Deregulated miR-146a-3p alleviates disease progression in atherosclerosis through inactivating NF-κB: An experimental study.

BACKGROUND: Atherosclerosis (AS), as a complex chronic inflammatory disease, is 1 of the main causes of cardiovascular and cerebrovascular diseases. This study aimed to confirm the direct interaction between miR-146a-3p and NF-κB, and explore the role of miR-146a-3p/NF-κB in the regulation of inflammation in AS. METHODS: Bioinformatic prediction and dual-luciferase reporter assay were used to confirm the interaction between miR-146a-3p and NF-κB. Lipopolysaccharides stimulation was performed to establish AS inflammatory cell model, and the levels of pro-inflammatory cytokines were estimated using an enzyme-linked immunosorbent assay. miR-146a-3p and NF-κB expression were evaluated using reverse transcription quantitative PCR, and their clinical value was examined using a receiver operating characteristic curve. RESULTS: Inflammatory cell model showed increased IL-1ß, IL-6, and TNF-α. NF-κB was a target gene of miR-146a-3p, and mediated the inhibitory effects of miR-146a-3p on inflammatory responses in the cell model. In patients with AS, miR-146a-3p/NF-κB was associated with patients' clinical data and inflammatory cytokine levels, and aberrant miR-146a-3p and NF-κB showed diagnostic accuracy to distinguish AS patients from healthy populations. CONCLUSION: miR-146a-3p might inhibit inflammation by targeting NF-κB in AS progression, and miR-146a-3p/ NF-κB might provide novel biomarkers and therapeutic targets for the prevention of AS and related vascular events.

Pericarotid Adipose Tissue is Associated with Circulatory Markers of Inflammation and Carotid Atherosclerosis.

Perivascular adipose tissue plays roles in vascular inflammation and atherosclerosis. The present study aimed to evaluate the association between pericarotid fat density (PFD) and circulatory inflammatory indicators, internal carotid artery (ICA) stenosis, and vulnerable carotid plaques. We retrospectively screened 498 consecutive patients who underwent both computed tomography angiography of the neck between January 2017 and December 2020. The PFD, ICA stenosis, and vulnerable carotid plaques were analyzed using established approaches. Laboratory data including C-reactive protein (CRP) levels, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were recorded. PFD was positively correlated with CRP, NLR, PLR, and SII, and negatively correlated with LMR. A higher PFD was independently associated with extracranial ICA stenosis (1.179 [1.003-1.387], P = .040) and vulnerable carotid plaques (1.046 [1.021-1.072], P = .001) after adjusting for systemic inflammatory indicators. These findings suggested higher PFD is independently associated with circulating inflammatory indicators, extracranial ICA stenosis, and vulnerable carotid plaque.

LncRNA MEG8 ameliorates Parkinson's disease neuro-inflammation through miR-485-3p/FBXO45 axis.

OBJECTIVE: Studies suggest that LncRNA maternally expressed 8, small nucleolar RNA host gene (MEG8) contributes to inflammatory regulation, while the function and potential mechanisms of MEG8 in Parkinson's disease (PD) are unknown. This study aimed to assess the clinical value and biological function of MEG8 in PD. METHODS: One hundred and two PD patients, eighty-six AD patients, and eighty healthy controls were enrolled in this study. Lipopolysaccharide (LPS)-induced microglia BV2 constructs an in vitro cell model. RT-qPCR was conducted to quantify the levels of MEG8, miR-485-3p, and FBXO45 in serum and cells. ROC curve was employed to examine the diagnostic value of MEG8 in PD. Serum and cellular pro-inflammatory factor secretion were quantified by ELISA. Dual-luciferase reporter and RIP assay to validate the targeting relationship between miR-485-3p and FBXO45. RESULTS: MEG8 and FBXO45 were significantly decreased in the serum of PD patients and LPS-induced bv2, while miR-485-3p was increased (P < 0.05). ROC curve confirmed that serum MEG8 has high sensitivity and specificity to identify PD patients from healthy controls and AD patients, respectively. Elevated MEG8 alleviated LPS-induced inflammatory factor overproduction compared with LPS-induced BV2 (P < 0.05), but this alleviating effect was eliminated by miR-485-3p (P < 0.05). The LPS-induced inflammatory response was suppressed by the low expression of miR-485-3p but significantly reversed by silencing of FBXO45. MEG8 was a sponge for miR-485-3p and inhibited its levels and promoted FBXO45 expression (P < 0.05). CONCLUSION: Elevated MEG8 is a potential diagnostic biomarker for PD and may mitigate inflammatory damage in PD via the miR-485-3p/FBXO45 axis.

Association between metabolic syndrome components and impulse control disorders in Parkinson's disease.

Background: Current evidence on management of impulse control disorders (ICDs) in Parkinson's disease (PD) remains scarce, and exploring modifiable risk factors is crucial. Objective: We evaluated the profiles of ICDs in PD patients and aimed to determine the associations between ICDs, metabolic syndrome components and other clinical features. Methods: We enrolled patients diagnosed with PD in this study and conducted comprehensive clinical assessments. Results: We recruited 39 PD patients with ICDs and 66 PD patients without ICDs. Out of the 39 patients with ICDs, 19 (48.7%) had one impulse control disorder, while 20 (51.3%) had two or more. The most commonly reported symptom of ICDs was compulsive eating (48.7%). Significant differences were observed between the PD patients with and without ICDs in terms of their HbA1c levels, history of diabetes mellitus, dopamine agonist use, levodopa equivalent dose of dopamine agonists (LED DA), and Hamilton Depression Rating Scale (HAMD) scores. HbA1c levels were significantly higher in the PD patients with compulsive eating. Stepwise logistic regression analyses were performed with the dependent variables of ICDs (yes/no) and compulsive eating (yes/no). Among the 105 PD patients, those with ICDs exhibited higher levels of HbA1c, HAMD score and LED DA than those without ICDs (p < 0.01). Among 39 PD patients with ICDs, those with compulsive eating exhibited higher levels of HbA1c (OR = 2.148, 95% CI = 1.004-4.594, p < 0.05). Among 105 PD patients, those with compulsive eating exhibited higher levels of HbA1c, LED DA and HAMD score (p < 0.05). Conclusion: This study provides insights into the profiles of ICDs in PD patients and their associations with various clinical features. Compulsive eating was the most common ICDs symptom reported. Notably, HbA1c levels were found to be higher in patients with compulsive eating, indicating that poor blood glucose control may be a potential risk factor for ICDs in PD. However, it should be noted that the higher HbA1c levels could also be a consequence of compulsive eating rather than a causal factor for ICDs in PD. Further research is needed to confirm the modifiable risk factors for ICDs in PD.