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ELife Mar 2024The etiology of hair loss remains enigmatic, and current remedies remain inadequate. Transcriptome analysis of aging hair follicles uncovered changes in immune pathways,...
The etiology of hair loss remains enigmatic, and current remedies remain inadequate. Transcriptome analysis of aging hair follicles uncovered changes in immune pathways, including Toll-like receptors (TLRs). Our findings demonstrate that the maintenance of hair follicle homeostasis and the regeneration capacity after damage depend on TLR2 in hair follicle stem cells (HFSCs). In healthy hair follicles, TLR2 is expressed in a cycle-dependent manner and governs HFSCs activation by countering inhibitory BMP signaling. Hair follicles in aging and obesity exhibit a decrease in both TLR2 and its endogenous ligand carboxyethylpyrrole (CEP), a metabolite of polyunsaturated fatty acids. Administration of CEP stimulates hair regeneration through a TLR2-dependent mechanism. These results establish a novel connection between TLR2-mediated innate immunity and HFSC activation, which is pivotal to hair follicle health and the prevention of hair loss and provide new avenues for therapeutic intervention.
Topics: Humans; Hair Follicle; Toll-Like Receptor 2; Hair; Alopecia
PubMed: 38483447
DOI: 10.7554/eLife.89335 -
Journal of Microbiology and... Apr 2024Phloroglucinol (PG) is one of the abundant isomeric benzenetriols in brown algae. Due to its polyphenolic structure, PG exhibits various biological activities. However,...
Phloroglucinol (PG) is one of the abundant isomeric benzenetriols in brown algae. Due to its polyphenolic structure, PG exhibits various biological activities. However, the impact of PG on anagen signaling and oxidative stress in human dermal papilla cells (HDPCs) is unknown. In this study, we investigated the therapeutic potential of PG for improving hair loss. A non-cytotoxic concentration of PG increased anagen-inductive genes and transcriptional activities of β-Catenin. Since several anagen-inductive genes are regulated by β-Catenin, further experiments were performed to elucidate the molecular mechanism by which PG upregulates anagen signaling. Various biochemical analyses revealed that PG upregulated β-Catenin signaling without affecting the expression of Wnt. In particular, PG elevated the phosphorylation of protein kinase B (AKT), leading to an increase in the inhibitory phosphorylation of glycogen synthase kinase 3 beta (GSK3β) at serine 9. Treatment with the selective phosphoinositide 3-kinase/AKT inhibitor, LY294002, restored the increased AKT/GSK3β/β-Catenin signaling and anagen-inductive proteins induced by PG. Moreover, conditioned medium from PG-treated HDPCs promoted the proliferation and migration of human epidermal keratinocytes via the AKT signaling pathway. Subsequently, we assessed the antioxidant activities of PG. PG ameliorated the elevated oxidative stress markers and improved the decreased anagen signaling in hydrogen peroxide (HO)-induced HDPCs. The senescence-associated β-galactosidase staining assay also demonstrated that the antioxidant abilities of PG effectively mitigated HO-induced senescence. Overall, these results indicate that PG potentially enhances anagen signaling and improves oxidative stress-induced cellular damage in HDPCs. Therefore, PG can be employed as a novel therapeutic component to ameliorate hair loss symptoms.
Topics: Humans; Phloroglucinol; Oxidative Stress; Hydrogen Peroxide; Signal Transduction; beta Catenin; Proto-Oncogene Proteins c-akt; Glycogen Synthase Kinase 3 beta; Phosphorylation; Hair Follicle; Dermis; Cell Proliferation; Cells, Cultured; Alopecia
PubMed: 38480001
DOI: 10.4014/jmb.2311.11047 -
International Journal of Molecular... Feb 2024Androgenetic alopecia is a highly prevalent condition mainly affecting men. This complex trait is related to aging and genetics; however, multiple other factors, for... (Review)
Review
Androgenetic alopecia is a highly prevalent condition mainly affecting men. This complex trait is related to aging and genetics; however, multiple other factors, for example, lifestyle, are also involved. Despite its prevalence, the underlying biology of androgenetic alopecia remains elusive, and thus advances in its treatment have been hindered. Herein, we review the functional anatomy of hair follicles and the cell signaling events that play a role in follicle cycling. We also discuss the pathology of androgenetic alopecia and the known molecular mechanisms underlying this condition. Additionally, we describe studies comparing the transcriptional differences in hair follicles between balding and non-balding scalp regions. Given the genetic contribution, we also discuss the most significant risk variants found to be associated with androgenetic alopecia. A more comprehensive understanding of this pathology may be generated through using multi-omics approaches.
Topics: Male; Humans; Hair Follicle; Alopecia; Genomics; Aging; Life Style
PubMed: 38473791
DOI: 10.3390/ijms25052542 -
Supportive Care in Cancer : Official... Mar 2024Scalp cooling is an increasingly recognized non-pharmacologic approach to minimize chemotherapy-induced alopecia (CIA). Several commercially available machine-based and...
BACKGROUND
Scalp cooling is an increasingly recognized non-pharmacologic approach to minimize chemotherapy-induced alopecia (CIA). Several commercially available machine-based and manual scalp cooling systems are available; however, literature reports of effectiveness are highly variable. The purpose of this study was to determine real-world tolerability and subjective effectiveness of a manual cold capping system in minimizing CIA across a variety of patient race and hair types. This study was a single-institution review of outcomes from manual cold capping.
METHODS
We identified retrospective cohort of adult patients who presented to discuss cold capping between January 14, 2019, and March 31, 2022. Data collected from medical records included demographics, decision to pursue/continue cold capping, diagnoses, chemotherapy regimens, hair characteristics (length, thickness, coarseness, type), and subjective perception of percentage of hair retained. Those with successful vs. unsuccessful cold capping (≥ 50% vs. < 50% of hair retained) were compared based on the patient-level factors of interest.
FINDINGS
A total of 100 patients initiated cold capping during the study period, and 95% of them completed cold capping. The majority of patients who started cold capping completed it. The median-reported percentage of hair maintained was 75%, and 82/89 (92.1% of patients) had favorable results, defined as ≥ 50% of hair retained. The only patient-level factor associated with favorable response was chemotherapy regimen, with fewer patients receiving doxorubicin-containing regimens having successful hair retention compared to other chemotherapy types (71.4% successful results vs. 95.7% for those receiving paclitaxel-containing regimens and 96.6% for those receiving docetaxel-containing regimens (p = 0.018). There was no difference in success based on patient race/ethnicity or hair characteristics.
INTERPRETATION
The overall effectiveness (92.1%) in this study is consistent to higher than many literature reports. One possible reason for the high success in our cohort is compliance with cold capping protocols, meaning applying the cap in the appropriate manner and wearing the cap for the prescribed durations, which may impact effectiveness.
Topics: Adult; Animals; Humans; Spheniscidae; Hypothermia, Induced; Retrospective Studies; Scalp; Antineoplastic Combined Chemotherapy Protocols; Alopecia; Antineoplastic Agents
PubMed: 38472496
DOI: 10.1007/s00520-024-08393-7 -
La Tunisie Medicale Oct 2023Trachyonychia means rough, longitudinally ridged nails with a sandy, brittle and thin aspect. It is a rare condition that occurs mainly in children. Studies on...
INTRODUCTION
Trachyonychia means rough, longitudinally ridged nails with a sandy, brittle and thin aspect. It is a rare condition that occurs mainly in children. Studies on trachyonychia are rare. We aimed to describe the clinical aspects and outcome of trachyonychia, as well as its treatment.
CASES
Two boys aged 11 and 14 years old and a girl aged 6 years presented with nail dystrophy of the fingers and toes. Patient 1 had also a scaly patch on the glans penis, and patient 2 was atopic. Trachyonychia associated with psoriasis was suspected in patient 1 and the idiopathic form was retained in the other two patients. All patients were treated with topical steroids for a few months. The patients did not show any improvement at the six-month follow-up. Only one patient was contacted again after two years and showed spontaneous healing.
COMMENTARIES
The diagnosis of trachyonychia is mainly clinical. In the literature, 62% of pediatric patients had an idiopathic form. However, a strong association was observed between trachyonychia and alopecia areata. Trachyonychia of childhood appears to have a good prognosis, with spontaneous improvement within six months to two years. Therapeutic abstention is the rule.
Topics: Male; Female; Humans; Child; Adolescent; Nail Diseases; Alopecia Areata
PubMed: 38465760
DOI: No ID Found -
The Journal of Dermatological Treatment Dec 2024
Topics: Humans; Alopecia Areata; Azetidines; Recurrence; Phenotype; Alopecia; Purines; Pyrazoles; Sulfonamides
PubMed: 38465657
DOI: 10.1080/09546634.2024.2324832 -
Skin Research and Technology : Official... Mar 2024MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression in diverse biological processes. They hold promise as therapeutic candidates for targeting human...
BACKGROUND
MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression in diverse biological processes. They hold promise as therapeutic candidates for targeting human disease pathways, although our understanding of their gene regulatory mechanism remains incomplete. Alopecia areata (AA) is a prevalent inflammatory ailment distinguished by the infiltration of T cells targeting the anagen-stage hair follicles. The scarcity of effective remedies for AA may stem from limited understanding regarding its precise cellular mechanism.
AIM
To investigate and examine the importance and role of the miR-200c-3p as a genetic indicator for AA, and its possible impact on disease progression.
SUBJECTS AND METHODS
Case-control study included 65 patients with AA and 65 matched healthy controls. A real-time PCR technique was used to measure the expression of miR-200c-3p for both groups. Bioinformatic tools were used for prediction with genes and gene-gene interaction, and protein-protein interaction.
RESULTS
The expression levels of miR-200c-3p were significantly higher in AA patients than in healthy controls. We predicted that miR-200c-3p plays a markable role in the development of AA by its effect on the EGFR tyrosine kinase inhibitor resistance pathway.
CONCLUSION
We were able to identify the influence of miR-200c-3p on both PLCG1 and RPS6KP1 genes which in turn regulate the EGFR tyrosine kinases resistance pathway that displayed the most substantial increase in activity. Our outcomes shed light on the era of the potential theranostic role of this innovative miRNA in AA.
Topics: Humans; Alopecia Areata; Genetic Markers; Case-Control Studies; MicroRNAs; ErbB Receptors
PubMed: 38454571
DOI: 10.1111/srt.13639 -
PloS One 2024Early-onset androgenetic alopecia (AGA) has been associated with various chronic conditions, including metabolic syndrome (MetS). Gaining a deep understanding of... (Review)
Review
BACKGROUND
Early-onset androgenetic alopecia (AGA) has been associated with various chronic conditions, including metabolic syndrome (MetS). Gaining a deep understanding of early-onset AGA may enable earlier intervention in individuals at high risks. This scoping review aims to explore the risk factors and etiology, associated conditions, and adverse effects on wellbeing in early-onset AGA.
METHODS
Electronic literature searches were conducted in MEDLINE, EMBASE and CENTRIAL. Eligible studies included case-control, cohort, cross-sectional, and meta-analysis studies. Selected studies needed to clearly define early-onset AGA cases or include only cases starting before the age of 40 and compare them with appropriate controls. The exclusion criteria comprised editorials, commentaries, case series, and non-systematic reviews, among others. Data extraction involved collecting study characteristics, methodologies, main outcomes, and findings. Descriptive tables were used to summarize key information and relevant variables when necessary.
RESULTS
Among the 65 eligible articles, 67.69% were case-control studies and 78.46% evaluated only male patients. "Early-onset" was defined as cases developing before the age of 30 years in 43.08% of the studies. The Hamilton-Norwood scale was the most frequently used method for evaluating the severity of alopecia in men (69.23%). Reported risk factors for early-onset AGA included a family history of AGA, cigarette smoking, unhealthy dietary habits, and a high body mass index. Early-onset AGA may also be associated with hormonal profiles, 5α-reductase enzyme activity, androgen receptor genes, and some susceptibility loci. Comorbidities investigated included MetS, cardiovascular disease, insulin resistance, dyslipidemia, and Parkinson's disease. Men with early-onset AGA may have reduced treatment efficacy with drug like rosuvastatin, metformin or lisinopril for dyslipidemia, prediabetes, or hypertension. Additionally, young men with AGA tended to suffer from psychological issues such as anxiety and low self-esteem compared to those without hair loss.
CONCLUSION
Early-onset AGA is a complex condition with various risk factors and etiology, associated comorbidities, and potential implications for treatment response and psychological health.
Topics: Adult; Humans; Male; Alopecia; Cross-Sectional Studies; Dyslipidemias; Metabolic Syndrome; Risk Factors; Female
PubMed: 38451966
DOI: 10.1371/journal.pone.0299212 -
Clinical Oral Investigations Mar 2024To evaluate the cytocompatibility, bioactivity, and anti-inflammatory potential of the new pre-mixed calcium silicate cement-based sealers Bioroot Flow (BrF) and AH Plus...
OBJECTIVES
To evaluate the cytocompatibility, bioactivity, and anti-inflammatory potential of the new pre-mixed calcium silicate cement-based sealers Bioroot Flow (BrF) and AH Plus Bioceramic Sealer (AHPbcs) on human periodontal ligament stem cells (hPDLSCs) compared to the epoxy resin-based sealer AH Plus (AHP).
MATERIALS AND METHODS
Standardized discs and 1:1, 1:2, and 1:4 eluates of BrF, AHPbcs and AHP after setting were prepared. The following assays were performed: cell attachment and morphology via SEM, cell viability via a MTT assay, cell migration/proliferation via a wound-healing assay, cytoskeleton organization via immunofluorescence staining; cytokine release via ELISA; osteo/cemento/odontogenic marker expression via RT-qPCR, and cell mineralized nodule formation via Alizarin Red S staining. HPDLSCs were isolated from extracted third molars from healthy patients. Comparisons were made with hPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media. Statistical significance was established at p < 0.05.
RESULTS
Both BrF and AHPbcs showed significantly positive results in the cytocompatibility assays (cell metabolic activity, migration, attachment, morphology, and cytoskeleton organization) compared with a negative control group, while AHP showed significant negative results. BrF exhibited an upregulation of at least one osteo/cementogenic marker compared to the negative and positive control groups. BrF showed a significantly higher calcified nodule formation than AHPbcs, the negative and positive control groups, while AHPbcs was higher than the negative control group. Both were also significantly higher than AHP group.
CONCLUSION
BrF and AHPbcs exhibit adequate and comparable cytocompatibility on hPDLSCs. BrF also promoted the osteo/cementogenic differentiation of hPDLSCs. Both calcium silicate-based sealers favored the downregulation of the inflammatory cytokine IL-6 and the calcified nodule formation from hPDLSCs. BrF exerted a significantly higher influence on cell mineralization than AHPbcs.
CLINICAL RELEVANCE
This is the first study to elucidate the biological properties and immunomodulatory potential of Bioroot Flow and AH Plus Bioceramic Sealer. The results act as supporting evidence for their use in root canal treatment.
Topics: Humans; Periodontal Ligament; Epoxy Resins; Cytokines; Alopecia; Root Canal Filling Materials; Calcium Compounds; Silicates
PubMed: 38441709
DOI: 10.1007/s00784-024-05593-7 -
European Journal of Medical Genetics Apr 2024GAPO syndrome is a rare genetic condition caused by bi-allelic variants in ANTXR1 gene & is an abbreviation for its core features - growth retardation, alopecia,... (Review)
Review
GAPO syndrome is a rare genetic condition caused by bi-allelic variants in ANTXR1 gene & is an abbreviation for its core features - growth retardation, alopecia, pseudo-anodontia & optic atrophy. Certain additional features involving various other systems have been reported over the years & contribute to the expanding spectrum of this evolving phenotype. We report GAPO syndrome in a 3.75 year old Indian female child, who presented with some unique features such as sagittal craniosynostosis with scaphocephaly & bilateral choroid plexus cysts, alongside the core phenotype. We also report a novel frameshift variant in our patient & offer first evidence for the prenatal onset of some features.
Topics: Child, Preschool; Female; Humans; Pregnancy; Alopecia; Anodontia; Growth Disorders; Microfilament Proteins; Optic Atrophies, Hereditary; Phenotype; Rare Diseases; Receptors, Cell Surface
PubMed: 38423276
DOI: 10.1016/j.ejmg.2024.104929