Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice

A close correlation between atherosclerosis, inflammation, and osteoporosis has been recognized, although the precise mechanism remains unclear. The growth factor progranulin (PGRN) is expressed in various cells such as macrophages, leukocytes, and chondrocytes. PGRN plays critical roles in a variety of diseases, such as atherosclerosis and arthritis by inhibiting Tumor Necrosis Factor-α (TNF-α) signaling. The purpose of this study was to investigate the effect of PGRN on bone metabolism. Forty-eight-week old female homozygous PGRN knockout mice (PGRN-KO) (n = 8) demonstrated severe low bone mass in the distal femur compared to age- and sex-matched wild type C57BL/6J mice (WT) (n = 8) [BV/TV (%): 5.8 vs. 16.6; p < 0.001, trabecular number (1/mm): 1.6 vs. 3.8; p < 0.001]. In vitro, PGRN inhibited TNF-α-induced osteoclastogenesis from spleen cells of PGRN-KO mice. Moreover, PGRN significantly promoted ALP activity, osteoblast-related mRNA (ALP, osteocalcin) expression in a dose-dependent manner and up-regulated osteoblastic differentiation by down-regulating phosphorylation of ERK1/2 in mouse calvarial cells. In conclusion, PGRN may be a promising treatment target for both atherosclerosis and inflammation-related osteoporosis.Noguchi T., Ebina K., Hirao M., et al. Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice. Biochemical and Biophysical Research Communications 465, 638 (2015); https://doi.org/10.1016/j.bbrc.2015.08.077

Promotion of allergic immune responses by intranasally-administrated nanosilica particles in mice

With the increase in use of nanomaterials, there is growing concern regarding their potential health risks. However, few studies have assessed the role of the different physical characteristics of nanomaterials in allergic responses. Here, we examined whether intranasally administered silica particles of various sizes have the capacity to promote allergic immune responses in mice. We used nanosilica particles with diameters of 30 or 70 nm (nSP30 or nSP70, respectively), and conventional micro-sized silica particles with diameters of 300 or 1000 nm (nSP300 or mSP1000, respectively). Mice were intranasally exposed to ovalbumin (OVA) plus each silica particle, and the levels of OVA-specific antibodies (Abs) in the plasma were determined. Intranasal exposure to OVA plus smaller nanosilica particles tended to induce a higher level of OVA-specific immunoglobulin (Ig) E, IgG and IgG1 Abs than did exposure to OVA plus larger silica particles. Splenocytes from mice exposed to OVA plus nSP30 secreted higher levels of Th2-type cytokines than mice exposed to OVA alone. Taken together, these results indicate that nanosilica particles can induce allergen-specific Th2-type allergic immune responses in vivo. This study provides the foundations for the establishment of safe and effective forms of nanosilica particles

急性期虚血性脳卒中患者から機械的血栓回収術で得られた血栓の年齢と組成は血栓回収術転帰および臨床転帰と関連していた

Introduction: Understanding the composition of stroke thrombi retrieved by mechanical thrombectomy is essential to clarify the pathogenesis of stroke. However, it is difficult to evaluate thrombus composition precisely and objectively. Immunohistochemical staining was used to evaluate thrombus composition and age. Materials and methods: Consecutive thrombi (n = 108) retrieved from patients who underwent mechanical thrombectomy for acute large-vessel ischemic stroke were retrospectively analyzed. Lytic features of granulocytes and CD163 were estimated as indicators of the age of the cardioembolic (CE) thrombus. Results: The stroke subtypes were as follows: CE, 74 cases; large artery atherosclerosis, 11; undetermined etiology, 12; and other determined etiology, 11. There were no statistical differences in thrombi composition according to stroke subtypes. The fibrin area was positively correlated with the red blood cell (RBC) and platelet areas. The following analysis was performed using CE only. Regarding age, the thrombus was judged as fresh in 30.0 % and older in 70.0 % based on the lytic features. The RBC areas of older thrombi were smaller than those of fresh thrombi. The puncture-to-reperfusion time of older thrombi was longer than that of fresh thrombi. Platelet-rich thrombi were associated with a greater number of maneuvers, a smaller prevalence of TICI 3, and unfavorable functional outcomes compared to platelet-poor thrombi. The number of CD163 positive cells in thrombi with anticoagulants was higher than in those without anticoagulants. Conclusion: Thrombus composition correlated with revascularization and clinical outcomes. The composition of an acute ischemic thrombus may reflect the pathophysiology of stroke and influence treatment efficacy.博士（医学）・甲第855号・令和4年12月22日Copyright © 2022 Elsevier Ltd. All rights reserved

Effect of amorphous silica nanoparticles on in vitro RANKL-induced osteoclast differentiation in murine macrophages

Amorphous silica nanoparticles (nSP) have been used as a polishing agent and/or as a remineralization promoter for teeth in the oral care field. The present study investigates the effects of nSP on osteoclast differentiation and the relationship between particle size and these effects. Our results revealed that nSP exerted higher cytotoxicity in macrophage cells compared with submicron-sized silica particles. However, tartrate-resistant acid phosphatase (TRAP) activity and the number of osteoclast cells (TRAP-positive multinucleated cells) were not changed by nSP treatment in the presence of receptor activator of nuclear factor κB ligand (RANKL) at doses that did not induce cytotoxicity by silica particles. These results indicated that nSP did not cause differentiation of osteoclasts. Collectively, the results suggested that nanosilica exerts no effect on RANKL-induced osteoclast differentiation of RAW264.7 cells, although a detailed mechanistic examination of the nSP70-mediated cytotoxic effect is needed

VLBI Astrometry of AGB Variables with VERA -- A Semiregular Variable S Crateris --

We present a distance measurement for the semiregular variable S Crateris (S Crt) based on its annual parallax. With the unique dual beam system of the VLBI Exploration for Radio Astrometry (VERA) telescopes, we measured the absolute proper motion of a water maser spot associated with S Crt, referred to the quasar J1147-0724 located at an angular separation of 1.23$^{\circ}$. In observations spanning nearly two years, we have detected the maser spot at the LSR velocity of 34.7 km s$^{-1}$, for which we measured the annual parallax of 2.33$\pm$0.13 mas corresponding to a distance of 430$^{+25}_{-23}$ pc. This measurement has an accuracy one order of magnitude better than the parallax measurements of HIPPARCOS. The angular distribution and three-dimensional velocity field of maser spots indicate a bipolar outflow with the flow axis along northeast-southwest direction. Using the distance and photospheric temperature, we estimate the stellar radius of S Crt and compare it with those of Mira variables.Comment: 9 pages, 4 figures, accepted for publication in PASJ (Vol.60, No.5, October 25, VERA special issue

Astrometry of H2_{2}O Masers in Nearby Star-Forming Regions with VERA. III. IRAS 22198+6336 in L1204G

We present results of multi-epoch VLBI observations with VERA (VLBI Exploration of Radio Astrometry) of the 22 GHz H$_{2}$O masers associated with a young stellar object (YSO) IRAS 22198+6336 in a dark cloud L1204G. Based on the phase-referencing VLBI astrometry, we derive an annual parallax of IRAS 22198+6336 to be 1.309$\pm$0.047 mas, corresponding to the distance of 764$\pm$27 pc from the Sun. Although the most principal error source of our astrometry is attributed to the internal structure of the maser spots, we successfully reduce the errors in the derived annual parallax by employing the position measurements for all of the 26 detected maser spots. Based on this result, we reanalyze the spectral energy distribution (SED) of IRAS 22198+6336 and find that the bolometric luminosity and total mass of IRAS 22198+6336 are 450$L_{\odot}$ and 7$M_{\odot}$, respectively. These values are consistent with an intermediate-mass YSO deeply embedded in the dense dust core, which has been proposed to be an intermediate-mass counterpart of a low-mass Class 0 source. In addition, we obtain absolute proper motions of the H$_{2}$O masers for the most blue-shifted components. We propose that the collimated jets aligned along the east-west direction are the most plausible explanation for the origin of the detected maser features.Comment: 15 pages, 7 figures, accepted for publication in PASJ (Vol.60, No.5, October 25, VERA special issue

退院時の6 分間歩行距離は退院3 か月後の身体活動量に影響する : 軽症脳梗塞患者における前向きコホート研究

研究論文Original Articles　【目的】本研究の目的は，急性期病院退院後の軽症脳梗塞患者の身体活動量に影響する退院時の要因を明らかにすることであった．【方法】研究デザインは，前向きコホート研究である．軽症脳梗塞患者を対象に身体活動量に関連する要因を退院時に測定し，退院2 週後と3 か月後の身体活動量をオムロン活動量計Active style Pro HJA-750C を用いて測定し，退院後の身体活動量に影響する退院時の要因を検討した．【結果】重回帰分析の結果，退院3 か月後の身体活動量に影響する要因として6 分間歩行距離（β＝ 0.675，p ＜ 0.001）のみが抽出された（自由度調整済みR2 ＝ 0.432，p ＜ 0.001）．【結論】急性期病院退院後の軽症脳梗塞患者の身体活動量には，退院時の6 分間歩行距離が影響することが明らかになった．退院3 か月後の身体活動量の向上には，退院時の6 分間歩行距離を高めることが重要であることが示唆された．【Object】The purpose of this study was to clarify the factors at the time of discharge that affect the physical activity level in patients with minor ischemic stroke after discharge from the acute care hospital.【Methods】This is a prospective cohort study.　We measured factors related to physical activity level at the time of discharge for patients with minor ischemic stroke, and used OMRON\u27s Active Style Pro HJA-750C to measure physical activity level 2 weeks and 3 months after discharge.　We used multiple regression analysis to examine factors at discharge that affect physical activity level after discharge.【Result】As a result of multiple regression analysis, only 6-minute walking distance ( β = 0.675, p <0.001) was extracted as a factor affecting physical activity level 3 months after discharge.【Conclusion】It was clarified that the 6-minute walking distance at the time of discharge affected the physical activity level of patients with minor ischemic stroke after discharge from the acute hospital. These results suggest that it is important to increase the walking distance for 6 minutes at the time of discharge in order to improve physical activity level 3 months after discharge

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals