Discovery of Lactoferrin as a Stimulant for hADSC-Derived EV Secretion and Proof of Enhancement of Resulting EVs through Skin Model.

Extracellular vesicles (EVs) are secreted from hADSCs in low concentrations, which makes it difficult to utilize them for the development of therapeutic products. To overcome the problem associated with low concentration, we proposed human lactoferrin (hLF) as a stimulant for the secretion of hADSC-derived EVs. hLF has been reported to upregulate intracellular Ca2+, which is known to be capable of increasing EV secretion. We cultured hADSCs in hLF-supplemented media and analyzed the changes in intracellular Ca2+ concentration. The characteristics of hADSC-derived EVs secreted by hLF stimulation were analyzed through their number, membrane protein markers, and the presence of hLFs to EVs. The function of hADSC-derived EVs was investigated through their effects on dermal fibroblasts. We found that hLF helped hADSCs effectively uptake Ca2+, resulting in an increase of EVs secretion by more than a factor of 4. The resulting EVs had enhanced proliferation and collagen synthesis effect on dermal fibroblasts when compared to the same number of hADSC-derived EVs secreted without hLF stimulation. The enhanced secretion of hADSC-derived EVs increased collagen synthesis through enhanced epidermal penetration, which resulted from increased EV numbers. In summary, we propose hLF to be a useful stimulant in increasing the secretion rate of hADSC-derived EVs.

Prescription Pattern of Antidepressants for Children and Adolescents in Korea Based on Nationwide Data.

Antidepressant prescription for youths has recently been on the increase. There is a growing concern over the increasing off-label usage of antidepressants. Current data on off-label antidepressant usage vary across countries and healthcare systems. Therefore, we examined the extent and pattern of antidepressant prescription for Korean children and adolescents using population-based data. Our data was retrieved from the Korean National Health Insurance Service National Sample Cohort of the year 2013. Among 0.2 million children and adolescents aged 6-18 years from the cohort, subjects who had received any antidepressant medication in the year 2013 were investigated for the prescribed medication, concomitant psychotropic medication, and the associated diagnosis. A total of 2,190 children and adolescents (boys, 55.4%) received antidepressant medication. The most common diagnosis was depressive disorders (n = 469, 21.4%), followed by attention-deficit/hyperactivity disorder (n = 442, 20.2%). Among the prescriptions (n = 3,370), escitalopram (n = 650, 24.1%) and fluoxetine (n = 553, 20.5%) were the two most frequently prescribed drugs. A majority of prescriptions (n = 2,039, 60.5%) included concomitant psychotropic agents, consisting of antipsychotics (n = 901, 26.7%), sedatives (n = 263, 26.3%), medication for attention-deficit/hyperactivity disorder (n = 822, 24.4%), and some others. Our study shows the prescription pattern of antidepressants for children and adolescents in Korea, of which a large proportion is off-label. The results call for close monitoring by clinicians treating this population.

Effects of the combination of respiratory muscle training and abdominal drawing-in maneuver on respiratory muscle activity in patients with post-stroke hemiplegia: a pilot randomized controlled trial.

PURPOSE: No study has examined the effects of the combination of respiratory muscle training (RMT) and abdominal drawing-in maneuver (ADIM) on respiratory muscle activity and function in stroke patients during early pulmonary rehabilitation. The purpose of this study was to investigate the effects of RMT combined with ADIM on decreased respiratory muscle activity and function in patients with post-stroke hemiplegia. METHODS: Thirty-seven subjects with post-stroke hemiplegia were randomly allocated to three groups; integrated training group (ITG), respiratory muscle training group (RMTG), and control group (CG). All of the subjects received routine therapy for stroke rehabilitation for 1 hour, five times a week for 6 weeks. Especially, the ITG received RMT using an incentive respiratory spirometer and ADIM using a Stabilizer, and the RMTG only received RMT using incentive respiratory spirometer for 15  minutes a day, five times a week for 6 weeks. Pulmonary function was evaluated using spirometry for measuring the forced vital capacity (FVC) and force expiratory volume in 1  second (FEV1). Additional surface electromyography (sEMG) analysis was included by measuring the respiratory muscle activity. RESULTS: Our results showed that changes between the pre- and post-test values of FVC (F = 12.50, P = 0.02) and FEV1 (F = 12.81, P = 0.01) (P < 0.05) in the ITG were significantly (P < 0.05) greater. Changes in EMG activation of the diaphragm (F = 13.75, P = 0.003) and external intercostal (F = 14.33, P = 0.002) (P < 0.01) muscles of patients in the ITG during maximal static inspiratory efforts were significantly (P < 0.05) greater than those in patients of the RMTG and the CG at post-test. CONCLUSIONS: Our findings suggested that RMT combined with ADIM could improve pulmonary function in patients with post-stroke hemiplegia.

Withanone-rich combination of Ashwagandha withanolides restricts metastasis and angiogenesis through hnRNP-K.

Ashwagandha is an important herb used in the Indian system of traditional home medicine, Ayurveda. Alcoholic extract (i-Extract) from its leaves and its component, withanone, were previously shown to possess anticancer activity. In the present study, we developed a combination of withanone and withaferin A, major withanolides in the i-Extract, that retained the selective cancer cell killing activity and found that it also has significant antimigratory, -invasive, and -angiogenic activities, in both in vitro and in vivo assays. Using bioinformatics and biochemical approaches, we demonstrate that these phytochemicals caused downregulation of migration-promoting proteins hnRNP-K, VEGF, and metalloproteases and hence are candidate natural drugs for metastatic cancer therapy.