Association of dietary flavonoid intakes with prevalence of chronic respiratory diseases in adults.

BACKGROUND AND AIMS: Flavonoids are a class of secondary plant metabolites that have been shown to have multiple health benefits, including antioxidant and anti-inflammatory. This study was to explore the association between dietary flavonoid consumption and the prevalence of chronic respiratory diseases (CRDs) in adults. METHODS AND RESULTS: The six main types of flavonoids, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols, were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 2017-2018 by the two 24-h recall interviews. The prevalence of CRDs, including asthma, emphysema, and chronic bronchitis, was determined through a self-administered questionnaire. The analysis included 15,753 participants aged 18 years or older who had completed a diet history interview. After adjustment for potential confounders, the inverse link was found with total flavonoids, anthocyanidins, flavanones, and flavones, with an OR (95%CI) of 0.86 (0.75-0.98), 0.84 (0.72-0.97), 0.80(0.69-0.92), and 0.85(0.73-0.98) for the highest group compared to the lowest group. WQS regression revealed that the mixture of flavonoids was negatively linked with the prevalence of CRDs (OR = 0.88 [0.82-0.95], P < 0.01), and the largest effect was mainly from flavanones (weight = 0.41). In addition, we found that flavonoid intake was negatively linked with inflammatory markers, and systemic inflammation significantly mediated the associations of flavonoids with CRDs, with a mediation rate of 12.64% for CRP (P < 0.01). CONCLUSION: Higher flavonoid intake was related with a lower prevalence of CRDs in adults, and this relationship may be mediated through systemic inflammation.

Association of N, N-diethyl-m-toluamide (DEET) with hyperuricemia among adult participants.

BACKGROUND: N,N-diethyl-m-toluamide (DEET) is a widely used active ingredient in insect repellents, and its effects on human health have been a matter of debate. This study aims to investigate the relationship between DEET exposure and hyperuricemia in the adult population. METHODS: Our study utilized a cross-sectional design and analyzed data from adult participants of the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. 3-diethyl-carbamoyl benzoic acid (DCBA) was used as a specific indicator of DEET exposure. DCBA was categorized using quartiles based on its distribution within the study population. Multiple linear regression models were employed to examine the association between DCBA exposure and serum uric acid (SUA) levels in adults. The relationship between DCBA and the prevalence of hyperuricemia in adults was assessed using multiple logistic regression models. Dose-response relationships were analyzed using restricted cubic spline regression. RESULTS: A total of 8708 participants were included in the study. The mean age of the participants was 46.49 years, and the total number of male participants was 50.93%. The median levels of DCBA and SUA were 2.07 ng/mL and 5.40 mg/dL, respectively. Hyperuricemia was found in 19.99% of the participants. In multivariate-adjusted linear regression models, it was found that higher SUA levels were associated with the highest quartile of DCBA compared with the lowest quartile of DCBA (ß [95% CI]: 0.19 [0.08, 0.30], Ptrend<0.001). After adjusting for confounders, a positive association was found between the prevalence of hyperuricemia and DCBA levels (OR [95% CI] quartile 4 vs. 1: 1.41 [1.14-1.74], Ptrend<0.001). Furthermore, linear associations were observed between DCBA concentrations and SUA levels (P for nonlinearity = 0.479) and the prevalence of hyperuricemia (P for nonlinearity = 0.755). CONCLUSION: Higher DCBA concentrations were found to have a positive association with the prevalence of hyperuricemia in the general adult population.

Circ_0040929 Serves as Promising Biomarker and Potential Target for Chronic Obstructive Pulmonary Disease.

Background: Circular RNAs (circRNAs) can act as essential regulators in many diseases, including chronic obstructive pulmonary disease (COPD). We aimed to explore the role and underlying mechanism of circ_0040929 in COPD. Methods: A cellular model of COPD was constructed by treating human bronchial epithelial cells (16HBE) with cigarette smoke extract (CSE). The levels of circ_0040929, microRNA-515-5p (miR-515-5p) and insulin-like growth factor-binding protein 3 (IGFBP3) were measured by quantitative real-time PCR. Cell proliferation was assessed by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays. Cell apoptosis was evaluated by flow cytometry. Protein expression was measured using Western blot assay. The levels of inflammatory factors and airway remodeling were assayed via enzyme-linked immunosorbent assay. The interaction between miR-515-5p and circ_0040929/IGFBP3 was confirmed by dual-luciferase reporter, RNA pull-down and RNA immunoprecipitation assays. Exosomes were detected using transmission electron microscopy. Results: Circ_0040929 expression and IGFBP3 expression were upregulated in the serum of smokers (n = 22) compared to non-smokers (n = 22) and more significantly upregulated in the serum of COPD patients (n = 22). However, miR-515-5p expression was decreased in the serum of smokers compared to non-smokers and further reduced in the serum of COPD. Circ_0040929 knockdown attenuated CSE-induced cell injury by increasing proliferation and reducing apoptosis, inflammation, and airway remodeling in 16HBE cells. MiR-515-5p was a direct target of circ_0040929, and miR-515-5p inhibition reversed the effect of circ_0040929 knockdown in CSE-treated 16HBE cells. IGFBP3 was a direct target of miR-515-5p, and miR-515-5p overexpression alleviated CSE-induced cell injury via targeting IGFBP3. Moreover, circ_0040929 regulated IGFBP3 expression by targeting miR-515-5p. Importantly, circ_0040929 was upregulated in serum exosomes from COPD patients. Conclusion: Circ_0040929 played a promoting role in CSE-induced COPD by regulating miR-515-5p/IGFBP3 axis, suggesting that it might be a novel potential target for COPD treatment.

DNA Methyltransferase 3b Accelerates the Process of Atherosclerosis.

Background: DNA methylation plays a key role in establishing cell type-specific gene expression profiles and patterns in atherosclerosis. The underlying mechanism remains unclear. Previous studies have shown that DNA methyltransferase 3b (DNMT3b) may play an important role in atherosclerosis. This study aimed to establish the regulatory role of DNMT3b in the development of atherosclerosis. Methods: We constructed a viral vector carrying Dnmt3b shRNA to transduce ApoE-/- mice. Meanwhile, healthy human peripheral blood Treg cells were treated with inhibitor of DNMT3b (AZA and EGCG) or transduced with DNMT3b shRNA. Results: It showed that Dnmt3b silencing attenuated atherosclerosis, including decreased lesion size and macrophage content and increased collagen and smooth muscle cells content in ApoE-/- mice. To further investigate the possible mechanisms, combined with previous studies by our group, we showed that Foxp3-TSDR methylation level was significantly reduced Foxp3 expression and peripheral blood Treg levels were significantly increased by Dnmt3b shRNA vector transduction in animals committed to western diet for 12 and 18 weeks. Consistently, inhibition of DNMT3b (AZA and EGCG) decreased the expression levels of DNMT3b, which can increase the expression levels of FOXP3, and increase the levels of TGF-ß and IL-10 and decrease the levels of IL-ß and IFN-γ. After transduction with DNMT3b shRNA, the effect was more obvious. Conclusions: DNMT3b accelerated atherosclerosis, and may be associated with FOXP3 hypermethylation status in regulatory T cells.

Diagnostic Value of FTO Combined with CEA or CYFRA21-1 in Nonsmall Cell Lung Cancer.

OBJECTIVE: To explore the diagnostic value of FTO combined with CEA or CYFRA21-1 for nonsmall cell lung cancer (NSCLC) and to provide a theoretical basis for molecular diagnosis of NSCLC. METHODS: Totally, 60 patients with nonsmall cell lung cancer (NSCLC) treated in our hospital between Feb. 2018 and Feb. 2019 were enrolled into the patient group (Pat group) and 50 healthy individuals with normal physical examination results in our hospital over the same time span into the control group (Con group). Serum of each participant was collected, and then qRT-PCR was adopted for quantification of serum FTO and the chemiluminescence method for quantification of serum CEA and CYFRA21-1. Additionally, corresponding ROC curves were drawn for diagnostic value analyses of FTO, CEA, and CYFRA21-1 in NSCLC and Cox regression analysis was performed for analysis of independent factors impacting the patients' 3-year prognosis. RESULTS: The Pat group presented notably higher FTO, CEA, and CYFRA21-1 levels than the Con group (all P < 0.05), and patients with a high FTO level faced notably higher probabilities of stage III + IV and lymph node metastasis (LNM) (both P < 0.05). Additionally, according to ROC curve-based analysis, with a high level in patients with NSCLC, FTO had high specificity and sensitivity in diagnosing NSCLC; joint detection of it with CEA or CYFRA21-1 demonstrated a higher sensitivity in NSCLC diagnosis and presented a higher specificity in diagnosing early NSCLC compared with detection of CEA or CYFRA21-1 alone. According to Cox regression analysis, clinical stage, LNM, and FTO were independent risk factors impacting the prognosis of patients with LC (all P < 0.05). CONCLUSION: FTO presents a high level in NSCLC cases, and joint detection of it with CEA or CYFRA21-1 delivered a higher specificity in diagnosing NSCLC in contrast to detection of CEA or CYFRA21-1 alone, so the joint detection is worth popularizing in clinical scenarios.

Curcumin reduces lung inflammation via Wnt/ß-catenin signaling in mouse model of asthma.

OBJECTIVES: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Curcumin has been found to have anti-inflammatory and antifibrosis effects. Researchers reported that curcumin regulated Wnt/ß-catenin signaling in lots of cells. However, whether curcumin regulates the levels of Wnt/ß-Catenin signaling in lung tissues and DCs (dendritic cells) remains unclear. In this study, we assessed the effects of curcumin on DCs and asthma. METHODS: C57BL/6 mice immunized with OVA (ovalbumin) were challenged thrice with an aerosol of OVA every second day for 8 days. Dexamethasone or curcumin was administered intraperitoneally to OVA-immunized C57BL/6 mice on day 24 once a day for 9 days. Mice were analyzed for effects of curcumin on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. DCs were isolated from mouse bone morrow. The surface markers CD40, CD86 and CD11c of DCs was detected by FACS (fluorescence activated cell sorting) and the function of DCs was detected by mixed lymphocyte reaction. The expression of GSK-3ß and ß-catenin was detected by Western Blot. RESULTS: Results showed that OVA increased the number of inflammatory factors in BALF (bronchoalveolar lavage fluid), elevated lung inflammation scores in mice. Curcumin dose-dependently reversed the alterations induced by OVA in the asthmatic mice. Curcumin activated Wnt/ß-catenin signaling pathway in DCs and asthmatic mouse lungs. CONCLUSIONS: Curcumin could influence the morphology and function of DCs, ease asthma symptom and inflammatory reaction through the activation of Wnt/ß-catenin signaling. These results provide new evidence new evidence for application of curcumin on asthma.