Dietary Lycopene Protects SKH-1 Mice Against Ultraviolet B-Induced Photocarcinogenesis

Lycopene, an acyclic hydrocarbon, non-provitamin A carotenoid, is a potent antioxidant with well-documented anticancer properties. In this study, we investigated the effects of dietary lycopene on sub-acute and chronic ultraviolet B (UVB)-induced skin carcinogenesis in SKH-1 mice. Groups of three mice were fed with a nonsupplemented or 1% lycopene diet for two weeks before and throughout two weeks of UVB irradiation (30 mJ/cm2 UVB, thrice weekly). The lycopene diet significantly reduced the formation of pyrimidine dimers (PDs) and the expression of proliferative cellular nuclear antigen (PCNA) in UVB-irradiated skin. Then groups of eighteen mice were each fed with control diet or with a 0.25% or 1% (w/w) lycopene-supplemented diet for 40 weeks, beginning one week before UVB irradiation (30 mJ/cm2 UVB, thrice weekly for 23 weeks) and continuing after termination of UVB. Lycopene significantly inhibited the onset and decreased the incidence, multiplicity, and tumor weights of UVB-induced skin tumors. UVB-induced epidermal hyperplasia and PCNA expression were still remarkably inhibited by dietary lycopene, even up to 40 weeks. No significant difference in protection was detected between the low and high concentrations of lycopene. These results demonstrate that dietary lycopene does protect against UVB-induced epidermal hyperplasia and carcinogenesis. J Drugs Dermatol. 2019;18(12):1244-1254.

Higher 17α-hydroxyprogesterone levels aggravated the severity of male adolescent acne in Northeast China.

BACKGROUND: The relationship between serum hormone levels and adolescent acne is not fully clarified. OBJECTIVE: To determine the relationship between levels of androstenedione, dehydroepiandrosterone sulfate (DHEA-S), testosterone, estradiol and 17α-hydroxyprogesterone (17-OHP) with adolescent acne in Northeast China. METHODS: A transversal study included 242 acne cases and 188 controls. All data were analyzed using SPSS version 17.0. RESULTS: Androstenedione and testosterone levels were significantly higher (p < 0.0001) in the cases than in the control group. In males, the difference in 17-OHP levels was statistically significant (p < 0.0001), as well as between mild and severe acne cases (p = 0.002). The estradiol level was significantly different (p < 0.0001) between cases and controls in females. CONCLUSION: Higher androstenedione and testosterone levels are significant risk factors in the occurrence of adolescent acne. A higher 17-OHP level aggravates the severity of male adolescent acne, while a higher estradiol level protects females against the onset of adolescent acne.

The effects of topical L-selenomethionine on protection against UVB-induced skin cancer when given before, during, and after UVB exposure.

Previous studies in mice have shown that topical L-selenomethionine (SeMet) can prevent UVB-induced skin cancer when applied continuously before, during, and after the radiation exposure. With topical application of SeMet, selenium levels were shown to increase in the skin and liver, as well as in tumor tissue. Thus, possibly, the timing of SeMet application could affect the degree of inhibition of UVB-tumorigenesis (or maybe even enhance tumorigenesis at some stage). The goal of this research was to determine whether topical SeMet best inhibits UV-induced skin cancer if (a) begun before and continued during and after UVB exposure, (b) if begun before UVB-exposure and discontinued when tumors are first clinically detected, or (c) if begun only after tumors are first detected and continued thereafter. Groups of ten Skh: 1 hairless, non-pigmented mice were treated topically with vehicle lotion, or with SeMet (0.05%) in that vehicle lotion applied either (a) before, during, and after UV exposure, (b) before UV radiation and continued only until the first tumor was detected, or (c) only after the first tumor was detected. In all cases, UV irradiation was discontinued at the time of detection of the first tumor. Optimal inhibition of skin cancer was achieved by application of topical SeMet before, during, and after exposure; significant protection was also attained with application only after the onset of tumors. Notably, statistically significant protection was not seen with SeMet application only prior to tumor detection. These results suggest that even beginning SeMet supplementation late in the process of tumorigenesis can help protect from UV-induced photodamage and skin cancer.

Local hyperthermia treatment of extensive viral warts in Darier disease: a case report and literature review.

BACKGROUND: Darier disease is an autosomal dominant hereditary skin disease that is susceptible to secondary bacterial or fungal infections, but rarely to human papillomavirus (HPV) infections. Multiple or extensive warts from HPV remain a therapeutic challenge, but local hyperthermia is effective. We treated a patient with Darier disease who had superimposed warts in the genital and neck regions. MATERIALS AND METHODS: The patient was treated with tolerable local hyperthermia with infrared light from a halogen lamp (surface temperature, 40°C) to a single target lesion on the genitalia (30 min daily) for 3 consecutive days. RESULTS: Within 2 weeks, the target lesion cleared and synchronous regression of untreated lesions on the neck was observed. CONCLUSIONS: In Darier disease, local hyperthermia treatment of HPV warts in 1 region was effective in treating multiple lesions, including lesions at a remote site, possibly by promoting an immune response against HPV.

Co-existence of cutaneous alternariosis and tinea corporis in a renal transplant recipient.

Alternariosis, caused by Alternaria spp., is a rare opportunistic infection often observed in immunocompromised patients. Alternaria is a ubiquitous saprophytic fungus that naturally is found on decaying plant materials. In this paper, a case of cutaneous alternariosis in association with tinea corporis is reported. The complicated infection was confirmed by histological examination and positive tissue culture. Although the cases of alternariosis in solid organ transplant recipients or Cushing's syndrome have been described elsewhere, this is the first report in a patient who had received two renal transplants who was co-infected with Alternaria spp. and Trichophyton rubrum.

Increased expression of MAP2 inhibits melanoma cell proliferation, invasion and tumor growth in vitro and in vivo.

Malignant melanoma (MM) is characterized by aggressive metastasis and high mortality rate. Microtubule-associated proteins 2 (MAP2) is expressed abundantly in majority of melanocytic nevi and primary melanomas, but absent in metastatic melanomas. To determine whether MAP2 correlates with tumor progression of MM, we investigated the effects of MAP2 inhibition on the biological behaviour of metastatic melanoma in vitro and in vivo. Our results demonstrated that adenovirus-mediated MAP2 induced apoptotic cell death and cell cycle arrest in metastatic human and mouse melanoma cell lines in vitro, and substantially inhibited the growth of melanomas in nude mice in vivo. In addition, intracellular expression of MAP2 was found to induce the morphologic alteration, suppress the migration and invasion and affect the assembly, stabilization and bundling of microtubules in melanoma cells. This is the first study that MAP2 expression significantly inhibits the growth of MM in vivo. Our results suggest that MAP2 may serve as a promising molecular target for therapy and chemoprevention of MM in humans.

Identification of Sporothix schenckii of various mtDNA types by nested PCR assay.

We employed a nested PCR assay to detect Sporothrix schenckii DNA of 38 strains (including all the 24 mtDNA types) collected from different areas of the world, in tissue of eight mice infected with ATCC10268 strain of the fungus, and the skin biopsies of nine patients with sporotrichosis. In addition, the same procedures were used with two strains of Ceratocystis minor and isolates of 10 species of other pathogenic fungi. The outer primers SS(1) and SS(2) and inner primers SS(3) and SS(4) of the 18S rRNA gene of S. schenckii were employed. A 152 bp fragment was detected in all 38 strains of S. schenckii, eight animal specimens and nine human skin biopsies, but not samples of C. minor and the other fungal species. The detection limit of 50 fg of S. schenckii DNA extract was determined with ethidium bromide staining. In summary, we demonstrated that nested PCR assay could identify S. schenckii of all the mtDNA types and in isolates recovered from different areas of the world. The nested PCR assay seems to be highly sensitive and specific and provides a rapid method for diagnosis of sporotrichosis under conditions of contamination avoidance.

Expression of survivin and human telomerase reverse transcriptase in extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare neoplasm of apocrine gland-bearing skin. It is known that over-expression of survivin and human telomerase reverse transcriptase (hTERT) correlates with malignancies. We investigated the expression of hTERT and survivin by Paget's cells and their role in the tissue invasion and recurrence of EMPD. METHOD: Forty-two patients were enrolled into the study. Expression of survivin and hTERT were analyzed by immunohistochemistry and in situ hybridization techniques. The variables including the expression level of survivin and hTERT, gender, age, lesion location, invasion level and number of surgeries were statistically analyzed using Fisher's exact test. RESULTS: Survivin was positively stained in 18 of 22 cases (81.8%), and hTERT in 18 of 29 cases (62.1%). Significantly higher level of survivin expression was detected in patients with multiple surgeries than those with single one (p = 0.0458). Expression of hTERT was significantly higher in the patients with micro-invasive and invasive lesions than those with non-invasive lesions (p = 0.0478). CONCLUSIONS: Over-expression of survivin and hTERT correlated strongly with recurrence and local invasion of EMPD lesions. EMPD has male gender predominance in Oriental population.

A Chinese experience of fractional ultrapulsed CO2laser for skin rejuvenation.

BACKGROUND AND OBJECTIVES: The ablative fractional CO2 laser has been successfully used in treating photoaged skin in the Caucasian population. However, its application in Asian skin has not been widely reported. The purpose of this study is to observe the efficacy and safety of the protocol 'ActiveFX' for photodamaged facial skin in Chinese patients. METHODS: A non-sequential fractional ultrapulsed CO2 laser with specific settings is used in addition to a new computer pattern generator (CPG). Twenty patients received a single-session, single-pass, ablative fractional treatment on a split face. The patients were evaluated at baseline, and 1 and 3 months (M1, M3) after the treatment using a quartile grading scale. They were also asked to assess their overall satisfaction using a 4-point scale. The improvement of the coarse wrinkles was also quantitatively analyzed with a 3D in vivo imaging system. RESULTS: At M1 and M3, the blinded investigator rated global improvement as 2.8 ± 0.95 and 3.00 ± 0.73, which was consistent with the patients' assessment (2.55 ± 0.83 at M1 and 3.15 ± 0.88 at M3). The roughness analysis (Rz) demonstrated a significant decrease in periorbital wrinkles (p < 0.0001). Minimal and reversible adverse side effects and rapid healing were noted. CONCLUSIONS: Non-sequential fractional ultrapulsed CO2 laser resurfacing (ActiveFX) is considered an excellent treatment modality for photodamaged Chinese facial skin.

Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1.

Skin cancers are by far the most common human malignancies. Retinoids have shown promising preventive and therapeutic effects against a variety of human malignancies. The aim of this study was to investigate the apoptosis-inducing effect of acitretin on human skin squamous cell carcinoma (SCC) SCL-1 cells. We found that acitretin preferentially inhibited the growth of SCL-1 cells in a dose- and time-dependent manner, but not of non-malignant keratinocyte HaCaT cells. This inhibition appeared to be due to induction of apoptosis as revealed by enzyme-linked immunosorbent assay. AnnexinV/propidium iodide assay and morphological observation confirmed the pro-apoptotic effect of acitretin on SCL-1 cells. We further demonstrated that apoptosis was induced within 1-2 days and involved activation of caspases-8, -9, -3 and poly (ADP-ribose) polymerase (PARP). Caspase-8 inhibitor effectively suppressed acitretin-induced apoptosis whereas caspase-9 inhibitor did not. Acitretin increased the levels of CD95 (Fas), CD95-ligand and Fas-associated death domain. Neutralizing ZB4 anti-Fas antibody significantly inhibited the apoptosis in SCL-1 cells induced by acitretin. These results suggest that acitretin is able to induce apoptosis in skin cancer cells possibly via death receptor CD95 apoptosis pathway without affecting the viability of normal keratinocyte.

Local hyperthermia induces apoptosis of keratinocytes in both normal skin and condyloma acuminata via different pathways.

Local hyperthermia has been successfully used in the treatment of viral warts. However, the mechanism of action of hyperthermia has largely remained unclear. In this study we evaluated the effect of local hyperthermia on the induction of apoptosis in human keratinocytes, and expression of apoptosis-related genes in both condyloma acuminata (CA) and normal skin. The study showed that higher hyperthermia increased the number of apoptotic keratinocytes in CA and normal skin. The temperature-dependent increased expression of Fas and Bax were observed in both CA and normal skin. In contrast, the expression of Bcl-2 in CA was decreased at both transcriptional and translational levels. Furthermore, the transcriptional expression of DR4 and DR5 were increased in a temperature-dependent manner in CA, but not in normal skin. These results suggest that different mechanisms of action might be involved in hyperthermia induced apoptosis in CA and normal skin.

Treatment of palmoplantar pustulosis with arotinoid ethylester.

Palmoplantar pustulosis (PPP) is a chronic recurring and refractory pustular dermatosis. To investigate the efficacy and safety of arotinoid ethylester in patients with PPP, sixteen adult subjects with PPP, who had taken no systemic medications for three months, were enrolled. All the subjects received 0.03 mg of arotinoid ethylester once daily as initial dosage. The number of pustules and lesion area index (LAI) were measured pre- and post-treatment. Repeated measures of one factor ANOVA was used to statistically analyze the data. After 3 months of treatment, pustules disappeared completely in all patients (F = 15.04; p < .0001); LAI decreased significantly (F = 24.54; p < .0001). Complete clearance (100% reduction of LAI and complete disappear of pustules) and near complete clearance (75%-99%) occurred in 6 and 8 patients, respectively; the other two patients exhibited partial clearance (50%-74%). Side effects were observed in 10 patients, but were mild to moderate and well tolerated. Our study suggested that arotinoid ethylester is an effective therapy for PPP with minimal side effects.

Protective effects of green tea extracts on photoaging and photommunosuppression.

OBJECTIVES: This study aimed to investigate whether the sunscreen-containing 2-5% green tea extracts (GTEs) protect ultraviolet irradiation (UVR)-induced photoaging and photoimmunosuppression. MATERIALS AND METHODS: Twenty volunteers were exposed to repetitive solar-simulated UVR (ssUVR) on the upper back at a dosage of 1.5 minimal erythema doses (MED) per day for four consecutive days. Thirty minutes before each UVR and 6, 24, and 48 h after the last UV exposure, the products containing vehicle, and 2-5% GTEs were applied onto five sites on the dorsal skin, respectively. The skin biopsies were obtained 72 h after the last UVR. The thickness of the stratum corneum and epidermis was measured under the microscope and the expression of cytokeratins (CK)-5/6, CK16, metalloproteinases (MMP)-2, MMP-9, and the CD1a(+) Langerhans cells (LCs) were determined using immunohistochemistry. RESULTS: Our results showed that UVR substantially induced cutaneous erythema, thickening of the epidermis, overexpression of CK5/6, CK16, MMP-2, MMP-9, and depletion of CD1a(+) LCs. The sunscreens containing different concentrations of GTEs conferred significant protection against the photoaging and photoimmunology-related biological events. Interestingly, the protective effects were not parallel to the concentrations of GTEs, with 2% and 3% GTEs showing the most efficacious photoprotection. CONCLUSIONS: GTEs-containing sunscreens have potential photoprotective effects on UVR-induced photoaging and photoimmunosuppression.

Protective effects of cyclooxygenase-2 inhibitors on narrow-band ultraviolet B-irradiated epidermal Ia+ Langerhans cells and Thy-1+ dendritic epidermal T cells in mice.

Cyclooxygenase (COX)-2 inhibitors are known to be used as chemopreventative agents against certain malignancies. Thus far, there has been very limited information on whether COX-2 inhibitors protect against chronic narrow-band UVB (NB-UVB)-induced immunosuppression. The present study investigated the effect of nonselective and specific COX-2 inhibitors, indomethacin and celecoxib, on epidermal Ia+ Langerhans cells (LCs) and Thy-1+ dendritic epidermal T cells (DETCs) in mice irradiated with NB-UVB. Sixty female BALB/c mice were divided randomly into the control group (sham) and the experimental groups (irradiated with NB-UVB for 17 weeks, further divided into five groups according to the diets containing different concentrations of either COX-2 inhibitors). Alterations in the density and morphology of epidermal Ia+ LCs and Thy-1+ DETCs in mice were documented using fluorescence microscopy. Chronic NB-UVB irradiation substantially decreased the density and altered the morphology of the epidermal Ia+ LCs and Thy-1+ DETCs in control mice. The dietary supplementation of both COX-2 inhibitors displayed a dosage-dependent protective effect on the murine dendritic cells irradiated by NB-UVB. In conclusion, COX-2 inhibitors protected against chronic NB-UVB-induced density and morphologic changes in epidermal Ia+ LCs and Thy-1+ DETCs in mice.

p53 gene mutations in SKH-1 mouse tumors differentially induced by UVB and combined subcarcinogenic benzo[a]pyrene and UVA.

We compared the frequency and spectra of p53 mutations in skin tumors from UVB-irradiated and benzo(a)pyrene-UVA-treated SKH-1 mice. Analysis of p53 mutations using a combination of polymerase chain reaction, denaturing high-performance liquid chromatography, and sequencing shows that the frequency and spectrum of p53 mutations in BaP-UVA-induced tumors are quite different from those in UVB-induced tumors. SKH-1 mice were treated with BaP-UVA or UVB for 30 weeks after which skin tumors were collected for analysis of p53 mutations. Among the 11 BaP-UVA-induced tumors with diameters of 5-10 mm, two displayed mutations in exon 8 yielding a mutation frequency of 18.2%. In contrast, the mutation frequency among BaP-UVA-induced tumors was 10.5%. In UVB-induced tumors, the mutation frequency in exon 8 was highly correlated with tumor size. A total of 77.8% of tumors with diameters larger than 10 mm contained p53 mutations. The overall mutation frequency among UVB-induced tumors was 17.9% in exon 8 and only 3.8% in exon 5. Hotspots for p53 mutation in UVB-induced tumors were found at codons 128 and 149 (exon 5), and at codons 268, 270, 271 and 273-276 (exon 8). In addition to widely recognized C-->T missense mutations, there were also tandem CC-->AG changes coupled with either an insertion of T, a C-->G substitution or G-->C/T mutations. All of the mutations were found at tri- or tetra-pyrimidine sites. Thirty-nine per cent of all p53 mutations occurred at codons 274 and 275; 53% occurred at codons 268-271. Two multiple mutation clusters were located at codons 268-271 and 274-276. Both BaP-UVA and UVB caused C-->T transitions at codon 275 in exon 8. A C-->T mutation at codon 294 was induced only by BaP-UVA treatment. In contrast to UVB treatment, BaP-UVA treatment did not induce any mutations in exon 5. We show that individually subcarcinogenic levels of BaP and UVA synergistically induce a novel p53-mutation fingerprint. This fingerprint could serve as a prognostic indicator for the development of BaP-UVA-induced skin tumors.

Efficacy and safety of innovative cosmeceuticals.

The research and development of cosmeceuticals is booming in recent years. Many substances, either from botanical, animal, or chemically synthesized sources, are tested or investigated as the active ingredients in cosmeceuticals. The interactions between cosmeceuticals and skin are complex, depending on the specific composites in cosmeceutical products, condition of the skin or general health status of a subject, and the environment where the action occurs. As such, careful preclinical or clinical evaluation of efficacy and safety is a prerequisite for the development of a specific cosmeceutical product. This article reviews some of the ingredients that are currently in use or might be potential candidates in cosmeceuticals of different categories.

Efficacy and safety of intense pulsed light in treatment of melasma in Chinese patients.

BACKGROUND: Melasma is commonly seen in the Asian population. Traditional therapies are less effective and may cause adverse effects. OBJECTIVE: The objective was to study the efficacy and safety of a new intense pulsed light (IPL) device in the treatment of melasma in Chinese patients. METHODS: Eighty-nine women with melasma were enrolled in this open-labeled study. Subjects received a total of four IPL treatments at 3-week intervals. Changes in facial hyperpigmentation and telangiectasis were evaluated using an objective, skin colorimeter (Mexameter, Courage & Khazaka), the melasma area and severity index (MASI), and a global evaluation by the patients and blind investigators. RESULTS: Sixty-nine of 89 patients (77.5%) obtained 51% to 100% improvement, according to the overall evaluation by dermatologists. Self-assessment by the patients indicated that 63 of 89 patients (70.8) considered more than 50% or more improvement. Mean MASI scores decreased substantially from 15.2 to 4.5. Mexameter results demonstrated a significant decrease in the degree of pigmentation and erythema beneath the melasma lesions. Patients with the epidermal-type melasma responded better to treatment than the mixed type. Adverse actions were minimal. CONCLUSION: IPL treatment is a good option for patients with melasma. Adverse actions of IPL were minimal and acceptable.

Water content and other aspects of brittle versus normal fingernails.

BACKGROUND: Previous authors have claimed that dehydration of the nail plate causes brittle nails. Some experts claim that normal nails contain 18% water, and brittle nails contain less than 16%. OBJECTIVE: We sought to test the hypothesis that brittle nails contain 2% less water than normal nails. We also examined the relationship between a number of health and behavioral variables and brittle nails. METHODS: In all, 102 participants with either brittle or normal nails had two nails clipped and then analyzed for water content by a blinded investigator in the laboratory. Participants filled out a detailed questionnaire designed to reveal information about health and behavior. RESULTS: The mean water content for normal nails was 11.90% and for brittle nails was 12.48%. There was no statistically significant difference between the two groups. The odds of having brittle nails was 3.23 times greater among participants who received a professional manicure (95% confidence interval 1.21, 8.59). The frequency of professional manicures was associated with the likelihood of having brittle nails. Frequency of hand moisturizer use was significantly associated with nail brittleness (95% confidence interval 1.35, 32.10). Family history was significantly associated with the likelihood of having brittle nails (95% confidence interval 1.65, 21.11). LIMITATIONS: Analyzing nails from living participants is limiting because samples can only be collected from the distal unattached nail plate. A small subanalysis was performed and showed that the nails were losing water between the time of clipping and laboratory analysis. Therefore, our water percentage results may not be representative of in vivo nail plate water contents. CONCLUSIONS: There was no significant difference in water content of brittle compared with normal nails.