Multiple early gastric cancers (EGCs) may develop in 6-14% of patients even after achieving curative endoscopic submucosal dissection (ESD); however, a useful biomarker for predicting recurrence is ...not available. The present study investigated whether the expression of CD44 variant 9 (CD44v9), a functional cancer stem cell marker, in the primary gastric cancer tissue represents an indicator of recurrence.
Eighty-eight patients who underwent ESD for EGC from 2008 to 2010 were enrolled and monitored for recurrence for 3 years. The expression levels of CD44v9 in the tissue of initial EGCs were evaluated by immunohistochemistry, and the recurrence rate was compared between CD44v9-positive and CD44v9-negative groups. The mucin phenotype and expression of microRNA-21 (miR-21) and programmed cell death protein 4 (PDCD4) were also analysed.
The recurrence rate of EGC was significantly higher in the CD44v9-positive group than in the CD44v9-negative group (hazard ratio (HR), 21.8; 95% confidence interval (CI), 5.71-83.1). However, mucin phenotypes and the expression of miR-21 and PDCD4 did not predict recurrence after ESD. Meanwhile, grade of gastric atrophy was also identified as a significant marker of multiple recurrence (HR, 4.95; 95% CI, 1.30-18.8).
CD44 variant 9 expression represents a potential predictive marker for recurrence in EGC.
Epigenetic therapy using DNA methylation inhibitors and histone deacetylase (HDAC) inhibitors has clinical promise for the treatment of human malignancies. To investigate roles of microRNAs (miRNAs) ...on epigenetic therapy of gastric cancer, the miRNA expression profile was analysed in human gastric cancer cells treated with 5-aza-2'-deoxycytidine (5-Aza-CdR) and 4-phenylbutyric acid (PBA). miRNA microarray analysis shows that most of miRNAs activated by 5-Aza-CdR and PBA in gastric cancer cells are located at Alu repeats on chromosome 19. Analyses of chromatin modification show that DNA demethylation and HDAC inhibition at Alu repeats activates silenced miR-512-5p by RNA polymerase II. In addition, activation of miR-512-5p by epigenetic treatment induces suppression of Mcl-1, resulting in apoptosis of gastric cancer cells. These results suggest that chromatin remodeling at Alu repeats plays critical roles in the regulation of miRNA expression and that epigenetic activation of silenced Alu-associated miRNAs could be a novel therapeutic approach for gastric cancer.
Five retrotransposon families of rice (Tos1-Tos5) have been reported previously. Here we report 15 new retrotransposon families of rice (Tos6-Tos20). In contrast to yeast and Drosophila ...retrotransposons, all of the rice retrotransposons examined appear inactive (or almost inactive) under normal growth conditions. Three of the rice retrotransposons (Tos10, Tos17, and Tos19) are activated under tissue culture conditions. The most active one, Tos17, was studied in detail. The copy number of Tos17 increased with prolonged culture period. In all of the plants regenerated from tissue cultures, including transgenic plants, 5 to 30 transposed Tos17 copies were detected. The transcript of Tos17 was only detected under tissue culture conditions, indicating that the transposition of Tos17 is mainly regulated at the transcriptional level. To examine the target-site specificity of Tos17 transposition, sequences flanking transposed Tos17 copies were analyzed. At least four out of eight target sites examined are coding regions. Other target sites may also be in genes because two out of four were transcribed. The regenerated plants with Tos17-insertions in the phytochrome A gene and the S-receptor kinase-related gene were identified. These results indicate that activation of Tos17 is an important cause of tissue culture-induced mutations. Tissue culture-induced activation of Tos17 may be a useful tool for insertional mutagenesis and functional analysis of genes.
Background
Streptozotocin (STZ) is known to induce type I diabetes and the loss of the interstitial cells of Cajal (ICC). However, the regulation of heme oxygenase‐1 (HO‐1) expression, which is ...reported to protect ICC, has not yet been elucidated in this model. The aim of this study was to investigate the alterations of HO‐1 expression and clarify the mechanism of ICC loss in the stomach using the rat model of STZ‐induced diabetes.
Methods
Streptozotocin (65 mg kg−1) was intraperitoneally administered to 8‐week‐old female Wistar rats. Cobalt protoporphyrin (CoPP), an HO‐1 inducer, was administered subcutaneously once a week after the STZ injection. The expressions of HO‐1 and the receptor tyrosine kinase c‐Kit (a marker for ICC) proteins were investigated by western blot analysis and immunofluorescence staining.
Key Results
Expression of c‐Kit, particularly in the gastric antrum, was significantly decreased at 8 weeks, not at 1 week, compared to those of the control group. Significantly increased induction of HO‐1 expression, especially in the gastric corpus but not in the antrum, was observed in the STZ group at 8 weeks after the STZ injection relative to control. CoPP administration significantly up‐regulated HO‐1 expression in the STZ diabetic group and significantly restored the previously reduced ICC in the gastric antrum.
Conclusions & Inferences
Up‐regulation of HO‐1 expression in the STZ diabetic model was limited to the gastric corpus and impaired up‐regulation of HO‐1 expression in the gastric antrum likely induced the disruption of the ICC network.
Background Gastrointestinal tract is one of the most susceptible organ systems to ischaemia. Not only mucosal injury but also alterations of the intestinal motility and loss of interstitial cells of ...Cajal (ICC) have been reported in response to ischaemia and reperfusion (I/R). However, there are few reports on the changes in the gastric motility after gastric I/R. The present study was designed to investigate the alterations in gastric emptying, the ICC and enteric nerves that regulate smooth muscle function in response to gastric I/R.
Methods Seven‐week‐old male Wistar rats were exposed to gastric I/R, and the gastric emptying rates at 12 and 48 h after I/R were evaluated by the phenol red method. Expressions of gene product of c‐kit receptor tyrosine kinase (c‐Kit), a marker of ICC, and of neuronal proteins were also examined.
Key Results Gastric emptying was transiently delayed at 12 h after I/R, but returned to normal by 48 h. Expression of c‐Kit protein as assessed by Western blotting and immunofluorescent staining of the smooth muscle layer, as well as expression of the mRNA of stem cell factor, the ligand for c‐Kit, were reduced at both 12 and 48 h after I/R. The expression of neuronal nitric oxide synthase (nNOS) protein as assessed by Western blotting and immunofluorescent staining was also decreased at 12 h after I/R, but was restored to normal by 48 h.
Conclusions & Inferences Gastric I/R evokes transient gastroparesis with delayed gastric emptying, associated with disruption of the ICC network and nNOS‐positive neurons.
Data-independent acquisition mass spectrometry (DIA-MS) is essential for information-rich spectral annotations in untargeted metabolomics. However, the acquired MS2 spectra are highly complex, posing ...significant annotation challenges. We have developed a correlation-based deconvolution (CorrDec) method that uses ion abundance correlations in multisample studies using DIA-MS as an update of our MS-DIAL software. CorrDec is based on the assumption that peak intensities of precursor and fragment ions correlate across samples and exploits this quantitative information to deconvolute complex DIA spectra. CorrDec clearly improved deconvolution of the original MS-DIAL deconvolution method (MS2Dec) in a dilution series of chemical standards and a 224-sample urinary metabolomics study. The primary advantage of CorrDec over MS2Dec is the ability to discriminate coeluting low-abundance compounds. CorrDec requires the measurement of multiple samples to successfully deconvolute DIA spectra; however, our randomized assessment demonstrated that CorrDec can contribute to studies with as few as 10 unique samples. The presented methodology improves compound annotation and identification in multisample studies and will be useful for applications in large cohort studies.
A highly efficient transformation procedure was developed for Lobelia erinus. Leaf or cotyledon discs were inoculated with Agrobacterium tumefaciens strain EHA105 harboring the binary vector plasmid ...pIG121Hm, which contains a beta-glucuronidase gene with an intron as a reporter gene and both the neomycin phosphotransferase II and hygromycin phosphotransferase genes as selectable markers. The hygromycin-resistant calli produced on the selection medium were transferred to MS medium supplemented with 0.5 mg/l benzyladenine and 0.2 mg/l indole-3-acetic acid for regeneration of adventitious shoots. Transgenic plants were obtained as a result of the high regeneration rate of the transformed calli, which was as high as 83%. In contrast, no transgenic plant was obtained by the procedure of direct shoot formation following inoculation with A. tumefaciens. Transgenic plants flowered 3-4 months after transformation. Integration of the transgenes was detected using PCR and Southern blot analysis, which revealed that one to several copies were integrated into the genomes of the host plants. The transformation frequency at the stage of whole plants was very high-45% per inoculated disc.
The concept of the exposome was introduced over 15 years ago to reflect the important role that the environment exerts on health and disease. While originally viewed as a call-to-arms to develop more ...comprehensive exposure assessment methods applicable at the individual level and throughout the life course, the scope of the exposome has now expanded to include the associated biological response. In order to explore these concepts, a workshop was hosted by the Gunma University Initiative for Advanced Research (GIAR, Japan) to discuss the scope of exposomics from an international and multidisciplinary perspective. This Global Perspective is a summary of the discussions with emphasis on (1) top-down, bottom-up, and functional approaches to exposomics, (2) the need for integration and standardization of LC- and GC-based high-resolution mass spectrometry methods for untargeted exposome analyses, (3) the design of an exposomics study, (4) the requirement for open science workflows including mass spectral libraries and public databases, (5) the necessity for large investments in mass spectrometry infrastructure in order to sequence the exposome, and (6) the role of the exposome in precision medicine and nutrition to create personalized environmental exposure profiles. Recommendations are made on key issues to encourage continued advancement and cooperation in exposomics.
Aims: The mechanism of the host cell invasion of Plesiomonas shigelloides and its capability to induce apoptosis were investigated.
Methods and Results: We performed a time course experiment on the ...bacterial adherence and invasion of the P. shigelloides P‐1 strain into Caco‐2 cells using an invasion assay and flow cytometry. The adherence of P. shigelloides to the Caco‐2 cells was almost completed within 10 min after the infection. Thereafter, P. shigelloides starts internalization within the Caco‐2 cells, which was completed within 60 min after the infection. Based on the invasion assay using nocodazole, cytochalasin D, and genistein, it became clear that the mechanism of the internalization depended on the signal transduction followed by the rearrangement of the cytoskeletal protein. Based on the DNA laddering and TUNEL methods, the cytotoxicity of the Caco‐2 cells by the invasion of P. shigelloides occurred through the induction of apoptosis.
Conclusions: This work demonstrated that the mechanism of invasion of P. shigelloides into Caco‐2 cells and the invasion of P. shigelloides induces apoptotic cell death.
Significance and Impact of the Study: This work revealed the virulence factor, which may be important for understanding of the pathogenesis of P. shigelloides.
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