Association between masticatory ability and oral functions

Mastication is the process of breaking ingested food with the teeth and mixing it with saliva to form a mass that is easy to swallow. However, few studies have reported on oral functions, such as occlusal force, tongue pressure, and mastication. The purpose of this study was to evaluate the association between masticatory function and oral functions, such as occlusal force and tongue pressure. In this study, there were 113 patients (41 men and 72 women; mean age, 68.4 ± 11.3 years) who visited dentists at the Hiroshima University Hospital, Hiroshima, Japan between April 2015 and November 2018. Masticatory function of the patients was evaluated using a masticatory ability test system. In addition, occlusal force was measured using a pressure-sensitive film and the maximum tongue pressure was measured with a tongue pressure measuring device according to a conventional method. The relationship of masticatory ability with occlusal force and tongue pressure was examined using multivariate analysis while considering patients? age, gender, and the number of remaining teeth. Masticatory ability was significantly related to occlusal force, maximum tongue pressure, age, body mass index, the number of remaining teeth, and occlusal contact area (p< 0.05). Multiple regression analysis identified that masticatory ability was significantly associated (p< 0.05) with occlusal force and maximum tongue pressure. Masticatory ability was significantly associated with occlusal force and maximum tongue pressure, indicating that the large muscle mass in the oral cavity is indispensable for improving masticatory function

Multiple hepatic sclerosing hemangioma mimicking metastatic liver tumor successfully treated by laparoscopic surgery: Report of a case

AbstractIntroductionHepatic sclerosing hemangioma is a very rare benign tumor, characterized by fibrosis and hyalinization occurring in association with degeneration of a hepatic cavernous hemangioma. We report here a rare case of multiple hepatic sclerosing hemangioma mimicking metastatic liver tumor that was successfully treated using laparoscopic surgery.Presentation of caseA 67-year-old woman with multiple liver tumors underwent single-incision laparoscopic sigmoidectomy under a diagnosis of advanced sigmoid cancer with multiple liver metastases. Examination of surgical specimens of sigmoid colon revealed moderately differentiated adenocarcinoma invading the serosa, and no lymph node metastases. Serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9 remained within normal limits throughout the course. Two months after sigmoidectomy, the patient underwent laparoscopic partial hepatectomy of S1 and S6 of the liver and cholecystectomy. Histopathological examination showed that the tumors mainly comprised hyalinized tissue and collagen fibers with sporadic vascular spaces on hematoxylin and eosin-stained sections, yielding a diagnosis of multiple hepatic sclerosing hemangioma. No evidence of recurrence has been seen as of 21 months postoperatively.DiscussionDifferentiating multiple sclerosing hemangiomas from metastatic liver tumors was quite difficult because the radiological findings were closely compatible with liver metastases. Laroscopic hepatectomy provided less blood loss, a shorter duration of hospitalization, and good cosmetic results.ConclusionSclerosing hemangioma should be included among the differential diagnoses of multiple liver tumors in patients with colorectal cancer. Laparoscopic hepatectomy is useful for diagnostic therapy for undiagnosed multiple liver tumors

Investigation of the effect of canagliflozin on the disposition index, a marker of pancreatic beta cell function, in patients with type 2 diabetes

This article is published in Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 18 November 2020, Volume 2020:13, Pages 4457-4468

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

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution