Inhibition of citrus flavonoids on 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumorigenesis in mice

The inhibitory effects of a formulated product from citrus peel extract,Gold Lotion(GL),on 12-O-tetradecanoylphorbol 13-acetate(TPA)-induced expression of inducible nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2)in mouse skin was reported in this study.It is found that in the TPA-induced skin inflammation model,the topical application of GL effectively inhibited the transcriptional activation of iNOS and its mRNA and protein in mouse skin.It is also discovered that GL significantly inhibited TPA-induced mouse skin inflammation by decreasing inflammatory gene parameters.Furthermore,GL dramatically inhibited 7,12-dimethylbenez[a]anthracene(DMBA)/TPA-induced skin tumor formation and reduced tumor incidence,tumor weight and tumor multiplicity of papillomas at 20 weeks.In essence,these in vivo data have revealed that GL is an effective anti-tumor agent that functions by down-regulating the protein levels of COX-2,ornithine decarboxylase(ODC),and vascular endothelial growth factor(VEGF)in mouse skin,suggesting that GL is a novel functional natural product capable of preventing inflammation-associated tumorigenesis.©2012 Production and hosting by Elsevier B.V.on behalf of Beijing Academy of Food Sciences.

Repeated Exposure to Cruciferous Allyl Nitrile Protects against Chemically Induced Skin Inflammation in the Mouse

Repeated exposure to cruciferous allyl nitrile can induce antioxidant and phase 2 detoxification enzymes in various tissues. In the present study, we examined the effect of five days repeated exposure to allyl nitrile at subtoxic levels (0 - 400 μmol/kg/day) on the mouse ear. There was an increase in catalase activity in the ear at 100 - 400 μmol/kg/day, while elevated quinone reductase activity was observed at 400 μmol/kg/day only. Next, after repeated allyl nitrile exposure (0 - 400 μmol/kg/day), the skin irritant croton oil was applied to the ear to induce skin acute inflammation (oedema). Compared with the 0 μmol/kg/day group, animals in the 100 and 400 μmol/kg/day pre-treatment groups showed reduced oedematous response to croton oil. The reduced oedematous response was inversely associated with enhanced myeloperoxidase activity used as index of the presence of neutrophils. These data suggest that repeated exposure to allyl nitrile at subtoxic levels contributes to protection against croton oil-induced ear dermatitis, potentially through decreasing reactive oxygen species and through infiltration of neutrophils.

Star fruit extract and C-glycosylated flavonoid components have potential to prevent air pollutant-induced skin inflammation and premature aging

Air pollution adversely affects skin,leading to skin inflammation and premature skin aging.Plant derived antioxidant compounds have been considered to be promising in discovery of effective agents for the protection of skin from the damage by air pollutants.Our previous studies demonstrated that Averrhoa carambola fruit(known as star fruit)is rich in flavonoid C-glycosides with unique structures and potent antioxidant activity.Thus,the star fruit extract(SFE)and main flavonoid C-glycoside components,carambolasides I,J,and P(1-3),carambolaflavone B(4),and isovitexin 2″-O-α-l-rhamnoside(5),were investigated for the activity against air pollutant stress in human epidermis.As a result,SFE and compounds 1-5 exhibited significant inhibitory activity against protein carbonylation in oxidative-stressed stratum corneum with the best activity being shown by compound 3.SFE and compounds 2-5 were also active against engine exhaust-induced protein carbonylation in stratum corneum.When further evaluated,SFE and com-pound 3 significantly inhibited gene expression of the key inflammation mediators IL-1αand COX-2 in PM-stressed keratinocytes.The results indicated that SFE and the flavonoid C-glycosides are potentially effective against air pollutant-induced skin inflammation and premature aging.

Pharmacodynamics of frigid zone plant Taxus cuspidata S.et Z.against skin melanin deposition,oxidation,inflammation and allergy

Background:Taxus cuspidata S.et Z.is a precious species of frigid zone plant belonging to the Taxaceae family,which possesses anticancer,anti-inflammatory,hypoglycemic,and antibacterial pharmacological properties.While taxane extracted from Taxus chinensis has been reported to elicit antioxidant activities,whether Taxus cuspidata S.et Z.has skin-protective actions against injuries remained unknown.This study aims to explore the pharmacological effects of three Taxus extracts on skin melanin deposition,oxidation,inflammation,and allergy so as to provide new ideas for the prevention and treatment of various diseases related to skin damage.Methods:Skin melanin deposition was evaluated by measuring melanin content in the skin of guinea pigs by alkali lysis method.Antioxidant capacity was evaluated by measuring superoxide dismutase(SOD)concentration and glutathione(GSH)content in skin tissue homogenates of Kunming mice by SOD assay kit and micro reduced GSH assay kit.The quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were used to examine the levels of both SOD and recombinant glutathione peroxidase 4(GPX4).Skin inflammation was evaluated by xylene-induced ear swelling test and egg-white-induced paw swelling test in mice.In a mouse model of skin allergy induced by 4-aminopyridine(4-AP),allergy was determined by licking body counts and histamine concentrations in tissue homogenates using enzyme-linked immunosorbent assay(ELISA)kits.Two proinflammatory factors tumor necrosis factor(TNF)-αand interleukin(IL)-1βwere measured by qRT-PCR.Hematoxylin and eosin(HE)staining was conducted to assess the degree of skin lesion.Results:All three Taxus extracts including Taxus chinensis essential oil,Taxus chinensis extract and Taxus chinensis extract compound reduced the melanin deposits in the back skin relative to the non-treated control animals,of which Taxus chinensis essential oil produced the greatest effect.In contrast,the three Taxus extracts elevated SOD and GSH levels in the skin tissues,and the highest increase was seen with Taxus chinensis essential oil.Three Taxus extracts,especially Taxus chinensis essential oil,effectively reduce the rate of ear and paw swelling.All three Taxus extracts reduced the number of body licks,the levels of TNF-αand IL-1β,and the histamine content in tissue homogenates of mice and alleviated skin damage.Consistently,Taxus chinensis essential oil yielded the greatest magnitude of decreases.Conclusion:While all three Taxus extracts possessed the anti-skin melanin deposition,oxidation,and allergy properties,Taxus chinensis essential oil produced the superior effects.

Local Proinflammatory Effects of Repeated Skin Exposure to Warfarin, An Anticoagulant Rodenticide in Rats

Objective： To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods： Rats were exposed to warfarin by applying 10 μg of warfarin‐sodium to 10‐12 cm 2 skin （range 0.8‐1 μg per 1 cm 2 ） for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results： Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury （increased malondialdehyde, MDA, production, evident histo‐morphological changes in epidermis and dermis depicting cell injury and death）. Increased numbers of proliferating cell nuclear antigen （PCNA ＋ ） cells indicated reparative processes in injured skin. Infiltration of CD3 ＋ cells （T lymphocytes） along with the increased production of tumor necrosis factor‐α （TNF‐α） by epidermal cells from warfarin‐treated skin and their co‐stimulatory effect in an in vitro T‐cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion： Presented data have documented tissue damage associated with immune/ inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.

Diet with high content of advanced glycation end products induces oxidative stress damage and systemic inflammation in experimental mice: protective effect of peanut skin procyanidins

Non-enzymatic glycation reaction in food can produce diet-derived advanced glycation end products(dAGEs),which have potential health risks.Thus,it is of great significance to find efficient substances to improve the negative effects induced by dAGEs on human health.This study investigated the intervening effects of peanut skin procyanidins(PSP)on the dAGEs-induced oxidative stress and systemic inflammation in experimental mice model.Results showed that the accumulation of AGEs in serum,liver,and kidney was significantly increased after mice were fed dAGEs(P<0.05).The expression of advanced glycation product receptor(RAGE)was also significantly increased in liver and kidney(P<0.05).PSP could not only effectively reduce the accumulation of AGEs in serum,liver and kidney of mice,but also reduce the expression of RAGE in liver and kidney of mice.And the levels of pro-inflammatory cytokines interleukin-6(IL-6),tumor necrosis factor(TNF-α),and IL-1βin serum of mice were significantly decreased(P<0.05),while the levels of antiinflammatory factor IL-10 were increased,and the inflammatory injury in mice was improved.In addition,the levels of superoxide dismutase(SOD),glutathione(GSH),catalase(CAT)in liver and kidney of mice were increased(P<0.05),and the level of malondialdehyde(MDA)was decreased(P<0.05),which enhanced the antioxidant capacity of mice in vivo,and improved the oxidative damage of liver and kidney.Molecular docking technique was used to confirm that the parent compound of procyanidins and its main metabolites,such as 3-hydroxyphenylacetic acid,could interact with RAGE,which might inhibit the activation of nuclear transcription factor(NF-κB),and ultimately reduce oxidative stress and inflammation in mice.

NLRP3 inflammasome activation and NETosis positively regulate each other and exacerbate proinflammatory responses:implications of NETosis inhibition for acne skin inflammation treatment

Inflammasomes are multiprotein complexes involved in the host immune response to pathogen infections.Thus,inflammasomes participate in many conditions,such as acne.Recently,it was shown that NETosis,a type of neutrophil cell death,is induced by bacterial infection and is involved in inflammatory diseases such as delayed wound healing in patients with diabetes.However,the relationship between inflammasomes and NETosis in the pathogenesis of inflammatory diseases has not been well studied.In this study,we determined whether NETosis is induced in P.acnes-induced skin inflammation and whether activation of the nucleotide-binding domain,leucine-rich family,and pyrin domain-containing-3(NLRP3)inflammasome is one of the key factors involved in NETosis induction in a mouse model of acne skin inflammation.We found that NETosis was induced in P.acnes-induced skin inflammation in mice and that inhibition of NETosis ameliorated P.acnes-induced skin inflammation.In addition,our results demonstrated that inhibiting inflammasome activation could suppress NETosis induction in mouse skin.These results indicate that inflammasomes and NETosis can interact with each other to induce P.acnes-induced skin inflammation and suggest that targeting NETosis could be a potential treatment for inflammasome-mediated diseases as well as NETosis-related diseases.

Anti Inflammatory Property of PDRN—An <i>in Vitro</i>Study on Cultured Macrophages

Skin aging and most age-related diseases are associated with a low-grade chronic inflammation. The nucleoside adenosine, a potent endogenous anti-inflammatory agent, is deeply involved in inflammatory diseases and, by interaction with the adenosine A2 receptor (A2AR) it immediately promotes a mechanism of defence against the inflammatory damage. The aim of our study was to investigate whether polydeoxyribonucleotide (PDRN), a mixture of deoxyribonucleotides polymers of different lengths that like adenosine, binds the A2A receptor, can reduce the inflammatory state in the macrophage cell line. RAW264.7, murine macrophage cells, were incubated with PDRN in the presence and in the absence of lipopolysaccaride (LPS), which was the major component of the outer membrane of gram-negative bacteria and which acted as a strong macrophage activator. We assessed the production of nitric oxide and the secretion of inflammatory mediators (i.e., TNF-α, IL-10, IL-12 and VEGF-A). Our data showed that PDRN produced a significant decrease of inflammation in macrophages pre-stimulated with LPS, assessed in terms of the nitric oxide content (p 2A receptor, contributed to a great extent towards reducing inflammation.

Study on the Repairing Effect of Cosmetics Containing <i>Artemisia annua</i>on Sensitive Skin

In view of the increasing sensitivity of consumer skin in recent years, cosmetics containing Artemisia annua extract was tested to evaluate its effectiveness in repairing sensitive skin. Through the experiment of xylene-induced ear swelling in mice, it was found that the inhibition rates of ear swelling in mice induced by xylene in three groups of cosmetics containing Artemisia annua extract reached 60.40%, 73.36% and 74.01%, respectively, close to the positive drug group. Twenty-five sensitive skin volunteers were selected for human clinical trial, and the skin TEWL value, cuticle hydration degree and skin heme (ultra-high concentration) were tested. The results showed that using cosmetics containing Artemisia annua extract for four weeks could effectively increase the hydration degree of cheek cuticle by 63.90% and reduce transepidermal waterloss (TEWL) by 21.51%. The skin heme (ultra-high concentration) decreased by 69.14% and the affected area decreased by 77.47%. The results show that the cosmetics containing Artemisia annua extract can inhibit inflammation, repair skin barrier, improve damaged skin, and reduce redness and other sensitive skin symptoms.

Apple of Sodom (<em>Calatropis procera</em>) Callus Extract, a Novel Skincare Active and Its Biological Activity in Skin Models When Combined with Dead Sea Water

Background: Calotropis procera (C. procera), is an authentic plant naturally grown in the flora of Dead Sea region. Despite its toxicity, C. procera presents healing properties. However, it has not been implemented yet in cosmetics as an active ingredient. Objective: The biological effects of C. procera callus extract on skin were elucidated solely and in combination with Dead Sea water (DSW). Methods: The capability of C. procera extract to protect against skin inflammation and irritation was tested on ex vivo human skin organ culture by LPS and SDS addition respectively. Viability and cytokine secretion were evaluated. The combination of C. procera extract with Dead Sea water was tested on full thickness skin equivalents. Gene expression and relevant biochemical markers for glycolysis, hypoxia and extracellular matrix balance were tested. Results: C. procera extract exhibits a protective biological activity against skin irritation and inflammation at the biochemical level. Furthermore, a combination of C. procera extract and DSW demonstrates a potential contribution for skin wellbeing via enhance energy production, resistance to hypoxia and extracellular matrix balance. Conclusions: Topical application of C. procera callus extract might support skin balance and wellbeing at the molecular level. Hence, it is recommended for new cosmetic formulae as standalone or in combination with Dead Sea water, in the effort to achieve anti-aging bio-activity that is working beyond skin aging symptoms, especially via skin calming effects and skin energy enhancement.

Fecal microbiota transplant and dermatologic disorders:A retrospective cohort study assessing the gut microbiome’s role in skin disease

BACKGROUND There is indication that fecal microbiota transplant(FMT)has the potential to alter the course of chronic skin disease,but few studies have investigated this phenomenon beyond case reports.Research with larger sample sizes is needed to provide a more thorough assessment of possible associations and to establish a broader foundation upon which to base hypotheses.AIM To identify associations between FMT and skin conditions,particularly infectious and inflammatory etiologies,and the role of dermatology post-FMT.METHODS We conducted a retrospective cohort study involving a chart review of all patients whom received FMT between January 2013 and December 2019 at a single academic medical center.Dermatologic follow-up was assessed for the two years after FMT or through March 2020 for more recent procedures.Dermatologic diagnoses and visits within the study time frame were recorded and assessed for trends.This study was exploratory in nature.Descriptive statistics were calculated,and the t-test,Pearson’s chi-squared test,and Fisher’s exact test were used to calculate P values.RESULTS Median age was 38(range,17-90).In total,109 patients who underwent 111 fecal microbiota transplant events were included.Twenty-six events(23.4%)involved a dermatology office visit post-procedure,and of these events,20 out of the 26(76.9%)had an infectious or inflammatory skin condition.The mean time to first visit was 10.0(±7.0)mo.The most common diagnoses were dermatophyte,wart(s),and dermatitis,though no specific diagnoses predominated in a way indicating FMT had a significant impact.More patients with a post-FMT skin disease diagnosis had a history of Crohn’s disease compared to those without(P=0.022),but results could be affected by a small sample size.CONCLUSION Our study is limited by its retrospective nature,but the findings allow a glimpse at dermatologic conditions post-FMT.Few significant associations were found,but potential associations between FMT and skin disease should be further investigated,preferably in prospective studies,to identify how FMT might be of use for treating infectious and inflammatory skin diseases.

<i>In Vitro</i>and <i>in Vivo</i>Anti-Inflammatory Effect of a Biotechnologically Modified Borage Seed Extract: Evidence for Lipid Pro-Resolving Mediators’ Implication in the Enhancement of Psoriatic and Atopic Dermatitis Lesions

Aim: Resolvins, maresins and lipoxins are lipid mediators issued from essential polyunsaturated fatty acids which are the first anti-inflammatory and pro-resolving signals identified during the resolution phase of inflammation. As borage oil and/or borage seed extracts have shown beneficial action in treatment of atopic dermatitis or eczema in human and canine, we have modified a borage oil component by using biotechnology in order to get a compound structurally related to a polyunsaturated fatty acid, and we have studied its ability to reduce inflammation mediators production through the generation of resolvins, maresins and/or lipoxins. Additionally, we have demonstrated the potent anti-inflammatory effect of this new compound which consists in borage seed oil aminopropanediol amides, through an in vivo study concerning subjects suffering from psoriasis or atopic dermatitis. Study Design/Methods: For the in vitro study, inflammation was induced in co-cultures of human dendritic cells and normal keratinocytes by the addition of PMA and the calcium ionophore A23187. Ability of our borage seed oil aminopropanediol amides to increase resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis was then measured. Pro-inflammatory cytokines (IL-1β, IL-6, IL-8) and PGE2 productions were also quantified. For the in vivo study, 36 subjects suffering from psoriasis or atopic dermatitis have used twice a day during 30 days, a formulation containing borage seed oil aminopropanediol amides. Before the beginning of the study and after 30 days’ treatment, the severity of psoriasis and of atopic dermatitis was evaluated by using the PGA and the SCORAD scoring scales, respectively. Results: Borage seed oil aminopropanediol amides were able to significantly increase the resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis. Concomitantly, they were also able to significantly inhibit the production of IL-1β, IL-6, IL-8 and PGE2 induced by the PMA and the calcium ionophore A23187 in the in vitro co-culture model used. Introduced in formulation, borage seed oil aminopropanediol amides significantly reduced the clinical manifestations of psoriasis and atopic dermatitis. Conclusion: Our in vitro and in vivo study clearly showed the anti-inflammatory activity of borage seed oil aminopropanediol amides and emphasized the putative role of pro-resolving lipid mediators in the treatment of atopic dermatitis, psoriasis or other inflammation-induced skin diseases.

苦参碱通过Hippo信号通路促进大鼠皮肤创面愈合及血管生成

目的探讨苦参碱(MT)对皮肤创面愈合的影响及可能机制。方法在48只大鼠中成功建立全层皮肤切除创伤模型,将模型大鼠随机分为阴性对照组(模型组,涂抹100μL等渗盐水)、阳性药物组(PD组,涂抹100μL的京万红软膏)、苦参碱组(MT组,涂抹浓度为200 ng/mL的苦参碱混合液100μL)、苦参碱+维替泊芬组(MT+VP组,涂抹苦参碱混合液100μL后,腹腔注射100 mg/kg维替泊芬),每组12只。各组每日给药1次,持续7 d。比较各组大鼠的创面愈合率、病理组织损伤情况、CD31阳性染色细胞比例,以及血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平。蛋白免疫印迹检测(Western blot)Hippo通路相关蛋白表达。结果造模后3、7、14 d时,与模型组创面愈合率[(14.02±1.87)%、(36.23±3.62)%、(65.53±3.85)%]相比,PD组[(21.36±2.51)%、(61.86±3.13)%、(94.26±0.26)%]和MT组[(21.57±2.24)%、(54.35±3.66)%、(94.18±3.13)%]均明显升高(P<0.05);与MT组相比,MT+VP组创面愈合率[(18.35±2.03)%、(43.68±3.54)%、(74.26±3.55)%]均明显降低(P<0.05)。造模后7 d,与模型组(186.75±18.53、85.73±10.15、57.96±5.85)相比,PD组(89.75±9.75、43.12±5.75、8.76±1.13)和MT组(92.57±23.62、46.62±6.54、12.36±1.06)的IL-1β、IL-6、TNF-α水平均明显降低(P<0.05),CD31阳性染色细胞百分比明显升高(P<0.05),MST1、LAST1和YAP蛋白磷酸化水平明显升高(P<0.05),而YAP核移位明显降低(P<0.05)。与MT组相比,MT+VP组IL-1β、IL-6、TNF-α水平均明显升高,CD31阳性染色细胞百分比明显降低,MST1、LAST1和YAP蛋白磷酸化水平明显降低,而YAP核移位明显增加(P<0.05)。与模型组皮肤创面完全愈合时间[(26.33±0.94)d]和瘢痕厚度[(0.58±0.11)mm]相比,PD组[(19.50±0.82)d、(0.24±0.04)mm]和MT组[(19.00±0.50)d、(0.25±0.04)mm]明显减少(P<0.05);与MT组相比,MT+VP组创面完全愈合时间[(22.33±0.94)d]和瘢痕厚度[(0.41±0.04)mm]均明显增加(P<0.05)。结论苦参碱能够通过抑制炎症反应、促进血管生成加速全层皮肤切除创伤大鼠的皮肤创面愈合,这一过程可能涉及苦参碱对Hippo-Yap通路的激活效应。

海藻糖敷料对激光损伤兔皮肤屏障功能的修复及体外促细胞生长、迁移和抗炎作用研究

目的:探究海藻糖敷料对激光损伤兔动物模型皮肤的修复作用,并探索其体外促细胞生长、迁移和抗炎作用。方法:试验兔脊柱两边各脱毛4个区域,随机分为正常组(N)、模型组(M)、对照组(P)和实验组(T)。除正常组外,其余各组使用激光照射造模;对照组及实验组分别使用透明质酸敷料及海藻糖敷料贴敷。于第0天、第3天、第7天、第14天和第21天对创面进行红斑和焦痂、水肿程度评分,以评价海藻糖敷料对皮肤修复效果。以L929细胞及HaCaT细胞为研究对象探索海藻糖敷料体外促细胞生长、迁移和抗炎作用。将细胞分为空白组(培养基)、正常组(细胞液+培养基)、对照组(细胞液+培养基+透明质酸)及实验组(细胞液+培养基+海藻糖)。使用MTT比色法检测各组L929细胞24 h、48 h及72 h增殖率,划痕试验检测各组L929细胞6 h、12 h和24 h迁移力;使用TNF-α及IFN-γ诱导HaCaT细胞建立炎症反应模型后,24 h后检测各组IL-6、IL-8和MDC表达水平。结果:创面给予敷料后7 d,实验组水肿评分[(1.1±0.3)分]较模型组[(1.2±0.4)分]显著降低(P<0.05);第14天,相较于模型组,实验组及对照组水肿、红斑焦痂评分有下降趋势但差异无统计学意义(P>0.05)。病理结果显示,对照组、实验组较模型组第14天炎细胞浸润微有减少。细胞实验结果显示,与正常组相比,对照组和实验组4 h、48 h及72 h的细胞增殖率均有明显增加;与正常组相比,对照组及实验组6 h、12 h和24 h的细胞迁移率均有明显增加(P<0.05);与细胞炎症模型组相比,实验组细胞上清液中IL-6、IL-8和MDC的表达水平明显降低(P<0.01)。结论:海藻糖敷料对激光所致兔皮肤屏障受损创面的组织炎症、愈合有一定修复作用;其机制可能与其能促进细胞增殖、细胞迁移及抑制炎症的功能相关。

天然植物多糖的提取、分离及其在皮肤领域的研究进展

植物多糖是一种从植物各部位中提取的天然高分子聚合物,由十个或十个以上的单糖单元通过糖苷键聚合而成。近年来,由于其丰富的生物活性、安全性、亲肤性等特点越来越受到人们的关注。多糖的结构和功能之间具有密切关系,不同的提取和纯化方法会对多糖的结构产生影响,进而改变其生物活性。本文阐述了植物多糖的提取、分离、纯化工艺,并同时对植物多糖具有的保湿补水、抗氧化、抗炎、抑菌、美白等功效进行了总结,以期为植物多糖在功能化妆品的开发和应用提供理论支撑。

Effects of hyperbaric oxygen preconditioning on ischemia-reperfusion inflammation and skin flap survival

Background Hyperbaric oxygen preconditioning （HBO） is a new method of ischemia preconditioning. In this study, we examined its effects on skin flap survival and the mechanisms involved. Methods Thirty-six rats were divided into three groups： HBO preconditioning, control, and sham groups. An extended epigastric adipocutaneous flap based on the right superficial epigastric artery and vein was raised. A 3-hour period of flap ischemia was induced by clamping the pedicle vessels with a microvascular clamp. At the end of ischemia induction, the clamp was removed and the flap was resutured. Rats in the HBO preconditioning group were treated with HBO four times before surgery. Microcirculation in the skin flap was measured on postoperative days 1, 3 and 5. The size of the flap was measured on postoperative day 5, before the animals were sacrificed. Samples of the skin flap were prepared and stained with hematoxylin and eosin. The levels of tumor necrosis factor （TNF）-α, interleukin （IL）-1β, and IL-6 in the flap samples were measured.

银屑平丸调节cGAS-STING信号通路对银屑病小鼠的保护作用

目的:探讨银屑平丸调节GMP-AMP合成酶(cGAS)-干扰素基因刺激因子(STING)信号通路对银屑病小鼠的保护作用。方法:取C57BL/6小鼠以咪喹莫特(IMQ)诱导银屑病模型,随机分为模型组、银屑平丸组、联合组,每组10只,另取10只C57BL/6小鼠作为对照组。用银屑平丸和RocA分组干预小鼠,检测其银屑病症状。HE染色检测小鼠皮肤组织病理变化;免疫组化染色检测各组小鼠皮肤组织中性粒细胞浸润情况;检测小鼠血清促炎因子与抗炎因子水平;免疫印迹法检测小鼠皮肤组织cGAS-STING通路蛋白表达。结果:与对照组相比,模型组小鼠皮肤组织发生明显病理损伤,银屑病皮损面积及严重程度指数(PASI)、抓痒次数、皮肤表皮层厚度、髓过氧化物酶(MPO)阳性表达,IL-1β、IL-6、IL-17、IL-23及cGAS与STING蛋白表达升高,IL-4、TGF-β、IL-10水平降低,差异有统计学意义(均P<0.05)。与模型组比较,银屑平丸组小鼠皮肤组织病理损伤减轻,PASI、抓痒次数、皮肤表皮层厚度、MPO阳性表达、IL-1β、IL-6、IL-17、IL-23水平及cGAS与STING蛋白表达降低,IL-4、TGF-β及IL-10升高,差异有统计学意义(均P<0.05)。楝酰胺可减弱银屑平丸对银屑病小鼠的作用。结论:银屑平丸通过阻止cGAS-STING信号通路激活传导而减轻银屑病小鼠免疫炎症,改善其皮肤组织损伤症状,发挥保护作用。

青蒿油对小鼠痤疮模型及皮肤微生态的干预作用研究

目的:评价青蒿油(artemisia naphta oil,AN)对痤疮丙酸杆菌(P.acnes)诱导的小鼠痤疮模型的疗效及皮肤微生态的影响。方法:将48只小鼠分为正常组、模型组、Base组、不同浓度AN干预组(0.5%、1.0%、1.5%、3.0%、5.0%AN组),每组6只。P.acnes注射耳朵皮内构建痤疮模型,小鼠右耳出现红肿后,Base组涂抹Base水对照干预,其余给予不同浓度的AN干预,每次涂抹1 mL,每天1次,17天后观察小鼠耳部厚度,HE染色观察皮肤病理,16S rRNA测序分析皮肤微生态变化,Western blot检测IL-6、IL-1β和TNF-α含量和TLR2、TLR4、P65、p-P65蛋白表达。结果:模型组小鼠耳部出现红肿、表皮层增厚、真皮层炎症细胞浸润,耳部菌群丰度和多样性降低,其中葡萄球菌、粘质沙门氏菌菌群丰度显著增加,双歧杆菌属、棒状杆菌属、Atopostipes菌群丰度显著下调;IL-6、IL-1β、TNF-α含量和TLR2、TLR4、p-P65/P65蛋白表达显著上升。Base组小鼠TLR2、TLR4、p-P65蛋白表达水平无明显改变。不同浓度AN处理后的小鼠耳部红肿、病理损伤减轻,耳部菌群丰度和多样性改善,葡萄球菌、粘质沙门氏菌显著下调,双歧杆菌属、棒状杆菌属、Atopostipes菌群丰度显著上调,且IL-6、IL-1β、TNF-α含量和TLR2、TLR4、p-P65/P65蛋白表达显著下降。结论:AN可降低促炎因子分泌,减轻皮肤炎症反应,增加皮肤有益菌的丰度,抑制病原菌生长,恢复皮肤微生态平衡,有效改善痤疮炎症样皮损变化。

青蒿油对银屑病小鼠模型的干预作用

目的 初步探究青蒿油(AN)对银屑病小鼠模型的干预作用及对血清炎性因子的影响。方法 构建银屑病小鼠模型,利用随机数字表法,将32只小鼠分为对照组、模型组、阴性对照(NC)组、0.5%AN组、1.0%AN组、1.5%AN组、3.0%AN组和5.0%AN组,每组4只。小鼠背部涂抹咪喹莫特乳膏构建银屑病小鼠模型,将不同浓度的AN按照相应分组进行喷雾给药,连续干预2周。观察各组小鼠皮损情况并进行银屑病面积严重程度指数(PASI)评分;收集各组小鼠皮损部位组织进行HE染色,观察皮损部位病理学改变;采用酶联免疫吸附测定(ELISA)法检测血清中炎性因子白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和IL-6水平。结果 与对照组比较,其余各组小鼠皮损区病理均可见表皮组织增厚,棘突增长并伴有大量炎性细胞浸润;血清中IL-1β、TNF-α、IL-6表达水平均显著上调;与模型组或NC比较,各AN干预组小鼠PASI评分、血清中IL-1β、TNF-α、IL-6表达水平均有不同程度的降低,病理损伤均呈现不同程度的好转。结论 3.0%及以上AN可缓解银屑病的皮损状况;0.5%AN即可缓解银屑病的炎性反应,其中1.0%、5.0%AN缓解效果显著。

特应性皮炎治疗药物的研究进展

特应性皮炎(AD)是一种慢性、复发性、炎症性皮肤病,常伴有其他特应性表现,可同时对儿童及成人造成影响。多项研究表明,AD患者的疾病负担较重,对公共卫生有重要影响。目前国内外大量研究表明,AD的发病机制涉及皮肤免疫炎症、皮肤屏障和皮肤菌群,提出表皮通透屏障功能受损是AD发病机制中的重要环节。因此,修复和保护皮肤屏障功能,维持皮肤微生态平衡对AD的治疗尤为重要。AD的治疗涉及基础治疗、外用药物治疗、物理治疗和系统药物治疗等多个方面。对于轻至中度患者而言,在基础治疗的基础上,可以采用外用药物和口服抗组胺药等进行治疗。而对于中重度患者,则可以选择系统治疗。其中,一些创新疗法以生物制剂为代表,取得了重要的进展,能够有效抑制2型炎症,有助于患者实现长期的病情控制。同时天然药物的挖掘和开发也越来越受到关注,将为AD患者的治疗提供更多选择。