Down Regulation of EGF and AZGP1 Were Associated with Clinical Characteristics in Chronic Rhinosinusitis with Nasal Polyps: An Observation Study.

Objective: The mechanisms underlying the chronic rhinosinusitis with nasal polyps (CRSwNP) remained unclear. This study aimed to identify differentially expressed genes (DEGs) in nasal polyps from CRSwNP patients compared to healthy controls and explore key genes and pathways associated with CRSwNP pathophysiology and prognosis. Methods: Three datasets were obtained from the Gene Expression Omnibus database and the intersecting DEGs were identified in CRSwNP patients. Gene Ontology (GO) and protein-protein interaction (PPI) network analysis were applied to investigate the function of DEGs. Nasal specimens from 90 CRSwNP and 45 controls were further collected and qRT-PCR was applied to verify the mRNA expression of hub genes, and moreover, their association with tissue eosinophilia and clinical characteristics in CRSwNP were analyzed. Results: Sixty-eight co-DEGs including 8 upregulated and 60 downregulated genes were identified and GO analyses identified the terms including positive regulation of ERK1 and ERK2 cascade, transforming growth factor beta receptor signaling pathway. PPI networks identified hub genes including EGF, ERBB4, AZGP1, CRISP3 and PIP which were validated to be significantly down-regulated in CRSwNP and showed well diagnostic prediction quality. In addition, lower mRNA expressions level of EGF and AZGP1 in eosinophilic CRSwNP compared with non-eosinophilic CRSwNP were found. Aberrant low expressions of EGF and AZGP1 protein in CRSwNP were identified, and there was good consistency between their mRNA expression level and protein relative expression level. Furthermore, the expressions of EGF and AZGP1 mRNA were significantly correlated with clinical severity parameters. Conclusion: Integrated analysis revealed 68 co-DEGs between nasal polyps and controls and identified hub genes, of which EGF and AZGP1 expression was significantly downregulated in eosinophilic CRSwNP and correlated with disease severity. Downregulation of EGF and AZGP1 may contribute to epithelial barrier dysfunction and type 2 inflammation in CRSwNP, suggesting them as potential diagnostic biomarkers and therapeutic targets.

An Integrated Analysis Reveals Ciliary Abnormalities in Antrochoanal Polyps.

Objective: The mechanisms underlying the antrochoanal polyps (ACPs) remained unclear. We aimed to identify the differentially expressed genes (DEGs) profile, the cilia-related genes expression levels and the morphological characteristics of ciliated cells in patients with ACPs. Methods: We obtained ACPs biopsy samples from 28 patients and uncinate process from 27 healthy controls. Whole-transcriptome RNA sequencing, immunofluorescence staining, quantitative polymerase chain reaction, and scanning electron microscopy were performed. Results: 3739 DEGs were detected between ACPs and controls, and Gene Ontology analysis on these DEGs implicated cilium assembly, cilium motility, cilia component, cilia function, inflammatory response and immune system process were included in ACPs pathogenesis. Gene set enrichment analysis implicated sets of genes regulated in processes associated with cilium organization, cilium morphogenesis, cilium movement, axoneme assembly, axonemal dynein complex assembly and cell projection assembly. The expression levels of cilia-related genes (FOXJ1, DNAI1, DNAH9, RSPH1, RSPH9 and RSPH4A) were validated by quantitative polymerase chain reaction (Fold change >2, P<0.05) and FOXJ1 was positive correlated with DNAI1, DNAH9, RSPH4, RSPH1, RSPH9, DNAH5, DNALI1 in ACPs (all P < 0.05). Based on our semi-quantitative scoring system, median scores of α-Tubulin, DNAI1 and RSPH4A were significantly higher in ACPs than in controls. In addition, loss of ciliated cells and a shorter cilia pattern were further confirmed by immunofluorescence staining and scanning electron microscopy in ACPs. Conclusion: The aberrant expression of cilia-related genes and ciliary structural impairment are an important pathological phenomenon in ACPs, and our findings may provide novel insights into understanding the mysterious mechanisms underlying ACPs.

A Google Trends analysis revealed global public interest and awareness of nasal polyps.

INTRODUCTION: Nasal polyps (NPs) is a common upper airway inflammatory disorder with a huge negative burden on both the quality of life and costs to patients. However, NPs patients remain undiagnosed and untreated in a timely, which may be due to a lack of disease-related awareness. Google Trends (GT) is an online and open tool, which can provide real-world data on health informatics worldwide. OBJECTIVES: This study aimed to explore global public interest and awareness in nasal polyps (NPs) by performing a GT analysis. METHODS: Data on relative search volume (RSV) for NPs globally were collected by the public website Google Trends from January 2007 to December 2021. Top-related topics, rising-related topics, and regions were extracted for further analysis. Seasonal variation analysis, the latitude difference analysis, and the rising-related topics between the developed countries and the developing countries were analyzed. A P value less than 0.05 was considered statistically significant. RESULTS: The average searching strength showed an overall increasing trend, although with slight fluctuation. The public interest of NPs focuses on the symptoms and treatment for NPs and changes with time. For seasonal variation countries, the peak for the RSV occurred in winter and the bottom in summer. A region in higher latitudes may yield more RSV than that in lower latitudes. The rising-related topics in the recent 5 years reflected the significant differences in treatment and public interest of NPs between the developed and developing countries. CONCLUSIONS: Google Trends analysis revealed global public interest and awareness of the evolution of trends and related topics in nasal polyps over time. Geographic distribution and seasonal variation may be potential trigger factors for NPs, and the public's interest in treatment especially biologics is rising.

Effect of Aerobic Exercise on Arterial Stiffness in Individuals with Different Smoking Statuses.

This study aimed to investigate the immediate effects of acute bout of aerobic exercise on arterial stiffness in individuals with different smoking statuses. A total of 940 male individuals (mean age of 36.82±7.76 years) in the Kailuan study cohort were selected to participate in the fifth National Physical Fitness Monitoring. All participants completed measurements of brachial - ankle pulse wave velocity (baPWV) before and after twice-quantitative cycle ergometer exercise. Four groups were defined: (1) non-smokers (n=231), (2) former smokers (n=165), (3) light smokers (1-10 cigarettes/day, n=254), (4) heavy smokers (>10 cigarettes/day, n=290). Generalized linear models were established to analyze between-group differences in the change in baPWV before and after acute aerobic exercise in individuals with different smoking statuses. Overall, after acute aerobic exercise, baPWV was immediately decreased significantly (-33.55 cm/s [95% CI, - 39.69 to -27.42]). Compared with non-smokers, former smokers, light smokers, and heavy smokers showed a greater decrease in baPWV (-12.17 cm/s [95%CI, - 30.08 to 5.75], - 18.43 cm/s [95%CI, -34.69 to - 2.16], and -22.46 cm/s [95%CI, - 38.39 to - 6.54]) respectively. There is a transient decrease in baPWV in individuals with different smoking statuses. Compared with non-smokers, baPWV decreased more significantly in light and heavy smokers.

Peripheral Circular RNA Profiling from Patients with Allergic Rhinitis Identified hsa_circRNA_404013 as a Potential Diagnostic Biomarker.

INTRODUCTION: The study of peripheral circular RNA (circRNA) expression profile in patients with allergic rhinitis (AR) was absent to date, and we aimed to obtain the circRNA expression profile and identify the candidate biomarker from AR. METHODS: circRNA chip was performed to screen differentially expressed circRNAs in the peripheral blood sample from AR patients and healthy controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed to further search the function of the differential expressed circRNAs. The real-time quantitative reverse transcription-polymerase chain reaction was further used to verify the candidate circRNA and also analyze its potential correlation with clinical parameters. RESULTS: Significantly up-regulated expression level of hsa_circRNA_404013 in AR was obtained by circRNA chip and further verified in 79 AR patients and 48 healthy controls. hsa_circRNA_404013 was significantly positively correlated with nasal discharge, nasal itching, the total nasal symptoms of AR, and brain-derived neurotrophic factor (BDNF) expression level in peripheral blood. Receiver operating characteristic curve analysis results showed that hsa_circRNA_404013 may be used as peripheral blood circulating marker for the diagnosis of AR with the area under curve of 0.8499 (95% CI: 0.783-0.916). In further bioinformatics analysis, hsa_circRNA_404013 may regulate the expression of BDNF through hsa-mir-182-5p contributing to the pathogenesis of AR. CONCLUSION: The expression profile of circRNAs from the peripheral blood sample of AR patients was obtained. The expression of hsa_circRNA_404013 was significantly up-regulated in the peripheral blood of AR patients, which may be used as a circulating marker for AR patients. Furthermore, hsa_circRNA_404013 may regulate the expression level of BDNF through hsa-mir-182-5p in AR pathogenesis.

Arterial stiffness acute changes following aerobic exercise in males with and without hypertension.

While regular exercise exposure is considered the most effective therapy to reduce arterial stiffness, the effect of acute exercise training on arterial stiffness in adults with different blood pressure (BP) levels remains unclear. The authors aimed to investigate the effects of acute aerobic exercise on arterial stiffness in male with different BP levels. This cross-sectional study utilized data for 1200 males aged 20-49 years from the Kailuan study cohort who participated in the fifth National Fitness Monitoring project. A total of 940 participants (621 in the non-hypertensive group and 319 in the hypertensive group) aged 36.82 ± 7.76 who completed a twice-quantitative cycle ergometer exercise and measure of brachial-ankle pulse wave velocity (baPWV) at both the baseline and immediately after exercise were included in this study. The baPWV was decreased after acute aerobic exercise in the non-hypertension and hypertension groups (Δ 40.29 [95% confidence interval [CI], -47.72 to -32.86] vs. Δ20.45 [95% CI, -31.32 to -9.58] cm/s). Participants without hypertension showed a greater decrease in baPWV (Δ 19.84 [95% CI, -33.83 to -5.84] cm/s) than participants with hypertension. Aerobic exercise had an acute positive effect on arterial stiffness. This study provides evidence of a greater reduction in arterial stiffness in individuals without hypertension than in those with hypertension.

The effect of acute aerobic exercise on arterial stiffness in individuals with different body fat percentages: A cross-sectional study.

Background: Body fat percentage were positively correlated with arterial stiffness, but the acute change in arterial stiffness after aerobic exercise in individuals with different body fat percentages remains unclear. This study was aimed to determine the effect of acute aerobic exercise on arterial stiffness in individuals with different body fat percentages. Methods: Individuals who both participated in the seventh survey of the Kailuan study and the fifth iteration of National Physical Fitness Monitoring were enrolled in our study. All participants underwent measurement of brachial-ankle pulse wave velocity, blood pressure, and heart rate before and after a two-stage load test on cycle ergometry. Additionally, the generalized linear model was established to analyse between-group differences of the change in brachial-ankle pulse wave velocity before and after exercise for individuals with different body fat percentages. Results: The participants (N = 940, 36.8 ± 7.7years old, all male) were divided into: Q1 10.0-19.3%, Q2 19.3-23.3%, Q3 23.3-27.1% and Q4 27.1-37.7% by body fat percentage quartile. Overall, after exercise, brachial-ankle pulse wave velocity decreased significantly (before, 1,375.1 ± 209.1; after, 1,341.5 ± 208.0cm/s; p < 0.01). After adjusting for confounding factors, the generalized linear model showed that the ß values and 95% confidence interval (CI) of Q1, Q2 and Q3 groups were -38.1 (95% CI: -57.3, -19.0), -8.5 (95% CI: -25.8, 3.7),-3.7 (95% CI: -20.5, 13.0), respectively, when compared with Q4. For an increase in body fat percentage by one standard deviation (5.8%), ß = 14.5 (95% CI: 7.3, 21.6). Similar results were obtained in sensitivity analyses. Conclusions: Acute aerobic exercise had a positive effect on the arterial stiffness of adults with different body fat percentages. Compared with individuals with high body fat percentages, the arterial stiffness of people with low body fat percentages had significant reduction after exercise.

Plasma membrane overgrowth causes fibrotic collagen accumulation and immune activation in Drosophila adipocytes.

Many chronic diseases are associated with fibrotic deposition of Collagen and other matrix proteins. Little is known about the factors that determine preferential onset of fibrosis in particular tissues. Here we show that plasma membrane (PM) overgrowth causes pericellular Collagen accumulation in Drosophila adipocytes. We found that loss of Dynamin and other endocytic components causes pericellular trapping of outgoing Collagen IV due to dramatic cortex expansion when endocytic removal of PM is prevented. Deposits also form in the absence of negative Toll immune regulator Cactus, excess PM being caused in this case by increased secretion. Finally, we show that trimeric Collagen accumulation, downstream of Toll or endocytic defects, activates a tissue damage response. Our work indicates that traffic imbalances and PM topology may contribute to fibrosis. It also places fibrotic deposits both downstream and upstream of immune signaling, consistent with the chronic character of fibrotic diseases.