Spectral and mass characterization of kinetic conversion from retinoids to retinoic acid in an in vitro 3-D human skin equivalent model.

To investigate the effect of retinoids, such as retinol (ROL), retinal (RAL), and retinyl palmitate (RP), on epidermal integrity, skin deposition, and bioconversion to retinoic acid (RA). 3-D human skin equivalent model (EpiDermFT™) was used. Epidermal cellular integrity measured by TEER values was significantly higher for a topical treatment of ROL and RAL than RP (p < 0.05). The skin deposition (µM) of ROL and RAL was approximately 269.54 ± 73.94 and 211.35 ± 20.96, respectively, greater than that of RP (63.70 ± 37.97) over 2 h incubation. Spectral changes were revealed that the CO maximum absorbance occurred between 1600∼1800 cm-1 and was greater from ROL than that from RAL and RP, indicating conjugation of R-OH to R-CHO or R-COOH could strongly occur after ROL treatment. Subsequently, a metabolite from the bioconversion of ROL and RAL was identified as RA, which has a product ion of m/z 283.06, by using liquid a chromatography-mass spectrometry (LC-MS) - total ion chromatogram (TIC). The amount of bioconversion from ROL and RAL to RA in artificial skin was 0.68 ± 0.13 and 0.70 ± 0.10 µM at 2 h and 0.60 ± 0.04 and 0.57 ± 0.06 µM at 24 h, respectively. RA was not detected in the skin and the receiver compartment after RP treatment. ROL could be a useful dermatological ingredient to maintain epidermal integrity more effectively, more stably deposit on the skin, and more steadily metabolize to RA than other retinoids such as RAL and RP.

The development of anin vitrohuman hair follicle organoid with a complexity similar to thatin vivo.

In vitrohair follicle (HF) models are currently limited toex vivoHF organ cultures (HFOCs) or 2D models that are of low availability and do not reproduce the architecture or behavior of the hair, leading to poor screening systems. To resolve this issue, we developed a technology for the construction of a humanin vitrohair construct based on the assemblage of different types of cells present in the hair organ. First, we demonstrated that epithelial cells, when isolatedin vitro, have similar genetic signatures regardless of their dissection site, and their trichogenic potential is dependent on the culture conditions. Then, using cell aggregation techniques, 3D spheres of dermal papilla (DP) were constructed, and subsequently, epithelial cells were added, enabling the production and organization of keratins in hair, similar to what is seenin vivo. These reconstructed tissues resulted in the following hair compartments: K71 (inner root-sheath), K85 (matrix region), K75 (companion layer), and vimentin (DP). Furthermore, the new hair model was able to elongate similarly toex vivoHFOC, resulting in a shaft-like shape several hundred micrometers in length. As expected, when the model was exposed to hair growth enhancers, such as ginseng extract, or inhibitors, such as TGF-B-1, significant effects similar to thosein vivowere observed. Moreover, when transplanted into skin biopsies, the new constructs showed signs of integration and hair bud generation. Owing to its simplicity and scalability, this model fully enables high throughput screening of molecules, which allows understanding of the mechanism by which new actives treat hair loss, finding optimal concentrations, and determining the synergy and antagonism among different raw materials. Therefore, this model could be a starting point for applying regenerative medicine approaches to treat hair loss.

Kinetic conversion of BIOGF1K enriched in compound K from in vitro 3-D human tissue model.

The purposes of current study were to investigate the effect of ginsenosides from BIOGF1K enriched in compound K (CK) and compound Y (CY) on the skin barrier function, the deposition in in vitro 3-D human tissue model (EpiDermFT™ Full Thickness 400), and to identify and quantify kinetic bioconversion of the ginsenosides in artificial skin by utilizing the Fourier transform infrared spectroscopy (FT-IR) and liquid chromatography mass spectrometry (LC-MS), respectively. Epidermal barrier integrity evaluated using transepithelial electrical resistance (TEER) was significantly higher in the BIOGF1K treatment than the CY or CK individual treatment throughout incubation (p < 0.05). Skin deposition (%) of CY and CK from BIOGF1K treatment was approximately 4 and 2 times higher than the CY and CK single component treatment, respectively. Total amount of CK found in human skin by deposition and bioconversion was approximately 1087.3, 528.82, and 867.76 µM after topical treatment of BIOGF1K, CK, and CY. Results from the current study reveal that topical treatment of BIOGF1K more effectively induced CK deposition as well as bioconversion of CY to CK than that of a single treatment of CY or CK, suggesting that BIOGF1K could be a useful cosmetic preparation for enhancing skin function.

Ginsenoside Re prevents 3-methyladenine-induced catagen phase acceleration by regulating Wnt/ß-catenin signaling in human dermal papilla cells.

Background: The human hair follicle undergoes cyclic phases-anagen, catagen, and telogen-throughout its lifetime. This cyclic transition has been studied as a target for treating hair loss. Recently, correlation between the inhibition of autophagy and acceleration of the catagen phase in human hair follicles was investigated. However, the role of autophagy in human dermal papilla cells (hDPCs), which is involved in the development and growth of hair follicles, is not known. We hypothesized that acceleration of hair catagen phase upon inhibition of autophagy is due to the downregulation of Wnt/ß-catenin signaling in hDPCs, and that components of Panax ginseng extract can increase the autophagic flux in hDPCs. Methods: We generated an autophagy-inhibited condition using 3-methyladenine (3-MA), a specific autophagy inhibitor, and investigated the regulation of Wnt/ß-catenin signaling using the luciferase reporter assay, qRT-PCR, and western blot analysis. In addition, cells were cotreated with ginsenoside Re and 3-MA and their roles in inhibiting autophagosome formation were investigated. Results: We found that the unstimulated anagen phase dermal papilla region expressed the autophagy marker, LC3. Transcription of Wnt-related genes and nuclear translocation of ß-catenin were reduced after treatment of hDPCs with 3-MA. In addition, treatment with the combination of ginsenoside Re and 3-MA changed the Wnt activity and hair cycle by restoring autophagy. Conclusions: Our results suggest that autophagy inhibition in hDPCs accelerates the catagen phase by downregulating Wnt/ß-catenin signaling. Furthermore, ginsenoside Re, which increased autophagy in hDPCs, could be useful for reducing hair loss caused by abnormal inhibition of autophagy.

Bioconversion of BIOGF1K, a compound-K-rich fraction from ginseng root and its effect on epidermal barrier function.

BIOGF1K, the ginseng root-based and hydrolyzed ginsenoside-rich fraction, is known to improve skin damage, but there are rare studies on the kinetic of ginsenosides in the epidermis and their effects on epidermal barrier function. The current study investigated the effect of BIOGF1K on epidermal barrier function and its kinetics on epidermal transport. HPLC and LC/MS were used to verify the ginsenosides and the metabolites of BIOGF1K. Human immortalized keratinocytes (HaCaT) and epidermis-dermis artificial skin were treated with BIOGF1K and their metabolites were analyzed by HPLC and LC/MS. The epidermal barrier function was evaluated by transepithelial electrical resistance (TEER). In BIOGF1K, ginsenoside Rg1, Rd, F1, F2, compound Mc, compound Y (CY), and compound K (CK) were detected and CK and CY were the most and second abundant ginsenosides. TEER of HaCaT with 100 and 200 µg/mL BIOGF1K treatment was significantly higher than the control during 600 min of incubation. CK was permeated to the epidermis in a time-dependent manner and its maximum transported rate was observed at 600 min. In the case of artificial skin, CY and CK were permeated to the epidermis-dermis skin as time-dependent. Also, 24 h after treatment of CY, CK was detected as 19.59% of CY. It was proposed that CY was hydrolyzed into CK while permeating the epidermis. Results from the current study suggest that bioconversion of BIOGF1K rich in CK effectively enhances epidermal barrier function and it could be a useful cosmeceutical to exhibit its functionality to the skin.

Bioconversion of retinol and its cell barrier function in human immortalized keratinocytes cells and artificial epidermis-dermis skin.

The current study aimed to characterize cellular uptake and bioconversion of retinol in fully differentiated human immortalized keratinocytes cells (HaCaT) and artificial skin by measuring the cell integrity of skin barriers, time-dependent transport of retinol, and bioconversion to its metabolites. The expression of epidermal differentiation related genes including Keratin 1 (KRT1), Keratin 10 (KRT10), and Involucrin (IVL) significantly increased in differentiated HaCaT. TEER of HaCaT did not decrease after incubating retinol compared to control (p > 0.05), indicating that retinol tends to maintain strength and integrity of epidermal barrier. TEER of artificial skin decreased treatment of retinol for 2 h, but it was recovered after 4 h. During retinol transport, metabolite was eluted at 13.37 and 13.82 min of basal medium of both keratinocytes and artificial skin, which was identified as retinoic acid by product ion of m/z 283.47. Retinol appeared to be accumulated in keratinocytes, but its uptake tends to be reduced in a time-dependent manner. Retinoic acid converted from retinol in keratinocytes was time dependently transported. In case of artificial skin, retinol was mostly found in apical at initial incubation time, but it was reduced during incubation for 24 h. Retinoic acid was time-dependently found in a basal, which was converted via epidermis-dermis. Results from the current study suggest that topical application of retinol to human skin optimal concentration and time exposure could maintain epidermal barrier function and promote skin function due to its remarkable bioconversion to retinoic acid in the epidermis-dermis.

Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion.

Bioactive peptides (BPs) are protein fragments that benefit human health. To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. The selected probiotics digested GTRs anaerobically to yield GTR-derived peptide fractions. To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs.

Kaempferol tetrasaccharides restore skin atrophy via PDK1 inhibition in human skin cells and tissues: Bench and clinical studies.

Skin aging is a major risk factor for the dermal diseases, and interventions to attenuate cellular senescence are expected to reduce the risk for age-related diseases involving skin atrophy. However, blocking cell death or extending proliferation causally results in side effects and an increased cancer risk. For identification of a safer approach, we focused on PDK1 inhibition, which could revert cellular senescence and reduce senescence factors in skin in vitro, in a human skin equivalent model and in an exploratory, placebo-controlled, interventional trial. Natural phytochemical kaempferol tetrasaccharides resulted in a significant reduction in cellular senescence, and an increase in collagen fiber was observed in the skin cell and human skin equivalent. Clinical enhancement in skin appearance was noted in multiple participants, and an immunohistochemical study revealed improvement in the histological appearance of skin tissue and extracellular matrix. This change was associated with relative improvement in histological markers of senescence and clinical appearance of the aged skin and an increase in collagen fiber, an essential factor for preventing skin atrophy and consistency of the basement membrane. These results indicate that PDK1 inhibition is a potentially effective antiaging intervention, suggesting a diagnostic role and preventive actions of PDK1 in senescence-associated skin atrophy.

Early onset female pattern hair loss: A case-control study for analyzing clinical features and genetic variants.

BACKGROUND: Female pattern hair loss (FPHL), the most common cause of alopecia in adult women, is classified into two subtypes: early onset and late onset (or postmenopausal). Little is known about the clinical features and genetic characteristics of early onset female pattern hair loss (eFPHL). OBJECTIVES: To investigate the clinical features and genetic characteristics of eFPHL. METHODS: Patients with eFPHL and controls without eFPHL were prospectively recruited. The demographic and clinical features were collected. Single nucleotide polymorphisms (SNPs) located around the selected 30 candidate genes potentially associated with eFPHL were evaluated. RESULTS: eFPHL patients (n = 63) manifested a decreased hair shaft density and cross-sectional area of the hair shaft compared to the control group (n = 341). eFPHL is associated with androgen-related features, including scalp greasiness, folliculitis, hirsutism, and polycystic ovary syndrome. Scalp pain and itching have been reported more frequently in patients with eFPHL. Forty-nine SNPs located around PPARGC1A, ABCC4, CYP11B2, FSHB, and CYP19A1 were found to be significant for eFPHL, including two PPARGC1A-associated SNPs: rs186530605 and rs192713767 (p = 3.94 × 10-11). CONCLUSIONS: This study provided clinical features and genetic variants for eFPHL, which could provide insight into the underlying pathologic etiology. Considering the limited number of patients, a large-scale study is required in the future.

Ceramide NPs derived from natural oils of Korean traditional plants enhance skin barrier functions and stimulate expressions of genes for epidermal homeostasis.

BACKGROUND: New ceramide (CER) NPs were prepared by linking fatty acids derived from oils of Korean traditional plants to phytosphingosine (PHS). The oils of Korean traditional plants were extracted from the seeds of Panax ginseng, Camellia sinensis, Glycine max napjakong, Glycine max seoritae, and Camellia japonica as sources of diverse fatty acids. AIMS: The aim of this study was to investigate signaling bioactivities of HP-C. sinensis ceramide NP that was column purified to remove any residual PHS and to evaluate the skin barrier functions of the HP-C. sinensis ceramide NP in human skin. METHODS: The expressions of genes related to epidermal differentiation were analyzed in vitro by qPCR. Human studies were also performed to determine the skin barrier functions with respect to TEWL and SC cohesion. RESULTS: The HP-C. sinensis CER NP significantly enhanced the expressions of FLG, CASP14, and INV indicates that the signaling biological activities of oil-derived ceramide NPs could be different depend on the natural oils. The control ceramide, C18-CER NP, had no effect on the expression of the three genes. HP-C. sinensis CER NP was selected for the in vivo human studies. Application of 0.5% HP-C. sinensis CER NP cream stimulated significantly faster recovery of a disrupted skin barrier than that of the control C18-CER NP. A significant enhancement of SC cohesion of the skin treated with 0.5% HP-C. sinensis CER NP was also observed. CONCLUSION: Taken all together, our results clearly demonstrate that HP-C. sinensis CER NP, P. ginseng CER NP, and other oil-derived CER NP could be a better choice for developing moisturizers to improve skin barrier function as they more closely mimic the endogenous CER composition of the actual human skin barrier.

3,4,5-Trimethoxycinnamate thymol ester inhibits melanogenesis in normal human melanocytes and 3D human epidermal equivalents via the PGC-1α-independent PPARγ partial agonism.

BACKGROUND: 3,4,5-Trimethoxycinnamate thymol ester (TCTE), an anti-melanogenic cosmetic agent prescribed currently, promotes adiponectin synthesis during adipogenesis in human bone marrow mesenchymal stem cells (hBM-MSCs). Adiponectin inhibits melanin biosynthesis and its biosynthesis is directly regulated by peroxisome proliferator-activated receptor (PPAR) γ. In this regard, TCTE may potentially affect PPARγ activity. However, contradicting effects of PPARγ agonists with different chemical structures on human melanogenesis have been reported. OBJECTIVE: A molecular target of TCTE was investigated to elucidate the association of both adiponectin and PPARγ with anti-melanogenic activity. METHODS: The adiponectin secretion-promoting activity of TCTE was tested in an adipogenesis model of hBM-MSCs. A molecular target of TCTE for adiponectin secretion was evaluated via time-resolved fluorescence resonance energy transfer-based receptor binding and transactivation of PPARs. RESULTS: TCTE significantly promoted adiponectin secretion (EC50, 27.9 µM) during adipogenesis in hBM-MSCs and directly bound to PPARγ (Ki, 13.2 µM). The TCTE-bound PPARγ increased the recruitment of SRC-1, SRC-3, and TRAP220/DRIP-1 coactivator peptides without affecting PGC-1α coactivation. In the docking analysis, the optimal ligand binding mode of TCTE exhibited typical ligand-receptor interactions of PPARγ partial agonists. The PPARγ partial agonism of TCTE was established experimentally and the anti-melanogenic activity of TCTE was decreased by treatment with a PPARγ antagonist in cultured normal human melanocytes and a 3D model of human epidermis. CONCLUSION: The anti-melanogenic activity of TCTE was associated with a PGC-1α-independent PPARγ partial agonism.

Induction of hair growth in hair follicle cells and organ cultures upon treatment with 30 kHz frequency inaudible sound via cell proliferation and antiapoptotic effects.

Androgenic alopecia is a hair loss disease mediated by dihydrotestosterone (DHT) and is currently treated using minoxidil, finasteride, or low-level laser therapy. However, these treatments have side-effects, indicating the need for an alternative treatment. In the present study, it was demonstrated that inaudible sound at 30 kHz significantly induced proliferative and anti-apoptotic effects in human dermal papilla cells (hDPCs) and outer root sheath keratinocytes. Cell viability assay, ELISA, reverse transcription quantitative PCR and TUNEL assays were performed to evaluate the effect of inaudible sound. Inaudible sound was also demonstrated to significantly inhibit the hair loss signals induced by DHT treatment in hDPCs. Furthermore, inaudible sound significantly induced hair follicle (HF) elongation and hair matrix keratinocyte proliferation in human HF organ culture. Overall, the results suggested that inaudible sound may be effective in treating hair loss and could be used to develop a new hair loss treatment approach.

Supervised Statistical Learning Prediction of Soybean Varieties and Cultivation Sites Using Rapid UPLC-MS Separation, Method Validation, and Targeted Metabolomic Analysis of 31 Phenolic Compounds in the Leaves.

Soybean (Glycine max; SB) leaf (SL) is an abundant non-conventional edible resource that possesses value-adding bioactive compounds. We predicted the attributes of SB based on the metabolomes of an SL using targeted metabolomics. The SB was planted in two cities, and SLs were regularly obtained from the SB plant. Nine flavonol glycosides were purified from SLs, and a validated simultaneous quantification method was used to establish rapid separation by ultrahigh-performance liquid chromatography-mass detection. Changes in 31 targeted compounds were monitored, and the compounds were discriminated by various supervised machine learning (ML) models. Isoflavones, quercetin derivatives, and flavonol derivatives were discriminators for cultivation days, varieties, and cultivation sites, respectively, using the combined criteria of supervised ML models. The neural model exhibited higher prediction power of the factors with high fitness and low misclassification rates while other models showed lower. We propose that a set of phytochemicals of SL is a useful predictor for discriminating characteristics of edible plants.

Molecule-Resolved Visualization of Particulate Matter on Human Skin Using Multimodal Nonlinear Optical Imaging.

Precise measurement of particulate matter (PM) on skin is important for managing and preventing PM-related skin diseases. This study aims to directly visualize the deposition and penetration of PM into human skin using a multimodal nonlinear optical (MNLO) imaging system. We successfully obtained PM particle signals by merging two different sources, C-C vibrational frequency and autofluorescence, while simultaneously visualizing the anatomical features of the skin via keratin, collagen, and elastin. As a result, we found morphologically dependent PM deposition, as well as increased deposition following disruption of the skin barrier via tape-stripping. Furthermore, PM penetrated more and deeper into the skin with an increase in the number of tape-strippings, causing a significant increase in the secretion of pro-inflammatory cytokines. Our results suggest that MNLO imaging could be a useful technique for visualizing and quantifying the spatial distribution of PM in ex vivo human skin tissues.

A novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids.

Excess glucocorticoids (GCs) with either endogenous or exogenous origins deteriorate skin barrier function. GCs bind to mineralocorticoid and GC receptors (MRs and GRs) in normal human epidermal keratinocytes (NHEKs). Inappropriate MR activation by GCs mediates various GC-induced cutaneous adverse events. We examined whether MR antagonists can ameliorate GC-mediated skin barrier dysfunction in NHEKs, reconstructed human epidermis (RHE), and subjects under psychological stress (PS). In a preliminary clinical investigation, topical MR antagonists improved skin barrier function in topical GC-treated subjects. In NHEKs, cortisol induced nuclear translocation of GR and MR, and GR and MR antagonists inhibited cortisol-induced reductions of keratinocyte differentiation. We identified 7,3',4'-trihydroxyisoflavone (7,3',4'-THIF) as a novel compound that inhibits MR transcriptional activity by screening 30 cosmetic compounds. 7,3',4'-THIF ameliorated the cortisol effect which decreases keratinocyte differentiation in NHEKs and RHE. In a clinical study on PS subjects, 7,3',4'-THIF (0.1%)-containing cream improved skin barrier function, including skin surface pH, barrier recovery rate, and stratum corneum lipids. In conclusion, skin barrier dysfunction owing to excess GC is mediated by MR and GR; thus, it could be prevented by treatment with MR antagonists. Therefore, topical MR antagonists are a promising therapeutic option for skin barrier dysfunction after topical GC treatment or PS.

Plant callus-derived shikimic acid regenerates human skin through converting human dermal fibroblasts into multipotent skin-derived precursor cells.

BACKGROUND: The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs. METHODS: Human dermal fibroblasts were treated with shikimic acid, a major component of Sequoiadendron giganteum callus extract. The characteristics of these reprogrammed cells were analyzed by qPCR, western blot, colony-forming assay, and immunofluorescence staining. Artificial human skin was used for CO2 laser-induced wound experiments. Human tissues were analyzed by immunohistochemistry. RESULTS: The reprogrammed cells expressed nestin (a neural precursor-specific protein), fibronectin, and vimentin and could differentiate into the ectodermal and mesodermal lineage. Nestin expression was induced by shikimic acid through the mannose receptor and subsequent MYD88 activation, leading to P38 phosphorylation and then CREB binding to the nestin gene promoter. Finally, we confirmed that shikimic acid facilitated the healing of cut injury and enhanced dermal reconstruction in a human artificial skin model. Moreover, in a clinical study with healthy volunteers, plant callus extracts increased the expression of stem cell markers in the basal layer of the epidermis and collagen deposit in the dermis. CONCLUSIONS: These results indicate that shikimic acid is an effective agent for tissue regeneration.

Clinical brightening efficacy and safety of Melasolv™ (3,4,5-trimethoxy cinnamate thymol ester, TCTE) in Southeast Asian women.

BACKGROUND: Skin darkening because of increased and irregular synthesis of melanin causes melasma, solar lentigo, and freckles. Melasolv™, produced in the early 2000s, shows potent depigmenting effect and has low cytotoxicity. It has been used as a brightening agent in cosmetics for decades. AIMS: This study was conducted to investigate whether Melasolv™ is effective for the skin of ASEAN (Southeast Asia) women. METHODS: We recruited ASEAN women in Singapore and divided them into two groups (active group vs. placebo group). Melasolv™ and placebo formulations were applied twice a day for 12 weeks. The changes in the pigmented spots were visually evaluated by an expert and assessed using a spectrophotometer and Mexameter at 0, 4, 8, and 12 weeks. RESULTS: The visual evaluation revealed significant improvements, in both size and color intensity, in the active group compared with those in the placebo group at 12 weeks. In the spectrophotometric evaluation, the L* value of the pigmented spots in the active group was significantly higher than that in the placebo group at 12 weeks. Similar results were obtained in the evaluation using the Mexameter. After 12 weeks, the melanin index of the pigmented spots significantly decreased, and it was significantly higher than that in the placebo group. There was no significant change in the erythema index. In the image analysis, there were no significant differences in skin color brightness and evenness in the active group compared with those in the placebo group. CONCLUSION: Melasolv™ can be effective used for skin brightening.

Chitosan-Alginate-Pectin-coated Suspended-Liquid-Encapsulating (CAPSuLE) marbles for therapeutic agent storage and delivery.

Developing a cutting-edge system capable of ensuring long-lasting functionality of therapeutic agents and implementing diverse delivery modes is challenging. A quasi-spherical triple-layered capsule containing suspended liquid droplets and allowing multi-modal delivery of therapeutic agents in the aqueous phase was developed, primarily by adopting the core principles for creating liquid marbles. A naturally derived wettable polysaccharide-pectin-was utilized as a liquid-air interfacial barrier to keep the liquid droplets in the core zone. To tailor the pectin-coated droplet as a therapeutic agent carrier, anionic alginate and cationic chitosan layers were sequentially formed via additional interactions: physically stacking substances with structural chirality (pectin-alginate) and inducing electrostatic association to create the reversible complex coacervates (alginate-chitosan). The resulting system, which is called a Chitosan-Alginate-Pectin-coated Suspended-Liquid-Encapsulating (CAPSuLE) marble, had sufficient mechanical strength to resist external harsh environments and exhibited unique features: ecofriendly sustainability, responsiveness to external stimuli, coacervate-driven coalescence for linking adjacent marbles, and a self-repairing ability. The proposed CAPSuLE system can facilitate the adoption of the liquid-marble concept to biomedical fields, extending its applicability in the fields of biology and applied engineering.

Characteristics of Advance Care Planning Interventions Across Dementia Stages: A Systematic Review.

PURPOSE: Little is known regarding how advance care planning (ACP) interventions change with the progression of dementia. Thus, the primary purpose of this systematic review is to compare characteristics of ACP interventions across dementia stages. We also identify the role of nurses in implementing ACP interventions for persons with dementia and their surrogates. DESIGN: A systematic review of ACP intervention studies. METHODS: After searching PubMed, Web of Science, EMBASE, PsycArticles, the Cumulative Index to Nursing and Allied Health Literture (CINAHL), and Scopus, the final sample included 11 studies representing 10 interventions. We conducted a quality assessment and extracted data on dementia stage, intervention characteristics, and the role of nurses in the intervention. The extracted data were categorized according to stages of dementia, and analyzed to identify commonalities and differences between intervention characteristics. FINDINGS: Three ACP interventions focused on mild dementia and seven on advanced dementia. We observed four primary findings. First, we found a major difference in intervention recipients between the two dementia stages. Second, most ACP interventions included structured discussions regarding the person's life goals and values, goals of care, and preferences concerning future care via individual, face-to-face interactions. Third, ACP interventions designed to promote ongoing discussions and documentation were lacking. Finally, nurses played important roles in implementing ACP interventions. CONCLUSIONS: The findings suggest more nurse-led, dementia-related ACP interventions. In addition, ACP interventions should promote ongoing discussions and documentation and target persons with dementia and their surrogates in various countries. CLINICAL RELEVANCE: Many persons with dementia and their surrogates have limited knowledge about ACP; thus, more nurse-led ACP programs that reflect dementia stages may help them prepare for the situations in which persons with dementia lack decision-making capacity.

Identifi cation of the Underlying Genetic Factors of Skin Aging in a Korean Population Study.

Genetic polymorphisms may affect the molecular mechanisms underlying determination of skin type. So far, several genetic studies have been reported; however, very few studies have been conducted to examine the relationship between genotype and skin phenotypes. In this study, the genome sequences of individuals tested for five cosmetic characteristics (wrinkles, moisture content, pigmentation, oil content, and ensitivity) were determined, and we also conducted five genome-wide association studies (GWASs) to identify predictive markers. Some single-nucleotide polymorphisms (SNPs) within those genes were more frequent in individuals exhibiting stronger traits. GWASs revealed that two genome-wide significant SNPs within FCRL5 and OCA2 genes were associated with wrinkles and pigmentation, respectively (p < 5 × 10-8), and that genomewide SNPs in 21 genes (wrinkles: FCRL5, REEP3, ADSS, and SPTLC1; moisture: TBX4, TRPM3, CEMIP2, CTSH, and TTC39C; pigmentation: OCA2, NCLN, TNS1, CDC42BPA, HS3ST4, and UNCX; oil: SYN2, CNDP1, GAS6, INSR, and TNFRSF19; and sensitivity: CREB5) might be associated with five skin phenotypes. Among these, a genome-wide significant SNP (rs117381658) and the SNP located downstream of FCRL5, which encodes a member of the immunoglobulin receptor family, were associated with an increased risk of wrinkles (p = 1.52 × 10-8). The other genome-wide significant SNP (rs74653330) was associated with a decreased risk of pigmentation (p = 1.04 × 10-8), which is located in the coding region of OCA2 that encodes for a transporter of melanin. Our study reports genetic factors associated with skin cosmetology parameters in the Korean population. We hope our findings will provide a foundation for further genetic and molecular studies related to custom cosmetics. Based on these findings, the industry will be able to provide consumers with ingredients capable of palliating the lack of function associated in genes with SNPs.