Anti-proliferative and anti-migratory properties of coffee diterpenes kahweol acetate and cafestol in human renal cancer cells

13301甲第5262号博士（医学）金沢大学博士論文本文Full 以下に掲載：Scientific Reports 11(1) pp.675 2021. Nature Research. 共著者：牧野 友幸, 泉 浩二, 平塚 薫, 加納 洋, 島田 貴史, 中野 泰斗, 門本 卓, 内藤 伶奈人, 岩本 大旭, 八重樫 洋, 重原 一慶, 角野 佳史, 仲田 浩規, 齋藤 洋平, 後藤 享子, 坂井 宣彦, 岩田 恭宜, 和田 隆志, 溝上

Morphological Changes and Durability of Skin and Mucosal Flaps in Intraoral and Pharyngeal Reconstructions: Long-term Follow-up and Literature Review for Potential Second Carcinomas

The long-term changes in tissues implanted in the oral cavity and pharynx after head and neck reconstruction have not been fully evaluated. This study aimed to clarify the morphological changes, long-term durability, and potential for secondary carcinogenesis in such tissues. In our single-center study, the rough morphological changes in 54 cases of intraoral and pharyngeal skin and mucosal flaps were evaluated more than 10 years after flap transfer. In addition, the literature on the development of second carcinomas from skin flaps was reviewed. The mean follow-up period for transferred flaps was 148 months. The reconstruction areas and the probability of morphological changes were significantly correlated (p=0.006), especially in cases with tongue, lower gingiva, and buccal mucosal reconstruction. Free jejunal flap surfaces were well maintained, whereas tubed skin flaps showed severe morphological changes in cases with pharyngeal reconstruction. None of the flaps in our series developed second primary carcinomas. Skin flaps generally had good durability for > 10 years in intraoral environments, while mucosal flaps had better durability for pharyngeal reconstruction. Second squamous carcinomas arising from skin flaps are extremely rare; however, surgeons should take this possibility into consideration and conduct meticulous and long-term follow-up

Radioligand Assay-Based Detection of Antibodies against SARS-CoV-2 in Hospital Workers Treating Patients with Severe COVID-19 in Japan.

This study aimed to clarify whether infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is prevalent among the staff of a hospital providing treatment to patients with severe coronavirus disease 2019 (COVID-19) using radioligand assay (RLA). One thousand samples from the staff of a general hospital providing treatment to patients with severe COVID-19 were assayed for SARS-CoV-2 nucleocapsid protein (N) IgG using RLA. Nine patients with COVID-19 who had been treated in inpatient settings and had already recovered were used as control subjects, and 186 blood donor samples obtained more than 10 years ago were used as negative controls. Four of the 1000 samples showed apparently positive results, and approximately 10 or more samples showed slightly high counts. Interestingly, a few among the blood donor samples also showed slightly high values. To validate the results, antibody examinations using ELISA and neutralizing antibody tests were performed on 21 samples, and chemiluminescence immunoassay (CLIA) was performed on 201 samples, both resulting in a very high correlation. One blood donor sample showed slightly positive results in both RLA and CLIA, suggesting a cross-reaction. This study showed that five months after the pandemic began in Japan, the staff of a general hospital with a tertiary emergency medical facility had an extremely low seroprevalence of the antibodies against SARS-CoV-2. Further investigation will be needed to determine whether the slightly high results were due to cross-reactions or a low titer of anti-SARS-CoV-2 antibodies. The quantitative RLA was considered sensitive enough to detect low titers of antibodies

Immunobiotic Lactobacillus jensenii as immune-health promoting factor to improve growth performance and productivity in post-weaning pigs

Background: Immunoregulatory probiotics (immunobiotics) have been proposed to improve piglets' immune system to avoid intestinal infections and reduce unproductive inflammation after weaning. Previously, it was demonstrated that Lactobacillus jensenii TL2937 (LjTL2937) attenuated the inflammatory response triggered by activation of Toll-like receptor 4 (TLR-4) in porcine intestinal epithelial (PIE) cells and antigen presenting cells (APCs) from porcine Peyer's patches (PP).Objective: In view of the critical importance of PIE-APCs interactions in the regulation of intestinal immune responses, we aimed to examine the effect of LjTL2937 on activation patterns of APCs from swine PPs in co-cultures with PIE cells. In addition, we investigated whether LjTL2937 was able to beneficially modulate intestinal immunity of piglets after weaning to improve immune-health status.Results: Stimulation of PIE-APCs co-cultures with LjTL2937 increased the expression of MHC-II, CD80/86, IL-10, and Bcl-3 in CD172a+CD11R1- and CD172a+CD11R1high APCs. In addition, the TL2937 strain caused the upregulation of three negative regulators of TLR4 in PIE cells: MKP-1, Bcl-3 and A20. These changes significantly reduced the inflammatory response triggered by TLR4 activation in PIE-APCs co-cultures. The in vivo experiments using castrated male piglets (crossbreeding (LWD) with Landrace (L), Large Yorkshire (W) and Duroc (D))of 3 weeks of age demonstrated that feeding with LjTL2937 significantly reduced blood complement activity and C reactive protein concentrations while no changes were observed in blood leukocytes, ratio of granulocytes to lymphocyte numbers, macrophages' activity and antibody levels. In addition, treatment with LjTL2937 significantly improved growth performance and productivity, and increased carcass quality.Conclusions: We demonstrated that the use of immunobiotics strains like LjTL2937, as supplemental additives for piglets feedings, could be used as a strategy to maintain and improve intestinal homeostasis; that is important for the development of the pig and for health and performance throughout the productive life of the animal.Fil: Suda, Yoshihito. Miyagi University. Department of Food, Agriculture and Environment; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Takahashi, Yu. Miyagi University. Department of Food, Agriculture and Environment; JapónFil: Hosoya, Shoichi. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; JapónFil: Tomosada, Yohsuke. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; JapónFil: Tsukida, Kohichiro. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; JapónFil: Shimazu, Tomoyuki. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Breading and Genetics ; JapónFil: Aso, Hisashi. Tohoku University. Graduate School of Agricultural Science. Cell Biology Laboratory; JapónFil: Tohno, Masanori. National Institute of Livestock and Grassland Science; JapónFil: Ishida, Mitsuharu. Miyagi University. Department of Food, Agriculture and Environment; JapónFil: Makino, Seiya. No especifíca;Fil: Ikegami, Shuji. No especifíca;Fil: Kitazawa, Haruki. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japó

Ultra-high-molecular-weight Polyethylene (UHMWPE) Wing Method for Strong Cranioplasty

We developed a new cranioplasty method that utilizes artificial bone made of ultra-high-molecular-weight polyethylene, with a wedge-shaped edge (UHMWPE Wing). This study shows the methods and data of case series and finite element analyses with the UHMWPE Wing. A circumferential wing was preoperatively designed for a custom-made artificial bone made of UHMWPE to achieve high fixed power and to minimize the usage of cranial implants. Here, we present 4 years of follow-up data and finite element analyses for patients treated with the UHMWPE Wing between February 2015 and February 2019. Eighteen consecutive patients underwent cranioplasty using our UHMWPE Wing design. There were no postoperative adverse events in 17 of the patients for at least 18 months. One case of hydrocephalus experienced screw loosening and graft uplift due to shunt malfunction. Placement of a ventriculo-peritoneal shunt immediately returned the artificial bone to normal position. Finite element analyses revealed that a model using the UHMWPE Wing had the highest withstand load and lowest deformation. This is the first report on the UHMWPE Wing method. This method may enable clinicians to minimize dead space and achieve high strength in cranioplasty

Biochar enriched compost elevates mungbean (Vigna radiata L.) yield under different salt stresses

Context: Organic amendments including biochar can improve crop production under salt stress. However, it is still not clear whether biochar enriched compost would enhance legume performance under salt stress after fresh application and in succeeding crops. Aim: The aim of the study was to examine the effect of biochar enriched compost in reducing the salinity stress after fresh application at increasing rates and in the succeeding crop. Methods: In a pot trial, biochar–compost was applied at four different rates (0, 1, 2, and 3%) while mungbean was grown under five different salt stress conditions (0, 2, 4, 8, and 12 dS m−1). In the field trial, the residual effect of different organic amendments (control, compost, cow urine, compost with cow urine, biochar–compost, and biochar–compost with cow urine) was evaluated under three different salt stress conditions (0, 3, and 6 dS m−1). Soil properties, plant performance, and nutrient uptake were determined. Key Results: Results revealed a significant biochar × salt treatment interaction in our pot culture. Biochar–compost application can minimise salt effects at a higher application rate resulting in better plant performance; however, these effects are minimal when salt was added at higher rates. We also observed a significant residual effect of biochar compost on biomass production (51.03%), seed yield (79.48%), and K+ uptake (77.95%) than the control treatment. We believe that biochar–compost buffered Na+ while improved plant water, and nutrient availability and uptake. In addition, biochar–compost might have increased nitrogen acquisition through enhanced biological nitrogen fixation. Conclusions: Biochar enriched compost enhances the yield of legume grown under salt stress. Implications: Our results suggest that biochar–compost can be one of the sustainable means for alleviating soil salinity

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

Sulfate adsorption on a volcanic ash soil (allophanic Andisol) under low pH conditions

The mechanisms of SO4 adsorption on clays have been investigated by many researchers. However, few researches have focused on the fraction of SO4 that is adsorbed in the diffuse layer to the total adsorbed SO4. We investigated SO4 adsorption in detail on an allophanic Andisol (volcanic ash soil.), especially the fraction of SO4 adsorbed in the diffuse layer to the total adsorbed SO4, conducting experiments under conditions of low pH (pH 3.3 and 4.3) and low ion concentrations (1.0 and 0.1 molc m^[-3]) to avoid a strong negative surface charge of the soil particles. SO4 and NO3 adsorption under their competitive conditions were measured by a batch method using mixtures of HNO3 and H2SO4. Exchangeable SO4 and NO3 were extracted with 1000 molc m^[-3] KCI. Strongly adsorbed SO4 was extracted with 10 molc m^[-3] NaOH after the extraction with 1000 molc m^[-3] KCI. The exchangeable SO4 made up to 72 to 77% of the total adsorbed SO4. These results suggested that both inner-sphere and outer-sphere complexes co-exist in the allophanic Andisol at low pH. SO4 was strongly selective over NO3 under these conditions. We compared adsorbed amounts calculated by the Gouy-Chapman model with the measured values at solution conditions of pH 3.3 and 1.0 molc m^[-3]. The model overestimated NO3 adsorption and underestimated SO4 adsorption. The difference is due to the fact that SO4 adsorption in the Stern layer is neglected. Next, we calculated SO4 adsorbed in the diffuse layer using the Stern-Gouy-Chapman model under the assumption that all the measured NO3 adsorbed was in the diffuse layer. Our results indicated that the SO4 in the diffuse layer made up only less than 6% of the total adsorbed SO4. Most of the adsorbed SO4 is likely to be found in direct contact with the soil surface