Активность

Several gastrointestinal epithelial cells are involved in taste signal transduction. Although rodent tissues are extensively used as a human gut model, recent studies show that the chemical sensing system in rodents differs from that in humans. Nonhuman primates in biomedical research are valuable animal models to advance our understanding of biological responses in humans. The 3D organoid culture produces functional gastrointestinal epithelial cells in vitro and can be generated from animal and human tissues. Here, we report the generation of intestinal chemosensory cells from nonhuman primates, macaques, using an organoid culture system. We were able to maintain macaque intestinal organoids in the proliferation medium for more than six months. Upon switching to differentiation medium, we observed a drastic change in organoid morphology and chemosensory cell marker protein expression. This switch from proliferation to differentiation was confirmed by transcriptome analysis of the duodenum, jejunum, and ileum organoids. We further observed that the supplementation of culture media with interleukin (IL)-4 or the Notch inhibitor dibenzazepine (DBZ) accelerated terminal cell differentiation into chemosensory cells. Overall, we generated monkey intestinal organoids for the first time. Cyclopamine purchase These organoids are suitable for studying the function of primate chemosensory cells.Glioblastoma multiforme (GBM), the most common brain tumor in adults, has an extremely poor prognosis, which is attributed to the aggressive properties of GBM cells, such as dysregulated proliferation and disseminative migration. We recently found that peptide TNIIIA2, derived from tenascin-C (TNC), which is highly expressed in GBM, contributes to the acquisition of these aggressive properties through β1-integrin activation. In general, cancer cells often acquire an additional malignant property that confers resistance to apoptosis due to loss of adhesion to the extracellular matrix, termed anoikis resistance. Our present results show that regulation of β1-integrin activation also plays a key role in both the development and loss of anoikis resistance in GBM cells. Despite being derived from a GBM with an extremely poor prognosis, the human GBM cell line T98G was susceptible to anoikis but became anoikis resistant via treatment with peptide TNIIIA2, which is able to activate β1-integrin. The TNIIIA2-conferred anoikis resistance of T98G cells was disrupted by further addition of peptide FNIII14, which has the ability to inactivate β1-integrin. Moreover, anchorage-independent survival of GBM cells in suspension culture was abrogated by peptide FNIII14, but not by RGD and CS-1 peptides, which are antagonistic for integrins α5β1, αvβ3, and α4β1. These results suggest that GBM cells develop anoikis resistance through activation of β1-integrin by TNC-derived peptide TNIIIA2, which is abundantly released into the tumor microenvironment of GBM. Inactivation of β1-integrin may provide a promising strategy to overcome the apoptosis resistance of cancer cells, including GBM.Upper gastrointestinal (GI) cancers such as oral (OC), esophageal (EC), and gastric (GC) cancers affect the digestive system, with a high mortality rate. Clinical symptoms are, however, not recognizable at early stages, and most patients are diagnosed in advanced stages. Therefore, the mechanism underlying the origin and development of upper GI cancer must be evaluated and also new therapeutic targets and effective methods should be identified and established to control GI cancers. Genome-wide approaches have introduced many long non-coding RNAs (lncRNAs) transcribed in various manners in malignant and normal tissues. It is found that the aberrant expression of specific lncRNAs is closely associated with the diagnosis or prognosis of the patients with upper GI cancers and involved in targeted therapy, which may improve the development of prevention strategies and advanced therapies. lncRNA-associated SNPs show amazing variations in interfering with the lncRNA function of regulating genes which contribute to important signaling pathways and carcinogenesis. Most data on genetic variations in lncRNAs have considered polymorphisms in focal amplifications and regulatory regions, which influence the levels of expression rather than lncRNA functionalities. The present study attempted to summarize lncRNA-related polymorphisms effective in the development of upper GI cancers. It is proposed that the individual and combined genotypes of lncRNA-related polymorphisms may predict cancer risk, and in some cases the clinical and therapeutic outcomes.This study aims to investigate contributing factors to potential collision risks during lane-changing processes from the perspective of vehicle groups and explore the unobserved heterogeneity of individual lane-changing maneuvers. Vehicular trajectory data, extracted from the Federal Highway Administration’s Next Generation Simulation dataset, are utilized and 579 lane-changing vehicle groups are examined. Stopping distance indexes are developed to evaluate the potential collision risks of lane-changing vehicle groups. Three mixed binary logit models and three mixed logit models with heterogeneity in means and variances are established based on different perception reaction time. Model estimation results show that several variables significantly affect the risk status of lane-changing vehicle groups, including the mean values of clearance distance and speed differences between the leading vehicle in the current lane and the subject vehicle, standard deviations of clearance distance, and speed differences between these two vehicles, as well as standard deviations of the speed difference between the subject vehicle and the following vehicle in the target lane. Interestingly, the influences of the last three variables differ considerably across the observations and the mean of the random parameter for standard deviations of clearance distance between CLV and SV is associated with the mean speed difference between CLV and SV. Since one of the explanations is individual heterogeneity, personalized designs for advanced driver assistance system would be an effective measure to reduce the risk.