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      Acute vaping in a golden Syrian hamster causes inflammatory response transcriptomic changes

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          Abstract

          E-cigarette vaping is a major aspect of nicotine consumption, especially for children and young adults. Although it is branded as a safer alternative to cigarette smoking, murine and rat models of subacute and chronic e-cigarette vaping exposure have shown many proinflammatory changes in the respiratory tract. An acute vaping exposure paradigm has not been demonstrated in the golden Syrian hamster, and the hamster is a readily available small animal model that has the unique benefit of becoming infected with and transmitting respiratory viruses, including SARS-CoV-2, without genetic alteration of the animal or virus. Using a 2-day, whole body vaping exposure protocol in male golden Syrian hamsters, we evaluated serum cotinine, bronchoalveolar lavage cells, lung, and nasal histopathology, and gene expression in the nasopharynx and lung through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Depending on the presence of nonnormality or outliers, statistical analysis was performed by ANOVA or Kruskal–Wallis tests. For tests that were statistically significant ( P < 0.05), post hoc Tukey–Kramer and Dunn’s tests, respectively, were performed to make pairwise comparisons between groups. In nasal tissue, RT-qPCR analysis revealed nicotine-dependent increases in gene expression associated with type 1 inflammation ( CCL-5 and CXCL-10), fibrosis [transforming growth factor-β ( TGF-β)], nicotine-independent increase oxidative stress response ( SOD-2), and a nicotine-independent decrease in vasculogenesis/angiogenesis (VEGF-A). In the lung, nicotine-dependent increases in the expression of genes involved in the renin-angiotensin pathway [angiotensin-converting enzyme ( ACE), ACE2], coagulation ( tissue factor, Serpine-1), extracellular matrix remodeling ( MMP-2, MMP-9), type 1 inflammation ( IL-1β, TNF-α, and CXCL-10), fibrosis ( TGF-β and Serpine-1), oxidative stress response ( SOD-2), neutrophil extracellular traps release ( ELANE), and vasculogenesis and angiogenesis ( VEGF-A) were identified. To our knowledge, this is the first demonstration that the Syrian hamster is a viable model of e-cigarette vaping. In addition, this is the first report that e-cigarette vaping with nicotine can increase tissue factor gene expression in the lung. Our results show that even an acute exposure to e-cigarette vaping causes significant upregulation of mRNAs in the respiratory tract from pathways involving the renin-angiotensin system, coagulation, extracellular matrix remodeling, type 1 inflammation, fibrosis, oxidative stress response, neutrophil extracellular trap release (NETosis), vasculogenesis, and angiogenesis.

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          Most cited references31

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          Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development

          Significance Since SARS-CoV-2 emerged in China, it has spread rapidly around the world. Effective vaccines and therapeutics for SARS-CoV-2−induced disease (coronavirus disease 2019;COVID-19) are urgently needed. We found that SARS-CoV-2 isolates replicate efficiently in the lungs of Syrian hamsters and cause severe pathological lesions in the lungs of these animals similar to commonly reported imaging features of COVID-19 patients with pneumonia. SARS-CoV-2−infected hamsters mounted neutralizing antibody responses and were protected against rechallenge with SARS-CoV-2. Moreover, passive transfer of convalescent serum to naïve hamsters inhibited virus replication in their lungs. Syrian hamsters are a useful small animal model for the evaluation of vaccines, immunotherapies, and antiviral drugs.
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            Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility

            Abstract Background A physiological small animal model that resembles COVID-19 with low mortality is lacking. Methods Molecular docking on the binding between angiotensin-converting enzyme 2 (ACE2) of common laboratory mammals and the receptor-binding domain of the surface spike protein of SARS-CoV-2 suggested that the golden Syrian hamster is an option. Virus challenge, contact transmission, and passive immunoprophylaxis were performed. Serial organ tissues and blood were harvested for histopathology, viral load and titre, chemokine/cytokine assay, and neutralising antibody titre. Results The Syrian hamster could be consistently infected by SARS-CoV-2. Maximal clinical signs of rapid breathing, weight loss, histopathological changes from the initial exudative phase of diffuse alveolar damage with extensive apoptosis to the later proliferative phase of tissue repair, airway and intestinal involvement with virus nucleocapsid protein expression, high lung viral load, and spleen and lymphoid atrophy associated with marked cytokine activation were observed within the first week of virus challenge. The lung virus titre was between 105-107 TCID50/g. Challenged index hamsters consistently infected naïve contact hamsters housed within the same cage, resulting in similar pathology but not weight loss. All infected hamsters recovered and developed mean serum neutralising antibody titre ≥1:427 fourteen days post-challenge. Immunoprophylaxis with early convalescent serum achieved significant decrease in lung viral load but not in lung pathology. No consistent non-synonymous adaptive mutation of the spike was found in viruses isolated from infected hamsters. Conclusions Besides satisfying the Koch’s postulates, this readily available hamster model is an important tool for studying transmission, pathogenesis, treatment, and vaccination against SARS-CoV-2.
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              Tobacco Product Use and Associated Factors Among Middle and High School Students — National Youth Tobacco Survey, United States, 2021

              Problem/Condition Commercial tobacco use is the leading cause of preventable disease, disability, and death in the United States. Most tobacco product use begins during adolescence. In recent years, tobacco products have evolved to include various combusted, smokeless, and electronic products. Period Covered 2021. Description of System The National Youth Tobacco Survey (NYTS) is an annual, cross-sectional, school-based, self-administered survey of U.S. middle school (grades 6–8) and high school (grades 9–12) students. A three-stage cluster sampling procedure is used to generate a nationally representative sample of U.S. students attending public and private schools. NYTS is the only nationally representative survey of U.S. middle and high school students that focuses exclusively on tobacco use patterns and associated factors. NYTS provides data to support the design, implementation, and evaluation of comprehensive youth tobacco use prevention and control programs and to guide tobacco regulatory activities. Since 2019, NYTS has been administered electronically via tablet computers. Because of emergency COVID-19 protocols that were in place across the United States during the 2021 NYTS fielding window (January 18–May 21, 2021), the 2021 survey was administered using a web URL to allow participation by eligible students learning under varying instructional models (in-person, distance/virtual, and hybrid). In total, 50.8% of student respondents reported completing the survey in a school building or classroom and 49.2% at home or some other place. CDC and the Food and Drug Administration (FDA) analyzed data from the 2021 NYTS to assess tobacco product use patterns and associated factors among U.S. middle and high school students. Overall, 20,413 students (out of 25,149 sampled students; student response rate: 81.2%) completed the questionnaire from 279 schools (out of 508 sampled schools; school response rate: 54.9%). The overall response rate, defined as the product of the student and school response rates, was 44.6%. The sample was weighted to represent approximately 11.97 million middle school students and 15.44 million high school students. Students with missing information about grade level were excluded from the school-level analyses (n = 135). Results In 2021, an estimated 34.0% of high school students (5.22 million) and 11.3% of middle school students (1.34 million) reported ever using a tobacco product (i.e., electronic cigarettes [e-cigarettes], cigarettes, cigars, smokeless tobacco, hookahs, pipe tobacco, heated tobacco products, nicotine pouches, and bidis [small brown cigarettes wrapped in a leaf]). Current (past 30-day) use of a tobacco product was 13.4% for high school students (2.06 million) and 4.0% for middle school students (470,000). E-cigarettes were the most commonly currently used tobacco product, cited by 11.3% of high school students (1.72 million) and 2.8% of middle school students (320,000), followed by cigarettes, cigars, smokeless tobacco, hookahs, nicotine pouches, heated tobacco products, and pipe tobacco. Current use of any tobacco product was reported by 14.2% of students identifying as lesbian, gay, or bisexual (LGB) (versus 7.9% of heterosexual); 18.9% of students identifying as transgender (versus 8.2% of not transgender); and 14.2% of students reporting severe psychological distress (versus 5.5% with no distress). Among students who currently used each respective tobacco product, frequent use (on ≥20 days of the past 30 days) ranged from 17.2% for nicotine pouches to 39.4% for e-cigarettes. Among current users of any tobacco product, 79.1% reported using a flavored tobacco product; by product, e-cigarettes were the most commonly used flavored tobacco product. Among current users of any tobacco product, the most commonly reported source of access was from a friend (32.8%). Among students who currently used e-cigarettes, 53.7% used a disposable device, 28.7% used a prefilled/refillable pod or cartridge device, 9.0% used a tank or mod system (a system that can be customized by the user), and 8.6% did not know the device type. Among students who had ever used e-cigarettes, the most common reason for first trying them was “a friend used them” (57.8%); among current e-cigarette users, the most commonly cited reason for current use was “I am feeling anxious, stressed, or depressed” (43.4%). Among all middle and high school students, 75.2% reported past-year recognition of any antitobacco public education campaign ads. Exposure to marketing or advertising for any tobacco product was reported by 75.7% of students who had contact with an assessed potential source of tobacco product advertisements or promotions (going to a convenience store, supermarket, or gas station; using the Internet; watching television or streaming services or going to the movies; or reading newspapers or magazines). Among students who reported using social media, 73.5% had ever seen e-cigarette–related content. Among all students, perceiving “no” or “little” harm from intermittent tobacco product use was highest for e-cigarettes (16.6%) and lowest for cigarettes (9.6%). Among students who currently used any tobacco product, 27.2% had experienced cravings during the past 30 days; 19.5% reported wanting to use a tobacco product within 30 minutes of waking. Moreover, 65.3% of students who currently used tobacco products were seriously thinking about quitting the use of all products, and 60.2% had stopped using all products for ≥1 day because they were trying to quit during the past 12 months. Interpretation In 2021, approximately one in 10 U.S. middle and high school students (9.3%) had used a tobacco product during the preceding 30 days. By school level, this represented more than one in eight high school students (13.4%) and approximately one in 25 middle school students (4.0%). E-cigarettes were the most commonly used tobacco product in 2021. Tobacco product use was higher among certain subpopulations, such as those identifying as LGB or transgender, or those reporting psychological distress. Importantly, approximately two thirds of students who currently used tobacco products were seriously thinking about quitting. However, factors that might continue to promote tobacco product use among U.S. youths, such as the availability of flavors, access to tobacco products, exposure to tobacco product marketing, and misperceptions about harm from tobacco product use, remained prevalent in 2021. Public Health Action The continued monitoring of all forms of youth tobacco product use and associated factors through surveillance efforts including NYTS is important to the development of public health policy and action at national, state, and local levels. The 2021 NYTS was successfully administered during the COVID-19 pandemic using a web URL to allow participation by eligible students learning under varying instructional models. As a result of these modifications to the fielding procedures, any comparison of results between 2021 NYTS findings with previous years, including the direct attribution of any potential changes in tobacco product use, is not possible. Parents, educators, youth advocates, and health care providers can help protect youths from the harms of tobacco products, including e-cigarettes. In addition, the comprehensive and sustained implementation of evidence-based tobacco control strategies, combined with FDA’s regulation of tobacco products, is important for reducing all forms of tobacco product use among U.S. youths.
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                Author and article information

                Journal
                Am J Physiol Lung Cell Mol Physiol
                Am J Physiol Lung Cell Mol Physiol
                AJPLUNG
                American Journal of Physiology - Lung Cellular and Molecular Physiology
                American Physiological Society (Rockville, MD )
                1040-0605
                1522-1504
                1 November 2022
                30 August 2022
                30 August 2022
                : 323
                : 5
                : L525-L535
                Affiliations
                [1] 1Department of Pediatrics, University of Iowa , Iowa City, Iowa
                [2] 2Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado
                [3] 3Department of Pediatrics, National Jewish Health , Denver, Colorado
                [4] 4Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus , Aurora, Colorado
                [5] 5Biomedical Sciences Department, Colorado State University , Fort Collins, Colorado
                Author notes
                Correspondence: D. M. Hinds ( daniel-hinds@ 123456uiowa.edu ).
                Author information
                https://orcid.org/0000-0002-1291-741X
                https://orcid.org/0000-0002-7853-6302
                https://orcid.org/0000-0003-2240-8632
                https://orcid.org/0000-0001-9340-8336
                Article
                L-00162-2022 L-00162-2022
                10.1152/ajplung.00162.2022
                9602905
                36041220
                0ba410d4-252a-4d13-b90b-50adb0588d93
                Copyright © 2022 the American Physiological Society.
                History
                : 23 May 2022
                : 21 July 2022
                : 28 August 2022
                Funding
                Funded by: Children's Hospital Colorado Research Institute, doi 10.13039/100006383;
                Award ID: CHC R7530S PEDS
                Award Recipient : Carl W. White
                Funded by: HHS | NIH | National Institute of Environmental Health Sciences (NIEHS), doi 10.13039/100000066;
                Award ID: U54ES027698-05
                Award Recipient : Carl W. White
                Funded by: HHS | NIH | National Institute of Environmental Health Sciences (NIEHS), doi 10.13039/100000066;
                Award ID: 3U54ES027698-05S1
                Award Recipient : Carl W. White
                Categories
                Research Article
                Electronic Cigarettes: Not All Good News?
                Custom metadata
                True

                Anatomy & Physiology
                e-cigarette,golden syrian hamster,proinflammatory,tissue factor,vaping
                Anatomy & Physiology
                e-cigarette, golden syrian hamster, proinflammatory, tissue factor, vaping

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