April 2024 - March 2025 Member Publications
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- Yao Z, Tasdighi E, Dardari ZA, Jha KK, Osuji N, Rajan T, Boakye E, Rodriguez CJ, Matsushita K, Simonsick EM, Lima JAC, Widome R, Cohen DL, Appel LJ, Khera A, Hall ME, Judd SE, Cole SA, Vasan RS, Benjamin EJ, Lotufo PA, Benseñor IM, El Khoudary SR, Barinas-Mitchell E, Janssen I, Psaty BM, Eaton CB, LaMonte MJ, Cawthon PM, Orwoll ES, Irvin MR, Bhatnagar A, DeFilippis AP, El-Shahaway O, Blaha MJ. Association Between Cigarette Smoking and Subclinical Markers of Cardiovascular Harm. J Am Coll Cardiol. 2025 Mar 18;85(10):1018-1034. doi: 10.1016/j.jacc.2024.12.032. PMID: 40074467.
Impact Statement: This large, multi-cohort study found strong, dose-dependent associations between smoking and subclinical markers of cardiovascular harm, with some markers remaining elevated even decades after cessation. These findings highlight the lasting cardiovascular impact of smoking and underscore the importance of tobacco regulation and cessation efforts. - Erhabor J, Yao Z, Tasdighi E, Benjamin EJ, Bhatnagar A, Blaha MJ. E-cigarette Use and Incident Cardiometabolic Conditions in the All of Us Research Program. Nicotine Tob Res. 2025 Mar 15:ntaf067. doi: 10.1093/ntr/ntaf067. Epub ahead of print. PMID: 40089810.
Impact Statement: This study found that exclusive e-cigarette use was associated with increased risk of COPD, and hypertension among adults aged 30–70, while dual use and exclusive combustible cigarette use were linked to significantly higher risks for multiple cardiometabolic conditions. These findings offer critical evidence to inform regulatory decisions on emerging tobacco products. - Anderson LB, Holm RH, Black C, Biddle DJ, Chiu WA, Bhatnagar A, Smith T. An environmental vulnerability index framework supporting targeted public health interventions at the census tracts level. J Expo Sci Environ Epidemiol. 2025 Mar 5. doi: 10.1038/s41370-025-00763-5. Epub ahead of print. PMID: 40044815.
Impact Statement: We create a comprehensive Environmental Vulnerability Index at the census tract level for Jefferson County, enabling highly targeted public health interventions directly aligned with most relevant risks. Its implementation can significantly advance health outcomes by guiding precise, localized actions to reduce environmental risks. - Erhabor J, Yao Z, Tasdighi E, Shahawy OE, Benjamin EJ, Bhatnagar A, Blaha MJ. Association of e-cigarette use, psychological distress, and substance use: Insights from the All of Us Research Program. Addict Behav. 2025 Mar 19;166:108322. doi: 10.1016/j.addbeh.2025.108322. Epub ahead of print. PMID: 40112576.
Impact Statement: This study leveraged data from over 68,000 U.S. adults in the All of Us Research Program to reveal strong associations between e-cigarette use, psychological distress, and substance use, offering critical insight into the social and behavioral context of vaping. These findings can guide targeted public health interventions to address co-occurring mental health and substance use concerns among e-cigarette users. - Nielsen G, Gondim DD, Cave MC, Heiger-Bernays WJ, Webster TF, Schlezinger JJ. Perfluorooctanoic acid increases serum cholesterol in a PPARα-dependent manner in female mice. Arch Toxicol. 2025 Mar 1. doi: 10.1007/s00204-025-03984-7. Epub ahead of print. PMID: 40021516.
Impact Statement: This study demonstrates that PFOA, a common PFAS, disrupts lipid homeostasis in mice through both PPARα-dependent and independent mechanisms, with notable sex-specific effects. Findings highlight the relevance of humanized models in understanding PFAS toxicity and underscore the need to consider sex and genetic variability in risk assessment. - Pagel PS, Huang J, Augoustides JGT, Schwartz AJ, Hessel EA 2nd, Kaplan JA. A History of the Journal of Cardiothoracic and Vascular Anesthesia: Nearly 40 Years and Counting. J Cardiothorac Vasc Anesth. 2025 Feb 25:S1053-0770(25)00176-4. doi: 10.1053/j.jvca.2025.02.035. Epub ahead of print. PMID: 40082094.
Impact Statement: The Journal of Cardiothoracic and Vascular Anesthesia has shaped the field for nearly four decades, setting the standard for subspecialty anesthesiology journals worldwide. Its enduring leadership and commitment to advancing clinical practice have solidified its position as the foremost publication in cardiac, thoracic, and vascular anesthesia. - Haysley J, Soliman-Aboumarie H, Huang J, Kalra DK. Perioperative atrial fibrillation. BJA Educ. 2025 Mar;25(3):99-106. doi: 10.1016/j.bjae.2024.10.006. Epub 2025 Jan 3. PMID: 40034815; PMCID: PMC11872467.
Impact Statement: This publication highlights the multifactorial nature of perioperative atrial fibrillation (POAF) after non-cardiac surgery and underscores the importance of accurate risk prediction, homeostatic management, and multidisciplinary care to reduce associated morbidity and mortality. It also emphasizes the need for validated predictive tools and individualized prevention strategies to improve patient outcomes. - Jana U, Rodriguez OL, Lees W, Engelbrecht E, Vanwinkle Z, Peres A, Gibson WS, Shields K, Schultze S, Dorgham A, Emery M, Deikus G, Sebra R, Eichler EE, Yaari G, Smith ML, Watson CT. The human immunoglobulin heavy chain constant gene locus is enriched for large complex structural variants and coding polymorphisms that vary in frequency among human populations. bioRxiv [Preprint]. 2025 Feb 12:2025.02.12.634878. doi: 10.1101/2025.02.12.634878. PMID: 39990387; PMCID: PMC11844466.
Impact Statement: This study provides a comprehensive high-quality catalog of immunoglobulin heavy chain constant (IGHC) haplotypes and variants from a diverse cohort, uncovering novel alleles and structural variants with significant population differentiation. These findings offer a crucial foundation for understanding the genetic diversity within the IGHC locus and its implications for antibody function and disease susceptibility. - Beier JI, Luo J, Vanderpuye CM, Brizendine P, Muddasani P, Bolatimi O, Heinig SA, Ekuban FA, Siddiqui H, Ekuban A, Gripshover TC, Wahlang B, Watson WH, Cave MC. Environmental Pollutants, Occupational Exposures, and Liver Disease. Semin Liver Dis. 2025 Mar 21. doi: 10.1055/a-2540-2861. Epub ahead of print. PMID: 40118102.
Impact Statement:The publication highlights the significant role of environmental pollutants in the development and progression of liver disease, emphasizing how even low level exposures, shaped by factors like diet and other social determinants of health, can drive liver pathology. It underscores the need for integrating environmental health into clinical practice and public health policy to address emerging environmental concerns.
Abdelrahim M, Khudri M, Elnakib A, Shehata M, Weafer K, Khalil A, Saleh GA, Batouty NM, Ghazal M, Contractor S, Barnes G, El-Baz A. AI-based non-invasive imaging technologies for early autism spectrum disorder diagnosis: A short review and future directions. Artif Intell Med. 2025 Mar;161:103074. doi: 10.1016/j.artmed.2025.103074. Epub 2025 Jan 31. PMID: 39919468.
Impact Statement: This review highlights recent advancements in non-invasive imaging technology, specifically structural MRI techniques, for early autism spectrum disorder (ASD) diagnosis. By addressing key questions on imaging biomarkers, brain cortex parcellation, available databases, and AI-driven diagnostic improvements, this work underscores the potential for more accurate and objective early ASD detection.Siegel NA, Zhao J, Benjamin EJ, Bhatnagar A, Hall JL, Stokes AC. Identifying Patterns of Tobacco Use and Associated Cardiovascular Disease Risk Through Machine Learning Analysis of Urine Biomarkers. JACC Adv. 2025 Feb 21;4(3):101630. doi: 10.1016/j.jacadv.2025.101630. Epub ahead of print. PMID: 39985885.
Impact Statement: Using cluster analysis, this study identified distinct biomarker exposure patterns linked to different tobacco product usage, revealing that cigarette and dual users had the highest levels of oxidative stress and inflammation. These findings highlight a potential tool for assessing emerging tobacco products and their associated cardiovascular risks, aiding future public health efforts.Zhang H, Zhou W, Wang X, Men H, Wang J, Xu J, Zhou S, Liu Q, Cai L. Exacerbation by knocking-out metallothionein gene of obesity-induced cardiac remodeling is associated with the activation of CARD9 signaling. Int J Biol Sci. 2025 Jan 13;21(3):1032-1046. doi: 10.7150/ijbs.105513. PMID: 39897024; PMCID: PMC11781176.
Impact Statement: We demonstrated that all insulin resistance, cardiac hypertrophy, and cardiac inflammation in an obese mouse model induced by a high-fat diet (HFD) were associated with upregulation of caspase recruitment domain-containing protein 9 (CARD9) and B-cell lymphoma/leukemia 10 (BCL10) and activation of p38 MAPK pathway. However, these changes were prevented by zinc supplementation with upregulation of metallothionein (MT). Now we also showed MT knockout (KO) aggravated HFD-induced obesity and systemic metabolic disorder, and cardiac hypertrophy and fibrosis, along with increased cardiac macrophages accumulation, CARD9 and BCL10 expression and NF-κB activation. Therefore, we concluded MT-KO in combined with HFD-induced obesity synergistically promotes cardiac remodeling, likely via trace metal dyshomeostasis-induced oxidative stress to trigger CARD9/BCL10-mediated NF-κB activation.He L, Wang Y, Yuan F, Morrissey S, Geller AE, Hu X, Xu R, Ma X, Zhang HG, McLeish K, Huang J, Zhang X, Yan J. Metabolomics Profiling Reveals Critical Roles of Indoxyl Sulfate in the Regulation of Innate Monocytes in COVID-19. Cells. 2025 Feb 11;14(4):256. doi: 10.3390/cells14040256. PMID: 39996729; PMCID: PMC11853107.
Impact Statement: Using paired samples from COVID-19 patients, we identified indoxyl sulfate, a small metabolite, as a potential biomarker through LC-MS. This biomarker may help monitor COVID-19 disease progression and guide more individualized treatment strategies for patients.Nguyen DC, Wells CK, Taylor MS, Martinez-Ondaro Y, Singhal R, Brittian KR, Brainard RE, Moore JB, Hill BG. Dietary Branched-Chain Amino Acids Modify Postinfarct Cardiac Remodeling and Function in the Murine Heart. J Am Heart Assoc. 2025 Feb 18;14(4):e037637. doi: 10.1161/JAHA.124.037637. Epub 2025 Feb 14. PMID: 39950451.
Impact Statement: This study demonstrates that branched chain amino acid (BCAA) levels in the diet influence cardiac remodeling after myocardial infarction, with low levels of BCAAs having a salutary effect on the post-infarcted heart. Given that the effects of diet on cardiac remodeling after injury is an area of research that is markedly underdeveloped, these studies provide a starting point for assessing how careful nutrition may be used as a tool to improve the health of patients that have suffered a heart attack.Adamson DT, Kavalukas S, Shaw MA, Weingartner LA. Engaging Clinical Learners Asynchronously With Social Annotation for Case-Based Discussions. Clin Teach. 2025 Apr;22(2):e70032. doi: 10.1111/tct.70032. PMID: 39933568.
Impact Statement: Using a social annotation platform for case-based learning in a surgical residency preparatory course led to high student engagement, with 95% of readings completed and an average of nine discussion comments per assignment. This approach offers a flexible instructional tool that fosters peer interaction and enhances asynchronous learning in clinical education.Kittle WM, Reeves MA, Fulkerson AE, Hamorsky KT, Morris DA, Kitterman KT, Merchant ML, Matoba N. Preclinical Long-Term Stability and Forced Degradation Assessment of EPICERTIN, a Mucosal Healing Biotherapeutic for Inflammatory Bowel Disease. Pharmaceutics. 2025 Feb 15;17(2):259. doi: 10.3390/pharmaceutics17020259. PMID: 40006626; PMCID: PMC11859197.
Impact Statement: Inflammatory bowel disease (IBD) disorders such as Crohn’s disease and ulcerative colitis are characterized by chronic and relapsing inflammation in the gastrointestinal (GI) tract. EPICERTIN, a biotherapeutic candidate for mucosal healing in IBD, was subjected to an extensive long-term stability testing. Our results demonstrate EPICERTIN stably for 2 years under the conditions tested, and highlights its potential for the treatment of IBD.O'Toole TE, Amraotkar AR, Gao H, Sears CG, Rai SN, Basner M, Bhatnagar A. Carnosine supplementation improves cognitive outcomes in younger participants of the NEAT trial. Neurotherapeutics. 2025 Mar;22(2):e00541. doi: 10.1016/j.neurot.2025.e00541. Epub 2025 Feb 6. PMID: 39919936.
Impact Statement: In this study, we examined how carnosine supplementation affected cognitive performance in members of the NEAT cohort. This was done using the computerized, validated Cognition platform, which is a series of 10 short tests analyzing different cognitive functions and employing different brain regions. Cumulative accuracy and speed scores were obtained for the whole platform as well as for each of the 10 individual tests. We found that carnosine improved speed and accuracy scores, but selectively in younger participants (23-35 years of age). These results suggest carnosine supplementation can improve cognitive function in younger individuals who are devoid of susceptibility factors or pre-existing conditions.Teng Y, Luo C, Qiu X, Mu J, Sriwastva MK, Xu Q, Liu M, Hu X, Xu F, Zhang L, Park JW, Hwang JY, Kong M, Liu Z, Zhang X, Xu R, Yan J, Merchant ML, McClain CJ, Zhang HG. Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites. Nat Commun. 2025 Feb 3;16(1):1295. doi: 10.1038/s41467-025-56498-2. PMID: 39900923; PMCID: PMC11790884.
Impact Statement: This study reveals a novel mechanism by which plant-derived nanoparticles, specifically ginger-derived exosome-like nanoparticles (GELN), enhance cancer immunotherapy by modulating gut microbiota and metabolic pathways. By increasing circulating docosahexaenoic acid (DHA) and inhibiting PD-L1 expression in tumor cells, GELN improves the efficacy of anti-PD-L1 therapy, offering new insights into diet-microbiome interactions in cancer treatment.Woolley CR, Chariker JH, Rouchka EC, Ford EE, Hudson E, Rasche KM, Whitley CS, Vanwinkle Z, Casella CR, Smith ML, Mitchell TC. Full-length mRNA sequencing resolves novel variation in 5' UTR length for genes expressed during human CD4 T-cell activation. Immunogenetics. 2025 Feb 5;77(1):14. doi: 10.1007/s00251-025-01371-1. PMID: 39904916; PMCID: PMC11794378.
Impact Statement: Using Isoform sequencing (Iso-Seq), we generated the first reference transcriptome of activated human CD4 T cells, uncovering novel splice- and end-variant transcripts, including previously unrecognized 5' UTR extensions in one-eighth of expressed genes. Our findings demonstrate how long-read sequencing reveals critical regulatory elements influencing transcript stability and protein expression, emphasizing the need to refine reference databases for a more comprehensive understanding of gene regulation.Jin L, Richardson A, Lynch J, Miller A, Sithu I, Lorkiewicz P, Srivastava S, Gao H, Riggs DW, Srivastava S, Conklin DJ. Role of the Transient Receptor Potential Ankyrin-1 in the Pulmonary, Vascular, and Systemic Effects of Short-Term Acrolein Inhalation in Mice: Implications for the Toxicity of Electronic Nicotine Delivery Systems. Cardiovasc Toxicol. 2025 Feb 25. doi: 10.1007/s12012-025-09978-2. Epub ahead of print. PMID: 40000582.
Impact Statement: Acrolein – a toxic aldehyde present in electronic cigarette-derived aerosol – induced respiratory braking and vascular dysfunction in mice via activation of an irritant receptor known as Transient Receptor Potential Ankyrin-1 (TRPA1) and independently of TRPA1, respectively. These data provide evidence that exposure to the toxic aldehydes present in electronic cigarettes such as acrolein elevates the risk of cardiopulmonary diseases. Regulatory actions should target the lowering of the levels of aldehydes in electronic cigarette-derived aerosols to protect public health.Saedi S, Tan Y, Watson SE, Sparks JD, Wintergerst KA, Cai L. Oxidative stress and pediatric diabetic cardiovascular complications: emerging research and clinical applications. Am J Physiol Heart Circ Physiol. 2025 Feb 28. doi: 10.1152/ajpheart.00673.2024. Epub ahead of print. PMID: 40019178.
Impact Statement: Diabetes and diabetic complications have been extensively investigated in the adult population, but relatively less in the pediatric populations. Oxidative stress has been considered as a very common pathogenic factor in both diabetic and its complications pathologies. With a focus of oxidative stress, therefore, this review has comprehensively summarized the trends of pediatric prevalence, diabetic pathogenesis and its cardiovascular complications and provide some prospectives for the future works.Zelko IN, Malovichko MV, McFall SA, Taylor BS, Chen H, Conklin DJ, Srivastava S. Chronic Inhaled Benzene Exposure Exacerbates Atherosclerosis in LDL Receptor-Null Mice. bioRxiv [Preprint]. 2025 Feb 2:2025.01.29.635519. doi: 10.1101/2025.01.29.635519. PMID: 39974913; PMCID: PMC11838383.
Impact Statement: Inhaled benzene exposure promotes atherosclerosis by increasing vascular inflammation, T-cell proliferation, and vascular smooth muscle cell alterations in LDLR-KO mice. These findings suggest that benzene compromises plaque stability, highlighting a potential new cardiovascular risk associated with this common environmental pollutant.- Zhang Y, Guo Y, Du L, Zhao J, Ci X, Yin J, Niu Q, Mo Y, Zhang Q, Nie J. Maternal Exposure of SD Rats to Benzo[a]Pyrene Impairs Neurobehavior and Hippocampal Synaptic Ultrastructure in Offspring via Downregulating Synaptic-Associated Factors. Environ Toxicol. 2025 Feb 18. doi: 10.1002/tox.24489. Epub ahead of print. PMID: 39967322.
Impact Statement: This study demonstrated that maternal Benzo[a]pyrene (BaP) exposure induced neurobehavioral deficits in offspring during the brain growth spurt (BGS) period by destroying the hippocampal synaptic ultrastructure, which was possibly associated with the downregulation of BDNF, Arc, SYP, and PSD95 in the hippocampus through increased DNMTs-mediated DNA methylation.
Yao Z, Tasdighi E, Dardari ZA, Jha KK, Osuji N, Rajan T, Boakye E, Rodriguez CJ, Matsushita K, Simonsick EM, Lima JAC, Widome R, Cohen DL, Appel LJ, Khera A, Hall ME, Judd S, Cole SA, Vasan RS, Benjamin EJ, Bhatnagar A, DeFilippis AP, Blaha MJ. Differential Associations of Cigar, Pipe, and Smokeless Tobacco Use Versus Combustible Cigarette Use With Subclinical Markers of Inflammation, Thrombosis, and Atherosclerosis: The Cross-Cohort Collaboration-Tobacco Working Group. Circulation. 2025 Jan 27. doi: 10.1161/CIRCULATIONAHA.124.070852. Epub ahead of print. PMID: 39866105.
Impact Statement: This study highlights that noncigarette tobacco products, including cigars, pipes, and smokeless tobacco, are associated with subclinical markers of cardiovascular harm, such as elevated inflammatory biomarkers and carotid plaque. These findings emphasize the need for regulatory policies that consider the cardiovascular risks of all tobacco products, not just cigarettes.Srivastava S, Krivokhizhina T, Keith R, Bhatnagar A, Srivastava S, Xie Z, Lorkiewicz P. High-throughput UPLC-ESI/MSMS method for simultaneous measurement of the urinary metabolites of volatile organic compounds and tobacco alkaloids. J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Feb 1;1252:124463. doi: 10.1016/j.jchromb.2025.124463. Epub 2025 Jan 10. PMID: 39826161.
Impact Statement: This study introduces a high-throughput UPLC-MS/MS method that enables simultaneous measurement of 35 urinary VOC metabolites and tobacco alkaloids with enhanced sensitivity and efficiency. By improving analyte coverage and accounting for tobacco use as a confounder, this method advances accurate VOC exposure assessment in population-based studies.Tasdighi E, Yao Z, Jha KK, Dardari ZA, Osuji N, Rajan T, Boakye E, Rodriguez CJ, Matsushita K, Simonsick EM, Lima JAC, Widome R, Cohen D, Appel LJ, Khera A, Hall ME, Judd S, Cole SA, Ramachandran VS, Benjamin EJ, Bhatnagar A, DeFilippis AP, Blaha MJ. Cigar, Pipe, and Smokeless Tobacco Use and Cardiovascular Outcomes From Cross Cohort Collaboration. JAMA Netw Open. 2025 Jan 2;8(1):e2453987. doi: 10.1001/jamanetworkopen.2024.53987. PMID: 39804647; PMCID: PMC11731180.
Impact Statement: This study demonstrates that noncigarette tobacco products, including cigars, pipes, and smokeless tobacco, are associated with increased risks of cardiovascular disease, heart failure, stroke, and mortality. These findings highlight the need for evidence-based regulatory policies to address the cardiovascular risks of all tobacco products, not just cigarettes.Habil MR, Salazar-González RA, Doll MA, Hein DW. Bioactivation, Mutagenicity, DNA Damage, and Oxidative Stress Induced by 3,4-Dimethylaniline. Biomolecules. 2024 Dec 7;14(12):1562. doi: 10.3390/biom14121562. PMID: 39766269; PMCID: PMC11674834.
Impact Statement:3,4-dimethylaniline (3,4-DMA) is an alkylaniline found in pharmaceuticals and personal care products, pesticides, tobacco smoke, and the dye industry. A DNA repair-deficient CHO cell model transfected with human CYP1A2 and N-acetyltransferase 1 (NAT1). We investigated how NAT1 genetic variants affect acetylation and kinetic constants (Km and Vmax) and investigated DNA damage, mutagenesis and oxidative stress induced by 3,4-DMA.Walls KM, Joh JY, Martinez MM, Hong KU, Hein DW. Metabolic effects of heterocyclic amines on insulin induced AKT phosphorylation and gluconeogenic gene expression are modified by N-acetyltransferase 2 genetic polymorphism. Pharmacogenet Genomics. 2025 Jan 29. doi: 10.1097/FPC.0000000000000559. Epub ahead of print. PMID: 39878101.
Impact Statement:Recent epidemiological studies reported significant associations between dietary heterocyclic amine (HCA) exposure and insulin resistance and type II diabetes. We investigated the role of N-acetyltransferase 2 (NAT2) genetic polymorphism in HCA-induced metabolic dysregulation. HCA treatment significantly reduced insulin-induced AKT phosphorylation and significantly increased expression of genes involved in gluconeogenesis (G6PC, PCK1, FOXO1, PPARA) in cryopreserved human hepatocytes from rapid but not from slow acetylators. The findings suggest that NAT2 genetic polymorphism modifies HCA-induced insulin resistance and gluconeogenic gene expression, implying that individuals with rapid acetylator phenotype may be at greater risk of dysregulated glucose homeostasis following exposure to HCAs.Sheneman KR, Cummins TD, Merchant ML, Hood JL, Uriarte SM, Lawrenz MB. Yersinia pestis actively inhibits the production of extracellular vesicles by human neutrophils. bioRxiv [Preprint]. 2024 Dec 21:2024.12.20.629761. doi: 10.1101/2024.12.20.629761. PMID: 39763979; PMCID: PMC11702605.
Impact Statement: Yersinia pestis, the bacteria causing the plague, disrupts the host immune response by interfering with signaling pathways required for inflammation, creating a non-inflammatory environment that supports bacterial colonization. This research focused on Y. pestis significantly affects neutrophil extracellular vesicles (EVs) produced during infection as a function of Y. pestis effector proteins. EVs from cells infected with the mutant strain were rich in antimicrobial and cytotoxic proteins, which were not present in EVs from Y. pestis-infected cells. Furthermore, EVs from Y. pestis-infected neutrophils lacked the inflammatory properties seen in those from mutant-infected cells. These findings suggest that Y. pestis actively inhibits the production of antimicrobial EVs, likely aiding in immune evasion.Zheng J, Dhakal H, Qing E, Shrestha R, Geller AE, Morrissey SM, Saxena D, Hu X, Li H, Li H, Wilhelmsen K, Wendt LH, Klumpp K, Hume PS, Janssen WJ, Brody R, Palmer KE, Uriarte SM, Ten Eyck PP, Meyerholz DK, Merchant ML, McLeish K, Gallagher T, Huang J, Yan J, Perlman S. CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection. J Clin Invest. 2025 Jan 7:e188222. doi: 10.1172/JCI188222. Epub ahead of print. PMID: 39773555.
Impact Statement: CXC motif chemokine 12 CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection.Ghare S, Warner D, Warner J, Chilton PM, Lee J, Zhang J, Wang M, Hardesty J, Treves R, Gabbard J, Anderson C, Batra L, Sreenivasan C, Kraenzle J, McCulley M, McCoy S, Zhang L, Feng W, Gondim DD, Barve S, Zheng J, Palmer K, McClain C, Kirpich I. Impact of chronic ethanol consumption and SARS-COV-2 on the liver and intestine: A pilot dose-response study in mice. Alcohol Clin Exp Res (Hoboken). 2025 Jan 5. doi: 10.1111/acer.15528. Epub ahead of print. PMID: 39757351.
Impact Statement: This study demonstrates that SARS-CoV-2 infection exacerbates alcohol-induced liver inflammation and increases early mortality in a dose-dependent manner in an experimental model of alcohol-associated liver disease. These findings highlight the potential for worsened liver dysfunction in individuals with chronic alcohol use during COVID-19 infection, underscoring the need for targeted health interventions.Williams PG, Sears L, Watson WH, Gunaratnam B, Feygin Y, Wright SP, Sullivan JE. Glutathione, Vitamin C, and Cysteine Use in Autistic Children With Disruptive Behavior: A Double-Blind, Placebo-Controlled Crossover Pilot Study. J Dev Behav Pediatr. 2025 Jan 9. doi: 10.1097/DBP.0000000000001334. Epub ahead of print. PMID: 39823357.
Impact Statement: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication differences and restricted interests. One proposed biologic mechanism underlying ASD is oxidative stress, leading to the clinical use of glutathione based on anecdotal reports of improved behavior in autistic children. In this pilot study, we tested this observation using a randomized clinical trial format to collect preliminary data on glutathione safety and efficacy. Treatment with glutathione or glutathione in combination with vitamin C and N-acetylcysteine did not result in improvements in behavior or biologic measures. The positive trends over the course of the study were likely due to the placebo effect or decreased anxiety associated with the study routine.Schubert M, Logsdon MC, Sears C, Miller E, Alobaydullah AA, Lain KL. Integrating Community-Based Doulas into the Maternity Health Care System in an Urban Hospital. MCN Am J Matern Child Nurs. 2024 Sep-Oct 01;49(5):261-267. doi: 10.1097/NMC.0000000000001032. Epub 2024 Aug 13. PMID: 39784695.
Impact Statement: This study demonstrates that integrating culturally congruent doulas into the health care system improved postpartum visit attendance and received positive feedback from both patients and providers. These findings highlight the potential of doula programs to address health disparities and improve maternal health outcomes for Black childbearing women.- Ritzenthaler JD, Ekuban A, Horsman B, Roman J, Watson WH. Alcohol-induced liver injury is mediated via α4-containing nicotinic acetylcholine receptors expressed in hepatocytes. Alcohol Clin Exp Res (Hoboken). 2025 Jan 23. doi: 10.1111/acer.15533. Epub ahead of print. PMID: 39853711.
Impact Statement: This study demonstrates that hepatocyte-specific α4 nicotinic acetylcholine receptors (nAChRs) play a critical role in alcohol-induced liver damage, including steatosis, inflammation, and injury. Targeting hepatocyte α4-containing nAChRs could serve as a potential therapeutic strategy for mitigating alcohol-associated liver disease (ALD).
Coleman JJ, Owen J, Wright JH, Eells TD, Antle B, McCoy M, Soma CS. Using Artificial Intelligence to Identify Effective Components of Computer-Assisted Cognitive Behavioural Therapy. Clin Psychol Psychother. 2024 Nov-Dec;31(6):e70023. doi: 10.1002/cpp.70023. PMID: 39625130.
Impact Statement: This study utilizes artificial intelligence to identify key interventions during clinician-supported computer-assisted cognitive-behavioral therapy (CCBT) sessions, revealing that therapist use of open questions and techniques like guided discovery and interpersonal effectiveness were particularly effective in reducing anxiety. The findings provide valuable insights into the specific therapeutic practices that drive CCBT outcomes, highlighting open questions as the most impactful technique for improving anxiety symptoms.Banerjee M, Lykoudi A, Hwang JY, Pan J, Rai SN, Park JW, States JC. Dysregulation of mRNA expression by hsa-miR-186 overexpression in arsenic-induced skin carcinogenesis. Toxicol Appl Pharmacol. 2024 Dec 22;495:117209. doi: 10.1016/j.taap.2024.117209. Epub ahead of print. PMID: 39719251.
Impact Statement: This study uncovers the complex interaction between miR-186 overexpression and chronic arsenic exposure in driving the development of arsenic-induced cutaneous squamous cell carcinoma (cSCC), revealing key pathways that are consistently dysregulated during transformation. By employing longitudinal RNA-seq analysis, the research highlights the role of stochasticity in cancer development and offers insights into the potential for personalized approaches in understanding carcinogenesis driven by environmental and genetic factors.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. Am J Epidemiol. 2024 Dec 16:kwae458. doi: 10.1093/aje/kwae458. Epub ahead of print. PMID: 39691946.
Impact Statement: The Green Heart Project investigates the impact of increasing greenery on community health in a racially diverse, low-to-middle-income area, measuring environmental pollutants and cardiovascular health outcomes before and after planting over 8,000 trees and shrubs. The study's community-driven design and ongoing health assessments aim to provide valuable insights into how urban greening can improve public health, particularly in underserved populations.fan A, Riggs DW, Koromia GA, Gao H, DeFilippis AP, Soliman EZ, Bhatnagar A, Carll AP. Smoking-associated electrocardiographic abnormalities predict cardiovascular mortality. Sci Rep. 2024 Dec 28;14(1):31189. doi: 10.1038/s41598-024-82503-7. PMID: 39730843; PMCID: PMC11680829.
Impact Statement: This study highlights the significant impact of smoking on cardiac conduction, revealing its association with abnormal ECG intervals that predict arrhythmia and cardiovascular mortality. The findings underscore the role of smoking in altering ventricular repolarization and atrioventricular depolarization, suggesting a potential mechanistic pathway for smoking-induced cardiac risk.Tinman JS, Nzama N, Patterson J, Harris LM, Kerr JC. "Don't Tell Nobody Nothing": A Phenomenological Study on Fear of HIV Disclosure Among Older African Americans During Incarceration Living in Kentucky, USA. J Assoc Nurses AIDS Care. 2024 Dec 24. doi: 10.1097/JNC.0000000000000514. Epub ahead of print. PMID: 39718385.
Impact Statement: This study highlights the unique challenges faced by older African Americans living with HIV in incarceration, emphasizing their fear of disclosure, stigma, and the critical need for supportive environments. The findings advocate for improved HIV awareness, stronger confidentiality protections, and the establishment of support networks within correctional settings to better address the needs of this vulnerable population.Hong KU, Aureliano AP, Walls KM, Hein DW. Investigation on regulation of N-acetyltransferase 2 expression by nuclear receptors in human hepatocytes. Front Pharmacol. 2024 Nov 18;15:1488367. doi: 10.3389/fphar.2024.1488367. PMID: 39624836; PMCID: PMC11608957.
Impact Statement: This study investigates the potential regulation of NAT2 expression by hepatic nuclear receptors, a key factor in drug metabolism and cardiometabolic disorders, but finds no significant modulation by FXR, PXR, LXR, or PPARα. These results highlight the need for further research to identify other transcriptional regulators of NAT2 and understand its role in metabolic disease.Gouwens KR, Nong Y, Chen N, Schulman-Geltzer EB, Collins HE, Hill BG, Nystoriak MA. Myocardial Hyperemia via Cardiomyocyte Catabolism of β-Hydroxybutyrate. Arterioscler Thromb Vasc Biol. 2024 Dec 12. doi: 10.1161/ATVBAHA.124.321848. Epub ahead of print. PMID: 39665139.
Impact Statement: This study shows that ketone body metabolism by cardiomyocytes is required for ketone-mediated increases in myocardial perfusion, underscoring the heart’s dynamic adaptability to metabolic states.Jobe T, Stephan J, Wells CK, De Silva M, Lorkiewicz PK, Hill BG, Wysoczynski M. Phase partitioning of the neutrophil oxidative burst is coordinated by accessory pathways of glucose metabolism and mitochondrial activity. J Biol Chem. 2024 Dec 13;301(1):108091. doi: 10.1016/j.jbc.2024.108091. Epub ahead of print. PMID: 39675714.
Impact Statement: This study reveals the dynamic relationship between neutrophil metabolism and reactive oxygen species (ROS) production during the respiratory burst, highlighting the role of various metabolic pathways in regulating the magnitude and duration of ROS production. By identifying key metabolic processes, such as the G3P shuttle, glycogenolysis, and serine biosynthesis, the research provides new insights into how neutrophil metabolism controls immune responses.Jing H, Wei M, Lu J, Zhou L, Huang J, Cheng W, Zhang Q, Qiao Z, Zhu J, Ye Y, Hu J, Liang J, Wang S. Outcomes and risk factors for cardiac surgery during pregnancy: a 13-year, two-centre, retrospective cohort study. J Thorac Dis. 2024 Nov 30;16(11):7561-7573. doi: 10.21037/jtd-24-787. Epub 2024 Nov 11. PMID: 39678879; PMCID: PMC11635234.
Impact Statement: This study underscores the high maternal and fetal risks associated with cardiac surgery during pregnancy, with maternal and fetal mortality rates of 4.3% and 35.7%, respectively. By identifying preoperative left ventricular ejection fraction, pulmonary hypertension, and intraoperative blood loss as key risk factors, the research provides valuable predictive markers for postoperative cardiovascular complications and mortality.Chen J, Smith K, Xu Q, Ali T, Cavallazzi R, Ghafghazi S, Clifford SP, Arnold FW, Kong M, Huang J; Center of Excellence for Research in Infectious Diseases (CERID) Post-COVID-19 Research Clinic Study Group. Long-term Effects of COVID-19 on Vascular Parameters-A Prospective Longitudinal Ultrasound Clinical Study. J Vasc Ultrasound. 2024 Jun;48(2):95-102. doi: 10.1177/15443167231210357. Epub 2024 May 10. PMID: 39641110; PMCID: PMC11619815.
Impact Statement: This study highlights the long-term vascular effects of COVID-19, including increased intima-media thickness (IMT) and altered arterial velocities, suggesting potential cardiovascular risks in post-COVID-19 individuals. While no instances of deep vein thrombosis were observed, the increased IMT may indicate early atherosclerotic changes, warranting further research into whether COVID-19-related vascular alterations require distinct treatment approaches.Meaza I, Cahill CR, Speer RM, Kouokam JC, Wise JP Sr. Particulate hexavalent chromium inhibits global transcription of genes in DNA repair pathways, particularly targeting homologous recombination repair, base excision repair, mismatch repair and microhomology-mediated end-joining. J Hazard Mater. 2024 Dec 15;485:136892. doi: 10.1016/j.jhazmat.2024.136892. Epub ahead of print. PMID: 39706010.
Impact Statement: This study provides a comprehensive analysis of the transcriptional changes induced by hexavalent chromium (Cr(VI)) exposure, revealing its downregulation of key genes involved in DNA repair pathways, including homologous recombination and mismatch repair. The findings offer crucial insights into how Cr(VI)-induced disruption of DNA repair mechanisms contributes to chromosome instability and lung carcinogenesis.Lei C, Luo C, Xu Z, Ding S, Sriwastva MK, Dryden G, Wang T, Xu M, Tan Y, Wang Q, Yang X, McClain CJ, Deng Z. Bacterial and host fucosylation maintain IgA homeostasis to limit intestinal inflammation in mice. Nat Microbiol. 2025 Jan;10(1):126-143. doi: 10.1038/s41564-024-01873-w. Epub 2024 Dec 17. PMID: 39690194.
Impact Statement: This study demonstrates that both host and bacterial fucosylation play a critical role in modulating gut immunity and maintaining immune homeostasis, with alterations in fucosylation contributing to inflammatory bowel disease (IBD) pathogenesis. The findings highlight the importance of fucosylation in IgA-mediated immune responses, bacterial translocation, and the immune landscape in Peyer's patches, providing new insights into gut inflammation and potential therapeutic strategies.Son HG, Ha DT, Xia Y, Li T, Blandin J, Oka T, Azin M, Conrad DN, Zhou C, Zeng Y, Hasegawa T, Strickley JD, Messerschmidt JL, Guennoun R, Erlich TH, Shoemaker GL, Johnson LH, Palmer KE, Fisher DE, Horn TD, Neel VA, Nazarian RM, Joh JJ, Demehri S. Commensal papillomavirus immunity preserves the homeostasis of highly mutated normal skin. Cancer Cell. 2024 Dec 7:S1535-6108(24)00448-3. doi: 10.1016/j.ccell.2024.11.013. Epub ahead of print. PMID: 39672169.
Impact Statement: This study reveals that T cell immunity to cutaneotropic papillomaviruses plays a crucial role in maintaining the homeostasis of ultraviolet radiation-damaged skin, specifically by preventing the expansion of mutant p53 clones. The findings underscore the importance of virome-immune system interactions in preserving aging human skin and suggest potential therapeutic strategies for preventing skin dysplasia and malignancy.Lu H, Wise SS, Toyoda JH, Speer RM, Croom-Perez TJ, Meaza I, Kouokam JC, Wise JL, Hoyle G, Chen N, Wise JP Jr, Kondo K, Toba H, Takizawa H, Wise JP Sr. Particulate hexavalent chromium exposure induces DNA double-strand breaks and inhibits homologous recombination repair in rat and human lung tissues. Chemosphere. 2024 Dec 24;370:143982. doi: 10.1016/j.chemosphere.2024.143982. Epub ahead of print. PMID: 39701314.
Impact Statement: This study reveals that particulate hexavalent chromium (Cr(VI)) induces DNA double-strand breaks and inhibits homologous recombination repair, contributing to chromosome instability, a key driver of Cr(VI)-induced lung cancer. The findings, observed in both experimental rat lung tissue and human lung tumors, underscore the critical role of Cr(VI)-mediated DNA damage and impaired repair mechanisms in the development of lung cancer.Wise RM, Wise JP Jr, Andersen JK, Ascnher M. Editorial: A Toxic Aging Coin perspective to investigate the intersection of toxicology and aging. Front Toxicol. 2024 Dec 12;6:1527706. doi: 10.3389/ftox.2024.1527706. PMID: 39726981; PMCID: PMC11669706.
Impact Statement: This collection emphasizes the dual impact of toxic substances on aging, addressing both how age modifies the effects of environmental toxicants and how exposure accelerates aging-related processes. It highlights the urgent need for interdisciplinary research to better understand how toxic agents influence aging mechanisms, with implications for public health policies and strategies to protect aging populations.Zelko IN, Hussain A, Malovichko MV, Wickramasinghe N, Srivastava S. Benzene metabolites increase vascular permeability by activating heat shock proteins and Rho GTPases. bioRxiv [Preprint]. 2024 Dec 7:2024.12.04.626801. doi: 10.1101/2024.12.04.626801. PMID: 39677674; PMCID: PMC11643022.
Impact Statement: This study demonstrates that benzene metabolites, particularly trans,trans-muconaldehyde (MA) and hydroquinone (HQ), contribute to endothelial dysfunction by promoting vascular permeability and altering key signaling pathways involving heat shock proteins and GTPases. These findings provide novel insights into the mechanisms underlying benzene-induced cardiovascular disease and highlight potential therapeutic targets for mitigating endothelial damage and vascular permeability.- Lypova N, Dougherty SM, Clem BF, Feng J, Yin X, Zhang X, Li X, Chesney JA, Imbert-Fernandez Y. PFKFB3-dependent redox homeostasis and DNA repair support cell survival under EGFR-TKIs in non-small cell lung carcinoma. Cancer Metab. 2024 Dec 18;12(1):37. doi: 10.1186/s40170-024-00366-y. PMID: 39696407; PMCID: PMC11658331.
Impact Statement: This study identifies PFKFB3 inhibition as a key strategy to sensitize lung cancer cells to EGFR TKI therapy by disrupting metabolic rewiring and enhancing oxidative stress, thus preventing the emergence of drug resistance. By targeting PFKFB3, this approach offers a potential therapeutic avenue to overcome therapy persistence and improve treatment outcomes in drug-resistant cancers.
Ali S, Alemu FW, Owen J, Eells TD, Antle B, Lee JT, Wright JH. Cost-Effectiveness of Computer-Assisted Cognitive Behavioral Therapy for Depression Among Adults in Primary Care. JAMA Netw Open. 2024 Nov 4;7(11):e2444599. doi: 10.1001/jamanetworkopen.2024.44599. PMID: 39541120; PMCID: PMC11565263.
Impact Statement: This study demonstrates that clinician-supported computer-assisted cognitive behavioral therapy (CCBT) is a cost-effective treatment for depression in a diverse primary care population, including individuals with low income and limited internet access. The findings have significant policy implications, highlighting CCBT as a viable solution to bridge the treatment gap for underserved communities and improve mental health outcomes.Ranker LR, Tofu DA, Lu M, Wu J, Bhatnagar A, Robertson RM, Wijaya D, Hong T, Fetterman JL, Xuan Z. Concurrent Mentions of Vaping and Alcohol on Twitter: Latent Dirichlet Analysis. J Med Internet Res. 2024 Nov 12;26:e51870. doi: 10.2196/51870. PMID: 39531640; PMCID: PMC11599884.
Impact Statement: This study highlights how social media discussions of alcohol and vaping co-use during the COVID-19 pandemic and regulatory changes often portrayed both behaviors positively, with debates centered on the perceived overregulation of vaping compared to alcohol. The findings suggest that social media analysis can offer valuable insights into public perceptions and concerns, aiding policymakers in navigating the evolving landscape of substance use regulation.Jalleh RJ, Jones KL, Islam MS, Cai L, Horowitz M. Surgical or medical treatment of obesity-associated type 2 diabetes-an increasing clinical conundrum. World J Diabetes. 2024 Oct 15;15(10):2036-2040. doi: 10.4239/wjd.v15.i10.2036. PMID: 39493561; PMCID: PMC11525724.
Impact Statement: This editorial highlights the comparative effectiveness of bariatric surgery and GLP-1 receptor agonist (GLP-1RA) therapy in managing type 2 diabetes (T2D) associated with obesity, noting their benefits for cardiovascular outcomes across different age groups. It calls for further trials to evaluate the long-term efficacy and safety of these treatments, especially considering the absence of postprandial hypoglycemia with GLP-1RAs and the growing need for data in younger and older populations.Wu Z, Chen SY, Zheng L. Sulforaphane Attenuates Ethanol-Induced Teratogenesis and Dysangiogenesis in Zebrafish Embryos. Int J Mol Sci. 2024 Oct 27;25(21):11529. doi: 10.3390/ijms252111529. PMID: 39519082; PMCID: PMC11546994.
Impact Statement: This study demonstrates that sulforaphane (SFN) can alleviate key features of Fetal Alcohol Spectrum Disorders (FASD), such as growth retardation, malformations, and vascular development deficits. These findings underscore the potential of SFN as a therapeutic approach for preventing and intervening in FASD.La Merrill MA, Smith MT, McHale CM, Heindel JJ, Atlas E, Cave MC, Collier D, Guyton KZ, Koliwad S, Nadal A, Rhodes CJ, Sargis RM, Zeise L, Blumberg B. Consensus on the key characteristics of metabolism disruptors. Nat Rev Endocrinol. 2024 Nov 29. doi: 10.1038/s41574-024-01059-8. Epub ahead of print. PMID: 39613954.
Impact Statement: This publication introduces 12 key characteristics (KCs) that provide a systematic framework for identifying metabolism-disrupting agents (MDAs) based on their effects on metabolic processes and disease pathways. By integrating these KCs into hazard identification, the approach offers a comprehensive method to better understand and mitigate the risks associated with MDAs, including chemicals, pharmaceuticals, and environmental agents.Xu M, Taylor MS, Hill BG, Li X, Rouchka EC, McClain CJ, Song M. Intestine epithelial-specific hypoxia-inducible factor-1α overexpression ameliorates western diet-induced MASLD. Hepatol Commun. 2024 Nov 25;8(12):e0572. doi: 10.1097/HC9.0000000000000572. PMID: 39585307; PMCID: PMC11596589.
Impact Statement: This study provides compelling evidence that both pharmacological and genetic activation of intestinal HIF-1α can ameliorate metabolic dysfunction and steatotic liver disease induced by a western diet, highlighting a sex-dependent effect. The results suggest that HIF-1α activation enhances glycolysis, epithelial cell proliferation, and gut barrier function, offering potential therapeutic avenues for treating metabolic liver diseases.Ghosh S, Singh R, Goap TJ, Sunnapu O, Vanwinkle ZM, Li H, Nukavarapu SP, Dryden GW, Haribabu B, Vemula PK, Jala VR. Inflammation-targeted delivery of Urolithin A mitigates chemical- and immune checkpoint inhibitor-induced colitis. J Nanobiotechnology. 2024 Nov 13;22(1):701. doi: 10.1186/s12951-024-02990-8. PMID: 39533380; PMCID: PMC11558909.
Impact Statement: This study introduces inflammation-targeting nanoparticles (ITNPs) as a novel approach to improve drug delivery for inflammatory bowel disease (IBD), enhancing therapeutic efficacy while reducing systemic side effects. By enabling targeted, sustained release of urolithin A and its analogues, ITNPs offer a promising alternative to conventional IBD treatments with greater precision and reduced dosage requirements.Yorek M, Jiang X, Liu S, Hao J, Yu J, Avellino A, Liu Z, Curry M, Keen H, Shao J, Kanagasabapathy A, Kong M, Xiong Y, Sauter ER, Sugg SL, Li B. FABP4-mediated lipid accumulation and lipolysis in tumor-associated macrophages promote breast cancer metastasis. Elife. 2024 Nov 8;13:RP101221. doi: 10.7554/eLife.101221. PMID: 39513934; PMCID: PMC11548877.
Impact Statement: This study identifies the FABP4/CEBPα pathway as a key mechanism through which unsaturated fatty acids promote lipid accumulation in tumor-associated macrophages (TAMs), enhancing breast cancer metastasis. By demonstrating the pivotal role of FABP4 in lipid metabolism within TAMs, the research highlights potential therapeutic targets to disrupt lipid-driven tumor progression in breast cancer.Robinson T, Knott K, Liu Z, Kong M, Telang S. Implementation of an EOS calculator-based protocol decreased infant antibiotic exposure in chorioamnionitis without correlation with placental histopathology. J Perinatol. 2025 Jan;45(1):104-110. doi: 10.1038/s41372-024-02167-z. Epub 2024 Nov 9. PMID: 39521889.
Impact Statement: The implementation of an Early Onset Sepsis (EOS) calculator protocol significantly reduced antibiotic exposure in infants born to mothers with clinical chorioamnionitis without missing any EOS cases. However, no correlation was found between EOS calculator-guided antibiotic treatment and placental histopathology, suggesting that the calculator's effectiveness may not be directly linked to histological findings.Sak M, Chariker JH, Park JW, Rouchka EC. Gene Expression and Alternative Splicing Analysis in a Large-Scale Multiple Sclerosis Study. Int J Mol Sci. 2024 Nov 7;25(22):11957. doi: 10.3390/ijms252211957. PMID: 39596026; PMCID: PMC11593658.
Impact Statement: This study uncovers novel gene expression changes, alternative splicing events, and RNA-binding motifs in multiple sclerosis (MS) tissues, offering insights into the disease's pathogenesis. The identification of unique genes and splicing mechanisms provides potential new targets for therapeutic development aimed at treating MS and its associated neurodegeneration.Jin A, Holm RH, Smith T, DuPré N, Kavalukas S. Does Wastewater Analysis Play a Role in Tracking Colorectal Cancer Hot Spots to Guide Geotargeted Neighborhood Interventions? ACS ES T Water. 2024 Sep 13;4(9):3623-3625. doi: 10.1021/acsestwater.4c00641. Epub 2024 Aug 15. PMID: 39600559; PMCID: PMC11588027.
Impact Statement: This study advocates for the use of wastewater-based surveillance to track environmental carcinogens and identify colorectal cancer (CRC) hot spots, providing a novel approach to address healthcare disparities and improve screening efforts in at-risk communities. By integrating wastewater data with environmental toxins, cancer registries, and biospecimens, this approach has the potential to guide targeted interventions and reduce CRC incidence in marginalized populations.Li K, Smith ML, Blazier JC, Kochan KJ, Wood JMD, Howe K, Kwitek AE, Dwinell MR, Chen H, Ciosek JL, Masterson P, Murphy TD, Kalbfleisch TS, Doris PA. Construction and evaluation of a new rat reference genome assembly, GRCr8, from long reads and long-range scaffolding. Genome Res. 2024 Nov 20;34(11):2081-2093. doi: 10.1101/gr.279292.124. PMID: 39516046; PMCID: PMC11610589.
Impact Statement: The newly constructed Rattus norvegicus reference genome assembly, GRCr8, offers a more complete and accurate representation of the rat genome, with significant improvements in chromosome size, gene annotation, and repetitive sequence inclusion. This updated assembly, now adopted by the Genome Reference Consortium, enhances the utility of the rat as an experimental model and provides a critical resource for further genomic and functional research.Gripshover TC, Treves RS, Rouchka EC, Chariker JH, Zheng S, Hudson E, Smith ML, Singal AK, McClain CJ, Hardesty JE. Visium spatial transcriptomics and proteomics identifies novel hepatic cell populations and transcriptomic signatures of alcohol-associated hepatitis. Alcohol Clin Exp Res (Hoboken). 2024 Nov 26. doi: 10.1111/acer.15494. Epub ahead of print. PMID: 39592394.
Impact Statement: This study provides a detailed analysis of the cellular and molecular alterations in alcohol-associated hepatitis (AH), revealing distinct changes in cell populations and gene/protein expression compared to non-ALD controls. These findings enhance our understanding of AH's cellular plasticity and offer potential targets for the development of novel therapeutic strategies.Anderson J, Owen EB, Mayes S, Sullivan JE, McDonald MJ. Pharmacokinetics and Safety of Endotracheal Lidocaine for Endotracheal Intubation in Critically Ill Children. Paediatr Drugs. 2024 Nov 8. doi: 10.1007/s40272-024-00662-6. Epub ahead of print. PMID: 39516449.
Impact Statement: This pilot study demonstrates that at the doses utilized for lidocaine administration via endotracheal tube (ETT) in critically ill pediatric patients, there was no detectable toxic serum concentrations and no adverse effects following suctioning. Lidocaine is often used in patients with head trauma or those at risk of increased intracranial pressure. It is administered via the endotracheal tube to blunt the cough reflex which may cause an increase in intracranial pressure. Additional studies are required with a broader range of doses to confirm both safety and efficacy.- Bolatimi OE, Hua Y, Ekuban FA, Gripshover TC, Ekuban A, Luulay B, Watson WH, Hardesty JE, Wahlang B. Low dose exposure to dioxins alters hepatic energy metabolism and steatotic liver disease development in a sex-specific manner. Environ Int. 2024 Nov 17;194:109152. doi: 10.1016/j.envint.2024.109152. Epub ahead of print. PMID: 39577358.
Impact Statement: This study highlights the sex-dependent effects of low-level dioxin mixtures on the development of steatotic liver disease, revealing more pronounced hepatic disruptions and metabolic dysfunctions in females compared to males. The findings underscore the need to reconsider current dioxin exposure thresholds and emphasize the potential risks associated with prolonged, low-level environmental exposure to these persistent pollutants.
Rajagopalan S, McAlister S, Jay J, Pham RD, Brook RD, Nasir K, Nieuwenhuijsen MJ, Landrigan P, Wiesler A, Sanborn CV, Carron JR, Brooks KH, Bhatnagar A, Al-Kindi S. Environmental sustainability in cardiovascular practice: current challenges and future directions. Nat Rev Cardiol. 2024 Oct 25. doi: 10.1038/s41569-024-01077-z. Epub ahead of print. PMID: 39455886.
Impact Statement: This publication highlights the critical need for environmental sustainability in cardiovascular care, aiming to reduce greenhouse gas emissions and pollution while potentially improving health outcomes and reducing healthcare costs. It outlines frameworks for sustainable practices, discusses carbon emissions and climate impacts of healthcare, and emphasizes prevention as a key strategy for minimizing the environmental footprint of cardiovascular care.Yao Z, Tasdighi E, Dardari ZA, Erhabor J, Jha KK, Osuji N, Rajan T, Boakye E, Rodriguez CJ, Lima JAC, Judd S, Feldman T, Fialkow JA, Ramachandran VS, El Shahawy O, Benjamin EJ, Bhatnagar A, DeFilippis AP, Nasir K, Blaha MJ. Use of E-Cigarette, Traditional Cigarettes, and C-Reactive Protein: The Cross Cohort Collaboration. Am Heart J. 2024 Oct 24:S0002-8703(24)00275-8. doi: 10.1016/j.ahj.2024.10.012. Epub ahead of print. PMID: 39461654.
Impact Statement: This cross-sectional study of 18,797 participants across six longitudinal cohorts found that exclusive electronic cigarette (EC) use was associated with significantly lower levels of high-sensitivity C-reactive protein (hs-CRP) compared to exclusive combustible cigarette use, suggesting a potentially reduced inflammatory response. However, hs-CRP levels in dual users and former smokers currently using ECs were similar to those of exclusive cigarette smokers, underscoring the importance of ongoing monitoring of EC use for tobacco regulation and public health.He L, Xu R, Ma X, Yin X, Mueller E, Feng W, Menze M, Kim S, McClain CJ, Zhang X. Multiomics Studies on Metabolism Changes in Alcohol-Associated Liver Disease. J Proteome Res. 2024 Nov 1;23(11):4962-4972. doi: 10.1021/acs.jproteome.4c00451. Epub 2024 Oct 17. PMID: 39418671.
Impact Statement: Quantification of polar metabolites and lipids in the liver of mice with experimental ALD shows that alcohol consumption drives metabolism toward lipid synthesis. Results from enzyme expression and activity detection indicated that the decreased activity of mitochondrial glycerol 3-phosphate dehydrogenase contributed to the disordered metabolism.Zou W, Huang J. In reply: Fibreoptic or flexible bronchoscopy during bronchial blocker placement: time to stop perpetuating a bronchoscopic misnomer? Can J Anaesth. 2024 Oct 7. doi: 10.1007/s12630-024-02846-7. Epub ahead of print. PMID: 39375283.
Impact Statement: This publication reply addresses the importance of using precise terminology, advocating for "flexible bronchoscope" instead of the misnomer "fibreoptic bronchoscope" in clinical settings. It also highlights the potential benefits of combining the loop-cinching and manual angulation techniques for improved bronchial blocker placement, calling for further study to validate these methods.Adelmann D, Reddy M, Zhou GP, Fukazawa K, Wang R, Kassel C, Nguyen-Buckley C, Bastidas J, De Marchi L, Wilson EA, Nazemian R, Fernandez-Bustamante A, Anderson A, Chadha RM, Huang J, Moguilevitch M, Townsend E, Rosenfeld DM, Kothari RP. The perioperative care in liver transplantation multicenter database: Building the foundation for research collaboration in liver transplantation. J Clin Anesth. 2024 Oct 21;99:111651. doi: 10.1016/j.jclinane.2024.111651. Epub ahead of print. PMID: 39437663.
Impact Statement: The Society for the Advancement of Transplant Anesthesia (SATA) Perioperative Care in Liver Transplantation Multicenter Database (SATA liver database) is a groundbreaking initiative that enables standardized, multicenter data collection for perioperative liver transplant care, currently engaging 17 U.S. transplant centers. By fostering data collaboration and facilitating comprehensive research, the SATA liver database is positioned to significantly advance patient outcomes and enhance clinical insights in liver transplantation.Polivka B, Krueger K, Bimbi O, Huntington-Moskos L, Nyenhuis S, Cramer E, Eldeirawi K. Integrating Real-Time Air Quality Monitoring, Ecological Momentary Assessment, and Spirometry to Evaluate Asthma Symptoms: Usability Study. JMIR Form Res. 2024 Oct 10;8:e60147. doi: 10.2196/60147. PMID: 39388233; PMCID: PMC11502973.
Impact Statement: This study demonstrates that integrating indoor air quality monitoring, ecological momentary assessment, and home spirometry is both acceptable and usable for adults with asthma, offering valuable insights into real-time environmental exposures and asthma outcomes. Participant feedback highlighted technical challenges and usability improvements that can enhance future research in this area.Alejandro B, Kim EJ, Hwang JY, Park JW, Smith M , Chung D. Genetic and phenotypic changes to Venezuelan equine encephalitis virus following treatment with β-D-N4-hydroxycytidine, an RNA mutagen. Sci Rep. 2024 Oct 25;14(1):25265. doi: 10.1038/s41598-024-76788-x. PMID: 39448734; PMCID: PMC11502654.
Impact Statement: This study provides a detailed understanding on how viruses adapt to new environments and how RNA mutagens can affect the viral population landscape. It's a big step toward developing more effective antiviral treatment.Lakshmanan J, Jaganathan VL, Zhang B, Werner G, Allen TS, Schultz DJ, Klinge CM , Harbrecht BG. Anticancer Properties Against Select Cancer Cell Lines and Metabolomics Analysis of Tender Coconut Water. Anticancer Agents Med Chem. 2024 Oct 15. doi: 10.2174/0118715206327789241008162423. Epub ahead of print. PMID: 39411967.
Impact Statement: Tender coconut water (TCW) stimulates the viability of primary rat hepatocytes but inhibits the viability of breast, liver, and colon cancer cells in vitro. Untargeted metabolomics was used to identify the TCW metabolites with anti-cancer activity. TCW contains 271 metabolites, primarily lipids and lipid-like molecules, phenylpropanoids and polyketides, and organic oxygen compounds. We reported that three components from TCW: 3-hydroxy-1-(4-hydroxyphenyl)propan-1-one, iondole-3-carbox aldehyde and caffeic acid that inhibited the growth of cancer cells and altered the transcript and protein abundance of genes involved in epithelial-to-mesenchymal transition and pathways in intracellular kinase signaling.Vielee ST, Buchanan WJ, Roof SH, Kahloon R, Evans E, Isibor J, Patel M, Meaza I, Lu H, Williams AR, Kouokam JC, Wise SS, Guo L, Wise RM, Wise JL, Cai L, Cai J, Wise JP Jr. Chromium Selectively Accumulates in the Rat Hippocampus after 90 Days of Exposure to Cr(VI) in Drinking Water and Induces Age- and Sex-Dependent Metal Dyshomeostasis. Toxics. 2024 Oct 3;12(10):722. doi: 10.3390/toxics12100722. PMID: 39453142; PMCID: PMC11510846.
Impact Statement: This study reveals that hexavalent chromium [Cr(VI)], a metal commonly polluting drinking water, selectively accumulated in the hippocampus of rats following a 90-day drinking water exposure at levels currently deemed safe. Our study considered both sexes and three age groups; though the most drastic accumulation of chromium was observed in the hippocampus of geriatric females, we further observed Cr(VI) disrupted essential metal homeostasis across all ages and both sexes. These findings highlight age- and sex-specific vulnerabilities to Cr(VI) exposure and underscore the need for further toxicological investigation into its broader impacts on brain health.Hardesty JE, McClain CJ. Current Pharmacotherapy and Nutrition Therapy of Alcohol-Associated Liver Disease. Clin Liver Dis. 2024 Nov;28(4):731-745. doi: 10.1016/j.cld.2024.06.018. Epub 2024 Aug 13. PMID: 39362718; PMCID: PMC11529778.
Impact Statement: Patients with alcohol-associated liver disease (ALD) consume large amounts of empty calories and are at risk for malnutrition. Malnutrition can present with micro- or macro-nutrient deficiencies. The standard-of-care drug treatment for severe alcohol-associated hepatitis (AH) is corticosteroids. While still in the standard treatment there are limitations in efficacy and certain patients do not respond to treatment (Lille score ≥.45). This article will focus on important concepts related to nutrition and ALD and on recent findings on predicting corticosteroid response and prognosis for AH patients.Brown K, Funk K, Figueroa Barrientos A, Bailey A, Shrader S, Feng W, McClain CJ, Song ZH. The Modulatory Effects and Therapeutic Potential of Cannabidiol in the Gut. Cells. 2024 Sep 26;13(19):1618. doi: 10.3390/cells13191618. PMID: 39404382; PMCID: PMC11475737.
Impact Statement: This review highlights the therapeutic potential of cannabidiol (CBD) in modulating gastrointestinal health, including its effects on intestinal permeability, the microbiome, and immune responses. Evidence suggests that CBD’s impact on the GI system may also benefit conditions beyond the gut, such as liver disease and multiple sclerosis, pointing to its broader therapeutic value.Kumar K, Bosch K, Vemuri V, Kratholm N, Rane M, Kakar SS. Withaferin A ameliorates ovarian cancer-induced renal damage through the regulation of expression of inflammatory cytokines. J Ovarian Res. 2024 Oct 11;17(1):199. doi: 10.1186/s13048-024-01519-9. PMID: 39394174; PMCID: PMC11468018.
Impact Statement: This study demonstrates that peritoneal ovarian cancer in NSG mice induces kidney damage and renal dysfunction, characterized by elevated inflammatory cytokines and plasma creatinine levels. Treatment with withaferin A (WFA) significantly mitigated these effects, highlighting its potential as a therapeutic agent to counteract ovarian cancer-induced kidney injury.Tomlinson MM, Kerstiens S, Smith C, Agbonlahor O, Clarke J, Vincent K, Walker KL, McLeish AC, Keith RJ, Smith T, Yeager RA, Wood LA, , Bhatnagar A,Hart JL. The association between perceived neighborhood safety and cardiovascular disease risk factors. Psychol Health Med. 2024 Oct 3:1-12. doi: 10.1080/13548506.2024.2410418. Epub ahead of print. PMID: 39360605.
Impact Statement: This study reveals a significant association between low perceived neighborhood safety and increased cardiovascular disease risk factors, with males particularly vulnerable to this link. The findings highlight the importance of addressing environmental safety to mitigate CVD risk, especially in men.Holm RH, Smith T. Does Wastewater-Based Surveillance Protect the Health of Incarcerated Individuals? Am J Public Health. 2024 Nov;114(11):1156-1157. doi: 10.2105/AJPH.2024.307857. PMID: 39356993; PMCID: PMC11447773.
Impact Statement: We discuss how wastewater-based surveillance (WBS) in carceral facilities can provide early detection of infectious diseases, guiding efficient resource allocation and reducing the need for widespread clinical testing. This approach not only enhances health protections for incarcerated populations but also supports broader public health by offering a proactive tool for disease monitoring and tactical public health interventions to prevent disease spread.Ritzenthaler JD, Watson WH, Roman J. α4 Nicotinic Acetylcholine Receptors in Lipopolysaccharide-Related Lung Inflammation. Int J Mol Sci. 2024 Oct 21;25(20):11305. doi: 10.3390/ijms252011305. PMID: 39457087; PMCID: PMC11509036.
Impact Statement: This study identifies a novel mechanism of acute lung injury in sepsis, demonstrating that lipopolysaccharide (LPS) activates α4 nicotinic acetylcholine receptors (α4 nAChRs) in immune cells, driving oxidative stress and proinflammatory gene expression. Targeting α4 nAChRs with specific inhibitors, such as DHβE, mitigates these effects, offering potential therapeutic insights for improving sepsis outcomes.Saedi S, Tan Y, Watson SE, Wintergerst KA, Cai L. Potential pathogenic roles of ferroptosis and cuproptosis in cadmium-induced or exacerbated cardiovascular complications in individuals with diabetes. Front Endocrinol (Lausanne). 2024 Oct 2;15:1461171. doi: 10.3389/fendo.2024.1461171. PMID: 39415790; PMCID: PMC11479913.
Impact Statement:Diabetes and its complications are major diseases that affect human health, however, whether if the individuals with diabetes are also exposed to environmental metals, there will be high risk for these population lack a clear answer. Therefore, this review has focused on collecting the available evidence to specifically discuss whether two kinds of metal-mediated cell death, ferroptosis, an iron-dependent cell death, and cuproptosis, a copper-dependent cell death, as main mechanistic pathogenesis play certain roles in the acceleration of diabetes and diabetic complications. In the end, we demonstrated the limited information that suggests the potential links, however, more direct evidence remains needed. This review also provides perspectives on the investigation for potential pathogenic roles of ferroptosis and cuproptosis in cadmium-induced or exacerbated cardiovascular complications in individuals with diabetes.Meaza I, Williams AR, Wise SS, Lu H, Pierce JW Sr. Carcinogenic Mechanisms of Hexavalent Chromium: From DNA Breaks to Chromosome Instability and Neoplastic Transformation. Curr Environ Health Rep. 2024 Oct 28. doi: 10.1007/s40572-024-00460-9. Epub ahead of print. PMID: 39466546.
Impact Statement: Hexavalent chromium [Cr(VI)] exposure induces DNA double-strand breaks, repair deficiencies, and chromosome instability, which are central to its carcinogenic mechanism and neoplastic transformation in cells, animals, and humans. This review highlights recent evidence of Cr(VI)'s genotoxic effects, including structural and numerical chromosome instability, emphasizing its role in lung cancer development and broader ecological impacts on wildlife.- Chaudhari M, Zelko I, Lorkiewicz P, Hoetker D, Nong Y, Doelling B, Brittian K, Bhatnagar A, Srivastava S, Baba SP. Metabolic pathways for removing reactive aldehydes are diminished in the skeletal muscle during heart failure. Skelet Muscle. 2024 Oct 18;14(1):24. doi: 10.1186/s13395-024-00354-2. PMID: 39425168; PMCID: PMC11488087.
Impact Statement:This study highlights the role of oxidative stress-induced aldehyde accumulation and reduced detoxifying capacity in heart failure-related muscle wasting. Findings suggest that decreased histidyl dipeptide levels and aldehyde-removing enzymes in skeletal muscle contribute to increased atrophy and inflammation, potentially exacerbating functional decline in heart failure patients.
Wu J, Trifiro BM, Ranker LR, Origgi JM, Benjamin EJ, Robertson RM, Bhatnagar A, Stokes AC, Xuan Z, Wijaya D, Plummer B, Cornacchione Ross J, Fetterman JL, Hong T. Health Warnings on Instagram Advertisements for Synthetic Nicotine E-Cigarettes and Engagement. JAMA Netw Open. 2024 Sep 3;7(9):e2434434. doi: 10.1001/jamanetworkopen.2024.34434. PMID: 39269702; PMCID: PMC11400217.
Impact Statement: This study reveals that 87% of synthetic nicotine e-cigarette posts on Instagram did not comply with FDA health warning regulations, suggesting that regulatory oversight is lacking in social media marketing. Strengthened enforcement of FDA-compliant health warnings could reduce youth engagement with tobacco-related content online.Baba SP, Amraotkar AR, Hoetker D, Gao H, Gomes D, Zhao J, Wempe MF, Rice PJ, DeFilippis AP, Rai SN, Pope CA 3rd, Bhatnagar A, O'Toole TE. Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trial. Amino Acids. 2024 Aug 31;56(1):55. doi: 10.1007/s00726-024-03414-5. PMID: 39215872; PMCID: PMC11365863.
Impact Statement: This publication details initial results from the NEAT clinical trial and validates our approach for increasing endogenous carnosine levels. This dietary supplementation strategy may be useful in combatting individual levels of oxidative stress and inflammation that arise as a consequence of exposure to PM2.5 or other environmental pollutants.Harris LM, Guerrero EG, Khachikian T, Serrett V, Marsh JC. Expert providers implement integrated and coordinated care in opioid use disorder treatment. Int J Drug Policy. 2024 Oct;132:104567. doi: 10.1016/j.drugpo.2024.104567. Epub 2024 Sep 5. PMID: 39241532.
Impact Statement: This study highlights the persistent challenges and innovative strategies employed by high-performing opioid use disorder treatment programs in Los Angeles County to integrate and coordinate medications for opioid use disorder (MOUD). Providers demonstrated resilience in overcoming barriers such as stigma and fragmented healthcare systems by adopting a multidisciplinary approach, leveraging community partnerships, and utilizing telehealth, ultimately improving patient outcomes and treatment retention.Zhong Y, Geng F, Mazik L, Yin X, Becker AP, Mohammed S, Su H, Xing E, Kou Y, Chiang CY, Fan Y, Guo Y, Wang Q, Li PK, Mo X, Lefai E, He L, Cheng X, Zhang X, Chakravarti A, Guo D. Combinatorial targeting of glutamine metabolism and lysosomal-based lipid metabolism effectively suppresses glioblastoma. Cell Rep Med. 2024 Sep 17;5(9):101706. doi: 10.1016/j.xcrm.2024.101706. Epub 2024 Sep 4. PMID: 39236712.
Impact Statement: This study unveils that pimozide inhibits lysosome hydrolytic function to suppress fatty acid and cholesterol release in glioblastoma (GBM), the most lethal brain tumor. Those findings underscore the promising therapeutic potential of effectively targeting GBM by combining glutamine metabolism inhibition with lysosome suppression.Monreal G, Koenig SC, Sangwan A, Guida R, Huang J, Demirors E, Melodia T, Jimenez JH, Slaughter MS. Feasibility Testing of the Bionet Sonar Ultrasound Transcutaneous Energy Transmission (UTET) System for Wireless Power and Communication of a LVAD. Cardiovasc Eng Technol. 2024 Sep 4. doi: 10.1007/s13239-024-00748-9. Epub ahead of print. PMID: 39230796.
Impact Statement: During early-stage development and testing, engineering challenges for Ultrasound #TranscutaneousEnergyTransmission size reduction and stable and safe operation were identified, with solutions and plans to address the limitations in future design iterations also presented.Jain A, Jung HJ, Aubee J, O'Neil JN, Muhammad LA, Khan S, Thompson K, Fluitt MB, Lee DL, Klinge CM, Khundmiri SJ. Role of NHERF1 in MicroRNA Landscape Changes in Aging Mouse Kidneys. Biomolecules. 2024 Aug 23;14(9):1048. doi: 10.3390/biom14091048. PMID: 39334814; PMCID: PMC11430241.
Impact Statement: During aging, the expression of sodium hydrogen regulatory factor 1 (NHERF1) is decreased in kidney proximal tubules. This research identified differential expression of miRNAs associated with aging in Nherf1-/- mice leading to increased protein levels of transcription factors NFATc2 and NFATC3, altered pathways in Wnt signaling and increases in cytokines IL-1β, IL-6, IL-17A, MCP1, and TNF- in mouse kidney.Hardesty JE, Warner JB, Wilkey DW, Phinney BS, Salemi MR, Merchant ML, McClain CJ, Warner DR, Kirpich IA. Hepatic Proteomic Changes Associated with Liver Injury Caused by Alcohol Consumption in Fpr2-/- Mice. Int J Mol Sci. 2024 Sep 11;25(18):9807. doi: 10.3390/ijms25189807. PMID: 39337294; PMCID: PMC11432144.
Impact Statement: This study reveals that FPR2 may regulate blood coagulation and antioxidant systems in alcohol-associated liver disease (ALD), with findings from a mouse model showing similarities to those in human patients with alcohol-associated hepatitis (AH). Proteomic analysis identified key pathways and protein alterations, suggesting potential therapeutic targets, though further research is needed for validation.Kalbfleisch TS, Smith ML, Ciosek JL, Li K, Doris PA. Three decades of rat genomics: approaching the finish(ed) line. Physiol Genomics. 2024 Sep 30. doi: 10.1152/physiolgenomics.00110.2024. Epub ahead of print. PMID: 39348459.
Impact Statement: We recently generated the new rat reference genome, named GRCr8, which is the most complete genome to date using a combination of long-read, single-molecule sequencing and optical mapping. This genome has resolved megabases of new content, specifically in repetitive, low complexity genomic regions such as the immune receptors and olfactory-associated genes. This paper highlights how this improved reference will support identifying pathogenic genomic variation in multiple models of disease that depend on rat models going forward.Zhu B, Gupta K, Cui K, Wang B, Malovichko MV, Han X, Li K, Wu H, Arulsamy KS, Singh B, Gao J, Wong S, Cowan DB, Wang D, Biddinger S, Srivastava S, Shi J, Chen K, Chen H. Targeting Liver Epsins Ameliorates Dyslipidemia in Atherosclerosis. bioRxiv [Preprint]. 2024 Aug 27:2024.08.26.609742. doi: 10.1101/2024.08.26.609742. PMID: 39253478; PMCID: PMC11383288.
Impact Statement: This study reveals that liver epsins play a pivotal role in promoting atherogenesis by mediating PCSK9-triggered degradation of LDL receptors, leading to elevated circulating LDL-C levels. Targeting liver epsins with siRNA-based therapies offers a promising approach to treating atherosclerosis by enhancing LDL-C clearance and inhibiting dyslipidemia.Price A, Simmons H, Gehring E, Davis L, Fischer G, Klipsch AR, Richmond E, Sullivan JE, Steiner SJ. Significant delays exist in industry-sponsored pediatric clinical drug trial start-up and enrollment processes. Contemp Clin Trials. 2024 Sep 24;146:107701. doi: 10.1016/j.cct.2024.107701. Epub ahead of print. PMID: 39326578.
Impact Statement: Many advances have been made in the last 20 years in pediatric therapeutics due to federal regulations and incentives to expedite pediatric drug development from the pre-term neonate to adolescents. However, significant barriers to advancing pediatric drug development continue despite the federal incentives. Twenty-four sites contributed data on 330 industry-sponsored pediatric drug studies. The average duration to final study budget approval was 121 (range 3-585) days, to final study Institutional Review Board (IRB) approval 51 (range 1-205) days, to Site Initiation Visit 204 (range 23-600) days, and to first patient consented 239 (range 30-534) days. There is an urgent need to improve how clinical trials are designed, implemented, and conducted to increase the number of approved therapeutic interventions for children. The delays and wide variation in all steps of the study process indicate multiple opportunities for improvement from the first contact with the site to the first patient being consented.- Yuan J, Mo Y, Zhang Y, Zhang Y, Zhang Q. HMGB1 derived from lung epithelial cells after cobalt nanoparticle exposure promotes the activation of lung fibroblasts. Nanotoxicology. 2024 Sep 19:1-17. doi: 10.1080/17435390.2024.2404074. Epub ahead of print. PMID: 39295432.
Impact Statement: In this publication, we demonstrated that exposure of human lung epithelial cells to cobalt nanoparticles (Nano-Co), rather than Nano-TiO2, caused a remarkable increase in the transcription, translation, and secretion of HMGB1 in a HIF-1α-dependent manner, which then promoted the activation of lung fibroblasts through RAGE-MAPKs pathway. These findings suggest a crucial role of HMGB1 in epithelial cell-fibroblast crosstalk in Nano-Co-induced pulmonary fibrosis, which may have important implications for understanding the pro-fibrotic potential of Nano-Co.
Poudel R, Li S, Hong H, Zhao J, Srivastava S, Robertson RM, Hall JL, Srivastava S, Hamburg NM, Bhatnagar A, Keith RJ. Catecholamine levels with use of electronic and combustible cigarettes. Tob Induc Dis. 2024 Aug 14;22. doi: 10.18332/tid/190687. PMID: 39144677; PMCID: PMC11320712.
Impact Statement: This study demonstrates that both e-cigarettes and combustible cigarettes significantly increase urinary catecholamine levels, indicating potential cardiovascular risks associated with their use. These findings suggest that catecholamines may serve as valuable biomarkers for assessing the harm caused by tobacco products, with implications for future regulatory research.Xin Y, Wang H, Cai L. Editorial: Cardiovascular diseases related to diabetes and obesity - volume IV. Front Endocrinol (Lausanne). 2024 Jul 18;15:1458742. doi: 10.3389/fendo.2024.1458742. PMID: 39092283; PMCID: PMC11291376.
Impact Statement: This editorial highlights new predictive indicators for obesity-related cardiovascular disease and diabetes complications, offering insights into early detection and intervention. The findings emphasize the need for continued research to validate these indicators and advance personalized treatment approaches for these chronic conditions.Cai L, Tan Y, Islam MS, Horowitz M, Wintergerst KA. Diabetic cardiomyopathy: Importance of direct evidence to support the roles of NOD-like receptor protein 3 inflammasome and pyroptosis. World J Diabetes. 2024 Aug 15;15(8):1659-1662. doi: 10.4239/wjd.v15.i8.1659. PMID: 39192865; PMCID: PMC11346090.
Impact Statement: This publication highlights the need for caution in interpreting the role of the NLRP3 inflammasome and pyroptosis in the development of diabetic cardiomyopathy (DCM), as current studies provide limited direct evidence. It calls for more comprehensive research to establish a clear causative link, which is crucial for developing effective treatments targeting these biomarkers.Haines D, Grell R, Huang J, Abrams B, Kertai MD. The Important Thing Is Not to Stop Questioning. Semin Cardiothorac Vasc Anesth. 2024 Aug 29:10892532241279627. doi: 10.1177/10892532241279627. Epub ahead of print. PMID: 39207841.
Impact Statement: Albert Einstein’s belief in the power of inquiry drives anesthesiologists worldwide to continuously enhance patient care through innovative practices and techniques. In this issue of Seminars in Cardiothoracic and Vascular Anesthesia, we delve into critical contemporary issues, showcasing advancements in pediatric cardiothoracic anesthesiology and highlighting the commitment to fostering a culture of intellectual curiosity that ultimately transforms patient outcomes.Carroll D, Kavalukas S. Management of Complications in Crohn's Disease. Adv Surg. 2024 Sep;58(1):19-34. doi: 10.1016/j.yasu.2024.04.002. Epub 2024 May 16. PMID: 39089776.
Impact Statement: This publication highlights that complications of Crohn's disease extend beyond traditional issues like surgical leaks and infections, emphasizing the critical roles of malnutrition and intestinal failure in patient management. It also discusses recent advancements in medical and surgical approaches, such as the Kono-S anastomosis and enhanced mesenteric resection techniques, which aim to improve outcomes and reduce the necessity for repeated surgeries.Thakurdesai A, Jha SK, Erinkitola I, Said A, Joshi T, Schwandt ML, Parajuli D, Singal AK, Kong M, Cave MC, Vatsalya V. The gut-immune-liver axis in patients with alcohol use disorder and clinically low serum zinc levels. Alcohol Clin Exp Res (Hoboken). 2024 Aug 2. doi: 10.1111/acer.15408. Epub ahead of print. PMID: 39095327.
Impact Statement: This study highlights the critical role of zinc deficiency in exacerbating gut-barrier dysfunction, immune response, and hepatocyte injury in alcohol use disorder (AUD) patients, with distinct differences between sexes. Findings suggest that zinc-deficient females may experience a shift from apoptosis to necrosis in liver cell death, signaling a progression of alcohol-associated liver disease (ALD).Gobejishvili L, McClain CJ. Back to phosphodiesterase inhibitors for liver disease: Are we ready for clinical trials? Hepatology. 2024 Aug 8. doi: 10.1097/HEP.0000000000001053. Epub ahead of print. PMID: 39116338.
Impact Statement: The study highlights the therapeutic potential of targeting PDE4 and PDE5 enzymes in liver diseases such as ALD and MASH, demonstrating benefits in preclinical models through reduced liver injury and metabolic improvements. These findings suggest that dual inhibition of PDE4B and PDE5A may offer an enhanced treatment approach, raising the question of readiness for clinical trials to explore this strategy in patients with liver disease.Chilton PM, Ghare SS, Charpentier BT, Myers SA, Rao AV, Petrosino JF, Hoffman KL, Greenwell JC, Tyagi N, Behera J, Wang Y, Sloan LJ, Zhang J, Shields CB, Cooper GE, Gobejishvili L, Whittemore SR, McClain CJ , Barve SS. Age-associated temporal decline in butyrate-producing bacteria plays a key pathogenic role in the onset and progression of neuropathology and memory deficits in 3×Tg-AD mice. Gut Microbes. 2024 Jan-Dec;16(1):2389319. doi: 10.1080/19490976.2024.2389319. Epub 2024 Aug 25. PMID: 39182227; PMCID: PMC11346541.
Impact Statement: This study demonstrates that age-related declines in butyrate-producing gut bacteria play a causal role in Alzheimer's disease (AD) progression, as shown by their impact on brain pathology and memory deficits in a mouse model. Oral administration of tributyrin, a butyrate prodrug, mitigated these declines, offering a promising therapeutic strategy for preventing or slowing AD.Shoctor NA, Brady MP, McLeish KR, Lightman RR, Davis-Johnson L, Lynn C, Dubbaka A, Tandon S, Daniels MW, Rane MJ , Barati MT, Caster DJ, Powell DW. Increased Urine Excretion of Neutrophil Granule Cargo in Active Proliferative Lupus Nephritis. Kidney360. 2024 Aug 1;5(8):1154-1166. doi: 10.34067/KID.0000000000000491. Epub 2024 Jul 2. PMID: 39207891; PMCID: PMC11371349.
Impact Statement: Neutrophil degranulation plays a crucial role in glomerular injury associated with proliferative lupus nephritis, highlighting the inflammatory processes at work. The detection of neutrophil granule proteins in urine presents a promising diagnostic marker for assessing glomerular inflammation in this condition.Alexander EM, Miller HA, Egger ME, Smith ML , Yaddanapudi K, Linder MW. The Correlation between Plasma Circulating Tumor DNA and Radiographic Tumor Burden. J Mol Diagn. 2024 Aug 22:S1525-1578(24)00179-X. doi: 10.1016/j.jmoldx.2024.07.001. Epub ahead of print. PMID: 39181324.
Impact Statement: Integrating plasma circulating tumor DNA (ctDNA) with conventional blood-based biomarkers and radiographic imaging can enhance precision medicine by addressing their individual limitations and improving the monitoring of malignant diseases. This approach emphasizes understanding tumor growth dynamics to better interpret ctDNA concentrations alongside traditional assessments, ultimately leading to more accurate evaluations of therapy response and tumor burden.Holm RH, Anderson LB, Ness HD, LaJoie AS, Smith T. Towards the outbreak tail, what is the public opinion about wastewater surveillance in the United States? J Water Health. 2024 Aug;22(8):1409-1418. doi: 10.2166/wh.2024.074. Epub 2024 Jul 5. PMID: 39212278.
Impact Statement: This study reveals that public support for wastewater surveillance remains robust, with over 90% endorsing its use for monitoring toxins and diseases, highlighting its potential as a vital public health tool. Despite varying levels of support for different surveillance applications, the findings indicate a strong public willingness to integrate wastewater-based epidemiology into broader health protection strategies.Thänert R, Schwartz DJ, Keen EC, Hall-Moore C, Wang B, Shaikh N, Ning J, Rouggly-Nickless LC, Thänert A, Ferreiro A, Fishbein SRS, Sullivan JE, Radmacher P, Escobedo M, Warner BB, Tarr PI, Dantas G. Clinical sequelae of gut microbiome development and disruption in hospitalized preterm infants. Cell Host Microbe. 2024 Aug 18:S1931-3128(24)00286-5. doi: 10.1016/j.chom.2024.07.027. Epub ahead of print. PMID: 39197454.
Impact Statement: This study reveals that preterm infants experience abnormal gut microbiota development, which is shaped by both antibiotic and non-antibiotic medications, leading to early-life health issues and long-term complications. Persistent low microbial diversity is linked to the development of necrotizing enterocolitis in neonates who develop necrotizing enterocolitis after day of life 40, highlighting the significant impact of medical interventions on microbiome composition in vulnerable neonates.Samala N, Kulkarni M, Lele RS, Gripshover TC, Wise JY, Rai SN, Cave MC . Associations between Per- and polyfluoroalkyl substance exposures and metabolic dysfunction associated steatotic liver disease (MASLD) in adult National Health and Nutrition Examination Survey 2017-2018. Toxicol Sci. 2024 Aug 16:kfae106. doi: 10.1093/toxsci/kfae106. Epub ahead of print. PMID: 39150893.
Impact Statement: This study assessed the relationship between PFAS exposures and biomarkers of metabolic dysfunction-associated steatotic liver disease (MASLD) in adults, using data from the NHANES 2017-2018 cohort. While some PFAS were linked to elevated liver enzyme levels, overall, the associations between PFAS and MASLD biomarkers were inconsistent, suggesting that PFAS may not pose a significant burden for liver disease in this population. More data are required to better understand the relationships between PFAS exposures and liver disease.Lin X, Chen C, Chen J, Zhu C, Zhang J, Su R, Chen S, Weng S, Chang X, Lin S, Chen Y, Li J, Lin L, Zhou J, Guo Z, Yu G, Shao W, Hu H, Wu S, Zhang Q, Li H, Zheng F. Long Noncoding RNA NR_030777 Alleviates Cobalt Nanoparticles-Induced Neurodegenerative Damage by Promoting Autophagosome-Lysosome Fusion. ACS Nano. 2024 Sep 10;18(36):24872-24897. doi: 10.1021/acsnano.4c05249. Epub 2024 Aug 28. PMID: 39197041; PMCID: PMC11394346.
Impact Statement: This study reveals that cobalt nanoparticles (CoNPs) cause significant neurodegenerative damage through autophagic dysfunction, leading to cognitive impairment and toxic protein accumulation. Importantly, the long noncoding RNA NR_030777 mitigates these effects by stabilizing the transcription factor EB (TFEB) mRNA, suggesting a potential therapeutic target for addressing CoNPs-induced CNS toxicity.
- Milanes JE, Yan VC, Pham CD, Muller F, Kwain S, Rees KC, Dominy BN, Whitehead DC, Millward SW, Bolejack M, Shek R, Tillery L, 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. PLoS Pathog. 2024 Aug 1;20(8):e1012412. doi: 10.1371/journal.ppat.1012412. PMID: 39088549; PMCID: PMC11321563.
Impact Statement: This study identifies (1-hydroxy-2-oxopiperidin-3-yl) phosphonic acid (HEX) as a potent inhibitor of Naegleria fowleri enolase, demonstrating its toxicity to pathogenic amoebae and potential to increase survival in infected rodent models. These findings highlight the need for further exploration of HEX as a promising therapeutic candidate for primary amoebic meningoencephalitis, a condition with a historically high mortality rate.
Jin L, Richardson A, Lynch J, Lorkiewicz P, Srivastava S, Fryar L, Miller A, Theis W, Shirk G, Bhatnagar A, Srivastava S, Riggs DW, Conklin DJ. Formaldehyde and the Transient Receptor Potential Ankyrin-1 Contribute to Electronic Cigarette Aerosol-induced Endothelial Dysfunction in Mice. Toxicol Sci. 2024 Jul 27:kfae096. doi: 10.1093/toxsci/kfae096. Epub ahead of print. PMID: 39067042.
Impact Statement: This study concludes that the use of Electronic cigarettes (E-cig) may increase cardiovascular disease risk due, in part, to the presence of formaldehyde – an abundant and reactive irritant in E-cig aerosols. Because the formaldehyde level in E-cig-derived aerosol was sufficient to induce vascular injury in mice, it should be lowered to reduce cardiovascular disease risk in people who use E-cig.Guo W, Zhong W, He L, Wei X, Hao L, Dong H, Yue R, Sun X, Yin X, Zhao J, Zhang X, Zhou Z. Reversal of hepatic accumulation of nordeoxycholic acid underlines the beneficial effects of cholestyramine on alcohol-associated liver disease in mice. Hepatol Commun. 2024 Jul 31;8(8):e0507. doi: 10.1097/HC9.0000000000000507. PMID: 39082957.
Impact Statement: This study demonstrated that sequestrant cholestyramine (CTM) treatment effectively reversed alcohol-induced liver injury in mice. The beneficial effects of bile acid sequestrant involve lowering toxic NorDCA levels. NorDCA not only worsens hepatic endoplasmic reticulum stress and inhibits autophagy but also mediates gut barrier disruption and systemic translocation of pathogen-associated molecular patterns in mice.Furmanek S, Salunkhe V, Pahwa S, Samanapally H, Nathala P, Xu Q, Han Y, Huang EC, Ali T, Deepti F, Glynn A, McGuffin T, Huang JJ, Farah I, Jones CM, Ramirez JA, Clifford SP, Arnold FW, Kong M, Roser L, Huang J. Association between echocardiographic features, troponin levels, and survival time in hospitalized COVID-19 patients with cardiovascular events. J Anesth Transl Med. 2024 Jun;3(2):36-44. doi: 10.1016/j.jatmed.2024.05.001. Epub 2024 May 8. PMID: 38993392; PMCID: PMC11238549.
Impact Statement: Significant associations between various echocardiographic parameters and troponin levels with reduced survival time among COVID-19 patients experiencing cardiovascular events. #Echo These findings highlight the potential utility of echocardiography and troponin assessment in predicting outcomes and guiding management strategies in this patient population.Moll V, Zhao M, Minear S, Swaminathan M, Kurz A, Huang J, Parr KG, Stanton K, Khanna AK; PREDICT AKI Group. Continuous Urine Output-Based Alert Identifies Cardiac Surgery-associated Acute Kidney Injury Earlier Than Serum Creatinine: A Prospective and Retrospective Observational Study. J Cardiothorac Vasc Anesth. 2024 Jun 19:S1053-0770(24)00396-3. doi: 10.1053/j.jvca.2024.06.021. Epub ahead of print. PMID: 39019742.
Impact Statement: Aute Kidney Injury Alert, based on continuous urine output and enabled by active drain line clearance, detected AKI stages 1 and 2 before serum creatine criteria. Early AKI detection allows for early kidney optimization, potentially improving patient outcomes.Moll V, Khanna AK, Kurz A, Huang J, Smit M, Swaminathan M, Minear S, Parr KG, Prabhakar A, Zhao M, Malbrain MLNG. Optimization of kidney function in cardiac surgery patients with intra-abdominal hypertension: expert opinion. Perioper Med (Lond). 2024 Jul 12;13(1):72. doi: 10.1186/s13741-024-00416-5. Erratum in: Perioper Med (Lond). 2024 Jul 29;13(1):85. doi: 10.1186/s13741-024-00444-1. PMID: 38997752; PMCID: PMC11245849.
Impact Statement: Cardiac surgery-associated acute kidney injury (#CSA-AKI) affects up to 42% of cardiac surgery patients. Abdominal perfusion pressure is calculated as mean arterial pressure minus #IntraAbdominalPressure (IAP). Current evidence on the pathophysiology, diagnosis, and therapy of IntraAbdominalPressure and abdominal compartment syndrome in the context of AKI.Majumder S, Pushpakumar SB, Almarshood H, Ouseph R, Gondim DD, Jala VR, Sen U. Toll-like receptor 4 mutation mitigates gut microbiota-mediated hypertensive kidney injury. Pharmacol Res. 2024 Aug;206:107303. doi: 10.1016/j.phrs.2024.107303. Epub 2024 Jul 11. PMID: 39002869; PMCID: PMC11287947.
Impact Statement: This study demonstrates that TLR4 plays a significant role in hypertension-induced gut dysbiosis, which contributes to renal inflammation and kidney dysfunction. Ablation of TLR4 attenuates these effects, reducing gut hyperpermeability, bacterial translocation, and preserving renal function in hypertensive conditions.Piell KM, Poulton CC, Stanley CG, Schultz DJ, Klinge CM. Integrated Metabolomics and Transcriptomics Analysis of Anacardic Acid Inhibition of Breast Cancer Cell Viability. Int J Mol Sci. 2024 Jun 27;25(13):7044. doi: 10.3390/ijms25137044. PMID: 39000156; PMCID: PMC11241071.
Impact Statement: We performed comprehensive, untargeted metabolomics analysis on six human breast cancer (BC) cell lines to identify the impact of the anti-cancer compound anacardic acid on metabolism. We identified key metabolic differences between control and AnAc-treated within each BC cell line and between MCF-7 estrogen receptor positive BC cells and the five triple negative BC (TNBC) cell lines as well as metabolic diversity among the four TNBC cell lines, reflecting TNBC heterogeneity. Integration of the transcriptome and metabolome data for MCF-7 and MDA-MB-231 BC cells key pathways involved in anti-cancer activity of anacardic acid. Our data suggest that anacardic acid differentially alters multiple pools of cellular building blocks, nutrients, and transcripts resulting in reduced BC cell viability.Patidar KR, Tu W, Cotter TG, Simonetto DA, Asgharpour A, Jan MY, Tang Q, Yu Y, Li Y, Taiwo M, Thevkar Nagesh P, Dasarathy S, Kamath PS, McClain CJ, Chalasani N, Szabo G, Bataller R, Mitchell M, Mehal WZ, Nagy LE, Shah VH, Gawrieh S, Sanyal AJ; AlcHepNet Investigators. Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone. Hepatology. 2024 Jul 19. doi: 10.1097/HEP.0000000000001019. Epub ahead of print. PMID: 39028887.
Impact Statement: This study reveals that patients with severe alcohol-associated hepatitis (sAH) treated with anakinra-plus-zinc (A+Z) experienced higher rates and severity of acute kidney injury (AKI) compared to those treated with prednisone. Elevated uNGAL levels in A+Z-treated patients with AKI suggest potential nephrotoxicity of A+Z in sAH patients.Xu M, Li M, Benz F, Merchant M, McClain CJ, Song M. Ileum Proteomics Identifies Distinct Pathways Associated with Different Dietary Doses of Copper-Fructose Interactions: Implications for the Gut-Liver Axis and MASLD. Nutrients. 2024 Jun 29;16(13):2083. doi: 10.3390/nu16132083. PMID: 38999831; PMCID: PMC11242941.
Impact Statement: This study identified specific pathways in the ileum that are altered by different dietary doses of copper and fructose, contributing to metabolic dysfunction-associated steatotic liver disease (MASLD) via the gut-liver axis. The proteomics analysis revealed distinct mechanisms, including oxidative phosphorylation, arachidonic acid metabolism, and tight junction regulation, that play a role in gut barrier dysfunction and MASLD development.Sayed K, Dolin CE, Wilkey DW, Li J, Sato T, Beier JI, Argemi J, Vatsalya V, McClain CJ, Bataller R, Wahed AS, Merchant ML, Benos PV, Arteel GE. A plasma peptidomic signature reveals extracellular matrix remodeling and predicts prognosis in alcohol-associated hepatitis. Hepatol Commun. 2024 Jul 31;8(8):e0510. doi: 10.1097/HC9.0000000000000510. PMID: 39082970.
Impact Statement: This study identified a plasma peptidome signature enriched with extracellular matrix fragments that serves as a novel, noninvasive predictor of 90-day mortality in patients with alcohol-associated hepatitis (AH). The findings offer improved accuracy over traditional models and present potential biomarkers for prognosis and new mechanistic insights into AH.Xu F, Ren Y, Teng Y, Mu J, Tang J, Sundaram K, Zhang L, Park JW, Hwang JY, Yan J, Dryden G, Zhang HG. Tryptophan As a New Member of RNA-Induced Silencing Complexes Prevents Colon Cancer Liver Metastasis. Adv Sci (Weinh). 2024 Jun 20:e2307937. doi: 10.1002/advs.202307937. Epub ahead of print. PMID: 39031551.
Impact Statement: By uncovering the critical role of tryptophan in regulating microRNA activity, this study offers a new therapeutic approach for targeting and inhibiting cancer metastasis. This could pave the path to improved prognosis for patients with colon cancer and other aggressive malignancies.Zaman F, Smith ML, Balagopal A, Durand CM, Redd AD, Tobian AAR. Spatial technologies to evaluate the HIV-1 reservoir and its microenvironment in the lymph node. mBio. 2024 Jul 26:e0190924. doi: 10.1128/mbio.01909-24. Epub ahead of print. PMID: 39058091.
Impact Statement: This study highlights the role of memory T follicular helper cells within the immune-privileged environment of the B cell follicle in harboring the HIV-1 reservoir, which contributes to viral rebound upon ART discontinuation. A spatiotemporal approach integrating genomics, transcriptomics, and proteomics to investigate these reservoir cells and their interactions holds promise for advancing HIV-1 cure strategies.Wise JP Jr, Wise RM, Hoffert A, Wise JTF, Specht AJ. Elevated Metal Levels in U.S. Honeys: Is There a Concern for Human Health? Biol Trace Elem Res. 2024 Jul 12. doi: 10.1007/s12011-024-04295-1. Epub ahead of print. PMID: 38995435.
Impact Statement: Metal contamination in honey has been reported worldwide but has largely been overlooked in the U.S. - our data addresses this knowledge gap and suggests there is a concern for high levels of lead and mercury, based on regulations set by the European Union. Currently the U.S. does not have any regulations for metal contamination in honey, we hope these data will help inform risk assessors and legislators to finally develop appropriate regulations and regular monitoring of honey.Zhang Y, Zhang Z, Mo Y, Zhang Y, Yuan J, Zhang Q. MMP-3 mediates copper oxide nanoparticle-induced pulmonary inflammation and fibrosis. J Nanobiotechnology. 2024 Jul 19;22(1):428. doi: 10.1186/s12951-024-02707-x. PMID: 39030581; PMCID: PMC11264740.
Impact Statement: This study demonstrated that short-term Nano-CuO exposure caused acute lung inflammation and injury, while long-term exposure induced chronic pulmonary inflammation and fibrosis. Knocking down MMP-3 significantly ameliorated Nano-CuO-induced pulmonary inflammation, injury, and fibrosis, and also attenuated Nano-CuO-induced cleaved osteopontin (OPN) level. Our study suggests that MMP-3 may play important roles in Nano-CuO-induced pulmonary inflammation and fibrosis via cleavage of OPN, which may provide a further understanding of the mechanisms underlying Nano-CuO-induced pulmonary toxicity.Mo Y, Zhang Y, Zhang Q. The pulmonary effects of nickel-containing nanoparticles: Cytotoxicity, genotoxicity, carcinogenicity, and their underlying mechanisms. Environ Sci Nano. 2024 May 1;11(5):1817-1846. doi: 10.1039/d3en00929g. Epub 2024 Mar 21. PMID: 38984270; PMCID: PMC11230653.
Impact Statement: Nickel-containing nanoparticles (NPs) have been increasingly used in industrial and biomedical fields due to their unique nanostructural and physicochemical properties; thus, the risk of occupational and environmental contamination by Ni-containing NPs is increasing. The respiratory system is a major and common point of contact for Ni-containing NPs; therefore, they may cause adverse health effects on the respiratory tract, especially the lungs. This review provides us with a comprehensive view of the pulmonary effects of Ni-containing NPs and their underlying mechanisms, which will shed light on our future studies including the urgency and necessity to produce engineered Ni-containing NPs with controlled and reduced toxicity, and also will provide a scientific basis for developing nanoparticle exposure limits and policies.Fruh V, Babalola T, Sears C, Wellenius GA, Webster TF, Mann KK, Harrington J, Tjønneland A, Raaschou-Nielsen O, Claus Henn B, Meliker JR. Dietary Minerals and Incident Cardiovascular Outcomes among Never-Smokers in a Danish Case-Cohort Study. Int J Environ Res Public Health. 2024 Jul 17;21(7):932. doi: 10.3390/ijerph21070932. PMID: 39063508; PMCID: PMC11277515.
Chen J, Li F, Lee J, Manirujjaman M, Zhang L, Song ZH, McClain C, Feng W. Peripherally Restricted CB1 Receptor Inverse Agonist JD5037 Treatment Exacerbates Liver Injury in MDR2-Deficient Mice. Cells. 2024 Jun 25;13(13):1101. doi: 10.3390/cells13131101. PMID: 38994954; PMCID: PMC11240654.
Sagheer U, Al-Kindi S, Abohashem S, Phillips CT, Rana JS, Bhatnagar A, Gulati M, Rajagopalan S, Kalra DK. Environmental Pollution and Cardiovascular Disease: Part 1 of 2: Air Pollution. JACC Adv. 2023 Dec 28;3(2):100805. doi: 10.1016/j.jacadv.2023.100805. PMID: 38939391; PMCID: PMC11198409.
Impact Statement: This publication sheds light on the crucial link between air pollution and cardiovascular disease (CVD), emphasizing that despite progress in high-income countries, CVD remains a pressing issue in low- to middle-income countries due to environmental factors. By detailing the pathophysiological mechanisms and offering strategies to mitigate pollution, this review underscores the need for targeted interventions to address the ongoing global burden of CVD.Sagheer U, Al-Kindi S, Abohashem S, Phillips CT, Rana JS, Bhatnagar A, Gulati M, Rajagopalan S, Kalra DK. Environmental Pollution and Cardiovascular Disease: Part 2 of 2: Soil, Water, and Other Forms of Pollution. JACC Adv. 2024 Jan 4;3(2):100815. doi: 10.1016/j.jacadv.2023.100815. PMID: 38939394; PMCID: PMC11198458.
Impact Statement: This review highlights the significant link between environmental pollution and cardiovascular disease (CVD), emphasizing the urgent need for improved understanding and action. By detailing major pollutants, their impact on CVD, and strategies for risk reduction, the article aims to raise awareness and drive proactive measures across healthcare, science, and policy.Cai L. Invited Perspective: New Insight into Cadmium-Related Osteoporosis Yields Hope for Prevention and Therapy. Environ Health Perspect. 2024 Jun;132(6):61301. doi: 10.1289/EHP15263. Epub 2024 Jun 19. PMID: 38896781; PMCID: PMC11218703.
Impact Statement: In the Jun issue of Environmental Health Perspectives, a mechanistic mouse study on cadmium (Cd)-induced osteoporosis has proposed a hypothesis that nuclear factor erythroid 2-related factor 2 (NRF2) and its Cap ‘n’ Collar and basic region Leucine Zipper (CNC-bZIP) family member nuclear factor erythroid 2-related factor 1 (NRF1) coordinate osteoclastogenesis during Cd exposure, for which I had a brief commentary to shed some new insights into cadmium-related osteoporosis, providing hope for its prevention and therapy.Wise JTF, Hein DW. N-Acetyltransferase Metabolism and DNA Damage Following Exposure to 4,4'-Oxydianiline in Human Bronchial Epithelial Cells. Toxicol Lett. 2024 Jun 19:S0378-4274(24)00129-2. doi: 10.1016/j.toxlet.2024.06.005. Epub ahead of print. PMID: 38906436.
Impact Statement: Waterpipe smoking is increasingly popular and understanding how chemicals found in hookah smoke may be harmful to human bronchial epithelial cells is of great importance. The publication shows that 4,4’-oxydianiline, the most prevalent aromatic amine identified in hookah smoke, is N-acetylated and induces DNA damage in human bronchial epithelial cells.Walls KM, Joh JY, Hong KU, Hein DW. Heterocyclic Amines Disrupt Lipid Homeostasis in Cryopreserved Human Hepatocytes. Cardiovasc Toxicol. 2024 Jun 8. doi: 10.1007/s12012-024-09874-1. Epub ahead of print. PMID: 38851663.
Impact Statement: Heterocyclic amines (HCAs) are mutagens generated when cooking meat at high temperatures or until well-done. Recent epidemiological studies reported that dietary HCA exposure may be linked to insulin resistance and type II diabetes. The publication shows that HCAs dysregulate lipid production, metabolism, and storage. HCA exposure may lead to fat accumulation in hepatocytes, which may contribute to hepatic insulin resistance and MASH.El Tahan MM, Cheng DC, Szegedi L, Mellin-Olsen J, Zdravkovic M, Lineburger EB, Filipescu D, Tritapepe L, Guarracino F, Neto CN, Garcia PC, Ángel Rodenas Monteagudo M, Granell MG, Guillén RV, Gaudard P, Abdulmomen A, Eldawlatly AA, Bubenek-Turconi SI, Stoica R, Licker M, Erdoes G, Mauermann E, Kirov M, Lomivorotov V, Saldien V, Momeni M, Huang J. A Multi-Country Survey on the Availability of Intraoperative Use of Echocardiography for Noncardiac Surgery. Semin Cardiothorac Vasc Anesth. 2024 Jun 6:10892532241256020. doi: 10.1177/10892532241256020. Epub ahead of print. PMID: 38842145.
Impact Statement: Echocardiography machines and skilled echocardiographers are still unavailable at many centers worldwide. National societies should aim to train a critical mass of certified TEE/TTE anesthesiologists and provide all anesthesiologists access to perioperative TEE/TTE machines in anesthesiology departments.Tang F, Han H, Fu S, Liu Q, Zhou S, Huang J, Xiao Y. Nonpharmacological Approaches to Managing Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2024 Jun 18:e011269. doi: 10.1161/CIRCHEARTFAILURE.123.011269. Epub ahead of print. PMID: 38887946.
Impact Statement: Nonpharmacological interventions hold promise for advancing heartfailure with preserved ejection fraction patient care and fostering a deeper understanding of these treatment approaches, which will facilitate new clinical applications and contribute to the development of more targeted therapies.Xie Z, Morris JD, Pan J, Cooke EA, Sutaria SR, Balcom D, Marimuthu S, Parrish LW, Aliesky H, Huang JJ, Rai SN, Arnold FW, Huang J, Nantz MH, Fu XA. Detection of COVID-19 by quantitative analysis of carbonyl compounds in exhaled breath. Sci Rep. 2024 Jun 24;14(1):14568. doi: 10.1038/s41598-024-61735-7. PMID: 38914586; PMCID: PMC11196736.
Impact Statement: This study demonstrates the efficacy of breath analysis in detecting COVID-19, showcasing high accuracy, sensitivity, and specificity for identifying infected patients and distinguishing between SARS-CoV-2 variants. Utilizing a microfabricated silicon microreactor and UHPLC-MS, this non-invasive method holds significant promise for rapid screening and early detection of COVID-19 and potentially other infectious respiratory diseases.Tomlinson MM, Pugh F, Nail AN, Newton JD, Udoh K, Abraham S, Kavalukas S, Guinn B, Tamimi RM, Laden F, Iyer HS, States JC, Ruther M, Ellis CT, DuPré NC. Heavy-metal associated breast cancer and colorectal cancer hot spots and their demographic and socioeconomic characteristics. Cancer Causes Control. 2024 Jun 25. doi: 10.1007/s10552-024-01894-0. Epub ahead of print. PMID: 38916703.
Impact Statement: This study reports an association between ambient carcinogenic metal exposures and the likelihood of residing in breast and colorectal cancer hotspots in Kentucky. It highlights that further epidemiologic research on environmental carcinogens and common cancers is needed that may play a role in observed cancer disparities due to environmental injustices.Gobejishvili L, Vatsalya V, Avila DV, Feygin YB, McClain CJ, Mokshagundam S, Barve S. Association of Circulating Markers of Microbial Translocation and Hepatic Inflammation with Liver Injury in Patients with Type 2 Diabetes. Biomedicines. 2024 May 31;12(6):1227. doi: 10.3390/biomedicines12061227. PMID: 38927434; PMCID: PMC11200675.
Impact Statement: This study reveals that increased microbial translocation and systemic inflammation are significant factors contributing to liver injury in patients with type 2 diabetes mellitus (T2DM), as evidenced by elevated serum markers of inflammation and hepatocyte death. The findings highlight the potential role of gut-liver axis disturbances in the pathogenesis of liver disease associated with T2DM, underscoring the need for further research to validate these observations and explore their clinical implications.Sears L, Smith MJ, Cai L, Zierold KM. The association of manganese overexposure and neurobehavioral function is moderated by arsenic: A metal mixture analysis of children living near coal ash storage sites. Neurotoxicology. 2024 Jun 11;103:78-86. doi: 10.1016/j.neuro.2024.06.005. Epub ahead of print. PMID: 38871300.
Impact Statement: This study investigated the effects of multiple heavy metal exposures on children and found that the known neurobehavioral problems associated with manganese overexposure are moderated by arsenic co-exposures. Findings provide a better understanding of the effects of multiple heavy metal exposures on child development.Pardo-Palacios FJ, Wang D, Reese F, Diekhans M, Carbonell-Sala S, Williams B, Loveland JE, De María M, Adams MS, Balderrama-Gutierrez G, Behera AK, Gonzalez Martinez JM, Hunt T, Lagarde J, Liang CE, Li H, Meade MJ, Moraga Amador DA, Prjibelski AD, Birol I, Bostan H, Brooks AM, Çelik MH, Chen Y, Du MRM, Felton C, Göke J, Hafezqorani S, Herwig R, Kawaji H, Lee J, Li JL, Lienhard M, Mikheenko A, Mulligan D, Nip KM, Pertea M, Ritchie ME, Sim AD, Tang AD, Wan YK, Wang C, Wong BY, Yang C, Barnes I, Berry AE, Capella-Gutierrez S, Cousineau A, Dhillon N, Fernandez-Gonzalez JM, Ferrández-Peral L, Garcia-Reyero N, Götz S, Hernández-Ferrer C, Kondratova L, Liu T, Martinez-Martin A, Menor C, Mestre-Tomás J, Mudge JM, Panayotova NG, Paniagua A, Repchevsky D, Ren X, Rouchka E, Saint-John B, Sapena E, Sheynkman L, Smith ML, Suner MM, Takahashi H, Youngworth IA, Carninci P, Denslow ND, Guigó R, Hunter ME, Maehr R, Shen Y, Tilgner HU, Wold BJ, Vollmers C, Frankish A, Au KF, Sheynkman GM, Mortazavi A, Conesa A, Brooks AN. Systematic assessment of long-read RNA-seq methods for transcript identification and quantification. Nat Methods. 2024 Jun 7. doi: 10.1038/s41592-024-02298-3. Epub ahead of print. PMID: 38849569.
Impact Statement: This publication establishes a benchmark for long-read RNA sequencing by demonstrating that longer, more accurate sequences enhance transcript detection and characterization, while greater read depth improves quantification accuracy. It provides valuable guidance for improving transcriptome analysis methods and suggests incorporating additional data for better detection of rare and novel transcripts.Engelbrecht E, Rodriguez OL, Shields K, Schultze S, Tieri D, Jana U, Yaari G, Lees WD, Smith ML, Watson CT. Resolving haplotype variation and complex genetic architecture in the human immunoglobulin kappa chain locus in individuals of diverse ancestry. Genes Immun. 2024 Jun 6. doi: 10.1038/s41435-024-00279-2. Epub ahead of print. PMID: 38844673.
Impact Statement: This study presents the first comprehensive haplotype-resolved assemblies of the IGK locus across a diverse cohort, revealing extensive genetic variation including novel single nucleotide and structural variants. These findings offer a crucial genomic reference, enhancing our understanding of population-specific variations and their functional implications in immunoglobulin genetics.Han D, Linares P, Holm RH, Chandran K, Smith T. Wastewater threshold as an indicator of COVID-19 cases in correctional facilities for public health response: A modeling study. Water Res. 2024 Jun 12;260:121934. doi: 10.1016/j.watres.2024.121934. Epub ahead of print. PMID: 38908309.
Impact Statement: This study is the first national program to derive a robust facility-specific model for predicting COVID-19 cases in prisons using only wastewater viral concentrations. This is the first research model put into practice in correctional health setting derived from data from that setting.Yeager R,, Keith RJ, Riggs DW, Fleischer D, Browning MHEM, Ossola A, Walker KL, Hart JL, , Srivastava S,, Rai SN, Smith T, Bhatnagar A,. Intra-neighborhood associations between residential greenness and blood pressure. Sci Total Environ. 2024 Jun 18;946:173788. doi: 10.1016/j.scitotenv.2024.173788. Epub ahead of print. PMID: 38901580.
Impact Statement: This study found that higher leaf surface area around homes is significantly associated with lower systolic blood pressure, especially within 150-250 meters and 500 meters of residences, but there was little association with grass cover. The effects of greenness on blood pressure varied with participant characteristics, highlighting the need for further research to understand causative links and to inform targeted greening interventions.Lu H, Wise SS, Speer RM, Croom-Perez TJ, Toyoda JH, Meaza I, Williams A, Pierce Wise J Jr, Kouokam JC, Young Wise J, Hoyle G, Zhu C, Ali AM, Pierce Wise J Sr. Acute particulate hexavalent chromium exposure induces DNA double strand breaks and activates homologous recombination repair in rat lung tissue. Toxicol Sci. 2024 Jun 12:kfae076. doi: 10.1093/toxsci/kfae076. Epub ahead of print. PMID: 38867691.
Impact Statement:This study demonstrates that acute exposure to hexavalent chromium (Cr(VI)) induces DNA double-strand breaks and activates homologous recombination repair in rat lungs, mirroring findings from cell culture studies. The research confirms that chromosome instability, a key feature of lung cancer, is driven by Cr(VI)-induced DNA damage and repair processes, with female rats showing greater susceptibility than males.- Vielee ST, Isibor J, Buchanan WJ, Roof SH, Patel M, Meaza I, Williams A, Toyoda JH, Lu H, Wise SS, Kouokam JC, Young Wise J, Abouiessa AM, Cai J, Cai L, Wise JP Jr. Employing a Toxic Aging Coin approach to assess hexavalent chromium (Cr[VI])-induced neurotoxic effects on behavior: Heads for age differences. Toxicol Appl Pharmacol. 2024 Jun 18;489:117007. doi: 10.1016/j.taap.2024.117007. Epub ahead of print. PMID: 38901695.
Impact Statement: This study reveals that exposure to hexavalent chromium (Cr(VI)) at the World Health Organization and the U.S. Environmental Protection Agency maximum contaminant levels (0.05 and 0.1 mg/L, respectively) significantly impairs behavior in adult rats, particularly affecting memory. These findings highlight the urgent need for age-inclusive toxicology research and suggest revisiting current Cr(VI) drinking water regulations to better protect human health.
Shrader SH, Mellen N, Cai J, Barnes GN, Song ZH. Cannabidiol is a behavioral modulator in BTBR mouse model of idiopathic autism. Front Neurosci. 2024 May 9;18:1359810. doi: 10.3389/fnins.2024.1359810. PMID: 38784096; PMCID: PMC11112039.
Impact Statement: This study demonstrates that cannabidiol (CBD) treatment effectively reduces repetitive behaviors and hyperactivity, and improves social deficits in an established mouse model of idiopathic autism. These findings highlight CBD's potential as a therapeutic option for addressing core and comorbid symptoms of Autism Spectrum Disorder (ASD).Vemuri V, Kratholm N, Nagarajan D, Cathey D, Abdelbaset-Ismail A, Tan Y, Straughn A, Cai L, Huang J, Kakar SS. Withaferin A as a Potential Therapeutic Target for the Treatment of Angiotensin II-Induced Cardiac Cachexia. Cells. 2024 May 3;13(9):783. doi: 10.3390/cells13090783. PMID: 38727319; PMCID: PMC11083229.
Impact Statement: Withaferin A ameliorates the cardiac dysfunction induced by Angiotensin II, suggesting that it could be an anticachectic agent that induces direct effects on cardiac muscles.Thakurdesai A, Rivera-Matos L, Nagra N, Busch B, Mais DD, Cave MC. Severe Drug-Induced Liver Injury Due to Self-administration of the Veterinary Anthelmintic Medication, Fenbendazole. ACG Case Rep J. 2024 May 2;11(5):e01354. doi: 10.14309/crj.0000000000001354. PMID: 38706451; PMCID: PMC11068125.
Impact Statement: The increasing off-label use of fenbendazole in humans, driven by social media claims of anticancer benefits, presents significant safety concerns, as evidenced by a case of severe drug-induced liver injury in a 67-year-old woman. This case highlights the urgent need for awareness and regulation to prevent potentially harmful self-medication practices.Liu H, Su P, Li Y, Hoover A, Hu S, King SA, Zhao J, Guan JL, Chen SY, Zhao Y, Tan M, Wu X. VAMP2 controls murine epidermal differentiation and carcinogenesis by regulation of nucleophagy. Dev Cell. 2024 May 22:S1534-5807(24)00321-6. doi: 10.1016/j.devcel.2024.05.004. Epub ahead of print. PMID: 38810653.
Impact Statement: This paper elucidates key molecular mechanisms involved in epidermal differentiation and identifies critical factors that mediate skin diseases and cancers, providing potential new targets for therapeutic interventions for skin disorders and skin cancer.Jin A, DuPré N, Holm R, Smith T, Kavalukas S. Environmental Levels of Volatile Organic Compounds, Race, and Socioeconomic Markers Correlate with Areas of High Colorectal Cancer Incidence. J Racial Ethn Health Disparities. 2024 May 16. doi: 10.1007/s40615-024-02030-z. Epub ahead of print. PMID: 38755478.
Impact Statement: This study highlights a significant correlation between elevated ambient VOC levels and increased colorectal cancer rates, particularly in socioeconomically disadvantaged communities. The findings emphasize the need to address environmental and socioeconomic factors in public health strategies to reduce health disparities and colorectal cancer incidence.Adhihetty PK, Halder S, Abu UO, Fu XA, Nantz MH. Cesium ion-guided detection of trichloroethylene in air. Talanta. 2024 May 1;276:126197. doi: 10.1016/j.talanta.2024.126197. Epub ahead of print. PMID: 38728800.
Impact Statement: This study introduces a novel approach using cesium-functionalized gold clusters to develop a highly selective sensor for trichloroethylene (TCE) and related volatile organic compounds (VOCs), showcasing unprecedented sensitivity down to 0.1 ppm. The sensor's efficacy hinges on the unique bidentate coordination of 1,2-dichloro groups with cesium cations, underscoring its potential for precise environmental monitoring applications.Long GA, Xu Q, Sunkara J, Woodbury R, Brown K, Huang JJ, Xie Z, Chen X, Fu XA, Huang J. A comprehensive meta-analysis and systematic review of breath analysis in detection of COVID-19 through Volatile organic compounds. Diagn Microbiol Infect Dis. 2024 Jul;109(3):116309. doi: 10.1016/j.diagmicrobio.2024.116309. Epub 2024 Apr 27. PMID: 38692202.
Impact Statement: Breath analysis is a promising detection tool for COVID-19 infection.Ward J, Hardin-Fanning F, LaJoie AS, Harris L,, Simpson A. Outdoor workers' perceptions of skin cancer prevention: a qualitative study. Ann Work Expo Health. 2024 May 14:wxae039. doi: 10.1093/annweh/wxae039. Epub ahead of print. PMID: 38742833.
Impact Statement: This study highlights the crucial role of trusted local healthcare providers and community testimonials in promoting primary and secondary skin cancer prevention among outdoor workers. Emphasizing secondary prevention strategies and fostering self-efficacy in conducting skin self-examinations are essential to effectively reduce skin cancer incidence in this high-risk population.Fulghum KL, Collins HE, Lorkiewicz PK, Cassel TA, Fan TWM, Hill BG. Exercise-induced changes in myocardial glucose utilization during periods of active cardiac growth. J Mol Cell Cardiol. 2024 Jun;191:50-62. doi: 10.1016/j.yjmcc.2024.04.014. Epub 2024 May 3. PMID: 38703412; PMCID: PMC11135805.
Impact Statement: This paper addresses how metabolism contributes to adaptation of the heart to exercise and shows in mice that metabolic remodeling precedes development of “athlete’s heart”.Antimisiaris D, Folz RJ, Huntington-Moskos L, Polivka BJ. Specific Medication Literacy in Older Adults with Asthma. J Nurse Pract. 2024 May;20(5):104979. doi: 10.1016/j.nurpra.2024.104979. Epub 2024 Mar 27. PMID: 38706630; PMCID: PMC11064973.
Impact Statement: The study highlights significant gaps in specific medication literacy (SML) among older adults, particularly in understanding side effects and drug interactions, which can impact their ability to self-monitor effectively. Findings suggest that targeted educational interventions are needed, especially for those diagnosed with asthma at a younger age and those living in disadvantaged neighborhoods.Roser LP, Samanapally H, Ali T, Xu Q, Han Y, Salunkhe V, Deepti F, McGuffin T, Huang EC, Furmanek S, Glynn A, Ramirez J, Jones CM, Mariyappa R, Hogue RJ, Williams AM, Huang JJ, Arnold FW, Clifford SP, Pahwa S, Kong M, Huang J. Different clinical characteristics and outcomes of adult hospitalized SARS-CoV-2 pneumonia patients complicated by cardiovascular events during the first, delta and omicron waves of COVID-19. Front Epidemiol. 2024 Apr 18;4:1342917. doi: 10.3389/fepid.2024.1342917. PMID: 38699405; PMCID: PMC11064795.
Impact Statement: Omicron patients with cardiovascular events showed lower heart injuries, lower mortality and longer time to mortality for non-survivors when compared to the first and delta waves.Ghooray DT, Xu M, Shi H, McClain CJ, Song M. Hepatocyte-Specific Fads1 Overexpression Attenuates Western Diet-Induced Metabolic Phenotypes in a Rat Model. Int J Mol Sci. 2024 Apr 29;25(9):4836. doi: 10.3390/ijms25094836. PMID: 38732052; PMCID: PMC11084797.
Impact Statement: The study demonstrates that adeno-associated virus serotype 8 (AAV8)-mediated hepatocyte-specific overexpression of Fads1 significantly improves glucose tolerance and insulin signaling in rats on a low-fat high-fructose diet, and reduces plasma triglycerides and hepatic cholesterol levels in rats on a high-fat high-fructose diet. These findings highlight FADS1 as a promising therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD) in a diet-dependent manner.Navarro-Corcuera A, Zhu Y, Ma F, Gupta N, Asplund H, Yuan F, Friedman S, Sansbury BE, Huang X, Cai B. Therapeutic Activity of Resolvin D1 (RvD1) in Murine MASH. bioRxiv [Preprint]. 2024 Apr 26:2024.04.22.590633. doi: 10.1101/2024.04.22.590633. PMID: 38712196; PMCID: PMC11071427.
Impact Statement: Administering resolvin D1 (RvD1) demonstrates significant therapeutic potential by reducing inflammation, preventing hepatocyte death, and promoting fibrosis regression in metabolic dysfunction-associated steatohepatitis (MASH). These effects are mediated through suppression of the Stat1-Cxcl10 signaling pathway, alleviation of ER stress-induced apoptosis, and modulation of MMP expression, underscoring RvD1's multifaceted role in ameliorating MASH progression.Steichen JM, Phung I, Salcedo E, Ozorowski G, Willis JR, Baboo S, Liguori A, Cottrell CA, Torres JL, Madden PJ, Ma KM, Sutton HJ, Lee JH, Kalyuzhniy O, Allen JD, Rodriguez OL, Adachi Y, Mullen TM, Georgeson E, Kubitz M, Burns A, Barman S, Mopuri R, Metz A, Altheide TK, Diedrich JK, Saha S, Shields K, Schultze SE, Smith ML, Schiffner T, Burton DR, Watson CT, Bosinger SE, Crispin M, Yates JR 3rd, Paulson JC, Ward AB, Sok D, Crotty S, Schief WR. Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates. Science. 2024 May 17;384(6697):eadj8321. doi: 10.1126/science.adj8321. Epub 2024 May 17. PMID: 38753769.
Impact Statement: This study demonstrates the successful priming of broadly neutralizing antibody (bnAb) precursor B cells using the germline-targeting immunogen N332-GT5 in rhesus macaques, marking a significant advance in HIV vaccine development. The findings highlight the potential of N332-GT5 to induce bnAb-precursor responses in humans, offering a promising avenue for future immunogen design and vaccine strategies.- Schiffner T, Phung I, Ray R, Irimia A, Tian M, Swanson O, Lee JH, Lee CD, Marina-Zárate E, Cho SY, Huang J, Ozorowski G, Skog PD, Serra AM, Rantalainen K, Allen JD, Baboo S, Rodriguez OL, Himansu S, Zhou J, Hurtado J, Flynn CT, McKenney K, Havenar-Daughton C, Saha S, Shields K, Schulze S, Smith ML, Liang CH, Toy L, Pecetta S, Lin YC, Willis JR, Sesterhenn F, Kulp DW, Hu X, Cottrell CA, Zhou X, Ruiz J, Wang X, Nair U, Kirsch KH, Cheng HL, Davis J, Kalyuzhniy O, Liguori A, Diedrich JK, Ngo JT, Lewis V, Phelps N, Tingle RD, Spencer S, Georgeson E, Adachi Y, Kubitz M, Eskandarzadeh S, Elsliger MA, Amara RR, Landais E, Briney B, Burton DR, Carnathan DG, Silvestri G, Watson CT, Yates JR 3rd, Paulson JC, Crispin M, Grigoryan G, Ward AB, Sok D, Alt FW, Wilson IA, Batista FD, Crotty S, Schief WR. Vaccination induces broadly neutralizing antibody precursors to HIV gp41. Nat Immunol. 2024 Jun;25(6):1073-1082. doi: 10.1038/s41590-024-01833-w. Epub 2024 May 30. PMID: 38816615; PMCID: PMC11147780.
Impact Statement: The development of germline-targeting epitope scaffold nanoparticles has overcome a significant barrier in vaccine design by successfully inducing rare broadly neutralizing antibody (bnAb)-precursor B cells with specific binding motifs in both stringent animal models and ex vivo human screens. This advancement paves the way for creating effective vaccines against HIV and other viruses with high antigenic diversity, targeting the elusive 10E8-class bnAbs.
Keith RJ, Hart JL, Bhatnagar A. Greenspaces And Cardiovascular Health. Circ Res. 2024 Apr 26;134(9):1179-1196. doi: 10.1161/CIRCRESAHA.124.323583. Epub 2024 Apr 25. PMID: 38662868.
Impact Statement: Living in areas with high surrounding greenness is associated with improved cardiovascular health and lower risk of mortality, thanks to the environmental, social, psychological, and physiological benefits of greenspaces. This narrative review synthesizes evidence on the positive effects of greenspaces on cardiovascular disease risk factors and highlights the need for further research to fully harness their potential for public health and climate change mitigation.Dunlap NE, Friedland RP, Cai L. Alzheimer's disease and low-dose radiation therapy: A new hope. Radiat Med Prot. 2024 Mar;5(1):1-6. doi: 10.1016/j.radmp.2024.01.002. Epub 2024 Feb 7. PMID: 38585336; PMCID: PMC10997373.
Impact Statement: Potential therapeutic application of low-dose radiation (LDR) for Alzheimer’s diseases (AD) has been explored since 2017, for which, a new Systematic Review based on available preclinical and clinical studies was published as milestone recently. Therefore, this mini-review provides a concise historical introduction for this research field and narrative discussion of AD radiotherapy as the new hope for the patients with AD.Horowitz M, Cai L, Islam MS. Glucagon-like-peptide-1 receptor agonists and the management of type 2 diabetes-backwards and forwards. World J Diabetes. 2024 Mar 15;15(3):326-330. doi: 10.4239/wjd.v15.i3.326. PMID: 38591090; PMCID: PMC10999054.
Impact Statement: As Editors-in-Chief of the journal, World Journal of Diabetes (WJD), the authors have highlighted the work by Alqifari et al published in the journal of WJD (2024), focusing on practical advice for the clinical use of glucagon-like-peptide-1 (GLP-1) receptor agonists (GLP-1RAs) in the management of type 2 diabetes by providing complementary information. This includes a brief historical perspective of the development of GLP-1RAs stimulated by recognition of the 'incretin effect', the substantially greater insulin increase to enteral when compared to euglycaemic intravenous glucose, the identification of the incretin hormones, GIP and GLP-1, and a final reminder for more information relating to the effects of GLP-1RAs to induce gastrointestinal symptoms and slow gastric emptying likely to allow their use to become more effective and personalized.Cai L. Perspective of Dose-Response: New Chapter With New "Exposome" and "-omics". Dose Response. 2024 Apr 25;22(2):15593258241248775. doi: 10.1177/15593258241248775. PMID: 38680850; PMCID: PMC11047227.
Impact Statement: This is an editorial from me as the new editor-in-chief (EIC) of the journal, Dose-Response, starting in March 2024. This editorial addressed the introduction of the concepts of "Exposome" and associated "Exposomics" into the toxicology research, therefore, the mission of "DR" will incorporate with these new concepts as the next chapter's principle and strategies, even though it remains adhered to the original goals. The EIC wish this journal can open a door for various discipline scientists and researchers to share their state-of-the-art discoveries to shed new insight to understand the impact of environmental and toxicological medicine and develop more specific and effective intervention strategies.Yang JY, Mondéjar-Parreño G, Jahng JWS, Lu Y, Hamburg N, Nadeau KC, Conklin DJ, Liao R, Chandy M, Wu JC. Elucidating effects of the environmental pollutant benzo[a]pyrene [BaP] on cardiac arrhythmogenicity. J Mol Cell Cardiol. 2024 Apr 20;191:23-26. doi: 10.1016/j.yjmcc.2024.04.013. Epub ahead of print. PMID: 38648962.
Impact Statement: The ability to reprogram adult human somatic cells into human induced pluripotent stem cells (iPSCs) has transformed cardiovascular research by providing a novel model system with a limitless supply of cardiovascular cell types for toxicity testing. Herein, we used iPSC-derived cardiomyocytes (iPSC-CMs) to illuminate the potential mechanism(s) of polyaromatic hydrocarbon benzo[a]pyrene-induced cardiotoxicity.Riggs DW, DuPre NC, James P, Rai SN, Yeager R, Sears CG, Laden F, Bhatnagar A. Association of Ecoregion Distribution of Greenness With Cardiovascular Mortality: A Longitudinal Ecological Study in the United States. Circ Res. 2024 Apr 26;134(9):1221-1223. doi: 10.1161/CIRCRESAHA.124.324427. Epub 2024 Apr 25. PMID: 38662855; PMCID: PMC11047167.
Impact Statement: This study reveals that the health benefits of living in greener areas, particularly reduced cardiovascular and all-cause mortality, vary significantly across different U.S. ecoregions. Understanding these variations is crucial for optimizing the health impacts of greenness, especially in the context of changing climates and diverse ecological characteristics.Monreal G, Koenig SC, Huang J, Slaughter MS. Anatomical and Hemodynamic Characterization of Totally Artificial Hearts. ASAIO J. 2024 May 1;70(5):338-347. doi: 10.1097/MAT.0000000000002209. Epub 2024 Apr 1. PMID: 38557701.
Impact Statement: This fun article studied spooky Halloween beating hearts to a cute colorful plush heart. They were imaged, instrumented (mock flow loops) to measure their pressure, volume, and flow, and qualitatively evaluated by 3rd party cardiac surgeons for anatomical accuracy and surgical considerations.Bradley J, Xu Q, Touloumes N, Lusciks E, Ali T, Huang EC, Chen J, Ghafghazi S, Arnold FW, Kong M, Huang J, Cavallazzi R; Center of Excellence for Research in Infectious Diseases (CERID) Post-COVID-19 Research Clinic Study Group. Association of pulmonary function test abnormalities and quality-of-life measures after COVID-19 infection. Am J Med Sci. 2024 Apr 16:S0002-9629(24)01170-4. doi: 10.1016/j.amjms.2024.04.010. Epub ahead of print. PMID: 38636655.
Impact Statement: This study reveals that post-COVID-19 patients with normal pulmonary function tests (PFTs) experience significant impairments in mobility and anxiety-related health-related quality of life (HRQoL) scores, suggesting that the presence of normal PFTs does not preclude long-term impacts on HRQoL. Conversely, no significant temporal association was found between abnormal PFTs and HRQoL scores, indicating that HRQoL impairments following COVID-19 infection may arise independently of PFT abnormalities.Taiwo MT, Huang E, Pathak V, Bellar A, Welch N, Dasarathy J, Streem D, McClain CJ, Mitchell MC, Barton BA, Szabo G, Dasarathy S, Schaefer EA, Luther J, Day LZ, Ouyang X, Arumugam S, Mehal WZ, Jacobs JM, Goodman RP, Rotroff DM, Nagy LE. Complement protein signatures in patients with alcohol-associated hepatitis. JCI Insight. 2024 Apr 4:e174127. doi: 10.1172/jci.insight.174127. Epub ahead of print. PMID: 38573776.
Impact Statement: This study identifies distinct complement protein signatures in severe alcohol-associated hepatitis (sAH) through a comprehensive proteomic analysis of human liver and serum samples. The findings highlight potential noninvasive diagnostic and prognostic biomarkers, such as serum collectin 11 and C1q binding protein, that can differentiate sAH from other alcohol-related liver conditions and predict patient outcomes.Asplund H, Dreyer HH, Singhal R, Rouchka EC, O'Toole TE, Haberzettl P, Conklin DJ, Sansbury BE. Exposure to Fine Particulate Matter Air Pollution Disrupts Erythrocyte Turnover. Circ Res. 2024 Apr 26;134(9):1224-1227. doi: 10.1161/CIRCRESAHA.124.324411. Epub 2024 Apr 25. PMID: 38662858; PMCID: PMC11059477.
Impact Statement: : Our study demonstrates that exposure to concentrated ambient PM2.5 significantly disrupts erythrocyte homeostasis, resulting in increased oxidative stress and impaired clearance by splenic macrophages. These findings suggest that PM2.5-induced alterations in erythrocyte dynamics may play a critical role in the exacerbation of cardiovascular disease, highlighting the need for further investigation into erythrocytes as key targets in air pollution-related pathology.Holm RH, Rempala GA, Choi B, Brick JM, Amraotkar AR, Keith RJ, Rouchka EC, Chariker JH, Palmer KE, Smith T, Bhatnagar A. Dynamic SARS-CoV-2 surveillance model combining seroprevalence and wastewater concentrations for post-vaccine disease burden estimates. Commun Med (Lond). 2024 Apr 9;4(1):70. doi: 10.1038/s43856-024-00494-y. PMID: 38594350; PMCID: PMC11004132.
Impact Statement: Despite wide scale assessments, it remains unclear how large-scale severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination affected the wastewater concentration of the virus or the overall disease burden as measured by hospitalization rates. Our study underscores the importance of continuing environmental surveillance post-vaccine and provides a proof-of-concept for environmental epidemiology monitoring of infectious disease for future pandemic preparedness.Gripshover TC, Wahlang B, Head KZ, Luo J, Bolatimi OE, Smith ML, Rouchka EC, Chariker JH, Xu J, Cai L, Cummins TD, Merchant ML, Zheng H, Kong M, Cave MC. Multiomics Analysis of PCB126's Effect on a Mouse Chronic-Binge Alcohol Feeding Model. Environ Health Perspect. 2024 Apr;132(4):47007. doi: 10.1289/EHP14132. Epub 2024 Apr 15. PMID: 38619879; PMCID: PMC11018247.
Impact Statement: This study reveals that PCB126 exposure exacerbates alcohol-associated liver disease (ALD) by significantly altering the transcriptome and essential metal levels in the liver. These findings suggest that PCB126 not only promotes steatosis and hepatomegaly but also contributes to the malnutrition aspect of ALD, highlighting the complex interplay between environmental pollutants and liver disease pathogenesis.- Zhao J, Gomes D, Yuan F, Feng J, Zhang X, O'Toole TE. Oral Polystyrene Consumption Potentiates Atherosclerotic Lesion Formation in ApoE-/- Mice. Circ Res. 2024 Apr 26;134(9):1228-1230. doi: 10.1161/CIRCRESAHA.124.324419. Epub 2024 Apr 25. PMID: 38662862; PMCID: PMC11047141
Impact Statement: Plastic particles of the micro- and nano-sized are ubiquitous contaminants in the environment and have found their way into water supplies, the food chain, and ambient air. While human exposure to these particles through ingestion, inhalation, and absorption is inevitable, the health consequences of these exposures is uncertain. Using a model of oral polystyrene consumption, these studies have determined that such exposures can exacerbate atherosclerotic lesion formation in disease-prone mice.