21 research outputs found
Differential effects of caffeine on hair shaft elongation, matrix and outer root sheath keratinocyte proliferation, and TGF-beta2-/IGF-1-mediated regulation of hair cycle in male and female human hair follicles in vitro.
BACKGROUND: Caffeine reportedly counteracts the suppression of hair shaft production by testosterone in organ-cultured male human hair follicles (HFs). OBJECTIVES: We aimed at investigating the impact of caffeine a) on additional key hair growth parameters, b) on major hair growth-regulatory growth factors and c) on male versus female HFs in the presence of testosterone. METHODS: Microdissected male and female human scalp HFs were treated in serum-free organ culture for 120 h with testosterone alone (0,5 mug/ml) or in combination with caffeine (0.005-0.0005%), and effects on hair shaft elongation, HF cycling (i.e. anagen-catagen transition), hair matrix keratinocyte proliferation and expression of a key catagen inducer, transforming growth factor beta2 (TGF-beta2), and anagen-prolonging insulin-like growth factor 1 (IGF-1) were evaluated by quantitative (immuno-) histomorphometry. Caffeine effects were further investigated in human outer root sheath keratinocytes (ORSK). RESULTS: Caffeine enhanced hair shaft elongation, prolonged anagen duration and stimulated hair matrix keratinocyte proliferation. Female HFs showed higher sensitivity to caffeine compared to male HFs. Caffeine counteracted testosterone-enhanced TGF-beta2 protein expression in male HFs. In female HFs, testosterone failed to induce TGF-beta2 expression, while caffeine reduced it. In male and female HFs, caffeine enhanced IGF-1 protein expression. In ORSK, caffeine stimulated cell proliferation, inhibited apoptosis/necrosis, up-regulated IGF-1 gene expression and protein secretion, while TGF-beta2 protein secretion was down-regulated. CONCLUSIONS: This study reveals new growth-promoting effects of caffeine on human hair follicles of both genders at different (molecular, cellular and organ) levels. This article is protected by copyright. All rights reserved
Tumour necrosis factor alpha, interferon gamma and substance P are novel modulators of extrapituitary prolactin expression in human skin
Synthesis of a Heparinoid Pentasaccharide Containing L-Guluronic Acid Instead of L-Iduronic Acid with Preserved Anticoagulant Activity
L-Iduronic acid is a key constituent of heparin and heparan sulfate polysaccharides due to its unique conformational plasticity, which facilitates the binding of polysaccharides to proteins. At the same time, this is the synthetically most challenging unit of heparinoid oligosaccharides; therefore, there is a high demand for its replacement with a more easily accessible sugar unit. In the case of idraparinux, an excellent anticoagulant heparinoid pentasaccharide, we demonstrated that L-iduronic acid can be replaced by an easier-to-produce L-sugar while maintaining its essential biological activity. From the inexpensive D-mannose, through a highly functionalized phenylthio mannoside, the L-gulose donor was prepared by C-5 epimerization in 10 steps with excellent yield. This unit was incorporated into the pentasaccharide by alpha-selective glycosylation and oxidized to L-guluronic acid. The complete synthesis required only 36 steps, with 21 steps for the longest linear route. The guluronate containing pentasaccharide inhibited coagulation factor Xa by 50% relative to the parent compound, representing an excellent anticoagulant activity. To the best of our knowledge, this is the first biologically active heparinoid anticoagulant which contains a different sugar unit instead of L-iduronic acid
Differential effects of caffeine on hair shaft elongation, matrix and outer root sheath keratinocyte proliferation, and TGF-尾2-/IGF-1-mediated regulation of hair cycle in male and female human hair follicles in vitro.
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