Enhancement of skin rejuvenation and hair growth through novel near-infrared light emitting diode (nNIR) lighting: in vitro and in vivo study.

The study aimed to explore the impact of a novel near-infrared LED (nNIR) with an extended spectrum on skin enhancement and hair growth. Various LED sources, including White and nNIRs, were compared across multiple parameters: cytotoxicity, adenosine triphosphate (ATP) synthesis, reactive oxygen species (ROS) reduction, skin thickness, collagen synthesis, collagenase expression, and hair follicle growth. Experiments were conducted on human skin cells and animal models. Cytotoxicity, ATP synthesis, and ROS reduction were evaluated in human skin cells exposed to nNIRs and Whites. LED irradiation effects were also studied on a UV-induced photoaging mouse model, analyzing skin thickness, collagen synthesis, and collagenase expression. Hair growth promotion was examined as well. Results revealed both White and nNIR were non-cytotoxic to human skin cells. nNIR enhanced ATP and collagen synthesis while reducing ROS levels, outperforming the commonly used 2chip LEDs. In the UV-induced photoaging mouse model, nNIR irradiation led to reduced skin thickness, increased collagen synthesis, and lowered collagenase expression. Additionally, nNIR irradiation stimulated hair growth, augmented skin thickness, and increased hair follicle count. In conclusion, the study highlighted positive effects of White and nNIR irradiation on skin and hair growth. However, nNIR exhibited superior outcomes compared to White. Its advancements in ATP content, collagen synthesis, collagenase inhibition, and hair growth promotion imply increased ATP synthesis activity. These findings underscore nNIR therapy's potential as an innovative and effective approach for enhancing skin and promoting hair growth.

Improvement of NASH and liver fibrosis through modulation of the gut-liver axis by a novel intestinal FXR agonist.

Farnesoid X receptor (FXR) plays a pivotal role in the regulation of bile acid homeostasis and is involved in the pathogenesis of nonalcoholic steatohepatitis (NASH). Although FXR agonists effectively alleviate pathological features of NASH, adverse effects such as disturbance of cholesterol homeostasis and occurrence of pruritus remain to be addressed. Here, we identified a novel FXR agonist, ID119031166 (ID166), and explored the pharmacological benefits of ID166 in the treatment of NASH. ID166, a potent and selective non-bile acid FXR agonist, exhibits preferential distribution in the intestine and shows no agonist activity against potential itch receptors including Mas-related G protein-coupled receptor X4 (MRGPRX4). Interestingly, ID166 significantly attenuated total nonalcoholic fatty liver disease (NAFLD) activity and liver fibrosis in a free choice diet-induced NASH hamster model. In addition, ID166 drastically modulated the relative abundance of five gut microbes and reduced the increase in plasma total bile acid levels to normal levels in NASH hamsters. Moreover, long-term treatment with ID166 significantly improved key histological features of NASH and liver fibrosis in a diet-induced NASH mouse model. In the NASH mouse livers, RNA-seq analysis revealed that ID166 reduced the gene expression changes associated with both NASH and liver fibrosis. Notably, ID166 exhibited no substantial effects on scratching behavior and serum IL-31 levels in mice. Our findings suggest that ID166, a novel FXR agonist with improved pharmacological properties, provides a preclinical basis to optimize clinical benefits for NASH drug development.

Ultrathin organosiloxane membrane for precision organic solvent nanofiltration.

Promising advances in membrane technology can lead to energy-saving and eco-friendly solutions in industrial sectors. This work demonstrates a highly selective membrane with ultrathin and highly interconnected organosiloxane polymer nanolayers by initiated chemical vapor deposition to effectively separate solutes within the molecular weight range of 150-300 g mol-1. We optimize the poly(1,3,5,7-tetravinyl-1,3,5,7-tetramethylcyclotetrasiloxane) membrane by adjusting both the thickness of the selective layer and the pore sizes of its support membranes. Notably, the 29 nm selective layer imparts a uniformly narrow molecular sieving property, providing a record-high solute-solute selectivity of 39.88 for different-sized solutes. Furthermore, a solute-solute selectivity of 11.04 was demonstrated using the real-world active pharmaceutical ingredient mixture of Acyclovir and Valacyclovir, key components for Herpes virus treatment, despite their molecular weight difference of less than 100 g mol-1. The highly interconnected membrane is expected to meet rigorous requirements for high-standard active pharmaceutical ingredient separation.

Investigating the Anti-Aging Effects of Caviar Oil on Human Skin.

BACKGROUND/AIM: As the largest organ of the human body, the skin serves as a critical barrier against environmental damage. However, many factors, such as genetics, sun exposure, and lifestyle choices can lead to skin damage creating wrinkles, sagging, and loss of elasticity. The use of skincare products containing natural ingredients has become increasingly popular as a way to combat the signs of aging. Caviar oil is one such ingredient that has gained attention due to its rich composition of fatty acids, vitamins, and minerals. The objective of this study was to investigate the potential anti-aging effects of caviar oil and to develop a product, Cavi Balm, which could potentially reduce wrinkles and skin sagging. MATERIALS AND METHODS: An in vitro model using the 3T3-L1 cell line was employed to assess the effect of caviar oil on adipocyte differentiation. An ex vivo study using human skin tissue was conducted to investigate the impact of caviar oil on collagen and elastin formation and the expression of matrix metalloproteinase-1,2,9 (MMP-1, MMP-2, MMP-9). Furthermore, 102 participants were enrolled in five clinical studies to evaluate the anti-aging efficacy of our product, "Cavi Balm", in facial and neck wrinkles, facial and eye area lifting, and various skin parameters, such as skin moisture, skin elasticity, skin density, skin tightening relief, skin clarity, and skin turnover. RESULTS: In vitro, caviar oil enhanced adipocyte differentiation, and increased lipid accumulation inside the cells. The ex vivo analysis revealed that caviar oil reduced the expression levels of MMP-1, MMP-2, and MMP-9, and increased the formation of elastin and collagen I, III. Moreover, in the clinical study, Cavi Balm improved skin parameters after one-time use, with more significant effects observed after four weeks of usage. CONCLUSION: Caviar oil has a substantial impact on mitigating skin aging and holds potential for application in anti-aging products.

Added Value of Structured Reporting for US of the Pediatric Appendix: Additional CT Examinations and Negative Appendectomy.

Purpose: This study aimed to determine the incremental value of using a structured report (SR) for US examinations of the pediatric appendix. Materials and Methods: Between January 2009 and June 2016, 1150 pediatric patients with suspected appendicitis who underwent US examinations of the appendix were included retrospectively. In November 2012, we developed a five-point scale SR for appendix US examinations. The patients were divided into two groups according to the form of the US report: free-text or SR. The primary clinical outcomes were compared between the two groups, including the rate of CT imaging following US examinations, the negative appendectomy rate (NAR), and the appendiceal perforation rate (PR). Results: In total, 550 patients were included in the free-text group and 600 patients in the SR group. The rate of additional CT examinations decreased by 5.3% in the SR group (8.2%, p = 0.003), and the NAR decreased by 8.4% in the SR group (7.8%, p = 0.028). There was no statistical difference in the appendiceal PR (37.6% vs. 48.0%, p = 0.078). Conclusion: The use of an SR to evaluate US examinations for suspected pediatric appendicitis results in lower CT use and fewer negative appendectomies without an increase in appendiceal PR.

Imaging Features and Pathological Correlation in Mixed Microcystic and Angiomatous Meningioma: A Case Report.

Meningiomas are the most common intracranial tumors. However, microcystic and angiomatous meningiomas are very rare subtypes that present unusual imaging findings. Hence, radiological diagnosis of these tumors can be challenging. We herein describe a case of mixed angiomatous and microcystic meningioma in an 81-year-old male. MRI revealed an extra-axial mass with high T2 signal intensity, measuring 1.5 cm in diameter, with multiple tiny intralesional cysts and entrapped peritumoral cyst formation. After tumor resection, a histopathological diagnosis of mixed angiomatous and microcystic meningioma was made.

The stem cell quiescence and niche signaling is disturbed in the hair follicle of the hairpoor mouse, an MUHH model mouse.

BACKGROUND: Hair follicle stem cells (HFSC) play an essential role in the maintenance of hair homeostasis; during the hair cycle, HFSC remain quiescent for most of its duration. The hairpoor mouse (+ /HrHp), an animal model of Marie-Unna hypotrichosis (MUHH), overexpresses hairless in the bulge, inner root sheath, and outer root sheath of HF and shows the same phenotype as in MUHH patients manifesting sparse hair with progression to alopecia with age. The aim of this study was to gain an understanding of the hair cycle and the status of HFSC during the hair cycle of the hairpoor mouse in order to delineate the pathogenesis of MUHH. METHODS: H&E staining was performed in order to define the state of the hair follicle. FACS analysis and immunostaining were performed at the 1st and 2nd telogen stages for observation of the HFSC. A label retaining assay was performed to determine the quiescent state of hair follicles. qRT-PCR was performed to determine expression of factors involved in niche signaling and Wnt signaling. RESULTS: We observed a drastic decrease in the number of hair follicles after the 1st telogen, followed by an intensified disturbance in the hair cycle with shorter anagen as well as 2nd telogen in the hairpoor mouse. A dramatic reduction in the number of CD34 expressing bulges as well as cells was observed at the telogen of the HFs, with prominent high proliferation of bulge cells, suggesting the loss of HFSC quiescence in the hairpoor mouse. The increased cell proliferation in HF was reiterated following the synchronization of the hair cycle, leading to acceleration of HF cycling. Reduced expression of Fgf18 and Bmp6, the factors involved in HFSC quiescence, was observed in the HFSC niche of the hairpoor mouse. In addition, disturbed expression of Wnt signaling molecules including Wnt7b, Wnt10b, and Sfrp1 was observed, which induced the telogen-to-anagen transition of HFs in the hairpoor mouse. CONCLUSIONS: These results indicate that the quiescent state of HFSC is not properly maintained in the hairpoor mouse, consequently leading HFs to the completely disarrayed hair cycle. These findings may provide an understanding of an underlying mechanism for development of alopecia with age in MUHH patients.

Identification of Survival-Specific Genes in Clear Cell Renal Cell Carcinoma Using a Customized Next-Generation Sequencing Gene Panel.

PURPOSE: Although mutations are associated with carcinogenesis, little is known about survival-specific genes in clear cell renal cell carcinoma (ccRCC). We developed a customized next-generation sequencing (NGS) gene panel with 156 genes. The purpose of this study was to investigate whether the survival-specific genes we found were present in Korean ccRCC patients, and their association with clinicopathological findings. MATERIALS AND METHODS: DNA was extracted from the formalin-fixed, paraffin-embedded tissue of 22 ccRCC patients. NGS was performed using our survival-specific gene panel with an Illumina MiSeq. We analyzed NGS data and the correlations between mutations and clinicopathological findings and also compared them with data from the Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) and Renal Cell Cancer-European Union (RECA-EU). RESULTS: We found a total of 100 mutations in 37 of the 156 genes (23.7%) in 22 ccRCC patients. Of the 37 mutated genes, 11 were identified as clinicopathologically significant. Six were novel survival-specific genes (ADAMTS10, CARD6, NLRP2, OBSCN, SECISBP2L, and USP40), and five were top-ranked mutated genes (AKAP9, ARID1A, BAP1, KDM5C, and SETD2). Only CARD6 was validated as an overall survival-specific gene in this Korean study (p = 0.04, r = -0.441), TCGA-KIRC cohort (p = 0.0003), RECA-EU (p = 0.0005). The 10 remaining gene mutations were associated with clinicopathological findings; disease-free survival, mortality, nuclear grade, sarcomatoid component, N-stage, sex, and tumor size. CONCLUSIONS: We discovered 11 survival-specific genes in ccRCC using data from TCGA-KIRC, RECA-EU, and Korean patients. We are the first to find a correlation between CARD6 and overall survival in ccRCC. The 11 genes, including CARD6, NLRP2, OBSCN, and USP40, could be useful diagnostic, prognostic, and therapeutic markers in ccRCC.

Transparent, Ultrahigh-Refractive Index Polymer Film (n ∼1.97) with Minimal Birefringence (Δn <0.0010).

High refractive index (RI) thin films are of critical importance for advanced optical devices, and the high refractive index polymers (HRIPs) constitute an interesting class of materials for high RI thin films due to low cost, good processability, light weight, and high flexibility. However, HRIPs have yet to realize their full potential in high RI thin film applications due to their relatively low RI, strong absorption in the blue light region, and limited film formation methods such as rapid vitrification. Herein, we report a development of a new HRIP thin film generated through a one-step vapor-phase process, termed sulfur chemical vapor deposition (sCVD), using elemental sulfur and divinyl benzene. The developed poly(sulfur-co-divinyl benzene) (pSDVB-sCVD) film exhibited RI (measured at 632.8 nm) exceeding 1.97, one of the highest RIs among polymers without metallic elements reported to date. Because the sCVD utilized vaporized sulfur with a unique sulfur-cracking step, formation of long polysulfide chains was suppressed efficiently, while high sulfur content as high as 85 wt % could be achieved with no apparent phase separation. Unlike most of inorganic high RI materials, pSDVB-sCVD was highly transparent in the entire visible range and showed extremely low birefringence of 10 × 10-4. The HRIP thin film with unprecedentedly high RI, together with outstanding transparency and low birefringence, will serve as a key component in a wide range of high-end optical device applications.

One-step vapor-phase synthesis of transparent high refractive index sulfur-containing polymers.

High refractive index polymers (HRIPs) have recently emerged as an important class of materials for use in a variety of optoelectronic devices including image sensors, lithography, and light-emitting diodes. However, achieving polymers having refractive index exceeding 1.8 while maintaining full transparency in the visible range still remains formidably challenging. Here, we present a unique one-step vapor-phase process, termed sulfur chemical vapor deposition, to generate highly stable, ultrahigh refractive index (n > 1.9) polymers directly from elemental sulfur. The deposition process involved vapor-phase radical polymerization between elemental sulfur and vinyl monomers to provide polymer films with controlled thickness and sulfur content, along with the refractive index as high as 1.91. Notably, the HRIP thin film showed unprecedented optical transparency throughout the visible range, attributed to the absence of long polysulfide segments within the polymer, which will serve as a key component in a wide range of optical devices.

Air Pollution and Atopic Dermatitis (AD): The Impact of Particulate Matter (PM10) on an AD Mouse-Model.

Air pollution reportedly contributes to the development and exacerbation of atopic dermatitis (AD). However, the exact mechanism underlying this remains unclear. To examine the relationship between air pollution and AD, a clinical, histological, and genetic analysis was performed on particulate matter (PM)-exposed mice. Five-week-old BALB/c mice were randomly divided into four groups (control group, ovalbumin (OVA) group, PM group, OVA + PM group; n = 6) and treated with OVA or PM10, alone or together. Cutaneous exposure to OVA and PM10 alone resulted in a significant increase in skin severity scores, trans-epidermal water loss (TEWL) and epidermal thickness compared to the control group at Week 6. The findings were further accentuated in the OVA + PM group showing statistical significance over the OVA group. A total of 635, 501, and 2149 genes were found to be differentially expressed following OVA, PM10, and OVA + PM10 exposure, respectively. Strongly upregulated genes included RNASE2A, S100A9, SPRR2D, THRSP, SPRR2A1 (OVA vs. control), SPRR2D, S100A9, STFA3, CHIL1, DBP, IL1B (PM vs. control) and S100A9, SPRR2D, SPRR2B, S100A8, SPRR2A3 (OVA + PM vs. control). In comparing the groups OVA + PM with OVA, 818 genes were differentially expressed with S100A9, SPRR2B, SAA3, S100A8, SPRR2D being the most highly upregulated in the OVA + PM group. Taken together, our study demonstrates that PM10 exposure induces/aggravates skin inflammation via the differential expression of genes controlling skin barrier integrity and immune response. We provide evidence on the importance of public awareness in PM-associated skin inflammation. Vigilant attention should be paid to all individuals, especially to those with AD.

TOMM20 as a potential therapeutic target of colorectal cancer.

Translocase of outer mitochondrial membrane 20 (TOMM20) plays an essential role as a receptor for proteins targeted to mitochondria. TOMM20 was shown to be overexpressed in various cancers. However, the oncological function and therapeutic potential for TOMM20 in cancer remains largely unexplored. The purpose of this study was to elucidate the underlying molecular mechanism of TOMM20's contribution to tumorigenesis and to explore the possibility of its therapeutic potential using colorectal cancer as a model. The results show that TOMM20 overexpression resulted in an increase in cell proliferation, migration, and invasion of colorectal cancer (CRC) cells, while siRNA-mediated inhibition of TOMM20 resulted in significant decreases in cell proliferation, migration, and invasion. TOMM20 expression directly impacted the mitochondrial function including ATP production and maintenance of membrane potential, which contributed to tumorigenic cellular activities including regulation of S phase cell cycle and apoptosis. TOMM20 was overexpressed in CRC compared to the normal tissues and increased expression of TOMM20 to be associated with malignant characteristics including a higher number of lymph nodes and perineural invasion in CRC. Notably, knockdown of TOMM20 in the xenograft mouse model resulted in a significant reduction of tumor growth. This is the first report demonstrating a relationship between TOMM20 and tumorigenesis in colorectal cancer and providing promising evidence for the potential for TOMM20 to serve as a new therapeutic target of colorectal cancer. [BMB Reports 2019; 52(12): 712-717].

Poly(rC) binding protein 2 acts as a negative regulator of IRES-mediated translation of Hr mRNA.

During the hair follicle (HF) cycle, HR protein expression is not concordant with the presence of the Hr mRNA transcript, suggesting an elaborate regulation of Hr gene expression. Here we present evidence that the 5' untranslated region (UTR) of the Hr gene has internal ribosome entry site (IRES) activity and this activity is regulated by the binding of poly (rC) binding protein 2 (PCBP2) to Hr mRNA. Overexpression and knockdown of PCBP2 resulted in a decrease in Hr 5' UTR IRES activity and an increase in HR protein expression without changing mRNA levels. We also found that this regulation was disrupted in a mutant Hr 5' UTR that has a mutation responsible for Marie Unna hereditary hypotrichosis (MUHH) in both mice and humans. These findings suggest that Hr mRNA expression is regulated at the post-transcriptional level via IRES-mediated translation control through interaction with PCPB2, but not in MUHH.

Decreased expression of VLDLR is inversely correlated with miR-200c in human colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers and has a high rate of morbidity and mortality worldwide. Very-low-density-lipoprotein receptor (VLDLR), a member of the low-density-lipoprotein receptor (LDLR) superfamily, is a multifunctional receptor that regulates cellular signaling by binding numerous ligands. Several studies reported the altered expression of VLDLR and suggested that VLDLR may play a critical role in tumor development by affecting cell proliferation and metastasis. However, the function of VLDLR and regulation of its expression by miRNAs have not been investigated in CRC. In the present study, we investigated the expression of VLDLR in CRC patients and found it to be significantly decreased in tumors in comparison with paired adjacent non-tumor tissues. Moreover, VLDLR over-expression inhibited the proliferation and migration of CRC cells. We also found that VLDLR expression was negatively regulated by miR-200c in CRC cells and that their expression levels were inversely correlated in CRC patients. These data suggest that VLDLR down-regulation mediated by the increased expression of miR-200c may be involved in the development of CRC.

Regulation of Srpr Expression by miR-330-5p Controls Proliferation of Mouse Epidermal Keratinocyte.

Srpr is a gene encoding α subunit of the signal recognition particle receptor which is involved in the targeting and translocation of nascent secretory and membrane proteins to the endoplasmic reticulum. Previous studies showed aberrant expression of Srpr in several cell types with abnormal growth rate. Although Srpr is expressed in various tissues including skin, the role of Srpr in keratinocytes and regulation of its expression by miRNAs have not been studied. In this study, we investigated the role of SRPR and regulation of its expression by miRNA in skin keratinocytes. We found that SRPR was highly expressed in epidermal keratinocytes and regulated keratinocyte proliferation by affecting cell cycle progression. We also demonstrated that miR-330-5p directly inhibits Srpr expression. These data suggest that miR-330-5p-mediated regulation of the SRPR level is needed for the regulation of proliferation of epidermal keratinocytes.

miR-330-5p inhibits proliferation and migration of keratinocytes by targeting Pdia3 expression.

The microRNAs (miRNAs) are a class of small non-coding RNA molecules that play important roles in cellular processes by regulating gene expression at the post-transcriptional level. In skin biology, several miRNAs have been shown to be associated with differentiation, migration and apoptosis of keratinocytes, and regulation of the hair cycle. Although the biological role of miR-330-5p has been reported in several cancers and cells, the function and molecular mechanism of miR-330-5p in skin keratinocytes have not been identified. In this study, we found that miR-330-5p inhibited the proliferation and migration of mouse keratinocytes. Among the candidate target genes of miR-330-5p searched using microarray analysis, we found that the expression of Pdia3 was directly regulated by miR-330-5p in the mouse keratinocyte. Moreover, inhibition of Pdia3 expression caused decreased proliferation and migration ability of mouse keratinocytes. Additionally, expressions of miR-330-5p and Pdia3 displayed an inverse correlation with respect to the hair cycle stage. These results indicated that regulation of Pdia3 expression by miR-330-5p is important in maintaining the hair cycle through regulation of the proliferation and migration capability of keratinocytes.

Identification of a novel U2HR mutation in a Korean woman with Marie Unna hereditary hypotrichosis.

Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant genodermatosis characterized by progressive non-scarring hair loss. Mutation of the U2HR gene, located in chromosome 8p21, is generally responsible for MUHH development. Until now, 17 mutations of U2HR have been identified from various ethnic backgrounds, but U2HR mutations have been identified mostly in Chinese families and only one Japanese patient with MUHH among Asian populations. Here, we report the first Korean case of MUHH with a novel heterozygous missense mutation (c.80C>T) in U2HR that has not been documented to date. Genetic analysis further revealed that this mutation is responsible for the hair morphology phenotype presented in this case. This finding contributes to expansion of the mutant spectrum of U2HR, supporting the possibility of racial differences in terms of genetic mutations of MUHH.

Increased expression of Dkk1 by HR is associated with alteration of hair cycle in hairpoor mice.

BACKGROUND: Hairless (Hr), a transcriptional corepressor expressed mainly in the skin, regulates hair follicle (HF) morphogenesis and hair cycling. Recently, we reported a new Hr mutant mouse, "Hairpoor" (Hr(Hp)), that resembles the human hair disorder Marie Unna hereditary hypotrichosis (MUHH) in the heterozygous state. The Wnt/ß-catenin signaling pathway is critical for homeostasis in various adult tissues including skin and HFs. One of the Wnt inhibitors, Dickkopf (Dkk), inhibits hair growth during the hair cycle as a catagen inducer of apoptosis, resulting in HF reductions. OBJECTIVE: To investigate regulation of Dkk1 by HR and its effect on hair formation. METHODS: The relative expression of Dkk1 in (+)/Hr(HP) and Hr(Hp)/Hr(Hp) mice during the hair cycle was investigated using real time PCR and Western blot analysis. Immunohistochemistry was performed in order to confirm abnormal expression of Dkk1 in HFs of (+)/Hr(HP) and Hr(Hp)/Hr(Hp) mice. To determine whether Dkk1 expression was also regulated by HR in vitro, an Hr-transient transfection experiment was performed. Alteration of the hair cycle in Hr(HP) heterozygous mice was identified by determination of the hair cycle and measurement of HF length. RESULTS: Dkk1 expression was increased in the skin of (+)/Hr(HP) and Hr(Hp)/Hr(Hp) mice, as well as in Hr-overexpressing mouse keratinocytes. Additionally, an earlier entrance of HFs into catagen and shortened HF length in (+)/Hr(HP) mice compared to wild-type mice was observed. CONCLUSION: Study results suggested that up-regulation of Dkk1 by HR contributed to abnormal development of HFs and failure in regeneration of HFs in Hr(Hp)/Hr(Hp) mice. These findings also indicated that alteration of the hair cycle in (+)/Hr(HP) mice was related to the up-regulation of Dkk1 by HR.