Hepatocyte Growth Factor has Unique Functions in Keratinocytes that differs from IL-17A and TNF and may contribute to Inflammatory Pathways in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that is difficult to control, and its mechanism remains unclear. Hepatocyte growth factor (HGF) has been reported to be significantly upregulated in the serum and skin of HS patients, especially in the lesions with tunnels. In this study, we examined the transcriptome of HGF-treated keratinocytes (KCs) and compared it with genetic profiling of HS lesions. HGF was highly expressed in HS skin, especially in the deep dermis, compared to healthy controls, and its source was mainly fibroblasts. HGF upregulated more genes in KCs than interleukin-17A or tumor necrosis factor-α, and these genes included multiple epithelial-mesenchymal transition (EMT)-related genes. Differentially expressed genes in HGF-stimulated KCs were involved in activation of EMT-related pathways. These HGF-induced genes were significantly upregulated in HS lesions compared to healthy skin and non-lesions and were more strongly associated with HS tunnels. In summary, HGF was highly expressed in HS and induced EMT-related genes in KCs; HGF-induced genes were highly associated with gene profiling of HS with tunnels, suggesting that HGF may be involved in HS tunnel formation via EMT.

Evaluation of the anti-aging effects of Zinc-α2-glycoprotein peptide in clinical and in vitro study.

BACKGROUND: Skin aging, characterized by the deterioration of skin density and elasticity, is a common concern among individuals seeking to maintain a youthful appearance. Zinc-α2-glycoprotein (ZAG) is secreted by various body fluids, and is associated with lipolysis and identified as an atopic dermatitis biomarker. This study evaluated the potential of ZAG peptides, which exert multiple benefits such as anti-aging. MATERIALS AND METHODS: We conducted a 4-week clinical trial on patients with noticeable periorbital wrinkles (n = 22) using a ZAG peptide-containing product. The effects of the products on skin density, elasticity, and the depth of periorbital wrinkles were evaluated using Cutometer Dual MPA580, Ultrascan, and Antera 3D CS, respectively. The effect of ZAG peptides on UVB-treated keratinocyte cells was evaluated in vitro to understand the mechanisms underlying its effects against impaired skin barrier function, collagen degradation, and senescence. In addition, the effects of ZAG peptides on cell viability and expression of aging and skin barrier-related genes were assessed using cell counting kit assay and quantitative reverse transcription-polymerase chain reaction, respectively. RESULTS: The patients demonstrated improved skin density, elasticity, and reduced periorbital wrinkles. Further, more than 85% patients scored the product as satisfactory regarding anti-aging effects. Furthermore, ZAG peptides reduced SA-ß-gal staining, downregulated the senescence-related genes, and upregulated the skin barrier function-related genes in UVB-irradiated keratinocyte cells. CONCLUSIONS: Our clinical and in vitro findings showed that ZAG peptides exert anti-aging effects and improve skin barrier functions, suggesting their promising potential as therapeutic agents to combat skin aging and improve skin health.

Exploring the Safety and Efficacy of Organic Light-Emitting Diode in Skin Rejuvenation and Wound Healing.

PURPOSE: Photobiomodulation (PBM), encompassing low-energy laser treatment and light-emitting diode (LED) phototherapy, has demonstrated positive impacts on skin rejuvenation and wound healing. Organic light-emitting diodes (OLEDs) present a promising advancement as wearable light sources for PBM. However, the biological and biochemical substantiation of their skin rejuvenation and wound healing effects remains limited. This study aimed to ascertain the safety and efficacy of OLEDs as a next-generation PBM modality through comprehensive in vitro and in vivo investigations. MATERIALS AND METHODS: Cell viability assays and human ex vivo skin analyses were performed after exposure to OLED and LED irradiation to examine their safety. Subsequent evaluations examined expression levels and wound healing effects in human dermal fibroblasts (HDFs) using quantitative reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and wound healing assays post-irradiation. Additionally, an in vivo study was conducted using a ultra violet (UV)-irradiated animal skin model to explore the impact of OLED exposure on dermal collagen density and wrinkles, employing skin replica and tissue staining techniques. RESULTS: OLED irradiation had no significant morphological effects on human skin tissue, but caused a considerably higher expression of collagen than the control and LED-treated groups. Moreover, OLED irradiation reduced the expression levels of matrix metalloproteinases (MMPs) more effectively than did LED on HDFs. OLED irradiation group in HDFs had significantly higher expression levels of growth factors compared to the control group, but similar to those in the LED irradiation group. In addition, OLED irradiation on photo-aged animal skin model resulted in increased collagen fiber density in the dermis while reducing ultra violet radiation-mediated skin wrinkles and roughness, as shown in the skin replica. CONCLUSION: This study established comparable effectiveness between OLED and LED irradiation in upregulating collagen and growth factor expression levels while downregulating MMP levels in vitro. In the UV-irradiated animal skin model, OLED exposure post UV radiation correlated with reduced skin wrinkles and augmented dermal collagen density. Accelerated wound recovery and demonstrated safety further underscore OLEDs' potential as a future PBM modality alongside LEDs, offering promise in the realms of skin rejuvenation and wound healing.

Silibinin Downregulates Types I and III Collagen Expression via Suppression of the mTOR Signaling Pathway.

Keloid scars are fibro-proliferative conditions characterized by abnormal fibroblast proliferation and excessive extracellular matrix deposition. The mammalian target of the rapamycin (mTOR) pathway has emerged as a potential therapeutic target in keloid disease. Silibinin, a natural flavonoid isolated from the seeds and fruits of the milk thistle, is known to inhibit the mTOR signaling pathway in human cervical and hepatoma cancer cells. However, the mechanisms underlying this inhibitory effect are not fully understood. This in vitro study investigated the effects of silibinin on collagen expression in normal human dermal and keloid-derived fibroblasts. We evaluated the effects of silibinin on the expressions of collagen types I and III and assessed its effects on the suppression of the mTOR signaling pathway. Our findings confirmed elevated mTOR phosphorylation levels in keloid scars compared to normal tissue specimens. Silibinin treatment significantly reduced collagen I and III expressions in normal human dermal and keloid-derived fibroblasts. These effects were accompanied by the suppression of the mTOR signaling pathway. Our findings suggest the potential of silibinin as a promising therapeutic agent for preventing and treating keloid scars. Further studies are warranted to explore the clinical application of silibinin in scar management.

Efficacy and safety of persimmon leaf formulated with green tea and sophora fruit extracts (BLH308) on hair growth: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Recent research suggests that persimmon leaf extract (PLE) has an effect on inflammatory skin diseases. Previously, PLE is revealed to inhibit not only nitric oxide production but also inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels in mouse macrophages in vitro. Moreover, it significantly reduced IL-6 production and 5α-reductase expression in human follicle dermal papilla cells (HFDPCs). This study aimed to determine whether the PLE-containing BLH308 complex improves hair growth in clinical trials. MATERIALS AND METHODS: A total of 88 participants were recruited, and were instructed to orally take BLH308 or the placebo twice a day for 24 weeks. The mean age of the test group was 38.52 ± 7.98 years and that of placebo group was 38.98 ± 8.80 years. The study was conducted for 24 weeks, and hair density, thickness, and gloss were evaluated. All participants completed a satisfaction survey questionnaire. RESULTS: The test group showed significantly increased hair density and hair diameter at week 24 compared with the placebo group (p = 0.0015 and p = 0.0001, respectively). Although not statistically significant, the degree of gloss also showed higher improvement in the test group compared to the placebo group. CONCLUSIONS: Our data demonstrated that oral consumption of the BLH308 complex containing PLE significantly increased hair density and thickness compared to the placebo group, showing its possible role in promoting hair growth.

Cutaneous neurogenic inflammation mediated by TRPV1-NGF-TRKA pathway activation in rosacea is exacerbated by the presence of Demodex mites.

BACKGROUND: Rosacea is a common chronic inflammatory skin condition that is often refractory to treatment, with frequent relapses. Alterations in the skin immunological response and Demodex mite infestation are the primary aetiologic factors targeted for treatment. Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a nociceptive cation channel that plays a role in cutaneous neurogenic pain and can be activated by various rosacea triggers. OBJECTIVES: We investigated the effects of TRPV1 modulation in rosacea, focussing on Demodex mite colonization and cutaneous neurogenic inflammation. METHODS: We examined mRNA expression levels according to Demodex population counts. An in vitro study using capsazepine as a TRPV1 antagonist was performed to assess the influence of TRPV1 in keratinocytes. A rosacea-like mouse model was generated by the injection of the 37-amino acid C-terminal cathelicidin peptide (LL37), and changes in the skin, dorsal root ganglion (DRG) and ears were examined. RESULTS: Increased Demodex mite population counts were associated with increased expression levels of TRPV1, tropomyosin receptor kinase A (TrkA) and nerve growth factor (NGF), and these levels could be reduced by capsazepine treatment in keratinocytes. In an in vivo study, the downstream effects of TRPV1 activation were investigated in the skin, DRG and ears of the rosacea-like mouse model. CONCLUSIONS: The findings of this study are instrumental for understanding the underlying causes of rosacea and could potentially lead to the development of new treatments targeting the NGF-TrkA-TRPV1 pathway. The identification of this pathway as a therapeutic target could represent a major breakthrough for rosacea research, potentially resulting in more effective and targeted rosacea treatments. This study contributes to an improved understanding of rosacea pathophysiology, which may lead to the development of more effective treatments in the future.

Age-related changes in scalp biophysical parameters: A comparative analysis of the 20s and 50s age groups.

BACKGROUND: Age-related changes in scalp parameters affect hair quality and scalp condition. However, detailed data on biophysical parameters of the scalp across age groups remain scarce. We aimed to investigate the differences in scalp parameters between individuals in their 20s and 50s and analyze their sex-specific variations. MATERIALS AND METHODS: Two hundred participants (160 women and 40 men) were equally divided into 20s and 50s age groups. Biophysical parameters of the scalp, including elasticity, pH, trans-epidermal water loss (TEWL), sebum production, desquamation, firmness, redness, and yellowness, were measured in the vertex, occipital, and temporal regions. Hair density and thickness were measured in the temporal region. The accumulation of advanced glycation end products (AGEs) in the skin was noninvasively measured in a subset of 60 women. RESULTS: Skin firmness and redness increased with age in women, whereas yellowness increased with age in both sexes. Sebum production and pH levels were significantly lower in the 50s age group than in the 20s age group, particularly in women. TEWL was lower in men in their 50s than in those in their 20s, particularly in the occipital region. A significant reduction in hair density was observed in the 50s age group in both sexes. AGE accumulation in the skin increased with age and was correlated with scalp skin yellowness. CONCLUSION: Age-related changes in scalp parameters have important implications for hair health and scalp condition. These findings emphasize the importance of considering age and sex when developing hair care strategies.

An Exploratory In Vivo Study on the Effect of Annurca Apple Extract on Hair Growth in Mice.

Hair loss is an important problem affecting the quality of life in modern society. Recent studies show that Annurca apple extract (AAE), enriched in procyanidin B2 and nutraceuticals, promotes hair growth and induces keratin production. In this study, we investigated the effects of AAE by orally administering AAE in six-week-old C57BL/6 mice once a day for 21 d. We observed improvement in hair length, thickness, weight, and density. The gene expression of two growth factors related to hair growth, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 7 (FGF-7), were measured using the quantitative reverse transcription polymerase chain reaction (qRT-PCR). The gene expression of both VEGFA and FGF-7 increased significantly in the AAE-treated group. Additionally, treatment with AAE suppressed the gene expression of type 1 5α-reductase. Histological analysis showed that protein levels of cytokeratin 5 and 10 were increased in the skin tissues of the AAE-treated group. These results suggest that AAE might be a potential therapeutic natural product that prevents hair loss by promoting the expression of hair growth-related factors.

Effect of Baicalin on Wound Healing in a Mouse Model of Pressure Ulcers.

One of the most frequent comorbidities that develop in chronically ill or immobilized patients is pressure ulcers, also known as bed sores. Despite ischemia-reperfusion (I/R)-induced skin lesion having been identified as a primary cause of pressure ulcers, wound management efforts have so far failed to significantly improve outcomes. Baicalin, or 5,6,7-trihydroxyflavone, is a type of flavonoid which has been shown to possess a variety of biological characteristics, including antioxidative and anti-inflammatory effects and protection of I/R injury. In vitro wound scratch assay was first used to assess the function of baicalin in wound healing. We established a mouse model of advanced stage pressure ulcers with repeated cycles of I/R pressure load. In this model, topically applied baicalin (100 mg/mL) induced a significant increase in the wound healing process measured by wound area. Histological examination of the pressure ulcer mouse model showed faster granulation tissue formation and re-epithelization in the baicalin-treated group. Next, baicalin downregulated pro-inflammatory cytokines (IL-6 and IL-1ß), while upregulating the anti-inflammatory IL-10. Additionally, baicalin induced an increase in several growth factors (VEGF, FGF-2, PDGF-ß, and CTGF), promoting the wound healing process. Our results suggest that baicalin could serve as a promising agent for the treatment of pressures ulcers.