Orally administrable peptides derived from egg yolk promote skeletal repair and ameliorate degenerative skeletal disorders in mouse models.

Introduction: Aging, genetic mutations, and other pathological conditions cause impairment of skeletal growth and bone metabolism, which affect activities of daily living and quality of life in all life stages. Although several drugs have been used in clinical settings and new drugs have been developed for the treatment of skeletal degenerative disorders such as osteoporosis and genetic disorders such as osteogenesis imperfecta (OI), there is clear demand for development of new drugs, especially orally available anabolic drugs that are applicable for a wide range of skeletal disorders.

Methods: To identify therapeutic candidates for skeletal disorders, peptide screening was performed.

Blocking the FSTL1-DIP2A Axis Improves Anti-tumor Immunity.

Immune dysfunction is a strong factor in the resistance of cancer to treatment. Blocking immune checkpoint pathways is a promising approach to improve anti-tumor immunity, but the clinical efficacies are still limited. We previously identified follistatin-like 1 (FSTL1) as a determinant of immune dysfunction mediated by mesenchymal stromal/stem cells (MSCs) and immunoregulatory cells.

Wnt5b-associated exosomes promote cancer cell migration and proliferation.

Wnt5b is a member of the same family of proteins as Wnt5a, the overexpression of which is associated with cancer aggressiveness. Wnt5b is also suggested to be involved in cancer progression, however, details remain unclarified. We analyzed the biochemical properties of purified Wnt5b and the mode of secretion of Wnt5b by cancer cells.

Basolateral secretion of Wnt5a in polarized epithelial cells is required for apical lumen formation.

Wnt5a regulates planar cell polarity in epithelial cells, but it remains to be determined whether Wnt5a and its receptors are sorted apically or basolaterally, and how Wnt5a signaling is involved in apical and basolateral polarization. We found that Wnt5a was secreted basolaterally in polarized kidney epithelial cells. The basolateral secretion of Wnt5a required Wntless (Wls), clathrin and adaptor protein 1 (AP-1).

The apical and basolateral secretion of Wnt11 and Wnt3a in polarized epithelial cells is regulated by different mechanisms.

Wnts are glycan- and lipid-modified morphogens that are important for cellular responses, but how Wnts are secreted in polarized epithelial cells remains unclear. Although Wntless (Wls) has been shown to interact with Wnts and support their secretion, the role of Wls in the sorting of Wnts to the final destination in polarized epithelial cells have not been clarified. Glycosylation was shown to be important for the sorting of some transmembrane and secreted proteins, but glycan profiles and their roles in the polarized secretion of Wnts has not yet been demonstrated.

Potential of collagen-like triple helical peptides as drug carriers: Their in vivo distribution, metabolism, and excretion profiles in rodents.

Collagen-model peptides composed of (X-Y-Gly)n sequences were used to study the triple helical structure of collagen. We report the stability of these collagen-like peptides in biological fluids, and their pharmacokinetics including distribution, metabolism, and excretion in animals. A typical collagen-model peptide, H-(Pro-Hyp-Gly)10-OH, was found to be extremely stable in the plasma and distributed mainly in the vascular blood space, and was eliminated through glomerular filtration in the kidneys.

Affinity-trap polyacrylamide gel electrophoresis: a novel method of capturing specific proteins by electro-transfer.

A method for the affinity capture of specific proteins from a complex mixture using a polyacrylamide gel technique is described. The approach is based on the orthogonal electro-transfer of proteins separated by ordinary polyacrylamide gel electrophoresis (PAGE) to a ligand-coupled polyacrylamide gel (Li-PAG), which is placed under the PAGE gel. Upon electro-transfer, the proteins orthogonally migrate from the PAGE into the Li-PAG, based on the net charge.