Skin Hair Follicles Research Articles

1431 Skin aging and hair follicle stem cell dysfunction caused by T cells with defective mitochondrial metabolism

1431 Skin aging and hair follicle stem cell dysfunction caused by T cells with defective mitochondrial metabolism

Transgenic HPV11-E2 protein modulates URR activity in vivo

In vitro experiments have shown that the E2 protein of human papillomaviruses (HPV) binds to the upstream regulatory region (URR) of the viral genome and modulates transcription. Additionally, it seems to be a necessary component for viral DNA replication together with E1. We have developed a transgenic mouse model containing the URR region of the low-risk virus HPV11 that regulates the expression of the lacZ reporter gene. Most interestingly, in these mice, the transgene was exclusively expressed in the bulge region of the hair follicle but not in any other tissues. Further experimental data indicate that in double transgenic mice that also express the HPV11-E2 protein under the control of the Ubiquitin C-promoter, the transcription of the reporter gene is modulated. When E2 is present, the expression of the reporter gene also occurs exclusively in the bulge region of the hair follicles as it does in the single transgenic mice, but the expression of the lacZ driven by the URR is increased and the statistical spread is greater. Even if the expression of the reporter gene occurs in the hair follicles of the dorsal skin of an animal uniform, E2 obviously has the capacity for both to induce and to repress the URR activity in vivo.

Three-dimensional correlative light and focused ion beam scanning electron microscopy reveals the distribution and ultrastructure of lanceolate nerve endings surrounding terminal hair follicles in human scalp skin.

Lanceolate nerve endings (LNEs) surrounding hair follicles (HFs) play an important role in detecting hair deflection. Complexes of the LNEs form a palisade-like structure along the longitudinal axis of hair roots in which axons are sandwiched between two processes of terminal Schwann cells (tSCs) at the isthmus of HFs. The structure and molecular mechanism of LNEs in animal sinus hair, pelage, and human vellus hairs have been investigated. Despite the high density of HFs in human scalp skin, the LNEs in human terminal HFs have not been investigated. In this study, we aimed to reveal the distribution and ultrastructure of LNEs in terminal HFs of human scalp skin. Using light-sheet microscopy and immunostaining, the LNEs were observed at one terminal HF but not at the other terminal HFs in the same follicular unit. The ultrastructure of the LNEs of terminal HFs in human scalp skin was characterized using correlated light and electron microscopy (CLEM). Confocal laser microscopy and transmission electron microscopy of serial transverse sections of HFs revealed that LNEs were aligned adjacent to the basal lamina outside the outer root sheath (ORS), at the isthmus of terminal HFs, and adjacent to CD200-positive ORS cells in the upper bulge region. Moreover, axons with abundant mitochondria were sandwiched between tSCs. Three-dimensional CLEM, specifically confocal laser microscopy and focused ion beam scanning electron microscopy, of stained serial transverse sections revealed that LNEs were wrapped with type I and type II tSCs, with the processes protruding from the space between the Schwann cells. Moreover, the ultrastructures of LNEs at miniaturized HFs were similar to those of LNEs at terminal HFs. Preembedding immunoelectron microscopy revealed that Piezo-type mechanosensitive ion channel component 2 (Piezo2), a gated ion channel, was in axons and tSCs and adjacent to the cell membrane of axons and tSCs, suggesting that LNEs function as mechanosensors. The number of LNEs increased as the diameter of the ORS decreased, suggesting that LNEs dynamically adapt to the HF environment as terminal HFs miniaturize into vellus-like hair. These findings will provide insights for investigations of mechanosensory organs, aging, and re-innervation during wound healing.

Skin permeation of curcumin nanocrystals: Effect of particle size, delivery vehicles, and permeation enhancer

Nanocrystals are characterized by high drug loading, low carrier toxicity, and great structural stability. Therefore, they are a promising and versatile strategy for enhancing the local delivery of insoluble drugs. They achieve this by improving skin adhesion, concentration gradients, and hair follicle accumulation, as well as generating corona diffusion (which forms through the overlap of dissolved drug molecules around a nanocrystal). The development of suitable formulations for enhancing the passive diffusion and/or follicular targeting of nanocrystals is of great importance to clinical practice. We sought to elucidate the influence of particle size, a penetration enhancer, and delivery vehicles on the follicular accumulation and passive dermal permeation of nanocrystals. For this purpose, curcumin nanocrystals (particle size: 60, 120, and 480 nm) were incorporated into xanthan gum gels (delivery vehicles) with propylene glycol (penetration enhancer). This evaluation was performed in a porcine skin model. The results showed that xanthan gum reduced the follicular penetration and passive skin accumulation of curcumin nanocrystals. The propylene glycol enhanced the skin penetration and retention of curcumin nanocrystals in vitro for 24 h. The curcumin nanocrystals of smaller particle size (i.e., 60 and 120 nm) displayed higher passive skin penetration versus those with larger particle size (i.e., 480 nm); however, the latter type showed deeper follicular accumulation. In conclusion, the delivery vehicles, penetration enhancer, and particle sizes examined in this study affect the dermal penetration and accumulation of curcumin nanocrystals. Hence, their effects should be adequately considered when designing formulations of such nanocrystals.

3D multicellular micropatterning biomaterials for hair regeneration and vascularization.

Hair loss caused by the abnormal functions of hair follicles in skin can seriously impact the quality of an individual's life. The development of sophisticated skin tissue-engineered constructs is required to enable the function recovery of hair follicles. However, effective hair regrowth in skin substitutes still remains a great challenge. In this study, a 3D multicellular micropattern was successfully fabricated by arranging the hair follicle-related cells orderly distributed in the interval of vascular-cell networks via bioprinting technology. By combining the stable biomimetic micropattern structure and the bio-inducing substrate incorporated with magnesium silicate (MS) nanomaterials, the 3D multicellular micropattern possessed significant follicular potential and angiogenic capacity in vitro. Furthermore, the 3D multicellular micropattern with MS incorporation contributed to efficient hair regrowth during skin tissue regeneration in both immunodeficient mice and androgenetic alopecia (AGA) mice models. Thus, this study proposes a novel 3D micropatterned multicellular system assembling a biomimetic micro-structure and modulating the cell-cell interaction for hair regeneration during skin reconstruction.

Гигантская базальноклеточная карцинома (клиническое наблюдение)

Basal cell skin cancer, or basal cell carcinoma (BCC), is the most common malignant tumor originating from skin keratinocytes or hair follicles. Giant BCCs are malignant skin neoplasms sized more than 5 cm with a greater tendency to invasion and metastasis than "standard" BCCs (sized less than 5 cm). Two or more foci in one person at the same time rarely occur. This paper describes a 69-year-old woman with skin lesions affecting the left scapula sized 20×10 cm and xiphoid process sized 7×4.5 cm that have existed for more than 15 years. During this period, the patient received various treatments with temporary insignificant improvement. Dermoscopy of the skin lesion of the scapula revealed pathological tree- like and tortuous vessels, homogeneous white and red zones, and ulcerations. Dermoscopy of skin lesion of the xiphoid process was uninformative because of rough surface hemorrhagic crusts. Cytology identified complexes of basaloid cells with atypia. Pathomorphologically, both tumors belonged to nodular BCC. For additional examination and treatment decisions, the patient was referred to the regional oncological dispensary. KEYWORDS: skin cancer, giant basal cell carcinoma, dermoscopy, pathomorphological examination, nodular type. FOR CITATION: Grekova Yu.N., Zilberberg N.V., Rimar O.G. Giant basal cell carcinoma (case report). Russian Medical Inquiry. 2023;7(6):383– 386 (in Russ.). DOI: 10.32364/2587-6821-2023-7-6-7.

An Unusual Mid-Line Nasal Mass in a Child: A Case Report

Congenital midline nasal masses are rare anomalies with a prevalence of 1 in 20,000 to 40,000 births. These masses include nasal glioma, dermoid cyst, lipoma, hemangioma, and encephalocele. Timely diagnosis and appropriate surgical management are essential for optimal outcomes. We report the case of a 3-year-old girl presenting with a firm, non-fixed, slightly erythematous midline nasal mass, which was present at birth but increased in size over time, and a right nasal encephalocele. Radiological evaluation, including computed tomography (CT) and magnetic resonance imaging (MRI), confirmed the presence of both lesions with no connection between them. Initially, the right nasal encephalocele was endoscopically repaired. Subsequently, an incision was made in the midline nasal dorsum, and the nasal dorsal mass was successfully excised. Postoperative recovery was uneventful, and the patient was discharged without complications. The pathological examination of the excised nasal dorsum sample revealed a dark-colored, thick, malodorous material and hair follicles on macroscopic inspection. Microscopic inspection revealed the presence of skin appendages and hair follicles, findings consistent with a dermoid cyst. This case report highlights the co-occurrence of an encephalocele and a dermoid cyst, emphasizing the importance of thorough radiographic evaluation for accurate diagnosis. The surgical management, a novel technique, included skin closure using an advancement flap without grafting, resulting in a faster patient recovery time and a reduced hospital stay.

Multifunctional Electrospinning Polyhydroxyalkanoate Fibrous Scaffolds with Antibacterial and Angiogenesis Effects for Accelerating Wound Healing

To treat large-scale wounds or chronic ulcers, it is highly desirable to develop multifunctional wound dressings that integrate antibacterial and angiogenic properties. While many biomaterials have been fabricated as wound dressings for skin regeneration, few reports have addressed the issue of complete skin regeneration due to the lack of vasculature and hair follicles. Herein, an instructive poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) fibrous wound dressing that integrates an antibacterial ciprofloxacin (CIP) and pro-angiogenic dimethyloxalylglycine (DMOG) is successfully prepared via electrospinning. The resultant dressings exhibit suitable flexibility with tensile strength and elongation at break up to 4.08 ± 0.18 MPa and 354.8 ± 18.4%, respectively. The in vitro results revealed that the groups of P34HB/CIP/DMOG dressings presented excellent biocompatibility on cell proliferation and significantly promote the spread and migration of L929 cells in both transwell and scratch assays. Capillary-like tube formation is also significantly enhanced in the P34HB/CIP/DMOG group dressings. Additionally, dressings from the P34HB/CIP and P34HB/CIP/DMOG groups show a broad spectrum of antimicrobial action against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. In vivo studies further demonstrated that the prepared dressings in the P34HB/CIP/DMOG group not only improved wound closure, increased re-epithelialization and collagen formation, as well as reduced inflammatory response but also increased angiogenesis and remodeling, resulting in complete skin regeneration and hair follicles. Collectively, this work provides a simple but efficient approach for the design of a versatile wound dressing with the potential to have a synergistic effect on the rapid stimulation of angiogenesis as well as antibacterial activity in full-thickness skin repair.

A Novel Simple In Vitro System Mimicking Natural Environment for the Biofilm Cultivation of Cutaneous Bacteria

Biofilms are microbial communities of cells embedded in extracellular matrix, and they are regarded as a major form of the natural and laboratory occurrence of bacteria. Cutaneous microbiota is represented by prokaryotic and eukaryotic organisms, which form biofilms in the different niches including the skin surface, glands, and hair follicles. Despite of a large number of in vitro studies dedicated to the biofilms of cutaneous bacteria, the methods used usually do not closely take into account the specific surroundings of certain skin parts. In this study, we introduce a new simple method of biofilm cultivation on the solid keratine/agarose pellets embedded in polyacrylamide gel. In such a model system, we tried to minimize the amount of liquid phase, which makes a model close to a human comedo, and provide a prominent biofilm formation of selected cutaneous bacteria.

Bio-Pulsed Stimulation Effectively Improves the Production of Avian Mesenchymal Stem Cell-Derived Extracellular Vesicles That Enhance the Bioactivity of Skin Fibroblasts and Hair Follicle Cells

Mesenchymal stem cell (MSC)-derived extracellular vesicles (exosomes) possess regeneration, cell proliferation, wound healing, and anti-senescence capabilities. The functions of exosomes can be modified by preconditioning MSCs through treatment with bio-pulsed reagents (Polygonum multiflorum Thunb extract). However, the beneficial effects of bio-pulsed small extracellular vesicles (sEVs) on the skin or hair remain unknown. This study investigated the in vitro mechanistic basis through which bio-pulsed sEVs enhance the bioactivity of the skin fibroblasts and hair follicle cells. Avian-derived MSCs (AMSCs) were isolated, characterized, and bio-pulsed to produce AMSC-sEVs, which were isolated, lyophilized, characterized, and analyzed. The effects of bio-pulsed AMSC-sEVs on cell proliferation, wound healing, and gene expression associated with skin and hair bioactivity were examined using human skin fibroblasts (HSFs) and follicle dermal papilla cells (HFDPCs). Bio-pulsed treatment significantly enhanced sEVs production by possibly upregulating RAB27A expression in AMSCs. Bio-pulsed AMSC-sEVs contained more exosomal proteins and RNAs than the control. Bio-pulsed AMSC-sEVs significantly augmented cell proliferation, wound healing, and gene expression in HSFs and HFDPCs. The present study investigated the role of bio-pulsed AMSC-sEVs in the bioactivity of the skin fibroblasts and hair follicle cells as mediators to offer potential health benefits for skin and hair.

RG6234, a GPRC5DxCD3 T-Cell Engaging Bispecific Antibody, Is Highly Active in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Updated Intravenous (IV) and First Subcutaneous (SC) Results from a Phase I Dose-Escalation Study

Background: Despite advances in treatment, almost all pts with newly diagnosed multiple myeloma (MM) eventually relapse and progression-free survival decreases with each subsequent line of therapy. New treatments that target novel antigens and/or have novel mechanisms of action (MOAs) are needed. GPRC5D is a G-protein coupled receptor that is overexpressed on malignant plasma cells. Expression on normal tissue is limited to skin (hair follicles and eccrine glands) and testis (seminiferous tubules). In a Phase I study (NCT04557150), RG6234, a GPRC5DxCD3 T-cell engaging bispecific antibody with a novel 2:1 configuration, was highly active in pts with RRMM and had a safety profile consistent with its MOA and target distribution when given IV (Hasselbalch Riley et al. EHA 2022). We report updated IV and first SC results. Methods: All pts had RRMM for which no established therapy was available, appropriate or tolerable and had received ≥1 prior IMiD and ≥1 prior PI. Prior CAR T-cells, antibody-drug conjugates and bispecific antibodies were allowed. RG6234 was initiated with step-up dosing, reaching the target dose 2 weeks after the initial step dose, and was given for up to 1 year unless disease progression or unacceptable toxicity occurred. All pts who received RG6234 in the dose-escalation phase of the study were included in the analysis (IV dose range: 6-10000µg; SC dose range: 30-7200µg). Results: At data cut-off (June 8, 2022), 51 pts had been enrolled into the IV cohorts (median age: 62 years; min-max: 27-78) and 54 into the SC cohorts (64 years; 46-79). Median number of prior lines was 5 (min-max: 2-15) and 4 (2-14), respectively. Many pts were triple-class refractory (IV: 63.3%; SC: 73.1%), some were penta-class refractory (IV: 30.6%; SC: 42.3%), and some had received prior anti-BCMA therapies (IV: 19.6%; SC: 20.4%). High-risk cytogenetics (t(4;14), t(14:16), del(17p)) were common (IV: 46.7% of 30 evaluable pts; SC: 50.0% of 28). Across all tested doses, cytokine release syndrome (CRS) was the most common adverse event (AE; IV: 82.4% of pts; SC: 77.8%). Grade (Gr) ≥3 CRS was uncommon (IV: 2.0%; SC: 1.9%) and most events were confined to Cycle 1. CRS management often involved tocilizumab (IV: 39.2% of pts; SC: 25.9%) and corticosteroids (IV: 52.9%; SC: 25.9%). ICANS-like AEs were infrequent and mostly mild (any Gr: 9 pts [8.6%]; Gr ≥3: 2 pts [1.9%]). AEs related to on-target, off-tumor effects included dermal and epidermal conditions (IV: 72.5%; Gr 3: 11.8%; SC: 81.5%; Gr 3: 14.8%), hair and nail changes (IV: 17.6% [all Gr 1-2]; SC: 22.2% [all Gr 1-2]), and AEs affecting the gastrointestinal mucosal epithelium or tongue (IV: 70.6% [all Gr 1-2]; SC: 74.1%; Gr 3: 5.6%). Gr ≥3 hematologic AEs were infrequent (anemia: IV 13.7%, SC 5.2%; thrombocytopenia: IV 13.8%, SC 18.5%; neutropenia: IV 11.8%, SC 16.7%). Infections were common (IV: 56.9%; Gr ≥3: 19.6%; SC: 37.0%; Gr ≥3: 24.1%). RG6234-related AEs leading to treatment discontinuation occurred in 2 pts (3.9%) in the IV group and 2 pts (3.7%) in the SC group. One RG6234-related Gr 5 (fatal) AE (1.9%) of acute respiratory failure was reported in the SC group. Median follow-up among efficacy evaluable pts in the IV group (7.1 months; min-max: 0.5-16.8; n=49 pts) was longer than in the SC group (3.9 months; min-max: 1.1-10.5; n=48 pts). Overall response rates were 71.4% and 60.4%, respectively (Figure). Responses were observed in 10/18 pts (55.6%) overall who had received prior anti-BCMA therapies and 18/28 pts (64.2%) who had high-risk cytogenetics. Median time to first response in the IV and SC cohorts was 1.4 months (95% CI: 1.2-1.8) and 1.6 months (1.2-2.1), respectively. Duration of response (DoR) data were immature at cut-off. Responses were ongoing in 24/35 pts (68.6%) in the IV cohorts and in 26/29 (89.7%) in the SC cohorts, with a maximum DoR of 12.9 months and 8.8 months, respectively. Biomarker data demonstrated rapid T-cell activation and T cell-mediated anti-MM activity irrespective of administration route (Dekhtiarenko et al. ASH 2022). Anti-drug antibody incidence was low (IV: 7.8%; SC: 1.8%), and impacted RG6234 PK and efficacy in one pt (1.0%) only. Conclusions: RG6234 is highly active in pts with heavily pretreated RRMM when administered IV or SC. AEs are consistent with its MOA and target distribution. Evaluation and optimization of IV and SC dosing is ongoing. Updated data will be presented. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Generation of human-induced pluripotent stem cell-derived adherent 3-dimensional skin hair-follicle organoids

Regenerating hair follicles (HFs) is a critical medical need for patients who suffer from serious hair loss. To generate equivalent hair-bearing skin systems that could mimic the complexity of native tissues with pluripotent stem cells, floating culture has been employed as a standard method; however, it is still necessary to improve limitations such as the heterogeneity of organoids and the difficulty of handling them, which increases during long-term culture. Here, we devise a floating-adherent combinatory culture system to establish skin HF organoids from human-induced pluripotent stem cells (hiPSCs). Specifically, embryoid bodies were generated in a free-floating environment, followed by the induction process, which occurred in adherent conditions. With our approach, hair germ-like buds were shown to protrude and extend faster. After 100 days of culture, mature cystic skin organoids stratified to form the epidermis, dermis, and outer root sheath, as evident from quantitative polymerase chain reaction and immunohistochemistry analysis. Dermal condensate cells (Sox2+, PDGFRα+, P75+), which are the precursors of HFs, were detected together with HF stem cells (NFATC1+, LGR5+), putative bulge stem cells (LHX2+, KRT15+) and melanocytes (PMEL+). Notably, our constructed HFs could recapitulate the sensory function of native tissues, as illustrated by the formation of a network of sensory neurons and Schwann cells connecting towards HF cells and epidermal progenitors. In summary, our results demonstrate a new protocol for the simplified and efficient induction of skin HFs from hiPSCs, thereby contributing to research on optimizing HF growth and investigating novel therapeutic strategies to treat alopecia.

A quantitative technique to analyze and evaluate microstructures of skin hair follicles based on mueller matrix polarimetry

In this study, we propose a quantitative technique to analyze and evaluate microstructures of skin hair follicles based on Mueller Matrix transmission microscopy. We measure the Mueller matrix polar decomposition (MMPD) parameter images to reveal the characteristic linear birefringence distribution induced by hair follicles in mouse skin tissue samples. The results indicate that the Mueller matrix-derived parameters can be used to reveal the location and structural integrity of hair follicles. For accurate hair follicle location identification and quantitative structural evaluations, we use the image segmentation method, sliding window algorithm, and image texture analysis methods together to process the Mueller matrix-derived images. It is demonstrated that the hair follicle regions can be more accurately recognized, and their locations can be precisely identified based on the Mueller matrix-derived texture parameters. Moreover, comparisons between manual size measurement and polarimetric calculation results confirm that the Mueller matrix parameters have good performance for follicle size estimation. The results shown in this study suggest that the technique based on Mueller matrix microscopy can realize automatically hair follicle identification, detection, and quantitative evaluation. It has great potential in skin structure-related studies and clinical dermatological applications.

MicroRNA-148a Controls Epidermal and Hair Follicle Stem/Progenitor Cells by Modulating the Activities of ROCK1 and ELF5

Skin and hair development is regulated by complex programs of gene activation and silencing and microRNA-dependent modulation of gene expression to maintain normal skin and hair follicle development, homeostasis, and cycling. In this study, we show that miR-148a, through its gene targets, plays an important role in regulating skin homeostasis and hair follicle cycling. RNA and protein analysis of miR-148a and its gene targets were analyzed using a combination of invitro and invivo experiments. We show that the expression of miR-148a markedly increases during telogen (bulge and hair germ stem cell compartments). Administration of antisense miR-148a inhibitor into mouse skin during the telogen phases of the postnatal hair cycle results in accelerated anagen development and altered stem cell activity in the skin. We also show that miR-148a can regulate colony-forming abilities of hair follicle bulge stem cells as well as control keratinocyte proliferation/differentiation processes. RNA and protein analysis revealed that miR-148a may control these processes by regulating the expression of Rock1 and Elf5 invitro and invivo. These data provide an important foundation for further analyses of miR-148a as a crucial regulator of these genes target in the skin and hair follicles and its importance in maintaining stem/progenitor cell functions during normal tissue homeostasis and regeneration.

The regulation mechanism of different hair types in inner Mongolia cashmere goat based on PI3K-AKT pathway and FGF21.

There is genetic diversity of hair types in the Inner Mongolia cashmere goat population. Previous studies have found that fibroblast growth factor 21 (FGF21) and PI3K-AKT signal pathways may be related to different hair types in Inner Mongolia cashmere goats. Therefore, the purpose of this study was to explore the effects of the PI3K-AKT signal pathway on different hair types, the expression of mRNA and protein expression sites of FGF21 in the hair follicles of cashmere goats with different hair types, so as to lay a foundation for understanding the molecular mechanism of different hair types and the role of skin hair follicle development. In this experiment, the skin tissues of long hair type (LHG) and short hair type (SHG) of Inner Mongolia cashmere goat were collected in three key periods of secondary hair follicle growth, namely, anagen (September), catagen (December), and telogen (March). The relative expression of FGF21 and PI3K-AKT signal pathway candidate gene mRNA in different periods and different hair types was detected by real-time fluorescence quantitative technique (qRT-PCR), and the expression site of FGF21 protein was located by immunohistochemical technique. Through qRT-PCR, it was found that the relative expression of FGF21, FGFR1, AKT3, BRCA1, PKN3, SPP1, and GNG4 was significantly different between LHG and SHG. The expression of FGF21 in the skin of LHG was significantly higher than that of SHG in the three periods. Through immunohistochemical test, it was found that FGF21 protein was mainly expressed in primary hair follicle connective tissue sheath, primary hair follicle outer root sheath, secondary hair follicle outer root sheath, and sebaceous glands. It was also found that the expression of LHG skin tissue in the outer root sheath of primary hair follicles was higher than that of SHG in three periods. In summary, it is suggested that the PI3K-AKT signal pathway may play an important role in the formation of different hair types in Inner Mongolia cashmere goats.

Differential distribution and genetic determination of eccrine sweat glands and hair follicles in the volar skin of C57BL/6 mice and SD rats

BackgroundEccrine sweat glands (ESGs) and hair follicles (HFs) are the prominent skin appendages regulating human body temperature. C57BL/6 mice and Sprague–Dawley (SD) rats are the most commonly used model animals for studying ESGs and HFs. Previous studies have shown the distribution of ESGs and HFs in volar hindfeet of C57BL/6 mice, but there are few or no reports on the distribution of ESGs and HFs in volar forefeet of C57BL/6 mice and volar feet of SD rats. Here, we investigated the differential distribution and genetic determination of ESGs and HFs in the volar skin of C57BL/6 mice and SD rats through gross observation, iodine-starch sweat test, double staining with Nile Blue A and Oil Red O, hematoxylin and eosin (HE) staining, double immunofluorescence staining of LIM Homeobox 2 (LHX2)/Na+-K+-ATPase α1(NKA) or LHX2/Na+-K+-2Cl－ cotransporter 1 (NKCC1), and qRT-PCR detection of ESG-related gene Engrailed 1 (En1) and HF-related gene LHX2.ResultsThe results showed ESGs but no HFs in the footpads of C57BL/6 mice and SD rats, both ESGs and HFs in the inter-footpads (IFPs) of C57BL/6 mice, and neither ESGs nor HFs in the IFPs of SD rats. The relative quantitative change in En1 was consistent with the differential distribution of ESGs, and the relative quantitative change of LHX2 was consistent with the differential distribution of HFs.ConclusionC57BL/6 mice and SD rats had their own characteristics in the distribution of ESGs and HFs in the volar skin, and researchers should choose mice or rats, and even forefeet or hindfeet as their research object according to different purposes. The study provides a basis for selection of optimal animal models to study development, wound healing and regeneration of skin appendages.

Is there a correlation between vitiligo and hearing loss? - review of the literature

Vitiligo is the most common cause of hipopigmentation occuring with a frequency of 0.5-2% relying on impairment of melanin production caused by the loss of melanocytes. Melanocytes are observed not only in the skin's epidermis and hair follicles but also in the mucosa, the uvea, mesencephalon and on the structures of inner ear – including the stria vascularis, the cochlea and the dark cell areas in the vestibular organs where they play role in regulation auditory and equilibrium functions. These rationale prompted scientists to study the link between hearing loss and vitiligo. Scientists' opinions are divided in this respect - some of them, as a result of their research, see a possible connection, others do not see a correlation between the two diseases. In this review, we present the latest studies evaluating the correlation of hearing impairment with vitiligo.

Pumpkin Seed Oil-Loaded Niosomes for Topical Application: 5α-Reductase Inhibitory, Anti-Inflammatory, and In Vivo Anti-Hair Loss Effects.

Pumpkin seed oil (PSO)-loaded niosomes were prepared from Tween 20 and cholesterol by ethanol injection. Confocal microscopy showed better skin permeation and hair follicle accumulation of the niosomes compared to the PSO solution. The PSO-loaded niosomes inhibited 5α-reductase activity in DU-145 cells and hindered IL-6 activity in RAW 264.7 cells. These effects indicated the great potential of PSO-loaded niosomes to reduce hair loss. The hair scalp serum with PSO-loaded niosomes did not show irritation to reconstructed human skin. This formulation presented a significant decrease in the percentage of fallen hairs by 44.42% in the in vivo 60-second hair count experiment and a significant increase in the anagen to telogen (A/T) ratio (1.4-fold) in the TrichoScan® evaluation after 8 weeks of treatment compared to the initial conditions, indicating the promising efficacy of PSO-loaded niosomes as a natural alternative for anti-hair loss therapy.

601 Pharmacological inhibition of the chemokine receptor CX3CR1 promotes hair growth

Macrophages are located around hair follicles in normal skin and typically peak in density during the mid-telogen stage of the hair cycle. Hair follicles chemotactically attract macrophages and T cells and are in range to regulate hair follicle stem cells (HFSCs) quiescence, proliferation, and differentiation during physiologic and injured states. The expression of the fractalkine receptor CX3CR1 has been identified as a key regulator of macrophage and T cell migration and function at sites of inflammation.

745 Regional expression of secreted WNT inhibitors dictates formation of hairless and poorly haired skin

Different regions of mammalian skin vary in characteristics such as thickness, and hair follicle and sweat gland presence, size and density, that are reflected in differential responses to injury and disease. Positional information resides in the upper dermis but the responsible molecular mechanisms are poorly understood. To uncover these, we carried out comparative scRNA-seq of mouse embryonic dorsal, ear and plantar skin. This revealed differential regional expression of several secreted Wnt inhibitors, including Dkk2 and Sostdc1, suggesting regional modulation of Wnt signaling as an important mechanism controlling skin heterogeneity. In line with this, we showed previously that Dkk2-null mice develop regenerative hair follicles in normally hairless plantar skin. However, hair follicles in other regions had normal density and size. Loss of Sostdc1 is known to cause ectopic hair formation in nipple skin, extra vibrissae, and larger hair follicle placodes in trunk skin. We hypothesized that Dkk2 and Sostdc1 function partially redundantly to control additional regional skin features. To test this, we generated mice lacking both inhibitors. Double mutants displayed elevated Wnt signaling in embryonic plantar and ear skin, increased formation of plantar hair compared with Dkk2 single mutants, and growth of abnormally dense, long, thick hair on the external ears. Thus, regional modulation of Wnt signaling controls both the formation of hairless versus hairy skin, and the size and density of hair follicles in haired skin. These data support a new paradigm in which, rather than being dictated by an activating dermal signal as postulated in classical models, hair follicle formation is a default pathway that is actively suppressed by secreted inhibitors in skin regions that lack hair follicles or are poorly haired.