Physiological effects of natural flagrance of “CEDROL” and cedrol for application to aromatherapy

匂い物質は，嗅覚神経系を介して行動発現や自律神経機能の調節などに関与する神経系（大脳辺縁系および視床下部）を賦活することにより，アロマセラピーの効果発現に関与していることが示唆されている．セドロールは，セダーウッド油から抽出した天然香料であり，セドロールを含むセダーウッドエッセンスはアロマセラピーに用いられていることから，自律神経機能に及ぼす作用が期待される．そこでセドロールを実験的に健常人に上気道から吸入させると，副交感神経の活動が有意に増大し，交感神経系の活動が有意に低下した．さらに，喉頭全摘除術を受けた被験者を用いて，上気道を介さずに下気道からセドロールを直接吸入させると，同様の効果が認められた．以上から，セドロールは嗅覚神経系だけでなく肺の迷走神経系を介して，交感神経系の活動や精神緊張を低下させる作用を有することが示唆された．これらのことは，セドロールがアロマセラピーに有用であることを示唆する．Odor substance is suggested to induce clinical effects of aromatherapy by stimulating the brain areas（limbic system and hypothalamus）involved in emotion and autonomic control through the olfactory system. Effects of pure compound （Cedrol） extracted from cedar wood oil on the cardiovascular system were investigated since cedar wood essence, which includes Cedrol, has been applied to aromatherapy. Vaporized Cedrol were presented to healthy human subjects via a face mask, which decreased sympathetic activity and increased parasympathetic activity. In the subsequent experiment, vaporized Cedrol was directly inhaled through the lower airway from a hole in the trachea of the totally laryngectomized subjects, but not through the upper airway. The experiment using the totally laryngectomized subjects replicated the similar results in healthy subjects who inhaled Cedrol through the nose. These results suggest that Cedrol acts on the peripheral nervous system （vagus nerve） innervating the lower airway and pulmonary system as well as the olfactory system in the upper airway. These results suggest usefulness of Cedrol for aromatherapy

Upregulated Fcrl5 disrupts B cell anergy causes autoimmune disease

B cell anergy plays a critical role in maintaining self-tolerance by inhibiting autoreactive B cell activation to prevent autoimmune diseases. Here, we demonstrated that Fc receptor-like 5 (Fcrl5) upregulation contributes to autoimmune disease pathogenesis by disrupting B cell anergy. Fcrl5—a gene whose homologs are associated with human autoimmune diseases—is highly expressed in age/autoimmunity-associated B cells (ABCs), an autoreactive B cell subset. By generating B cell-specific Fcrl5 transgenic mice, we demonstrated that Fcrl5 overexpression in B cells caused systemic autoimmunity with age. Additionally, Fcrl5 upregulation in B cells exacerbated the systemic lupus erythematosus-like disease model. Furthermore, an increase in Fcrl5 expression broke B cell anergy and facilitated toll-like receptor signaling. Thus, Fcrl5 is a potential regulator of B cell-mediated autoimmunity by regulating B cell anergy. This study provides important insights into the role of Fcrl5 in breaking B cell anergy and its effect on the pathogenesis of autoimmune diseases

Non-restorative Sleep Caused by Autonomic and Electroencephalography Parameter Dysfunction Leads to Subjective Fatigue at Wake Time in Shift Workers

Sleep is a physiological state that plays important role in the recovery of fatigue. However, the relationship between the physiological status of sleep and subjective fatigue remains unknown. In the present study, we hypothesized that the non-recovery of fatigue at wake time due to non-restorative sleep might be ascribed to changes in specific parameters of electroencephalography (EEG) and heart rate variability (HRV) in poor sleepers. Twenty healthy female shift-working nurses participated in the study. Subjective fatigue was assessed using the visual analog scale (VAS) at bedtime and wake time. During sleep on the night between 2 consecutive day shifts, the EEG powers at the frontal pole, HRV based on electrocardiograms, and distal-proximal gradient of skin temperature were recorded and analyzed. The results indicated that the subjects with high fatigue on the VAS at wake time exhibited (1) a decrease in deep non-rapid eye movement (NREM) (stageN3) sleep duration in the first sleep cycle; (2) a decrease in REM latency; (3) a decrease in ultra-slow and delta EEG powers, particularly from 30 to 65 min after sleep onset; (4) a decrease in the total power of HRV, particularly from 0 to 30 min after sleep onset; (5) an increase in the very low frequency component of HRV; and (6) a smaller increase in the distal-proximal gradient of skin temperature, than those of the subjects with low fatigue levels. The correlational and structural equation modeling analyses of these parameters suggested that an initial decrease in the total power of HRV from 0 to 30 min after sleep onset might inhibit the recovery from fatigue during sleep (i.e., increase the VAS score at wake time) via its effects on the ultra-slow and delta powers from 30 to 65 min after sleep onset, stageN3 duration in the first sleep cycle, REM latency, and distal-proximal gradient of skin temperature. These findings suggest an important role of these physiological factors in recovery from fatigue during sleep, and that interventions to modify these physiological factors might ameliorate fatigue at wake time

Delayed Re-Epithelialization in Periostin-Deficient Mice during Cutaneous Wound Healing

BACKGROUND: Matricellular proteins, including periostin, are important for tissue regeneration. METHODS AND FINDINGS: Presently we investigated the function of periostin in cutaneous wound healing by using periostin-deficient ⁻/⁻ mice. Periostin mRNA was expressed in both the epidermis and hair follicles, and periostin protein was located at the basement membrane in the hair follicles together with fibronectin and laminin γ2. Periostin was associated with laminin γ2, and this association enhanced the proteolytic cleavage of the laminin γ2 long form to produce its short form. To address the role of periostin in wound healing, we employed a wound healing model using WT and periostin⁻/⁻ mice and the scratch wound assay in vitro. We found that the wound closure was delayed in the periostin⁻/⁻ mice coupled with a delay in re-epithelialization and with reduced proliferation of keratinocytes. Furthermore, keratinocyte proliferation was enhanced in periostin-overexpressing HaCaT cells along with up-regulation of phosphorylated NF-κB. CONCLUSION: These results indicate that periostin was essential for keratinocyte proliferation for re-epithelialization during cutaneous wound healing

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

Giant cranial angiolipoma with arteriovenous fistula: A case report.

BACKGROUND: Angiolipomas are benign mesenchymal tumors comprising mature adipocytes and abnormal blood vessels, commonly found in the subcutaneous tissue of the trunk and rarely in the skull. Furthermore, sporadic cases of angiolipoma with arteriovenous fistula (AVF) have been reported. CASE DESCRIPTION: We reported the case of a 72-year-old woman who presented with head swelling, seizures, and cognitive dysfunction. Computed tomography and magnetic resonance imaging revealed a right frontal bone tumor exceeding a sagittal suture of up to 10.7 cm. Angiography revealed AVF and varices formation. Endovascular embolization was performed to treat the AVF and reduce blood loss during surgical resection. Two days after the embolization, a craniotomy was performed; however, uncontrollable bleeding was observed at the time of tumor resection. Postoperatively, the patient was symptom-free and has been stable for 2 years without recurrence. CONCLUSION: Despite careful preoperative evaluation and treatment planning, the patient in this case report was difficult to treat. Such cases require adequate preparation