Activity

ur findings suggest a reasonable approach to improve the production of exosomes for various therapeutic applications.

To our knowledge, this is the first study showing that PdNPs stimulate exosome biogenesis and release and simultaneously increase the levels of cytokines and chemokines by modulating various physiological processes. Our findings suggest a reasonable approach to improve the production of exosomes for various therapeutic applications.

Peptides can be rationally designed as non-covalent inhibitors for molecularly targeted therapy. However, it remains challenging to efficiently deliver the peptides into the targeted cells, which often severely affects their therapeutic efficiency.

Herein, we created a novel non-covalent peptide inhibitor against nuclear export factor CRM1 by a structure-guided drug design method and targetedly delivered the peptide into cancer cells by a nanoparticle-mediated gene expression system for use as a cancer therapy.

The nuclear export signal (NES)-optimized CRM1 peptide inhibitor colocalized with CRM1 to the nuclear envelope and inhibited nuclear export in cancer cell lines in vitro. The crystal structures of the inhibitors complexed with CRM1 were solved. In contrast to the covalent inhibitors, the peptides were similarly effective against cells harboring the CRM1 C528S mutation. Moreover, a plasmid encoding the peptides was delivered by a iRGD-modified nanoparticle to efficiently target and transfect the cancer cells in vivo after intravenous administration. The peptides could be selectively expressed in the tumor, resulting in the efficient inhibition of subcutaneous melanoma xenografts without obvious systemic toxicity.

This work provides an effective strategy to design peptide-based molecularly targeted therapeutics, which could lead to the development of future targeted therapy.

This work provides an effective strategy to design peptide-based molecularly targeted therapeutics, which could lead to the development of future targeted therapy.

Daily physical activity is reduced in patients with chronic obstructive pulmonary disease (COPD) and a reduced level of physical activity has been shown to be an important predictor for the prognosis, such as increased risk of exacerbation and mortality. However, there has not yet been a useful biomarker of the physical activity. In our previous cross-sectional study, we showed that the level of one of the possible myokines, which is an anti-aging factor, growth differentiation factor 11 (GDF11), was decreased in the plasma from patients with COPD and correlated with the physical activity. To clarify this relationship, we conducted a longitudinal evaluation of such factors.

Twenty-four COPD patients were enrolled and prospectively followed. We measured the levels of plasma GDF11 and systemic inflammatory markers with immunoblotting or ELISA, respectively. selleck chemical We also evaluated lung function and daily physical activity using a triaxial accelerometer and the incidence of exacerbation.

The change in the plasma level of GDF11, but not systemic inflammatory markers, was positively correlated with the change in the physical activity in an intensity-dependent manner (between the change in the number of steps and GDF11; r = 0.41, p = 0.047). In the multiple regression analysis, the relationship was confirmed (β = 0.93, p < 0.001). In addition, patients who maintained their plasma level of GDF11 showed a significantly lower incidence in exacerbations of COPD than those with decreased levels of GDF11 (p = 0.041).

The longitudinal change in the plasma level of GDF11 was positively correlated with the change in the daily physical activity in COPD. GDF11 could be a useful humoral factor that reflects the physical activity in COPD.

The longitudinal change in the plasma level of GDF11 was positively correlated with the change in the daily physical activity in COPD. GDF11 could be a useful humoral factor that reflects the physical activity in COPD.

In COPD patients of GOLD groups A and B, a high degree of treatment with inhaled corticosteroids (ICS) has been reported, which is regarded as overtreatment according to GOLD recommendations. We investigated which factors predict ICS use and which relationship it has to clinical and functional outcomes, or healthcare costs.

We used pooled data from visits 1 and 3 of the COSYCONET cohort (n=2741, n=2053, interval 1.5 years) including patients categorized as GOLD grades 1-4 and GOLD group A or B at both visits (n=1080). Comparisons were performed using ANOVA, and regression analyses using propensity matching and inverse probability weighting to adjust for differences between ICS groups. These were defined as having ICS at both visits (always) vs no ICS at both visits (never). Measures were divided into predictors of ICS treatment and outcomes.

Among 1080 patients, 608 patients were eligible for ICS groups (n=297 never, n=311 always). Prior to matching, patients with ICS showed significantly (p<0.05 each) impaired lung function, symptoms and exacerbation history. After matching, the outcomes generic quality of life and CO diffusing capacity were increased in ICS patients (p<0.05 each). Moreover, costs for respiratory medication, but not total health care costs, were significantly elevated in the ICS group by 780€ per year.

ICS therapy in COPD GOLD A/B patients can have small positive and negative effects on clinical outcomes and health care costs, indicating that the clinical evaluation of ICS over-therapy in COPD requires a multi-dimensional approach.

ICS therapy in COPD GOLD A/B patients can have small positive and negative effects on clinical outcomes and health care costs, indicating that the clinical evaluation of ICS over-therapy in COPD requires a multi-dimensional approach.

Eosinophil counts increase during chronic obstructive pulmonary disease (COPD) exacerbation and influence the response to different agents (such as inhaled and systemic corticosteroids), as well as increase the production of other inflammatory cytokines. However, few studies have evaluated the association between peripheral blood eosinophils with mortality rate.

To evaluate the association between peripheral blood eosinophils and mortality rate in COPD patients over a nine-year period.

This cohort included 133 COPD patients assessed at baseline by spirometry, pulse oximetry (SpO

), complete blood count, body composition, dyspnea intensity [Modified Medical Research Council (mMRC)] and the six-minute distance test (6MWD). The Kaplan-Meier curve followed by a Log rank test was used to evaluate mortality rate related to eosinophil cutoff point categorization. Multivariate Cox regression analysis was performed to identify the association between eosinophils and mortality with all subjects evaluated at baseline, adjusted for age, gender, mMRC, 6MWT, forced expiratory volume in the first second (FEV

) and SpO

.