Browsing by Author "Silveyra, Patricia"
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Item Acute Exposure to Ozone Affects Circulating Estradiol Levels and Gonadotropin Gene Expression in Female Mice(MDPI, 2025-02-05) Rousselle, Dustin; Silveyra, Patricia; Medicine, School of MedicineOzone, a critical air pollutant, has been shown to lead to systemic inflammation that can alter bodily functions, including hormone secretion, fertility, and the hypothalamic-pituitary-gonadal (HPG) axis. This study aimed to quantify changes in hormone production and follicle development after acute exposure to ozone using an animal model to identify the potential mechanisms underlying the observed effects of air pollution exposures on fertility and hormone secretion. To accomplish this, regularly cycling 8-week-old female C57BL/6J mice were exposed to 2 ppm of ozone or filtered air (control) for 3 h on the day of proestrus. Blood, ovaries, brain tissues, and pituitary glands were collected at 4 h after exposure to evaluate hormone levels, ovarian follicle distribution, and gene expression. Ovaries were also harvested at 24 h post-exposure. We found that at 4 h after ozone exposure, mice had significantly higher (30%) circulating estradiol levels than mice exposed to filtered air. This effect was accompanied by a decrease in mRNA expression of gonadotropin genes (LH, FSH) and gonadotropin-releasing hormone in the pituitary gland. Analysis of ovarian tissue at 4 h and 24 h after exposure showed no significant changes in follicle composition or the expression of steroidogenesis genes. We conclude that acute ozone exposure affects sex hormone levels and disrupts the HPG axis. Future studies addressing chronic or long-term effects of air pollution exposure are needed to elucidate the mechanisms by which ambient ozone affects endocrine function.Item All trans-retinoic acid modulates hyperoxia-induced suppression of NF-kB-dependent Wnt signaling in alveolar A549 epithelial cells(Public Library of Science, 2022-08-10) Tsotakos, Nikolaos; Ahmed, Imtiaz; Umstead, Todd M.; Imamura, Yuka; Yau, Eric; Silveyra, Patricia; Chroneos, Zissis C.; Medicine, School of MedicineIntroduction: Despite recent advances in perinatal medicine, bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth. Inflammation, the main cause for BPD, results in arrested alveolarization. All trans-retinoic acid (ATRA), the active metabolite of Vitamin A, facilitates recovery from hyperoxia induced cell damage. The mechanisms involved in this response, and the genes activated, however, are poorly understood. In this study, we investigated the mechanisms of action of ATRA in human lung epithelial cells exposed to hyperoxia. We hypothesized that ATRA reduces hyperoxia-induced inflammatory responses in A549 alveolar epithelial cells. Methods: A549 cells were exposed to hyperoxia with or without treatment with ATRA, followed by RNA-seq analysis. Results: Transcriptomic analysis of A549 cells revealed ~2,000 differentially expressed genes with a higher than 2-fold change. Treatment of cells with ATRA alleviated some of the hyperoxia-induced changes, including Wnt signaling, cell adhesion and cytochrome P450 genes, partially through NF-κB signaling. Discussion/conclusion: Our findings support the idea that ATRA supplementation may decrease hyperoxia-induced disruption of the neonatal respiratory epithelium and alleviate development of BPD.Item Association Between Head Impact Exposure, Psychological Needs, and Indicators of Mental Health Among U.S. High School Tackle Football Players(Elsevier, 2023) Kercher, Kyle A.; Steinfeldt, Jesse A.; Rettke, Devin J.; Zuidema, Taylor R.; Walker, Miata J.; (Martinez) Kercher, Vanessa M.; Silveyra, Patricia; Seo, Dong-Chul; Macy, Jonathan T.; Hulvershorn, Leslie A.; Kawata, Keisuke; Psychiatry, School of MedicinePurpose: Age of first exposure to tackle football and head impact kinematics have been used to examine the effect of head impacts on mental health outcomes. These measures coupled with retrospective and cross-sectional designs have contributed to conflicting results. The purpose of this study was to identify the effect of one season of head impact exposure, age of first exposure to football, and psychological need satisfaction on acute mental health outcomes in adolescent football players. Methods: This prospective single-season cohort study used sensor-installed mouthguards to collect head impact exposure along with surveys to assess age of first exposure to football, psychological satisfaction, depressive symptoms, anxiety symptoms, and thriving from football players at four high schools (n = 91). Linear regression was used to test the association of head impact exposure, age of first exposure, and psychological satisfaction with acute mental health outcomes. Results: A total of 9,428 impacts were recorded with a mean of 102 ± 113 impacts/player. Cumulative head impact exposure and age of first exposure were not associated with acute mental health outcomes at postseason or change scores from preseason to postseason. Greater psychological satisfaction was associated with fewer depressive symptoms (β = -0.035, SE = 0.008, p = < .001), fewer anxiety symptoms (β = -0.021, SE = 0.008, p = .010), and greater thriving scores (β = 0.278, SE = 0.040, p = < .001) at postseason. Discussion: This study does not support the premise that greater single-season head impact exposure or earlier age of first exposure to tackle football is associated with worse acute mental health indicators over the course of a single season in adolescent football players.Item Investigating omega-3 fatty acids' neuroprotective effects in repetitive subconcussive neural injury: Study protocol for a randomized placebo-controlled trial(Public Library of Science, 2025-04-24) Beauregard, Lauren H.; Bazarian, Jeffrey J.; Johnson, Blair D.; Cheng, Hu; Ellis, Gage; Kronenberger, William; Calder, Philip C.; Chen, Zhongxue; Silveyra, Patricia; Quinn, Patrick D.; Newman, Sharlene D.; Mickleborough, Timothy D.; Kawata, Keisuke; Psychiatry, School of MedicineSoccer (football) is the most popular sport globally, with 265 million players across all ages and sexes. Repetitive subconcussive head impacts due to heading of the soccer ball can pose threats to healthy brain development and aging. Omega-3 fatty acids, especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may have neuroprotective effects, but it remains unclear what aspects of neural health benefit from DHA+EPA when faced with subconcussive head impacts. In a randomized placebo-controlled trial, 208 soccer players will complete baseline measures including demographics, blood sampling, dietary recalls, and psychological assessment. Participants will be randomly assigned to ingest DHA+EPA [3.4g/d: DHA 2.4g+EPA 1.0g] or placebo daily for 8 weeks followed by a subconcussion intervention phase. During the subconcussion intervention, participants will perform a session of 20 controlled soccer headings, with a second session 24 hours later. Blood samples, neuroimaging data, autonomic reactivity, and clinical measures (symptoms, oculomotor, cognition) will be collected pre-heading and 24-hour post-1st session, 24-hour post-2nd session, and 7-day post-2nd session. The primary hypothesis is that DHA+EPA pretreatment will promote neuronal and astrocyte resiliency to subconcussive head impacts, as assessed by blood biomarkers of brain injury, axonal microstructure measured by diffusion tensor imaging, and whole-brain resting-state connectivity. It is proposed that pretreatment will preserve autonomic function, as assessed by the cold pressor test (CPT), as well as oculomotor and cognitive function, even after head impacts. Data from this trial will help clarify the combined effect of DHA+EPA on brain molecular, cellular, and physiological health in response to subconcussive head impacts. If the hypotheses are confirmed, the findings will support a highly practical intervention for mitigating the neurodegenerative cascade triggered by head impacts.Item New voices for a better society(National Academy of Science, 2024) Diem, Stephanie J.; Bayon, Baindu L.; Mahmoud, Hussam; Garcia-Cazarin, Mary L.; Martin, Michael J.; Rittschof, Clare C.; Silveyra, Patricia; Boland-Reeves, Alison; Najib, Dalal; Wasson, Flannery; Epidemiology, Richard M. Fairbanks School of Public HealthItem Sensitivity of Mouse Lung Nuclear Receptors to Electronic Cigarette Aerosols and Influence of Sex Differences: A Pilot Study(MDPI, 2024-06-20) Sharma, Shikha; Rousselle, Dustin; Parker, Erik; Damilola Ekpruke, Carolyn; Alford, Rachel; Babayev, Maksat; Commodore, Sarah; Silveyra, Patricia; Medicine, School of MedicineThe emerging concern about chemicals in electronic cigarettes, even those without nicotine, demands the development of advanced criteria for their exposure and risk assessment. This study aims to highlight the sensitivity of lung nuclear receptors (NRs) to electronic cigarette e-liquids, independent of nicotine presence, and the influence of the sex variable on these effects. Adult male and female C57BL/6J mice were exposed to electronic cigarettes with 0%, 3%, and 6% nicotine daily (70 mL, 3.3 s, 1 puff per min/30 min) for 14 days, using the inExpose full body chamber (SCIREQ). Following exposure, lung tissues were harvested, and RNA extracted. The expression of 84 NRs was determined using the RT2 profiler mRNA array (Qiagen). Results exhibit a high sensitivity to e-liquid exposure irrespective of the presence of nicotine, with differential expression of NRs, including one (females) and twenty-four (males) in 0% nicotine groups compared to non-exposed control mice. However, nicotine-dependent results were also significant with seven NRs (females), fifty-three NRs (males) in 3% and twenty-three NRs (female) twenty-nine NRs (male) in 6% nicotine groups, compared to 0% nicotine mice. Sex-specific changes were significant, but sex-related differences were not observed. The study provides a strong rationale for further investigation.Item Sex Differences in Airway Remodeling and Inflammation: Clinical and Biological Factors(Frontiers Media, 2022-04-29) Ekpruke, Carolyn Damilola; Silveyra, Patricia; Medicine, School of MedicineAsthma is characterized by an increase in the contraction and inflammation of airway muscles, resulting in airflow obstruction. The prevalence of asthma is lower in females than in males until the start of puberty, and higher in adult women than men. This sex disparity and switch at the onset of puberty has been an object of debate among many researchers. Hence, in this review, we have summarized these observations to pinpoint areas needing more research work and to provide better sex-specific diagnosis and management of asthma. While some researchers have attributed it to the anatomical and physiological differences in the male and female respiratory systems, the influences of hormonal interplay after puberty have also been stressed. Other hormones such as leptin have been linked to the sex differences in asthma in both obese and non-obese patients. Recently, many scientists have also demonstrated the influence of the sex-specific genomic framework as a key player, and others have linked it to environmental, social lifestyle, and occupational exposures. The majority of studies concluded that adult men are less susceptible to developing asthma than women and that women display more severe forms of the disease. Therefore, the understanding of the roles played by sex- and gender-specific factors, and the biological mechanisms involved will help develop novel and more accurate diagnostic and therapeutic plans for sex-specific asthma management.Item Sex Differences in E-Cigarette Use and Related Health Effects(MDPI, 2023-11-18) Alam, Fatima; Silveyra, Patricia; Medicine, School of MedicineBackground: Electronic cigarettes (e-cigarettes) comprise a variety of products designed to deliver nicotine, flavorings, and other substances. To date, multiple epidemiological and experimental studies have reported a variety of health issues associated with their use, including respiratory toxicity, exacerbation of respiratory conditions, and behavioral and physiological effects. While some of these effects appear to be sex- and/or gender-related, only a portion of the research has been conducted considering these variables. In this review, we sought to summarize the available literature on sex-specific effects and sex and gender differences, including predictors and risk factors, effects on organ systems, and behavioral effects. Methods: We searched and selected articles from 2018-2023 that included sex as a variable or reported sex differences on e-cigarette-associated effects. Results: We found 115 relevant studies published since 2018 that reported sex differences in a variety of outcomes. The main differences reported were related to reasons for initiation, including smoking history, types of devices and flavoring, polysubstance use, physiological responses to nicotine and toxicants in e-liquids, exacerbation of lung disease, and behavioral factors such as anxiety, depression, sexuality, and bullying. Conclusions: The available literature supports the notion that both sex and gender influence the susceptibility to the negative effects of e-cigarette use. Future research needs to consider sex and gender variables when addressing e-cigarette toxicity and other health-related consequences.Item Sex-Specific Anti-Inflammatory Effects of a Ketogenic Diet in a Mouse Model of Allergic Airway Inflammation(MDPI, 2025-03-26) Ekpruke, Carolyn D.; Borges-Sosa, Omar; Hassel, Christiane A.; Rousselle, Dustin; Dinwiddie, Lyidia; Babayev, Maksat; Bakare, Ahmed; Silveyra, Patricia; Medicine, School of MedicineAsthma, a chronic inflammatory airway disease, leads to airflow obstruction and exhibits sex differences in prevalence and severity. Immunomodulatory diets, such as the ketogenic diet (high fat, low carbohydrate, moderate protein), may offer complementary benefits in managing airway inflammation. While anti-inflammatory effects of ketogenic diets are documented in cardiovascular diseases, their impact on asthma, especially regarding sex-specific differences, remains unexplored. Few studies on diet and asthma have considered sex as a biological factor. To test the hypothesis that a ketogenic diet affects airway inflammation in a sex-specific manner, we used a mouse allergic airway inflammation model. Male and female C57BL/6J mice (3-4 weeks old, n = 5-6/group) were fed a ketogenic diet or normal chow for 12 weeks. From weeks 7 to 12, mice were challenged intranasally with house dust mite allergens (HDM) 5 days/week to induce airway inflammation. Lung tissue was analyzed 72 h post-exposure using flow cytometry to assess immune cell populations, and data were analyzed with two-way ANOVA. The ketogenic diet increased body weight in allergen-exposed mice, with a greater effect in males than females (p = 0.0512). Significant sex-diet interactions were noted for alveolar macrophages, CD103+, CD11B+, and plasmacytoid dendritic cells (p < 0.05). Eosinophil reductions were observed in males but not females on the ketogenic diet. The diet also increased NKT cells and decreased NK cells in males but not females (p < 0.001). These findings highlight sex-specific effects of ketogenic diets on lung immune responses, with stronger impacts in males.Item Thirdhand vaping exposures are associated with pulmonary and systemic inflammation in a mouse model(OAE, 2023) Commodore, Sarah; Sharma, Shikha; Ekpruke, Carolyn Damilola; Pepin, Robert; Hansen, Angela M.; Rousselle, Dustin; Babayev, Maksat; Ndeke, Jonas M.; Alford, Rachel; Parker, Erik; Dickinson, Stephanie; Sharma, Sunita; Silveyra, Patricia; Medicine, School of MedicineThirdhand smoke (THS) is the accumulation of secondhand smoke on surfaces that ages with time. THS exposure is a potential health threat to children, partners of smokers, and workers in environments with current or past smoking, and needs further investigation. In this study, we hypothesized that thirdhand Electronic Nicotine Delivery Systems (ENDS) exposures elicit lung and systemic inflammation due to resuspended particulate matter (PM) and inorganic compounds that remain after active vaping has ceased. To test our hypothesis, we exposed C57BL/6J mice to cotton towels contaminated with ENDS aerosols from unflavored vape fluid (6 mg nicotine in 50/50 propylene glycol/vegetable glycerin) for 1h/day, five days/week, for three weeks. We assessed protein levels in serum and bronchoalveolar lavage fluid (BALF) using a multiplex protein assay. The mean ± sd for PM10 and PM2.5 measurements in exposed mouse cages were 8.3 ± 14.0 and 4.6 ± 7.5 μg/m3, compared to 6.1 ± 11.2 and 3.7 ± 6.6 μg/m3 in control cages respectively. Two compounds, 4-methyl-1, 2-dioxolane and 4-methyl-cyclohexanol, were detected in vape fluid and on ENDS-contaminated towels, but not on control towels. Mice exposed to ENDS-contaminated towels had lower levels of serum Il-7 (P = 0.022, n = 7), and higher levels of Il-13 in the BALF (P = 0.006, n = 7) than those exposed to control towels (n = 6). After adjusting for sex and age, Il-7 and Il-13 levels were still associated with thirdhand vaping exposure (P = 0.010 and P = 0.017, respectively). This study provides further evidence that thirdhand ENDS aerosols can contaminate surfaces, and subsequently influence lung and systemic health upon exposure.