Core-Shell Arginine-Containing Chitosan Microparticles for Enhanced Transcorneal Permeation of Drugs

Chitosan oligosaccharide (C) was functionalized with l-arginine (A) and short hydrocarbon chains (C₈) to design an amphiphilic copolymer, henceforth CAC₈, leading to microparticles (MPs) consisting of an arginine-decorated hydrophilic shell and inner hydrophobic domains allowing the encapsulation of high amount hydrophobic drugs such as sorafenib tosylate (>10% w/w). l-arginine side chains were selected in order to impart the final MPs enhanced transcorneal penetration properties, thus overcoming the typical biological barriers which hamper the absorption of drugs upon topical ocular administration. The mucoadhesive properties and drug release profile of the CAC₈ MPs (CAC₈-MPs) were studied, showing that CAC₈-MPs can strongly interact with mucin, and thus gradually release their payload in situ to potentially improve the bioavailability of the drug after topical administration. In vitro transcorneal studies also showed that CAC₈-MPs are endowed with effective permeation enhancer ability combined with negligible toxicity.     

Influence of pitch size and age category on the physical and physiological responses of young football players during small-sided games using GPS devices

ABSTRACT

This study aimed to compare the physical and physiological responses of young football players of different categories during small-sided games (SSGs) played on different pitch sizes. Forty-eight (24 U-13 and 24 U-14) athletes played a 3 vs. 3 + 1 SSG in two experimental conditions: regular (36 × 27 m) and large pitch sizes (40 × 29 m). The total distance covered, the distances covered at different speed zones (0 to 6.9 km/h, 6.9 to 14.3, and 14.3 to 21.4), maximum heart rate, and mean heart rate were recorded. The results showed that older athletes covered larger distances during SSGs (p = 0.001; d = 0.937; large effect) and lower distances at the lowest (0–6.9 km/h) speed zone (p = 0.001; d = 0.657; moderate-to-large effect). Neither the physical nor physiological variables (except for distance covered between 14.3 and 21.4 km/h) differed between pitch sizes. This result indicates that pitch size may not impact the physical or physiological responses of U-13 and U-14 players during SSGs, but differences between categories were found. In conclusion, the development of tactical skills may be desirable to better explore the available space in the same age categories.     

Oncogenic properties and signaling basis of the PAX8-GLIS3 fusion gene

Hyalinizing trabecular tumors of the thyroid are rare and mostly benign epithelial neoplasms of follicular cell origin, which have recently been shown to be underpinned by the PAX8-GLIS3 fusion gene. In our study, we sought to investigate the potential oncogenic mechanisms of the PAX8-GLIS3 fusion gene. Forced expression of PAX8-GLIS3 was found to increase proliferation, clonogenic potential and migration of human nonmalignant thyroid (Nthy-ori 3-1) and embryonic kidney (HEK-293) cells. Moreover, in xenografts, Nthy-ori 3-1 PAX8-GLIS3 expressing cells generated significantly larger and more proliferative tumors compared to controls. These oncogenic effects were found to be mediated through activation of the Sonic Hedgehog (SHH) pathway. Targeting of smoothened (SMO), a key protein in the SHH pathway, using the small molecule inhibitor Cyclopamine partially reversed the increased proliferation, colony formation and migration in PAX8-GLIS3 expressing cells. Our data demonstrate that the oncogenic effects of the PAX8-GLIS3 fusion gene are, at least in part, due to an increased activation of the SHH pathway.