Enhancement of Efficacy of Retinoids through Enhancing Retinoid-Induced RAR Activity and Inhibiting Hydroxylation of Retinoic Acid, and Its Clinical Efficacy on Photo-Aging.

Retinoids, one of the most robust bioactive materials, have been widely used to improve various dermatological and pathological conditions. The body has an endogenous mechanism that modulates the exogenous retinoid above physiological concentrations, which limits the bioavailability or pharmacological efficacy of retinoids. Considering that most retinoids trigger extensive irritation in users, it is necessary to enhance the pharmacological efficacy of retinoids, thereby achieving a higher efficacy at a lower dosage. Here, we present approaches for enhancing the efficacy of retinol by enhancing retinoid-induced RAR gamma (RAR-γ) activity and inhibiting the hydroxylation of retinoic acid. Using both in vitro and ex vivo experiments, retinoid boosters were demonstrated to enhance pharmacological efficacy. A small pilot study was conducted to investigate the efficacy for improvement of facial wrinkles, whose results revealed that these boosters could enhance the pharmacological efficacy of topical applications of both retinol and retinoic acid for cosmetic use. These results promote not only a higher compliance among retinoids users, but also provide significant insights into the mechanisms underlying the action of retinoids.

Sugar-Triggered Burst Drug Releasing Poly-Lactic Acid (PLA) Microneedles and Its Fabrication Based on Solvent-Casting Approach.

Microneedles have emerged as a novel transdermal delivery tool that enables the delivery of various products such as drugs, vaccines, or cosmetic ingredients. Although the demand for solid microneedles composed of biocompatible polymer is increasing, the manufacture of microneedles using poly-lactic acid (PLA) with rapid drug-releasing is yet to be established and the process is still in its infancy. Here, we propose a novel strategy for the fabrication of PLA solid microneedles which enable a drug to be burst-released based on a solvent-casting process. This approach offers extreme simplicity, broad geometric capability, cost-effectiveness, and scalability based on high fidelity-replicas. It was verified that microneedles of various heights (250-500 µm) could be fabricated with appropriate mechanical strength to penetrate the stratum corneum layer of skin. By adding sugar in the composition of PLA microneedle, it was observed that both hydrophilic and hydrophobic drugs can be rapidly released within 30 min. Our burst drug-releasing PLA microneedle having both characteristics of solid microneedle and soluble microneedle and its fabrication approach based on solvent-casting will contribute to getting microneedle technology close to commercialization and beyond existing technical limitations.

Anti-Irritant Strategy against Retinol Based on the Genetic Analysis of Korean Population: A Genetically Guided Top-Down Approach.

Retinol, one of the most powerful cosmetic materials for anti-aging supported by a solid scientific background, exhibits a wide range of type and severity of irritation while showing limited user compliance. The lack of understanding of the mechanism of retinol-induced irritation has been the main hurdle in the development of anti-irritation strategies. Here, we identified 30 genetic markers related to the susceptibility to retinol-induced irritation in the Korean population. Based on the genetic analysis, a novel formula against retinol-induced irritation was developed, which mitigated the molecular pathogenesis-as indicated by the genetic markers-of the retinol-induced irritation. In human tests, this formula effectively decreased retinol-induced irritation. Furthermore, a polygenic risk score model for irritation was constructed and validated. Our comprehensive approach for the analysis of retinol-induced irritation will not only aid the development of anti-irritation strategies to ensure higher user compliance but also contribute to improving the current knowledge about the biological effects of retinoids.

Development of a pVEC peptide-based ribonucleoprotein (RNP) delivery system for genome editing using CRISPR/Cas9 in Chlamydomonas reinhardtii.

Recent technical advances related to the CRISPR/Cas9-based genome editing system have enabled sophisticated genome editing in microalgae. Although the demand for research on genome editing in microalgae has increased over time, methodological research has not been established to date for the delivery of a ribonucleoprotein (Cas9/sgRNA complex) using a cell penetrating peptide into microalgal cell lines. Here, we present a ribonucleoprotein delivery system for Chlamydomonas reinhardtii mediated by the cell penetrating peptide pVEC (LLIILRRRIRKQAHAHSK) which is in a non-covalent form. Using this technically simple method, the ribonucleoprotein was successfully delivered into C. reinhardtii. Gene Maa7 and FKB12 were disrupted, and their distinguishing patterns of Indel mutations were analyzed with the observation of several insertions of sequences not originating from the genome DNA, such as chloroplast DNA, into the expected loci. In addition, the cytotoxicity of Cas9 and the ribonucleoprotein was investigated according to the concentration and time in the algal cells. It was observed that Cas9 alone without the sgRNA induces a more severe cytotoxicity compared to the ribonucleoprotein. Our study will not only contribute to algal cell biology and its genetic engineering for further applications involving various organisms but will also provide a deeper understating of the basic science of the CRISPR/Cas9 system.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: A case report.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare neurodegenerative disorder characterized by cerebral white matter abnormalities, myelin loss, and axonal swellings. ALSP is caused by mutations in colony stimulating factor 1 receptor gene. We report an ASLP patient with asymptomatic intracranial calcifications distributed in white matter found incidentally in a health screening.

A novel electroporation system for efficient molecular delivery into Chlamydomonas reinhardtii with a 3-dimensional microelectrode.

Electroporation is one of the most widely used transfection methods because of its high efficiency and convenience among the various transfection methods. Previous micro-electroporation systems have some drawbacks such as limitations in height and design, time-consuming and an expensive fabrication process due to technical constraints. This study fabricates a three dimensional microelectrode using the 3D printing technique. The interdigitated microstructure consisting of poly lactic acid was injected by a 3D printer and coated with silver and aluminum with a series of dip-coatings. With the same strength of electric field (V cm(-1)), a higher efficiency for molecular delivery and a higher cellular viability are achieved with the microelectrode than with a standard cuvette. In addition, this study investigates chemicophysical changes such as Joule heating and dissolved metal during electroporation and showed the micro-electroporation system had less chemicophysical changes. It was concluded that the proposed micro-electroporation system will contribute to genetic engineering as a promising delivery tool, and this combination of 3D printing and electroporation has many potential applications for diverse designs or systems.

The effect of anodized implants coated with combined rhBMP-2 and recombinant human vascular endothelial growth factors on vertical bone regeneration in the marginal portion of the peri-implant.

OBJECTIVES: The aim of this study was to evaluate the effect of anodized implants coated with combined rhBMP-2 and recombinant human vascular endothelial growth factors (rhVEGFs) on vertical bone regeneration in the marginal portion of the peri-implant. STUDY DESIGN: Supra-alveolar defects were created in 3 male beagle dogs. Each animal received 8 implants that were either coated with a single growth factor (rhBMP-2) or combined growth factors (rhBMP-2 + rhVEGF), or an anodized implant (the control group). The amount of the vertical bone regeneration, the bone-implant contact, and the intrathread bone density were investigated using histomorphometric analysis at 8 weeks. RESULTS: The bone morphogenetic protein (BMP) group and the BMP-VEGF group showed vertical alveolar bone regeneration and enhanced bone-implant contact in the microthread compared with the control group (P < .05). CONCLUSIONS: Anodized implants coated with rhBMP-2 and rhBMP - 2 + rhVEGF can induce vertical alveolar bone regeneration, but the combined effect of rhBMP-2 and rhVEGF was not verified.