Post-translational regulation of the major drug transporters in the families of organic anion transporters and organic anion-transporting polypeptides.

The organic anion transporters (OATs) and organic anion-transporting polypeptides (OATPs) belong to the solute carrier (SLC) transporter superfamily and play important roles in handling various endogenous and exogenous compounds of anionic charge. The OATs and OATPs are often implicated in drug therapy by impacting the pharmacokinetics of clinically important drugs and, thereby, drug exposure in the target organs or cells. Various mechanisms (e.g. genetic, environmental, and disease-related factors, drug-drug interactions, and food-drug interactions) can lead to variations in the expression and activity of the anion drug-transporting proteins of OATs and OATPs, possibly impacting the therapeutic outcomes. Previous investigations mainly focused on the regulation at the transcriptional level and drug-drug interactions as competing substrates or inhibitors. Recently, evidence has accumulated that cellular trafficking, post-translational modification, and degradation mechanisms serve as another important layer for the mechanisms underlying the variations in the OATs and OATPs. This review will provide a brief overview of the major OATs and OATPs implicated in drug therapy and summarize recent progress in our understanding of the post-translational modifications, in particular ubiquitination and degradation pathways of the individual OATs and OATPs implicated in drug therapy.

A low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminium garnet laser for the treatment of café-au-lait macules.

BACKGROUND: Café-au-lait macules (CALMs) are a common pigmentary disorder. Although a variety of laser modalities have been used to treat CALMs, their efficacies vary and dyspigmentation may develop. OBJECTIVE: We evaluated the clinical efficacy and safety of a low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminium garnet (Nd:YAG) laser for the treatment of CALMs. METHODS: In a preliminary investigation, 6 patients underwent a split-lesion comparative study with 532- and 1064-nm Q-switched Nd:YAG laser treatment. In total, 32 patients with 39 CALMs were enrolled in a subsequent prospective trial to evaluate the treatment with a low-fluence 1064-nm Q-switched Nd:YAG laser. RESULTS: In the preliminary study, the 1064-nm treatment group had a more favorable response and a shorter recovery time. In a subsequent prospective trial of a 1064-nm laser, 74.4% of the lesions showed a clinical response with clearance of ≥50.0%. The treatment regimen was well tolerated; 15.4% of patients experienced adverse events. LIMITATIONS: The study participants were followed for 6 months, and there were no relevant treatment controls in the prospective trial group. CONCLUSION: Low-fluence 1064-nm Q-switched Nd:YAG laser therapy afforded good clinical improvement for treating CALMs.

Photocatalysis of Cr- and Fe-Doped CeO2 Nanoparticles to Selective Oxidation of 5-Hydroxymethylfurfural.

Oxygen vacancies (Vo) present in CeO2 nanoparticles (NPs) can effectively boost their photocatalytic activity under ultraviolet (UV) light. To improve photocatalytic performance, Cr- and Fe-doped CeO2 NPs with increased Vo were prepared using a simple method of doping Cr and Fe ions into CeO2 NPs, which was confirmed by an in-depth analysis of the structural and electronic changes. Through photocatalytic degradation (PCD) experiments with 5-hydroxymethylfurfural (HMF), we found that the PCD rates of the two doped CeO2 NPs were faster than that of the CeO2 NPs. In addition, the conversion of HMF to 2,5-furandicarboxylic acid (FDCA) using the doped CeO2 NPs occurred only through the mechanism of the selective oxidation to 5-hydroxymethyl-2-furancarboxylic acid (HMFCA), exhibiting better efficiency than using CeO2 NPs.

The Effect of Micro-Spicule Containing Epidermal Growth Factor on Periocular Wrinkles.

BACKGROUND: Micro-needle patches have been recently used to increase skin permeability, which improves drug delivery, and for cosmetic purposes. However, these patches may often have limited efficacy due to insufficient skin penetration and reduced compliance caused by discomfort. OBJECTIVE: We evaluated the efficacy and the safety of soluble micro-spicule containing epidermal growth factor (MS-EGF) for the treatment of periocular wrinkles. METHODS: Twenty healthy volunteers aged 33 to 54 years were enrolled in a randomized, controlled, split-face study. For 4 weeks, a periocular wrinkle was treated daily with either a soluble MS-EGF cream or a cream containing EGF alone. All subjects underwent 8 weeks of follow-up. Efficacy was assessed using an ultrasonic measurement of dermal depth and density, digital skin image analysis, 5-point photonumeric scale for periocular wrinkles and subjective satisfaction. RESULTS: MS-EGF group showed statistically significant increase of dermal depth and density compared to EGF alone group after 4 and 8 weeks. In addition, there was a marked improvement shown in clinical and 3-dimensional skin image in MS-EGF group. The treatments were well-tolerated; no significant side-effect was noted. CONCLUSION: The MS-EGF formulation may represent an effective and biocompatible advance in the treatment of periocular wrinkles.

Corrigendum: The Effect of Micro-Spicule Containing Epidermal Growth Factor on Periocular Wrinkles.

[This corrects the article on p. 187 in vol. 29, PMID: 28392646.].

Hyaluronic Acid Decreases Lipid Synthesis in Sebaceous Glands.

Hyaluronic acid (HA) is the major glycosaminoglycan in the extracellular matrix and has been implicated in several functions in skin cells. However, evidence is lacking regarding the HA signaling in sebaceous glands, and its potential role needs to be clarified. We investigated the role of HA in lipid production in sebaceous glands in an experimental study of human sebocytes followed by a clinical study. We first examined the effects of HA on sebaceous glands in hamsters and intradermal injection of HA into hamster auricles decreased both the size of sebaceous glands and the level of lipid production. We demonstrated that human skin sebaceous glands in vivo and sebocytes in vitro express CD44 (HA binding receptor) and that HA downregulates lipid synthesis in a dose-dependent manner. To evaluate the clinical relevance of HA in human skin, 20 oily participants were included in a double-blind, placebo-controlled, split-face study, and the HA-treated side showed a significant decrease in sebum production. The results of this study indicate that HA plays a functional role in human sebaceous gland biology and HA signaling is an effective candidate in the management of disorders in which sebum production is increased.

Comparison of Vitamin D Levels in Patients with and without Acne: A Case-Control Study Combined with a Randomized Controlled Trial.

BACKGROUND: Vitamin D plays an important role in the immune system, and its deficiency has been implicated in various skin diseases, including atopic dermatitis and psoriasis. Acne is a common inflammatory skin disease; however, the association with vitamin D remains unclear. OBJECTIVES: We evaluated vitamin D levels in patients with acne to determine the effect of vitamin D supplementation. METHODS: This study included 80 patients with acne and 80 healthy controls. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured, and demographic data were collected. Vitamin D-deficient patients were treated with oral cholecalciferol at 1000 IU/day for 2 months. RESULTS: Deficiency in 25(OH)D was detected in 48.8% of patients with acne, but in only 22.5% of the healthy controls. The level of 25(OH)D was inversely associated with the severity of acne, and there was a significant negative correlation with inflammatory lesions. In a subsequent trial, improvement in inflammatory lesions was noted after supplementation with vitamin D in 39 acne patients with 25(OH)D deficiency. LIMITATIONS: Limitations of the study include the small number of patients in the supplementation study and the natural fluctuation of acne. CONCLUSIONS: Vitamin D deficiency was more frequent in patients with acne, and serum 25(OH)D levels were inversely correlated with acne severity, especially in patients with inflammatory lesions.

Sox9 is a ß-catenin-regulated transcription factor that enhances the colony-forming activity of squamous cell carcinoma cells.

Squamous cell carcinoma (SCC) is a common skin cancer, of which the incidence is relatively high, ranking second among the non­melanoma skin cancers. It is known that numerous intracellular signal regulators are involved in the pathogenesis of SCC. The Wnt/ß-catenin signaling pathway serves an important role in cancer development. However, the downstream effectors of ß­catenin remain to be clearly elucidated yet. The present study investigated the functional importance of Wnt/ß­catenin signaling in cutaneous SCC. ß­catenin expression was reduced using recombinant adenovirus expressing specific microRNA (miR). Knockdown of ß­catenin resulted in a marked reduction of the colony-forming activity of the SCC cells, SCC12. In an attempt to identify the ß­catenin downstream genes, it was found that Sox9 was regulated by ß­catenin in SCC12 cells. Overexpression of a constitutively active form of ß­catenin led to the induction of Sox9, while knockdown of ß­catenin resulted in downregulation of Sox9. When the expression of Sox9 was reduced using specific miR, colony-forming activity of the SCC12 cells was significantly reduced. When Sox9 was overexpressed in cells where ß­catenin was knocked down, it partially restored the colony­forming potential. Taken together, the present results suggested that Sox9 is a ß-catenin downstream transcription factor and is positively involved in SCC development.