歯髄幹細胞からの分泌因子は、顎関節変形性関節症の治療に多面的な効果を示す

Objective: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression. Design: To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model. Results: SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1β, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration. Conclusions: Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA

永久歯の先天的欠如に関する臨床統計調査

永久歯の先天性欠如（以下，先欠とする）は，最も高頻度に発現する顎顔面領域の先天異常であり，様々な不正咬合を引き起こし，交換期における咬合誘導あるいは，永久歯列期における歯の排列に際して苦慮することが多い．しかし，歯科矯正用アンカースクリューの登場により，治療方針に多様性が生まれ，先欠を有する患者に対して，欠損部位・歯数に影響されない，顎顔面骨格形態に則した治療方針が選択できる症例が増加している．このような症例の治療計画を立案する際には，先欠が顎顔面骨格形態へ与える影響を明らかにしておく必要がある．そこで，今回我々は不正咬合患者における第三大臼歯を除く永久歯の先欠の実態把握，ならびに先欠が顎顔面骨格形態に及ぼす影響の解明を目的として臨床統計学的な検討を行った． 2011年4月から2016年3月までの5年間に不正咬合を主訴として徳島大学病院矯正歯科を受診した患者のうち，口唇裂・口蓋裂やその他の先天異常を有する患者，矯正歯科治療の既往を有する患者および先欠の確認が不可能であった患者を除外した653名（男性233名，女性420名）を対象とし，調査を行った．その結果，以下の所見を得た． 1．先欠を有する患者は96名（14.7％）であり，男女比は1.13：1と男性がやや多かった．1人あたりの先欠歯数としては，1歯のみの欠損が最も多く，49.0％を占めた． 2．歯種別発現頻度は，上下顎ともに第二小臼歯，側切歯の順で高かった． 3．先欠を有する患者を上顎先欠群，下顎先欠群，上下顎先欠群に分類し，比較検討を行ったところ，前歯部被蓋関係については，下顎先欠群においてoverjetが最も大きかった．顎骨の前後的位置関係については，下顎先欠群において∠ANBが大きく，∠SNBが小さくなる傾向を認め，上顎先欠群，上下顎先欠群では∠SNAが小さくなる傾向を認めた． 以上の所見より，先欠が顎顔面骨格の成長・発育に影響を及ぼす可能性が示されたことから，先欠に関連した顎顔面骨格形態の特徴を考慮した治療計画の立案が重要であることが示唆された

口唇裂・口蓋裂患者の歯数異常に関する調査

口唇裂・口蓋裂患者は，軟組織や骨の癒合不全だけでなく，永久歯の先天欠如や過剰などの歯数異常が認められ，歯科矯正学的対応に苦慮することも多い．そこで，口唇裂・口蓋裂患者における永久歯の歯数異常の実態を明らかにすることを目的として，1995年1月から2011年12月までの17年間に出生し，徳島大学病院矯正歯科を受診した口唇裂・口蓋裂患者（症候群を含まない）を対象とした調査を行い，以下の結果を得た． 1．調査資料が揃っている患者101名の男女比は，1：1.02であった． 2．顎裂保有者82名の顎裂部位は，1 ▼ 3の型が最も多く，次いで1 ▼23の型であった．（▼は顎裂部位を示す） 3．永久歯における歯数異常の発現率は63.4％であり，歯の欠如のみを有するものが50.5％，過剰歯のみを有するものは8.9％，歯の欠如と過剰歯をともに有するものは4.0％であった． 4．歯の欠如の歯種別頻度は，側切歯が最も多く，次いで第二小臼歯の順であった． 5．顎裂保有者のみを対象とすると，歯の欠如の発現頻度は披裂側で59.8％，非披裂側で24.3％であった． 以上のことから，口唇裂・口蓋裂患者での先天欠如歯の発現率は高いため，治療計画立案時に補綴治療を含めた包括的歯科治療の必要性が示唆された

Atropisomeric Chiral Diiododienes (Z,Z)-2,3-Di(1-iodoalkylidene)tetralins : Synthesis, Enantiomeric Resolution, and Application in Asymmetric Catalysis

The C2-symmetric tetralin-fused 1,4-diiodo-1,3-butadiene derivatives, (Z,Z)-2,3-di(1-iodoalkylidene)tetralin 1a-c, are atropisomeric and can be resolved into the two persistent axially chiral enantiomers by HPLC on a chiral stationary phase. The enantiomerically pure compounds can serve as chiral organocatalysts for dearomatizing spirolactonization to show good performances in up to 73 % ee

Non-HDL-C and CVD

Aims: We aimed to investigate the association between non-high-density lipoprotein cholesterol (non-HDL-C) levels and the risk of cardiovascular disease (CVD) and its subtypes. Methods: In this contemporary cohort study, we analyzed the data of 63,814 Japanese employees aged ≥ 30 years, without known CVD in 2012 and who were followed up for up to 8 years. The non-HDL-C level was divided into 5 groups: ＜110, 110-129, 130-149, 150-169, and ≥ 170 mg/dL. The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for CVD and its subtypes associated with each non-HDL-C group, considering 130-149 mg/dL as the reference group. Results: During the study period, 271 participants developed CVD, including 78 myocardial infarctions and 193 strokes (102 ischemic strokes, 89 hemorrhagic strokes, and 2 unknowns). A U-shaped association between non-HDL-C and stroke was observed. In the analysis of stroke subtypes, the multivariable-adjusted HR (95% CI) for hemorrhagic stroke was 2.61 (1.19–5.72), 2.02 (0.95–4.29), 2.10 (1.01–4.36), and 1.98 (0.96-4.08), while that for ischemic stroke was 1.54 (0.77-3.07), 0.91 (0.46-1.80), 0.73 (0.38-1.41), and 1.50 (0.87-2.56) in the ＜110, 110-129, 150-169, and ≥ 170 mg/dL groups, respectively. Individuals with elevated non-HDL-C levels had a higher risk of myocardial infarction. Conclusions: High non-HDL-C levels were associated with an increased risk of myocardial infarction. Moreover, high and low non-HDL-C levels were associated with a high risk of stroke and its subtypes among Japanese workers

Genetic Predisposition to Ischemic Stroke

Background and Purpose—The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk.Methods—We genotyped 13 214 Japanese individuals with IS and 26 470 controls (derivation samples) and generated both multilocus genetic risk scores and polyGRS, using the same derivation data set. The predictive abilities of each scoring system were then assessed using 2 independent sets of Japanese samples (KyushuU and JPJM data sets).Results—In both validation data sets, polyGRS was shown to be significantly associated with IS, but weighted multilocus genetic risk scores was not. Comparing the highest with the lowest polyGRS quintile, the odds ratios for IS were 1.75 (95% confidence interval, 1.33–2.31) and 1.99 (95% confidence interval, 1.19–3.33) in the KyushuU and JPJM samples, respectively. Using the KyushuU samples, the addition of polyGRS to a nongenetic risk model resulted in a significant improvement of the predictive ability (net reclassification improvement=0.151; P<0.001).Conclusions—The polyGRS was shown to be superior to weighted multilocus genetic risk scores as an IS prediction model. Thus, together with the nongenetic risk factors, polyGRS will provide valuable information for individual risk assessment and management of modifiable risk factors

Oral Supplementation of the Vitamin D Metabolite 25(OH)D(3)Against Influenza Virus Infection in Mice

Vitamin D is a fat-soluble vitamin that is metabolized by the liver into 25-hydroxyvitamin D [25(OH)D] and then by the kidney into 1,25-dihydroxyvitamin D [1,25(OH)(2)D], which activates the vitamin D receptor expressed in various cells, including immune cells, for an overall immunostimulatory effect. Here, to investigate whether oral supplementation of 25-hydroxyvitamin D-3[25(OH)D-3], a major form of vitamin D metabolite 25(OH)D, has a prophylactic effect on influenza A virus infection, mice were fed a diet containing a high dose of 25(OH)D(3)and were challenged with the influenza virus. In the lungs of 25(OH)D-3-fed mice, the viral titers were significantly lower than in the lungs of standardly fed mice. Additionally, the proinflammatory cytokines IL-5 and IFN-gamma were significantly downregulated after viral infection in 25(OH)D-3-fed mice, while anti-inflammatory cytokines were not significantly upregulated. These results indicate that 25(OH)D(3)suppresses the production of inflammatory cytokines and reduces virus replication and clinical manifestations of influenza virus infection in a mouse model