Dietary polyphenol oleuropein and its metabolite hydroxytyrosol are moderate skin permeable elastase and collagenase inhibitors with synergistic cellular antioxidant effects in human skin fibroblasts.

Oleuropein (OLE) and hydroxytyrosol (HT) are dietary polyphenols with skin beneficial effects but their effects on skin-ageing-related enzymes are not clear. Herein, we evaluated their inhibitory effects on elastase and collagenase. OLE and HT (62.5-1 000 µM) showed moderate anti-elastase and anti-collagenase effects (5.1-26.3%, 5.8-12.2% and 12.6-31.0%, 11.6-31.9% inhibition, respectively). Combinations of OLE and HT (1:1 ratio) exerted synergistic inhibitory effects on elastase, which were supported by their combination index (CI), kinetic assay and computational docking. Moreover, HT (100 µM) reduced hydrogen peroxide (H2O2)-induced cytotoxicity and reactive oxygen species (ROS) in human dermal fibroblast cells by 21.8 and 15.2%, respectively. In addition, combinations of OLE and HT (6.25/6.25-100/100 µM) exerted synergistic cytoprotective effects by reducing ROS levels by 7.6-37.3% with CIs of 0.17-0.44, respectively. The findings from this study support the cosmeceutical activities of OLE and HT but further research is warranted to evaluate their anti-skin-ageing effects using in vivo models.

A new method for wind speed forecasting based on copula theory.

How to determine representative wind speed is crucial in wind resource assessment. Accurate wind resource assessments are important to wind farms development. Linear regressions are usually used to obtain the representative wind speed. However, terrain flexibility of wind farm and long distance between wind speed sites often lead to low correlation. In this study, copula method is used to determine the representative year's wind speed in wind farm by interpreting the interaction of the local wind farm and the meteorological station. The result shows that the method proposed here can not only determine the relationship between the local anemometric tower and nearby meteorological station through Kendall's tau, but also determine the joint distribution without assuming the variables to be independent. Moreover, the representative wind data can be obtained by the conditional distribution much more reasonably. We hope this study could provide scientific reference for accurate wind resource assessments.

2940-nm Er:YAG fractional laser enhanced the effect of topical drug for psoriasis.

We observed the promoting effects of the 2940-nm erbium:YAG (Er:YAG) fractional laser in topical drug delivery for psoriasis. A total of five (four males and one female) recalcitrant psoriasis patients were given laser treatment eight times at 1-week intervals with the following parameters: 5-11% spot density and 100-µm energy depth. The psoriatic skin lesions on the left knee and the corresponding lesions at the right ones of each psoriasis patient were randomly divided into two groups: laser + topical drug group (L) and drug alone group (D). The psoriatic lesions in both groups were treated with the same topical treatment (calcipotriol ointment). The corresponding psoriatic lesions in the L group received extra 2940-nm Er:YAG laser irradiation before topical treatment. The photos of psoriatic lesions were taken before each treatment. The final photos were obtained from the patients at the seventh day after the final treatment. Drug alone or in combination with laser Er:YAG both reduced psoriatic lesions. However, with the increase in the number of treatments, increasing differences were observed between the treatment and the control sides. The therapeutic outcomes in the L groups were better than those in the D groups. Psoriasis area and severity index (PASI) scores for five cases of both groups were decreased. However, the scores in the L groups were lower than those in the D groups. The use of 2940 nm Er:YAG promoted the absorption of topical drugs for psoriasis, improving the therapeutic effect.

Water security assessment in Haihe River Basin using principal component analysis based on Kendall tau.

Kendall tau has reasonable theoretic background than Pearson correlation. It can be applied more widely in all aspects. Instead of using widely adopted Pearson correlation or its extensions in a large number of principal component analysis (PCA) instances, we introduce the Kendall tau into the PCA method. PCA is a well-known statistical data analysis algorithm and is aimed to extract feature from high-dimensional data. It is designed to reduce the number of variables to a small number of indices while attempting to preserve the relationships present in the original data. This paper uses PCA based on Kendall tau in water security assessment of Haihe River Basin.

Short-Term Efficacy and Safety of IL-17, IL-12/23, and IL-23 Inhibitors Brodalumab, Secukinumab, Ixekizumab, Ustekinumab, Guselkumab, Tildrakizumab, and Risankizumab for the Treatment of Moderate to Severe Plaque Psoriasis: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The role of interleukin-12 (IL-12), interleukin-23 (IL-23), and interleukin-17 (IL-17) has been recognized in psoriasis pathogenesis, and new drugs targeting this axis have already been developed which may provide a new therapeutic approach for patients with moderate to severe psoriasis. OBJECTIVE: To compare the direct and indirect evidences of the efficacy and safety of brodalumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tildrakizumab, and risankizumab in the short-term treatment of moderate to severe plaque psoriasis using network meta-analysis (NMA). METHODS: A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for the available relevant studies. NMA was conducted by Stata 15.0 software using relative risks (RR) with 95% confidence interval to assess the clinical effectiveness and safety. Ranked the efficacy and safety for each drug accordance with the surface under the cumulative ranking curve (SUCRA). RESULTS: This meta-analysis included 28 studies. All the interventions performed better than placebo in short-term achievement. Based on the result of SUCRA, ixekizumab 80 mg every 2 weeks ranked the highest in short-term achievement of PASI 75 (SUCRA = 93.0%). Brodalumab 210 mg ranked the highest in short-term achievement of PASI 100 (SUCRA = 85.0%). Secukinumab 300 mg ranked the highest in short-term achievement of sPGA 0/1 or IGA 0/1 or PGA 0/1 (SUCRA = 98.1%). In terms of having a risk of adverse events, the rates were higher in brodalumab, secukinumab, ixekizumab, and ustekinumab 45 mg compared with placebo. Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of adverse events during short-term treatment (SUCRA = 4.5%). Guselkumab 50 mg ranked the highest in the risk of serious adverse events during short-term treatment (SUCRA = 25.9%). Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of discontinuations due to adverse events during short-ter treatment (SUCRA = 10.7%). CONCLUSIONS: IL-17, IL-12/23, and IL-23 inhibitors had high efficacy in the achievement of PASI 75, PASI 100, and sPGA 0/1 or IGA 0/1 or PGA 0/1 in moderate to severe plaque psoriasis after 12 or 16 weeks of treatment. IL-17 inhibitors showed superior efficacy. However, its clinical safety was poor. Risankizumab appeared to have relatively high efficacy and low risk. The clinical tolerance of other biological agents needs to be further observed.

Serum levels of adipokines and cytokines in psoriasis patients: a systematic review and meta-analysis.

PURPOSE: To evaluate the association of serum levels of adipokines and cytokines with psoriasis. MATERIALS AND METHODS: A comprehensive literature search was performed in PubMed, ScienceDirect and Web of Science for the available relevant studies published before December 1, 2016. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs) with 95% confidence interval to combine the effect estimations. We also conducted stratified analysis, meta-regression analysis and sensitivity analysis. RESULTS: Sixty-three studies containing 2876 psoriasis patients and 2237 healthy controls were included in this meta-analysis. The pooled serum levels of TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-18, IL-22, chemerin, lipocalin-2, resistin, sE-selectin, fibrinogen and C3 were higher in psoriasis patients compared with healthy controls (all P < 0.05). In contrast, adiponectin levels were lower. Serum levels of IL-1ß, IL-4, IL-10, IL-12, IL-17, IL-21, IL-23, visfatin and omentin were not significantly different between psoriasis patients and controls (all P > 0.05). However, increased serum levels of IL-17 correlated with psoriasis in men. For other biomarkers, age, gender and psoriasis area and severity index did not explain the differences in effect size between the studies. CONCLUSIONS: Serum levels of TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-18, IL-22, chemerin, lipocalin-2, resistin, sE-selectin, fibrinogen, complement 3, and adiponectin correlate with psoriasis and can be used as potential biomarkers for psoriasis and response to the treatment. Future studies are needed to identify additional players involved in the pathogenesis of psoriasis and to fully decipher the underlying mechanism.

Retinoic acid ameliorates photoaged skin through RAR­mediated pathway in mice.

Retinoic acid (RA), the bioactive metabolite of vitamin A, has demonstrated efficacy in the treatment of photoaged skin; however, the mechanism of action of RA remains unclear. The aim of the present study was to examine whether the therapeutic effects of RA on photoaged skin are mediated by retinoic acid receptor (RAR) and/or retinoid X receptor (RXR) in mice, and to investigate the underlying mechanism. Photoaged skin in Imprinting Control Region mice was induced by repeated exposure to ultraviolet (UV) irradiation. Mice were randomly divided into nine groups: Normal; UV control; all­trans retinoic acid (ATRA); ATRA + RAR antagonist; ATRA + RXR antagonist; RAR agonist; RAR agonist + RAR antagonist; RXR agonist; and RXR agonist + RXR antagonist. Masson's trichrome staining was used to examine skin collagen fibers. Hydroxyproline assays were used to determine collagen content. The protein expression of matrix metalloproteinase (MMP)­3, MMP­13, type I procollagen, c­Jun and c­Fos was detected using western blot analysis. The results demonstrated that ATRA and RAR agonist ameliorated the UV­induced damage to skin collagen fibers, and increased the collagen content in photoaged skin through RAR. Furthermore, ATRA and RAR agonist stimulated type I procollagen protein expression, and inhibited MMP­3, MMP­13 and c­Jun protein expression through RAR in photoaged skin. However, ATRA and RAR agonist exhibited no significant effect on the protein expression of c­Fos in photoaged skin. These findings suggest that RA ameliorates photoaged skin through a RAR­mediated signaling pathway in mice.

[Effects of bFGF and alpha-MSH on adhesion and migration of human melanocytes in vitro].

OBJECTIVE: To observe the effect of basic fibroblast growth factor (bFGF) and alpha-melanocyte stimulating hormone (alpha-MSH) on adhesion and migration of melanocytes in vitro. METHODS: Human melanocytes were obtained from normal human foreskins. Culture dishes covered with fibronectin were used to perform melanocytes adhesion assay, and cell motility was assessed using the Transwell micropore filter method. RESULT: bFGF and alpha-MSH increased melanocytes adhesion on culture dishes covered with fibronectin. bFGF stimulated melanocytes migration through micropore filter while alpha-MSH had no significant effects. CONCLUSION: bFGF and alpha-MSH could promote the adhesion and migration of melanocytes, which suggests that two agents may play a role in the repigmentation of vitiligo.

[Mechanism of receptor for retinoids inducing apoptosis of human melanoma cell line A375].

OBJECTIVE: To investigate the mechanism of receptors for retinoids inducing apoptosis of human melanoma cell line A375. METHODS: The effects of 3 kinds of retinoids (9-cis-RA, at-RA and 13-cis-RA), of TTNPB (RAR agonist) and of Methoprene acid (Ma, RXR agonist) on apoptosis of A375 cells were studied by detecting the expression of Bcl-2/Bax and by using. Annexin V/PI staining analysis, TUNEL detection and active Caspase-3 analysis. RESULTS: Retinoids and TTNPB could up-regulate the expression of Bax and down-regulate the expression of Bcl-2. The results of TUNEL and Annexin V/PI staining analysis showed that all of retinoids and TTNPB could induce apoptosis of A375 cells, compared with control group (P < 0.05); the effect of TTNPB was significantly greater than that of others (P < 0.05), but Ma was similar to the control (P > 0.05). Active Caspase-3 analysis showed that TTNPB and all of retinoids could up-regulate the expression of Caspase-3, and the effect of TTNPB was significantly greater than that of others (P < 0.05). CONCLUSION: Caspase-3 pathway is involved in the process for retinoids inducing apoptosis of A375 cells. The activation of RAR may have relation with retinoids inducing apoptosis of A375 cells, but may have no longer relation with RXR.

Increased ßTrCP are associated with imiquimod-induced psoriasis-like skin inflammation in mice via NF-κB signaling pathway.

Psoriasis is a common inflammatory skin disease characterized by T cell-mediated hyperproliferation of keratinocytes, increased angiogenesis and inflammation. Accumulating evidence suggests that some keratinocyte differentiation events are controlled by the ubiquitin/proteasome system. ß-transducin repeat-containing protein (ßTrCP) serve as substrate recognition component of E3 ubiquitin ligases that control stability of important regulators of signal transduction including the nuclear factor (NF)-κB signaling, a key regulatory element in inflammatory pathways related to psoriasis, suggesting a potential role of ßTrCP in psoriasis pathogenesis. However, no published study has investigated the role of ßTrCP in the etiology of psoriasis. Here, we combined an in vitro cell model of tumor necrosis factor (TNF)-α-induced keratinocyte inflammation and an animal model of imiquimod (IMQ)-induced psoriasis-like inflammation to investigate the pathogenic mechanisms in psoriasis-like dermatitis and assess its ßTrCP/NF-κB dependency. Daily application of IMQ on mouse back skin induced inflamed scaly skin lesions resembling plaque type psoriasis. These lesions were associated with elevated ßTrCP levels, reduced inhibitor κB (IκB), and enhanced NF-κB activation in epidermal tissues. Furthermore, ßTrCP knockdown via siRNA in in TNF-α-stimulated HaCaT and normal human epidermal keratinocytes (NHEK) cells significantly inhibited the over-activation of NF-κB and expression of intercellular adhesion molecule 1 (ICAM-1), demonstrating a pivotal role of ßTrCP in regulation the TNF-α-activated NF-κB inflammatory pathways. Moreover, downregulation of ßTrCP through lentiviral shRNA ameliorates IMQ-induced psoriasis-like skin lesions in vivo. In conclusion, ßTrCP is involved in the NF-κB signaling mediated-, psoriasis-related inflammation and represent a novel target for developing agents to treat psoriasis.

Effects of single herbal drugs on adhesion and migration of melanocytes.

OBJECTIVE: To find herbs with effects on adhesion and migration of melanocytes in vitro. MATERIALS AND METHODS: Ethanol extracts from 14 herbs were tested. Normal human melanocytes were obtained from neonatal foreskin, and the 48-well culture dish covered with fibronectin was used for the melanocyte adhesion assay. Motility was assessed by using the micropore filter method. RESULTS: The extracts of Danshen (Radix Salviae Miltiorrhizae), Tusizi (Semen Cuscutae) and Honghua (Flos Carthami) could enhance melanocyte adhesion to fibronectin, while Cijili (Fructus Tribuli) and Huangqi (Radix Astragali) promote melanocyte migration in vitro. Buguzhi (Fructus Psoraleae), Nü Zhen Zi (Fructus Ligustri Lucidi) and Baizhi (Radix Angelicae Dahuricae) could promote both adhesion and migration of melanocytes. CONCLUSION: The above herbs may play a role through promoting adhesion and/or migration of melanocytes in the treatment of vitiligo.

[Receptor-related mechanism of proliferation inhibilion and apoptosis induetion of human tongue squamous cell line Tca8113 by retinoids].

OBJECTIVE: To investigate the receptor-related mechanism of retinoids inhibiting proliferation and inducing apoptosis of human oral squamous cell carcinoma cell line Tca8113. METHODS: The effects of 3 retinoids (namely 9-cis-RA, at-RA and 13-cis-RA), TTNPB (RAR agonist) and methoprene acid (Ma, RXR agonist) on proliferation and cell cycle of Tca8113 cells were analyzed by MTT assay and flow cytometry. The roles of these agents in inducing apoptosis of Tca8113 cells were also evaluated by detecting the expression of Bcl-2/Bax, TUNEL and active caspase-3 analysis. RESULTS: Both retinoids and TTNPB could inhibit the proliferation of Tca8113 cells, and the effect of TTNPB was the most powerful in all the reagents, but MA had no such effect. At the concentration of 1 x 10(-5) mol/L, all the agents except for Ma could increase the percentage of G(1)/G(0)-stage cells after incubation of the cells for 24 h and 48 h. Retinoids and TTNPB could up-regulate the expression of Bax and down-regulate Bcl-2 expression. The results of TUNEL demonstrated that retinoids and TTNPB, but not Ma, could induce apoptosis of Tca8113 cells as compared with the control group (P<0.05). Except for Ma, all the agents up-regulated caspase-3 expression, and the effect of TTNPB was the strongest (P<0.05). CONCLUSIONS: Retinoids can suppress the proliferation of and induce apoptosis of Tca8113 cells, the effect of which involves activation of RAR but not RXR. caspase-3 pathway is involved in apoptosis-inducing effects of retinoids.

[Effect of topical application of a recombinant adenovirus carrying promyelocytic leukemia gene in a psoriasis-like mouse model].

OBJECTIVE: To investigate the effects of topical treatment with adenovirus-mediated promyelocytic leukemia gene (PML) gene in a psoriasis-like mouse model. METHODS: The effect of adenovirus-mediated PML gene on the granular layer of mouse tail scale epidermis and epithelial mitosis were observed on longitudinal histological sections prepared from the tail skin and vaginal epithelium of the mice. RESULTS: Adenovirus-mediated PML gene significantly inhibited mitosis of mouse vaginal epithelial cells and promoted the formation of granular layer in mouse tail scale epidermis. CONCLUSION: The therapeutic effect of PML gene in the psoriasis-like mouse model may be associated with increased granular cells and suppressed epidemic cell proliferation.

[Expression of promyelocytic leukaemia protein in Bowen's disease, skin squamous cell carcinoma and basal cell carcinoma].

OBJECTIVE: To investigate the expression of promyelocytic leukaemia (PML) protein of PML protein in Bowen's disease (BD), skin squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) and explore the role of PML in the pathogenesis of these diseases. METHODS: PML protein in normal skin tissues and lesions of Bowen's disease, SCC and BCC were detected with immunohistochemistry. RESULTS: Normal skin tissues did not express PML protein. In BCC, PML showed rather low expressions in the skin lesions (8.69% in cell nuclei and 4.35% in cytoplasm). The lesions in BD and SCC (grade I and II) showed obvious overexpression of PML protein in the cell nuclei and cytoplasm, and its expression in the cell nuclei of these lesions was significantly higher than that in grade III-IV SCC. CONCLUSION: PML protein may play an important role in the early stage of SCC, and its overexpression may contribute to the carcinogenesis and metastasis of SCC.

Acitretin exerted a greater influence on T-helper (Th)1 and Th17 than on Th2 cells in treatment of psoriasis vulgaris.

T-helper (Th) cells, including Th1, Th2 and Th17 cells, may play an important role in the pathogenesis of psoriasis vulgaris (PV). Acitretin is an effective treatment for PV; however, its influence on Th cells during the treatment of PV is unclear. This study aimed to investigate the influence of acitretin on Th1, Th2 and Th17 cells in PV patients. PV patients (n = 30) received acitretin p.o. (20 mg/day) for 8 weeks. Sera and skin biopsies were obtained before and after treatment. Double-labeled immunofluorescence was used to analyze T, Th1, Th2 and Th17 cells in skin lesions. Enzyme-linked immunosorbent assay and western blot were used to analyze the expressions of interferon (IFN)-γ, interleukin (IL)-4 and IL-17 in sera and skin lesions. The expressions of IFN-γ mRNA, IL-4 mRNA and IL-17 mRNA in skin lesions were detected by in situ hybridization. Acitretin decreased the quantity of T, Th1 and Th17 cells in PV lesions, but had no significant influence on Th2 cells. Acitretin also decreased the expression of IFN-γ and IL-17 in serum and lesions. The expressions of IFN-γ mRNA and IL-17 mRNA decreased significantly after 8 weeks of therapy. However, acitretin had no significant influence on the expression of IL-4 protein and mRNA. Acitretin can reverse Th1 and Th17 preponderance in PV patients to some degree. This may be due to the mechanism of acitretin on PV; however, Th2 cells were not affected by acitretin treatment.

Epidemiologic study of the predisposing factors in erythema toxicum neonatorum.

BACKGROUND: Erythema toxicum neonatorum (ETN) is a very common disease, but its predisposing factors are still unknown. OBJECTIVE: To determine the predisposing factors of ETN. METHODS: Seven hundred and eighty-three neonates born in the same hospital during the same period were investigated, and the factors predisposing to ETN were evaluated in a case-control study. RESULTS: (1) The incidence of ETN is about 43.68%, and it is significantly higher in males than in females (p < 0.001). (2) Term birth (p < 0.05), first-pregnancy birth (p < 0.001), the birth season (summer and autumn, p < 0.005), being fed with milk powder substitute or a mixed diet (p < 0.001) and vaginal delivery (p < 0.001) are the predisposing factors of ETN. (3) The severity of ETN in neonates born by vaginal delivery is significantly correlated with the total length of labor (p < 0.001). CONCLUSION: Our findings suggest that environmental factors play an important role in the onset of ETN.