RESUMEN
Arrhythmogenic cardiomyopathy (ACM), a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes, accounts for 20% of sudden cardiac death and lacks effective treatment. It is often caused by mutations in desmosome proteins, with Desmoglein-2 (DSG2) mutations as a common etiology. However, the mechanism underlying the accumulation of fibrofatty in ACM remains unknown, which impedes the development of curative treatment. Here we investigated the fat accumulation and the underlying mechanism in a mouse model of ACM induced by cardiac-specific knockout of Dsg2 (CS-Dsg2 -/-). Heart failure and cardiac lipid accumulation were observed in CS-Dsg2 -/- mice. We demonstrated that these phenotypes were caused by decline of fatty acid (FA) β-oxidation resulted from impaired mammalian target of rapamycin (mTOR) signaling. Rapamycin worsened while overexpression of mTOR and 4EBP1 rescued the FA β-oxidation pathway in CS-Dsg2 -/- mice. Reactivation of PPARα by fenofibrate or AAV9-Pparα significantly alleviated the lipid accumulation and restored cardiac function. Our results suggest that impaired mTOR-4EBP1-PPARα-dependent FA β-oxidation contributes to myocardial lipid accumulation in ACM and PPARα may be a potential target for curative treatment of ACM.
RESUMEN
Objective:To explore the association between serum 25-hydroxyvitamin D [25-(OH)D] and high-sensitivity C reactive protein (hs-CRP) levels in health check-ups population.Methods:A total of 746 patients who underwent health check-ups at an enterprise unit in Hefei city were selected as the study subjects with an average age of (47.2±15.6) years and 489 males, accounting for 65.5%. Demographical and disease information was collected through questionnaires. Serum 25-(OH)D and hs-CRP levels were measured. The subjects were divided into three groups according to the 25-(OH)D level: non-deficient group (≥50 nmol/L), deficient group (25 nmol/L to 49.9 nmol/L), severely deficient group (<25 nmol/L). C-reactive protein was divided into normal group and high value group by 75% percentile. Multivariate logistic regression was used to analyze the relationship between 25-(OH)D and hs-CRP levels.Results:The proportions of high CRP levels in the severely deficient, deficient, and non-deficient groups were 29.8%, 26.4%, and 17.0%, respectively, and the difference was statistically significant (χ2=6.471， P<0.05). Logistic regression analysis showed that, compared with the non-deficient group of 25-(OH)D, the odds ratios values (95% CI) of the high values of hs-CRP in the deficient group and the severely deficient group of 25-(OH)D were 1.851(1.122 to 3.053) and 2.369(1.227 to 4.573), respectively. Conclusions:Serum 25-(OH)D level is a risk factor for hs-CRP in adults. Nutritional intervention in vitamin D deficient population may be beneficial to reduce the level of inflammation.
RESUMEN
Objective To determine the effect of neoadjuvant chemotherapy (NAC) for cervix cancer on cell proliferation and apoptosis. Methods A total of 24 patients with squamous carcinoma of the cervix (SCC) were treated with one cycle of cisplatin combined with hydroxycamptothecine, bleomycin regimen. The expression of proliferating cell nuclear antigen (PCNA) and apoptosis index (AI) were detected before and after NAC with flow cytometry and TUNEL. Results Clinical response was 58.3% (14/24). Before and after NAC, the expression of PCNA were (0.386?0.078) and (0.125?0.040) respectively and AI were (0.052?0.027) and (0.248?0.078). Significant difference of PCNA and AI could be observed before and after NAC (t=22.859, t=16.06, P