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Hajsadeghi S, Iranpour A, Mirshafiee S, Nekouian R, Mollababaei M, Motevalli H, Yasin Ahmadi SA, Dakkali MS. Impact of smoking on microRNAs in significant coronary artery disease. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2025; 63:49-59. [PMID: 39543851 DOI: 10.2478/rjim-2024-0031] [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: 09/05/2024] [Indexed: 11/17/2024]
Abstract
BACKGROUND Given the importance of coronary artery disease (CAD) and the range of cardiovascular disease phenotypes in smokers, as well as the potential genetic and epigenetic factors, we were motivated to explore the impact of smoking on some selected microRNAs associated with significant CAD. METHODS A total of 60 individuals were selected in four groups including non-smoker without significant CAD (S-A-), non-smokers with significant CAD (S-A+), smokers without significant CAD (S+A-) and smokers with significant CAD (S+A+). Micro-RNA expression was investigated using real-time PCR. General linear model was used to calculate fold change (FC) considering S-A- as the reference group. RESULTS For mir-34a, down-regulation was observed in S+A- (FC =0.13, P =0.007) and S+A+ (FC =0.23, P =0.036) groups. For mir-126-3p, down-regulation was observed in S-A+ group (FC =0.05, P =0.024). For mir-199, up-regulation was observed for S+A- group (FC =9.38, P =0.007). The only significant interaction between pack-years of smoking and number of significantly narrowed vessels (≥75% stenosis) was for mir-199 which was in favor of down-regulation (P =0.006), while the main effects were in favor of up-regulation (P <0.05). CONCLUSION Mir-34a expression may be affected by smoking, whereas mir-126-3p expression may be affected by atherosclerosis, the most common reason of CAD. The significant down-regulation of mir-199 for the interaction of smoking dose and severity of CAD was a notable finding showing the harmful consequence of this interaction. Further studies are needed for this micro-RNA.
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Affiliation(s)
- Shokoufeh Hajsadeghi
- Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Aida Iranpour
- Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Shayan Mirshafiee
- Department of Cardiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Nekouian
- Department of Medical Biotechnology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Mollababaei
- Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Hamed Motevalli
- Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Seyyed Amir Yasin Ahmadi
- Preventive Medicine and Public Health Research Center, Psychosocial Health Research Institute, Iran University of Medical Sciences, Tehran, Iran
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Lykkesfeldt J, Carr AC, Tveden-Nyborg P. The pharmacology of vitamin C. Pharmacol Rev 2025; 77:100043. [PMID: 39986139 DOI: 10.1016/j.pharmr.2025.100043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 01/14/2025] [Indexed: 02/24/2025] Open
Abstract
Ascorbic acid, the reduced form of vitamin C, is a ubiquitous small carbohydrate. Despite decades of focused research, new metabolic functions of this universal electron donor are still being discovered and add to the complexity of our view of vitamin C in human health. Although praised as an unsurpassed water-soluble antioxidant in plasma and cells, the most interesting functions of vitamin C seem to be its roles as specific electron donor in numerous biological reactions ranging from the well-known hydroxylation of proline to cofactor for the epigenetic master regulators ten-eleven translocation enzymes and Jumonji domain-containing histone-lysine demethylases. Some of these functions may have important implications for disease prevention and treatment and have spiked renewed interest in, eg, vitamin C's potential in cancer therapy. Moreover, some fundamental pharmacokinetic properties of vitamin C remain to be established including if other mechanisms than passive diffusion governs the efflux of ascorbate anions from the cell. Taken together, there still seems to be much to learn about the pharmacology of vitamin C and its role in health and disease. This review explores new avenues of vitamin C and integrates our present knowledge of its pharmacology. SIGNIFICANCE STATEMENT: Vitamin C is involved in multiple biological reactions of which most are essential to human health. Hundreds of millions of people are considered deficient in vitamin C according to accepted guidelines, but little is known about the long-term consequences. Although the complexity of vitamin C's physiology and pharmacology has been widely disregarded in clinical studies for decades, it seems clear that a deeper understanding of particularly its pharmacology holds the key to unravel and possibly exploit the potential of vitamin C in disease prevention and therapy.
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Affiliation(s)
- Jens Lykkesfeldt
- Section of Biomedicine, Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
| | - Anitra C Carr
- Nutrition in Medicine Research Group, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand
| | - Pernille Tveden-Nyborg
- Section of Biomedicine, Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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3
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Chen C, Huo C, Mattey-Mora PP, Bidulescu A, Parker MA. Assessing the association between e-cigarette use and cardiovascular disease: A meta-analysis of exclusive and dual use with combustible cigarettes. Addict Behav 2024; 157:108086. [PMID: 38917766 DOI: 10.1016/j.addbeh.2024.108086] [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: 02/22/2024] [Revised: 06/03/2024] [Accepted: 06/07/2024] [Indexed: 06/27/2024]
Abstract
BACKGROUND Growing evidence highlights the impact of e-cigarette use on cardiovascular health, prompting a crucial examination of its association with cardiovascular disease (CVD) in both exclusive e-cigarette and dual use scenarios with combustible cigarettes. This meta-analysis assessed the association between e-cigarette use and CVD by synthesizing the existing literature. METHODS Pertinent observational studies were identified using multiple electronic databases, from August 22nd, 2006, to April 10th, 2024. A meta-analysis was conducted using random-effect models. Risk of bias was assessed using the National Institutes of Health (NIH) Study Quality Assessment Tools. FINDINGS A total of 20 observational studies involving 8,499,444 participants were included in the meta-analysis. Dual use (e-cigarettes and combustible cigarette) increased the odds of CVD by 2.56 times (95 % CI: 2.11, 3.11) compared to never use of both. Current e-cigarette use combined with former combustible cigarette increased the odds of CVD by 2.02 times (95 % CI: 1.58, 2.58) compared to never use of either. Exclusive current e-cigarette use did not show a statistically significant association with CVD odds compared to never use of either (OR = 1.24, 95 % CI: 0.93, 1.67). CONCLUSIONS Dual use of e-cigarettes and combustible cigarettes was significantly associated with CVD, but results failed to show a significant association between exclusive e-cigarette use and CVD. Robust and longitudinal studies are needed to understand the long-term implications of e-cigarette use and CVD. Public health efforts should focus on awareness, smoking cessation, and regulating both e-cigarettes and combustible cigarettes.
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Affiliation(s)
- Chen Chen
- Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA.
| | - Cuiqiong Huo
- Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA.
| | - Paola P Mattey-Mora
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
| | - Aurelian Bidulescu
- Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA.
| | - Maria A Parker
- Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA.
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Yoo K, Park YS, Kim HJ, Kim JH. Association of smoking cessation with dynapenia among older lifetime smokers in Korea. Tob Induc Dis 2024; 22:TID-22-150. [PMID: 39220716 PMCID: PMC11365039 DOI: 10.18332/tid/191822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 07/30/2024] [Accepted: 08/02/2024] [Indexed: 09/04/2024] Open
Abstract
INTRODUCTION Muscle strength is known to play an important role in the health of older adults. The health burden of cigarette smoking among older adults remains significant. We investigated the association between smoking cessation and dynapenia among older lifetime smokers in Korea. METHODS This study is a secondary dataset analysis of cross-sectional data from theKorea National Health and Nutrition Examination Survey (KNHANES) 2016- 2019. We included 1450 participants aged 65-79 years, excluding those who had never smoked. Dynapenia was defined as grip strength <28 kg for men and <18 kg for women based on the Asian Working Group for Sarcopenia 2019 criteria. Multivariable logistic regression analysis evaluated the association between smoking cessation and dynapenia. RESULTS Compared with current smokers, the adjusted odds ratio (AOR) of dynapenia in former smokers was 0.66 (95% CI: 0.44-0.99). The AORs for smoking cessation periods of ≤10 years, 10-20 years, 20-30 years, and >30 years were 0.67 (95% CI: 0.39-1.16), 0.61 (95% CI: 0.36-1.03), 0.65 (95% CI: 0.37-1.14), and 0.52 (95% CI: 0.25-1.06), respectively. The AOR for dynapenia significantly decreased with the years since smoking cessation (p for trend=0.043). CONCLUSIONS Our findings suggest that smoking cessation can reduce the likelihood of dynapenia among older lifetime smokers, with a decreasing likelihood trend associated with longer cessation periods.
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Affiliation(s)
- Keunjoong Yoo
- Department of Family Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Yong Soon Park
- Department of Family Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Hye Jin Kim
- Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Jeong Hyeon Kim
- Department of Family Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea
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Cho Y, Park HS, Seo DH, Ahn SH, Hong S, Suh YJ, Chon S, Woo JT, Baik SH, Lee KW, Kim SH. The Association of Smoking Status with Diabetic Microvascular Complications in Korean Patients with Type 2 Diabetes. Yonsei Med J 2024; 65:427-433. [PMID: 39048318 PMCID: PMC11284303 DOI: 10.3349/ymj.2023.0355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 02/16/2024] [Accepted: 03/05/2024] [Indexed: 07/27/2024] Open
Abstract
PURPOSE Few studies have investigated the association between smoking and microvascular complications in the Asian population with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between smoking status and microvascular complications in Korean patients with T2DM. MATERIALS AND METHODS From the Korean National Diabetes Program cohort, we included 2316 Korean male with T2DM who had baseline clinical information available, including their smoking status, and underwent diabetic complication studies. RESULTS Compared to non-smokers, current smokers had higher odds of any-microvascular complications [adjusted odds ratio (aOR) 1.45, 95% confidence interval (CI) 1.07-1.97, p=0.016]. The odds of neuropathy were significantly higher; however, the odds of retinopathy were significantly lower in current smokers than in nonsmokers (all p<0.05). Among those who underwent repeated complication tests after 3 years, the risk of newly developed retinopathy was significantly increased in ex-smokers [aOR 3.77 (95% CI 1.61-8.87), p=0.002]. Within ex-smokers, long smoking duration and smoking cessation within the recent 5 years were associated with an increased risk of newly developed retinopathy (all p<0.05). CONCLUSION Male smokers had higher odds of having overall diabetic microvascular complications, including neuropathy. However, the odds of having retinopathy were significantly lower among current smokers. More attention and research are needed regarding the increased risk of retinopathy development in ex-smokers who have recently stopped smoking after a long history of smoking.
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Affiliation(s)
- Yongin Cho
- Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Hye-Sun Park
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Da Hea Seo
- Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Seong Hee Ahn
- Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Seongbin Hong
- Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Young Ju Suh
- Department of Biomedical Sciences, Inha University College of Medicine, Incheon, Korea
| | - Suk Chon
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jeong-Taek Woo
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea
| | - Sei Hyun Baik
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Kwan Woo Lee
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
| | - So Hun Kim
- Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea.
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Woo SD, Park HS, Yang EM, Ban GY, Park HS. 8-Iso-prostaglandin F2α as a biomarker of type 2 low airway inflammation and remodeling in adult asthma. Ann Allergy Asthma Immunol 2024; 133:73-80.e2. [PMID: 38615737 DOI: 10.1016/j.anai.2024.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 03/31/2024] [Accepted: 04/01/2024] [Indexed: 04/16/2024]
Abstract
BACKGROUND Although 8-iso-prostaglandin F2a has been proposed as a potential biomarker for oxidative stress in airway diseases, its specific role in asthma remains poorly understood. OBJECTIVE To evaluate the diagnostic potential of 8-iso-prostaglandin F2a in assessing airway inflammation, airway remodeling, airway hyperresponsiveness, and oxidative stress in asthma. METHODS Blood and urine concentrations of 8-iso-prostaglandin F2a were quantified using liquid chromatography-tandem mass spectrometry in 128 adults with asthma who had maintained antiasthma medications. Their correlations with clinical data, sputum cell counts, lung function parameters, and serum markers of epithelial/neutrophil activity and airway remodeling were then analyzed. RESULTS The urinary 8-iso-prostaglandin F2a concentrations were significantly higher in patients with noneosinophilic asthma than in those with eosinophilic asthma (P < .05). The area under the curve was 0.678, indicating moderate diagnostic accuracy for noneosinophilic asthma. There were significant correlations with neutrophilic inflammation markers and airway remodeling markers (all P < .05). Negative correlations were observed with forced expiratory volume in 1 second (%), forced expiratory volume in 1 second/forced vital capacity, forced expiratory flow at 25% to 75% of forced vital capacity, and serum club cell protein 16 levels (all P < .05). High 8-iso-prostaglandin F2a concentrations were also noted in obese and smoking subgroups (all P < .05). However, the serum 8-iso-prostaglandin F2a concentrations were not correlated with these asthma-related parameters. CONCLUSION Urinary 8-iso-prostaglandin F2a concentrations are a potential biomarker for phenotyping severe asthma, particularly noneosinophilic asthma, offering oxidative stress-induced epithelial inflammation/remodeling as an additional target in asthma management.
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Affiliation(s)
- Seong-Dae Woo
- Department of Pulmonary, Allergy, and Critical Care Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea
| | - Hee Sun Park
- Department of Pulmonary, Allergy, and Critical Care Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea
| | - Eun-Mi Yang
- Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Ga-Young Ban
- Department of Pulmonary, Allergy, and Critical Care Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine Institute for Life Sciences, Seoul, Korea
| | - Hae-Sim Park
- Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea.
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Amer R, Koriat A. Aqueous humor perturbations in chronic smokers: a proteomic study. Sci Rep 2024; 14:11279. [PMID: 38760463 PMCID: PMC11101467 DOI: 10.1038/s41598-024-62039-6] [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: 08/21/2023] [Accepted: 05/13/2024] [Indexed: 05/19/2024] Open
Abstract
The detrimental effects of smoking are multisystemic and its effects on the eye health are significant. Smoking is a strong risk factor for age-related nuclear cataract, age-related macular degeneration, glaucoma, delayed corneal epithelial healing and increased risk of cystoid macular edema in patients with intermediate uveitis among others. We aimed to characterize the aqueous humor (AH) proteome in chronic smokers to gain insight into its perturbations and to identify potential biomarkers for smoking-associated ocular pathologies. Compared to the control group, chronic smokers displayed 67 (37 upregulated, 30 downregulated) differentially expressed proteins (DEPs). Analysis of DEPs from the biological point of view revealed that they were proteins involved in complement activation, lymphocyte mediated immunity, innate immune response, cellular oxidant detoxification, bicarbonate transport and platelet degranulation. From the molecular function point of view, DEPs were involved in oxygen binding, oxygen carrier activity, hemoglobin binding, peptidase/endopeptidase/cysteine-type endopeptidase inhibitory activity. Several of the upregulated proteins were acute phase reactant proteins such as clusterin, alpha-2-HS-glycoprotein, fibrinogen, alpha-1-antitrypsin, C4b-binding protein and serum amyloid A-2. Further research should confirm if these proteins might serve as biomarkers or therapeutic target for smoking-associated ocular diseases.
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Affiliation(s)
- Radgonde Amer
- Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel.
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
| | - Adi Koriat
- Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel
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Abellán Alemán J, Sabaris RC, Pardo DE, García Donaire JA, Romanos FG, Iriso JI, Penagos LM, Iglesias LJN, de Salinas APM, Pérez-Monteoliva NRR, Lezcano PSR, Saborido MT, Roca FV. Documento de consenso sobre tabaquismo y riesgo vascular. HIPERTENSION Y RIESGO VASCULAR 2024; 41 Suppl 1:S1-S85. [PMID: 38729667 DOI: 10.1016/s1889-1837(24)00075-8] [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: 05/12/2024]
Abstract
Consensus statement on smoking and vascular risk About 22% of the Spanish population are daily smokers. Men are more likely to smoke than women. In Spain, women between 15-25 years of age smoke as much or more than men. Every smoker should be assessed for: physical dependence on nicotine (Fagerström test), social and psychological dependence (Glover Nilsson test), level of motivation to quit (Richmond test), probability of therapy success (Henri-Mondor and Michael-Fiore tests), and stage of behavioral change development (Prochaska and DiClementi). Advice on smoking cessation is highly cost-effective and should always be provided. Smoking is an enhancer of cardiovascular risk because it acts as a pathogen agent in the development of arteriosclerosis and is associated with ischemic heart disease, stroke, and peripheral artery disease. Smoking increases the risk of chronic lung diseases (COPD) and is related to cancers of the lung, female genitalia, larynx, oropharynx, bladder, mouth, esophagus, liver and biliary tract, and stomach, among others. Combined oral contraceptives should be avoided in women smokers older than 35 years of age due to the risk of thromboembolism. In smoking cessation, the involvement of physicians, nurses, psychologists, etc. is important, and their multidisciplinary collaboration is needed. Effective pharmacological treatments for smoking cessation are available. Combined treatments are recommended when smoker's dependence is high. For individuals who are unable to quit smoking, a strategy based on tobacco damage management with a total switch to smokeless products could be a less dangerous alternative for their health than continuing to smoke.
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Affiliation(s)
- José Abellán Alemán
- Sociedad Murciana de Hipertensión Arterial y Riesgo Cardiovascular, Cátedra de Riesgo Cardiovascular, Universidad Católica de Murcia, Murcia, España.
| | - Rafael Crespo Sabaris
- Sociedad Riojana de Hipertensión y Riesgo Vascular, Centro de Salud de Entrena, La Rioja, España
| | - Daniel Escribano Pardo
- Sociedad Aragonesa de Hipertensión y Riesgo Vascular, Centro de Salud Oliver, Zaragoza, España
| | - José Antonio García Donaire
- Sociedad Española de Hipertensión, Unidad de Hipertensión, Servicio de Medicina Interna, Hospital Clínico Universitario San Carlos, Madrid, España
| | - Fernando García Romanos
- Sociedad de Hipertensión y Riesgo Vascular de las Illes Balears, Centro de Salud Santa Catalina, Palma de Mallorca, España
| | - Jesús Iturralde Iriso
- Sociedad Vasca de Hipertensión y Riesgo Vascular, Centro de Salud la Habana-Cuba, Vitoria-Gasteiz, España
| | - Luis Martín Penagos
- Sociedad Cántabra de Hipertensión y Riesgo Vascular, Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander, España
| | - L Javier Nieto Iglesias
- Sociedad Castilla-La Mancha de Hipertensión y Riesgo Vascular, Unidad de Hipertensión y Riesgo Vascular, Servicio de Nefrología, Hospital General Universitario de Ciudad Real, Ciudad Real, España
| | - Alfonso Pobes Martínez de Salinas
- Sociedad Asturiana de Hipertensión y Riesgo Vascular, Área de Gestión Clínica, Interáreas de Nefrología VII y VIII del SESPA, Asturias, España
| | | | - Pablo Sánchez-Rubio Lezcano
- Sociedad Aragonesa de Hipertensión y Riesgo Vascular, Servicio de Medicina Interna, Hospital General Universitario San Jorge, Huesca, España
| | - Maribel Troya Saborido
- Sociedad Catalana de Hipertensión y Riesgo Vascular, Servicio de Nefrología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, España
| | - Francisco Valls Roca
- Sociedad Valenciana de Hipertensión y Riesgo Vascular, Centro de Salud de Beniganim, Valencia, España
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Seo YS, Park KH, Park JM, Jeong H, Kim B, Jeon JS, Yu J, Kim SK, Lee K, Lee MY. Short-term inhalation exposure to cigarette smoke induces oxidative stress and inflammation in lungs without systemic oxidative stress in mice. Toxicol Res 2024; 40:273-283. [PMID: 38525133 PMCID: PMC10959912 DOI: 10.1007/s43188-023-00223-y] [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: 10/11/2023] [Revised: 12/23/2023] [Accepted: 12/27/2023] [Indexed: 03/26/2024] Open
Abstract
Smoking is a well-established risk factor for various pathologies, including pulmonary diseases, cardiovascular disorders, and cancers. The toxic effects of cigarette smoke (CS) are mediated through multiple pathways and diverse mechanisms. A key pathogenic factor is oxidative stress, primarily induced by excessive formation of reactive oxygen species. However, it remains unclear whether smoking directly induces systemic oxidative stress or if such stress is a secondary consequence. This study aimed to determine whether short-term inhalation exposure to CS induces oxidative stress in extrapulmonary organs in addition to the lung in a murine model. In the experiment, 3R4F reference cigarettes were used to generate CS, and 8-week-old male BALB/c mice were exposed to CS at a total particulate matter concentration of either 0 or 800 µg/L for four consecutive days. CS exposure led to an increase in neutrophils, eosinophils, and total cell counts in bronchoalveolar lavage fluid. It also elevated levels of lactate dehydrogenase and malondialdehyde (MDA), markers indicative of tissue damage and oxidative stress, respectively. Conversely, no significant changes were observed in systemic oxidative stress markers such as total oxidant scavenging capacity, MDA, glutathione (GSH), and the GSH/GSSG ratio in blood samples. In line with these findings, CS exposure elevated NADPH oxidase (NOX)-dependent superoxide generation in the lung but not in other organs like the liver, kidney, heart, aorta, and brain. Collectively, our results indicate that short-term exposure to CS induces inflammation and oxidative stress in the lung without significantly affecting oxidative stress in extrapulmonary organs under the current experimental conditions. NOX may play a role in these pulmonary-specific events.
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Affiliation(s)
- Yoon-Seok Seo
- College of Pharmacy, BK21 FOUR Team and Integrated Research Institute for Drug Development, Dongguk University, Goyang-si, Gyeonggi-do 10326 Republic of Korea
| | - Kwang-Hoon Park
- College of Pharmacy, BK21 FOUR Team and Integrated Research Institute for Drug Development, Dongguk University, Goyang-si, Gyeonggi-do 10326 Republic of Korea
| | - Jung-Min Park
- College of Pharmacy, BK21 FOUR Team and Integrated Research Institute for Drug Development, Dongguk University, Goyang-si, Gyeonggi-do 10326 Republic of Korea
| | - Hyuneui Jeong
- Biosafety Research Institute and College of Veterinary Medicine, Jeonbuk National University, Iksan-si, Jeollabuk-do 54596 Republic of Korea
| | - Bumseok Kim
- Biosafety Research Institute and College of Veterinary Medicine, Jeonbuk National University, Iksan-si, Jeollabuk-do 54596 Republic of Korea
| | - Jang Su Jeon
- College of Pharmacy, Chungnam National University, Daejeon, 34134 Republic of Korea
| | - Jieun Yu
- College of Pharmacy, Chungnam National University, Daejeon, 34134 Republic of Korea
| | - Sang Kyum Kim
- College of Pharmacy, Chungnam National University, Daejeon, 34134 Republic of Korea
| | - Kyuhong Lee
- Inhalation Toxicology Center for Airborne Risk Factor, Korea Institute of Toxicology, Jeongeup-si, Jeollabuk-do 56212 Republic of Korea
| | - Moo-Yeol Lee
- College of Pharmacy, BK21 FOUR Team and Integrated Research Institute for Drug Development, Dongguk University, Goyang-si, Gyeonggi-do 10326 Republic of Korea
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Huneault HE, Chen CY, Cohen CC, Liu X, Jarrell ZR, He Z, DeSantos KE, Welsh JA, Maner-Smith KM, Ortlund EA, Schwimmer JB, Vos MB. Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease. Metabolites 2024; 14:191. [PMID: 38668319 PMCID: PMC11052520 DOI: 10.3390/metabo14040191] [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: 02/10/2024] [Revised: 03/21/2024] [Accepted: 03/26/2024] [Indexed: 04/28/2024] Open
Abstract
Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11-16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.
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Affiliation(s)
- Helaina E. Huneault
- Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA; (J.A.W.); (M.B.V.)
| | - Chih-Yu Chen
- Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA; (C.-Y.C.); (X.L.); (E.A.O.)
| | - Catherine C. Cohen
- Section of Nutrition, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (C.C.C.); (K.M.M.-S.)
| | - Xueyun Liu
- Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA; (C.-Y.C.); (X.L.); (E.A.O.)
| | - Zachery R. Jarrell
- Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, GA 30322, USA;
| | - Zhulin He
- Pediatric Biostatistics Core, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA;
| | - Karla E. DeSantos
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, GA 30322, USA;
- Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
| | - Jean A. Welsh
- Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA; (J.A.W.); (M.B.V.)
- Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
| | - Kristal M. Maner-Smith
- Section of Nutrition, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (C.C.C.); (K.M.M.-S.)
| | - Eric A. Ortlund
- Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA; (C.-Y.C.); (X.L.); (E.A.O.)
| | - Jeffrey B. Schwimmer
- Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, CA 92123, USA;
- Department of Pediatrics, School of Medicine, University of California, San Diego, CA 92093, USA
| | - Miriam B. Vos
- Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA; (J.A.W.); (M.B.V.)
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, GA 30322, USA;
- Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
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Xu W, Wang H, Sun Q, Hua T, Bai J, Zhang Q, Liu Q, Ni X. TXNIP-NLRP3-GSDMD axis-mediated inflammation and pyroptosis of islet β-cells is involved in cigarette smoke-induced hyperglycemia, which is alleviated by andrographolide. ENVIRONMENTAL TOXICOLOGY 2024; 39:1415-1428. [PMID: 37987454 DOI: 10.1002/tox.24046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/25/2023] [Accepted: 10/31/2023] [Indexed: 11/22/2023]
Abstract
Epidemiologic surveys have indicated that cigarette smoking is an important risk factor for diabetes, but its mechanisms remain unclear. Andrographolide, an herb traditionally utilized in medicine, provides anti-inflammatory benefits for various diseases. In the present work, 265 patients with Type 2 diabetes (T2D) were investigated, and male C57BL/6 mice were exposed to cigareete smoke (CS) and/or to intraperitoneally injected andrographolide for 3 months. To elucidate the mechanism of CS-induced hyperglycemia and the protective mechanism of andrographolide, MIN6 cells were exposed to cigarette smoke extract (CSE) and/or to andrographolide. Our data from 265 patients with T2D showed that urinary creatinine and serum inflammatory cytokines (interleukin 6 (IL-6), IL-8, IL-1β, and tumor necrosis factor α (TNF-α)) increased with smoking pack-years. In a mouse model, CS induced hyperglycemia, decreased insulin secretion, and elevated inflammation and pyroptosis in β-cells of mice. Treatment of mice with andrographolide preserved pancreatic function by reducing the expression of inflammatory cytokines; the expression of TXNIP, NLRP3, cleaved caspase 1, IL-1β; and the N-terminal of gasdermin D (GSDMD) protein. For MIN6 cells, CSE caused increasing secretion of the inflammatory cytokines IL-6 and IL-1β, and the expression of TXNIP and pyroptosis-related proteins; however, andrographolide alleviated these changes. Furthermore, silencing of TXNIP showed that the blocking effect of andrographolide may be mediated by TXNIP. In sum, our results indicate that CS induces hyperglycemia through TXNIP-NLRP3-GSDMD axis-mediated inflammation and pyroptosis of islet β-cells and that andrographolide is a potential therapeutic agent for CS-induced hyperglycemia.
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Affiliation(s)
- Wenchao Xu
- The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, People's Republic of China
- Changzhou Center for Disease Control and Prevention, Changzhou Advanced Institute of Public Health, Nanjing Medical University, Changzhou, People's Republic of China
| | - Hailan Wang
- The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
- Environmental health effects and risk assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, People's Republic of China
| | - Qian Sun
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, People's Republic of China
| | - Tianqi Hua
- Changzhou Center for Disease Control and Prevention, Changzhou Advanced Institute of Public Health, Nanjing Medical University, Changzhou, People's Republic of China
| | - Jun Bai
- Environmental health effects and risk assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, People's Republic of China
| | - Qingbi Zhang
- Environmental health effects and risk assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, People's Republic of China
| | - Qizhan Liu
- The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Xinye Ni
- The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, People's Republic of China
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de Faria RR, de Siqueira SF, Haddad FA, Del Monte Silva G, Spaggiari CV, Martinelli M. The Six Pillars of Lifestyle Medicine in Managing Noncommunicable Diseases - The Gaps in Current Guidelines. Arq Bras Cardiol 2024; 120:e20230408. [PMID: 38198361 PMCID: PMC10735241 DOI: 10.36660/abc.20230408] [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: 06/20/2023] [Revised: 08/29/2023] [Accepted: 10/25/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Noncommunicable diseases (NCDs), also known as chronic diseases that are long-lasting, are considered the major cause of death and disability worldwide, and the six pillars of lifestyle medicine (nutrition, exercise, toxic control, stress management, restorative sleep, and social connection) play an important role in a holistic management of their prevention and treatment. In addition, medical guidelines are the most accepted documents with recommendations to manage NCDs. OBJECTIVE The present study aims to analyze the lack of lifestyle pillars concerning the major Brazilian medical guidelines for NCDs and identify evidence in the literature that could justify their inclusion in the documents. METHOD Brazilian guidelines were selected according to the most relevant causes of death in Brazil, given by the Mortality Information System, published by the Brazilian Ministry of Health in 2019. Journals were screened in the PUBMED library according to the disease and non-mentioned pillars of lifestyle. RESULTS Relevant causes of deaths in Brazil are acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic obstructive pulmonary diseases (COPD). Six guidelines related to these NCDs were identified, and all address aspects of lifestyle, but only one, regarding cardiovascular prevention, highlights all six pillars. Despite this, a literature search involving over 50 articles showed that there is evidence that all the pillars can help control each of these NCDs. CONCLUSION Rarely are the six pillars of lifestyle contemplated in Brazilian guidelines for AMI, DM, and COPD. The literature review identified evidence of all lifestyle pillars to offer a holistic approach for the management and prevention of NCDs.
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Affiliation(s)
- Rafaella Rogatto de Faria
- Cultivare Prevenção e Promoção da SaúdePesquisa e DesenvolvimentoSão PauloSPBrasilCultivare Prevenção e Promoção da Saúde – Pesquisa e Desenvolvimento, São Paulo, SP – Brasil
- Hospital das Clínicas da FMUSPMedicina do EsporteSão PauloSPBrasilMedicina do Esporte – Hospital das Clínicas da FMUSP, São Paulo, SP – Brasil
| | - Sergio Freitas de Siqueira
- Cultivare Prevenção e Promoção da SaúdePesquisa e DesenvolvimentoSão PauloSPBrasilCultivare Prevenção e Promoção da Saúde – Pesquisa e Desenvolvimento, São Paulo, SP – Brasil
- Hospital das Clínicas da FMUSPInstituto do CoraçãoSão PauloSPBrasilInstituto do Coração (InCor), Hospital das Clínicas da FMUSP, São Paulo, SP – Brasil
| | - Francisco Aguerre Haddad
- Cultivare Prevenção e Promoção da SaúdePesquisa e DesenvolvimentoSão PauloSPBrasilCultivare Prevenção e Promoção da Saúde – Pesquisa e Desenvolvimento, São Paulo, SP – Brasil
- Pontifícia Universidade Católica de São PauloSão PauloSPBrasilPontifícia Universidade Católica de São Paulo, São Paulo, SP – Brasil
| | - Gustavo Del Monte Silva
- Cultivare Prevenção e Promoção da SaúdePesquisa e DesenvolvimentoSão PauloSPBrasilCultivare Prevenção e Promoção da Saúde – Pesquisa e Desenvolvimento, São Paulo, SP – Brasil
- Pontifícia Universidade Católica de São PauloSão PauloSPBrasilPontifícia Universidade Católica de São Paulo, São Paulo, SP – Brasil
| | - Caio Vitale Spaggiari
- Hospital das Clínicas da FMUSPInstituto do CoraçãoSão PauloSPBrasilInstituto do Coração (InCor), Hospital das Clínicas da FMUSP, São Paulo, SP – Brasil
| | - Martino Martinelli
- Cultivare Prevenção e Promoção da SaúdePesquisa e DesenvolvimentoSão PauloSPBrasilCultivare Prevenção e Promoção da Saúde – Pesquisa e Desenvolvimento, São Paulo, SP – Brasil
- Hospital das Clínicas da FMUSPInstituto do CoraçãoSão PauloSPBrasilInstituto do Coração (InCor), Hospital das Clínicas da FMUSP, São Paulo, SP – Brasil
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13
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Halliwell B. Understanding mechanisms of antioxidant action in health and disease. Nat Rev Mol Cell Biol 2024; 25:13-33. [PMID: 37714962 DOI: 10.1038/s41580-023-00645-4] [Citation(s) in RCA: 152] [Impact Index Per Article: 152.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/17/2023] [Indexed: 09/17/2023]
Abstract
Several different reactive oxygen species (ROS) are generated in vivo. They have roles in the development of certain human diseases whilst also performing physiological functions. ROS are counterbalanced by an antioxidant defence network, which functions to modulate ROS levels to allow their physiological roles whilst minimizing the oxidative damage they cause that can contribute to disease development. This Review describes the mechanisms of action of antioxidants synthesized in vivo, antioxidants derived from the human diet and synthetic antioxidants developed as therapeutic agents, with a focus on the gaps in our current knowledge and the approaches needed to close them. The Review also explores the reasons behind the successes and failures of antioxidants in treating or preventing human disease. Antioxidants may have special roles in the gastrointestinal tract, and many lifestyle features known to promote health (especially diet, exercise and the control of blood glucose and cholesterol levels) may be acting, at least in part, by antioxidant mechanisms. Certain reactive sulfur species may be important antioxidants but more accurate determinations of their concentrations in vivo are needed to help assess their contributions.
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Affiliation(s)
- Barry Halliwell
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Neurobiology Research Programme, Life Sciences Institute, Centre for Life Sciences, National University of Singapore, Singapore, Singapore.
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14
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Gao Z, Xiu M, Liu J, Wu F, Zhang X. Smoking, Symptoms Improvement, and Total Antioxidant Capacity in Patients with Drug-naive First-episode Schizophrenia: A Prospective Cohort Study. Curr Neuropharmacol 2024; 22:1733-1741. [PMID: 37859307 PMCID: PMC11284715 DOI: 10.2174/1570159x22666231019105328] [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: 02/20/2023] [Revised: 04/08/2023] [Accepted: 04/26/2023] [Indexed: 10/21/2023] Open
Abstract
BACKGROUND It has been hypothesized that smoking is associated with the severity of negative symptoms. Until now, no studies have investigated whether the impact of smoking on negative symptoms is dependent on antioxidants. This study was designed to evaluate the effect of smoking on therapeutic response and total antioxidants capacity (TAOC) in antipsychotic-naïve first-episode (ANFE) patients. METHODS The severity of the patient's symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). A total of 237 ANFE patients were recruited and treated with risperidone (oral tablets, 4-6 mg/day twice a day) for 12 weeks. PANSS was assessed at baseline and a 12-week follow-up. Plasma TAOC levels were also assayed at baseline and week 12. RESULTS Relative to nonsmokers with ANFE SZ, smokers had higher PANSS negative subscores. There was no significant difference in TAOC changes after 12 weeks of treatment with risperidone between smokers and non-smokers. However, we found greater improvement in negative symptoms in smokers compared to non-smokers. Further analysis in smokers with SZ demonstrated that improvements in negative symptoms were not associated with changes in TAOC. CONCLUSION Our study suggested that smoking affected the severity of baseline negative symptoms and further contributed to their reduction after risperidone treatment. However, improvement in negative symptoms was not dependent on the changes in TAOC.
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Affiliation(s)
- Zhiyong Gao
- The Affiliated Kangning Hospital of Wenzhou Medical University Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, China
| | - Meihong Xiu
- Peking University Huilongguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China
| | - Jiahong Liu
- The Affiliated Kangning Hospital of Wenzhou Medical University Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, China
| | - Fengchun Wu
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xiangyang Zhang
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
- Department of Biomedical Engineering, Guangzhou Medical University, Guangzhou, China
- Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China
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15
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Kai JY, Zhou M, Li DL, Zhu KY, Wu Q, Zhang XF, Pan CW. Smoking, dietary factors and major age-related eye disorders: an umbrella review of systematic reviews and meta-analyses. Br J Ophthalmol 2023; 108:51-57. [PMID: 36575624 DOI: 10.1136/bjo-2022-322325] [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: 07/29/2022] [Accepted: 11/24/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND There is accumulating evidence of the associations between age-related eye diseases (AREDs) and smoking or dietary factors. We aimed to provide an umbrella review of the published literature pertaining to smoking or dietary intake as risk factors for major AREDs including cataract, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy. METHODS We searched for pertinent systematic reviews or meta-analyses in PubMed and Web of Science until 16 April 2022. We reperformed the meta-analysis of each association using random effects models. The heterogeneity and 95% prediction interval were calculated. The presence of small-study effect or excess significance bias was also assessed. RESULTS In total, 64 associations from 25 meta-analyses and 41 associations from 10 qualitative systematic reviews were evaluated. There was convincing (class I) evidence for only one association, namely current smoking and cataract. Two factors had highly suggestive (class II) evidence, namely ever smoking associated with cataract and fish consumption associated with AMD. We also found suggestive (class III) evidence for associations between the dietary intake of omega-3 polyunsaturated fatty acid, lutein, zeaxanthin, vitamin C and the risk of cataract. CONCLUSIONS Smoking as a risk factor for cataract was the most robust association we identified. We also identified several dietary elements associated with AREDs. Large prospective studies are warranted to further examine the associations discussed in this review. PROSPERO REGISTRATION NUMBER CRD42022339082.
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Affiliation(s)
- Jia-Yan Kai
- School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Miao Zhou
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China
| | - Dan-Lin Li
- School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Ke-Yao Zhu
- Pasteurien College of Soochow University, Suzhou, China
| | - Qian Wu
- School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Xiao-Feng Zhang
- Department of Ophthalmology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China
| | - Chen-Wei Pan
- School of Public Health, Medical College of Soochow University, Suzhou, China
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Ataka E, Matsukuma Y, Ueki K, Tsuchimoto A, Okabe Y, Masutani K, Nakamura M, Nakano T, Kitazono T. Cumulative smoking dose is associated with subclinical renal injury: a pathological study in individuals without chronic kidney disease. Nephrol Dial Transplant 2023; 38:2799-2808. [PMID: 37355777 DOI: 10.1093/ndt/gfad124] [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: 04/05/2023] [Indexed: 06/26/2023] Open
Abstract
BACKGROUND Epidemiological studies have identified smoking as an independent risk factor for development of chronic kidney disease. However, the early renal pathological lesions have not been clearly elucidated. METHODS We investigated time-zero biopsy specimens from 547 living kidney donors and evaluated the relationships between smoking and renal histological changes, including arteriolar hyalinization, intimal thickening of small-medium arteries, global glomerulosclerosis, and interstitial fibrosis and tubular atrophy (IF/TA). RESULTS A total of 199 subjects (36.4%) had smoking history; 92 (16.8%) and 107 (19.6%) subjects had <20 pack-years and ≥20 pack-years of smoking, respectively. Cumulative smoking dose was significantly associated with prevalence of arteriolar hyalinization: the multivariable-adjusted odds ratio (OR) per 20 pack-year increase was 1.50 (95% confidence interval 1.15-1.97). The ORs for smokers with <20 pack-years and ≥20 pack-years versus never-smokers were 1.76 (1.01-3.09) and 2.56 (1.48-4.44), respectively. Smoking was also associated with prevalence of >10% global glomerulosclerosis: the OR per 20 pack-year increase was 1.24 (0.96-1.59). The ORs for smokers with <20 pack-years and ≥20 pack-years versus never-smokers were 1.50 (0.98-2.78) and 2.11 (1.18-3.79), respectively. The ORs for these pathological changes increased significantly depending on cumulative smoking dose. Intimal thickening of small-medium arteries and IF/TA were not associated with smoking status. The prevalence of arteriolar hyalinization remained higher in patients with ≥10 years since smoking cessation than in never-smokers [OR 2.23 (1.03-4.83)]. CONCLUSIONS Subclinical pathological injury caused by smoking is potentially associated with renal arteriolar hyalinization and glomerular ischaemia.
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Affiliation(s)
- Eri Ataka
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuta Matsukuma
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenji Ueki
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akihiro Tsuchimoto
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yasuhiro Okabe
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kosuke Masutani
- Department of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toshiaki Nakano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Kang J, Kim T, Han KD, Jung JH, Jeong SM, Yeo YH, Jung K, Lee H, Cho JH, Shin DW. Risk factors for early-onset lung cancer in Korea: analysis of a nationally representative population-based cohort. Epidemiol Health 2023; 45:e2023101. [PMID: 38037323 PMCID: PMC10876445 DOI: 10.4178/epih.e2023101] [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: 05/15/2023] [Accepted: 11/03/2023] [Indexed: 12/02/2023] Open
Abstract
OBJECTIVES We examined the associations of socioeconomic factors, health behaviors, and comorbidities with early-onset lung cancer. METHODS The study included 6,794,287 individuals aged 20-39 years who participated in a Korean national health check-up program from 2009 to 2012. During the follow-up period, 4,684 participants developed lung cancer. Multivariable Cox regression analysis was used to estimate the independent associations of potential risk factors with incident lung cancer. RESULTS Older age (multivariable hazard ratio [mHR], 1.13; 95% confidence interval [CI], 1.12 to 1.14) and female sex (mHR, 1.62; 95% CI, 1.49 to 1.75) were associated with increased lung cancer risk. Current smoking was also associated with elevated risk (<10 pack-years: mHR, 1.12; 95% CI, 1.01 to 1.24; ≥10 pack-years: mHR, 1.30; 95% CI, 1.18 to 1.45), but past smoking was not. Although mild alcohol consumption (<10 g/day) was associated with lower lung cancer risk (mHR, 0.92; 95% CI, 0.86 to 0.99), heavier alcohol consumption (≥10 g/day) was not. Higher income (highest vs. lowest quartile: mHR, 0.86; 95% CI, 0.78 to 0.94), physical activity for at least 1,500 metabolic equivalent of task-min/wk (vs. non-exercisers: mHR, 0.83; 95% CI, 0.69 to 0.99) and obesity (vs. normal weight: mHR, 0.89; 95% CI, 0.83 to 0.96) were associated with lower lung cancer risk, whereas metabolic syndrome was associated with increased risk (mHR, 1.13; 95% CI, 1.03 to 1.24). CONCLUSIONS In young adults, age, female sex, smoking, and metabolic syndrome were risk factors for early-onset lung cancer, while high income, physical activity, and obesity displayed protective effects.
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Affiliation(s)
- Jihun Kang
- Department of Family Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan,
Korea
| | - Taeyun Kim
- Division of Pulmonology, Department of Internal Medicine, The Armed Forces Goyang Hospital, Goyang,
Korea
| | - Kyung-Do Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul,
Korea
| | - Jin-Hyung Jung
- Department of Medical Statistics, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Su-Min Jeong
- Department of Medicine, Seoul National University College of Medicine, Seoul,
Korea
| | - Yo Hwan Yeo
- Department of Family Medicine, Hallym University Sacred Heart Hospital, Dongtan,
Korea
| | - Kyuwon Jung
- Korea Central Cancer Registry, Division of Cancer Registration and Surveillance, National Cancer Center, Goyang,
Korea
| | - Hyun Lee
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul,
Korea
| | - Jong Ho Cho
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Dong Wook Shin
- Supportive Care Center, Samsung Comprehensive Cancer Center/Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
- Department of Digital Health, SAIHST, Sungkyunkwan University, Seoul,
Korea
- Center for Clinical Epidemiology, SAIHST, Sungkyunkwan University, Seoul,
Korea
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Desai JK, Trangadia BJ, Patel UD, Patel HB, Kalaria VA, Kathiriya JB. Neurotoxicity of 4-nonylphenol in adult zebrafish: Evaluation of behaviour, oxidative stress parameters and histopathology of brain. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 334:122206. [PMID: 37473849 DOI: 10.1016/j.envpol.2023.122206] [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: 05/10/2023] [Revised: 07/10/2023] [Accepted: 07/13/2023] [Indexed: 07/22/2023]
Abstract
Nonylphenol and its derivatives use as plasticizer or additives in manufacturing industries. Effluents originated from industrial areas are being added to soil, ground water, river and marine water intentionally or unintentionally. Complex mixture of these contaminants enter the food chain and produce sub-lethal deleterious effects mainly on nervous and reproductive systems of aquatic animals and human beings. The information pertaining to oxidative stress-mediated alterations in brain of zebrafish would be helpful to understand the toxicity potential of such compounds in aquatic animals. The aim of the present study was to evaluate the behavioural changes, status of oxidative stress markers; sod, cat, and NF-E2-related factor 2 (nrf2) mRNA gene expression profile; and histopathological changes in the brain of adult zebrafish exposed to 4-nonylphenol (4NP) at concentration of 100 and 200 μg/L of water for 21 days. Zebrafish were divided into four groups viz; control (C1), vehicle (C2, ethanol 10 μg/L of water), treatment 1 (T1, 4-NP, 100 μg/L) and treatment 2 (T2, 4-NP, 200 μg/L). Both exposure levels of 4-NP adversely affected the exploratory behaviour of zebrafish and produced anxiety-like symptom. Concentration-dependent reduction in activity of superoxide dismutase and catalase; and glutathione level, with increased level of malondialdehyde recorded in the brain of exposed zebrafish. Gene expression analysis showed down regulation of sod, cat, nrf2 genes in brain of zebrafish from toxicity groups indicating 4-NP induced oxidative stress in brain. However, noticeable histological alterations were not observed in 4-NP exposed brain of zebrafish.
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Affiliation(s)
- Jay K Desai
- Department of Veterinary Pathology, College of Veterinary Science and Animal Husbandry, Kamdhenu University, Junagadh, 362001, Gujarat, India.
| | - Bhavesh J Trangadia
- Department of Veterinary Pathology, College of Veterinary Science and Animal Husbandry, Kamdhenu University, Junagadh, 362001, Gujarat, India.
| | - Urvesh D Patel
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Science and Animal Husbandry, Kamdhenu University, Junagadh, 362001, Gujarat, India
| | - Harshad B Patel
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Science and Animal Husbandry, Kamdhenu University, Junagadh, 362001, Gujarat, India
| | - Vinay A Kalaria
- Department of Veterinary Pathology, College of Veterinary Science and Animal Husbandry, Kamdhenu University, Junagadh, 362001, Gujarat, India
| | - Jaysukh B Kathiriya
- Department of Veterinary Public Health & Epidemiology, College of Veterinary Science and Animal Husbandry, Kamdhenu University, Junagadh, 362001, Gujarat, India
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Seo YS, Park JM, Kim JH, Lee MY. Cigarette Smoke-Induced Reactive Oxygen Species Formation: A Concise Review. Antioxidants (Basel) 2023; 12:1732. [PMID: 37760035 PMCID: PMC10525535 DOI: 10.3390/antiox12091732] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/28/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023] Open
Abstract
Smoking is recognized as a significant risk factor for numerous disorders, including cardiovascular diseases, respiratory conditions, and various forms of cancer. While the exact pathogenic mechanisms continue to be explored, the induction of oxidative stress via the production of excess reactive oxygen species (ROS) is widely accepted as a primary molecular event that predisposes individuals to these smoking-related ailments. This review focused on how cigarette smoke (CS) promotes ROS formation rather than the pathophysiological repercussions of ROS and oxidative stress. A comprehensive analysis of existing studies revealed the following key ways through which CS imposes ROS burden on biological systems: (1) ROS, as well as radicals, are intrinsically present in CS, (2) CS constituents generate ROS through chemical reactions with biomolecules, (3) CS stimulates cellular ROS sources to enhance production, and (4) CS disrupts the antioxidant system, aggravating the ROS generation and its functions. While the evidence supporting these mechanisms is chiefly based on in vitro and animal studies, the direct clinical relevance remains to be fully elucidated. Nevertheless, this understanding is fundamental for deciphering molecular events leading to oxidative stress and for developing intervention strategies to counter CS-induced oxidative stress.
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Affiliation(s)
| | | | | | - Moo-Yeol Lee
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Goyang-si 10326, Gyeonggi-do, Republic of Korea; (Y.-S.S.); (J.-M.P.); (J.-H.K.)
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20
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Wiśniewski K, Popęda M, Price B, Bieńkowski M, Fahlström A, Drummond K, Adamides AA. Glucose-6-phosphate dehydrogenase and 8-iso-prostaglandin F2α as potential predictors of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. J Neurosurg 2023; 139:698-707. [PMID: 36640097 DOI: 10.3171/2022.12.jns222332] [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: 10/14/2022] [Accepted: 12/07/2022] [Indexed: 01/15/2023]
Abstract
OBJECTIVE Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (aSAH), which is responsible for significant death and disability. The dynamic balance between the production and elimination of reactive oxygen species (ROS) in patients with DCI is suspected be shifted to favor ROS formation. The authors assessed the relationship between F2-isoprostanes (F2-IsoPs), oxidative stress biomarkers, and glucose-6-phosphate dehydrogenase (G6PD), which are responsible for nicotinamide adenine dinucleotide phosphate (NADPH) production for glutathione system function, with post-aSAH DCI. METHODS The authors assessed 45 aSAH patients for F2-IsoP and G6PD concentration using commercial ELISA on days 2, 4, and 6 after aSAH. The authors examined the correlation between plasma F2-IsoP and G6PD concentrations and clinical factors with DCI occurrence and aSAH outcome. RESULTS Expectedly, the most important clinical predictors of DCI were Hunt and Hess grade and modified Fisher (mFisher) grade. Plasma F2-IsoP and G6PD concentrations were greater in aSAH patients than the control group (p < 0.01). F2-IsoP concentrations were greater and G6PD concentrations were lower in patients with DCI than those without (p < 0.01). Plasma F2-IsoP and G6PD concentrations on day 2 were correlated with DCI occurrence (p < 0.01). Plasma F2-IsoP concentrations on days 2 and 6 were correlated with outcome at 1 and 12 months (p < 0.01). CONCLUSIONS Decreased G6PD indirectly informs the reduced antioxidant response, especially for the glutathione system. G6PD concentration was lower in patients with DCI than those without, which may explain the increased F2-IsoP concentrations. mFisher grade, plasma F2-IsoP concentration, and G6PD concentration on day 2 after aSAH, in combination, may serve as predictors of DCI. Further research is necessary to investigate the therapeutic utility of F2-IsoPs and antioxidants in clinical practice.
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Affiliation(s)
- Karol Wiśniewski
- 1Department of Neurosurgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia
- 2Department of Neurosurgery and Neurooncology, Medical University of Łódź, Łódzkie, Poland
| | - Marta Popęda
- 3Department of Pathomorphology, Medical University of Gdańsk, Pomorskie, Poland
| | - Benjamin Price
- 1Department of Neurosurgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Michał Bieńkowski
- 3Department of Pathomorphology, Medical University of Gdańsk, Pomorskie, Poland
| | - Andreas Fahlström
- 1Department of Neurosurgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia
- 4Department of Medical Sciences, Section of Neurosurgery, Uppsala University, Uppsala, Sweden; and
| | - Katharine Drummond
- 1Department of Neurosurgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia
- 5Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia
| | - Alexios A Adamides
- 1Department of Neurosurgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia
- 5Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia
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21
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Dikalov SI, Gutor S, Dikalova AE. Pathological mechanisms of cigarette smoking, dietary, and sedentary lifestyle risks in vascular dysfunction: mitochondria as a common target of risk factors. Pflugers Arch 2023; 475:857-866. [PMID: 36995495 PMCID: PMC10911751 DOI: 10.1007/s00424-023-02806-y] [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: 01/31/2023] [Revised: 03/15/2023] [Accepted: 03/16/2023] [Indexed: 03/31/2023]
Abstract
In the past century, the lifespan of the human population has dramatically increased to the 80 s, but it is hindered by a limited health span to the 60 s due to an epidemic increase in the cardiovascular disease which is a main cause of morbidity and mortality. We cannot underestimate the progress in understanding the major cardiovascular risk factors which include cigarette smoking, dietary, and sedentary lifestyle risks. Despite their clinical significance, these modifiable risk factors are still the major contributors to cardiovascular disease. It is, therefore, important to understand the specific molecular mechanisms behind their pathological effects to develop new therapies to improve the treatment of cardiovascular disease. In recent years, our group and others have made a progress in understanding how these risk factors can promote endothelial dysfunction, smooth muscle dysregulation, vascular inflammation, hypertension, lung, and heart diseases. These factors, despite differences in their nature, lead to stereotypical alterations in vascular metabolism and function. Interestingly, cigarette smoking has a tremendous impact on a very distant site from the initial epithelial exposure, namely circulation and vascular cells mediated by a variety of stable cigarette smoke components which promote vascular oxidative stress and alter vascular metabolism and function. Similarly, dietary and sedentary lifestyle risks facilitate vascular cell metabolic reprogramming promoting vascular oxidative stress and dysfunction. Mitochondria are critical in cellular metabolism, and in this work, we discuss a new concept that mitochondria are a common pathobiological target for these risk factors, and mitochondria-targeted treatments may have a therapeutic effect in the patients with cardiovascular disease.
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Affiliation(s)
- Sergey I Dikalov
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, 2200 Pierce Ave, PRB 554, Nashville, TN, 37232, USA.
| | - Sergey Gutor
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, 2200 Pierce Ave, PRB 554, Nashville, TN, 37232, USA
| | - Anna E Dikalova
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, 2200 Pierce Ave, PRB 554, Nashville, TN, 37232, USA
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22
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Dongiovanni P, Meroni M, Casati S, Goldoni R, Thomaz DV, Kehr NS, Galimberti D, Del Fabbro M, Tartaglia GM. Salivary biomarkers: novel noninvasive tools to diagnose chronic inflammation. Int J Oral Sci 2023; 15:27. [PMID: 37386003 PMCID: PMC10310701 DOI: 10.1038/s41368-023-00231-6] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 05/23/2023] [Accepted: 06/05/2023] [Indexed: 07/01/2023] Open
Abstract
Several chronic disorders including type 2 diabetes (T2D), obesity, heart disease and cancer are preceded by a state of chronic low-grade inflammation. Biomarkers for the early assessment of chronic disorders encompass acute phase proteins (APP), cytokines and chemokines, pro-inflammatory enzymes, lipids and oxidative stress mediators. These substances enter saliva through the blood flow and, in some cases, there is a close relation between their salivary and serum concentration. Saliva can be easily collected and stored with non-invasive and cost-saving procedures, and it is emerging the concept to use it for the detection of inflammatory biomarkers. To this purpose, the present review aims to discuss the advantages and challenges of using standard and cutting-edge techniques to discover salivary biomarkers which may be used in diagnosis/therapy of several chronic diseases with inflammatory consequences with the pursuit to possibly replace conventional paths with detectable soluble mediators in saliva. Specifically, the review describes the procedures used for saliva collection, the standard approaches for the measurement of salivary biomarkers and the novel methodological strategies such as biosensors to improve the quality of care for chronically affected patients.
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Affiliation(s)
- Paola Dongiovanni
- Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Marica Meroni
- Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Sara Casati
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
| | - Riccardo Goldoni
- Department of Electronics, Information and Bioengineering (DEIB), Politecnico di Milano, Milan, Italy
- Istituto di Elettronica e di Ingegneria dell'Informazione e delle Telecomunicazioni, CNR, Pisa, Italy
| | - Douglas Vieira Thomaz
- Laboratory of Medicinal Pharmaceutical Chemistry, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil
| | - Nermin Seda Kehr
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- Department of Chemistry, İzmir Institute of Technology, Gülbahçe Kampüsü, Urla İzmir, Turkey
| | - Daniela Galimberti
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- Neurology-Neurodegenerative Diseases, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Massimo Del Fabbro
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- UOC Maxillo-Facial Surgery and Dentistry Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Gianluca M Tartaglia
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- UOC Maxillo-Facial Surgery and Dentistry Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy
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Behl TA, Stamford BA, Moffatt RJ. The Effects of Smoking on the Diagnostic Characteristics of Metabolic Syndrome: A Review. Am J Lifestyle Med 2023; 17:397-412. [PMID: 37304742 PMCID: PMC10248373 DOI: 10.1177/15598276221111046] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/20/2023] Open
Abstract
Metabolic syndrome is a growing epidemic that increases the risk for cardiovascular disease, diabetes, stroke, and mortality. It is diagnosed by the presence of three or more of the following risk factors: 1) obesity, with an emphasis on central adiposity, 2) high blood pressure, 3) hyperglycemia, 4) dyslipidemia, with regard to reduced high-density lipoprotein concentrations, and 5) dyslipidemia, with regard to elevated triglycerides. Smoking is one lifestyle factor that can increase the risk for metabolic syndrome as it has been shown to exert negative effects on abdominal obesity, blood pressure, blood glucose concentrations, and blood lipid profiles. Smoking may also negatively affect other factors that influence glucose and lipid metabolism including lipoprotein lipase, adiponectin, peroxisome proliferator-activated receptors, and tumor necrosis factor-alpha. Some of these smoking-related outcomes may be reversed with smoking cessation, thus reducing the risk for metabolic disease; however, metabolic syndrome risk may initially increase post cessation, possibly due to weight gain. Therefore, these findings warrant the need for more research on the development and efficacy of smoking prevention and cessation programs.
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Affiliation(s)
- Taylor A. Behl
- Department of Nutrition and Integrative Physiology, Florida State
University, Tallahassee, FL, USA (TAB); School of Business, Education,
and Mathematics, Flagler College, St Augustine, FL, USA (TAB); Department of Kinesiology and
Integrative Physiology, Hanover College, Hanover, IN, USA (BAS); and Human Performance Development
Group, Tallahassee, FL, USA (BAS, RJM)
| | - Bryant A. Stamford
- Department of Nutrition and Integrative Physiology, Florida State
University, Tallahassee, FL, USA (TAB); School of Business, Education,
and Mathematics, Flagler College, St Augustine, FL, USA (TAB); Department of Kinesiology and
Integrative Physiology, Hanover College, Hanover, IN, USA (BAS); and Human Performance Development
Group, Tallahassee, FL, USA (BAS, RJM)
| | - Robert J. Moffatt
- Department of Nutrition and Integrative Physiology, Florida State
University, Tallahassee, FL, USA (TAB); School of Business, Education,
and Mathematics, Flagler College, St Augustine, FL, USA (TAB); Department of Kinesiology and
Integrative Physiology, Hanover College, Hanover, IN, USA (BAS); and Human Performance Development
Group, Tallahassee, FL, USA (BAS, RJM)
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24
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Azzopardi D, Haswell LE, Frosina J, McEwan M, Gale N, Thissen J, Meichanetzidis F, Hardie G. Assessment of biomarkers of exposure and potential harm, and physiological and subjective health measures in exclusive users of nicotine pouches and current, former and never smokers. Biomarkers 2023; 28:118-129. [PMID: 36484137 DOI: 10.1080/1354750x.2022.2148747] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background: Oral nicotine pouches (NPs) are smokeless, tobacco-free products that have a potential role in tobacco harm reduction strategies.Methods: In a cross-sectional study in Sweden/Denmark, several recognised biomarkers of potential harm (BoPHs) linked to smoking-related diseases/their initiating biological processes, and biomarkers of exposure (BoEs) to tobacco/tobacco smoke toxicants were compared among exclusive adult users of Velo NPs and current/former/never smokers. Over 24 h, participants used their usual product (Velo NP or cigarette) as normal, and BoEs/BoPHs were assessed via blood/24-h urine/exhaled breath/physiological assessments.Results: Among the primary endpoints, total NNAL (16.9 ± 29.47 vs 187.4 ± 228.93 pg/24 h), white blood cell count (5.59 ± 1.223 vs 6.90 ± 1.758 × 109/L), and COHb (4.36 ± 0.525 vs 8.03 ± 2.173% saturation) were significantly lower among Velo users than among smokers (91%, 19% and 46% lower, respectively, all P < 0.0001), while fractional exhaled NO, previously shown to be lower in smokers, was significantly higher (23.18 ± 17.909 vs 11.20 ± 6.980 ppb) among Velo users (107% higher, P < 0.0001). Furthermore, sICAM-1 tended to be lower (185.9 ± 42.88 vs 204.5 ± 64.85 ng/mL) among Velo users than smokers (9% lower). Several secondary endpoints, including six BoEs (3-HPMA (246.7 ± 91.07 vs 1165.7 ± 718.35 μg/24 h), 3-OH-B[a]P (82.4 ± 217.58 vs 258.3 ± 190.20 pg/24 h), HMPMA (135.1 ± 77.85 vs 368.8 ± 183.15 μg/24 h), MHBMA (0.22 ± 0.166 vs 3.39 ± 2.943 μg/24 h), S-PMA (0.10 ± 0.059 vs 3.53 ± 2.736 µg/24 h) and total NNN (7.5 ± 24.84 vs 9.7 ± 5.93 ng/24 h)), were significantly lower among Velo users (78.8%, 68.1%, 63.4%, 93.5%, 97.2% and 22.7% lower, respectively, P < 0.0001-0.0011), while total nicotine equivalents was significantly higher among Velo users (22.6 ± 12.69 vs 12.1 ± 7.92 mg/24 h, P < 0.0001), although Velo user levels are comparable to those previously reported among oral tobacco users, and Velo user and smoker mean levels were similar in Denmark.Conclusion: As compared with smokers, exclusive users of Velo NPs have significantly less exposure to tobacco toxicants and more favourable BoPHs associated with initiating biological processes of smoking-related diseases.International Standard Registered Clinical Trial number: ISRCTN16988167.
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Affiliation(s)
- David Azzopardi
- British American Tobacco (Investments) Ltd., R&D Centre, Southampton, UK
| | - Linsey E Haswell
- British American Tobacco (Investments) Ltd., R&D Centre, Southampton, UK
| | - Justin Frosina
- British American Tobacco (Investments) Ltd., R&D Centre, Southampton, UK
| | - Michael McEwan
- British American Tobacco (Investments) Ltd., R&D Centre, Southampton, UK
| | - Nathan Gale
- British American Tobacco (Investments) Ltd., R&D Centre, Southampton, UK
| | - Jesse Thissen
- British American Tobacco (Investments) Ltd., R&D Centre, Southampton, UK
| | | | - George Hardie
- British American Tobacco (Investments) Ltd., R&D Centre, Southampton, UK
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25
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Zhang C, Miao X, Wang B, Thomas RJ, Ribeiro AH, Brant LCC, Ribeiro ALP, Lin H. Association of lifestyle with deep learning predicted electrocardiographic age. Front Cardiovasc Med 2023; 10:1160091. [PMID: 37168659 PMCID: PMC10165078 DOI: 10.3389/fcvm.2023.1160091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 04/04/2023] [Indexed: 05/13/2023] Open
Abstract
Background People age at different rates. Biological age is a risk factor for many chronic diseases independent of chronological age. A good lifestyle is known to improve overall health, but its association with biological age is unclear. Methods This study included participants from the UK Biobank who had undergone 12-lead resting electrocardiography (ECG). Biological age was estimated by a deep learning model (defined as ECG-age), and the difference between ECG-age and chronological age was defined as Δage. Participants were further categorized into an ideal (score 4), intermediate (scores 2 and 3) or unfavorable lifestyle (score 0 or 1). Four lifestyle factors were investigated, including diet, alcohol consumption, physical activity, and smoking. Linear regression models were used to examine the association between lifestyle factors and Δage, and the models were adjusted for sex and chronological age. Results This study included 44,094 individuals (mean age 64 ± 8, 51.4% females). A significant correlation was observed between predicted biological age and chronological age (correlation coefficient = 0.54, P < 0.001) and the mean Δage (absolute error of biological age and chronological age) was 9.8 ± 7.4 years. Δage was significantly associated with all of the four lifestyle factors, with the effect size ranging from 0.41 ± 0.11 for the healthy diet to 2.37 ± 0.30 for non-smoking. Compared with an ideal lifestyle, an unfavorable lifestyle was associated with an average of 2.50 ± 0.29 years of older predicted ECG-age. Conclusion In this large contemporary population, a strong association was observed between all four studied healthy lifestyle factors and deaccelerated aging. Our study underscores the importance of a healthy lifestyle to reduce the burden of aging-related diseases.
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Affiliation(s)
- Cuili Zhang
- Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Correspondence: Cuili Zhang ; Honghuang Lin
| | - Xiao Miao
- Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Biqi Wang
- Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, United States
| | - Robert J. Thomas
- Department of Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, Beth Israel DeaconessMedical Center, Boston, MA, United States
| | - Antônio H. Ribeiro
- Department of Information Technology, Uppsala University, Uppsala, Sweden
| | - Luisa C. C. Brant
- Faculty of Medicine and Telehealth Center, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Antonio L. P. Ribeiro
- Faculty of Medicine and Telehealth Center, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Honghuang Lin
- Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, United States
- Correspondence: Cuili Zhang ; Honghuang Lin
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26
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Mewborn E, Stanfill A. Oxidative Stress Underpins Clinical, Social, and Genetic Risk Factors for Atherosclerotic Cardiovascular Disease. CLINICAL MEDICINE INSIGHTS-CARDIOLOGY 2023; 17:11795468231170779. [PMID: 37153696 PMCID: PMC10155032 DOI: 10.1177/11795468231170779] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 03/31/2023] [Indexed: 05/10/2023]
Abstract
Background Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide and is poorly predicted with current risk estimation tools. The biological mechanisms relating ASCVD risk factors to oxidative stress (OS) and how this accumulates ASCVD risk are misunderstood. Purpose To develop a comprehensive conceptual model explaining how expanded clinical, social, and genetic ASCVD risk factors accumulate ASCVD risk through OS. Conclusions OS (primarily from excess reactive oxygen species) and inflammation are present along the entire ASCVD pathophysiologic continuum. An expanded list of clinical and social ASCVD risk factors (including hypertension, obesity, diabetes, kidney disease, inflammatory diseases, substance use, poor nutrition, psychosocial stress, air pollution, race, and genetic ancestry) influence ASCVD largely through increased OS. Many risk factors exert a positive feedback mechanism to increase OS. One genetic risk factor, haptoglobin (Hp) genotype, is associated with higher ASCVD risk in diabetes and hypothesized to do the same in those with insulin resistance due to the Hp 2-2 genotype increasing OS. Implications Understanding the biological mechanisms of OS informs how these ASCVD risk factors relate to each other and compound ASCVD risk. Individualized ASCVD risk estimation should include a comprehensive, holistic perspective of risk factors to better address the clinical, social, and genetic influences of OS. Preventing and reducing OS is key to preventing ASCVD development or progression.
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Affiliation(s)
- Emily Mewborn
- University of Tennessee Health Science
Center, Memphis, TN, USA
- Emily Mewborn, University of Tennessee
Health Science Center, 874 Union Avenue, Suite G022B, Memphis, TN 38163, USA.
| | - Ansley Stanfill
- University of Tennessee Health Science
Center, Memphis, TN, USA
- Department of Acute and Tertiary Care,
College of Nursing, University of Tennessee Health Science Center, Memphis, TN,
USA
- Department of Genetics, Genomics, and
Informatics, College of Medicine, University of Tennessee Health Science Center,
Memphis, TN, USA
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27
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Wallace RL, Ogunmoroti O, Zhao D, Vaidya D, Heravi A, Guallar E, Ndumele CE, Lima JA, Ouyang P, Budoff MJ, Allison M, Thomas I, Fashanu OE, Hoogeveen R, Post WS, Michos ED. Associations of urinary isoprostanes with measures of subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA). ATHEROSCLEROSIS PLUS 2022; 51:13-21. [PMID: 36969704 PMCID: PMC10037087 DOI: 10.1016/j.athplu.2022.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 11/23/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022]
Abstract
Background Urinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis. Methods Urinary levels of 8-isoprostane and 2,3-dinor-8-F2-isoprostane were measured in 1089 participants (mean ± SD 62 ± 8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors. Results In adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F2-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline. Conclusions Higher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD. Trial registration The MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.
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Avtaar Singh SS, Nappi F. Pathophysiology and Outcomes of Endothelium Function in Coronary Microvascular Diseases: A Systematic Review of Randomized Controlled Trials and Multicenter Study. Biomedicines 2022; 10:3010. [PMID: 36551766 PMCID: PMC9775403 DOI: 10.3390/biomedicines10123010] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 11/17/2022] [Accepted: 11/18/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Coronary macrovascular disease is a concept that has been well-studied within the literature and has long been the subject of debates surrounding coronary artery bypass grafting (CABG) vs. Percutaneous Coronary Intervention (PCI). ISCHEMIA trial reported no statistical difference in the primary clinical endpoint between initial invasive management and initial conservative management, while in the ORBITA trial PCI did not improve angina frequency score significantly more than placebo, albeit PCI resulted in more patient-reported freedom from angina than placebo. However, these results did not prove the superiority of the PCI against OMT, therefore do not indicate the benefit of PCI vs. the OMT. Please rephrase the sentence. We reviewed the role of different factors responsible for endothelial dysfunction from recent randomized clinical trials (RCTs) and multicentre studies. METHODS A detailed search strategy was performed using a dataset that has previously been published. Data of pooled analysis include research articles (human and animal models), CABG, and PCI randomized controlled trials (RCTs). Details of the search strategy and the methods used for data pooling have been published previously and registered with Open-Source Framework. RESULTS The roles of nitric oxide (NO), endothelium-derived contracting factors (EDCFs), and vasodilator prostaglandins (e.g., prostacyclin), as well as endothelium-dependent hyperpolarization (EDH) factors, are crucial for the maintenance of vasomotor tone within the coronary vasculature. These homeostatic mechanisms are affected by sheer forces and other several factors that are currently being studied, such as vaping. The role of intracoronary testing is crucial when determining the effects of therapeutic medications with further studies on the horizon. CONCLUSION The true impact of coronary microvascular dysfunction (CMD) is perhaps underappreciated, which supports the role of medical therapy in determining outcomes. Ongoing trials are underway to further investigate the role of therapeutic agents in secondary prevention.
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Affiliation(s)
| | - Francesco Nappi
- Department of Cardiac Surgery, Centre Cardiologique du Nord of Saint-Denis, 93200 Saint-Denis, France
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Bashir H, Majid S, Khan MS, Bhat MH, Hamid R, Ashraf R, Faiz S. Inter-relationship of Pro- and Anti- inflammatory Biomarkers with the development of Type 2 Diabetes Mellitus. Heliyon 2022; 8:e11329. [DOI: 10.1016/j.heliyon.2022.e11329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 07/03/2022] [Accepted: 10/24/2022] [Indexed: 11/06/2022] Open
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Bellamri M, Walmsley SJ, Brown C, Brandt K, Konorev D, Day A, Wu CF, Wu MT, Turesky RJ. DNA Damage and Oxidative Stress of Tobacco Smoke Condensate in Human Bladder Epithelial Cells. Chem Res Toxicol 2022; 35:1863-1880. [PMID: 35877975 PMCID: PMC9665352 DOI: 10.1021/acs.chemrestox.2c00153] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Smoking is a major risk factor for bladder cancer (BC), with up to 50% of BC cases being attributed to smoking. There are 70 known carcinogens in tobacco smoke; however, the principal chemicals responsible for BC remain uncertain. The aromatic amines 4-aminobiphenyl (4-ABP) and 2-naphthylamine (2-NA) are implicated in BC pathogenesis of smokers on the basis of the elevated BC risk in factory workers exposed to these chemicals. However, 4-ABP and 2-NA only occur at several nanograms per cigarette and may be insufficient to induce BC. In contrast, other genotoxicants, including acrolein, occur at 1000-fold or higher levels in tobacco smoke. There is limited data on the toxicological effects of tobacco smoke in human bladder cells. We have assessed the cytotoxicity, oxidative stress, and DNA damage of tobacco smoke condensate (TSC) in human RT4 bladder cells. TSC was fractionated by liquid-liquid extraction into an acid-neutral fraction (NF), containing polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, phenols, and aldehydes, and a basic fraction (BF) containing aromatic amines, heterocyclic aromatic amines, and N-nitroso compounds. The TSC and NF induced a time- and concentration-dependent cytotoxicity associated with oxidative stress, lipid peroxide formation, glutathione (GSH) depletion, and apurinic/apyrimidinic (AP) site formation, while the BF showed weak effects. LC/MS-based metabolomic approaches showed that TSC and NF altered GSH biosynthesis pathways and induced more than 40 GSH conjugates. GSH conjugates of several hydroquinones were among the most abundant conjugates. RT4 cell treatment with synthetic hydroquinones and cresol mixtures at levels present in tobacco smoke accounted for most of the TSC-induced cytotoxicity and the AP sites formed. GSH conjugates of acrolein, methyl vinyl ketone, and crotonaldehyde levels also increased owing to TSC-induced oxidative stress. Thus, TSC is a potent toxicant and DNA-damaging agent, inducing deleterious effects in human bladder cells at concentrations of <1% of a cigarette in cell culture media.
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Affiliation(s)
- Madjda Bellamri
- Masonic Cancer Center, University of Minnesota, MN 55455
- Department of Medicinal Chemistry, University of Minnesota, MN 55455
| | - Scott J. Walmsley
- Masonic Cancer Center, University of Minnesota, MN 55455
- Division of Biostatistics, Institute of Health Informatics, University of Minnesota, MN 55455
| | - Christina Brown
- Masonic Cancer Center, University of Minnesota, MN 55455
- Department of Medicinal Chemistry, University of Minnesota, MN 55455
| | - Kyle Brandt
- Masonic Cancer Center, University of Minnesota, MN 55455
- Department of Medicinal Chemistry, University of Minnesota, MN 55455
| | - Dmitri Konorev
- Masonic Cancer Center, University of Minnesota, MN 55455
- Department of Medicinal Chemistry, University of Minnesota, MN 55455
| | - Abderrahman Day
- Masonic Cancer Center, University of Minnesota, MN 55455
- Department of Medicinal Chemistry, University of Minnesota, MN 55455
| | - Chia-Fang Wu
- Department of Environmental and Occupational Medicine, Kaohsiung Medical University, CS Building, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan
| | - Ming Tsang Wu
- Department of Environmental and Occupational Medicine, Kaohsiung Medical University, CS Building, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan
| | - Robert J. Turesky
- Masonic Cancer Center, University of Minnesota, MN 55455
- Department of Medicinal Chemistry, University of Minnesota, MN 55455
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Dahdah A, Jaggers RM, Sreejit G, Johnson J, Kanuri B, Murphy AJ, Nagareddy PR. Immunological Insights into Cigarette Smoking-Induced Cardiovascular Disease Risk. Cells 2022; 11:3190. [PMID: 36291057 PMCID: PMC9600209 DOI: 10.3390/cells11203190] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/28/2022] [Accepted: 10/07/2022] [Indexed: 01/19/2023] Open
Abstract
Smoking is one of the most prominent addictions of the modern world, and one of the leading preventable causes of death worldwide. Although the number of tobacco smokers is believed to be at a historic low, electronic cigarette use has been on a dramatic rise over the past decades. Used as a replacement for cigarette smoking, electronic cigarettes were thought to reduce the negative effects of burning tobacco. Nonetheless, the delivery of nicotine by electronic cigarettes, the most prominent component of cigarette smoke (CS) is still delivering the same negative outcomes, albeit to a lesser extent than CS. Smoking has been shown to affect both the structural and functional aspects of major organs, including the lungs and vasculature. Although the deleterious effects of smoking on these organs individually is well-known, it is likely that the adverse effects of smoking on these organs will have long-lasting effects on the cardiovascular system. In addition, smoking has been shown to play an independent role in the homeostasis of the immune system, leading to major sequela. Both the adaptive and the innate immune system have been explored regarding CS and have been demonstrated to be altered in a way that promotes inflammatory signals, leading to an increase in autoimmune diseases, inflammatory diseases, and cancer. Although the mechanism of action of CS has not been fully understood, disease pathways have been explored in both branches of the immune system. The pathophysiologically altered immune system during smoking and its correlation with cardiovascular diseases is not fully understood. Here we highlight some of the important pathological mechanisms that involve cigarette smoking and its many components on cardiovascular disease and the immune systems in order to have a better understanding of the mechanisms at play.
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Affiliation(s)
- Albert Dahdah
- Division of Cardiac Surgery, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Robert M. Jaggers
- Division of Cardiac Surgery, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Gopalkrishna Sreejit
- Division of Cardiac Surgery, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Jillian Johnson
- Division of Cardiac Surgery, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Babunageswararao Kanuri
- Division of Cardiac Surgery, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Andrew J. Murphy
- Division of Immunometabolism, Baker Heart and Diabetes Institute, Melbourne, VIC 3010, Australia
| | - Prabhakara R. Nagareddy
- Division of Cardiac Surgery, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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Abstract
Information on the Omega-3 Index (O3I) in the United Kingdom (UK) are scarce. The UK-Biobank (UKBB) contains data on total plasma omega-3 polyunsaturated fatty acids (n3-PUFA%) and DHA% measured by NMR. The aim of our study was to create an equation to estimate the O3I (eO3I) from these data. We first performed an interlaboratory experiment with 250 random blood samples in which the O3I was measured in erythrocytes by gas chromatography, and total n3% and DHA% were measured in plasma by NMR. The best predictor of eO3I included both DHA% and a derived metric, the total n3%-DHA%. Together these explained 65% of the variability (r=0.832, p<0.0001). We then estimated the O3I in 117,108 UKBB subjects and correlated it with demographic and lifestyle variables in multivariable adjusted models. The mean (SD) eO3I was 5.58% (2.35%) this UKBB cohort. Several predictors were significantly correlated with eO3I (all p<0.0001). In general order of impact and with directionality (- = inverse, + = direct): oily-fish consumption (+), fish oil supplement use (+), female sex (+), older age (+), alcohol use (+), smoking (-), higher waist circumference and BMI (-), lower socioeconomic status and less education (-). Only 20.5% of eO3I variability could be explained by predictors investigated, and oily-fish consumption accounted for 7.0% of that. With the availability of the eO3I in the UKBB cohort we will be in a position to link risk for a variety of diseases with this commonly-used and well-documented marker of n3-PUFA biostatus.
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Martins TGDS, Sipahi AM, Mendes MA, Fowler SB, Schor P. Metaboloma use in ophthalmology. REVISTA BRASILEIRA DE OFTALMOLOGIA 2022; 81. [DOI: 10.37039/1982.8551.20220056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2025] Open
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Mołek P, Chmiel J, Ząbczyk M, Malinowski KP, Natorska J, Undas A. Elevated 8-isoprostane concentration is associated with thromboembolic events in patients with atrial fibrillation. Int J Cardiol 2022; 365:1-7. [PMID: 35868355 DOI: 10.1016/j.ijcard.2022.07.034] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 06/27/2022] [Accepted: 07/17/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND Enhanced oxidative stress occurs in atrial fibrillation (AF), however its impact on the efficacy and safety of anticoagulation is unknown. We sought to evaluate whether 8-isoprostaglandin F2 (8-isoprostane) levels are associated with clinical outcomes in anticoagulated AF patients. METHODS In a study involving 243 AF patients (median age 69 years), we measured serum 8-isoprostane, along with prothrombotic markers, including plasma fibrin clot permeability, clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (VWF), and fibrinolytic proteins. Ischemic cerebrovascular events, major bleeding, and death were recorded during a median follow-up of 53 months while on anticoagulation, largely on non-vitamin K antagonist oral anticoagulants (NOACs). RESULTS Increased 8-isoprostane levels were observed in women, in patients with arterial hypertension, and those with paroxysmal or persistent AF. Patients with 8-isoprostane levels ≥559 pg/mL (the top quartile) compared with those with 8-isoprostane <250 pg/mL (the bottom quartile) had higher fibrinogen, lower VWF, higher plasminogen activator inhibitor 1, along with lower fibrin clot permeability with no difference in CHA2DS2-VASc score, CLT or ETP. Patients who experienced thromboembolic events (n = 20, 1.9%/year) had 48.6% higher 8-isoprostane concentrations compared to the remainder (P <0.01). Levels of 8-isoprostane >459 pg/mL based on the optimal cut-off value were associated with thromboembolic events during follow-up (hazard ratio 2.87, 95% confidence interval 1.17-7.03, P = 0.02). There were no associations between 8-isoprostane and major bleeding (2.0%/year) or all-cause mortality (1.9%/year). CONCLUSIONS Increased 8-isoprostane levels partly through altered fibrin clot structure are associated with thromboembolic events despite anticoagulant therapy in AF patients.
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Affiliation(s)
- Patrycja Mołek
- Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland
| | - Jakub Chmiel
- Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland
| | - Michał Ząbczyk
- Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland
| | - Krzysztof P Malinowski
- Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland; Department of Bioinformatics and Telemedicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Joanna Natorska
- Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland
| | - Anetta Undas
- Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland.
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Sun Y, Yan Y, Kang X. Packed-Fiber Solid Phase-Extraction Coupled with HPLC-MS/MS for Rapid Determination of Lipid Oxidative Damage Biomarker 8-Iso-Prostaglandin F 2α in Urine. Molecules 2022; 27:molecules27144417. [PMID: 35889290 PMCID: PMC9318247 DOI: 10.3390/molecules27144417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 07/06/2022] [Accepted: 07/08/2022] [Indexed: 11/27/2022] Open
Abstract
The 8-iso-prostaglandin F2α (8-iso-PGF2α) biomarker is used as the gold standard for tracing lipid oxidative stress in vivo. The analysis of urinary 8-iso-PGF2α is challenging when dealing with trace amounts of 8-iso-PGF2α and the complexity of urine matrixes. A packed-fiber solid-phase extraction (PFSPE)−coupled with HPLC-MS/MS−method, based on polystyrene (PS)-electrospun nanofibers, was developed for the specific determination of 8-iso-PGF2α in urine and compared with other newly developed LC-MS/MS methods. The method, which simultaneously processed 12 samples within 5 min on a self-made semi-automatic array solid-phase extraction processor, was the first to introduce PS-electrospun nanofibers as an adsorbent for the extraction of 8-iso-PGF2α and was successfully applied to real urine samples. After optimizing the PFSPE conditions, good linearity in the range of 0.05−5 ng/mL with R2 > 0.9996 and a satisfactory limit of detection of 0.015 ng/mL were obtained, with good intraday and interday precision (RSD < 10%) and recoveries of 95.3−103.8%. This feasible method is expected to be used for the batch quantitative analysis of urinary 8-iso-PGF2α.
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Affiliation(s)
- Ying Sun
- Key Laboratory of Child Development and Learning Science (Ministry of Education), School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China;
| | - Yan Yan
- Key Laboratory of Environmental Medicine and Engineering (Ministry of Education), School of Public Health, Southeast University, Nanjing 210096, China;
| | - Xuejun Kang
- Key Laboratory of Child Development and Learning Science (Ministry of Education), School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China;
- Key Laboratory of Environmental Medicine and Engineering (Ministry of Education), School of Public Health, Southeast University, Nanjing 210096, China;
- Correspondence: ; Tel.: +86-025-83795664 (ext. 1011)
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Sources of Variation in Food-Related Metabolites during Pregnancy. Nutrients 2022; 14:nu14122503. [PMID: 35745237 PMCID: PMC9227758 DOI: 10.3390/nu14122503] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/10/2022] [Accepted: 06/14/2022] [Indexed: 12/04/2022] Open
Abstract
The extent to which variation in food-related metabolites are attributable to non-dietary factors remains unclear, which may explain inconsistent food-metabolite associations observed in population studies. This study examined the association between non-dietary factors and the serum concentrations of food-related biomarkers and quantified the amount of variability in metabolite concentrations explained by non-dietary factors. Pregnant women (n = 600) from two Canadian birth cohorts completed a validated semi-quantitative food frequency questionnaire, and serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry. Hierarchical linear modelling and principal component partial R-square (PC-PR2) were used for data analysis. For proline betaine and DHA (mainly exogenous), citrus foods and fish/fish oil intake, respectively, explained the highest proportion of variability relative to non-dietary factors. The unique contribution of dietary factors was similar (15:0, 17:0, hippuric acid, TMAO) or lower (14:0, tryptophan betaine, 3-methylhistidine, carnitine) compared to non-dietary factors (i.e., ethnicity, maternal age, gestational age, pre-pregnancy BMI, physical activity, and smoking) for metabolites that can either be produced endogenously, biotransformed by gut microbiota, and/or derived from multiple food sources. The results emphasize the importance of adjusting for non-dietary factors in future analyses to improve the accuracy and precision of the measures of food intake and their associations with health and disease.
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A New Biomarker in The Distinction Between Stable Coronary Artery Disease and Acute Coronary Syndrome:Thiols. JOURNAL OF CONTEMPORARY MEDICINE 2022. [DOI: 10.16899/jcm.981853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Backraund; Thiols are important elements for oxidation reactions and under oxidative stress. The aim of this study was to determine thiole levels, an antioxidative marker in CAD patients with stable and acute coronary syndrome.
Methods; 210 of the patients included in the study were diagnosed with acute coronary syndrome (ACS), 205 consisted of patients with stable angina pectoris (SAP). Thiol groups levels and thiol/disulphide homeostasis was measured by spectrophotometrically.
Results: Native thiol and total thiol levels, disulfide/natural thiol and disulfide/total thiol ratios were decreased in the ACS groups compared to the SAP groups
Conclusions: Thiol levels and thiol / disulfide ratios can be used as markers to evaluate acute coronary syndrome.
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Mokhtary N, Mousavi SN, Sotoudeh G, Qorbani M, Dehghani M, Koohdani F. Deletion allele of Apo B gene is associated with higher inflammation, oxidative stress and dyslipidemia in obese type 2 diabetic patients: an analytical cross-sectional study. BMC Endocr Disord 2022; 22:73. [PMID: 35317787 PMCID: PMC8939110 DOI: 10.1186/s12902-022-00991-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 03/16/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND We decided to compare some inflammatory, and oxidative stress markers, as well as lipid profiles between the obese and non-obese patients with type 2 diabetes considering ApoB gene polymorphism. METHODS one-hundred sixty two patients with type 2 diabetes were included in this study. ApoB genotyping was conducted by the polymerase chain reaction. Serum interleukin-(IL-18), pentraxin-3 (PTX-3), and high sensitive- C reactive protein (hs-CRP) was measured as the inflammatory markers. Moreover, copper-zinc superoxide dismutase (Cu/Zn-SOD), total antioxidant capacity (TAC) and 8-isoprostane F2α were analyzed for oxidative stress assessment. Anthropometric indices and lipid profiles were measured. RESULTS Adjusted for confounders, serum hs-CRP (p = 0.04), LDL-C (p = 0.01), LDL-C/HDL-C (p = 0.04), and TG (p = 0.02) were significantly lower at the Homozygous Insertion (Ins)/Ins vs. deletion (Del) allele carriers in the obese patients. Serum TAC was significantly lower at the obese Del allele carriers than Ins/Ins Homozygous (p = 0.03). Serum hs-CRP (p = 0.006), and 8-IsoprostanF2α (P = 0.04) were significantly higher in the obese Del allele carriers than non-obese. Serum Cu/Zn-SOD was significantly higher in the non-obese Del allele carriers than obese (p = 0.04). CONCLUSION Inflammation, dyslipidemia, and oxidative stress are higher in the Obese Del allele carriers with type 2 diabetes which prone them to other chronic disorders.
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Affiliation(s)
- Nasim Mokhtary
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyedeh Neda Mousavi
- Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
- Department of Nutrition, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Gity Sotoudeh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mostafa Qorbani
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Maryam Dehghani
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fariba Koohdani
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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Bazid HAS, Attia AM, Yousef AM, Fawal AN, Mostafa MI. Evaluating the Serum and Seminal Plasma Levels of Zinc and Cadmium in Smokers and Their Relation to the Semen Parameters. Biol Trace Elem Res 2022; 200:1002-1009. [PMID: 33860457 DOI: 10.1007/s12011-021-02720-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 04/11/2021] [Indexed: 01/07/2023]
Abstract
Cigarette smoking appears to have adverse effects of male reproductivity. The interplay between zinc and cadmium presumably plays a role in mediating toxic effects of smoking. This work was conducted to study serum and seminal plasma zinc and cadmium level in smokers compared to non-smokers. Seventy males were included: 35 smokers (group I) (smoking ˃20 cigarettes/day with mild smoking index <400) and 35 age-matched non-smokers (group II). Semen analysis was performed according to the WHO laboratory manual 2010. Atomic absorption spectrophotometer was used to detect zinc and cadmium amounts in both blood plasma and semen of any groups. Smoker group showed significantly lower sperm density, motility (P=0.001), and sperm viability (P=0.002) and higher abnormally formed sperms. Seminal zinc level was significantly lower in smokers (P=0.038).There was significant negative correlation between seminal zinc and smoking index and significant positive correlation between seminal zinc levels and sperm motility (P=0.008) and viability percentage (P=0.001). Seminal cadmium level was significantly higher in smoker (P=0.022). Significant positive correlation between seminal cadmium and both age and smoking index (P=0.003) and significant negative correlation between seminal cadmium and sperm density (P=0.005), motility (P=0.047), and viability (P=0.039). Seminal zinc level was negatively correlated to seminal cadmium level (P=0.020). Smoking has deleterious effects on semen quality hence fertility through several toxicants and chemicals. Reduced zinc levels and elevated cadmium levels were evident in smokers which have significant role in the adverse effects on the semen parameters.
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Affiliation(s)
- Heba A S Bazid
- Dermatology and Andrology Department, Faculty of Medicine, Menoufia University, 93 Misr wa Elsudan street, Cairo, 11646, Egypt.
| | - Abdalla M Attia
- Dermatology and Andrology Department, Faculty of Medicine, Menoufia University, 93 Misr wa Elsudan street, Cairo, 11646, Egypt
| | - Amira M Yousef
- Dermatology and Andrology Department, Faculty of Medicine, Menoufia University, 93 Misr wa Elsudan street, Cairo, 11646, Egypt
| | - Asmaa N Fawal
- Dermatology and Andrology Department, Faculty of Medicine, Menoufia University, 93 Misr wa Elsudan street, Cairo, 11646, Egypt
| | - Mohammed I Mostafa
- Clinical Pathology Department, Medical Research Division, National Research Center, Cairo, Egypt
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Costabile G, Vitale M, Della Pepa G, Cipriano P, Vetrani C, Testa R, Mena P, Bresciani L, Tassotti M, Calani L, Del Rio D, Brighenti F, Napoli R, Rivellese AA, Riccardi G, Giacco R. A wheat aleurone-rich diet improves oxidative stress but does not influence glucose metabolism in overweight/obese individuals: Results from a randomized controlled trial. Nutr Metab Cardiovasc Dis 2022; 32:715-726. [PMID: 35123855 DOI: 10.1016/j.numecd.2021.12.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 12/16/2021] [Accepted: 12/17/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND AND AIMS Aleurone is the innermost layer of wheat bran, rich in fiber, minerals, vitamins, phenolic compounds, and betaine. The metabolic effects of aleurone rich foods are still unknown. Our aim was to investigate the effects of consuming a Wheat Aleurone rich diet vs. a Refined Wheat diet for 8 weeks on fasting and postprandial glycemic and lipid metabolism, inflammation, and oxidative stress in overweight/obese individuals. METHODS AND RESULTS According to a randomized cross-over study design, 23 overweight/obese individuals, age 56 ± 9 years (M±SD), were assigned to two isoenergetic diet - Wheat Aleurone and Refined Wheat diets - for 8 weeks. The diets were similar for macronutrient composition but different for the aleurone content (40-50 g/day in the Wheat Aleurone diet). After each diet, fasting and postprandial plasma metabolic profile, ferulic acid metabolites and 8-isoprostane concentrations in 24-h urine samples were evaluated. Compared with the Refined Wheat Diet, the Wheat Aleurone Diet increased fasting plasma concentrations of betaine by 15% (p = 0.042) and decreased the excretion of 8-isoprostane by 33% (p = 0.035). Conversely, it did not affect the fasting and postprandial glucose, insulin and triglyceride responses, homocysteine, and C-Reactive Protein concentrations, nor excretion of phenolic metabolites. CONCLUSION An 8-week Wheat Aleurone Diet improves the oxidative stress and increases plasma betaine levels in overweight/obese individuals with an increased cardiometabolic risk. However, further studies with longer duration and larger sample size are needed to evaluate the benefits of aleurone-rich foods on glucose and lipid metabolism in individuals with more severe metabolic abnormalities. CLINICAL TRIAL REGISTRY NUMBER NCT02150356, (https://clinicaltrials.gov).
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Affiliation(s)
- Giuseppina Costabile
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy.
| | - Marilena Vitale
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Giuseppe Della Pepa
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Paola Cipriano
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Claudia Vetrani
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Roberta Testa
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Pedro Mena
- Human Nutrition Unit, Department of Food and Drug, University of Parma, Via Volturno, 39, 43125, Parma, Italy
| | - Letizia Bresciani
- Human Nutrition Unit, Department of Food and Drug, University of Parma, Via Volturno, 39, 43125, Parma, Italy
| | - Michele Tassotti
- Human Nutrition Unit, Department of Food and Drug, University of Parma, Via Volturno, 39, 43125, Parma, Italy
| | - Luca Calani
- Human Nutrition Unit, Department of Food and Drug, University of Parma, Via Volturno, 39, 43125, Parma, Italy
| | - Daniele Del Rio
- Human Nutrition Unit, Department of Food and Drug, University of Parma, Via Volturno, 39, 43125, Parma, Italy
| | - Furio Brighenti
- Human Nutrition Unit, Department of Food and Drug, University of Parma, Via Volturno, 39, 43125, Parma, Italy
| | - Raffaele Napoli
- Department of Translational Medical Sciences, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Angela A Rivellese
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Gabriele Riccardi
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Rosalba Giacco
- Institute of Food Sciences, National Research Council, Via Roma 64, 8 Avellino, Italy
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Simms L, Yu F, Palmer J, Rudd K, Sticken ET, Wieczorek R, Chapman F, Czekala L, Stevenson M, O’Connell G. Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes to Predict the Cardiotoxicity Potential of Next Generation Nicotine Products. FRONTIERS IN TOXICOLOGY 2022; 4:747508. [PMID: 35295225 PMCID: PMC8915889 DOI: 10.3389/ftox.2022.747508] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 01/20/2022] [Indexed: 12/20/2022] Open
Abstract
Combustible cigarette smoking is an established risk factor for cardiovascular disease. By contrast, the cardiotoxicity potential of non-combustible next generation nicotine products (NGPs), which includes heated tobacco products (HTPs) and electronic vaping products (EVPs), and how this compares relative to combustible cigarettes is currently an area of scientific exploration. As such, there is a need for a rapid screening assay to assess this endpoint. The Cardio quickPredict is a metabolomics biomarker-based assay that uses human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) to screen for potential structural and functional cardiac toxicants based on the changes of four metabolites, lactic acid, arachidonic acid, thymidine, and 2'-deoxycytidine. The study aims were to investigate the cardiotoxicity potential of NGPs compared to cigarettes, in addition to nicotine. To accomplish this, hiPSC-CM were exposed to smoke or aerosol bubbled PBS samples: reference cigarette (1R6F); three variants of HTP; and three EVP variants. The 1R6F bPBS was the most active, having cardiotoxic potential at 0.3-0.6% bPBS (0.4-0.9 μg/mL nicotine), followed by HTP, which displayed cardiotoxic potential at a 10 times higher concentration, 3.3% bPBS (4.1 μg/mL nicotine). Both 1R6F and HTP bPBS (at 10-fold higher concentration than 1R6F) affected all four predictive metabolites, whereas none of the EVP bPBS samples were active in the assay up to the maximal concentration tested (10% bPBS). Nicotine tested on its own was predicted to have cardiotoxic potential at concentrations greater than 80 μg/mL, which is higher than expected physiological levels associated with combustible cigarette smoking. The application of this rapid screening assay to NGP research and the associated findings adds to the weight-of-evidence indicating that NGPs have a tobacco harm reduction potential when compared to combustible cigarettes. Additionally, this technique was shown to be sensitive and robust for the assessment of different NGPs and may be considered as part of a larger overall scientific framework for NGP assessments.
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Affiliation(s)
- Liam Simms
- Imperial Brands PLC, Bristol, United Kingdom
| | - Fan Yu
- Imperial Brands PLC, Bristol, United Kingdom
| | - Jessica Palmer
- Stemina Biomarker Discovery Inc., Madison, WI, United States
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Williams PT. Quantile-specific heritability of 8-isoprostane and the modulating effects of smoking, alcohol, cardiovascular disease and diabetes on 8-isoprostane-gene interactions. Free Radic Biol Med 2022; 178:262-270. [PMID: 34883250 PMCID: PMC10101173 DOI: 10.1016/j.freeradbiomed.2021.11.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 11/16/2021] [Accepted: 11/17/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Urinary 8-isoprostane provides a significantly heritable measure of oxidative stress. Prior reports suggest that genetic variants may modulate oxidative stress due to smoking, other environmental factors, and disease. Alternatively, these apparent modulations may reflect a dependence of genetic effects on 8-isoprostane concentrations. METHOD To test whether genetic effects on 8-isoprostane concentrations are quantile-dependent, quantile-specific offspring-parent (βOP) and full-sib regression slopes (βFS) were estimated by applying quantile regression to the age- and sex-adjusted creatinine-standardized urinary 8-isoprostane concentrations of Framingham Heart Study families. Quantile-specific heritabilities were calculated as h2 = 2βOP/(1+rspouse) and h2 = {(1+8rspouseβFS)0.5-1}/(2rspouse)). RESULTS Spouse 8-isoprostane concentrations were weakly concordant (rspouse = 0.06). 8-isoprostane heritability (h2±SE) increased significantly with increasing percentiles of its distribution (Plinear trend = 0.0009, Pquadratic trend = 0.0007, Pcubic trend = 0.003) when estimated from βOP, and when estimated from βFS (Plinear trend = 0.005, Pquadratic trend = 0.09, Pcubic trend = 0.06). Compared to the 10th percentile, βOP-estimated h2 was over 22-fold greater at the 90th percentile (Pdifference = 9.2 × 10-5), and 5.3-fold greater when estimated from βFS (Pdifference = 0.004). Significantly higher 8-isoprostane heritability in smokers than nonsmokers (0.352 ± 0.147 vs. 0.061 ± 0.036, Pdifference = 0.01), and heavier than lighter drinkers (0.449 ± 0.216 vs. 0.078 ± 0.037, Pdifference = 0.01) were eliminated when corrected for the higher 8-isoprostane concentrations of the smokers and heavier drinkers. CONCLUSION Heritability of oxidative stress as measured by 8-isoprostane is quantile-dependent, which may contribute to the larger reported effects on oxidative stress by UCP2 -866G > A, IL6 -572C > G and LTA 252A > G polymorphisms in smokers than nonsmokers, by the UCP2 -866G > A polymorphism in coronary heart disease patients, by the ESRRG rs1890552 A > G polymorphism in type 2 diabetics, by the CYBA 242C > T polymorphism after exercise training, by the PLIN 11482G > A/14995A > T haplotype before weight loss, and by the CYBA -930A > G and GSTP1 I105V haplotypes in patients with pulmonary edema.
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Affiliation(s)
- Paul T Williams
- Lawrence Berkeley National Laboratory, Molecular Biophysics & Integrated Bioimaging Division, 1 Cyclotron Road, Berkeley, CA, 94720, USA.
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Park J, Park B, Kang EJ, Lee J. CT Imaging Findings in Non-Atherosclerotic Coronary Artery Disease. JOURNAL OF THE KOREAN SOCIETY OF RADIOLOGY 2022; 83:70-83. [PMID: 36237354 PMCID: PMC9238194 DOI: 10.3348/jksr.2021.0165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 12/13/2021] [Accepted: 01/07/2022] [Indexed: 11/24/2022]
Abstract
급성 관동맥 증후군(acute coronary syndrome)은 대부분 죽상경화 관상동맥 질환(atherosclerotic coronary artery disease)에 의해 발생하지만, 비죽상경화 관상동맥 질환에서도 발생할 수 있다. 고식적 관상동맥 혈관조영술은 동맥 내강의 협착이나 확장 등의 형상에 대한 정보만을 제공하고, 동맥경화반이나 동맥벽에 대한 평가가 어려워 관상동맥 이상의 원인 질환의 진단에 낮은 특이도를 보인다. 반면, 관상동맥 전산화단층촬영 혈관조영술은 혈관경화반의 특징, 혈관벽의 조영증강뿐 아니라 연접한 대동맥이나 폐동맥의 변화 등도 함께 관찰할 수 있어, 비죽상경화 관상상동맥질환의 진단 및 다양한 원인 감별에 도움이 된다. 따라서 이 종설에서는 다양한 비죽상경화 관상동맥 질환들을 소개하고, 이의 병태생리 및 대표적인 관상동맥 전산화단층촬영 혈관조영술의 영상 소견에 대해 설명하고자 한다.
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Affiliation(s)
- Jongmin Park
- Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Byunggeon Park
- Department of Radiology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea
| | - Eun-Ju Kang
- Department of Radiology, Dong-A University Medical Center, Dong-A University College of Medicine, Busan, Korea
| | - Jongmin Lee
- Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Korea
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Klein LW. Pathophysiologic Mechanisms of Tobacco Smoke Producing Atherosclerosis. Curr Cardiol Rev 2022; 18:e110422203389. [PMID: 35410615 PMCID: PMC9893148 DOI: 10.2174/1573403x18666220411113112] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/11/2022] [Accepted: 02/24/2022] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION Despite the convincing epidemiologic association between smoking and vascular disease, the pathophysiologic mechanisms by which smoking initiates and contributes to the progression of atherosclerosis remain incompletely understood. A precise dose-dependent correlation has never been demonstrated, suggesting that the biological relationship is complex and influenced by individual genetic and possibly environmental factors. Although endothelial dysfunction and intimal damage appear to be central to atherogenesis, how tobacco products cause this effect has not been established. The purpose of this review is to describe the current state of knowledge of the main pathophysiologic pathways of how tobacco smoking abets atherosclerosis. Constituents of Tobacco Smoke: Tobacco combustion produces a mixture of organic substances. derived from burning organic materials. The predominant gaseous phase constituents include carbon monoxide, acetaldehyde, formaldehyde, acrolein, and other carbonyls, as well as nicotine and tobacco-specific nitrosamines. Potential Pathophysiologic Mechanisms: Smoking-induced changes in coronary vasomotor tone, platelet activation, and endothelial integrity are major components of both the development of atherosclerosis and its clinical presentation. Smoking may initiate and accelerate the progression of atherosclerosis by injuring the vascular intima. Other potential mechanisms include intimal damage and endothelial dysfunction, oxidative stress and injury, thrombosis, lipid abnormalities, and inflammation. CONCLUSION Smoking tobacco products contributes measurably to the incidence of acute vascular events and chronic disease. The causative compound, the exact mechanism of injury, and whether the atherogenic effect is modifiable are not known.
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Affiliation(s)
- Lloyd W. Klein
- Department of Medicine, Cardiology Division, University of California, San Francisco, CA
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Godo S, Takahashi J, Yasuda S, Shimokawa H. Endothelium in Coronary Macrovascular and Microvascular Diseases. J Cardiovasc Pharmacol 2021; 78:S19-S29. [PMID: 34840261 PMCID: PMC8647695 DOI: 10.1097/fjc.0000000000001089] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 06/05/2021] [Indexed: 01/09/2023]
Abstract
ABSTRACT The endothelium plays a pivotal role in the regulation of vascular tone by synthesizing and liberating endothelium-derived relaxing factors inclusive of vasodilator prostaglandins (eg, prostacyclin), nitric oxide (NO), and endothelium-dependent hyperpolarization factors in a distinct blood vessel size-dependent manner. Large conduit arteries are predominantly regulated by NO and small resistance arteries by endothelium-dependent hyperpolarization factors. Accumulating evidence over the past few decades has demonstrated that endothelial dysfunction and coronary vasomotion abnormalities play crucial roles in the pathogenesis of various cardiovascular diseases. Structural and functional alterations of the coronary microvasculature have been coined as coronary microvascular dysfunction (CMD), which is highly prevalent and associated with adverse clinical outcomes in many clinical settings. The major mechanisms of coronary vasomotion abnormalities include enhanced coronary vasoconstrictive reactivity at epicardial and microvascular levels, impaired endothelium-dependent and endothelium-independent coronary vasodilator capacities, and elevated coronary microvascular resistance caused by structural factors. Recent experimental and clinical research has highlighted CMD as the systemic small artery disease beyond the heart, emerging modulators of vascular functions, novel insights into the pathogenesis of cardiovascular diseases associated with CMD, and potential therapeutic interventions to CMD with major clinical implications. In this article, we will summarize the current knowledge on the endothelial modulation of vascular tone and the pathogenesis of coronary macrovascular and microvascular diseases from bench to bedside, with a special emphasis placed on the mechanisms and clinical implications of CMD.
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Affiliation(s)
- Shigeo Godo
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and
| | - Jun Takahashi
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and
| | - Satoshi Yasuda
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and
| | - Hiroaki Shimokawa
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and
- Graduate School, International University of Health and Welfare, Narita, Japan
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Gale N, McEwan M, Camacho OM, Hardie G, Proctor CJ, Murphy J. Changes in biomarkers after 180 days of tobacco heating product use: a randomised trial. Intern Emerg Med 2021; 16:2201-2212. [PMID: 34196886 PMCID: PMC8563516 DOI: 10.1007/s11739-021-02798-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 06/15/2021] [Indexed: 01/14/2023]
Abstract
The aim of this study was to investigate whether biomarkers of exposure (BoE) and potential harm (BoPH) are modified when smokers switch from smoking cigarettes to exclusive use of a tobacco heating product (THP) in an ambulatory setting. Participants in this randomised, controlled study were healthy volunteer smokers assigned either to continue smoking or switch to a THP, and a control group of smokers who abstained from cigarette smoking. Various BoE and BoPH related to oxidative stress, cardiovascular and respiratory diseases, and cancer were assessed at baseline and up to 180 days. In continuing smokers, BoE and BoPH remained stable between baseline and day 180, while THP users' levels of most BoE reduced significantly, becoming similar to those in controls abstaining from cigarette smoking. Also at 180 days, significant changes in numerous BoPH, including total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, 8-epi-prostaglandin F2α type III, fractional concentration of exhaled nitric oxide and white blood cell count, were directionally consistent with lessened health impact. Our findings support the notion that the deleterious health impacts of cigarette smoking may be reduced in smokers who completely switch to using THPs.
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Affiliation(s)
- Nathan Gale
- British American Tobacco (Investments) Limited, Research and Development, Regents Park Road, Southampton, SO15 8TL, UK.
| | - Michael McEwan
- British American Tobacco (Investments) Limited, Research and Development, Regents Park Road, Southampton, SO15 8TL, UK
| | - Oscar M Camacho
- British American Tobacco (Investments) Limited, Research and Development, Regents Park Road, Southampton, SO15 8TL, UK
| | - George Hardie
- British American Tobacco (Investments) Limited, Research and Development, Regents Park Road, Southampton, SO15 8TL, UK
| | | | - James Murphy
- R. J. Reynolds Tobacco Company, 401 N Main Street, Winston-Salem, NC27101, USA
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Fois SS, Canu S, Fois AG. The Role of Oxidative Stress in Sarcoidosis. Int J Mol Sci 2021; 22:ijms222111712. [PMID: 34769145 PMCID: PMC8584035 DOI: 10.3390/ijms222111712] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 10/24/2021] [Accepted: 10/26/2021] [Indexed: 01/15/2023] Open
Abstract
Sarcoidosis is a rare, systemic inflammatory disease whose diagnosis and management can pose a challenge for clinicians and specialists. Scientific knowledge on the molecular pathways that drive its development is still lacking, with no standardized therapies available and insufficient strategies to predict patient outcome. In recent years, oxidative stress has been highlighted as an important factor in the pathogenesis of sarcoidosis, involving several enzymes and molecules in the mechanism of the disease. This review presents current data on the role of oxidative stress in sarcoidosis and its interaction with inflammation, as well as the application of antioxidative therapy in the disease.
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Affiliation(s)
- Sara Solveig Fois
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Viale San Pietro 43, 07100 Sassari, Italy;
- Correspondence:
| | - Sara Canu
- Respiratory Diseases Operative Unit, University Hospital of Sassari, 07100 Sassari, Italy;
| | - Alessandro Giuseppe Fois
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Viale San Pietro 43, 07100 Sassari, Italy;
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Araki M, Yonetsu T, Kurihara O, Nakajima A, Lee H, Soeda T, Minami Y, Higuma T, Kimura S, Takano M, Yan BP, Adriaenssens T, Boeder NF, Nef HM, Kim CJ, McNulty I, Crea F, Kakuta T, Jang IK. Age and Phenotype of Patients With Plaque Erosion. J Am Heart Assoc 2021; 10:e020691. [PMID: 34569250 PMCID: PMC8649143 DOI: 10.1161/jaha.120.020691] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Background A recent study reported that the outcome of patients with plaque erosion treated with stenting is poor when the underlying plaque is lipid rich. However, the detailed phenotype of patients with plaque erosion, particularly as related to different age groups, has not been systematically studied. Methods and Results Patients with acute coronary syndromes caused by plaque erosion were selected from 2 data sets. Demographic, clinical, angiographic, and optical coherence tomography findings of the culprit lesion were compared between 5 age groups. Among 579 erosion patients, male sex and current smoking were less frequent, and hypertension, diabetes, and chronic kidney disease were more frequent in older patients. ST‐segment–elevation myocardial infarction was more frequent in younger patients. Percentage of diameter stenosis on angiogram was greater in older patients. The prevalence of lipid‐rich plaque (27.3% in age <45 years and 49.4% in age ≥75 years, P<0.001), cholesterol crystal (3.9% in age <45 years and 21.8% in age ≥75 years, P=0.027), and calcification (5.5% in age <45 years and 54.0% in age ≥75 years, P<0.001) increased with age. After adjusting risk factors, younger patients were associated with the presence of thrombus, and older patients were associated with greater percentage of diameter stenosis and the presence of lipid‐rich plaque and calcification. Conclusions The demographic, clinical, angiographic, and plaque phenotypes of patients with plaque erosion distinctly vary depending on age. This may affect the clinical outcome in these patients. Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT03479723, NCT02041650.
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Affiliation(s)
- Makoto Araki
- Cardiology Division Massachusetts General HospitalHarvard Medical School Boston MA
| | - Taishi Yonetsu
- Department of Interventional Cardiology Tokyo Medical and Dental University Tokyo Japan
| | - Osamu Kurihara
- Cardiology Division Massachusetts General HospitalHarvard Medical School Boston MA
| | - Akihiro Nakajima
- Cardiology Division Massachusetts General HospitalHarvard Medical School Boston MA
| | - Hang Lee
- Biostatistics Center Massachusetts General HospitalHarvard Medical School Boston MA
| | - Tsunenari Soeda
- Department of Cardiovascular Medicine Nara Medical University Kashihara Nara Japan
| | - Yoshiyasu Minami
- Department of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara Kanagawa Japan
| | - Takumi Higuma
- Division of Cardiology Department of Internal Medicine St. Marianna University School of Medicine Kanagawa Japan
| | - Shigeki Kimura
- Division of Cardiology Kameda Medical Center Chiba Japan
| | - Masamichi Takano
- Cardiovascular Center Nippon Medical School Chiba Hokusoh Hospital Inzai Chiba Japan
| | - Bryan P Yan
- Department of Medicine and Therapeutics Faculty of Medicine The Chinese University of Hong Kong Hong Kong
| | - Tom Adriaenssens
- Department of Cardiovascular Medicine University Hospitals Leuven Leuven Belgium
| | - Niklas F Boeder
- Department of Cardiology University of Giessen Giessen Germany
| | - Holger M Nef
- Department of Cardiology University of Giessen Giessen Germany
| | - Chong Jin Kim
- Division of Cardiology Kyung Hee University Hospital Seoul South Korea
| | - Iris McNulty
- Cardiology Division Massachusetts General HospitalHarvard Medical School Boston MA
| | - Filippo Crea
- Fondazione Policlinico Universitario A Gemelli IRCCS Roma Italy
| | - Tsunekazu Kakuta
- Department of Cardiology Tsuchiura Kyodo General Hospital Tsuchiura Ibaraki Japan
| | - Ik-Kyung Jang
- Cardiology Division Massachusetts General HospitalHarvard Medical School Boston MA.,Division of Cardiology Kyung Hee University Hospital Seoul South Korea
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Mizumura K, Gon Y. Iron-Regulated Reactive Oxygen Species Production and Programmed Cell Death in Chronic Obstructive Pulmonary Disease. Antioxidants (Basel) 2021; 10:antiox10101569. [PMID: 34679704 PMCID: PMC8533398 DOI: 10.3390/antiox10101569] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/30/2021] [Accepted: 09/30/2021] [Indexed: 01/01/2023] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation. However, the pathogenesis of COPD remains unclear. Currently, it is known to involve the loss of alveolar surface area (emphysema) and airway inflammation (bronchitis), primarily due to exposure to cigarette smoke (CS). CS causes epithelial cell death, resulting in pulmonary emphysema. Moreover, CS induces iron accumulation in the mitochondria and cytosol, resulting in programmed cell death. Although apoptosis has long been investigated as the sole form of programmed cell death in COPD, accumulating evidence indicates that a regulated form of necrosis, called necroptosis, and a unique iron-dependent form of non-apoptotic cell death, called ferroptosis, is implicated in the pathogenesis of COPD. Iron metabolism plays a key role in producing reactive oxygen species (ROS), including mitochondrial ROS and lipid peroxidation end-products, and activating both necroptosis and ferroptosis. This review outlines recent studies exploring CS-mediated iron metabolism and ROS production, along with the regulation of programmed cell death in COPD. Elucidating the mechanisms of these pathways may provide novel therapeutic targets for COPD.
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Luther JM, Ray J, Wei D, Koethe JR, Hannah L, DeMatteo A, Manning R, Terker AS, Peng D, Nian H, Yu C, Mashayekhi M, Gamboa J, Brown NJ. GSK2256294 Decreases sEH (Soluble Epoxide Hydrolase) Activity in Plasma, Muscle, and Adipose and Reduces F2-Isoprostanes but Does Not Alter Insulin Sensitivity in Humans. Hypertension 2021; 78:1092-1102. [PMID: 34455816 PMCID: PMC8429121 DOI: 10.1161/hypertensionaha.121.17659] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 07/27/2021] [Indexed: 01/28/2023]
Abstract
[Figure: see text].
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Affiliation(s)
- James M. Luther
- Vanderbilt University Medical Center Department of Medicine, Division of Clinical Pharmacology
| | - Justina Ray
- Icahn School of Medicine at Mount Sinai, Department of Medicine, New York, New York
| | - Dawei Wei
- Vanderbilt University Medical Center Department of Medicine, Division of Clinical Pharmacology
| | - John R. Koethe
- Vanderbilt University Medical Center, Department of Medicine, Division of Infectious Diseases
| | - Latoya Hannah
- Vanderbilt University Medical Center, Department of Medicine, Division of Infectious Diseases
| | - Anthony DeMatteo
- Vanderbilt University Medical Center Department of Medicine, Division of Clinical Pharmacology
| | - Robert Manning
- Vanderbilt University Medical Center Department of Medicine, Division of Clinical Pharmacology
| | - Andrew S Terker
- Vanderbilt University Medical Center, Department of Medicine, Division of Nephrology and Hypertension
| | - Dungeng Peng
- Vanderbilt University Medical Center Department of Medicine, Division of Clinical Pharmacology
| | - Hui Nian
- Vanderbilt University Medical Center, Department of Biostatistics
| | - Chang Yu
- Vanderbilt University Medical Center, Department of Biostatistics
| | - Mona Mashayekhi
- Vanderbilt University Medical Center, Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism
| | - Jorge Gamboa
- Vanderbilt University Medical Center Department of Medicine, Division of Clinical Pharmacology
| | - Nancy J. Brown
- Vanderbilt University Medical Center Department of Medicine, Division of Clinical Pharmacology
- Yale School of Medicine
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