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1.
Methods Mol Biol ; 2787: 81-94, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38656483

RESUMEN

Plant genetics plays a key role in determining root hair initiation and development. A complex network of genetic interactions therefore closely monitors and influences root hair phenotype and morphology. The significance of these genes can be studied by employing, for instance, loss-of-function mutants, overexpression plant lines, and fluorescently labeled constructs. Confocal laser scanning microscopy is a great tool to visually observe and document these morphological features. This chapter elaborates the techniques involved in handling of microscopic setup to acquire images displaying root hair distribution along the fully elongated zone of Arabidopsis thaliana roots. Additionally, we illustrate an approach to visualize early fate determination of epidermal cells in the root apical meristem, by describing a method for imaging YFP tagged transgenic plant lines.


Asunto(s)
Arabidopsis , Microscopía Confocal , Raíces de Plantas , Microscopía Confocal/métodos , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Raíces de Plantas/citología , Arabidopsis/genética , Plantas Modificadas Genéticamente/genética , Meristema/crecimiento & desarrollo , Meristema/genética
2.
Artículo en Inglés | MEDLINE | ID: mdl-38656569

RESUMEN

Hair follicle stem cells (HFSCs) are adult stem cells located in the outer root sheath of the follicle bulge with high neural plasticity, which promise a potential for the stem cell therapy for neurological diseases. Hirschsprung's disease (HD) is characterized by the absence of ganglia in the distant bowel. In this study, we elucidated the capacity of HFSCs to differentiate into neuronal cells in the aganglionic colon from embryonic rat. HFSCs were isolated from adult Sprague-Dawley (SD) rats and formed spheres that could be passaged. The cultured HFSCs expressed neural crest stem cells (NCSCs) markers such as SOX10, CD34, and nestin, which indicated their neural crest lineage. Subsequent differentiation assays demonstrated that these cells could give rise to neural progeny that expressed neuronal or glial markers. The aganglionic colon from the embryonic intestine was applied as in vitro explant to test the capacity of proliferation and differentiation of HFSCs. The HFSCs expressing GFP or RFP integrated in intestinal explants and maintained proliferative capacity. Moreover, the HFSCs differentiated into Tuj1- or S100ß-positive cells in the cultured intestinal explants. The results proposed that the HFSCs might be an alternative source of neural stem cells for the HD therapy.

3.
Vet Parasitol Reg Stud Reports ; 50: 101017, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38644040

RESUMEN

Rhipicephalus (Boophilus) microplus causes considerable livestock production losses. Knowledge of the traits that influence tick resistance contributes to the development of breeding strategies designed to improve herd productivity. Within this context, this study evaluated the resistance of Caracu, a tropically adapted cattle breed, to R. microplus. Tick count, hair length, coat thickness, and coat color were evaluated in 202 naturally tick-infested females (cows and heifers) over a period of 18 months. Blood samples were collected from all animals during the winter season for hematological analysis. Data were analyzed using Pearson correlations, generalized linear models, and principal component analysis. Correlation coefficients of tick count with coat color, coat thickness, and hair length were estimated within each season. Hematological parameters were only included in the winter season analysis and were analyzed by the restricted maximum likelihood method using log-transformed data. No differences in blood parameters were observed between animals with and without ticks. However, tick count was negatively correlated with erythrocytes (-0.29) and hematocrit (-0.24) and positively correlated with mean corpuscular hemoglobin (0.21) and mean corpuscular hemoglobin concentration (0.25). These findings suggest that higher tick counts lead to a decrease in erythrocytes but also to an increase in the amount of hemoglobin per erythrocyte, which could reduce the damage caused by low erythrocyte levels due to tick hematophagy, delaying or preventing anemia. Although tick infestation on pasture was demonstrated by the infestation of all staff members during herd management, none of the animals exhibited high tick counts, providing evidence of resistance of Caracu animals to R. microplus. Tick infestation was influenced by age class (cows > heifers), season (spring and summer > fall and winter), coat thickness (>1.5 mm > <1.5 mm), and hair length (>6 mm > <6 mm). Three components were extracted by principal component analysis, which accounted for 69.46% of data variance. The findings of this study will contribute to the development of efficient strategies aimed at reducing economic losses due to tick infestation and could be applied in animal breeding to select for tick resistance traits, reducing chemical control strategies and consequently improving sustainable livestock production.


Asunto(s)
Enfermedades de los Bovinos , Rhipicephalus , Infestaciones por Garrapatas , Animales , Bovinos , Infestaciones por Garrapatas/veterinaria , Infestaciones por Garrapatas/parasitología , Femenino , Enfermedades de los Bovinos/parasitología , Rhipicephalus/fisiología , Estaciones del Año , Cabello/parasitología , Factores de Edad , Resistencia a la Enfermedad , Pelaje de Animal , Clima Tropical
4.
Acta Otolaryngol ; : 1-9, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38662892

RESUMEN

BACKGROUND: Recycling of synaptic vesicles plays an important role in vesicle pool replenishment, neurotransmitter release and synaptic plasticity. Clathrin-mediated endocytosis (CME) is considered to be the main mechanism for synaptic vesicle replenishment. AP-2 (adaptor-related protein complex 2) and myosin Ⅵ are known as key proteins that regulate the structure and dynamics of CME. OBJECTIVE: This study aims to reveal the spatiotemporal expression of AP-2/myosin Ⅵ in inner hair cells (IHCs) of the mouse cochlea and its correlation with auditory function. MATERIAL AND METHODS: Immunofluorescence was used to detect the localization and expression of AP-2 and myosin Ⅵ in cochlear hair cells (HCs) of CBA/CaJ mice of various ages. qRT-PCR was used to verify the differential expression of AP-2 and myosin Ⅵ mRNA in the mouse cochlea, and ABR tests were administered to mice of various ages. A preliminary analysis of the correlation between AP-2/myosin Ⅵ levels and auditory function was conducted. RESULTS: AP-2 was located in the cytoplasmic region of IHCs and was mainly expressed in the basal region of IHCs and the area near ribbon synapses, while myosin Ⅵ was expressed in the cytoplasmic region of IHCs and OHCs. Furthermore, AP-2 and myosin Ⅵ were not significant detected in the cochleae of P7 mice; the expression level reached a peak at P35 and then decreased significantly with age. The expression patterns and expression levels of AP-2 and myosin Ⅵ in the cochleae of the mice were consistent with the development of the auditory system. CONCLUSIONS AND SIGNIFICANCE: AP-2 and myosin Ⅵ protein expression may differ in mice of different ages, and this variation probably leads to a difference in the efficiency in CME; it may also cause a defect in IHC function.

5.
Dermatol Reports ; 16(1): 9745, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38623369

RESUMEN

Minoxidil is a widely utilized medication androgenic alopecia. An original investigation on its potential to cause hair darkening in treated people is lacking. We conducted an observational study using two face-validated questionnaires that dermatologists altered to assess minoxidil's hair discolouration risk. This Saudi Arabian survey collected data in October and November 2022. One questionnaire targeted the population, while the other targeted dermatologists. Survey 1 included 453 patients, 56.7% of whom were 18-24 and mostly female. It's interesting that 26% (n=118) detected hair greying and 14.8% (n=67) noticed other color changes. With P-values of 0.0001, longer-term minoxidil users and those with a family history of hair greying had higher hair discolouration. Dermatologists completed Survey 2 (57 participants). Nearly 60% of dermatologists have ten years of experience. 42.1% of dermatologists saw grey hair after minoxidil use. 17.5% of doctors blame minoxidil for hair graying. This observational study examined the data of over 400 patients to determine if minoxidil could cause hair discoloration. Based on the data, we hypothesize that this drug may cause hair discoloration with prolonged use and in people with a family history of hair greying.

6.
Skin Res Technol ; 30(4): e13700, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38634195

RESUMEN

BACKGROUND: Stromal vascular fraction (SVF) cells derived from adipose tissue and platelet-rich plasma (PRP) are among novel treatments for androgenetic alopecia (AGA). We aimed to investigate the effect of adding SVF to PRP and compare it to administering PRP injection alone. METHODS: Eighteen patients were randomly divided into two groups of nine. The PRP group was treated with PRP at all three visits at 1-month intervals, while the SVF-PRP group received an SVF injection on the first visit and a PRP injection on the second and third visits. Each group was evaluated at baseline and 20 weeks after the therapy's initiation. RESULTS: Changes in mean hair diameter and hair count compared to baseline were significant in both groups. The PRP group experienced a greater increase in mean hair count than the SVF-PRP group, and the SVF-PRP group had a marginally greater increase in hair diameter than the PRP group. These differences were not statistically significant compared to each other. The patient and physician assessment scores exceeded the mean (on a scale from 0: poor to 3: excellent) in both groups. CONCLUSION: Adding one SVF injection to two PRP treatment sessions versus three PRP injections alone had no significant difference in evaluated variables. If additional research demonstrates the same results, we suggest that multiple SVF injection sessions may be required to produce a statistically significant difference compared to PRP injection alone. Moreover, considering lower cost and greater accessibility of PRP, it can be used before SVF in the treatment of AGA.


Asunto(s)
Plasma Rico en Plaquetas , Fracción Vascular Estromal , Humanos , Alopecia/terapia , Cabello , Tejido Adiposo , Resultado del Tratamiento
7.
J Transl Med ; 22(1): 370, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637842

RESUMEN

JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC50 of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under in vivo and in vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.


Asunto(s)
Desarrollo de Medicamentos , Cabello , Ratones , Animales , Humanos , Ratones Desnudos , Descubrimiento de Drogas , Janus Quinasa 3
8.
Orphanet J Rare Dis ; 19(1): 169, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637854

RESUMEN

BACKGROUND: Cartilage-hair hypoplasia (CHH) is a rare syndromic immunodeficiency with metaphyseal chondrodysplasia and increased risk of malignancy. In this cross-sectional observational study, we examined HPV status and oral microbiome in individuals with CHH. Oral brush samples were collected from 20 individuals with CHH (aged 5-59 years) and 41 controls (1-69 years). Alpha HPVs (43 types) were tested by nested PCR followed by bead-based probe hybridization. Separately, beta-, gamma-, mu- and nu- HPV types were investigated, and a genome-based bacterial microbiome sequencing was performed. RESULTS: We found a similar alpha HPV prevalence in individuals with CHH (45%) and controls (36%). The HPV types of individuals with CHH were HPV-16 (25%), 27, 28, and 78, and of controls HPV-3, 16 (21%), 27, and 61. Beta HPV positivity and combined beta/gamma/mu/nu prevalence was detected in 11% and 11% of individuals with CHH and in 5% and 3% of the controls, respectively. Individuals with CHH differed from the controls in bacterial microbiota diversity, richness, and in microbial composition. Individuals with CHH had lower abundance of species Mitsuokella sp000469545, Parascardovia denticolens, Propionibacterium acidifaciens, UMGS1907 sp004151455, Salinicola halophilus, Haemophilus_A paraphrohaemolyticus, Fusobacterium massiliense, and Veillonella parvula, and higher abundance of Slackia exigua. CONCLUSIONS: Individuals with CHH exhibit similar prevalence of HPV DNA but different bacterial microbiota on their oral mucosa compared to healthy controls. This may partly explain the previously observed high prevalence of oral diseases in CHH, and regular oral examination is warranted.


Asunto(s)
Cabello/anomalías , Enfermedad de Hirschsprung , Microbiota , Osteocondrodisplasias , Osteocondrodisplasias/congénito , Infecciones por Papillomavirus , Enfermedades de Inmunodeficiencia Primaria , Humanos , Virus del Papiloma Humano , Infecciones por Papillomavirus/epidemiología , Prevalencia , Estudios Transversales , Osteocondrodisplasias/genética
9.
Front Neurol ; 15: 1356614, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38638308

RESUMEN

Tmc1 and Tmc2 are essential pore-forming subunits of mechanosensory transduction channels localized to the tips of stereovilli in auditory and vestibular hair cells of the inner ear. To investigate expression and function of Tmc1 and Tmc2 in vestibular organs, we used quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization - hairpin chain reaction (FISH-HCR), immunostaining, FM1-43 uptake and we measured vestibular evoked potentials (VsEPs) and vestibular ocular reflexes (VORs). We found that Tmc1 and Tmc2 showed dynamic developmental changes, differences in regional expression patterns, and overall expression levels which differed between the utricle and saccule. These underlying changes contributed to unanticipated phenotypic loss of VsEPs and VORs in Tmc1 KO mice. In contrast, Tmc2 KO mice retained VsEPs despite the loss of the calcium buffering protein calretinin, a characteristic biomarker of mature striolar calyx-only afferents. Lastly, we found that neonatal Tmc1 gene replacement therapy is sufficient to restore VsEP in Tmc1 KO mice for up to six months post-injection.

10.
Ecol Evol ; 14(4): e11286, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38654714

RESUMEN

Cave-adapted animals evolve a suite of regressive and constructive traits that allow survival in the dark. Most studies aiming at understanding cave animal evolution have focused on the genetics and environmental underpinnings of regressive traits, with special emphasis on vision loss. Possibly as a result of vision loss, other non-visual sensory systems have expanded and compensated in cave species. For instance, in many cave-dwelling fish species, including the blind cavefish of the Mexican tetra, Astyanax mexicanus, a major non-visual mechanosensory system called the lateral line, compensated for vision loss through morphological expansions. While substantial work has shed light on constructive adaptation of this system, there are still many open questions regarding its developmental origin, synaptic plasticity, and overall adaptive value. This review provides a snapshot of the current state of knowledge of lateral line adaption in A. mexicanus, with an emphasis on anatomy, synaptic plasticity, and behavior. Multiple open avenues for future research in this system, and how these can be leveraged as tools for both evolutionary biology and evolutionary medicine, are discussed.

11.
Front Endocrinol (Lausanne) ; 15: 1361715, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38654925

RESUMEN

Introduction: Hair cortisol level has recently been identified as a promising marker for detecting long-term cortisol levels and a marker of hypothalamic-pituitary-adrenal cortex (HPA) axis activity. However, research on the association between obesity and an altered cortisol metabolism remains controversial. Objective: This study aimed to investigate the relationship between hair cortisol levels and overweight and obesity in participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: This was a cross-sectional study involving 2,499 participants from the second follow-up (visit 3, 2017-2019) attending research centers in Rio de Janeiro and Rio Grande do Sul states. Hair samples were collected, and cortisol levels were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Cortisol levels were classified as low (< 40 pg/mg), medium (40-128 pg/mg), or high (> 128 pg/mg). The participants were classified as eutrophic, overweight, or obese according to their weight (kg) and height (m2). Odds ratios (ORs) with 95% confidence intervals (95%CI) were estimated. Results: Of the 2499 individuals, 30% had eutrophic weight, 40% were overweight, and 30% were obese. Notably, cortisol levels gradually increased with increasing body weight. Among participants with high hair cortisol levels, 41.2% were classified as overweight and 34.2% as obese. Multinomial logistic regression analysis indicated that participants with high cortisol levels were 43% (OR =1.43; 95%CI: 1.02-2.03) more likely to be overweight and 72% (OR =1.72; 95%CI:1.20-2.47) more likely to be obese than participants with low hair cortisol levels. After adjustment for all covariates, high cortisol levels remained associated with obesity (OR = 1.54; 95%CI:1.02-2.31) and overweight (OR =1.33; 95%CI:0.91-1.94). Conclusion: In the ELSA-Brazil cohort, hair stress were positively associated with overweight and obesity. These results underscore the importance of considering stress and cortisol as potential factors in obesity prevention and intervention efforts, and highlight a novel aspect of the complex relationship between stress and obesity in the Brazilian population.


Asunto(s)
Cabello , Hidrocortisona , Obesidad , Sobrepeso , Humanos , Hidrocortisona/metabolismo , Hidrocortisona/análisis , Cabello/química , Cabello/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Obesidad/metabolismo , Obesidad/epidemiología , Estudios Transversales , Sobrepeso/metabolismo , Sobrepeso/epidemiología , Brasil/epidemiología , Adulto , Estudios Longitudinales , Biomarcadores/análisis , Biomarcadores/metabolismo , Anciano , Estudios de Cohortes
12.
Compr Psychoneuroendocrinol ; 18: 100234, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38660593

RESUMEN

Background: Hair has become an increasingly valuable medium to investigate the association between chronic stress, stable differences in systemic cortisol secretion and later health. Assessing cortisol in hair has many advantages, notably its non-invasive and retrospective nature, the need for a single biospecimen and convenient storage until analysis. However, few studies offered empirical evidence documenting the long-term temporal stability of hair cortisol concentration (HCC) prior to analysis, especially in humans. Yet, knowing how long hair samples can be stored without compromising the accuracy of cortisol measurement is of crucial importance when planning data collection and analysis. This study examined the stability of HCC in hair samples assayed twice, five years apart. Methods: We randomly selected from a larger distribution of HCC measured in 17-year-old participants 39 hair samples to be reanalyzed five years later, under the same general conditions. Samples were assayed in duplicate using a luminescence immunoassay and compared with the original HCC using the Lin's concordance correlation coefficient (CCC), Bland-Altman plot analysis and Wilcoxon rank test. Results: Findings indicated a good concordance and temporal stability between the two samples assayed five years apart (CCC [95% confidence interval] = 0.84 [0.72-0.91]), although a small decrease in HCC was noted 5 years later (8.4% reduction, p = 0.001). Conclusion: Our study confirms that hair samples, when stored at room temperature and away from sunlight, can be assayed for at least five years without risking a loss of precision in HCC measurement.

13.
bioRxiv ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38645220

RESUMEN

Death of mechanosensory hair cells in the inner ear is a common cause of auditory and vestibular impairment in mammals, which have a limited ability to regrow these cells after damage. In contrast, non-mammalian vertebrates including zebrafish can robustly regenerate hair cells following severe organ damage. The zebrafish inner ear provides an understudied model system for understanding hair cell regeneration in organs that are highly conserved with their mammalian counterparts. Here we quantitatively examine hair cell addition during growth and regeneration of the larval zebrafish inner ear. We used a genetically encoded ablation method to induce hair cell death and observed gradual regeneration with correct spatial patterning over two weeks following ablation. Supporting cells, which surround and are a source of new hair cells, divide in response to hair cell ablation, expanding the possible progenitor pool. In parallel, nascent hair cells arise from direct transdifferentiation of progenitor pool cells uncoupled from progenitor division. These findings reveal a previously unrecognized mechanism of hair cell regeneration with implications for how hair cells may be encouraged to regenerate in the mammalian ear.

14.
Compr Psychoneuroendocrinol ; 18: 100231, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38645423

RESUMEN

For numerous issues of convenience and acceptability, hair hormone data have been increasingly incorporated in the field of war trauma and forced displacement, allowing retrospective examination of several biological metrics thought to covary with refugees' mental health. As a relatively new research method, however, there remain several complexities and uncertainties surrounding the use of hair hormones, from initial hair sampling to final statistical analysis, many of which are underappreciated in the extant literature, and restrict the potential utility of hair hormones. To promote awareness, we provide a narrative overview of our experiences collecting and analyzing hair hormone data in a large cohort of Syrian refugee children (n = 1594), across two sampling waves spaced 12 months apart. We highlight both the challenges faced, and the promising results obtained thus far, and draw comparisons to other prominent studies in this field. Recommendations are provided to future researchers, with emphasis on longitudinal study designs, thorough collection and reporting of hair-related variables, and careful adherence to current laboratory guidelines and practices.

15.
Biomed Eng Lett ; 14(3): 367-392, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38645592

RESUMEN

Bioelectric medicine (BEM) refers to the use of electrical signals to modulate the electrical activity of cells and tissues in the body for therapeutic purposes. In this review, we particularly focused on the microcurrent stimulation (MCS), because, this can take place at the cellular level with sub-sensory application unlike other stimuli. These extremely low-level currents mimic the body's natural electrical activity and are believed to promote various physiological processes. To date, MCS has limited use in the field of BEM with applications in several therapeutic purposes. However, recent studies provide hopeful signs that MCS is more scalable and widely applicable than what has been used so far. Therefore, this review delves into the landscape of MCS, shedding light on the multifaceted applications and untapped potential of MCS in the realm of healthcare. Particularly, we summarized the hierarchical mediation from cell to whole body responses by MCS including its physiological applications. Our final objective of this review is to contribute to the growing body of literature that unveils the captivating potential of BEM, with MCS poised at the intersection of technological innovation and the intricacies of the human body.

16.
Elife ; 122024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38651641

RESUMEN

Inhibitory G alpha (GNAI or Gαi) proteins are critical for the polarized morphogenesis of sensory hair cells and for hearing. The extent and nature of their actual contributions remains unclear, however, as previous studies did not investigate all GNAI proteins and included non-physiological approaches. Pertussis toxin can downregulate functionally redundant GNAI1, GNAI2, GNAI3, and GNAO proteins, but may also induce unrelated defects. Here, we directly and systematically determine the role(s) of each individual GNAI protein in mouse auditory hair cells. GNAI2 and GNAI3 are similarly polarized at the hair cell apex with their binding partner G protein signaling modulator 2 (GPSM2), whereas GNAI1 and GNAO are not detected. In Gnai3 mutants, GNAI2 progressively fails to fully occupy the sub-cellular compartments where GNAI3 is missing. In contrast, GNAI3 can fully compensate for the loss of GNAI2 and is essential for hair bundle morphogenesis and auditory function. Simultaneous inactivation of Gnai2 and Gnai3 recapitulates for the first time two distinct types of defects only observed so far with pertussis toxin: (1) a delay or failure of the basal body to migrate off-center in prospective hair cells, and (2) a reversal in the orientation of some hair cell types. We conclude that GNAI proteins are critical for hair cells to break planar symmetry and to orient properly before GNAI2/3 regulate hair bundle morphogenesis with GPSM2.


Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP Gi-Go , Células Ciliadas Auditivas , Morfogénesis , Animales , Ratones , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/genética , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/fisiología , Polaridad Celular , Subunidad alfa de la Proteína de Unión al GTP Gi2/metabolismo , Subunidad alfa de la Proteína de Unión al GTP Gi2/genética
17.
Cell Rep ; 43(4): 114025, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38564333

RESUMEN

Type I spiral ganglion neurons (SGNs) convey sound information to the central auditory pathway by forming synapses with inner hair cells (IHCs) in the mammalian cochlea. The molecular mechanisms regulating the formation of the post-synaptic density (PSD) in the SGN afferent terminals are still unclear. Here, we demonstrate that brain-specific angiogenesis inhibitor 1 (BAI1) is required for the clustering of AMPA receptors GluR2-4 (glutamate receptors 2-4) at the PSD. Adult Bai1-deficient mice have functional IHCs but fail to transmit information to the SGNs, leading to highly raised hearing thresholds. Despite the almost complete absence of AMPA receptor subunits, the SGN fibers innervating the IHCs do not degenerate. Furthermore, we show that AMPA receptors are still expressed in the cochlea of Bai1-deficient mice, highlighting a role for BAI1 in trafficking or anchoring GluR2-4 to the PSDs. These findings identify molecular and functional mechanisms required for sound encoding at cochlear ribbon synapses.


Asunto(s)
Cóclea , Audición , Densidad Postsináptica , Receptores AMPA , Receptores Acoplados a Proteínas G , Ganglio Espiral de la Cóclea , Animales , Receptores AMPA/metabolismo , Ratones , Ganglio Espiral de la Cóclea/metabolismo , Audición/fisiología , Cóclea/metabolismo , Densidad Postsináptica/metabolismo , Ratones Noqueados , Células Ciliadas Auditivas Internas/metabolismo , Ratones Endogámicos C57BL , Sinapsis/metabolismo
18.
Int Immunopharmacol ; 133: 112070, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38640716

RESUMEN

Skin, the largest organ of body, is a highly immunogenic tissue with a diverse collection of immune cells. Highly polymorphic human leukocyte antigen (HLA) molecules have a central role in coordinating immune responses as recognition molecules. Nevertheless, HLA gene expression patterns among diverse cell types within a specific organ, like the skin, have yet to be thoroughly investigated, with stromal cells attracting much less attention than immune cells. To illustrate HLA expression profiles across different cell types in the skin, we performed single-cell RNA sequencing (scRNA-seq) analyses on skin datasets, covering adult and fetal skin, and hair follicles as the skin appendages. We revealed the variation in HLA expression between different skin populations by examining normal adult skin datasets. Moreover, we evaluated the potential immunogenicity of multiple skin populations based on the expression of classical HLA class I genes, which were well represented in all cell types. Furthermore, we generated scRNA-seq data of developing skin from fetuses of 15 post conception weeks (PCW), 17 PCW, and 22 PCW, delineating the dynamic expression of HLA genes with cell type-dependent variation among various cell types during development. Notably, the pseudotime trajectory analysis unraveled the significant variance in HLA genes during the evolution of vascular endothelial cells. Moreover, we uncovered the immune-privileged properties of hair follicles at single-cell resolution. Our study presents a comprehensive single-cell transcriptomic landscape of HLA genes in the skin, which provides new insights into variation in HLA molecules and offers a clue for allogeneic skin transplantation.

19.
Histochem Cell Biol ; 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38641701

RESUMEN

Chemotherapy-induced alopecia (CIA) represents one of the most severe side effects of chemotherapy, which forces some patients to reject cancer treatment. The exact pathophysiological mechanisms of CIA are not clearly understood, which makes it difficult to discover efficient preventive or therapeutic procedures for this adverse effect. N-acetylcysteine (NAC) has a strong antioxidant activity as it stimulates glutathione synthesis and acts as an oxygen radical scavenger. The current study tried to investigate the efficacy of NAC in preserving biochemical parameters and hair follicle structure against cyclophosphamide (CYP) administration. In total, 40 adult female C57BL/6 mice were induced to enter anagen by depilation (day 0) and divided into four groups: group I (control), group II (CYP) received a single dose of CYP [150 mg/kg body weight (B.W.)/intraperitoneal injection (IP)] at day 9, group III (CYP & NAC) received a single dose of CYP at day 9 as well as NAC (500 mg/kg B.W./day/IP) from day 6-16, and group IV (NAC) received NAC from day 6-16. CYP administration in group II induced an increase in malondialdehyde (MDA), decrease in superoxide dismutase (SOD), histological hair follicle dystrophy, disruption of follicular melanogenesis, overexpression of p53, and loss of ki67 immunoreactivity. NAC coadministration in group III reversed CYP-induced alterations in the biochemical parameters and preserved hair follicle structure, typical follicular melanin distribution as well as normal pattern of p53 and ki67 expression. These findings indicated that NAC could be used as an efficient and safe therapeutic option for hair loss induced by chemotherapy.

20.
J Endocrinol Invest ; 2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38644453

RESUMEN

PURPOSE: Testosterone therapy represents the cornerstone of gender affirming hormone therapy (GAHT) among t-AFAB (transgender Assigned Female At Birth) people. Minoxidil is a vasodilator drug approved for topical use for the treatment of androgenetic alopecia. The aim of the present study was to evaluate the efficacy of topical minoxidil in enhancing beard growth in a group of t-AFAB people on GAHT. METHODS: Sixteen t-AFAB individuals with an incomplete beard development, on GAHT for at least 6 months, were enrolled. Topical minoxidil was applied to the interested facial areas. Before starting (T0), after 3 (T3) and 6 (T6) months, we evaluated facial hair growth using the Ferriman-Gallwey modified score (FGm). RESULTS: Subjects were 26 (2.7) years old and on GAHT for 18.5 [15-54] months; using a paired match evaluation, a statistically significant facial hair growth was observed over time, in particular at T6 (median upper lip FGm 3.5 [3-4] vs 2 [1-2] at T0 and chin FGm 4 [3.25-4] vs 1 [1-2] at T0; p ≤ 0.002). Comparing the minoxidil group with a control group (n = 16) matched for age and BMI who developed a full-grown beard only with GAHT, a logistic multivariable analysis identified hirsutism before GAHT was independently positively associated with the development of a full beard [OR 15.22 (95% CI 1.46-158.82); p = 0.023]. CONCLUSIONS: This is the first study demonstrating the efficacy of topical minoxidil in enhancing facial hair growth among t-AFAB people on GAHT. Further studies will be necessary to assess whether the obtained improvements will persist after discontinuing the medication.

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