No abstract

Background/Aims: Myocardial apoptosis plays an important role in doxorubicin (Dox) cardiotoxicity. MicroRNA-29 (miR-29) is suggested to function as an anti-fibrotic factor with potential therapeutic effects on cardiac fibrosis. However, it has not been shown whether there is an association between miR-29b and myocardial apoptosis. Methods: Male Wistar rats were transfected with miR-29b agomir by local delivery to the myocardium prior to Dox treatment. Rat cardiomyocytes were pretreated with miR-29b mimics or inhibitor followed by Dox incubation in vitro. Cardiac function and underlying mechanisms were evaluated by echocardiography, immunofluorescence, flow cytometry, real-time PCR, and western blotting. Results: Our results revealed that miR-29b is the only member of the miR-29 family that was significantly downregulated in myocardium from Dox-treated rats. Delivery of miR-29b agomir to myocardium resulted in a marked improvement of cardiac function. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining showed that rescue of miR-29b expression inhibited Dox-induced myocardial apoptosis, concomitantly with increased Bcl-2 expression and decreased Bax expression and caspase-3 activity. In vitro, miR-29b overexpression mitigated, whereas inhibition of miR-29b promoted, Dox-induced cardiomyocyte apoptosis. Mechanistically, miR-29b negatively regulated Bax expression by directly targeting the 3′ untranslated region of Bax. In Dox-treated cardiomyocytes, upregulation of miR-29b resulted in a significant decrease in Bax expression, with an increase in Bcl-2 expression, accompanied by inhibition of mitochondrial membrane depolarization, cytochrome c release, and caspase activation. However, inhibition of miR-29b produced the opposite effects by further augmenting the effects of Dox. Conclusions: These data demonstrate that miR-29b prevents Dox-induced myocardial apoptosis through inhibition of the mitochondria-dependent pathway by directly targeting Bax, suggesting that miR-29b is a potential novel therapeutic target for the treatment of Dox cardiotoxicity.

Cardiac microvascular endothelial cells (CMECs) dysfunction induced by hypoxia is an important pathophysiological event in myocardium ischemic injury, whereas, the underlying mechanism is not fully clarified. FoxO transcription factors regulate target genes involved in apoptosis and cellular reactive oxygen species (ROS) production. Therefore, the present study was designed to elucidate the potential role of FoxOs on the hypoxia-induced ROS formation and apoptosis in CMECs. Exposure to low oxygen tension stimulated ROS accumulation and increased apoptosis in CMECs within 6–24 h. Hypoxia also significantly increased the expressions of HIF-1α and FoxO3a. However, hypoxia decreased the phosphorylation of Akt and FoxO3a, correlated with increased nuclear accumulation. Conversely, the expression of FoxO1 was not significantly altered by hypoxia. After inhibition of HIF-1α by siRNA, we observed that hypoxia-induced ROS accumulation and apoptosis of CMECs were decreased. Meanwhile, knockdown of HIF-1α also inhibited hypoxia induced FoxO3a expression in CMECs, but did not affect FoxO1 expression. Furthermore, hypoxia-induced ROS formation and apoptosis in CMECs were correlated with the disturbance of Bcl-2 family proteins, which were abolished by FoxO3a silencing with siRNA. In conclusion, our data provide evidence that FoxO3a leads to ROS accumulation in CMECs, and in parallel, induces the disturbance of Bcl-2 family proteins which results in apoptosis.

β3-adrenergic receptor (AR) and the downstream signaling, nitric oxide synthase (NOS) isoforms, have been emerged as novel modulators of heart function and even potential therapeutic targets for cardiovascular diseases. However, it is not known whether β3-AR plays cardioprotective effects against myocardial infarction (MI) injury. Therefore, the present study was designed to determine the effects of β3-AR on MI injury and to elucidate the underlying mechanism. MI model was constructed by left anterior descending (LAD) artery ligation. Animals were administrated with β3-AR agonist BRL37344 (BRL) or β3-AR inhibitor SR59230A (SR) respectively at 0.1 mg/kg/hour one day after MI operation. The scar area, cardiac function and the apoptosis of myocardial were assessed by Masson's trichrome stain, echocardiography and TUNEL assay respectively. Western blot analysis was performed to elucidate the expressions of target proteins. β3-AR activation with BRL administration significantly attenuated fibrosis and decreased scar area after MI. Moreover, BRL also preserved heart function, and reduced the apoptosis of cardiomyocyte induced by MI. Furthermore, BRL treatment altered the phosphorylation status of endothelial NOS (eNOS) and increased the expression of neuronal NOS (nNOS). These results suggested that β3-AR stimulation has a substantial effect on recovery of heart function. In addition, the activations of both eNOS and nNOS may be associated with the cardiac protective effects of β3-AR.

Background Angiosarcoma is an aggressive and malignant neoplasm. Primary hepatic angiosarcoma is extremely rare and accounts for only approximately 5% of all angiosarcomas. Therefore, many doctors do not know enough about this disease; this lack of knowledge motivated us to perform this study. Methods We carried out a systematic review of the literature published worldwide from 1990 to 2019 to study the main characteristics, demographics, treatment and prognosis of primary hepatic angiosarcoma. Result A total of 219 patients were included in this study. Patients were mainly middle-aged and elderly at diagnosis, with an average age at onset of 56.7 years. The vast majority of patients (61.5%) presented with abdominal pain or distension. Of 143 patients with clear records of metastasis, 31.5% (45 patients) had distant metastasis. The median overall survival time was only 6 months, and the 1- and 2-year survival rates were 30.4 and 17.3%, respectively. Sex, age, tumor size and metastasis at diagnosis showed no correlation with survival rate. Hepatic rupture was a significant predictor of survival. Surgery is a major treatment choice, and adjuvant chemotherapy can improve the prognosis of patients. Hepatic artery embolization is mainly used in cases of tumor rupture. However, liver transplantation is not advised. Conclusion We presented an overview of the demographics, tumor characteristics and treatment outcomes of the largest number of primary hepatic angiosarcoma patients investigated to date. We highlight the use of routine physical examinations and surgery combined with adjuvant chemotherapy to improve the outcomes in these cases.

ObjectiveTo reduce radiation dose while maintaining image quality in low-dose chest computed tomography (CT) by combining adaptive statistical iterative reconstruction (ASIR) and automatic tube current modulation (ATCM).MethodsPatients undergoing cancer screening (n = 200) were subjected to 64-slice multidetector chest CT scanning with ASIR and ATCM. Patients were divided into groups 1, 2, 3, and 4 (n = 50 each), with a noise index (NI) of 15, 20, 30, and 40, respectively. Each image set was reconstructed with 4 ASIR levels (0% ASIR, 30% ASIR, 50% ASIR, and 80% ASIR) in each group. Two radiologists assessed subjective image noise, image artifacts, and visibility of the anatomical structures. Objective image noise and signal-to-noise ratio (SNR) were measured, and effective dose (ED) was recorded.ResultsIncreased NI was associated with increased subjective and objective image noise results (P<0.001), and SNR decreased with increasing NI (P<0.001). These values improved with increased ASIR levels (P<0.001). Images from all 4 groups were clinically diagnosable. Images with NI = 30 and 50% ASIR had average subjective image noise scores and nearly average anatomical structure visibility scores, with a mean objective image noise of 23.42 HU. The EDs for groups 1, 2, 3 and 4 were 2.79±1.17, 1.69±0.59, 0.74±0.29, and 0.37±0.22 mSv, respectively. Compared to group 1 (NI = 15), the ED reductions were 39.43%, 73.48%, and 86.74% for groups 2, 3, and 4, respectively.ConclusionsUsing NI = 30 with 50% ASIR in the chest CT protocol, we obtained average or above-average image quality but a reduced ED.

The present study suggest that LXR agonists protect the endothelium against atherosclerotic insults by increasing ABCA1 and ABCG1 expression, and improve the endothelial-dependent vasomotor function probably by promoting Akt and eNOS phosphorylation.

Myocardial infarction (MI) is a coronary artery-related disease and ranks as the leading cause of sudden death globally. Resveratrol (Res) is a bioactive component and has presented antioxidant, anti-inflammatory and anti-microbial properties. However, the effect of Res on ferroptosis during MI progression remains elusive. Here, we aimed to explore the function of Res in the regulation of ferroptosis and myocardial injury in MI. We observed that the treatment of Res attenuated the MI-related myocardium injury and fibrosis in the rats. The expression of collagen 1 and α-SMA was induced in MI rats, in which the treatment of Res could decrease the expression. Treatment of Res suppressed the levels of IL-6 and IL-1β in MI rats. The GSH levels were inhibited and MDA, lipid ROS, and Fe2+ levels were induced in MI rats, in which the treatment of Res could reverse the phenotypes. Meanwhile, the expression of GPX4 and SLC7A11 was reduced in MI rats, while the treatment of Res could rescue the expression in the model. Meanwhile, Res relieved oxygen-glucose deprivation (OGD)-induced cardiomyocyte injury. Importantly, Res repressed OGD-induced cardiomyocyte ferroptosis in vitro. Mechanically, we identified that Res was able to enhance GPX4 expression by inducing KAT5 expression. We confirmed that KAT5 alleviated OGD-induced cardiomyocyte injury and ferroptosis. The depletion of KAT5 or GPX4 could reverse the effect of Res on OGD-induced cardiomyocyte injury. Thus, we concluded that Res attenuated myocardial injury by inhibiting ferroptosis via inducing KAT5/GPX4 in myocardial infarction. Our finding provides new evidence of the potential therapeutic effect of Res on MI by targeting ferroptosis.