Flash Fabrication of Orally Targeted Nanocomplexes for Improved Transport of Salmon Calcitonin across the Intestine.

Salmon calcitonin (sCT) is a potent calcium-regulating peptide hormone and widely applied for the treatment of some bone diseases clinically. However, the therapeutic usefulness of sCT is hindered by the frequent injection required, owing to its short plasma half-life and therapeutic need for a high dose. Oral delivery is a popular modality of administration for patients because of its convenience to self-administration and high patient compliance, while orally administered sCT remains a great challenge currently due to the existence of multiple barriers in the gastrointestinal (GI) tract. Here, we introduced an orally targeted delivery system to increase the transport of sCT across the intestine through both the paracellular permeation route and the bile acid pathway. In this system, sCT-based glycol chitosan-taurocholic acid conjugate (GC-T)/dextran sulfate (DS) ternary nanocomplexes (NC-T) were produced by a flash nanocomplexation (FNC) process in a kinetically controlled mode. The optimized NC-T exhibited well-controlled properties with a uniform and sub-60 nm hydrodynamic diameter, high batch-to-batch reproducibility, good physical or chemical stability, as well as sustained drug release behaviors. The studies revealed that NC-T could effectively improve the intestinal uptake and permeability, owing to its surface functionalization with the taurocholic acid ligand. In the rat model, orally administered NC-T showed an obvious hypocalcemia effect and a relative oral bioavailability of 10.9%. An in vivo assay also demonstrated that NC-T induced no observable side effect after long-term oral administration. As a result, the orally targeted nanocomplex might be a promising candidate for improving the oral transport of therapeutic peptides.

Dynamics of serum phosphorus, calcium, and hormones during egg laying cycle in Hy-Line Brown laying hens.

Understanding serum dynamic patterns of P, Ca, and P-Ca metabolism related hormones would help us in developing feeding strategies that can be used to reduce dietary inorganic P input and decrease P excretion in laying hens. In the current study, Hy-Line Brown laying hens (35-wk-old, n = 15) were fed with a corn-soybean meal-based commercial laying hen diet containing 0.24% non-phytate P, 3.59% Ca, 2,040 IU/kg vitamin D3, 2,500 FTU/kg phytase, 2,636 kcal/kg ME, and 15.9% crude protein. Blood samples from each laying hen were collected immediately after the first oviposition; 3, 6, 9, 12, 15, 18, and 21 h after the first oviposition; and immediately after the second oviposition. As a result, after the first oviposition, serum P and Ca levels of the laying hens were gradually increased, peaked in 6 h, and then gradually decreased all the way down until the second oviposition. Similarly, serum fibroblast growth factor 23 (FGF-23) level was gradually increased after the first oviposition, but peaked in 9 h, and then gradually decreased all the way down until the second oviposition. Serum 1,25-dihydroxy-cholecalciferol [1,25(OD)2D3] level was linearly and quadratically decreased during the egg laying cycle we observed. The serum levels of parathyroid hormone, calcitonin, and alkaline phosphatase were erratically fluctuated during the egg laying cycle in patterns that are very different from that of serum P, Ca, FGF-23, and 1,25(OD)2D3. In conclusion, the result that serum FGF-23 peaked after serum P indicates that the dynamics in serum FGF-23 levels might be driven by serum P levels during the egg laying cycle.

Vitamin D Supplementation and Nordic Walking Training Decreases Serum Homocysteine and Ferritin in Elderly Women.

The aim of the study was to verify if coupling 12 weeks of vitamin D supplementation and Nordic walking training favoured lowering the homocysteine (Hcy) level. Ninety-four elderly women were divided into three groups: Nordic walking (NW), supplemented (SG) and control (CG). The NW and SG groups received a weekly dose of 28,000 IU of vitamin D3. A blood analysis was performed at baseline, 1h after the first training session and at the end of the experiment. The amino acid profile (methionine and cysteine) and homocysteine concentration were determined. Additionally, the concentration of myokine was assessed. The first session of NW training reduced serum homocysteine, particularly among women with baseline homocysteine above 10 µmol·L-1: 12.37 ± 2.75 vs. 10.95 ± 3.94 µmol·L-1 (p = 0.05). These changes were accompanied by shifts in the cysteine (p = 0.09) and methionine (p = 0.01) concentration, regardless of the Hcy concentration. Twelve weeks of training significantly decreased the homocysteine (9.91 ± 2.78, vs. 8.90 ± 3.14 µmol·L-1, p = 0.05) and ferritin (94.23 ± 62.49 vs. 73.15 ± 47.04 ng·mL-1, p = 0.05) concentrations in whole NW group. Also, in the NW group, ferritin correlated with the glucose level (r = 0.51, p = 0.00). No changes in the myokine levels were observed after the intervention. Only the brain-derived neurotrophic factor dropped in the NW (42.74 ± 19.92 vs. 31.93 ± 15.91 ng·mL-1, p = 0.01) and SG (37.75 ± 8.08 vs. 16.94 ± 12.78 ng·mL-1, p = 0.00) groups. This study presents a parallel decrease of homocysteine and ferritin in response to regular training supported by vitamin D supplementation.