Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding.

Understanding molecular mechanisms for regeneration of hair follicles provides new opportunities for developing treatments for hair loss and other skin disorders. Here we show that fibroblast growth factor 9 (Fgf9), initially secreted by γδ T cells, modulates hair follicle regeneration after wounding the skin of adult mice. Reducing Fgf9 expression decreases this wound-induced hair neogenesis (WIHN).

Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.

Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D(2) synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D(2) (PGD(2)), is similarly elevated in bald scalp.

A novel podophyllotoxin derivative (YB-1EPN) induces apoptosis and down-regulates express of P-glycoprotein in multidrug resistance cell line KBV200.

Our group synthesized a new potent anti-tumor podophyllotoxin derivative, YB-1EPN. In our study, we found that it was more potent than etoposide (VP-16). Interestingly, we found that the KBV200 cell line and K562/A02 cell line were rendered resistant towards VP-16 but not towards YB-1EPN.

4-Des-oxy-4β-[(5-meth-oxy-1H-indol-3-yl)oxalylamino]podophyllotoxin methanol solvate.

The main mol-ecule of the title solvate, C(33)H(30)N(2)O(10)·CH(3)OH, is a new anti-tumor agent, which shows cytotoxicity against MDR cancer cell lines. It has been synthesized by coupling 4β-amino-podophyllotoxin with (5-meth-oxy-1H-indol-3-yl)glyoxyl chloride and structurally characterized. There are two crystallographically independent mol-ecules in the asymmetric unit, which differ in the dihedral angles between the aromatic rings.

Efficient in vivo targeting of epidermal stem cells by early gestational intraamniotic injection of lentiviral vector driven by the keratin 5 promoter.

At the present time, no efficient in vivo method for gene transfer to skin stem cells exists. In this study, we hypothesized that early in gestation, specific epidermal stem cell populations may be accessible for gene transfer. To test this hypothesis, we injected lentiviral vectors encoding the green fluorescence protein marker gene driven by either the cytomegalovirus promoter or the keratin 5 (K5) promoter into the murine amniotic space at early developmental stages between embryonic days 8 and 12.

Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding.

The mammalian hair follicle is a complex 'mini-organ' thought to form only during development; loss of an adult follicle is considered permanent. However, the possibility that hair follicles develop de novo following wounding was raised in studies on rabbits, mice and even humans fifty years ago. Subsequently, these observations were generally discounted because definitive evidence for follicular neogenesis was not presented.

Capturing and profiling adult hair follicle stem cells.

The hair follicle bulge possesses putative epithelial stem cells. Characterization of these cells has been hampered by the inability to target bulge cells genetically. Here, we use a Keratin1-15 (Krt1-15, also known as K15) promoter to target mouse bulge cells with an inducible Cre recombinase construct or with the gene encoding enhanced green fluorescent protein (EGFP), which allow for lineage analysis and for isolation of the cells.

Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge.

Putative epithelial stem cells in the hair follicle bulge are thought to play pivotal roles in the homeostasis, aging, and carcinogenesis of the cutaneous epithelium. Elucidating the role of bulge cells in these processes has been hampered by the lack of gene promoters that target this area with specificity. Here we describe the isolation of the mouse keratin 15 (K15) promoter and demonstrate its utility for preferentially targeting hair follicle bulge cells in adult K15/lacZ transgenic mice.

A deviant immune response to viral proteins and transgene product is generated on subretinal administration of adenovirus and adeno-associated virus.

The immune response after ocular exposure to foreign antigens varies substantially from that of a typical systemic response. Anterior chamber associated immune deviation (ACAID) has been well documented. The immune response of the subretinal space has not been studied in as much detail.

Melatonin delays photoreceptor degeneration in the rds/rds mouse.

Photoreceptors in retinitis pigmentosa (RP), a group of inherited retinal degenerative diseases, die through apoptosis. Since melatonin protects against neuronal apoptotic death, we tested its ability to slow photoreceptor degeneration in the rds/rds mouse, an animal model for RP. Shortly after birth, rds/rds mice were given daily i.