CircDDX17 inhibits invasive progression of pituitary adenomas by sponging miR-1279 and regulating CADM2 expression

PurposeIncreasing evidence has revealed that circDDX17 plays significant regulatory roles in tumor progression. In the present study, we investigated the role of circDDX17 in pituitary adenomas (PAs).MethodsReverse transcription–quantitative PCR was performed to detect the expression of Circular RNA DDX17 (circDDX17), microRNA-1279 (miR-1279), and cell adhesion molecule 2 (CADM2) in PA tissues. Cell abilities of migration and invasion were examined by wound healing and transwell assays. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were applied to confirm the associations among circDDX17, miR-1279, and CADM2. Xenograft tumor experiments were performed to investigate the roles of circDDX17 in vivo.ResultsIn the present study, we found that circDDX17 was downregulated in PA tissues correlated with invasion, tumor size, and progression-free survival of patients with PA. Enforced expression of circDDX17 significantly inhibited migration and invasion through miR-1279. Notably, CADM2 was verified as the direct binding target of miR-1279, and silencing the expression of CADM2 reverses the tumor suppressing effects induced by circDDX17 overexpression. We demonstrated that circDDX17 upregulated the expression of CADM2 by sponging miR-1279, which suppressed the invasive biological behaviors of PA.ConclusionCircDDX17 may serve as a tumor suppressor and potential promising biomarker and effectively therapeutic target for the management of PA

Reticulation is a Risk Factor of Progressive Subpleural non-Fibrotic Interstitial Lung Abnormalities

Rationale: Interstitial lung abnormalities (ILAs) are being increasingly identified in clinical practice. In particular for subpleural non-fibrotic ILAs, the risk of progression over time and the risk factors for progressive behavior are still largely unknown. Objectives: To determine the age band prevalence of ILAs and the risk of radiological progression of subpleural non-fibrotic ILAs over time in a large health check-up population, and to identify how reticulation contributes to the risk of radiological progression. Methods: Based on ILAs definition by the Fleischner Society, low-dose chest CT images from community-dwelling population undergone health check-up were evaluated for ILAs. Multivariable logistic regression was used to assess the risk of radiological progression. Measurements and Main Results: Among 155,539 individuals, 3,300 (2.1%) were confirmed to have ILAs: the vast majority (81.7%) were defined as subpleural non-fibrotic ILAs. The prevalence of ILAs increased linearly with age (P for trend<0.0001). Of 454 individuals with subpleural non-fibrotic ILAs, 198 (43.6%) had radiological progression over 4 years. The presence of reticulation on initial imaging was an independent predictor of radiological progression (OR 1.9; 95%CI 1.2-3.0, P=0.0040). No difference in radiological progression was identified between subpleural non-fibrotic ILAs with extensive reticulation and subpleural fibrotic ILAs (73.0% vs. 68.8%, P=0.7626). Conclusions: The prevalence of ILAs increases linearly with age. Nearly half of subpleural non-fibrotic ILAs progress radiologically over 4 years. The presence of reticulation is a risk factor for radiological progression. Subpleural non-fibrotic ILAs with extensive reticulation are likely to be a feature of subpleural fibrotic ILAs

Table_2_Apolipoprotein E knockout may affect cognitive function in D-galactose-induced aging mice through the gut microbiota–brain axis.XLSX

The gut microbiota plays an important role in central nervous system (CNS) disorders. Apolipoprotein E (ApoE) can affect the composition of the gut microbiota and is closely related to the CNS. However, the mechanism by which ApoE affects cognitive dysfunction through the gut microbiota–brain axis has thus far not been investigated. In this study, we used wild-type mice and ApoE knockout (ApoE–/–) mice to replicate the aging model and examined the effects of ApoE deletion on cognitive function, hippocampal ultrastructure, synaptophysin (SYP) and postsynaptic density 95 (PSD-95) in aging mice. We also explored whether ApoE deletion affects the gut microbiota and the metabolite profile of the hippocampus in aging mice and finally examined the effect of ApoE deletion on lipids and oxidative stress in aging mice. The results showed that the deletion of ApoE aggravated cognitive dysfunction, hippocampal synaptic ultrastructural damage and dysregulation of SYP and PSD-95 expression in aging mice. Furthermore, ApoE deletion reduced gut microbial makeup in aging mice. Further studies showed that ApoE deletion altered the hippocampal metabolic profile and aggravated dyslipidemia and oxidative stress in aging mice. In brief, our findings suggest that loss of ApoE alters the composition of the gut microbiota, which in turn may affect cognitive function in aging mice through the gut microbiota–brain axis.</p

Table_1_Apolipoprotein E knockout may affect cognitive function in D-galactose-induced aging mice through the gut microbiota–brain axis.XLSX

The gut microbiota plays an important role in central nervous system (CNS) disorders. Apolipoprotein E (ApoE) can affect the composition of the gut microbiota and is closely related to the CNS. However, the mechanism by which ApoE affects cognitive dysfunction through the gut microbiota–brain axis has thus far not been investigated. In this study, we used wild-type mice and ApoE knockout (ApoE–/–) mice to replicate the aging model and examined the effects of ApoE deletion on cognitive function, hippocampal ultrastructure, synaptophysin (SYP) and postsynaptic density 95 (PSD-95) in aging mice. We also explored whether ApoE deletion affects the gut microbiota and the metabolite profile of the hippocampus in aging mice and finally examined the effect of ApoE deletion on lipids and oxidative stress in aging mice. The results showed that the deletion of ApoE aggravated cognitive dysfunction, hippocampal synaptic ultrastructural damage and dysregulation of SYP and PSD-95 expression in aging mice. Furthermore, ApoE deletion reduced gut microbial makeup in aging mice. Further studies showed that ApoE deletion altered the hippocampal metabolic profile and aggravated dyslipidemia and oxidative stress in aging mice. In brief, our findings suggest that loss of ApoE alters the composition of the gut microbiota, which in turn may affect cognitive function in aging mice through the gut microbiota–brain axis.</p