Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. Herein, we demonstrated that discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase that predominantly transduces signals from fibrillar collagens, plays a critical role in the induction of fibrosis and angiogenesis in the lung. In vitro cell studies showed that DDR2 can synergize the actions of both transforming growth factor (TGF)-β and fibrillar collagen to stimulate lung fibroblasts to undergo myofibroblastic changes and vascular endothelial growth factor (VEGF) expression. In addition, we confirmed that late treatment of the injured mice with specific siRNA against DDR2 or its kinase inhibitor exhibited therapeutic efficacy against lung fibrosis. Thus, this study not only elucidated novel mechanisms by which DDR2 controls the development of pulmonary fibrosis, but also provided candidate target for the intervention of this stubborn disease.

Discoidin domain receptor 2 (DDR2) is a unique receptor tyrosine kinase (RTK) that signals in response to collagen binding and is implicated in tumour malignant phenotypes such as invasion and metastasis. Although it has been reported that DDR2 expression is up-regulated in activated endothelial cells (ECs), functional studies are lacking. Herein, we found that enforced expression of DDR2 promoted proliferation, migration and tube formation of primary human umbilical vein endothelial cells (HUVECs). The results of immunohistochemical analysis showed a strikingly high level of DDR2 in human tumour ECs. Most significantly, we discovered that a host deficiency of DDR2 inhibits subcutaneous angiogenesis induced by either VEGF or tumour cells. In addition, the remaining tumour vessels in DDR2-deficient mice exhibit some normalized properties. These vascular phenotypes are accompanied by the up-regulation of anti-angiogenic genes and down-regulation of pro-angiogenic genes, as well as by alleviated tumour hypoxia. By use of a tail vein metastasis model of melanoma, we uncovered that loss of stromal DDR2 also suppresses tumour metastasis to the lung. Hence, our current data disclose a new mechanism by which DDR2 affects tumour progression, and may strengthen the feasibility of targeting DDR2 as an anticancer strategy.

Antioxidants induce the proliferation of cancers by decreasing the expression of p53. Propofol, one of the most extensively used intravenous anesthetics, provides its antioxidative activity via activation of the nuclear factor E2-related factor-2 (Nrf2) pathway, but the mechanisms involved in the effects remain unknown. Thus, we aimed to investigate the function of p53 and Nrf2 in the human breast cancer cell line MDA-MB-231 following treatment with propofol. The cells were treated with propofol (2, 5 and 10 µg/ml) for 1, 4 and 12 h, and MTT assay was used to evaluate cell proliferation, and a wound healing assay was used to evaluate cell migration. Cell apoptosis, caspase-3 activity, and western blot analysis for p53 and Nrf2 protein were also assessed. Finally, PIK-75, a potent Nrf2 inhibitor, was used to confirm the effects of Nrf2 after treatment with propofol. Treatment of MDA-MB‑231 cells with propofol resulted in increased proliferation and migration in a dose- and time-dependent manner. After treatment with propofol for 12 h, the Nrf2 protein expression was increased, while the percentage of apoptotic cells, caspase-3 activity, and expression of p53 were significantly decreased. Additionally, treatment with the Nrf2 inhibitor increased the percentage of apoptotic cells, inhibited the migration almost completely, and decreased the degree of proliferation, while the expression of p53 was not affected. In conclusion, propofol increased the proliferation of human breast cancer MDA-MB‑231 cells, which was at least partially associated with the inhibition of the expression of p53, and induced cell migration, which was involved in the activation of the Nrf2 pathway.

sn-1,2-Diacylglycerol (DAG), a key intermediate in lipid metabolism, activates protein kinase C and is a fusogen. Phosphoinositides, the main sources of DAG in cell signaling, contain mostly stearoyl and arachidonoyl in the sn-1 and -2 positions, respectively. The polymorphic behavior of sn-1-stearoyl-2-arachidonoylglycerol (SAG) was studied by differential scanning calorimetry, x-ray powder diffraction, and solid state magic angle spinning (MAS) 13 C NMR. Three ␣ phases were found in the dry state. X-ray diffraction indicated that the acyl chains packed in a hexagonal array in the ␣ phase, and the two sub-␣ phases packed with pseudo-hexagonal symmetry. In the narrow angle range strong diffractions of ϳ31 and ϳ62 Å were present. High power protondecoupled MAS 13

Moth lacewings (Ithonidae) are a rare group of Neuroptera with an unusual subterranean larval life‐style. We examined external and internal head structures of an older‐instar larva of Ithone Newman with a broad spectrum of techniques. Larval autapomorphies, likely correlated with the subterranean habits, are the compact and shovel‐shaped head, unusually massive mandibular‐maxillary stylets, and a C‐shaped postcephalic body. Other cephalic autapomorphies are the massive X‐shaped tentorium, incurved antennae, and a strongly developed M. verticopharyngalis. The visual organs are distinctly simplified but a single functional stemma on each side of head is retained despite of the subterranean habits. In contrast to previous studies, a well‐developed gular sclerite is present in Ithonidae, possibly a secondary acquisition. A cephalic gland complex and poison channel are present, with an unexpected additional lateral accessory gland and an additional lateral channel. The poison glands and dual channels very clearly indicate that the larvae are predators, contradicting the phytophagous habits formerly postulated. Compared with soil‐inhabiting scarabaeoid beetle larvae, striking differences of head structures are due to different feeding habits and phylogenetic constraints. Morphological similarities like a C‐shaped postcephalic body and strongly developed legs suitable for burrowing in soil are evolutionary parallels associated with the subterranean life‐style in the two non‐related groups. Bayesian phylogenetic analysis was carried out with an updated morphological matrix. The results were compared with a phylogeny based on anchored hybrid enrichment data. The evolutionary transformations of selected characters were evaluated using phylogenies estimated from both datasets.