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The ear pinna is a complex tissue consisting of the dermis, cartilage, muscles, vessels, and nerves. Ear pinna healing is a model of regeneration in mammals. In some mammals, including rabbits, punch wounds in the ear pinna close spontaneously; in common-use laboratory mice, they remain for life. Agents inducing ear pinna healing are potential regenerative drugs. We tested the effects of selected bioactive agents on 2 mm ear pinna wound closure in BALB/c mice. Our previous research demonstrated that a DNA methyltransferase inhibitor, zebularine, remarkably induced ear pinna regeneration. Although experiments with two other demethylating agents, RG108 and hydralazine, were unsuccessful, a histone deacetylase inhibitor, valproic acid, was another epigenetic agent found to increase ear hole closure. In addition, we identified a pro-regenerative activity of 4-ketoretinoic acid, a retinoic acid metabolite. Attempts to counteract the regenerative effects of the demethylating agent zebularine, with folates as methyl donors, failed. Surprisingly, a high dose of methionine, another methyl donor, promoted ear hole closure. Moreover, we showed that the regenerated areas of ear pinna were supplied with nerve fibre networks and blood vessels. The ear punch model proved helpful in testing the pro-regenerative activities of small-molecule compounds and observations of peripheral nerve regeneration. [ABSTRACT FROM AUTHOR] more...

With the aging of the world population and the improvement of people＇s living standards，more and more people are looking forward to and making efforts to let the body tissue regenerate，which made regenerative medicine a frontier and hot spot in medical research． As an important part of the human body，the skeleton plays a role in supporting，protecting，movement and so on． With aging，bone density decreases gradually，and may evolve into osteoporosis． People develop kyphosis and become not flexible． Bones break easily and are hard to restore，which seriously affects individuals’quality of life and safety． Using regenerative drugs to achieve bone regeneration is expected to overcome the problem of osteoporosis fundamentally． Studies had shown that epimedium flavonoids with different glycosylation number，type or location could exert anti-osteoporosis action，however their strength of activity were significant different． By studying Chinese and international literature and research，we hypothesize that the intensity of epimedium flavonoids’bone regenerate mechanism is closely related to its pharmacokinetics: the number of glycosylation and membrane permeability are negatively correlated; the number of glycosylation and solubility are positively correlated; glycosylation type and position determine membrane transport mode; the intracellular disposal changes glycosylation structure，and transforms them into more active flavonoids． In this review，from the perspective of pharmacokinetics，the influences of different glycosylation number，type or location on membrane transport and osteogenic differentiation in the bone cells microenvironment were discussed in depth． [ABSTRACT FROM AUTHOR] more...