Hair Bulb Research Articles

Hoxc13 is a crucial regulator of murine hair cycle.

Hair follicles undergo cyclical growth and regression during postnatal life. Hair regression is an apoptosis-driven process strictly controlled by micro- and macro-environmental signals. However, how these signals are controlled remains largely unknown. Hoxc13, a member of the Hox gene family, is reported to play an important role in hair follicle differentiation. In the present study, we observed that Hoxc13 was highly expressed in the outer root sheath, matrix, medulla and inner root sheath of hair follicles in a hair cycle-dependent manner. We therefore investigated the role of Hoxc13 in hair follicle cycling. Injection of ShRNA (ShHoxc13) to suppress Hoxc13 in early anagen promoted premature catagen entry, shown by significantly decreased hair length and hair bulb size, increased percentage of catagen hair follicles, hair cycle score and TUNEL+ cells and inhibited proliferation. In contrast, local injection of recombinant Hoxc13 polypeptide (rhHoxc13) during the late anagen phase prolonged the anagen phase. Additionally, rhHoxc13 injections during the telogen phase significantly promoted hair growth and induced the anagen progression. At the molecular level, the expression of phosphorylated smad2 (p-smad2), a key factor of active TGF-β1 signaling, was up-regulated in the ShHoxc13-treated hair follicles and down-regulated in rhHoxc13-treated hair follicles, suggesting that Hoxc13 might block anagen-catagen transition by inhibiting the TGF-β1 signaling. Taken together, our data strongly suggest that Hoxc13 is a novel and crucial regulator of the hair cycle. This might also provide an understanding of the mechanism of the 'hair cycle clock' and the development of alopecia treatments.

The effects of gamma rays on the regeneration of hair follicles are carried over to later hair cycles

Purpose: The purpose of this study was to determine whether the effects of gamma rays on the regeneration of hair follicles are carried over to later hair cycles.Materials and methods: The whole bodies of C57BL/10JHir mice in the 1st telogen phase were irradiated with 60Co γ-rays. Mice were examined for the effects on hair follicles, including their number, morphology and pigmentation in the 3rd anagen phase. Effects of γ-rays on hair follicle stem cells were investigated by the indirect immunolabeling of keratin 15 (K15).Results: Decreased hair follicle density and induction of curved hair follicles were observed in the dermis of irradiated skin. In addition, white hair and hypopigmented hair bulbs were found. The number of K15-positive hair follicle stem cells in the hair bulge region of irradiated skin appeared to decrease slightly but not significantly.Conclusions: These results suggest that the effects of γ-rays are carried over to a later hair cycle to affect the number, structure and pigmentation of hair follicles in the 3rd anagen phase when stem cells and committed progenitors for keratinocytes and melanocytes are irradiated in the 1st telogen phase.

Cutaneous metabolic pathway of tyrosine as a precursor to melanin in Asinara’s white donkey, Equus asinus L., 1758

L-tyrosine (L-Tyr) is a conditionally indispensable amino acid for Equids. The biologic role of L-Tyr is ubiquitous, being involved in the production of hair and skin pigments. The white donkeys of <em>Asinara</em> island display a peculiar white coat, with life-long hypopigmentation of skin, hairs and eyes. Our results underline how the white phenotype is due to a disorder of melanin biosynthesis, detected in skin biopsies and on hair bulbs through immunohistochemical and enzymatic assays. The metabolic pathway of L-Tyr is compatible with the clinical frame of ocular-cutaneous albinism (OCA). The enzymatic activity in hair bulbs for the conversion of L-Tyr to L-3,4-dihydroxyphenilalanine (L-DOPA) tested negative, but positive for L-DOPA conversion into eumelanin in the 100% of the <em>Asinara</em>’s white donkey. This is the case of a negative-tyrosinase albinism, which contemporarily excludes dietary deficiencies of phenylalanine (Phe) or L-Tyr and potential incapability of Tyr intestinal uptake or Tyr conversion from Phe. The tyrosinase (TYR) residual activity positively and significantly (P=0.012) correlates (P=0.897) with the albino phenotype of the <em>Asinara</em>’s white donkey. These results definitely point to the fact that <em>Asinara</em>’s white donkey population owes its phenotype to TYR residual activity, thus on genetic basis. From a comparative point of view, the albino form of the <em>Asinara</em>’s white donkeys is similar to the human OCA type 1, from which however differs for positively testing to L-DOPA conversion, upon incubation of hair bulbs in L-DOPA solutions.

Collagenase IV plays an important role in regulating hair cycle by inducing VEGF, IGF-1, and TGF-β expression.

BackgroundIt has been reported that collagenases (matrix metalloproteinase 2 [MMP-2] and matrix metalloproteinase 9 [MMP-9]) are associated with hair cycle, whereas the mechanism of the association is largely unknown.MethodsThe mice were randomly allocated into four groups: saline, and 5, 10, and 15 nM SB-3CT. Immunohistochemical analysis was employed to examine MMP-2 and MMP-9 protein. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay were performed to determine mRNA and protein levels of VEGF, IGF-1, TGF-β, and GAPDH. Growing hair follicles from anagen phase III–IV were scored based on hematoxylin and eosin staining. Hair regrowth was also evaluated.ResultsResults showed that mRNA expressions of enzymes changed with a peak at late anagen and a trough at telogen after depilation. Immunostaining showed that the highest expression of MMP-2 was more than that of MMP-9, and the highest expression of enzymes changed during anagen. The localizations of MMP-2 changed from dermal papilla, keratinocyte strand, out of root sheath, and basal plate at early anagen, to hair bulb, inner root sheath, and outer root sheath at late anagen. The localization of MMP-9 changed from partial keratinocyte to dermal papilla at early anagen and to outer root sheath at late anagen. VEGF, IGF-1, and TGF-β have been shown to regulate hair growth. We found mRNA and protein expressions of VEGF and IGF-1 fluctuated with a peak at anagen and a decrease at catagen to telogen. In contrast, mRNA and protein expressions of TGF-β changed with highest and lowest levels at anagen and telogen, respectively. With selective inhibitor of collagenase IV, SB-3CT, mice showed significant suppressed hair growth and decreased expression of VEGF, IGF-1, and TGF-β. The MMPs agonist also significantly increased expression of VEGF, IGF-1, and TGF-β. Meanwhile, SB-3CT treatment significantly suppressed hair growth.ConclusionAll these data suggest that the type IV collagenases, MMP-2 and MMP-9, play important roles in hair cycle, and this could be mediated by induced expression of VEGF, IGF-1, and TGF-β.

Topical sulfonylurea as a novel therapy for hypertrichosis secondary to diazoxide, and potentially for other conditions with excess hair growth

It is hypothesized that a topical application of a sulfonylurea drug, which can inhibit the ATP-sensitive potassium-gated channels (Kir6.X/SUR) present in human hair bulb tissues, will inhibit hair growth in a targeted manner. Diazoxide is used to treat severe hypoglycemia due to hyperinsulinism of infancy. However, this often results in hypertrichosis that can be severe enough to prevent its use. Diazoxide blocks insulin release from the pancreas by opening the SUR1/Kir6.2 channels in ß-cells. Diazoxide can also act on two potassium-gated channels in the skin that affect hair growth, namely SUR1/Kir6.2 and SUR2B/Kir6.1, thus causing hypertrichosis. It is proposed that a topical sulfonylurea will inhibit the excessive hair growth due to diazoxide, but will not impact the beneficial effects of diazoxide on beta cells. This approach can also be applied to rare cases of Cantú syndrome, caused by mutations in ABCC9 (coding for SUR2) or in KCNJ8 (coding for Kir6.1) that is characterized by congenital hypertrichosis. More importantly, this approach may also be effective in treating other forms of hypertrichosis or hirsutism, that are quite common, yet very distressing to patients worldwide.

Abstract 889: Mouse model for chemotherapy-induced alopecia with transplantation of human hair follicles onto immune deficient mouse

Abstract Optimized research models of chemotherapy-induced alopecia (CIA) require for further understanding the pathogenesis and protection of CIA. The present study was aimed to develop a new mouse model for CIA by follicular unit transplantation of human hair follicles onto the immune-deficient mice. At 22 weeks after transplantation, single dose of cyclophosphamide (Cph) was treated in mice of Cph100 (100mg/kg) and Cph150 (150mg/kg) groups. On day 6 of treatment, hair follicles showed dystrophic anagen representing with swollen dermal papilla and ectopic melanin clumping in the hair bulb. In addition, up-regulated P53 expression and apoptotic matrix keratinocytes, and down-regulated expression of Ki67 and melanogenic protein in the hair bulb were also noted in both groupsin Cph100 and Cph150. Subsequently, hair follicles in Cph100 appeared to recover as anagen hair follicles after 9 days. Ki67 and melanogenic protein expression returned as the levels analogous to the control. On the other hands, hair follicles of Cph150 prematurely entered dystrophic catagen-telogen phase after 9 days of treatment. Ki67 and melanogenic protein expression in immunofluorescence staining were barely visible. Those findings indicate that this model represented two pathways of dystrophic anagen pathway in Cph100 and dystrophic catagen pathway in Cph150. Our model will be a useful tool for the further understanding of the impact of chemotherapy on the human hair follicle. Citation Format: Ohsang Kwon, Ji-Seon Yoon, Mira Choi, Chang Yup Shin, Kyu Han Kim. Mouse model for chemotherapy-induced alopecia with transplantation of human hair follicles onto immune deficient mouse. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 889. doi:10.1158/1538-7445.AM2015-889

Metodologies used in the extraction of deoxyribonucleic acid

The objective was to do a review the literature regarding the methodologies used in the extraction process of deoxyribonucleic acid. The nucleic acids may be extracted from various organic materials. Different methodologies are used for extraction, which should ensure the quality of the samples according to the objectives of the research and studied species, such as proteinase K, phenol / chloroform, hair bulbs, cards for blood, among other commercial kits and protocols adapted

Time-course mass spectrometry imaging for depicting drug incorporation into hair.

In order to investigate the incorporation of drugs into hair, matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MS/MS) imaging was performed on the longitudinal sections of single scalp hair shafts sampled from volunteers after a single oral administration of methoxyphenamine (MOP), a noncontrolled analogue of methamphetamine. Hair specimens were collected by plucking out with the roots intact, and these specimens were prepped by an optimized procedure based on freeze-sectioning to detect the drug inside the hair shaft and hair root. Time-course changes in the imaging results, with confirmatory quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for each 1-mm segment of single hair strands, revealed a substantial concentration of the drug first onto the hair bulbs after ingestion, while only a small portion appeared to be incorporated into the hair matrix, forming a 2-3 mm distinctive drug band with tailing. Comparable amount of the drug also appeared to be incorporated into the keratinized hair shaft in the upper dermis zone, forming another distinct drug band of about 2 mm, which both moved toward the distal side, following the strand's growth rate. These findings provide forensically crucial information: there are two major drug incorporation sites, at least for MOP, which cause overlap of the recordings and deteriorates its chronological resolution down to about 11 days or perhaps longer.

Management of hypotrichosis of the eyelashes: focus on bimatoprost.

Prominent eyelashes are generally recognized as enhancing beauty and are often desired by women. Until recently, the options available to augment the prominence of eyelashes were limited to makeup, over-the-counter products, artificial eyelashes, and eyelash transplantation. Originally approved for the treatment of ocular hypertension, the prostamide, bimatoprost, is now approved for the treatment of hypotrichosis of the eyelashes. Bimatoprost ophthalmic solution 0.03%, applied once daily to the skin of the upper eyelid margin using sterile single-use-per-eye applicators, increases eyelash growth, including length, thickness, and darkness. The effectiveness of bimatoprost for eyelash growth has been demonstrated by clinician ratings, digital image analysis, and patient-reported measures of satisfaction. The effects of bimatoprost treatment on eyelash length, thickness, and darkness are believed to result from longer anagen duration, increased hair bulb thickness, and increased melanogenesis, respectively. Dermally applied bimatoprost appears to be associated with a lower incidence of adverse events than administration of the medication as an eyedrop. This more favorable safety and tolerability profile is likely mediated by decreased exposure of ocular tissues to bimatoprost when applied dermally. Taken together, available data suggest that cutaneous application of bimatoprost ophthalmic solution 0.03% safely and effectively enhances upper eyelash growth.

Blood supply--susceptible formation of melanin pigment in hair bulb melanocytes of mice.

Background:Allogeneic skin grafts onto C57BL/6 mice are rejected, and the rejected skin is replaced by surrounding skin with black hair. In contrast, syngeneic skin grafts are tolerated, and gray hair grows on the grafts.Methods:To explore the mechanism of gray hair growing on the tolerated skin grafts, we prepared full-thickness skin (2-cm square) autografts, 2 (2 cm + 2 cm) horizontal or vertical parallel incisions, and U-shaped (2 cm × 2 cm × 2 cm) flaps with or without pedicle vessels. The grafts, incisions, and flaps were fixed by suturing with string and protected by a transparent bandage. On day 14 after the operation, the bandages were removed to observe the color of the hair growing on the skin.Results:Skin autografts from wild-type or hepatocyte growth factor-transgenic (Tg) C57BL/6 mice survived with gray hair, whereas those from steel factor (Kitl)-Tg C57BL/6 mice survived with black hair. In addition, U-shaped flaps lacking both of the 2 main feeding vessels of wild-type mice had gray hair at the tip of the flaps. Light microscopy after staining with hematoxylin and eosin or dihydroxyphenylalanine showed that the formation of melanin pigment in the follicles, but not in the interadnexal skin, was susceptible to the blood supply.Conclusions:Melanin pigment formation in the hair bulb melanocytes appeared to be susceptible to the blood supply, and melanocytosis was promoted in the follicles and in the epidermis of Kitl-Tg C57BL/6 mice.

DMRT3 is associated with gait type in Mangalarga Marchador horses, but does not control gait ability.

The Mangalarga Marchador (MM) is a Brazilian horse breed known for a uniquely smooth gait. A recent publication described a mutation in the DMRT3 gene that the authors claim controls the ability to perform lateral patterned gaits (Andersson et al. 2012). We tested 81 MM samples for the DMRT3 mutation using extracted DNA from hair bulbs using a novel RFLP. Horses were phenotypically categorized by their gait type (batida or picada), as recorded by the Brazilian Mangalarga Marchador Breeders Association (ABCCMM). Statistical analysis using the plink toolset (Purcell, 2007) revealed significant association between gait type and the DMRT3 mutation (P = 2.3e-22). Deviation from Hardy-Weinberg equilibrium suggests that selective pressure for gait type is altering allele frequencies in this breed (P = 1.00e-5). These results indicate that this polymorphism may be useful for genotype-assisted selection for gait type within this breed. As both batida and picada MM horses can perform lateral gaits, the DMRT3 mutation is not the only locus responsible for the lateral gait pattern.

Effects of Chinese Herbal Extracts on Tyrosinase Activity and Melanogenesis

Tyrosinase is a key enzyme for the biosynthesis pathway of melanin pigment, which is the most important determinant of the colour of skin and hair colour. Hair turns grey due to a decrease in the production of melanin in the hair bulb, which gives the hair its colour. In previous study, Chinese herbal have been found to increase melanin production and prevent the graying of hair. We demonstrated that 2, 3, 5, 4′-Tetrahydroxystilbene 2-O-β- D-glucoside (THSG), gallic acid, physcion, and emodin are the major compounds of Fallopia multiflora in high performance liquid chromatography (HPLC) analysis. In our preliminary screening using mushroom tyrosinase, 2, 3, 5, 4′-Tetrahydroxystilbene 2-O-β-D-glucoside, gallic acid, and physcion were found to show significant increased activity for tyrosinase. We also investigated that Chinese herbal extracts (Fallopia multiflora, Ligustrum lucidum ait, Angelica sinensis, and other Chinese herbal) to show significant increased activity for mushroom tyrosinase and melanogenesis in mouse melanocytes. Therefore, Chinese herbal extracts can be a potential agent for hair blackening to be used in cosmetic products.

Acquired Dermal Melanocytosis of the Dorsum in a Middle-Aged Asian Woman.

Dear Editor: Here, we describe a case of acquired dermal melanocytosis involving the dorsum in an Asian woman. A 45-year-old Korean woman presented with a 3-year history of a relatively well-demarcated, pale, blue-grayish, asymptomatic round patch on her interscapular back area (Fig. 1). Hypertrichosis was not observed within the lesion. Physical examination revealed no other similar lesions elsewhere. The patient denied any history of preceding inflammatory changes, trauma, bruises, tattoos, or metal contact on her back. She also denied taking heavy metals or any medicines that may result in hyperpigmentation and had no family history of similar skin lesions. Histopathologic examination revealed multiple spindle-shaped brown pigment-containing cells scattered among collagen fibers in the dermis (Fig. 2A, B). Immunohistochemical staining demonstrated these cells were positive for S100 protein (Fig. 2C) and negative for HMB-45 (data not shown). In addition, the brown pigment stained positive with Fontana-Masson stain, which is indicative of melanin (Fig. 2D), but not with Perls Prussian blue stain for hemosiderin (data not shown). Furthermore, immunohistochemistry revealed CD68-positive cells scattered in the dermis (Fig. 2E). Therefore, the patient was diagnosed with acquired dermal melanocytosis of the back, but no treatment was administered in accordance with the patient's wishes. Fig. 1 A relatively well-demarcated pale blue-grayish round patch on the interscapular area. Fig. 2 Histopathologic examinations and immunohistochemistry. (A, B) Multiple spindle-shaped brown pigment-containing cells scattered among collagen fibers in the dermis (HE A: ×100, B: ×200). (C) Immunohistochemical staining showed ... Dermal melanocytosis is defined by the presence of melanin-containing dendritic melanocytes in the dermis and can be differentiated on the basis of lesion onset and location1. Congenital forms of dermal melanocytosis include Mongolian spot, nevus of Ota, and nevus of Ito. Acquired forms of dermal melanocytosis include nevus of Hori and nevus of Sun, which involve the bilateral and unilateral malar areas, respectively. Acquired dermal melanocytosis located in areas besides the face is very rare; previously reported non-facial sites include the extremities and back1,2. Some of these reported cases were associated with malignancies including melanoma, physical trauma, oral estrogen, and eczema2. Although the pathogenesis of acquired dermal melanocytosis is unclear, one possibility is that dermal melanocytes may pre-exist in an immature state; they subsequently become activated by various stimuli including ultraviolet exposure, sex hormones, and inflammation3,4. This is supported by the observation that dermal melanocytes are also found in the normal-appearing skin neighboring the lesions of acquired dermal melanocytosis5. Nevertheless, the origin of the pre-existing dermal immature melanocytes is not fully understood. They may descend from the basal layer of the epidermis, migrate from hair bulbs, or improperly migrate during the embryonic period4. Acquired dermal melanocytosis does not usually fade; the pigment persists in contrast with Mongolian spots. This persistence may be associated with the extracellular sheath encircling dermal melanocytes, which has been observed in ultrastructural studies4. The extracellular sheaths of Mongolian spots usually fade over time, whereas those of nevus of Ota gradually thicken over time. Extracellular sheaths are also observed in acquired dermal melanocytosis and presumably play a role in protecting dermal melanocytes4. In conclusion, we report a case of acquired dermal melanocytosis with an unusual location that has not been described previously.

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.

Methotrexate Treatment for Alopecia Areata with Greater than 50% Involvement

Alopecia areata is a non-scarring alopecia that can present as patches of hair loss (areata, AA), complete scalphair loss (totalis, AT) or complete scalp and body hair loss (universalis, AU). It is an autoimmune disease mediated via CD8+ T-cell activation and NKG28 signaling targeting the hair bulb. Previous reports indicate that systemic treatment with methotrexate (MTX) benefits patients with AT or AU when used alone or with systemic corticosteroid administration. This study evaluates the utilization of MTX as a treatment modality in patients with alopecia areata who have greater than 50% hair loss.

A Pilot Study of the Hair-Trapping Method in Asiatic Black Bears (Ursus thibetanus): Determination of Optimal Survey Period for Estimating Population Size

In order to establish methodology for population estimation of Asiatic black bears using the hair-trapping method, hair-trapping devices were located within a study area, and basic data were collected to determine the optimal survey period for hair sampling. Bear hairs collected were classified as three types (guard hair; G, underfur; U, and intermediate hair; I) depending on hair-bulb thickness. After DNA extraction, six microsatellite loci and amelogenin locus were amplified in order to identify individual bears and sex, respectively. The number of hairs collected by hair-trapping devices decreased dramatically in late August, while those that had lost part of the hair bulb increased after September. The success rate of genetic analysis was over 90% prior to the month of July and rapidly decreased in August. Based on the results of the generalized linear model, it was determined that sampling session had the most significant impact on the success rate of genetic analysis of all the explanatory variables examined. Higher rates of U-type hairs within samples used in DNA extraction resulted in lower success rates of genetic analysis. It was concluded that the optimal survey period for estimating population size using the hair-trapping method was between June and early August.

Stimulatory effect of Brazilian propolis on hair growth through proliferation of keratinocytes in mice.

Propolis is a natural honeybee hive product with the potential for use in the treatment of dermatological conditions, such as cutaneous abrasions, burns, and acne. In this study, we investigated whether propolis stimulates hair growth in mice. Ethanol-extracted propolis, which contains various physiologically active substances such as caffeic acid and kaempferol, stimulated anagen induction in shaved back skin. Anagen induction occurred without any detectable abnormalities in the shape of the hair follicles (HFs), hair stem cells in the bulge, proliferating hair matrix keratinocytes in the hair bulb, or localization of versican in the dermal papilla. Propolis treatment also stimulated migration of hair matrix keratinocytes into the hair shaft in HFs during late anagen in the depilated back skin. Organotypic culture of skin containing anagen stage HFs revealed significant stimulation of hair matrix keratinocyte proliferation by propolis. Furthermore, propolis facilitated the proliferation of epidermal keratinocytes. These results indicate that propolis stimulates hair growth by inducing hair keratinocyte proliferation.

Hair type-specific function of canonical Wnt activity in adult mouse skin.

Wnt/β-catenin signalling is a key regulator of hair follicle (HF) morphogenesis and life-long HF regeneration. In a recently published issue of Experimental Dermatology, Lei etal. report that sustained WNT10B supply and pathway activation in regenerating mouse HF increased the width of hair bulbs, hair shafts and the dermal papilla (DP), and enlarged the CD34(+) HF bulge cell compartment. Notably, WNT10B affected primarily zigzag HFs, while size and morphology of other HF types remained largely unaffected. Thus, these findings raise a number of questions regarding a HF type-specific function of Wnt/β-catenin and on the role of the WNT-stimulated DP in this process.

MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway.

Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators β-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify β-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging.

Analysis of human β-papillomavirus and Merkel cell polyomavirus infection in skin lesions and eyebrow hair bulbs from a cohort of patients with chronic lymphocytic leukaemia.

Research demonstrates an increased incidence of skin cancer in immunocompromised hosts, including patients with chronic lymphocytic leukaemia (CLL) and organ transplant recipients (OTRs). Active human β-papillomavirus (β-HPV) infection has been found in OTR skin lesions, suggesting its possible involvement in skin carcinogenesis. Merkel cell polyomavirus (MCPyV) has also been reported in cases of skin cancer. To investigate the potential correlations between patient clinical features and skin cancer development, and the presence of β-HPV and MCPyV DNA and protein markers in skin lesions and hair bulbs from patients with CLL. The clinical features of 293 patients with CLL were analysed according to the presence or absence of skin lesions. β-HPV and MCPyV infection was investigated in skin lesions and hair bulbs from the study cohort by both polymerase chain reaction (PCR) analysis and immunohistochemical screening. No significant correlations were observed between any of the analysed haematological parameters and the development of skin cancer. PCR analysis revealed the presence of β-HPV and MCPyV DNA in skin lesions, and 83% of positivity for MCPyV DNA in hair bulbs, while systematic immunohistochemical analysis of all the lesions failed to detect any expression of the viral proteins β-HPV E4, L1 or MCPyV LTAg. Overall, the data indicate that carriage of β-HPV and MCPyV in the lesional skin and hair bulbs from patients with CLL without any evident reactivation at skin tumour sites most likely represents coincidental rather than causal infection. This contrasts with previous findings in relation to OTR-derived skin lesions.