Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer.

Mucins have been associated with survival in various cancer patients, but there have been no studies of mucins in small bowel carcinoma (SBC). In this study, we investigated the relationships between mucin expression and clinicopathologic factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC lesions compared to the normal epithelium, and expression of these mucins was related to clinicopathologic factors, as follows: MUC1 [tumor location (p = 0.019), depth (p = 0.017) and curability (p = 0.007)], MUC5AC [tumor location (p = 0.063) and lymph node metastasis (p = 0.059)], and MUC16 [venous invasion (p = 0.016) and curability (p = 0.016)]. Analysis of 58 cases with survival data revealed five factors associated with a poor prognosis: poorly-differentiated or neuroendocrine histological type (

Efficacy of Mucosal Cutting Biopsy for the Histopathological Diagnosis of Gastric Submucosal Tumors

Background: Gastrointestinal stromal tumors occur frequently. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is performed commonly for diagnosis. However, the success rate of histological diagnosis is insufficient when the submucosal tumor (SMT) is small. Recently, another technique, mucosal cutting biopsy (MCB) has been reported. The aim of this study is to evaluate the efficacy and safety of MCB. Method: Between January 2012 and August 2018, MCB and EUS-FNA were performed 16 and 31 times for diagnosing gastric SMT. The diagnostic rate, the rate of successful immunohistochemistry, and the safety were reviewed. Difficult locations for EUS-FNA were also evaluated. Results: The mean SMT sizes measured on MCB and EUS-FNA were 21.2 and 36.2 mm. The diagnostic rates of MCB and EUS-FNA were almost the same (88 vs. 81%), but successful immunohistochemistry was significantly higher in the MCB group (93 vs. 59%, p = 0.03). In the subgroup of SMTs < 20 mm, the successful histological diagnosis rate from EUS-FNA was relatively low. There were no complications. Failures of EUS-FNA were more frequent in the middle third of the stomach. Conclusions: MCB was an effective procedure for diagnosing gastric SMT, especially in the case of small SMTs located at the middle third of the stomach

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

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

Estimating postoperative left ventricular volume : Identification of responders to surgical ventricular reconstruction

Objectives: The postoperative left ventricular end-systolic volume index and ejection fraction are benchmarks of surgical ventricular reconstruction but remain unpredictable. This study aimed to identify who could be associated with a higher long-term survival by adding surgical ventricular reconstruction to coronary artery bypass grafting than coronary artery bypass grafting alone (responders to surgical ventricular reconstruction). Methods: The subjects were 293 patients (median age, 63 years; 255 men) who underwent coronary artery bypass grafting for ischemic heart disease with left ventricular dysfunction in 16 cardiovascular centers in Japan. The relationships among surgical ventricular reconstruction, postoperative end-systolic volume index, ejection fraction, and survival were analyzed to identify responders to surgical ventricular reconstruction. Results: Surgical ventricular reconstruction was performed in 165 patients (56%). The end-systolic volume index and ejection fraction significantly improved (end-systolic volume index, 91 to 64 mL/m2; ejection fraction, 28% to 35%) for all patients. The postoperative end-systolic volume index and ejection fraction were estimated, and surgical ventricular reconstruction was found to be significantly associated with both end-systolic volume index (14.5 mL/m2 reduction, P < .001) and ejection fraction (3.1% increase, P = .003). During the median follow-up of 6.8 years, 69 patients (24%) died. Only the postoperative ejection fraction was significantly associated with survival (hazard ratio, 0.925; 95% confidence interval, 0.885-0.968), although this effect was limited to those with postoperative end-systolic volume index of 40 to 80 mL/m2 in the subgroup analysis (hazard ratio, 0.932; 95% confidence interval, 0.894-0.973). Conclusions: Adding surgical ventricular reconstruction to coronary artery bypass grafting could reduce the mortality risk by increasing ejection fraction for those with a postoperative end-systolic volume index within a specific range. The postoperative end-systolic volume index could demarcate responders to surgical ventricular reconstruction, and its estimation can help in surgical decision making

A Ricin B chain-Ribonuclease A Hybrid Protein : A new tool for introduction of a foreign protein into targeted cells

The groESL operon of a halophilic lactic acid bacterium, Tetragenococcus halophila, was cloned and sequenced. The nucleotide sequence of 2,853-bp revealed the presence of two open reading frames corresponding to the groES and groEL genes. The molecular masses of GroES and GroEL proteins were calculated to be 10,153 and 56,893 Da, respectively. They showed high similarities with the corresponding proteins of other lactic acid bacteria such as Lactobacillius zeae. CIRCE （Controlling Inverted Repeat of Chaperone Expression） element was identified in the upstream region of groES. Northern blot hybridization hag demonstrated that the groES and groEL genes are transcribed as a bicistronic mRNA of 2.2 kb, and transcriptionally induced 3.8-fold by heat shock （45 ℃） for 30 min. The amotmt of groESL mRNA was also increased about 4-fold by high NaCl condition. Primer extension analysis indicated that the expression of T. halophila groESL was governed by the constitutive promoter both under normal and stress conditions