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

Production, Absorption, and Blood Flow Dynamics of Short-Chain Fatty Acids Produced by Fermentation in Piglet Hindgut during the Suckling–Weaning Period

Luminal short-chain fatty acids (SCFA) are rapidly absorbed from the intestine and subsequently utilized by the host as substrate for metabolic energy production. In pigs, the energy contribution of SCFA is thought to be 30–76%. However, since absorption and blood flow dynamics of SCFA in pigs, particularly during the suckling–weaning period, remain unclear, we aimed to elucidate these phenomena. Thirty-two piglets were used in the present work. Cecal vein blood and digesta, and portal and abdominal vein blood were sampled from suckling (7-, 14-, 21- and 28-day-old) and weaned (weaning at 21 and 28 days of age) piglets. Four piglets from each group were euthanized. SCFA concentrations in blood samples were analyzed by a highly sensitive gas chromatography-mass spectrometry technique. Age at weaning tended to affect SCFA absorption. For example, acetate and propionate concentrations in the cecal vein tended to be higher in piglets weaned at day 21 than at day 28. SCFA concentrations in the abdominal vein tended to differ from those in other veins. Mucosal gene expression analysis suggested that monocarboxylate transporter 1 and occludin were associated in absorption of SCFA from the lumen into the blood of piglets

Tongue thickness measured by ultrasonography is associated with tongue pressure in the Japanese elderly.

The term "oral frailty" reflects the fact that oral health is associated with physical frailty and mortality. The gold standard methods for evaluating the swallowing function have several problems, including the need for specialized equipment, the risk of radiation exposure and aspiration, and general physicians not possessing the requisite training to perform the examination. Hence, several simple and non-invasive techniques have been developed for evaluating swallowing function, such as those for measuring tongue pressure and tongue thickness. The aim of this study was to investigate the relationship between tongue thickness ultrasonography and tongue pressure in the Japanese elderly. We evaluated 254 elderly patients, who underwent tongue ultrasonography and tongue pressure measurement. To determine tongue thickness, we measured the vertical distance from the surface of the mylohyoid muscle to the tongue dorsum using ultrasonography. The results of the analyses revealed that tongue thickness was linearly associated with tongue pressure in both sexes. In male participants, dyslipidemia, lower leg circumference, and tongue pressure were independently and significantly associated with tongue thickness. In female participants, body mass index and tongue pressure were independently and significantly associated with tongue thickness. The optimal cutoff for tongue thickness to predict the tongue pressure of < 20 kPa was 41.3 mm in males, and 39.3 mm in females. In the Japanese elderly, tongue thickness using ultrasonography is associated with tongue pressure. Tongue thickness and tongue pressure, which are sensitive markers for oral frailty, decrease with age. We conclude that tongue ultrasonography provides a less invasive technique for determining tongue thickness and predicts oral frailty for elderly patients

Immunohistochemical analysis of CYP2A6 protein expression in human bladder cancer.

<p>(A) CYP2A6 immunoreactivity in a representative primary bladder tumor containing superficial and invasive lesions. (B and C) CYP2A6 distribution in indicated types of lesions. Images are obtained at low (B) and high (C) magnification. (D) Quantification of CYP2A6 immunoreactivity in primary bladder cancers. Primary bladder tumors (n = 104) were classified into those with superficial papillary lesions (n = 53), invasive aggregated lesions (n = 108), and invasive scattered lesions (n = 132). *p < 0.01 (invasive aggregated versus superficial papillary lesions and invasive scattered versus invasive aggregated lesions; Student’s <i>t</i>-test).</p