東北大学研究者紹介

研究者詳細

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顔写真

シラト　ミドリ

白土　翠

Midori Shirato

所属

大学院歯学研究科　先端フリーラジカル制御学講座

職名

講師

学位

博士（歯学）（東北大学）
PhD (Odontological Science) （University of Gothenburg）

researchmap

https://researchmap.jp/7000022422

J-GLOBAL ID

201801021280775695

経歴 2

2026年4月～継続中

東北大学大学院歯学研究科　講師
2018年4月～ 2026年3月

東北大学大学院歯学研究科　助教

学歴 3

University of Gothenburg　Institute of Odontology in Sahlgrenska Academy (Doctoral course)

2021年1月～ 2025年12月
東北大学大学院歯学研究科

2009年4月～ 2013年3月
岩手医科大学　歯学部

2002年4月～ 2008年3月

研究キーワード 1

バイオフィルム

研究分野 2

ライフサイエンス / 補綴系歯学 /
ライフサイエンス / 保存治療系歯学 /

論文 29

Reduced dental caries incidence in rats with hydrogel-encapsulated fructose-glucose sports-fuel. 国際誌査読有り

Keisuke Nakamura, Midori Shirato, Shunichi Shishido, Peter Lingström

Scientific reports　2026年4月1日

DOI： 10.1038/s41598-026-46781-7 　

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Hydrogel-encapsulated fructose-glucose (FRU-GLU) was developed as an ergogenic aid in endurance sports. This study aimed to assess the incidence of dental caries in rats subjected to daily administration of hydrogel-encapsulated FRU-GLU. Hydrogel-encapsulated FRU-GLU was prepared in two forms: spherical beads (BEADS) and gel (GEL; Gel 100, Maurten, Gothenburg, Sweden). A control sugar (CONT) was prepared by blending the alginate gel with FRU-GLU to attain a texture similar to that of GEL. All three formulations contained 27% FRU and 33% GLU. Twenty-four male Wistar rats (3-week-old) were allocated to the BEADS, GEL, and CONT groups (n = 8) on Day 0. Between Day 6 and Day 10, cariogenic bacteria (Streptococcus mutans) were inoculated into the oral cavity of all animals. Additionally, oral administration of sugars (approximately 1 g) began on Day 6 and was repeated daily throughout the 12-week study period. After euthanasia, maxillary and mandibular molars underwent micro-CT analysis. Analysis of 288 molars revealed a significantly lower incidence of distinct dental caries in the BEADS (17.7%) and GEL (21.9%) groups than that in the CONT group (39.6%). Therefore, the use of hydrogel-encapsulated FRU-GLU as a sports fuel may alleviate concerns about the development of dental caries.
Impact of hydrogen peroxide photolysis on viable bacterial count and composition of in vivo dental biofilm-an ex vivo study. 国際誌査読有り

Midori Shirato, Anna Lehrkinder, Keisuke Nakamura, Taro Kanno, Peter Lingström, Ulf Örtengren

BMC oral health　26　(1)　206-206　2025年12月30日

DOI： 10.1186/s12903-025-07588-6 　

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BACKGROUND: A bactericidal technique utilizing hydrogen peroxide (H₂O₂) photolysis, which generates hydroxyl radicals, was developed. Since it has demonstrated the potential to kill in vitro Streptococcus mutans biofilms, this technique has the possibility to be applied to dental caries. However, its efficacy on in vivo cariogenic dental biofilms remains unclear. This study aimed to evaluate the bactericidal effect of H₂O₂ photolysis on in vivo biofilms obtained from volunteers, focusing on its potential application in dental caries treatment. METHODS: Sixteen participants, prescreened for the presence of S. mutans and/or lactobacilli in their saliva, wore custom-made splints with hydroxyapatite (HA) discs for 5 days. The discs with 5-day-old biofilms were subjected to H₂O₂ photolysis or control treatments such as H₂O₂, light-emitting diode (LED) irradiation, or water for 90 s, followed by bacterial culturing and quantitative real-time polymerase chain reaction (qPCR). Statistical significances were assessed using the Steel–Dwass test. Scanning electron microscopy (SEM) and 16S rRNA gene sequencing were also used for biofilm evaluation. Discs with treated-biofilms were reinserted for an additional 5 days to evaluate biofilm regrowth and community shifts. RESULTS: SEM confirmed biofilm formation on HA surfaces. Bactericidal assays showed that the 90-s treatment with H₂O₂ photolysis significantly reduced viable bacterial counts, achieving a 3.5 log colony-forming unit (CFU)/specimen for total bacteria and a 2.6 log CFU/specimen for total streptococci, compared with 5.9- and 5.4 log CFU/specimen in the untreated controls, respectively (p < 0.05). qPCR confirmed that the bacterial proportion was initially equivalent across the groups and remained unchanged after regrowth. The 16 S sequencing revealed a diverse microbial community dominated by Streptococcus spp. No significant differences in alpha or beta diversity were observed between the treatment groups even after regrowth. CONCLUSION: These findings suggest that the H₂O₂ photolysis technique can kill bacteria within in vivo biofilms. The observed bactericidal effect supports the potentiality of H₂O₂ photolysis as a promising adjunctive approach for dental caries.
Therapeutic Potential of Proanthocyanidins in Dentistry: A Focus on Periodontal Disease and on Dental Implants in Osteoporotic Patients. 国際誌査読有り

Yoshimi Niwano, Shunichi Shishido, Midori Shirato, Hidetsugu Kohzaki, Keisuke Nakamura

Antioxidants (Basel, Switzerland)　14　(7)　2025年7月10日

DOI： 10.3390/antiox14070850 　

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Proanthocyanidins (PACs), also called condensed tannins, are oligomers or polymers composed of flavan-3-ols. This review aimed to explore the potential role of PACs in ameliorating oral health problems, with a particular focus on their effects within the intestine-especially the colon, where most orally ingested PACs are believed to accumulate. Previous studies suggest that PACs can be beneficial in periodontal disease as well as in the osseointegration of dental implants in patients with osteoporosis. Periodontal disease is worsened by lipopolysaccharides (LPS) that enter the bloodstream due to disrupted tight junctions of intestinal epithelial cells, along with inflammatory cytokines released by activated macrophages. A similar mechanism is thought to affect osseointegration: LPS-induced inflammatory cytokines originating in the intestine can enter the bloodstream, contributing to bone loss and impaired integration of dental implants. PACs absorbed by intestinal epithelial cells can function as prooxidants, triggering the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which strengthens the gut barrier. This enhanced barrier reduces the levels of LPS and inflammatory cytokines in the blood, leading to the alleviation of periodontal inflammation and increased alveolar bone density, thereby promoting better osseointegration of dental implants.
Mutagenicity assessment of high-power 1.6-THz pulse laser radiation. 国際誌査読有り

Midori Shirato, Yuma Takida, Taro Kanno, Hiroshi Matsuura, Yoshimi Niwano, Hiroaki Minamide, Keisuke Nakamura

Photochemistry and photobiology　100　(1)　146-158　2024年

DOI： 10.1111/php.13840 　

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The effect of terahertz (THz) radiation has been studied in medicine. However, there is a lack of scientific information regarding its possible mutagenicity. Therefore, the present study aimed to assess the mutagenicity of 1.6 THz laser irradiation. The Ames test was conducted using five bacterial tester strains. The bacteria were subjected to (i) 1.6 THz laser irradiation at 3.8 mW/cm2 for 60 min using a tabletop THz pulse laser system, (ii) ultraviolet irradiation, (iii) treatment with positive control chemicals (positive control) or (iv) treatment with the solvent used in the positive control (negative control). After treatment, the bacterial suspensions were cultured on minimal glucose agar to determine the number of revertant colonies. In addition, the comet assay was performed using fibroblasts (V79) to assess possible DNA damage caused by the THz laser irradiation. The Ames test demonstrated that the THz laser irradiation did not increase the number of revertant colonies compared to that in the negative control group, whereas the ultraviolet irradiation and positive control treatment increased the number of revertant colonies. Thus, 1.6 THz laser irradiation is unlikely to be mutagenic. The comet assay additionally suggests that the THz laser irradiation unlikely induce cellular DNA damage.
Inhibition of tooth demineralization caused by Streptococcus mutans biofilm via antimicrobial treatment using hydrogen peroxide photolysis. 国際誌査読有り

Midori Shirato, Keisuke Nakamura, Taichi Tenkumo, Yoshimi Niwano, Taro Kanno, Keiichi Sasaki, Peter Lingström, Ulf Örtengren

Clinical oral investigations　27　(2)　739-750　2023年2月

DOI： 10.1007/s00784-022-04821-2 　

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OBJECTIVES: An antimicrobial technique utilizing hydroxyl radicals generated by the photolysis of 3% H2O2 has been developed recently. The present study aimed to evaluate the effect of H2O2 photolysis treatment on tooth demineralization caused by Streptococcus mutans biofilm. MATERIALS AND METHODS: To induce tooth demineralization, S. mutans biofilm was allowed to form on the maxillary first molars collected from Wistar rats via 24-h culturing. The samples were immersed in 3% H2O2 and irradiated with 365-nm LED (H2O2 photolysis treatment). Viable bacterial counts in the biofilm were evaluated immediately after treatment and after an additional 30-h culturing by colony counting. The acidogenicity of the biofilm, re-established 30 h after treatment, was assessed by measuring the pH. The effect of H2O2 photolysis treatment on tooth demineralization was assessed by measuring the depth of the radiolucent layer in micro-CT images. RESULTS: H2O2 photolysis significantly reduced viable bacterial counts in the biofilm to 3.7 log colony forming units (CFU)/sample, while the untreated group had 7.9 log CFU/sample. The pH of the biofilm re-established after treatment (6.6) was higher than that of the untreated group (5.3). In line with the pH measurement, the treatment group had a significantly lower depth of radiolucent layer in dentin than the untreated group. CONCLUSIONS: H2O2 photolysis treatment was effective not only in killing the biofilm-forming S. mutans but also in lowering the acidogenicity of the biofilm. Thus, this technique could inhibit tooth demineralization. CLINICAL RELEVANCE: H2O2 photolysis can be applicable as a new dental caries treatment.
Metabolic Fate of Orally Ingested Proanthocyanidins through the Digestive Tract 査読有り

Yoshimi Niwano, Hidetsugu Kohzaki, Midori Shirato, Shunichi Shishido, Keisuke Nakamura

Antioxidants　12　(1)　17-17　2022年12月22日
出版者・発行元： MDPI AG
DOI： 10.3390/antiox12010017 　

eISSN：2076-3921

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Proanthocyanidins (PACs), which are oligomers or polymers of flavan-3ols with potent antioxidative activity, are well known to exert a variety of beneficial health effects. Nonetheless, their bioaccessibility and bioavailability have been poorly assessed. In this review, we focused on the metabolic fate of PACs through the digestive tract. When oligomeric and polymeric PACs are orally ingested, a large portion of the PACs reach the colon, where a small portion is subjected to microbial degradation to phenolic acids and valerolactones, despite the possibility that slight depolymerization of PACs occurs in the stomach and small intestine. Valerolactones, as microbiota-generated catabolites of PACs, may contribute to some of the health benefits of orally ingested PACs. The remaining portion interacts with gut microbiota, resulting in improved microbial diversity and, thereby, contributing to improved health. For instance, an increased amount of beneficial gut bacteria (e.g., Akkermansia muciniphila and butyrate-producing bacteria) could ameliorate host metabolic functions, and a lowered ratio of Firmicutes/Bacteroidetes at the phylum level could mitigate obesity-related metabolic disorders.
Putative Mechanisms Underlying the Beneficial Effects of Polyphenols in Murine Models of Metabolic Disorders in Relation to Gut Microbiota 査読有り

Yoshimi Niwano, Hidetsugu Kohzaki, Midori Shirato, Shunichi Shishido, Keisuke Nakamura

Current Issues in Molecular Biology　44　(3)　1353-1375　2022年3月18日
出版者・発行元： MDPI AG
DOI： 10.3390/cimb44030091 　

eISSN：1467-3045

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The beneficial effects of polyphenols on metabolic disorders have been extensively reported. The interaction of these compounds with the gut microbiota has been the focus of recent studies. In this review, we explored the fundamental mechanisms underlying the beneficial effects of polyphenols in relation to the gut microbiota in murine models of metabolic disorders. We analyzed the effects of polyphenols on three murine models of metabolic disorders, namely, models of a high-fat diet (HFD)-induced metabolic disorder, dextran sulfate sodium (DSS)-induced colitis, and a metabolic disorder not associated with HFD or DSS. Regardless of the model, polyphenols ameliorated the effects of metabolic disorders by alleviating intestinal oxidative stress, improving inflammatory status, and improving intestinal barrier function, as well as by modulating gut microbiota, for example, by increasing the abundance of short-chain fatty acid-producing bacteria. Consequently, polyphenols reduce circulating lipopolysaccharide levels, thereby improving inflammatory status and alleviating oxidative imbalance at the lesion sites. In conclusion, polyphenols likely act by regulating intestinal functions, including the gut microbiota, and may be a safe and suitable therapeutic agent for various metabolic disorders.
Anti-Osteoporotic Mechanisms of Polyphenols Elucidated Based on In Vivo Studies Using Ovariectomized Animals. 国際誌査読有り

Yoshimi Niwano, Hidetsugu Kohzaki, Midori Shirato, Shunichi Shishido, Keisuke Nakamura

Antioxidants (Basel, Switzerland)　11　(2)　2022年1月23日

DOI： 10.3390/antiox11020217 　

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Polyphenols are widely known for their antioxidant activity, i.e., they have the ability to suppress oxidative stress, and this behavior is mediated by the autoxidation of their phenolic hydroxyl groups. Postmenopausal osteoporosis is a common health problem that is associated with estrogen deficiency. Since oxidative stress is thought to play a key role in the onset and progression of osteoporosis, it is expected that polyphenols can serve as a safe and suitable treatment in this regard. Therefore, in this review, we aimed to elucidate the anti-osteoporotic mechanisms of polyphenols reported by in vivo studies involving the use of ovariectomized animals. We categorized the polyphenols as resveratrol, purified polyphenols other than resveratrol, or polyphenol-rich substances or extracts. Literature data indicated that resveratrol activates sirtuin 1, and thereafter, suppresses osteoclastogenic pathways, such as the receptor activator of the nuclear factor kappa B (RANK) ligand (RANKL) pathway, and promotes osteoblastogenic pathways, such as the wingless-related MMTV integration site pathway. Further, we noted that purified polyphenols and polyphenol-rich substances or extracts exert anti-inflammatory and/or antioxidative effects, which inhibit RANKL/RANK binding via the NF-κB pathway, resulting in the suppression of osteoclastogenesis. In conclusion, antioxidative and anti-inflammatory polyphenols, including resveratrol, can be safe and effective for the treatment of postmenopausal osteoporosis based on their ability to regulate the imbalance between bone formation and resorption.
Gene transfection achieved by utilizing antibacterial calcium phosphate nanoparticles for enhanced regenerative therapy. 国際誌

Chen Xiang, Taichi Tenkumo, Toru Ogawa, Yoshiaki Kanda, Keisuke Nakamura, Midori Shirato, Viktoriya Sokolova, Matthias Epple, Yuya Kamano, Hiroshi Egusa, Keiichi Sasaki

Acta biomaterialia　119　375-389　2021年1月1日

DOI： 10.1016/j.actbio.2020.11.003 　

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Protamine-coated multi-shell calcium phosphate (CaP) was developed as a non-viral vector for tissue regeneration therapy. CaP nanoparticles loaded with different amounts of plasmid DNA encoding bone morphogenetic protein 2 (BMP-2) and insulin-like growth factor 1 (IGF-1) were used to treat MC3T3E1 cells, and the yield of the released BMP-2 or IGF-1 was measured using ELISA 3 days later. Collagen scaffolds containing CaP nanoparticles were implanted into rat cranial bone defects, and BMP-2 and IGF-1 yields, bone formation, and bone mineral density enhancement were evaluated 28 days after gene transfer. The antibacterial effects of CaP nanoparticles against Streptococcus mutans and Aggregatibacter actinomycetemcomitans increased with an increase in the protamine dose, while they were lower for Staphylococcus aureus and Porphyromonas gingivalis. In the combination treatment with BMP-2 and IGF-1, the concentration ratio of BMP-2 and IGF-1 is an important factor affecting bone formation activity. The calcification activity and OCN mRNA of MC3T3E1 cells subjected to a BMP-2:IGF-1 concentration ratio of 1:4 was higher at 14 days. During gene transfection treatment, BMP-2 and IGF-1 were released simultaneously after gene transfer; the loaded dose of the plasmid DNA encoding IGF-1 did not impact the BMP-2 or IGF-1 yield or new bone formation ratio in vitro and in vivo. In conclusion, two growth factor-releasing systems were developed using an antibacterial gene transfer vector, and the relationship between the loaded plasmid DNA dose and resultant growth factor yield was determined in vitro and in vivo.
Proanthocyanidin-rich grape seed extract improves bone loss, bone healing, and implant osseointegration in ovariectomized animals 査読有り

Taichi Tenkumo, Alkebaier Aobulikasimu, Yoshinori Asou, Midori Shirato, Shunichi Shishido, Taro Kanno, Yoshimi Niwano, Keiichi Sasaki, Keisuke Nakamura

Scientific Reports　10　(1)　2020年12月
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1038/s41598-020-65403-4 　

eISSN：2045-2322
Reactions of dental pulp to hydrogen peroxide photolysis-based antimicrobial chemotherapy under ultraviolet-A irradiation in rats. 国際誌査読有り

Keisuke Nakamura, Midori Shirato, Shunichi Shishido, Yoshimi Niwano, Taro Kanno, Keiichi Sasaki, Peter Lingström, Ulf Örtengren

Journal of photochemistry and photobiology. B, Biology　212　112042-112042　2020年11月

DOI： 10.1016/j.jphotobiol.2020.112042 　

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Hydrogen peroxide photolysis-based antimicrobial chemotherapy that utilizes ultraviolet-A irradiation (UVA-H2O2 photolysis) has been previously proposed as a method of treatment of cariogenic biofilm. Therefore, in the present study, we aimed to assess time-dependent reactions in the dental pulp of rats after UVA-H2O2 photolysis. Maxillary first molars were treated. UVA irradiation (wavelength: 365 nm) with 3 wt% H2O2 was performed for 90 s at a radiant emittance of 500-2000 mW/cm2 on the rats for 3 consecutive days or only 1 day. The animals were sacrificed at Days 1, 3, 7, and 21 after the treatment for the histological evaluation of inflammatory cells and immunohistochemistry of heat shock protein (HSP)-25, a marker of odontoblasts. Tertiary dentin formation was evaluated at Day 21 by histomorphometry and micro-CT analysis. UVA-H2O2 photolysis elicited little infiltration of inflammatory cells, but disturbances in the odontoblast layer and/or presence of localized degenerative tissue were observed on Day 3. This condition was followed by a healing process that was characterized by the reappearance of HSP-25 positive odontoblast-like cells at Day 7 and tertiary dentin formation at Day 21. The amount of tertiary dentin formed was dependent on the intensity of treatment; repeated UVA irradiations of H2O2 at 2000 mW/cm2 resulted in the largest amount of tertiary dentin formation at the pulp horn regions. Our findings suggest that UVA-H2O2 photolysis treatment can be used to treat dental caries clinically because the post-treatment inflammatory reaction was minimal and tertiary dentin formation was substantial, which may prove effective in protecting dental pulp from external irritants. As a cautionary consideration, the radiant emittance of the UVA irradiation should be carefully optimized before clinical application.
Bactericidal activity and recovery effect of hydroxyl radicals generated by ultraviolet irradiation and silver ion application on an infected titanium surface. 国際誌査読有り

Taichi Tenkumo, Kirika Ishiyama, Oleg Prymak, Keisuke Nakamura, Midori Shirato, Toru Ogawa, Makiko Miyashita, Masatoshi Takahashi, Matthias Epple, Taro Kanno, Keiichi Sasaki

Scientific reports　10　(1)　8553-8553　2020年5月22日

DOI： 10.1038/s41598-020-65411-4 　

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This study investigated the bactericidal effect, the underlying mechanisms of treatment, and recovery of biocompatibility of the infected titanium surface using a combination treatment of silver ion application and ultraviolet-A (UV-A) light irradiation. Streptococcus mutans and Aggregatibacter actinomycetemcomitans were used in suspension and as a biofilm on a titanium surface to test for the bactericidal effect. The bactericidal effect of the combination treatment was significantly higher than that of silver ion application or UV-A light irradiation alone. The bactericidal effect of the combination treatment was attributable to hydroxyl radicals, which generated from the bacterial cell wall and whose yield increased with the silver concentration. To assess the biocompatibility, proliferation and calcification of MC3T3E1 cells were evaluated on the treated titanium surface. The treated titanium screws were implanted into rat tibias and the removal torques were measured 28 days post-surgery. The titanium surface that underwent the combination treatment exhibited recovery of biocompatibility by allowing cellular proliferation or calcification at levels observed in the non-infected titanium surfaces. The removal torque 28 days after surgery was also comparable to the control values. This approach is a novel treatment option for peri-implantitis.
Oral mucosal irritation potential of antimicrobial chemotherapy involving hydrogen peroxide photolysis with high-power laser irradiation for the treatment of periodontitis. 国際誌査読有り

Midori Shirato, Keisuke Nakamura, Taichi Tenkumo, Yuki Kano, Kirika Ishiyama, Taro Kanno, Keiichi Sasaki, Yoshimi Niwano, Hiroshi Matsuura

Journal of photochemistry and photobiology. B, Biology　201　111633-111633　2019年12月

DOI： 10.1016/j.jphotobiol.2019.111633 　

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In the present study, we assessed the oral mucosal irritation potential of antimicrobial chemotherapy involving hydrogen peroxide (H2O2) photolysis with a 405-nm laser device at an output power of ≥100 mW in hamsters. Twenty-four cheek pouches from 12 male Syrian hamsters received 7-min treatment with pure water (PW), 3% H2O2, laser irradiation of PW at 100 mW, laser irradiation of 3% H2O2 at 100 mW, laser irradiation of PW at 200 mW, or laser irradiation of 3% H2O2 at 200 mW (n = 4 each). The diameter of the irradiation area was set at 3 mm; accordingly, the calculated irradiances (optical power densities) of the 100- and 200-mW laser lights were approximately 1400 and 2800 mW/cm2, respectively. In addition, 12 cheek pouches from six animals received laser irradiation of 3% H2O2 at 100 mW for 1, 3, or 5 min (n = 4 each). Each treatment was repeated three times at 1-h intervals. Macroscopic and histological changes were evaluated 24 h after the last treatment. In addition, in vitro bactericidal activity of the treatment against periodontal pathogens was evaluated. We found that 405-nm laser irradiation of 3% H2O2 caused moderate to severe oral mucosal irritation when performed at powers of 100 and 200 mW for ≥3 min, while the same treatment performed at 100 mW for 1 min resulted in mild irritation. Moreover, 1-min H2O2 photolysis at 100 mW caused a >4-log decrease in viable bacterial counts. These findings suggest that 1-min H2O2 photolysis, which can effectively kill periodontal pathogens, may be acceptable when a 405-nm laser device is used at 100 mW. However, use of the laser at a lower power would be preferable for the prevention of unnecessary oral mucosal irritation.
医師主導治験におけるラジカル殺菌歯周病治療器の臨床効果の検証無作為化比較試験査読有り

佐々木啓一, 菅野太郎, 中村圭祐, 石山希里香, 山田康友, 白土翠, 庭野吉己, 萱場千恵, 池田浩治, 高木愛理, 山口拓洋

日本歯周病学会会誌　61　(春季特別)　127-127　2019年5月
出版者・発行元： (NPO)日本歯周病学会
ISSN：0385-0110

eISSN：1880-408X
Hydroxyl radicals generated by hydrogen peroxide photolysis recondition biofilm-contaminated titanium surfaces for subsequent osteoblastic cell proliferation. 国際誌査読有り

Keisuke Nakamura, Midori Shirato, Taichi Tenkumo, Taro Kanno, Anna Westerlund, Ulf Örtengren, Keiichi Sasaki, Yoshimi Niwano

Scientific reports　9　(1)　4688-4688　2019年3月18日

DOI： 10.1038/s41598-019-41126-z 　

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Titanium dental implants have been successfully used for decades; however, some implants are affected by peri-implantitis due to bacterial infection, resulting in loss of supporting bone. This study aimed to evaluate the effect of an antimicrobial chemotherapy employing H2O2 photolysis-developed to treat peri-implantitis-on biofilm-contaminated titanium surfaces in association with osteoblastic cell proliferation on the treated surface. Titanium discs were sandblasted and acid-etched, followed by contamination with a three-species biofilm composed of Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mitis. This biofilm model was used as a simplified model of clinical peri-implantitis biofilm. The discs were subjected to ultrasound scaling, followed by H2O2 photolysis, wherein 365-nm LED irradiation of the disc immersed in 3% H2O2 was performed for 5 min. We analysed proliferation of mouse osteoblastic cells (MC3T3-E1) cultured on the treated discs. Compared with intact discs, biofilm contamination lowered cell proliferation on the specimen surface, whereas H2O2 photolysis recovered cell proliferation. Thus, H2O2 photolysis can recover the degraded biocompatibility of biofilm-contaminated titanium surfaces and can potentially be utilised for peri-implantitis treatment. However, to verify the findings of this study in relation to clinical settings, assessment using a more clinically relevant multi-species biofilm model is necessary.
Potential adverse effects of antimicrobial chemotherapy based on ultraviolet-A irradiation of polyphenols against the oral mucosa in hamsters and wounded skin in rats. 国際誌査読有り

Keisuke Nakamura, Taichi Tenkumo, Takayuki Mokudai, Midori Shirato, Kirika Ishiyama, Taro Kanno, Keiichi Sasaki, Yoshimi Niwano

Journal of photochemistry and photobiology. B, Biology　187　96-105　2018年10月

DOI： 10.1016/j.jphotobiol.2018.08.006 　

ISSN：1011-1344

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Antimicrobial chemotherapy based on ultraviolet-A (UVA) irradiation of polyphenol solution has been proposed as an adjunctive treatment for dental caries. However, the safety of this treatment has not been thoroughly evaluated. Therefore, the aim of the present study was to assess the influence of this treatment on the oral mucosa in hamsters and wounded skin in rats. An oral mucosal irritation test was performed in hamsters. The cheek pouch was everted and treated with UVA irradiation (wavelength: 365 nm) of pure water, 1 mg/mL of caffeic acid, or 1 mg/mL of grape seed extract using a light-emitting diode at an irradiance of 275 mW/cm2. Each treatment was performed for 2 or 5 min and repeated three times. Macroscopic and histological evaluations were performed 24 h after the last treatment. We also examined the effects of the treatment on the healing process of skin wounds in rats. Full-thickness skin wounds created on the back of the rats were treated for 2 min as described above, but only once. The wound area was then assessed daily for 9 days. The results demonstrated that the treatment induced oral mucosal irritation depending on the irradiation time; however, it did not influence the wound healing process. The oral mucosal irritation potential of three treatment sessions performed for 2 and 5 min was minimal and mild to moderate, respectively, according to histological analysis. These findings suggest that the duration of treatment based on UVA irradiation of polyphenols in the oral cavity should be as short as possible, considering the clinical efficacy of the antimicrobial effects and the irritation potential.
Surface properties of dental zirconia ceramics affected by ultrasonic scaling and low-temperature degradation. 国際誌査読有り

Kosuke Nakazawa, Keisuke Nakamura, Akio Harada, Midori Shirato, Ryoichi Inagaki, Ulf Örtengren, Taro Kanno, Yoshimi Niwano, Hiroshi Egusa

PloS one　13　(9)　e0203849　2018年

DOI： 10.1371/journal.pone.0203849 　

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Zirconia (3Y-TZP) dental prostheses are widely used in clinical dentistry. However, the effect of ultrasonic scaling performed as a part of professional tooth cleaning on 3Y-TZP dental prostheses, especially in conjunction with low-temperature degradation (LTD), has not been fully investigated. The present study aimed to evaluate the influence of ultrasonic scaling and LTD on the surface properties of 3Y-TZP in relation to bacterial adhesion on the treated surface. 3Y-TZP specimens (4 × 4 × 2 mm) were polished and then subjected to autoclaving at 134°C for 100 h to induce LTD, followed by 10 rounds of ultrasonic scaling using a steel scaler tip for 1 min each. Surface roughness, crystalline structure, wettability, and hardness were analyzed by optical interferometry, X-ray diffraction analysis, contact angle measurement, and nano-indentation technique, respectively. Subsequently, bacterial adhesion onto the treated 3Y-TZP surface was evaluated using Streptococcus mitis and S. oralis. The results demonstrated that the combination of ultrasonic scaling and LTD significantly increased the Sa value (surface roughness parameter) of the polished 3Y-TZP surface from 1.6 nm to 117 nm. LTD affected the crystalline structure, causing phase transformation from the tetragonal to the monoclinic phase, and decreased both the contact angle and surface hardness. However, bacterial adhesion was not influenced by these changes in surface properties. The present study suggests that ultrasonic scaling may be acceptable for debridement of 3Y-TZP dental prostheses because it did not facilitate bacterial adhesion even in the combination with LTD, although it did cause slight roughening of the surface.
Adjunctive antimicrobial chemotherapy based on hydrogen peroxide photolysis for non-surgical treatment of moderate to severe periodontitis: a randomized controlled trial. 国際誌査読有り

Taro Kanno, Keisuke Nakamura, Kirika Ishiyama, Yasutomo Yamada, Midori Shirato, Yoshimi Niwano, Chie Kayaba, Koji Ikeda, Airi Takagi, Takuhiro Yamaguchi, Keiichi Sasaki

Scientific reports　7　(1)　12247-12247　2017年9月25日

DOI： 10.1038/s41598-017-12514-0 　

ISSN：2045-2322
Time-kill kinetic analysis of antimicrobial chemotherapy based on hydrogen peroxide photolysis against Streptococcus mutans biofilm. 国際誌査読有り

Midori Shirato, Keisuke Nakamura, Taro Kanno, Peter Lingström, Yoshimi Niwano, Ulf Örtengren

Journal of photochemistry and photobiology. B, Biology　173　434-440　2017年8月

DOI： 10.1016/j.jphotobiol.2017.06.023 　

ISSN：1011-1344
Photo-irradiated caffeic acid exhibits antimicrobial activity against Streptococcus mutans biofilms via hydroxyl radical formation. 国際誌査読有り

Keisuke Nakamura, Midori Shirato, Taro Kanno, Peter Lingström, Ulf Örtengren, Yoshimi Niwano

Scientific reports　7　(1)　6353-6353　2017年7月25日

DOI： 10.1038/s41598-017-07007-z 　

ISSN：2045-2322
Antimicrobial activity of hydroxyl radicals generated by hydrogen peroxide photolysis against Streptococcus mutans biofilm. 国際誌査読有り

Keisuke Nakamura, Midori Shirato, Taro Kanno, Ulf Örtengren, Peter Lingström, Yoshimi Niwano

International journal of antimicrobial agents　48　(4)　373-80　2016年10月

DOI： 10.1016/j.ijantimicag.2016.06.007 　

ISSN：0924-8579

eISSN：1872-7913
Cytoprotective Effect of Short-Term Pretreatment with Proanthocyanidin on Human Gingival Fibroblasts Exposed to Harsh Environmental Conditions 査読有り

Michiko Kurauchi, Yoshimi Niwano, Midori Shirato, Taro Kanno, Keisuke Nakamura, Hiroshi Egusa, Keiichi Sasaki

PLOS ONE　9　(11)　e113403　2014年11月

DOI： 10.1371/journal.pone.0113403 　

ISSN：1932-6203
Synergistic Effect of Proanthocyanidin on the Bactericidal Action of the Photolysis of H2O2 査読有り

Hiroyo Ikai, Keisuke Nakamura, Taro Kanno, Midori Shirato, Luiz Meirelles, Keiichi Sasaki, Yoshimi Niwano

BIOCONTROL SCIENCE　18　(3)　137-141　2013年9月

DOI： 10.4265/bio.18.137 　

ISSN：1342-4815

eISSN：1884-0205
Photo-Irradiation of Proanthocyanidin as a New Disinfection Technique via Reactive Oxygen Species Formation 査読有り

Keisuke Nakamura, Midori Shirato, Hiroyo Ikai, Taro Kanno, Keiichi Sasaki, Masahiro Kohno, Yoshimi Niwano

PLOS ONE　8　(3)　e60053　2013年3月

DOI： 10.1371/journal.pone.0060053 　

ISSN：1932-6203
In vitro evaluation of the risk of inducing bacterial resistance to disinfection treatment with photolysis of hydrogen peroxide. 国際誌査読有り

Hiroyo Ikai, Yu Odashima, Taro Kanno, Keisuke Nakamura, Midori Shirato, Keiichi Sasaki, Yoshimi Niwano

PloS one　8　(11)　e81316　2013年

DOI： 10.1371/journal.pone.0081316 　

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The purpose of the present study was to evaluate the risk of inducing bacterial resistance to disinfection treatment with photolysis of H2O2 and comparing this with existing antibacterial agents. We tested seven antibacterial agents, including amoxicillin, cefepime hydrochloride, erythromycin, ofloxacin, clindamycin hydrochloride, ciprofloxacin hydrochloride, and minocycline hydrochloride, as positive controls for validation of the assay protocol. For all of the agents tested, at least one of the four bacterial species (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Streptococcus salivarius) was resistant to these agents by repeated exposure to subinhibitory concentrations of the agents up to 10 times. In contrast, antibacterial activity against any of the bacterial species tested (S. aureus, E. faecalis, E. coli, S. salivarius, Pseudomonas aeruginosa, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans) was not affected by repeated exposure to the disinfection treatment up to 40 times. This finding suggested that the risk of inducing bacterial resistance by disinfection treatment was low. The active ingredient of this disinfection treatment is hydroxyl radicals generated by photolysis of H2O2. Therefore, hydroxyl radicals interact with several cell structures and different metabolic pathways in microbial cells, probably resulting in a lack of development of bacterial resistance. In conclusion, disinfection treatment with photolysis of H2O2 appears to be a potential alternative for existing antimicrobial agents in terms of a low risk of inducing bacterial resistance.
過酸化水素光分解殺菌法に対する熱エネルギーの相乗的効果査読有り

白土翠, 猪飼紘代, 中村圭祐, 林栄成, 菅野太郎, 佐々木啓一, 庭野吉己

日本歯科医師会雑誌　65　(5)　615-615　2012年8月
出版者・発行元： (公社)日本歯科医師会
ISSN：0047-1763
Novel Denture-Cleaning System Based on Hydroxyl Radical Disinfection 査読有り

Taro Kanno, Keisuke Nakamura, Hiroyo Ikai, Eisei Hayashi, Midori Shirato, Takayuki Mokudai, Atsuo Iwasawa, Yoshimi Niwano, Masahiro Kohno, Keiichi Sasaki

INTERNATIONAL JOURNAL OF PROSTHODONTICS　25　(4)　376-380　2012年7月

ISSN：0893-2174
Synergistic effect of thermal energy on bactericidal action of photolysis of H₂O₂ in relation to acceleration of hydroxyl radical generation. 査読有り

Shirato M, Ikai H, Nakamura K, Hayashi E, Kanno T, Sasaki K, Kohno M, Niwano Y

Antimicrobial agents and chemotherapy　56　(1)　295-301　2012年1月

DOI： 10.1128/AAC.05158-11 　

ISSN：0066-4804
Photolysis of Hydrogen Peroxide, an Effective Disinfection System via Hydroxyl Radical Formation 査読有り

Hiroyo Ikai, Keisuke Nakamura, Midori Shirato, Taro Kanno, Atsuo Iwasawa, Keiichi Sasaki, Yoshimi Niwano, Masahiro Kohno

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY　54　(12)　5086-5091　2010年12月

DOI： 10.1128/AAC.00751-10 　

ISSN：0066-4804

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MISC 3

カフェイン酸に対するUV-A照射で得られる殺菌作用と口腔粘膜刺激性の評価

中村圭祐, 天雲太一, 目代貴之, 白土翠, 石山希里香, 菅野太郎, 佐々木啓一, 庭野吉己

日本防菌防黴学会年次大会要旨集　45th　2018年
Bactericidal effect of hydroxyl radical generated by photolysis of hydrogen peroxide

Hiroyo Ikai, Keisuke Nakamura, Midori Shirato, Taro Kanno, Atsuo Iwasawa, Yoshimi Niwano, Keiichi Sasaki, Masahiro Kohno

Interface Oral Health Science 2011　86-88　2012年1月1日

DOI： 10.1007/978-4-431-54070-0_14 　
Booster effect of thermal energy on bactericidal action of hydroxyl radical generated by photolysis of H<inf>2</inf>O<inf>2</inf>

Midori Shirato, Hiroyo Ikai, Keisuke Nakamura, Eisei Hayashi, Taro Kanno, Keiichi Sasaki, Masahiro Kohno, Yoshimi Niwano

Interface Oral Health Science 2011　150-152　2012年1月1日

DOI： 10.1007/978-4-431-54070-0_38

共同研究・競争的資金等の研究課題 6

グルカンの光化学反応を介した革新的殺菌技術の確立：インプラント周囲炎治療への応用

中村圭祐, 宍戸駿一, 菅野太郎, 松浦寛, 庭野吉己, 白土翠

2026年4月1日～ 2030年3月31日
閉経女性歯科インプラント成功率の改善：ポリフェノールの骨結合強化メカニズムの解明

庭野吉己, 宍戸駿一, 中村圭祐, 白土翠

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Shumei University

2023年4月1日～ 2026年3月31日

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プロアントシアニジン (PA) の酸化促進作用をin vitroで検証した。PAのフェノール性水酸基の自然酸化による過酸化水素 (H2O2)の生成をAmplex Red assayにより定量するとともに遷移金属(Fe2+など)存在下および非存在下での水酸化ラジカル (・OH) の生成を電子スピン共鳴 (ESR)-スピントラッピング法により測定した。以下に示すようにPAの酸化促進作用をPA濃度依存的な過酸化水素およびFe2+存在下での水酸化ラジカル生成から確認した。 <BR> Ⅰ. 過酸化水素の生成の検証：PAを純水に溶解し、濃度1.0 mg/mLとし、希釈して0.5, 0.25 mg/mLを調製した。37℃ （サーモブロック）、遮光条件で3, 6, 24, 48 時間インキュベート後に測定した。その結果、24時間以上でPAの濃度依存的に過酸化水素を検出した。 <BR> Ⅱ. Amplex Red法でH2O2生成を確認できた24時間以上の条件でESR測定：1) PAを純水に溶解させ、濃度 1.0, 0.5, 0.25 mg/mLの溶液をそれぞれ調製した。PA溶液 966 u1;L + DMPO (スピントラップ剤、8.9 M) 34 u1;Lで混和し、37℃（ヒートブロック）、遮光、24 時間保管後にESR測定した。結果、PA濃度に関係なく微量のDMPO-OH (・OHのスピントラップ)を検出した。DMPOが自動酸化されている可能性が示唆された。2) PAを純水に溶解させ、濃度 1.0, 0.5, 0.25 mg/mLの溶液をそれぞれ調製した。37℃（ヒートブロック）、遮光、24時間保管後、PA溶液 160 u1;L + DMPO溶液 (3 M) 20 u1;L + FeSO4 (2.5 M) 20 uL 混和60 秒後にESR測定した。結果、PA濃度依存的にDMPO-OHを検出した。
超高齢社会におけるプラーク制御法の確立－活性酸素を応用したバイオフィルム不活化－

白土翠, 宍戸駿一, 中村圭祐

2022年4月1日～ 2025年3月31日
ブラックライト照射によるホルミシス効果を応用した象牙質形成誘導の基盤技術確立

中村圭祐, 宍戸駿一, 白土翠

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Tohoku University

2022年4月1日～ 2025年3月31日
リン酸カルシウム遺伝子導入剤による機能性抗菌コーティングのインプラント周囲炎応用

天雲太一, 石山希里香, 中村圭祐, 白土翠

2020年4月1日～ 2023年3月31日

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インプラント治療は表面性状の発展に伴い治療の成功率が飛躍的に向上することで、世界的に普及する治療方法となった半面、インプラント周囲炎の報告も増加している。しかし、インプラント周囲炎に対する有効な治療方法はまだないことが歯科治療において大きな問題となっている。インプラント治療では、細菌などで汚染した表面の殺菌療法だけでは不十分で、その後に骨の再付着を誘導するようなシステムの確立が重要となる。そこで、本研究ではラジカル殺菌処置後に抗菌性リン酸カルシウム遺伝子導入ナノ粒子によるコーティング層を構築することで、再感染予防と再オステオインテグレーションの獲得をする新しいインプラント周囲組織再生療法を確立することを目的としている。まず、「リン酸カルシウムコーティング層の作製条件」を検証したところ、照射強度や照射時間は一定量を超えると、リン酸カルシウムの粒子の付着量に変化がなくなり、上限があることが明らかにしてきた。また、殺菌効果については、同じ照射強度、照射時間でも対象となる細菌の濃度には適正濃度があること、その適正濃度は細菌の種類によって異なることが明らかとなった。一方、「CaP コーティング層の表面性状、生体親和性」について解析したところ、菌種によってはリン酸カルシウム自体が細菌の増殖を助長していることが確認された。そこで、新たにこれまでと異なる抗菌ペプチドを付与したリン酸カルシウムナノ粒子を製作し、同細菌に対して殺菌試験を行ったところ、リン酸カルシウム自体による細菌増殖効果が抑制されることが明らかとなった。現在は同リン酸カルシウムナノ粒子の遺伝子導入効率や生体親和性をインプラント周囲に存在する歯周組織関連細胞を用いて検証している。
過酸化水素光分解殺菌法を応用した低侵襲齲蝕治療の確立

白土翠

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Early-Career Scientists

研究機関：Tohoku University

2019年4月1日～ 2022年3月31日

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過酸化水素光分解殺菌法とは、過酸化水素に波長≦400 nmの光を照射することで生成される活性酸素を利用した新しい殺菌技術である。本研究では、その技術を齲蝕治療の分野に応用することを目的とし、齲蝕関連細菌のバイオフィルム（細菌の集合体・口腔内では歯垢として存在）に対する殺菌効果および、齲蝕進行抑制効果を検証した。一連の研究で、本殺菌法は口腔内で齲蝕を引き起こす歯垢に対する高い殺菌効果を発揮し、その殺菌効果に伴って齲蝕の進行を抑制できる可能性が示唆された。

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