Inverse androgenic alopecia.

A man in his 50s presented to our clinic with obvious progressive hair thinning in the occipital area below the creeping alopecia crown vertex accompanied by the typical Hamilton-Norwood pattern of male androgenetic alopecia (MAGA) hair loss. Based on his clinical features, trichoscopy findings and histological features, as well as his good response to conventional anti-MAGA therapeutic drugs, such as finasteride and minoxidil, a novel isotype of MAGA, named inverse-MAGA, was first identified, and this isotype should be widely evaluated in future studies.

mTOR signaling in hair follicle and hair diseases: recent progress.

Mammalian target of rapamycin (mTOR) signaling pathway is a major regulator of cell proliferation and metabolism, playing significant roles in proliferation, apoptosis, inflammation, and illness. More and more evidences showed that the mTOR signaling pathway affects hair follicle circulation and maintains the stability of hair follicle stem cells. mTOR signaling may be a critical cog in Vitamin D receptor (VDR) deficiency-mediated hair follicle damage and degeneration and related alopecia disorders. This review examines the function of mTOR signaling in hair follicles and hair diseases, and talks about the underlying molecular mechanisms that mTOR signaling regulates.

Melanocyte stem cells and hair graying.

OBJECTIVES: To explore the relationship between melanocyte stem cells in the hair follicle bulge and hair graying so as to fully understand their key role in the pathogenesis of hair graying. METHODS: The published articles about "hair graying, hair color, pigmentation disorders" and "melanocyte stem cells, melanocyte" were searched and analyzed in PubMed to explore their relationship. RESULTS: Melanocytes in hair bulb are involved in the pathogenesis of hair graying as well as the melanocyte stem cells in hair follicle bulge also play important roles in the formation of hair graying through some ways. CONCLUSION: Loss of melanocyte stem cells in hair follicle bulge is one of the main reasons of hair graying, and more researches are needed to explain the underlying mechanisms of ectopic differentiation of melanocyte stem cells in different individual.

Effects of Natural Polyphenols on Skin and Hair Health: A Review.

The skin is the largest organ of the body and plays multiple essential roles, ranging from regulating temperature, preventing infections, to ultimately affecting human health. A hair follicle is a complex cutaneous appendage. Skin diseases and hair loss have a significant effect on the quality of life and psychosocial adjustment of individuals. However, the available traditional drugs for treating skin and hair diseases may have some insufficiencies; therefore, a growing number of researchers are interested in natural materials that could achieve satisfactory results and minimize adverse effects. Natural polyphenols, named for the multiple phenolic hydroxyl groups in their structures, are promising candidates and continue to be of scientific interest due to their multifunctional biological properties and safety. Polyphenols have a wide range of pharmacological effects. In addition to the most common effect, antioxidation, polyphenols have anti-inflammatory, bacteriostatic, antitumor, and other biological effects associated with reduced risk of a number of chronic diseases. Various polyphenols have also shown efficacy against different types of skin and hair diseases, both in vitro and in vivo, via different mechanisms. Thus, this paper reviews the research progress in natural polyphenols for the protection of skin and hair health, especially focusing on their potential therapeutic mechanisms against skin and hair disorders. A deep understanding of natural polyphenols provides a new perspective for the safe treatment of skin diseases and hair loss.

A novel 7­hypoxia­related long non­coding RNA signature associated with prognosis and proliferation in melanoma.

Hypoxia­related long non­coding RNAs (lncRNAs) are important indicators of the poor prognosis of cancers. The present study aimed to explore the potential relationship between melanoma and hypoxia­related lncRNAs. The transcriptome and clinical data of patients with melanoma were downloaded from The Cancer Genome Atlas database. The prognostic hypoxia­related lncRNAs were screened out using Pearson's correlation test and univariate Cox analysis. As a result, a hypoxia­related­lncRNA signature based on the expression of 7 lncRNAs was constructed, with one unfavourable [MIR205 host gene (MIR205HG)] and six favourable (T cell receptor ß variable 11­2, HLA­DQB1 antisense RNA 1, AL365361.1, AC004847.1, ubiquitin specific peptidase 30 antisense RNA 1 and AC022706.1) lncRNAs as prognostic factors for melanoma. Patients with melanoma were divided into high­ and low­risk groups based on the risk score obtained. Survival analyses were performed to assess the prognostic value of the present risk model. Potential tumour­associated biological pathways associated with the present signature were explored using gene set enrichment analysis. The CIBERSORT algorithm demonstrated the important role of the hypoxia­related lncRNAs in regulating tumour­infiltrating immune cells. Clinical samples collected from our center partly confirmed our findings. Cell Counting Kit­8 and flow cytometry assays indicated the suppression of proliferation of melanoma cells following inhibition of MIR205HG expression. Indicators of the canonical Wnt/ß­catenin signalling pathway were detected by western blotting. The present study demonstrated that MIR205HG could promote melanoma cell proliferation partly via the canonical Wnt/ß­catenin signalling pathway. These findings indicated a 7­hypoxia­related­lncRNA signature that can serve as a novel predictor of melanoma prognosis.

Vitamin D Modulation of Mitochondrial Oxidative Metabolism and mTOR Enforces Stress Adaptations and Anticancer Responses.

The relationship between the active form of vitamin D3 (1,25-dihydroxyvitamin D, 1,25(OH)2D) and reactive oxygen species (ROS), two integral signaling molecules of the cell, is poorly understood. This is striking, given that both factors are involved in cancer cell regulation and metabolism. Mitochondria (mt) dysfunction is one of the main drivers of cancer, producing more mitochondria, higher cellular energy, and ROS that can enhance oxidative stress and stress tolerance responses. To study the effects of 1,25(OH)2D on metabolic and mt dysfunction, we used the vitamin D receptor (VDR)-sensitive MG-63 osteosarcoma cell model. Using biochemical approaches, 1,25(OH)2D decreased mt ROS levels, membrane potential (ΔΨmt), biogenesis, and translation, while enforcing endoplasmic reticulum/mitohormetic stress adaptive responses. Using a mitochondria-focused transcriptomic approach, gene set enrichment and pathway analyses show that 1,25(OH)2D lowered mt fusion/fission and oxidative phosphorylation (OXPHOS). By contrast, mitophagy, ROS defense, and epigenetic gene regulation were enhanced after 1,25(OH)2D treatment, as well as key metabolic enzymes that regulate fluxes of substrates for cellular architecture and a shift toward non-oxidative energy metabolism. ATACseq revealed putative oxi-sensitive and tumor-suppressing transcription factors that may regulate important mt functional genes such as the mTORC1 inhibitor, DDIT4/REDD1. DDIT4/REDD1 was predominantly localized to the outer mt membrane in untreated MG-63 cells yet sequestered in the cytoplasm after 1,25(OH)2D and rotenone treatments, suggesting a level of control by membrane depolarization to facilitate its cytoplasmic mTORC1 inhibitory function. The results show that 1,25(OH)2D activates distinct adaptive metabolic responses involving mitochondria to regain redox balance and control the growth of osteosarcoma cells. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Cloves Regulate Na+-K+-ATPase to Exert Antioxidant Effect and Inhibit UVB Light-Induced Skin Damage in Mice.

The purpose of this study was to observe the effect of cloves (Syzygium aromaticum (L.) Merr. & L.M. Perry) on the mouse skin using a UVB-induced skin injury mouse model. The serum, liver, and skin indexes of mice were determined by kits, H&E tissue staining, and qPCR assay. The compound composition of cloves was determined by HPLC. The results showed that cloves increased the activity of Na+-K+-ATPase in the skin and then maintained the sodium and potassium pump in the damaged skin muscle membrane. Cloves alleviated the oxidative stress injury induced by UVB irradiation by normalizing the related oxidative stress indexes (T-SOD, CAT, AGEs, and H2O2) in serum and skin. Inhibition of the proinflammatory cytokines TNF-α, IL-1ß, and IL-6 and increased activation of anti-inflammatory cytokines IL-4 and IL-10 occurred after treatment with cloves, which ultimately reduced the inflammatory damage to the body. Further results showed that cloves upregulate SOD1, SOD2, CAT, GSH, IL-10, IκB-α, AMPK, SIRT1, LKB1, PGC-1α, APPL1, and FoxO1 and downregulate NF-κB p65, TNF-α, IL-6, and mTOR mRNA expression in the skin tissues of UVB-damaged mice. The results of composition analysis showed that the five most abundant compounds in cloves are rutin, isoquercitrin, ferulic acid, dihydroquercetin, and quercitrin. Cloves regulate the skin sarcomembrane Na+-K+-ATPase through these five compounds, and because they regulate the oxidation, inflammation, and ATP energy consumption of the body, they subsequently protect the skin from UVB damage.

A pilot study of minimal invasion combined PDL/Nd:YAG laser in treating facial epidermoid cyst.

OBJECTIVES: To compare the efficacy and complication of minimal invasion and combined pulsed dye laser/Nd:YAG laser and traditional surgical excision in the treatment of facial epidermoid cyst. METHODS: A total of 100 patients with facial epidermoid cyst aged from 16 to 65 years and cyst diameter ranged from 0.3 to 3.0 cm were treated and followed up. Patients were divided into the minimal invasion and combined pulsed dye laser/Nd:YAG laser treatment group and traditional surgical excision group. All patients were followed up for 12 months including scar size, recurrence rate, incidence of complications, and patient global satisfaction. RESULTS: The mean operative time in the minimal invasion and combined pulsed dye laser/Nd:YAG laser treatment was 15.23 ± 7.02 minutes, which is significantly shorter than that of surgical excision (27.26 ± 10.12 minutes, P < .05). After 12 months, the average scar size in minimal invasion and combined pulsed dye laser/Nd:YAG laser group was 0.54 ± 0.35 cm, while that of traditional surgical excision group was 1.77 ± 0.81 cm (P < .05). No statistical difference was found between two groups in the wounds split, hematoma, early and late recurrence rates (P > .05), while the patients' global satisfaction in the pulsed dye laser/Nd:YAG laser group is much higher than that of the traditional surgical excision group. CONCLUSION: The treatment of minimal invasion and combined pulsed dye laser/Nd:YAG laser is effective and safe for medium-size facial epidermoid cysts. For facial epidermoid cyst ranging for 0.3 cm to 3.0 cm, considering the cosmetic factors, minimal invasion and combined pulsed dye laser/Nd:YAG laser should be particularly recommended.

Protective Effect of Lemon Peel Polyphenols on Oxidative Stress-Induced Damage to Human Keratinocyte HaCaT Cells Through Activation of the Nrf2/HO-1 Signaling Pathway.

Lemon peel can be used as traditional Chinese medicine. Flavonoids are the most important components in lemon peel, which can be developed as natural medicine without side effects. This study investigated the protective effect of lemon peel polyphenols (LPP) on human keratinocyte HaCaT cells under oxidative stress. The active components of LPP were determined by high performance liquid chromatography. The abilities of LPP to scavenge DPPH and ABTS+ free radicals were studied for detection of antioxidation in vitro. Cell survival rates were determined by MTT assay. The antioxidant enzyme activity and antioxidant index of cells were determined using kit. The mRNA and protein expression of cells were determined by qPCR and western blot. The ability of LPP to scavenge DPPH and ABTS+ free radicals were stronger than those of vitamin C (Vc) at the same concentration. As expected, compared with the normal group of cells, the model group had decreased cell survival, increased lactate dehydrogenase (LDH), decreased levels of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH), and increased malondialdehyde (MDA) content. qPCR and western blot results indicated that the expression of Bcl-2-related X protein (Bax), caspases-3, erythroid-derived nuclear factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were decreased and the expression of B-cell lymphoma-2 (Bcl-2) was increased in the model group, compared with the normal group. LPP treatment improved cell survival rate, reduced intracellular LDH and MDA levels, increased intracellular SOD, CAT, GSH levels, down-regulated Bax, caspases-3, Nrf2, HO-1 expression, and up-regulated Bcl-2 expression. Component analyses found that LPP contains gallic acid, neochlorogenic acid, (+)-catechin, caffeic acid, (-)-Catechin gallate, isochlorogenic acid A, rosmarinic acid, and protocatechuic acid. LPP was found to regulate the Nrf2/HO-1 signaling pathway through 8 active substances to protect HaCaT cells against oxidative stress in vitro.

DNA damage-inducible transcript 4 is an innate guardian for human squamous cell carcinoma and an molecular vector for anti-carcinoma effect of 1,25(OH)2 D3.

Cutaneous squamous cell carcinoma (SCC) is one of the most common non-melanoma skin cancers worldwide. While its exact tumorigenesis mechanisms is far from well-established and less satisfied therapeutic strategy can be clinically used nowadays. In this study, we intended to investigate the role of DNA damage-inducible transcript 4 (DDIT4) in human SCC. Firstly, we identified DDIT4 is significantly suppressed in human SCC tissue and cultured A431 cell line, and reduced DDIT4 accelerates keratinocytes proliferation but impedes the autophagy flux through mTORC1 pathway by affecting the downstream S6 Kinase1, 4E-BP1, Beclin1 and LC3 II/I. While 1,25(OH)2 D3 enhanced DDIT4 expression and activated autophagy and inhibit mTORC1 to take the effect of anti-proliferation and activating autophagy. Further, formation of direct vitamin D receptor (VDR)-DDIT4 transcription complex was verified by ChIP-qPCR, which showed the molecular mechanism of how 1,25(OH)2 D3 promotes DDIT4 transcription. Thirdly, xenograft tumor-bearing mice model treated by gradient concentrations of 1,25(OH)2 D3 revealed the obvious anti-carcinoma effect of 1,25(OH)2 D3 in vivo and DDIT4 acted the molecular vector of 1,25(OH)2 D3 through mTORC1. Lastly, elevated DDIT4 expression was verified in human actinic keratoses tissue, and chronic long-term ultraviolet (UV) irradiation on mouse disclosed UV could promote DDIT4 expression inside epidermis. Conclusively, our research suggested a novel molecular mechanism about the human SCC tumorigenesis and the pharmacological mechanism about how 1,25(OH)2 D3 take its anti-carcinoma role on human SCC, as well as a striking paradoxes that how UV irradiation plays the tumorigenesis effect but synchronously take a protective role in the early stage of SCC carcinogenesis.

A Mal De Meleda patient with severe flexion contractures of hands and feet: A case report in West China.

RATIONALE: Palmoplantar keratoderma (PPK) is a genetically heterogeneous group of skin diseases, which is characterized by erythema and hyperkeratosis. Mal de Meleda (MDM) is a rare type of PPK with an estimated prevalence in the general population of 1 in 100,000. PATIENT CONCERNS: In this study, we report a MDM patient with severe lesion in skin and flexion contractures of fingers and toes. DIAGNOSES: MDM was diagnosed based on clinical manifestations and gene test. INTERVENTIONS: This patient was treated with oral acitretin and topical tazarotene. OUTCOMES: Physical examinations indicated that the hyperkeratosis was in remission, but the erythema was expanding to her elbows progressively. Due to the adverse events (e.g., dry eyes and lips), the patient stopped taking the oral drug. LESSONS: MDM is a rare subtype of PPK, which is inherited in an autosomal recessive pattern and has characteristics that skin lesions on hands and feet appear soon after birth and develop progressively. MDM can lead to severe flexion contractures in some cases. The reliable method for the diagnosis of MDM is gene test.

Absence of vitamin D receptor (VDR)-mediated PPARγ suppression causes alopecia in VDR-null mice.

Vitamin D receptor (VDR) mutations in humans and mice cause alopecia. VDR-null (VDR-/-) mice exhibit lack of postmorphogenic hair cycles as a result of impaired keratinocyte stem cell (KSC) function. To identify the molecular basis for abnormal KSC function, RNA sequencing of wild-type (WT) and VDR-/- KSCs was performed. These studies demonstrated that >80% of differentially expressed genes are up-regulated in VDR-/- KSCs; thus, the VDR is a transcriptional suppressor in WT KSCs. Peroxisome proliferator-activated receptor γ (PPARγ), PPARγ coactivator 1ß (PGC1ß), and lipoprotein lipase (LPL) were among the up-regulated genes identified. Chromatin immunoprecipitation analyses demonstrated that these genes are direct VDR targets in WT keratinocytes. Notably, VDR occupancy of the PPARγ regulatory region precludes PPARγ occupancy of this site, based on the observation that PPARγ interacts with these sequences in VDR-/- but not WT keratinocytes. This contrasts with the VDR and PPARγ co-occupancy observed on PGC1ß and LPL gene regulatory regions identified. Studies in mice with keratinocyte-specific PPARγ haploinsufficiency were performed to identify the functional consequences of enhanced PPARγ expression. PPARγ haploinsufficiency normalized PPARγ mRNA levels in VDR-/- keratinocytes and restored anagen responsiveness in vivo in VDR-/- mice, resulting in hair regrowth. Thus, absence of VDR-mediated PPARγ suppression underlies alopecia in VDR-/- mice.-Saini, V., Zhao, H., Petit, E. T., Gori, F., Demay, M. B. Absence of vitamin D receptor (VDR)-mediated PPARγ suppression causes alopecia in VDR-null mice.

DNA Damage-Inducible Transcript 4 Is an Innate Surveillant of Hair Follicular Stress in Vitamin D Receptor Knockout Mice and a Regulator of Wound Re-Epithelialization.

Mice and human patients with impaired vitamin D receptor (VDR) signaling have normal developmental hair growth but display aberrant post-morphogenic hair cycle progression associated with alopecia. In addition, VDR-/- mice exhibit impaired cutaneous wound healing. We undertook experiments to determine whether the stress-inducible regulator of energy homeostasis, DNA damage-inducible transcript 4 (Ddit4), is involved in these processes. By analyzing hair cycle activation in vivo, we show that VDR-/- mice at day 14 exhibit increased Ddit4 expression within follicular stress compartments. At day 29, degenerating VDR-/- follicular keratinocytes, but not bulge stem cells, continue to exhibit an increase in Ddit4 expression. At day 47, when normal follicles and epidermis are quiescent and enriched for Ddit4, VDR-/- skin lacks Ddit4 expression. In a skin wound healing assay, the re-epithelialized epidermis in wildtype (WT) but not VDR-/- animals harbor a population of Ddit4- and Krt10-positive cells. Our study suggests that VDR regulates Ddit4 expression during epidermal homeostasis and the wound healing process, while elevated Ddit4 represents an early growth-arresting stress response within VDR-/- follicles.

The Vitamin D Receptor Regulates Tissue Resident Macrophage Response to Injury.

Ligand-dependent actions of the vitamin D receptor (VDR) play a pleiotropic role in the regulation of innate and adaptive immunity. The liganded VDR is required for recruitment of macrophages during the inflammatory phase of cutaneous wound healing. Although the number of macrophages in the granulation tissue 2 days after wounding is markedly reduced in VDR knockout (KO) compared with wild-type mice, VDR ablation does not alter macrophage polarization. Parabiosis studies demonstrate that circulatory chimerism with wild-type mice is unable to rescue the macrophage defect in the wounds of VDR KO mice and reveal that wound macrophages are of local origin, regardless of VDR status. Wound cytokine analyses demonstrated a decrease in macrophage colony-stimulating factor (M-CSF) protein levels in VDR KO mice. Consistent with this, induction of M-CSF gene expression by TGFß and 1,25-dihydroxyvitamin D was impaired in dermal fibroblasts isolated from VDR KO mice. Because M-CSF is important for macrophage self-renewal, studies were performed to evaluate the response of tissue resident macrophages to this cytokine. A decrease in M-CSF induced proliferation and cyclin D1 expression was observed in peritoneal resident macrophages isolated from VDR KO mice, suggesting an intrinsic macrophage abnormality. Consistent with this, wound-healing assays in mice with macrophage-specific VDR ablation demonstrate that a normal wound microenvironment cannot compensate for the absence of the VDR in macrophages and thus confirm a critical role for the macrophage VDR in the inflammatory response to injury.

Methylation-mediated loss of SFRP2 enhances melanoma cell invasion via Wnt signaling.

Wnt signaling plays an essential role in the initiation and progression of melanoma tumors. The Secreted Frizzled Related Proteins (SFRPs) are a family of proteins that suppress Wnt signaling. The methylation of SFRPs reduces their activity, and hence augments Wnt signaling. However, whether the methylation of SFRP2, a member of SFRPs, may be involved in the pathogenesis of melanoma is not known. Here we investigated the expression levels of SFRP2 in melanoma specimens. We found that SFRP2 mRNA wassignificantly decreased and methylation of SFRP2 gene was significantly increased in malignant melanoma tumors ascompared to the paired adjacent non-tumor tissue. Moreover, SFRP2 expression was significantly decreased in the malignant melanoma celllines, HTB63, A2058 and A375, but not in the non-transformed melanocyte cell line, Hermes 3A. The demethylation of SFRP2 gene by 5'-aza-deoxycytidine (5-aza-dCyd) in melanoma cell lines restored SFRP2 expression, at both mRNA and protein levels, and suppressed cell invasion. Furthermore, the demethylation of SFRP2 geneappeared to inhibit nuclear retention of a key Wnt signaling factor, ß-catenin, in melanoma cell lines. Together, these data suggest that SFRP2may function as a melanoma invasion suppressor byinterfering with Wnt signaling, and the methylation of SFRP2 gene may promote pathogenesis of melanoma.

Treatment of axillary bromhidrosis through a mini-incision with subdermal vascular preservation: a retrospective study in 396 patients.

BACKGROUND: Axillary bromhidrosis is a condition presenting as malodor caused by an interaction between the discharge of apocrine glands and bacteria. Topical agents, liposuction, and elective surgery are currently the main therapeutic modalities. However, the efficiency of these treatments and incidences of side effects are various and frequent, and depend on patient characteristics, surgical technique, and other unknown factors. METHODS: We report a retrospective study of outcomes in 396 patients treated by mini-incision with subdermal vascular preservation. RESULTS: At 2 years postoperatively, 87.1% of patients had achieved very satisfactory results. Short-term side effects included hematomas, epidermal erosions, infections, necrosis, incision dehiscence, and skin ripples. Long-term side effects comprised comedones, epidermoid cysts, relapsing cyst infections, skin gauffers, scars, keloids, and persistent malodor. Some patients reported unsatisfactory cosmetic results, including skin gauffers, scars, or epidermoid cyst formations. CONCLUSIONS: Two discrete aspects of the procedure that must be considered are the extent of apocrine gland clearance, which must be thorough in order to achieve the resolution of malodor, and the maintenance of an intact subdermal vascular plexus to support the regrowth of skin flaps after surgery and to avoid the occurrence of severe side effects.

The Effects of IL-22 on the Inflammatory Mediator Production, Proliferation, and Barrier Function of HUVECs.

The aim of this study was to investigate the effects of interleukin (IL)-22 on proliferation function and inflammatory mediator production and barrier function of human umbilical vein endothelial cells (HUVECs). The expression of mRNA was detected by RT-PCR. The proliferation ability of cells was evaluated using a cell counting kit assay. Real-time quantitative PCR and Western blot were used to detect the expression of inflammatory mediators. The endothelial barrier permeability was assessed by measuring permeability to FITC-labeled dextran. The distribution of occludin was detected by immunofluorescence. IL-22R1 mRNA expression was noted in HUVECs. IL-22 could enhance the proliferation ability of HUVECs and suppress lipopolysaccharide (LPS)-induced proliferation inhibition in these cells. IL-22 also enhanced the production of CCL2 and CCL20 by HUVECs. Besides, IL-22 could improve barrier function and decrease LPS-induced increased cellular permeability and inhibit the LPS-induced destruction of occludin in HUVECs. IL-22 may play a protective role in the development of vasculitis.

Portulaca oleracea L. aids calcipotriol in reversing keratinocyte differentiation and skin barrier dysfunction in psoriasis through inhibition of the nuclear factor κB signaling pathway.

Psoriasis affects 2-4% of the population worldwide and its treatment is currently far from satisfactory. Calcipotriol and Portulaca oleracea have been reported to exhibit the capacity to inhibit inflammation in psoriatic patients and improve their clinical condition. However, the efficacy of a combination regimen of these two components remains unknown. The aim of the present study was to explore the therapeutic efficacy of P. oleracea extract combined with calcipotriol on plaque psoriasis and its potential mechanism. Eleven patients with plaque psoriasis were treated with humectant containing the active ingredients of P. oleracea extract, with or without 0.005% calcipotriol ointment in a right-left bilateral lesion self-control study. Differences were evaluated by investigation of the clinical efficacy, adverse effects, skin barrier function, histological structure, expression and proliferation of keratinocytes, differentiation markers (cytokeratin 10, filaggrin and loricrin), inflammatory factors [tumor necrosis factor (TNF)-α and interleukin (IL)-8], as well as the status of the nuclear factor κB (NF-κB) pathway. The combination of P. oleracea and calcipotriol was revealed to decrease adverse effects, reduce transepidermal water loss, potently reverse keratinocyte differentiation dysfunction, and inhibit the expression of TNF-α and IL-8 and the phosphorylation of the NF-κB inhibitor IκBα. This treatment is therefore anticipated to be suitable for use as a novel adjuvant therapy for psoriatic patients.

The role of nuclear hormone receptors in cutaneous wound repair.

The cutaneous wound repair process involves balancing a dynamic series of events ranging from inflammation, oxidative stress, cell migration, proliferation, survival and differentiation. A complex series of secreted trophic factors, cytokines, surface and intracellular proteins are expressed in a temporospatial manner to restore skin integrity after wounding. Impaired initiation, maintenance or termination of the tissue repair processes can lead to perturbed healing, necrosis, fibrosis or even cancer. Nuclear hormone receptors (NHRs) in the cutaneous environment regulate tissue repair processes such as fibroplasia and angiogenesis. Defects in functional NHRs and their ligands are associated with the clinical phenotypes of chronic non-healing wounds and skin endocrine disorders. The functional relationship between NHRs and skin niche cells such as epidermal keratinocytes and dermal fibroblasts is pivotal for successful wound closure and permanent repair. The aim of this review is to delineate the cutaneous effects and cross-talk of various nuclear receptors upon injury towards functional tissue restoration.

The vitamin D receptor is required for activation of cWnt and hedgehog signaling in keratinocytes.

Alopecia (hair loss) in vitamin D receptor (VDR)-null mice is due to absence of ligand-independent actions of the VDR that are required for initiation of postmorphogenic hair cycles. Investigations were undertaken to determine whether the VDR is required for the induction of signaling pathways that play an important role in this process. The induction of cWnt and hedgehog target genes that characterizes early anagen was found to be dramatically attenuated in VDR(-/-) mice, relative to wild-type (WT) mice. To determine whether this reflects impaired responsiveness to cWnt ligands, in vitro studies were performed in primary keratinocytes. These studies demonstrated impaired induction of cWnt target genes in response to Wnt3a in VDR(-/-) keratinocytes, relative to wild-type keratinocytes. Chromatin immunoprecipitation analyses revealed that the VDR was recruited to the regulatory regions of cWnt and hedgehog target genes in WT keratinocytes but not in VDR(-/-) or Lef1(-/-) keratinocytes. Lef1 was enriched on these same regulatory regions in WT keratinocytes but not in VDR(-/-) keratinocytes. In vivo studies were performed to determine whether activation of the hedgehog pathway could bypass the defect in cWnt signaling observed in the absence of the unliganded VDR. In WT, but not VDR(-/-), mice, hedgehog agonist treatment resulted in an induction of cWnt and hedgehog target genes and the generation of mature anagen hair follicles. Thus, these studies demonstrate that the unliganded VDR interacts with regulatory regions in the cWnt and hedgehog target genes and is required for the induction of these pathways during the postnatal hair cycle.