Oxidant stress-sensitive circRNA Mdc1 controls cardiomyocyte chromosome stability and cell cycle re-entry during heart regeneration.

Targeting cardiomyocyte plasticity has emerged as a new strategy for promoting heart repair after myocardial infarction. However, the precise mechanistic network underlying heart regeneration is not completely understood. As noncoding RNAs, circular RNAs (circRNAs) play essential roles in regulating cardiac physiology and pathology. The present study aimed to investigate the potential roles of circMdc1 in cardiac repair after injury and elucidate its underlying mechanisms. Here, we identified that circMdc1 levels were upregulated in postnatal mouse hearts but downregulated in the regenerative myocardium. The expression of circMdc1 in cardiomyocytes is sensitive to oxidative stress, which was attenuated by N-acetyl-cysteine. Enforced circMdc1 expression inhibited cardiomyocyte proliferation, while circMdc1 silencing led to cardiomyocyte cell cycle re-entry. In vivo, the cardiac-specific adeno-associated virus-mediated knockdown of circMdc1 promoted cardiac regeneration and heart repair accompanied by improved heart function. Conversely, circMdc1 overexpression blunted the regenerative capacity of neonatal hearts after apex resection. Moreover, circMdc1 was able to block the translation of its host gene Mdc1 specifically by binding to PABP, affecting DNA damage and the chromosome stability of cardiomyocytes. Furthermore, overexpression of Mdc1 caused damaged mouse hearts to regenerate and repair after myocardial infarction in vivo. Oxidative stress-sensitive circMdc1 plays an important role in cardiac regeneration and heart repair after injury by regulating DNA damage and chromosome stability in cardiomyocytes by blocking the translation of the host gene Mdc1.

Light Emitting Diodes Photobiomodulation Improves Cardiac Function by Promoting ATP Synthesis in Mice With Heart Failure.

Heart failure (HF) is the common consequences of various cardiovascular diseases, often leading to severe cardiac output deficits with a high morbidity and mortality. In recent years, light emitting diodes-based therapy (LEDT) has been widely used in multiple cardiac diseases, while its modulatory effects on cardiac function with HF still remain unclear. Therefore, the objective of this study was to investigate the effects of LED-Red irradiation on cardiac function in mice with HF and to reveal its mechanisms. In this study, we constructed a mouse model of HF. We found that LED-Red (630 nm) was an effective wavelength for the treatment of HF. Meanwhile, the application of LED-Red therapy to treat HF mice improved cardiac function, ameliorate heart morphology, reduced pulmonary edema, as well as inhibited collagen deposition. Moreover, LED-Red therapy attenuated the extent of perivascular fibrosis. Besides, LED-Red irradiation promoted calcium transients in cardiomyocytes as well as upregulated ATP synthesis, which may have positive implications for contractile function in mice with HF. Collectively, we identified that LED-Red exerts beneficial effects on cardiac function in HF mice possibly by promoting the synthesis of ATP.

Real-World Outcomes of Revascularization Strategies in Patients With Left Ventricular Dysfunction and Three-Vessel Coronary Disease Stratified by Mitral Regurgitation.

Aims: Limited information exists regarding optimal revascularization options for patients with triple-vessel coronary artery disease (TVD), heart failure (HF), and different degrees of mitral regurgitation (MR). Thus, we aimed to compare the effect of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) surgery in the indicated patients. Methods and Results: In the real-world prospective study, 1190 patients with multi-vessel disease and decreased left ventricular systolic function but without severe MR, who underwent PCI or CABG, were enrolled and followed-up for 4.7 ± 1.8 years. The primary endpoint was a composite of cardiovascular death and HF hospitalization. Secondary endpoints were the individual components of the primary outcome. Risk of the primary endpoint was higher in the PCI than in the CABG group (HR = 1.38, 95%CI: 1.14-1.67, and P < 0.01), particularly in patients with moderate MR (HR = 1.85, 95%CI: 1.35-2.55, and P < 0.01). In patients with no-mild MR, the risk of the primary endpoint did not differ significantly between PCI and CABG (P = 0.09). Treatment with PCI was associated with an increased risk for cardiovascular death and HF hospitalization in the moderate MR cohort, while PCI was comparable to CABG in the no-mild MR cohort. Conclusions: In this real-world study, for patients with HF and TVD, CABG was related to lower adverse outcome rates compared to PCI. Assessment of MR can aid in selecting optimal revascularization therapies and in risk stratification.

PM2.5 exposure impairs sperm quality through testicular damage dependent on NALP3 inflammasome and miR-183/96/182 cluster targeting FOXO1 in mouse.

Exposure to ambient fine particular matter (PM2.5) has been clearly associated with male reproductive disorders. However, very limited toxicological studies were carried out to investigate the potential mechanisms underlying the PM2.5-induced sperm quality decline. In the present study, we established a real time whole-body PM2.5 exposure mouse model to investigate the effects of PM2.5 on sperm quality and its potential mechanisms. Sixty male C57BL/6 mice were randomly subjected to three groups: filtered air group, unfiltered air group and concentrated air group. Half of the mice from each group were sacrificed for study when the exposure duration accumulated to 8 weeks and the rest of the mice were sacrificed when exposed for 16 weeks. Our results suggested that PM2.5 exposure could induce significant increases in circulating white blood cells and inflammation in lungs. PM2.5 exposure induced apparently DNA damages and histopathologic changes in testes. There were significantly decreased sperm densities of mice, which were paralleled with the down-regulated testosterone levels in testes tissue of mice after exposure to PM2.5 for 16 weeks. The numbers of motile sperms were decreased and sperms with abnormal morphology were increased after PM2.5 exposure in a time-depended and dose-depended manner. PM2.5 exposure significantly increased the expression of the major components of the NACHT, LRR and PYD domains-containing protein3 (NALP3) inflammasome, accompanied by the increased expression of miR-183/96/182 targeting FOXO1 in testes. The present data demonstrated that sperm quality decline induced by PM2.5 could be partly explained by the inflammatory reaction in testes which might be a consequence of systemic inflammation. The molecular mechanism was depended on the activation of NALP3 inflammasome accompanied by miR-183/96/182 targeting FOXO1 in testes.

Non-invasive assessment of liver quality in transplantation based on thermal imaging analysis.

BACKGROUND AND OBJECTIVE: Liver quality evaluation is one of the vital steps for predicting the success of liver transplantation. Current evaluation methods, such as biopsy and visual inspection, which are either invasive or lack of consistent standards, provide limited predictive value of long-term transplant viability. Objective analytical models, based on the real-time infrared images of livers during perfusion and preservation, are proposed as novel methods to precisely evaluate donated liver quality. METHODS: In this study, by using principal component analysis to extract infrared image features as predictors, we construct a multivariate logistic regression model for single liver quality evaluation, and a multi-task learning logistic regression model for cross-liver quality evaluation. RESULTS: The single liver quality predictions show testing errors of 0%. The leave-one-liver-out predictions show testing errors ranging from 9% to 36%. CONCLUSIONS: It is found that there is a strong correlation between the viability of livers and the infrared image features in both single liver and cross-liver quality evaluations. These analytical methods also determine that the selected significant infrared image features indicate regional difference in viability and show that more stringent pre-implantation evaluation may be needed to predict transplant outcomes.

[Plain radiograph and CT features of 112 patients with SARS in acute stage].

OBJECTIVE: To retrospectively analyze the X-ray and CT features of patients with suggestive of SARS at the early stages. METHODS: The study comprised 112 patients (43 men, 69 women; aged from 16 to 82 year) with clinically proved SARS. Chest radiograph was performed in all the patients and CT of thorax in 22 patients during the first week of the onset. RESULTS: In the early stage, the most common findings were patchy ground-glass opacification (GGO) (79.5% on X-ray and 81. 8% on CT) and mixed lesions of GGO with irregular consolidation (21.4% on X-ray and 45.5% on CT) and/or granulomas (14.3% on X-ray and 27.3% on CT). A majority of lesions were located in the middle and lower field (70.9%) with peripheral distribution (69%). Other findings on CT included intralobular and interlobular septal thickening (carzy-paving pattern) (36.4%), bronchiectasis (18.2%) and small pleural effusion (22.7%). CONCLUSION: Common radiologic findings of SARS are ground-glass opacification and mixed lesions of GGO with irregular consolidation and/or granulomas and lower location and peripheral distribution.

[Localized Castleman disease with paraneoplastic pemphigus and pulmonary involvement: clinical features and histopathology].

OBJECTIVE: To investigate the clinical, histopathologic and CT features of localized Castleman disease complicated with paraneoplastic pemphigus (PNP) and pulmonary involvement. METHODS: The clinical, laboratory, histopathologic records and data of computed tomographic (CT) images of 4 patients of Castleman disease with PNP were reviewed. RESULTS: All of the four patients presented with PNP which was confirmed by pathological and immunological studies and also developed lung abnormalities, including bronchiolitis obliterans (n = 3), lung abscess (n = 1) and multiple lung infarction (n = 1), 2 to 5 months after the onset of PNP. Castleman's tumor, which was found incidentally during routine examination, manifested as a solitary and huge mass (5 to 14 cm in size) which markedly enhanced homogeneously on CT in the retroperitoneum (n = 3) and mediastinum (n = 1). Histologically, three cases were of hyaline-vascular type and the other one was of mixed type. Complete remission of PNP occurred 2 weeks to 8 months after surgical resection of the tumor. The condition of two patients with bronchiolitis obliterans failed to be improved. They had been presenting dyspnea and irritable cough 3 to 15 months after surgery. CONCLUSION: PNP and lung abnormalities are rare and severe complications of localized Castleman's disease. Early diagnosis and surgery are very important for prognosis.