Combined therapy of 5-aminolevulinic acid photodynamic therapy and intense pulsed light for rosacea.

Rosacea is difficult to treat. Therefore, new alternative modalities are necessary to demonstrate. The present study was conducted to assess the efficacy and safety of the combined therapy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and intense pulsed light (IPL) for rosacea to provide a new treatment option for rosacea. The study was conducted from November 2017 to April 2019 at the Department of Dermatology, The First Hospital of China Medical University. Patients aged 18-65 years and diagnosed clinically as erythematotelangiectatic (ET) or papulopustular (PP) rosacea were enrolled. Three times of ALA-PDT at 10 days interval followed by 3 times of IPL at 3-4 weeks interval were defined as 1 session and applied to the whole face of each patient. ALA-PDT: 5% ALA, red light (fluency dose 60-100 mW/cm2, 20 min); IPL: 560/590/640 nm, double/triple-pulse mode, pulse width 3.0 to 4.5 ms, delay time 30-40 ms, energy fluency 14-17 J/cm2. Ten patients were enrolled in the study. Among them, 4 patients received only 1 session, while 6 patients received 2 sessions. After all treatments, 50% of patients achieved 75-100% improvement, and 30% achieved 50-75% improvement. Forty percent of patients were graded very satisfaction and 30% graded moderate satisfaction. All noninvasive measurements showed no significant differences among all time points (p > 0.05). The side effects were pain, burning sensation, itching, erythema, desquamation, slight edema, slight exudation, and hyperpigmentation. All of which were tolerable and recovered in a few days. The combined therapy of ALA-PDT and IPL showed an effective option for rosacea with a safety profile.

Investigation of optimal energy or density of a fractional CO2 laser system in the treatment of stable non-segmental vitiligo.

BACKGROUND: Fractional carbon dioxide (CO2) laser has been considered to be an add-on to conventional treatments of vitiligo. OBJECTIVE: This study aimed to evaluate the optimal energy and density of the fractional CO2 laser system in stable non-segmental vitiligo (NSV) patients. METHOD: 48 patients were treated with fractional CO2 laser and sequential phototherapies of narrowband ultraviolet B (NB-UVB), after the CO2 laser treatment, a compound betamethasone solution was topically applied. For the fractional CO2 laser, coverages of 8% and 12.6% were set as low density (Ld) and high density (Hd), and energies of 60 mJ and 80 mJ were set as low energy (Le) and high energy (He), respectively. The patients were randomly assigned to Group A (HeHd), Group B (HeLd) or Group C (LeLd). RESULTS: Either after 3 or 6 months of enrollment, the efficacy of Group C was better than Group B (p < 0.05). No difference was seen between Group A and Group B or Group A and Group C (p > 0.05). More patients complained higher pain score in Group A as compared with Group C (p < 0.05). CONCLUSION: The optimal parameters of the fractional CO2 laser were energy at 60 mJ and density at 8%.

Effects of Oral Carotenoids on Oxidative Stress: A Systematic Review and Meta-Analysis of Studies in the Recent 20 Years.

Carotenoids protect organs, tissues, and cells from the damaging action of singlet oxygen, oxygen radicals, and lipid peroxides. This systematic review was sought to evaluate the influence of oral carotenoids on antioxidant/oxidative markers, blood carotenoids levels, and lipid/lipoprotein parameters in human subjects. A comprehensive review of relevant literature was conducted in PubMed, Web of Sciences, and the Cochrane library, from 2000 to December 2020. Randomized controlled trials, case-controlled trials, or controlled trials were identified. A total of eighteen trials were included, with the target populations being healthy subjects in 16 studies, athletes in 1 study, and pregnant women in 1 study. The meta-analysis results showed that carotenoids complex supplementation significantly increased the levels of antioxidative parameters ferric-reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) [standardized mean difference (SMD) = 0.468; 95% CI: 0.159-0.776, p = 0.003; SMD = 0.568; 95% CI: 0.190-0.947, p = 0.003] and decreased the blood triglyceride (TG) level (SMD = -0.410, 95% CI: -0.698 to -0.122, p = 0.005). Oral carotenoids supplement significantly increased the blood levels of ß-carotene (SMD = 0.490, 95% CI: 0.123-0.858, p = 0.009), α-tocopherol (SMD = 0.752, 95%CI: 0.020-1.485, p = 0.044), and the intaking durations were 8 weeks. The levels of antioxidative enzymes and other lipid/lipoprotein parameters were not different between subjects receiving carotenoids and controls (p > 0.05). In conclusion, our systematic review showed that the carotenoids complex is beneficial for alleviating potential oxidative stress via interacting with free radicals or decreasing blood TG levels. The intaking duration of carotenoids should be 8 weeks to reach enough concentration for function.

A multi center real world observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature.

Treatment of high risk human papillomavirus infection in low grade cervical squamous intraepithelial lesion with mild local thermotherapy: Three case reports.

INTRODUCTION: Mild local hyperthermia at 44°C has been proven efficacious in the treatment of cutaneous warts induced by human papillomavirus (HPV), while its effect on cervical intraepithelial neoplasia (CIN) caused by high risk type of HPVs has not been reported. PATIENT CONCERNS: Three patients with low grade CIN and positive high risk HPV types (HPV 16, 31, 52, 56, 58) are reported in this study. DIAGNOSIS: The diagnosis was based on identification of HPV types and abnormal cytological findings. INTERVENTIONS: The 3 patients were treated with local hyperthermia from ceramic heating (surface temperature, 44°C) to cervix. The treatment was delivered once a day for 3 consecutive days, plus two similar treatments 10 ± 3 days later, with each session lasting 30 minutes. HPV and cytology test were performed 3 months thereafter. OUTCOMES: All the 3 patients recovered to normal cytological findings. Two of the patients were negative for HPV, the remaining patient with pre-treatment HPV 56 and 58 positivity changed to HPV58 positive alone. CONCLUSION: This pilot observation inspires that mild local hyperthermia be recommended as a new method in the treatment of CIN patients with persistent HPV infection, once validated by qualified RCT.

Cytoprotective effects of a proprietary red maple leaf extract and its major polyphenol, ginnalin A, against hydrogen peroxide and methylglyoxal induced oxidative stress in human keratinocytes.

Phytochemicals from functional foods are common ingredients in dietary supplements and cosmetic products for anti-skin aging effects due to their antioxidant activities. A proprietary red maple (Acer rubrum) leaf extract (Maplifa™) and its major phenolic compound, ginnalin A (GA), have been reported to show antioxidant, anti-melanogenesis, and anti-glycation effects but their protective effects against oxidative stress in human skin cells remain unknown. Herein, we investigated the cytoprotective effects of Maplifa™ and GA against hydrogen peroxide (H2O2) and methylglyoxal (MGO)-induced oxidative stress in human keratinocytes (HaCaT cells). H2O2 and MGO (both at 400 µM) induced toxicity in HaCaT cells and reduced their viability to 59.2 and 61.6%, respectively. Treatment of Maplifa™ (50 µg mL-1) and GA (50 µM) increased the viability of H2O2- and MGO-treated cells by 22.0 and 15.5%, respectively. Maplifa™ and GA also showed cytoprotective effects by reducing H2O2-induced apoptosis in HaCaT cells by 8.0 and 7.2%, respectively. The anti-apoptotic effect of Maplifa™ was further supported by the decreased levels of apoptosis associated enzymes including caspases-3/7 and -8 in HaCaT cells by 49.5 and 19.0%, respectively. In addition, Maplifa™ (50 µg mL-1) and GA (50 µM) reduced H2O2- and MGO-induced reactive oxygen species (ROS) by 84.1 and 56.8%, respectively. Furthermore, flow cytometry analysis showed that Maplifa™ and GA reduced MGO-induced total cellular ROS production while increasing mitochondria-derived ROS production in HaCaT cells. The cytoprotective effects of Maplifa™ and GA in human keratinocytes support their potential utilization for cosmetic and/or dermatological applications.

Phenolic-enriched maple syrup extract protects human keratinocytes against hydrogen peroxide and methylglyoxal induced cytotoxicity.

Reactive carbonyl species including methylglyoxal (MGO) are oxidation metabolites of glucose and precursors of advanced glycation end products (AGEs). They are important mediators of cellular oxidative stress and exacerbate skin complications. Published data supports that certain phenolic compounds can exert cellular protective effects by their antioxidant activity. A phenolic-enriched maple syrup extract (MSX) was previously reported to show protective effects against AGEs- and MGO-induced cytotoxicity in human colon cells but its skin protective effects remain unknown. The protective effects of MSX were evaluated against hydrogen peroxide (H2 O2 )- and MGO-induced cytotoxicity in human keratinocytes (HaCaT cells). Cellular viability and antioxidant activity were evaluated by the luminescent cell viability CellTiter-Glo assay and the reactive oxygen species (ROS) assay, respectively. A single-cell gel electrophoresis (Comet assay) was used to measure the strand breaks in the DNA of HaCaT cells. MSX (at 50 µg/mL) ameliorated H2 O2 - and MGO-induced cytotoxicity by increasing cell viability by 21.5% and 25.9%, respectively. MSX reduced H2 O2 - and MGO-induced ROS production by 69.4% and 56.6%, respectively. MSX also reduced MGO-induced DNA damage by 47.5%. MSX showed protective effects against H2 O2 - and MGO-induced cytotoxicity in HaCaT cells supporting its potential for dermatological and/or cosmeceutical applications.

A decade retrospective study of light/laser devices in treating nasal rosacea.

Background: Large-scale retrospective studies of light/laser in treating nasal rosacea were lacking.Objective: The study was aimed to perform a decade retrospection of the patients with nasal rosacea who were treated with light/laser devices.Methods: A study between 2008 and 2017 was performed retrospectively. Categorization of rosacea type (erythema/telangiectasia, ET; papules/pustules, PP; rhinophyma, RP) was made according to the photographs. Device settings, treatment regimens and treatment sessions of light/laser facilities were summarized. Efficacy was evaluated using a grading scale.Results: In all, 807 patients received light/laser treatments. The subtypes of nasal rosacea were ET (n = 196), PP (n = 95), RP (n = 42), ET + PP (n = 334), ET + RP (n = 15), PP + RP (n = 88), and ET + PP + RP (n = 37). The lesions of ET or PP were mainly treated with noninvasive devices (Intense pulsed light, IPL; Dye pulse light, DPL; Dual wavelength laser system, DW) and those of RP were treated with the Fractional carbon dioxide (FCO2) laser. For the mixed subtypes, the general disposal orders of lesions were ET, PP, and later RP, and the fundamental orders of devices application were IPL, DPL, DW, and FCO2 laser. For all types of rosacea except for RP (2-4 sessions), most of the patients received 4-6 sessions of treatments. Of all subtypes of ET, PP, RP, ET + PP, ET + RP, PP + RP, and ET + PP + RP, the patients who achieved more than 50% improvement accounted for 74.5%, 58.3%, 83.3%, 69.2%, 73.3%, 61.4%, and 51.4%, respectively.Conclusion: The multiple, sequential light/laser devices can be safely used in nasal rosacea with various degrees efficacies based on different types.

Randomized trial of electrodynamic microneedle combined with 5% minoxidil topical solution for the treatment of Chinese male Androgenetic alopecia.

Background: In treating androgenetic alopecia, 5% minoxidil is a commonly used topical drug. By using electrodynamic microneedle at the same time may increase absorption of minoxidil and further stimulate hair growth.Objective: A 24-week, randomized, evaluator blinded, comparative study was performed to evaluate the efficacy of treating Chinese male androgenetic alopecia using microneedle combined with 5% minoxidil topical solution. Methods: Randomized subjects received topical 5% minoxidil (group 1, n = 20), local electrodynamic microneedle treatments (group 2, n = 20), or local electrodynamic microneedle treatments plus topical 5% minoxidil (group 3, n = 20). A total of 12 microneedle treatments were performed every 2 weeks with 2ml 5% minoxidil delivery in group three during each microneedle treatment. Patient receiving topical 5% minoxidil applied 1 ml of the solution twice daily over the course of the study. A total of 60 Chinese male subjects with Norwood-Hamilton type III-VI androgenetic alopecia were treated.Results: The mean improvement in total hair density from baseline to 24 weeks was 18.8/cm2 in group 1, 23.4/cm2 in group 2, and 38.3/cm2 in group 3. The hair growth in the three groups was significantly different (P = 0.002), but there were no significant differences in toxicity found between the three groups.Conclusions: Treatment with microneedle plus topical 5% minoxidil was associated with the best hair growth.

A cream of herbal mixture to improve melasma.

BACKGROUND: Melasma is an acquired, common hyperpigmented disorder on the face. While many therapeutic approaches are available, their efficacy is moderate. OBJECTIVE: To investigate the safety and efficacy of a cream containing herbal mixture for melasma. METHODS: A total of 90 volunteers with melasma were enrolled in this randomized, double-blind, controlled clinical study, and they were randomly divided into three groups (A, B, and C). Patients in group A were treated with a cream containing herbal mixture, while groups B and C were treated with arbutin cream and placebo, respectively, twice daily for 12 weeks. Melasma area and severity index (MASI) score, melanin index (MI), erythema index (EI), changes in density of inflammatory cells, and adverse events were evaluated every 4 weeks. RESULTS: Although MASI scores declined significantly in both groups A and B (P < 0.05), a greater reduction was seen in group A (13.00-9.82 = 3.18 for group A; 12.65-10.84 = 1.81 for group B). Moreover, the cream containing herbal mixture, but not arbutin cream and placebo, significantly reduced EI and density of inflammatory cells after 12-week treatment (P < 0.05). No adverse reactions were observed in either group A or group C. In group B, two subjects experienced mild erythema and itching, which disappeared after stop using the arbutin cream. CONCLUSION: The cream containing herbal mixture is safe and effective for melasma.

Local hyperthermia cleared multifarious viral warts in a patient with Cushing's syndrome.

A female Cushing's syndrome patient had been suffering from extensive viral warts for months. She was diagnosed with flat warts, common warts and plantar warts. The plantar warts on her right foot were initially treated using local hyperthermia at 44°C for 30 min according to a defined protocol, followed by treatment targeting a common wart on her left thumb. In response to hyperthermia, the flat warts on her eyelid dissipated within 12 weeks, and when combined with a 1 week administration of imiquimod, the common warts and plantar warts completely disappeared within 8 weeks. There were no signs of recurrence and during this treatment her Cushing's syndrome was alleviated. This pioneer trial suggests that local hyperthermia may serve as an effective mean for treating multiple cutaneous warts under the conditions of a systemic immuno-compromised disease.

DNAJA4 deficiency enhances NF-kappa B-related growth arrest induced by hyperthermia in human keratinocytes.

BACKGROUND: Hyperthermia is an effective treatment against cancer and human papillomavirus (HPV) infection. Previous studies have shown that heat shock proteins are crucial to the action of hyperthermia. OBJECTIVES: To examine the effects of hyperthermia in combination with DNAJA4-deficiency on human keratinocytes and Condyloma acumunatum (CA) tissues. METHODS: HaCaT cells were subjected to 44°C (compared to 37°C) waterbath for 30min for stimulation. Foreskin or CA tissues obtained from patients undergoing circumcision or pathological examination were bisected and subjected to similar treatments. DNAJA4-knockout (KO) HaCaT cells were generated with CRISPR/Cas9 technology. mRNA and protein expressions were determined using rt-qPCR and western-blotting. Cell cycle distribution, apoptosis and senescence were analyzed by flow cytometry. RESULTS: DNAJA4 was induced in HaCaT cells, foreskin and CA tissues subjected to hyperthermia at both transcriptional and translational levels. NF-kB,3 was activated by hyperthermia in HaCaT cells, and further enhanced by DNAJA4-deficiency. Transcription of TNF-α4; IL-1B,5 TNFAIP36 and IL-87 were induced in HaCaT cells subjected to hyperthermia. DNAJA4-knockout promoted transcriptions of TNF-α and IL-1B, whereas decreased that of TNFAIP3 and IL-8. Reduced cell survival, proliferation and viability were demonstrated using flow cytometry and MTS assays. Furthermore, NF-kB inhibitors reversed most of the phenotypes observed. CONCLUSIONS: Hyperthermia reduced HaCaT cell proliferation and promoted cytokine expressions responsible for anti-viral activity, mainly through a NF-kB dependent pathway. DNAJA4-deficiency enhanced the activation of NF-kB by hyperthermia in HaCaT cells, indicating that DNAJA4 may be a promising therapeutic target for use in the treatment of cutaneous HPV infections.

Sea Buckthorn (Hippophaë rhamnoides L.) Oil Improves Atopic Dermatitis-Like Skin Lesions via Inhibition of NF-κB and STAT1 Activation.

BACKGROUND AND OBJECTIVES: The objective of this study was to evaluate the topical effects of sea buckthorn (SBT) oil on atopic dermatitis (AD)-like lesions in a mouse model generated by repeated topical administration of DNCB in BALB/c mice. METHODS: DNCB was applied repeatedly on the dorsal skin of mice to induce AD-like lesions. Following AD induction, SBT oil was applied daily on the dorsal skin for 4 weeks. The severity of skin lesions was examined macroscopically and histologically. We further measured the production of MDC/CCL22 and TARC/CCL17 in IFN-γ/TNF-α activated HaCaT cells. RESULTS: Topically applied SBT oil in DNCB-treated mice ameliorated the severity score of dermatitis, decreased epidermal thickness, reduced spleen and lymph node weights, and prevented mast cell infiltration. In addition, SBT oil suppressed the Th2 chemokines TARC and MDC via dose-dependent inhibition of NF-κB, JAK2/STAT1, and p38-MAPK signaling pathways in IFN-γ/TNF-α-activated HaCaT cells. CONCLUSION: These results suggest that SBT oil had a beneficial effect on AD-like skin lesions, partially via inhibition of the Th2 chemokines TARC and MDC in inflamed skin.

Combination of fractional QSRL and IPL for melasma treatment in Chinese population.

BACKGROUND: Melasma is the most common and distressing pigmentary disorder presenting to dermatology clinics. Various treatment protocols for melasma have been suggested in the previous literature and applied in various clinical settings. However, no satisfactory therapy has been widely accepted. OBJECTIVE: To evaluate the efficiency and safety of a combination treatment with fractional Q-switched ruby laser (QSRL) and intense pulsed light (IPL) for melasma in Chinese population. METHODS: Fifty-three Chinese melasma patients were enrolled in this study. Each patient underwent 2 courses of treatments at 2-week interval. One course was composed of 3 successive sessions of 694-nm fractional QSRL at intervals of two weeks followed by one IPL. The efficacy was evaluated by non-invasive measurements and subjective assessments. The adverse effects were recorded. RESULTS: Mean melanin index (MI) and erythema index (EI) significantly decreased from 216.1 and 381.8 pre-treatment to 167.8 and 310.3 post-treatment, respectively. Mean melasma area and severity index (MASI) decreased dramatically from 14.66 before treatment to 5.70 after the final treatment. These values remained at low levels at 3-month follow-up. The percentage of patients who achieved moderate or significant improvements was 73.6%. Adverse effects of QSRL and IPL were minimal. CONCLUSION: The combination treatment of fractional QSRL and IPL would be a promising modality for managing melasma in Chinese patients.

HSPB1 deficiency sensitizes melanoma cells to hyperthermia induced cell death.

Hyperthermia has shown clinical potency as a single agent or as adjuvant to other therapies in cancer treatment. However, thermotolerance induced by thermosensitive genes such as the heat shock proteins can limit the efficacy of hyperthermic treatment. In the present study, we identified HSPB1 (HSP27) is hyperthermically inducible or endogenously highly expressed in both murine and human melanoma cell lines. We used a siRNA strategy to reduce HSPB1 levels and showed increased intolerance to hyperthermia via reduced cell viability and/or proliferation of cells. In the investigation of underlying mechanisms, we found knock down of HSPB1 further increased the proportion of apoptotic cells in hyperthermic treated melanoma cells when compared with either single agent alone, and both agents leaded to cell cycle arrest at G0/G1 or G2/M phases. We concluded that hyperthermia combined with silencing of HSPB1 enhanced cell death and resulted in failure to thrive in melanoma cell lines, implying the potential clinical utility of hyperthermia in combination with HSPB1 inhibition in cancer treatment.

Treatment of infraorbital dark circles using 694-nm fractional Q-switched ruby laser.

The objective of this study was to evaluate the efficacy and safety of using a 694-nm fractional Q-switched ruby laser to treat infraorbital dark circles. Thirty women with infraorbital dark circles (predominant color: dark/brown) participated in this open-labeled study. The participants received eight sessions of 694-nm fractional Q-switched ruby laser treatment using a fluence of 3.0-3.5 J/cm2, at an interval of 7 days. The melanin deposition in the lesional skin was observed in vivo using reflectance confocal microscopy (RCM). The morphological changes were evaluated using a global evaluation, an overall self-assessment, and a Mexameter. Twenty-eight of the 30 patients showed global improvements that they rated as excellent or good. Twenty-six patients rated their overall satisfaction as excellent or good. The melanin index indicated a substantial decrease from 240.44 (baseline) to 194.56 (P < 0.05). The RCM results showed a dramatic decrease in melanin deposition in the upper dermis. The adverse effects were minimal. The characteristic finding of dark/brown infraorbital dark circles is caused by increased melanin deposition in the upper dermis. The treatment of these infraorbital dark circles using a 694-nm fractional QSR laser is safe and effective.