Protective role of histone deacetylase 4 from ultraviolet radiation-induced DNA lesions

Ultraviolet B (UVB) exposure is a core factor that leads to skin disease or carcinogenesis through the insufficient repair of DNA lesions. UVB-induced DNA lesions are mainly removed by the nucleotide excision repair (NER) mechanism. The expression of histone deacetylase 4 (HDAC4) is altered in the skin upon UVB exposure, indicating its possible implication in UVB-induced DNA lesions repair. Here, we investigated the role of HDAC4 in the NER removal of the main classes of UVB-induced DNA lesions consisting of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). We found that UVB irradiation increased HDAC4 expression at both the mRNA and protein levels. HDAC4 interacted with NER factor XPC, which played an important role in effectively removing the UVB-induced DNA lesions. This study provides an understanding of the HDAC4 function in DNA repair, which will allow the development of efficient strategies to protect the skin from UVR-induced diseases.     

P38 and JNK signal pathways are involved in the regulation of phlorizin against UVB‐induced skin damage

Phlorizin is well known to inhibit sodium/glucose cotransporters in the kidney and intestine for the treatment of diabetes, obesity and stress hyperglycaemia. However, the effects of phlorizin against ultraviolet B (UVB) irradiation and its molecular mechanism are still unknown. We examined the effects of phlorizin on skin keratinocyte apoptosis, reactive oxygen species (ROS) production, pro‐inflammatory responses after UVB irradiation and the changes of some signal molecules by in vitro and in vivo assay. We observed that phlorizin pretreatments inhibited HaCaT cell apoptosis and overproduction of ROS induced by UVB. Phlorizin also decreased the expression of UVB‐induced pro‐inflammatory cytokines, such as interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6) and interleukin‐8 (IL‐8) at the mRNA level. Topical application of phlorizin on UVB‐exposed skin of nude mice prevented the formation of scaly skin and erythema, inhibited the increase of epidermal thickness and reduced acute inflammation infiltration in skin. Additionally, PCR, Western blot and immunohistochemical data showed that phlorizin reversed the overexpression of cyclooxygenase‐2 (Cox‐2) induced by UVB irradiation both in vitro and in vivo. The activation of p38 and JNK mitogen‐activated protein kinases (MAPK) after UVB irradiation was also inhibited by phlorizin. These findings suggest that phlorizin is effective in protecting skin against UVB‐induced skin damage by decreasing ROS overproduction, Cox‐2 expression and the subsequent excessive inflammation reactions. It seemed that p38 and JNK MAPK signal pathways are involved in the regulation of the protective function of phlorizin.     

UVB下调IFN-γ诱导的正常人角质形成细胞表面抗原的表达

目的：研究中波紫外线（UVB）对IFN-γ体外诱导的正常人角质形成细胞(KC)表面抗原表达的影响及可能机制。方法：分离培养原代人KC，用适当浓度的IFN-γ对细胞进行预处理，再用生理剂量的UVB照射细胞。流式细胞术测定照射前后细胞表面CD40、CD54、MHC-II的表达，放射免疫法测定照射前后细胞上清液中α-MSH浓度，ELISA测定上清液中IL-6、IL-8、TNF-α等细胞因子浓度。结果：KC低水平表达CD40、CD54、MHC-II抗原，IFN-γ处理后，细胞活性增强，表面抗原的表达显著增加，再用UVB照射后，细胞活性下降，表面抗原表达明显下调，而上清液中α-MSH的浓度则逐渐上升，照后72 h达最高峰。KC经可溶性CD40配体(sCD40L)处理后，IL-8的释放和CD54的表达加强。结论：UVB能抑制IFN-γ诱导的KC表面抗原的表达，这可能与UVB诱导KC自分泌产生α-MSH等免疫抑制物有关。     

Evaluation of the UVB‐screening capacity and restorative effects exerted by farnesol gel on UVB‐caused sunburn

Farnesol, a natural 15‐carbon organic compound, has various microbiological and cellular activities. It has been found to exert apoptosis‐inducing effects against carcinoma cells as well as antiallergic and anti‐inflammatory effects in vivo. In the current study, a series of formulations composed of various concentrations of hydroxypropyl methylcellulose (HPMC) with the addition of hyaluronan (HA) and xanthan gum (XG) was designed to evaluate the UVB‐screening and H₂O₂‐eliminating effects of farnesol in normal fibroblasts. Farnesol at 0.005, 0.0075, and 0.01% exhibited significant capacity for H₂O₂ scavenging; at 0.0025%, it showed insignificant effects. Under 120‐min UVB exposure, screening with plural gel composed of 0.0025% farnesol, 0.5% HA, and 0.5% XG containing 1.5% or 2% HPMC retained normal fibroblast viability. After 60‐min exposure to UVB, screening with plural gel composed of farnesol, HA, XG, and 0.5%, 1.0%, 1.5%, or 2% HPMC decreased the ratio of the G1 phase and increased ratio of the S phase in comparison with the accumulated cell cycle of the normal fibroblasts without screening. The gel with 2% HPMC displayed the strongest cell cycle‐reversal ability. In vivo histopathological results showed that the prepared plural gels with 0.5% or 2% HPMC and farnesol, HA, and XG had greater antiphotoaging and reparative effects against UVB‐induced changes and damage in the skin. In conclusion, the current in vitro and in vivo results demonstrated that the prepared plural composed of 0.0025% farnesol, 0.5% HA, 0.5% XG, and 2% HPMC possessed the greatest UVB‐screening capacity and the strongest restorative effects on UVB‐induced sunburned skin.     

窄谱UVB联合中医治疗副银屑病的疗效分析

目的:分析窄谱UVB联合中医治疗副银屑病的疗效。方法:回顾性研究笔者科室门诊在2006年1月~2013年1月治疗的副银屑病患者共32例,将患者随机分为治疗组和对照组各16例,两组患者均采用干扰素300万U进行基础治疗。对照组采用单纯中医方法治疗;治疗组采用窄谱中波紫外线(UVB)联合中医方法治疗。治疗过程中观察患者的临床症状,疗程完成后对患者的临床疗效进行评判。结果:治疗组痊愈12例,显效3例,有效1例,无效0,对照组痊愈4例,显效4例,有效6例,无效2例。两组患者的临床疗效比较,差异有统计学意义(P0.05)。治疗组患者有3例发生皮肤红斑症状,对照组有2例出现胃肠道不适反应,未经特殊治疗后缓解,未影响正常治疗。两组患者的不良反应发生率差异无显著性(P0.05)。结论:窄谱UVB联合中医治疗副银屑病疗效较好,安全、可靠,其远期效果及并发症需进一步加大样本研究。     

药物联合窄谱UVB治疗银屑病68例临床疗效观察及护理分析

目的：探讨采取药物联合窄谱UVB治疗银屑病的临床疗效以及护理的效果。方法2013年2月~2014年2月,选取来本院皮肤科就诊的患有银屑病的68例患者。以随机数字法将上述68例患者分成观察组和对照组各34例。观察组对患者使用外用药物涂抹并联合窄谱UVB进行治疗,而对照组则使用常规外用涂抹的药物进行治疗。两组患者在进行为期2个月的治疗与护理后比较两组患者的临床效果、不良反应以及护理效果满意度等情况。结果观察组在总有效率、不良反应和满意度方面的对比均高于对照组,差异有统计学意义（P＜0.05）。结论采用药物联合窄谱UVB治疗银屑病的临床治疗效果良好,患者对治疗结果普遍反应为满意,患者及家属对于护理的结果也普遍满意,值得在临床上广泛推广。     

复方丙酸氯倍他索软膏联合UVB治疗寻常型银屑病的临床疗效及护理

目的探讨用复方丙酸氯倍他索软膏联合UVB照射，并配合护理措施治疗寻常型银屑病的临床疗效。方法治疗组于患处外涂复方丙酸氯倍他索软膏，每天2次，行UVB全身照射，1周2～3次，并配合适当的护理措施。对照组于患处外涂复方丙酸氯倍他索软膏，每天2次。根据PASI评分标准评价疗效。结果治疗组有效率88．46％，对照组有效率65．38％，经统计学处理，x^2=7．8000，P〈0．01；治疗组复发率19．05％，对照组复发率53．85％，经统计学处理，x^2=4．4472，P〈0．05。结论复方丙酸氯倍他索软膏联合UVB照射并配合适当的护理措施是治疗寻常型银屑病的有效方法。