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Platelet rich plasma (PRP) was tested as a potential therapy for androgenetic alopecia (AGA) through two different clinical protocols in which one population (18 participants) received half-head treatment with autologous non-activated PRP (A-PRP) produced by CPunT Preparation System (Biomed Device, Modena, Italy) and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group) received treatment with calcium-activated PRP (AA-PRP) produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System). For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs) and in total hair density (65± 5 hair cm2), whereas negligible improvements in hair count (1.1± 1.4 hairs) and density (1.9 ± 10.2 hair cm2) were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus -73 ± 30 hair cm2 hair densities, Regen versus Arthrex). Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.

Hair follicle development and hair growth are regulated by multiple factors and multiple signalling pathways. The hair follicle, as an important skin appendage, is the basis for hair growth, and it has the functions of safeguarding the body, perceiving the environment and regulating body temperature. Hair growth undergoes a regular hair cycle, including anagen, catagen and telogen. A small amount of physiological shedding of hair occurs under normal conditions, always in a dynamic equilibrium. Hair loss occurs when the skin or hair follicles are stimulated by oxidative stress, inflammation or hormonal disorders that disrupt the homeostasis of the hair follicles. Numerous researches have indicated that oxidative stress is an important factor causing hair loss. Here, we summarize the signalling pathways and intervention mechanisms by which oxidative stress affects hair follicle development and hair growth, discuss existing treatments for hair loss via the antioxidant pathway and provide our own insights. In addition, we collate antioxidant natural products promoting hair growth in recent years and discuss the limitations and perspectives of current hair loss prevention and treatment.

We designed formulations based on minoxidil (MXD) nanoparticles (N-MXD) and examined whether N-MXD can increase drug delivery into the follicles. In addition, we investigated the effect of N-MXD on hair growth in C57BL/6 mice. N-MXD (1%) was prepared as follows: methylcellulose, p-hydroxyalkylbenzoates, mannitol, and MXD were dispersed in purified water and milled using zirconia beads under refrigeration (5500 rpm, 30 s×15 times, intermittent milling). C57BL/6 mice were used to evaluate hair-growth effects. The expression levels of mRNA and protein for vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) were determined by real-time PCR and ELISA methods, respectively. The ratio of solid-MXD was approximately 60% in N-MXD, and the MXD nanoparticles (90-300 nm) were oblong in shape. For the design of nanomedicines, usability is important. Therefore, we measured the stability and toxicity after N-MXD treatment. No agglutination of MXD nanoparticles was detected for 2 weeks, and no redness or MXD powder residue was observed in the skin after repetitive applications of N-MXD. Next, we evaluated hair-growth effects by N-MXD treatment. MXD contents in the skin tissue from N-MXD were lower than for commercially available MXD formulations (CA-MXD). Conversely, MXD contents in the hair bulbs were higher for N-MXD than for CA-MXD, and the drug efficacy of N-MXD was also higher than that of CA-MXD. In addition, the mRNA and protein levels of IGF-1 and VEGF were enhanced by the repetitive application of N-MXD and CA-MXD, and the enhanced IGF-1 and VEGF levels were significantly higher for N-MXD than for CA-MXD. We designed a novel nanomedicine based on MXD nanoparticles and showed that N-MXD can deliver MXD into hair bulbs via hair follicles and that the therapeutic efficiency for hair growth is higher than for CA-MXD (solution type).

Background. Androgenetic alopecia (AGA) represents the most frequent clinical complaint encountered by dermatologists and is characterized by a progressive miniaturization of the hair follicle. However, the efficacy and safety of current medical treatment remain limited, and more personalized therapeutic approaches for AGA are needed. Therefore, the present study is aimed at investigating the efficacy and safety of botulinum toxin type A (BTA) in patients with AGA. Methods. 63 patients with AGA meeting the inclusion criteria were included in this study and treated with BTA injection or BTA injection combined with oral finasteride (FNS). In the scalp, 30 sites were injected with 100 U of BTA in each site and patients received BTA after every 3 months for a total of 4 times. Hair counts, head photographs, evaluation scores, and self-assessment were assessed in patients with AGA. Results. Hair counts in both groups at all time points were significantly higher as compared with those before treatment. After 4 times of treatment, hair counts in the BTA+FNS group were higher than those in the BTA group. Hair growth and density were significantly augmented, and the area of hair loss was attenuated after each treatment as revealed by head photographs. The effective rates of BTA and BTA+FNS groups were 73.3% and 84.8%, respectively, following 4 times treatment. Conclusion. BTA is a safe and effective therapeutic strategy for the treatment of AGA without adverse effects, and BTA combined with FNS exhibited a superior therapeutic effect than BTA alone.

Dermal papilla cells (DPCs) are located at the bottom of the hair follicle and play a critical role in hair growth, shape, and cycle. Epidermal growth factor receptor (EGFR) and Wnt/β-catenin signaling pathways are essential in promoting keratinocyte activation as well as hair follicle formation in DPCs. Piperonylic acid is a small molecule that induces EGFR activation in keratinocytes. However, the effects of piperonylic acid on DPCs in regard to the stimulation of hair growth have not been studied. In the present study, piperonylic acid was shown to activate the Wnt/β-catenin signaling pathway in addition to the EGFR signaling pathway in DPCs. Piperonylic acid suppressed DKK1 expression, which presumably promoted the accumulation of β-catenin in the nucleus. In addition, piperonylic acid promoted cyclin D upregulation and cell growth and increased the expression of alkaline phosphatase (ALP), a DPC marker. In a clinical study, the group that applied a formulation containing piperonylic acid had a significantly higher number of hairs per unit area than the placebo group. These results identify piperonylic acid as a promising new candidate for hair loss treatment.

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that plays a vital role in regulating behavior, mood, memory, and gastrointestinal homeostasis. Although recent studies have identified an intestine-hair follicle link, potentially implicating 5-HT, its exact relationship with hair growth remains unclear. Here we investigated the effects of serotonin signaling on hair follicle homeostasis. Gene expression analysis showed significant upregulation of hair growth-related genes in dermal papilla cells treated with 5-HT. The hair growth-promoting effects of 5-HT were examined using hair follicle organoids and hair follicle organ cultures. The addition of 5-HT to hair follicle organoids and hair follicles promoted hair shaft elongation. Similar effects were observed with sumatriptan succinate, a 5-HT receptor agonist. These results suggest that targeting serotonin signaling can advance alopecia therapy.

Understanding the underlying mechanisms regulating hair regeneration is crucial, especially given the increasing demand for effective drugs to treat hair loss, which remain not fully elucidated. In the present study, we found that lipid metabolism was attenuated in the scalp tissues of patients with androgenetic alopecia. Lipid supplementation in the culture medium upregulated hair growth-related genes and promoted the proliferation of human dermal papilla cells (DPCs). By using RNA-sequencing analysis and HIF-1α knockdown in DPCs, we found that HIF-1α is a potential candidate that governs lipid-reinforced upregulation of trichogenic genes. Finally, we assessed the hair growth-promoting effects of lipids using in vitro hair follicle organoids and found that lipids accelerated the elongation of hair-shaft-like structures. Our results highlight the importance of lipids in promoting hair growth through HIF-1 signaling, suggesting that this may be a promising target for the treatment of hair loss.

Androgenetic alopecia (AGA) is the most common form of hair loss characterized by miniaturization of hair follicles. Low-level light therapy (LLLT) and microneedling have shown potential in promoting hair regrowth. This study aims to evaluate the efficacy of an innovative light-emitting diode (LED) helmet cooperated with a novel light-guiding microneedle patch (LMNP) for stimulating hair growth in AGA. In this randomized clinical trial, 16 AGA patients received treatments using light-guiding microneedle patches (LMNPs) illuminated by a LED helmet equipped with green (522 nm) and red (633 nm) LEDs, delivering 50 mW/cm2 power and 40 J/cm2 energy. Treatments were applied weekly for 24 weeks, targeting the frontal recession area. The right side of the scalp was treated with green light and the left with red light, each combined with a LMNP featuring 900 µm height needles at a density of 105 per square centimeter. Hair density and diameter, along with patient and physician satisfaction scores, were assessed monthly. Both red and green LED treatments with LMNP, significantly enhanced hair density and diameter. Satisfaction scores, as reported by both physicians and participants, increased over time. Comparative analyses revealed no statistically significant differences in average satisfaction scores or in changes in hair density and diameter between the groups by the end of the study. Additionally, no serious adverse effects were reported, highlighting the safety of the treatments. The combined Light sources which is portable LED helmet and LMNPs shows promise as a non-invasive, effective treatment for AGA, with similar efficacy between red and green wavelengths.

Considerable global demand exists for the development of novel drugs for the treatment of alopecia. A recent report demonstrated that oxytocin promotes hair growth activity in human dermal papilla (DP) cells; however, its application in drugs or cosmetic products is challenging because rapid degradation and relatively large molecular weight prevent long-term topical administration on the scalp. Here, we examined cinnamic acid, a small molecule activator for oxytocin receptor (OXTR) expression. Treatment with cinnamic acid led to upregulation of OXTR and trichogenic gene expression in human DP cells. Furthermore, inhibition of OXTR with an antagonist, L-371,257, suppressed hair growth-related gene expression in DP cells. These findings suggest that cinnamic acid enhances the hair growth ability of DP cells via oxytocin signaling. Additionally, we tested the hair growth-promoting effects of cinnamic acid using hair follicle organoids in vitro and observed that cinnamic acid significantly promoted the growth of hair peg-like sprouting. These promising results may be useful for developing hair growth-promoting products targeting oxytocin.

Hair loss (alopecia) is a common disorder caused by an interruption in the body’s cycle of hair production. This pathology negatively affects the psychoemotional state of patients and significantly reduces their quality of life. The currently available medical treatments (including minoxidil therapy) are effective in arresting the progression of the disease; however, they allow only partial regrowth of hair at best. A significant clinical result occurs only with regular drug use. There is still great interest in finding new drugs for the treatment of alopecia. In this study, we aimed to examine the effect of an aqueous dispersion of unmodified fullerene C60 (ADF) on hair growth. ADF, produced by a unique technology, is biocompatible and non-toxic. Nu/nu mice were subcutaneously injected (2 μg/animal) every two days for a period of 11 days with ADF and, for control purposes, with phosphate-buffered saline (PBS). It was shown that ADF stimulated hair growth. Histological analysis of the nu/nu mice skin areas showed that animals treated with ADF had significantly more (about twice as many) hair follicles in the anagen phase compared to mice treated with PBS. The effect on hair growth persisted even after discontinuation of ADF administration. Analysis of gene expression demonstrated that ADF affected the Wnt-signaling pathway, increased the expression of the Wnt10b (wingless-type Mouse Mammary Tumor Virus integration site family, member 10B) factor, angiogenetic factors, and downregulated tumor necrosis factor-alpha levels. We propose that the mechanism of ADF action is likely related to its ability to attract macrophages to the hair follicle microenvironment and promote their polarization to the M2 phenotype. In addition, using molecular modeling, we tried to substantiate our hypothesis about the interaction of ADF with the adenosine A2A receptor, which may cause a decrease in tumor necrosis factor-alpha production. Thus, ADF may become a promising drug for the development of new approaches to the treatment of alopecia associated with immune disorders.