Anagen Phase Of Hair Follicles Research Articles

Mathematical Modeling of Alopecia Areata: Unraveling Hair Cycle Dynamics, Disease Progression, and Treatment Strategies

Abstract This paper describes the model development process in detail, including the formulation of equations and parameters based on existing knowledge of hair cycle dynamics and immune system interactions. Various analyses are conducted to gain insights into the behavior of the model. Illustrative simulations are performed to observe the temporal dynamics of the disease progression under different conditions. Sensitivity analysis using eFAST (Extended Fourier Amplitude Sensitivity Test) is employed to identify the most influential parameters affecting the length of the anagen phase in hair follicles affected by alopecia areata. The findings of the study shed light on the complex dynamics of alopecia areata and contribute to a deeper understanding of the disease mechanisms. The model provides a valuable tool for studying autoimmune hair loss diseases and may have implications for the diagnosis and treatment of such conditions. By simulating the immune response and its effects on hair follicles, the model offers insights into potential treatment strategies that can target immune dysregulation. The temporal mathematical model presented in this dissertation provides a comprehensive framework for investigating alopecia areata and understanding its underlying dynamics. The integration of hair cycle dynamics and immune system interactions enhances our knowledge of the disease and opens avenues for future advancements in diagnosis and treatment approaches.

Investigate the role of Zinc and Ferritin in Iraqi patients with alopecia areata

Alopecia areata (AA) is an auto-immune disease in which there is an inflammation around the anagen phase of hair follicles. Many nutritional elements were found to modulate this immune response. Zinc and ferritin have many vital roles inside the body and are considered among the most important nutritional factors in immune modulation and division of hair follicle matrix cells. This study aimed to investigate the role of zinc and ferritin in patients with alopecia areata. A case control study including a total of 40 patients with AA who were attending the outpatient clinic at Al-Kindy Teaching Hospital, Baghdad during the period from 2nd June 2019 to 31st March 2020. Other 65 age- and gender- matched apparently healthy subjects. Demographic of the patients and controls and clinical data of the patients were recorded through direct interview. Blood samples were collected from all participants, and serum level of zinc and ferritin were measured using enzyme linked immunosorbent assay(Elisa). Results revealed that in three-fourth of the patients, only scalp was involved in the lesion, while mixed lesion was reported in the 25% of the patients. Single and multiple lesions were reported in 42.5% and 57.5% of the patients respectively. Median serum level of ferritin in patients was 23.0 μg/L (range=3-98 μg/L) which was lower than that of controls (median = 27.0 μg/L, range= 10-166 μg/L) with a significant difference. Likewise, median serum level of zinc was 59.5 μg/dl (range= 15-175 μg/dl) in patients compared with 71.5 μg/dl (range= 21-201 μg/dl) in controls with a significant difference. Zinc level showed a significant positive correlation with age (r= 0.334, p= 0.041) and negative correlation with lesion size (r= -0.327, p= 0.045). In conclusion, multiple lesions in the scalp are the most common presentation of patients with AA. Low levels of ferritin and/or zinc could be involved in the pathogenesis of AA and increase the risk of disease severity.

Hair Growth Regulation by Fibroblast Growth Factor 12 (FGF12)

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

Dexpanthenol Promotes Cell Growth by Preventing Cell Senescence and Apoptosis in Cultured Human Hair Follicle Cells.

Dexpanthenol (D-panthenol) is a precursor of vitamin B5 (pantothenic acid) and is widely used for dietary supplements and topical applications. D-panthenol has long been used in hair care products for the purpose of anti-hair loss, its effects and the underlying mechanisms, however, were barely reported. In this study, the effects of D-panthenol on human hair follicle cells, including dermal papilla cells (hDPCs) and outer root sheath cells (hORSCs), were investigated. D-panthenol enhanced the cell viability, increasing the cellular proliferation marker Ki67 in cultured hDPCs. The markers for apoptosis (Caspase3/9) and cell senescence (p21/p16), reported to be expressed in aged or resting phase follicles, were significantly reduced by D-panthenol. Anagen-inducing factors (ALP; β-catenin; versican), which trigger or elongate the anagen phase, were stimulated by D-panthenol. On the other hand, D-panthenol reduced TGF-β1 expressions in both mRNA and protein levels. The expression of VEGF, which is important for peripheral blood vessel activation; was up-regulated by D-panthenol treatment. In cultured hORSCs, cell proliferation and viability were enhanced, while the mRNA expression of cell senescence markers (p21/p16) was significantly down-regulated. The expressions of both VEGF and its receptor (VEGFR) were up-regulated by D-panthenol. In conclusion, our data suggest that the hair growth stimulating activity of D-panthenol was exerted by increasing the cell viability, suppressing the apoptotic markers, and elongating the anagen phase in hair follicles.

28383 The effectiveness of thread-embedding therapy for treating scarring and nonscarring alopecia

Background: Thread embedding therapy has recently gained attention as a safe and noninvasive treatment for hair loss. Although the mechanism of action is unclear, current hypothesis suggests that embedded polydioxanone (PDO) threads stimulate microcirculation and neo-collagenesis, thereby enhancing anagen phase in hair follicles. However, the clinical evidence on the effectiveness of PDO threading on hair regrowth is scarce.

Effects of photoperiod on circadian clock genes in skin contribute to the regulation of hair follicle cycling of Inner Mongolia white cashmere goats.

This study investigated how the effects of photoperiod on circadian clock genes in the skin contribute to the regulation of hair follicle cycling of Inner Mongolia white cashmere goats. Twenty-four female (non-pregnant) Inner Mongolia white cashmere goats aged 1-1.5years old with similar live weights (mean, 20.36±2.63kg) were randomly allocated into two groups: a natural daily photoperiod group (NDPP group:10-16hr Light, n=12) and a short daily photoperiod group (SDPP group: 7hr Light:17hr Dark, n=12). All goats were housed in individual pens from May 15 to October 15, 2015 and were fed the same diets. We detected the mRNA expression of brain and muscle arnt-like protein-1 (Bmal1), circadian locomotor output control kaput (Clock), cryptochrome-1 (Cry1), period homolog-1 (Per1) and Rev-erbα genes in the goat skin. ANOVA revealed a significant 24hr (10:00hr, 14:00hr, 18:00hr, 22:00hr, 02:00hr, 06:00hr, 10:00hr) variation between the SDPP and NDPP groups for three months (July, September, and October). In summary, the current results confirm that an intrinsic oscillating molecular clock exists in goat skin, and that the clock is important for potential timing mechanisms at the anagen phase of hair follicles, which would contribute to the regulation mechanisms of hair follicle cell proliferation.

Do Kimchi and Cheonggukjang Probiotics as a Functional Food Improve Androgenetic Alopecia? A Clinical Pilot Study.

PurposeProbiotic supplementation demonstrates beneficial effects on serum lipid profiles. We hypothesized that probiotics could benefit patients presenting with alopecia, secondary to improved blood flow to the scalp.Materials and MethodsOur study included men with stage II to V patterns of hair loss based on the Hamilton–Norwood classification and women with stage I to III patterns of hair loss based on the Ludwig classification. All patients were administered 80 mL of Mogut® (a kimchi and cheonggukjang probiotic product) twice a day. Hair growth and numbers were measured using the Triple Scope System® (KC Technology, Korea) at baseline and after 1 and 4 months of administration of a kimchi and cheonggukjang probiotic product.ResultsAt baseline, the mean hair count was 85.98±20.54 hairs/cm2 and the mean thickness was 0.062±0.011 mm in all patients (n=46). Hair count and thickness had significantly increased at 1 month (90.28±16.13 hairs/cm2 and 0.068±0.008 mm, respectively) and at 4 months (91.54±16.29 hairs/cm2 and 0.066±0.009 mm, respectively). In this study, we found that a kimchi and cheonggukjang probiotic product could promote hair growth and reverse hair loss without associated adverse effects such as diarrhea.ConclusionsWe suggest that the observed improvements in hair count and thickness resulted from initiation of the anagen phase in hair follicles in response to probiotics.

In vivo and in vitro evaluation of hair growth potential of Cacumen Platycladi, and GC-MS analysis of the active constituents of volatile oil

Ethnopharmacological relevanceCacumen Platycladi (CP) is the leaves of Platycladus orientalis which has been traditionally used to resist alopecia and promote hair growth. However, no study has been reported on the effects of CP on proliferation of dermal papilla cells (DPCs). And there is also no complete and systematic research on hair re-growth efficacies of CP. Aim of the studyTo evaluate the hair-growth activity of their extracts on the proliferation of DPCs and the promotion of hair reproduction in C57BL/6 mice. Materials and methodsFor the DPCs, different extract fractions of CP were investigated. The hair growth effect of CP volatile oil on C57BL/6 mice was evaluated for 28 days. Meanwhile, the chemical constituents of the volatile oil from Cacumen Platycladi were isolated and identified by GC-MS. ResultsThe study showed that the extracts of CP could promote the proliferation of DPCs, and the activity of volatile oil was the best. CP volatile oil (100 μg/mL) resulted in stronger proliferation of DPCs by 239.8% compared with control (100%) and minoxidil (130.3%) during the 48 h incubation. And no obvious cytotoxic activity was observed when volatile oil was dosed up to 500 μg/mL. At different growth stages, mice treated with 0.2 g/kg CP volatile oil required shorter time than 2% minoxidil. Hair length for 0.2 g/kg CP volatile oil treated group was longer than those of minoxidil and control. Further histological observation indicated that CP volatile oil could prolonged the anagen phase of hair follicles. Moreover, thirty four components, with contents of 81.9% of the total volatile oils, were separaed and identified. ConclusionThe CP volatile oil may have the potential therapeutic agent for the treatment of alopecia.

A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study.

BackgroundSpermidine has been shown both in vitro and in mice models to have an anagen-prolonging effect on hair follicles (HFs).ObjectivesTo evaluate the effects of a spermidine-based nutritional supplement on the anagen phase of HFs in healthy human subjects in a randomized, double-blind, placebo-controlled trial.MethodsOne hundred healthy males and females were randomized to receive a tablet containing a spermidine-based nutritional supplement or a placebo once daily for 90 days. At the beginning and the end of the treatment period, 100 HFs were plucked and subjected to microscopic evaluation to determine the number of anagen V–VI HFs, and immunohistochemical examination was performed to quantify the Ki-67 and c-Kit levels in the hair bulbs. Pull test was performed after three and six months.ResultsThe spermidine-based nutritional supplement increased the number of anagen V–VI HFs after three months of treatment, accompanied by increased Ki-67, a marker for cellular proliferation, and decreased c-Kit, a marker for apoptosis, levels. All results were also significantly better when compared to the placebo group. The pull test remained negative after six months in all patients receiving the spermidine supplement, while 68% of the subjects in the placebo group had a positive pull test.ConclusionsThis preliminary study shows that a spermidine-based nutritional supplement can prolong the anagen phase in humans, and therefore might be beneficial for hair loss conditions. Further studies are needed to evaluate its effects in specific different clinical settings.

Low-level laser treatment stimulates hair growth via upregulating Wnt10b and β-catenin expression in C3H/HeJ mice.

This study was conducted in order to evaluate the role of low-level laser treatment (LLLT) in hair growth in C3H/HeJ mice. Healthy C57BL/6 mice were randomly divided into two groups: with and without low-level laser treatment. The skin color of each mouse was observed each day. Skin samples were collected for H&E, immunofluorescence, PCR, and western blot analysis, to observe the morphology of hair follicles and detect the expression levels of Wnt10b and β-catenin. Observation of skin color demonstrated that black pigmentation started significantly earlier in the laser group than in the control group. Hair follicle number in both groups showed no difference; however, the hair follicle length presented a significant difference. Wnt10b protein was detected on the second day in hair matrix cells in the LLLT group but not in the control group. PCR and western blot results both illustrated that expression of Wnt10b and β-catenin was significantly higher in the LLLT group than in the control group. Our study illustrated that low-level laser treatment can promote hair regrowth by inducing anagen phase of hair follicles via initiating the Wnt10b/β-catenin pathway.

A new path in defining light parameters for hair growth: Discovery and modulation of photoreceptors in human hair follicle.

Though devices for hair growth based on low levels of light have shown encouraging results, further improvements of their efficacy is impeded by a lack of knowledge on the exact molecular targets that mediate physiological response in skin and hair follicle. The aim of this study was to investigate the expression of selected light-sensitive receptors in the human hair follicle and to study the impact of UV-free blue light on hair growth ex vivo. The expression of Opsin receptors in human skin and hair follicles has been characterized using RT-qPCR and immunofluorescence approaches. The functional significance of Opsin 3 was assessed by silencing its expression in the hair follicle cells followed by a transcriptomic profiling. Proprietary LED-based devices emitting two discrete visible wavelengths were used to access the effects of selected optical parameters on hair growth ex vivo and outer root sheath cells in vitro. The expression of OPN2 (Rhodopsin) and OPN3 (Panopsin, Encephalopsin) was detected in the distinct compartments of skin and anagen hair follicle. Treatment with 3.2 J/cm2 of blue light with 453 nm central wavelength significantly prolonged anagen phase in hair follicles ex vivo that was correlated with sustained proliferation in the light-treated samples. In contrast, hair follicle treatment with 3.2 J/cm2 of 689 nm light (red light) did not significantly affect hair growth ex vivo. Silencing of OPN3 in the hair follicle outer root sheath cells resulted in the altered expression of genes involved in the control of proliferation and apoptosis, and abrogated stimulatory effects of blue light (3.2 J/cm2 ; 453 nm) on proliferation in the outer root sheath cells. We provide the first evidence that (i) OPN2 and OPN3 are expressed in human hair follicle, and (ii) A 453 nm blue light at low radiant exposure exerts a positive effect on hair growth ex vivo, potentially via interaction with OPN3. Lasers Surg. Med. 49:705-718, 2017. © 2017 Wiley Periodicals, Inc.

Morphogenetic types of cuticles and melanin granules in the anagen phase of hair follicles

Our studies on the scalp and hair follicles have a particular interest in the formation of white hair and melanin; however, representative images of white hair and melanin formation have been difficult to find. The morphogenetic types of melanosomes and cuticles in hair follicles are diverse. The generated form of melanin granules include soft melanosomes that penetrate through the outer root sheath (ORS) of the hair follicle where they remain between the ORS and the inner root sheath (IRS) as irregular large masses of soft melanosomes. Subsequently, they break into small fragments, pass though the IRS and reach the hair cuticle layers. The melanosomes then adhere to the cuticle layers; however, and a portion of them continue penetrating the hair, finally entering the hair cortex where they become regular melanin granules. However, white hair roots are not formed in this manner as contain little melanosomes and melanin granules. The types of cuticle layers formed in both white and black hair roots include the curved board, mass and cogwheel types. Key words: Morphogenetic type, white and black hairs, hair root, melanin granules, cuticles.

Abstract 1718: Topical botanical extract for management of chemotherapy-induced alopecia.

Abstract Introduction Chemotherapy-induced alopecia (CIA) is considered the most visible and emotionally distressing side effect of cancer therapy. But there are no approved pharmacologic treatments available for CIA and the main physical treatment with scalp cooling is considered of relative to poor quality. In the course of CIA, the rapidly growing and dividing cell populations in anagen phase of hair follicles are damaged by the systemic chemotoxic agents and undergo premature apoptosis, inducing early onset of catagen. The intrinsic pathway of apoptosis is essentially mitochondrial dependent and executed by members of anti-apoptotic Bcl-2. It has been suggested that early onset of catagen also serves as the major universal down-stream factor of androgenetic alopecia (AGA). Pharmacological inhibition of apoptosis pathways has been proposed to prevent CIA. Considering the complexity of hair growth and cycling in human and the sensitivity of cancer patients, AGA subjects could potentially be recruited as CIA mimic for proof of concept study. We present our study of a GMP-grade botanical extract (hereafter “the Product”) on AGA subjects using Bcl-2 as a biomarker. Bcl-2 expression levels in non-alopecia and AGA subjects were checked and compared. The number of anagen (A) and telogen (T) hairs before and after the Product application was recorded by phototrychogram to evaluate the respective A/T ratio. By increasing intracellular level of Bcl-2, topical application of the Product may provide with a promising avenue for the future study to manage CIA. Study Design Hairs in the anagen and telogen phase were identified and counted using Phototrichogram on 19 AGA male subjects before and after 1.5 and 3 months topical application of the Product. The respective A/T ratio of AGA male subjects at day 1, day 44, and day 86 was calculated. Histomorphometrical Analysis: using scalp biopsy, Bcl-2+ cells analysis has been performed by determining their fractional area (%) in the epidermis of 25 male non-alopecia subjects and 15 AGA subjects before and after 3 months topical application of the Product. Results After the Product application, the A/T ratio was raised from 2.96 (day 1) to 4.30 (day 44), and remained at 4.35 all along the study period (day 86). Average epidermal fraction of Bcl-2+ cells in AGA subjects before vs after the Product application significantly increased by 89% (from 1.72 to 3.24; p = 0.001, paired t-test), but remained below the normal level of Bcl-2 in non-alopecia subjects (4.73). No Adverse Events were reported. Conclusion The anti-hair loss Product is a safe Bcl-2 up-regulating agent that can prevent premature apoptosis (early onset of catagen) in AGA subjects. It may be used as topical management for CIA in cancer patients receiving chemo- or radiotherapies, in a dosage and a formulation to be investigated. Citation Format: JiaWei Liu, Lei Zhang, Saad Harti. Topical botanical extract for management of chemotherapy-induced alopecia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1718. doi:10.1158/1538-7445.AM2013-1718