Role of circular RNAs in lung cancer.

Lung cancer remains a global public health concern with significant research focus on developing better diagnosis/prognosis biomarkers and therapeutical targets. Circular RNAs (circRNAs) are a type of single-stranded RNA molecules that covalently closed and have ubiquitous expression. These molecules have been implicated in a variety of disease mechanisms, including lung cancer, as they exhibit oncogenic or tumor suppressor characteristics. Recent research has shown an important role that circRNAs play at different stages of lung cancer, particularly in lung adenocarcinoma. In this review, we summarize the latest research on circRNAs and their roles within lung cancer diagnosis, as well as on disease mechanisms. We also discuss the knowledge gaps on these topics and possible future research directions.

Transcriptomics analysis of allergen-induced inflammatory gene expression in the Four-Core Genotype mouse model.

Sex differences in allergic inflammation have been reported, but the mechanisms underlying these differences remain unknown. Contributions of both sex hormones and sex-related genes to these mechanisms have been previously suggested in clinical and animal studies. Here, Four-Core Genotypes (FCG) mouse model was used to study the inflammatory response to house dust mite (HDM) challenge and identify differentially expressed genes (DEGs) and regulatory pathways in lung tissue. Briefly, adult mice (8-10 wk old) of the FCG (XXM, XXF, XYM, XYF) were challenged intranasally with 25 µg of HDM or vehicle (PBS-control group) 5 days/wk for 5 wk (n = 3/10 group). At 72 h after the last exposure, we analyzed the eosinophils and neutrophils in the bronchoalveolar lavage (BAL) of FCG mice. We extracted lung tissue and determined DEGs using Templated Oligo-Sequencing (TempO-Seq). DEG analysis was performed using the DESeq2 package and gene enrichment analysis was done using Ingenuity Pathway Analysis. A total of 2,863 DEGs were identified in the FCG. Results revealed increased eosinophilia and neutrophilia in the HDM-treated group with the most significantly expressed genes in XYF phenotype and a predominant effect of female hormones vs. chromosomes. Regardless of the sex hormones, mice with female chromosomes had more downregulated genes in the HDM group but this was reversed in the control group. Interestingly, genes associated with inflammatory responses were overrepresented in the XXM and XYF genotypes treated with HDM. Sex hormones and chromosomes contribute to inflammatory responses to HDM challenge, with female hormones exerting a predominant effect mediated by inflammatory DEGs.NEW & NOTEWORTHY Gene expression profiling helps to provide deep insight into the global view of disease-related mechanisms and responses to therapy. Using the Four-Core Genotype mouse model, our findings revealed the influence of sex hormones and sex chromosomes in the gene expression of lungs exposed to an aeroallergen (House Dust Mite) and identified sex-specific pathways to better understand sex disparities associated with allergic airway inflammation.

Lung proinflammatory microRNA and cytokine expression in a mouse model of allergic inflammation: role of sex chromosome complement and gonadal hormones.

Epigenetic alterations such as dysregulation of miRNAs have been reported to play important roles in interactions between genetic and environmental factors. In this study, we tested the hypothesis that induction of lung inflammation by inhaled allergens triggers a sex-specific miRNA regulation that is dependent on chromosome complement and hormonal milieu. We challenged the four core genotypes (FCGs) model through intranasal sensitization with a house dust mite (HDM) solution (or PBS as a control) for 5 wk. The FCG model allows four combinations of gonads and sex chromosomes: 1) XX mice with ovaries (XXF), 2) XY mice with testes (XYM), 3) XX mice with testes (XXM), and 4) XY mice with ovaries (XYF). Following the challenge (n = 5-7/group), we assessed the expression of 84 inflammatory miRNAs in lung tissue using a PCR array and cytokine levels in bronchoalveolar lavage fluid (BAL) by a multiplex protein assay (n = 4-7 animals/group). Our results showed higher levels of the chemokine KC (an Il-8 homolog) and IL-7 in BAL from XYF mice challenged with HDM. In addition, IL-17A was significantly higher in BAL from both XXF and XYF mice. A three-way interaction among treatment, gonads, and sex chromosome revealed 60 of 64 miRNAs that differed in expression depending on genotype; XXF, XXM, XYF, and XYM mice had 45, 32, 4, and 52 differentially expressed miRNAs, respectively. Regulatory networks of miRNAs identified in this study were implicated in pathways associated with asthma. Female gonadal hormonal effects may alter miRNA expression and contribute to the higher susceptibility of females to asthma.NEW & NOTEWORTHY miRNAs play important roles in regulating gene and environmental interactions. However, their role in mediating sex differences in allergic responses and lung diseases has not been elucidated. Our study used a targeted omics approach to characterize the contributions of gonadal hormones and chromosomal components to lung responses to an allergen challenge. Our results point to the influence of sex hormones in miRNA expression and proinflammatory markers in allergic airway inflammation.

Impact on oxidative stress of oral, high-dose, iron supplementation for management of iron deficiency after bariatric surgery, a preliminary study.

OBJECTIVES: High-dose oral iron supplementation for patients who develop iron deficiency after bariatric surgery may induce oxidative stress in the gastrointestine. The study's objective was to test this hypothesis by determining the impact of high-dose oral iron on systemic oxidative stress. METHODS: We used archived plasma samples from a randomized controlled clinical trial (NCT02404012) comparing FeSO4 (195 mg/day, NatureMade®, West Hills, CA) with a heme iron polypeptide (HIP, 60.4 mg/day, Proferrin®, Colorado Biolabs, Lafayette, CO) for 8 weeks. Systemic oxidative stress was measured using malondialdehyde and total antioxidant capacity (MDA, Abcam, ab238537 and TAC, Abcam, ab65329 Cambridge, UK) assays. Data was log-transformed and presented as means and standard deviations; a mixed model was used to determine the effects of time (0, 2, 4, and 8 weeks) and treatment (FeSO4 versus HIP) on oxidative stress. RESULTS: The FeSO4 (N = 8) and HIP (N = 5) participants were balanced in body mass index (35.0 ± 5.5 kg/m2), race (93 % White), time post-surgery (7.3 ± 3.3 years), as well as serum concentrations of iron (P > 0.05). The FeSO4 group tended to be older (44.3 ± 4.5 years) and they had lower concentrations of serum ferritin (6.5 ± 2.7 µg/mL) than the HIP (38.2 ± 9.3 years, and 12.9 ± 16.8 µg/mL) group (P = 0.080, and P = 0.017 respectively). We observed a larger increase in serum iron in the FeSO4 group during the 8 weeks of Fe supplementation, compared to that in the HIP group (p = 0.004). We observed a decreasing trend in MDA over the 8 weeks (p = 0.080) in the FeSO4 treatment group. There were no significant differences in TAC between and within FeSO4 and HIP groups over the 8 week supplementation period. CONCLUSIONS: This preliminary study suggests that high-dose oral iron supplementation for iron deficiency does not adversely impact systemic oxidative stress in patients undergoing bariatric surgery.

Thirdhand vaping exposures are associated with pulmonary and systemic inflammation in a mouse model.

Thirdhand 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.

PFAS in drinking water and serum of the people of a southeast Alaska community: A pilot study.

Per- and polyfluoroalkyl substances (PFAS) have become a target of rigorous scientific research due to their ubiquitous nature and adverse health effects. However, there are still gaps in knowledge about their environmental fate and health implications. More attention is needed for remote locations with source exposures. This study focuses on assessing PFAS exposure in Gustavus, a small Alaska community, located near a significant PFAS source from airport operations and fire training sites. Residential water (n = 25) and serum (n = 40) samples were collected from Gustavus residents and analyzed for 39 PFAS compounds. In addition, two water samples were collected from the previously identified PFAS source near the community. Fourteen distinct PFAS were detected in Gustavus water samples, including 6 perfluorinated carboxylic acids (PFCAs), 7 perfluorosulfonic acids (PFSAs), and 1 fluorotelomer sulfonate (FTS). ΣPFAS concentrations in residential drinking water ranged from not detected to 120 ng/L. High ΣPFAS levels were detected in two source samples collected from the Gustavus Department of Transportation (14,600 ng/L) and the Gustavus Airport (228 ng/L), confirming these two locations as a nearby major source of PFAS contamination. Seventeen PFAS were detected in serum and ΣPFAS concentrations ranged from 0.0170 to 13.1 ng/mL (median 0.0823 ng/mL). Perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) were the most abundant PFAS in both water and serum samples and comprised up to 70% of ΣPFAS concentrations in these samples. Spearman's correlation analysis revealed PFAS concentrations in water and sera were significantly and positively correlated (r = 0.495; p = 0.0192). Our results confirm a presence of a significant PFAS source near Gustavus, Alaska and suggest that contaminated drinking water from private wells contributes to the overall PFAS body burden in Gustavus residents.