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1
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Cox A, Nowshad F, Callaway E, Jayaraman A. Integrated Metagenomic and Metabolomic Analysis of In Vitro Murine Gut Microbial Cultures upon Bisphenol S Exposure. Metabolites 2024; 14:713. [PMID: 39728494 DOI: 10.3390/metabo14120713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 12/12/2024] [Accepted: 12/13/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND The gut microbiota are an important interface between the host and the environment, mediating the host's interactions with nutritive and non-nutritive substances. Dietary contaminants like Bisphenol A (BPA) may disrupt the microbial community, leaving the host susceptible to additional exposures and pathogens. BPA has long been a controversial and well-studied contaminant, so its structural analogues like Bisphenol S (BPS) are replacing it in consumer products, but have not been well studied. METHODS This study aimed to determine the impact of BPS on C57BL/6 murine gut microbiota using shotgun metagenomic sequencing and the metabolomic profiling of in vitro anaerobic cultures. RESULTS The results demonstrated that a supraphysiologic BPS dose did not overtly distort the metagenomic or metabolomic profiles of exposed cultures compared to controls. A distinct BPS-associated metabolite profile was not observed, but several metabolites, including saturated fatty acids, were enriched in the BPS-exposed cultures. In the absence of a BPS-associated enterotype, Lactobacillus species specifically were associated with BPS exposure in a discriminant model. CONCLUSIONS Our study provides evidence contrasting the effects of BPS in the gut microbiome to its predecessor, BPA, but also emphasizes the role of inter-animal variation in microbiome composition, indicating that further study is needed to characterize BPS in this context.
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Affiliation(s)
- Amon Cox
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA
| | - Farrhin Nowshad
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA
| | - Evelyn Callaway
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA
| | - Arul Jayaraman
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA
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2
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Yaacoub S, Boudaka A, AlKhatib A, Pintus G, Sahebkar A, Kobeissy F, Eid AH. The pharmaco-epigenetics of hypertension: a focus on microRNA. Mol Cell Biochem 2024; 479:3255-3271. [PMID: 38424404 PMCID: PMC11511726 DOI: 10.1007/s11010-024-04947-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 01/20/2024] [Indexed: 03/02/2024]
Abstract
Hypertension is a major harbinger of cardiovascular morbidity and mortality. It predisposes to higher rates of myocardial infarction, chronic kidney failure, stroke, and heart failure than most other risk factors. By 2025, the prevalence of hypertension is projected to reach 1.5 billion people. The pathophysiology of this disease is multifaceted, as it involves nitric oxide and endothelin dysregulation, reactive oxygen species, vascular smooth muscle proliferation, and vessel wall calcification, among others. With the advent of new biomolecular techniques, various studies have elucidated a gaping hole in the etiology and mechanisms of hypertension. Indeed, epigenetics, DNA methylation, histone modification, and microRNA-mediated translational silencing appear to play crucial roles in altering the molecular phenotype into a hypertensive profile. Here, we critically review the experimentally determined associations between microRNA (miRNA) molecules and hypertension pharmacotherapy. Particular attention is given to the epigenetic mechanisms underlying the physiological responses to antihypertensive drugs like candesartan, and other relevant drugs like clopidogrel, aspirin, and statins among others. Furthermore, how miRNA affects the pharmaco-epigenetics of hypertension is especially highlighted.
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Affiliation(s)
- Serge Yaacoub
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Ammar Boudaka
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Ali AlKhatib
- Department of Nutrition and Food Sciences, Lebanese International University, Beirut, Lebanon
| | - Gianfranco Pintus
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro, 07100, Sassari, Italy
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Firas Kobeissy
- Department of Neurobiology, Center for Neurotrauma, Multiomics and Biomarkers (CNMB), Morehouse School of Medicine, Neuroscience Institute, Atlanta, GA, USA
| | - Ali H Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar.
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3
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Dong Y, Xu W, Liu S, Xu Z, Qiao S, Cai Y. Serum albumin and liver dysfunction mediate the associations between organophosphorus pesticide exposure and hypertension among US adults. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 948:174748. [PMID: 39019272 DOI: 10.1016/j.scitotenv.2024.174748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/03/2024] [Accepted: 07/11/2024] [Indexed: 07/19/2024]
Abstract
BACKGROUND Human health is commonly threatened by organophosphorus pesticides (OPPs) due to their widespread use and biological characteristics. However, the combined effect of mixtures of OPPs metabolites on the risk of hypertension and potential mechanism remain limited. OBJECTIVES To comprehensively investigate the effects between OPPs exposure on hypertension risk and explore and underlying mechanism among US general population. METHODS This cross-sectional study collected US adults who had available data on urine OPPs metabolites (dialkyl phosphate compounds, DAPs) from the National Health and Nutrition Examination Survey (NHANES) to assess the relationships of DAPs with hypertension risk. Survey-weighted logistic regression, restricted cubic spline (RCS), and mixed exposure analysis models [weighted quantile sum regression (WQS) and Bayesian kernel machine regression (BKMR)] were used to analyze individual, dose-response and combined associations between urinary DAPs metabolites and hypertension risk, respectively. Mediation analysis determined the potential intermediary role of serum albumin and liver function in the above associations. RESULTS Compared with the reference group, participants with the highest tertile levels of DEP, DMTP, DETP, and DMDTP experienced increased risk of hypertension by 1.21-fold (95%CI: 1.02-1.36), 1.20-fold (95%CI: 1.02-1.42), 1.19-fold (95%CI: 1.01-1.40), and 1.17-fold (95%CI: 1.03-1.43), respectively. RCS curve also showed positive exposure-response associations of individual DAPs with hypertension risk. WQS and BKMR analysis further confirmed DAP mixtures were significantly associated with increased risk of hypertension, with DEP identified as a major contributor to the combined effect. Mediation analysis indicated that serum albumin and AST/ALT ratios played crucial mediating roles in the relationships between individual and mixed urinary DAPs and the prevalence of hypertension. CONCLUSION Our findings provided more comprehensive and novel perspectives into the individual and combined effects of urinary OPPs matabolites on the increased risk of hypertension and the possible driving mechanism, which would be of great significance for environmental control and early prevention of hypertension.
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Affiliation(s)
- Yinqiao Dong
- Department of Public Health, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200335, China; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Wei Xu
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Shiping Liu
- National Children's Medical Center, Shanghai Children's Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Zhongqing Xu
- Department of General Practice, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200335, China
| | - Shan Qiao
- Department of Health Promotion Education and Behaviors, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA.
| | - Yong Cai
- Department of Public Health, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200335, China.
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4
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Xega V, Liu JL. Beyond reproduction: unraveling the impact of sex hormones on cardiometabolic health. MEDICAL REVIEW (2021) 2024; 4:284-300. [PMID: 39135604 PMCID: PMC11317208 DOI: 10.1515/mr-2024-0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 05/07/2024] [Indexed: 08/15/2024]
Abstract
This review thoroughly explores the multifaceted roles of sexual hormones, emphasizing their impact beyond reproductive functions and underscoring their significant influence on cardiometabolic regulation. It analyzes the broader physiological implications of estrogen, testosterone, and progesterone, highlighting their effects on metabolic syndrome, lipid metabolism, glucose homeostasis, and cardiovascular health. Drawing from diverse molecular, clinical, and therapeutic studies, the paper delves into the intricate interplay between these hormones and cardiometabolic processes. By presenting a comprehensive analysis that goes beyond traditional perspectives, and recognizing sexual hormones as more than reproductive agents, the review sheds light on their broader significance in health and disease management, advocating for holistic and personalized medical approaches.
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Affiliation(s)
- Viktoria Xega
- MeDiC Program, The Research Institute of McGill University Health Centre, Montreal, Canada
| | - Jun-Li Liu
- Division of Endocrinology and Metabolism, Department of Medicine, McGill University, Montreal, Canada
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5
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Ekici M, Çakır Biçer N, Yirün A, Demirel G, Erkekoğlu P. Evaluation of Exposure to Bisphenol Analogs through Canned and Ready-to-Eat Meal Consumption and Their Possible Effects on Blood Pressure and Heart Rate. Nutrients 2024; 16:2275. [PMID: 39064718 PMCID: PMC11279681 DOI: 10.3390/nu16142275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 07/02/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
Bisphenols are endocrine-disrupting chemicals used in plastics and resins for food packaging. This study aimed to evaluate the exposure to bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) associated with the consumption of fresh, canned, and ready-to-eat meals and determine the effects of bisphenols on blood pressure and heart rate. Forty-eight healthy young adults were recruited for this study, and they were divided into the following three groups: fresh, canned, and ready-to-eat meal groups. Urine samples were collected 2, 4, and 6 h after meal consumption, and blood pressure and heart rate were measured. The consumption of ready-to-eat meals significantly increased urine BPA concentrations compared with canned and fresh meal consumption. No significant difference in BPS and BPF concentrations was observed between the groups. The consumption of ready-to-eat meals was associated with a significant increase in systolic blood pressure and pulse pressure and a marked decrease in diastolic blood pressure and heart rate. No significant differences were noted in blood pressure and heart rate with canned and fresh meal consumption. It can be concluded that total BPA concentration in consumed ready-to-eat meals is high. High BPA intake causes increase in urinary BPA concentrations, which may, in turn, lead to changes in some cardiovascular parameters.
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Affiliation(s)
- Merve Ekici
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Agri Ibrahim Cecen University, 04100 Agri, Turkey;
- Department of Nutrition and Dietetics, Institute of Health Sciences, Acıbadem Mehmet Ali Aydınlar University, 34638 Istanbul, Turkey
| | - Nihan Çakır Biçer
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Acıbadem Mehmet Ali Aydınlar University, 34638 Istanbul, Turkey
| | - Anıl Yirün
- Department of Toxicology, Faculty of Pharmacy, Cukurova University, 01250 Adana, Turkey; (A.Y.); (G.D.)
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, 06430 Ankara, Turkey;
| | - Göksun Demirel
- Department of Toxicology, Faculty of Pharmacy, Cukurova University, 01250 Adana, Turkey; (A.Y.); (G.D.)
| | - Pınar Erkekoğlu
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, 06430 Ankara, Turkey;
- Department of Vaccine Technology, Vaccine Institute, Hacettepe University, 06430 Ankara, Turkey
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6
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Charkiewicz AE, Omeljaniuk WJ, Nikliński J. Bisphenol A-What Do We Know? A Global or Local Approach at the Public Health Risk Level. Int J Mol Sci 2024; 25:6229. [PMID: 38892416 PMCID: PMC11172700 DOI: 10.3390/ijms25116229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 05/31/2024] [Accepted: 06/02/2024] [Indexed: 06/21/2024] Open
Abstract
BPA has demonstrated enormous multisystem and multi-organ toxicity shown mainly in animal models. Meanwhile, the effects of its exposure in humans still require years of observation, research, and answers to many questions. Even minimal and short-term exposure contributes to disorders or various types of dysfunction. It is released directly or indirectly into the environment at every stage of the product life cycle, demonstrating its ease of penetration into the body. The ubiquity and general prevalence of BPA influenced the main objective of the study, which was to assess the toxicity and health effects of BPA and its derivatives based on the available literature. In addition, the guidelines of various international institutions or regions of the world in terms of its reduction in individual products were checked. Bisphenol A is the most widely known chemical and perhaps even the most studied by virtually all international or national organizations, but nonetheless, it is still controversial. In general, the level of BPA biomonitoring is still too high and poses a potential threat to public health. It is beginning to be widely argued that future toxicity studies should focus on molecular biology and the assessment of human exposure to BPA, as well as its substitutes. The effects of its exposure still require years of observation, extensive research, and answers to many questions. It is necessary to continue to deepen the knowledge and interest of many organizations, companies, and consumers around the world in order to make rational purchases as well as future choices, not only consumer ones.
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Affiliation(s)
| | - Wioleta Justyna Omeljaniuk
- Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, 15-222 Bialystok, Poland
| | - Jacek Nikliński
- Department of Clinical Molecular Biology, Medical University of Bialystok, 15-269 Bialystok, Poland
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7
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Xie L, Huang B, Zhao X, Zhu N. Exploring the mechanisms underlying effects of bisphenol a on cardiovascular disease by network toxicology and molecular docking. Heliyon 2024; 10:e31473. [PMID: 38813174 PMCID: PMC11133888 DOI: 10.1016/j.heliyon.2024.e31473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 05/15/2024] [Accepted: 05/16/2024] [Indexed: 05/31/2024] Open
Abstract
Background Globally, cardiovascular disease (CVD) has emerged as a leading cause of mortality. Bisphenol A (BPA), recognized as one of the most prevalent and widely distributed endocrine-disrupting chemicals (EDCs), has been consistently linked to the progression of CVD. This research centers on unraveling the molecular mechanisms responsible for the toxic effects of BPA exposure on CVD. Key targets and pathways involved in action of BPA on CVD were investigated by network toxicology. Binding abilities of BPA to core targets were evaluated by molecular docking. Methods and results Based on information retrieved from ChEMBL, DrugBank, and OMIM databases, a total of 27 potential targets were found to be associated with the influence of BPA on CVD. Furthermore, the STRING and Cytoscape software were employed to identify three central genes-ESR1, PPARG, and PTGS2-and to construct both the protein-protein interaction network and an interaction diagram of potential targets. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes, KEGG) pathway enrichment analyses via WebGestalt revealed key biological processes (BP), cellular components (CC), molecular functions (MF), and pathways, such as the calcium signaling pathway, inflammatory mediator regulation of TRP channels, gap junction, adrenergic signaling in cardiomyocytes, cGMP-PKG signaling pathway, and cAMP signaling pathway, predominantly involved in BPA-induced CVD toxicity. By using molecular docking investigations, it proved that BPA binds to ESR1, PPARG, and PTGS2 steadily and strongly. Conclusion This study not only establishes a theoretical framework for understanding the molecular toxicity mechanism of BPA in cardiovascular disease (CVD) but also introduces an innovative network toxicology approach to methodically investigate the influence of environmental contaminants on CVD. This methodology sets the stage for drug discovery efforts targeting CVD linked to exposure to endocrine-disrupting chemicals (EDCs).
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Affiliation(s)
- Lina Xie
- Department of Neurosurgery, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, China
| | - Bingwu Huang
- Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, China
| | - Xuyong Zhao
- Department of Cardiology, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, China
| | - Ning Zhu
- Department of Cardiology, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, China
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8
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Sattar S, Nadeem A, Shehzad W, Ur Rehman H, Javed M. A biochemical and histological evaluation of in vivo exposure of bisphenol P for multi-organ toxicity and pathology in rats. Toxicol Ind Health 2024; 40:194-205. [PMID: 38346931 DOI: 10.1177/07482337241233312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2024]
Abstract
Bisphenol P (BPP) is a structural analog of bisphenol A (BPA) and is increasingly used as a substitute of BPA in commercial and household applications. In recent years, BPP has been frequently detected in terrestrial and aquatic ecosystems. Very little epidemiological and experimental information are available on the toxicity potential of BPP in human and animal systems, which is very concerning in view of its increasing use. The current study evaluated the biochemical and histopathological effects of BPP in rats. The seven experimental groups (n = 5 rats/group) included BPA5 (5 mg), BPA50 (50 mg), BPA100 (100 mg), BPP5 (5 mg), BPP50 (50 mg), and BPP100 (100 mg) while the remaining one group served as untreated control. At the end of treatment, the organs (liver, kidney, heart, and lung) of rats were harvested for oxidative stress and histopathological analyses. A significant (p < .05) decrease was observed in the weight of the liver, lungs, and kidneys in the BPP100 group similar to the BPA100 group compared with the control group. Further, a significant (p < .05) decrease was also observed for concentrations of antioxidant enzymes (catalase, peroxidase, superoxide dismutase, and glutathione peroxidase) in the liver, lungs, kidneys, and heart at the highest two doses of BPP similar to the respective BPA groups compared with the control group. The two highest doses of BPP induced histopathological changes in the liver such as nuclei distortion, excessive necrosis of hepatocytes, nuclei shrinkage and pyknosis of cells with disrupted cell structure (BPP100), and cellular congestion and degeneration of hepatocytes (BPP50) similar to the two respective doses of BPA. The BPP treated groups also showed varying histopathological changes in kidney tissue, heart tissue, and lung tissue similar to BPA treated rats. In conclusion, the present study indicated that BPP has the potential to induce oxidative stress and alter the histomorphological architecture of different organs and is as deleterious as BPA.
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Affiliation(s)
- Saadia Sattar
- Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Asif Nadeem
- Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan
- Department of Biotechnology, Virtual University of Pakistan, Lahore, Pakistan
| | - Wasim Shehzad
- Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Habib Ur Rehman
- Department of Physiology, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Maryam Javed
- Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan
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Fardoun M, Kobeissy F, Eid AH. Estrogen Receptor and the Gender Bias in Raynaud's Phenomenon. Curr Med Chem 2024; 31:133-137. [PMID: 36803760 DOI: 10.2174/0929867330666230220123237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 01/15/2023] [Accepted: 01/25/2023] [Indexed: 02/22/2023]
Affiliation(s)
- Manal Fardoun
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Firas Kobeissy
- Department of Neurobiology and Neuroscience, Morehouse School of Medicine, Atlanta, Georgia, USA
| | - Ali H Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar
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10
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Haider MZ, Sahebkar A, Eid AH. Selective Activation of G Protein-coupled Estrogen Receptor 1 Attenuates Atherosclerosis. Curr Med Chem 2024; 31:4312-4319. [PMID: 37138482 DOI: 10.2174/0929867330666230501231528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 02/14/2023] [Accepted: 02/24/2023] [Indexed: 05/05/2023]
Abstract
Atherosclerosis remains a leading contributor to cardiovascular disease-associated morbidity and mortality. Interestingly, atherosclerosis-associated mortality rate is higher in men than women. This suggested a protective role for estrogen in the cardiovasculature. These effects of estrogen were initially thought to be mediated by the classic estrogen receptors, ER alpha, and beta. However, genetic knockdown of these receptors did not abolish estrogen's vasculoprotective effects suggesting that the other membranous Gprotein coupled estrogen receptor, GPER1, maybe the actual mediator. Indeed, in addition to its role in vasotone regulation, this GPER1 appears to play important roles in regulating vascular smooth cell phenotype, a critical player in the onset of atherosclerosis. Moreover, GPER1-selective agonists appear to reduce LDL levels by promoting the expression of LDL receptors as well as potentiating LDL re-uptake in liver cells. Further evidence also show that GPER1 can downregulate Proprotein Convertase Subtilisin/ Kexin type 9, leading to suppression of LDL receptor breakdown. Here, we review how selective activation of GPER1 might prevent or suppress atherosclerosis, with less side effects than those of the non-selective estrogen.
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Affiliation(s)
- Mohammad Zulqurnain Haider
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar
| | - Amirhossein Sahebkar
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, 9177899191, Iran
| | - Ali H Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar
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Bagheri M, Zandieh MA, Daryab M, Samaei SS, Gholami S, Rahmanian P, Dezfulian S, Eary M, Rezaee A, Rajabi R, Khorrami R, Salimimoghadam S, Hu P, Rashidi M, Ardakan AK, Ertas YN, Hushmandi K. Nanostructures for site-specific delivery of oxaliplatin cancer therapy: Versatile nanoplatforms in synergistic cancer therapy. Transl Oncol 2024; 39:101838. [PMID: 38016356 DOI: 10.1016/j.tranon.2023.101838] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 10/24/2023] [Accepted: 11/17/2023] [Indexed: 11/30/2023] Open
Abstract
As a clinically approved treatment strategy, chemotherapy-mediated tumor suppression has been compromised, and in spite of introducing various kinds of anticancer drugs, cancer eradication with chemotherapy is still impossible. Chemotherapy drugs have been beneficial in improving the prognosis of cancer patients, but after resistance emerged, their potential disappeared. Oxaliplatin (OXA) efficacy in tumor suppression has been compromised by resistance. Due to the dysregulation of pathways and mechanisms in OXA resistance, it is suggested to develop novel strategies for overcoming drug resistance. The targeted delivery of OXA by nanostructures is described here. The targeted delivery of OXA in cancer can be mediated by polymeric, metal, lipid and carbon nanostructures. The advantageous of these nanocarriers is that they enhance the accumulation of OXA in tumor and promote its cytotoxicity. Moreover, (nano)platforms mediate the co-delivery of OXA with drugs and genes in synergistic cancer therapy, overcoming OXA resistance and improving insights in cancer patient treatment in the future. Moreover, smart nanostructures, including pH-, redox-, light-, and thermo-sensitive nanostructures, have been designed for OXA delivery and cancer therapy. The application of nanoparticle-mediated phototherapy can increase OXA's potential in cancer suppression. All of these subjects and their clinical implications are discussed in the current review.
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Affiliation(s)
- Mohsen Bagheri
- Radiology Resident, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Arad Zandieh
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Mahshid Daryab
- Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyedeh Setareh Samaei
- Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Sarah Gholami
- Young Researcher and Elite Club, Babol Branch, Islamic Azad University, Babol, Iran
| | - Parham Rahmanian
- Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Sadaf Dezfulian
- Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mahsa Eary
- Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Aryan Rezaee
- Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Romina Rajabi
- Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Ramin Khorrami
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Peng Hu
- Department of Emergency, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Mohsen Rashidi
- Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Alireza Khodaei Ardakan
- Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran.
| | - Yavuz Nuri Ertas
- Department of Biomedical Engineering, Erciyes University, Kayseri, Turkey; ERNAM-Nanotechnology Research and Application Center, Erciyes University, Kayseri, Turkey
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
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12
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Muncke J, Andersson AM, Backhaus T, Belcher SM, Boucher JM, Carney Almroth B, Collins TJ, Geueke B, Groh KJ, Heindel JJ, von Hippel FA, Legler J, Maffini MV, Martin OV, Peterson Myers J, Nadal A, Nerin C, Soto AM, Trasande L, Vandenberg LN, Wagner M, Zimmermann L, Thomas Zoeller R, Scheringer M. A vision for safer food contact materials: Public health concerns as drivers for improved testing. ENVIRONMENT INTERNATIONAL 2023; 180:108161. [PMID: 37758599 DOI: 10.1016/j.envint.2023.108161] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 08/17/2023] [Accepted: 08/17/2023] [Indexed: 09/29/2023]
Abstract
Food contact materials (FCMs) and food contact articles are ubiquitous in today's globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. To identify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs.
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Affiliation(s)
- Jane Muncke
- Food Packaging Forum Foundation, Zurich, Switzerland.
| | - Anna-Maria Andersson
- Dept. of Growth and Reproduction, Rigshospitalet and Centre for Research and Research Training in Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Thomas Backhaus
- Dept of Biological and Environmental Sciences, University of Gothenburg, Sweden
| | - Scott M Belcher
- Dept. of Biological Sciences, North Carolina State University, Raleigh, NC, USA
| | | | | | | | - Birgit Geueke
- Food Packaging Forum Foundation, Zurich, Switzerland
| | - Ksenia J Groh
- Department of Environmental Toxicology, Eawag, Swiss Federal Institute of Aquatic Science and Technology, Dübendorf, Switzerland
| | - Jerrold J Heindel
- Healthy Environment and Endocrine Disruptor Strategies, Durham, NC, USA
| | - Frank A von Hippel
- Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA
| | - Juliette Legler
- Dept. of Population Health Sciences, Faculty of Veterinary Medicine, University of Utrecht, Netherlands
| | | | - Olwenn V Martin
- Plastic Waste Innovation Hub, Department of Arts and Science, University College London, UK
| | - John Peterson Myers
- Dept. of Chemistry, Carnegie Mellon University, Pittsburgh, PA, USA; Environmental Health Sciences, Charlottesville, VA, USA
| | - Angel Nadal
- IDiBE and CIBERDEM, Miguel Hernández University of Elche, Alicante, Spain
| | - Cristina Nerin
- Dept. of Analytical Chemistry, I3A, University of Zaragoza, Zaragoza, Spain
| | - Ana M Soto
- Department of Immunology, Tufts University School of Medicine, Boston, MA, USA; Centre Cavaillès, Ecole Normale Supérieure, Paris, France
| | - Leonardo Trasande
- College of Global Public Health and Grossman School of Medicine and Wagner School of Public Service, New York University, New York, NY, USA
| | - Laura N Vandenberg
- Department of Environmental Health Sciences, School of Public Health & Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA
| | - Martin Wagner
- Dept. of Biology, Faculty of Natural Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | | | - R Thomas Zoeller
- Department of Environmental Health Sciences, School of Public Health & Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA
| | - Martin Scheringer
- RECETOX, Masaryk University, Brno, Czech Republic; Department of Environmental Systems Science, ETH Zurich, Switzerland.
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13
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Davis AP, Wiegers TC, Wiegers J, Wyatt B, Johnson RJ, Sciaky D, Barkalow F, Strong M, Planchart A, Mattingly CJ. CTD tetramers: a new online tool that computationally links curated chemicals, genes, phenotypes, and diseases to inform molecular mechanisms for environmental health. Toxicol Sci 2023; 195:155-168. [PMID: 37486259 PMCID: PMC10535784 DOI: 10.1093/toxsci/kfad069] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2023] Open
Abstract
The molecular mechanisms connecting environmental exposures to adverse endpoints are often unknown, reflecting knowledge gaps. At the Comparative Toxicogenomics Database (CTD), we developed a bioinformatics approach that integrates manually curated, literature-based interactions from CTD to generate a "CGPD-tetramer": a 4-unit block of information organized as a step-wise molecular mechanism linking an initiating Chemical, an interacting Gene, a Phenotype, and a Disease outcome. Here, we describe a novel, user-friendly tool called CTD Tetramers that generates these evidence-based CGPD-tetramers for any curated chemical, gene, phenotype, or disease of interest. Tetramers offer potential solutions for the unknown underlying mechanisms and intermediary phenotypes connecting a chemical exposure to a disease. Additionally, multiple tetramers can be assembled to construct detailed modes-of-action for chemical-induced disease pathways. As well, tetramers can help inform environmental influences on adverse outcome pathways (AOPs). We demonstrate the tool's utility with relevant use cases for a variety of environmental chemicals (eg, perfluoroalkyl substances, bisphenol A), phenotypes (eg, apoptosis, spermatogenesis, inflammatory response), and diseases (eg, asthma, obesity, male infertility). Finally, we map AOP adverse outcome terms to corresponding CTD terms, allowing users to query for tetramers that can help augment AOP pathways with additional stressors, genes, and phenotypes, as well as formulate potential AOP disease networks (eg, liver cirrhosis and prostate cancer). This novel tool, as part of the complete suite of tools offered at CTD, provides users with computational datasets and their supporting evidence to potentially fill exposure knowledge gaps and develop testable hypotheses about environmental health.
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Affiliation(s)
- Allan Peter Davis
- Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA
| | - Thomas C Wiegers
- Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA
| | - Jolene Wiegers
- Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA
| | - Brent Wyatt
- Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA
| | - Robin J Johnson
- Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA
| | - Daniela Sciaky
- Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA
| | - Fern Barkalow
- Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA
| | - Melissa Strong
- Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA
| | - Antonio Planchart
- Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA
- Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina 27695, USA
| | - Carolyn J Mattingly
- Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA
- Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina 27695, USA
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14
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Lee G, Kim S, Lee I, Kang H, Lee JP, Lee J, Choi YW, Park J, Choi G, Choi K. Association between environmental chemical exposure and albumin-to-creatinine ratio is modified by hypertension status in women of reproductive age. ENVIRONMENTAL RESEARCH 2023; 231:116234. [PMID: 37236389 DOI: 10.1016/j.envres.2023.116234] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 05/02/2023] [Accepted: 05/24/2023] [Indexed: 05/28/2023]
Abstract
Chemicals have been identified as a potential risk factor of renal dysfunction. However, studies that consider both multiple chemicals and non-chemical risk factors, such as hypertension, are rare. In this study, we assessed the associations between exposure to several chemicals, including major metals, phthalates, and phenolic compounds, and the albumin-to-creatinine ratio (ACR). A group of Korean adult women in reproductive age (n = 438, aged between 20 and 49 years), who had previously been studied for association of several organic chemicals, was chosen for this purpose. We constructed multivariable linear regression models for individual chemicals and weighted-quantile sum (WQS) mixtures, by hypertension status. Among the study population, approximately 8.5% of the participants exhibited micro/macro-albuminuria (ACR ≥30 mg/g), and 18.5% and 3.9% exhibited prehypertension and hypertension, respectively. Blood cadmium and lead levels showed a stronger association with ACR only among women with prehypertension or hypertension. Among organic chemicals, depending on the statistial model, benzophenone-1 (BP-1) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) showed a significant association regardless of hypertension status, but most associations disappeared in the (pre)hypertensive group. These findings clearly indicate that hypertension status can modify and may potentiate the association of environmental chemicals with ACR. Our observations suggest that low-level environmental pollutant exposure may have potential adverse effects on kidney function among general adult women. Considering the prevalence of prehypertension in the general population, efforts to reduce exposure to cadmium and lead are necessary among adult women to minimize the risk of adverse kidney function.
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Affiliation(s)
- Gowoon Lee
- Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea; Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea
| | - Sunmi Kim
- Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea; Chemical Analysis Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea
| | - Inae Lee
- Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea; Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea
| | - Habyeong Kang
- Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea; College of Health Science, Korea University, Seoul, Republic of Korea
| | - Jung Pyo Lee
- Department of Internal Medicine, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeonghwan Lee
- Department of Internal Medicine, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Young Wook Choi
- Department of Internal Medicine, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Jeongim Park
- Department of Natural Sciences, Soonchunhyang University, Asan, Republic of Korea
| | - Gyuyeon Choi
- Department of Obstetrics and Gynecology, Soonchunhyang University Hospital, Seoul, Republic of Korea
| | - Kyungho Choi
- Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea; Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea.
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15
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Molina-López AM, Bujalance-Reyes F, Ayala-Soldado N, Mora-Medina R, Lora-Benítez A, Moyano-Salvago R. An Overview of the Health Effects of Bisphenol A from a One Health Perspective. Animals (Basel) 2023; 13:2439. [PMID: 37570248 PMCID: PMC10417040 DOI: 10.3390/ani13152439] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/26/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
Bisphenol A (BPA) is a chemical compound, considered as an "emerging pollutant", that appears ubiquitously, contaminating the environment and food. It is an endocrine disruptor, found in a multitude of consumer products, as it is a constituent of polycarbonate used in the manufacture of plastics and epoxy resins. Many studies have evaluated the effects of BPA, using a wide range of doses and animal models. In this work, we carried out a review of relevant research related to the effects of BPA on health, through studies performed at different doses, in different animal models, and in human monitoring studies. Numerous effects of BPA on health have been described; in different animal species, it has been reported that it interferes with fertility in both females and males and causes alterations in their offspring, as well as being associated with an increase in hormone-dependent pathologies. Similarly, exposure to BPA has been related to other diseases of great relevance in public health such as obesity, hypertension, diabetes, or neurodevelopmental disorders. Its ubiquity and nonmonotonic behavior, triggering effects at exposure levels considered "safe", make it especially relevant when both animal and human populations are constantly and inadvertently exposed to this compound. Its effects at low exposure levels make it essential to establish safe exposure levels, and research into the effects of BPA must continue and be focused from a "One Health" perspective to take into account all the factors that could intervene in the development of a disease in any exposed organism.
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Affiliation(s)
- Ana M. Molina-López
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Unidad de Investigación Competitiva Zoonosis y Enfermedades Emergentes desde la Perspectiva de Una Salud ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Darwin, E-14071 Córdoba, Spain;
| | - Francisca Bujalance-Reyes
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Universidad de Córdoba, Campus de Rabanales, Edificio Darwin, E-14071 Córdoba, Spain; (F.B.-R.); (R.M.-M.); (A.L.-B.)
| | - Nahúm Ayala-Soldado
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Universidad de Córdoba, Campus de Rabanales, Edificio Darwin, E-14071 Córdoba, Spain; (F.B.-R.); (R.M.-M.); (A.L.-B.)
| | - Rafael Mora-Medina
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Universidad de Córdoba, Campus de Rabanales, Edificio Darwin, E-14071 Córdoba, Spain; (F.B.-R.); (R.M.-M.); (A.L.-B.)
| | - Antonio Lora-Benítez
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Universidad de Córdoba, Campus de Rabanales, Edificio Darwin, E-14071 Córdoba, Spain; (F.B.-R.); (R.M.-M.); (A.L.-B.)
| | - Rosario Moyano-Salvago
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Unidad de Investigación Competitiva Zoonosis y Enfermedades Emergentes desde la Perspectiva de Una Salud ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Darwin, E-14071 Córdoba, Spain;
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16
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Akash MSH, Rasheed S, Rehman K, Imran M, Assiri MA. Toxicological evaluation of bisphenol analogues: preventive measures and therapeutic interventions. RSC Adv 2023; 13:21613-21628. [PMID: 37476040 PMCID: PMC10354593 DOI: 10.1039/d3ra04285e] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 07/12/2023] [Indexed: 07/22/2023] Open
Abstract
Bisphenol A (BPA) is a prominent endocrine-disrupting compound that shares structural similarities with estrogen. It is widely used, particularly in the production of food packaging, canned goods, and dental sealants. Of the eight bisphenol analogues, BPA is the most frequently utilized chemical in packaging food items, canned foods and dental sealants. However, chronic exposure to BPA can pose severe health risks, particularly in children. To ensure public safety, it is crucial to adopt proper precautionary measures to minimize BPA exposure. This article explores the toxic effects of bisphenols on various body systems and mechanisms, shedding light on their impact on the reproductive and endocrine system, obesity, albuminuria, and the generation of reactive oxygen species. Understanding the detrimental effects of bisphenols on these systems and mechanisms is vital for developing strategies to mitigate their harmful consequences. Furthermore, the article delves into the biotransformation processes of bisphenols, focusing on their occurrence in vertebrates, invertebrates, plants, and microorganisms. Investigating the biotransformation pathways provides valuable insights into the fate of bisphenols in various organisms and ecosystems. Lastly, the article emphasizes preventive measures to avoid bisphenol exposure and highlights the potential use of plant-based bioactive compounds for treatment strategies. By implementing effective preventive measures, such as utilizing BPA-free products and adopting safer alternatives, individuals can reduce their exposure to bisphenols. Additionally, exploring the potential of plant-based bioactive compounds as therapeutic agents offers promising avenues for addressing the adverse effects of bisphenols. The findings presented herein contribute to a better understanding of the novelty, significance, and potential implications of bisphenol research in the field, aiding in the development of safer practices and interventions to safeguard public health.
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Affiliation(s)
| | - Sumbal Rasheed
- Department of Pharmaceutical Chemistry, Government College University Faisalabad Pakistan
| | - Kanwal Rehman
- Department of Pharmacy, The Women University Multan Pakistan
| | - Muhammad Imran
- Research Center for Advanced Materials Science (RCAMS), King Khalid University Abha Saudi Arabia
- Department of Chemistry, Faculty of Science, King Khalid University Abha Saudi Arabia
| | - Mohammed A Assiri
- Research Center for Advanced Materials Science (RCAMS), King Khalid University Abha Saudi Arabia
- Department of Chemistry, Faculty of Science, King Khalid University Abha Saudi Arabia
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17
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Nevola R, Tortorella G, Rosato V, Rinaldi L, Imbriani S, Perillo P, Mastrocinque D, La Montagna M, Russo A, Di Lorenzo G, Alfano M, Rocco M, Ricozzi C, Gjeloshi K, Sasso FC, Marfella R, Marrone A, Kondili LA, Esposito N, Claar E, Cozzolino D. Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma. BIOLOGY 2023; 12:984. [PMID: 37508414 PMCID: PMC10376683 DOI: 10.3390/biology12070984] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 06/29/2023] [Accepted: 07/03/2023] [Indexed: 07/30/2023]
Abstract
Several chronic liver diseases are characterized by a clear gender disparity. Among them, hepatocellular carcinoma (HCC) shows significantly higher incidence rates in men than in women. The different epidemiological distribution of risk factors for liver disease and HCC only partially accounts for these gender differences. In fact, the liver is an organ with recognized sexual dysmorphism and is extremely sensitive to the action of androgens and estrogens. Sex hormones act by modulating the risk of developing HCC and influencing its aggressiveness, response to treatments, and prognosis. Furthermore, androgens and estrogens are able to modulate the action of other factors and cofactors of liver damage (e.g., chronic HBV infection, obesity), significantly influencing their carcinogenic power. The purpose of this review is to examine the factors related to the different gender distribution in the incidence of HCC as well as the pathophysiological mechanisms involved, with particular reference to the central role played by sex hormones.
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Affiliation(s)
- Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
- Liver Unit, Ospedale Evangelico Betania, 80147 Naples, Italy; (V.R.); (P.P.); (D.M.); (N.E.); (E.C.)
| | - Giovanni Tortorella
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | - Valerio Rosato
- Liver Unit, Ospedale Evangelico Betania, 80147 Naples, Italy; (V.R.); (P.P.); (D.M.); (N.E.); (E.C.)
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | - Simona Imbriani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | - Pasquale Perillo
- Liver Unit, Ospedale Evangelico Betania, 80147 Naples, Italy; (V.R.); (P.P.); (D.M.); (N.E.); (E.C.)
| | - Davide Mastrocinque
- Liver Unit, Ospedale Evangelico Betania, 80147 Naples, Italy; (V.R.); (P.P.); (D.M.); (N.E.); (E.C.)
| | - Marco La Montagna
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | - Antonio Russo
- Department of Mental Health and Public Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | - Giovanni Di Lorenzo
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | - Maria Alfano
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | - Maria Rocco
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | - Carmen Ricozzi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | - Klodian Gjeloshi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
| | | | - Nicolino Esposito
- Liver Unit, Ospedale Evangelico Betania, 80147 Naples, Italy; (V.R.); (P.P.); (D.M.); (N.E.); (E.C.)
| | - Ernesto Claar
- Liver Unit, Ospedale Evangelico Betania, 80147 Naples, Italy; (V.R.); (P.P.); (D.M.); (N.E.); (E.C.)
| | - Domenico Cozzolino
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (G.T.); (L.R.); (S.I.); (M.L.M.); (G.D.L.); (M.A.); (M.R.); (C.R.); (K.G.); (F.C.S.); (R.M.); (A.M.); (D.C.)
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18
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Han E, Pan Y, Li L, Cai J. Bisphenol A detection based on nano gold-doped molecular imprinting electrochemical sensor with enhanced sensitivity. Food Chem 2023; 426:136608. [PMID: 37348395 DOI: 10.1016/j.foodchem.2023.136608] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/27/2023] [Accepted: 06/10/2023] [Indexed: 06/24/2023]
Abstract
A facile electrochemical sensor based on nano gold-doped molecularly imprinted polymer (MIP) was proposed to realize the selective detection of bisphenol A (BPA) with enhanced sensitivity. Initially, gold-doped MIP (Au@MIP) film was constructed by electropolymerizing p-aminobenzoic acid (PABA) and BPA with in situ gold reduction to distribute gold nanoparticles nearby the imprinted cavities. Subsequently, the template molecules were further extracted from the polymer film, then the MIP could rebind with the template molecules to achieve specific detection of BPA. The nano gold-doped MIP increased the effective surface area and promoted conductivity when BPA was oxidized in the imprinted cavities, which improved the determination sensitivity. Under optimal conditions, the prepared sensor displayed a linear range from 0.5 to 100 μM for BPA detection with a detection limit of 52 nM. The designed sensor was further used to detect BPA in food samples, obtaining satisfactory recoveries from 96.7% to 107.6%.
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Affiliation(s)
- En Han
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, PR China.
| | - Yingying Pan
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, PR China
| | - Lei Li
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, PR China
| | - Jianrong Cai
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, PR China.
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19
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Chen S, Tao Y, Wang P, Li D, Shen R, Fu G, Wei T, Zhang W. Association of urinary bisphenol A with cardiovascular and all-cause mortality: National Health and Nutrition Examination Survey (NHANES) 2003-2016. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:51217-51227. [PMID: 36807039 DOI: 10.1007/s11356-023-25924-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 02/09/2023] [Indexed: 04/16/2023]
Abstract
Bisphenol A (BPA), one of the most widely consumed endocrine disrupting chemicals, has been found to be associated with a variety of diseases, especially cardiovascular diseases. However, few studies have investigated the association of BPA with long-term health outcomes. This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2003-2016. The NHANES data were linked to mortality data (with a follow-up point of December 31, 2019). The urinary BPA concentration was estimated by adjusting for urinary creatinine (BPA/Cr, ng/mg). Complex sampling-weighted multivariate Cox proportional hazards models were used to compare the hazard ratios (HRs) of cardiovascular and all-cause mortality among participants with different urinary BPA concentrations. This study included 9243 adult participants. The median follow-up duration was 9.1 years. During this period, 1200 all-cause deaths occurred, of which 374 were cardiovascular deaths. Compared to the lowest BPA/Cr quartile group, the adjusted HRs of the highest BPA/Cr quartile group were 1.76 (95% CI, 1.23-2.52) for cardiovascular mortality and 1.21 (95% CI, 0.98-1.49) for all-cause mortality. In addition, there was a significant interaction between sex and BPA/Cr (P for interaction = 0.044) for the risk of cardiovascular mortality. The adjusted HR for cardiovascular mortality in female participants was 2.80 (95% CI, 1.56-5.02), while that in male participants was only 1.34 (95% CI, 0.79-2.24). Higher urinary BPA is associated with an increased risk of cardiovascular mortality among US adults. The effect of BPA on cardiovascular mortality may be more pronounced in women than in men.
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Affiliation(s)
- Shuaijie Chen
- Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Cardiology, Lishui Hospital, College of Medicine, Zhejiang University, Lishui, China
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Yecheng Tao
- Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Peng Wang
- Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Duanbin Li
- Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ruming Shen
- Department of Cardiology, Lishui Hospital, College of Medicine, Zhejiang University, Lishui, China
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Guosheng Fu
- Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Tiemin Wei
- Department of Cardiology, Lishui Hospital, College of Medicine, Zhejiang University, Lishui, China
| | - Wenbin Zhang
- Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
- College of Medicine, Zhejiang University, Hangzhou, China.
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20
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Xie Y, Ren Z, Chen H, Tang H, Zhu M, Lv Z, Bao H, Zhang Y, Liu R, Shen Y, Zheng Y, Miao D, Guo X, Chen H, Wang S, Pei J. A novel estrogen-targeted PEGylated liposome co-delivery oxaliplatin and paclitaxel for the treatment of ovarian cancer. Biomed Pharmacother 2023; 160:114304. [PMID: 36724638 DOI: 10.1016/j.biopha.2023.114304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/14/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023] Open
Abstract
Ovarian cancer is the second cause of death among gynecological malignancies. In this study, we designed a novel estrogen-targeted PEGylated liposome loaded with oxaliplatin and paclitaxel (ES-SSL-OXA/PTX) which could target estrogen receptor (ER) highly expressed on the surface of SKOV-3 cells to enhance therapeutic efficacy and reduce the side effects for SKOV-3 tumor therapy. ES-SSL-OXA/PTX was prepared by thin film hydration method and exhibited a uniform spherical morphology. Encapsulation efficiency (EE) were determined by HPLC method with the results of 44.10% for OXA and 65.85% for PTX. The mean particle size and polydispersity index (PDI) were 168.46 nm and 0.145, respectively. In vivo and in vitro targeting study confirmed that ES-SSL-OXA/PTX has optimum specific targeting ability. Meanwhile, In vitro and in vivo antitumor results of ES-SSL-OXA/PTX exhibited a superior antiproliferative effect on SKOV-3 cells and a stronger anti-tumor efficacy with the tumor inhibition rate of 85.24%. The pharmacokinetics results of ES-SSL-OXA/PTX showed a prolonged half-life time and a slowed clearance rate. The preliminary safety study of acute toxicity and long-term toxicity demonstrated ES-SSL-OXA/PTX exhibited a reduced toxicity profile. Based on the above results, ES-SSL-OXA/PTX could be a promising novel formulation for the treatment of ovarian cancer in future clinic.
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Affiliation(s)
- Yizhuo Xie
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Zhihui Ren
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Hongyu Chen
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Huan Tang
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Ming Zhu
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Zhe Lv
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Han Bao
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Yan Zhang
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Rui Liu
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Yujia Shen
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Yucui Zheng
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Dongfanghui Miao
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Xin Guo
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Hongli Chen
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Shanshan Wang
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Jin Pei
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, China.
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21
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Guo X, Ke Y, Wu B, Song Q, Sun C, Li Y, Wang H, Su W, Liang Q, Lowe S, Bentley R, Song EJ, King B, Zhou Q, Xie R, Deng F. Exploratory analysis of the association between organophosphate ester mixtures with high blood pressure of children and adolescents aged 8-17 years: cross-sectional findings from the National Health and Nutrition Examination Survey. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:22900-22912. [PMID: 36308653 DOI: 10.1007/s11356-022-23740-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 10/17/2022] [Indexed: 06/16/2023]
Abstract
Epidemiological studies on the effect of organophosphate esters (OPEs) on high blood pressure (BP) among children and adolescents are scant. Therefore, the main objective of the present study was to explore the effect of exposure to OPEs on high BP among children and adolescents. A total of 1340 participants were included in the current analyses. Multivariable logistic regression models were implemented to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to examine the association between OPE metabolites and high BP. We also assessed the modified effect of sex, age, and overweight/obesity on this association. Furthermore, quantile g-computation (Qgcomp) and Bayesian kernel machine regression (BKMR) were exhibited to analyze the association between multiple OPE metabolite mixtures and high BP. After adjusting for covariates, the highest (vs. lowest) tertiles of bis (1-choloro-2-propyl) phosphate (BCPP), bis-2-chloroethyl phosphate (BCEP), and di-n-butyl phosphate (DBUP) were associated with 1.23 (95% CI: 0.83, 1.83), 1.27 (95% CI: 0.85, 1.92), and 1.01 (95% CI: 0.67, 1.53) odds ratios for high BP, respectively. In the Qgcomp, a quartile increase in OPE metabolite mixtures was weakly associated with an elevated risk of high BP (adjusted OR: 1.06, 95CI%: 0.81, 1.37). The results from BKMR showed a positive trend of association between OPE metabolite mixture on the risk of high BP. In conclusion, our study demonstrated that higher levels of BCPP, BCEP, and DBUP were weakly associated with high BP among US children and adolescents. Moderate evidence suggested OPE metabolite mixtures had positive joint effects on high BP. Consequently, longitudinal studies with repeated measurements are warranted to examine the relationships between multiple OPE metabolites and high blood pressure among children and adolescents.
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Affiliation(s)
- Xianwei Guo
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China
| | - Yujie Ke
- Children's Hospital of Anhui Medical University, 39 Wangjiang East Road, Hefei, 230051, Anhui, People's Republic of China
| | - Birong Wu
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China
| | - Qiuxia Song
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China
| | - Chenyu Sun
- AMITA Health Saint Joseph Hospital Chicago, 2900 N. Lake Shore Drive, Chicago, IL, 60657, USA
| | - Yaru Li
- Internal Medicine, Swedish Hospital, 5140 N California Ave, Chicago, IL, 60625, USA
| | - Hao Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China
| | - Wanying Su
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China
| | - Qiwei Liang
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China
- Children's Hospital of Anhui Medical University, 39 Wangjiang East Road, Hefei, 230051, Anhui, People's Republic of China
| | - Scott Lowe
- College of Osteopathic Medicine, Kansas City University, 1750 Independence Ave, Kansas City, MO, 64106, USA
| | - Rachel Bentley
- College of Osteopathic Medicine, Kansas City University, 1750 Independence Ave, Kansas City, MO, 64106, USA
| | - Evelyn J Song
- Division of Hospital Medicine, Department of Medicine, University of California, San Francisco, CA, USA
| | - Bethany King
- Internal Medicine, MercyOne Des Moines Medical Center, 1111 6Th Avenue, Des Moines, IA, 50314, USA
| | - Qin Zhou
- Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Ruijin Xie
- School of Medicine, Jiangnan University, No. 1800, Lihu Avenue, Wuxi, 214122, People's Republic of China
| | - Fang Deng
- Children's Hospital of Anhui Medical University, 39 Wangjiang East Road, Hefei, 230051, Anhui, People's Republic of China.
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22
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Lu L, Ni R. Association between polycyclic aromatic hydrocarbon exposure and hypertension among the U.S. adults in the NHANES 2003-2016: A cross-sectional study. ENVIRONMENTAL RESEARCH 2023; 217:114907. [PMID: 36436553 DOI: 10.1016/j.envres.2022.114907] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 11/06/2022] [Accepted: 11/21/2022] [Indexed: 06/16/2023]
Abstract
The global burden of hypertension, the major cause of cardiovascular disease (CVD) globally, remains unresolved. Exposure to PM2.5 has been linked to hypertension (HTN) in adults and the elderly globally according to previous studies. Nonetheless, evidence on the association of polycyclic aromatic hydrocarbon (PAH) exposure and HTN risk in the general adult population in the United States was limited. To investigate the relationship between PAH exposure and HTN in adults in the United States, cross-sectional data during 2003 and 2016 from the National Health and Nutrition Examination Survey (NHANES) on a stratified multistage random sample of the civilian non-institutionalized population were utilized. After eliminating individuals with incomplete information of interest, the final analysis contained 8951 subjects aged ≥20. In the multivariate logistic regression model, 1-hydroxynaphthalene and 2-hydroxyfluorene were found positively associated with increased risk of HTN among overall participants after adjusting for the covariates. 1-hydroxynaphthalene and 2-hydroxynaphthalene showed positive associations with HTN risk among overweight participants. In the Bayesian kernel machine regression (BKMR) model, 1-hydroxynaphthalene and 2-hydroxyfluorene presented great importance to HTN risk among overall individuals. In the male subgroup analyses by BKMR, 2-hydroxyfluorene presented a positive effect on HTN risk when the remaining OH-PAHs were set at their 25th, 50th, and 75th percentile. Our findings highlight the complexities of estimating the risk of HTN associated with mixed PAH exposure, and additional longitudinal studies are required to determine the exact link between PAH exposure and HTN risk, as well as the underlying mechanisms.
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Affiliation(s)
- Lingyi Lu
- Xuhui District Center for Disease Control and Prevention, Shanghai, 200237, China
| | - Rong Ni
- Xuhui District Center for Disease Control and Prevention, Shanghai, 200237, China.
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23
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Wang H, Li Y, Liu C, Lu T, Zhai Q, Wang H, Zhang J. Inhibition of VDAC1 prevents oxidative stress and apoptosis induced by bisphenol A in spermatogonia via AMPK/mTOR signaling pathway. J Toxicol Sci 2023; 48:109-119. [PMID: 36858637 DOI: 10.2131/jts.48.109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2023]
Abstract
Bisphenol A (BPA), one of the main components of industrial products, is clinically associated with the increased male infertility rate. However, the underlying molecular mechanism of the BPA-resulted reproductive toxicity is not fully elucidated. Voltage-dependent anion channel 1 (VDAC1) is a pore protein and located at the outer mitochondrial membrane. As a mitochondrial gatekeeper, VDAC1 controls the release of reactive oxygen species (ROS) and the metabolic and energetic functions of mitochondria, and serves as a critical player in mitochondrial-mediated apoptosis. Herein, we explored the role of VDAC1 in BPA-induced apoptosis of spermatogonia. The results showed that BPA increased spermatogonia cell line GC-1 spg cell apoptosis and intracellular ROS level, and suppressed AMPK/mTOR signaling pathway at a dose of 80 μM for 48 hr. Lentivirus-mediated short hairpin RNA targeting VDAC1 (Lv-shVDAC1) silenced VDAC1 expression and enhanced BPA-restricted cell viability. Knockdown of VDAC1 inhibited the apoptosis of BPA-treated GC-1 spg cells determined by with changes of the expressions of pro-apoptotic and anti-apoptotic proteins. Knockdown of VDAC1 also alleviated the BPA-triggered intracellular ROS generation and oxidative stress. Moreover, silence of VDAC1 increased AMPKα1/2 phosphorylation and suppressed mTOR phosphorylation under BPA exposure. Dorsomorphin, an AMPK inhibitor, partially abolished the effects of VDAC1 gene silencing on BPA-stimulated GC-1 spg cells. In conclusion, inhibition of VDAC1 attenuated the BPA-induced oxidative stress and apoptosis and promoted the cell viability in spermatogonia through modulating AMPK/mTOR signaling pathway.
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Affiliation(s)
- Haixu Wang
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of The Fourth Military Medical University, China
| | - Yan Li
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of The Fourth Military Medical University, China
| | - Chuang Liu
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of The Fourth Military Medical University, China
| | - Tianxiang Lu
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of The Fourth Military Medical University, China
| | - Qian Zhai
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of The Fourth Military Medical University, China
| | - Hongna Wang
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of The Fourth Military Medical University, China
| | - Jianfang Zhang
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of The Fourth Military Medical University, China
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24
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Easson S, Singh RD, Connors L, Scheidl T, Baker L, Jadli A, Zhu HL, Thompson J. Exploring oxidative stress and endothelial dysfunction as a mechanism linking bisphenol S exposure to vascular disease in human umbilical vein endothelial cells and a mouse model of postnatal exposure. ENVIRONMENT INTERNATIONAL 2022; 170:107603. [PMID: 36335898 DOI: 10.1016/j.envint.2022.107603] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 10/17/2022] [Accepted: 10/25/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND Structural analogues used to replace bisphenol A (BPA) since the introduction of new regulatory restrictions are considered emerging environmental toxicants and remain understudied with respect to their biological actions and health effects. Studies reveal a link between BPA exposure and vascular disease in human populations, whereas the vascular effects of BPA substitutes remain largely unknown. OBJECTIVES To determine the effect of BPS, a commonly used BPA substitute, on redox balance, nitric oxide (NO) availability and microvascular NO-dependent dilation. METHODS In human umbilical vein endothelial cells (HUVEC), production of reactive oxygen species (ROS) and NO after exposure to BPS was measured using fluorescent probes for DCFDA and DAF-FM diacetate, respectively. The contribution of endothelial NO synthase (eNOS) uncoupling to ROS generation was determined by measuring ROS in the presence or absence of an eNOS inhibitor (L-NAME) or eNOS co-factor, BH4, while the contribution of mitochondria-derived ROS was determined by treating cells with mitochondria-specific antioxidants prior to BPS exposure. Bioenergetic profiles were assessed using Seahorse extracellular flux analysis and mitochondria membrane polarization was measured with TMRE and JC-1 assays. In a mouse model of low dose BPS exposure, NO-mediated endothelial function was assessed in pressurized microvessels by inducing endothelium-dependent dilation in the presence or absence of L-NAME. RESULTS BPS exposure (≥25 nM) reduced NO and increased ROS production in HUVEC, the latter corrected by treating cells with L-NAME or BH4. BPS exposure led to a loss of mitochondria membrane potential but had no impact on bioenergetic parameters except for a decrease in the spare respiratory capacity. Treatment of HUVEC with mitochondria-specific antioxidants abolished the effect of BPS on NO and ROS. NO-mediated vasodilation was impaired in male mice exposed to BPS. DISCUSSION Exposure to BPS may promote cardiovascular disease by perturbing NO-mediated vascular homeostasis through the induction of oxidative stress.
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Affiliation(s)
- Sarah Easson
- Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada
| | - Radha Dutt Singh
- Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Canada
| | - Liam Connors
- Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Canada
| | - Taylor Scheidl
- Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Canada
| | - Larissa Baker
- Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada
| | - Anshul Jadli
- Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Canada
| | - Hai-Lei Zhu
- Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada
| | - Jennifer Thompson
- Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Canada.
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25
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Dong Y, Chen L, Gao D, Li Y, Chen M, Ma T, Ma Y, Liu J, Zhang Y, Ma Q, Wang X, Song Y, Zou Z, Ma J. Endogenous sex hormones homeostasis disruption combined with exogenous phthalates exposure increase the risks of childhood high blood pressure: A cohort study in China. ENVIRONMENT INTERNATIONAL 2022; 168:107462. [PMID: 35998410 DOI: 10.1016/j.envint.2022.107462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/25/2022] [Accepted: 08/08/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND The structural similarity between sex hormones and exogenous phthalates (PAEs) enabled them as disrupters in regulating childhood blood pressure (BP). We aim to explore the association of sex hormones homeostasis and PAEs metabolites with childhood high BP (HBP). METHODS A cohort study was conducted with 1416 children aged 7-13 years at baseline and with 824, 819, and 801 children completing three waves' follow up. Serum testosterone (TT) and estradiol (E2) in children during three consecutive waves of surveys were measured by radioimmunoassay, and then TT/E2 ratio calculated as TT divided by E2 were used to represent sex hormones homeostasis. Seven urinary PAEs metabolites were measured in children of first wave. The BP Z-Scores and HBP across waves were obtained by sex, age, and height specific percentiles. Log-binomial regression models with adjusted risk ratios (aRR) after adjusting for confounders were utilized. RESULTS The prevalence of HBP at the baseline survey was 25.5%, and increased from 26.3% in the first wave of survey to 35.0% in the third wave of survey. PAEs were negatively correlated with E2, while positively correlated with TT and TT/E2 ratio. A positive association of the serum TT levels, TT/E2 ratio, and total PAEs was found with HBP prevalence (in wave 1, 2 and 3 with TT (aRR): 1.63, 1.37 and 1.45; with TT/E2: 1.63, 1.42 and 1.20; with PAEs: 1.40, 1.32 and 1.32), persistent HBP (with TT (aRR): 2.19; TT/E2: 2.16; PAEs: 2.57), occasional HBP (with TT (aRR): 1.94; TT/E2: 1.72; PAEs: 1.38), and new HBP incidence (with TT (aRR): 1.44; TT/E2: 1.57; PAEs: 1.67), but E2 had a negative association with HBP phenotypes (HBP prevalence in wave 1, 2 and 3 (aRR): 0.77, 0.93, and 1.10; persistent HBP: 0.47; occasional HBP: 0.96; new HBP incidence: 0.81). The E2 and PAEs had antagonistic effects on HBP risks in children, particularly in girls and those with high BMI group, but the TT levels, TT/E2 ratio and PAEs had synergistic effects on HBP risks in children, particularly in boys and those with high BMI group. CONCLUSION Exogenous PAEs exposure and endogenous sex hormones homeostasis disruption independently increase the risks of HBP. Moreover, the exogenous PAEs exposure could disrupt the endogenous sex hormones homeostasis in children, thereby combinedly increased risks of childhood HBP.
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Affiliation(s)
- Yanhui Dong
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
| | - Li Chen
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
| | - Di Gao
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
| | - Yanhui Li
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
| | - Manman Chen
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
| | - Tao Ma
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
| | - Ying Ma
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
| | - Jieyu Liu
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
| | - Yi Zhang
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
| | - Qi Ma
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
| | - Xinxin Wang
- School of Public Health and Management, Ningxia Medical University, Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, Shengli Street, Xingqing District, 750004, China
| | - Yi Song
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China.
| | - Zhiyong Zou
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China.
| | - Jun Ma
- Institute of Child and Adolescent Health, School of Public Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
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Estrogen normalizes maternal HFD-induced vascular dysfunction in offspring by regulating ATR. Hypertens Res 2022; 45:1743-1753. [PMID: 35999282 DOI: 10.1038/s41440-022-01002-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/23/2022] [Accepted: 07/15/2022] [Indexed: 12/26/2022]
Abstract
Previous studies have shown that female offspring are resistant to fetal high-fat diet (HFD)-induced programming of heightened vascular contraction; however, the underlying mechanisms remain unclear. The present study tested the hypothesis that estrogen plays a key role in protecting females from fetal programming of increased vascular contraction induced by maternal HFD exposure. Pregnant rats were fed a normal diet (ND) or HFD (60% kcal from fat). Ovariectomy (OVX) and 17β-estradiol (E2) replacement were performed on 8-week-old female offspring. Aortas were isolated from adult female offspring. Maternal HFD exposure increased angiotensin II (Ang II)-induced contractions of the aorta in adult OVX offspring, which was abrogated by E2 replacement. The AT1 receptor (AT1R) antagonist losartan (10 μM), but not the AT2 receptor (AT2R) antagonist PD123319 (10 μM), completely blocked Ang II-induced contractions in both ND and HFD offspring. In addition, HFD exposure caused a decrease in endothelium-dependent relaxations induced by acetylcholine (ACh) in adult OVX but not OVX-E2 offspring. However, it had no effect on sodium nitroprusside (SNP)-induced endothelium-independent aorta relaxation in any of the six groups. Maternal HFD feeding increased AT1R, but not AT2R, leading to an increased AT1R/AT2R ratio in HFD-exposed OVX offspring, associated with selective decreases in DNA methylation at the AT1aR promoter, which was ameliorated by E2 replacement. Our results indicated that estrogen play a key role in sex differences of maternal HFD-induced vascular dysfunction and development of hypertensive phenotype in adulthood by differently regulating vascular AT1R and AT2R gene expression through a DNA methylation mechanism.
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Tang H, Xie Y, Zhu M, Jia J, Liu R, Shen Y, Zheng Y, Guo X, Miao D, Pei J. Estrone-Conjugated PEGylated Liposome Co-Loaded Paclitaxel and Carboplatin Improve Anti-Tumor Efficacy in Ovarian Cancer and Reduce Acute Toxicity of Chemo-Drugs. Int J Nanomedicine 2022; 17:3013-3041. [PMID: 35836838 PMCID: PMC9274295 DOI: 10.2147/ijn.s362263] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 06/27/2022] [Indexed: 12/29/2022] Open
Abstract
Purpose Ovarian cancer is the most lethal gynecologic malignancy. The combination of paclitaxel (PTX) and carboplatin (CBP) is the first-line remedy for clinical ovarian cancer. However, due to the limitations of adverse reaction and lacking of targeting ability, the chemotherapy of ovarian cancer is still poorly effective. Here, a novel estrone (ES)-conjugated PEGylated liposome co-loaded PTX and CBP (ES-PEG-Lip-PTX/CBP) was designed for overcoming the above disadvantages. Methods ES-PEG-Lip-PTX/CBP was prepared by film hydration method and could recognize estrogen receptor (ER) over-expressing on the surface of SKOV-3 cells. The characterizations, stability and in vitro release of ES-PEG-Lip-PTX/CBP were studied. In vitro cellular uptake and its mechanism were observed by fluorescence microscope. In vivo targeting effect in tumor-bearing mice was determined. Pharmacokinetics and biodistribution were studied in ICR mice. In vitro cytotoxicity and in vivo anti-tumor efficacy were evaluated on SKOV-3 cells and tumor-bearing mice, respectively. Finally, the acute toxicity in ICR mice was explored for assessing the preliminary safety of ES-PEG-Lip-PTX/CBP. Results Our results showed that ES-PEG-Lip-PTX/CBP was spherical shape without aggregation. ES-PEG-Lip-PTX/CBP exhibited the optimum targeting effect on uptake in vitro and in vivo. The pharmacokinetics demonstrated ES-PEG-Lip-PTX/CBP had improved the pharmacokinetic behavior. In vitro cytotoxicity showed that ES-PEG-Lip-PTX/CBP maximally inhibited SKOV-3 cell proliferation and its IC50 values was 1.6 times lower than that of non-ES conjugated liposomes at 72 h. The in vivo anti-tumor efficacy study demonstrated that ES-PEG-Lip-PTX/CBP could lead strong SKOV-3 tumor growth suppression with a tumor volume inhibitory rate of 81.8%. Meanwhile, acute toxicity studies confirmed that ES-PEG-Lip-PTX/CBP significantly reduced the toxicity of the chemo drugs. Conclusion ES-PEG-Lip-PTX/CBP was successfully prepared with an optimal physicochemical and ER targeting property. The data of pharmacokinetics, anti-tumor efficacy and safety study indicated that ES-PEG-Lip-PTX/CBP could become a promising therapeutic formulation for human ovarian cancer in the future clinic.
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Affiliation(s)
- Huan Tang
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China
| | - Yizhuo Xie
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China
| | - Ming Zhu
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China
| | - Juan Jia
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China
| | - Rui Liu
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China
| | - Yujia Shen
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China
| | - Yucui Zheng
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China
| | - Xin Guo
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China
| | - Dongfanghui Miao
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China
| | - Jin Pei
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China
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Yang W, Braun JM, Vuong AM, Percy Z, Xu Y, Xie C, Deka R, Calafat AM, Ospina M, Werner E, Yolton K, Cecil KM, Lanphear BP, Chen A. Maternal urinary OPE metabolite concentrations and blood pressure during pregnancy: The HOME study. ENVIRONMENTAL RESEARCH 2022; 207:112220. [PMID: 34656632 PMCID: PMC8810616 DOI: 10.1016/j.envres.2021.112220] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 10/11/2021] [Accepted: 10/12/2021] [Indexed: 05/03/2023]
Abstract
BACKGROUND Few studies have examined the association between maternal exposure to organophosphate esters (OPEs) and systolic/diastolic blood pressure (SBP/DBP) during pregnancy. METHODS We analyzed data from 346 women with a singleton live birth in the HOME Study, a prospective birth cohort in Cincinnati, Ohio, USA. We quantified four OPE metabolites in maternal spot urine samples collected at 16 and 26 weeks pregnancy, standardized by specific gravity. We calculated intraclass correlation coefficients (ICCs). We extracted the first two recorded BP measurements (<20 weeks), the two highest recorded BP measurements (≥20 weeks), and diagnoses of hypertensive disorders of pregnancy (HDP) via chart review. Women with two BP measurements ≥140/90 mmHg or HDP noted in the chart at ≥20 weeks pregnancy were defined as HDP cases. We used linear mixed models and modified Poisson regression with covariate adjustment to estimate associations between OPE concentrations as continuous variables or in tertiles with maternal BP and HDP. RESULTS ICCs of OPEs were 0.17-0.45. Diphenyl phosphate (DPHP) had the highest geometric mean concentration among OPE metabolites. Increasing the average bis(2-chloroethyl) phosphate (BCEP) concentrations were positively associated with two highest recorded DBP ≥20 weeks pregnancy. Compared with women in the 1st DPHP tertile, women in the 3rd tertile at 16 weeks pregnancy had 1.72 mmHg (95% CI: -0.01, 3.46) higher DBP <20 weeks pregnancy, and women in the 3rd tertile of the average DPHP concentrations had 2.25 mmHg (95% CI: 0.25, 4.25) higher DBP ≥20 weeks pregnancy. 33 women (9.5%) were identified with HDP. Di-n-butyl phosphate (DNBP) concentrations at 16 weeks were positively associated with HDP, with borderline significance (RR = 2.98, 95% CI 0.97-9.15). Other OPE metabolites were not significantly associated with HDP. CONCLUSION Maternal urinary BCEP and DPHP concentrations were associated with increased BP during pregnancy. Maternal urinary DNBP concentrations were associated with HDP, with borderline significance.
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Affiliation(s)
- Weili Yang
- Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Joseph M Braun
- Department of Epidemiology, Brown University, Providence, RI, USA
| | - Ann M Vuong
- Department of Epidemiology and Biostatistics, University of Nevada Las Vegas, Las Vegas, NV, USA
| | - Zana Percy
- Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Yingying Xu
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Changchun Xie
- Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Ranjan Deka
- Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Antonia M Calafat
- National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Maria Ospina
- National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Erika Werner
- Department of Epidemiology, Brown University, Providence, RI, USA; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Women and Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Kimberly Yolton
- Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Kim M Cecil
- Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Bruce P Lanphear
- Child and Family Research Institute, BC Children's Hospital, Vancouver, BC, Canada; Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
| | - Aimin Chen
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA.
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Koriem KMM. Fertaric acid amends bisphenol A-induced toxicity, DNA breakdown, and histopathological changes in the liver, kidney, and testis. World J Hepatol 2022; 14:535-550. [PMID: 35582291 PMCID: PMC9055189 DOI: 10.4254/wjh.v14.i3.535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/10/2021] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bisphenol A (BPA) is present in many plastic products and food packaging. On the other hand, fertaric acid (FA) is a hydroxycinnamic acid. AIM To investigate the effect of FA on BPA-related liver, kidney, and testis toxicity, DNA breakdown, and histopathology in male rats. METHODS Thirty male albino rats were divided into five equal groups (6 rats/group): Control, paraffin oil, FA-, BPA-, and FA + BPA-treated groups. The control and paraffin oil groups were administered orally with 1 mL distilled water and 1 mL paraffin oil, respectively. The FA-, BPA-, and FA+ BPA-treated groups were administered orally with FA (45 mg/kg, bw) dissolved in 1 mL distilled water, BPA (4 mg/kg, bw) dissolved in 1 mL paraffin oil, and FA (45 mg/kg, bw) followed by BPA (4 mg/kg, bw), respectively. All these treatments were given once a day for 6 wk. RESULTS BPA induced a significant decrease in serum alkaline phosphatase, acid phosphatase, sodium, potassium and chloride, testosterone, dehydroepiandrosterone sulfate, glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, and testis protein levels but a highly significant increase in serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, lactate dehydrogenase, bilirubin, urea, creatinine, uric acid, luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin, blood urea nitrogen, and testis cholesterol levels. Also, FA inhibited the degradation of liver, kidney, and testis DNA content. Oral administration of FA to BPA-treated rats restored all the above parameters to normal levels. CONCLUSION FA ameliorates BPA-induced liver, kidney, and testis toxicity, DNA breakdown, and histopathological changes.
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Mączka W, Grabarczyk M, Wińska K. Can Antioxidants Reduce the Toxicity of Bisphenol? Antioxidants (Basel) 2022; 11:antiox11020413. [PMID: 35204295 PMCID: PMC8869647 DOI: 10.3390/antiox11020413] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 02/14/2022] [Accepted: 02/16/2022] [Indexed: 12/18/2022] Open
Abstract
BPA is still the subject of extensive research due to its widespread use, despite its significant toxicity resulting not only from its negative impact on the endocrine system but also from disrupting the organism’s oxidative homeostasis. At the molecular level, bisphenol A (BPA) causes an increased production of ROS and hence a change in the redox balance, mitochondrial dysfunction, and modulation of cell signaling pathways. Importantly, these changes accumulate in animals and humans, and BPA toxicity may be aggravated by poor diet, metabolic disorders, and coexisting diseases. Accordingly, approaches using antioxidants to counteract the negative effects of BPA are being considered. The preliminary results that are described in this paper are promising, however, it should be emphasized that further studies are required to determine the optimal dosage and treatment regimen to counteract BPA toxicity. It also seems necessary to have a more holistic approach showing, on the one hand, the influence of BPA on the overall human metabolism and, on the other hand, the influence of antioxidants in doses that are acceptable with the diet on BPA toxicity. This is due in part to the fact that in many cases, the positive effect of antioxidants in in vitro studies is not confirmed by clinical studies. For this reason, further research into the molecular mechanisms of BPA activity is also recommended.
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Carli F, Ciociaro D, Gastaldelli A. Assessment of Exposure to Di-(2-ethylhexyl) Phthalate (DEHP) Metabolites and Bisphenol A (BPA) and Its Importance for the Prevention of Cardiometabolic Diseases. Metabolites 2022; 12:167. [PMID: 35208241 PMCID: PMC8878475 DOI: 10.3390/metabo12020167] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/26/2022] [Accepted: 02/04/2022] [Indexed: 02/04/2023] Open
Abstract
Exposomics analyses have highlighted the importance of biomonitoring of human exposure to pollutants, even non-persistent, for the prevention of non-communicable diseases such as obesity, diabetes, non-alcoholic fatty liver disease, atherosclerosis, and cardiovascular diseases. Phthalates and bisphenol A (BPA) are endocrine disrupting chemicals (EDCs) widely used in industry and in a large range of daily life products that increase the risk of endocrine and cardiometabolic diseases especially if the exposure starts during childhood. Thus, biomonitoring of exposure to these compounds is important not only in adulthood but also in childhood. This was the goal of the LIFE-PERSUADED project that measured the exposure to phthalates (DEHP metabolites, MEHP, MEHHP, MEOHP) and BPA in Italian mother-children couples of different ages. In this paper we describe the method that was set up for the LIFE PERSUADED project and validated during the proficiency test (ICI/EQUAS) showing that accurate determination of urinary phthalates and BPA can be achieved starting from small sample size (0.5 mL) using two MS techniques applied in cascade on the same deconjugated matrix.
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Affiliation(s)
| | | | - Amalia Gastaldelli
- Institute of Clinical Physiology, National Research Council, Via Giuseppe Moruzzi 1, 56124 Pisa, Italy; (F.C.); (D.C.)
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Sahebnasagh A, Saghafi F, Negintaji S, Hu T, Shabani-Borujeni M, Safdari M, Ghaleno HR, Miao L, Qi Y, Wang M, Liao P, Sureda A, Simal-Gándara J, Nabavi SM, Xiao J. Nitric Oxide and Immune Responses in Cancer: Searching for New Therapeutic Strategies. Curr Med Chem 2022; 29:1561-1595. [PMID: 34238142 DOI: 10.2174/0929867328666210707194543] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 05/05/2021] [Accepted: 05/15/2021] [Indexed: 02/08/2023]
Abstract
In recent years, there has been an increasing interest in understanding the mysterious functions of nitric oxide (NO) and how this pleiotropic signaling molecule contributes to tumorigenesis. This review attempts to expose and discuss the information available on the immunomodulatory role of NO in cancer and recent approaches to the role of NO donors in the area of immunotherapy. To address the goal, the following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane Library, Pubmed, Medline, and EMBASE from 1980 through March 2020. Valuable attempts have been made to develop distinctive NO-based cancer therapy. Although the data do not allow generalization, the evidence seems to indicate that low/moderate levels may favor tumorigenesis, while higher levels would exert antitumor effects. In this sense, the use of NO donors could have an important therapeutic potential within immunotherapy, although there are still no clinical trials. The emerging understanding of NO-regulated immune responses in cancer may help unravel the recent features of this "doubleedged sword" in cancer physiological and pathologic processes and its potential use as a therapeutic agent for cancer treatment. In short, in this review, we discuss the complex cellular mechanism in which NO, as a pleiotropic signaling molecule, participates in cancer pathophysiology. We also debate the dual role of NO in cancer and tumor progression and clinical approaches for inducible nitric oxide synthase (iNOS) based therapy against cancer.
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Affiliation(s)
- Adeleh Sahebnasagh
- Clinical Research Center, Department of Internal Medicine, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Fatemeh Saghafi
- Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Sina Negintaji
- Student Research Committee, School of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Tingyan Hu
- School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong
| | - Mojtaba Shabani-Borujeni
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammadreza Safdari
- Department of Orthopedic Surgery, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Hassan Rezai Ghaleno
- Department of Surgery, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Lingchao Miao
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao
| | - Yaping Qi
- Purdue Quantum Science and Engineering Institute, Purdue University, West Lafayette, IN 47907, USA
| | - Mingfu Wang
- School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong
| | - Pan Liao
- Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA
| | - Antoni Sureda
- Research Group on Community Nutrition and Oxidative Stress, and Balearic Islands Health Research Institute (IdISBa), University of the Balearic Islands, Palma de Mallorca, Spain
- CIBEROBN (Physiopathology of Obesity and Nutrition CB12/03/30038), Instituto de Salud Carlos III, Madrid, Spain
| | - Jesus Simal-Gándara
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Spain
| | - Seyed Mohammad Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Spain
- International Research Centre for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
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Querio G, Antoniotti S, Geddo F, Tullio F, Penna C, Pagliaro P, Gallo MP. Ischemic heart disease and cardioprotection: Focus on estrogenic hormonal setting and microvascular health. Vascul Pharmacol 2021; 141:106921. [PMID: 34592428 DOI: 10.1016/j.vph.2021.106921] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/14/2021] [Accepted: 09/23/2021] [Indexed: 12/12/2022]
Abstract
Ischemic Heart Disease (IHD) is a clinical condition characterized by insufficient blood flow to the cardiac tissue, and the consequent inappropriate oxygen and nutrients supply and metabolic waste removal in the heart. In the last decade a broad scientific literature has underlined the distinct mechanism of onset and the peculiar progress of IHD between female and male patients, highlighting the estrogenic hormonal setting as a key factor of these sex-dependent divergences. In particular, estrogen-activated cardioprotective pathways exert a pivotal role for the microvascular health, and their impairment, both physiologically and pathologically driven, predispose to vascular dysfunctions. Aim of this review is to summarize the current knowledge on the estrogen receptors localization and function in the cardiovascular system, particularly focusing on sex-dependent differences in microvascular vs macrovascular dysfunction and on the experimental models that allowed the researchers to reach the current findings and sketching the leading estrogen-mediated cardioprotective mechanisms.
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Affiliation(s)
- Giulia Querio
- Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy
| | - Susanna Antoniotti
- Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy
| | - Federica Geddo
- Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy
| | - Francesca Tullio
- Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
| | - Claudia Penna
- Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
| | - Pasquale Pagliaro
- Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.
| | - Maria Pia Gallo
- Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy.
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Nasser SA, Afify EA, Kobeissy F, Hamam B, Eid AH, El-Mas MM. Inflammatory Basis of Atherosclerosis: Modulation by Sex Hormones. Curr Pharm Des 2021; 27:2099-2111. [PMID: 33480335 DOI: 10.2174/1381612827666210122142811] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 12/17/2020] [Indexed: 11/22/2022]
Abstract
Atherosclerosis-related cardiovascular diseases (CVDs) are the leading cause of death globally. Several lines of evidence are supportive of the contributory role of vascular inflammation in atherosclerosis. Diverse immune cell types, including monocytes/macrophages, T-cells and neutrophils, as well as specialized proresolving lipid mediators, have been successfully characterized as key players in vascular inflammation. The increased prevalence of atherosclerotic CVD in men in comparison to age-matched premenopausal women and the abolition of sex differences in prevalence during menopause strongly suggest a pivotal role of sex hormones in the development of CVD. Indeed, many animal and human studies conclusively implicate sex hormones as a crucial component in driving the immune response. This is further corroborated by the effective identification of sex hormone receptors in vascular endothelial cells, vascular smooth muscle cells and immune cells. Collectively, these findings suggest a cellular communication between sex hormones and vascular or immune cells underlying the vascular inflammation in atherosclerosis. The aim of this review is to provide an overview of vascular inflammation as a causal cue underlying atherosclerotic CVDs within the context of the modulatory effects of sex hormones. Moreover, the cellular and molecular signaling pathways underlying the sex hormones- immune system interactions as potential culprits for vascular inflammation are highlighted with detailed and critical discussion. Finally, the review concludes by speculations on the potential sex-related efficacy of currently available immunotherapies in mitigating vascular inflammation. Conceivably, a deeper understanding of the immunoregulatory influence of sex hormones on vascular inflammation-mediated atherosclerosis permits sex-based management of atherosclerosis-related CVDs.
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Affiliation(s)
- Suzanne A Nasser
- Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, P.O. Box 11-5020, Beirut, Lebanon
| | - Elham A Afify
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Firas Kobeissy
- Department of Biochemistry and Molecular Genetics, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon
| | - Bassam Hamam
- Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, P.O. Box 146404, Beirut, Lebanon
| | - Ali H Eid
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Mahmoud M El-Mas
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
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El-Dahan KS, Machtoub D, Massoud G, Nasser SA, Hamam B, Kobeissy F, Zouein FA, Eid AH. Cannabinoids and myocardial ischemia: Novel insights, updated mechanisms, and implications for myocardial infarction. Curr Med Chem 2021; 29:1990-2010. [PMID: 34102966 DOI: 10.2174/0929867328666210608144818] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/13/2021] [Accepted: 04/14/2021] [Indexed: 11/22/2022]
Abstract
Cannabis is the most widely trafficked and abused illicit drug due to its calming psychoactive properties. It has been increasingly recognized as having potential health benefits and relatively less adverse health effects as compared to other illicit drugs; however, growing evidence clearly indicates that cannabis is associated with considerable adverse cardiovascular events. Recent studies have linked cannabis use to myocardial infarction (MI); yet, very little is known about the underlying mechanisms. A MI is a cardiovascular disease characterized by a mismatch in the oxygen supply and demand of the heart, resulting in ischemia and subsequent necrosis of the myocardium. Since cannabis is increasingly being considered a risk factor for MI, there is a growing need for better appreciating its potential health benefits and consequences. Here, we discuss the cellular mechanisms of cannabis that lead to an increased risk of MI. We provide a thorough and critical analysis of cannabinoids' actions, which include modulation of adipocyte biology, regional fat distribution, and atherosclerosis, as well as precipitation of hemodynamic stressors relevant in the setting of a MI. By critically dissecting the modulation of signaling pathways in multiple cell types, this paper highlights the mechanisms through which cannabis may trigger life-threatening cardiovascular events. This then provides a framework for future pharmacological studies which can identify targets or develop drugs that modulate cannabis' effects on the cardiovascular system as well as other organ systems. Cannabis' impact on the autonomic outflow, vascular smooth muscle cells, myocardium, cortisol levels and other hemodynamic changes are also mechanistically reviewed.
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Affiliation(s)
- Karim Seif El-Dahan
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Lebanon
| | - Dima Machtoub
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Lebanon
| | - Gaelle Massoud
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Lebanon
| | - Suzanne A Nasser
- Department of Pharmacology and Therapeutics, Beirut Arab University, P.O. Box 11-5020, Beirut, Lebanon
| | - Bassam Hamam
- Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, P.O. Box 146404, Beirut, Lebanon
| | - Firas Kobeissy
- Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon
| | - Fouad A Zouein
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Lebanon
| | - Ali H Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha. Qatar
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García-Arévalo M, Lorza-Gil E, Cardoso L, Batista TM, Araujo TR, Ramos LAF, Areas MA, Nadal A, Carneiro EM, Davel AP. Ventricular Fibrosis and Coronary Remodeling Following Short-Term Exposure of Healthy and Malnourished Mice to Bisphenol A. Front Physiol 2021; 12:638506. [PMID: 33912069 PMCID: PMC8072349 DOI: 10.3389/fphys.2021.638506] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 03/03/2021] [Indexed: 11/15/2022] Open
Abstract
Bisphenol-A (BPA) is an endocrine disruptor associated with higher risk of insulin resistance, type 2 diabetes, and cardiovascular diseases especially in susceptible populations. Because malnutrition is a nutritional disorder associated with high cardiovascular risk, we sought to compare the effects of short-term BPA exposure on cardiovascular parameters of healthy and protein-malnourished mice. Postweaned male mice were fed a normo- (control) or low-protein (LP) diet for 8 weeks and then exposed or not to BPA (50 μg kg−1 day−1) for the last 9 days. Systolic blood pressure was higher in BPA or LP groups compared with the control group. However, diastolic blood pressure was enhanced by BPA only in malnourished mice. Left ventricle (LV) end diastolic pressure (EDP), collagen deposition, and CTGF mRNA expression were higher in the control or malnourished mice exposed to BPA than in the respective nonexposed groups. Nevertheless, mice fed LP diet exposed to BPA exhibited higher angiotensinogen and cardiac TGF-β1 mRNA expression than mice treated with LP or BPA alone. Wall:lumen ratio and cross-sectional area of intramyocardial arteries were higher either in the LP or BPA group compared with the control mice. Taken together, our data suggest that short-term BPA exposure results in LV diastolic dysfunction and fibrosis, and intramyocardial arteries inward remodeling, besides potentiate protein malnutrition-induced hypertension and cardiovascular risk.
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Affiliation(s)
- Marta García-Arévalo
- Department of Structural and Functional Biology, Institute of Biology, Campinas, Brazil.,Obesity and Comorbidities Research Center-OCRC, UNICAMP, Campinas, Brazil
| | - Estela Lorza-Gil
- Department of Structural and Functional Biology, Institute of Biology, Campinas, Brazil.,Obesity and Comorbidities Research Center-OCRC, UNICAMP, Campinas, Brazil
| | - Leandro Cardoso
- Department of Structural and Functional Biology, Institute of Biology, Campinas, Brazil
| | - Thiago Martins Batista
- Department of Structural and Functional Biology, Institute of Biology, Campinas, Brazil.,Obesity and Comorbidities Research Center-OCRC, UNICAMP, Campinas, Brazil
| | - Thiago Reis Araujo
- Department of Structural and Functional Biology, Institute of Biology, Campinas, Brazil.,Obesity and Comorbidities Research Center-OCRC, UNICAMP, Campinas, Brazil
| | | | - Miguel Arcanjo Areas
- Department of Structural and Functional Biology, Institute of Biology, Campinas, Brazil
| | - Angel Nadal
- Instituto de Biología Molecular y Celular, Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche, Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders, Universidad Miguel Hernández, Elche, Spain
| | - Everardo Magalhães Carneiro
- Department of Structural and Functional Biology, Institute of Biology, Campinas, Brazil.,Obesity and Comorbidities Research Center-OCRC, UNICAMP, Campinas, Brazil
| | - Ana Paula Davel
- Department of Structural and Functional Biology, Institute of Biology, Campinas, Brazil
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Endocrine-Disrupting Chemicals and Infectious Diseases: From Endocrine Disruption to Immunosuppression. Int J Mol Sci 2021; 22:ijms22083939. [PMID: 33920428 PMCID: PMC8069594 DOI: 10.3390/ijms22083939] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/07/2021] [Accepted: 04/08/2021] [Indexed: 01/08/2023] Open
Abstract
Endocrine-disrupting chemicals (EDCs) are hormonally active compounds in the environment that interfere with the body's endocrine system and consequently produce adverse health effects. Despite persistent public health concerns, EDCs remain important components of common consumer products, thus representing ubiquitous contaminants to humans. While scientific evidence confirmed their contribution to the severity of Influenza A virus (H1N1) in the animal model, their roles in susceptibility and clinical outcome of the coronavirus disease (COVID-19) cannot be underestimated. Since its emergence in late 2019, clinical reports on COVID-19 have confirmed that severe disease and death occur in persons aged ≥65 years and those with underlying comorbidities. Major comorbidities of COVID-19 include diabetes, obesity, cardiovascular disease, hypertension, cancer, and kidney and liver diseases. Meanwhile, long-term exposure to EDCs contributes significantly to the onset and progression of these comorbid diseases. Besides, EDCs play vital roles in the disruption of the body's immune system. Here, we review the recent literature on the roles of EDCs in comorbidities contributing to COVID-19 mortality, impacts of EDCs on the immune system, and recent articles linking EDCs to COVID-19 risks. We also recommend methodologies that could be adopted to comprehensively study the role of EDCs in COVID-19 risk.
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Makowska K, Gonkowski S. Changes Caused by Low Doses of Bisphenol A (BPA) in the Neuro-Chemistry of Nerves Located in the Porcine Heart. Animals (Basel) 2021; 11:ani11030780. [PMID: 33799766 PMCID: PMC7999793 DOI: 10.3390/ani11030780] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/07/2021] [Accepted: 03/08/2021] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Bisphenol A (BPA) is a substance commonly used in the plastics industry, which is a part of many everyday items. It may leach from plastics and penetrate food, water, soil and air. It is known that BPA negatively affects living organisms. It impairs the functions of the intestine, neurons, reproductive organs, endocrine glands and immune cells. Previous studies have also reported that BPA negatively influences the cardiovascular system, leading to heart arrhythmia, intensification of atherosclerosis, blood hypertension and increased risk of a heart attack. However, many aspects of the influence of BPA on the heart are still poorly understood. One of these aspects is the BPA impact on heart innervation. Therefore, this article aimed to investigate the influence of low doses of BPA on the number of nerves containing selected active substances taking part in neuronal stimuli conduction located in the porcine heart apex. The results indicate that even relatively low doses of BPA are not neutral to the cardiovascular system, because they affect the neurochemical characterization of nerves in the heart. These changes may underlie the negative effects of BPA on the heart. Abstract Bisphenol A (BPA) contained in plastics used in the production of various everyday objects may leach from these items and contaminate food, water and air. As an endocrine disruptor, BPA negatively affects many internal organs and systems. Exposure to BPA also contributes to heart and cardiovascular system dysfunction, but many aspects connected with this activity remain unknown. Therefore, this study aimed to investigate the impact of BPA in a dose of 0.05 mg/kg body weight/day (in many countries such a dose is regarded as a tolerable daily intake–TDI dose of BPA–completely safe for living organisms) on the neurochemical characterization of nerves located in the heart wall using the immunofluorescence technique. The obtained results indicate that BPA (even in such a relatively low dose) increases the number of nerves immunoreactive to neuropeptide Y, substance P and tyrosine hydroxylase (used here as a marker of sympathetic innervation). However, BPA did not change the number of nerves immunoreactive to vesicular acetylcholine transporter (used here as a marker of cholinergic structures). These observations suggest that changes in the heart innervation may be at the root of BPA-induced circulatory disturbances, as well as arrhythmogenic and/or proinflammatory effects of this endocrine disruptor. Moreover, changes in the neurochemical characterization of nerves in the heart wall may be the first sign of exposure to BPA.
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Affiliation(s)
- Krystyna Makowska
- Department of Clinical Diagnostics, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 14, 10-957 Olsztyn, Poland
- Correspondence: ; Tel.: +48-44895234460
| | - Slawomir Gonkowski
- Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-957 Olsztyn, Poland;
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Tsen CM, Liu JH, Yang DP, Chao HR, Chen JL, Chou WC, Ho YC, Chuang CY. Study on the correlation of bisphenol A exposure, pro-inflammatory gene expression, and C-reactive protein with potential cardiovascular disease symptoms in young adults. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:10.1007/s11356-021-12805-0. [PMID: 33625709 DOI: 10.1007/s11356-021-12805-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 02/01/2021] [Indexed: 06/12/2023]
Abstract
Bisphenol A (BPA) is a plasticizer used in the manufacture of polycarbonate and epoxy resins. It was found that higher urinary BPA levels are more likely to be associated with coronary artery disease (CVD). In recent years, the increasing incidence of CVD among young people is observed, which may be related with inflammation rather than the traditional triple-H risk factors. BPA is an endocrine-disrupting chemical, and can induce oxidative stress and chronic inflammation since its estrogenic effect. Inflammatory responses could come from the stimulation of IκB kinases (IKKs) by estrogen receptors (ERs). Therefore, this study investigated the association of BPA exposure with the gene expression of pro-inflammatory response (ERs and IKKs), an inflammation biomarker of CVD (C-reactive protein, CRP), and physiologic index potency of CVD development symptoms in young adults. This study divided BPA exposure levels into high and low groups based on the median plasma BPA level (4.34 ng/mL), and found that the high BPA group obviously had higher BMI, blood pressure, plasma CRP levels, and gene expression of ERβ and IKKβ. BMI and gene expression of IKKβ were also positively correlated with plasma CRP secretion. Furthermore, the study subjects with potential CVD development symptoms had the increased levels of BPA (OR 2.10, 95% CI 0.83-5.39), CRP (OR 2.61, 95% CI 1.03-10.6) and IKKβ (OR 4.29, 95% CI 1.51-15.6). These results indicated that exposure to BPA is potentially associated with expression of pro-inflammatory genes related to CRP secretion, which may promote the risk of CVD development symptoms in young adults. This study highlighted the possible connection between BPA exposure and CVD development but the mechanism between them needs to be further explored.
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Affiliation(s)
- Chao-Ming Tsen
- Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Sec. 2 Kuang-Fu Road, Hsinchu, 300, Taiwan
- Residue Control Division, Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Taichung, Taiwan
| | - Jia-Hong Liu
- Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Sec. 2 Kuang-Fu Road, Hsinchu, 300, Taiwan
| | - Da-Peng Yang
- Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Sec. 2 Kuang-Fu Road, Hsinchu, 300, Taiwan
| | - How-Ran Chao
- Emerging Compounds Research Center, Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Pingtung County, Taiwan
| | - Jyh-Larng Chen
- Department of Environmental Engineering and Health, College of Health Science, Yuanpei University, Hsinchu, Taiwan
| | - Wei-Chun Chou
- Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Sec. 2 Kuang-Fu Road, Hsinchu, 300, Taiwan
- Institute of Computational Comparative Medicine, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United States
| | - Yi-Chen Ho
- Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Sec. 2 Kuang-Fu Road, Hsinchu, 300, Taiwan
- Service System Technology Center, Industrial Technology Research Institute, Hsinchu, Taiwan
| | - Chun-Yu Chuang
- Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Sec. 2 Kuang-Fu Road, Hsinchu, 300, Taiwan.
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Reactive Oxygen Species: Modulators of Phenotypic Switch of Vascular Smooth Muscle Cells. Int J Mol Sci 2020; 21:ijms21228764. [PMID: 33233489 PMCID: PMC7699590 DOI: 10.3390/ijms21228764] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 09/29/2020] [Accepted: 10/07/2020] [Indexed: 02/07/2023] Open
Abstract
Reactive oxygen species (ROS) are natural byproducts of oxygen metabolism in the cell. At physiological levels, they play a vital role in cell signaling. However, high ROS levels cause oxidative stress, which is implicated in cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and restenosis after angioplasty. Despite the great amount of research conducted to identify the role of ROS in CVD, the image is still far from being complete. A common event in CVD pathophysiology is the switch of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. Interestingly, oxidative stress is a major contributor to this phenotypic switch. In this review, we focus on the effect of ROS on the hallmarks of VSMC phenotypic switch, particularly proliferation and migration. In addition, we speculate on the underlying molecular mechanisms of these cellular events. Along these lines, the impact of ROS on the expression of contractile markers of VSMCs is discussed in depth. We conclude by commenting on the efficiency of antioxidants as CVD therapies.
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Flavonoids in adipose tissue inflammation and atherosclerosis: one arrow, two targets. Clin Sci (Lond) 2020; 134:1403-1432. [PMID: 32556180 DOI: 10.1042/cs20200356] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 06/09/2020] [Accepted: 06/10/2020] [Indexed: 02/07/2023]
Abstract
Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.
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Wehbe N, Slika H, Mesmar J, Nasser SA, Pintus G, Baydoun S, Badran A, Kobeissy F, Eid AH, Baydoun E. The Role of Epac in Cancer Progression. Int J Mol Sci 2020; 21:ijms21186489. [PMID: 32899451 PMCID: PMC7555121 DOI: 10.3390/ijms21186489] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/28/2020] [Accepted: 07/29/2020] [Indexed: 12/14/2022] Open
Abstract
Cancer continues to be a prime contributor to global mortality. Despite tremendous research efforts and major advances in cancer therapy, much remains to be learned about the underlying molecular mechanisms of this debilitating disease. A better understanding of the key signaling events driving the malignant phenotype of cancer cells may help identify new pharmaco-targets. Cyclic adenosine 3',5'-monophosphate (cAMP) modulates a plethora of biological processes, including those that are characteristic of malignant cells. Over the years, most cAMP-mediated actions were attributed to the activity of its effector protein kinase A (PKA). However, studies have revealed an important role for the exchange protein activated by cAMP (Epac) as another effector mediating the actions of cAMP. In cancer, Epac appears to have a dual role in regulating cellular processes that are essential for carcinogenesis. In addition, the development of Epac modulators offered new routes to further explore the role of this cAMP effector and its downstream pathways in cancer. In this review, the potentials of Epac as an attractive target in the fight against cancer are depicted. Additionally, the role of Epac in cancer progression, namely its effect on cancer cell proliferation, migration/metastasis, and apoptosis, with the possible interaction of reactive oxygen species (ROS) in these phenomena, is discussed with emphasis on the underlying mechanisms and pathways.
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Affiliation(s)
- Nadine Wehbe
- Department of Biology, American University of Beirut, P.O. Box 11-0236 Beirut, Lebanon; (N.W.); (J.M.)
| | - Hasan Slika
- Department of Pharmacology and Therapeutics, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236 Beirut, Lebanon;
| | - Joelle Mesmar
- Department of Biology, American University of Beirut, P.O. Box 11-0236 Beirut, Lebanon; (N.W.); (J.M.)
| | - Suzanne A. Nasser
- Department of Pharmacology, Beirut Arab University, P.O. Box 11-5020 Beirut, Lebanon;
| | - Gianfranco Pintus
- Department of Biomedical Sciences, University of Sharjah, P.O. Box 27272 Sharjah, UAE;
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43, 07100 Sassari, Italy
| | - Serine Baydoun
- Department of Radiology, American University of Beirut, P.O. Box 11-0236 Beirut, Lebanon;
| | - Adnan Badran
- Department of Basic Sciences, University of Petra, P.O. Box 961343, Amman 11196, Jordan;
| | - Firas Kobeissy
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon;
| | - Ali H. Eid
- Department of Pharmacology and Therapeutics, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236 Beirut, Lebanon;
- Department of Pharmacology and Therapeutics, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon
- Correspondence: (A.H.E.); (E.B.); Tel.: +961-1-350-000 (ext. 4891) (A.H.E. & E.B.)
| | - Elias Baydoun
- Department of Biology, American University of Beirut, P.O. Box 11-0236 Beirut, Lebanon; (N.W.); (J.M.)
- Correspondence: (A.H.E.); (E.B.); Tel.: +961-1-350-000 (ext. 4891) (A.H.E. & E.B.)
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Cimmino I, Fiory F, Perruolo G, Miele C, Beguinot F, Formisano P, Oriente F. Potential Mechanisms of Bisphenol A (BPA) Contributing to Human Disease. Int J Mol Sci 2020; 21:E5761. [PMID: 32796699 PMCID: PMC7460848 DOI: 10.3390/ijms21165761] [Citation(s) in RCA: 235] [Impact Index Per Article: 47.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/06/2020] [Accepted: 08/07/2020] [Indexed: 12/19/2022] Open
Abstract
Bisphenol A (BPA) is an organic synthetic compound serving as a monomer to produce polycarbonate plastic, widely used in the packaging for food and drinks, medical devices, thermal paper, and dental materials. BPA can contaminate food, beverage, air, and soil. It accumulates in several human tissues and organs and is potentially harmful to human health through different molecular mechanisms. Due to its hormone-like properties, BPA may bind to estrogen receptors, thereby affecting both body weight and tumorigenesis. BPA may also affect metabolism and cancer progression, by interacting with GPR30, and may impair male reproductive function, by binding to androgen receptors. Several transcription factors, including PPARγ, C/EBP, Nrf2, HOX, and HAND2, are involved in BPA action on fat and liver homeostasis, the cardiovascular system, and cancer. Finally, epigenetic changes, such as DNA methylation, histones modification, and changes in microRNAs expression contribute to BPA pathological effects. This review aims to provide an extensive and comprehensive analysis of the most recent evidence about the potential mechanisms by which BPA affects human health.
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Affiliation(s)
| | | | | | | | | | - Pietro Formisano
- Department of Translational Medicine, Federico II University of Naples and URT “Genomic of Diabetes” of Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), 80131 Naples, Italy; (I.C.); (F.F.); (G.P.); (C.M.); (F.B.); (F.O.)
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EPAC in Vascular Smooth Muscle Cells. Int J Mol Sci 2020; 21:ijms21145160. [PMID: 32708284 PMCID: PMC7404248 DOI: 10.3390/ijms21145160] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 07/09/2020] [Accepted: 07/19/2020] [Indexed: 02/07/2023] Open
Abstract
Vascular smooth muscle cells (VSMCs) are major components of blood vessels. They regulate physiological functions, such as vascular tone and blood flow. Under pathological conditions, VSMCs undergo a remodeling process known as phenotypic switching. During this process, VSMCs lose their contractility and acquire a synthetic phenotype, where they over-proliferate and migrate from the tunica media to the tunica interna, contributing to the occlusion of blood vessels. Since their discovery as effector proteins of cyclic adenosine 3′,5′-monophosphate (cAMP), exchange proteins activated by cAMP (EPACs) have been shown to play vital roles in a plethora of pathways in different cell systems. While extensive research to identify the role of EPAC in the vasculature has been conducted, much remains to be explored to resolve the reported discordance in EPAC’s effects. In this paper, we review the role of EPAC in VSMCs, namely its regulation of the vascular tone and phenotypic switching, with the likely involvement of reactive oxygen species (ROS) in the interplay between EPAC and its targets/effectors.
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