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.

Platelet-Rich Plasma: Advances and Controversies in Hair Restoration and Skin Rejuvenation.

BACKGROUND: Platelet-rich plasma (PRP) and its combined therapeutic modalities have catalyzed new possibilities in dermatology; however, limitations in evidence and lack of consensus remain among clinicians regarding optimal composition, protocol, technique, and application. OBJECTIVE: To provide an update and analysis of the evidence for PRP in hair restoration and skin rejuvenation through review of recent available data, highlighting controversies and expert insights to guide future studies, and stimulate discourse and innovations benefitting patients. METHODS: A structured review and expert analysis of PubMed publications before October 2023, with a focus on recent literature from January 2020 through October 2023. RESULTS AND CONCLUSION: Growing literature supports the utility and benefits of PRP and related autologous products for applications for skin and hair, with strongest evidence for androgenetic alopecia and skin rejuvenation. However, this is limited by lack of consensus regarding best practices and protocols. Randomized, controlled trials with uniform metrics comparing outcomes of various compositions of autologous blood products, preparation methods, dosimetry, and frequency of treatments are still required. This will allow the medical discourse to grow beyond the realm of expert opinion into consensus, standardization, and more wide spread adoption of best practices that will benefit patients.

Efficacy and safety of combined microneedling therapy for androgenic alopecia: A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: To provide dermatologists with more clinical experience in treating androgenetic alopecia, we evaluated the effect and safety of combined microneedling therapy for androgenetic alopecia. METHODS: Studies on combined microneedling for hair loss were comprehensively searched by us in PubMed, Excerpta Medica Database, and the Cochrane Library Database. The literature search spanned the period from 2012 to 2022. Inclusion and exclusion criteria were developed, and the literature was screened according to this criteria. The Cochrane Risk of Bias Tool was used to assess the quality of the studies. The researcher applied Revman 5.3 and Stata 15.1 software to analyze the data after extracting information from the data. RESULTS: Finally, 13 RCTs involving 696 AGA patients were included to compare the clinical effectiveness and adverse events of combined MN therapy with single MN therapy or single drug therapy for AGA. The results of meta-analysis showed as follows: (1) Hair density and diameter changes: The combined MN group was significantly better than any single treatment group, and the differences were statistically significant (MD = 13.36, 95% CI = [8.55, 18.16], Z = 5.45, p < 0.00001; MD = 18.11, 95% CI = [13.70, 22.52], Z = 8.04, p < 0.00001; MD = 13.36, 95% CI = [8.55, 18.16], Z = 5.45, p < 0.00001; MD = 2.50, 95% CI = [0.99, 4.02], Z = 3.23, p = 0.001); (2) the evaluation of satisfaction for efficacy: The doctor satisfaction rating of the combined MN group was significantly higher than that of any single treatment group, with statistical difference (RR = 2.03, 95% CI = [1.62, 2.53], Z = 6.24, p < 0.00001). The difference between the two groups regarding patients satisfaction was not significant (RR = 3.44, 95% CI = [0.67, 17.59], Z = 1.49, p = 0.14). (3) Safety: There was no statistical difference in the incidence of adverse reactions between combination therapy and monotherapy (RR = 0.83, 95% CI = [0.62, 1.12], Z = 1.22, p = 0.22). CONCLUSION: The combined MN group showed statistically significant improvement in hair density and diameter, and good safety compared with monotherapy.

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.

The role of platelet-rich plasma in androgenetic alopecia: A systematic review.

BACKGROUND: Androgenetic alopecia (AGA), also referred to as male or female pattern hair loss, is the commonest cause of chronic hair loss and affects up to 80% of men by the age of 70. Despite a high prevalence, there are few approved therapies, which show minimal efficacy. OBJECTIVES: This systematic review aims to evaluate the efficacy of platelet-rich plasma (PrP) in the treatment of AGA in male patients. METHODS: MEDLINE, EMBASE, Cochrane (CENTRAL), CINAHL, clinicaltrials.gov, Google Scholar and the Science Citation Index database were searched to identify eligible studies. All randomized controlled trials (RCTs) and prospective cohort studies related to PrP use in AGA were included. Primary outcomes included changes in hair density and hair count. Methodological quality was assessed using bias assessment tools. RESULTS: Eight RCTs and one cohort study were included in the review with a total of 291 participants. Six studies reported a statistically significant increase in hair density in the PrP group versus the control. Five studies reported a statistically significant increase in hair count with PrP. Seven studies showed moderate risk and two showed low risk of bias. CONCLUSION: In a methodologically robust review on the effectiveness of PrP on male AGA, PrP demonstrated some potential to be used therapeutically. However, the low quality of evidence, moderate risk of bias, and high heterogeneity of included studies limit inferences and call for more robust designs to investigate this further.

Neurotensin counteracts hair growth inhibition induced by chronic restraint stress.

Stress has been considered as a potential trigger for hair loss through the neuroendocrine-hair follicle (HF) axis. Neurotensin (NTS), a neuropeptide, is known to be dysregulated in the inflammatory-associated skin diseases. However, the precise role of NTS in stress-induced hair loss is unclear. To investigate the function and potential mechanisms of NTS in stress-induced hair growth inhibition, we initially detected the expression of neurotensin receptor (Ntsr) and NTS in the skin tissues of stressed mice by RNA-sequencing and ELISA. We found chronic restraint stress (CRS) significantly decreased the expression of both NTS and Ntsr in the skin tissues of mice. Intracutaneous injection of NTS effectively counteracted CRS-induced inhibition of hair growth in mice. Furthermore, NTS regulated a total of 1093 genes expression in human dermal papilla cells (HDPC), with 591 genes being up-regulated and 502 genes being down-regulated. GO analysis showed DNA replication, cell cycle, integral component of plasma membrane and angiogenesis-associated genes were significantly regulated by NTS. KEGG enrichment demonstrated that NTS also regulated genes related to the Hippo signalling pathway, axon guidance, cytokine-cytokine receptor interaction and Wnt signalling pathway in HDPC. Our results not only uncovered the potential effects of NTS on stress-induced hair growth inhibition but also provided an understanding of the mechanisms at the gene transcriptional level.

Utilization of response surface design for development and optimization of rosuvastatin calcium-loaded nano-squarticles for hair growth stimulating VEGF and IGF production: in-vitro and in-vivo evaluation.

INTRODUCTION: Countless individuals experience negative emotions as hair loss pattern affects their self-esteem and well-being. Rosuvastatin calcium (Ca-RUV) was reported to stimulate the growth of the hair in the applied area, hence, it was selected as a potential hair loss treatment drug. SIGNIFICANCE: This study aims to develop and optimize (Ca-RUV) loaded squarticles (SQRs) and assess their ability to deliver and release Ca-RUV in the hair follicle for the promotion of hair growth. METHODS: A response surface design was utilized to study the effect of varying Pluronic® F68 (PF68) and the percentage of liquid lipids within the core of the SQRs and the effects of particle size, entrapment efficiency, and drug released percentage after 24 h (%Q24) were assessed. The optimized formula was subjected to DSC, XRD, and in-vivo evaluation in rats. RESULTS: SQRs stabilized by 0.8% PF68 and contained 37.5% liquid lipids showed an acceptable particle size (250 nm), drug entrapment efficiency (75%), and %Q24 (100%). The in-vivo studies illustrated the ability of the formula to regrow hair in animals after 10 days due to the elevation of the vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) to their normal values and by 9% and 54%, respectively, relative to standard therapy minoxidil (5%). CONCLUSION: Thus, it can be concluded that the optimized formula of Ca-RUV loaded SQRs showed superior in-vivo results in the promotion of hair growth in a shorter period relative to the marketed product. Therefore, the formula can offer a viable option for the treatment of hair loss.

Modulation of hair growth by topical drug delivery enhanced by STAR particles.

Topical treatments to modulate hair growth are generally limited by low drug bioavailability due to poor skin permeability. Here, we studied the use of STAR particles, which are millimeter-sized ceramic particles with protruding microneedles, to form micropores in the skin to increase skin permeability to hair growth-modulating drugs. STAR particle design and fabrication were optimized, and the resulting STAR particles were shown to reduce lag time and increase skin permeability to minoxidil and acyclovir by more than three-fold compared to no treatment in pig skin ex vivo. In rats, STAR particles also improved topical delivery of minoxidil and acyclovir, which resulted in an increase or a decrease in the number, length and/or thickness of hairs and/or the number of anagen-phase hair follicles after minoxidil or acyclovir treatment, respectively. Clinical exam and histological evaluation showed no evidence of skin irritation or other adverse effects of the treatments. We conclude that STAR particles can increase topical delivery of minoxidil and acyclovir to improve modulation of hair growth promotion and inhibition, respectively.

Signalling by senescent melanocytes hyperactivates hair growth.

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.

Novel Insights into the Role of Keratinocytes-Expressed TRPV3 in the Skin.

TRPV3 is a non-selective cation channel that is highly expressed in keratinocytes in the skin. Traditionally, keratinocytes-expressed TRPV3 is involved in multiple physiological and pathological functions of the skin, such as itching, heat pain, and hair development. Although the underlying mechanisms by which TRPV3 functions in vivo remain obscure, recent research studies suggest that several cytokines and EGFR signaling pathways may be involved. However, there have also been other studies with opposite results that question the role of TRPV3 in heat pain. In addition, an increasing number of studies have suggested a novel role of TRPV3 in promoting skin regeneration, indicating that TRPV3 may become a new potential target for regulating skin regeneration. This paper not only reviews the role of keratinocytes-expressed TRPV3 in the physiological and pathological processes of itching, heat pain, hair development, and skin regeneration, but also reviews the relationship between TRPV3 gene mutations and skin diseases such as atopic dermatitis (AD) and Olmsted syndrome (OS). This review will lay a foundation for further developing our understanding of the mechanisms by which TRPV3 is involved in itching, heat pain, and hair development, as well as the treatments for TRPV3-related skin diseases.

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.

Recetario médico-farmacológicos para el cuidado y el embellecimiento del cabello: fuentes árabes medievales / [Medical-pharmacological recipes for hair care and beautification: medieval Arabic sources]

El cuidado y el embellecimiento del cabello forman parte de la tradición de todas las culturas y, a lo largo de la historia, los hombres y las mujeres se han preocupado por su aspecto, no solo desde el punto de vista estético sino también desde el punto de vista terapéutico. Un cabello sano indica una piel sana y, por lo tanto, un cuerpo sano. El trabajo que aquí presentamos recoge una colección de recetas de carácter médico-farmacológico destinadas al cuidado y el embellecimiento del cabello. Para ello, y partiendo de la Materia Médica de Dioscórides, obra de cabecera de la ciencia árabe, se han seleccionado una serie de fuentes árabes medievales de las que se han extraído dichas recetas. Los autores elegidos son: Al-Idrīsī, Abū l-Qāsim al-Zahrāwī, Abū l-ʿAlā’ Zuhr, Ibn Zuhr e Ibn al-Bayttār (AU)

En pos de la belleza. Cuidado de rostro y cabellos en el corpus textual hebreo de medicina / [In pursuit of beauty. Face and hair care in the Hebrew textual corpus of medicine]

Este trabajo presenta el resultado preliminar de una investigación en curso sobre tres géneros o tipologías textuales hebreas de (o con) contenido cosmético poco estudiados hasta ahora: recetarios, libros de medicina general y recetas sueltas. El análisis se ha basado en una muestra de textos concretos, con el fin de que sirvan como estudio de caso, en los que nos hemos centrado en las recetas y procedimientos dedicados a rostro y cabellos, por los que todos ellos revelan una preocupación notoria. Por un lado, se han examinado los diversos propósitos de las recetas, así como los ingredientes, técnicas y procedimientos. Por otro, hemos prestado atención a cómo se articulan el conocimiento y las técnicas cosméticas en distintos contextos médicos que no siempre tienen como objetivo aparente la salud femenina pero que se desarrollan en el marco de los discursos sobre la diferencia sexual y en la intersección de género, clase social y etnicidad. (AU)

Gender-Difference in Hair Length as Revealed by Crispr-Based Production of Long-Haired Mice with Dysfunctional FGF5 Mutations.

Fibroblast growth factor 5 (FGF5) is an important molecule required for the transition from anagen to catagen phase of the mammalian hair cycle. We previously reported that Syrian hamsters harboring a 1-bp deletion in the Fgf5 gene exhibit excessive hair growth in males. Herein, we generated Fgf5 mutant mice using genome editing via oviductal nucleic acid delivery (GONAD)/improved GONAD (i-GONAD), an in vivo genome editing system used to target early embryos present in the oviductal lumen, to study gender differences in hair length in mutant mice. The two lines (Fgf5go-malc), one with a 2-bp deletion (c.552_553del) and the other with a 1-bp insertion (c.552_553insA) in exon 3 of Fgf5, were successfully established. Each mutation was predicted to disrupt a part of the FGF domain through frameshift mutation (p.Glu184ValfsX128 or p.Glu184ArgfsX128). Fgf5go-malc1 mice had heterogeneously distributed longer hairs than wild-type mice (C57BL/6J). Notably, this change was more evident in males than in females (p < 0.0001). Immunohistochemical analysis revealed the presence of FGF5 protein in the dermal papilla and outer root sheath of the hair follicles from C57BL/6J and Fgf5go-malc1 mice. Histological analysis revealed that the prolonged anagen phase might be the cause of accelerated hair growth in Fgf5go-malc1 mice.

Hair-Growth-Promoting Effects of the Fish Collagen Peptide in Human Dermal Papilla Cells and C57BL/6 Mice Modulating Wnt/ß-Catenin and BMP Signaling Pathways.

Fish-derived collagen has recently emerged as an alternative collagen source with bioactive properties, including the enhancement of hair and skin health. It is also cost-effective and has high bioavailability, in addition to having fewer side-effects compared to collagen from porcine skin or bovine skin. Collagen peptides (CPs) extracted from the scales of Mozambique tilapia (Oreochromis mossambicus) reportedly promote hair and skin health. This study sought to evaluate the effects of CPs on hair growth using in vitro and in vivo models. CP significantly enhanced hair regrowth and the proliferation of human dermal papilla cells (hDPCs) in vitro. CP was orally administered to C57BL/6 mice for 6 weeks to confirm the hair-growth-promoting effects. The mice were divided into four groups: negative control (distilled water), positive control (1 mg/kg of finasteride), CP500 (500 mg/kg of CP), and CP1000 (1000 mg/kg of CP). CP treatment significantly enhanced the proliferation of hDPCs compared to 0.2 µM finasteride, in addition to enhancing hair regrowth. Particularly, CP1000 treatment achieved a hair-growth index similar to that of the PC. In H&E staining, the CP groups exhibited a high A/T ratio. Furthermore, CP increased the expression of hair growth factors (IGF-1, VEGF, krt27, Gprc5d, and Ki67) and decreased the growth inhibitory factor (TGF-ß1). Furthermore, CP significantly upregulated the Wnt/ß-catenin pathways and downregulated the BMP pathways. Therefore, these results indicate that CP could be used as food supplements and nutraceuticals for hair loss prevention as well as hair regrowth during alopecia.

Hair Growth Regulation by Fibroblast Growth Factor 12 (FGF12).

The fibroblast growth factor (FGF) family has various biological functions, including cell growth, tissue regeneration, embryonic development, metabolism, and angiogenesis. In the case of hair growth, several members of the FGF family, such as FGF1 and FGF2, are involved in hair growth, while FGF5 has the opposite effect. In this study, the regulation of the hair growth cycle by FGF12 was investigated. To observe its effect, the expression of FGF12 was downregulated in mice and outer root sheath (ORS) by siRNA transfection, while FGF12 overexpression was carried out using FGF12 adenovirus. For the results, FGF12 was primarily expressed in ORS cells with a high expression during the anagen phase of hair follicles. Knockdown of FGF12 delayed telogen-to-anagen transition in mice and decreased the hair length in vibrissae hair follicles. It also inhibited the proliferation and migration of ORS cells. On the contrary, FGF12 overexpression increased the migration of ORS cells. FGF12-overexpressed ORS cells induced the telogen-to-anagen transition in the animal model. In addition, FGF12 overexpression regulated the expression of PDGF-CC, MDK, and HB-EGF, and treatment of these factors exhibited hair growth promotion. Altogether, FGF12 promoted hair growth by inducing the anagen phase of hair follicles, suggesting the potential for hair loss therapy.

Role of the soluble epoxide hydrolase in the hair follicle stem cell homeostasis and hair growth.

Polyunsaturated fatty acids (PUFAs) are used as traditional remedies to treat hair loss, but the mechanisms underlying their beneficial effects are not well understood. Here, we explored the role of PUFA metabolites generated by the cytochrome P450/soluble epoxide hydrolase (sEH) pathway in the regulation of the hair follicle cycle. Histological analysis of the skin from wild-type and sEH-/- mice revealed that sEH deletion delayed telogen to anagen transition, and the associated activation of hair follicle stem cells. Interestingly, EdU labeling during the late anagen stage revealed that hair matrix cells from sEH-/- mice proliferated at a greater rate which translated into increased hair growth. Similar effects were observed in in vitro studies using hair follicle explants, where a sEH inhibitor was also able to augment whisker growth in follicles from wild-type mice. sEH activity in the dorsal skin was not constant but altered with the cell cycle, having the most prominent effects on levels of the linoleic acid derivatives 12,13-epoxyoctadecenoic acid (12,13-EpOME), and 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME). Fitting with this, the sEH substrate 12,13-EpOME significantly increased hair shaft growth in isolated anagen stage hair follicles, while its diol; 12,13-DiHOME, had no effect. RNA sequencing of isolated hair matrix cells implicated altered Wnt signaling in the changes associated with sEH deletion. Taken together, our data indicate that the activity of the sEH in hair follicle changes during the hair follicle cycle and impacts on two stem cell populations, i.e., hair follicle stem cells and matrix cells to affect telogen to anagen transition and hair growth.

Sodium pentaborate pentahydrate promotes hair growth through the Wnt/ß-catenin pathway and growth factors.

BACKGROUND: Boron (B) is an element involved in many physiological processes in humans and accelerates wound healing and increases angiogenesis. This study aimed to evaluate the possible effects of sodium pentaborate pentahydrate (NaB) on hair growth and reveal its effects on Wnt-1, ß-catenin, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor-ß1 (TGF-ß1) signaling pathways, which are important molecular mechanisms involved in hair growth. METHODS: Thirty-five Sprague-Dawley/Wistar albino rats were randomly divided into five groups: non-shaved control, shaved control, NaB 1 mg (shaved + NaB 1 mg elemental B/kg CA), NaB 2 mg (shaved + NaB 2 mg elemental B/kg CA), and NaB 4 mg (shaved + NaB 4 mg elemental B/kg CA). Hair density was measured using the trichoscopy method. Dorsal skin samples were examined histopathologically at the end of the 42nd day, and follicle count, follicle diameter, and subcutaneous tissue thickness were recorded. Wnt-1, ß-catenin, PDGF, VEGF, TGF-ß1, and collagen I levels were analyzed with the Western blot method. RESULTS: In trichoscopy measurements, hair density increased in the NaB 4 mg group (90.9%). In histopathological examination, anagen follicles were observed to increase in the NaB 1 mg and 2 mg groups (p < 0.05). Follicle diameter increased in all NaB groups (p < 0.05). The Wnt-1, ß-catenin, PDGF, VEGF, TGF-ß1, and collagen I level increased in the NaB 1 mg and 2 mg groups (p < 0.05), but they were similar in the NaB 4 mg group compared to the control groups (p > 0.05). CONCLUSION: NaB 1 and 2 mg B/kg supplementation induces the anagen phase in rats via Wnt-1, ß-catenin, VEGF, PDGF, and TGF-ß1 signaling pathways. NaB 4 mg B/kg suppresses these pathways and adversely affects hair growth.

CXCL12 inhibits hair growth through CXCR4.

CXCL12 and its receptors, which are highly expressed in the skin, are associated with various cutaneous diseases, including androgenic alopecia. However, their expression and role during the hair cycle are unknown. This study aims to investigate the expression of CXCL12 and its receptor, CXCR4, in the vicinity of hair follicles and their effect on hair growth. CXCL12 was highly expressed in dermal fibroblasts (DFs) and its level was elevated throughout the catagen and telogen phases of the hair cycle. CXCR4 is expressed in the dermal papilla (DP) and outer root sheath (ORS). In hair organ culture, hair loss was induced by recombinant CXCL12 therapy, which delayed the telogen-to-anagen transition and decreased hair length. In contrast, the suppression of CXCL12 using a neutralizing antibody and siRNA triggered the telogen-to-anagen transition and increased hair length in hair organ culture. Neutralization of CXCR7, one of the two receptors for CXCL12, only slightly affected hair growth. However, inhibition of CXCR4, the other receptor for CXCL12, increased hair growth to a considerable extent. In addition, in hair organ culture, the conditioned medium from DFs with CXCL12 siRNA considerably increased the hair length and induced proliferation of DP and ORS cells. CXCL12, through CXCR4 activation, increased STAT3 and STAT5 phosphorylation in DP and ORS cells. In contrast, blocking CXCL12 and CXCR4 decreased the phosphorylation of STAT3 and STAT5. In summary, these findings suggest that CXCL12 inhibits hair growth via the CXCR4/STAT signaling pathway and that CXCL12/CXCR4 pathway inhibitors are a promising treatment option for hair growth.