Nanoemulsion with wine lees: a green approach.

Bioactive substances can be found in wine lees, a waste from the winemaking industry. This work developed two formulations, a nanoemulsion with coconut oil (NE-OC) and a nanoemulsion with coconut oil and 0.5% of wine lees extract (NE-OC-Ext), to investigate their effect on untreated, bleached, and bleached-colored hair. The oil-in-water (O/W) nanoemulsions were prepared with coconut oil, TweenTM 80, SpanTM 80, AristoflexTM AVC, Conserve NovaMit MFTM, wine lees extract, and deionized water. The hydration measurements were carried out using a Corneometer® CM 825 with the capacitance method. Scanning electron microscopy (SEM) was used to characterize the effect of formulations on hair fibers. Differential Thermal Analysis (DTA) was to assess the thermal stability and compatibility of wine lees and coconut oil in formulations. Compared to NE-OC, NE-OC-Ext showed a greater hydration effect on bleached-colored hair. DTA showed that NE-OC-Ext presented a smaller number of exothermic degradation events than those of NE-OC, suggesting good interaction and compatibility of the wine lees extract in this formulation. This study highlights the value of wine lees, a residue from the winemaking process, and its possibility of use as raw material for the cosmetic hair industry since it shows a greater moisturizing potential in colored hair.

Promotion of hair growth by a conditioned medium from human umbilical cord mesenchymal stem cells cultivated in a 3D scaffold of gelatin sponge.

BACKGROUND: This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model. METHODS: CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter. RESULTS: Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth. CONCLUSION: GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.

Transient stimulation of TRPMLs enhance the functionality of hDPCs and facilitate hair growth in mice.

Autophagy is essential for eliminating aging and organelle damage that maintaining cellular homeostasis. However, the dysfunction of autophagy has been proven in hair loss such as AGA. Despite the crucial role of TRPML channels in regulating autophagy, their specific function in hair growth remains unclarified. To investigate the biological functions and associated molecular mechanisms of TRPMLs in hair growth, Animal experiments were conducted to confirm the function of TRLMLs activation in promoting hair growth. Subsequently, we analyzed molecular mechanisms in human dermal papilla cells (hDPCs) activated by TRPMLs through transcriptome sequencing analysis. MLSA1(a TRPML agonist) promoted hair regeneration and accelerated hair cycle transition in mice. The activation of TRPMLs upregulated calcium signaling inducing hDPCs to secrete hair growth promoting factors and decrease hair growth inhibiting factors. In addition, activation of TRPMLs triggered autophagy and reduced the generation of ROS, thereby delaying the senescence of hDPCs. All these findings suggested that TRPMLs activation could promote hair growth by regulating hDPCs secretion of hair growth-related factors. Moreover, it may play a prominent role in preventing hDPCs from ROS damage induced by H2O2 or DHT. Targeting TRPMLs may represent a promising therapeutic strategy for treating hair loss.

Pilose antler extract promotes hair growth in androgenic alopecia mice by promoting the initial anagen phase.

Androgenetic alopecia (AGA) is a prevalent disease in worldwide, local application or oral are often used to treat AGA, however, effective treatments for AGA are currently limited. In this work, we observed the promoting the initial anagen phase effect of pilose antler extract (PAE) on hair regeneration in AGA mice. We found that PAE accelerated hair growth and increased the degree of skin blackness by non-invasive in vivo methods including camera, optical coherence tomography and dermoscopy. Meanwhile, HE staining of sagittal and coronal skin sections revealed that PAE augmented the quantity and length of hair follicles, while also enhancing skin thickness and hair papilla diameter. Furthermore, PAE facilitated the shift of the growth cycle from the telogen to the anagen phase and expedited the proliferation of hair follicle stem cells and matrix cells in mice with AGA. This acceleration enabled the hair follicles to enter the growth phase at an earlier stage. PAE upregulated the expression of the sonic hedgehog (SHH), smoothened receptor, glioma-associated hemolog1 (GLI1), and downregulated the expression of bone morphogenetic protein 4 (BMP4), recombinant mothers against decapentaplegic homolog (Smad) 1 and 5 phosphorylation. This evidence suggests that PAE fosters hair growth and facilitates the transition of the growth cycle from the telogen to the anagen phase in AGA mice. This effect is achieved by enhancing the proliferation of follicle stem cells and matrix cells through the activation of the SHH/GLI pathway and suppression of the BMP/Smad pathway.

Ellagic acid inhibits dihydrotestosterone-induced ferroptosis and promotes hair regeneration by activating the wnt/ß-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Androgenic alopecia (AGA) is the most prevalent form of hair loss in clinical practice and affects the physical and psychological well-being of adolescents. Paeonia lactiflora Pallas (PL), which is widely used in traditional Chinese medicine, enhances blood function and promotes hair growth, and ellagic acid (EA), a polyphenol in PL extract, shows strong antioxidant, anti-aging, and anti-inflammatory properties and also plays a role in the treatment of various skin conditions. However, its role and mechanism of action in AGA remain unclear. AIM OF THE STUDY: To determine whether EA can rescue slow hair regeneration by regulating dihydrotestosterone (DHT)-induced ferroptosis in AGA mice and clarify the effect of EA on DHT-induced ferroptosis in dermal papilla cells (DPCs). MATERIALS AND METHODS: Male C57BL/6 mice were used to establish a DHT-induced AGA mouse model, whereas DPCs were used to establish a DHT-induced cellular model. Thereafter, we investigated the therapeutic mechanism of action of EA via immunofluorescence, western blot analysis, immunohistochemistry, electron microscopy, and molecular docking. RESULTS: EA stimulated hair regeneration in mice and reversed DHT-induced increases in iron content, lipid peroxidation, and DHT-induced mitochondrial dysfunction by activating the Wnt/ß-catenin signaling pathway. Further, ß-catenin knockdown suppressed the inhibitory effect of EA on DHT-induced ferroptosis in DPCs. CONCLUSION: EA inhibits DHT-induced ferroptosis and promotes hair regrowth in mice by activating the Wnt/ß-catenin signaling pathway. Thus, it has potential for use as a treatment option for AGA.

The role of fractional laser-assisted drug delivery in enhancing the efficacy of topical bimatoprost solution in the treatment of alopecia areata: An intra-patient comparative randomized clinical trial.

BACKGROUND: Transepidermal drug delivery is a novel therapeutic technique to boost efficacy of topical drugs. AIM: In this clinical trial we evaluate the efficacy of the combination of fractional carbon dioxide (FCO2) laser and bimatoprost solution compared to bimatoprost alone in the treatment of alopecia areata. METHODS: This is a prospective intra-patient comparative randomized clinical trial on 20 patients with alopecia areata. In each participant two patches were chosen to randomly receive either topical 0.03% bimatoprost solution (twice a day for 12 weeks) alone or in combination with FCO2 laser (every 2 weeks for 12 weeks). Then response to treatment was evaluated by the measurement of the severity of alopecia tool score system (SALT) score, percentage of hair regrowth, physician assessment and patients' satisfaction. RESULTS: SALT score was reduced significantly during treatment sessions and after a 3-month follow-up in both treatment groups (p = 0.000). The mean percentage of improvement in SALT score in the combination therapy and monotherapy groups were 46.43 ± 4.35% and 21.16 ± 4.06% at the end of the study and 46.42 ± 5.75% and16.11 ± 3.10% at the end of the follow-up period, respectively (p = 0.000). A general linear model of two-way analysis demonstrated a significantly superior outcome in the combination therapy group compared to the monotherapy group during time (F1.6, 13.2 = 43.8. p = 0.000). CONCLUSION: Fractional ablative laser can be considered as an assistant method for enhancing of efficacy of topical drugs especially in refractory cases of patchy alopecia areata.

Investigator-blinded, controlled, and randomized comparative study on 1565 nm non-ablative fractional laser versus 5% minoxidil for treatment of androgenetic alopecia.

BACKGROUND: Characterized by progressive hair loss due to an excessive response to androgens, androgenetic alopecia (AGA) affects up to 50% of males and females. Minoxidil is one of approved medications for AGA but inadequate responses occur in many patients. AIMS: To determine whether 1565 nm non-ablative fractional laser (NAFL) could yield better therapeutic benefits for patients with AGA as compared with 5% minoxidil. METHODS: Thirty patients with AGA were enrolled; they were randomly assigned into the laser or minoxidil treatment groups. For the laser treatment group, patients were treated by 1565 nm NAFL at 10 mJ, 250 spots/cm2 with 2 weeks intervals for 4 sessions in total. For the minoxidil treatment group, 1-milliliter of topical 5% minoxidil solution was applied to hair loss area twice a day. RESULTS: The primary outcomes were the changes in numerous hair growth indexes at the Week 10 as compared with the baselines. Both 1565 nm NAFL and 5% minoxidil led to significantly greater hair densities and diameters in patients at the Week 10 than the baselines (p < 0.01). As compared with 5% minoxidil, 1565 nm NAFL showed significantly greater improvements in total hair number, total hair density (hair/cm2), terminal hair number, terminal hair density (hair/cm2), number of hair follicle units, and average hair number/number of hair follicle units. CONCLUSIONS: Our data demonstrate that 1565 nm NAFL exhibits superior clinical efficacy in some aspects of hair growth to the topical minoxidil. It is a safe and effective modality in treating AGA.

Preparation and in vitro evaluation of protective effects of Silibinin-loaded polymeric micelles on human hair against UV-B radiation.

BACKGROUND: The purpose of this study was to investigate the protective effect of Silibinin-loaded polymeric micelles from human hair against UV-B radiation. METHODS: Eight formulations with different concentrations of Silibinin, Pluronic F-127, and Labrasol-Labrafil were made by a solvent evaporation method, and the selected formulation was chosen by examining their properties like particle size and loading efficiency. Six groups of human hair, including a group that received the selected formulation, were exposed to UV-B radiation and by calculating its factors such as peak-to-valley roughness, RMS roughness, FTIR, and the amount of protein loss, the protective effect of the selected formulation was judged. RESULTS: According to the results, the loading efficiency and particle size of the selected formulation were 45.34% and 43.19 nm. The Silibinin release profile had two parts, fast and slow, which were suitable for creating a drug depot on hair. Its zeta potential also confirmed the minimum electrostatic interference between the formulation and hair surface. The zeta potential of selected formulation was -5.9 mv. Examination of AFM images showed that the selected formulation was able to prevent the increase in peak-to-valley roughness and RMS roughness caused by UV-B radiation. RMS roughness after 600 h of UV radiation in Groups 5 and 6 was significantly lower than the negative control group and the amount of this factor did not differ significantly between 0 and 600, so it can be concluded that the selected formulation containing Silibinin and the positive control group was able to prevent the increase of RMS roughness and hair destruction. In other hands, the two positive control groups and the selected formulation containing Silibinin were able to effectively reduce hair protein loss. CONCLUSION: Silibinin-loaded polymeric micelles were able to effectively protect hair from structural and chemical changes caused by UV-B radiation.

Combined microneedling with topical vitamin D3 or bimatoprost versus microneedling alone in the treatment of alopecia areata: A comparative randomized trial.

INTRODUCTION: Alopecia areata (AA) is a challenging disease with variable treatment outcomes. Hair follicles express vitamin D receptors. Therefore, vitamin D3 may be promising for AA treatment through immunomodulatory mechanisms. The efficacy of bimatoprost in scalp AA treatment was reported by few studies. OBJECTIVE: To evaluate the efficacy and safety of microneedling (MN) with topical vitamin D3 versus MN with bimatoprost in comparison with MN alone in the treatment of localized AA. PATIENTS AND METHODS: Seventy-five patients with localized AA were divided into three groups. The first group: 25 patients were treated with MN alone. The second group: 25 patients treated with MN combined with topical vitamin D3. The third group: 25 patients treated with MN combined with bimatoprost solution. The response was evaluated clinically and dermoscopically. RESULTS: At the end of the study, all groups showed a statistically significant decrease in the SALT score compared to the baseline. The clinical response (regrowth scale): vitamin D and bimatoprost groups showed a statistically significant higher regrowth scale compared to MN alone group (p-value = 0.000). After treatment, hair regrowth was significantly higher in MN combined with bimatoprost than in MN combined with topical vitamin D3. However, after 3 months of follow-up, there was no statistically significant difference between both groups. Side effects were mild and transient in all groups. CONCLUSION: Topical vitamin D3 and bimatoprost combined with MN are safe and effective therapeutic options for localized AA.

Preparation of topical bimatoprost with enhanced skin infiltration and in vivo hair regrowth efficacy in androgenic alopecia.

To prepare a topical formulation of bimatoprost (BIM) with high skin permeability, we designed a solvent mixture system composed of ethanol, diethylene glycol monoethyl ether, cyclomethicone, and butylated hydroxyanisole, serving as a volatile solvent, nonvolatile co-solvent, spreading agent, and antioxidant, respectively. The ideal topical BIM formulation (BIM-TF#5) exhibited 4.60-fold higher human skin flux and a 529% increase in dermal drug deposition compared to BIM in ethanol. In addition, compared to the other formulations, BIM-TF#5 maximally activated human dermal papilla cell proliferation at a concentration of 5 µM BIM, equivalent to 10 µM minoxidil. Moreover, BIM-TF#5 (0.3% [w/w] BIM) significantly promoted hair regrowth in the androgenic alopecia mouse model and increased the area covered by hair at 10 days by 585% compared to the vehicle-treated mice, indicating that entire telogen area transitioned into the anagen phase. Furthermore, at day 14, the hair weight of mice treated with BIM-TF#5 (5% [w/w] BIM) was 8.45- and 1.30-fold greater than in the 5% (w/w) BIM in ethanol and 5% (w/v) minoxidil treated groups, respectively. In the histological examination, the number and diameter of hair follicles in the deep subcutis were significantly increased in the BIM-TF#5 (0.3 or 5% [w/w] BIM)-treated mice compared to the mice treated with vehicle or 5% (w/w) BIM in ethanol. Thus, our findings suggest that BIM-TF#5 is an effective formulation to treat scalp alopecia, as part of a novel therapeutic approach involving direct prostamide F2α receptor-mediated stimulation of dermal papilla cells within hair follicles.

Hair-growth promoting effect and anti-inflammatory mechanism of Ginkgo biloba polysaccharides.

The aim of this study was to optimize the separation and purification technology of water-soluble Ginkgo biloba leaves polysaccharides (WGBP), analyze its composition characteristics, observe its hair-growth promoting effect in alopecia areata mice, clarify the polysaccharide fraction with bioactive activities, and explore its anti-inflammation mechanism. We isolated acidic polysaccharides (WGBP-A2) and purified a RG-I type polysaccharide (WGBP-A2b) with a molecular weight of 44 kDa. Results showed that WGBP-A2 could significantly increase the contents of VEGF and HGF in the skin tissue of alopecia areata mice, decrease the contents of Inflammatory factors in the serum. On a cellular level, the expressions of p-p65 and p-IκBα, TNF-α and IL-1ß in HUVECs treated with WGBP-A2b were down-regulated. The bioinformatic analysis showed that the inflammation signaling pathway was significantly changed. Its specific mechanism may be related to its regulating the expression of p-p65 p-IκBα, TNF-α and IL-1ß proteins in the inflammation signaling pathway.

Topical Cyperus rotundus essential oil for treatment of axillary hyperpigmentation: a randomized, double-blind, active- and placebo-controlled study.

BACKGROUND: The oil of the grass Cyperus rotundus (purple nutsedge) is an effective and safe treatment option for a variety of conditions. It has anti-inflammatory and antipigmenting properties. There have been no clinical trials comparing topical C. rotundus oil with skin-lightening treatments for axillary hyperpigmentation. AIM: To assess the efficacy of C. rotundus essential oil (CREO) in treating axillary hyperpigmentation, and compare with another active treatment hydroquinone (HQ) and a placebo (cold cream) in this study. METHODS: The study included 153 participants, who were assigned to one of three study groups: CREO, HQ group or placebo group. A tri-stimulus colorimeter was used to assess pigmentation and erythema. Two independent experts completed the Physician Global Assessment, and the patients completed a self-assessment questionnaire. RESULTS: CREO had significantly (P < 0.001) better depigmenting effects than HQ. CREO and HQ did not differ significantly in terms of depigmentation effects (P > 0.05); however, there were statistically significant differences in anti-inflammatory effects and decrease in hair growth (P < 0.05) in favour of CREO. CONCLUSIONS: CREO is a cost-effective and safe treatment for axillary hyperpigmentation.

Exoproduction and Biochemical Characterization of a Novel Serine Protease from Ornithinibacillus caprae L9T with Hide-Dehairing Activity.

This study is the first report on production and characterization of the enzyme from an Ornithinibacillus species. A 4.2-fold increase in the extracellular protease (called L9T) production from Ornithinibacillus caprae L9T was achieved through the one-factor-at-a-time approach and response surface methodological optimization. L9T protease exhibited a unique protein band with a mass of 25.9 kDa upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This novel protease was active over a range of pH (4-13), temperatures (30-80°C) and salt concentrations (0-220 g/l), with the maximal activity observed at pH 7, 70°C and 20 g/l NaCl. Proteolytic activity was upgraded in the presence of Ag+, Ca2+ and Sr2+, but was totally suppressed by 5 mM phenylmethylsulfonyl fluoride, which suggests that this enzyme belongs to the serine protease family. L9T protease was resistant to certain common organic solvents and surfactants; particularly, 5 mM Tween 20 and Tween 80 improved the activity by 63 and 15%, respectively. More importantly, L9T protease was found to be effective in dehairing of goatskins, cowhides and rabbit-skins without damaging the collagen fibers. These properties confirm the feasibility of L9T protease in industrial applications, especially in leather processing.

Case Report: Successful Use of Minoxidil to Promote Facial Hair Growth in an Adolescent Transgender Male.

Increasing numbers of trans and gender diverse young people are presenting to health services seeking gender-affirming medical care. While testosterone therapy in transgender males is generally effective in inducing masculinization, some adolescents encounter barriers to accessing such treatment or may not wish to experience all the changes that usually accompany testosterone. Here, we describe the case of a 17 year old trans male who presented with gender dysphoria but was initially unable to start testosterone therapy. Due to a desire for facial hair, he was therefore treated with topical minoxidil, an easily accessible, over-the-counter medication that has been used to treat androgenic alopecia for several decades. In this case, minoxidil was applied regularly to the lower face and, after three months of treatment, he developed obvious pigmented facial hair that was sufficient to help him avoid being misgendered. The only reported side effect was excessive skin dryness. Unexpectedly, despite no direct application to other areas, there was also an increase in pigmented body hair, suggestive of systemic absorption and effect. Given its long-standing use and safety record in the management of alopecia, minoxidil might thus represent a useful treatment option for trans males who desire an increase in facial hair.

Anti-aging and anti-oxidant activities of murine short interspersed nuclear element antisense RNA.

Short interspersed nuclear elements (SINEs) play a key role in regulating gene expression, and SINE RNAs are involved in age-related diseases. We investigated the anti-aging effects of a genetically engineered murine SINE B1 antisense RNA (B1as RNA) and explored its mechanism of action in naturally senescent BALB/c (≥14 months) and moderately senscent C57BL/6N (≥9 months) mice. After tail vein injection, B1as RNA was available in the blood of mice for approximately 30 min, persisted for approximately 2-4 h in most detected tissues and persisted approximately 48 h in lungs. We found that treatment with B1as RNA improved stamina and promoted hair re-growth in aged mice. Treatment with B1as RNA also partially rescued the increase in mitochondrial DNA copy number in liver and spleen tissues observed in aged and moderately senescent mice. Finally, treatment with B1as RNA increased the activities of superoxide dismutase and glutathione peroxidase in aged and moderately senescent mice, reduced these animals' malondialdehyde and reactive oxygen species levels, and modulated the expression of several aging-associated genes, including Sirtuin 1, p21, p16Ink4a, p15Ink4b and p19Arf, and anti-oxidant genes (Sesn1 and Sesn 2). These data suggest that B1as RNA inhibits the aging process by enhancing antioxidant activity, promoting the scavenging of free radicals, and modulating the expression of aging-associated genes. This is the first report describing the anti-aging activity of SINE antisense RNA, which may serve as an effective nucleic acid drug for the treatment of age-related diseases.

Glutamic acid promotes hair growth in mice.

Glutamic acid is the main excitatory neurotransmitter acting both in the brain and in peripheral tissues. Abnormal distribution of glutamic acid receptors occurs in skin hyperproliferative conditions such as psoriasis and skin regeneration; however, the biological function of glutamic acid in the skin remains unclear. Using ex vivo, in vivo and in silico approaches, we showed that exogenous glutamic acid promotes hair growth and keratinocyte proliferation. Topical application of glutamic acid decreased the expression of genes related to apoptosis in the skin, whereas glutamic acid increased cell viability and proliferation in human keratinocyte cultures. In addition, we identified the keratinocyte glutamic acid excitotoxic concentration, providing evidence for the existence of a novel skin signalling pathway mediated by a neurotransmitter that controls keratinocyte and hair follicle proliferation. Thus, glutamic acid emerges as a component of the peripheral nervous system that acts to control cell growth in the skin. These results raise the perspective of the pharmacological and nutritional use of glutamic acid to treat skin diseases.

Exosomes Derived from Fisetin-Treated Keratinocytes Mediate Hair Growth Promotion.

Enhanced telomerase reverse transcriptase (TERT) levels in dermal keratinocytes can serve as a novel target for hair growth promotion. Previously, we identified fisetin using a system for screening food components that can activate the TERT promoter in HaCaT cells (keratinocytes). In the present study, we aimed to clarify the molecular basis of fisetin-induced hair growth promotion in mice. To this end, the dorsal skin of mice was treated with fisetin, and hair growth was evaluated 12 days after treatment. Histochemical analyses of fisetin-treated skin samples and HaCaT cells were performed to observe the effects of fisetin. The results showed that fisetin activated HaCaT cells by regulating the expression of various genes related to epidermogenesis, cell proliferation, hair follicle regulation, and hair cycle regulation. In addition, fisetin induced the secretion of exosomes from HaCaT cells, which activated ß-catenin and mitochondria in hair follicle stem cells (HFSCs) and induced their proliferation. Moreover, these results revealed the existence of exosomes as the molecular basis of keratinocyte-HFSC interaction and showed that fisetin, along with its effects on keratinocytes, caused exosome secretion, thereby activating HFSCs. This is the first study to show that keratinocyte-derived exosomes can activate HFSCs and consequently induce hair growth.