Kumamoto University
  • Kumamoto, Japan
Recent publications
This study focused on resilience and examined the effects of individual differences such as self-regulation and learning style on learning. Resilience and self-regulation have a strong relation. Thus, in this study, the value of self-regulation was used the value of resilience instead. The instructional design method was applied to develop text, interactive, and video teaching materials. The teaching materials were designed to support Japanese driver’s license holders to recognize learning goals and to create opportunities for reflection when learning about automated driving level 3. If the teaching material development method is effective, it is assumed that the low resilience and self-regulation can be compensated. As a result, developing teaching materials that support goal setting and reflection was effective, and this study found that the influence of learning style differs depending on the media used.
Oral microbiota is associated with human diseases including cancer. Emerging evidence suggests that proton pump inhibitors (PPIs), which allow the oral microbiome to translocate into the gut, negatively influence the efficacy of immune checkpoint blockade (ICB) in cancer patients. However, currently there is no effective treatment that restores the decreased efficacy. To address this issue, we retrospectively evaluated 118 advanced or recurrent non-small cell lung cancer (NSCLC) patients treated with ICB and analyzed 80 fecal samples of patients with lung cancer by 16S metagenomic sequencing. Clostridium butyricum therapy using C. butyricum MIYAIRI 588 (CBM588), a live biotherapeutic bacterial strain, was shown to improve the ICB efficacy in lung cancer. Thus, we investigated how CBM588 affects the efficacy of ICB and the gut microbiota of lung cancer patients undergoing PPI treatment. We found that PPI treatment significantly decreased the efficacy of ICB in NSCLC patients, however, CBM588 significantly restored the diminished efficacy of ICB and improved survival. In addition, CBM588 prolonged overall survival in patients receiving PPIs and antibiotics together. The fecal analysis revealed that PPI users had higher abundance of harmful oral-related pathobionts and lower abundance of beneficial gut bacteria for immunotherapy. In contrast, patients who received CBM588 had lesser relative abundance of potentially harmful oral-related bacteria in the gut. Our research suggests that manipulating commensal microbiota by CBM588 may improve the therapeutic efficacy of ICB in cancer patients receiving PPIs, highlighting the potential of oral-related microbiota in the gut as a new therapeutic target for cancer immunotherapy.
Bipolar disorder (BD) is a severe psychiatric disorder characterized by repeated conflicting manic and depressive states. In addition to genetic factors, complex gene–environment interactions, which alter the epigenetic status in the brain, contribute to the etiology and pathophysiology of BD. Here, we performed a promoter-wide DNA methylation analysis of neurons and nonneurons derived from the frontal cortices of mutant Polg1 transgenic (n = 6) and wild-type mice (n = 6). The mutant mice expressed a proofreading-deficient mitochondrial DNA (mtDNA) polymerase under the neuron-specific CamK2a promoter and showed BD-like behavioral abnormalities, such as activity changes and altered circadian rhythms. We identified a total of 469 differentially methylated regions (DMRs), consisting of 267 neuronal and 202 nonneuronal DMRs. Gene ontology analysis of DMR-associated genes showed that cell cycle-, cell division-, and inhibition of peptide activity-related genes were enriched in neurons, whereas synapse- and GABA-related genes were enriched in nonneurons. Among the DMR-associated genes, Trim2 and Lrpprc showed an inverse relationship between DNA methylation and gene expression status. In addition, we observed that mutant Polg1 transgenic mice shared several features of DNA methylation changes in postmortem brains of patients with BD, such as dominant hypomethylation changes in neurons, which include hypomethylation of the molecular motor gene and altered DNA methylation of synapse-related genes in nonneurons. Taken together, the DMRs identified in this study will contribute to understanding the pathophysiology of BD from an epigenetic perspective.
Background Genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to emerge in 2020 and have been spreading globally during the coronavirus disease 2019 (COVID-19) pandemic. Despite the presence of different COVID-19 vaccines, the discovery of effective antiviral therapeutics for the treatment of patients infected with SARS-CoV-2 are still urgently needed. A natural amino acid, 5-aminolevulinic acid (5-ALA), has exhibited both antiviral and anti-inflammatory activities. In a previous study, we demonstrated an in vitro antiviral effect of 5-ALA against SARS-CoV-2 infection without significant cytotoxicity. In the present study, we sought to investigate whether 5-ALA with or without sodium ferrous citrate (SFC) can inhibit in vitro both the original SARS-CoV-2 Wuhan strain and its variants, including the Alpha, Beta, Gamma and Delta strains. Methods The antiviral activity of ALA with or without SFC was determined in Vero-E6 cell. The virus inhibition was quantified by real time RT-PCR. Results Co-administration of 5-ALA and SFC inhibited the Wuhan, Alpha and Delta variants of SARS-CoV-2 with IC 50 values of 235, 173 and 397 µM, respectively, and the Beta and Gamma variants with IC 50 values of 1311 and 1516 µM. Conclusion Our study suggests that 5-ALA with SFC warrants accelerated clinical evaluation as an antiviral drug candidate for treating patients infected with SARS-CoV-2 variants.
We developed a new environment-sensing device based on the opto-ionic-electronic phenomena of an octahedral molybdenum metal (Mo6) cluster. When the Mo6 cluster is electrochemically deposited on a transparent electrode in an organic solvent containing a trace amount of water, the water permeates the deposited film. During the process, some ligand species that stabilize the frame structure of the Mo6 cluster are substituted with hydroxyl groups, and the negatively charged frame structure of the Mo6 cluster unit is stabilized by hydronium counterions. As a result, the transparent film of the Mo6 cluster fabricated by this method exhibits ionic-electronic mixed conduction of the hydronium ion. The ionic conduction greatly changes depending on the temperature and humidity in the atmosphere, and the electrical conductivity greatly changes depending on the wavelength and intensity of the irradiated light. These unique multisensing properties present new possibilities for environmental sensing applications.
Background Brain metastasis of colorectal cancer is infrequent, and isolated brain metastases are more infrequent. Thus, when neurological symptoms, such as paralysis or disturbance of consciousness appear, there is a high probability that the cancer has spread to other organs. Case presentation Here, we present a 64-year-old man with a progressive headache, decreased motivation, and aphasia who was diagnosed with a brain tumor in the left frontal region. He underwent a craniotomy, and the brain tumor was diagnosed as adenocarcinoma. We performed a colonoscopy and diagnosed rectal cancer without other distant metastases. After whole-brain radiotherapy (WBRT), low anterior resection for primary rectal tumor was performed using a robotic system. The patient was discharged in good condition and received postoperative adjuvant therapy for rectal cancer. He showed no signs of recurrence after 1 year of follow-up. Conclusions We described a rare case of rectal cancer that was diagnosed after resection of isolated brain metastasis. A good prognosis was achieved with surgery and WBRT.
Background Shanghai fever is a rare community-acquired enteric illness with sepsis caused by Pseudomonas aeruginosa . Cases of Shanghai fever in pediatric patients have been reported; however, to the best of our knowledge, there are no reports of adult cases. Case presentation A 65-year-old man visited the emergency department with sudden onset of abdominal pain. He was diagnosed as treatment-related myelodysplastic syndrome after treatment of follicular lymphoma. Moderate tenderness in the middle right abdominal quadrants was noted. Computed tomography showed abdominal free air with a small amount of effusion to the surrounding edematous small intestine, and we performed emergency exploration. During operation, we found multiple bowel perforations with patchy necrotic lesions. The patient was admitted to an intensive care unit postoperatively. Blood culture showed Pseudomonas aeruginosa . His condition improved; however, on the 8th postoperative day, the abdominal drain tube showed turbid drainage. We performed re-operation and found anastomotic leakage with two new bowel perforations. After the re-operation, the patient showed signs of septic shock and his general condition got worse, and the patient died due to multiple organ failure on the 12th postoperative day. Conclusion Shanghai fever may occur in an adult patient with neutropenia.
The coronavirus disease 2019 (COVID 19) pandemic continues to pose a threat to global health. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) has spread rapidly worldwide and became dominant in many countries. A natural 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) has demonstrated antiviral activity in Wuhan, Alpha, Beta, Gamma, and Delta variants of SARS-CoV-2 infections in vitro. In this study, we report antiviral activity of 5-ALA, 5-ALA with SFC led to IC 50 of 329 and 765/191, respectively after infection with Omicron variant of SARS-CoV-2 in vitro. Our finding suggests that 5-ALA could be used as antiviral drug candidate to treat Omicron variant infected patients.
Background Gastric cancer is relatively prone to metastasis, although distant metastasis is rare during the early stage of disease. Here we report a rare case of schwannoma-associated Virchow metastasis of a patient with early-stage gastric cancer. Case presentation A 73-year-old man, diagnosed with early-stage gastric cancer, underwent preoperative scrutiny, and was only suspected to have Virchow metastasis. Owing to atypical metastatic findings, a lymph node biopsy was performed to confirm the diagnosis and to determine the treatment strategy. The pathology results of the biopsy showed a diagnosis of schwannoma, the patient was judged to be surgically resectable, and a laparoscopic gastrectomy was performed to achieve a radical resection. The patient is currently under outpatient observation with no apparent recurrence. Conclusion Systemic chemotherapy is generally administered according to the physician’s clinical judgment, although the results of a lymph node biopsy contribute to a more curative treatment. When nonspecific metastases are found, it is important to make a reliable diagnosis and to select a treatment that achieves a cure.
Background Hypoxia and inflammation tumor microenvironment (TME) play a crucial role in tumor development and progression. Although increased understanding of TME contributed to gastric cancer (GC) progression and prognosis, the direct interaction between macrophage and GC cells was not fully understood. Methods Hypoxia and normoxia macrophage microarrays of GEO database was analyzed. The peripheral blood mononuclear cell acquired from the healthy volunteers. The expression of C-X-C Motif Chemokine Ligand 8 ( CXCL8 ) in GC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR), western-blot, Elisa and immunofluorescence. Cell proliferation, migration, and invasion were evaluated by cell counting kit 8 (CCK8), colony formation, real-time imaging of cell migration and transwell. Flow Cytometers was applied to identify the source of cytokines. Luciferase reporter assays and chromatin immunoprecipitation were used to identify the interaction between transcription factor and target gene. Especially, a series of truncated and mutation reporter genes were applied to identify precise binding sites. The corresponding functions were verified in the complementation test and in vivo animal experiment. Results Our results revealed that hypoxia triggered macrophage secreted CXCL8 , which induced GC invasion and proliferation. This macrophage-induced GC progression was CXCL8 activated C-X-C Motif Chemokine Receptor 1/2 ( CXCR1/2 ) on the GC cell membrane subsequently hyperactivated Janus kinase 1/ Signal transducer and activator of transcription 1 ( JAK/STAT1 ) signaling pathway. Then, the transcription factor STAT1 directly led to the overexpression and secretion of Interleukin 10 ( IL-10 ). Correspondingly, IL-10 induced the M2-type polarization of macrophages and continued to increase the expression and secretion of CXCL8 . It suggested a positive feedback loop between macrophage and GC. In clinical GC samples, increased CXCL8 predicted a patient’s pessimistic outcome. Conclusion Our work identified a positive feedback loop governing cancer cells and macrophage in GC that contributed to tumor progression and patient outcome.
Background Placental mesenchymal dysplasia (PMD) is a morphological abnormality resembling partial hydatidiform moles. It is often associated with androgenetic/biparental mosaicism (ABM) and complicated by Beckwith–Wiedemann syndrome (BWS), an imprinting disorder. These phenomena suggest an association between PMD and aberrant genomic imprinting, particularly of CDKN1C and IGF2 . The existence of another type of PMD containing the biparental genome has been reported. However, the frequency and etiology of biparental PMD are not yet fully understood. Results We examined 44 placental specimens from 26 patients with PMD: 19 of these were macroscopically normal and 25 exhibited macroscopic PMD. Genotyping by DNA microarray or short tandem repeat analysis revealed that approximately 35% of the macroscopic PMD specimens could be classified as biparental, while the remainder were ABM. We performed a DNA methylation analysis using bisulfite pyrosequencing of 15 placenta-specific imprinted differentially methylated regions (DMRs) and 36 ubiquitous imprinted DMRs. As expected, most DMRs in the macroscopic PMD specimens with ABM exhibited the paternal epigenotype. Importantly, the biparental macroscopic PMD specimens exhibited frequent aberrant hypomethylation at seven of the placenta-specific DMRs. Allelic expression analysis using single-nucleotide polymorphisms revealed that five imprinted genes associated with these aberrantly hypomethylated DMRs were biallelically expressed. Frequent aberrant hypomethylation was observed at five ubiquitous DMRs, including GRB10 but not ICR2 or ICR1, which regulate the expression of CDKN1C and IGF2 , respectively. Whole-exome sequencing performed on four biparental macroscopic PMD specimens did not reveal any pathological genetic abnormalities. Clinical and molecular analyses of babies born from pregnancies with PMD revealed four cases with BWS, each exhibiting different molecular characteristics, and those between BWS and PMD specimens were not always the same. Conclusion These data clarify the prevalence of biparental PMD and ABM-PMD and strongly implicate hypomethylation of DMRs in the pathogenesis of biparental PMD, particularly placenta-specific DMRs and the ubiquitous GRB10 , but not ICR2 or ICR1. Aberrant hypomethylation of DMRs was partial, indicating that it occurs after fertilization. PMD is an imprinting disorder, and it may be a missing link between imprinting disorders and placental disorders incompatible with life, such as complete hydatidiform moles and partial hydatidiform moles.
Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier : NCT00628745.
TEM in situ straining was applied to an Al bicrystal with a {111}Σ3 grain boundary. The activated slip systems in both grains were determined based on the dislocation line configurations and the crystallographic orientation of the applied load. The resolved shear stress for activation of the dislocation transfer at the GB, τgb, was directly evaluated from the dislocation motion and the simultaneously obtained stress-strain curve. The evaluated τgb value agrees with those obtained in a previous study on macroscopic tensile tests. From the geometry of the dislocation reaction, it was presumed that the pile-up lattice dislocations are dissociated into the lattice dislocations in the adjacent grain and the GB dislocation. It was determined that the activated slip system in the adjacent grain was dominated by local energetic and geometric conditions rather than the global condition such as the combination of Schmid low and applied stress.
The microscopic structure of a new infrared-driven amorphous white-light-generating material was explored by X-ray diffraction, EXAFS and Reverse Monte Carlo simulation. In this material, structural disorder appears to be prerequisite for this nonlinear optical effect. The results are consistent with quantum chemical predictions, but it is also found that the molecular cores are distorted, which is identified as a crystallization inhibitor. Sulfur atoms thereby form a uniform vibrational network, which may be responsible for the high capability of the material to absorb infrared radiation.
In this study, to develop a heat exchanger having small-scale and high performance, the heat transfer performance and the pressure drop in a gas flow are evaluated for six types of unidirectional porous copper tubes fabricated by explosive compaction. Furthermore, correlation equations for the effective heat transfer coefficient and the friction factor are constructed. The maximum enhancement ratio of the effective heat transfer coefficient in the porous copper tubes is four times as high as a swirl tube, which is a typical heat transfer promoter. The performance of these porous tubes becomes high with increasing the Reynolds number based on the superficial velocity. The correlation equation for effective heat transfer coefficient can predict with the error within ±10% regarding 70% of obtained experimental data, that for the friction factor is high accuracy regarding when the number of pores is relatively small and the pore diameter is relatively large.
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1,433 members
Hari Prasad Devkota
  • Graduate School of Pharmaceutical Sciences
Seiji Okada
  • Center for AIDS Research
Toshifumi Mukunoki
  • X-Earth Center, Department of Civil and Environmental Engineering
Toru Takeo
  • Center for Animal Resources and Development
Yuichi Oike
  • Department of Molecular Genetics
2-39-1 Kurokami, 860-8555, Kumamoto, Japan