長時間高強度の運動はグルココルチコイドを介して単純ヘルペスウイルス感染症に対して変動性免疫応答を誘導する

京都大学新制・課程博士博士(医学)甲第23467号医博第4774号新制||医||1053(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 森信 暁雄, 教授 上野 英樹, 教授 小柳 義夫学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Cancer stem cells induced by chronic stimulation with prostaglandin E2 exhibited constitutively activated PI3K axis

Previously, our group has demonstrated establishment of Cancer Stem Cell (CSC) models from stem cells in the presence of conditioned medium of cancer cell lines. In this study, we tried to identify the factors responsible for the induction of CSCs. Since we found the lipid composition could be traced to arachidonic acid cascade in the CSC model, we assessed prostaglandin E2 (PGE2) as a candidate for the ability to induce CSCs from induced pluripotent stem cells (iPSCs). Mouse iPSCs acquired the characteristics of CSCs in the presence of 10 ng/mL of PGE2 after 4 weeks. Since constitutive Akt activation and pik3cg overexpression were found in the resultant CSCs, of which growth was found independent of PGE2, chronic stimulation of the receptors EP-2/4 by PGE2 was supposed to induce CSCs from iPSCs through epigenetic effect. The bioinformatics analysis of the next generation sequence data of the obtained CSCs proposed not only receptor tyrosine kinase activation by growth factors but also extracellular matrix and focal adhesion enhanced PI3K pathway. Collectively, chronic stimulation of stem cells with PGE2 was implied responsible for cancer initiation enhancing PI3K/Akt axis

Regulatory Roles of Estrogens in Psoriasis

Psoriasis is a common chronic inflammatory skin disease of the interleukin (IL)-23/IL-17 axis. The severity of psoriasis has been reported as higher in men than in women. The immunoregulatory role of female sex hormones has been proposed to be one of the factors responsible for sex differences. Among female sex hormones, estrogens have been suggested to be significantly involved in the development of psoriasis by various epidemiological and in vitro studies. For example, the severity of psoriasis is inversely correlated with serum estrogen levels. In vitro, estrogens suppress the production of psoriasis-related cytokines such as IL-1β and IL-23 from neutrophils and dendritic cells, respectively. Furthermore, a recent study using a mouse psoriasis model indicated the inhibitory role of estrogens in psoriatic dermatitis by suppressing IL-1β production from neutrophils and macrophages. Understanding the role and molecular mechanisms of female sex hormones in psoriasis may lead to better control of the disease

High fat diet exacerbates murine psoriatic dermatitis by increasing the number of IL-17-producing γδ T cells

Abstract Psoriasis is a common, chronic inflammatory skin disease characterized by epidermal hyperplasia via the IL-23/IL-17 axis. Various studies have indicated the association between obesity and psoriasis, however, the underlying mechanisms remains unclarified. To this end, we focused on high-fat diet (HFD) in this study, because HFD is suggested as a contributor to obesity, and HFD-fed mice exhibit exacerbated psoriatic dermatitis. Using murine imiquimod (IMQ)-induced psoriasis and HFD-induced obesity models, we have revealed a novel mechanism of HFD-induced exacerbation of psoriatic dermatitis. HFD-fed mice exhibited aggravated psoriatic dermatitis, which was accompanied with increased accumulation of IL-17A-producing Vγ4+ γδ T cells in the skin. HFD also induced the increase of Vγ4+ γδ T cells in other organs such as skin draining lymph nodes, which preceded the increase of them in the skin. In addition, HFD-fed mice displayed increased expression of several γδ T cell-recruiting chemokines in the skin. On the other hand, ob/ob mice, another model of murine obesity on normal diet, did not exhibit aggravated psoriatic dermatitis nor accumulation of γδ T cells in the dermis. These results indicate that HFD is a key element in exacerbation of IMQ-induced psoriatic dermatitis, and further raise the possibility of HFD as a factor that links obesity and psoriasis

Predictors of Activities of Daily Living in Intensive Care Unit Survivors: A Propensity Score Matching Analysis

Objectives: Increased long-term impairment is common among intensive care unit (ICU) survivors. However, predictors of activities of daily living (ADL) in ICU survivors are poorly understood. We aimed to focus on the trajectory of physical function and explore the clinical variables that affect ADL at hospital discharge. Methods: We enrolled 411 patients admitted to the ICU from April 2018 to October 2020. Physical function was evaluated at ICU admission, ICU discharge, and hospital discharge. We assessed physical function (grip strength, arm and calf circumference, quadriceps thickness, and Barthel index). Patients were assigned to the high or low ADL group based on their Barthel index at discharge. Propensity score matching analysis was performed to minimize selection biases and differences in clinical characteristics. Results: After matching propensity scores, 114 of the 411 patients (aged 65±15 years) were evaluated. The high ADL group showed better physical function at ICU discharge and hospital discharge than the low ADL group. An overall decreasing trend in muscle mass was observed over time; the rates of decline were lower in the high ADL group than in the low ADL group. The cutoff values for relative changes in calf circumference and quadriceps thickness to predict high ADL were −7.89% (sensitivity: 77.8%, specificity: 55.6%) and −28.1% (sensitivity: 81.0%, specificity: 58.8%), respectively. Conclusions: The relative decreases in calf circumference and quadriceps thickness during hospitalization were lower in patients who maintained their ADL. Assessment of the trajectory of physical function can predict ADL status at hospital discharge among ICU survivors

Measurement of the B+/B0B^+/B^0 production ratio in e+e−e^+e^- collisions at the Υ(4S)\Upsilon(4S) resonance using B→J/ψ(ℓℓ)KB \rightarrow J/\psi(\ell\ell) K decays at Belle

We measure the ratio of branching fractions for the $\Upsilon (4S)$ decays to $B^+B^-$ and $B^0\bar{B}{}^0$ using $B^+ \rightarrow J/\psi(\ell\ell) K^+$ and $B^0 \rightarrow J/\psi(\ell\ell) K^0$ samples, where $J/\psi(\ell\ell)$ stands for $J/\psi \to \ell^+\ell^-$ ($\ell = e$ or $\mu$), with $711$ fb$^{-1}$ of data collected at the $\Upsilon(4S)$ resonance with the Belle detector. We find the decay rate ratio of $\Upsilon(4S) \rightarrow B^+B^-$ over $\Upsilon(4S) \rightarrow B^0\bar{B}{}^0$ to be $1.065\pm0.012\pm 0.019 \pm 0.047$, which is the most precise measurement to date. The first and second uncertainties are statistical and systematic, respectively, and the third uncertainty is systematic due to the assumption of isospin symmetry in $B \to J/\psi(\ell\ell) K$

Measurement of branching fractions of Λc+→pKS0KS0\Lambda_c^+\to{}pK_S^0K_S^0 and Λc+→pKS0η\Lambda_c^+\to{}pK_S^0\eta at Belle

We present a study of a singly Cabibbo-suppressed decay $\Lambda_c^+\to{}pK_S^0K_S^0$ and a Cabibbo-favored decay $\Lambda_c^+\to{}pK_S^0\eta$ based on 980 $\rm fb^{-1}$ of data collected by the Belle detector, operating at the KEKB energy-asymmetric $e^+e^-$ collider. We measure their branching fractions relative to $\Lambda_c^+\to{}pK_S^0$: $\mathcal{B}(\Lambda_c^+\to{}pK_S^0K_S^0)/\mathcal{B}(\Lambda_c^+\to{}pK_S^0)={(1.48 \pm 0.08 \pm 0.04)\times 10^{-2}}$ and $\mathcal{B}(\Lambda_c^+\to{}pK_S^0\eta)/\mathcal{B}(\Lambda_c^+\to{}pK_S^0)={(2.73\pm 0.06\pm 0.13)\times 10^{-1}}$. Combining with the world average $\mathcal{B}(\Lambda_c^+\to{}pK_S^0)$, we have the absolute branching fractions: $\mathcal{B}(\Lambda_c^+\to{}pK_S^0K_S^0) = {(2.35\pm 0.12\pm 0.07 \pm 0.12 )\times 10^{-4}}$ and $\mathcal{B}(\Lambda_c^+\to{}pK_S^0\eta) = {(4.35\pm 0.10\pm 0.20 \pm 0.22 )\times 10^{-3}}$. The first and second uncertainties are statistical and systematic, respectively, while the third ones arise from the uncertainty on $\mathcal{B}(\Lambda_c^+\to{}pK_S^0)$. The mode $\Lambda_c^+\to{}pK_S^0K_S^0$ is observed for the first time and has a statistical significance of $>\!10\sigma$. The branching fraction of $\Lambda_c^+\to{}pK_S^0\eta$ has been measured with a threefold improvement in precision over previous results and is found to be consistent with the world average

Measurement of the Ωc0\Omega_c^0 lifetime at Belle II

We report on a measurement of the $\Omega_c^0$ lifetime using $\Omega_c^0 \to \Omega^-\pi^+$ decays reconstructed in $e^+e^-\to c\bar{c}$ data collected by the Belle II experiment and corresponding to $207~{\rm fb^{-1}}$ of integrated luminosity. The result, $\rm\tau(\Omega_c^0)=243\pm48( stat)\pm11(syst)~fs$, agrees with recent measurements indicating that the $\Omega_c^0$ is not the shortest-lived weakly decaying charmed baryon