The joint impact on being overweight of self reported behaviours of eating quickly and eating until full : cross sectional survey

Objective To examine whether eating until full or eating quickly or combinations of these eating behaviours are associated with being overweight

Dietary fiber intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study

OBJECTIVES: It has been hypothesized that dietary fiber intake has a beneficial impact on prevention of dementia, but the epidemiological evidence is scant. We sought to examine whether dietary fiber intake is inversely associated with risk of dementia requiring care under the national insurance (disabling dementia). METHODS: The study setting was the Circulatory Risk in Communities Study, involving 3739 Japanese individuals aged 40-64 years at the dietary surveys (1985-99). Dietary fiber intake was estimated using the 24-hour dietary recall method. Incident disabling dementia was followed up from 1999 through 2020. Disabling dementia was further classified into that with or without a history of stroke. Hazard ratios of disabling dementia according to quartiles of total, soluble, and insoluble fiber intake were calculated using the Cox proportional hazards model. RESULTS: During a median 19.7-year follow-up, a total of 670 cases of disabling dementia developed. Dietary fiber intake was inversely associated with risk of dementia: the multivariate hazards ratios (95% confidence intervals) were 0.83 (0.67-1.04), 0.81 (0.65-1.02), and 0.74 (0.57-0.96) for individuals with the second, third, and highest quartiles of dietary fiber intake, respectively, as compared with the lowest quartile (P for trend = 0.03). The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke. As for fiber-containing foods, potatoes, but not vegetables or fruits, showed a similar association. CONCLUSIONS: Dietary fiber intake, especially soluble fiber, was inversely associated with risk of disabling dementia in a general Japanese population

Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations

金沢大学医薬保健学総合研究科先進的地域医療研究講座 = Department of Advanced Research in Community MedicineTo clarify the molecular and clinicopathological characteristics of colorectal serrated lesions, we assessed the DNA methylation of cancer-associated genes in a cohort of BRAF-mutant precancerous lesions from 94 individuals. We then compared those results with the lesions’ clinicopathological features, especially colorectal subsites. The lesions included hyperplastic polyps (n = 16), traditional serrated adenomas (TSAs) (n = 15), TSAs with sessile serrated adenomas (SSAs) (n = 6), SSAs (n = 49) and SSAs with dysplasia (n = 16). The prevalence of lesions exhibiting the CpG island methylator phenotype (CIMP) was lower in the sigmoid colon and rectum than in other bowel subsites, including the cecum, ascending, transverse and descending colon. In addition, several cancer-associated genes showed higher methylation levels within lesions in the proximal to sigmoid colon than in the sigmoid colon and rectum. These results indicate that the methylation status of lesions with BRAF mutation is strongly associated with their location, histological findings and neoplastic pathways. By contrast, no difference in aberrant DNA methylation was observed in normal-appearing background colonic mucosa along the bowel subsites, which may indicate the absence of an epigenetic field defect

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature

Brick dust molecules are usually poorly soluble in water and lipoidal components, making it difficult to formulate them in dosage forms that provide efficient pharmacological effects. A co-amorphous system is an effective strategy to resolve these issues. However, their glass transition temperatures (Tg) are relatively lower than those of polymeric amorphous solid dispersions, suggesting the instability of the co-amorphous system. This study aimed to formulate a stable co-amorphous system for brick dust molecules by utilizing sodium taurocholate (NaTC) with a higher Tg. A novel neuropeptide Y5 receptor antagonist (AntiY5R) and NaTC with Tg of 155 °C were used as the brick dust model and coformer, respectively. Ball milling formed a co-amorphous system for AntiY5R and NaTC (AntiY5R-NaTC) at various molar ratios. Deviation from the theoretical Tg value and peak shifts in Fourier-transform infrared spectroscopy indicated intermolecular interactions between AntiY5R and NaTC. AntiY5R-NaTC at equal molar ratios resulting in an 8.5-fold increase in AntiY5R solubility over its crystalline form. The co-amorphous system remained amorphous for 1 month at 25 °C and 40 °C. These results suggest that the co-amorphous system formed by utilizing NaTC as a coformer could stably maintain the amorphous state and enhance the solubility of brick dust molecules