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Viral infection often triggers asthma exacerbation and contributes to airway remodeling. Cell signaling in viral infection is mainly mediated through TLR3. Many mediators are involved in airway remodeling, but matrix metalloproteinases (MMPs) are key players in this process in asthma. However, the role of TLR3 activation in production of MMPs is unknown. In this study, we examined the effects of polyinosinic-polycytidylic acid [poly(I:C)], a ligand for TLR3, on production of MMPs in human lung fibroblasts, with a focus on nitrosative stress in TLR3 modulation of MMP production. After lung fibroblasts were treated with poly(I:C), production of MMP-1, -2, and -9 and inducible NO synthase (iNOS) was assessed. The roles of NF-κB and IFN regulatory factor-3 (IRF-3) in the poly(I:C)-mediated production of MMPs and the responsiveness to poly(I:C) of normal lung fibroblasts and asthmatic lung fibroblasts were also investigated. Poly(I:C) augmented production of MMPs and iNOS in fibroblasts, and an iNOS inhibitor diminished this production of MMPs. Poly(I:C) stimulated translocation of NF-κB and IRF-3 into the nucleus in fibroblasts and inhibition of NF-κB or IRF-3 abrogated the poly(I:C)-induced increase in both iNOS expression and release of MMPs. Poly(I:C)-induced production of iNOS and MMPs was greater in asthmatic fibroblasts than in normal fibroblasts. We conclude that viral infection may induce nitrosative stress and subsequent MMP production via NF-κB– and IRF-3–dependent pathways, thus potentiating viral-induced airway remodeling in asthmatic airways.

Objectives: To evaluate the impact of sarcopenia and myosteatosis on urinary incontinence after prostatectomy. Methods: We retrospectively reviewed consecutive patients who underwent robotassisted radical prostatectomy without nerve sparing between December 2012 and March 2019. Psoas muscle index and average total psoas density, which were measured on preoperative computed tomography images at level L3, were used to evaluate sarcopenia and myosteatosis, respectively. In addition, several magnetic resonance imaging variables associated with pelvic muscles, the urethra and the prostate were measured. Urinary continence was defined as non-use or use of just one incontinence pad per day. Logistic regression analyses aimed to identify the predictors of urinary incontinence 3 and 12 months after surgery. Results: Overall, 121 patients were included in the analysis. The incidence rates of urinary incontinence 3 and 12 months after surgery were 42% (51/121 cases) and 16% (19/121 cases), respectively. Logistic multivariable analysis showed that low average total psoas density was the only significant independent predictor of urinary incontinence 3 months after surgery (P < 0.01), and low obturator internus muscle thickness (P = 0.01), short membranous urethral length (P = 0.01) and low average total psoas density (P < 0.01) were significant independent predictors of urinary incontinence 12 months after surgery. By contrast, psoas muscle index was not statistically associated with urinary incontinence after surgery. Conclusions: Myosteatosis (low average total psoas density) could be a novel predictor of urinary incontinence after robot-assisted radical prostatectomy.

Among patients with controlled asthma at baseline, the rate of change in FEV1 is highly variable. Severe exacerbations are strongly associated with a rapid loss of lung function.