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医学部 附属病院 総合周産期母子医療センター |
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講師 |
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Brief early antibiotic exposure (≤2 days) is not associated with disruption of gut microbiome in very low birth weight infants. 査読あり
Aoki Y, Tate M, Ochiai K, Tsuchimochi K, Mizuguchi U, Okazaki K, Moritake H
Frontiers in microbiology 16 1742512 2026年1月
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Aoki Y., Dai H., Furuta F., Akamatsu T., Oshima T., Takahashi N., Goto Y.i., Oka A., Itoh M.
Cell Communication and Signaling 21 ( 1 ) 126 2023年6月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cell Communication and Signaling
Background: Microglial cells play an important role in the immune system in the brain. Activated microglial cells are not only injurious but also neuroprotective. We confirmed marked lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression in microglial cells in pathological lesions in the neonatal hypoxic-ischemic encephalopathy (nHIE) model brain. LOX-1 is known to be an activator of cytokines and chemokines through intracellular pathways. Here, we investigated a novel role of LOX-1 and the molecular mechanism of LOX-1 gene transcription microglial cells under hypoxic and ischemic conditions. Methods: We isolated primary rat microglial cells from 3-day-old rat brains and confirmed that the isolated cells showed more than 98% Iba-1 positivity with immunocytochemistry. We treated primary rat microglial cells with oxygen glucose deprivation (OGD) as an in vitro model of nHIE. Then, we evaluated the expression levels of LOX-1, cytokines and chemokines in cells treated with or without siRNA and inhibitors compared with those of cells that did not receive OGD-treatment. To confirm transcription factor binding to the OLR-1 gene promoter under the OGD conditions, we performed a luciferase reporter assay and chromatin immunoprecipitation assay. In addition, we analyzed reactive oxygen species and cell viability. Results: We found that defects in oxygen and nutrition induced LOX-1 expression and led to the production of inflammatory mediators, such as the cytokines IL-1β, IL-6 and TNF-α; the chemokines CCL2, CCL5 and CCL3; and reactive oxygen/nitrogen species. Then, the LOX-1 signal transduction pathway was blocked by inhibitors, LOX-1 siRNA, the p38-MAPK inhibitor SB203580 and the NF-κB inhibitor BAY11-7082 suppressed the production of inflammatory mediators. We found that NF-κB and HIF-1α bind to the promoter region of the OLR-1 gene. Based on the results of the luciferase reporter assay, NF-κB has strong transcriptional activity. Moreover, we demonstrated that LOX-1 in microglial cells was autonomously overexpressed by positive feedback of the intracellular LOX-1 pathway. Conclusion: The hypoxic/ischemic conditions of microglial cells induced LOX-1 expression and activated the immune system. LOX-1 and its related molecules or chemicals may be major therapeutic candidates. [MediaObject not available: see fulltext.].
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Yoshinori Aoki, Tatsuo Kono, Mikako Enokizono, Kaoru Okazaki
BMC pediatrics 21 ( 1 ) 224 2021年5月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
Background: Neonatal encephalopathy due to acute perinatal asphyxia is a major cause of perinatal brain damage. Moderate to severe neonatal encephalopathy is associated with high mortality and morbidity rates. However, the neurodevelopmental outcomes in neonates with mild neonatal encephalopathy are unclear. The primary aim of this single-center observational study was to assess the short-term outcomes in term neonates with mild neonatal encephalopathy due to perinatal asphyxia. A secondary aim was to identify predictors of poor prognosis by identifying the characteristics of these infants according to their short-term outcomes.
Methods: We retrospectively investigated all infants with perinatal asphyxia at Tokyo Metropolitan Children's Medical Center from January 2014 to December 2019. An abnormal short-term outcome was defined as any one of the following: seizures or abnormal electroencephalography, abnormal brain magnetic resonance imaging obtained within the first 4 weeks of life, and abnormal neurological examination findings at discharge.
Results: In total, 110 term infants with perinatal asphyxia during the study period were screened and 61 were diagnosed with mild neonatal encephalopathy. Eleven (18 %) of these infants had an abnormal short-term outcome. The median Thompson score at admission was significantly higher in infants with abnormal short-term outcomes than in those with normal short-term outcomes (5 [interquartile range, 4-5.5] vs. 2 [interquartile range, 1-3], p < 0.01). Receiver operating characteristic curve analysis showed that a cutoff value of 4 had high sensitivity and specificity (90.9 and 83.0 %, respectively) for prediction of an abnormal short-term outcome.
Conclusions: 18 % of infants with mild encephalopathy had an abnormal short-term outcome, such as abnormal brain magnetic resonance imaging findings. The Thompson score at admission may be a useful predictor of an abnormal short-term outcome in infants with mild neonatal encephalopathy. -
青木 良則, 楯 真由美, 土持 皓平, 盛武 浩
Frontiers in microbiology 16 1742512 2026年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Frontiers Media SA
Early empirical antibiotic therapy is common in preterm and very low birth weight (VLBW) infants but may disrupt the developing gut microbiome. However, the effects of brief antibiotic courses remain unclear, particularly in the most immature infants. In this prospective multicenter cohort study, we examined gut microbiome trajectories in VLBW infants (many of whom were extremely preterm) receiving no antibiotics, a short course (≤2 days), or prolonged exposure (≥3 days). Serial stool samples were analyzed using 16S rRNA gene sequencing. Microbiome composition and diversity in the short-course group were similar to those in unexposed infants at all timepoints, indicating that brief antibiotic exposure did not disrupt microbial development. In contrast, prolonged exposure was associated with transient dysbiosis characterized by reduced Bifidobacterium abundance and lower alpha diversity, with partial recovery by discharge. These findings suggest that limiting empirical antibiotic therapy to ≤2 days (48 h) when infection is unconfirmed may not disrupt microbiome development even in highly immature preterm VLBW infants, supporting evidence-based antibiotic stewardship in neonatal intensive care.
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Novel SKIC3 variants in tricho-hepato-enteric syndrome with hemochromatosis 査読あり
青木 良則, 阿萬 紫, 山下 篤, 山口 昌俊, 児玉 由紀, 盛武 浩
Human Genome Variation 12 14 2025年7月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Springer Nature
Tricho-hepato-enteric syndrome (THES), a rare autosomal recessive disorder caused by variants in the SKIC3 or SKIC2 gene, is characterized by intractable diarrhea, woolly hair, growth restriction and liver disease. Here we report a neonatal case of THES with neonatal hemochromatosis, in which the novel compound heterozygous SKIC3 variants NM_014639.4:c.815_816del p.(Gly272AlafsTer9) and NM_014639.4:c.2284G>A p.(Gly762Arg) were identified. Further research is needed to elucidate the mechanisms underlying iron metabolism dysregulation in THES.
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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新生児低酸素性虚血性脳症における、LOX-1をターゲットとした新規治療法の開発
研究課題/領域番号：24K18861 2024年04月 - 2027年03月
独立行政法人日本学術振興会 科学研究費基金 若手研究
担当区分：研究代表者
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低酸素性虚血性脳症におけるミクログリアでのLOX-1の役割解明と新規治療法の開発
研究課題/領域番号：20K16875 2020年04月 - 2023年03月
独立行政法人日本学術振興会 科学研究費補助金 若手研究
担当区分：研究代表者