol Heart Circ Physiol. 2023 Apr 28. doi: 10.1152/ajpheart.00219.2023. Epub ahead of print. PMID: 37115630.
Impact Statement: The American Journal of Physiology-Heart and Circulatory Physiology has made updates to its article types, including renaming "Rapid Report" to "Short Report" to allow authors to present compelling findings without completing the entire story. They have also renamed "Innovative Methodology" to "Methods and Resources," emphasizing the promotion of standardization and the provision of valuable tools and protocols for cardiovascular research.Hassanein T, McClain CJ, Vatsalya V, Stein LL, Flamm SL, Martin P, Cave MC, Mitchell M Jr, Barton B, Nagy L, Szabo G, McCullough A, Dasarathy S, Shah J, Blevins C, Scott D, Krebs W, Brown JE, Lin W. Safety, Pharmacokinetics, & Efficacy Signals of Larsucosterol (DUR-928) in Alcohol-associated Hepatitis. Am J Gastroenterol. 2023 Mar 31. doi: 10.14309/ajg.0000000000002275. Epub ahead of print. PMID: 37011138.
Impact Statement: A study assessing larsucosterol in individuals with alcohol-associated hepatitis demonstrated positive outcomes, including improved biochemical parameters and reduced disease severity. These findings support further investigation of larsucosterol's efficacy in larger clinical trials.Turaga SM, Sardiu ME, Vishwakarma V, Mitra A, Bantis LE, Madan R, Merchant ML, Klein JB, Samuel G, Godwin AK. Identification of small extracellular vesicle protein biomarkers for pediatric Ewing Sarcoma. Front Mol Biosci. 2023 Apr 13;10:1138594. doi: 10.3389/fmolb.2023.1138594. PMID: 37122563; PMCID: PMC10140755.
Impact Statement: Researchers identified a specific protein biomarker, UGT3A2, that is highly specific to Ewing Sarcoma (EWS) tumor cells and their small extracellular vesicles. This discovery has the potential to improve the early diagnosis and monitoring of EWS.Liu S, He L, Bannister OB, Li J, Schnegelberger RD, Vanderpuye CM, Althouse AD, Schopfer FJ, Wahlang B, Cave MC, Monga SP, Zhang X, Arteel GE, Beier JI. Western diet unmasks transient low-level vinyl chloride-induced tumorigenesis; potential role of the (epi-)transcriptome. Toxicol Appl Pharmacol. 2023 Apr 14;468:116514. doi: 10.1016/j.taap.2023.116514. Epub ahead of print. PMID: 37061008.
Impact Statement: Using an experimental model, the study investigated how exposure to the industrial toxicant, vinyl chloride, affects the liver with time. The findings demonstrated that vinyl chloride at low concentrations for 12 weeks can lead to liver cancer after 1 year, particularly when vinyl chloride exposure was combined with western (high caloric) diet intake and calls for the need to reconsider current vinyl chloride safety restrictions.Wahlang B. Sex differences in toxicant-associated fatty liver disease. J Endocrinol. 2023 Apr 1:JOE-22-0247. doi: 10.1530/JOE-22-0247. Epub ahead of print. PMID: 37074385.
Impact Statement: The publication is part of the Journal of Endocrinology “Rising Stars” Collection and features Dr. Wahlang as one of the rising stars in the field of environmental endocrinology and toxicology. The publication reviews what is currently known about sex differences in liver diseases associated with environmental chemical exposures and existing knowledge gaps. The review also discusses the need for integration of sex and gender in environmental health research, and how this will enable better risk assessment in human population studies.Ottinger MA, Harry GJ, Malecki K, Wise JP Sr. Editorial: Healthspan and neural aging: Merging the exposome and one environmental health - From molecular mechanisms to epidemiology. Front Aging Neurosci. 2023 Mar 14;15:1172967. doi: 10.3389/fnagi.2023.1172967. PMID: 36998315; PMCID: PMC10043411.
Impact Statement: Studying the relationship between our environment and aging processes is essential for promoting healthy aging and developing effective interventions. By understanding how environmental factors, such as chemicals and social determinants, impact our susceptibility to age-related diseases, we can inform policies and strategies to support a healthier and longer lifespan for everyone.Yuan J, Mo Y, Zhang Y, Zhang Y, Zhang Q. Nickel nanoparticles induce autophagy and apoptosis via HIF-1α/mTOR signaling in human bronchial epithelial cells. Environ Pollut. 2023 Apr 18;329:121670. doi: 10.1016/j.envpol.2023.121670. Epub ahead of print. PMID: 37080518.
Impact Statement: Our findings suggest that Nano-Ni exposure causes increased levels of autophagy and apoptosis via the HIF-1α/mTOR signaling axis. Nano-Ni-induced autophagy has a protective role against Nano-Ni-induced apoptosis. Our findings provide us with further insight into Nano-Ni-induced toxicity.Wise JTF, Yin X, Ma X, Zhang X, Hein DW. Stable Isotope Tracing Reveals an Altered Fate of Glucose in N-Acetyltransferase 1 Knockout Breast Cancer Cells. Genes (Basel). 2023 Mar 31;14(4):843. doi: 10.3390/genes14040843. PMID: 37107601; PMCID: PMC10137864.
Impact Statement: The data generated in this study show that N-acetyltransferase 1 (NAT1) expression is important for the proper functioning of mitochondria and the flux of glucose through the TCA/Krebs cycle in breast cancer cells. Metabolism changes in the fate of glucose in NAT1 knock out breast cancer cells offer more insight into the role of NAT1 in energy metabolism and the growth of breast cancer cells. The findings provide further evidence that NAT1 may be a useful therapeutic target for breast cancer.- Ayangeakaa SD, Kerr J, Combs R, Harris L, Sears J, Parker K, Sterrett-Hong E. Understanding Influences on Intention to Use Pre-exposure Prophylaxis (PrEP) Among African American Young Adults. J Racial Ethn Health Disparities. 2023 Apr;10(2):899-910. doi: 10.1007/s40615-022-01278-7. Epub 2022 Mar 15. PMID: 35290648.
Erhabor J, Boakye E, Osuji N, Obisesan O, Osei AD, Mirbolouk H, Stokes AC, Dzaye O, El-Shahawy O, Rodriguez CJ, Hirsch GA, Benjamin EJ, DeFilippis AP, Robertson RM, Bhatnagar A, Blaha MJ. Patterns of tobacco product use and substance misuse among adolescents in the United States. Prev Med Rep. 2023 Apr 15;33:102207. doi: 10.1016/j.pmedr.2023.102207. PMID: 37223579; PMCID: PMC10201858.
Impact Statement: Our study, based on data from the 2019 Youth Risk Behavior Survey, reveals that while the majority of youth report no tobacco product use, a significant proportion engage in e-cigarette use either alone, in combination with one other tobacco product, or with two or more other tobacco products. These patterns of tobacco use are associated with substantially higher rates of substance misuse, including binge drinking, across a range of substances, emphasizing the urgent need for targeted education and counseling interventions to address the issue of substance abuse among youth, especially those who engage in poly-tobacco use.Posa DK, Miller J, Hoetker D, Ramage MI, Gao H, Zhao J, Doelling B, Bhatnagar A, Wigmore SJ, Skipworth RJE, Baba SP. Skeletal muscle analysis of cancer patients reveals a potential role for carnosine in muscle wasting. J Cachexia Sarcopenia Muscle. 2023 May 18. doi: 10.1002/jcsm.13258. Epub ahead of print. PMID: 37199284.
Impact Statement: This study highlights the potential importance of carnosine, a histidyl dipeptide, in preventing muscle wasting in cancer patients. The findings suggest that depletion of carnosine in skeletal muscle may contribute to muscle wasting, and increasing carnosine levels could be a promising therapeutic intervention to combat this condition. These insights offer hope for future interventions that could improve the quality of life for cancer patients by preserving muscle mass and function.Heindel JJ, Alvarez JA, Atlas E, Cave MC, Chatzi VL, Collier D, Corkey B, Fischer D, Goran MI, Howard S, Kahan S, Kayhoe M, Koliwad S, Kotz CM, La Merrill M, Lobstein T, Lumeng C, Ludwig DS, Lustig RH, Myers P, Nadal A, Trasande L, Redman LM, Rodeheffer MS, Sargis RM, Stephens JM, Ziegler TR, Blumberg B. Obesogens and Obesity: State-of-the-Science and Future Directions Summary from a HEEDS Workshop. Am J Clin Nutr. 2023 May 23:S0002-9165(23)63923-1. doi: 10.1016/j.ajcnut.2023.05.024. Epub ahead of print. PMID: 37230178.
Impact Statement: This report summarizes a scientific workshop that examined the role of obesogenic chemicals in contributing to the obesity pandemic. The findings highlight a consensus among relevant stakeholders that environmental obesogens are real and significant contributors to weight gain at both the individual and societal levels, emphasizing the need for further research and potential mitigation strategies to address this pressing public health concern and prevent obesity.Habil MR, Salazar-González RA, Doll MA, Hein DW. Effect of N-acetyltransferase 2 genetic polymorphism on 4,4'-methylenebis(2-chloroaniline)-induced genotoxicity and oxidative stress. Arch Toxicol. 2023 Jun;97(6):1773-1781. doi: 10.1007/s00204-023-03508-1. Epub 2023 May 4. PMID: 37142755.
Impact Statement: 4,4'-Methylenebis(2-chloroaniline) or MOCA has been linked to hepatomas in animal studies while limited epidemiologic studies reported the association of exposure to MOCA and urinary bladder and breast cancer. We investigated MOCA-induced genotoxicity and oxidative stress in DNA repair-deficient Chinese hamster ovary (CHO) cells stably transfected with human metabolizing enzymes CYP1A2 and N-acetyltransferase 2 (NAT2) variants as well as in rapid, intermediate, and slow NAT2 acetylator cryopreserved human hepatocytes. Our findings show that N-acetylation and genotoxicity of MOCA is NAT2 genotype dependent and suggest that individuals possessing NAT2*7B are at higher risk to MOCA-induced mutagenicity. DNA damage, and oxidative stress.Song K, Wang S, Han J, Jiang L, Xu J, Akca O, Adkins K, Koenig HM, Slaughter MS, Clifford SP, Huang Y, Huang J. Intraoperative Fraction of Inspired Oxygen and Lung Injury in Coronary Artery Bypass Grafting: Study Protocol for a Randomised Controlled Trial. Turk J Anaesthesiol Reanim. 2023 Apr;51(2):112-120. doi: 10.5152/TJAR.2023.22974. PMID: 37140576.
Impact Statement: This is one of the first randomised controlled observer-blinded trials that prospectively evaluates the influence of higher inspired oxygen fractions on early postoperative respiratory and oxygenation outcomes in cardiac surgery patients using cardiopulmonary bypass.Latif RK, Clifford SP, Baker JA, Lenhardt R, Haq MZ, Huang J, Farah I, Businger JR. Traumatic hemorrhage and chain of survival. Scand J Trauma Resusc Emerg Med. 2023 May 24;31(1):25. doi: 10.1186/s13049-023-01088-8. PMID: 37226264; PMCID: PMC10207757.
Impact Statement: Trauma is the number one cause of death among Americans between the ages of 1 and 46 years, costing more than $670 billion a year. An algorithm is proposed for achieving these goals in a timely fashion as the median time from onset of hemorrhagic shock and death is 2 h.Grande M, Eldeirawi KM, Huntington-Moskos L, Polivka B, Nyenhuis SM. The Association of Food Insecurity With Asthma Control in Adults During COVID-19. J Allergy Clin Immunol Pract. 2023 May 3:S2213-2198(23)00469-5. doi: 10.1016/j.jaip.2023.04.028. Epub ahead of print. PMID: 37146886.
Impact Statement: This study highlights the importance of understanding the relationship between food insecurity and asthma control in adults during the COVID-19 pandemic. The findings demonstrate that adults with higher levels of food insecurity are more likely to have uncontrolled asthma, emphasizing the need for healthcare providers to screen and address food insecurity when managing individuals with asthma to improve their overall asthma control and well-being.Juin SK, Ouseph R, Gondim DD, Jala VR, Sen U. Diabetic Nephropathy and Gaseous Modulators. Antioxidants (Basel). 2023 May 12;12(5):1088. doi: 10.3390/antiox12051088. PMID: 37237955; PMCID: PMC10215699.
Impact Statement: This publication, led by Dr. Utpal Sen, provides an overview of recent research on the role of gaseous signaling molecules, known as gasotransmitters, in diabetic nephropathy (DN), the leading cause of vascular morbidity and mortality in diabetes patients. By summarizing the advances in understanding the physiological relevance of these molecules and their interactions with other factors, such as the extracellular matrix, we shed light on the underlying mechanisms of DN progression and highlight the potential of gasotransmitters as therapeutic interventions to ameliorate this devastating disease.Hardesty JE, Warner JB, Song YL, Floyd A, McClain CJ, Warner DR, Kirpich IA. Fpr2-/- Mice Developed Exacerbated Alcohol-Associated Liver Disease. Biology (Basel). 2023 Apr 23;12(5):639. doi: 10.3390/biology12050639. PMID: 37237453; PMCID: PMC10215685.
Impact Statement: Our study investigates the role of formyl peptide receptor 2 (FPR2) in alcohol-associated liver disease (ALD), the most common chronic liver disease. We found that mice lacking FPR2 experienced more severe liver injury, inflammation, and compromised regeneration compared to normal mice when exposed to chronic-binge ethanol administration, highlighting the crucial role of FPR2 in the pathogenesis of ALD. This research provides valuable insights into the mechanisms underlying ALD and may contribute to the development of novel therapeutic strategies for this debilitating condition, offering hope for improved outcomes and reduced healthcare burden for individuals affected by ALD.Naughton CC, Holm RH, Lin NJ, James BP, Smith T. Online dashboards for SARS-CoV-2 wastewater data need standard best practices: An environmental health communication agenda. J Water Health. 2023 May;21(5):615-624. doi: 10.2166/wh.2023.312. PMID: 37254909.
Impact Statement: This study underscores the need to standardize the presentation of SARS-CoV-2 (and other pathogen) wastewater data across online dashboards globally, which we show to vary greatly leading to potential public health miscommunication. Our findings could lead to improved risk communication, enabling better use of this important data on a global scale, informing public health responses to COVID-19 and enhancing the efficacy of future pandemic management efforts.Keith RJ, Holm RH, Amraotkar AR, Bezold MM, Brick JM, Bushau-Sprinkle AM, Hamorsky KT, Kitterman KT, Palmer KE, Smith T, Yeager R, Bhatnagar A. Stratified Simple Random Sampling Versus Volunteer Community-Wide Sampling for Estimates of COVID-19 Prevalence. Am J Public Health. 2023 May 18:e1-e10. doi: 10.2105/AJPH.2023.307303. Epub ahead of print. PMID: 37200600.
Impact Statement: This study demonstrates the importance of using structured targeted sampling approaches to assess the prevalence of SARS-CoV-2 infection in the community. The findings show that these sampling methods provide more accurate estimates of disease prevalence compared to administratively reported data based on incident cases. The study highlights the significance of using targeted sampling, particularly among marginalized populations, to obtain more reliable and representative data for public health planning and interventions.Schwartz DJ, Shalon N, Wardenburg K, DeVeaux A, Wallace MA, Hall-Moore C, Ndao IM, Sullivan JE, Radmacher P, Escobedo M, Burnham CD, Warner BB, Tarr PI, Dantas G. Gut pathogen colonization precedes bloodstream infection in the neonatal intensive care unit. Sci Transl Med. 2023 May 3;15(694):eadg5562. doi: 10.1126/scitranslmed.adg5562. Epub 2023 May 3. PMID: 37134153.
Impact Statement: Bacterial bloodstream infections (BSIs) cause late-onset sepsis that affects up to half of extremely preterm infants and results in substantial morbidity and mortality. Bacterial species associated with these BSIs in these infants are known to commonly colonize the preterm infant gut microbiome. Data was analyzed from 550 fecal metagenomes from 115 hospitalized preterm neonates. Recent exposure to certain antibiotics was associated with an increase in the presence of Enterobacteriaceae and Enterococcaceae in these infants. Additional metagenomic sequencing from 19 infants with BSE and 37 non-BSI controls showed that infants with BSI caused by Enterobacteriaceae were more likely than infants BSI caused by other organisms to have received certain antibiotics in the previous 10 days before the BSI. Additional studies are needed to evaluate BSI risk prediction strategies based on gut microbiome abundance in hospitalized preterm infants with the goal of preventing BSI in these infants leading to decreased morbidity and mortality.Piell KM, Petri BJ, Head KZ, Wahlang B, Xu R, Zhang X, Pan J, Rai SN, de Silva K, Chariker JH, Rouchka EC, Tan M, Li Y, Cave MC, Klinge CM. Disruption of the mouse liver epitranscriptome by long-term aroclor 1260 exposure. Environ Toxicol Pharmacol. 2023 May 1;100:104138. doi: 10.1016/j.etap.2023.104138. Epub ahead of print. PMID: 37137421.
Impact Statement: This study compared the effect of low fat diet (LFD) for 34 wks and high fat diet (HFD) for 23 wks with and without co-exposure to the PCB mixture Aroclor1260 on global RNA modifications in male mouse liver. The results demonstrate that diet and Ar1260 exposure alter the liver epitranscriptome in pathways associated with non-alcoholic fatty liver disease (NAFLD).Yeager R, Browning MHEM, Breyer E, Ossola A, Larson LR, Riggs DW, Rigolon A, Chandler C, Fleischer D, Keith R, Walker K, Hart JL, Smith T, Bhatnagar A. Greenness and equity: Complex connections between intra-neighborhood contexts and residential tree planting implementation. Environ Int. 2023 May 12;176:107955. doi: 10.1016/j.envint.2023.107955. Epub ahead of print. PMID: 37196566.
Impact Statement: This study investigates the complex relationship between neighborhood greenness, socioeconomic status (SES), and barriers to residential tree planting. The findings highlight the need for a deeper understanding of local socioeconomic inequities and barriers to tree planting, particularly among low-SES residents, to ensure effective and equitable implementation of large-scale tree planting initiatives. By shedding light on these dynamics, the research provides valuable insights for future efforts to improve human health, climate adaptation, and environmental equity through community greening initiatives.- Zhang Y, Mo Y, Zhang Y, Yuan J, Zhang Q. MMP-3-mediated cleavage of OPN is involved in copper oxide nanoparticle-induced activation of fibroblasts. Part Fibre Toxicol. 2023 May 22;20(1):22. doi: 10.1186/s12989-023-00532-y. PMID: 37217992; PMCID: PMC10201731.
Impact Statement: Copper oxide nanoparticles (Nano-CuO) are one of the most produced and used nanomaterials. Previous studies have shown that exposure to Nano-CuO caused acute lung injury, inflammation, and fibrosis. However, the mechanisms underlying Nano-CuO-induced lung fibrosis are still unclear. Our results demonstrated that Nano-CuO exposure caused increased production of MMP-3 from lung epithelial BEAS-2B cells and U937* macrophages, which cleaved osteopontin (OPN), resulting in the activation of lung fibroblasts MRC-5. Our findings suggest that MMP-3-cleaved OPN may play a key role in Nano-CuO-induced activation of lung fibroblasts.
Erhabor J, Boakye E, Osuji N, Obisesan O, Osei AD, Mirbolouk H, Stokes AC, Dzaye O, El-Shahawy O, Rodriguez CJ, Hirsch GA, Benjamin EJ, DeFilippis AP, Robertson RM, Bhatnagar A, Blaha MJ. Psychosocial stressors and current e-cigarette use in the youth risk behavior survey. BMC Public Health. 2023 Jun 6;23(1):1080. doi: 10.1186/s12889-023-16031-w. PMID: 37280552; PMCID: PMC10242777.
Impact Statement: The study demonstrates a significant association between psychosocial stressors and adolescent e-cigarette use, highlighting the potential importance of interventions, such as targeted school-based programs that address stressors and promote stress management, as possible means of reducing adolescent e-cigarette use. Future research directions include exploring underlying mechanisms linking stressors to e-cigarette use and evaluating the effectiveness of interventions addressing stressors in reducing adolescent e-cigarette use.April-Sanders AK, Daviglus ML, Lee UJ, Perreira KM, Kaplan RC, Blaha MJ, Pirzada A, Giachello AL, Bhatnagar A, Robertson RM, Thanh-Huyen TV, Rodriguez CJ. Prevalence of electronic cigarette use and its determinants in us persons of Hispanic/Latino background: The Hispanic community health study / study of Latinos (HCHS/SOL). Am J Med Open. 2023 Jun;9:100029. doi: 10.1016/j.ajmo.2022.100029. Epub 2022 Nov 24. PMID: 37388413; PMCID: PMC10310062.
Impact Statement: This study found that Hispanic/Latino individuals who are young adults, male, US-born, and have high acculturation were more likely to report current electronic nicotine delivery systems (ENDS) use. These findings could inform preventive and regulatory interventions targeted to Hispanics/Latinos.Boakye E, Uddin SMI, Osuji N, Meinert J, Obisesan OH, Mirbolouk M, Tasdighi E, El-Shahawy O, Erhabor J, Osei AD, Rajan T, Patatanian M, Holbrook JT, Bhatnagar A, Biswal SS, Blaha MJ. Examining the association of habitual e-cigarette use with inflammation and endothelial dysfunction in young adults: The VAPORS-Endothelial function study. Tob Induc Dis. 2023 Jun 10;21:75. doi: 10.18332/tid/162327. PMID: 37305426; PMCID: PMC10257221.
Impact Statement: The publication suggest that e-cigarette use may not be significantly associated with endothelial dysfunction and systemic inflammation in relatively young and healthy individuals. Longer term studies with larger sample sizes are needed to validate these findings.Cai L. Impact of Nutrition or FDA-Approved Medicine Repurposing on Metabolic Syndrome and Diabetic Complications. Nutrients. 2023 May 29;15(11):2515. doi: 10.3390/nu15112515. PMID: 37299478; PMCID: PMC10255908.
Impact Statement: This publication includes research on obesity and diabetes, focusing on their underlying causes and potential interventions using nutrients and natural products. The findings emphasize the importance of studying these conditions to develop effective strategies for managing and preventing their complications.Nault R, Cave MC, Ludewig G, Moseley HNB, Pennell KG, Zacharewski T. A Case for Accelerating Standards to Achieve the FAIR Principles of Environmental Health Research Experimental Data. Environ Health Perspect. 2023 Jun;131(6):65001. doi: 10.1289/EHP11484. Epub 2023 Jun 23. PMID: 37352010; PMCID: PMC10289218.
Impact Statement: This manuscript reveals ways to optimize the reuse of environmental health science data using the FAIR principles. The content was developed by several collaborating Superfund Research Centers (also including Michigan State, UK and Iowa) with the support of a data science supplement from NIEHS/Superfund.Hong KU, Hein DW. N-acetyltransferase 2 haplotype modifies risks for both dyslipidemia and urinary bladder cancer. Pharmacogenet Genomics. 2023 May 29. doi: 10.1097/FPC.0000000000000500. Epub ahead of print. PMID: 37306342.
Impact Statement: A novel haplotype in N-acetyltransferase 2 (NAT2) comprised of seven, non-coding variants (rs1495741, rs4921913, rs4921914, rs4921915, rs146812806, rs35246381, rs35570672) has been linked to both dyslipidemia and urinary bladder cancer by multiple, independent genome wide association studies. We speculate that rs1495741 (and its associated haplotype) belongs to a distal regulatory element of human NAT2 gene (e.g., enhancer or silencer), and the genetic variation at the newly discovered haplotype results in a differential level of NAT2 gene expression. Understanding how this NAT2 haplotype contributes to urinary bladder cancer and dyslipidemia will ultimately help devise strategies to identify and protect susceptible individuals.Jin L, Liang Y, Yu Y, Miao P, Huang Y, Xu L, Wang H, Wang C, Huang J, Guo K. Evaluation of the Effect of New Multimodal Analgesia Regimen for Cardiac Surgery: A Prospective, Randomized Controlled, Single-Center Clinical Study. Drug Des Devel Ther. 2023 Jun 7;17:1665-1677. doi: 10.2147/DDDT.S406929. PMID: 37309414; PMCID: PMC10257907.
Impact Statement: Multimodal regimen by paracetamol, gabapentin, ketamine, lidocaine, dexmedetomidine and sufentanil among cardiac surgery patients, reduced perioperative opioid consumption along with rescue analgesia rate with similar length of stay and the incidences of postoperative complications.Ander M, Mugve N, Crouch C, Kassel C, Fukazawa K, Izaak R, Deshpande R, McLendon C, Huang J. Regional anesthesia for transplantation surgery - A white paper part 1: Thoracic transplantation surgery. Clin Transplant. 2023 Jun 12:e15043. doi: 10.1111/ctr.15043. Epub ahead of print. PMID: 37306898.
Impact Statement: Society for the Advancement of Transplant Anesthesia (SATA) identified experts in both transplantation surgery and regional anesthesia to review available literature concerning these topics. The goal of this task force was to provide an overview of these publications to help guide transplantation anesthesiologists in utilizing regional anesthesia.Hartson KR, Huntington-Moskos L, Sears CG, Genova G, Mathis C, Ford W, Rhodes RE. Use of Electronic Ecological Momentary Assessment Methodologies in Physical Activity, Sedentary Behavior, and Sleep Research in Young Adults: Systematic Review. J Med Internet Res. 2023 Jun 29;25:e46783. doi: 10.2196/46783. PMID: 37384367.
Impact Statement: This publication showcases how advanced technology allows researchers to study physical activity, sedentary behavior, and sleep in young adults through real-time data collection. The study highlights the growing use of electronic ecological momentary assessment (eEMA) but also identifies the need for standardized reporting and inclusion of diverse populations to improve research in this area.Vatsalya V, Royer AJ, Jha SK, Parthasarathy R, Tiwari H, Feng W, Ramchandani VA, Kirpich IA, McClain CJ. Drinking and laboratory biomarkers, and nutritional status characterize the clinical presentation of early-stage alcohol-associated liver disease. Adv Clin Chem. 2023;114:83-108. doi: 10.1016/bs.acc.2023.02.001. Epub 2023 May 5. PMID: 37268335.
Impact Statement: This publication thoroughly investigates the early-stage of alcohol-associated liver disease (ALD) caused by chronic and heavy alcohol consumption, shedding light on the complex interactions between different pathways, including nutritional changes. It provides valuable insights into identifying and understanding this condition through clinical markers and laboratory measures.Bhayana S, Zhao Y, Merchant M, Cummins T, Dougherty JA, Kamigaki Y, Pathmasiri W, McRitchie S, Mariani LH, Sumner S, Klein JB, Li L, Smoyer WE; Pediatric Nephrology Research Consortium. Multiomics Analysis of Plasma Proteomics and Metabolomics of Steroid Resistance in Childhood Nephrotic Syndrome Using a "Patient-Specific" Approach. Kidney Int Rep. 2023 Mar 23;8(6):1239-1254. doi: 10.1016/j.ekir.2023.03.015. PMID: 37284673; PMCID: PMC10239920.
Impact Statement: Nephrotic syndrome (NS) occurs commonly in children with glomerular disease, resistance to the mainstay treatment, glucocorticoids (GCs), develops in 15% to 20% of children, increasing the risk of chronic kidney disease compared to steroid sensitive NS (SSNS). We employed a novel "patient-specific" bioinformatic approach to merge paired pre-GC- and post-GC-treatment proteomic and metabolomic data and identify candidate SRNS biomarkers and altered molecular pathways in SRNS versus SSNS. Joint pathway analyses revealed perturbations in nicotinate or nicotinamide and butanoate metabolic pathways in patients with SRNS. Patients with SSNS had perturbations of lysine degradation, mucin type O-glycan biosynthesis, and glycolysis or gluconeogenesis pathways. These studies confirmed that a novel "patient-specific" bioinformatic approach can integrate disparate omics datasets and discover candidate SRNS biomarkers not observed by separate proteomic or metabolomic analysis.Li J, Sato T, Hernández-Tejero M, Beier JI, Sayed K, Benos PV, Wilkey DW, Humar A, Merchant ML, Duarte-Rojo A, Arteel GE. The plasma degradome reflects later development of NASH fibrosis after liver transplant. Sci Rep. 2023 Jun 20;13(1):9965. doi: 10.1038/s41598-023-36867-x. PMID: 37340062; PMCID: PMC10282030.
Impact Statement: Liver transplantation (LT) is an effective therapy for cirrhosis but the incidence of post-LT NASH reoccurance, accelerated progression to fibrosis/cirrhosis, and decreased survival is alarmingly high. The inflammation induced hepatic ECM remodeling has been demonstrated to alter the circulating ECM and parenchymal peptide fragments (i.e., 'degradome') in plasma, making it a useful diagnostic/prognostic tool in chronic liver disease. Proteomic methods and supervised modeling of the degradome data was used to investigate whether liver injury caused by post-LT NASH would yield a unique degradome profile that is predictive of severe post-LT NASH fibrosis. A retrospective analysis of 22 biobanked samples from the Starzl Transplantation Institute (12 with post-LT NASH after 5 years and 10 without) was conducted on ~ 2700 identifiable peptide features. The ECM degradome was significantly altered in patients that later developed fibrosis and heatmap analysis clustered the 2 patient groups well. A similar degradome profile was observed when the plasma degradome patterns were compared being obesity sensitive (C57Bl6/J) and insensitive (AJ) mouse strains. The plasma degradome profile of post-LT patients yielded stark difference based on later development of post-LT NASH fibrosis. This approach could yield new "fingerprints" that can serve as minimally-invasive biomarkers of negative outcomes post-LT.Benner SE, Zhu X, Hussain S, Florman S, Eby Y, Fernandez RE, Ostrander D, Rana M, Ottmann S, Hand J, Price JC, Pereira MR, Wojciechowski D, Simkins J, Stosor V, Mehta SA, Aslam S, Malinis M, Haidar G, Massie A, Smith ML, Odim J, Morsheimer M, Quinn TC, Laird GM, Siliciano R, Balagopal A, Segev DL, Durand CM, Redd AD, Tobian AAR. HIV-positive liver transplant does not alter the latent viral reservoir in recipients with ART-suppressed HIV. J Infect Dis. 2023 Jun 28:jiad241. doi: 10.1093/infdis/jiad241. Epub ahead of print. PMID: 37379584.
Impact Statement: This study investigated whether receiving a liver transplant from an HIV-positive donor affects the viral reservoir in HIV-positive recipients. The results showed that the viral reservoir remained stable after liver transplantation, regardless of whether the donor was HIV-positive or HIV-negative.Holm RH, Pocock G, Severson MA, Huber VC, Smith T, McFadden LM. Using wastewater to overcome health disparities among rural residents. Geoforum. 2023 Aug;144:103816. doi: 10.1016/j.geoforum.2023.103816. Epub 2023 Jun 26. PMID: 37396346; PMCID: PMC10292026.
Impact Statement: This commentary addresses the disparities in rural health during the SARS-CoV-2 pandemic and proposes the use of wastewater surveillance as an innovative tool to address these disparities. By reviewing successful implementations in South Africa, we conclude that wastewater surveillance can help monitor diseases in underserved areas, improve disease detection among rural residents, and potentially identify future global outbreaks.- Holm RH, Osborne Jelks N, Schneider R, Smith T. Beyond COVID-19: Designing Inclusive Public Health Surveillance by Including Wastewater Monitoring. Health Equity. 2023 Jun 15;7(1):377-379. doi: 10.1089/heq.2022.0055. PMID: 37351532; PMCID: PMC10282970.
Impact Statement: This work emphasizes the importance of expanding wastewater testing to include vulnerable and underserved communities, particularly when clinical testing data are insufficient, in order to ensure rapid response to public health threats and equitable protection of health in the United States.
Helmy E, Elnakib A, ElNakieb Y, Khudri M, Abdelrahim M, Yousaf J, Ghazal M, Contractor S, Barnes GN, El-Baz A. Role of Artificial Intelligence for Autism Diagnosis Using DTI and fMRI: A Survey. Biomedicines. 2023 Jun 29;11(7):1858. doi: 10.3390/biomedicines11071858. PMID: 37509498; PMCID: PMC10376963.
Impact Statement: This survey underscores how artificial intelligence (AI), particularly deep learning, is transforming the landscape of Autism Spectrum Disorder (ASD) diagnosis and early detection through analysis of brain MRI data, offering a rapid and objective alternative to current subjective methods. By highlighting the current capabilities and potential future applications of AI in healthcare settings, the study signals a promising direction for enhancing ASD diagnostic practices.Boakye E, Erhabor J, Obisesan O, Tasdighi E, Mirbolouk M, Osuji N, Osei AD, Lee J, DeFilippis AP, Stokes AC, Hirsch GA, Benjamin EJ, Robertson RM, Bhatnagar A, El Shahawy O, Blaha MJ. Comprehensive review of the national surveys that assess E-cigarette use domains among youth and adults in the United States. Lancet Reg Health Am. 2023 Jun 7;23:100528. doi: 10.1016/j.lana.2023.100528. PMID: 37497394; PMCID: PMC10366460.
Impact Statement: This review emphasizes the importance of tracking e-cigarette usage in various populations for effective tobacco regulation. Examining 13 prominent surveys, the study identifies essential tools and gaps in monitoring, offering recommendations to enhance surveillance precision and inform policy decisions.Xie Z, Chen JY, Gao H, Keith RJ, Bhatnagar A, Lorkiewicz P, Srivastava S. Global Profiling of Urinary Mercapturic Acids Using Integrated Library-Guided Analysis. Environ Sci Technol. 2023 Jul 25;57(29):10563-10573. doi: 10.1021/acs.est.2c09554. Epub 2023 Jul 11. PMID: 37432892.
Impact Statement: Our workflow allowed profiling of known and unreported Urinary mercapturic acids (MAs) from endogenous and environmental sources, and the levels of several MAs were increased in smokers. Our method can also be expanded and applied to other exposure-wide association studies.Tasdighi E, Jha KK, Dardari ZA, Osuji N, Rajan T, Boakye E, Hall ME, Rodriguez CJ, Stokes AC, El Shahawy O, Benjamin EJ, Bhatnagar A, DeFilippis AP, Blaha MJ. Investigating the association of traditional and non-traditional tobacco product use with subclinical and clinical cardiovascular disease: The Cross-Cohort Collaboration-Tobacco working group rationale, design, and methodology. Tob Induc Dis. 2023 Jul 7;21:89. doi: 10.18332/tid/166517. PMID: 37427074; PMCID: PMC10326890.
Impact Statement: This study presents the Cross-Cohort Collaboration (CCC)-Tobacco dataset, bringing together 23 prospective cohorts comprising over 322,000 participants, to address gaps in understanding cardiovascular disease risks associated with non-traditional tobacco products. Through analysis of diverse demographics and tobacco usage profiles, this dataset offers a distinct opportunity to comprehensively investigate subclinical and clinical CVD risks, including within underrepresented groups.Li Y, Cai T, Liu H, Liu J, Chen SY, Fan H. Exosome-shuttled miR-126 mediates ethanol-induced disruption of neural crest cell-placode cell interaction by targeting SDF1. Toxicol Sci. 2023 Jul 25:kfad068. doi: 10.1093/toxsci/kfad068. Epub ahead of print. PMID: 37490477.
Impact Statement: We established a well-designed cell co-culture system to investigate the reciprocal interaction between human NCCs (hNCCs) and human PCs (hPCs), and also monitored the migration behavior of NCCs and PCs in zebrafish embryos. We found that ethanol exposure resulted in a disruption of coordinated hNCCs-hPCs interaction, as well as in zebrafish embryos. Treating hNCCs-hPCs with exosomes derived from ethanol-exposed hNCCs (ExoEtOH) mimicked ethanol-induced impairment of hNCCs-hPCs interaction. We also observed that SDF1, a chemoattractant, was downregulated in ethanol-treated hPCs and zebrafish embryos. Meanwhile, miR-126 level in ExoEtOH was significantly higher than that in control exosomes (ExoCon). We further validated that ExoEtOH-encapsulated miR-126 from hNCCs can be transferred to hPCs to suppress SDF1 expression in hPCs. Knockdown of SDF1 replicated ethanol-induced abnormalities either in vitro or in zebrafish embryos. On the contrary, overexpression of SDF1 or inhibiting miR-126 strongly rescued ethanol-induced impairment of hNCCs-hPCs interaction and developmental defects.Chen SY, Kannan M. Neural crest cells and fetal alcohol spectrum disorders: Mechanisms and potential targets for prevention. Pharmacol Res. 2023 Jul 17;194:106855. doi: 10.1016/j.phrs.2023.106855. Epub ahead of print. PMID: 37460002.
Impact Statement: Fetal alcohol spectrum disorders (FASD) are the most prevalent nongenetic birth defect in Western countries and a leading known cause of intellectual disability. This review article provides an overview of the current knowledge on the detrimental effects of ethanol on neural crest cell (NCC) induction, migration, differentiation, and survival. It also explores the intricate molecular mechanisms underpinning these effects. The article also spotlights potential therapeutic strategies for preventing or mitigating the detrimental effects of ethanol on NCCs and reducing the risk of FASD. Overall, this article offers a comprehensive overview of the current understanding of the impact of ethanol on NCCs and its role in FASD, and highlights the remarkable contributions of Dr. Shao-yu Chen’s laboratory to FASD research over the past three decades.Tang XL, Nasr M, Zheng S, Zoubul T, Stephan JK, Uchida S, Singhal R, Khan A, Gumpert A, Bolli R, Wysoczynski M. Bone Marrow and Wharton's Jelly Mesenchymal Stromal Cells are Ineffective for Myocardial Repair in an Immunodeficient Rat Model of Chronic Ischemic Cardiomyopathy. Stem Cell Rev Rep. 2023 Jul 28. doi: 10.1007/s12015-023-10590-6. Epub ahead of print. PMID: 37500831.
Impact Statement: This study found human Wharton's jelly (WJ) and bone marrow (BM) mesenchymal stromal cells (MSCs) have a small but not significant effect on cardiac structure and function when injected intramyocardially in immunodeficient rats chronically after MI.Price SL, Thibault D, Garrison TM, Brady A, Guo H, Kehl-Fie TE, Garneau-Tsodikova S, Perry RD, van Opijnen T, Lawrenz MB. Droplet Tn-Seq identifies the primary secretion mechanism for yersiniabactin in Yersinia pestis. EMBO Rep. 2023 Jul 28:e57369. doi: 10.15252/embr.202357369. Epub ahead of print. PMID: 37501563.
Impact Statement: Dr. Guo participated in a research lead by Dr. Lawrenz, which had revealed the yersiniabactin secretion mechanism that has eluded researchers for over 30 years and identified a potential therapeutic target for bacteria that use yersiniabactin for metal acquisition.Walls KM, Hong KU, Hein DW. Induction of glucose production by heterocyclic amines is dependent on N-acetyltransferase 2 genetic polymorphism in cryopreserved human hepatocytes. Toxicol Lett. 2023 Jul 1;383:192-195. doi: 10.1016/j.toxlet.2023.07.002. Epub 2023 Jul 7. PMID: 37423373.
Impact Statement: Recent epidemiological studies reported significant associations between dietary heterocyclic amine (HCA) exposure and insulin resistance and type II diabetes, and our laboratory recently reported that HCAs induce insulin resistance and glucose production in human hepatocytes. The current study for the first time showed that insulin resistance and glucose production following HCA exposures in human hepatocytes is modified by the N-acetyltransferase 2 genetic polymorphism, reflective of precision environmental health.Head KZ, Bolatimi OE, Gripshover TC, Tan M, Li Y, Audam TN, Jones SP, Klinge CM, Cave MC, Wahlang B. Investigating the effects of long-term Aroclor 1260 exposure on fatty liver disease in a diet-induced obesity mouse model. Front Gastroenterol (Lausanne). 2023;2:1180712. doi: 10.3389/fgstr.2023.1180712. Epub 2023 May 12. PMID: 37426695; PMCID: PMC10327714.
Impact Statement: The publication focused on understanding the longer-term impact (31 weeks) of PCB exposures on the liver and demonstrated that with longer duration of exposure, PCBs were able to induce more severe liver injury outcomes including liver cancer development. To our knowledge, this is the first study to demonstrate that PCBs, at doses relevant to current environmental exposure patterns, resulted in progressive liver disease outcomes, and underscores the importance of considering ‘duration of exposure’ when assessing hepatotoxicity indices for these chemicals.Klinge CM. Opportunities and challenges in microRNA research and clinical application. Endocrinology. 2023 Jul 25:bqad115. doi: 10.1210/endocr/bqad115. Epub ahead of print. PMID: 37490849.
Impact Statement: This is an invited commentary on a recent review paper discussing the current state of miRNA research and clinical applications that was published in Endocrinology.Xu R, Vatsalya V, He L, Ma X, Feng W, McClain CJ, Zhang X. Altered urinary tryptophan metabolites in alcohol-associated liver disease. Alcohol (Hanover). 2023 Jul 11. doi: 10.1111/acer.15148. Epub ahead of print. PMID: 37431708.
Impact Statement: This study found that Tryptophan (Trp) metabolism differs between Alcohol-associated liver disease (ALD) patients and healthy controls even though the concentration of Trp was not affected. Two Trp metabolites, quinolinic acid and indoxyl sulfate, correlate highly with the severity of ALD.de Carvalho Ribeiro M, Iracheta-Vellve A, Babuta M, Calenda CD, Copeland C, Zhuang Y, Lowe PP, Hawryluk D, Catalano D, Cho Y, Barton B, Dasarathy S, McClain C, McCullough AJ, Mitchell MC, Nagy LE, Radaeva S, Lien E, Golenbock DT, Szabo G. Alcohol-induced extracellular ASC specks perpetuate liver inflammation and damage in alcohol-associated hepatitis even after alcohol cessation. Hepatology. 2023 Jul 1;78(1):225-242. doi: 10.1097/HEP.0000000000000298. Epub 2023 Mar 3. PMID: 36862512.
McClain CJ, Kirpich I, Song M, Vatsalya V. Keratin 18-M65: A biomarker for early-stage alcohol-associated liver disease. Alcohol (Hanover). 2023 Jul;47(7):1257-1260. doi: 10.1111/acer.15117. Epub 2023 Jun 14. PMID: 37526591.
Impact Statement: This article provides critical insights into the application of the K18 biomarker as a potential tool for identifying early and aggressive alcohol-associated liver disease (ALD), particularly relevant for patients entering alcohol treatment programs.Liu L, Li F, Shao T, Zhang L, Lee J, Dryden G, McClain CJ, Zhao C, Feng W. FGF21 Depletion Attenuates Colitis through Intestinal Epithelial IL-22-STAT3 Activation in Mice. Nutrients. 2023 Apr 26;15(9):2086. doi: 10.3390/nu15092086. PMID: 37432218; PMCID: PMC10181108.
Impact Statement: This study uncovers a novel role for Fibroblast Growth Factor 21 (FGF21) in inflammatory bowel disease (IBD) and its potential impact on disease severity. By utilizing an experimental IBD model and comparing FGF21 knockout (KO) and wild-type (WT) mice, the research reveals that FGF21 deficiency mitigates the severity of colitis induced by dextran sodium sulfate (DSS). This effect is associated with enhanced activation of the IL-22-STAT3 signaling pathway in intestinal epithelial cells, shedding light on a potential avenue for therapeutic interventions targeting IBD.Anderson LB, Kanneganti D, Houk MB, Holm RH, Smith T. Generative AI as a Tool for Environmental Health Research Translation. Geohealth. 2023 Jul 26;7(7):e2023GH000875. doi: 10.1029/2023GH000875. PMID: 37502196; PMCID: PMC10369501.
Impact Statement: We demonstrate how generative AI, like ChatGPT, can be used to create Plain Language Summaries (PLS) of published studies and excels at insight synthesis, such as targeting an eighth-grade reading level or emphasizing key findings and real-world applications. In the field of environmental health science, this no-cost technology offers the potential to enhance research translation to a wide range of community and public policy stakeholders.Blair LK, Howard J, Peiper NC, Little BB, Taylor KC, Baumgartner R, Creel L, DuPre NC. Residence in urban or rural counties in relation to opioid overdose mortality among Kentucky hospitalizations before and during the COVID-19 pandemic. Int J Drug Policy. 2023 Jul 18;119:104122. doi: 10.1016/j.drugpo.2023.104122. Epub ahead of print. PMID: 37473677.
Impact Statement: his study investigated the impact of residence in urban or rural counties on opioid overdose mortality in Kentucky during the opioid epidemic, and how this relationship was influenced by the COVID-19 pandemic. Prior to the pandemic, patients in urban counties had significantly higher odds of opioid overdose death compared to rural counties, but during the pandemic, the distinction between urban and rural areas diminished, with opioid overdose mortality rates converging. The COVID-19 pandemic introduced challenges that exacerbated opioid mortality trends, affecting both urban and rural populations, reflecting the complex interplay between social, economic, and healthcare factors.Minooei F, Gilbert NM, Zhang L, Sarah NeCamp M, Mahmoud MY, Kyser AJ, Tyo KM, Watson WH, Patwardhan R, Lewis WG, Frieboes HB, Lewis AL, Steinbach-Rankins JM. Rapid-dissolving electrospun nanofibers for intra-vaginal antibiotic or probiotic delivery. Eur J Pharm Biopharm. 2023 Jul 19:S0939-6411(23)00181-9. doi: 10.1016/j.ejpb.2023.07.009. Epub ahead of print. PMID: 37479065.
Impact Statement: This study introduces a novel and promising approach to address microbiological imbalances in the female genitourinary system by utilizing rapid-dissolving electrospun polyethylene oxide (PEO) fibers for the delivery of antibiotics and probiotics. The research demonstrates the successful prevention and treatment of Gardnerella infections through this platform, offering an innovative strategy to enhance therapeutic options for genitourinary health while showcasing the feasibility of this approach in both in vitro and in vivo settings.Sarkar OS, Donninger H, Al Rayyan N, Chew LC, Stamp B, Zhang X, Whitt A, Li C, Hall M, Mitchell RA, Zippelius A, Eaton J, Chesney JA, Yaddanapudi K. Monocytic MDSCs exhibit superior immune suppression via adenosine and depletion of adenosine improves efficacy of immunotherapy. Sci Adv. 2023 Jun 30;9(26):eadg3736. doi: 10.1126/sciadv.adg3736. Epub 2023 Jun 30. PMID: 37390211; PMCID: PMC10313166.
Impact Statement: This study found adenosine metabolism shapes the behavior of monocytes in tumors and depletion of adenosine improves efficacy of cancer therapy.Ayangeakaa SD, Kerr J, Combs RM, Harris LM, Sears JS, Parker K, Sterrett-Hong E. Sociocultural and structural influences on HIV Pre-Exposure Prophylaxis (PrEP) Engagement and Uptake among African American Young adults. BMC Public Health. 2023 Jul 26;23(1):1427. doi: 10.1186/s12889-023-16273-8. PMID: 37495954; PMCID: PMC10369814.
- Little BB, Shakib S, Pena Reyes ME, Karimi S, Vu GT, Dupré N, McKinney WP, Mitra R. COVID-19 infection and mortality among non-pregnant indigenous adults in Mexico 2020-2022: Impact of marginalisation. J Glob Health. 2023 Jul 28;13:06030. doi: 10.7189/jogh.13.06030. PMID: 37506193; PMCID: PMC10386760.
Petri BJ, Cave MC, Klinge CM. Changes in m6A in Steatotic Liver Disease. Genes (Basel). 2023 Aug 19;14(8):1653. doi: 10.3390/genes14081653. PMID: 37628704; PMCID: PMC10454815.
Impact Statement: This is a review paper in which we summarized the readers, writers, and erasers of N6-methyladenosine (m6A), the current methods of detecting m6A in specific genes, and the state of knowledge about m6A and other RNA modifications in steatotic liver disease.Chen N, Cheng D, Sodipo MO, Barnard ME, DuPre NC, Tamimi RM, Warner ET. Impact of age, race, and family history on COVID-19-related changes in breast cancer screening among the Boston mammography cohort study. Breast Cancer Res Treat. 2023 Aug 25. doi: 10.1007/s10549-023-07083-y. Epub ahead of print. PMID: 37624552.
Impact Statement: After the COVID-19 lockdown period, the return to breast cancer screening was lower in women 50 years and older, and it was lower in non-White women for diagnostic imaging. Careful attention must be paid to ensure equitable resumption of breast cancer screening and care that was greatly impacted by the COVID-19 pandemic.Hein DW, Salazar-González RA, Doll MA, Zang Y. The effect of the rs1799931 G857A (G286E) polymorphism on N-acetyltransferase 2-mediated carcinogen metabolism and genotoxicity differs with heterocyclic amine exposure. Arch Toxicol. 2023 Oct;97(10):2697-2705. doi: 10.1007/s00204-023-03577-2. Epub 2023 Aug 18. PMID: 37592049.
Impact Statement: Cultures of DNA-repair deficient Chinese hamster ovary cells transfected with human CYP1A2 and NAT2 genetic variants were incubated with heterocyclic amine (HCA)carcinogens present in the human diet. HCA generation of DNA damage and reactive oxygen species varied with NAT2 genetic variant and HCA. The findings document the role of NAT2 genetic polymorphism in genotoxicity from HCA exposures.Schulman-Geltzer EB, Collins HE, Hill BG, Fulghum KL. Coordinated Metabolic Responses Facilitate Cardiac Growth in Pregnancy and Exercise. Curr Heart Fail Rep. 2023 Aug 15. doi: 10.1007/s11897-023-00622-0. Epub ahead of print. PMID: 37581772.
Impact Statement: This publication highlights the importance of metabolic adaptations in promoting physiological cardiac growth during pregnancy and exercise, revealing distinct yet interconnected mechanisms. Understanding the metabolic mechanisms that contribute to cardiac remodeling could identify actionable avenues to optimize cardiovascular health and prevent harmful cardiac remodeling, benefitting pregnant individuals and those engaged in regular exercise.Petri BJ, Piell KM, Wilt AE, Howser AD, Winkler L, Whitworth MR, Valdes BL, Lehman NL, Clem BF, Klinge CM. microRNA regulation of the serine synthesis pathway in endocrine-resistant breast cancer cells. Endocr Relat Cancer. 2023 Aug 1:ERC-23-0148. doi: 10.1530/ERC-23-0148. Epub ahead of print. PMID: 37650685.
Impact Statement: In this research paper, we identified four miRNAs that were downregulated by HNRNPA2B1 in breast cancer cells that regulate the transcript and protein levels of two key enzymes in the serine synthesis pathway (SSP), phosphoserine aminotransferase 1 (PSAT1) and phosphoglycerate dehydrogenase (PHGDH). These miRNAs directly target the PSAT1 3'UTR (miR-145-5p and miR-424-5p) and the PHGDH 3'UTR (miR-34b-5p and miR-876-5p) in dual luciferase assays. Transient transfection of these miRNAs restored endocrine-therapy sensitivity in LCC9 and ZR-75-1-4-OHT tamoxifen-resistant breast cancer cells. Overall, our data suggest a role for decreased HNRNPA2B1-regulated miRNAs in endocrine-resistance and upregulation of the SSP to promote tumor progression in ER+ breast cancer.Keck JW, Lindner J, Liversedge M, Mijatovic B, Olsson C, Strike W, Noble A, Adatorwovor R, Lacy P, Smith T, Berry SM. Wastewater Surveillance for SARS-CoV-2 at Long-Term Care Facilities: Mixed Methods Evaluation. JMIR Public Health Surveill. 2023 Aug 29;9:e44657. doi: 10.2196/44657. PMID: 37643001; PMCID: PMC10467632.
Impact Statement: The study demonstrated that wastewater surveillance could potentially serve as an effective early warning system for detecting SARS-CoV-2 in long-term care facilities (LTCFs). While the surveillance efficiently detected SARS-CoV-2 and additional pathogens of interest, it acknowledged some challenges that need to be addressed for broad adoption in these settings.Groswald AM, Gripshover TC, Watson WH, Wahlang B, Luo J, Jophlin LL, Cave MC. Investigating the Acute Metabolic Effects of the N-Methyl Carbamate Insecticide, Methomyl, on Mouse Liver. Metabolites. 2023 Aug 1;13(8):901. doi: 10.3390/metabo13080901. PMID: 37623845; PMCID: PMC10456691.
Impact Statement: This publication demonstrates that methomyl, an n-methyl carbamate insecticide, disrupts hepatic metabolism and may act as an endocrine disruptor, highlighting potential health risks. These findings emphasize the need for further research into the impact of n-methyl carbamate insecticides on metabolic health and diseases like toxicant-associated steatotic liver disease (TASLD).- Ghosh S, Erickson D, Chua MJ, Collins J, Jala VR. The microbial metabolite Urolithin A reduces C. difficile toxin expression and repairs toxin-induced epithelial damage. bioRxiv [Preprint]. 2023 Jul 24:2023.07.24.550342. doi: 10.1101/2023.07.24.550342. PMID: 37546803; PMCID: PMC10402075.
Cai L, Tan Y, Watson S, Wintergerst K. Diabetic cardiomyopathy - Zinc preventive and therapeutic potentials by its anti-oxidative stress and sensitizing insulin signaling pathways. Toxicol Appl Pharmacol. 2023 Oct 15;477:116694. doi: 10.1016/j.taap.2023.116694. Epub 2023 Sep 20. PMID: 37739320.
Impact Statement: Oxidative stress and insulin resistance are two key mechanisms for the development of diabetic cardiomyopathy. In this review, we discussed how zinc and metallothionein protect the heart from type 1 or type 2 diabetes through its anti-oxidative function and insulin-mediated PI3K/Akt signaling activation. Ultimately, there is pre-clinical and clinical evidence for the preventive and therapeutic potential of zinc supplementation through its anti-oxidative stress and sensitizing insulin signaling actions to reduce risk of heart disease and improve health outcomes of patients living with diabetes.Islam MS, Cai L, Horowitz M. Recent therapeutic targets for the prevention and management of diabetic complications. World J Diabetes. 2023 Sep 15;14(9):1330-1333. doi: 10.4239/wjd.v14.i9.1330. PMID: 37771330; PMCID: PMC10523234.
Impact Statement: Diabetes and associated complications remain major global public health issues, for which although a number of novel therapeutic approaches have been reported recently, some of them have not received comparable attention. Therefore, this editorial briefly discussed some recent therapeutic approaches to the prevention and management of diabetes and its associated complications, as well as potential directions for future research and development in this area.Clark BJ, Klinge CM. Structure-function of DHEA binding proteins. Vitam Horm. 2023;123:587-617. doi: 10.1016/bs.vh.2022.12.002. Epub 2022 Dec 16. PMID: 37717999.
Impact Statement: The extensive influence of Dehydroepiandrosterone (DHEA) and its sulfated metabolite, DHEA-S, on diverse biological systems, including the central nervous system, cardiovascular system, and reproductive system, is underscored by their ability to engage multiple receptors and signaling pathways. This comprehensive review provides an updated and comprehensive understanding of the intricate physiological, biochemical, and molecular mechanisms underlying the multifaceted effects of DHEA and DHEA-S, shedding light on their critical role in modulating various physiological processes.Wang L, Zhou M, Kong X, Wu S, Ding C, Hu X, Guo H, Yan J. Specific Targeting of STAT3 in B Cells Suppresses Progression of B Cell Lymphoma. Int J Mol Sci. 2023 Sep 4;24(17):13666. doi: 10.3390/ijms241713666. PMID: 37686472; PMCID: PMC10563066.
Impact Statement: The findings of this publication indicate that specifically targeting STAT3 siRNA to B cell lymphoma cell lines can significantly decrease STAT3 activity and inhibit tumor progression in vitro and in vivo, suggesting its potential utilization for cancer treatment.Harris LM, Marsh JC, Khachikian T, Serrett V, Kong Y, Guerrero EG. What can we learn from COVID-19 to improve opioid treatment? Expert providers respond. J Subst Use Addict Treat. 2023 Nov;154:209157. doi: 10.1016/j.josat.2023.209157. Epub 2023 Aug 29. PMID: 37652210.
Impact Statement: Using the COVID-19 pandemic and subsequent organizational challenges as a backdrop, this study explores providers from Opioid Use Disorder (OUD) outpatient treatment programs perspectives about strategies and policies that, if made permanent, can potentially improve access to and quality of OUD treatment. Providers identified three primary areas for strategic innovation designed to improve access and quality: (1) designing better medication utilization, (2) increasing telemedicine capacity, (3) improving reimbursement policies. These strategies for system transformation enable us to use lessons from the COVID-19 pandemic to direct policy and programmatic reform, such as expanding eligibility for take-home medication and enhancing access to telehealth services.Huang J, Mariyappa R, Byrne KR, Clifford SP. Right Ventricular Dysfunction During Left Ventricular Assist Device Implantation: Roles of Anesthesiologists. ASAIO J. 2023 Oct 1;69(10):915-917. doi: 10.1097/MAT.0000000000002049. Epub 2023 Sep 27. PMID: 37773148.
Impact Statement: This publication sheds light on the critical impact of anesthesia induction on right ventricular (RV) dysfunction before left ventricular assist device (LVAD) implantation, highlighting the complex interplay of various factors during surgery. Their findings emphasize the necessity for meticulous perioperative management, ventilation optimization, and tailored anesthetic choices to mitigate RV dysfunction in LVAD patients, underlining the importance of anesthesiologists' vigilance in improving both short-term and long-term clinical outcomes for these complex cases.Lindsey ML, LeBlanc AJ, Bertrand L, Bradshaw AD, Kleinbongard P. Improving rigor and reproducibility in cardiovascular research. Am J Physiol Heart Circ Physiol. 2023 Oct 1;325(4):H866-H868. doi: 10.1152/ajpheart.00524.2023. Epub 2023 Sep 1. PMID: 37656129.
Impact Statement: Reports of failures by laboratories to repeat experiments performed by other laboratories have launched a whole discussion in the biomedical research community centered on the importance of establishing rigor and reproducibility in research and how to implement plans to achieve this goal. In this editorial, we highlight the three themes that arose in the articles published for a recent call for papers on “Innovation in Improving Rigor and Reproducibility in Cardiovascular Research” collection: 1) improving methods and models, 2) incorporating sex as a biological variable, and 3) testing assumptions.Elnagdy M, Wang Y, Rodriguez W, Zhang J, Bauer P, Wilkey DW, Merchant M, Pan J, Farooqui Z, Cannon R, Rai S, Maldonado C, Barve S, McClain CJ, Gobejishvili L. Increased expression of phosphodiesterase 4 in activated hepatic stellate cells promotes cytoskeleton remodeling and cell migration. J Pathol. 2023 Nov;261(3):361-371. doi: 10.1002/path.6194. Epub 2023 Sep 21. PMID: 37735782.
Impact Statement: This publication reveals, for the first time, that PDE4 enzymes play a pivotal role in promoting cytoskeleton remodeling and hepatic stellate cell migration, shedding light on their significance in the development of liver fibrosis, and offers potential therapeutic insights. Targeted inhibition of PDE4 with rolipram not only hindered fibrogenesis and collagen deposition but also mitigated the expression of key fibrosis-related genes, showcasing the promise of this approach in combating liver disease.Marin-Ramirez A, Mahoney T, Smith T, Holm RH. Predicting wastewater treatment plant influent in mixed, separate, and combined sewers using nearby surface water discharge for better wastewater-based epidemiology sampling design. Sci Total Environ. 2023 Sep 27;906:167375. doi: 10.1016/j.scitotenv.2023.167375. Epub ahead of print. PMID: 37774884.
Impact Statement: This publication presents a methodology to optimize wastewater sampling during high hydrologic activity. By integrating readily available environmental data, it enhances our ability to monitor public health indicators in wastewater, leading to timely and informed public health interventions.10. Petri BJ, Piell KM, Wahlang B, Head KZ, Rouchka EC, Park JW, Hwang JY, Banerjee M, Cave MC, Klinge CM. Altered splicing factor and alternative splicing events in a mouse model of diet- and polychlorinated biphenyl-induced liver disease. Environ Toxicol Pharmacol. 2023 Sep 7;103:104260. doi: 10.1016/j.etap.2023.104260. Epub ahead of print. PMID: 37683712.
Impact Statement: This paper reports the identification of 101 splice factors showing altered transcript abundance in the livers of high fat diet (HFD)-fed C57Bl/6 J male mice after co-exposure to the PCB mixture Ar1260 and PCB126. We identified four transcripts (Tnrc6c, Dhrs3, Mapsk7, and Wdr59) and of m6A writers, erasers, or readers with altered skipped exon frequencies in the livers from the HFD-fed mice after Aroclor1260 + PCB126 co-exposure. These data suggest that PCB-exposure contributes to dysregulated splicing in the liver transcriptome that may play a role in metabolic dysfunction-associated steatotic liver disease (MASLD) progression.- Luo J, Watson WH, Gripshover TC, Qaissi Z, Wahlang B. Sex-specific effects of acute chlordane exposure in the context of steatotic liver disease, energy metabolism and endocrine disruption. Food Chem Toxicol. 2023 Oct;180:114024. doi: 10.1016/j.fct.2023.114024. Epub 2023 Sep 4. PMID: 37666290.
Impact Statement: This study reveals that chlordane, an organochlorine pesticide (OCP) that is environmentally persistant, significantly impacts liver health and metabolism differently in male and female mice, shedding light on potential risks to human liver function and hormone regulation associated with pesticide exposure. These findings emphasize the need for further research to better understand the sex-specific effects of chlordane and other organochlorine pesticides on liver disease and metabolic disruption in humans.
Ali MT, Gebreil A, ElNakieb Y, Elnakib A, Shalaby A, Mahmoud A, Sleman A, Giridharan GA, Barnes G, Elbaz AS. A personalized classification of behavioral severity of autism spectrum disorder using a comprehensive machine learning framework. Sci Rep. 2023 Oct 9;13(1):17048. doi: 10.1038/s41598-023-43478-z. PMID: 37813914; PMCID: PMC10562430.
Impact Statement: In this study, we've developed an advanced artificial intelligence model that dissects Autism Spectrum Disorder (ASD) into its behavioral components and accurately identifies specific brain regions associated with ASD severity. By leveraging magnetic resonance imaging (MRI) data and behavioral assessments, our AI-based system achieved an impressive 96% accuracy in classifying ASD severity across various behavioral groups, offering a promising approach to expedite diagnosis and potentially improve outcomes for individuals with ASD by streamlining the diagnostic process and pinpointing brain regions crucial for ASD identification and understanding.Zhang W, Cheng Y, Zhang L, Wei Y, Xie H, Huang J. Association between emergence delirium and brain status parameters in children undergoing general anesthesia: A prospective observational study. Paediatr Anaesth. 2023 Oct 3. doi: 10.1111/pan.14779. Epub ahead of print. PMID: 37788105.
Impact Statement: Both anxiety index and comfort index derived from #electroencephalogram wavelet analysis were associated with emergence delirium in pediatric patients undergoing general anesthesia for dental surgery. Wavelet index and pain threshold index were not associated with emergence #delirium during general anesthesia for dental surgery in #children.Sutaria SR, Morris J, Xie Z, Cooke E, Silvers S, Long G, Balcom D, Marimuthu S, Parrish L, Aliesky H, Arnold F, Huang J, Fu X, Nantz M. A feasibility study on exhaled breath analysis using UV spectroscopy to detect COVID-19. J Breath Res. 2023 Oct 24. doi: 10.1088/1752-7163/ad0646. Epub ahead of print. PMID: 37875100.
Impact Statement: UV absorbance measurements on exhaled #breath samples collected from silicon microreactors can be used to detect #COVID-19. There were statistically significant differences in measured UV absorbance values between healthy and symptomatic COVID-19 positive subjects in the wavelength range from 235 nm to 305 nm.Yan H, Chen J, Luo J, Li G, Li A, Li W, Jiang M, Li J, Huang J, Fang F, Cang J. Prophylatic use of IV nalmefene to prevent epidural opioid-induced pruritus: A multicenter, randomized clinical trial. J Clin Anesth. 2023 Oct 19;92:111301. doi: 10.1016/j.jclinane.2023.111301. Epub ahead of print. PMID: 37865021.
Impact Statement:A single dose of 0.5 μg/kg #nalmefene intravenously significantly reduced the incidence and severity of epidural-opioid induced #pruritus within 24 h after surgery without affecting the efficacy of epidural analgesia.Vatsalya V, Verster JC, Sagaram M, Royer AJ, Hu H, Parthasarathy R, Schwandt ML, Kong M, Ramchandani VA, Feng W, Agrawal R, Zhang X, McClain CJ. Novel paradigms for the gut-brain axis during alcohol withdrawal, withdrawal-associated depression, and craving in patients with alcohol use disorder. Front Psychiatry. 2023 Sep 29;14:1203362. doi: 10.3389/fpsyt.2023.1203362. PMID: 37840804; PMCID: PMC10570744.
Impact Statement: This study illuminates the intricate link between gut function, immune response, and symptoms associated with Alcohol Use Disorder (AUD), uncovering how specific markers in the gut-immune system correlate with withdrawal, depression, and craving tendencies in patients. By revealing the role of gut dysfunction and proinflammatory markers, this research paves the way for understanding a novel gut-brain axis, offering potential insights into targeted interventions for managing withdrawal symptoms, depression, and cravings in individuals with AUD.Meaza I, Williams AR, Lu H, Kouokam JC, Toyoda JH, Croom-Perez TJ, Wise SS, Aboueissa AE, Wise JP Sr. Prolonged particulate hexavalent chromium exposure induces RAD51 foci inhibition and cytoplasmic accumulation in immortalized and primary human lung bronchial epithelial cells. Toxicol Appl Pharmacol. 2023 Oct 5;479:116711. doi: 10.1016/j.taap.2023.116711. Epub ahead of print. PMID: 37805091.
Impact Statement: This study translates the mechanism behind hexavalent chromium's (Cr(VI)) carcinogenic impact on human lung cells, involving how acute and prolonged exposure to Cr(VI) induces DNA double-strand breaks (DSBs) and disrupts the repair process, leading to chromosomal instability from one lung cell type to a second lung cell type, specifically the type in which lung tumors originate. Demonstrating this mechanism occurs in multiple cell types deepens our understanding of this mechanism and strengthens the evidence that this mechanism is the key to understanding and potentially mitigating Cr(VI)-induced lung tumors.Montoya-Durango D, Walter MN, Rodriguez W, Wang Y, Chariker JH, Rouchka EC, Maldonado C, Barve S, McClain CJ, Gobejishvili L. Dysregulated Cyclic Nucleotide Metabolism in Alcohol-Associated Steatohepatitis: Implications for Novel Targeted Therapies. Biology (Basel). 2023 Oct 10;12(10):1321. doi: 10.3390/biology12101321. PMID: 37887031; PMCID: PMC10604143.
Impact Statement: This study delineates a significant decrease in specific gut microbiome-derived metabolites, such as serotonin and indole-3-propionic acid, in patients with advanced Alcohol-Associated Liver Disease (ALD), shedding light on the intricate interplay between altered gut microbial metabolites, liver pathologies, and host metabolism. By revealing disruptions in metabolite concentrations and hepatic enzyme expression, particularly in severe ALD cases, this research unveils the complex alterations in gut-derived metabolites, offering valuable insights into potential pathways for targeted interventions to alleviate the progression and severity of ALD through modulating gut microbiome-associated metabolites and hepatic metabolism.Mrdjen M, Huang E, Pathak V, Bellar A, Welch N, Dasarathy J, Streem D, McClain CJ, Mitchell M, Radaeva S, Barton B, Szabo G, Dasarathy S, Wang Z, Hazen SL, Brown JM, Nagy LE. Dysregulated meta-organismal metabolism of aromatic amino acids in alcohol-associated liver disease. Hepatol Commun. 2023 Oct 12;7(11):e0284. doi: 10.1097/HC9.0000000000000284. PMID: 37820283; PMCID: PMC10578770.
Impact Statement: This study highlights significant decreases in specific gut microbiome-derived metabolites in individuals with advanced stages of Alcohol-Associated Liver Disease (ALD), shedding light on the intricate interplay between altered gut microbiota, host metabolism, and disease progression. By revealing disruptions in metabolite concentrations and hepatic enzyme expression, particularly in severe ALD cases, this research offers insights into the complex relationship between gut microbial metabolites and the progression of liver disease, potentially paving the way for targeted therapeutic interventions to mitigate the effects of ALD.Ghare SS, Charpentier BT, Ghooray DT, Zhang J, Vadhanam MV, Reddy S, Joshi-Barve S, McClain CJ, Barve SS. Tributyrin Mitigates Ethanol-Induced Lysine Acetylation of Histone-H3 and p65-NFκB Downregulating CCL2 Expression and Consequent Liver Inflammation and Injury. Nutrients. 2023 Oct 17;15(20):4397. doi: 10.3390/nu15204397. PMID: 37892472; PMCID: PMC10610222.
Impact Statement: This research uncovers the pivotal role of protein acetylation in regulating the expression of hepatic CCL2, a key factor contributing to inflammation and injury in Alcohol-Associated Liver Disease (ALD). By revealing how ethanol-induced acetylation changes impact gene expression and subsequent liver inflammation, and demonstrating the potential therapeutic effect of tributyrin in reversing these alterations, this study provides crucial insights into the mechanisms underlying ALD progression, offering a promising avenue for targeted interventions to mitigate liver injury and inflammation in this condition.Anderson LB, Ness HD, Holm RH, Smith T. Wastewater-Informed Digital Advertising as a COVID-19 Geotargeted Neighborhood Intervention: Jefferson County, Kentucky, 2021-2022. Am J Public Health. 2023 Oct 19:e1-e4. doi: 10.2105/AJPH.2023.307439. Epub ahead of print. PMID: 37856730.
Impact Statement: This publication demonstrates the potential of using localized public health clinical case data and wastewater pathogen data to implement a geotargeted digital messaging intervention. This approach offers a more responsive and targeted solution for environmental health risks.Klaassen F, Holm RH, Smith T, Cohen T, Bhatnagar A, Menzies NA. Predictive power of wastewater for nowcasting infectious disease transmission: A retrospective case study of five sewershed areas in Louisville, Kentucky. Environ Res. 2023 Oct 12:117395. doi: 10.1016/j.envres.2023.117395. Epub ahead of print. PMID: 37838198.
Impact Statement: This research underscores the potential value of wastewater data in enhancing infectious disease nowcasting, particularly when clinical surveillance data are limited or absent, offering a valuable alternative for early pandemic monitoring or in resource-constrained settings. Although the addition of wastewater data only marginally improved predictive performance compared to models using traditional case and death reports, its inclusion significantly enhanced agreement with estimates derived from models utilizing death data, emphasizing its utility in augmenting disease trend predictions.Jin L, Xie Z, Lorkiewicz P, Srivastava S, Bhatnagar A, Conklin DJ. Endothelial-dependent Relaxation of Alpha-Pinene and Two Metabolites, Myrtenol and Verbenol, in Isolated Murine Blood Vessels. Am J Physiol Heart Circ Physiol. 2023 Oct 27. doi: 10.1152/ajpheart.00380.2023. Epub ahead of print. PMID: 37889254.
Impact Statement: Because the positive associations between greenness exposure and human cardiovascular health may be a result of exposure to plant-derived compounds, we explored the direct vascular action of alpha-pinene, an abundant plant compound, and two of its metabolites. Surprisingly, both alpha-pinene and its metabolites, myrtenol and verbenol, relax blood vessels by release of nitric oxide from the endothelium – a novel finding that may explain some of the beneficial health effects of greenness.Lykoudi A, Ferragut Cardoso AP, Wise SS, Banerjee M, States JC. Clonal variability in chromosomal instability as a potential driver in the acquisition of tumorigenic phenotype in chronic arsenic-exposed and hsa-miR-186 overexpressing human keratinocytes. Toxicol Appl Pharmacol. 2023 Oct 20;479:116730. doi: 10.1016/j.taap.2023.116730. Epub ahead of print. PMID: 37866707.
Impact Statement: Long-term exposure to arsenic in drinking water affects millions globally, ranking as the second most prevalent cause of skin cancer, with arsenic-triggered chromosomal instability contributing significantly to this risk. Investigating the role of hsa-miR-186, researchers found its heightened presence in arsenic-induced skin cancer, suggesting its potential involvement in the malignant transformation of cells by disrupting mitotic progression, highlighting a critical link between molecular variability and the development of arsenic-induced skin carcinogenesis.- Browning MHEM, Locke DH, Konijnendijk C, Labib SM, Rigolon A, Yeager R, Bardhan M, Berland A, Dadvand P, Helbich M, Li F, Li H, James P, Klompmaker J, Reuben A, Roman LA, Tsai WL, Patwary M, O'Neil-Dunne J, Ossola A, Wang R, Yang B, Yi L, Zhang J, Nieuwenhuijsen M. Measuring the 3-30-300 rule to help cities meet nature access thresholds. Sci Total Environ. 2023 Oct 11:167739. doi: 10.1016/j.scitotenv.2023.167739. Epub ahead of print. PMID: 37832672.
Impact Statement: The 3-30-300 rule serves as benchmark for healthy access to nature, suggesting that urban residents should at least be able to see 3 trees from a window, have 30% canopy cover, and live within 300m of a park. This publication aids society and public health by providing guidance for scientists, practitioners, and policymakers to measure the 3-30-300 benchmarks and focus intervention efforts. - Cai L, Holm RH, Biddle DJ, Zhang CH, Talley D, Smith T, States JC. Wastewater-based epidemiology for comprehensive communitywide exposome surveillance: A gradient of metals exposure. medRxiv [Preprint]. 2023 Sep 29:2023.09.26.23295844. doi: 10.1101/2023.09.26.23295844. PMID: 37808726; PMCID: PMC10557802.
Erhabor J, Boakye E, Obisesan O, Osei AD, Tasdighi E, Mirbolouk H, DeFilippis AP, Stokes AC, Hirsch GA, Benjamin EJ, Rodriguez CJ, El Shahawy O, Robertson RM, Bhatnagar A, Blaha MJ. E-Cigarette Use Among US Adults in the 2021 Behavioral Risk Factor Surveillance System Survey. JAMA Netw Open. 2023 Nov 1;6(11):e2340859. doi: 10.1001/jamanetworkopen.2023.40859. PMID: 37921768; PMCID: PMC10625038.
Impact Statement: These findings suggest that e-cigarette use remained common during the COVID-19 pandemic, particularly among young adults aged 18 to 24 years (18.3% prevalence). Notably, 71.5% of individuals aged 18 to 20 years who reported current e-cigarette use had never used combustible cigarettes. These results underscore the rationale for the implementation and enforcement of public health policies tailored to young adults.Hopkins CD, Wessel C, Chen O, El-Kersh K, Cathey D, Cave MC, Cai L, Huang J. A hypothesis: Potential contributions of metals to the pathogenesis of pulmonary artery hypertension. Life Sci. 2023 Nov 24;336:122289. doi: 10.1016/j.lfs.2023.122289. Epub ahead of print. PMID: 38007143.
Impact Statement: Metals may initiate or exacerbate the pathogenesis of PAH pulmonary arterial hypertension, by providing potential mechanism by which metals interact with hypoxia-inducible factor and tumor suppressor p53 to modulate their downstream cellular proliferation pathways.Hopkins CD, Wessel C, Chen O, El-Kersh K, Cave MC, Cai L, Huang J. Potential Roles of Metals in the Pathogenesis of Pulmonary and Systemic Hypertension. Int J Biol Sci. 2023 Sep 25;19(16):5036-5054. doi: 10.7150/ijbs.85590. PMID: 37928257; PMCID: PMC10620830.
Impact Statement: This review explores non-essential and essential metals and potential roles of their dyshomeostasis in pulmonaryhypertension and RightVentricle dysfunction.Warner JB, Hardesty JE, Song YL, Floyd AT, Deng Z, Jebet A, He L, Zhang X, McClain CJ, Hammock BD, Warner DR, Kirpich IA. Hepatic Transcriptome and Its Regulation Following Soluble Epoxide Hydrolase Inhibition in Alcohol-Associated Liver Disease. Am J Pathol. 2023 Nov 3:S0002-9440(23)00410-8. doi: 10.1016/j.ajpath.2023.09.016. Epub ahead of print. PMID: 37925018.
Impact Statement: Alcohol-associated liver disease (ALD) is a serious public health problem with limited pharmacologic options. The goal of the current study was to investigate the efficacy of pharmacologic inhibition of soluble epoxide hydrolase (sEH), an enzyme involved in lipid metabolism, in experimental ALD, and to examine the underlying mechanisms.Dong Z, Chen X, Ritter J, Bai L, Huang J. American society of anesthesiologists physical status classification significantly affects the performances of machine learning models in intraoperative hypotension inference. J Clin Anesth. 2024 Feb;92:111309. doi: 10.1016/j.jclinane.2023.111309. Epub 2023 Nov 2. PMID: 37922642.
Impact Statement: Different ASA physical status classes present different data distributions, and thus calls for distinct machine learning models to improve prediction accuracy and reduce predictive uncertainty. Uncertainty quantification enabled by Bayesian inference provides valuable information for clinicians as an additional metric to evaluate performance of machine learning models for medical decision making.Stanifer S, Delidow B, Rademacher K, Huntington-Moskos L, Kennoy K, Thaxton-Wiggins A, Wilmhoff C, Hahn EJ. Evaluation of a Faculty Fellows Program in Science Communication. J Appalach Health. 2023 Aug 1;5(2):85-99. doi: 10.13023/jah.0502.07. PMID: 38022491; PMCID: PMC10629883.
Impact Statement: This study demonstrates the significant positive impact of the Faculty Fellows in Science Communication (FFSC) program on enhancing self-efficacy in science communication across diverse audiences among faculty in environmental health science and education in Appalachia Kentucky. The findings underscore the program's effectiveness in empowering participants to engage with peers within and outside their departments, as well as lay audiences, offering valuable insights into tailored communication strategies and innovative methods to bridge the science communication gap.Condon S, Jophlin LL. Past, Present, and Future Therapies for Alcohol-Associated Hepatitis. Clin Ther. 2023 Nov 16:S0149-2918(23)00405-8. doi: 10.1016/j.clinthera.2023.10.013. Epub ahead of print. PMID: 37980219.
Impact Statement: This manuscript examines the evolution of therapies for acute alcohol-associated hepatitis from the early 1900’s to present, with consideration of the limitations of historical clinical trials and the caveats of landmark studies. Emerging therapies, only made possible by decades of prior work, are highlighted.Beare JE, Fleissig Y, Kelm NQ, Reed RM, LeBlanc AJ, Hoying JB, Kaufman CL. Mimicking Clinical Rejection Patterns in a Rat Osteomyocutaneous Flap Model of Vascularized Composite Allotransplantation. J Surg Res. 2023 Nov 16;295:28-40. doi: 10.1016/j.jss.2023.08.057. Epub ahead of print. PMID: 37979234.
Impact Statement: This research presents a novel rat osteomyocutaneous flap model employing varying tacrolimus doses, closely mirroring rejection patterns observed in clinical hand transplant programs. The findings highlight the crucial role of ischemia reperfusion injury (IRI) and microvascular changes in chronic rejection (CR) and vasculopathy, offering an adaptable experimental platform to investigate rejection mechanisms and potential interventions in vascularized composite allotransplantation (VCA).Tornai D, Mitchell M, McClain CJ, Dasarathy S, McCullough A, Radaeva S, Kroll-Desrosiers A, Lee J, Barton B, Szabo G. A novel score of IL-13 and age predicts 90-day mortality in severe alcohol-associated hepatitis: A multicenter plasma biomarker analysis. Hepatol Commun. 2023 Nov 22;7(12):e0296. doi: 10.1097/HC9.0000000000000296. PMID: 37994498; PMCID: PMC10666984.
Impact Statement: This study reveals crucial predictors of short-term mortality specifically in severe alcoholic hepatitis (AH) patients, uncovering eight biomarkers associated with 28- and 90-day mortality. Furthermore, the development of a composite score integrating IL-13 and age demonstrates superior prognostic accuracy for 90-day mortality compared to the widely used MELD score, offering a promising tool for better prognostication in this high-risk patient population irrespective of treatment type.Berrueta L, Muñoz-Vergara D, Martin D, Thompson R, Sansbury BE, Spite M, Badger GJ, Langevin HM. Effect of stretching on inflammation in a subcutaneous carrageenan mouse model analyzed at single-cell resolution. J Cell Physiol. 2023 Nov 1. doi: 10.1002/jcp.31133. Epub ahead of print. PMID: 37909412.
Impact Statement: This study investigates the impact of stretching on inflammation resolution at a cellular level in a mouse model. Findings indicate that 10-minute stretching sessions twice daily reduce inflammation, alter the production of specific lipid mediators, and influence gene expression in macrophages, offering insights into potential mechanisms for managing inflammatory responses.- Torre D, Fstkchyan YS, Ho JSY, Cheon Y, Patel RS, Degrace EJ, Mzoughi S, Schwarz M, Mohammed K, Seo JS, Romero-Bueno R, Demircioglu D, Hasson D, Tang W, Mahajani SU, Campisi L, Zheng S, Song WS, Wang YC, Shah H, Francoeur N, Soto J, Salfati Z, Weirauch MT, Warburton P, Beaumont K, Smith ML, Mulder L, Villalta SA, Kessenbrock K, Jang C, Lee D, De Rubeis S, Cobos I, Tam O, Hammell MG, Seldin M, Shi Y, Basu U, Sebastiano V, Byun M, Sebra R, Rosenberg BR, Benner C, Guccione E, Marazzi I. Nuclear RNA catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation. Mol Cell. 2023 Nov 14:S1097-2765(23)00903-6. doi: 10.1016/j.molcel.2023.10.036. Epub ahead of print. PMID: 37995687.
Impact Statement: Our genome includes thousands of fragments of viral genes leftover from prehistoric infections of our ancestors. This paper details how these viral remnants have been co-opted by our cells to help regulate gene expression during embryonic development. Furthering our understanding of this developmental regulation may be important for the development of future stem cell therapies.
Bhatnagar A, Keith R, Yeager R, Riggs D, Sears C, Bucknum B, Smith T, Fleischer D, Chandler C, Walker KL, Hart JL, Srivastava S, Turner J, Rai S. The Green Heart Project: Objectives, Design, and Methods. medRxiv [Preprint]. 2023 Dec 5:2023.12.05.23299461. doi: 10.1101/2023.12.05.23299461. PMID: 38105951; PMCID: PMC10723507.
Impact Statement: The Green Heart Project, initiated in 2018 in a low-to-middle-income mixed-race residential area of Louisville, KY, conducted a comprehensive study assessing the impact of increased urban greenery on environmental and community health. Through meticulous data collection, including sociodemographic factors, pollutant exposure, and cardiovascular function assessments, the project aims to provide valuable insights into the long-term effects of planting over 8,000 trees and shrubs in designated clusters, contributing to ongoing research on the benefits of urban green spaces.Chaudhari M, Zelko I, Lorkiewicz P, Hoetker D, Doelling B, Brittian K, Bhatnagar A, Srivastava S, Baba SP. Metabolic Pathways for Removing Reactive Aldehydes are Diminished in Atrophic Muscle During Heart Failure. Res Sq [Preprint]. 2023 Nov 21:rs.3.rs-3621159. doi: 10.21203/rs.3.rs-3621159/v1. PMID: 38045249; PMCID: PMC10690332.
Impact Statement: This study reveals a critical link between heart failure-induced muscle wasting and diminished metabolic pathways responsible for removing lipid peroxidation products and synthesizing histidyl dipeptides in skeletal muscle. The findings underscore the potential contribution of oxidative stress, specifically the reduced capacity to remove toxic aldehydes and decreased synthesis of histidyl dipeptides, to the pathogenesis of muscle atrophy in heart failure patients, highlighting novel targets for therapeutic intervention.Conklin DJ, Haberzettl P, MacKinlay KG, Murphy D, Jin L, Yuan F, Srivastava S, Bhatnagar A. Aldose Reductase (AR) Mediates and Perivascular Adipose Tissue (PVAT) Modulates Endothelial Dysfunction of Short-Term High-Fat Diet Feeding in Mice. Metabolites. 2023 Nov 24;13(12):1172. doi: 10.3390/metabo13121172. PMID: 38132854; PMCID: PMC10744918.
Impact Statement: This study highlights the significant role of aldose reductase (AR) in mediating endothelial dysfunction (ED) associated with short-term high-fat diet (HFD) feeding, particularly in the context of perivascular adipose tissue (PVAT). The findings suggest that vascular-localized AR could serve as a potential target for temporally selective intervention to mitigate ED and its associated complications in the context of increased adiposity, providing insights into the complex interplay between PVAT, AR, and vascular health.Xie Z, Sutaria SR, Chen JY, Gao H, Conklin DJ, Keith RJ, Srivastava S, Lorkiewicz P, Bhatnagar A. Evaluation of urinary limonene metabolites as biomarkers of exposure to greenness. Environ Res. 2023 Dec 22;245:117991. doi: 10.1016/j.envres.2023.117991. Epub ahead of print. PMID: 38141921.
Impact Statement: This study explores the establishment of cause-and-effect relationships between greenspaces and human health by incorporating quantitative measures of greenness exposure at the individual level. The identification and validation of urinary metabolites of limonene, such as uroterpenol glucuronide and dihydroperillic acid glucuronide, as potential biomarkers, offer a promising avenue for personalized assessment of exposure to green environments, providing valuable insights into the physical and mental health benefits associated with living in areas rich in vegetation.Barnard ME, DuPré NC, Heine JJ, Fowler EE, Murthy DJ, Nelleke RL, Chan A, Warner ET, Tamimi RM. Reproductive risk factors for breast cancer and association with novel breast density measurements among Hispanic, Black, and White women. Breast Cancer Res Treat. 2023 Dec 14. doi: 10.1007/s10549-023-07174-w. Epub ahead of print. PMID: 38095811.
Impact Statement: This study elucidates the racial and ethnic variations in breast density, a factor strongly associated with breast cancer risk. The findings highlight the influence of reproductive factors, specifically age at menarche, parity, and oral contraceptive use, on breast density, and provide insights into potential contributors to differences in breast cancer incidence across diverse populations.Kerr J, Smith A, Nzama N, Bullock NAA, Chandler C, Osezua V, Johnson K, Rozema I, Metzger IW, Harris LM, Bond K, LaPreze D, Rice BM. Systematic Review of Neighborhood Factors Impacting HIV Care Continuum Participation in the United States. J Urban Health. 2023 Dec 13. doi: 10.1007/s11524-023-00801-3. Epub ahead of print. PMID: 38093034.
Impact Statement: Social determinants, including neighborhood factors, play an important role in undermining HIV prevention. Social and economic disenfranchisement of neighborhoods negatively impacts HIV care continuum participation among persons living with HIV. This systematic review found that five key neighborhood factors (socioeconomic status, segregation, social disorder, stigma, and care access) were associated with challenged HIV care continuum participation. Structural interventions addressing neighborhood social and economic challenges may have favorable downstream effects for improving HIV care continuum participation.Qin X, Chen X, Zhao X, Yao L, Li B, Pan G, Xu J, Jiang R, Zhao Z, Liang Z, Guo X, Huang J, Li X. Evaluation of brain function in adult patent ductus arteriosus surgery: A multimodal monitoring approach. Curr Probl Cardiol. 2023 Dec 23;49(2):102334. doi: 10.1016/j.cpcardiol.2023.102334. Epub ahead of print. PMID: 38142948.
Impact Statement: Moderate hypothermia during cardiopulmonary bypass in adult PDA repair with combined rSO2 and BIS monitoring can reduce neurological complications post-surgery.Bradley J, Huang J, Kalra A, Reicher J. External validation of Fibresolve, a machine-learning algorithm, to non-invasively diagnose idiopathic pulmonary fibrosis. Am J Med Sci. 2023 Dec 24:S0002-9629(23)01475-1. doi: 10.1016/j.amjms.2023.12.009. Epub ahead of print. PMID: 38147938.
Impact Statement: In patients with suspected idiopathic pulmonary fibrosis with non-definite usual interstitial pneumonia on high resolution CT, Fibresolve can positively identify cases of idiopathic pulmonary fibrosis with high sensitivity.Sun J, Duncan S, Pal S, Kong M. Directed Acyclic Graph Assisted Method For Estimating Average Treatment Effect. J Biopharm Stat. 2023 Dec 27:1-20. doi: 10.1080/10543406.2023.2296047. Epub ahead of print. PMID: 38151852.
Impact Statement: This method establishes a framework for estimating the causal exposure (or treatment) effect by collaboratively constructing a directed acyclic graph and controlling a minimal set of confounding variables. It is particularly valuable for investigating the causal impact of environmental exposure on outcomes.Watson CT, Rodriguez OL, Engelbrecht E, Safonova Y, Marasco WA, Smith ML. Looking to the future of antibody genetics: resolving the roles of immunoglobulin diversity in gene regulation, function, and immunity. Genes Immun. 2023 Dec 14. doi: 10.1038/s41435-023-00238-3. Epub ahead of print. PMID: 38097744.
Impact Statement: This publication presents a commentary on the study published by Watson, Marasco, and Smith in Nature Communications in July 2023. That study defined complete genotypes and genomic variation within the immunoglobulin heavy chain locus (IGH) and demonstrated that IGH genomic variation directly impacts which antibody chains are available for expression, which differs widely person-to-person. This article highlights the paradigm-shifting nature of this discovery, and outlines a research-based plan for implementing this knowledge into enhancing the design and efficacy of vaccines and immunotherapies.Sokoloski KJ, Holm RH, Smith M, Ford EE, Rouchka EC, Smith T. What is the functional reach of wastewater surveillance for respiratory viruses, pathogenic viruses of concern, and bacterial antibiotic resistance genes of interest? Hum Genomics. 2023 Dec 18;17(1):114. doi: 10.1186/s40246-023-00563-8. PMID: 38105239; PMCID: PMC10726489.
Impact Statement:This publication emphasizes the significance of high-throughput sequencing in wastewater-based epidemiology for the broad and unbiased detection of human pathogens, antibiotic resistance genes, and other health-relevant entities. The call for collaborative networks among public health agencies, researchers, and community stakeholders highlights the need for a more inclusive public health infrastructure, positioning high-throughput sequencing of wastewater samples as a gold standard for comprehensively understanding and addressing community health, especially in the context of potential public health emergencies or pandemics.Holm RH, Nyirenda R, Smith T, Chigwechokha P. Addressing the challenges of establishing quality wastewater or non-sewered sanitation-based surveillance, including laboratory and epidemiological considerations, in Malawi. BMJ Glob Health. 2023 Nov;8(11):e013307. doi: 10.1136/bmjgh-2023-013307. PMID: 37918872; PMCID: PMC10626866.
Impact Statement: . This publication emphasizes the significance of high-throughput sequencing in wastewater-based epidemiology for the broad and unbiased detection of human pathogens, antibiotic resistance genes, and other health-relevant entities. The call for collaborative networks among public health agencies, researchers, and community stakeholders highlights the need for a more inclusive public health infrastructure, positioning high-throughput sequencing of wastewater samples as a gold standard for comprehensively understanding and addressing community health, especially in the context of potential public health emergencies or pandemics- States JC, Barchowsky A. Invited Perspective: Humanized Mice for Arsenic Metabolism-A Better Model for Investigating Arsenic-Induced Diseases? Environ Health Perspect. 2023 Dec;131(12):121308. doi: 10.1289/EHP13932. Epub 2023 Dec 27. PMID: 38150314; PMCID: PMC10752413.
Impact Statement: This invited commentary discusses an accompanying research article (https://doi.org/10.1289/EHP13932) that reports on use of a new mouse model for arsenic toxicology. The model has great potential for better understanding how arsenic exposure may impact human health. The commentary also discusses potential shortcomings and unanswered questions.
Missed Publication from November 2023:
1. Mo Y, Mo L, Zhang Y, Zhang Y, Yuan J, Zhang Q. High glucose enhances the activation of NLRP3 inflammasome by ambient fine particulate matter in alveolar macrophages. Part Fibre Toxicol. 2023 Nov 2;20(1):41. doi: 10.1186/s12989-023-00552-8. PMID: 37919797; PMCID: PMC10621103.
Impact Statement: Epidemiological studies have demonstrated that individuals with preexisting conditions, including diabetes mellitus (DM), are more susceptible to air pollution. However, the underlying mechanisms remain unclear. Our study demonstrated that exposure of mouse alveolar macrophages to PM2.5 in a high glucose setting enhanced PM2.5-induced production of IL-1β through activation of the NLRP3 inflammasome and nuclear translocation of NF-κB due to PM2.5-induced oxidative stress, leading to MMP-9 upregulation. Our study provides a further understanding of the potential mechanisms underlying the susceptibility of individuals with DM to air pollution and suggests potential therapeutic targets.
January 2024 Member Publications:
Behrooz L, Xie W, Goghari A, Robertson R, Bhatnagar A, Stokes A, Hamburg NM. Electronic cigarette use and chest pain in US adults: Evidence from the PATH study. Tob Induc Dis. 2024 Jan 19;22. doi: 10.18332/tid/175732. PMID: 38250630; PMCID: PMC10798225.
Impact Statement: This study found exclusive e-cigarette use is associated with a lower rate of chest pain compared to combustible cigarette use and dual use.Riggs DW, Baumgartner KB, Baumgartner R, Boone S, Judd SE, Bhatnagar A. Long-term exposure to air pollution and risk of stroke by ecoregions: The REGARDS study. Environ Pollut. 2024 Jan 25;345:123367. doi: 10.1016/j.envpol.2024.123367. Epub ahead of print. PMID: 38280465.
Impact Statement: This study provides crucial insights into the complex relationship between long-term exposure to air pollution and stroke risk, highlighting the influence of surrounding ecology on these associations. The findings reveal that the impact of air pollution on stroke risk varies significantly across different ecoregions, emphasizing the importance of considering the type, quality, and quantity of the surrounding environment when assessing the effects of air pollution on public health outcomes.Abouleisa RRE, Tang XL, Ou Q, Salama AM, Woolard A, Hammouri D, Abdelhafez H, Cayton S, Abdulwali SK, Arai M, Sithu ID, Conklin DJ, Bolli R, Mohamed TMA. Gene therapy encoding cell cycle factors to treat chronic ischemic heart failure in rats. Cardiovasc Res. 2024 Jan 4:cvae002. doi: 10.1093/cvr/cvae002. Epub ahead of print. PMID: 38175760.
Impact Statement: This study establishes the long-term efficacy of TNNT2-4Fpolycistronic-NIL gene therapy in inducing cardiomyocyte (CM) cell cycle re-entry and improving left ventricular (LV) function in a rat model of chronic ischemic heart failure (IHF), a clinically relevant setting with significant pathophysiological differences from subacute IHF. The findings offer a promising therapeutic avenue for the treatment of chronic IHF, addressing a condition with high clinical prevalence and highlighting the potential of gene therapies in revolutionizing approaches to combat this life-threatening disease.Zhao J, Adiele N, Gomes D, Malovichko M, Conklin DJ, Ekuban A, Luo J, Gripshover T, Watson WH, Banerjee M, Smith ML, Rouchka EC, Xu R, Zhang X, Gondim DD, Cave MC, O'Toole TE. Obesogenic polystyrene microplastic exposures disrupt the gut-liver-adipose axis. Toxicol Sci. 2024 Jan 30:kfae013. doi: 10.1093/toxsci/kfae013. Epub ahead of print. PMID: 38291899.
Impact Statement: Microplastics derived from the physicochemical degradation of larger polymers are ubiquitous contaminants in the environment and have found their way into water supplies and the food chain. Despite evidence that these particles can be found in several human tissues, the health impacts of such exposure are not clear. Using a mouse model of exposure, polystyrene beads in drinking water, we found that consumption of these beads was associated with obesity, adipose inflammation, changes in the gut microbiome, and altered liver metabolism and signal transduction. This study identifies the wide-ranging physiological impact of microplastics consumption.Taylor MJ, Chitwood CP, Xie Z, Miller HA, van Berkel VH, Fu XA, Frieboes HB, Suliman SA. Disease diagnosis and severity classification in pulmonary fibrosis using carbonyl volatile organic compounds in exhaled breath. Respir Med. 2024 Feb;222:107534. doi: 10.1016/j.rmed.2024.107534. Epub 2024 Jan 18. PMID: 38244700.
Impact Statement: This paper investigated analysis of carbonyl compounds including ketones and aldehydes in exhaled breath for detection and evaluation of severity of pulmonary fibrosis. The results indicated that there were higher levels of many aldehydes for pulmonary fibrosis subjects than healthy controls.Harris LM, Kerr JC, Skidmore BD, Ghare S, Reyes-Vega A, Remenik-Zarauz V, Samanapally H, Anwar RU, Rijal R, Bryant K, Hall MT, Barve S. A conceptual analysis of SBIRT implementation alongside the continuum of PrEP awareness: domains of fit and feasibility. Front Public Health. 2024 Jan 8;11:1310388. doi: 10.3389/fpubh.2023.1310388. PMID: 38259734; PMCID: PMC10801388.
Impact Statement: This conceptual analysis underscores the potential of integrating Screening, Brief Intervention, and Referral to Treatment (SBIRT) into the Pre-Exposure Prophylaxis (PrEP) Care Continuum, offering a strategic approach to enhance HIV prevention initiatives. By applying the Transtheoretical Model of Change and the PrEP Awareness Continuum, the study reveals how SBIRT can effectively bridge identified gaps, providing a client-centered, destigmatized mechanism to boost PrEP awareness, initiation, and overall success in combating Human Immunodeficiency Virus (HIV) transmission.Kerr J, Combs R, Sterrett-Hong E, Harris L, Northington T, Krigger K, Parker K. Evaluation of a community-informed multimedia intervention to increase PrEP awareness and intention among African American young adults. AIDS Care. 2024 Feb 1:1-7 doi: 10.1080/09540121.2023.2297739. Epub ahead of print. PMID: 38301133.
Impact Statement: This study showcases the impact of a community-informed multimedia campaign in increasing PrEP awareness and use intentions among African American young adults in Louisville, Kentucky. The findings not only reveal a significant improvement in PrEP awareness over time but also demonstrate that participants with higher campaign affinity exhibit greater PrEP intentions, emphasizing the effectiveness of community-engaged health communication strategies in addressing HIV prevention disparities within specific populations.Ander M, Mugve N, Crouch C, Kassel C, Fukazawa K, Isaak R, Deshpande R, McLendon C, Huang J. Regional anesthesia for transplantation surgery - A White Paper Part 2: Abdominal transplantation surgery. Clin Transplant. 2024 Jan;38(1):e15227. doi: 10.1111/ctr.15227. PMID: 38289879.
Impact Statement: Transplantation surgery continues to evolve and improve through advancements in transplant technique and technology. With the increased availability of ultrasound machines as well as the continued development of Enhanced Recovery after Surgery (ERAS) protocols, regional anesthesia has become an essential component of providing analgesia and minimizing opioid use perioperatively.Ghosh S, Erickson D, Chua MJ, Collins J, Jala VR. The microbial metabolite urolithin A reduces Clostridioides difficile toxin expression and toxin-induced epithelial damage. mSystems. 2024 Jan 9:e0125523. doi: 10.1128/msystems.01255-23. Epub ahead of print. PMID: 38193707.
Impact Statement: Therapy for Clostridioides difficile infections includes the use of antibiotics, immunosuppressors, and fecal microbiota transplantation. However, these treatments have several drawbacks, including the loss of colonization resistance, the promotion of autoimmune disorders, and the potential for unknown pathogens in donor samples. To date, the potential benefits of microbial metabolites in CDI-induced colitis have not been fully investigated. Here, we report for the first time that the microbial metabolite urolithin A has the potential to block toxin production from C. difficile and enhance gut barrier function to mitigate CDI-induced colitis.Sagaram M, Frimodig J, Jayanty D, Hu H, Royer AJ, Bruner R, Kong M, Schwandt ML, Vatsalya V. One-month assessment of Th-cell axis related inflammatory cytokines, IL-17 and IL-22 and their role in alcohol-associated liver disease. Front Immunol. 2023 Dec 14;14:1202267. doi: 10.3389/fimmu.2023.1202267. PMID: 38162671; PMCID: PMC10755956.
Impact Statement: This study examined plasma levels of two key cytokines, Il-17 and Il-22, which construct the proinflammatory vs. anti-inflammatory axes across the spectrum of alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). IL-17 was highly elevated in the severe alcohol-associated hepatitis group, and IL-17 showed a strong positive association with MELD. Baseline IL-22 levels differentiated AH patients from the AUD patients, and showed positive association with the stages of ALD.Fromer MW, Xu Q, Shindorf ML, Mouw TJ, Kong M, Myers J, Feygin Y, Ghosh I, Martin RCG 2nd, McMasters KM, Philips P, Scoggins CR, Ellis CT, Egger ME. Diagnosis of Pancreatic Cancer after Cholecystectomy in the Elderly. Am Surg. 2024 Jan 11:31348241227165. doi: 10.1177/00031348241227165. Epub ahead of print. PMID: 38205662.
Impact Statement: This study reveals a significant association between recent cholecystectomy and the diagnosis of pancreatic adenocarcinoma, with a 4.7-fold higher rate of cholecystectomy in the year preceding cancer diagnosis compared to a non-cancer population. The findings underscore the potential relevance of cholecystectomy as a factor in pancreatic cancer diagnosis among elderly patients and highlight demographic and clinical differences between those with and without cancer, providing valuable insights into the epidemiological aspects of pancreatic adenocarcinoma.Egger ME, Feygin Y, Kong M, Poddar T, Ghosh I, Xu Q, McCabe RM, McMasters KM, Ellis CT. Variation in Lymph Node Assessment for Colon Cancer at the Tumor, Surgeon, and Hospital Level. J Am Coll Surg. 2024 Jan 11. doi: 10.1097/XCS.0000000000000963. Epub ahead of print. PMID: 38205923.
Impact Statement: This study challenges the common assumption that surgeon characteristics primarily influence the adherence to the ≥12 lymph nodes examined quality standard for resected colon cancer. The findings demonstrate that a substantial portion (71%) of the variation in achieving the 12 lymph node standard is attributed to non-modifiable tumor-level factors, shedding light on the need for a nuanced understanding of the contributors to quality metrics in colon cancer resection and highlighting potential areas for improvement in achieving standardized outcomes.Cai J, Song M, Li M, Merchant M, Benz F, McClain C, Klein J. Site-Specific Identification of Protein S-Acylation by IodoTMT0 Labeling and Immobilized Anti-TMT Antibody Resin Enrichment. J Proteome Res. 2023 Dec 29. doi: 10.1021/acs.jproteome.3c00525. Epub ahead of print. PMID: 38157263.
Impact Statement: This study introduces a site-specific method for the identification of protein S-acylation, addressing the limitations of the widely used aminolysis with hydroxylamine method, and discusses efforts to enhance the method's performance and identification confidence. The findings reveal a substantial increase in the number of newly identified S-acylation sites, underscoring the importance of stringent criteria and highlighting significant variations in S-acylation abundance across different samples, with implications for understanding the regulation of protein function through reversible post-translational modification.Sundaram K, Teng Y, Mu J, Xu Q, Xu F, Sriwastva MK, Zhang L, Park JW, Zhang X, Yan J, Zhang SQ, Merchant ML, Chen SY, McClain CJ, Dryden GW, Zhang HG. Outer Membrane Vesicles Released from Garlic Exosome-like Nanoparticles (GaELNs) Train Gut Bacteria that Reverses Type 2 Diabetes via the Gut-Brain Axis. Small. 2024 Jan 15:e2308680. doi: 10.1002/smll.202308680. Epub ahead of print. PMID: 38225709.
Impact Statement: This study introduces a novel approach wherein gut microbiota can be trained by diet-derived exosome-like nanoparticles (ELNs) to release outer membrane vesicles (OMVs), exemplified by garlic ELN (GaELNs) training on Akkermansia muciniphila, effectively reversing high-fat diet-induced type 2 diabetes (T2DM) in mice and inhibiting brain inflammation. The findings elucidate a molecular mechanism demonstrating how OMVs from plant nanoparticle-trained gut bacteria regulate gene expression in the brain, offering potential implications for the treatment of metabolic syndrome-induced brain dysfunction.Chigwechokha P, Nyirenda RL, Dalitsani D, Namaumbo RL, Kazembe Y, Smith T, Holm RH. Vibrio cholerae and Salmonella Typhi culture-based wastewater or non-sewered sanitation surveillance in a resource-limited region. J Expo Sci Environ Epidemiol. 2024 Jan 4. doi: 10.1038/s41370-023-00632-z. Epub ahead of print. PMID: 38177335.
Impact Statement: This work represents a significant advancement in public health surveillance in resource-limited settings, offering a cost-effective and scalable method to monitor and respond to outbreaks of diseases such as Vibrio cholerae and Salmonella serotype Typhi. By demonstrating the feasibility and effectiveness of using local diagnostic methods for disease detection in wastewater, this work has the potential to improve disease control and prevention efforts, particularly in regions where traditional clinical surveillance systems may be impractical or unavailable.Kucera C, Ramalingam A, Srivastava S, Bhatnagar A, Carll AP. Nicotine Formulation Influences the Autonomic and Arrhythmogenic Effects of Electronic Cigarettes. Nicotine Tob Res. 2023 Nov 27:ntad237. doi: 10.1093/ntr/ntad237. Epub ahead of print. PMID:38011908.
Impact Statement: This study provides evidence that the chemical formulation and concentration of nicotine in pod-based e-cigarettes, specifically protonated nicotine salts, significantly promote vaping-induced heart arrhythmias in mice, challenging the perceived harmlessness of e-cigarette nicotine. This underscores the necessity for regulatory frameworks to address and potentially reduce nicotine concentration and acidity in e-liquids to enhance global e-cigarette user safety.Lin X, Wang W, Chang X, Chen C, Guo Z, Yu G, Shao W, Wu S, Zhang Q, Zheng F, Li H. ROS/mtROS promotes TNTs formation via the PI3K/AKT/mTOR pathway to protect against mitochondrial damages in glial cells induced by engineered nanomaterials. Part Fibre Toxicol. 2024 Jan 15;21(1):1. doi: 10.1186/s12989-024-00562-0. PMID: 38225661; PMCID: PMC10789074.
Impact Statement: Despite their biophysical properties, various types of nanomaterials promote Tunneling nanotubes (TNTs) formation and mitochondrial transfer, preventing cell apoptosis and disrupting ATP production induced by nanomaterials. ROS/mtROS and the activation of the downstream PI3K/AKT/mTOR pathway are common mechanisms to regulate TNTs formation and mitochondrial transfer. Our study reveals that engineered nanomaterials share the same molecular mechanism of TNTs formation and intercellular mitochondrial transfer, and the proposed adverse outcome pathway contributes to a better understanding of the intercellular protection mechanism against nanomaterials-induced neurotoxicity.Jophlin L, Liu TY, McClain CJ. Nutritional deficiencies in alcohol use disorder/alcohol-associated liver disease. Curr Opin Gastroenterol. 2024 Mar 1;40(2):112-117. doi: 10.1097/MOG.0000000000000999. Epub 2024 Jan 2. PMID: 38193343.
Katsaros G, Smith SA, Shacklette S, Trivedi J, Garr S, Parrish LW, Xie Z, Fu XA, Powell K, Pantalos G, van Berkel V. Identification of a marker of infection in the breath using a porcine pneumonia model. JTCVS Open. 2023 Oct 30;16:1063-1069. doi: 10.1016/j.xjon.2023.10.025. PMID: 38204632; PMCID: PMC10775109.
Sayed K, Dolin CE, Wilkey DW, Li J, Sato T, Beier JI, Argemi J, Bataller R, Wahed AS, Merchant ML, Benos PV, Arteel GE. A plasma peptidomic signature reveals extracellular matrix remodeling and predicts prognosis in alcohol-related hepatitis. medRxiv [Preprint]. 2023 Dec 14:2023.12.13.23299905. doi: 10.1101/2023.12.13.23299905. Update in: Hepatol Commun. 2024 Jul 31;8(8):e0510. doi: 10.1097/HC9.0000000000000510. PMID: 38168372; PMCID: PMC10760272.
Cai L, Horowitz M, Islam MS. Potential therapeutic targets for the prevention of diabetic nephropathy: Glycyrrhetinic acid. World J Diabetes. 2023 Dec 15;14(12):1717-1720. doi: 10.4239/wjd.v14.i12.1717. PMID: 38222784; PMCID: PMC10784793.
Toyoda JH, Martino J, Speer RM, Meaza I, Lu H, Williams AR, Bolt AM, Kouokam JC, Aboueissa AE, Wise JP Sr. Hexavalent Chromium Targets Securin to Drive Numerical Chromosome Instability in Human Lung Cells. Int J Mol Sci. 2023 Dec 23;25(1):256. doi: 10.3390/ijms25010256. PMID: 38203427; PMCID: PMC10778806.
- Milanes JE, Yan VC, Pham CD, Muller F, Kwain S, Rees KC, Dominy BN, Whitehead DC, Millward SW, Bolejack M, Abendroth J, Phan IQ, Staker B, Moseman EA, Zhang X, Ma X, Jebet A, Yin X, Morris JC. Enolase inhibitors as therapeutic leads for Naegleria fowleri infection. bioRxiv [Preprint]. 2024 Jan 17:2024.01.16.575558. doi: 10.1101/2024.01.16.575558. Update in: PLoS Pathog. 2024 Aug 1;20(8):e1012412. doi: 10.1371/journal.ppat.1012412. PMID: 38293107; PMCID: PMC10827119.
Banerjee M, Srivastava S, Rai SN, States JC. Chronic arsenic exposure induces malignant transformation of human HaCaT cells through both deterministic and stochastic changes in transcriptome expression. Toxicol Appl Pharmacol. 2024 Feb 17;484:116865. doi: 10.1016/j.taap.2024.116865. Epub ahead of print. PMID: 38373578.
Impact Statement: Carcinogenesis occurs both as a result of combined deterministic and stochastic (random) changes in gene expression. However, existing data analysis paradigms for transcriptomic studies preferentially select for deterministic lockstep changes eliminating the importance of stochastic processes in carcinogenesis. In this work, we devised a relatively simple statistical approach that can differentiate between deterministic and stochastic processes operative in carcinogenesis and the pathways and networks they modulate using a cell line model of arsenic-induced skin carcinogenesis. This work will lead to a comprehensive understanding of how cells become cancerous and the role of clonal and tumor heterogeneity in the process.Cai L, Tan Y, Holland B, Wintergerst K. Diabetic Cardiomyopathy and Cell Death: Focus on Metal-Mediated Cell Death. Cardiovasc Toxicol. 2024 Feb;24(2):71-84. doi: 10.1007/s12012-024-09836-7. Epub 2024 Feb 6. PMID: 38321349.
Impact Statement: After we published first review “Diabetic cardiomyopathy and cell death” in 2003, this review provided an update with the potential role of metal-mediated cell death, ferroptosis and cuproptosis in the development of diabetic cardiomyopathy, to advance the knowledge and continue to drive efforts to develop more advanced therapeutic approaches to prevent cell death, particularly metal-dependent cell death, and, ultimately, to reduce or prevent the development of diabetic cardiomyopathy.Tomlinson MM, Wallis AB, Harris MJ, DuPré NC, Baumgartner RN, Okonofua F. Menstrual hygiene management among adolescent girls in West Africa: A systematic review. Afr J Reprod Health. 2024 Feb 28;28(1):123-156. doi: 10.29063/ajrh2024/v28i1.12. PMID: 38308560.
Impact Statement: This literature review addresses some of the unmet menstrual hygiene needs for West African girls, highlighting the need for more research and intervention implementation in these areas. At present, lack of private toilets, education, and products causes girls to miss school days, putting them at risk for lower educational achievement and economic opportunity as compared to their male peers.Ding T, Weng Y, Huang J, Zou W. Manual angulation of the Arndt endobronchial blocker to improve the ease of lung isolation. Can J Anaesth. 2024 Feb 16. doi: 10.1007/s12630-024-02709-1. Epub ahead of print. PMID: 38366211.
Impact Statement: Manual angulation of theArndt Endobronchial #Blocker as an innovative, easy, effective, and safe techniquefor #lungisolation using this device.Haines D, Kertai MD, Abrams B, Huang J. Understanding Physiology and Using Technology to Care for Challenging Patients. Semin Cardiothorac Vasc Anesth. 2024 Feb 20:10892532241233106. doi: 10.1177/10892532241233106. Epub ahead of print. PMID: 38378200.
Impact Statement: Innovation and the advancement of medical knowledge is paramount to the goals and objectives of caring for challenging patients.Condon S, Hu H, Kong M, Cave MC, McClain CJ. ALT Poorly Predicts Nonalcoholic Fatty Liver Disease (NAFLD) and Liver Fibrosis as Determined by Vibration-Controlled Transient Elastography in Adult National Health and Nutrition Examination Survey 2017-2018: ALT Poorly Predicts NAFLD and Hepatic Fibrosis. Am J Med Sci. 2024 Jan 31:S0002-9629(24)01055-3. doi: 10.1016/j.amjms.2024.01.022. Epub ahead of print. PMID: 38307172.
Impact Statement: ALT is the most widely used liver chemistry for NAFLD evaluation. Our study revealed that ALT is an inaccurate marker for NAFLD as measured by FibroScan® with CAP greater than or equal to 300 dB/m. Accuracy improved specific risk factors were considered. These data also showed that ALT was a poor marker for liver fibrosis. We conclude that there is no single ALT level that accurately predicts hepatic steatosis or fibrosis.Xu Q, Antimisiaris D, Kong M. Statistical methods for assessing drug interactions using observational data. J Appl Stat. 2022 Sep 20;51(2):298-323. doi: 10.1080/02664763.2022.2123460. PMID: 38283050; PMCID: PMC10810670.
Impact Statement: We propose using marginal structural models to assess the average treatment effect and causal interaction of two drugs by controlling confounding variables. The method will facilitate the investigation of the causal effects of multiple treatments or exposures while controlling for confounding variables such as demographics and comorbidity conditions.Sun R, Lei C, Xu Z, Gu X, Huang L, Chen L, Tan Y, Peng M, Yaddanapudi K, Siskind L, Kong M, Mitchell R, Yan J, Deng Z. Neutral ceramidase regulates breast cancer progression by metabolic programming of TREM2-associated macrophages. Nat Commun. 2024 Feb 1;15(1):966. doi: 10.1038/s41467-024-45084-7. PMID: 38302493; PMCID: PMC10834982.
Impact Statement: We find that deletion of neutral ceramidase in multiple breast cancer models in female mice accelerates tumor growth, and metabolite ceramide leads to reprogramming of macrophages toward immune suppressive TREM2+ tumor associated macrophages, which promote CD8 T cells exhaustion.Egger ME, Alexander E, Van Meter T, Kong M, Maung AA, Valdes R Jr, Hall MB, Linder MW. Corresponding ctDNA and tumor burden dynamics in metastatic melanoma patients on systemic treatment. Transl Oncol. 2024 Feb 1;42:101883. doi: 10.1016/j.tranon.2024.101883. Epub ahead of print. PMID: 38306914.
Impact Statement: We evaluated the relationship between longitudinal radiographic measures of tumor burden and plasma circulating tumor DNA (ctDNA) concentrations. We found that measurements of plasma ctDNA during therapy are a better surrogate for responding versus non-responding disease compared to absolute tumor burden.Gawrieh S, Dasarathy S, Tu W, Kamath PS, Chalasani NP, McClain CJ, Bataller R, Szabo G, Tang Q, Radaeva S, Barton B, Nagy LE, Shah VH, Sanyal AJ, Mitchell MC. Randomized-controlled trial of anakinra plus zinc vs. prednisone for severe alcohol-associated hepatitis. J Hepatol. 2024 Feb 9:S0168-8278(24)00109-0. doi: 10.1016/j.jhep.2024.01.031. Epub ahead of print. PMID: 38342441.
Impact Statement: There is no approved treatment for severe alcohol-associated hepatitis (SAH). In this double-blind randomized trial, patients with SAH treated with prednisone using the Lille stopping rule on Day-7 had higher 90-day overall and transplant-free survival and lower rate of acute kidney injury compared to patients treated with a combination of anakinra and zinc. The data support continued use of glucocorticoids for patients with SAH, with treatment discontinuation for those with Lille score > 0.45 on Day-7.Walter MN, Montoya-Durango D, Rodriguez W, Wang Y, Zhang J, Chariker JH, Rouchka EC, Maldonado C, Bennett A, McClain CJ, Barve S, Gobejishvili L. Hepatocyte-specific mitogen-activated protein kinase phosphatase 1 in sexual dimorphism and susceptibility to alcohol induced liver injury. Front Immunol. 2024 Feb 1;15:1316228. doi: 10.3389/fimmu.2024.1316228. PMID: 38370409; PMCID: PMC10871047.
Impact Statement: Hepatocyte Mkp1 plays a significant role in alcohol induced liver injury. Alcohol downregulates Mkp1 expression in hepatocytes in a sex dependent manner and could play a role in sexual dimorphism in increased female susceptibility to alcohol.Augenstein II, Nail AN, Ferragut Cardoso AP, States JC, Banerjee M. Chronic arsenic exposure suppresses proteasomal and autophagic protein degradation. Environ Toxicol Pharmacol. 2024 Feb 23;107:104398. doi: 10.1016/j.etap.2024.104398. Epub ahead of print. PMID: 38403142.
Impact Statement: Chronic arsenic exposure causes proteome-wide changes across target tissues, but the mechanisms involved are not clearly understood. In this work, we demonstrate that chronic arsenic exposure suppresses both the arms of protein degradation pathway, viz., autophagy and ubiquitin proteasomal system across skin and lung cell line models. This work will help us better understand how environmental exposure impact proteome-wide changes during carcinogenesis and identify possible therapeutic targets.Xin Y, Wise JY, Rajesh M, Cai L. Editorial: Cardiovascular diseases related to diabetes and obesity, volume III. Front Endocrinol (Lausanne). 2024 Feb 13;15:1381446. doi: 10.3389/fendo.2024.1381446. PMID: 38414820; PMCID: PMC10897048.
Impact Statement: The escalating global burden of obesity, diabetes mellitus (DM), and cardiovascular disease (CVD) demands urgent attention. Through comprehensive clinical studies and reviews, this Research Topic underscores the critical need for early detection and intervention strategies, highlighting novel markers like metabolic insulin resistance scores and triglyceride-glucose indices, offering a pathway towards individualized therapeutic regimens and enhanced patient outcomes in the face of these intertwined chronic diseases.- Dong J, Browning M, Reuben A, McAnirlin O, Yuan S, Stephens C, Maisonet M, Zhang K, Hart JE, James P, Yeager R. The paradox of high greenness and poor health in rural Central Appalachia. Environ Res. 2024 Feb 1:118400. doi: 10.1016/j.envres.2024.118400. Epub ahead of print. PMID: 38309568.
Impact Statement: While extensive evidence reflects that those living in greener areas have better health, rural Central Appalachia is a major exception. In this paper, we describe potential reasons for this, draw attention to public health challenges in Central Appalachia, and provide recommendations for future research and public health action.
Riggs DW, Bhatnagar A. Invited Perspective: A Natural Prescription for Hypertension? Environ Health Perspect. 2024 Mar;132(3):31301. doi: 10.1289/EHP14482. Epub 2024 Mar 1. PMID: 38427032; PMCID: PMC10906658.
Impact Statement: The publication will raise awareness about the significant impact of green spaces on public health, highlighting how living in neighborhoods with ample greenery can lower the risk of hypertension and other health issues. By emphasizing the positive health effects of urban greenery, it could influence urban planning policies to prioritize the integration of green spaces into city landscapes, ultimately promoting healthier living environments and mitigating the adverse effects of urbanization on public health.Ranker LR, Wu J, Hong T, Wijaya D, Benjamin EJ, Bhatnagar A, Robertson RM, Fetterman JL, Xuan Z. Social media use, brand engagement, and tobacco product initiation among youth: Evidence from a prospective cohort study. Addict Behav. 2024 Feb 28;154:108000. doi: 10.1016/j.addbeh.2024.108000. Epub ahead of print. PMID: 38461745.
Impact Statement: This study adds to a growing evidence-base describing the exposure of youth to tobacco-related social media content. Such content-often generated by tobacco companies-may contribute to youth tobacco initiation.Amraotkar AR, Hoetker D, Negahdar MJ, Ng CK, Lorkiewicz P, Owolabi US, Baba SP, Bhatnagar A, O'Toole TE. Comparative evaluation of different modalities for measuring in vivo carnosine levels. PLoS One. 2024 Mar 27;19(3):e0299872. doi: 10.1371/journal.pone.0299872. PMID: 38536838; PMCID: PMC10971688.
Impact Statement: Carnosine is an endogenous peptide (beta-alanine-L-histidine) and dietary supplement with anti-oxidant and metal chelating properties. Yet common methods to measure levels of carnosine in bodily tissues involve invasive procedures or are cumbersome and costly. This study examines the utility of different approaches and tissues for the assessment of carnosine levels, especially in the context of large-scale clinical studies.Xie W, Berlowitz JB, Raquib R, Harlow AF, Benjamin EJ, Bhatnagar A, Stokes AC. Association of cigarette and electronic cigarette use patterns with all-cause mortality: A national cohort study of 145,390 US adults. Prev Med. 2024 Mar 28;182:107943. doi: 10.1016/j.ypmed.2024.107943. Epub ahead of print. PMID: 38552720.
Impact Statement: The addition of e-cigarette use to smoking does not reduce mortality risk compared with exclusive smoking. However, transitioning completely from cigarettes to e-cigarettes may be associated with mortality risk reduction. Further research is needed to verify these findings in larger cohorts and over longer periods of follow-up.Piell KM, Petri BJ, Xu J, Cai L, Rai SN, Li M, Wilkey DW,Merchant ML, Cave MC, Klinge CM. Chronic Aroclor 1260 exposure alters the mouse liver proteome, selenoproteins, and metals in steatotic liver disease. Environ Toxicol Pharmacol. 2024 Mar 27;107:104430. doi: 10.1016/j.etap.2024.104430. Epub ahead of print. PMID: 38552755.
Impact Statement: This paper reports that a single oral exposure of male C57Bl/6J mice to the PCB mixture Aroclor 1260 while on a normal diet that resulted in metabolic dysfunction-associated steatotic liver disease (MASLD) after 34 wks. altered the abundance of 128 liver proteins including four selenoproteins. Metallomic analysis of the livers revealed that liver selenium, copper, and zinc were increased and iron was reduced. These data demonstrate that Ar1260 exposure alters the (seleno)proteome, Se, and metals in MASLD-associated pathways.Chandy M, Hill T 3rd, Jimenez-Tellez N, Wu JC, Sarles SE, Hensel E, Wang Q, Rahman I, Conklin DJ. Addressing Cardiovascular Toxicity Risk of Electronic Nicotine Delivery Systems in the Twenty-First Century: "What Are the Tools Needed for the Job?" and "Do We Have Them?". Cardiovasc Toxicol. 2024 Mar 31. doi: 10.1007/s12012-024-09850-9. Epub ahead of print. PMID: 38555547.
Impact Statement: At present we are unsure of the risk that Electronic Nicotine Delivery Systems (ENDS) use poses to the human cardiovascular system. There are multiple technologies that are being coupled together as a cardiovascular toxicity testing platform to assess ENDS toxicity and risk. As with any new approach method (NAM), there remains uncertainties as to how robustly these potential NAM platforms will predict population-relevant effects in humans – but this will never be known until the work is attempted.Schulman-Geltzer EB, Fulghum KL, Singhal RA, Hill BG, Collins HE. Cardiac Mitochondrial Metabolism During Pregnancy and the Postpartum Period. Am J Physiol Heart Circ Physiol. 2024 Mar 29. doi: 10.1152/ajpheart.00127.2024. Epub ahead of print. PMID: 38551485.
Impact Statement: This study sheds light on the dynamic changes in maternal cardiac mitochondria during pregnancy and post-birth, indicating an enhanced capacity to utilize specific energy sources after birth. Understanding these metabolic adaptations could lead to targeted interventions to support maternal cardiac health during the peripartum period, potentially reducing the risk of cardiac complications postpartum.Mathis M, Steffner KR, Subramanian H, Gill GP, Girardi NI, Bansal S, Bartels K, Khanna AK, Huang J. Overview and Clinical Applications of Artificial Intelligence and Machine Learning in Cardiac Anesthesiology. J Cardiothorac Vasc Anesth. 2024 May;38(5):1211-1220. doi: 10.1053/j.jvca.2024.02.004. Epub 2024 Feb 15. PMID: 38453558; PMCID: PMC10999327.
Impact Statement: Review of 3 recent applications relevant to cardiac #anesthesiology, including depth of anesthesia monitoring, operating room resource optimization, and transthoracic/transesophageal echocardiography, as conceptual examples to explore strengths and limitations of artificialintelligence within healthcare, and characterize this evolving landscape.Hwang JY, Kook TL, Paulus SM, Park JW. Translation of Circular RNAs: Functions of Translated Products and Related Bioinformatics Approaches. Curr Bioinform. 2024;19(1):3-13. doi: 10.2174/1574893618666230505101059. Epub 2023 Oct 3. PMID: 38500957; PMCID: PMC10947221.
Impact Statement: This paper offers a deeper understanding of circRNA, its functions, translation of circRNA, and tools for circRNA analysis. This deeper understanding of circRNA and the development of analysis tools pave the way for significant advancements in cancer research.Wechman S, Jala VR, Bermudez-Humaran LG, Gomez-Gutierrez JG. Editorial: Recombinant microbes-mediated cancer immunotherapy. Front Immunol. 2024 Feb 22;15:1386574. doi: 10.3389/fimmu.2024.1386574. PMID: 38455064; PMCID: PMC10917935.
Impact Statement: This publication presents research in cancer immunotherapy, highlighting the potential of microbial-based treatments to stimulate immune responses against tumors and improve therapeutic outcomes. By elucidating mechanisms of action and demonstrating efficacy in preclinical models, these studies pave the way for the development of innovative cancer therapies that harness the power of the immune system to combat malignancies effectively.Xu R, Liu H, Yuan F, Kim S, Kirpich I, McClain CJ, Zhang X. Lipid Wizard: Analysis Software for Comprehensive Two-Dimensional Liquid Chromatography-Mass Spectrometry-Based Lipid Profiling. Anal Chem. 2024 Apr 9;96(14):5375-5383. doi: 10.1021/acs.analchem.3c04419. Epub 2024 Mar 24. PMID: 38523323.
Impact Statement: The lipid profiling platform, comprehensive two-dimensional liquid chromatography-mass spectrometry (HILCxRPC-MS), developed in CREAM can simultaneously quantify over 4000 lipids in one experiment. Lipid Wizard software assigns lipids based on their precursor ion m/z value, the first and the second dimensional retention times, to greatly increase the confidence of lipid assignment for large-scale lipidomics studies.Kouokam JC, Speer RM, Meaza I, Toyoda JH, Lu H, Wise JP Sr. Transcriptomic analysis reveals particulate hexavalent chromium regulates key inflammatory pathways in human lung fibroblasts as a possible mechanism of carcinogenesis. Toxicol Appl Pharmacol. 2024 Mar 11;485:116889. doi: 10.1016/j.taap.2024.116889. Epub ahead of print. PMID: 38479592.
Impact Statement: This study used a transcriptomics approach to demonstrate that hexavalent chromium regulates key inflammatory pathways in human lung fibroblasts. These findings provide novel insights into the mechanisms by which hexavalent chromium causes lung cancer.Lindsey ML, Brunt KR, Kleinbongard P, Carter JR, Ripplinger CM, Kassiri Z, Hansell Keehan K, LeBlanc AJ, Kirk JA. The heart of physiological reports. Physiol Rep. 2024 Mar;12(5):e15962. doi: 10.14814/phy2.15962. PMID: 38439748; PMCID: PMC10912920.
Impact Statement: This editorial celebrates Physiological Reports' 10-year anniversary, highlighting its role in the cardiovascular research community as a platform for sound science in basic, translational, and clinical physiology. With a strong reputation for solid publications, Physiol Reports offers a viable option for cardiovascular researchers, including those whose work may not meet the criteria for publication in other journals like AJP Heart and Circ, providing a valuable outlet for impactful research findings.Lindsey ML, Kirk JA, LeBlanc AJ, Brunt KR, Carter JR, Hansell Keehan K, Ripplinger CM, Kleinbongard P, Kassiri Z. Looking Backward to Plan for Forward. Am J Physiol Heart Circ Physiol. 2024 Mar 29. doi: 10.1152/ajpheart.00154.2024. Epub ahead of print. PMID: 38551484.
Impact Statement: On January 1, 2024, the executive editorial team of the American Journal of Physiology Heart and Circulatory Physiology (AJP-Heart and Circ) began its second 3-year term. The purpose of this editorial is to highlight the successes of the first term and showcase plans for the next term.Hardesty J, Hawthorne M, Day L, Warner J, Warner D, Gritsenko M, Asghar A, Stolz A, Morgan T, McClain C , Jacobs J, Kirpich IA. Steroid responsiveness in alcohol-associated hepatitis is linked to glucocorticoid metabolism, mitochondrial repair, and heat shock proteins. Hepatol Commun. 2024 Mar 4;8(3):e0393. doi: 10.1097/HC9.0000000000000393. PMID: 38437061; PMCID: PMC10914234.
Impact Statement: This publication identifies hepatic protein expression patterns associated with corticosteroid response and survival in alcohol-associated hepatitis patients, informing personalized treatment approaches and prognostic strategies. These findings have the potential to improve patient management and outcomes, thereby contributing to public health by enhancing the effectiveness of interventions for alcohol-associated hepatitis.Wise JTF, Lu H, Meaza I, Wise SS, Williams AR, Wise JY, Mason MD, Wise JP Sr. Prolonged Particulate Hexavalent Chromium Exposure Induces DNA Double-Strand Breaks and Inhibits Homologous Recombination Repair in Primary Rodent Lung Cells. Biol Trace Elem Res. 2024 Mar 18. doi: 10.1007/s12011-024-04136-1. Epub ahead of print. PMID: 38499919.
Impact Statement: This study reveals prolonged exposure to hexavalent chromium [Cr(VI)] in rodent lung cells leads to DNA double-strand breaks and subsequent inhibition of repair mechanisms, mirroring similar effects observed in human lung cells. The findings suggest that rodent models can be valuable in studying metal-induced lung carcinogenesis and further distinguish these responses from those observed in whales, where repair mechanisms are not inhibited after exposure to Cr(VI).Lu H, Toyoda JH, Wise SS, Browning CL, Speer RM, Croom-Pérez TJ, Bolt A, Meaza I, Wise JP. A whale of a tale: whale cells evade the driving mechanism for hexavalent Chromium-Induced chromosome instability. Toxicol Sci. 2024 Mar 27:kfae030. doi: 10.1093/toxsci/kfae030. Epub ahead of print. PMID: 38539048.
Impact Statement: The study demonstrates whale lung cells resist hexavalent chromium [Cr(VI)]-induced chromosome instability, a key mechanism for Cr(VI) carcinogenesis in humans. Cr(VI) causes the same amount of DNA breaks in human and whale cells, but unlike human lung cells, whale cells maintain effective DNA repair and avoid structural changes that lead to cancer, providing insights into the whales' lower cancer rates despite long-term Cr(VI) exposure and suggesting whales may provide insights into have to help prevent human cancer.- Zhang, C. H., Sears, C. G., Guinn, B., & Zierold, K. M. (2024). EXPLORING ENVIRONMENTAL INJUSTICE IN EXPOSURE TO AIRBORNE LEAD RELEASED FROM INDUSTRIAL FACILITIES IN KENTUCKY, UNITED STATES. Geographical Review, 1–18. https://doi.org/10.1080/00167428.2024.2325976
Impact Statement: The findings of this study contribute to raising public awareness about the persistent risks associated with exposure to airborne lead from industrial facilities across Kentucky. Insights into racial/economic inequalities in lead exposure highlighted by the study can inform public health policies to tackle environmental injustices and health disparities.