p-Coumaric Acid Attenuates UVB-Induced Release of Stratifin from Keratinocytes and Indirectly Regulates Matrix Metalloproteinase 1 Release from Fibroblasts

Ultraviolet (UV) radiation-induced loss of dermal extracellular matrix is associated with skin photoaging. Recent studies demonstrated that keratinocyte-releasable stratifin (SFN) plays a critical role in skin collagen metabolism by inducing matrix metalloproteinase 1 (MMP1) expression in target fibroblasts. In the present study, we examined whether SFN released from UVB-irradiated epidermal keratinocytes increases MMP1 release from dermal fibroblasts, and whether these events are affected by p-coumaric acid (p-CA), a natural phenolic compound with UVB-shielding and antioxidant properties. HaCaT cells were exposed to UVB in the absence and presence of p-CA, and the conditioned medium was used to stimulate fibroblasts in medium transfer experiments. The cells and media were analyzed to determine the expressions/releases of SFN and MMP1. UVB exposure increased SFN release from keratinocytes into the medium. The conditioned medium of UVB-irradiated keratinocytes increased MMP1 release from fibroblasts. The depletion of SFN using a siRNA rendered the conditioned medium of UVB-irradiated keratinocytes ineffective at stimulating fibroblasts to release MMP1. p-CA mitigated UVB-induced SFN expression in keratinocytes, and attenuated the MMP1 release by fibroblasts in medium transfer experiments. In conclusion, the present study demonstrated that the use of UV absorbers such as p-CA would reduce UV-induced SFN-centered signaling events involved in skin photoaging.     

Fluorofenidone inhibits UV‐A induced senescence in human dermal fibroblasts via the mammalian target of rapamycin‐dependent SIRT1 pathway

The aim of this study was to investigate the protective effect of fluorofenidone (5‐methyl‐1‐[3‐fluorophenyl]‐2‐[1H]‐pyridone, AKF‐PD) on ultraviolet (UV)‐A‐induced senescence in human dermal fibroblasts (HDF) and examine the mechanisms involved. HDF were treated with AKF‐PD. Senescence‐associated (SA)‐β‐galactosidase level, cell viability and expression of p16 were evaluated. In addition, UV‐A‐irradiated HDF were treated with AKF‐PD, rapamycin and MHY1485; SA‐β‐galactosidase staining, 3‐(4 5‐dimethylthiazol‐2‐yl)‐2 5‐diphenyltetrazolium bromide assay and western blot for SIRT1 were performed; and phosphorylated mammalian target of rapamycin (p‐mTOR) expression and reactive oxygen species (ROS) levels were measured. Intracellular ROS was detected by the 2′,7′‐dichlorofluroescein diacetate probe. Our results showed that AKF‐PD substantially attenuated the changes of p16 expression, SA‐β‐galactosidase staining and cellular proliferation induced by UV‐A irradiation in HDF. AKF‐PD rescued the increased mTOR phosphorylation and reduced SIRT1 expression induced by UV‐A irradiation in HDF. AKF‐PD and rapamycin together had a synergistic effect on p‐mTOR reduction and SIRT1 increase. mTOR activator MHY1485 partly blocked the above effects. Moreover, intracellular ROS level induced by UV‐A irradiation could partly decrease by AKF‐PD, and MHY1485 could reduce this effect. Our results indicated that AKF‐PD could alleviate HDF senescence induced by UV‐A‐irradiation by inhibiting the p‐mTOR and increasing SIRT1. Moreover, AKF‐PD may be a potential treatment material for skin.     

Stem cells and the skin

Stem cells live long lives, renew themselves, and differentiate into more mature, less potent, specialized cells, such as epidermal keratinocytes and dermal fibroblasts. Stem cells can be embryonic, if derived from an embryo, or adult/somatic if derived from postembryonic tissue. By producing new skin cells, stem cell division and differentiation can potentially rejuvenate skin and restore hair. To reproduce, stem cells can undergo symmetric nondifferentiative or differentiative divisions, or asymmetric differentiative divisions. Asymmetric divisions reproduce the stem cell and provide a more differentiated, but less potent transient amplifying cell. Divisions and differentiation of transient amplifying cells regenerate tissues by producing cells of a specific lineage, for example, keratinocytes. Epidermal stem cells lie in niches in the interfollicular epidermis, sebaceous gland, and in the bulge regions of hair follicles. These epidermal stem cells renew the epidermis, the sebaceous glands, and hair follicles after mature cells die. Dermal stem cells lie in the hair papillae, around pericytes, and elsewhere among other dermal cells. These form pericytes, myoblasts, fibroblasts, chondrocytes, and other specialized dermal cells. Along with other signaling pathways, the Wnt signaling pathway controls stem cell fate. Wnt signals enlist two functionally and chemically different gene coactivators to direct the time and type of replicative divisions. Stem cells may help to heal wounds, repair damaged tissues, regenerate aged skin, and reinvigorate growth of skin, hair, nails, and mucous membranes.     

Rosacea or photodamaged skin? Use of brimonidine gel in differentiating erythema in the two conditions

In this case report, we detail the response of a 37‐year‐old Caucasian man with an overlap of erythematotelangiectatic rosacea and telangiectatic photoaging to brimonidine tartrate gel. With the application of brimonidine only on half of his face, skin analysis images, clinician's and patient's assessment showed that there was significant improvement in the erythema. This case has lent insight into how brimonidine can be used to assess the extent of photoaging by eliminating the erythema of rosacea to some degree. We propose that it can be used as a non‐invasive test to differentiate between the two conditions, sparing patients from skin biopsies and molecular analysis.     

Effects of sunscreen on skin cancer and photoaging

Application of sunscreen to the skin is widely used as an adjunct strategy, along with wearing protective clothing and seeking shade, to protect against skin cancer and photoaging that result from excessive sun exposure. Many epidemiological studies of case–control and cohort study design have studied the effects of sunscreen use on skin cancer, and more recently photoaging, but their findings have been mostly uninformative. This review of results of randomized controlled trials shows that the evidence, though limited, supports beneficial effects of sunscreen application on the occurrence of skin cancers and skin photoaging.     

虾青素/天然DNA/壳聚糖纳米粒对紫外诱导的小鼠皮肤光老化的改善作用

目的 探究虾青素/天然DNA/壳聚糖纳米粒（Ast/DC）对紫外诱导的小鼠皮肤光老化的改善作用。方法 分子自组装结合溶剂蒸发法制备Ast/DC。紫外照射脱毛小鼠30 d模拟皮肤光老化,研究Ast/DC对小鼠皮肤表观形态、组织纤维结构以及皮肤中超氧化物歧化酶（SOD）等抗氧化因子表达水平等的影响;并用Franz扩散池模拟透皮吸收过程研究纳米载体对虾青素的经皮递送效果。结果 将平均粒径为266 nm、Zeta电位为32.7 mV的Ast/DC（虾青素有效剂量为1.5 μg?cm-2?d-1）涂抹于紫外照射小鼠的背部,可维持其皮肤正常形态和结构,在角质层厚度、胶原纤维和弹性纤维结构等方面与未经紫外照射小鼠相比无明显差异;并且皮肤组织中的谷胱甘肽（GSH）、SOD和过氧化氢酶（CAT）表达水平较光老化小鼠分别显著提高31.4%、25.1%和41.7%（P＜0.05）。当虾青素有效涂抹剂量低至0.33 μg?cm-2?d-1时,Ast/DC仍能显著提高皮肤组织中的抗氧化因子表达水平,且优于游离虾青素;相较于光老化模型小鼠,低剂量Ast/DC组小鼠和虾青素油（Ast/oil）组小鼠中GSH含量分别提高26.4%和15.1%。同时,Ast/DC的24 h累积透皮吸收量比游离虾青素提高20.7%。结论Ast/DC能有效保护小鼠皮肤,抵御紫外照射引起的皮肤光老化。     

光甘草定醇质体与立方液晶纳米粒皮肤滞留量比较及抗豚鼠皮肤光老化作用观察

目的 制备光甘草定醇质体与立方液晶纳米粒,通过测定2种纳米制剂在离体豚鼠皮肤中的滞留量优选出适合光老化经皮给药的制剂。建立光老化模型,通过观察优选制剂对豚鼠光老化模型的治疗效果来评价药物的疗效。方法 采用注入法制备光甘草定醇质体,高压均质法制备光甘草定立方液晶纳米粒,利用Franz扩散装置考察光甘草定醇质体、立方液晶纳米粒凝胶离体鼠皮中的滞留量,优选出光甘草定经皮给药治疗光老化的纳米制剂。紫外线照射背部剃毛豚鼠建立皮肤光老化模型。雌性豚鼠随机分为模型组、基质（给予空白凝胶0.5 g/只）组、维甲酸（阳性对照,0.5 g/只）组和甘草定立方液晶纳米粒凝胶高、低剂量（0.50、0.25 g/只）组,治疗2周后,通过肉眼观察、HE染色、Masson染色等评价其治疗效果,用水份测定仪观察其对豚鼠皮肤含水量的影响。结果 2种纳米制剂凝胶的鼠皮滞留量最高者为光甘草定立方液晶纳米粒凝胶。豚鼠皮肤光老化模型建立成功,HE染色、Masson染色等结果表明光甘草定立方液晶纳米粒对光老化有明显的治疗效果,使光老化皮肤的含水量显著升高（P<0.05）。结论 光甘草定立方液晶纳米粒在离体鼠皮中的滞留较高,对豚鼠皮肤光老化模型治疗效果显著,为光甘草定的临床应用提供了新的方法与思路。