52 research outputs found
"Erwachsenenbildung bisher nur gedanklich verankert": Ergebnisse einer Befragung von Weiterbildungsverbänden zum DQR
Abstract Background Molecular biomarkers capable of predicting recurrence patterns and prognosis are helpful for risk stratification and providing appropriate treatment to patients with hepatocellular carcinoma (HCC). In this study, we focused on G protein-coupled receptor 155 (GPR155), a cell surface signaling protein, as a candidate biomarker. Methods We analyzed GPR155 expression, DNA methylation, and copy number in HCC cell lines. The clinical significance of GPR155 expression was evaluated using 144 pairs of surgically resected liver and normal tissues with subgroup analysis based on hepatitis virus infection. Results GPR155 mRNA expression levels were differential and were decreased in 89% of HCC cell lines. No DNA methylation was detected, whereas copy number alterations were present in five (56%) HCC cell lines. GPR155 mRNA expression level was independent of background liver status and significantly lower in HCC tissues than corresponding normal liver tissues. The expression patterns of GPR155 protein by immunohistochemical staining were significantly associated with those of GPR155 mRNA. Downregulation of GPR155 was significantly associated with more aggressive HCC phenotypes including high preoperative α-fetoprotein, poor differentiation, serosal infiltration, vascular invasion, and advanced disease stage. Patients with downregulation of GPR155 were more likely to have worse prognosis after curative resection irrespective of hepatitis virus infection. Patients who experienced extrahepatic (distant) recurrences had significantly lower GPR155 expression than those with intrahepatic (liver confined) recurrences. Conclusions Downregulation of GPR155 may serve as a prognosticator that also predicts initial recurrence sites independent of hepatitis virus infection
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
Emerging evidence of molecular biomarkers in hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the third
most common cause of cancer-related death worldwide.
Patients with HCC generally present at an advanced
stage resulting in death within 6-20 months. Therefore,
novel treatment modalities and sensitive prognostic
markers that can decrease the mortality rate of HCC are
required. HCC is a complex and heterogeneous tumor
with multiple genetic aberrations. It has been well
described that accumulation of genetic and epigenetic
changes leads to the clonal selection of cancer cells
harboring aggressive tumor behavior. Aberrant
expression of cancer-related genes is one of the
hallmarks of cancer cells and plays a role in
hepatocarcinogenesis. Epigenetic alterations, such as the
alteration of DNA methylation and histone modification
in cancer cells, can also induce the activation and
inactivation of cancer-related genes. Studies have shed
light on the link between HCC-related genes and
molecules, and a better understanding of the mechanisms
of HCC pathogenesis could be translated into clinical
biomarker tools. Moreover, analyses of genetic and
epigenetic alterations have identified potential
biomarkers that might be targeted therapeutically. In this
review, we update the current knowledge of biomarkers
in HCC, examine recently published literature, and
introduce some representative molecules in each
category
Expression of sushi domain containing two reflects the malignant potential of gastric cancer
Anomalous Temperature Behavior of Lamellar Microdomain Structures in Binary Blends of Polystyrene- block
Protective effect of taurine on mucosal ulcerogenic responses induced by exogenous and endogenous monochloramine in rat stomachs
NONLINEAR DYNAMICS ON PARAMETRIC ROLL RESONANCE WITH REALISTIC NUMERICAL MODELLING
Abstract This paper describes latest collaborative researches between Japan and the UK on parametric roll resonance of a container ship in following and head seas with realistic modelling of restoring moment as a nonlinear function of wave steepness in experimental, geometrical and analytical approaches. Firstly, captive model experiments were conducted, and demonstrated that the Froude-Krylov prediction could overestimate the amplitude of its variation. Secondly, Poincare mapping technique applied to the numerical model with measured time-varying restoring moment was used for tracing stable steady states, and revealed symmetry-breaking, period-doubling, chaos and capsizing associated with parametric roll resonance. Thirdly, an averaging method was applied to the same numerical model, and confirmed good agreement with the Poincare mapping as well as subcritical bifurcation. Finally, by utilising the present numerical model and methodology, it is shown that a requirement of higher metacentric height does not always improve safety for capsizing associated with parametric roll resonance
Polaprezinc exerts a salutary effect on the impaired helaing of acute gastric lesions in diabetic rats
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