Successful construction of a small-diameter bioartificial vascular graft remains a great challenge. This study reports on novel tissue engineering vascular grafts (TEVGs) constructed by endothelial progenitor cells and heparin-coated decellularized vessels (DV). The DVs were fabricated from canine carotid arteries with observable depletion of cellular components. After heparin coating, the scaffolds possessed excellent antithrombogeneity. Canine endothelial progenitor cells harvested from peripheral blood were expanded and seeded onto heparin-coated DVs and cocultured in a custom-made bioreactor to construct TEVGs. Thereafter, the TEVGs were implanted into the carotid arteries of cell-donor dogs. After 3 months of implantation, the luminal surfaces of TEVGs exhibited complete endothelium regeneration, however, only a few disorderly cells and thrombosis overlaid the luminal surfaces of control DVs grafts, and immunofluorescent staining showed that the seeded cells existed in the luminal sides and the medial parts of the explanted TEVGs and partially contributed to the endothelium formation. Specifically, TEVGs exhibited significantly smaller hyperplastic neointima area compared with the DVs, not only at midportion (0.64 ± 0.08 vs. 2.13 ± 0.12 mm(2) , p < 0.001), but also at anastomotic sites (proximal sites, 1.03 ± 0.09 vs. 3.02 ± 0.16 mm(2), p < 0.001; distal sites, 1.84 ± 0.15 vs. 3.35 ± 0.21 mm(2), p < 0.001). Moreover, TEVGs had a significantly higher patency rate than the DVs after 3 months of implantation (19/20 vs. 12/20, p < 0.01). Overall, this study provided a new strategy to develop small-diameter TEVGs with excellent biocompatibility and high patency rate.

To overcome shortcomings of current small-diameter vascular prostheses, we developed a novel allogenic vascular graft from a decellularized scaffold modified through heparin immobilization and vascular endothelial growth factor (VEGF) coating. The VEGF coating and release profiles were assayed by enzyme-linked immunosorbent assay, the biological activity of modified surface was validated by human umbilical vein endothelial cells seeding and proliferation for 10 days in vitro. In vivo, we implanted either a modified or a nonmodified scaffold as bilateral carotid allogenic graft in canines (n = 15). The morphological examination of decellularized scaffolds showed complete removal of cellular components while the extracellular matrix structure remained intact. After modification, the scaffolds possessed local sustained release of VEGF up to 20 days, on which the cells cultured showed significantly higher proliferation rate throughout the time after incubation compared with the cells cultured on nonmodified scaffolds (P < 0.0001). After 6 months of implantation, the luminal surfaces of modified scaffolds exhibited complete endothelium regeneration, however, only a few disorderly cells and thrombosis overlay the luminal surfaces of nonmodified scaffolds. Specifically, the modified scaffolds exhibited significantly smaller hyperplastic neointima area compared with the nonmodified, not only at midportion (0.56 +/- 0.07 vs. 2.04 +/- 0.12 mm(2), P < 0.0001), but also at anastomotic sites (1.76 +/- 0.12 vs. 3.67 +/- 0.20 mm(2), P < 0.0001). Moreover, modified scaffolds had a significantly higher patency rate than the nonmodified after 6 months of implantation (14/15 vs. 7/15, P = 0.005). Overall, this modified decellularized scaffold provides a promising direction for fabrication of small-diameter vascular grafts.

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In mammals, female fecundity is determined by the size of the primordial follicle (PF) pool, which is established during the perinatal period. As a non-renewable resource, the preservation of dormant PFs is crucial for sustaining female reproduction throughout life. Although studies have revealed that several oocyte-derived functional genes and pathways, such as newborn ovary homeobox (NOBOX) and 3-phosphoinositide-dependent protein kinase-1, participate in maintaining the PF pool, our understanding of the underlying molecular mechanisms is still incomplete. Here, we demonstrate that E-cadherin (E-cad) plays a crucial role in the maintenance of PFs in mice. E-cad is specifically localized to the cytomembrane of oocytes in PFs. Knockdown of E-cad in neonatal ovaries resulted in significant PF loss owing to oocyte apoptosis. In addition, the expression pattern of NOBOX is similar to that of E-cad. Knockdown of E-cad resulted in a decreased NOBOX level, whereas overexpression of Nobox partially rescued the follicle loss induced by silencing E-cad. Furthermore, E-cad governed NOBOX expression by regulating the shuttle protein, β-catenin, which acts as a transcriptional co-activator. Notably, E-cad, which is a transmembrane protein expressed in the oocytes, was also responsible for maintaining the PF structure by facilitating cell–cell adhesive contacts with surrounding pregranulosa cells. In conclusion, E-cad in oocytes of PFs plays an indispensable role in the maintenance of the PF pool by facilitating follicular structural stability and regulating NOBOX expression. These findings shed light on the physiology of sustaining female reproduction.

The inflammatory response plays a vital role in cerebral aneurysm (CA) formation and progression. Tanshinone IIA (Tan IIA) is one of the major active components of Chinese medicine Danshen ( Salvia miltiorrhiza Bunge) and is widely used for the treatment of cardiovascular diseases, due to its anti-inflammatory effects. The aim of the present study was to investigate whether Tan IIA can attenuate CA formation in rat models, and determine its underlying mechanisms. CAs were induced in rats surgically and through high-salt diet treatments. The Tan IIA-treated group displayed relatively mild symptoms, as compared with the control group. Tan IIA treatment reduced macrophage infiltration and nuclear factor (NF)-κB activation in aneurysmal walls. Next, lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells were used to examine the anti-inflammatory effects of Tan IIA on macrophages. It was found that Tan IIA reversed LPS-induced differentiation of RAW 264.7 cells and suppressed NF-κB pathway activation. In conclusion, these findings demonstrated that Tan IIA can suppress CA formation by inhibiting inflammatory responses in macrophages.

Gap junctions (GJs) are indispensable for communication between cumulus cells (CCs) and oocytes in coordinating the gonadotropin-induced meiotic maturation of oocytes. Of all proteins that constitute GJs, phosphorylated connexin43 (pCx43) is vital for mediating the actions of gonadotropins. In this study, the mechanism of Cx43 phosphorylation in response to follicle stimulating hormone (FSH) stimulation was examined using an in vitro model of mouse cumulus-oocyte complexes (COCs). The results confirmed that Cx43 phosphorylation occurred twice during FSH treatment. Importantly, the second Cx43 phosphorylation was closely related to cAMP level reduction within oocytes, which initiated oocyte maturation. Exploration of the underlying mechanism revealed that the CC-specific protein kinase C ε (PKCε) level was upregulated by FSH stimulation. PKCε was a kinase downstream from mitogen-activated protein kinase (MAPK) and was responsible for Cx43 phosphorylation. Interestingly, MAPK was involved in both Cx43 phosphorylation processes, while PKCε was only involved in the second. In conclusion, PKCε-mediated MAPK signals might contribute to Cx43 phosphorylation in CCs during FSH-induced oocyte meiotic resumption. Our findings contribute to a better understanding of the molecular regulation mechanism of oocyte maturation in response to FSH in vitro.

A 67-year-old man who received endoscopic submucosal dissection for an early squamous esophageal cancer was hospitalized for dysphagia. The mucosal defect was over three quarters of the circumference, and the distal edge of the resection scar formed the stenosis after 8 months. After experiencing conservative treatment, probe expansion, and esophageal stent placement, the symptom of deglutition disorder in the patient was improved, but persistent hemorrhage and progressive anemia occurred in the short term. An enhanced neck and chest computed tomography (CT) showed a contrast agent leaked from the aberrant right subclavian artery to the esophagus. A pseudoaneurysm of the aberrant right subclavian artery and subclavian artery-esophageal fistula were diagnosed by CT angiography. Although false aneurysms developing after iatrogenic injury and trauma have been reported, those caused by esophageal stent placement because of esophageal stricture after endoscopic submucosal dissection have not. When persistent hemorrhage and progressive anemia develop after esophageal stent placement, an enhanced CT should be performed to exclude the false aneurysm.