Peptide mimetic NC114 induces growth arrest by preventing PKCδ activation and FOXM1 nuclear translocation in colorectal cancer cells.

The peptide mimetic, NC114, is a promising anticancer compound that specifically kills colorectal cancer cells without affecting normal colon epithelial cells. In our previous study, we observed that NC114 inhibited the Wnt/β-catenin pathway, with significant downregulation of both Ser 675-phosphorylated β-catenin and its target genes, cyclin D1 and survivin. However, the molecular mechanism responsible for its cytotoxic effect has not yet been fully characterized.

Microscopic image-based classification of adipocyte differentiation by machine learning.

Adipocyte differentiation is a sequential process involving increased expression of peroxisome proliferator-activated receptor gamma (PPARγ), adipocyte-specific gene expression, and accumulation of lipid droplets in the cytoplasm. Expression of the transcription factors involved is usually detected using canonical biochemical or biomolecular procedures such as Western blotting or qPCR of pooled cell lysates. While this provides a useful average index for adipogenesis for some populations, the precise stage of adipogenesis cannot be distinguished at the single-cell level, because the heterogenous nature of differentiation among cells limits the utility of averaged data.

Microscopic image-based covariation network analysis for actin scaffold-modified insulin signaling.

To infer a "live" protein network in single cells, we developed a novel Protein Localization and Modification-based Covariation Network (PLOM-CON) analysis method using a large set of quantitative data on the abundance (quantity), post-translational modification state (quality), and localization/morphological information of target proteins from microscope immunostained images. The generated network exhibited synchronized time-dependent behaviors of the target proteins to visualize how a live protein network develops or changes in cells under specific experimental conditions. As a proof of concept for PLOM-CON analysis, we applied this method to elucidate the role of actin scaffolds, in which actin fibers and signaling molecules accumulate and form membrane-associated protein condensates, in insulin signaling in rat hepatoma cells.

Establishment and phenotyping of disease model cells created by cell-resealing technique.

Cell-based assays are growing in importance for screening drugs and investigating their mechanisms of action. Most of the assays use so-called "normal" cell strain because it is difficult to produce cell lines in which the disease conditions are reproduced. In this study, we used a cell-resealing technique, which reversibly permeabilizes the plasma membrane, to develop diabetic (Db) model hepatocytes into which cytosol from diabetic mouse liver had been introduced.

L-cysteine reversibly inhibits glucose-induced biphasic insulin secretion and ATP production by inactivating PKM2.

Increase in the concentration of plasma L-cysteine is closely associated with defective insulin secretion from pancreatic β-cells, which results in type 2 diabetes (T2D). In this study, we investigated the effects of prolonged L-cysteine treatment on glucose-stimulated insulin secretion (GSIS) from mouse insulinoma 6 (MIN6) cells and from mouse pancreatic islets, and found that the treatment reversibly inhibited glucose-induced ATP production and resulting GSIS without affecting proinsulin and insulin synthesis. Comprehensive metabolic analyses using capillary electrophoresis time-of-flight mass spectrometry showed that prolonged L-cysteine treatment decreased the levels of pyruvate and its downstream metabolites.

[Ulcerative colitis in remission with cerebral abscess and septic pulmonary emboli: a case report].

A 69-year-old man with a 4-year history of ulcerative colitis (UC) presented at our hospital with high fever, dysarthria, and right hemiparesis. Computed tomography (CT) of the head revealed a low-density area in the left temporal lobe. Chest CT exposed multiple pulmonary nodules in his right lung.

A resealed-cell system for analyzing pathogenic intracellular events: perturbation of endocytic pathways under diabetic conditions.

Cell-based assay systems that can serve as cellular models of aberrant function in pathogenic organs would be novel and useful tools for screening drugs and clarifying the molecular mechanisms of various diseases. We constructed model cells that replicated the conditions in diabetic hepatocytes by using the cell resealing technique, which enables the exchange of cytosol. The plasma membrane of HeLa cells was permeabilized with the streptococcal toxin streptolysin O, and cytosol that had been prepared from wild-type or db/db diabetic mice was introduced into the resulting semi-intact cells.

Molecular size as a limiting characteristic for bioconcentration in fish.

The relationships between the bioconcentration factor (BCF) of chemicals in fish and their size, as characterized by molecular weight (MW), effective cross sectional diameter (Deff), and maximum diameter (Dmax) have been investigated using an experimental data set of 737 new and 441 existing chemicals monitored by the Japanese Chemical Substances Control Law (CSCL). Substances with BCF > or = 5000 (very high bioconcentration potential) typically have MW < 550, Deff < 1.1 nm and Dmax < 2.