Abstract
In this study, we focused on contents described in the ‘Ansei period Komagome Fuji Shrine area map and illustration’. We verified the contents of the ‘Ansei period map’ and considered the ...aspects of gardeners' farmland in this area. Consequently, the following findings were obtained.
(1) Most of the farmers in this area also work as gardeners.
(2) A large number of farmers surnamed “Takagi,” “Utsumi,” and “Shimizu” already owned the lands in several distant places.
(3) From the address on the 1912 cadastral map, many locations matched the houses on the Ansei period map.
In this study, we focused on contents described in the ‘Ansei period Komagome Fuji Shrine area map and illustration'. We verified the contents of the ‘Ansei period map’ and considered the aspects of ...gardeners’ farmland in this area. Consequently, the following findings were obtained.・Most of the farmers in this area were also works as gardeners.・A large number of farmers surname ‘Takagi', 'Utsumi’ and ‘Shimizu’ already owned the lands in several distant places.・From the address on the 1912 land registration map, many locations were matched the houses on the Ansei period map.
The connection between gene regulation and metabolism is an old issue that warrants revisiting in order to understand both normal as well as pathogenic processes in higher eukaryotes. Metabolites ...affect the gene expression by either binding to transcription factors or serving as donors for post-translational modification, such as that involving acetylation and methylation. The focus of this review is heme, a prosthetic group of proteins that includes hemoglobin and cytochromes. Heme has been shown to bind to several transcription factors, including Bach1 and Bach2, in higher eukaryotes. Heme inhibits the transcriptional repressor activity of Bach1, resulting in the derepression of its target genes, such as globin in erythroid cells and heme oxygenase-1 in diverse cell types. Since Bach2 is important for class switch recombination and somatic hypermutation of immunoglobulin genes as well as regulatory and effector T cell differentiation and the macrophage function, the heme-Bach2 axis may regulate the immune response as a signaling cascade. We discuss future issues regarding the topic of the iron/heme-gene regulation network based on current understanding of the heme-Bach axis, including the concept of “iron immunology” as the synthesis of the iron metabolism and the immune response.
Background
We previously showed that fibrinogen is a major determinant of the growth of a murine model of colorectal cancer (CRC).
Objective
Our aim was to define the mechanisms coupling fibrin(ogen) ...to CRC growth.
Results
CRC tumors transplanted into the dorsal subcutis of Fib− mice were less proliferative and demonstrated increased senescence relative to those grown in Fib+ mice. RNA‐seq analyses of Fib+ and Fib− tumors revealed 213 differentially regulated genes. One gene highly upregulated in tumors from Fib− mice was stratifin, encoding 14‐3‐3σ, a master regulator of proliferation/senescence. In a separate cohort, we observed significantly increased protein levels of 14‐3‐3σ and its upstream and downstream targets (i.e., p53 and p21) in tumors from Fib− mice. In vitro analyses demonstrated increased tumor cell proliferation in a fibrin printed three‐dimensional environment compared with controls, suggesting that fibrin(ogen) in the tumor microenvironment promotes tumor growth in this context via a tumor cell intrinsic mechanism. In vivo analyses showed diminished activation of focal adhesion kinase (FAK), a key negative regulator of p53, in Fib− tumors. Furthermore, nuclear magnetic resonance–based metabolomics demonstrated significantly reduced metabolic activity in tumors from Fib− relative to Fib+ mice. Together, these findings suggest that fibrin(ogen)‐mediated engagement of colon cancer cells activates FAK, which inhibits p53 and its downstream targets including 14‐3‐3σ and p21, thereby promoting cellular proliferation and preventing senescence.
Conclusions
These studies suggest that fibrin(ogen) is an important component of the colon cancer microenvironment and may be exploited as a potential therapeutic target.
Gastric cancer incidence and mortality have been decreasing in Japan. These decreases are likely due to a decrease in prevalence of Helicobacter pylori infection. Our aim was to characterize the ...trends in prevalence of H. pylori infection focused on birth‐year. We carried out a cross‐sectional study that included 4285 subjects who were born from 1926 to 1989. We defined H. pylori infection by the serum H. pylori antibody titer. Individuals having H. pylori infection and those with negative H. pylori antibody titer and positive pepsinogen test were defined as high‐risk individuals for gastric cancer. We estimated the birth‐year percent change (BPC) of the prevalence by Joinpoint regression analysis. The prevalence of H. pylori infection among the subjects born from 1927 to 1949 decreased from 54.0% to 42.0% with a BPC of −1.2%. It was followed by a rapid decline in those born between 1949 (42.0%) and 1961 (24.0%) with a BPC of −4.5%, which was followed by those born between 1961 (24.0%) and 1988 (14.0%) with a BPC of −2.1%. The proportion of high‐risk individuals for gastric cancer among the subjects born from 1927 to 1942 decreased from 62.0% to 55.0% with a BPC of −0.8%. A subsequent rapid declining trend was observed in those born between 1942 (55.0%) and 1972 (18.0%) with a BPC of −3.6%, and then it became stable. These remarkable declining trends in the prevalence of H. pylori infection by birth‐year would be useful to predict the future trend in gastric cancer incidence in Japan.
Drastic declining trends in prevalence of Helicobacter pylori infection by birth‐year in a Japanese population in Joinpoint Regression Analysis.
Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding ...butyrate to pregnant mice influences the newborn's susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells.
Second-hand smoke exposure has been associated with poor mental health. However, among Japanese adults, little is known about the association between second-hand smoking and depressive symptoms. We ...examined this association in a cross-sectional study among a Japanese general adult population sample.
Japanese adults were recruited from the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2012 and 2017. Second-hand smoke exposure and smoking status were assessed using a self-administered questionnaire. Based on their frequency of exposure to second-hand smoke, non-smokers and smokers were categorized as "almost never," "sometimes," and "almost every day". Depressive symptoms were defined by a Kessler 6 score ≥5 points. We performed a multivariable Poisson regression analysis to obtain adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for depressive symptoms.
Overall, 5,121 participants (4,547 non-smokers and 574 smokers) were included whose mean age was 63.6 (standard deviation SD, 10.3) years for non-smokers and 59.33 (SD, 10.2) years for smokers. The association between second-hand smoking and depressive symptoms was significant among non-smokers, but not among smokers. Among non-smokers, PRs compared with "almost never" were 1.25 (95% CI, 1.09-1.42) for "sometimes" and 1.41 (95% CI, 1.09-1.84) for "almost every day" (P for trend <0.001); among smokers, PRs compared with "almost never" were 1.30 (95% CI, 0.82-2.06) for "sometimes" and 1.44 (95% CI, 0.90-2.33) for "almost every day" (P for trend = 0.144).
Second-hand smoking and depressive symptoms were associated among non-smokers. Our findings indicate the importance of tobacco smoke control for mental health.
Thyroid dysfunction that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is becoming increasingly recognized. However, only a few reports in Japan have addressed this issue ...to date. In this study, we sought to clarify whether infection with SARS-CoV-2 affected thyroid hormone levels and whether these hormones could be better predictors of prognosis in patients with coronavirus disease 2019 (COVID-19). Accordingly, we retrospectively examined 147 cases wherein thyroid hormones were measured at the time of admission among 848 Japanese patients with COVID-19 admitted to the Hyogo Prefectural Kakogawa Medical Center. All patients underwent thyroid function testing upon hospital admission. More than half (59.1%) of the patients were euthyroid. Twenty-four percent of patients had serum thyroid-stimulating hormone (TSH) levels lower than the reference range with normal serum free thyroxine (fT4) levels, and 3.4% of the patients had low TSH with high fT4 levels. Over 70% of the patients with moderate and severe COVID-19 had low serum free triiodothyronine (fT3) levels. Serum TSH and fT3 levels were inversely correlated with disease severity. The mortality rate in patients with low serum fT3 levels was significantly higher than that in those with normal serum fT3 levels.
Several studies have investigated a possible association between the ABO blood group and the risk of pancreatic cancer (PC), but this association has not been fully evaluated in Asian populations. ...The present study aimed to assess the impact of genotype‐derived ABO blood types, particularly ABO alleles, on the risk of PC in a Japanese population. We conducted a case–control study using 185 PC and 1465 control patients who visited Aichi Cancer Center in Nagoya, Japan. Using rs8176719 as a marker for the O allele, and rs8176746 and rs8176747 for the B allele, all participants’ two ABO alleles were inferred. The impact of ABO blood type on PC risk was examined by multivariate analysis, with adjustment for potential confounders to estimate odds ratios (OR) and 95% confidence intervals (CI). An increased risk of PC was observed with the addition of any non‐O allele (trend P = 0.012). Compared with subjects with the OO genotype, those with AO and BB genotypes had significantly increased OR of 1.67 (CI, 1.08–2.57) and 3.28 (CI, 1.38–7.80), respectively. Consistent with earlier reports showing a higher risk of PC for individuals with the non‐O blood type, the previously reported protective allele (T) for rs505922 was found to be strongly correlated (r2 = 0.96) with the O allele. In conclusion, this case–control study showed a statistically significant association between ABO blood group and PC risk in a Japanese population. Further studies are necessary to define the mechanisms by which the ABO gene or closely linked genetic variants influence PC risk. (Cancer Sci 2011; 102: 1076–1080)
Background: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene–environment interactions in lifestyle-related diseases, including cancers, among the ...Japanese. This report describes the study design and baseline profile of the study participants.Methods: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history and collected peripheral blood samples.Results: The baseline survey included 92,610 adults (mean age: 55.2 standard deviation, 9.4 years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65–69 years for men and 60–64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women.Conclusions: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.
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