Dipeptidyl peptidase-4 is highly expressed in bronchial epithelial cells of untreated asthma and it increases cell proliferation along with fibronectin production in airway constitutive cells

DPP4 mRNA showed significant correlation with iNOS mRNA in the freshly isolated BECs from snBA. (PPTX 1447 kb

A Comparison of Magnifying Chromoendoscopy Versus Narrow Band Imaging in the Diagnosis of Depth of Invasion for Early Colorectal Cancers

Although chromoendoscopy and narrow band imaging (NBI) are widely used in diagnosing the invasion depth of colorectal cancers, comparative studies of these modalities are lacking. This meta-analysis compared the performance of these two modalities in colorectal cancer diagnosis. MEDLINE, EMBASE, and Cochrane Library were searched for relevant original articles published up to December 20th, 2010. Major criteria for article inclusion were: (i) magnifying chromoendoscopy or NBI was used as a diagnostic modality and pit pattern or vascular pattern was used as a diagnostic classification; (ii) sensitivity and specificity were reported; (iii) absolute numbers of true-positive, false-positive, true-negative, and false-negative cases, or their equivalent, were provided; and (iv) pathology of biopsy, endoscopy, or surgical treatment was used as the reference standard. Sensitivity and specificity were pooled using a random effects model. Regression analysis was performed to compare the discriminatory power between chromoendoscopy and NBI by including a dummy variable. We made the assumption that a positive regression coefficient implied a better discriminatory power for NBI, and vice versa. Of 1846 screened articles, 16 fulfilled all inclusion criteria. Pooled sensitivity for chromoendoscopy and NBI was 0.85 (95% CI: 0.82-0.87) and 0.80 (0.76-0.85), respectively, and specificity was 0.98 (0.97-0.99) and 0.98 (0.97-0.99), respectively. The regression coefficient for chromoendoscopy versus NBI was -0.02 (95%CI: -1.18-1.71). These results indicate that chromoendoscopy and NBI may have similar power for the diagnostic assessment of colonic neoplasms. However, other factors such as convenience, time, and cost still must be taken into account in making the final diagnostic choice

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

Dihydrotestosterone inhibits tumor necrosis factor alpha induced interleukin-1alpha mRNA expression in rheumatoid fibroblast-like synovial cells.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects multiple synovial joints. Proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF)alpha play important roles as principle inflammatory and destructive components of the disease. RA is known to be associated with significant gender differences in its prevalence and clinical features. We found that a potent androgen, 5alpha-dihydrotestosterone (DHT) inhibits IL-1alpha mRNA expression induced by TNFalpha and the DHT effect was inhibited by an androgen receptor antagonist, hydroxyflutamide (OHF). DHT inhibited the NF-kappaB activation induced by TNFalpha in a manner dependent on the androgen receptor (AR). These results suggest that DHT inhibits the TNFalpha-induced IL-1alpha mRNA expression by inhibiting NF-kappaB activation, and contributes to the gender differences of the disease