Pathogenesis Of Androgenetic Alopecia Research Articles

Causal effects of omega-6 and LDL-C on androgenetic alopecia: A Mendelian randomization study.

Increasing studies have reported a causal relationship between androgenetic alopecia (AGA) and lipid-related metabolites. However, the relationships between HDL-C, LDL-C, Omega-6, and Omega-3 with AGA remain unclear. Some research findings are even contradictory. Therefore, we designed this study to explore this issue. In this study, we selected seven exposure factors, screened SNPs with significant associations, removed linkage disequilibrium and weak instrumental variables, and conducted bidirectional MR analysis. The study found that omega-6 and LDL-C, especially total cholesterol in medium LDL and total cholesterol in small LDL, are risk factors for the occurrence of androgenetic alopecia. In summary, we found that various lipid-related metabolites have a causal relationship with the occurrence of androgenetic alopecia, providing new insights into the pathogenesis of androgenetic alopecia and offering references for clinical treatment of androgenetic alopecia.

Network Pharmacology Reveals Curcuma aeruginosa Roxb. Regulates MAPK and HIF-1 Pathways to Treat Androgenetic Alopecia.

Androgenetic alopecia (AGA) is the most prevalent hair loss disorder worldwide, driven by excessive sensitivity or response to androgen. Herbal extracts, such as Curcuma aeruginosa Roxb., have shown promise in AGA treatment due to their anti-androgenic activities and hair growth effects. However, the precise mechanism of action remains unclear. Hence, this study aims to elucidate the active compounds, putative targets, and underlying mechanisms of C. aeruginosa for the therapy of AGA using network pharmacology and molecular docking. This study identified 66 bioactive compounds from C. aeruginosa, targeting 59 proteins associated with AGA. Eight hub genes were identified from the protein-protein interaction network, namely, CASP3, AKT1, AR, IL6, PPARG, STAT3, HIF1A, and MAPK3. Topological analysis of components-targets network revealed trans-verbenol, myrtenal, carvone, alpha-atlantone, and isoaromandendrene epoxide as the core components with potential significance in AGA treatment. The molecular docking verified the binding affinity between the hub genes and core compounds. Moreover, the enrichment analyses showed that C. aeruginosa is involved in hormone response and participates in HIF-1 and MAPK pathways to treat AGA. Overall, this study contributes to understanding the potential anti-AGA mechanism of C. aeruginosa by highlighting its multi-component interactions with several targets involved in AGA pathogenesis.

Association between PITX2 polymorphism and androgenetic alopecia in the Indian population.

Background Androgenetic alopecia, also known as male pattern baldness, is a common form of hair loss influenced by environmental, hormonal, and genetic factors. According to recent research, the PITX2 gene may play a key role in the pathophysiology of androgenetic alopecia (AGA). Objective This study examines the association between genetic variants of the PITX2 gene and AGA risk. Methods The genomic DNA was extracted from peripheral blood samples collected from 70 male AGA patients and 60 non-androgenetic alopecia controls. The isolated DNA was quantified and the genotype for three PITX2 polymorphisms (rs2200733, rs10033464, and rs13143308) was identified using TaqMan assays. The statistical analysis was done to determine the allele frequency of genetic variants between AGA and non-AGA groups. Result The demographic profile of the study population showed that the AGA and non-AGA groups differed in age. The AGA group had higher blood pressure, a higher prevalence of smoking, alcohol consumption, metabolic syndrome, insulin resistance, and a higher incidence of family history. Through genetic analysis, significant correlations were found between AGA risk and specific PITX2 polymorphisms, significantly with the rs2200733 allele (OR = 6.08, p < 0.001*), the rs1003464 G allele (OR = 2.02, p < 0.019*) and the rs13143308 showed GT genotype (OR = 4.26, p < 0.001*). Conclusion Based on our findings, the PITX2 polymorphisms may play a vital role in the development of AGA. This study also found the interactions between genetic and environmental factors in AGA pathogenesis.

The evaluation of serum vitamin D3 in androgenetic alopecia: a case-control study

Background: Androgenetic alopecia (AGA) is a common hereditary condition characterized by progressive hair loss influenced by androgens. Vitamin D has been implicated in various hair disorders, yet its association with AGA, particularly in South Asian populations, remains inconclusive. Methods: We conducted a case-control study involving 100 male subjects from eastern Uttar Pradesh, India, comprising 50 AGA cases and 50 age-matched controls. Serum vitamin D levels were measured, and participants underwent clinical evaluations. Statistical analyses were performed using unpaired t tests and chi-square tests. Results: Vitamin D deficiency (&lt;20 ng/ml) was significantly more prevalent in AGA cases (56%) compared to controls (24%) (p&lt;0.001), with an odds ratio of 4.0303. Mean serum vitamin D levels were significantly lower in cases (33.1±10.6 ng/ml) than controls (40.3±9.51 ng/ml) (p=0.0005). Severe AGA cases exhibited lower vitamin D levels compared to mild to moderate cases, although the difference was not statistically significant (p=0.32). Conclusions: This study highlights the importance of vitamin D in AGA pathogenesis and suggests the need for routine monitoring of serum vitamin D levels in AGA patients. Further large-scale studies are warranted to confirm these findings and investigate the efficacy of vitamin D supplementation as a therapeutic intervention for AGA.

Study on the Efficacy and Potential Mechanism of Topical Shen Bai Hair Growing Decoction against Androgenetic Alopecia Based on Ultrahigh Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry and RNA-seq.

Androgenetic alopecia (AGA) is a major problem that can happen to people of all ages, leading to psychological problems, such as anxiety and depression. Topical Shen Bai hair growing decoction (TSBHGD) is based on the pathogenesis of AGA, combined with Traditional Chinese Medicine theory, improved by the Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital according to its clinical treatment experience. This study was designed to demonstrate the therapeutic efficacy of TSBHGD against AGA, analyze the chemical components of TSBHGD as well as the skin-retained and blood-retained components in mice after topical administration of TSBHGD, and clarify the mechanism of its therapeutic efficacy. It was demonstrated that TSBHGD could suppress TNF-α and IL-6 levels and improve pathological phenomena such as hair loss, reduced follicle density, and dermal thickness caused by testosterone solution. Totally 35 components were identified in TSBHGD extracts, 12 skin-retained components were identified in drug-containing skin, and 7 blood-retained components were identified in drug-containing plasma, according to ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. Transcriptomic sequencing revealed that some of the genes in AGA mice had altered expression patterns, which could be reversed by TSBHGD. Through network pharmacology analysis, it was found that TSBHGD mainly regulated eight signaling pathways, among which the apoptosis signaling pathway ranked first with a significance of 0.00149. Finally, both Bcl-2 and Caspase family proteins in the apoptosis signaling pathway were examined by Western blot. It was confirmed that TSBHGD could inhibit the apoptosis level in AGA mice's skin tissue to exert an anti-AGA effect. This will facilitate the development of new-generation herbal compound formulas with precise efficacy and provide novel ideas for AGA therapy.

Natural bioactive compounds as potential sources for alleviation and treatment of androgenetic alopecia: A research advance

AbstractAlopecia is a common chronic skin disease, which can be categorized as androgenetic alopecia (AGA), scarring line alopecia, genetic alopecia, and chemical alopecia due to the different reasons. Among which AGA caused by metabolism of the androgen system accounts for the majority. Due to the high prevalence of AGA and the lack of an effective cure, the urgent search for a safe and effective anti‐AGA drug has been our aim. With the advantages of its own wide source and low toxicity and side effects, the use of natural bioactive compounds and their extracts in the treatment of AGA has been a research hotspot. The objective of this work is to compile and synthesize experimental findings on natural bioactive compounds that possess the potential to alleviate AGA. On the basis of the known pathogenesis of AGA, combined with the target analysis of AGA by network pharmacology, identify natural bioactive compounds and their signaling pathways for the treatment of alopecia and hair growth promotion, and select representative hotspot compounds, to reveal their specific mechanisms and abstract the commonalities. Based on previous extensive research, hundreds of AGA targets (e.g., Wnt, TGF, and VEGF) closely regulate neogenesis, tissue development, and vascular function, to collect and summarize compounds such as ginseng, baicalein, curcumin, and so on, which have great potential to improve hair growth. Our work will inspire future research based on their mechanisms of action, providing more complete evidence and ideas for the feasibility of developing natural anti‐AGA drugs.

Efficacy of derinat as a treatment for murine and androgenetic alopecia (AGA) patients

BackgroundAndrogenetic alopecia (AGA), one of the most common types of hair loss, is associated with oxidative stress, inflammation and aging. Derinat, a transient receptor potential canonical channels (TRPCs) inhibitor, restrains TRPCs-mediated increase intracellular Ca2+ signaling, which initiates the skin aging process with intracellular reactive oxygen species (ROS) accumulation. This study investigated whether Derinat protected skin from oxidative stress-induced damage and aging, thus inhibiting AGA pathogenesis.MethodsThe lifespan of Caenorhabditis elegans was measured to examine the capacity of Derinat to oppose the oxidative stress induced-aging process, which drives the hair cycle from anagen to catagen phase. The experiments that used BALB/c-nu and C57BL/6 mice determined the effects of Derinat on hair cycle and oxidative stress in skin. To further apply Derinat to clinical study, the resulting relationship between AGA pathogenesis and TRPCs-regulated oxidative stress was confirmed using the bioinformatics approach. We consequently used the parameters of hair density, hair diameter, hair recovery and quality of life index to evaluate the effect of Derinat treatment on AGA subjects.ResultsDerinat restrained the oxidative stress induced-aging process sufficiently to extend the lifespan of worms. Derinat also changed the hair growth patterns of mice by maintenance of the hair cycle at the anagen phase. This efficacy was due to reduction of TRPCs-mediated ROS accumulation. Because the bioinformatics analysis found that AGA pathogenesis is associated with TRPCs-regulated oxidative stress and inflammation, treatment with Derinat in AGA subjects increased positive outcomes of oral medication while mitigating the impairment of AGA subjects’ quality of life.ConclusionsDerinat restrains AGA pathogenesis and may provide a new therapeutic approach for treating AGA. ClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov, date of registration 07/11/2022.Trial registrationClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov, date of registration 07/11/2022

Adipose transcriptome in the scalp of androgenetic alopecia.

Previous studies have shown how adipocytes can modulate the activity of hair follicle stem cells. However, the role of adipocytes in the pathogenesis of androgenetic alopecia (AGA) remains unknown. We aimed to determine signaling pathways related to the adipose tissue changes in the human scalp with AGA through RNA-seq analysis. RNA was isolated from the adipose tissues derived from the bald (frontal) and normal (occipital) scalps of male patients with AGA (n = 4). The pooled RNA extracts from these samples were subjected to RNA sequencing, followed by differential gene expression and pathway analysis. Our gene expression analysis identified 1,060 differentially expressed genes, including 522 upregulated and 538 downregulated genes in the bald AGA scalp. Biological pathways pertaining to either adipose tissue metabolism or the hair cycle were generated in our pathway analysis. Downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway was noted to be significant in the bald scalp. Expression of adipogenic markers (e.g., PPARG, FABP4, PLN1, and ADIPOQ) was also decreased in the bald site. These findings imply that adipogenesis becomes downregulated in AGA, specifically within the bald scalp adipose. Our results lead to the hypothesis that PPARγ-mediated adipogenesis in the scalp adipose, via crosstalk with signaling pathways involved in hair cycling, might play a role in AGA.

Bioinformatic analysis of gene expression data reveals Src family protein tyrosine kinases as key players in androgenetic alopecia.

Androgenetic alopecia (AGA) is a common progressive scalp hair loss disorder that leads to baldness. This study aimed to identify core genes and pathways involved in premature AGA through an in-silico approach. Gene expression data (GSE90594) from vertex scalps of men with premature AGA and men without pattern hair loss was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the bald and haired samples were identified using the limma package in R. Gene ontology and Reactome pathway enrichment analyses were conducted separately for the up-regulated and down-regulated genes. The DEGs were annotated with the AGA risk loci, and motif analysis in the promoters of the DEGs was also carried out. STRING Protein-protein interaction (PPI) and Reactome Functional Interaction (FI) networks were constructed using the DEGs, and the networks were analyzed to identify hub genes that play could play crucial roles in AGA pathogenesis. The in-silico study revealed that genes involved in the structural makeup of the skin epidermis, hair follicle development, and hair cycle are down-regulated, while genes associated with the innate and adaptive immune systems, cytokine signaling, and interferon signaling pathways are up-regulated in the balding scalps of AGA. The PPI and FI network analyses identified 25 hub genes namely CTNNB1, EGF, GNAI3, NRAS, BTK, ESR1, HCK, ITGB7, LCK, LCP2, LYN, PDGFRB, PIK3CD, PTPN6, RAC2, SPI1, STAT3, STAT5A, VAV1, PSMB8, HLA-A, HLA-F, HLA-E, IRF4, and ITGAM that play crucial roles in AGA pathogenesis. The study also implicates that Src family tyrosine kinase genes such as LCK, and LYN in the up-regulation of the inflammatory process in the balding scalps of AGA highlighting their potential as therapeutic targets for future investigations.

The Association of Serum Adipokines, Insulin Resistance and Vitamin D Status in Male Patients with Androgenetic Alopecia.

The frequent coexistence of obesity and metabolic syndrome in patients with Androgenetic alopecia (AGA), may indicate a common pathogenetic pathway with adipokines being a possible implicating cytokine. This study was conducted to investigate the changes in serum levels of adipokines, insulin resistance, vitamin D status and their relationship with AGA, and the relationship between serum levels of adipokines and insulin resistance. 80 male patients with AGA were selected as the experimental group and 60 healthy males served as the control group. Both the AGA group and healthy control group were divided into 2 groups according to the presence or absence of insulin resistance (IR): the IR group and the NIR group. Serum levels of leptin, adiponectin, resistin, visfatin, insulin and 25(OH)D were evaluated in all subjects. Compared with the control group, AGA patients showed higher serum levels of leptin and lower adiponectin/leptin (Adpn/Lep) ratio (P<0.05), and both were positively correlated with the severity of the disease. Compared with the AGA NIR group, serum leptin levels were increased in the AGA IR group (P<0.05). AGA IR group and AGA NIR group possessed lower Adpn/Lep ratio when compared with the healthy IR group and healthy NIR group respectively (P<0.05). The multi-factor logistic regression analysis results showed decreased Adpn/Lep level and increased leptin level as risk factors for AGA. AGA Patients had lower vitamin D levels than healthy controls (P<0.05). Patients with AGA show an imbalance between pro- and anti-inflammatory adipokines, and probably be involved in AGA pathogenesis. Insulin resistance may influence levels of adipokines, but the present findings cannot indicate insulin resistance plays a role in the onset of AGA. The insufficiency and deficiency of vitamin D are common health concern in our subjects and may be involved in the dysfunction of adipocytes and the development of AGA.

Investigation of hub genes and immune infiltration in androgenetic alopecia using bioinformatics analysis

Androgenetic alopecia (AGA) is a type of non-scarring hair loss. Current drugs for AGA are accompanied by adverse reactions and a high recurrence rate. Thus, the discovery of diagnostic biomarkers and therapeutic targets for AGA remains imperatively warranted. The GSE90594 dataset, which contained scalp skin biopsies from 14 male AGA cases and healthy volunteers, was used to identify the differentially expressed genes (DEGs). Functional enrichment analysis was subsequently performed. Next, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database combined with the cytoHubba plugin of Cytoscape were used to obtain the key genes of AGA. Thereafter, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was performed to evaluate the relative abundance of immune cells between male AGA patients and healthy controls. The correlation between key genes and infiltrating immune cells was analyzed to obtain the significant immune-cell related genes (IRGs), then intersected with the DEGs between immortalized balding and non-balding human dermal papilla cells (DPCs) of the GSE93766 dataset as well as the DEGs obtained by the GSE90594 dataset, thus obtaining the hub genes of AGA. Finally, the hub genes were validated using GSE36169, which contained expression profiling of tissues biopsied from haired and bald scalps of five individuals with AGA. A total of 234 DEGs were obtained from the GSE90594 dataset, which were mainly enriched in the extracellular matrix (ECM)-related pathways and immune-related activities. The STRING database and ten algorithms in the cytoHubba plugin of Cytoscape disclosed 21 key DEGs. The results of the CIBERSORT algorithm revealed the relative abundances of 20 kinds of immune cells between diseased and healthy individuals, and yielded 15 IRGs involved in the pathogenesis of AGA. Next, the intersection analysis identified four hub genes of AGA, comprising COL1A2, PCOLCE, ITGAX, and LOX. The GSE36169 dataset validated the expression pattern of hub genes in the haired scalp of AGA patients. We discovered that the hub genes identified are closely linked with the causative factors of AGA, which could be used as the viable diagnostic and therapeutic target in the clinical applications.

279 The use of PRP to target dysregulated pathways in androgenetic alopecia

Androgenetic alopecia (AGA) is the most common type of progressive hair loss; however, its treatment remains limited in scope, thus driving the need for alternative therapies for hair restoration. The pathogenesis of androgenetic alopecia is not completely understood but involves disruption of the Wnt/β-catenin signaling pathway, resulting in premature termination of the anagen growth phase in hair follicles. This manifests clinically as the transformation of terminal hair into thinner vellus-like hair, a process known as hair follicle miniaturization.

Pathogenesis of Androgenetic Alopecia

The pathogenesis of androgenetic alopecia (AGA) is a complex interplay of genetic, hormonal, and environmental factors. In scalp follicles of susceptible individuals, androgens promote miniaturization of hair and shorten hair growth in the anagen stage, ultimately leading to AGA. The major circulating androgen, testosterone, is converted to the more potent androgen dihydrotestosterone by the enzyme 5α-reductase (5αR). Androgen receptors (ARs) and 5αR are significantly more in balding scalp hair follicles than those from nonbalding follicles. Genetic predisposition plays a crucial role in AGA. Various genetic loci including AR gene and the ectodysplasin A2 receptor (EDA2R) (AR/EDA2R locus in Xq11-q12) have been strongly implicated. The basic pathology of AGA is progressive miniaturization of the terminal hair follicles and eventual conversion of terminal hair to vellus hair. The duration of the anagen phase diminishes progressively with each cycle, while the length of telogen phase remains constant or may be prolonged. This eventually results in a reduction of the anagen to telogen ratio. With each successive shortening of hair cycle, the length of each hair shaft is reduced, and it becomes too short for the growing hair to attain even the minimum length required to reach the skin surface, resulting in an empty follicular pore. Hair follicle miniaturization leads to conversion of terminal hairs into secondary vellus hairs. Although many mechanisms have been proposed, the actual mechanism of hair miniaturization has not yet been fully elucidated. This article attempts to collate the existing information regarding the pathogenesis of AGA.

Expression of Signal Transducer and Activator of Transcription-3 in Androgenetic Alopecia: A Case-Control Study

Background: Signal transducer and activator of transcription (STAT)-3 belongs to a group of latent transcription factors phosphorylated and activated by several protein tyrosine kinases, including members of Janus kinases (JAKs) family. It has been implicated that the JAK-STAT pathway activation could promote quiescence in the hair cycle, and topical treatment of mouse and human skin with JAK inhibitors was shown to result in rapid hair growth. Objective: Our aim was to assess the tissue expression of STAT3 in patients with androgenetic alopecia and correlate it with disease severity and clinical parameters. Methods: Twenty-five androgenetic alopecia patients who served as both cases and controls were included in this study. Full clinical examination was done and tissue STAT3 gene expression was then measured by real-time polymerase chain reaction. Results: Scalp tissue affected by androgenetic alopecia shows significantly higher STAT3 gene expression levels compared to unaffected (androgen independent) areas (p < 0.001), but no statistically significant relation was found between tissue STAT3 expression level and severity of hair loss (p = 0.660). Limitations: Limited sample size. Conclusion: This study demonstrated an upregulation in STAT3 gene expression in androgenetic alopecia. Further studies are needed to assess the possible role of the JAK-STAT pathway in the pathogenesis of androgenetic alopecia.

Treatment of Androgenetic Alopecia Using PRP to Target Dysregulated Mechanisms and Pathways.

Androgenetic alopecia (“AGA”) is the most prevalent type of progressive hair loss, causing tremendous psychological and social stress in patients. However, AGA treatment remains limited in scope. The pathogenesis of androgenetic alopecia is not completely understood but is known to involve a hair follicle miniaturization process in which terminal hair is transformed into thinner, softer vellus-like hair. This process is related to the dysregulation of the Wnt/β-catenin signaling pathway, which causes premature termination of the anagen growth phase in hair follicles. Historically used for wound healing, platelet rich plasma (“PRP”) has recently been at the forefront of potential AGA treatment. PRP is an autologous preparation of plasma that contains a high number of platelets and their associated growth factors such as EGF, IGF-1, and VEGF. These factors are known to individually play important roles in regulating hair follicle growth. However, the clinical effectiveness of PRP is often difficult to characterize and summarize as there are wide variabilities in the PRP preparation and administration protocols with no consensus on which protocol provides the best results. This study follows the previous review from our group in 2018 by Cervantes et al. to analyze and discuss recent clinical trials using PRP for the treatment of AGA. In contrast to our previous publication, we include recent clinical trials that assessed PRP in combination or in direct comparison with standard of care procedures for AGA such as topical minoxidil and/or oral finasteride. Overall, this study aims to provide an in-depth analysis of PRP in the treatment of AGA based on the evaluation of 17 recent clinical trials published between 2018 and October 2021. By closely examining the methodologies of each clinical trial included in our study, we additionally aim to provide an overall consensus on how PRP can be best utilized for the treatment of AGA.

Observations that suggest a contribution of altered dermal papilla mitochondrial function to androgenetic alopecia.

Androgenetic alopecia (AGA) is a prevalent hair loss condition in males that develops due to the influence of androgens and genetic predisposition. With the aim of elucidating genes involved in AGA pathogenesis, we modelled AGA with three-dimensional culture of keratinocyte-surrounded dermal papilla (DP) cells. We co-cultured immortalised balding and non-balding human DP cells (DPCs) derived from male AGA patients with epidermal keratinocyte (NHEK) using multi-interfacial polyelectrolyte complexation technique. We observed up-regulated mitochondria-related gene expression in balding compared with non-balding DP aggregates which indicated altered mitochondria metabolism. Further observation of significantly reduced electron transport chain complex activity (complexes I, IV and V), ATP levels and ability to uptake metabolites for ATP generation demonstrated compromised mitochondria function in balding DPC. Balding DP was also found to be under significantly higher oxidative stress than non-balding DP. Our experiments suggest that application of antioxidants lowers oxidative stress levels and improves metabolite uptake in balding DPC. We postulate that the observed up-regulation of mitochondria-related genes in balding DP aggregates resulted from an over-compensatory effort to rescue decreased mitochondrial function in balding DP through the attempted production of new functional mitochondria. In all, our three-dimensional co-culturing revealed mitochondrial dysfunction in balding DPC, suggesting a metabolic component in the aetiology of AGA.

Weekly treatment with SAMiRNA targeting the androgen receptor ameliorates androgenetic alopecia

Androgenetic alopecia (AGA) is the most common type of hair loss in men and women. Dihydrotestosterone (DHT) and androgen receptor (AR) levels are increased in patients with AGA, and DHT-AR signaling correlates strongly with AGA pathogenesis. In this study, treatment with self-assembled micelle inhibitory RNA (SAMiRNA) nanoparticle-type siRNA selectively suppressed AR expression in vitro. Clinical studies with application of SAMiRNA to the scalp and massaging to deliver it to the hair follicle confirmed its efficacy in AGA. For identification of a potent SAMiRNA for AR silencing, 547 SAMiRNA candidates were synthesized and screened. SAMiRNA-AR68 (AR68) was the most potent and could be efficiently delivered to human follicle dermal papilla cells (HFDPCs) and hair follicles, and this treatment decreased the AR mRNA and protein levels. We confirmed that 10 µM AR68 elicits no innate immune response in human PBMCs and no cytotoxicity up to 20 µM with HFDP and HaCaT cells. Clinical studies were performed in a randomized and double-blind manner with two different doses and frequencies. In the low-dose (0.5 mg/ml) clinical study, AR68 was applied three times per week for 24 weeks, and through quantitative analysis using a phototrichogram, we confirmed increases in total hair counts. In the 24-week long high-dose (5 mg/ml) clinical study, AR68 showed average additional hair growth of 1.3-1.9 hairs/cm2 per month, which is comparable to finasteride. No side effects were observed. Therefore, SAMiRNA targeting AR mRNA is a potential novel topical treatment for AGA.

Up-regulation of androgen receptor by heat shock protein 27 and miR-1 induces pathogenesis of androgenic alopecia.

The pathogenesis of androgenetic alopecia (AGA) is related to the level of androgen and its metabolic pathways. The binding of androgen and androgen receptor (AR) depends on the assistance of heat shock protein 27 (HSP27). HSP27 combined with microRNAs (miR)-1 can regulate AR levels. However, it is not clear whether HSP27 and miR-1 jointly participate in the pathogenesis of AGA. This study aims to investigate the role of AR up-regulation in the pathogenesis of AGA and underlying mechanisms. A total of 46 male AGA patients (AGA group), who admitted to the First Affiliated Hospital of Guangzhou Medical University from September 2019 to February 2020, and 52 healthy controls admitted to the same period were enrolled in this study. Serum levels of dihydrotestosterone (DHT) and HSP27 in patients and healthy controls were measured by ELISA. Western blotting was used to detect the protein expression of HSP27 and AR in scalp tissues of patients and the healthy controls. The levels of HSP27, AR, and miR-1 were analyzed using real-time PCR. Human dermal papilla cells were transfected with HSP27 siRNA to inhibit the expression of HSP27. MiR-1 and miR-1 inhibitors were transfected simultaneously or separately into cells and then the changes in AR protein expression were detected. The levels of DHT and HSP27 in the AGA group were (361.4±187.7) pg/mL and (89.4±21.8) ng/mL, respectively, which were higher than those in the control group [(281.8±176.6) pg/mL and (41.2±13.7) ng/mL, both P<0.05]. However, there was no significant difference in serum HSP27 and AR levels among AGA patients with different degrees of hair loss (P>0.05). Correlation analysis showed that there was a positive correlation between HSP27 level and DHT level in the AGA patients (P<0.05). The level of HSP27 mRNA in scalp tissue was negatively correlated with that of miR-1 mRNA (P<0.05). Compared with the control group, the levels of HSP27 protein, AR protein, HSP27 mRNA, and AR mRNA in scalp tissues of AGA group were significantly increased (P<0.05). The up-regulation of HSP27 in scalp tissues of AGA patients was closely related to the increased levels of AR. However, the level of miR-1 in scalp tissues of AGA patients was significantly down-regulated, contrary to the expression of AR (P<0.05). Further in cell studies showed that inhibition of HSP27 or miR-1 expression in human dermal papilla cells could inhibit the expression of AR, and inhibition of both HSP27 and miR-1 expression was found to have an accumulative effect on AR, with statistically significant differences (all P<0.05). HSP27 could combine with miR-1 to up-regulate AR levels, which is closely related to the development of AGA.

Clinical Evaluation of Intradermal Platelet Rich Plasma Administration along with Oral Biotin Supplement for the Management of Androgenetic Alopecia in Adult Males: A Randomised Clinical Tria

Introduction: Androgenetic Alopecia (AA) is characterised by progressive-patterned hair loss from the scalp affecting males and females alike. Miniaturisation of the hair follicle with associated hereditary tendency is one of the major primary causal factors for the pathogenesis of AA. Various treatment modalities have been proposed for the management of AA including minoxidil, finastride, etc.; however, they are associated with known side-effects. Aim: To evaluate the effect of intradermal Platelet Rich Plasma (PRP) administration, along with oral biotin supplement for the management of AA in males. Materials and Methods: The present randomised clinical study was conducted at Department of Dermatology, B.J. Medical College and Hospital, Ahmedabad, Gujarat, India from January 2012 to May 2013. A total of 40 healthy adult males of Indian origin, with a history of hair loss, completed the 12 month trial. They were equally randomised into two groups. Subjects enrolled in group A (n=20) received intradermal administration of autologous PRP, every 15 days for three months along with oral biotin tablets, once daily for three months, while those in group B (n=20) received oral biotin tablets, once daily for three months. Hair regrowth was evaluated using a standardised 7-point rating scale at 3, 6, 9 and 12 months intervals, by the same investigator. Chi-square test was used to statistically assess the data. The p-value for significance was established at &lt;0.05. Results: Individuals in group A had mean age of 32.3±6.1 years and showed statistically significant (p-value &lt;0.05) increase in hair regrowth at 6 months, 9 and 12 months; compared to Group B with mean age of 30.7±5.2 years. Conclusion: Intradermal administration of PRP along with oral biotin tablet supplementation resulted in a statistically significant increase in hair regrowth, without any remarkable side-effects. PRP is a safe and effective treatment modality in adult males, with AA.

Serum Paroxonase 1 level may be an Indicator and Predictor of the Severity of Androgenetic Alopecia

Background:Androgenetic alopecia (AGA) is a common stressful form of hair loss caused by androgen excess, genetic factors, and exposure to oxidative stress (OS) with the formation of reactive oxygen species (ROS). Paraoxonase 1 (PON1) is an enzyme synthesized in the liver bound to high-density lipoproteins to prevent lipid peroxidation.Aim:The aim of our work is to estimate serum PON1 level in patients with AGA and correlate its levels with disease severity which may help in determining if there is a role of ROS in pathogenesis of AGA.Subjects and Methods:This study was carried out as a case and control on 40 patients with AGA (diagnosed by typical clinical and dermoscopic finding) versus 40 control subjects. Blood samples were taken from all subjects to assess serum PON1enzyme using enzyme-linked immunosorbent assay kits.Results:There was a significant decrease in serum PON1 concentration level in AGA patients in comparison to controls, in addition, there was a significant decrease correlated with AGA severity (P < 0,001). The study proved that PON1 is considered highly sensitive and specific for AGA cases and a good predictive factor of AGA in healthy subjects.Conclusion:This is the first study done to reveal that the level of PON1 significantly decreased in AGA patients, which may give additional proof that OS has role in the pathogenesis of AGA and hence may help in the management of AGA by adding antioxidants in treatment.