Perspective Chapter: Improving Children’s Foot Health and Shoe Education from the Foot Health Education Project

With the aim of improving the foot health of infants and school-age children, Kinjo University in Japan has established the Foot Health Education Project in 2014, under which university faculty members, students, and industrial organizations have conducted joint activities. The results of surveys on approximately 3000 children to date have shown high prevalence rates of bunionette, undeveloped foot arch, floating toes, and a paucity of wearers of right-size shoes. Under such circumstances, a follow-up survey has been conducted to examine whether changes in foot morphology can be reversed by wearing right-size shoes. The results have suggested that wearing right-size shoes facilitated the development of foot arch and improved floating toes. We plan to continue surveys and share the trends obtained from survey results and possible measures with community residents. In addition, we plan to establish scientific evidence that is useful for education and that contributes to the healthy development of children’s feet

Activity and Durability of Ternary PtRuIr/C for Methanol Electro-oxidation

Carbon supported Pt(1)Ru(1)Ir(x) (0 <= x <= 2) nanoparticles were prepared by it compare nation reductive pyrolysis method and their electrocatalytic activity toward methanol electro-oxidation at 25, 40, and 60 degrees C was investigated. The mass activity (current normalized by the mass of Pt) for methanol electro-oxidation increased as it function of Ir coefficient and cell temperature. Despite the increase in methanol electro-oxidation activity, the addition of Ir does not affect the CO tolerance of the ternary electrocatalyst. The addition of Ir also enhances the durability of the catalyst. The enhancement in activity and durability is discussion based on CO stripping measurements and X-ray photoelectron spectroscopy analysis of the catalysts. (C) 2009 The Electrochemical Society. [DOI: 10.1149/1.3060111] All rights reserved.ArticleJOURNAL OF THE ELECTROCHEMICAL SOCIETY. 156(3):B397-B402 (2009)journal articl

Treatment Response Predictors of Neoadjuvant Therapy for Locally Advanced Gastric Cancer : Current Status and Future Perspectives

Neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) has been recognized as an effective therapeutic option because it is expected to improve the curative resection rate by reducing the tumor size and preventing recurrence of micrometastases. However, for patients resistant to NAC, not only will operation timing be delayed, but they will also suffer from side effects. Thus, it is crucial to develop a comprehensive strategy and select patients sensitive to NAC. However, the therapeutic effect of NAC is unpredictable due to tumor heterogeneity and a lack of predictive biomarkers for guiding the choice of optimal preoperative treatment in clinical practice. This article summarizes the related research progress on predictive biomarkers of NAC for gastric cancer. Among the many investigated biomarkers, metabolic enzymes for cytotoxic agents, nucleotide excision repair, and microsatellite instability, have shown promising results and should be assessed in prospective clinical trials. Noninvasive liquid biopsy detection, including miRNA and exosome detection, is also a promising strategy

Insight into the population dynamics of pathogenic bacteria causing grapevine crown gall in snowfall areas: snow cover protects the proliferation of pathogenic bacteria

Grapevine crown gall (GCG) is a significant bacterial disease caused by tumorigenic Allorhizobium vitis (TAV) and is prevalent worldwide. TAV infects grapevines through wounds such as freezing injuries. Although grapevines typically avoid being wounded under snow cover, GCG occurs in many commercial vineyards in snowy regions. This study investigated the TAV population in GCG gall tissues, grapevine skins, and snow on grapevine skins from six infected vineyards located in Hokkaido, Japan, an area known for heavy snowfall. TAV was isolated not only from gall tissues but also from skins and snow on skins throughout the year. Hierarchical Bayesian model (HBM) analysis revealed that the number of TAV cells in gall tissues was affected by cultivar and low temperature, while those in skins were affected by location and low temperature. Additionally, Bayesian changepoint detection (BCD) showed that the number of TAV cells in gall and skin tissues increased during winter, including the snowfall season. Furthermore, the TAV population in grapevine skins under the snow was significantly higher than those above the snow, indicating that TAV under the snow is protected by the snow and can survive well during the snowfall season. This study highlights the ability of TAV to overwinter on/in galls and skins under the snow and act as inoculum for the next season

Resveratrol inhibits development of colorectal adenoma via suppression of LEF1; comprehensive analysis with connectivity map

Although many chemopreventive studies on colorectal tumors have been reported, no effective and safe preventive agent is currently available. We searched for candidate preventive compounds against colorectal tumor comprehensively from United States Food and Drug Administration (FDA)-approved compounds by using connectivity map (CMAP) analysis coupled with in vitro screening with colorectal adenoma (CRA) patient-derived organoids (PDOs). We generated CRA-specific gene signatures based on the DNA microarray analysis of CRA and normal epithelial specimens, applied them to CMAP analysis with 1309 FDA-approved compounds, and identified 121 candidate compounds that should cancel the gene signatures. We narrowed them down to 15 compounds, and evaluated their inhibitory effects on the growth of CRA-PDOs in vitro. We finally identified resveratrol, one of the polyphenolic phytochemicals, as a compound showing the strongest inhibitory effect on the growth of CRA-PDOs compared with normal epithelial PDOs. When resveratrol was administered to ApcMin/+ mice at 15 or 30 mg/kg, the number of polyps (adenomas) was significantly reduced in both groups compared with control mice. Similarly, the number of polyps (adenomas) was significantly reduced in azoxymethane-injected rats treated with 10 or 100 mg/resveratrol compared with control rats. Microarray analysis of adenomas from resveratrol-treated rats revealed the highest change (downregulation) in expression of LEF1, a key molecule in the Wnt signaling pathway. Treatment with resveratrol significantly downregulated the Wnt-target gene (MYC) in CRA-PDOs. Our data demonstrated that resveratrol can be the most effective compound for chemoprevention of colorectal tumors, the efficacy of which is mediated through suppression of LEF1 expression in the Wnt signaling pathway

Gastric cancer with autoimmune gastritis

Background: Autoimmune gastritis is known to be associated with neoplastic lesions but the relationship between autoimmunity and tumorigenesis have not been sufficiently clarified. The aim of this study is to assess the clinicopathological characteristics of gastric cancer cases associated with autoimmune gastritis. Methods: A total of 24 patients diagnosed as early gastric cancer with autoimmune gastritis were registered. Chart reviews with the data including age, gender, state of Helicobacter pylori infection, comorbidity, and concomitant gastric diseases were conducted. As for the characteristics of gastric cancer, location, size, morphological type, histopathology, invasion depth, and the presence of metachronous or simultaneous lesion were assessed. These data from autoimmune gastritis group were compared with those from 301 patients of early gastric cancer as a control group. Results: The gastric cancer associated with autoimmune gastritis was located in the upper, middle, and lower parts in 28.1%, 53.1%, and 18.8%, respectively. The morphological types are as follows: 0-I, 9.4%; 0-IIa, 28.1%; 0-IIb, 15.6%; 0-IIc, 46.9%; and 0-III, 0.0%. The mean tumor size was 21.8 mm. While 90.6% were confined to the mucosa, 9.4% showed submucosal invasion. The histological classifications are as follows: tub1, 50.0%; tub2, 15.6%; pap, 21.9%; sig, 9.4%; and por, 3.1%. More numbers of female, protruded types, larger tumor size, papillary tumor, and that in the upper location were observed in autoimmune gastritis group compared to control group. Conclusion: Early gastric cancer associated with autoimmune gastritis demonstrated different characteristics from those without autoimmune gastritis including variety of tumor morphologies and histological types with female dominancy

Cancer genome profiling for GI cancers

In Japan, cancer genome profiling (CGP) for cancer patients without standard treatment has been covered by public insurance since June 2019. This study analyzed data of 122 patients with gastrointestinal tumors who underwent CGP to clarify cancer genome medicine’s current status and possible problems at the Tokushima University Hospital. The major types of cancer included pancreatic (n = 30), colorectal (n = 25), biliary tract (n = 15), gastric (n = 11), and hepatocellular carcinoma (n = 8). CGP tests included F1CDx in 70 patients (57%), F1LCDx in 36 (30%), TSO500 in 14 (11%), and NCC Oncopanel in 2 (2%). Actionable gene alterations were identified in 72 patients (59%), but only 5 patients (4%) were treated for pancreatic (n = 1), colorectal (n = 3), and small bowel cancers (n = 1). The main reasons for not receiving genotype-matched therapy included the lack of appropriate drugs or clinical trials that matched the actionable gene alterations (n = 40) and the inability to participate in clinical trials (n = 10). There is still not a sufficient number of patients receiving genotype-matched treatment for gastrointestinal cancers. To promote cancer genome medicine in regional areas, attempts to improve access to genotype-matched therapies are required, as well as to promote the development of new molecular-targeted drugs and clinical trials for these drugs

Comparison of the role of alcohol consumption and qualitative abdominal fat on NAFLD and MAFLD in males and females

The clinical difference between nonalcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) between the two sexes is unclear. This study aimed to determine the influences of alcohol consumption and qualitative abdominal fat between male and female patients with NAFLD and MAFLD. This cross-sectional study examined 11,766 participants who underwent health check-ups comparing lifestyle habits, biochemical features, and noninvasive liver fibrosis scores, between non-MAFLD and MAFLD groups. Furthermore, differences in alcohol consumption and qualitative abdominal fat were examined between male and female patients with NAFLD and MAFLD. The prevalence of metabolic dysregulation, ratio of visceral fat area to subcutaneous fat area, and noninvasive liver fibrosis scores were significantly higher in male patients with MAFLD than in those with NAFLD (p  70 g/week, several noninvasive liver fibrosis scores were significantly higher in the MAFLD group than in the NAFLD group (all p < 0.05). The influences of alcohol consumption and qualitative abdominal fat on NAFLD and MAFLD were different between sexes. The development of liver fibrosis should be considered in male patients with MAFLD who exceed mild drinking

肝細胞癌においてmiR125b-5pはAtaxin1による上皮間葉転換を介してソラフェニブ耐性を示す

The mechanism of resistance to sorafenib in hepatocellular carcinoma (HCC) remains unclear. We analyzed miRNA expression profiles in sorafenib-resistant HCC cell lines (PLC/PRF5-R1/R2) and parental cell lines (PLC/PRF5) to identify the miRNAs responsible for resistance. Drug sensitivity, migration/invasion capabilities, and epithelial-mesenchymal transition (EMT) properties were analyzed by biochemical methods. The clinical relevance of the target genes to survival in HCC patients were assessed using a public database. Four miRNAs were significantly upregulated in PLC/PRF5-R1/-R2 compared with PLC/PRF5. Among them, miR-125b-5p mimic-transfected PLC/PRF5 cells (PLC/PRF5-miR125b) and showed a significantly higher IC50 for sorafenib compared with controls, while the other miRNA mimics did not. PLC/PRF5-miR125b showed lower E-cadherin and higher Snail and vimentin expression—findings similar to those for PLC/PRF5-R2—which suggests the induction of EMT in those cells. PLC/PRF5-miR125b exhibited significantly higher migration and invasion capabilities and induced sorafenib resistance in an in vivo mouse model. Bioinformatic analysis revealed ataxin-1 as a target gene of miR-125b-5p. PLC/PRF5 cells transfected with ataxin-1 siRNA showed a significantly higher IC50, higher migration/invasion capability, higher cancer stem cell population, and an EMT phenotype. Median overall survival in the low-ataxin-1 patient group was significantly shorter than in the high-ataxin-1 group. In conclusion, miR-125b-5p suppressed ataxin-1 and consequently induced Snail-mediated EMT and stemness, leading to a poor prognosis in HCC patients.The mechanism of resistance to multikinase inhibitors in hepatocellular carcinoma (HCC) remains unclear. We analyzed miRNA expression profiles in sorafenib-resistant HCC cell lines (PLC/PRF5-R1/R2) and parental cell lines (PLC/PRF5) to identify the responsible miRNAs and target genes involved in the mechanism of resistance. Four miRNAs were significantly upregulated. Among them, we found that miR-125-5p induced sorafenib resistance in HCC cells and in a mouse model. We also revealed that miR-125-5p suppressed ataxin-1 as a target gene and consequently induced Snail-mediated epithelial-mesenchymal transition (EMT) and cancer stemness. Moreover, we demonstrated that ataxin-1 expression has an impact on the prognosis of patients with HCCs. In the future, by comparing the expression status of miR-125b-5p/ataxin-1 and the effect of sorafenib in the clinical setting, it is expected that miR-125b-5p will be established as an effective drug selection marker for treatment selection in patients with HCC

Sessile serrated adenoma/polyp-cancer sequenceにおいてS100Pは遺伝子脱メチル化により発現し、細胞増殖を促進する

Background/Aims: Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor lesion of colon cancer. Although the relevance of DNA hypermethylation in the SSA/P-cancer sequence is well documented, the role of DNA hypomethylation is unknown. We investigated the biological relevance of DNA hypomethylation in the SSA/P-cancer sequence by using 3-dimensional organoids of SSA/P. Methods: We first analyzed hypomethylated genes using datasets from our previous DNA methylation array analysis on 7 SSA/P and 2 cancer in SSA/P specimens. Expression levels of hypomethylated genes in SSA/P specimens were determined by RT-PCR and immunohistochemistry. We established 3-dimensional SSA/P organoids and performed knockdown experiments using a lentiviral shRNA vector. DNA hypomethylation at CpG sites of the gene was quantitated by MassARRAY analysis. Results: The mean number of hypomethylated genes in SSA/P and cancer in SSA/P was 41.6 ± 27.5 and 214 ± 19.8, respectively, showing a stepwise increment in hypomethylation during the SSA/P-cancer sequence. S100P, S100α2, PKP3, and MUC2 were most commonly hypomethylated in SSA/P specimens. The mRNA and protein expression levels of S100P, S100α2, and MUC2 were significantly elevated in SSA/P compared with normal colon tissues, as revealed by RT-PCR and immunohistochemistry, respectively. Among these, mRNA and protein levels were highest for S100P. Knockdown of the S100P gene using a lentiviral shRNA vector in 3-dimensional SSA/P organoids inhibited cell growth by >50% (p < 0.01). The mean diameter of SSA/P organoids with S100P gene knockdown was significantly smaller compared with control organoids. MassARRAY analysis of DNA hypomethylation in the S100P gene revealed significant hypomethylation at specific CpG sites in intron 1, exon 1, and the 5′-flanking promoter region. Conclusion: These results suggest that DNA hypomethylation, including S100P hypomethylation, is supposedly associated with the SSA/P-cancer sequence. S100P overexpression via DNA hypomethylation plays an important role in promoting cell growth in the SSA/P-cancer sequence