Gastroduodenal Mucosal Injury in Patients Taking Low-Dose Aspirin and the Role of Gastric Mucoprotective Drugs: Possible Effect of Rebamipide

The present study was conducted to investigate the prevalence of mucosal injury in patients taking low-dose aspirin in Japan and examine the effect of gastric mucoprotective drugs on aspirin-related gastroduodenal toxicity. We selected 530 patients who had taken low-dose aspirin for 1 month or more after undergoing esophagogastroduodenoscopy from 2005 through 2006 at Teikyo University Hospital, Tokyo, Japan. Endoscopic records were retrospectively reviewed to determine the presence of massive bleeding and mucosal injury (ulcer or erosion). The influence of clinical factors, including co-administration of gastroprotective drugs, was also examined. Hemorrhage was observed in 25 patients (3.7%) and mucosal injury (36.2%) in 192 patients. The presence of Helicobacter pylori antibody was a significant risk factor associated with mucosal injury. Patients taking any gastroprotective drug showed a significantly lower rate of mucosal injury than those not taking these drugs. Patients taking rebamipide concomitantly with proton pump inhibitors or histamine 2 receptor antagonists had mucosal injury less frequently than those taking acid suppressants plus other mucoprotective drugs. In conclusion, these results show the possible gastroprotective effects of rebamipide, suggesting that it may be a good choice in aspirin users with gastroduodenal toxicity that is not suppressed by acid suppressants alone

Self-trapped electrons and holes in PbBr2_2 crystals

We have directly observed self-trapped electrons and holes in PbBr$_{2}$ crystals with electron-spin-resonance (ESR) technique. The self-trapped states are induced below 8 K by two-photon interband excitation with pulsed 120-fs-width laser light at 3.10 eV. Spin-Hamiltonian analyses of the ESR signals have revealed that the self-trapping electron centers are the dimer molecules of Pb$_2$$^{3+}$ along the crystallographic a axis and the self-trapping hole centers are those of Br$_2$$^-$ with two possible configurations in the unit cell of the crystal. Thermal stability of the self-trapped electrons and holes suggests that both of them are related to the blue-green luminescence band at 2.55 eV coming from recombination of spatially separated electron-hole pairs.Comment: 8 pages (7 figures, 2 tables), ReVTEX; revised the text and figures 1, 4, and

Self-trapped states and the related luminescence in PbCl2_2 crystals

We have comprehensively investigated localized states of photoinduced electron-hole pairs with electron-spin-resonance technique and photoluminescence (PL) in a wide temperature range of 5-200 K. At low temperatures below 70 K, holes localize on Pb$^{2+}$ ions and form self-trapping hole centers of Pb$^{3+}$. The holes transfer to other trapping centers above 70 K. On the other hand, electrons localize on two Pb$^{2+}$ ions at higher than 50 K and form self-trapping electron centers of Pb$_2$$^{3+}$. From the thermal stability of the localized states and PL, we clarify that blue-green PL band at 2.50 eV is closely related to the self-trapped holes.Comment: 8 pages (10 figures), ReVTEX; removal of one figure, Fig. 3 in the version

Establishment of a reborn MMV-microarray technology: realization of microbiome analysis and other hitherto inaccessible technologies

BACKGROUND: With the accelerating development of bioscience, the problem of research cost has become important. We previously devised and developed a novel concept microarray with manageable volumes (MMV) using a soft gel. It demonstrated the great potential of the MMV technology with the examples of 1024-parallel-cell culture and PCR experiments. However, its full potential failed to be expressed, owing to the nature of the material used for the MMV chip. RESULTS: In the present study, by developing plastic-based MMVs and associated technologies, we introduced novel technologies such as C2D2P (in which the cells in each well are converted from DNA to protein in 1024-parallel), NGS-non-dependent microbiome analysis, and other powerful applications. CONCLUSIONS: The reborn MMV-microarray technology has proven to be highly efficient and cost-effective (with approximately 100-fold cost reduction) and enables us to realize hitherto unattainable technologies

D3h -Symmetric Porphyrin-Based Rigid Macrocyclic Ligands for Multicofacial Multinuclear Complexes in a One-Nanometer-Sized Cavity.

The one-step synthesis of D3h -symmetric cyclic porphyrin trimers 1 composed of three 2,2\u27-[4,4\u27-bis(methoxycarbonyl)]bipyridyl moieties and three porphyrinatozinc moieties was achieved from a nickel-mediated reductive coupling of meso-5,15-bis(6-chloro-4-methoxycarbonylpyrid-2-yl)porphyrinatozinc. Although cyclic trimers 1 were obtained as a mixture that included other cyclic and acyclic porphyrin oligomers, an extremely specific separation was observed only for cyclic trimers 1 when using columns of silica gel modified with pyrenylethyl, cyanopropyl, and other groups. Structural analysis of cyclic trimers 1 was carried out by means of NMR spectroscopy and X-ray crystallography. Treatment of an η(3) -allylpalladium complex with a cyclic trimer gave a tris(palladium) complex containing three η(3) -allylpalladium groups inside the space, which indicated that the bipyridyl moieties inside the ring could work as bidentate metalloligands.The one-step synthesis of D3h -symmetric cyclic porphyrin trimers 1 composed of three 2,2\u27-[4,4\u27-bis(methoxycarbonyl)]bipyridyl moieties and three porphyrinatozinc moieties was achieved from a nickel-mediated reductive coupling of meso-5,15-bis(6-chloro-4-methoxycarbonylpyrid-2-yl)porphyrinatozinc. Although cyclic trimers 1 were obtained as a mixture that included other cyclic and acyclic porphyrin oligomers, an extremely specific separation was observed only for cyclic trimers 1 when using columns of silica gel modified with pyrenylethyl, cyanopropyl, and other groups. Structural analysis of cyclic trimers 1 was carried out by means of NMR spectroscopy and X-ray crystallography. Treatment of an η(3) -allylpalladium complex with a cyclic trimer gave a tris(palladium) complex containing three η(3) -allylpalladium groups inside the space, which indicated that the bipyridyl moieties inside the ring could work as bidentate metalloligands

Decline in Left Ventricular Ejection Fraction during Follow-up in Patients with Severe Aortic Stenosis

Objectives: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. Background: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. Methods: Among 3, 815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. Results: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p 10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140

White blood cell count and cardiovascular biomarkers of atherosclerosis.

OBJECTIVE: To investigate the association with white blood cells (WBC) and atherosclerotic parameters including cardio-ankle vascular index (CAVI) and carotid intima-media thickness (CIMT) in the general population. METHODS: We investigated the relationship between WBC count and metabolic syndrome components, CAVI and CIMT in 3738 Japanese study participants. RESULTS: WBC count weakly correlated with CAVI in men (beta = 0.61, p = 0.043), but not in women (beta = 0.35, p = 0.17). On the other hand, WBC did not correlate with CIMT in either men or women (p = 0.41 and p = 0.71, respectively). CONCLUSION: WBC count was associated with lipids, blood pressure and body mass index, although the correlations with CAVI and CIMT were weak or absent

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