Baicalin increases hair follicle development by increasing canonical Wnt/ß­catenin signaling and activating dermal papillar cells in mice.

Baicalin is a traditional Chinese herbal medicine commonly used for hair loss, the precise molecular mechanism of which is unknown. In the present study, the mechanism of baicalin was investigated via the topical application of baicalin to reconstituted hair follicles on mice dorsa and evaluating the effect on canonical Wnt/ß­catenin signaling in the hair follicles and the activity of dermal papillar cells. The results indicate that baicalin stimulates the expression of Wnt3a, Wnt5a, frizzled 7 and disheveled 2 whilst inhibiting the Axin/casein kinase 1α/adenomatous polyposis coli/glycogen synthase kinase 3ß degradation complex, leading to accumulation of ß­catenin and activation of Wnt/ß­catenin signaling. In addition, baicalin was observed to increase the alkaline phosphatase levels in dermal papillar cells, a process which was dependent on Wnt pathway activation. Given its non­toxicity and ease of topical application, baicalin represents a promising treatment for alopecia and other forms of hair loss. Further studies of baicalin using human hair follicle transplants are warranted in preparation for future clinical use.

Tight junctions form a barrier in porcine hair follicles.

Follicular penetration has gained increasing interest regarding (i) safety concerns about (environmentally born) xenobiotics available to the hair follicle (HF), e.g. nanomaterials or allergens which should not enter the skin, and (ii) the possibility for non-invasive follicular drug and antigen delivery. However, not much is known about barriers in the HF which have to be surpassed upon uptake and/or penetration into surrounding tissue. Thus, aim of this work was a detailed investigation of this follicular barrier function, as well as particle uptake into the HF of porcine skin which is often used as a model system for human skin for such purposes. We show that follicular tight junctions (TJs) form a continuous barrier from the infundibulum down to the suprabulbar region, complementary to the stratum corneum in the most exposed upper follicular region, but remaining as the only barrier in the less accessible lower follicular regions. In the bulbar region of the HF no TJ barrier was found, demonstrating the importance of freely supplying this hair-forming part with e.g. nutrients or hormones from the dermal microenvironment. Moreover, the dynamic character of the follicular TJ barrier was shown by modulating its permeability using EDTA. After applying polymeric model-nanoparticles (154 nm) to the skin, transmission electron microscopy revealed that the majority of the particles were localized in the upper part of the HF where the double-barrier is present. Only few penetrated deeper, reaching regions where TJs act as the only barrier, and no particles were observed in the bulbar, barrier-less region. Lastly, the equivalent expression and distribution of TJ proteins in human and porcine HF further supports the suitability of porcine skin as a predictive model to study the follicular penetration and further biological effects of dermally applied nanomaterials in humans.

Modeling Clinical States and Metabolic Rhythms in Bioarcheology.

Bioarcheology is cross disciplinary research encompassing the study of human remains. However, life's activities have, up till now, eluded bioarcheological investigation. We hypothesized that growth lines in hair might archive the biologic rhythms, growth rate, and metabolism during life. Computational modeling predicted the physical appearance, derived from hair growth rate, biologic rhythms, and mental state for human remains from the Roman period. The width of repeat growth intervals (RI's) on the hair, shown by confocal microscopy, allowed computation of time series of periodicities of the RI's to model growth rates of the hairs. Our results are based on four hairs from controls yielding 212 data points and the RI's of six cropped hairs from Zweeloo woman's scalp yielding 504 data points. Hair growth was, ten times faster than normal consistent with hypertrichosis. Cantú syndrome consists of hypertrichosis, dyschondrosteosis, short stature, and cardiomegaly. Sympathetic activation and enhanced metabolic state suggesting arousal was also present. Two-photon microscopy visualized preserved portions of autonomic nerve fibers surrounding the hair bulb. Scanning electron microscopy found evidence that a knife was used to cut the hair three to five days before death. Thus computational modeling enabled the elucidation of life's activities 2000 years after death in this individual with Cantu syndrome. This may have implications for archeology and forensic sciences.

Fluorine-induced apoptosis and lipid peroxidation in human hair follicles in vitro.

Fluoride is an essential trace element for human body; however, exposure to high amounts of fluoride has been documented to be correlated with an increasing risk of hair loss. To date, little is known about the mechanism(s) of how fluoride affects hair follicles. Here, we demonstrated that middle (1.0 mmol/L) and high (10.0 mmol/L) concentrations of sodium fluoride (NaF) significantly inhibited hair follicle elongation in vitro, but low NaF (0.1 mmol/L) showed little influence. Moreover, treatment with high levels of NaF resulted in a marked increase in terminal dUTP nick end labeling-positive cells in the outer layer of the outer root sheath, the dermal sheath, and the lower bulb matrix surrounding dermal papilla. Furthermore, the enhanced apoptosis was coupled with an increased oxidative stress manifested as higher malondialdehyde content. Additionally, the presence of selenium considerably antagonized the effects of middle NaF on hair follicles, with regard to either the suppression of hair growth or the induction of oxidative stress and apoptosis. In conclusion, exposure to high levels of fluoride compromises hair follicle growth and accelerate cell apoptosis in vitro. The toxicity of fluoride can be reduced by selenium, at least partially via the suppression of intracellular oxidative stress.