Keratinocytes are immunocompetent cells important for the structural and barrier function of skin. Psoriatic keratinocytes are characterized by the enhanced proliferation and reduced differentiation rates as well as by the elevated production of proinflammatory cytokines and chemoattractants. In this research we have knocked-down a scaffold protein IQGAP3 using shRNA in HaCaT keratinocytes (HaCaT_shIQ3) in order to test the hypothesis if IQGAP3 mediates the psoriatic phenotype of keratinocytes. IQGAP interacts with cell adhesion molecules, with the cytoskeleton, with signaling molecules to regulate cell morphology, motility and kinase pathways. Earlier we have identified IQGAP3 to be overexpressed in skin of psoriatic patients and to be stimulated by the proinflammatory cytokines IL17, TNFa and IFNg. RNA-seq of the HaCaT_shIQ3 cells has shown that among the GO enriched by the downregulated genes were: positive regulation of MAPK cascade, negative regulation of inflammatory response, epidermis development, negative chemotaxis, cell adhesion, keratinization, keratinocyte differentiation, intracellular signal transduction. Among the GO enriched by the upregulated genes were positive regulation of macrophage cytokine production, extracellular matrix organization, positive regulation of I-kB/NF-kB signaling, calcium transport, cell adhesion, positive regulation of inflammatory response, lipid metabolic process, positive regulation of IL6 production, NO biosynthetic process. Almost all the onthologies mentioned above are involved in psoriatic process, highlighting the importance of the IQGAP3 for this disease. Using xCELLigence real time cell analysis system we have evaluated the growth rates of HaCaT_shIQ3. Compared to the control cells, HaCaT_shIQ3 demonstrated slower growing rates, delayed wound healing and were in a lesser degree growthstimulated by psoriatic proinflammatory cytokines. Thus we concluded IQGAP3 to be an important mediator of the psoriatic phenotype of keratinocytes.

Famotidine (FMT) is a competitive histamine-2 (H2) receptor antagonist that inhibits gastric acid secretion for the treatment of Gastroesophageal reflux disease. To study the promoting effect and mechanism of terpenes, including l-menthol, borneol, and geraniol, as chemical enhancers, FMT was used as a model drug. Attenuated total reflectance-Fourier transform IR spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to explore the effects of terpenes on the skin. Hairless mouse skin was mounted on Franz-type diffusion cell, and skin permeation experiment of FMT hydrogel was carried out. The results suggested that the thermodynamic activity influenced the permeability of the drug, and the main mechanism of terpenes to enhance skin permeation of the drug was based on increasing the fluidity of the intercellular lipids. Moreover, it was revealed that l-menthol simultaneously relaxed the packing structure and lamellar structure, whereas geraniol had a great influence on the lamellar structure only. Collectively, all terpenes had a promoting effect on skin permeation of FMT, indicating their potential as chemical enhancers to change the microstructure of stratum corneum and improve the permeation of FMT through the skin, and it has great potential to be used in transdermal formulations of FMT.

The admixture of a steroid ointment and a moisturizing cream is frequently prescribed to patients suffering from atopic dermatitis. For the mixing operation, a revolution/rotation-type hybrid mixer is widely used in pharmacy. The purpose of this study was to monitor the mixed state of the admixtures during the mixing process of the hybrid mixer. The key technology used in this study was magnetic resonance imaging (MRI). Two different commercial mometasone furoate-containing ointments were used as a test steroid ointment. After layering the moisturizing cream and the steroid ointment in an ointment bottle, the sample was mixed for a predetermined period using the hybrid mixer. According to MRI transverse relaxation time (T 2 ) mapping for nondestructive monitoring, it was confirmed that the Flumeta ® ointment-containing admixture became homogeneous by mixing for 60 s or more. As for the mometasone furoate ointment 0.1%-containing admixture, the mixed state, after becoming homogeneous, was separated into two layers again by the prolonged mixing process. From the 1 H-NMR spectra of the phase-separated layers, re-separation was caused by removing aqueous components from the bottom of the samples. MRI is a powerful tool for monitoring the mixed state of the admixture during the mixing process. We believe that our findings offer profound insights into the clinical practice of the mixing operation using a hybrid mixer.