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Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and deadly lung disease with limited therapeutic options. Bone morphogenetic protein 4 (BMP4), a multifunctional growth factor that belongs to the transforming growth factor-ß superfamily, is able to relieve pulmonary fibrosis in mice; nevertheless, the potential mechanism of action remains largely unknown. Growing evidence supports the notion that reiterant damage to the alveolar epithelial cells (AECs) is usually the "prime mover" for pulmonary fibrosis. Here, we examined the effect and mechanisms of BMP4 on bleomycin (BLM)-induced activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and epithelial-mesenchymal transition (EMT) in vivo and in vitro. Methods: The in vivo impact of BMP4 was investigated in a BLM mouse model. Histopathologic changes were analyzed by hematoxylin-eosin (H&E) and Masson's trichrome staining. The NLRP3 inflammasome activation was determined by quantitative real time polymerase chain reaction (qRT-PCR) and immunofluorescence staining. Biomarkers of EMT were measured by qRT-PCR, Western blot and immunofluorescence staining. The in vitro impact of BMP4 on BLM-induced NLRP3 inflammasome activation and EMT was explored in A549 AECs. We also evaluated whether BMP4 inhibited BLM-activated ERK1/2 signaling to address the possible molecular mechanisms. Results: BMP4 was significantly downregulated in the mouse lungs from BLM-induced pulmonary fibrosis. BMP4+/- mice presented with more severe lung fibrosis in response to BLM, and accelerated NLRP3 inflammasome activation and EMT process compared with that in BMP4+/+ mice. Whereas overexpression of BMP4 by injecting adeno-associated virus (AAV) 9 into mice attenuated BLM-induced fibrotic changes, NLRP3 inflammasome activation, and EMT in the mouse lungs, thus exerting protective efficacy against lung fibrosis. In vitro, BMP4 significantly reduced BLM-induced activation of NLRP3 inflammasome and EMT in human alveolar epithelial A549 cells. Mechanically, BMP4 repressed BLM-induced activation of ERK1/2 signaling in vivo and in vitro, suggesting that ERK1/2 inactivation contributes to BMP4-induced effects on BLM-induced activation of NLRP3 inflammasome and EMT. Conclusions: Our findings suggest that BMP4 can suppress NLRP3 inflammasome activation and EMT in AECs via inhibition of ERK1/2 signaling pathway, thus has a potential for the treatment of pulmonary fibrosis.
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Objective: This study aimed to explore the relationship between serum lipoprotein(a) (LP(a)) levels and early neurological deterioration (END) in patients with acute ischemic stroke (AIS) after thrombolysis. Methods: In total, 236 patients with AIS after thrombolysis were enrolled in this study. Serum LP(a) levels were measured on admission after thrombolysis. END was defined as an increase of at least two points in the NIHSS score within 48 hours after thrombolysis. Binary logistic regression analysis was used to assess the association between serum LP(a) levels and END. Results: Overall, patients with END had higher LP(a) than those without END (high LP(a): 38.3% vs 22.2%, intermediate LP(a): 40.3% vs 41.8%, low LP(a): 21.3% vs 36.0%, p<0.005). In the multivariate analysis, high LP(a) (defined as LP(a) level≥ 300 mg/L) was an independent risk factor for END post-thrombolysis (OR=3.154, 95% CI=1.067-9.322, p=0.038). Conclusion: Our findings demonstrated that LP(a) was an independent risk factor for END post-thrombolysis and that LP(a) level≥ 300 mg/L could be associated with END post-thrombolysis in this study population.
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Objective: To evaluate the efficacy and adverse effects of hypoglossal nerve stimulation in adolescents with down syndrome and obstructive sleep apnea. Methods: A systematic search was conducted using PubMed, Web of Science, Embase, and Scopus databases. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search strategy used a combination of Medical Subject Headings and free words with "OR" and "AND." Articles were screened to extract data reporting apnea-hypopnea index, quality of life, voltage, follow-up duration, and complications. All included participants were adolescents with down syndrome and obstructive sleep apnea. Results: A total of 92 articles were identified, of which 9 articles met the inclusion criteria. A total of 106 patients were included. All the studies showed that patients receiving hypoglossal nerve stimulation experienced a significant decrease in apnea-hypopnea index (at least 50%). The pooled AHI was significantly lower in patients following treatment (mean AHI reduction 17.43 events/h, 95% confidence interval 13.98-20.88 events/h, P < 0.001) after 2 case reports were excluded. The pooled OSA-18 were significantly decreased in 88 patients after treatment (mean OSA-18 reduction 1.67, 95% confidence interval 1.27-2.08, P < 0.001) after excluding 5 studies. Four investigations examined the necessity to optimize stimulation voltage for arousal during treatment. The most common complication was pain or discomfort in the tongue or mouth. Most studies had relatively short patient follow-up periods, with the most extended follow-up being 44-58 months. Conclusion: Hypoglossal nerve stimulation significantly reduces apnea-hypopnea index and improves the quality of life; and thus, could be a potential alternative therapy for obstructive sleep apnea in adolescents with down syndrome. The adolescent's age, potential complications, adverse events, long-term efficacy, and comfort, needs to be considered while performing hypoglossal nerve stimulation.
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BACKGROUND: Patients with Parkinson's disease (PD) are at a lower risk of suffering cardiovascular events, but the underlying factors for this decreased risk remain unclear. Serum triglycerides (TG) and total cholesterol (TC), and their expression relative to high-density lipoprotein cholesterol (TG/HDL-C and TC/HDL-C), are independent predictors of cardiovascular events. This study aimed to determine if PD patients have decreased lipid levels and lipid ratios, which may underlie the decreased risk of coronary heart disease (CHD). METHODS: This retrospective study included 92 PD patients (PD group), 450 control subjects with no CHD (OD group), and 450 CHD patients (CHD group). We analyzed serum lipid levels and lipid ratios in each group. RESULTS: There were significant differences in TC (F = 10.459, p < 0.0001), TG (F = 46.856, p < 0.0001), low density lipoprotein cholesterol (LDL-C) (F = 6.910, p = 0.001), high density lipoprotein cholesterol HDL-C (F = 30.694, p < 0.0001), TC/HDL-C (F = 32.675, p < 0.0001), and TG/HDL-C (F = 45.554, p < 0.0001) between all three groups; TC/LDL-C (F = 2.518, p = 0.081) was not significantly different between groups. Compared to the CHD group, PD patients had lower TC (p < 0.0001), TG (p < 0.0001), LDL-C (p = 0.001), TG/HDL-C (p < 0.0001), and TC/HDL-C (p < 0.0001); TC/LDL-C (p = 0.563) and HDL-C (p = 0.196) were not significantly different. TC and LDL-C levels were positively correlated within individual groups (all p < 0.0001). In addition, TG and HDL-C were negatively correlated in the OD and CHD groups (p < 0.0001); no significant negative association was observed in the PD group (p = 0.077). TG/HDL and LDL-C levels were inversely correlated in the CHD group (p < 0.0001) and weakly positively correlated in the PD (p = 0.159) and OD (p = 0.199) groups. CONCLUSIONS: TC/HDL and TG/HDL ratios were significantly lower in PD patients compared to CHD patients, suggesting there is a strong correlation between lipid ratios and incidence of CHD in PD patients.
