Soluble Frizzled-related proteins promote exosome-mediated Wnt re-secretion.

Wnt proteins are thought to be transported in several ways in the extracellular space. For instance, they are known to be carried by exosomes and by Wnt-carrier proteins, such as sFRP proteins. However, little is known about whether and/or how these two transport systems are related.

Understanding and manipulating extracellular behaviors of Wnt ligands.

Wnt, a family of secreted signaling proteins, serves diverse functions in embryogenesis, organogenesis, cancer, and stem cell functions. In the context of development, Wnt has been considered a representative morphogen, forming concentration gradients to give positional information to cells or tissues. However, although gradients are often illustrated in schemata, the reality of concentration gradients, or in other words, actual spatial distribution of Wnt ligands, and their behaviors in the extracellular space still remain poorly known.

Dissection of N-deacetylase and N-sulfotransferase activities of NDST1 and their effects on Wnt8 distribution and signaling in Xenopus embryos.

Wnt is a family of secreted signaling proteins involved in the regulation of cellular processes, including maintenance of stem cells, carcinogenesis, and cell differentiation. In the context of early vertebrate embryogenesis, graded distribution of Wnt proteins has been thought to regulate positional information along the antero-posterior axis. However, understanding of the molecular basis for Wnt spatial distribution remains poor.

The CagA oncoprotein disrupts Wnt/PCP signaling and promotes hyperproliferation of pyloric gland base cells.

strains that deliver the oncoprotein CagA into gastric epithelial cells are the major etiologic agents of upper gastric diseases including gastric cancer. CagA promotes gastric carcinogenesis through interactions with multiple host proteins. Here, we show that CagA also disrupts Wnt-dependent planar cell polarity (Wnt/PCP), which orients cells within the plane of an epithelium and coordinates collective cell behaviors such as convergent extension to enable epithelial elongation during development.

Intercellular exchange of Wnt ligands reduces cell population heterogeneity during embryogenesis.

Wnt signaling is required to maintain bipotent progenitors for neural and paraxial mesoderm cells, the neuromesodermal progenitor (NMP) cells that reside in the epiblast and tailbud. Since epiblast/tailbud cells receive Wnt ligands produced by one another, this exchange may average out the heterogeneity of Wnt signaling levels among these cells. Here, we examined this possibility by replacing endogenous Wnt3a with a receptor-fused form that activates signaling in producing cells, but not in neighboring cells.

Alignment of the cell long axis by unidirectional tension acts cooperatively with Wnt signalling to establish planar cell polarity.

Planar cell polarity (PCP) is the aligned cell polarity within a tissue plane. Mechanical signals are known to act as a global cue for PCP, yet their exact role is still unclear. In this study, we focused on PCP in the posterior neuroectoderm of Xenopus laevis and investigated how mechanical signals regulate polarity.

Distance of Peritoneum to Inferior Mesenteric Artery Predicts the Operation Time During Laparoscopic Colectomy for Sigmoid or Rectosigmoid Colon Cancer.

Background/aim: Obesity is a major technical limiting factor for laparoscopic surgery because abundant visceral fat is known to extend the operation time. However, special hardware is needed to assess it. We hypothesized that the depth from the peritoneum to the bifurcation of the inferior mesenteric artery (IMA) defined as 'peritoneum to IMA distance (PID)' might be a simple predictive factor for extended operation time during laparoscopic colectomy.

Taking antithrombic therapy during emergency laparoscopic cholecystectomy for acute cholecystitis does not affect the postoperative outcomes: a propensity score matched study.

Background: Continuing antithrombic therapy (ATT) during surgery increases the risk of bleeding. However, it is difficult to discontinue the ATT in emergency surgery. Therefore, safety of emergency laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) is still unclear.

Optogenetic relaxation of actomyosin contractility uncovers mechanistic roles of cortical tension during cytokinesis.

Actomyosin contractility generated cooperatively by nonmuscle myosin II and actin filaments plays essential roles in a wide range of biological processes, such as cell motility, cytokinesis, and tissue morphogenesis. However, subcellular dynamics of actomyosin contractility underlying such processes remains elusive. Here, we demonstrate an optogenetic method to induce relaxation of actomyosin contractility at the subcellular level.

Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc.

How morphogen gradients control patterning and growth in developing tissues remains largely unknown due to lack of tools manipulating morphogen gradients. Here, we generate two membrane-tethered protein binders that manipulate different aspects of Decapentaplegic (Dpp), a morphogen required for overall patterning and growth of the Drosophila wing. One is "HA trap" based on a single-chain variable fragment (scFv) against the HA tag that traps HA-Dpp to mainly block its dispersal, the other is "Dpp trap" based on a Designed Ankyrin Repeat Protein (DARPin) against Dpp that traps Dpp to block both its dispersal and signaling.

Regulation of Wnt/PCP signaling through p97/VCP-KBTBD7-mediated Vangl ubiquitination and endoplasmic reticulum-associated degradation.

The four-pass transmembrane proteins Vangl1 and Vangl2 are dedicated core components of Wnt/planar cell polarity (Wnt/PCP) signaling that critically regulate polarized cell behaviors in many morphological and physiological processes. Here, we found that the abundance of Vangl proteins is tightly controlled by the ubiquitin-proteasome system through endoplasmic reticulum-associated degradation (ERAD). The key ERAD component p97/VCP directly binds to Vangl at a highly conserved VCP-interacting motif and recruits the E3 ligase KBTBD7 via its UBA-UBX adaptors to promote Vangl ubiquitination and ERAD.

Quantitative analyses reveal extracellular dynamics of Wnt ligands in embryos.

The mechanism of intercellular transport of Wnt ligands is still a matter of debate. To better understand this issue, we examined the distribution and dynamics of Wnt8 in embryos. While Venus-tagged Wnt8 was found on the surfaces of cells close to Wnt-producing cells, we also detected its dispersal over distances of 15 cell diameters.

Purse-string suture after ligating by endoloop for closing of the appendiceal stump is an alternative for endostapler in selected cases: A propensity score-matched study.

Introduction: The closure of the appendiceal stump is a crucial part of a laparoscopic appendectomy, and an endoloop or endostapler is generally used. The endoloop can be more cost effective than the endostapler. However, reports have shown that the endoloop has a higher postoperative abdominal abscess rate than the endostapler in complicated appendicitis.

Improvement of Phycocyanobilin Synthesis for Genetically Encoded Phytochrome-Based Optogenetics.

Optogenetics is a powerful technique using photoresponsive proteins, and the light-inducible dimerization (LID) system, an optogenetic tool, allows to manipulate intracellular signaling pathways. One of the red/far-red responsive LID systems, phytochrome B (PhyB)-phytochrome interacting factor (PIF), has a unique property of controlling both association and dissociation by light on the second time scale, but PhyB requires a linear tetrapyrrole chromophore such as phycocyanobilin (PCB), and such chromophores are present only in higher plants and cyanobacteria. Here, we report that we further improved our previously developed PCB synthesis system (SynPCB) and successfully established a stable cell line containing a genetically encoded PhyB-PIF LID system.

Heparan Sulfate Proteoglycan Clustering in Wnt Signaling and Dispersal.

Wnt, a family of secreted signal proteins, serves diverse functions in animal development, stem cell systems, and carcinogenesis. Although Wnt is generally considered a morphogen, the mechanism by which Wnt ligands disperse is still debated. Heparan sulfate proteoglycans (HSPGs) are extracellular regulators involved in Wnt ligand dispersal.

[Preoperative Chemotherapy with DCF for Advanced Esophageal Cancer].

We conducted a retrospective study to evaluate the efficacy and the problem of the neoadjuvant chemotherapy using DCF for cStage Ⅲ/Ⅳ(squamous cell)esophageal cancer. Eleven patients from January 2017 to December 2018 were enrolled into this study. The median age was 67 years old, male/female ratio was 9:2, performance status was 0 in all patients, and UICC cStage Ⅲ/Ⅳa was 7:4.

[Adjuvant Chemotherapy for High-Risk Stage Ⅱ Colon Cancer].

Background: This study was designed to clarify effects of postoperative adjuvant chemotherapy for high-risk Stage Ⅱ colorectal cancer.

Method: The subjects were 99 patients with high-risk Stage Ⅱcolorectal cancer who underwent surgery at our department from October 2013 to March 2018. Patients were classified into adjuvant chemotherapy group and nonadjuvant chemotherapy group.

Undiagnosed synovial hemangioma of the knee: a case report.

Background: Synovial hemangioma of the knee is a rare benign tumor. Very rarely, the growth of bone is affected by long-term neglect of an intra-articular tumor. Our patient had not only various clinical symptoms but also dysplasia of the femoral bone.

Feasibility and Effectiveness of Gastrectomy for Elderly Gastric Cancer Patients.

Background/aim: The benefits of gastrectomy for elderly gastric cancer (GC) patients remain unknown. The aim of this study was to evaluate the validity of gastrectomy.

Patients And Methods: Patients who had R0 or R1 resection and diagnosed as pathological Stage I-III GC were enrolled in this study.

Laparoscopic anatomical liver resection using indocyanine green fluorescence imaging.

Background: Anatomical liver resections guided by a demarcation line after portal staining or inflow clamping of the target area have been established as essential methods for curative treatment of hepatocellular carcinoma (HCC) and have subsequently been applied to other malignancies. However, laparoscopic anatomical liver resection (LALR) procedures are very difficult to reproduce, and the confirmation of demarcation of the hepatic segment on a monitor is also challenging. Recently, indocyanine green (ICG) fluorescence imaging has been used to identify hepatic tumors and segmental boundaries during hepatectomy.

Assembly of protein complexes restricts diffusion of Wnt3a proteins.

Members of the Wnt protein family play roles in many aspects of embryogenesis and homeostasis. Despite their biological significance, characteristics of Wnt proteins still remain unclear, mainly due to their insolubility after the removal of serum. Here we examine Wnt proteins in serum-containing media by using analytical ultracentrifugation with a fluorescence detection system.

Omental abscess due to a spilled gallstone after laparoscopic cholecystectomy.

Omental abscess due to a spilled gallstone is extremely rare after laparoscopic cholecystectomy. Herein, we report a 68-year-old man who presented with left upper abdominal pain after laparoscopic cholecystectomy for gangrenous cholecystitis. Seven months prior to admission, gallbladder perforation with spillage of pigment gallstones and bile occurred during laparoscopic cholecystectomy.

Ripply3 is required for the maintenance of epithelial sheets in the morphogenesis of pharyngeal pouches.

During tissue development, the morphogenesis of epithelial sheets is regulated by many factors, including mechanical force, although the underlying mechanisms remain largely unknown. In the pharyngeal region of the vertebrate embryo, endodermal epithelium is reiteratively folded outward to form pharyngeal pouches, making partitions between the pharyngeal arches. Ripply3, encoding a member of the Ripply family of adaptor proteins, is required for the pouch formation posterior to the 2nd pharyngeal pouch.