Microcirculation changes in gingival tissue after ultrasonic tooth preparation in beagle dog

Abstract: Ultrasonic wave technology is widely used during dental treatments. We previously demonstrated that this method protects the gingival tissue. However, the physiological change on the gingival microvasculature caused by this method remains unclear. Objective: The aim of this study was to investigate the relationship between the morphological and physiological effects on gingival microcirculation when preparing teeth, using the conventional dental turbine or ultrasonic method. Methodology: The lower premolar teeth of beagle dogs were prepared along the gingival margin by using a dental turbine or ultrasonic wave instrument. Gingival vasculature changes were investigated using scanning electron microscopy for corrosion resin casts. Gingival blood flow at the preparation site was determined simultaneously by laser Doppler flowmetry. These assessments were performed immediately (Day 0), at 7 days and 30 days after tooth preparation. Results: At day 0, in the turbine group, blood vessels were destroyed and some resin leaked. Furthermore, gingival blood flow at the site was significantly increased. In contrast, the ultrasonic group demonstrated nearly normal vasculature and gingival blood flow similar to the non-prepared group for 30 days after preparation. No significant alterations occurred in gingival circulation 30 days after either preparation; however, the turbine group revealed obvious morphological changes. Conclusions: Based on multiple approach analyses, this study demonstrated that ultrasonic waves are useful for microvascular protection in tooth preparation. Compared with a dental turbine, ultrasonic wave instruments caused minimal damage to gingival microcirculation. Tooth preparation using ultrasonic wave instruments could be valuable for protecting periodontal tissue

PPAR beta/delta activation of CD300a controls intestinal immunity

Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPAR beta/delta (peroxisome proliferator-activated receptor beta/delta) directly regulates CD300a in macrophages that express the immunoreceptor tyrosine based-inhibitory motif (ITIM)-containing receptor. In mice lacking CD300a, high-fat diet (HFD) causes chronic intestinal inflammation with low numbers of intestinal lymph capillaries and dramatically expanded mesenteric lymph nodes. As a result, these mice exhibit triglyceride malabsorption and reduced body weight gain on HFD. Peritoneal macrophages from Cd300a(-/-) mice on HFD are classically M1 activated. Activation of toll-like receptor 4 (TLR4)/MyD88 signaling by lipopolysaccharide (LPS) results in prolonged IL-6 secretion in Cd300a(-/-) macrophages. Bone marrow transplantation confirmed that the phenotype originates from CD300a deficiency in leucocytes. These results identify CD300a-mediated inhibitory signaling in macrophages as a critical regulator of intestinal immune homeostasis

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

生活習慣病にみられる微小血管変化に関するSEM研究

自然発症2型糖尿病モデルラットを用いて、生活習慣病において全身や口腔の器官にみられる微小循環について形態学的な検討を行った。本糖尿病ラットと対照とした通常ラットの上行大動脈に樹脂を注入し、腎、網膜、舌、口蓋、歯肉、骨髄の腐食血管鋳型を作製した。これらを走査型電子顕微鏡にて観察し、糖尿病モデルと対照とで比較検討した。その結果、歯肉組織中の微小循環系の形態については糖尿病モデルと対照とで明瞭な差異はほとんど認められなかったものの、その他の器官では微小循環系の形態に明らかな違いが観察された。糖尿病によって、全身の器官のみならず口腔の器官にも微小循環系に大きな損傷が生じることが明らかになった。自然発症2型糖尿病モデルラットを用いて、生活習慣病において全身や口腔の器官にみられる微小循環について形態学的な検討を行った。本糖尿病ラットと対照とした通常ラットの上行大動脈に樹脂を注入し、腎、網膜、舌、口蓋、歯肉、骨髄の腐食血管鋳型を作製した。これらを走査型電子顕微鏡にて観察し、糖尿病モデルと対照とで比較検討した。その結果、歯肉組織中の微小循環系の形態については糖尿病モデルと対照とで明瞭な差異はほとんど認められなかったものの、その他の器官では微小循環系の形態に明らかな違いが観察された。糖尿病によって、全身の器官のみならず口腔の器官にも微小循環系に大きな損傷が生じることが明らかになった

Alteration of the redox state with reactive oxygen species for 5-fluorouracil-induced oral mucositis in hamsters.

Oral mucositis is often induced in patients receiving cancer chemotherapy treatment. It has been reported that oral mucositis can reduce quality of life, as well as increasing the incidence of mortality. The participation of reactive oxygen species (ROS) in the pathogenesis of oral mucositis is well known, but no report has actually demonstrated the presence of ROS. Thus, the purpose of this study was thus to demonstrate the involvement of ROS and the alteration of the redox state in oral mucositis using an in vivo L-band electron spin resonance (ESR) technique. An oral mucositis animal model induced by treatment of 5-fluorouracil with 10% acetic acid in hamster cheek pouch was used. Lipid peroxidation was measured as the level of malondialdehyde determined by the thiobarbituric acid reaction. The rate constants of the signal decay of nitroxyl compounds using in vivo L-band ESR were calculated from the signal decay curves. Firstly, we established the oral mucositis animal model induced by treatment of 5-fluorouracil with acetic acid in hamster cheek pouch. An increased level of lipid peroxidation in oral mucositis was found by measuring malondialdehyde using isolated hamster cheek pouch ulcer. In addition, as a result of in vivo L-band ESR measurements using our model animals, the decay rate constants of carbamoyl-PROXYL, which is a reagent for detecting the redox balance in tissue, were decreased. These results suggest that a redox imbalance might occur by excessive generation of ROS at an early stage of oral mucositis and the consumption of large quantities of antioxidants including glutathione in the locality of oral mucositis. These findings support the presence of ROS involved in the pathogenesis of oral mucositis with anti-cancer therapy, and is useful for the development of novel therapies drugs for oral mucositis