Gastric cancer cell-derived extracellular vesicles disrupt endothelial integrity and promote metastasis.

The endothelium is the critical barrier that controls transendothelial communications. Blood vessels in cancer tissue are poorly developed and highly permeable. However, it is poorly understood how circulating cancer cells released through these "leaky" vessels break the intact vasculature of remote organs to metastasize. We investigated the roles of cancer cell-derived extracellular vesicles (CEVs) in regulating cancer metastasis by analyzing samples from gastric cancer patients, performing in vitro experiments, and studying mouse models. We made several novel observations. First, the rate of metastasis was closely associated with plasma levels of CEVs in patients with gastric cancer. Second, cultured endothelial cells endocytosed CEVs, resulting in cytoskeletal rearrangement, low expression of the junction proteins cadherin and CD31, and forming large intercellular gaps to allow the transendothelial migration of cancer cells. The dynamin inhibitor Dynasore prevented these CEV-induced changes of endothelial cells by blocking CEVs endocytosis. Third, CEVs disrupted the endothelial barrier of cancer-bearing mice to promote cancer metastasis. Finally, lactadherin promoted the clearance of circulating CEVs to reduce metastasis. These results demonstrate the essential role of CEVs in promoting the metastasis of gastric cancer.

The Role of miR-23b in Cancer and Autoimmune Disease.

Short-stranded miRNAs are single-stranded RNA molecules involved in the regulation of gene expression. miRNAs are involved in a variety of cellular physiological processes, including cell proliferation, differentiation, and apoptosis. miR-23b have been identified to act both as oncogenes and as tumor suppressors. In addition, miR-23b is related to inflammation resistance to various autoimmune diseases and restrained inflammatory cell migration. The characterization of the specific alterations in the patterns of miR-23b expression in cancer and autoimmune disease has great potential for identifying biomarkers for early disease diagnosis, as well as for potential therapeutic intervention in various diseases. In this review, we summarize the ever-expanding role of miR-23b and its target genes in different models and offer insight into how this multifunctional miRNA modulates tumor cell proliferation and apoptosis or inflammatory cell activation, differentiation, and migration.

Montelukast alleviates inflammation in experimental autoimmune encephalomyelitis by altering Th17 differentiation in a mouse model.

Montelukast is a leukotriene receptor antagonist that is known to prevent allergic rhinitis and asthma. Blocking the Cysteinyl leukotriene receptor (CysLTR1), one of the primary receptors of leukotrienes, has been demonstrated to be efficacious in ameliorating experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through disrupting chemotaxis of infiltrating T cells. However, the role of CysLTR1 in the pathogenesis of MS is not well understood. Here, we show that MS patients had higher expression of CysLTR1 in the circulation and central nervous system (CNS). The majority of CD4+ T cells expressed CysLTR1 in MS lesions. Among T-cell subsets, Th17 cells had the highest expression of CysLTR1, and blocking CysLTR1 signalling abrogated their development in vitro. Inhibition of CysLTR1 by montelukast suppressed EAE development in both a prophylactic and therapeutic manner and inhibited myelin loss in EAE mice. Similarly, the in vivo results showed that montelukast inhibited Th17 response in EAE mice and that Th17 cells treated with montelukast had reduced encephalitogenic in adoptive EAE. Our findings strongly suggest that targeting Th17 response by inhibiting CysLTR1 signalling could be a promising therapeutic strategy for the treatment of MS and CNS inflammatory diseases.

Robot-assisted Percutaneous Cannulated Screw Fixation of Femoral Neck Fractures: Preliminary Clinical Results.

OBJECTIVE: To assess the clinical efficacy of TiRobot-assisted percutaneous cannulated screw fixation in the treatment of femoral neck fractures. METHODS: From September 2015 to July 2017, 26 patients with unilateral femoral neck fractures were treated with TiRobot-assisted percutaneous cannulated screw fixation. The femoral necks were fixed using three cannulated screws with robot assistance applying the following procedure: image acquisition, path planning, and needle and screw placement. The results of the treatment, including operation duration, frequency of fluoroscopy use, implant placement accuracy, intraoperative bleeding, total drilling, surgical complications, fracture healing time, fracture healing rate, and Harris scores at the last follow-up, were recorded and compared with 23 similar patients who underwent conventional manual positioning surgery. RESULTS: A total of 147 cannulated screws were placed in all patients. The TiRobot group had shorter operation duration (62.6 ± 8.7 min vs 72.4 ± 10.3 min) and fracture healing time (5.1 ± 2.4 months vs 5.9 ± 2.8 months) than the conventional group (P > 0.05). The robot group had significantly less use of fluoroscopy (26.5 ± 7.4 times vs 51.3 ± 9.4 times), intraoperative bleeding (8.2 ± 5.3 mL vs 36.4 ± 12.5 mL), and total drilling (9.4 ± 4.2 times vs 18.3 ± 9.1 times) than the conventional group (all P < 0.05). The screw parallelism was significantly improved (24.0 ± 0.6 points vs 21.5 ± 1.2 points) and the neck-width coverage (72.0 ± 6.7 mm2 vs 53.8 ± 10.4 mm2 ) was significantly enlarged compared to the conventional group (P < 0.05). Only three guiding needles were used to penetrate the femoral head during manual insertion in the TiRobot group, which was significantly lower than that in the conventional group (3/78, 3.8% vs 9/69, 13.0%; P < 0.05). Other complications such as wound infection, vascular or nerve injury, screw loosening, and secondary screw displacement, did not occur in the two groups. There was no significant difference between the two groups in fracture healing rate (88.4% vs 82.6%) and Harris scores at the last follow up (88.2 ± 3.6 points vs 87.3 ± 4.7 points; P > 0.05). CONCLUSION: TiRobot-assisted percutaneous cannulated screw fixation of femoral neck fractures is advantageous over conventional surgery with manual positioning due to easier manipulation, more accurate screw insertion, less invasion, and less radiation exposure, suggesting that it is a better method to stabilize femoral neck fractures.