Gene expression profile of human follicle dermal papilla cells in response to Camellia japonica phytoplacenta extract.

Camellia japonica L. is a flowering tree with several medicinal and cosmetic applications. Here, we investigated the efficacy of C. japonica placenta extract (CJPE) as a potential therapeutic agent for promotion of hair growth and scalp health by using various in vitro and in vivo assays. Moreover, we performed transcriptome analysis to examine the relative expression of human follicle dermal papilla cells (HFDPC) in response to CJPE by RNA-sequencing (RNA-seq). In vitro assays revealed upregulation of the expression of hair growth marker genes in HFDPC after CJPE treatment. Moreover, in vivo clinical tests with 42 adult female participants showed that a solution containing 0.5% CJPE increased the moisture content of the scalp and decreased the scalp's sebum content, dead scalp keratin, and erythema. Furthermore, RNA-seq analysis revealed key genes in HFDPC which are associated with CJPE. Interestingly, genes associated with lipid metabolism and cholesterol efflux were upregulated. Genes upregulated by CJPE are associated with several hormones, including parathyroid, adrenocorticotropic hormone, α-melanocyte-stimulating hormone (alpha-MSH), and norepinephrine, which are involved in hair follicle biology. Furthermore, some upregulated genes are associated with the regulation of axon guidance. In contrast, many genes downregulated by CJPE are associated with structural components of the cytoskeleton. In addition, CJPE suppressed genes associated with muscle structure and development. Taken together, this study provides extensive evidence that CJPE may have potential as a therapeutic agent for scalp treatment and hair growth promotion.

Topical application of Cinnamomum hydroethanolic extract improves wound healing by enhancing re-epithelialization and keratin biosynthesis in streptozotocin-induced diabetic mice.

Context: Cinnamomum verum J. Presl. (Lauraceae) has a high number of polyphenols with insulin-like activity, increases glucose utilization in animal muscle, and might be beneficial for diabetic patients.Objective: This study evaluated the effectiveness of an ointment prepared from Cinnamomum verum hydroethanolic extract on wound healing in diabetic mice.Materials and methods: A total of 54 male BALB/c mice were divided into three groups: (1) diabetic non-treated group mice that were treated with soft yellow paraffin, (2 and 3) mice that were treated with 5 and 10% C. verum. Two circular full-thickness excisional wounds were created in each mouse, and the trial lasted for 16 d following induction of the wound. Further evaluation was made on the wound contraction ratio, histopathology parameters and mRNA levels of cyclin D1, insulin-like growth factor 1 (IGF-1), glucose transporter-1 (GLUT-1), total antioxidant capacity, and malondialdehyde of granulation tissue contents. HPLC apparatus was utilized to identify the compounds.Results: The HPLC data for cinnamon hydroethanolic extract identified cinnamaldehyde (11.26%) and 2-hydroxyl cinnamaldehyde (6.7%) as the major components. A significant increase was observed in wound contraction ratio, fibroblast proliferation, collagen deposition, re-epithelialization and keratin biosynthesis in the C. verum-treated groups in comparison to the diabetic non-treated group (p < 0.05). The expression level of cyclin D1, IGF1, GLUT 1 and antioxidant capacity increased in the C. verum-treated groups in comparison to the diabetic non-treated group (p < 0.05).Conclusions: Topical administration of C. verum accelerated wound healing and can possibly be employed in treating the wounds of diabetic patients.

Annurca Apple Polyphenols Ignite Keratin Production in Hair Follicles by Inhibiting the Pentose Phosphate Pathway and Amino Acid Oxidation.

Patterned hair loss (PHL) affects around 50% of the adult population worldwide. The negative impact that this condition exerts on people's life quality has boosted the appearance of over-the-counter products endowed with hair-promoting activity. Nutraceuticals enriched in polyphenols have been recently shown to promote hair growth and counteract PHL. Malus pumila Miller cv. Annurca is an apple native to Southern Italy presenting one of the highest contents of Procyanidin B2. We have recently shown that oral consumption of Annurca polyphenolic extracts (AAE) stimulates hair growth, hair number, hair weight and keratin content in healthy human subjects. Despite its activity, the analysis of the molecular mechanism behind its hair promoting effect is still partially unclear. In this work we performed an unprecedented metabolite analysis of hair follicles (HFs) in mice topically treated with AAE. The metabolomic profile, based on a high-resolution mass spectrometry approach, revealed that AAE re-programs murine HF metabolism. AAE acts by inhibiting several NADPH dependent reactions. Glutaminolysis, pentose phosphate pathway, glutathione, citrulline and nucleotide synthesis are all halted in vivo by the treatment of HFs with AAE. On the contrary, mitochondrial respiration, ß-oxidation and keratin production are stimulated by the treatment with AAE. The metabolic shift induced by AAE spares amino acids from being oxidized, ultimately keeping them available for keratin biosynthesis.

Huang Qi Decoction Prevents BDL-Induced Liver Fibrosis Through Inhibition of Notch Signaling Activation.

Notch signaling has been demonstrated to be involved in ductular reactions and fibrosis. Previous studies have shown that Huang Qi Decoction (HQD) can prevent the progression of cholestatic liver fibrosis (CLF). However, whether HQD affects the Notch signaling pathway is unclear. In this study, CLF was established by common bile duct ligation (BDL) in rats. At the end of the first week, the rats were randomly divided into a model group (i.e., BDL), an HQD group, and a sorafenib positive control group (SORA) and were treated for 3 weeks. Bile duct proliferation and liver fibrosis were determined by tissue staining. Activation of the Notch signaling pathway was evaluated by analyzing expressions of Notch-1, -2, -3, and -4, Jagged (JAG) 1, and Delta like (DLL)-1, -3, and -4. The results showed that HQD significantly reduced the deposition of collagen and the Hyp content of liver tissue and inhibited the activation of HSCs compared with the BDL group. In addition, HQD significantly decreased the protein and mRNA expressions of TGF-[Formula: see text]1 and [Formula: see text]-SMA. In contrast, HQD significantly enhanced expression of the Smad 7 protein. HQD also reduced biliary epithelial cell proliferation, and reduced the mRNA levels of CK7, CK8, CK18, SRY-related high mobility group-box gene (SOX) 9, epithelial cell adhesion molecule (EpCAM) and the positive areas of CK19 and OV6. In addition, the mRNA and protein expressions of Notch-3, -4, JAG1, and DLL-1, -3 were significantly reduced in the HQD compared to the BDL group. These results demonstrated that HQD may prevent biliary liver fibrosis through inhibition of the Notch signaling pathway, and it may be a potential treatment for cholestatic liver disease.

Topical photodynamic therapy is very effective for oral verrucous hyperplasia and oral erythroleukoplakia.

BACKGROUND: Oral verrucous hyperplasia (OVH) and oral erythroleukoplakia (OEL) are two oral precancerous lesions with relatively high malignant transformation potential. One of the best cancer prevention strategies is to use a conservative and effective treatment modality to eliminate oral precancers to stop their further malignant transformation. Our previous studies have shown that the topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) using the 635-nm light-emitting diode (LED) light is very effective for OVH and OEL lesions. METHODS: Because the laser machine is a more-popular light source than the LED device in PDT clinics, in this study 40 OVH and 40 OEL lesions were treated once a week with the same PDT protocol but using the 635-nm laser light to evaluate whether this laser light-mediated topical ALA-PDT was also effective for OVH and OEL lesions. RESULTS: We found that all the 40 OVH lesions exhibited complete response (CR) after an average of 3.6 PDT treatments. Of the 40 OEL lesions, 38 showed CR after an average of 3.4 PDT treatments and two showed partial response (PR). Better PDT outcomes were significantly associated with OVH and OEL lesions with the smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer. CONCLUSION: This study indicates that the laser light-mediated topical ALA-PDT is also very effective for OVH and OEL lesions. Therefore, we suggest that topical ALA-PDT using either the LED or laser light may serve as the first-line treatment of choice for OVH and OEL lesions.

Managing acne vulgaris effectively.

The management of acne is a gratifying experience. Available treatments are effective, relatively nontoxic and generally safe. However, there is no quick fix. Antibiotics, hormone therapies and topical therapies are maintenance treatments. Isotretinoin can induce remission, as can some of the newer physical modalities of lights, lasers and radiofrequency devices. Effective management of acne often requires using a combination of treatments that act on different parts of the pathogenic process of acne development.

Pharmacology of RALGA, a mixture of retinaldehyde and glycolic acid.

BACKGROUND: Retinoids and alpha-hydroxy acids (AHAs) are major compounds in topical therapy. They exert distinct but potentially complementary activities. However, their association is limited by their respective irritating potential. Recently, the first association between a retinoid and an AHA has been achieved; this formulation (RALGA) associates retinaldehyde (RAL)--a precursor of retinoic acid (RA)--and glycolic acid (GA)--an AHA. OBJECTIVE: To study the pharmacological properties of RALGA. METHODS: The bioavailability of RAL into the skin after topical RALGA was studied by HPLC, and its bioconversion to RA was analysed by measuring the enzyme activity of retinaldehyde dehydrogenase and the RA content in the epidermis and dermis. The retinoid activity of RALGA was studied on the modulation of Hhb4 keratin mRNA on the tail of C57BL/6 mice, and its comedolytic properties on the size and density of dermal cysts and the morphology of sebaceous glands in hairless mice. RESULTS: Epidermal and dermal concentrations of RAL and RA were higher after RALGA treatment, as compared to both RAL 0.1% alone and RA 0.05% alone; this indicates that the presence of GA favours the bioavailability and biotransformation of RAL into RA. The retinoid activity of RALGA (suppression of Hhb4 mRNA keratin) was similar to that of RAL alone, indicating that the presence of GA does not interfere with specific retinoid activity; GA alone had no effect in this test, which confirms the specificity of Hhb4 mRNA keratin modulation for retinoid activity. The diameter and the density of dermal cysts as well as the size of sebaceous glands were significantly decreased by RALGA. CONCLUSION: These observations indicate that the addition of an AHA such as GA to a retinoid such as RAL results in a better bioavailability of the retinoid, thus a higher delivery of RA, which potentiates the biological activities of the retinoid. This combination allows a delivery of high amounts of RA in the skin while preventing the side-effects usually observed with high concentrations of topical RA.

Vitamin C enhances differentiation of a continuous keratinocyte cell line (REK) into epidermis with normal stratum corneum ultrastructure and functional permeability barrier.

A continuous rat epidermal cell line (rat epidermal keratinocyte; REK) formed a morphologically well-organized epidermis in the absence of feeder cells when grown for 3 weeks on a collagen gel in culture inserts at an air-liquid interface, and developed a permeability barrier resembling that of human skin. By 2 weeks, an orthokeratinized epidermis evolved with the suprabasal layers exhibiting the differentiation markers keratin 10, involucrin, and filaggrin. Granular cells with keratohyalin granules and lamellar bodies, and corneocytes with cornified envelopes and tightly packed keratin filaments were present. Morphologically, vitamin C supplementation of the culture further enhanced the normal wavy pattern of the stratum corneum, the number of keratohyalin granules present, and the quantity and organization of intercellular lipid lamellae in the interstices of the stratum corneum. The morphological enhancements observed with vitamin C correlated with improved epidermal barrier function, as indicated by reduction of the permeation rates of tritiated corticosterone and mannitol, and transepidermal water loss, with values close to those of human skin. Moreover, filaggrin mRNA was increased by vitamin C, and western blots confirmed higher levels of profilaggrin and filaggrin, suggesting that vitamin C also influences keratinocyte differentiation in aspects other than the synthesis and organization of barrier lipids. The unique REK cell line in organotypic culture thus provides an easily maintained and reproducible model for studies on epidermal differentiation and transepidermal permeation.

The future of vitamin D in dermatology.

BACKGROUND: Vitamin D3 analogs have been found to be effective in treating psoriasis. OBJECTIVE: We attempted to identify the targets and actions of vitamin D3 in the skin and to explore the availability of synthetic vitamin D3 analogs with selective actions on particular cell types or cell functions. METHODS: A review of the literature focused on the cellular targets of vitamin D3 in the skin and within the immune system. Furthermore, the use of novel vitamin D3 analogs in skin diseases other than psoriasis was reviewed. RESULTS: The vitamin D receptor has been detected in most skin cells, which means that keratinization, hair growth, melanogenesis, fibrogenesis, angiogenesis, and immune-mediated processes are potential targets for vitamin D3. Vitamin D3 analogs have been synthesized with a higher therapeutic index or a higher degree of selectivity than the natural form of vitamin D3. CONCLUSION: Vitamin D3 analogs with wide-ranging clinical applications may become available for dermatology.

Solubilization of keratin debris in conservative treatment of middle ear cholesteatoma: an in vitro study.

A variety of solutions were tested in vitro to find a suitable solvent which could be used in clinical practice for cholesteatoma debris. Though a little weak as a solvent, a liquid soap composed mainly of plant oil did not cause irritation of the middle ear mucosa, and was thought to be a promising solvent with which to rinse away tenacious debris, especially when used in combination with hydrogen peroxide.