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Article ; Online: Neutrophil extracellular traps inhibit osteoclastogenesis.

Numazaki, Kento / Tada, Hiroyuki / Nishioka, Takashi / Nemoto, Eiji / Matsushita, Kenji / Mizoguchi, Itaru / Sugawara, Shunji

Biochemical and biophysical research communications

2024 Volume 705, Page(s) 149743

Abstract: Neutrophil extracellular traps (NETs) released by neutrophils upon inflammation or infection, act as an innate immune defense against pathogens. NETs also influence inflammatory responses and cell differentiation in host cells. Osteoclasts, which are ... ...

Abstract	Neutrophil extracellular traps (NETs) released by neutrophils upon inflammation or infection, act as an innate immune defense against pathogens. NETs also influence inflammatory responses and cell differentiation in host cells. Osteoclasts, which are derived from myeloid stem cells, are critical for the bone remodeling by destroying bone. In the present study, we explores the impact of NETs, induced by the inflammatory agent calcium ionophore A23187, on the differentiation and activation of osteoclasts, potentially through suppressing RANK expression. Our results collectively suggested that the inhibition of RANKL-mediated osteoclastogenesis by NETs might lead to the suppression of excessive bone resorption during inflammation.
MeSH term(s)	Humans ; Osteogenesis ; Extracellular Traps ; Osteoclasts ; Neutrophils ; Bone Resorption ; Cell Differentiation ; Inflammation ; RANK Ligand
Chemical Substances	RANK Ligand
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2024.149743
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Article ; Online: Prevalence and associated factors of non-traumatic knee pain in high school volleyball players: a cross-sectional study.

Mizoguchi, Yasuaki / Suzuki, Kenta / Shimada, Naoki / Naka, Hiroyuki / Hall, Toby / Akasaka, Kiyokazu

The Physician and sportsmedicine

2024

Abstract: Objectives: This study aimed to determine the prevalence of knee pain among high school volleyball attackers, identify associated factors, and explore the relationship between knee pain and lower back pain (LBP).: Methods: A cross-sectional study ... ...

Abstract	Objectives: This study aimed to determine the prevalence of knee pain among high school volleyball attackers, identify associated factors, and explore the relationship between knee pain and lower back pain (LBP). Methods: A cross-sectional study involving 82 high school volleyball attackers (15-17 years) used questionnaires, interviews, and field-based assessments to collect data on demographics, volleyball-specific factors, flexibility, and jumping ability. Logistic regression analysis was used to identify factors associated with knee pain. Results: The prevalence of knee pain was 19.5%. Factors significantly associated with knee pain were a history of LBP (OR, 4.64; 95% CI, 1.28 to 16.8; Conclusion: Factors associated with knee pain include a history of LBP and reduced flexibility on the heel-buttock distance test. The study highlights the need for a comprehensive approach, considering the coexistence of LBP and focusing on improving anterior thigh flexibility.
Language	English
Publishing date	2024-04-26
Publishing country	England
Document type	Journal Article
ZDB-ID	753046-8
ISSN	2326-3660 ; 0091-3847
ISSN (online)	2326-3660
ISSN	0091-3847
DOI	10.1080/00913847.2024.2348439
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Article ; Online: New Strategies for the Treatment of Neuropsychiatric Disorders Based on Reelin Dysfunction.

Tsuneura, Yumi / Nakai, Tsuyoshi / Mizoguchi, Hiroyuki / Yamada, Kiyofumi

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: Reelin is an extracellular matrix protein that is mainly produced in Cajal-Retzius cells and controls neuronal migration, which is important for the proper formation of cortical layers in the developmental stage of the brain. In the adult brain, Reelin ... ...

Abstract	Reelin is an extracellular matrix protein that is mainly produced in Cajal-Retzius cells and controls neuronal migration, which is important for the proper formation of cortical layers in the developmental stage of the brain. In the adult brain, Reelin plays a crucial role in the regulation of
MeSH term(s)	Animals ; Gene Expression Regulation, Developmental ; Humans ; Learning ; Mental Disorders/drug therapy ; Mental Disorders/metabolism ; Mice ; Molecular Targeted Therapy ; Reelin Protein/genetics ; Reelin Protein/metabolism
Chemical Substances	Reelin Protein ; RELN protein, human (EC 3.4.21.-) ; Reln protein, mouse (EC 3.4.21.-)
Language	English
Publishing date	2022-02-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031829
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Article ; Online: A machine learning model that emulates experts' decision making in vancomycin initial dose planning.

Matsuzaki, Tetsuo / Kato, Yoshiaki / Mizoguchi, Hiroyuki / Yamada, Kiyofumi

Journal of pharmacological sciences

2022 Volume 148, Issue 4, Page(s) 358–363

Abstract: Vancomycin is a glycopeptide antibiotic that is a primary treatment for methicillin-resistant Staphylococcus aureus infections. To enhance its clinical effectiveness and prevent nephrotoxicity, therapeutic drug monitoring (TDM) of trough concentrations ... ...

Abstract	Vancomycin is a glycopeptide antibiotic that is a primary treatment for methicillin-resistant Staphylococcus aureus infections. To enhance its clinical effectiveness and prevent nephrotoxicity, therapeutic drug monitoring (TDM) of trough concentrations is recommended. Initial vancomycin dosing regimens are determined based on patient characteristics such as age, body weight, and renal function, and dosing strategies to achieve therapeutic concentration windows at initial TDM have been extensively studied. Although numerous dosing nomograms for specific populations have been developed, no comprehensive strategy exists for individually tailoring initial dosing regimens; therefore, decision making regarding initial dosing largely depends on each clinician's experience and expertise. In this study, we applied a machine-learning (ML) approach to integrate clinician knowledge into a predictive model for initial vancomycin dosing. A dataset of vancomycin initial dose plans defined by pharmacists experienced in vancomycin TDM (i.e., experts) was used to build the ML model. Although small training sets were used, we established a predictive model with a target attainment rate comparable to those of experts, another ML model, and commonly used vancomycin dosing software. Our strategy will help develop an expert-like predictive model that aids in decision making for initial vancomycin dosing, particularly in settings where dose planning consultations are unavailable.
MeSH term(s)	Decision Making ; Humans ; Machine Learning ; Methicillin-Resistant Staphylococcus aureus ; Retrospective Studies ; Vancomycin/therapeutic use
Chemical Substances	Vancomycin (6Q205EH1VU)
Language	English
Publishing date	2022-02-20
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2104264-0
ISSN	1347-8648 ; 1347-8613
ISSN (online)	1347-8648
ISSN	1347-8613
DOI	10.1016/j.jphs.2022.02.005
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Article ; Online: New Strategies for the Treatment of Neuropsychiatric Disorders Based on Reelin Dysfunction

Yumi Tsuneura / Tsuyoshi Nakai / Hiroyuki Mizoguchi / Kiyofumi Yamada

International Journal of Molecular Sciences, Vol 23, Iss 1829, p

2022 Volume 1829

Abstract	Reelin is an extracellular matrix protein that is mainly produced in Cajal-Retzius cells and controls neuronal migration, which is important for the proper formation of cortical layers in the developmental stage of the brain. In the adult brain, Reelin plays a crucial role in the regulation of N -methyl-D-aspartate receptor-dependent synaptic function, and its expression decreases postnatally. Clinical studies showed reductions in Reelin protein and mRNA expression levels in patients with psychiatric disorders; however, the causal relationship remains unclear. Reelin-deficient mice exhibit an abnormal neuronal morphology and behavior, while Reelin supplementation ameliorates learning deficits, synaptic dysfunctions, and spine loss in animal models with Reelin deficiency. These findings suggest that the neuronal deficits and brain dysfunctions associated with the down-regulated expression of Reelin are attenuated by enhancements in its expression and functions in the brain. In this review, we summarize findings on the role of Reelin in neuropsychiatric disorders and discuss potential therapeutic approaches for neuropsychiatric disorders associated with Reelin dysfunctions.
Keywords	reelin ; neuropsychiatric disorders ; development ; ADAMTS-3 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Orexinergic neurons contribute to autonomic cardiovascular regulation for locomotor exercise.

Narai, Emi / Yoshimura, Yuki / Honaga, Takaho / Mizoguchi, Hiroyuki / Yamanaka, Akihiro / Hiyama, Takeshi Y / Watanabe, Tatsuo / Koba, Satoshi

The Journal of physiology

2024

Abstract: While the hypothalamic orexinergic nervous system is established as having a pivotal role in the long-term regulation of various organismic functions, including wakefulness, metabolism and hypertensive states, whether this system contributes to the rapid ...

Abstract	While the hypothalamic orexinergic nervous system is established as having a pivotal role in the long-term regulation of various organismic functions, including wakefulness, metabolism and hypertensive states, whether this system contributes to the rapid autonomic cardiovascular regulation during physical activity remains elusive. This study aimed to elucidate the role of the orexinergic nervous system in transmitting volitional motor signals, i.e. central command, to drive somatomotor and sympathetic cardiovascular responses. We first found that this system is activated by voluntary locomotor exercise as evidenced by an increased expression of Fos, a marker of neural activation, in the orexinergic neurons of Sprague-Dawley rats engaged in spontaneous wheel running. Next, using transgenic Orexin-Cre rats for optogenetic manipulation of orexinergic neurons, we found that optogenetic excitation of orexinergic neurons caused sympathoexcitation on a subsecond timescale under anaesthesia. In freely moving conscious rats, this excitatory stimulation rapidly elicited exploration-like behaviours, predominantly locomotor activity, along with pressor and tachycardiac responses. Meanwhile, optogenetic inhibition of orexinergic neurons during spontaneous wheel running immediately suppressed locomotor activities and blood pressure elevation without affecting basal cardiovascular homeostasis. Taken together, these findings demonstrate the essential role of the orexinergic nervous system in the central circuitry that transmits central command signals for locomotor exercise. This study not only offers insights into the brain circuit mechanisms precisely regulating autonomic cardiovascular systems during voluntary exercise but also likely contributes to our understanding of brain mechanisms underlying abnormal cardiovascular adjustments to exercise in pathological conditions, such as hypertension. KEY POINTS: The hypothalamic orexinergic nervous system plays various roles in the long-term regulation of autonomic and endocrine functions, as well as motivated behaviours. We present a novel, rapid role of the orexinergic nervous system, revealing its significance as a crucial substrate in the brain circuit mechanisms that coordinate somatomotor and autonomic cardiovascular controls for locomotor exercise. Our data demonstrate that orexinergic neurons relay volitional motor signals, playing a necessary and sufficient role in the autonomic cardiovascular regulation required for locomotor exercise in rats. The findings contribute to our understanding of how the brain precisely regulates autonomic cardiovascular systems during voluntary exercise, providing insights into the central neural mechanisms that enhance physical performance moment-by-moment during exercise.
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP285791
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Article ; Online: Five-year clinical outcomes of scanning carbon-ion radiotherapy for prostate cancer.

Takakusagi, Yosuke / Koge, Hiroaki / Kano, Kio / Shima, Satoshi / Tsuchida, Keisuke / Mizoguchi, Nobutaka / Yoshida, Daisaku / Kamada, Tadashi / Katoh, Hiroyuki

PloS one

2024 Volume 19, Issue 3, Page(s) e0290617

Abstract: Background: Carbon-ion radiotherapy (CIRT) has been associated with favorable clinical outcomes in patients with prostate cancer. At our facility, all patients are treated using scanning CIRT (sCIRT). We retrospectively analyzed five-year clinical ... ...

Abstract	Background: Carbon-ion radiotherapy (CIRT) has been associated with favorable clinical outcomes in patients with prostate cancer. At our facility, all patients are treated using scanning CIRT (sCIRT). We retrospectively analyzed five-year clinical outcomes of prostate cancer treated with sCIRT to investigate treatment efficacy and toxicity. Methods: In this study, we included 253 consecutive prostate cancer patients treated with sCIRT at the Kanagawa Cancer Center from December 2015 to December 2017. The total dose of sCIRT was set at 51.6 Gy (relative biological effect) in 12 fractions over three weeks. We employed the Phoenix definition for biochemical relapse. The overall survival (OS), biochemical relapse-free (bRF) rate, and cumulative incidence of late toxicity were estimated using the Kaplan-Meier method. Toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. Results: The median age of the patients was 70 years (range: 47-86 years). The median follow-up duration was 61.1 months (range: 4.1-80.3 months). Eight (3.2%), 88 (34.8%), and 157 (62.1%) patients were in the low-risk, intermediate-risk, and high-risk groups, respectively, according to the D'Amico classification system. The five-year OS and bRF were 97.5% and 93.3%, respectively. The five-year bRF rates for the low-risk, intermediate-risk, and high-risk groups were 87.5%, 93.7%, and 93.4%, respectively (p = 0.7215). The five-year cumulative incidence of Grade 2 or more late genitourinary and gastrointestinal toxicity was 7.4% and 1.2%, respectively. Conclusion: The results of this study show that sCIRT has a favorable therapeutic effect and low toxicity in the treatment of prostate cancer.
MeSH term(s)	Male ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Neoplasm Recurrence, Local ; Prostatic Neoplasms ; Treatment Outcome ; Carbon ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated/methods
Chemical Substances	Carbon (7440-44-0)
Language	English
Publishing date	2024-03-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0290617
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Article ; Online: Retrospective Analysis of Neutrophil-to-Lymphocyte Ratio in Patients with Melanoma Who Received Ipilimumab Monotherapy or Ipilimumab in Combination with Nivolumab in Japan.

Matsumura, Yuka / Kawarada, Yuki / Matsuo, Momo / Yokota, Kenji / Mizoguchi, Hiroyuki / Akiyama, Masashi / Yamada, Kiyofumi

Biological & pharmaceutical bulletin

2023 Volume 46, Issue 3, Page(s) 427–431

Abstract: Studies have reported an association between elevated neutrophil-to-lymphocyte ratio (NLR) and poor prognosis in patients with melanoma treated with ipilimumab. However, it remains unclear whether NLR is useful in Japanese patients with melanoma, and if ... ...

Abstract	Studies have reported an association between elevated neutrophil-to-lymphocyte ratio (NLR) and poor prognosis in patients with melanoma treated with ipilimumab. However, it remains unclear whether NLR is useful in Japanese patients with melanoma, and if so, what is the optimal cut-off value. We retrospectively examined 38 patients who received ipilimumab from August 2015 to November 2021 at Nagoya University Hospital. We divided patients into two groups: 1-2 versus 3-4 cycles of ipilimumab. In univariate analysis, baseline neutrophil count and NLR were significantly higher in patients who discontinued ipilimumab within 2 cycles. With receiver operating characteristic analysis, the optimal NLR cut-off value was found to be 3.4 (area under the curve, 0.75; 95% confidence interval, 0.58-0.92). In multivariate logistic regression analysis, baseline NLR >3.4 was an independent risk factor for ipilimumab discontinuation (odds ratio, 15.6; 95% confidence interval, 3.0-82) that was significantly associated with shorter progression-free survival (PFS) (p = 0.003, log-rank test). In conclusion, NLR >3.4 is useful for selecting Japanese patients with melanoma who might have better PFS with ipilimumab-containing treatment. Because the optimal NLR cut-off value in this study was lower than values in American and European studies, it possibly differs by race. Hence, it should be extrapolated to Japanese patients with caution.
MeSH term(s)	Humans ; Nivolumab ; Ipilimumab ; Retrospective Studies ; Neutrophils ; Japan ; Melanoma ; Lymphocytes
Chemical Substances	Nivolumab (31YO63LBSN) ; Ipilimumab
Language	English
Publishing date	2023-03-01
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1150271-x
ISSN	1347-5215 ; 0918-6158
ISSN (online)	1347-5215
ISSN	0918-6158
DOI	10.1248/bpb.b22-00750
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Article ; Online: Alzheimer's Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment.

Nakai, Tsuyoshi / Yamada, Kiyofumi / Mizoguchi, Hiroyuki

International journal of molecular sciences

2021 Volume 22, Issue 11

Abstract: Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder. It is widely accepted that AD is mainly caused by the accumulation of extracellular amyloid β (Aβ) and intracellular neurofibrillary tau tangles. Aβ begins to ... ...

Abstract	Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder. It is widely accepted that AD is mainly caused by the accumulation of extracellular amyloid β (Aβ) and intracellular neurofibrillary tau tangles. Aβ begins to accumulate years before the onset of cognitive impairment, suggesting that the benefit of currently available interventions would be greater if they were initiated in the early phases of AD. To understand the mechanisms of AD pathogenesis, various transgenic mouse models with an accelerated accumulation of Aβ and tau tangles have been developed. However, none of these models exhibit all pathologies present in human AD. To overcome these undesirable phenotypes,
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Protein Precursor/genetics ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Biomarkers/metabolism ; Cognitive Dysfunction/metabolism ; Cognitive Dysfunction/pathology ; Disease Models, Animal ; Gene Knock-In Techniques ; Mice ; Mice, Transgenic ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Protein Precursor ; Biomarkers ; tau Proteins
Language	English
Publishing date	2021-05-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22115549
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Article ; Online: Efficacy of semi-customized exercises in preventing low back pain in high school volleyball players: A randomized controlled trial.

Mizoguchi, Yasuaki / Akasaka, Kiyokazu / Otsudo, Takahiro / Shimada, Naoki / Naka, Hiroyuki

Medicine

2022 Volume 101, Issue 36, Page(s) e30358

Abstract: Background: Low back pain (LBP) is a common injury in high school volleyball players. We hypothesized that a prevention program could decrease the incidence of LBP in high school volleyball players. This study was an in-season cluster-randomized ... ...

Abstract	Background: Low back pain (LBP) is a common injury in high school volleyball players. We hypothesized that a prevention program could decrease the incidence of LBP in high school volleyball players. This study was an in-season cluster-randomized controlled trial. Methods: We block-randomized 8 high school volleyball teams comprising 70 players aged 15 to 17 years into the intervention (4 teams, 34 players) and control (4 teams, 36 players) groups. The intervention program consisted of 9 physical function tests as well as 1 or 2 self-selected preventive exercises, including dynamic thoracic mobility, trunk stabilization exercises, and static stretching, performed during warm-up. Both groups were followed up for 4 weeks, during which the incidence of LBP was recorded. Physical function tests (back endurance; spinal and back flexibility; active or passive shoulder and trunk range of motion; ankle joint mobility; and iliopsoas, quadriceps, and hamstrings flexibility) were conducted before and after the intervention. Results: The intervention group had a significantly lower incidence of LBP (8.8%) than the control group (33.3%) (relative risk, 3.78; 95% confidence interval, 1.17-12.23; P = .017, 1 - β = 0.99). Lumbar extension accounted for nearly 70% of LBP incidences. Most players in the intervention group demonstrated improved physical function associated with the exercises. Conclusion: The semi-customized prevention program decreased the incidence of LBP and enhanced the physical function parameter in high school volleyball players.
MeSH term(s)	Humans ; Low Back Pain/epidemiology ; Low Back Pain/prevention & control ; Muscle Stretching Exercises ; Range of Motion, Articular ; Schools ; Volleyball
Language	English
Publishing date	2022-08-17
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000030358
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