Effect of Actomyosin Contractility on Lamellipodial Protrusion Dynamics on a Micropatterned Substrate

Actin polymerization-driven protrusion of the lamellipodia is a requisite initial step during actin-based cell migration, and is closely associated with attachment to the substrate. Although tremendous progress has been made in recent years toward elucidating the molecular details of focal adhesions, our understanding of the basic coordination of protrusion and adhesion, and how the two fundamental processes relate to actomyosin contractility is still inadequate. Therefore, to highlight the effect of cell–substrate interactions on the protrusive dynamics of the lamellipodia and to correlate protrusion with actomyosin activities, this study investigated the migration of fish epidermal keratocytes on fibronectin micropatterns intercalated with adhesion-suppressed gaps of varying widths. We show that insufficient adhesion associated with the gaps could limit lamellipodial protrusion such that the percentage of migrating cells decreases with an increase in gap width, and protrusion across the gaps is accompanied by ruffling. Moreover, our results suggest that up-regulating actomyosin contractility enhances the mechanical integrity of the actin cytoskeleton, leading to an increase in the width of the lamellipodia, and consequently, an increase in the percentage of cells migrating across the gaps. Thus, we demonstrate that the protrusion dynamics at the leading edge of migrating cells are functionally involved in the global mechanical regulation of actin cytoskeletal components that enable cell migration

A Comparison of Long-Term Anti-Inflammatory Effect of Two ICS/LABA Combination Inhalers; Fix-Dosed Maintenance Therapy with Budesonide/Formoterol and Salmeterol/Fluticasone

Background: The clinical usefulness of fixed-dose maintenance therapy with salmeterol/fluticasone (SFC) and budesonide/formoterol combination inhaler (BUD/FM) has been established, though evidence of the long-term anti-inflammatory effects of these 2 inhalers are limited. Methods: Patients with moderate persistent adult asthma who had received SFC 50/250 μg bid with well-control status were recruited. After switching to 8-week therapy with fixed-dose BUD/FM 4 puffs (640/18 μg) (phase-1), patients chose either SFC or BUD/FM. FeNO and ACT score were evaluated every 8 weeks until the end of the 52-week treatment period for both treatment groups (phase-2). Results: In total, 103 patients were examined: BUD/FM was chosen by 34 patients (BUD/FM group), while SFC was chosen by 23 (SFC group). Thirty-six received SFC consistently from the beginning of the study (control). Patients in the BUD/FM and SFC groups showed significant improvements in ACT scores and FeNO levels in phase-1; these beneficial effects persisted for 52 weeks in the BUD/FM group. On the other hand, in the SFC group, although the FeNO level decreased from 54.3 ± 26.4 ppb to 41.9 ± 18.3 ppb in phase-1, it increased to 54.5 ± 26.2 ppb, a level similar to the baseline prior to the beginning of BUD/FM therapy, at 8 weeks in phase-2, and remained at 50-odd ppb thereafter. Conclusions: These results suggest that maintenance therapy with fixed-dose BUD/FM is a useful treatment option exerting an airway anti-inflammatory effect for a period as long as 1 year, even for asthmatics who could not accomplish total control with SFC

The impact of co-existing seasonal allergic rhinitis caused by Japanese Cedar Pollinosis (SAR-JCP) upon asthma control status

Background: Seasonal Allergic Rhinitis Caused by Japanese Cedar Pollinosis (SAR-JCP) is a most common allergic rhinitis, affecting about 40% in Japan, but the influence from SAR-JCP upon asthma is controversial. The purpose of this study is to investigate the effect of coexistence of SAR-JCP upon control status of asthma using SACRA (Self-Assessment of Allergic Rhinitis and Asthma Questionnaire). Methods: The design was prospective, single-center, observational study. Asthmatic patients were classified into 3 groups, patients without rhinitis, those with perennial rhinitis or those with SAR-JCP from the results of SACRA. The control status of asthma were evaluated by Visual Analog Scale (VAS) in SACRA and Asthma Control Test (ACT) score. They were evaluated twice, from September to January (nonpollen-season) and February to April (pollen-season) and compared. Results: 451 patients were enrolled and 325 cases (72%) were diagnosed as having comorbidity of rhinitis, among which 173 with only perennial rhinitis, while 152 with SAR-JCP. There was no significant difference in asthma control level measured by VAS and ACT score among 3 groups during nonpollen-season. The asthma control level measured by VAS (1.91–2.95) and ACT score (22.7–21.6) got worse during pollen-season among patients with SAR-JCP, even though 84% received treatment for rhinitis. Although it differed according to criteria, asthma control during pollen-season was impaired in 18–38% asthmatic patients with SAR-JCP. Conclusion: It is possible to minimize the influence of AR on asthma control by obtaining an accurate diagnosis and providing sufficient treatment for rhinitis