研究者詳細 - 山本　直史

論文 - 山本　直史

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Establishment of a rapid and quantitative method for detecting the range of infection exposure in preclinical dental education. 国際誌

Ayaka Ueda, Yuki Shinoda-Ito, Kazu Takeuchi-Hatanaka, Takashi Ito, Shintaro Ono, Kimito Hirai, Kazuhiro Omori, Tadashi Yamamoto, Shogo Takashiba

BMC oral health 25 ( 1 ) 199 - 199 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUNDS: Safe dental treatments that prevent nosocomial and cross-infections are essential for patients and dental workers. However, dental students sometimes pay inadequate attention to infection control, especially in preclinical practice, because of too much focus on technical training, such as the use of equipment, etc. The spread of infections such as SARS-CoV-2, antibiotic-resistant bacteria, and oral bacteria are sometimes lethal for medically compromised patients. Thus, the rapid and inexpensive detection system to detect and measure dental practice-related infection spread during preclinical treatment is highly desired for dental education. This study aimed to establish a method to quantify and visualize infected areas using dental phantoms for safe and effective preclinical dental practices. METHODS: At first, we developed artificial saliva as an in vitro study, including food-derived bacteria and fluorescence dye, which is safe for application to preclinical practice education. In vitro study, the correlation between adenosine triphosphate (ATP) levels and Lactobacillus colony numbers in yogurt was examined using the ATP fluorescent method, with colony counting on yogurt only and a mixture of yogurt and ultraviolet (UV)-sensitive hand lotion. The mixed liquid of yogurt and hand lotion was used as artificial saliva. Second, we used this artificial saliva in preclinical education. The degree of contamination of personal protective equipment and dental chairs in preclinical practice using this artificial saliva was determined using the ATP fluorescent method and measuring the luminescence areas among 10 dentists, 10 dental residents, and 10 fifth-grade dental students. RESULTS: ATP levels and Lactobacillus colony numbers in yogurt were positively correlated with yogurt alone and a mixture of yogurt and UV-sensitive hand lotions (correlation coefficient ≒ 1). Preclinical education using a mixture of artificial saliva successfully quantified and visualized infectious areas and droplets, which revealed significant differences in ATP amounts in personal protective equipment among groups according to years of experience as dental practitioners (p < 0.05). CONCLUSIONS: An education system for infection control constructed using artificial saliva containing Lactobacillus and a UV-sensitive fluorescent hand lotion quantified the infectious areas and degrees. Thus, this method is effective in preclinical practice using dental phantoms.

DOI： 10.1186/s12903-025-05584-4

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Effectiveness of oral health care intervention for stroke patients following the introduction of Oral Health Assessment Tool. 査読

Kazuyuki Matsunaga, Ayaka Yoshida-Tsuboi, Ken Inohara, Yasuko Yoshida, Kanako Nakahama, Kazuki Sasaki, Fumie Souda, Yuka Terasawa, Yutaka Shimoe, Kazu Takeuchi-Hatanaka, Tadashi Yamamoto, Kazuhiro Omori, Tatsuo Kohriyama, Shogo Takashiba

Geriatrics & gerontology international 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: This study aimed to evaluate the effectiveness of oral health assessment tools in facilitating oral health care interventions by dental care providers for acute stroke patients within 48 h of admission, following a reform of the nursing system. METHODS: Data were gathered from a retrospective cohort study conducted at a stroke center, comparing 10 months before and after the implementation of the reformed system, with a 2-month interval. Parameters assessed included stroke type, severity measured using the National Institutes of Health Stroke Scale, stroke history, stroke-related factors, number of teeth, hospitalization cost and duration, occurrence of fever and pneumonia, stroke treatment, days from admission to dental intervention, and intervention frequency. RESULTS: Implementation of the new system significantly reduced the time before dental intervention (P < 0.001), increased the frequency of interventions (P < 0.001), and allowed for the management of more severe cases (P = 0.007). However, there was a slight increase in the occurrence of fevers and the days of fever (P = 0.039 and P = 0.015, respectively). Multiple regression analysis showed that fever days were positively correlated with stroke severity and the number of days from admission to dental intervention (P < 0.001 and P = 0.013, respectively). Even after propensity score matching adjusting for stroke severity, these associations persisted. Additional multiple regression analysis was performed after this, but fever days were positively correlated with stroke severity and sex (P < 0.001 and P = 0.008, respectively), as well as with the presence of other factors affecting the occurrence of fever. CONCLUSIONS: Although the frequency and duration of fevers increased slightly, this approach, incorporating oral health assessment tools, made it possible to provide early dental intervention, particularly for patients with severe strokes. Geriatr Gerontol Int 2024; ••: ••-••.

DOI： 10.1111/ggi.15035

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B-catenin binds to Gsk-3b in liquid-liquid phase separation compartment inHEK293 cells 査読

Kato M, Tanai A, Fukuhara Y, Zheng X, Sitosari H, Yamamoto T, Ikegami M, Okamura H

33 ( 4 ) 213 - 218 2024年10月

Resolvin D2-induced reparative dentin and pulp stem cells after pulpotomy in a rat model 査読

Mitsuhiro Yoneda, Hidetaka Ideguchi, Shin Nakamura, Zulema Arias, Mitsuaki Ono, Kazuhiro Omori, Tadashi Yamamoto, Shogo Takashiba

Heliyon 10 ( 13 ) e34206 - e34206 2024年7月

Bacterial DNA and serum IgG antibody titer assays for assessing infection of human-pathogenic and dog-pathogenic Porphyromonas species in dogs 査読

Masako Tai-Tokuzen, Takashi Ito, Kazuya Tamura, Haruko Hirayama, Hirohito Ogawa, Shin Nakamura, Keisuke Okubo, Kazuhiro Omori, Tadashi Yamamoto, Katsumi Mominoki, Shogo Takashiba

Heliyon 10 ( 11 ) e31872 - e31872 2024年6月

Ligneous periodontitis exacerbated by Behçet's disease in a patient with plasminogen deficiency and a stop-gained variant PLG c.1468C > T: a case report. 査読国際誌

Yuki Shinoda-Ito, Anna Hirai, Kazuhiro Omori, Hidetaka Ideguchi, Hideki Yamamoto, Fumino Kato, Kyoichi Obata, Tatsuo Ogawa, Keisuke Nakano, Takato Nakadoi, Eri Katsuyama, Soichiro Ibaragi, Tadashi Yamamoto, Hitoshi Nagatsuka, Akira Hirasawa, Shogo Takashiba

BMC oral health 23 ( 1 ) 843 - 843 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. CASE PRESENTATION: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. CONCLUSIONS: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

DOI： 10.1186/s12903-023-03586-8

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歯内治療が原因で菌血症となった単心室症患者の一症例査読

大森一弘, 杜徳尚, 井手口英隆, 岡本憲太郎, 佐光秀文, 児玉加奈子, 山本直史, 赤木禎治, 笠原真悟, 伊藤浩, 高柴正悟

日本成人先天性心疾患学会雑誌 12 ( 2 ) 30 - 36 2023年5月

記述言語：日本語出版者・発行元：(一社)日本成人先天性心疾患学会

歯科治療は,観血的処置にはみえなくても菌血症を起こすリスクが高い.今回,感染性心内膜炎(IE)高リスクに分類されるフォンタン手術後の患者が歯科治療に起因すると考えられる感染症を起こし,緊急入院に至る症例を経験した.患者は20歳の男性.多脾症候群,右室型単心室に対して,両側両方向性グレン手術とフォンタン手術の手術歴がある.2021年6月,近医で下顎左側第二大臼歯(#37)の慢性根尖性歯周炎の診断のもと,予防的抗菌薬の投与なく歯内治療を開始した.2021年7月,治療中の#37部の自発痛,悪寒,戦慄,発熱を自覚し,当院循環器内科を緊急受診した.履歴から歯性感染が疑われたため,当院歯周科へ緊急紹介され,#37急性根尖性歯周炎と診断した.IE高リスク患者のため緊急入院となり,経験的抗菌療法を開始した.入院5日目,抗菌薬持続投与下で#37の歯内治療を再開,入院12日目に歯内治療を終了,入院13日目に退院した.今回の症例を教訓に,患者自身が歯科治療に先立ち予防的抗菌薬投与の必要性を簡便に提示できる患者カードを作成した.本カードが適切に運用され,歯科治療由来のIE発症リスクが軽減されることを期待する.(著者抄録)

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Personalized Preclinical Training in Dental Ergonomics and Endodontics in Undergraduate Dentistry Students (Pilot Study). 査読

Zulema Arias, Stephanie Haines, Tadashi Yamamoto, Kazu Hatanaka, Keisuke Yamashiro, Norihiro Sonoi, Shogo Takashiba

Acta medica Okayama 77 ( 2 ) 147 - 159 2023年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

The curriculum at the Department of Pathophysiology in the Periodontal Sciences program at Okayama University includes normative preclinical training (NPT) using phantoms. NPT is given to the whole class of 5 th year students divided in groups of 8 students/instructor. In 2019, an innovative personalized preclinical training (PPT) pilot study was implemented for this group of students whereby two students, each with their own dental unit, were coached by one instructor. The main topics covered were dental ergonomics and endodontics. We aimed to evaluate the effectiveness of PPT in dental ergonomics and endodontics toward increasing the knowledge and future clinical skills of students who had already undergone NPT. A test on endodontics was taken before and after PPT. A questionnaire was completed to assess their perception of improvement regarding the above-mentioned topics. Test scores and questionnaire results both showed that the students' level of knowledge and awareness of future clinical skills was significantly higher after PPT. This pilot study demonstrated that PPT increased the students' knowledge and future clinical skills. As preclinical training forms the foundation for clinical practice, investment in future research regarding this personalized approach is likely to enhance students' understanding and clinical performance.

DOI： 10.18926/AMO/65144

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The Fungal Metabolite (+)-Terrein Abrogates Inflammatory Bone Resorption via the Suppression of TNF-α Production in a Ligature-Induced Periodontitis Mouse Model 査読

Hidefumi Sako, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Hidetaka Ideguchi, Saki Yoshimura-Nakagawa, Kyosuke Sakaida, Chiaki Nagata-Kamei, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

Journal of Fungi 9 ( 3 ) 314 - 314 2023年3月

掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Current periodontal treatment focuses on the mechanical removal of the source of infection, such as bacteria and their products, and there is no approach to control the host inflammatory response that leads to tissue destruction. In order to control periodontal inflammation, we have previously reported the optimization of (+)-terrein synthesis methods and the inhibitory effect of (+)-terrein on osteoclast differentiation in vitro. However, the pharmacological effect of (+)-terrein in vivo in the periodontitis model is still unknown. In this study, we investigated the effect of synthetic (+)-terrein on inflammatory bone resorption using a ligature-induced periodontitis mouse model. Synthetic (+)-terrein (30 mg/kg) was administered intraperitoneally twice a week to the mouse periodontitis model. The control group was treated with phosphate buffer. One to two weeks after the induction of periodontitis, the periodontal tissues were harvested for radiological evaluation (micro-CT), histological evaluation (HE staining and TRAP staining), and the evaluation of inflammatory cytokine production in the periodontal tissues and serum (quantitative reverse-transcription PCR, ELISA). The synthetic (+)-terrein-treated group suppressed alveolar bone resorption and the number of osteoclasts in the periodontal tissues compared to the control group (p < 0.05). In addition, synthetic (+)-terrein significantly suppressed both mRNA expression of TNF-α in the periodontal tissues and the serum concentration of TNF-α (both p < 0.05). In conclusion, we have demonstrated that synthetic (+)-terrein abrogates alveolar bone resorption via the suppression of TNF-α production and osteoclast differentiation in vivo. Therefore, we could expect potential clinical effects when using (+)-terrein on inflammatory bone resorption, including periodontitis.

DOI： 10.3390/jof9030314

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患者自身が管理するPHRを活用した安全安心な歯科医療環境の構築査読

高柴正悟, 田上順次, 齋藤正寛, 高橋慶壮, 横瀬敏志, 細矢哲康, 三谷章雄, 山本直史

日本歯科医学会誌(0286-164X)42巻 Page58-64(2023.03) 42 58 - 64 2023年3月

Autophagy as a potential mechanism underlying the biological effect of 1,25-Dihydroxyvitamin D3 on periodontitis: a narrative review. 査読国際誌

Xiaoting Chen, Zulema Arias, Kazuhiro Omori, Tadashi Yamamoto, Yuki Shinoda-Ito, Shogo Takashiba

BMC oral health 23 ( 1 ) 90 - 90 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

The major active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is known for its wide bioactivity in periodontal tissues. Although the exact mechanisms underlying its protective action against periodontitis remain unclear, recent studies have shown that 1,25D3 regulates autophagy. Autophagy is vital for intracellular pathogen invasion control, inflammation regulation, and bone metabolic balance in periodontal tissue homeostasis, and its regulation could be an interesting pathway for future periodontal studies. Since vitamin D deficiency is a worldwide health problem, its role as a potential regulator of autophagy provides new insights into periodontal diseases. Based on this premise, this narrative literature review aimed to investigate the possible connection between 1,25D3 and autophagy in periodontitis. A comprehensive literature search was conducted on PubMed using the following keywords (e.g., vitamin D, autophagy, periodontitis, pathogens, epithelial cells, immunity, inflammation, and bone loss). In this review, the latest studies on the protective action of 1,25D3 against periodontitis and the regulation of autophagy by 1,25D3 are summarized, and the potential role of 1,25D3-activated autophagy in the pathogenesis of periodontitis is analyzed. 1,25D3 can exert a protective effect against periodontitis through different signaling pathways in the pathogenesis of periodontitis, and at least part of this regulatory effect is achieved through the activation of the autophagic response. This review will help clarify the relationship between 1,25D3 and autophagy in the homeostasis of periodontal tissues and provide perspectives for researchers to optimize prevention and treatment strategies in the future.

DOI： 10.1186/s12903-023-02802-9

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歯内治療が原因で菌血症となった単心室症患者の一症例査読

大森一弘, 杜徳尚, 井手口英隆, 岡本憲太郎, 佐光秀文, 児玉加奈子, 山本直史, 赤木禎治, 笠原真悟, 伊藤浩, 高柴正悟

日本成人先天性心疾患学会雑誌 12 ( 2 ) 1 - 8 2023年2月

Reattachment of Fractured Tooth Fragment by Multidisciplinary Treatment Approach 査読

Zulema Arias, Heber Falú Hinojosa Ledezma, Claudia Patricia Osorio Terán, Kazuhiro Omori, Tadashi Yamamoto, Mohammed Zahedul Islam Nizami, Shogo Takashiba

The Bulletin of Tokyo Dental College 2023年

Graphene Oxide-based Endodontic Sealer: An in Vitro Study. 査読

Mohammed Zahedul Islam Nizami, Melahat Gorduysus, Yuki Shinoda-Ito, Tadashi Yamamoto, Yuta Nishina, Shogo Takashiba, Zulema Arias

Acta medica Okayama 76 ( 6 ) 715 - 721 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

The failure of endodontic treatment is directly associated with microbial infection in the root canal or periapical areas. An endodontic sealer that is both bactericidal and biocompatible is essential for the success of root canal treatments. This is one of the vital issues yet to be solved in clinical dental practice. This in vitro study assessed the effectiveness of graphene oxide (GO) composites GO-CaF2 and GO-Ag-CaF2 as endodontic sealer materials. Dentin slices were coated with either the GO-based composites or commonly used root canal sealers (non-eugenol zinc oxide sealer). The coated slices were treated in 0.9% NaCl, phosphate-buffered saline (PBS), and simulated body fluid (SBF) at 37˚C for 24 hours to compare their sealing effect on the dentin surface. In addition, the radiopacity of these composites was examined to assess whether they complied with the requirements of a sealer for good radiographic visualization. Scanning electron microscopy showed the significant sealing capability of the composites as coating materials. Radiographic images confirmed their radiopacity. Mineral deposition indicated their bioactivity, especially of GO-Ag-CaF2, and thus it is potential for regenerative application. They were both previously shown to be bactericidal to oral microbes and cytocompatible with host cells. With such a unique assemblage of critical properties, these GO-based composites show promise as endodontic sealers for protection against reinfection in root canal treatment and enhanced success in endodontic treatment overall.

DOI： 10.18926/AMO/64122

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Treatment resistance of rheumatoid arthritis relates to infection of periodontal pathogenic bacteria: a case-control cross-sectional study. 査読国際誌

Kazu Takeuchi-Hatanaka, Yoshinobu Koyama, Kentaro Okamoto, Kyosuke Sakaida, Tadashi Yamamoto, Shogo Takashiba

Scientific reports 12 ( 1 ) 12353 - 12353 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Recent studies have shown that periodontitis is associated with rheumatoid arthritis (RA) and periodontal bacteria, such as Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are involved in the pathogenesis of RA via citrullinated proteins. Smoking has also been shown to be involved in the pathogenesis of RA; however, the extent of this involvement is still poorly understood. In addition, RA and polymyalgia rheumatica (PMR) are sometimes difficult to differentiate; however, the relationship between PMR and the factors from smoking and periodontal bacteria is unclear. The aim of this study was to clarify the relationship between periodontal pathogenic bacterial infections and smoking in patients with RA or PMR. This case-control study included 142 patients with untreated RA or PMR. This study evaluated the serum antibody titers against periodontal pathogenic bacterial antigens and an anti-citrullinated peptide antibody (ACPA). In patients with RA, the relationship between antibody titers and disease activity of RA and response after 3 months of treatment was also investigated. Additionally, the effects of smoking were evaluated. Although there was no significant difference in serum antibody titer against periodontal pathogenic bacteria between the ACPA-positive RA group and the ACPA-negative PMR group, we found an association between the elevated antibody titer against Pg and the degree of ACPA value, especially between negative group and high-value positive group (≥ 100 U/mL). The antibody titers against Aa and Pg did not differ depending on disease activity score 28 (DAS28) at baseline; however, patients with high antibody titers had poor RA therapeutic response as judged by DAS28 after 3 months. We could not find any association between smoking and any of these parameters. Periodontal pathogenic bacteria, especially Pg, are associated with elevated ACPA levels. Our findings suggest that Pg and Aa infections interfere with the therapeutic response of RA.

DOI： 10.1038/s41598-022-16279-z

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Analysis of subgingival microbiota in monozygotic twins with different severity and progression risk of periodontitis. 査読国際誌

Tadashi Yamamoto, Makoto Taniguchi, Kazuyuki Matsunaga, Yusuke Kawata, Mari Kawamura, Keisuke Okubo, Keisuke Yamashiro, Kazuhiro Omori, Shogo Takashiba

Clinical case reports 10 ( 4 ) e05725 2022年4月

担当区分：筆頭著者,　責任著者記述言語：英語

The study aims to reveal the composition of subgingival bacteria in monozygotic twins with discordant in severity and progression risk of periodontitis. Microbiome analysis indicated that most bacteria were heritable but differed in their abundance and immune response. The dysbiotic bacteria can be considered as risk markers for periodontitis progression.

DOI： 10.1002/ccr3.5725

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Estimation of periodontal pocket surface area in small to medium dogs: a proof-of-concept study. 査読国際誌

Kazuya Tamura, Masako Tokuzen-Tai, Yasir Dilshad Siddiqui, Hitomi Tamura-Naito, Yoshiharu Nagahara, Kazu Hatanaka-Takeuchi, Tadashi Yamamoto, Shogo Takashiba

BMC veterinary research 18 ( 1 ) 13 - 13 2022年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Periodontal disease is the most common dental disease in dogs. Although the systemic effects of periodontal disease have not been clarified in veterinary science, it is necessary to evaluate the effects of periodontal disease in clinical trials in the future. There have been a few clinical attempts made, however, to assess the severity of periodontal inflammation and its impact on the systemic health of dogs. Meanwhile, in the field of dentistry for humans, the periodontal inflamed surface area (PISA) and periodontal epithelial surface area (PESA) have been used to quantitatively assess the degree of periodontal disease affecting a single tooth as well as the overall extent of periodontitis. Recent studies have also suggested the use of these assessments to examine the relationship between periodontal inflammation and systemic health. RESULTS: The estimation formula for a dog's periodontal pocket surface area (PPSA), an alternative to PISA and PESA in humans, was established using body weight and periodontal pocket depth. Actual values were measured using extracted teeth from various dog breeds and sizes (2.3-25.0 kg of body weight) to obtain universal regression equations for PPSA. Altogether, 625 teeth from 73 dogs of 16 breeds were extracted and subsequently analyzed for morphological information. PPSA was measured in 61 dogs of 10 breeds with periodontal disease using the established estimation formulas, and the correlation between PPSA and preoperative blood chemistry data was analyzed accordingly. A strong correlation was found between PPSA and serum globulin (r = 0.71) while moderate correlations were found for C-reactive protein (r = 0.54) and serum albumin (r = -0.51). CONCLUSIONS: Estimation formulas using body weight and the 6-point probing depth were established for determining PPSA. Direct correlations between PPSA and several blood test results were observed in the study sample. Taken together, these results suggest that PPSA could be useful for evaluating the effects of periodontitis on systemic conditions in dogs.

DOI： 10.1186/s12917-021-03116-0

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Enzymatic measurement of short-chain fatty acids and application in periodontal disease diagnosis. 査読国際誌

Kazu Hatanaka, Yasushi Shirahase, Toshiyuki Yoshida, Mari Kono, Naoki Toya, Shin-Ichi Sakasegawa, Kenji Konishi, Tadashi Yamamoto, Kuniyasu Ochiai, Shogo Takashiba

PloS one 17 ( 7 ) e0268671 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

Periodontal disease is a chronic inflammatory condition caused by periodontal pathogens in the gingival sulcus. Short-chain fatty acids (SCFAs) produced by causal bacteria are closely related to the onset and progression of periodontal disease and have been reported to proliferate in the periodontal sulcus of patients experiencing this pathology. In such patients, propionic acid (C3), butyric acid (C4), isobutyric acid (IC4), valeric acid (C5), isovaleric acid (IC5), and caproic acid (C6), henceforth referred to as [C3-C6], has been reported to have a detrimental effect, while acetic acid (C2) exhibits no detrimental effect. In this study, we established an inexpensive and simple enzymatic assay that can fractionate and measure these acids. The possibility of applying this technique to determine the severity of periodontal disease by adapting it to specimens collected from humans has been explored. We established an enzyme system using acetate kinase and butyrate kinase capable of measuring SCFAs in two fractions, C2 and [C3-C6]. The gingival crevicular fluid (GCF) and saliva of 10 healthy participants and 10 participants with mild and severe periodontal disease were measured using the established enzymatic method and conventional gas chromatography-mass spectrometry (GC-MS). The quantification of C2 and [C3-C6] in human GCF and saliva was well correlated when using the GC-MS method. Furthermore, both C2 and [C3-C6] in the GCF increased with disease severity. However, while no significant difference was observed between healthy participants and periodontal patients when using saliva, [C3-C6] significantly differed between mild and severe periodontal disease. The enzymatic method was able to measure C2 and [C3-C6] separately as well as using the GC-MS method. Furthermore, the C2 and [C3-C6] fractions of GCF correlated with disease severity, suggesting that this method can be applied clinically. In contrast, the quantification of C2 and [C3-C6] in saliva did not differ significantly between healthy participants and patients with periodontal disease. Future studies should focus on inflammation rather than on tissue destruction.

DOI： 10.1371/journal.pone.0268671

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Malnutrition delayed wound healing after tooth extraction by HMGB1-related prolonged inflammation. 査読国際誌

Yao Zhang, Hidetaka Ideguchi, Hiroaki Aoyagi, Keisuke Yamashiro, Tadashi Yamamoto, Masahiro Nishibori, Shogo Takashiba

International immunopharmacology 96 107772 - 107772 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Malnutrition causes prolonged inflammation, resulting in delayed wound healing. High mobility group box-1 (HMGB1) is a damage-associated molecular pattern that is present in the nuclei of macrophages and is secreted into the extracellular milieu in response to stimuli. It stimulates the production of interleukin-1β (IL-1β) through the receptors for advanced glycation end products (RAGE), inducing an inflammatory response, which is an essential response to initiate wound healing. We hypothesized that malnutrition may interfere with this cascade, causing abnormal inflammation and ultimately delaying wound healing. We used tooth-extracted mice with malnutrition fed with low-casein diet for two weeks. On days 3 and 7 after tooth extraction, the wound tissue was histologically observed and analyzed for several factors in the inflammation-regeneration lineage, including IL-1β, mesenchymal stem cells, myeloperoxidase activity, HMGB1, macrophage polarization, and adenosine 5-triphosphate (ATP). On day 7, delayed wound healing was observed with the following findings under malnutrition conditions: decreased mRNA expression of genes for regeneration and mesenchymal stem cell (MSC) accumulation, an obvious increase in myeloperoxidase and IL-1β mRNA expression, an increase in HMGB1 levels, and an increase in ATP concentration in tissues with elevated proportion of M2 macrophages. These results suggest that the significantly increased secretion of HMGB1 associated with the upregulated production of ATP and IL-1β secretion via the RAGE pathway may interfere with the resolution of inflammation and wound healing under the state of malnutrition.

DOI： 10.1016/j.intimp.2021.107772

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The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C α/βII Phosphorylation. 査読国際誌

Kyosuke Sakaida, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Saki Nakagawa, Hidefumi Sako, Chiaki Kamei, Satoshi Yamamoto, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

Frontiers in pharmacology 12 674366 - 674366 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKCα/βII, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.

DOI： 10.3389/fphar.2021.674366

PubMed

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