Transforming growth factor-β (TGF-β) triggers apoptosis in endothelial cells, while the mechanisms underlying this action are not entirely understood. Using genetic and pharmacological tools, we demonstrated that TGF-β induced a moderate apoptotic response in human cultured endothelial cells, which was dependent upon upregulation of the Nox4 NADPH oxidase and production of reactive oxygen species (ROS). In contrast, we showed that ectopic expression of Nox4 via viral vectors (vNox4) produced an antiapoptotic effect. TGF-β caused ROS-dependent p38 activation, whereas inhibition of p38 blunted TGF-β-induced apoptosis. However, vNox4, but not TGF-β, activated Akt, and inhibition of Akt attenuated the antiapoptotic effect of vNox4. Akt activation induced by vNox4 was accompanied by inactivation of the protein tyrosine phosphatase-1B (PTP1B) function and enhanced vascular endothelial growth factor receptor (VEGFR)-2 phosphorylation. Moreover, we showed that TGF-β enhanced Notch signaling and increased expression of the arterial marker EphrinB2 in a redox-dependent manner. In summary, our results suggest that Nox4 and ROS have pivotal roles in mediating TGF-β-induced endothelial apoptosis and phenotype specification. Redox mechanisms may influence endothelial cell functions by modulating p38, PTP1B/VEGFR/Akt and Notch signaling pathways.

Objective: This retrospective study aimed to analyze the ultrasound (US) imaging features of solitary papillary thyroid carcinoma (PTC) located in the isthmus and to assess the risk factors for lymph node metastasis (LNM) and tumor capsular invasion. Methods: We included a total of 135 patients with solitary PTC located in the isthmus. All the cases underwent US, total thyroidectomy, and prophylactic central lymph node dissection. Patients' demographic and thyroid isthmus nodules' US characteristics, as well as risk factors associated with LNM and tumor capsular invasion, were analyzed. Results: It was revealed that the occurrence of LNM was higher in male patients than in female patients (P < 0.001). As risk factors, the size of PTC in the isthmus was found to be associated with LNM and tumor capsular invasion (P = 0.005 and 0.000, respectively). The area under the receiver operating characteristic curve (AUC) of the size of the isthmus PTC was 0.64 [95% confidence interval (CI) = 0.55-0.72], indicating a probability for LNM. The AUC value for tumor capsular invasion was 0.77 (95% CI: 0.68-0.83). When the threshold was set to 1.1 cm, the larger size indicated that there was a probability of occurrence of LNM with sensitivity and specificity of 47.4 and 73.7%, respectively. When the threshold was set to 0.7 cm, the larger size indicated that there was potentially a tumor capsular invasion, with sensitivity and specificity of 80.6 and 56.3%, respectively. Wider-than-tall nodules were found to be significantly different from those in LNM and tumor capsular invasion (P = 0.038 and 0.030, respectively). There were significant differences in tumor capsular invasion in extrathyroidal extension (ETE) compared with smooth or ill-defined and lobulated or irregular nodules (P = 0.017). Conclusions: This study showed that the incidence of LNM in male patients was higher than that in female ones. When a US image shows a thyroid isthmus nodule with a wider-than-tall shape, LNM and tumor capsular invasion were likely to occur. When a US image shows a thyroid isthmus nodule with an ETE, tumor capsular invasion was likely to occur. ETE and wider-than-tall may be indicators of FNA under US guidance, even though the size of thyroid isthmus nodule may be <1 cm.

Rapeseed oil is one of the most important vegetable oils in Germany. It has a favorable fatty acid composition but also contains a certain amount of erucic acid (EA). As the result of toxicological considerations regarding this fatty acid, the European Food Safety Authority (EFSA) established a tolerable daily intake (TDI) for EA of 7 mg/kg body weight in 2016. On this basis, the maximum EA levels for vegetable oils allowed in the European Union have been reduced shortly from 50 to 20 g/kg, and for infant formula and follow‐on formula from 10 to 4 g/kg. However, rapeseed oil is also recommended for the preparation of homemade food for infants and children. Little is known about the actual EA concentrations of rapeseed oils on the German retail market. Current data are especially important for the necessary reassessment of its recommendation in infant and child nutrition based on the established TDI. Three hundred representative rapeseed oil samples were purchased in retail stores across Germany. EA concentrations, determined by GC‐FID, were in a range of 0.17–9.68 g/kg, with 241 samples being even below 4 g/kg. All oils were below the maximum level valid at the time of this investigation, and even below the newly established lower maximum level of 20 g/kg. The major part also met the requirements for infant and follow‐on formula. The representative results provide valuable current data for the necessary reassessment of the dietary recommendations for infant and child nutrition based on the established TDI.

Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas, and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.

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Rationale:Pseudoaneurysm (PA) with associated arteriovenous fistula (AVF) is most often secondary to vascular catheterization, percutaneous biopsy, surgery, or trauma. PA-AVF occurs mainly in large or median arterial territories but rarely in the superficial arterioles of the breast.Patient concerns:A 30-year-old woman underwent vacuum-assisted removal of breast fibroadenomas under ultrasonic guidance. On the follow-up visit, the patient complained of a painful enlarging lump in her left breast.Diagnoses:An iatrogenic breast PA-AVF was diagnosed.Interventions:The patient was treated with surgical excision and ligation under local anesthesia.Outcomes:At the 1-month follow-up, the wound was found to have healed well, and breast PA-AVF was eradicated.Lessons:Vacuum-assisted removal has been the first-line intervention for benign mass resection because of minimal invasion, but the risk of serious vascular complications remains. Careful duplex ultrasound examination prior to the procedure is highly recommended.

Introduction: Recent studies have shown that YAP is closely related to the pathological process of cardiovascular diseases. But the role of YAP in cardiac injury of diabetic cardiomyopathy (DCM) is still unclear. Methods: Diabetic cardiomyopathy rat model was established and divided into control group, DCM group, LV-SC-shRNA group and LV-YAP-shRNA group. LV-SC-shRNA group and LV-YAP-shRNA group were injected with lentivirus expressing SC-shRNA and YAP-shRNA via tail vein, respectively. Primary rat cardiac fibroblasts (CFs) were stimulated with high concentration of glucose and treated with recombinant lentivirus expressing either SC-shRNA or YAP-shRNA to observe the expression of CTGF and fibronectin, so as to observe the effect of inhibiting YAP on the pathogenesis of DCM. Results: Compared with control group, high glucose markedly increased YAP mRNA and protein expression in DCM and CFs. Inhibition of YAP decreased myocardial fibrosis and improved cardiac function in the DCM model and decreased the expression of CTGF and fibronectin in CFs. The result suggested that YAP plays a key role in the pathological progression of DCM, and the underlying mechanisms may be associated with TEAD and CTGF. Discussion: We found that the expression of YAP was increased both in vivo and in vitro, suggesting that YAP is closely related to DCM, and YAP knockdown can reduce myocardial fibrosis in rat model of DCM by reducing the expression of PAI-1, collagen I, collagen III, CTGF and profilin, as well as the expression of CTGF and fibronectin in CFs. This study revealed that YAP plays an important role in the pathological process of diabetic cardiomyopathy, and down-regulation of YAP expression may provide a new therapeutic target for DCM.