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

Efficacy and Practicality of Opioid Therapy in Japanese Chronic Noncancer Pain Patients

Background: Many Japanese adults suffer from chronic pain. However, 50% of these individuals discontinue treatment despite the persistence of pain. Both clinicians and patients in Japan tend to be concerned about the safety and efficacy of opioid therapy, and the use of opioids in chronic non-cancer pain remains less common in Japan than elsewhere. Aims: This study examined the effects of opioid therapy on the daily lives of patients with chronic noncancer pain in Japan, where use of opioids for this type of pain remains uncommon. Design: Prospective cross-sectional questionnaire study. Setting: Data were collected over two periods, between March and April 2014 at one hospital, and between February and April 2015 at the other hospital. Subjects were recruited at the respective clinics by the study interviewer between March 1, 2014 and April 15, 2014 and between February 1, 2015 and April 15, 2015. Participants/Subjects: This study included 34 outpatients with chronic non-cancer pain who were being treated with opioid analgesics at pain clinics in two hospitals in Sapporo. Methods: Thirty-four Japanese patients receiving opioid medications for chronic noncancer pain in outpatient pain clinics were enrolled. Participants underwent interviews and completed the Japanese versions of the Short Form 36 (SF-36v2) and the Coping Strategies Questionnaire (CSQ). Results: Sleep disruption, claiming compensation for work-related accidents, and current pain level were negatively correlated with opioid effectiveness (p < .05). Additionally, opioid effectiveness was negatively correlated with the catastrophizing subscale of the CSQ (r = -0.50, p < .01). The effects of opioid therapy had a low positive correlation with the emotional functioning role subscale of the SF-36v2 (r = 0.38, p < .05). Daily equivalent morphine dose was positively correlated with opioid therapy duration, interference with appetite, and current pain intensity. Morphine dose was also positively correlated with scores for the catastrophizing subscale of the CSQ(r = 0.36, p < .05) and negatively correlated with scores in all subdomains of the SF-36v2. Conclusions: It is important to focus on adaptive, cognitive, and emotional factors, such as emotional role functioning, to determine the efficacy of opioid treatment for chronic noncancer pain. Moreover, patients with catastrophizing significantly increased their morphine doses, resulting in an increased risk of overdose. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the American Society for Pain Management Nursing