1,2,4-trihydroxybenzene induces non-apoptotic cell death via the structural damage of intracellular organelles.

Benzene occurs naturally and is widely applied in the production process of petrochemical products. It is mainly exposed through the respiratory tract and dermal and metabolized in the liver, leading to systemic health effects, and 1,2,4-trihydroxybenzene (THB) is a benzene metabolite used as a hair dye ingredient in some countries. In an effort to identify a toxic mechanism of THB, we first analyzed the hair of consumers who used a shampoo containing THB, and contrary to our expectations, THB was not persistent in the hair. Following, we treated THB to human keratinocytes and HeLa Chang liver cells. Membrane damage was observed in both cell lines, which was more notable in HeLa Chang liver cells than in keratinocytes. Thus, we decided on HeLa Chang liver cells as target cells for further study. Cell viability decreased sharply between 20 µg/ml and 40 µg/mL, inducing G2/M phase arrest and non-apoptotic cell death. The expression of carcinogenesis-, DNA damage-, and transcriptional dysregulation-related genes were notably up-regulated, and the structure and function of mitochondria were disrupted. The volume of the ER and acidic compartments decreased, and intracellular ROS and calcium ion levels increased. More interestingly, we found that THB formed unique structures within the cells, especially around the nuclear membrane, and that those structures seemed to dig into the nucleus over time. A reverse docking analysis also showed that SULT1A1, CYP2E1, and CAT, known to play a significant role in protecting cells from harmful factors, might be potential target proteins for THB. Taken together, we suggest that THB induces non-apoptotic cell death via structural damage of intracellular organelles, especially the nuclear membrane.

The root strategy of the C4 grasses tends to be 'do-it-yourself'.

Root resource acquisition strategies play a crucial role in understanding plant water uptake and drought adaptation. However, the interrelationships among mycorrhizal associations, root hair development, and fine root strategies, as well as the disparities between C3 and C4 grasses, remain largely unknown. A pot experiment was conducted to determine leaf gas exchange, root morphology, root hair, mycorrhizal fungi, and biomass allocation of three C4 grasses and four C3 grasses, common species of grasslands in Northeast China, under the control and drought conditions. Compared to the C3 grasses, the C4 grasses increased specific surface area by decreasing tissue density, yet exhibited root hair factor at only 21 % of the C3 grasses. Under the drought conditions, the C4 grasses exhibited more intense and extensive adjustments in root traits, characterized by shifts toward a more conservative morphology with increased root diameter and tissue density, as well as reduced mycorrhizal colonization rates. These adaptations led to a decrease in root absorptive function, which was compensated in the C4 grasses by greater root biomass partitioning and root hair factor. Variances in root strategies between plants functional groups were closely related to leaf photosynthetic rate, water and nitrogen use efficiency. We observed that the C4 grasses prefer direct acquisition of soil resources through the fine root pathway over the root hair or mycorrhizal pathway, suggesting a 'do-it-yourself' approach. These findings provide valuable insights into how plant communities of different photosynthetic types might respond to future climate change.

FGF7 and FGF10 Promote Fate Transition of Human Epidermal Cell-derived Organoids to an Eccrine Gland Phenotype.

Rationale: Reconstruction of hair follicles (HFs) and eccrine sweat glands (ESGs) is essential for functional skin regeneration. In skin reconstruction research, we found that foreskin-derived epidermal cells reconstructed HF organoids unidirectionally, but not ESG organoids. Methods: To investigate key genes and pathways influencing the fate of ESG and HF, a transcriptome profiling of ESG placode-containing skin and HF placode-containing skin was employed, and key DEGs were identified and validated by RT-qPCR and immunofluorescence staining in mice and rats. Subsequently, adult human epidermal cell-derived organoids were reconstructed to probe functional roles and mechanisms of FGF7 and FGF10 by series of approaches integrating RT-qPCR, immunofluorescence-staining, WB, apoptosis assay, and pathway interference assay. Results: All members of FGF7 subfamily were among the key DEGs screened, the differential expression of FGF7 and FGF10 and their receptors FGFR1/FGFR2 was verified between ESG placode-containing skin and HF placode-containing skin. In vivo and in vitro Matrigel plug models showed that both FGF7 and FGF10 promoted fate transition of human epidermal cell-derived organoids to ESG phenotype organoids, FGF7 and FGF10 had a synergistic effect, and mainly function through the FGFR1/2-MEK1/2-ERK1/2 pathway. Conclusions: Adult epidermal cells can be manipulated to reconstruct personalized HF and ESG to meet different needs.

Preparation and In Vitro Evaluation of Protective Effects of Quercetin-Loaded Solid Lipid Nanoparticles on Human Hair Against UV-B Radiation.

BACKGROUND: The aim of this study was to investigate the protective effect of quercetin loaded on solid lipid nanoparticles (SLN) in protecting human hair from ultraviolet-B (UV-B) light in vitro. METHODS: In this study, solvent-emulsified diffusion method was used to fabricate nanoparticle formulations and then particle size, loading, and drug release tests were performed from different formulations. Variables include oily part proportion, liquid to solid oil part ratio, and surfactant to lipid ratio. The optimal formulation was prepared by examining the eight formulations and optimizing them. Six groups of hair with different treatments were exposed to UV light for 600 h and the changes were investigated by examining four factors: RMS (root mean square average, the microscopic profile peaks and valleys), peak to valley roughness, the amount of chemical changes by Fourier transform infrared spectroscopy (FTIR), and the amount of protein loss. RESULTS: The selected formulation had a suitable particle size, loading percent, and release rate for penetration to hair. Quercetin-loaded SLN controlled RMS factor, peak to valley roughness, and reduced chemical changes and protein loss compared to other treatments. CONCLUSION: The optimize formulation showed positive effects in protecting the hair strands from UV-B radiation.

Impact of Photobiomodulation on the Quality of Life of Men and Women With Androgenetic Alopecia.

OBJECTIVES: Androgenetic alopecia (AGA) is the most common cause of hair loss in men and women, and it can affect the psychological and social activities of individuals, thus reducing their quality of life. Photobiomodulation (PBM) is a recent adjuvant treatment for this condition with promising results for hair regrowth. We aimed to assess the health-related quality of life of men and women with AGA before and after PBM sessions. METHODS: This is a single-center prospective observational study conducted with 42 men and 43 women with AGA. All participants answered a sociodemographic questionnaire in an interview and individually answered the Brazilian version of Skindex-29 (self-application). After 24 PBM sessions, two 20-minute sessions per week, with 48 to 72 hours of interval between sessions, participants answered the Skindex-29 again. RESULTS: Women had a large reduction in Skindex-29 total score after PBM (p<0.01; d=0.82) and lower scores in the emotions (p<0.01; d=0.89), psychosocial functioning (p<0.01; d=0.60), and symptoms domains (p=0.03; d=0.38). Men presented a moderate reduction in Skindex-29 total score after PBM (p<0.01; d=0.68), largely lower scores in the emotions domain (p<0.01; d=0.82) and a small reduction in the psychosocial functioning domain (p<0.01; d=0.47). CONCLUSIONS: The use of PBM in AGA is associated with improving the quality of life of men and women. This enhancement was higher regarding emotions, the major domain affected in the AGA population. Women had larger impacts on all domains of Skindex-29 after the use of PBM.

Evaluation of hair surface structure and morphology of patients with lichen planopilaris (LPP) by atomic force microscopy (AFM).

BACKGROUND: Lichen planopilaris (LPP) is a chronic lymphocytic skin disease manifested by progressive scarring alopecia. The diagnosis of LPP is made based on histopathological examination, although it is not always definite. The current study evaluates the effectiveness of non-invasive atomic force microscopy (AFM) hair examination in detecting morphological differences between healthy and diseased hair. MATERIALS AND METHODS: Here, three to five hairs from lesional skin of 10 LPP patients were collected and examined at nine locations using AFM. At least four images were taken at each of the nine sites. Metric measurements were taken and metric (length, width, and scale step height) and morphological features (striated and smooth surface of scales, the presence of endocuticle and cortex, shape of scales edges, scratches, pitting, cracks, globules, and wavy edge) were compared with hair from healthy controls. In addition, areas on diseased hair where the process of pathological, unnatural delamination of the hair fiber occurs are described. RESULTS: There was a statistically significant difference in the number of scratches in the initial sections of the LPP hair, in the intensity of wavy edges along the entire length of the tested hair, and in the number of scales with pitting in the middle section of the hair. In addition, a statistically significant higher number of scales with striated surface was found in LPP group starting at 3.5 cm from the root continuing towards the free end of the hair. Other morphological changes such as presence of cortex, globules, oval indentations, and rod-like macrofibrillar elements were also assessed, however, detailed results are not presented, as the differences shown in the number of these morphological changes were not significantly different. CONCLUSION: This publication outlines the differences between virgin, healthy Caucasian hair, and the hair of LPP patients. The results of this study can be used for further research and work related to LPP. This is the first attempt to characterize the hair of LPP patients using AFM.

The ideal range of laser hair removal for microtia patients undergoing two-stage ear reconstruction.

Although the technologies for auricular reconstruction in microtia have improved, issues such as low hairlines or excessive hair growth can still pose aesthetic problems for the reconstructed ear. Laser depilation has been reported as a solution for hair problems. However, few studies have discussed the appropriate region for hair removal. A retrospective analysis was performed on 276 patients with unilateral microtia who underwent the Nagata two-stage ear reconstruction. The gender ratio of male to female was 2.5 (198 males/78 females). Intense pulsed light depilation was used to remove hair. To determine the proper hair removal area, we measured the extent of hair removal. Before the first stage, the average vertical distance between the upper point (after localization) and hairline was 3.42 ± 4.75 mm (-10-20 mm). After the first stage, the average vertical distance between the upper point of the reconstructed ear and the hairline was 1.27 ± 2.41 mm (-10-15 mm). By using chi-square test to assess differences in hair removal success rates among various regions, we aimed to identify the suitable depilation region. Before the first stage, a depilation vertical distance ≥ 10 mm led to a 92.1% success rate. After the first stage surgery, among the patients needing additional hair removal, a vertical depilation distance ≥ 4 mm resulted in an 81.3% success rate. Based on our observation, we suggested that a depilation region of ≥ 10 mm (before the first surgery) or ≥ 4 mm (after the first surgery) would be the ideal range for laser hair removal.

Terminalia bellirica (Gaertn.) Roxb. extracts reshape the perifollicular microenvironment and regulate the MAPK pathway for androgenetic alopecia treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia bellirica (Gaertn.) Roxb. (TBR), a popular herbal remedy in India and Southeast Asia, has been demonstrated to possess multiple pharmacological activities. However, systematic studies on the medicinal effects and mechanism of TBR for the androgenetic alopecia (AGA) treatment are deficient. MATERIALS AND METHODS: Human Umbilical Vein Endothelial Cells (HUVECs) and testosterone-induced AGA mice were used to evaluate the hair regrowth activity of TBR extracts. Chemical constituents and potential active components of TBR extracts were analyed by UPLC-Q-TOF-MS in vitro/vivo. The hair regrowth mechanisms of TBR were elucidated through network pharmacology and experimental validation. RESULTS: Totally 28 chemical constituents in TBR were identified, of which 15 were predicted as potential active components for AGA therapy. TBR could significantly scavenge ROS, promote VEGF level/cell migration of HUVECs, and inhibiting type II 5α-reductase activity (the inhibit rate: 82.35 ± 1.02 %). Pharmacodynamic evaluation suggested that TBR effectively led to hair regrowth in C57BL6 mice compared to minoxidil. TBR promoted the hair follicle (HF) transition from the telogen phase to anagen phase by decreasing MDA levels, increasing VEFG expression and up-regulating phosphorylated P38/ERK protein levels in the MAPK signaling pathway. CONCLUSIONS: TBR reversed AGA via inhibiting SRD5A2 activity and stimulating the MAPK pathway. Meantime, TBR could remodel the follicle microenvironment by reducing oxidative stress and increasing angiogenesis.

Deep Hair Phenomics: Implications in Endocrinology, Development, and Aging.

Hair quality is an important indicator of health in humans and other animals. Current approaches to assess hair quality are generally non-quantitative or are low throughput due to technical limitations of 'splitting hairs'. We developed a deep learning-based computer vision approach for the high throughput quantification of individual hair fibers at a high resolution. Our innovative computer vision tool can distinguish and extract overlapping fibers for quantification of multivariate features including length, width, and color to generate single-hair phenomes (shPhenome) of diverse conditions across the lifespan of mice. Using our tool, we explored the effects of hormone signaling, genetic modifications, and aging on hair follicle output. Our analyses revealed hair phenotypes resultant of endocrinological, developmental, and aging-related alterations in the fur coats of mice. These results demonstrate the efficacy of our deep hair phenomics tool for characterizing factors that modulate the hair follicle and developing new diagnostic methods for detecting disease through the hair fiber. Finally, we have generated a searchable, interactive web tool for the exploration of our hair fiber data at skinregeneration.org.

Standard operating protocol for utilizing energy-based devices in aesthetic practice.

BACKGROUND: Lasers and other energy-based devices are increasingly becoming popular in aesthetic practice. Many centers employ doctors or technicians to perform these procedures where treating doctor and operating doctor may be different. Hence the need for standard operative protocols, to be followed while performing these procedures to avoid mistakes, complications and to get optimum results. In the current review article, group of doctors who have worked with these energy-based devices over many years worked together and suggested the protocols to be followed for the most commonly used energy-based procedures. AIM: To provide Standard operating protocols for the operator and staff to ensure, efficacy, safety, for the patient and for the devices. METHODS: The following protocols have been drafted based on the best practices followed by the authors in their clinics and reflect their consensus opinion. The objective is to provide operating protocols in a standard format, which can be of use by practicing dermatologists and their staff. The protocols include both general guidelines for the laser room and specific protocols for different machines. The draft follows the following schema: General instructions for all the energy-based devices. Specific protocols for different devices: Laser hair removal, fractional lasers, Q-switched lasers, fractional microneedling radiofrequency and cryolipolysis. CONCLUSIONS: The protocols proposed help to maintain the uniformity and avoid complications. However, these instructions are generalized and not machine or lesion specific. There may be variations in the protocols depending on the treatment lesion and treating doctor as well as machine.

Off-Label Use of Naltrexone in Pica and Other Compulsive Behaviors: A Report of Two Cases.

Pica is known to the medical community as an eating disorder in which individuals may ingest non-food items due to a nutritional deficiency and cause unintentional physical harm to themselves. This article discusses the cases of children with pica in addition to other comorbidities such as trichotillomania, depression, autism, and anxiety. Both patients were trialed on typical first-line treatments to address pica symptoms, including antidepressants, psychotherapy, and neurology consults, which were ineffective in treating pica symptoms. The introduction of naltrexone resulted in significant improvements, including decreased pica symptoms and improvements in depression, anxiety, and overall behaviors. These effects of naltrexone were further bolstered by the effects that occurred when both patients discontinued naltrexone for some time.

Clinical considerations and endocrinological implications in the detransition process.

Detransition, the process of reverting to one's gender assigned at birth after a period of transition, or moving away from the original transition goal, presents unique challenges in healthcare. This paper introduces the clinical issue and provides a comprehensive overview of the ethical, psychological, legal, surgical, and endocrinological considerations involved in supporting individuals who choose to detransition. It emphasises the importance of patient-centred care, informed consent, and the need for expanded research to address the specific needs of this population. The paper highlights the complexities of endocrine management, surgical reversals, and the necessity for comprehensive support systems. Key psychotherapeutic interventions, including trauma-focused Cognitive Behavioural Therapy (CBT), Eye Movement Desensitization and Reprocessing (EMDR), and third-wave approaches like Compassion-Focused Therapy (CFT), are recommended to manage associated trauma and shame. By adopting a holistic approach, healthcare providers can better assist individuals navigating the complexities of detransition.

Two new mouse alleles of Ocm and Slc26a5.

The genes Ocm (encoding oncomodulin) and Slc26a5 (encoding prestin) are expressed strongly in outer hair cells and both are involved in deafness in mice. However, it is not clear if they influence the expression of each other. In this study, we characterise the auditory phenotype resulting from two new mouse alleles, Ocmtm1e and Slc26a5tm1Cre. Each mutation leads to absence of detectable mRNA transcribed from the mutant allele, but there was no evidence that oncomodulin regulates expression of prestin or vice versa. The two mutants show distinctive patterns of auditory dysfunction. Ocmtm1e homozygotes have normal auditory brainstem response thresholds at 4 weeks old followed by progressive hearing loss starting at high frequencies, while heterozygotes show largely normal thresholds until 6 months of age, when signs of worse thresholds are detected. In contrast, Slc26a5tm1Cre homozygotes have stable but raised thresholds across all frequencies tested, 3 to 42 kHz, at least from 4 to 8 weeks old, while heterozygotes have raised thresholds at high frequencies. Distortion product otoacoustic emissions and cochlear microphonics show deficits similar to auditory brainstem responses in both mutants, suggesting that the origin of hearing impairment is in the outer hair cells. Endocochlear potentials are normal in the two mutants. Scanning electron microscopy revealed normal development of hair cells in Ocmtm1e homozygotes but scattered outer hair cell loss even at 4 weeks old when thresholds appeared normal, indicating that there is not a direct relationship between numbers of outer hair cells present and auditory thresholds.

Semaphorin7A patterns neural circuitry in the lateral line of the zebrafish.

In a developing nervous system, axonal arbors often undergo complex rearrangements before neural circuits attain their final innervation topology. In the lateral line sensory system of the zebrafish, developing sensory axons reorganize their terminal arborization patterns to establish precise neural microcircuits around the mechanosensory hair cells. However, a quantitative understanding of the changes in the sensory arbor morphology and the regulators behind the microcircuit assembly remain enigmatic. Here, we report that Semaphorin7A (Sema7A) acts as an important mediator of these processes. Utilizing a semi-automated three-dimensional neurite tracing methodology and computational techniques, we have identified and quantitatively analyzed distinct topological features that shape the network in wild-type and Sema7A loss-of-function mutants. In contrast to those of wild-type animals, the sensory axons in Sema7A mutants display aberrant arborizations with disorganized network topology and diminished contacts to hair cells. Moreover, ectopic expression of a secreted form of Sema7A by non-hair cells induces chemotropic guidance of sensory axons. Our findings propose that Sema7A likely functions both as a juxtracrine and as a secreted cue to pattern neural circuitry during sensory organ development.

Exploring Variation in Ovine KRTAP19-5 and Its Effect on Fine Wool Fibre Curvature in Chinese Tan Sheep.

Sheep's wool is known to have unique biological, physical and chemical properties. The fibre primarily consists of proteins, but these have amino acid sequence variation, and at the phenotypic level wool fibre varies considerably. This can affect its utility and value. Unravelling the genetic factors that underpin the protein and phenotypic variability is crucial if we are to contemplate improving wool quality. Accordingly, this study investigates the high glycine and tyrosine content keratin-associated protein 19-5 gene (KRTAP19-5) in sheep. PCR-single strand confirmation polymorphism analysis, coupled with DNA sequencing of a region spanning whole coding sequence, revealed six sequence variants containing seven single nucleotide polymorphisms (SNPs). Five of the SNPs were located within the coding region, with four leading to amino acid changes if expressed. In 247 Chinese Tan sheep derived from 10 sire-lines, and renowned for their distinct 'spring-like' crimped wool at up to approximately 35 days after birth, one of the variants was found to be associated with decreased curvature of the fine wool fibres in the fleece. No associations were detected with other fibre traits or with variation in the heterotypic hair fibres of the Tan sheep. While these findings may be useful for developing gene markers to alter mean wool fibre curvature and improve sheep breeding, many other genes and environmental factors are known to contribute to variation in fibre traits.

Synthesis of Keratin Nanoparticles Extracted from Human Hair through Hydrolysis with Concentrated Sulfuric Acid: Characterization and Cytotoxicity.

Human hair, composed primarily of keratin, represents a sustainable waste material suitable for various applications. Synthesizing keratin nanoparticles (KNPs) from human hair for biomedical uses is particularly attractive due to their biocompatibility. In this study, keratin was extracted from human hair using concentrated sulfuric acid as the hydrolysis agent for the first time. This process yielded KNPs in both the supernatant (KNPs-S) and precipitate (KNPs-P) phases. Characterization involved scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), Zeta potential analysis, X-ray diffraction (XRD), and thermogravimetric analysis (TG). KNPs-S and KNPs-P exhibited average diameters of 72 ± 5 nm and 27 ± 5 nm, respectively. The hydrolysis process induced a structural rearrangement favoring ß-sheet structures over α-helices in the KNPs. These nanoparticles demonstrated negative Zeta potentials across the pH spectrum. KNPs-S showed higher cytotoxicity (CC50 = 176.67 µg/mL) and hemolytic activity, likely due to their smaller size compared to KNPs-P (CC50 = 246.21 µg/mL), particularly at concentrations of 500 and 1000 µg/mL. In contrast, KNPs-P did not exhibit hemolytic activity within the tested concentration range of 32.5 to 1000 µg/mL. Both KNPs demonstrated cytocompatibility with fibroblast cells in a dose-dependent manner. Compared to other methods reported in the literature and despite requiring careful washing and neutralization steps, sulfuric acid hydrolysis proved effective, rapid, and feasible for producing cytocompatible KNPs (biomaterials) in single-step synthesis.