Human Hair Loss Research Articles

Association study reveals a susceptibility locus with male pattern baldness in the Han Chinese population.

Male pattern baldness (MPB), also known as androgenetic alopecia, represents the most prevalent form of progressive hair loss in humans. It is characterized by a distinctive pattern of hair loss progression from the scalp; however, its underlying mechanism remains elusive and is influenced by hereditary, immune, and environmental factors. Genome-wide association studies (GWASs) have uncovered numerous risk genes/loci among European individuals with MPB. However, the validation of these susceptibility genes/loci within Han Chinese men remains largely unexplored. The aim of this study was to investigate whether the 71 susceptibility loci identified in a recent GWAS among European men also confer risk for MPB in Chinese men. Forty-seven single nucleotide polymorphisms (SNPs) previously reported in GWASs of MPB were selected and genotyped in independent individuals comprising 499 Han Chinese cases and 1,489 controls using the Sequenom MassArray system. After stringent quality control measures, 25 SNPs were subjected to statistical analyses. Cochran-Armitage trend test was used to evaluate the association between SNPs and disease susceptibility. To address multiple tests, Bonferroni correction was conducted, setting the threshold for statistical significance at a p-value <2 × 10-3 (0.05/25). The rs13405699 SNP located at 2q31.1 exhibited a significant association with MPB in Han Chinese men (p = 4.84 × 10-5, OR = 1.37, 95% CI: 1.18-1.59). Moreover, the difference in rs13405699 genotype distribution between MPB cases and controls was statistically significant (p = 7.00 × 10-5). Genotype-based association analysis suggested that the recessive model provided the best fit for the rs13405699 polymorphism. This study represents the first confirmation of the association between the rs13405699 SNP at 2q31.1 and MPB within the Han Chinese population, thereby enhancing our understanding of the genetic underpinnings of MPB.

Current Protocols: Alopecia Areata Mouse Models for Drug Efficacy and Mechanism Studies.

Alopecia areata is the second most common form of hair loss in humans after androgenetic alopecia. Although a variety of animal models for alopecia areata have been described, currently the C3H/HeJ mouse model is the most commonly used and accepted. Spontaneous hair loss occurs in 15%-25% of older mice in which the lesions wax and wane, similar to the human disease, with alopecia being more common and severe in female mice. Full-thickness skin grafts from mice with spontaneous alopecia areata to young, normal-haired, histocompatible mice provide a highly reproducible model with progressive lesions that makes it useful for drug efficacy and mechanism-based studies. As alopecia areata is a cell-mediated autoimmune disease, transfer of cultured lymph node cells from affected mice to unaffected, histocompatible recipients also promotes disease development and provides an alternative, nonsurgical protocol. Protocols are presented to produce these models such that they can be used to study alopecia areata and to develop novel drug therapies. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Full-thickness skin grafts to reproducibly induce alopecia areata in C3H/HeJ mice Basic Protocol 2: Adoptive transfer of cultured lymphoid cells provides a nonsurgical method to induce alopecia areata in C3H/HeJ mice.

Artificial neural networks algorithms for prediction of human hair loss related autoimmune disorder problem

&lt;p&gt;In this study, artificial neural networks (ANNs) are being used to diagnose hair loss in patients. An autoimmune condition known as Alopecia Areata (AA) results in hair loss in the affected area. The most recent figures from throughout the world show that AA affects 1 in 1000 persons and has a 2% incidence rate. Based on the look of photographs with healthy hair in the dataset, machine learning techniques were employed to classify the conditions. Before making predictions, each of these ANNs algorithms creates a prediction model using pictures of healthy hair. The aim of this study is to evaluate the accuracy of neural networks for alopecia detection in human subjects. The study presents a classification framework for distinguishing between healthy hairs (HHs) and Alopecia Areata (AA). The framework incorporates Contrast Limited Adaptive Histogram Equalization (CLAHE) enhancement and segmentation techniques to enhance the quality of the images. Additionally, Data Augmentation (DA) is employed to generate additional data and improve the precision of the proposed framework. To extract features from the images, two powerful techniques are utilized. The Visual Geometry Group (VGG), which consists of very deep convolutional networks designed for large-scale image recognition, is employed. VGG networks have proven to be effective in learning complex features directly from data, eliminating the need for manual feature extraction. Additionally, a Convolutional Neural Network (CNN), a deep learning network architecture specifically designed for image processing tasks, is employed. To create a machine learning model for classification, the Support Vector Machine (SVM) approach is utilized. SVM is a widely used algorithm in supervised learning, capable of solving both classification and regression problems. Its versatility and effectiveness make it a suitable choice for the classification task in this study. By combining the CLAHE enhancement, segmentation, data augmentation, feature extraction using VGG and CNN, and classification using SVM, the proposed framework aims to accurately classify HHs and AA cases.&lt;/p&gt;

Double mutation of claudin-1 and claudin-3 causes alopecia in infant mice.

Hair follicles (HFs) undergo cyclic phases of growth, regression, and rest in association with hair shafts to maintain the hair coat. Nonsense mutations in the tight junction protein claudin (CLDN)-1 cause hair loss in humans. Therefore, we evaluated the roles of CLDNs in hair retention. Among the 27 CLDN family members, CLDN1, CLDN3, CLDN4, CLDN6, and CLDN7 were expressed in the inner bulge layer, isthmus, and sebaceous gland of murine HFs. Hair phenotypes were observed in Cldn1 weaker knockdown and Cldn3-knockout (Cldn1Δ/Δ Cldn3-/- ) mice. Although hair growth was normal, Cldn1Δ/Δ Cldn3-/- mice showed striking hair loss in the first telogen. Simultaneous deficiencies in CLDN1 and CLDN3 caused abnormalities in telogen HFs, such as an aberrantly layered architecture of epithelial cell sheets in bulges with multiple cell layers, mislocalization of bulges adjacent to sebaceous glands, and dilated hair canals. Along with the telogen HF abnormalities, which shortened the hair retention period, there was an enhanced proliferation of the epithelium surrounding HFs in Cldn1Δ/Δ Cldn3-/- mice, causing accelerated hair regrowth in adults. Our findings suggested that CLDN1 and CLDN3 may regulate hair retention in infant mice by maintaining the appropriate layered architecture of HFs, a deficiency of which can lead to alopecia.

Protective Activity against Oxidative Stress in Dermal Papillae with Extracted Herbal Essential Oils

Dermal papilla cells (DPCs) are a rich source of nutrients and secrete multiple growth factors that can affect hair growth. As oxidative stress leads to hair loss in humans, it is considered to be one of the factors that can impair the function of DPCs. Herb-derived phytochemicals exhibit potent antioxidant activities; therefore, this study investigated whether a set of essential oils (lavender, lemongrass, rosemary, and chamomile oils) promote the hair-growth activity of DPCs. Intracellular reactive oxygen species (ROS) increased markedly in ultraviolet B-irradiated DPCs (50 mJ/cm2) and were efficiently blocked by essential oils. Essential oils upregulated the mRNA and protein levels of phase II enzymes (detoxifying and antioxidant), including heme oxygenase-1, NAD(P)H quinone oxidoreductase-1, and glutathione S-transferase pi. They also upregulated and activated nuclear factor E2-related factor 2, an essential transcription factor for phase II enzymes. Regarding biomarkers for hair growth, essential oils significantly increased vascular endothelial cell growth factor and insulin-like growth factor-1 mRNA levels. In conclusion, phytochemicals in essential oils enhance hair growth through ROS-scavenging activity in DPCs.

The Emergent Power of Human Cellular vs Mouse Models in Translational Hair Research

Different animal models have been used for hair research and regeneration studies based on the similarities between animal and human skins. Primary knowledge on hair follicle (HF) biology has arisen from research using mouse models baring spontaneous or genetically engineered mutations. These studies have been crucial for the discovery of genes underlying human hair cycle control and hair loss disorders. Yet, researchers have become increasingly aware that there are distinct architectural and cellular features between the mouse and human HFs, which might limit the translation of findings in the mouse models. Thus, it is enticing to reason that the spotlight on mouse models and the unwillingness to adapt to the human archetype have been hampering the emergence of the long-awaited human hair loss cure. Here, we provide an overview of the major limitations of the mainstream mouse models for human hair loss research, and we underpin a future course of action using human cell bioengineered models and the emergent artificial intelligence.

LB1017 A novel link between human hair follicle neuroimmunology and mitochondrial biology: Substance P increases intrafollicular oxidative stress and mitochondrial biogenesis

Substance P (SP) is the prototypic neuropeptide associated with emotional stress and neurogenic perifollicular inflammation and is released by sensory nerve fibers. It also promotes human hair follicle (HF) immune privilege collapse and catagen development ex vivo, and has thus been implicated in stress-related hair loss, ranging from telogen effluvium to alopecia areata. Since SP stimulates the mitochondrial release of reactive oxygen species, we have asked how SP impacts on human HF mitochondrial biology. When organ-cultured anagen scalp HFs were treated with SP (10-10 and 10-12M), this showed that the mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1), a key enzymatic marker of oxidative phosphorylation, and mitochondrial activity and biogenesis, was significantly upregulated. This was coupled with significantly increased expression of the mitochondrial mass and biogenesis marker, VDAC1/porin, a channel found in the mitochondrial membrane. SP also significantly increased mTORC1 activity (measured by p-S6 immunofluorescence), a known promoter of ROS production. Since we had previously shown that stress-induced HF greying is associated with VDAC1/porin upregulation, these SP effects suggest a hitherto unknown strong mitochondrial response of human scalp HFs to this stress- and sensory nerve fiber-associated neuropeptide. This invites therapeutic interventions with SP antagonists that target this novel link between mitochondrial biology and neuroimmunology of the HF under conditions of perceived stress in the future management of stress-associated human hair greying and hair loss.

Exploring the impact of ovariectomy on hair growth: can ovariectomized mouse serve as a model for investigating female pattern hair loss in humans?

Female pattern hair loss (FPHL), a type of hair disease common in pre- and postmenopausal women, is characterized by thinning of hair to O-type, mainly at the crown. Although a mouse model of this disease has recently been established, its details are still unknown, and thus, warrants further analysis. In this study, 3week-old and 7- to 8week-old C57BL/6 female mice were divided into two groups: one group underwent ovariectomy (OVX), while the other underwent sham surgery. In the 3week-old mice, the dorsal skin was collected at seven weeks of age, while in the 7- to 8week-old mice, it was collected at 12 and 24weeks of age. In the former group, both the pore size of the hair follicles (HFs) and diameter of the hair shaft of telogen HFs decreased upon OVX; while in the latter group, these factors increased significantly. Notably, the thickness of the dermis and subcutis increased significantly in the OVX group. It needs to be further elucidated whether OVX mouse could serve as an ideal mouse model for FPHL, but our results upon evaluation of skin thickness indicate that it could be used to establish a novel treatment for non-hair-related diseases, such as post-menopause-related skin condition.

MiR-129-5p Participates in Hair Follicle Growth by Targeting HOXC13 in Rabbit.

Mammalian hair formation is critically determined by the growth of hair follicles (HF). MiRNAs are crucial in the periodic development of hair follicles; they maintain epidermal homeostasis by targeting genes and influencing the activity of signaling pathways and related regulators. Our study discovered miR-129-5p to be overexpressed in the skin of Angora rabbits during catagen, and was negatively correlated with HOXC13 expression (Pearson’s R = −0.313, p < 0.05). The dual-Luciferase reporter gene detection system and Western blotting confirmed that miR-129-5p targeted HOXC13. In addition, miR-129-5p overexpression was found to significantly inhibit the expression of hair follicle development-related genes (HFDRGs), such as BCL2, WNT2, CCND1, and LEF1 (p < 0.01), and promoted the expression of SFRP2, TGF-β1, and FGF2 (p < 0.01), which was the same as the knockdown of HOXC13. In contrast, the knockout of miR-129-5p was the opposite, and it demonstrated similar results to the overexpression of HOXC13. CCK8 and flow cytometry demonstrated that miR-129-5p mimics significantly promoted the apoptosis of dermal papilla cells (DPCs) and inhibited proliferation (p < 0.01), while the inhibitor was found to reduce the apoptosis of DPCs and promote proliferation (p < 0.01). These results showed that miR-129-5p can participate in the periodic development of HF by targeting HOXC13, and it can induce apoptosis and inhibit proliferation of DPCs. These results will help to understand the role and mechanism of miR-129-5p in the periodic development of HF, and will provide support for subsequent studies, not only providing a theoretical basis for genetically improving the quality of hair in animals in the future, but also a new theory and method for diagnosing and treating hair loss in humans.

Effects of watercress extract fraction on R-spondin 1-mediated growth of human hair.

Hair loss and greying affect men and women of all ages, often causing psychosocial difficulties. Dickkopf-1 (DKK1), a major hair loss factor secreted from dermal papilla (DP) cells in response to the secretion of dihydrotestosterone (DHT), has been reported to induce and accelerate androgenetic alopecia (AGA). In addition, DKK1 acts as a potent suppressor of melanogenesis and is closely related to hair colour. R-spondin 1 (RSPO1) is a secretory agonist of Wnt signalling known to antagonize the effects of DKK1, including DKK1-mediated hair follicle suppression. In this study, we investigated the effect of watercress extract (WCE) on the secretion of RSPO1 and DKK1 from DP cells as well as its anti-hair loss effect in human hair follicles and patients. The in vitro secretion of RSPO1 and DKK1 was measured by ELISA. Human hair follicles were collected from the scalp of a female donor and used for ex vivo organ culture to investigate the effects of WCE on human hair loss. Finally, a 6-month human clinical trial was conducted to examine the effect of WCE-containing lotion on hair growth in a male panel. WCE significantly upregulated RSPO1secretion and suppressed DKK1secretion in a dose-dependent manner, even in the presence of DHT. WCE-treated hair follicles elongated 1.6-fold compared with the control, and the level of RSPO1 production in DP as well as RSPO1 bound to the outer root sheath (ORS) increased. In the clinical trial, the hair lotion containing 2% WCE increased hair thickness and density to improve against hair loss symptoms. WCE exhibited a strong anti-androgenic effect through its ability to suppress DKK1secretion and antagonize DKK1 via RSPO1. These findings highlighted the potential use of WCE for the treatment of hair loss.

Single-cell sequencing reveals the new existence form of dermal papilla cells in the hair follicle regeneration of cashmere goats.

The problem of human hair loss has caused widespread concern, however, such research is difficult because the periodicity is not obvious and the deeper levels knowledge of dermal papilla (DP) stem cells' differentiation are limited. Here, cashmere goats which have obvious periodicity of hair follicles were used, based on unbiased scRNA sequencing, we constructed DP cell lineage differentiation trajectory and revealed the key genes, signals and functions involved in cell fate decisions. And then we revealed the molecular landscape of hair follicle on regeneration. Revealed that DP cells differentiate into four intermediate cell states at different periodicity: Intermediate-cell-10 showed important functions in the growth and maintenance of cashmere; intermediate-cell-1 acting on apoptosis and cashmere shedding; intermediate-cell-0 initiated new follicular cycles, the migration of hair follicles and the occurrence of cashmere; and intermediate-cell-15 are suggested to be DP progenitor cells. In general, we provide new insights for hair regrowth. At the same time, it provides a new research ideas, directions and molecular landscape for the mechanism of dermal papilla cells.

Regulation of Cytokines and Dihydrotestosterone Production in Human Hair Follicle Papilla Cells by Supercritical Extraction-Residues Extract of Ulmus davidiana.

This study was conducted to examine the anti-hair loss mechanism of the supercritical fluid extraction-residues extract of Ulmus davidiana by the regulation of cytokine production and hormone function in human dermal follicle papilla cells (HDFPCs). To investigate the modulatory effects on H2O2-induced cytokines, we measured transforming growth factor-beta and insulin-like growth factor 1 secreted from HDFPCs. To investigate the regulatory effects of supercritical extraction-residues extract of Ulmus davidiana on dihydrotestosterone hormone production, cells were co-incubated with high concentrations of testosterone. The supercritical extraction-residues extract of Ulmus davidiana significantly inhibited the secretion of transforming growth factor-beta but rescued insulin-like growth factor 1 in a dose-dependent manner. The supercritical extraction-residues extract of Ulmus davidiana markedly reduced dihydrotestosterone production. These results suggest that the supercritical fluid extract residues of Ulmus davidiana and their functional molecules are candidates for preventing human hair loss.

Ticks, Hair Loss, and Non-Clinging Babies: A Novel Tick-Based Hypothesis for the Evolutionary Divergence of Humans and Chimpanzees.

Human straight-legged bipedalism represents one of the earliest events in the evolutionary split between humans (Homo spp.) and chimpanzees (Pan spp.), although its selective basis is a mystery. A carrying-related hypothesis has recently been proposed in which hair loss within the hominin lineage resulted in the inability of babies to cling to their mothers, requiring mothers to walk upright to carry their babies. However, a question remains for this model: what drove the hair loss that resulted in upright walking? Observers since Darwin have suggested that hair loss in humans may represent an evolutionary strategy for defence against ticks. The aim of this review is to propose and evaluate a novel tick-based evolutionary hypothesis wherein forest fragmentation in hominin paleoenvironments created conditions that were favourable for tick proliferation, selecting for hair loss in hominins and grooming behaviour in chimpanzees as divergent anti-tick strategies. It is argued that these divergent anti-tick strategies resulted in different methods for carrying babies, driving the locomotor divergence of humans and chimpanzees.

Current insight into the functions of microRNAs in common human hair loss disorders: a mini review.

Alopecia areata (AA) and Androgenic alopecia (AGA) are the most common multifactorial hair loss disorders that have a serious psychological impact on the affected individuals, while frontal fibrosing alopecia (FFA) is comparatively less common. However, due to the unknown etiology and the effect of many adverse factors, the prognosis of these conditions is challenging to predict. Moreover, no approved therapy has been available to date to prevent or treat these disorders. MicroRNAs (miRNAs) are a group of evolutionary conserved small non-coding RNA molecules with significant roles in the posttranscriptional gene regulation either through mRNA degradation or translational repression. A number of biological processes are controlled by these molecules, including cell growth and differentiation, proliferation, inflammation, immune responses, and apoptosis. Recently, a handful of studies have demonstrated the impact of miRNAs on common hair loss-related disorders; however, the exhaustive molecular mechanisms are still unclear. In this review, we discussed the functional implications of miRNAs in common hair loss-related disorders and addressed their efficacy to be used for theranostic purposes shortly.

Concealed Ovulation May Have Driven Breast Development from Puberty and Body Hair Loss in Humans

Concealed Ovulation May Have Driven Breast Development from Puberty and Body Hair Loss in Humans

Phytotherapeutic Interventions using Rodent Models of Hair Loss: Current Research and Future Strategy

Hair follicles are special additions to mammalian skin with intricate differentiation and growth characteristics. They constantly undergo cycles of regression and regeneration throughout the lifespan of animal. Several rodent models have been studied for androgenetic alopecia and alopecia areata in humans with only handful of products approved by United States Food and Drug Administration; topical minoxidil (men and women) and oral finasteride (only men) for hair loss indication. This review summarizes rodent models of human hair loss to emphasize their role in testing traditional medicinal plants as hair growth promoters. Review also discusses the mechanisms of action of various herbs. Currently, both natural and synthetic products are in use to remedy alopecia. Although, use of natural products has shown measurable efficacy, the option is open to test chemically synthesized active fractions of plants as monotherapy or polytherapy to facilitate approval by regulatory agencies. Overall, purpose of this review is to discuss the rodent models of efficacy and how modifications in herbal preparations may bring more alternatives and a better value to the products in future.

A mutation in MAP2 is associated with prenatal hair follicle density.

Hairlessness is usually a rare trait in pigs; however, in this study, we found hairless (HR) pigs at a relatively high frequency in 1 pig herd. We observed that, the lower hair shaft density of HR pigs could be mainly attributed to the lower hair follicle density, and during the embryonic period, d 39-45 were a critical stage for the formation of the hair follicle. In this regard, d 41 during gestation was a particularly important point. Hair follicle morphogenesis occurring at an early stage of embryo development is similar to humans and mice. Further analyses of association studies based on single-nucleotide polymorphism chip as well as sequence data, mRNA sequencing, immunohistochemistry, and comparative genomics demonstrated that microtubule-associated protein 2 (MAP2) is a key gene responsible for hair follicle density and 1 missense mutation of A-to-G at rs328005415 in MAP2, causing a valine-to-methionine substitution leads to the HR phenotype. Considering the high homology between pigs and humans, our research has some significance for the study of the mechanisms of skin development, hair morphogenesis, and hair loss in humans by showing that the pig may be a more appropriate model in which to study these processes.-Jiang, Y., Jiang, Y., Zhang, H., Mei, M., Song, H., Ma, X., Jiang, L., Yu, Z., Zhang, Q., Ding, X. A mutation in MAP2 is associated with prenatal hair follicle density.

Effects of a gintonin-enriched fraction on hair growth: an in vitro and in vivo study

BackgroundGinseng has been widely used as a health-promoting tonic. Gintonin present in ginseng acts as a lysophosphatidic acid (LPA) receptor ligand that activates six LPA receptor subtypes. The LPA6 subtype plays a key role in normal hair growth, and mutations in the LPA6 receptor impair normal human hair growth. Currently, human hair loss and alopecia are concerning issues that affect peoples' social and day-to-day lives. ObjectiveWe investigated the in vitro and in vivo effects of a gintonin-enriched fraction (GEF) on mouse hair growth. MethodsHuman hair follicle dermal papilla cells (HFDPCs) and six-week-old male C57BL/6 mice were used. The mice were divided into the four groups: control, 1% minoxidil, 0.75% GEF, and 1.5% GEF. The dorsal hair was removed to synchronize the telogen phase. Each group was treated topically, once a day, for 15 days. We analyzed hair growth activity and histological changes. ResultsGEF induced transient [Ca2+]i, which stimulated HFDPC proliferation and caused 5-bromo-2′-deoxyuridine (BrdU) incorporation in a concentration-dependent manner. GEF-mediated HFDPC proliferation was blocked by the LPA receptor antagonist and Ca2+ chelator. HFDPC treatment with GEF stimulated vascular endothelial growth factor release. Topical application of GEF and minoxidil promoted hair growth in a dose-dependent manner. Histological analysis showed that GEF and minoxidil increased the number of hair follicles and hair weight. ConclusionTopical application of GEF promotes mouse hair growth through HFDPC proliferation. GEF could be one of the main components of ginseng that promote hair growth and could be used to treat human alopecia.

Research on the Balance of Thiol-Disulfide in Blood Serum in Women with Telogen Effluvium.

Backgrounds:Telogen effluvium (TE) is the most common reason for hair loss in humans. Although the exact etiopathogenesis of TE has not been revealed clearly and completely, multifactorial etiologies are to be blamed. In recent years, since oxidative stress (OS) has been shown to play an important role in the etiopathogenesis of so many diseases, the effects of OS on several skin diseases are researched and analyzed. Thiols are antioxidant components that include sulfur group, and the balance of thiol-disulfide has an important role in the formation and prevention of OS. This balance is destroyed in many diseases and its effect on TE is not clearly understood yet.Objectives:In this study, we aimed to search the thiol–disulfide balance that could reveal OS in patients with TE.Materials and Methods:Fifty-two patients with TE and control group of 46 persons were included in the study. Native thiol, disulfide, and total thiol levels were evaluated by a new, automatic spectrophotometric method. Disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol rates were calculated.Results:There was no statistical difference between TE patients and control group in terms of native thiol, disulfide, and total thiol levels. Thiol–disulfide balance was fixed and not affected in TE patients.

Hair Sciences: The Hypertrichosis Side Effect of Cyclosporine Is Mediated Through the Activation of the Anagen-Promoting Wnt/β-catenin Pathway

1. Vlad Ratushny, MD, PhD (vratushny{at}maderm.org) 1. Beverly, Massachusetts, USA ![Figure][1] The study reviewed in this month’s column is titled, “Identifying novel strategies for treating human hair loss disorders: cyclosporine A suppresses the Wnt inhibitor, SFRP1, in the