氢醌对K562细胞着色性干皮病基因D甲基化的影响

目的：了解不同剂量苯代谢物氢醌（ HQ）对人白血病细胞株K562细胞着色性干皮病基因D（ XPD）甲基化水平的影响。方法：分别以终浓度为0、15、30和60μmol/L HQ溶液重复处理K562细胞48 h,采用MTT比色法检测K562细胞增殖能力,采用亚硫酸氢盐处理后测序法检测XPD甲基化水平;观察各组细胞存活率及甲基化率。结果：HQ 0、15、30、60μmol/L 处理后,K562细胞存活率分别为（100.00±0.00）％、（85.46±0.60）％、（63.46±7.02）％和（51.20±6.49）％,15μmol/L 组与0μmol/L 组比较,差异无统计学意义（ P ＞0.05）,30μmol/L和60μmol/L组与0μmol/L组比较,差异有统计学意义（P＜0.05）;XPD基因甲基化水平分别依次为1.03％（3/290）、0.34％（1/290）、0.34％（1/290）和0.70％（2/290）,15、30、60μmol/L组与0μmol/L组比较,差异无统计学意义（χ2=1.531,P＞0.05）。结论：HQ对K562细胞生长有明显的抑制作用,但对细胞中XPD基因甲基化水平无影响。     

The Use of Cellulose Nanocrystals for Potential Application in Topical Delivery of Hydroquinone

Nanotechnology‐based drug delivery systems can enhance drug permeation through the skin and improve the drug stability. The biodegradability and biocompatibility of cellulose nanocrystals have made these nanoparticles good candidates to use in biomedical applications. The hyperpigmentation is a common skin disorder that could be caused by number of reasons such as sun exposure and pregnancy. Hydroquinone could inhibit the production of melanin and eliminate the discolorations of skin. This study is aimed at introducing cellulose nanocrystals as suitable carriers for drug delivery to skin. Prepared cellulose nanocrystals were characterized by dynamic light scattering and atomic force microscopy. The size of cellulose nanocrystals determined using dynamic light scattering was 301 ± 10 nm. Hydroquinone–cellulose nanocrystal complex was prepared by incubating of hydroquinone solution in cellulose nanocrystals suspension. The size of hydroquinone–cellulose nanocrystal complex determined using dynamic light scattering was 310 ± 10 nm. The hydroquinone content of the hydroquinone–cellulose complex was determined using UV/vis spectroscopy. Hydroquinone was bound to cellulose nanocrystals representing 79.3 ± 2% maximum binding efficiency when 1.1 mg hydroquinone was added to 1 mL of cellulose nanocrystals suspension (2 mg cellulose nanocrystal). The hydroquinone–cellulose nanocrystal complex showed an approximately sustained release profile of hydroquinone. Approximately, 80% of bound hydroquinone released in 4 h.     

吸水链霉菌17997产生氢醌型格尔德霉素及其生物合成中间产物

目的 了解格尔德霉素生物合成PKS后修饰过程中的一些细节.方法 对格尔德霉素产生菌吸水链霉菌17997及其格尔德霉素生物合成聚酮合酶(polyketide synthase,PKS)后修饰基因阻断变株(gdmP-和gdmN-)在ISPII平板不同时间的培养物进行乙酸乙酯提取,硅胶板TLC和NaOH显色分析,检测GDM及其生物合成中间产物,并利用LC-MS对中间产物进行鉴定.结果 吸水链霉菌17997原株、gdmN-和gdmP-变株在培养时间72～96h,发现氢醌型格尔德霉素(GQH2)、氢醌型4,5-双氢-7-去氨甲酰基-7-羟基格尔德霉素(H2GQH2-dC)和氢醌型4,5-双氢格尔德霉素(H2GQH2)分别为主要组分,相应的醌型化合物为次要组分;之后,这些氢醌型化合物随培养时间延长逐渐消失,相应的醌型化合物成为主要组分.双向硅胶板TLC分析证实GQH2、H2GQH2-dC和H2GQH2均可在空气中自发氧化为相应的醌型化合物.结论 在吸水链霉菌17997的GDM生物合成PKS后修饰过程中,首次提出GQH2自发氧化为GDM可能是氢醌型向醌型转变的位点,同时它也是GDM生物合成最后一步.     

Effects of hydroquinone on retinal and vascular cells in vitro

Aim:

To explore the molecular pathophysiology that might explain the epidemiologic association between cigarette smoke and age-related macular degeneration (AMD) by examining the effects of hydroquinone (HQ), a toxic compound present in high concentration in cigarette smoke-related tar, on human retinal pigment epithelial cells (ARPE-19), rat retinal neurosensory cells (R-28), and human microvascular endothelial cells (HMVEC).

Materials and Methods:

ARPE-19, R-28, and HMVEC were treated for 24 h with four different concentrations of HQ (500 μM, 200 μM, 100 μM, 50 μM). Cell viability, caspase-3/7 activation, DNA laddering patterns, and lactate dehydrogenase (LDH) levels were analyzed.

Results:

At 50 μM HQ, R-28 cells showed a significant decrease in cell viability compared with the dimethyl sulfoxide (DMSO)-treated controls. At the 100–500 μM concentrations, all three cell lines showed significant cell death (P < 0.001). In the ARPE-19, R-28, and HMVEC cultures, the caspase-3/7 activities were not increased at any of the HQ concentration.

Conclusion:

Our findings suggest that the mechanism of cell death in all three cell lines was through non-apoptotic pathway. In addition, neuroretinal R-28 cells were more sensitive to HQ than the ARPE-19 and HMVEC cultures.     

Exogenous ochronosis in ethnic Chinese Asians: a clinicopathological study,diagnosis and treatment

Background Exogenous ochronosis is believed to be an uncommon complication of treatment with hydroquinone‐ containing skin‐lightning agents. It is widely believed that the condition is found almost exclusively in dark‐skinned individuals and uncommon in other skin‐types. Aims To show that exogenous ochronosis may be present in ethnic Chinese Asians. Materials & Methods Facial skin biopsies were obtained from suspicious lesions in ethnic Chinese patients presenting at a private dermatology clinic. Clinical photographs, ultraviolet (UV) photographs and digital dermatoscopic pictures were also obtained. Results 15 patients of ethnic Chinese origin had histologically‐confirmed exogenous ochronosis. Discussion The difficulties in differentiating exogenous ochronosis from melasma are discussed and there is a likelihood of under‐reporting as the clinical presentation of the condition may be misleading. Conclusion Exogenous ochronosis may exist amongst ethnic Chinese patients with fairer skin‐types, contrary to the commonly‐accepted perception that it is more prevalent in darker skin‐types.     

Depigmentation therapies for normal skin in vitiligo universalis

If vitiligo involves most of the body, it might be easier to depigment the normal remaining skin rather than to attempt repigmentation. We reviewed the literature to date regarding available therapies for depigmenting the normal skin in vitiligo universalis. Our review revealed that the threshold regarding what percentage of body surface area qualifies as depigmentation is variable among practitioners. Monobenzyl ether of hydroquinone (MBEH) is the most widely used depigmenting agent and has few side‐effects. Tretinoin in combination with MBEH is able to speed depigmentation of the skin. Monomethylether of hydroquinone has also been used successfully for depigmentation. Eighty‐eight per cent phenol is also effective in depigmenting the skin but its application on large areas is toxic for liver and kidney. Different types of lasers are also available to destruct the melanocytes selectively, but this technique can be painful and expensive. Cryotherapy is a cheap depigmenting therapy but, because of scarring risk, it should only be used by experienced dermatologists. No trials have compared the efficacy of the above‐mentioned well‐established depigmentation agents/techniques. Certain drugs such as imatinib, imiquimod and diphencyprone, which are used to treat other diseases, caused depigmentation as a side‐effect. Some depigmentation agents used for branding cattle can also serve as topical depigmentation agents. In conclusion, comparative clinical trials are needed to compare the efficacy of various depigmentation agents/techniques. In particular, topical imatinib, imiquimod and diphencyprone may be considered as potential depigmenting agents, which require further investigation. This review revealed that MBEH is safe and effective depigmenting agent.     

Topical therapies for melasma and disorders of hyperpigmentation

ABSTRACT: Facial hyperpigmentation is usually a reflection of an increased amount of melanin either within the epidermis, the dermis, or both (mixed pattern). The increase in melanin content is due to an increased number of functioning melanocytes (melanocytosis), an increased amount of melanin production without a numerical alteration of melanocytes (melanosis), or both. Topical hypo/depigmenting agents are most effective in those disorders where the increased melanin pigment (secondary to melanocytosis or melanosis) is within the epidermis. In patients with melasma, one of the more common causes of facial hyperpigmentation, two major groups of hypo/depigmenting agents have been used: phenolic derivatives and nonphenolic compounds. Hydroquinone, a phenolic derivative, has been used most extensively. It is applied to areas of involvement, either alone or in combination with one or two of the following: tretinoin, salicylic acid, glycolic acid, or corticosteroid. Phenolic thioethers are a new class of phenolic derivatives, and they exhibit both cytocidal and cytostatic effects selectively on melanocytes. Nonphenolic depigmenting agents include azelaic acid and kojic acid. If the facial hyperpigmentation is not improved by first-line topical therapies, chemical peels may be used in combination. The precise cause of melasma is not known, and multiple factors have been implicated. However, a genetic predisposition and exposure to ultraviolet (UV) light are very important factors. Avoidance of direct exposure to sunlight and application of broad-spectrum sunscreens are required during and after the period of active treatment. In addition to melasma, other causes of facial hyperpigmentation include Riehl's melanosis, photocontact dermatitis, the sequelae of inflammatory diseases such as acne vulgaris and cutaneous lupus, and nevus of Ota.     

白藜芦醇对对苯二酚所致遗传损伤的保护作用

目的：：研究白藜芦醇对对苯二酚(hydroquinone,HQ)染毒所致人外周血淋巴细胞遗传损伤的保护作用。方法：使用 HQ作用于人外周血淋巴细胞后,再用不同浓度的白藜芦醇孵育细胞。采用微核实验、姐妹染色单体交换实验及单细胞凝胶电泳技术,对白藜芦醇的抗诱变性进行研究。本研究设4个实验组、空白对照组和阳性对照组。结果：白藜芦醇对 HQ所致畸变有着明显的抑制作用,并呈现出显著的剂量效应关系。低剂量组与阳性对照组作用比较,差异有统计学意义(P<0.05)。中高剂量组作用尤为显著(P<0.01)。结论：白藜芦醇可降低苯的代谢物 HQ对人外周血淋巴细胞损伤的致畸作用。