Cryptochromes (CRYs) are blue-light photoreceptors that mediate various light responses in plants and animals. The signaling mechanism by which CRYs regulate light responses involves their physical interactions with COP1. Here, we report that CRY1 interacts physically with SPA1 in a blue-light-dependent manner. SPA acts genetically downstream from CRYs to regulate light-controlled development. Blue-light activation of CRY1 attenuates the association of COP1 with SPA1 in both yeast and plant cells. These results indicate that the blue-light-triggered CRY1-SPA1 interaction may negatively regulate COP1, at least in part, by promoting the dissociation of COP1 from SPA1. This interaction and consequent dissociation define a dynamic photosensory signaling mechanism.

AIMTo analyze the diagnostic value of a circular RNA (circRNA), circ-LDLRAD3, in pancreatic cancer.METHODSExpression levels of circ-LDLRAD3 were tested in both cells and clinical samples; the latter included 30 paired pancreatic cancer tissues and adjacent non-tumorous tissues, 31 plasma samples from patients with pancreatic cancer, and 31 plasma samples from healthy volunteers. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to measure expression levels of circ-LDLRAD3 in cells and clinical samples; then, the relationship between clinicopathological factors of patient samples and expression of circ-LDLRAD3 in pancreatic cancer was analyzed. The diagnostic value of circ-LDLRAD3 was verified by receiver operating characteristic (ROC) curve analysis.RESULTSCirc-LDLRAD3 was up-regulated in pancreatic cancer cell lines (P < 0.01), pancreatic cancer tissues (P < 0.01), and plasma samples from patients with pancreatic cancer (P < 0.01). High expression of circ-LDLRAD3 was significantly associated with venous invasion, lymphatic invasion, and metastasis. The area under the ROC curve of circ-LDLRAD3 alone or combination with CA19-9 was 0.67 and 0.87, respectively, with a sensitivity and specificity of 0.5738 (alone) and 0.7049 (alone), and 0.8033 (combination) and 0.9355 (combination), respectively.CONCLUSIONThese data suggest that circ-LDLRAD3 may be a biomarker in the diagnosis of pancreatic cancer.

EUS-guided intraoperative interstitial brachytherapy had a moderate local tumor effect and showed some clinical benefit in 30% of the patients in this study. Combination of this form of treatment with external radiation and/or chemotherapy should be tested in future trials.

Different imaging techniques can bring different information which will contribute to the final diagnosis and further management of the patients. Even from the time of Hippocrates, palpation has been used in order to detect and characterize a body mass. The so-called virtual palpation has now become a reality due to elastography, which is a recently developed technique. Elastography has already been proving its added value as a complementary imaging method, helpful to better characterize and differentiate between benign and malignant masses. The current applications of elastography in lymph nodes (LNs) assessment by endoscopic ultrasonography will be further discussed in this paper, with a review of the literature and future perspectives.

BackgroundEndoscopic full-thickness resection (EFTR) is a mini-invasive technique for gastric subepithelial tumors originating from the muscularis propria, which enables a full-thickness resection of tumors and can provide a complete basis for pathological diagnosis. Gastric fistula closure after EFTR is a challenge for endoscopists. In this study, we introduced EFTR with fistula closure using the over-the-scope clip (OTSC) system for gastric subepithelial tumors originating from the muscularis propria.ObjectivesTo evaluate the feasibility and safety of fistula closure with OTSC by a retrospective analysis on the cases of EFTR with defect closure using OTSC for gastric subepithelial tumors originating from the muscularis propria in our hospital.MethodsThe patients were selected who underwent EFTR for gastric subepithelial tumors originating from the muscularis propria (tumor diameter ≤2 cm) in our hospital from October 2013 to March 2014. After a full-thickness resection of tumors, the bilateral gastric mucous membranes of defect were clamped using twin graspers and then drawn into the transparent cap of OTSC, and the OTSC was released to close the defect after full suctioning. The success rate of defect closure with OTSC was observed, and the endoscopic follow-up was performed at 1 week, 1 and 6 months after operation to check OTSC closure.ResultsTotally 23 patients were included into the study. The full-thickness resection rate of gastric tumors in the muscularis propria was 100 % (23/23), the success rate of defect closure was 100 %, and the average time of defect closure was 4.9 min (range 2–12 min). All patients experienced no postoperative complications such as bleeding and perforation. The postoperative follow-up time was 1–6 months (mean 3 months), and no OTSC detachment was found.ConclusionsOTSC can be used to perform EFTR with defect closure for gastric tumors in the muscularis propria (tumor diameter ≤2 cm). It is simple, convenient, safe and effective.Electronic supplementary materialThe online version of this article (doi:10.1007/s00464-015-4076-2) contains supplementary material, which is available to authorized users.

Autotaxin (ATX), which is highly expressed and secreted by adipocytes, functions as the key enzyme to generate lysophosphatidic acid (LPA) from lysophosphatidylcholine. Adipose tissue is the main source of circulating ATX that modulates plasma LPA levels. Upregulation of ATX expression in obese patients and mice is closely related with insulin resistance and impaired glucose tolerance. However, the mechanism of ATX expression in adipocytes remains largely unknown. In this study, we found that glycoprotein 130 (gp130)-mediated Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) activation was required for abundant ATX expression in adipocytes. Through gp130, the interleukin 6 (IL-6) family cytokines, such as IL-6, leukemia inhibitory factor, cardiotrophin-1, and ciliary neurotrophic factor, upregulated ATX expression in adipocytes. ATX contributes to the induction of insulin resistance and lipolysis in IL-6-stimulated adipocytes. Oral administration of gp130 inhibitor SC144 suppressed ATX expression in adipose tissue, decreased plasma ATX, LPA, and FFA levels, and significantly improved insulin sensitivity and glucose tolerance in high-fat diet-fed obese mice. In summary, our results indicate that the activation of gp130-JAK-STAT3 pathway by IL-6 family cytokines has an important role in regulating ATX expression in adipocytes and that gp130 is a promising target in the management of obesity-associated glucose metabolic diseases.

Caveolin-1 (Cav-1) plays an important role in modulating cellular signalling, but its role in metastasis is not well defined. A significant reduction in Cav-1 levels was detected in lymph node metastases as compared with primary tumour of head and neck squamous cell carcinoma (HNSCC) specimens (P<0.0001), confirming the downregulation of Cav-1 observed in a highly metastatic M4 cell lines derived from our orthotopic xenograft model. To investigate the function of Cav-1 in metastasis of HNSCC, we compared stable clones of M4 cells carrying human cav-1 cDNA (CavS) with cells expressing an empty vector (EV) in vitro and in the orthotopic xenograft model. Overexpression of Cav-1 suppressed growth of the CavS tumours compared with the EV tumours. The incidence of lung metastases was significantly lower in animals carrying CavS tumours than those with EV tumours (P=0.03). In vitro, CavS cells displayed reduced cell growth, invasion, and increased anoikis compared with EV cells. In CavS cells, Cav-1 formed complex with integrin β1 and Src. Further application of integrin β1 neutralising antibody or Src inhibitor PP2 to EV cells illustrated similar phenotypes as CavS cells, suggesting that Cav-1 may play an inhibitory role in tumorigenesis and lung metastasis through regulating integrin β1- and Src-mediated cell–cell and cell–matrix interactions.

There is a lack of consensus on how endoscopic ultrasound (EUS)-guided pseudocyst drainage and endoscopic necrosectomy should be performed. This survey was carried out amongst members of the EUS Journal Editorial Board to describe their practices in performing this procedure. This was a worldwide multi-institutional survey amongst members of the EUS Journal Editorial Board in May 2017. The responses to a 22-question survey with respect to the practice of EUS-guided pseudocyst drainage and endoscopic necrosectomy were obtained. Twenty-two endoscopists responded to the questionnaire as follows: 72.7% (16/22) were of the opinion that lumen-apposing metal stents (LAMS) should be the standard of care for the creation of an endoscopic cystenterostomy in patients with pancreatic walled-off necrosis (WON); 95.5% (21/22) recommended large diameter (d=15 mm) LAMS for drainage in patients with WON; 54.5% (12/22) would not dilate LAMS after placement into the WOPN; 86.4% (19/22) would not perform endoscopic necrosectomy during the same procedure as the creation of the cystenterostomy; 45.5% (10/22) recommend that agents, such as diluted hydrogen peroxide, should be used to lavage the peri-pancreatic fluid collection (PFC) cavity in patients with WON; and 45.5% (10/22) considered a naso-cystic or other tube to be necessary for lavage of WON after initial drainage. The mean optimal interval recommended for endoscopic necrosectomy procedures after EUS-guided drainage was 6.23 days. The mean optimal interval recommended for repeat imaging in patients undergoing endoscopic necrosectomy was 12.32 days. The mean time recommended for LAMS removal was 4.59 weeks. This is the first worldwide survey on the practice of EUS-guided pseudocyst drainage and endoscopic necrosectomy. There were wide variations in practice and randomized studies are urgently needed to establish the best approach for management of this condition. There is also a pressing need to establish a best practice consensus.