The C. elegans insulin-like peptides (ILPs)

Insulin and insulin-like peptides (ILPs) are conserved in living organisms to modulate homeostasis by functioning as ligands. For understanding of molecular mechanisms regulated by the ligands, the nematode Caenorhabditis elegans is a good model since: 1) the C. elegans genome size is small with over 40% homology to the human genome, 2) numerous genetic methods are available, and 3) the worms are transparent throughout the life cycle, so that the secretion of peptide hormones can be followed at cellular level in living preparations by GFP-tagged peptides. In this review, we describe the general appearance of the insulin/insulin-like growth factor (IGF)-1 signaling (IIS), and then focus on physiological functions, secretion, and transcriptional regulation of the C. elegans ILPs

Pulse Duration Dependence of Novel Metal Alloying on Fe/Cr/Ni Thin Films by Ultra-Short Pulsed Laser Irradiation

We examined the possibility of suppressing elemental segregation of high-entropy alloys (HEAs) using femtosecond laser irradiation. Thin films of iron (Fe), chromium (Cr), and nickel (Ni) were deposited on the surfaces of n-type SiC and p-type GaN substrates. The thicknesses of the Fe, Cr, and Ni films were 12, 7, and 11 nm, respectively. Laser irradiation was performed from the substrate side by focusing on the interface between the Fe film and substrate. Scanning transmission electron microscopy (STEM) bright-field images superimposed on the elemental maps of Fe, Cr, and Ni showed a more homogenous mixing of Fe, Cr, and Ni in the femtosecond-laser-modified region than in the picosecond-laser-modified region. In particular, the Ni distribution showed a significant improvement in homogeneity. In other words, the Ni mixture was more homogeneous in the femtosecond laser-modified region than in the picosecond laser-modified region. Although the duration of the picosecond laser pulse was sufficiently long for atomic diffusion, segregation still occurred during the cooling process following laser irradiation

A Case of Autoimmune Hepatitis Associated with Idiopathic Thrombocytopenic Purpura and Chronic Thyroiditis

Autoimmune hepatitis (AIH) is frequently associated with extrahepatic autoimmune disorders such as rheumatoid arthritis, Sjogren\u27s syndrome, and chronic thyroiditis, but the association with idiopathic (immune) thrombocytopenic purpura (ITP) is rare. We report a 46-year-old Japanese woman who presented with severe thrombocytopenia, elevated levels of aminotransferases, immunoglobulin (Ig) G, and platelet-associated IgG (PAIgG), positive anti-nuclear antibody, and hypothyroidism. After a diagnosis of coexisting AIH, ITP, and chronic thyroiditis, the patient was treated with 30 mg/day of prednisolone orally. The patient responded to such treatment: showing an increase in the number of platelets and decrease of serum levels of aminotransferases, IgG, and PAIgG to within normal ranges. Discrimination of ITP from liver cirrhosis as a cause of severe thrombocytopenia seen in chronic liver disease is important because complications and therapy are quite different. Prednisolone as a treatment for All should be also effective for ITP, and therefore, ITP should be considered when liver dysfunction is accompanied by severe thrombocytopenia, particularly in the autoimmune types of liver diseases

Stable lines and clones of long-term proliferating normal, genetically unmodified murine common lymphoid progenitors.

Common lymphoid progenitors (CLPs) differentiate to T and B lymphocytes, dendritic cells, natural killer cells, and innate lymphoid cells. Here, we describe culture conditions that, for the first time, allow the establishment of lymphoid-restricted, but uncommitted, long-term proliferating CLP cell lines and clones from a small pool of these cells from normal mouse bone marrow, without any genetic manipulation. Cells from more than half of the cultured CLP clones could be induced to differentiate to T, B, natural killer, dendritic, and myeloid cells in vitro. Cultured, transplanted CLPs transiently populate the host and differentiate to all lymphoid subsets, and to myeloid cells in vivo. This simple method to obtain robust numbers of cultured noncommitted CLPs will allow studies of cell-intrinsic and environmentally controlled lymphoid differentiation programs. If this method can be applied to human CLPs, it will provide new opportunities for cell therapy of patients in need of myeloid-lymphoid reconstitution

Clinicopathological Features and Outcomes of Endoscopic Submucosal Dissection for Superficial Cancer of the Pharynx

The efficacy and safety of endoscopic submucosal dissection (ESD) for superficial cancer of the pharynx are still unclear. To identify clinicopathological features of superficial pharyngeal cancer, and the efficacy and safety of ESD, we retrospectively assessed 70 pharyngeal cancers in 59 patients who underwent ESD. Of these patients, 61.0% and 50.8% had a history of esophageal cancer and head and neck cancer, respectively. The median tumor size was 15 mm, and 75.7% of the lesions were located at the piriform sinus. The en bloc resection rate was 94.9%. Treatment-related adverse events occurred in 8 cases, but there was no treatment-related death. The lateral margin was positive for neoplasm in 3 lesions (4.3%) and inconclusive in 27 lesions (38.6%), but no local recurrence was observed. Cervical lymph node metastasis was observed in 6 patients, and was successfully treated by cervical lymph node dissection. The three-year overall survival rate was 91.5% (95%CI: 76.6-97.3%) and the cause-specific survival rate was 97.6% (95%CI: 84.9-99.7%). In conclusion, ESD for superficial pharyngeal cancer was safe and effective. “Resect and watch” is probably a feasible and rational strategy for treatment of patients with superficial pharyngeal cancer

Difficult Stones in the Common Bile Duct Successfully Treated by Electrohydraulic Lithotripsy using a Double Lumen Balloon Catheter and Rotating Hemostatic Valve under 180 Degree Revolving X-ray System.

The effectiveness of electrohydraulic lithotripsy (EHL) for stones in the common bile duct (CBD) is well established. It is recommended that the procedure is performed under cholangioscopic control for correct positioning of the probe onto the surface of the stones and prevention of complications arising from contact between the tip of the probe and biliary mucosa. However problems are encountered if insertion of the babyscope into the bile duct is not successful particularly in the presence of duct stenosis or technical difficulties, or when the mother-baby system can not be prepared. For the latter reason, large difficult stones in the CBD were treated by EHL using a double lumen balloon catheter and rotating hemostatic valve (EHLB) under 180 degree revolving X-ray system. The tip of the EHL probe was placed at 2-3 mm out of the balloon catheter, which was used to avoid contact between the tip of the probe and mucosa of the CBD under fluoroscopic control. Rotating hemostatic valve was used to allow examination of the effect of EHL without changing the catheter or pulling out the probe during operation. After endoscopic sphincterotomy, the device was delivered close to the surface of the stone under fluoroscopic guidance. After inflation of the balloon, we confirmed that the tip of the device was set at almost the center of the CBD by 180 degree revolving X-ray system. Partial fragmentation and complete removal of the stones was achieved by combined treatment including EHLB, basket or balloon catheter for stone extraction. There were no serious procedure-related complications

The iron chelator deferasirox induces apoptosis by targeting oncogenic Pyk2/β-catenin signaling in human multiple myeloma

Deregulated iron metabolism underlies the pathogenesis of many human cancers. Recently, low expression of ferroportin, which is the only identified non-heme iron exporter, has been associated with significantly reduced overall survival in multiple myeloma (MM); however, the altered iron metabolism in MM biology remains unclear. In this study we demonstrated, by live cell imaging, that MM cells have increased intracellular iron levels as compared with normal cells. In experiments to test the effect of iron chelation on the growth of MM cells, we found that deferasirox (DFX), an oral iron chelator used to treat iron overload in clinical practice, inhibits MM cell growth both in vivo and in vitro. Mechanistically, DFX was found to induce apoptosis of MM cells via the inhibition of proline-rich tyrosine kinase 2 (Pyk2), which is known to promote tumor growth in MM. Inhibition of Pyk2 is caused by the suppression of reactive oxygen species, and leads to downregulation of the Wnt/β-catenin signaling pathway. Taken together, our findings indicate that high levels of intracellular iron, which might be due to low ferroportin expression, play a role in MM pathophysiology. Therefore, DFX may provide a therapeutic option for MM that is driven by deregulated iron homeostasis and/or Pyk2/Wnt signaling

The <em>C. elegans</em> insulin-like peptides (ILPs)

Insulin and insulin-like peptides (ILPs) are conserved in living organisms to modulate homeostasis by functioning as ligands. For understanding of molecular mechanisms regulated by the ligands, the nematode Caenorhabditis elegans is a good model since: 1) the C. elegans genome size is small with over 40% homology to the human genome, 2) numerous genetic methods are available, and 3) the worms are transparent throughout the life cycle, so that the secretion of peptide hormones can be followed at cellular level in living preparations by GFP-tagged peptides. In this review, we describe the general appearance of the insulin/insulin-like growth factor (IGF)-1 signaling (IIS), and then focus on physiological functions, secretion, and transcriptional regulation of the C. elegans ILPs