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We designed formulations based on minoxidil (MXD) nanoparticles (N-MXD) and examined whether N-MXD can increase drug delivery into the follicles. In addition, we investigated the effect of N-MXD on hair growth in C57BL/6 mice. N-MXD (1%) was prepared as follows: methylcellulose, p-hydroxyalkylbenzoates, mannitol, and MXD were dispersed in purified water and milled using zirconia beads under refrigeration (5500 rpm, 30 s×15 times, intermittent milling). C57BL/6 mice were used to evaluate hair-growth effects. The expression levels of mRNA and protein for vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) were determined by real-time PCR and ELISA methods, respectively. The ratio of solid-MXD was approximately 60% in N-MXD, and the MXD nanoparticles (90-300 nm) were oblong in shape. For the design of nanomedicines, usability is important. Therefore, we measured the stability and toxicity after N-MXD treatment. No agglutination of MXD nanoparticles was detected for 2 weeks, and no redness or MXD powder residue was observed in the skin after repetitive applications of N-MXD. Next, we evaluated hair-growth effects by N-MXD treatment. MXD contents in the skin tissue from N-MXD were lower than for commercially available MXD formulations (CA-MXD). Conversely, MXD contents in the hair bulbs were higher for N-MXD than for CA-MXD, and the drug efficacy of N-MXD was also higher than that of CA-MXD. In addition, the mRNA and protein levels of IGF-1 and VEGF were enhanced by the repetitive application of N-MXD and CA-MXD, and the enhanced IGF-1 and VEGF levels were significantly higher for N-MXD than for CA-MXD. We designed a novel nanomedicine based on MXD nanoparticles and showed that N-MXD can deliver MXD into hair bulbs via hair follicles and that the therapeutic efficiency for hair growth is higher than for CA-MXD (solution type).

Background: Isoconazole nitrate (ISN), an antifungal agent that inhibits ergosterol synthesis by blocking lanosterol 14α-demethylation, is widely used to treat candidiasis, and improving its skin retention and permeability can enhance its therapeutic efficacy. Therefore, we developed an ISN nanoparticle (ISN-NP) gel by wet-bead milling in the presence of methylcellulose (MC). Methods: These ISN nanoparticles were incorporated into a carboxypolymethylene hydrogel (Carbopol). The ISN concentration was measured using HPLC, and Wistar rats and Candida albicans were used to evaluate skin absorption and antifungal activity, respectively. Results: The ISN-NP gel exhibited a particle size distribution ranging from 60 to 220 nm, with the nanoparticles remaining stable. In addition, the ISN-NP gel demonstrated superior antifungal activity against Candida albicans. The Carbopol gel maintained appropriate viscosity and physical stability, and the ISN nanoparticles were released from the gel. Compared with microparticle-based gels (ISN-MP gels), the ISN-NP gel showed significantly enhanced drug release and transdermal permeation, with 1.54- and 1.7-fold increases, respectively. Conclusions: These findings indicate that incorporating ISN nanoparticles (nanocrystalline ISN) into a Carbopol-based gel matrix provides a promising strategy to enhance the topical delivery of this poorly water-soluble antifungal drug. Overall, this nanogel system represents a valuable platform for transdermal delivery in clinical applications.

Taurine, a sulfur-containing amino acid, occurs at high concentrations in the skin, and plays a role in maintaining the homeostasis of the skin. We investigated the effects of aging on the content and localization of taurine in the skin of mice and rats. Taurine was extracted from the skin samples of hairless mice and Sprague Dawley rats, and the taurine content of the skin was determined by high-performance liquid chromatography (HPLC). The results of the investigation revealed that the taurine content in both the dermis and epidermis of hairless mice declined significantly with age. Similar age-related decline in the skin taurine content was also observed in rats. In contrast, the taurine content in the sole remained unchanged with age. An immunohistochemical analysis also revealed a decreased skin taurine content in aged animals compared with younger animals, although no significant differences in the localization of taurine were observed between the two age groups. Supplementation of the drinking water of aged mice with 3% (w/v) taurine for 4 weeks increased the taurine content of the epidermis, but not the dermis. The present study showed for the first time that the taurine content of the skin decreased with age in mice and rats, which may be related to the impairment of the skin homeostasis observed with aging. The decreased taurine content of the epidermis in aged animals was able to be rescued by taurine supplementation.

The skin microbiome and sebum may be associated with inflammation-related diseases of the scalp. To assess the pathogenesis and progression of androgenetic alopecia (AGA), we analyzed the composition of sebum and the bacterial and fungal microbiomes of the scalps of 118 Japanese male individuals with and without AGA, then discussed their roles in the pathogenesis of AGA. Sebum triglyceride and palmitic acid contents were higher in the AGA group than in the non-AGA group. Malassezia restricta, a lipophilic fungus that consumes palmitic acid, was abundant on the scalps of patients with AGA. Cutibacterium, Corynebacterium, and Staphylococcus were the most common genera in both groups, and patients with AGA exhibited scalp dysbiosis (increased abundance of Cutibacterium and decreased abundance of Corynebacterium). Our findings suggest that both sebum and the bacterial and fungal microbiomes of the scalp may be involved in the development of AGA.

Taurine is a sulfur-containing amino acid derivative that can be found in the majority of mammalian tissues. Taurine is also present in the skin and is involved in maintaining skin homeostasis by exerting osmoregulatory and antioxidant effects. Previous studies have indicated that taurine treatment is effective against age-, ultraviolet- or detergent-induced skin dysfunction. To determine the mechanism responsible for the beneficial actions of taurine in the skin, the present study aimed to evaluate the effects of taurine on epidermal components (ceramides and filaggrin) and on the dermal extracellular matrix, in three-dimensionally (3D) cultured epidermis and dermal fibroblasts, respectively. These cells were cultured in the presence of 3-50 mM taurine, and cells or culture medium were collected for analysis. The effects of taurine on transepidermal water loss (TEWL) in the skin and the expression of inflammatory cytokines, including IL-1α, IL-1β and IL-1 receptor antagonist, were investigated in acetone-treated 3D-cultured epidermis using a Tewameter and reverse transcription-quantitative PCR (RT-qPCR), respectively. The mRNA expression levels of MMP-1 and hyaluronic acid (HA) production were measured in skin dermal fibroblasts using RT-qPCR and ELISA, respectively. Taurine was found to suppress acetone-induced elevation in TEWL in 3D-cultured epidermis. Taurine also stimulated the mRNA expression of ceramide synthase 4 and filaggrin, a major structural protein in the stratum corneum, in 3D-cultured epidermis. In skin dermal fibroblasts, taurine inhibited the IL-1α-stimulated mRNA and protein expression of MMP-1. In addition, taurine treatment increased HA synthase-2 mRNA expression and in turn HA production. Results from the present study suggest that the protective effect of taurine on the skin is associated with the enhancement of epidermal barrier component expression and modulation of dermal extracellular matrix metabolism.

We previously found that 1% minoxidil (MXD) nanoparticles prepared using a bead mill method led to an increase I n hair follicle delivery and hair growth in C57BL/6 mice. In the present study, we designed a nanoparticle formulation containing 5% MXD (MXD-NPs) using the bead mill method and investigated the hair-growth effect of MXD-NPs and a commercially available MXD solution (CA-MXD). Hair growth and in vivo permeation studies were conducted using C57BL/6 mice. Moreover, we examined the MXD contents in the upper (hair bulge) and the lower hair follicle (hair bulb) and observed the hair follicle epithelial stem cells (HFSC) by immunohistochemical staining using the CD200 antibody. The mean particle size of the MXD in the MXD-NPs was 139.8 nm ± 8.9 nm. The hair-growth effect of the MXD-NPs was higher than that of CA-MXD, and the MXD content in the hair bulge of mice treated with MXD-NPs was 7.4-fold that of the mice treated with CA-MXD. In addition, the activation of HFSC was observed around the bulge in the MXD-NPs-treated mice. We showed that MXD-NPs enable the accumulation of MXD in the upper hair follicles more efficiently than CA-MXD, leading the activation of HFSC and the hair growth.

Modified Leeming and Notman agar medium (mLNA) has been widely utilized to grow lipophilic fungi belonging to the genus Malassezia . We developed a new artificial-sebum-containing mLNA to obtain higher yields of Malassezia species. The olive oil in mLNA was replaced with an artificial sebum composed of triglyceride (triolein), diglyceride (glyceryl distearate), fatty acids (palmitic acid, myristic acid, pentadecanoic acid, and oleic acid), and squalene. Furthermore, the Tween 60 was replaced with self-emulsifying glyceryl stearate. Nine human-associated Malassezia species grew well on the artificial-sebum-containing mLNA, and the most predominant fungus on human skin, Malassezia restricta , exhibited double wet cell weight in artificial sebum-containing mLNA compared to wet cell weight in standard mLNA.

Microwave dielectric measurements were performed in the frequency range from 1 mHz up to 30 GHz using a time domain reflectometry (TDR) method for emulsions and gels. Flat-end sample cells have been used in the TDR measurement to contact a small spot of the surface of those viscoelastic and solid samples without any destruction. Relaxation processes due to various water structures were observed for these aqueous systems. Relaxation parameters thus obtained offer information about these water structures and amounts. The relaxation strength obtained from the high frequency process due to free water can be an adequate measure of water content in spite of some ambiguities for different water structures in some materials. Comparisons of actual water contents in emulsion with those estimated from the relaxation strength indicate that water structure is affected by the interaction between water and micelle. Unfreezable water observed in DNA gel under the freezing point consists of bound water and a fraction of free water. Bound water molecules are still unfreezable to keep the double helical structure of DNA, when the fraction of free water is frozen at lower temperatures. These water structures determine physical properties of moist materials. TDR measuring technique with the flat-end cell is effective to investigate water structures in viscoelastic moist materials and to evaluate physical properties and structures of complex molecular systems.

Abstract Introduction We aimed to determine the prospective association of smoking status, smoking intensity, and smoking cessation with the risk of hearing loss in a large Japanese cohort. Methods The cohort study included 50195 employees, who were aged 20–64 years and free of hearing loss at baseline. Participants were followed up for a maximum of 8 years. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression models were used to investigate the association between smoking and hearing loss. Results During follow-up, 3532 individuals developed high-frequency hearing loss, and 1575 developed low-frequency hearing loss. The hazard ratio (HR) associated with current smokers was 1.6 (95% confidence interval [CI] = 1.5 to 1.7) and 1.2 (95% CI = 1.1 to 1.4) for high- and low-frequency hearing loss, respectively, as compared with never smokers. The risk of high- and low-frequency hearing loss increased with the number of cigarettes smoked per day (both p for trend <.001). The HR associated with former smokers was 1.2 (95% CI = 1.1 to 1.3) and 0.9 (95% CI = 0.8 to 1.1) for high- and low-frequency hearing loss, respectively. The analysis by quitting years showed a decline in risk of hearing loss after quitting smoking, even among those who quitted less than 5 years before baseline. Conclusions Smoking is associated with increased risk of hearing loss, especially at the high frequency, in a dose–response manner. The excess risk of hearing loss associated with smoking disappears in a relatively short period after quitting. Implications The prospective association between smoking and hearing loss has not been well studied. To the best of our knowledge, our study is the largest to date investigating the association between smoking and incident hearing loss. Our results indicate that smoking is associated with increased risk of hearing loss in a dose–response manner. Quitting smoking virtually eliminates the excess risk of hearing loss, even among quitters with short duration of cessation. These results suggest that smoking may be a causal factor for hearing loss, although further research would be required to confirm this. If so, this would emphasize the need for tobacco control to prevent or delay the development of hearing loss.

Although the sex-determining gene Sry has been identified in mammals, no comparable genes have been found in non-mammalian vertebrates. Here, we used recombinant breakpoint analysis to restrict the sex-determining region in medaka fish (Oryzias latipes) to a 530-kilobase (kb) stretch of the Y chromosome. Deletion analysis of the Y chromosome of a congenic XY female further shortened the region to 250 kb. Shotgun sequencing of this region predicted 27 genes. Three of these genes were expressed during sexual differentiation. However, only the DM-related PG17 was Y specific; we thus named it DMY. Two naturally occurring mutations establish DMY's critical role in male development. The first heritable mutant--a single insertion in exon 3 and the subsequent truncation of DMY--resulted in all XY female offspring. Similarly, the second XY mutant female showed reduced DMY expression with a high proportion of XY female offspring. During normal development, DMY is expressed only in somatic cells of XY gonads. These findings strongly suggest that the sex-specific DMY is required for testicular development and is a prime candidate for the medaka sex-determining gene.