血中cell-free DNAを用いた心筋梗塞の早期診断法の確立

• Project/Area Number: 23K21524
• Project/Area Number (Other): 21H03212 (2021-2023)
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund (2024); Single-year Grants (2021-2023)
• Section: 一般
• Review Section: Basic Section 58040:Forensics medicine-related
• Research Institution: Shimane University
• Principal Investigator: 藤原 純子 島根大学, 学術研究院医学・看護学系, 講師 (20346381)
• Project Period (FY): 2021-04-01 – 2026-03-31
• Project Status: Granted (Fiscal Year 2024)
• Budget Amount: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000); Fiscal Year 2025: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2024: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2022: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: cell-free DNA / 心筋梗塞 / アポトーシス / ネクローシス / Origin / マイクロチップ電気泳動

Outline of Research at the Start

継続課題のため、記入しない。

Outline of Annual Research Achievements

cell-free DNA (cfDNA) は,細胞死（アポトーシスやネクローシス）の際に血中に放出される細胞外遊離DNA断片を指す．申請者はこれまでに心筋梗塞患者でcfDNA濃度が有意に上昇し,150-200bp/500-600bpのcfDNAフラグメント濃度比が他の心疾患患者と比較して有意に高いことを明らかにした．さらにアポトーシスに加えNETosisがcfDNA放出に関与することを明らかにした．NETosisは細胞質や細胞核の縮小・DNAの断片化は伴わなず２ー３時間で完了する細胞死であり，ネクローシスともアポトーシスとも異なる第3の細胞死と言われる．
cfDNAはリキッドバイオプシーとして腫瘍のモニタリングに用いられ,侵襲性が低く早期診断が行えるとして注目されている．急性前骨髄球性白血病（APL）治療には三酸化二ヒ素（ATO）が用いられるが，ATO投与されたAPL患者における血清中cfDNA濃度やそのフラグメントパターンについては明らかになっていない．そこで，APL患者におけるcfDNA濃度とそのフラグメントパターンを明らかにした．血清中cfDNA濃度はヒ素投与に伴って上昇し，アポトーシスに加え，主にNETosisにより血液中に放出されることが示唆された．

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

現在もcfDNAに関する論文を投稿中である．

Strategy for Future Research Activity

今後は，死後血液中cfDNA濃度等が死後経過推定に有用であるか検討を行う予定である．

Research Products

• [Journal Article] Speciation analysis of inorganic Sb leached from InSb thin films by hydride generation?microwave plasma-atomic emission spectroscopy (2023)
  • Author(s): Fujihara Junko、Nishimoto Naoki
  • Journal Title: Journal of the Iranian Chemical Society Volume: 20 Issue: 10 Pages: 2555-2560
  • DOI: 10.1007/s13738-023-02853-3
  • Peer Reviewed
• [Journal Article] Review of Zinc Oxide Nanoparticles: Toxicokinetics, Tissue Distribution for Various Exposure Routes, Toxicological Effects, Toxicity Mechanism in Mammals, and an Approach for Toxicity Reduction (2023)
  • Author(s): Fujihara Junko、Nishimoto Naoki
  • Journal Title: Biological Trace Element Research Volume: 202 Issue: 1 Pages: 9-23
  • DOI: 10.1007/s12011-023-03644-w
  • Peer Reviewed
• [Journal Article] Bismuth-assisted low-temperature growth of flexible GaSb thin films by multi-cathode RF magnetron sputtering (2023)
  • Author(s): Nishimoto Naoki、Fujihara Junko
  • Journal Title: Journal of Materials Science Volume: 58 Issue: 27 Pages: 11174-11186
  • DOI: 10.1007/s10853-023-08735-6
  • Peer Reviewed
• [Journal Article] Systemic administration of Porphyromonas gingivalis lipopolysaccharide induces glial activation and depressive-like behavior in rats (2023)
  • Author(s): Mamunur R, Hashioka S, Azis IA, Jaya MA, Jerin SJF, Kimura-Kataoka K, Fujihara J, Inoue K, Inagaki M, Takeshita H
  • Journal Title: J Integr Neurosci Volume: 22 Issue: 5 Pages: 120-120
  • DOI: 10.31083/j.jin2205120
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cell-free DNA Release in the Plasma of Patients with Cardiac Disease is Associated with Cell Death Processes (2022)
  • Author(s): Fujihara Junko、Takinami Yoshikazu、Kimura-Kataoka Kaori、Kawai Yasuyuki、Takeshita Haruo
  • Journal Title: Indian Journal of Clinical Biochemistry Volume: 38 Issue: 1 Pages: 67-72
  • DOI: 10.1007/s12291-022-01034-y
  • Peer Reviewed
• [Journal Article] Improvement of the structural properties and environmental stability of flexible InSb thin films by dopant-assisted crystallization (2022)
  • Author(s): Nishimoto Naoki、Fujihara Junko
  • Journal Title: Applied Physics A Volume: 128 Issue: 7 Pages: 550-550
  • DOI: 10.1007/s00339-022-05694-8
  • Peer Reviewed
• [Journal Article] Comparison of serum cell-free DNA between postmortem and living samples (2021)
  • Author(s): Fujihara Junko、Takinami Yoshikazu、Kawai Yasuyuki、Kimura-Kataoka Kaori、Takeshita Haruo
  • Journal Title: Clinica Chimica Acta Volume: 519 Pages: 255-259
  • DOI: 10.1016/j.cca.2021.05.013
  • Peer Reviewed
• [Journal Article] Dermal absorption of gallium antimonide in vitro and pro-inflammatory effects on human dermal fibroblasts (2021)
  • Author(s): Fujihara Junko、Nishimoto Naoki
  • Journal Title: Toxicology in Vitro Volume: 71 Pages: 105064-105064
  • DOI: 10.1016/j.tiv.2020.105064
  • Peer Reviewed
• [Journal Article] Cytotoxicity and pro-inflammatory effect of GaSb thin films in L929 cells (2021)
  • Author(s): Fujihara Junko、Nishimoto Naoki
  • Journal Title: International Journal of Modern Physics B Volume: 35 Issue: 29 Pages: 2150297-2150297
  • DOI: 10.1142/s0217979221502970
  • Peer Reviewed
• [Journal Article] Characterization of flexible dilute nitride InSbN thin films and exploratory study for epidermal optoelectronics (2021)
  • Author(s): Nishimoto Naoki、Fujihara Junko
  • Journal Title: Materials Chemistry and Physics Volume: 274 Pages: 125160-125160
  • DOI: 10.1016/j.matchemphys.2021.125160
  • Peer Reviewed
• [Journal Article] The indicators associated with increasing suicide trends: Need for harmony in discussing suicide in legal medicine and other fields (2021)
  • Author(s): Inoue Ken、Apbassova Madina、Hoshi Masaharu、Takeichi Nobuo、Noso Yoshihiro、Ohira Yoshiyuki、Shabdarbayeva Dariya、Chaizhunusova Nailya、Zhunussov Yersin T.、Fujihara Junko、Kimura-Kataoka Kaori、Fujita Yasuyuki、Takeshita Haruo
  • Journal Title: Legal Medicine Volume: 50 Pages: 101820-101820
  • DOI: 10.1016/j.legalmed.2020.101820
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 法中毒学の新しい展開 (2022)
  • Author(s): 藤原純子
  • Organizer: 法中毒学会 第41年会
  • Invited