Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds

Abstract Argonaute 2 bound mature microRNA (Ago2‐miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation‐related Ago2‐miRNAs (miR‐139‐5p, miR‐142‐3p, miR‐142‐5p, and miR‐223) and show that miR‐223 is critical for infection control. miR‐223Y/− mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin‐6 expression, and markedly improved repair of Staphylococcus aureus‐infected wounds. We also showed that the expression of miR‐223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR‐223Y/−‐derived neutrophils, or miR‐223 antisense oligodeoxynucleotides in S. aureus‐infected wild‐type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR‐223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR‐223 might be of therapeutic benefit for infected wounds in the clinic

Reduced FOXO1 Expression Accelerates Skin Wound Healing and Attenuates Scarring

The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1 +/- mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a-/- mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1+/- mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring

Influence of ankle invertor muscle fatigue on workload of the lower extremity joints during single-leg landing in the sagittal and frontal planes

Background: Insufficient rigidity of the foot owing to its ligaments and muscles can decrease the attenuation of the ground reaction force during landing. Therefore, dysfunction of the ankle invertors may increase the proximal joint load during landing. Research question: What are the effects of the fatigued ankle invertors on workload in the lower extremity joints during single-leg landing? Methods: Twenty-seven young adults (13 men and 14 women) performed landing trials in the forward and medial directions before and after exercise-induced fatigue of the ankle invertors. The exercise consisted of repeated concentric and eccentric ankle inversions until the maximum torque was below 80% of the baseline value. Negative joint workload during the landing tasks was calculated for the hip, knee, and ankle in the sagittal and frontal planes. Additionally, lower extremity work (the sum of the work of the hip, knee, and ankle) was calculated. Results: Invertor fatiguing exercise resulted in a significant increase in negative joint work in the frontal and sagittal plane hip and the frontal plane knee during medial landing, whereas no significant change in negative joint work was observed during forward landing. Significance: These findings suggested that ankle invertor dysfunction may induce a high load on the proximal joints and have direction-specific effects

菓子類の認知度および嗜好性について

菓子類について,洋菓子,和菓子,中華菓子にわけ年代別の認知度・嗜好度を調べた結果,以下のことが明らかとなった。1.洋菓子の認知度は年代別での差はほとんどみられなかった。2.洋菓子の嗜好度はクレープ,ワッフル,クッキー,タルトに年代別の有意差がみられた。20歳代以下に好まれていた。3.和菓子はきんつば,鹿の子の20歳代以下の認知度が低かった。4.和菓子の嗜好度は羊かんに有意差がみられ,30歳以上に好まれた。5.中華菓子の認知度は年代別に関わらず低く,ゴマ団子の認知度が高かった。6.中華菓子の嗜好度は中華パイに有意差がみられ,20歳代以下に好まれた。7.よく食べる菓子の年代別比較では洋菓子,スナック類に有意差がみられ,これらは20歳代以下に好まれていた。以上のことより,認知度の高い菓子類は好まれ,認知度の低い菓子は好まれない傾向にあった。現在市場に出ている菓子類は洋菓子が中心であり,和菓子は限られた種類しかない。また洋菓子類は,クリーム類や果物類などが同時に食べることができ,味に面白さがある。一方,和菓子については,市場で見ることも少なく,認知度も低く食べる機会が少ないことなどから,食べたことがなく,また好まないという結果であった。若い年代が,年齢が経るとどのような嗜好に変化していくのか興味あることである。中華菓子については,わが国では市場においても一般的な菓子ではないといえよう。栄養面から考えれば,洋菓子のほうが和菓子よりも,脂質が含まれることからエネルギー量は高い。また和菓子の材料である豆類は,機能性に富んだ食材であるので健康にも寄与する。今後このような観点も含め,洋菓子と和菓子の嗜好の差の理由なども検討していきたい