Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.393
Filtrar
1.
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
2.
Ups J Med Sci ; 1292024.
Artículo en Inglés | MEDLINE | ID: mdl-38571883

RESUMEN

The Grey allele in horses is causing premature hair greying and susceptibility to melanoma. The causal mutation is a 4.6 kb tandem duplication in intron 6 of the Syntaxin 17 gene. A recent study demonstrated that the most common allele at the Grey locus (G3) involves three tandem copies of this sequence, whilst a more rare allele (G2) has two tandem copies and the wild-type allele (G1) only one copy. The G3 allele is causing fast greying and high incidence of skin melanoma, whereas the G2 allele is causing slow greying and no obvious increase in melanoma incidence. Further somatic copy number expansion has been documented in melanoma tissue from Grey horses. Functional studies showed that this intronic sequence acts as a weak melanocyte-specific enhancer that becomes substantially stronger by the copy number expansion. The Grey mutation is associated with upregulated expression of both Syntaxin 17 and the neighbouring NR4A3 gene in Grey horse melanomas. It is still an open question which of these genes is most important for the phenotypic effects or if causality is due to the combined effect of upregulation of both genes. Interestingly, RNAseq data in the Human Protein Atlas give support for a possible role of NR4A3 because it is particularly upregulated in human skin cancer, and it belongs to a cluster of genes associated with skin cancer and melanin biosynthesis. The Grey mutation and its association with melanoma provide a possibility to study the path to tumour development in numerous Grey horses carrying exactly the same predisposing mutation.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/genética , Melanoma/veterinaria , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/veterinaria , Proteínas Qa-SNARE/genética , Proteínas Qa-SNARE/metabolismo , Mutación , Cabello/metabolismo , Cabello/patología
4.
Front Endocrinol (Lausanne) ; 15: 1282564, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38638132

RESUMEN

Objective: We compared hair cortisol (HC) with classic tests of the hypothalamic-pituitary-adrenal (HPA) axis in chronic kidney disease (CKD) and assessed its association with kidney and cardiometabolic status. Design and methods: A cross-sectional study of 48 patients with CKD stages I-IV, matched by age, sex, and BMI with 24 healthy controls (CTR) was performed. Metabolic comorbidities, body composition, and HPA axis function were studied. Results: A total of 72 subjects (age 52.9 ± 12.2 years, 50% women, BMI 26.2 ± 4.1 kg/m2) were included. Metabolic syndrome features (hypertension, dyslipidaemia, glucose, HOMA-IR, triglycerides, waist circumference) and 24-h urinary proteins increased progressively with worsening kidney function (p < 0.05 for all). Reduced cortisol suppression after 1-mg dexamethasone suppression (DST) (p < 0.001), a higher noon (12:00 h pm) salivary cortisol (p = 0.042), and salivary cortisol AUC (p = 0.008) were seen in CKD. 24-h urinary-free cortisol (24-h UFC) decreased in CKD stages III-IV compared with I-II (p < 0.001); higher midnight salivary cortisol (p = 0.015) and lower suppressibility after 1-mg DST were observed with declining kidney function (p < 0.001). Cortisol-after-DST cortisol was >2 mcg/dL in 23% of CKD patients (12.5% in stage III and 56.3% in stage IV); 45% of them had cortisol >2 mcg/dL after low-dose 2-day DST, all in stage IV (p < 0.001 for all). Cortisol-after-DST was lineally inversely correlated with eGFR (p < 0.001). Cortisol-after-DST (OR 14.9, 95% CI 1.7-103, p = 0.015) and glucose (OR 1.3, 95% CI 1.1-1.5, p = 0.003) were independently associated with eGFR <30 mL/min/m2). HC was independently correlated with visceral adipose tissue (VAT) (p = 0.016). Cortisol-after-DST (p = 0.032) and VAT (p < 0.001) were independently correlated with BMI. Conclusion: Cortisol-after-DST and salivary cortisol rhythm present progressive alterations in CKD patients. Changes in cortisol excretion and HPA dynamics in CKD are not accompanied by significant changes in long-term exposure to cortisol evaluated by HC. The clinical significance and pathophysiological mechanisms explaining the associations between HPA parameters, body composition, and kidney damage warrant further study.


Asunto(s)
Cabello , Hidrocortisona , Insuficiencia Renal Crónica , Humanos , Estudios Transversales , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Cabello/metabolismo , Hidrocortisona/metabolismo , Estudios de Casos y Controles , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Dexametasona/uso terapéutico , Factores de Riesgo de Enfermedad Cardiaca , Estudios Prospectivos , Sistema Hipotálamo-Hipofisario
5.
Sci Rep ; 14(1): 9459, 2024 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658668

RESUMEN

Analysis of endocannabinoids (ECs) and N-acylethanolamines (NAEs) in hair is assumed to retrospectively assess long-term EC/NAE concentrations. To inform their use, this study investigated stability of EC/NAE hair concentrations in mothers, fathers, and their children across the perinatal period as well as associations between family members. In a prospective cohort study, EC (AEA, 1-AG/2-AG) and NAE (SEA, PEA, OEA) levels were quantified in hair samples taken four times in mothers (n = 336) and their partners (n = 225) from pregnancy to two years postpartum and in offspring (n = 319) from shortly after birth to two years postpartum. Across the perinatal period, maternal and paternal hair ECs/NAEs showed poor multiple-test consistency (16-36%) and variable relative stability, as well as inconsistent absolute stability for mothers. Regarding children, hair ECs/NAEs evidenced poor multiple-test consistency (4-19%), no absolute stability, and either no or variable relative stability. Hair ECs/NAEs showed small to medium significant associations across the perinatal period within couples and parent-child dyads. Findings suggest hair ECs/NAEs during the perinatal period possess variable stability in adults, albeit more stability in fathers than mothers in this time. This highlights the need to further investigate factors associated with changes in hair ECs/NAEs across time. The first two years of life may be a dynamic phase for the endocannabinoid system in children, potentially characterized by complex within-family correspondence that requires further systematic investigation.


Asunto(s)
Endocannabinoides , Etanolaminas , Padre , Cabello , Madres , Humanos , Endocannabinoides/metabolismo , Endocannabinoides/análisis , Femenino , Cabello/química , Cabello/metabolismo , Masculino , Etanolaminas/metabolismo , Etanolaminas/análisis , Adulto , Embarazo , Preescolar , Lactante , Estudios Prospectivos , Recién Nacido , Niño
6.
In Vivo ; 38(3): 1199-1202, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38688645

RESUMEN

BACKGROUND/AIM: Hair-follicle keratinocytes contain high levels of cysteine, which is derived from methionine, rapidly proliferate, and form the hair shaft. The high proliferation rate of hair-follicle keratinocytes resembles that of aggressive cancer cells. In the present study, we determined the effect of a methionine-deficient diet on hair loss (alopecia) in mice with or without homocysteine supplementation. MATERIALS AND METHODS: Mice were fed a normal rodent diet (2020X, ENVIGO) (Group 1); a methionine-choline-deficient diet (TD.90262, ENVIGO) (Group 2); a methionine-choline-deficient diet with a 10 mg/kg/day supply of homocysteine administered by intra-peritoneal (i.p.) injection for 2 weeks (Group 3). In Group 2, mice were fed a methionine-choline-deficient diet for an additional 2 weeks but with 10 mg/kg/day of i.p. l-homocysteine and the mice were observed for two additional weeks. Subsequently, the mice were fed a standard diet that included methionine. Hair loss was monitored by photography. RESULTS: After 14 days, hair loss was observed in Group 2 mice on a methionine-restricted diet but not in Group 3 mice on the methionine-restricted diet which received i.p. homocysteine. In Group 2, at 2 weeks after methionine restriction, hair loss was not rescued by homocysteine supplementation. However, after restoration of methionine in the diet, hair growth resumed. Thus, after 2 weeks of methionine restriction, only methionine restored hair loss, not homocysteine. CONCLUSION: Hair maintenance requires methionine in the diet. Future experiments will determine the effects of methionine restriction on hair-follicle stem cells.


Asunto(s)
Folículo Piloso , Cabello , Homocisteína , Metionina , Animales , Metionina/deficiencia , Metionina/metabolismo , Metionina/administración & dosificación , Ratones , Cabello/crecimiento & desarrollo , Cabello/metabolismo , Homocisteína/metabolismo , Folículo Piloso/metabolismo , Folículo Piloso/efectos de los fármacos , Folículo Piloso/crecimiento & desarrollo , Ratones Endogámicos C57BL , Alopecia/metabolismo , Alopecia/etiología , Alopecia/patología , Modelos Animales de Enfermedad , Dieta , Queratinocitos/metabolismo
7.
Nat Commun ; 15(1): 2328, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38499530

RESUMEN

Cornified skin appendages, such as hair and nails, are major evolutionary innovations of terrestrial vertebrates. Human hair and nails consist largely of special intermediate filament proteins, known as hair keratins, which are expressed under the control of the transcription factor Hoxc13. Here, we show that the cornified claws of Xenopus frogs contain homologs of hair keratins and the genes encoding these keratins are flanked by promoters in which binding sites of Hoxc13 are conserved. Furthermore, these keratins and Hoxc13 are co-expressed in the claw-forming epithelium of frog toe tips. Upon deletion of hoxc13, the expression of hair keratin homologs is abolished and the development of cornified claws is abrogated in X. tropicalis. These results indicate that Hoxc13-dependent expression of hair keratin homologs evolved already in stem tetrapods, presumably as a mechanism for protecting toe tips, and that this ancestral genetic program was coopted to the growth of hair in mammals.


Asunto(s)
Queratinas Específicas del Pelo , Factores de Transcripción , Animales , Humanos , Factores de Transcripción/metabolismo , Piel/metabolismo , Cabello/metabolismo , Queratinas/genética , Queratinas/metabolismo , Anfibios , Mamíferos/metabolismo
8.
Environ Sci Technol ; 58(13): 5739-5749, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38456395

RESUMEN

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.


Asunto(s)
Dietilhexil Ftalato , Ácidos Ftálicos , Humanos , Embarazo , Recién Nacido , Femenino , Plastificantes , Meconio/metabolismo , Dietilhexil Ftalato/metabolismo , Dietilhexil Ftalato/toxicidad , Ácidos Ftálicos/metabolismo , Cabello/metabolismo , Organofosfatos , Biotransformación , Ésteres/metabolismo , Exposición a Riesgos Ambientales/análisis
9.
ACS Appl Bio Mater ; 7(3): 1513-1525, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38354359

RESUMEN

Skin is the body barrier that constrains the infiltration of particles and exogenous aggression, in which the hair follicle plays an important role. Recent studies have shown that small particles can penetrate the skin barrier and reach the hair follicle, making them a potential avenue for delivering hair growth-related substances. Interestingly, keratin-based microspheres are widely used as drug delivery carriers in various fields. In this current study, we pursue the effect of newly synthesized 3D spherical keratin particles on inducing hair growth in C57BL/6 male mice and in human hair follicle dermal papilla cells. The microspheres were created from partially sulfonated, water-soluble keratin. The keratin microspheres swelled in water to form spherical gels, which were used for further experiments. Following topical application for a period of 20 days, we observed a regrowth of hair in the previously depleted area on the dorsal part of the mice in the keratin microsphere group. This observation was accompanied by the regulation of hair-growth-related pathways as well as changes in markers associated with epidermal cells, keratin, and collagen. Interestingly, microsphere keratin treatment enhanced the cell proliferation and the expression of hair growth markers in dermal papilla cells. Based on our data, we propose that 3D spherical keratin has the potential to specifically target hair follicle growth and can be employed as a carrier for promoting hair growth-related agents.


Asunto(s)
Cabello , Queratinas , Masculino , Ratones , Humanos , Animales , Queratinas/metabolismo , Queratinas/farmacología , Microesferas , Ratones Endogámicos C57BL , Cabello/metabolismo , Agua
10.
PLoS One ; 19(2): e0297080, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38408073

RESUMEN

BACKGROUND: Hair loss/thinning is a common side effect of tamoxifen in estrogen receptor (ER) positive breast cancer therapy. Some nutraceuticals known to promote hair growth are avoided during breast cancer therapy for fear of phytoestrogenic activity. However, not all botanical ingredients have similarities to estrogens, and in fact, no information exists as to the true interaction of these ingredients with tamoxifen. Therefore, this study sought to ascertain the effect of nutraceuticals (+/- estrogen/tamoxifen), on proliferation of breast cancer cells and the relative expression of ERα/ß. METHODS: Kelp, Astaxanthin, Saw Palmetto, Tocotrienols, Maca, Horsetail, Resveratrol, Curcumin and Ashwagandha were assessed on proliferation of MCF7, T47D and BT483 breast cancer cell lines +/- 17ß-estradiol and tamoxifen. Each extract was analysed by high performance liquid chromatography (HPLC) prior to use. Cellular ERα and ERß expression was assessed by qRT-PCR and western blot. Changes in the cellular localisation of ERα:ERß and their ratio following incubation with the nutraceuticals was confirmed by immunocytochemistry. RESULTS: Estradiol stimulated DNA synthesis in three different breast cancer cell lines: MCF7, T47D and BT483, which was inhibited by tamoxifen; this was mirrored by a specific ERa agonist in T47D and BT483 cells. Overall, nutraceuticals did not interfere with tamoxifen inhibition of estrogen; some even induced further inhibition when combined with tamoxifen. The ERα:ERß ratio was higher at mRNA and protein level in all cell lines. However, incubation with nutraceuticals induced a shift to higher ERß expression and a localization of ERs around the nuclear periphery. CONCLUSIONS: As ERα is the key driver of estrogen-dependent breast cancer, if nutraceuticals have a higher affinity for ERß they may offer a protective effect, particularly if they synergize and augment the actions of tamoxifen. Since ERß is the predominant ER in the hair follicle, further studies confirming whether nutraceuticals can shift the ratio towards ERß in hair follicle cells would support a role for them in hair growth. Although more research is needed to assess safety and efficacy, this promising data suggests the potential of nutraceuticals as adjuvant therapy for hair loss in breast cancer patients receiving endocrine therapy.


Asunto(s)
Neoplasias de la Mama , Tamoxifeno , Humanos , Femenino , Tamoxifeno/farmacología , Tamoxifeno/uso terapéutico , Neoplasias de la Mama/genética , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Estradiol/farmacología , Estrógenos/farmacología , Células MCF-7 , Suplementos Dietéticos , Alopecia/tratamiento farmacológico , Cabello/metabolismo , Línea Celular Tumoral , Proliferación Celular
11.
Adv Healthc Mater ; 13(8): e2303095, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38175177

RESUMEN

Androgenetic alopecia (AGA) is a prevalent systemic disease caused by diverse factors, for which effective treatments are currently limited. Herein, the oleogel (OG) containing copper-curcumin (CuR) nanoparticles is developed, designated as CuRG, which is also combined with traditional naturopathic scraping (Gua Sha, SCR) as a multifunctional therapy for AGA. With the assistance of lipophilic OG and SCR, CuR can efficaciously penetrate the epidermal and dermal regions where most hair follicles (HFs) reside, thereby releasing curcumin (CR) and copper ions (Cu2+) subcutaneously to facilitate hair regeneration. Concomitantly, the mechanical stimulation induced by SCR promotes the formation of new blood vessels, which is conducive to reshaping the microenvironment of HFs. This study validates that the combination of CuRG and SCR is capable of systematically interfering with different pathological processes, ranging from improvement of perifollicular microenvironment (oxidative stress and insufficient vascularization), regulation of inflammatory responses to degradation of androgen receptor, thus potentiating hair growth. Compared with minoxidil, a widely used clinical drug for AGA therapy, the designed synergistic system displays augmented hair regeneration in the AGA mouse model.


Asunto(s)
Cobre , Curcumina , Animales , Ratones , Cobre/farmacología , Curcumina/farmacología , Alopecia/tratamiento farmacológico , Alopecia/metabolismo , Alopecia/patología , Cabello/metabolismo , Compuestos Orgánicos
12.
Biochem Biophys Res Commun ; 699: 149551, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38277730

RESUMEN

V-ATPase is an ATP hydrolysis-driven proton pump involved in the acidification of intracellular organelles and systemic acid-base homeostasis through H+ secretion in the renal collecting ducts. V-ATPase dysfunction is associated with hereditary distal renal tubular acidosis (dRTA). ATP6V1B1 encodes the B1 subunit of V-ATPase that is integral to ATP hydrolysis and subsequent H+ transport. Patients with pathogenic ATP6V1B1 mutations often exhibit an early onset of sensorineural hearing loss. However, the mechanisms underlying this association remain unclear. We employed morpholino oligonucleotide-mediated knockdown and CRISPR/Cas9 gene editing to generate Atp6v1ba-deficient (atp6v1ba-/-) zebrafish as an ortholog model for ATP6V1B1. The atp6v1ba-/- zebrafish exhibited systemic acidosis and significantly smaller otoliths compared to wild-type siblings. Moreover, deficiency in Atp6v1ba led to degeneration of inner ear hair cells, with ultrastructural changes indicative of autophagy. Our findings indicate a critical role of ATP6V1B1 in regulating lysosomal pH and autophagy in hair cells, and the results provide insights into the pathophysiology of sensorineural hearing loss in dRTA. Furthermore, this study demonstrates that the atp6v1ba-/- zebrafish model is a valuable tool for further investigation into disease mechanisms and potential therapies for acidosis-related hearing impairment.


Asunto(s)
Acidosis Tubular Renal , Acidosis , Pérdida Auditiva Sensorineural , Compuestos Organometálicos , ATPasas de Translocación de Protón Vacuolares , Animales , Humanos , Pez Cebra/metabolismo , ATPasas de Translocación de Protón Vacuolares/genética , ATPasas de Translocación de Protón Vacuolares/metabolismo , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/patología , Mutación , Acidosis Tubular Renal/genética , Células Ciliadas Auditivas/patología , Concentración de Iones de Hidrógeno , Cabello/metabolismo , Adenosina Trifosfato
13.
Toxicol Appl Pharmacol ; 483: 116809, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38211931

RESUMEN

Xanthohumol (XN) is a prominent prenylated flavonoid present in the hop plant (Humulus lupulus L.). Despite undoubted pro-healing properties of hop plant, there is still a need for clinical investigations confirming these effects as well as the underlying molecular mechanisms. The present study was designed to (1) establish the role of XN in non-invasive inflammation induced by chemical damage to zebrafish hair cells, (2) clarify if it influences cell injury severity, neutrophil migration, macrophage activation, cell regeneration, and (3) find out whether it modulates the gene expression profile of chosen immune and stress response markers. All experiments were performed on 3 dpf zebrafish larvae. After fertilization the embryos were transferred to appropriate XN solutions (0.1 µM, 0.3 µM and 0.5 µM). The 40 min 10 µM CuSO4 exposure evoked severe damage to posterior lateral line hair cells triggering a robust acute inflammatory response. Four readouts were selected as the indicators of XN role in the process of inflammation: 1) hair cell death, 2) neutrophil migration towards damaged hair cells, 3) macrophage activation and recruitment to damaged hair cells, 4) hair cell regeneration. The assessments involved in vivo confocal microscopy imaging and qPCR based molecular analysis. It was demonstrated that XN (1) influences death pathway of damaged hair cells by redirecting their severe necrotic phenotype into apoptotic one, (2) impacts the immune response via regulating neutrophil migration, macrophage recruitment and activation (3) modulates gene expression of immune system markers and (4) accelerates hair cell regeneration.


Asunto(s)
Humulus , Propiofenonas , Animales , Humulus/química , Humulus/metabolismo , Pez Cebra/metabolismo , Flavonoides/química , Propiofenonas/toxicidad , Propiofenonas/química , Propiofenonas/metabolismo , Inmunidad Innata , Inflamación/inducido químicamente , Cabello/metabolismo
14.
Exp Dermatol ; 33(1): e14990, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38071436

RESUMEN

Stress has been considered as a potential trigger for hair loss through the neuroendocrine-hair follicle (HF) axis. Neurotensin (NTS), a neuropeptide, is known to be dysregulated in the inflammatory-associated skin diseases. However, the precise role of NTS in stress-induced hair loss is unclear. To investigate the function and potential mechanisms of NTS in stress-induced hair growth inhibition, we initially detected the expression of neurotensin receptor (Ntsr) and NTS in the skin tissues of stressed mice by RNA-sequencing and ELISA. We found chronic restraint stress (CRS) significantly decreased the expression of both NTS and Ntsr in the skin tissues of mice. Intracutaneous injection of NTS effectively counteracted CRS-induced inhibition of hair growth in mice. Furthermore, NTS regulated a total of 1093 genes expression in human dermal papilla cells (HDPC), with 591 genes being up-regulated and 502 genes being down-regulated. GO analysis showed DNA replication, cell cycle, integral component of plasma membrane and angiogenesis-associated genes were significantly regulated by NTS. KEGG enrichment demonstrated that NTS also regulated genes related to the Hippo signalling pathway, axon guidance, cytokine-cytokine receptor interaction and Wnt signalling pathway in HDPC. Our results not only uncovered the potential effects of NTS on stress-induced hair growth inhibition but also provided an understanding of the mechanisms at the gene transcriptional level.


Asunto(s)
Cabello , Neurotensina , Animales , Humanos , Ratones , Alopecia/metabolismo , Folículo Piloso/metabolismo , Neuropéptidos/metabolismo , Neurotensina/genética , Neurotensina/metabolismo , Neurotensina/farmacología , Receptores de Neurotensina/genética , Receptores de Neurotensina/metabolismo , Cabello/crecimiento & desarrollo , Cabello/metabolismo
15.
J Invest Dermatol ; 144(2): 284-295.e16, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37716648

RESUMEN

Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss-of-function variants in desmosomal genes leads to a variety of skin- and heart-related phenotypes. In this study, we report TUFT1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair, and mild palmoplantar keratoderma but without a cardiac phenotype, we identified a homozygous splice-site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of TUFT1 protein. Patients' skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that TUFT1 is positioned within the desmosome and that its location is dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1-knockout mouse model mimicked the patients' phenotypes. Altogether, this study reveals TUFT1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair, and palmoplantar keratoderma.


Asunto(s)
Enfermedades del Cabello , Queratodermia Palmoplantar , Anomalías Cutáneas , Animales , Humanos , Ratones , Desmoplaquinas/genética , Desmoplaquinas/metabolismo , Desmosomas/metabolismo , Cabello/metabolismo , Enfermedades del Cabello/genética , Enfermedades del Cabello/metabolismo , Queratodermia Palmoplantar/genética , Queratodermia Palmoplantar/metabolismo , Piel/metabolismo , Anomalías Cutáneas/metabolismo
16.
Hormones (Athens) ; 23(1): 113-120, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37792214

RESUMEN

PURPOSE: The role of endocannabinoids (ECs) in the regulation of the hypothalamic-pituitary-adrenocortical axis has already been studied; however, data are scarce in humans. The aim of our study was to analyze EC [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and cortisol (F) levels in hair samples of patients with adrenal incidentalomas (AIs) in comparison with those found in controls and assess their association with the hormone profile. METHODS: Forty-four patients with AIs [32 with non-functioning AIs (NFAIs) and 12 with possible autonomous secretion (PACS)] and 44 controls were recruited. Basal and post-1 mg overnight dexamethasone suppression test (ODST) F, adrenocorticotropic hormone, dehydroepiandrosterone sulfate, and 24-h urinary free cortisol were analyzed. After hair collection, EC and F levels were measured by liquid chromatography tandem-mass spectrometry. RESULTS: There was no difference between the groups regarding age, sex, and metabolic status. Significantly decreased hair AEA and 2-AG levels were found in patients with AIs compared to controls (p < 0.001 and p = 0.002, respectively) as well as between NFAI or PACS and controls (p < 0.001 or p = 0.002 and p = 0.038 or p = 0.02, respectively). Among the AI patients, EC levels tended to be lower in the PACS group. AEA hair levels were negatively correlated with F levels post-1 mg ODST (rs = -0.257, p = 0.033). We found no significant difference comparing hair F between the groups. CONCLUSION: Our findings suggest that hair EC measurement could be a potential biomarker in the evaluation of patients with AIs, whereas hair F analysis is not a useful diagnostic test for mild hypercortisolemia.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Hidrocortisona , Humanos , Hidrocortisona/metabolismo , Neoplasias de las Glándulas Suprarrenales/metabolismo , Estudios de Casos y Controles , Endocannabinoides , Dexametasona , Cabello/metabolismo
17.
J Cosmet Dermatol ; 23(3): 986-998, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37905348

RESUMEN

BACKGROUND: Hair loss occurs due to various biological and environmental causes, which can have psychosocial consequences. The Wnt/ß-catenin signaling is well-known for its role in hair growth and regeneration, as it induces the proliferation and differentiation of hair cells. When the leucine-rich G protein-coupled receptor 5 (Lgr5) interacts with the R-spondins, the frizzled receptor (FZD), a Wnt receptor, becomes stabilized, resulting in an increased ß-catenin activity. AIM: We investigated whether the octapeptide that binds to Lgr5 enhances proliferation and differentiation of human primary hair cells through the activation of Wnt/ß-catenin signaling. METHODS: The binding affinity of the octapeptide to Lgr5 was evaluated using surface plasmon resonance (SPR). We confirmed changes in proliferation and related factors like ß-catenin activation and growth factors (GFs) expression in human hair follicle dermal papilla cells (HHFDPCs). Additionally, we observed the proliferation and the expression of differentiation markers in human hair follicle outer root sheath cells (HHFORSCs), human hair follicle germinal matrix cells (HHFGMCs), and human hair follicle stem cells (HHFSCs). We used three-dimensional HHFDPC spheroid culture treated with dihydrotestosterone (DHT) to create in vitro conditions that mimic androgenetic alopecia, and we studied the effects of octapeptide on Wnt expression and HHFSC differentiation. RESULTS: The binding of the octapeptide to Lgr5 was confirmed using SPR analysis. In HHFDPCs, treatment with octapeptide resulted in a concentration-dependent increase in proliferation. We also observed increased nuclear translocation of ß-catenin and increased expression of its downstream targets. HHFDPCs treated with octapeptide exhibited increased expression of growth factors and phosphorylation of Akt and ERK. In addition, we confirmed that octapeptide increased proliferation and induced differentiation in HHFORSCs, HHFGMCs, and HHFSCs. Under the HHFDPC spheroid culture conditions, we found that octapeptide restored the inhibition of Wnt-5a and Wnt-10b expressions by DHT. In HHFSCs treated with HHFDPC spheroid culture media, we observed that octapeptide recovered the inhibition of differentiation by DHT. CONCLUSION: We found that octapeptides activated the Wnt/ß-catenin signaling and induced the proliferation and differentiation of human primary hair cells by acting as an exogenous ligand for Lgr5. In addition, octapeptides recovered inhibited hair regeneration characters by DHT in androgenetic alopecia-mimic in vitro model. These findings suggest that octapeptides may be a promising therapeutic option for treating hair loss.


Asunto(s)
Folículo Piloso , beta Catenina , Humanos , beta Catenina/metabolismo , Cabello/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Vía de Señalización Wnt , Dihidrotestosterona/metabolismo , Alopecia/tratamiento farmacológico , Alopecia/metabolismo , Péptidos y Proteínas de Señalización Intercelular/farmacología , Proliferación Celular
18.
J Proteome Res ; 23(1): 409-417, 2024 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-38009783

RESUMEN

A fast and sensitive direct extraction (DE) method developed in our group can efficiently extract proteins in 30 min from a 5 cm-long hair strand. Previously, we coupled DE to downstream analysis using gel electrophoresis followed by in-gel digestion, which can be time-consuming. In searching for a better alternative, we found that a combination of DE with a bead-based method (SP3) can lead to significant improvements in protein discovery in human hair. Since SP3 is designed for general applications, we optimized it to process hair proteins following DE and compared it to several other in-solution digestion methods. Of particular concern are genetically variant peptides (GVPs), which can be used for human identification in forensic analysis. Here, we demonstrated improved GVP discovery with the DE and SP3 workflow, which was 3 times faster than the previous in-gel digestion method and required significantly less instrument time depending on the number of gel slices processed. Additionally, it led to an increased number of identified proteins and GVPs. Among the tested in-solution digestion methods, DE combined with SP3 showed the highest sequence coverage, with higher abundances of the identified peptides. This provides a significantly enhanced means for identifying proteins and GVPs in human hair.


Asunto(s)
Péptidos , Proteínas , Humanos , Proteínas/análisis , Péptidos/análisis , Electroforesis , Cabello/química , Cabello/metabolismo
19.
J Psychosom Res ; 176: 111566, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38100896

RESUMEN

BACKGROUND: Stress is an important predictor of long-term conditions. We examine whether hair cortisol (a biomarker of stress) is associated with incidence and accumulation of multiple long-term conditions (MLTC). METHODS: We included data from 4295 individuals aged ≥50 years within the English Longitudinal Study of Ageing dataset with data on hair cortisol, sociodemographic and health behaviour variables. Cox proportional hazards models were used to quantify the association between hair cortisol at baseline and accumulation of MLTC between 2012/2013 and 2018/2019, both for individuals with and without MLTC at baseline. RESULTS: Our cohort included 1458 (34.0%) individuals who accumulated MLTC between 2012/2013 and 2018/2019. The proportion of individuals with zero, 1, and ≥ 2 conditions at baseline who accumulated MLTC were 12.0% (n = 127), 40.4% (n = 520), and 41.7% (n = 811), respectively. Higher cortisol levels were associated with higher risk of accumulation of MLTC in both unadjusted [HR:1.15(1.05-1.25)] and models adjusted for sociodemographic and health behaviours [HR:1.12(1.02-1.22)]. For individuals without MLTC at baseline, higher cortisol levels were significantly associated with higher risk of developing MLTC in unadjusted [HR: 1.20(1.05-1.36)] and adjusted models [HR: 1.16(1.02-1.32)]. CONCLUSION: The study provides the first evidence of the role of stress in the development and accumulation of MLTC. This modifiable risk factor could be targeted to reduce the risk of MLTC. However, further work is needed to better understand the mechanisms and pathways that link stress and accumulation of MLTC.


Asunto(s)
Cabello , Hidrocortisona , Humanos , Estudios de Cohortes , Estudios Longitudinales , Hidrocortisona/metabolismo , Cabello/metabolismo , Envejecimiento
20.
Biomed Pharmacother ; 170: 115913, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38154270

RESUMEN

The plant Justicia procumbens is traditionally used in Asia to treat fever, cough, and pain. Previous studies have reported its anticancer and anti-asthmatic properties. However, its potential for preventing androgenic alopecia (AGA) has not yet been reported. AGA is a widespread hair loss condition primarily caused by male hormones. In this study, we examined the hair loss-preventing effects of an aqueous extract of J. procumbens (JPAE) using human hair follicle dermal papilla cell (HFDPC) and a mouse model of testosterone-induced AGA. JPAE treatment increased HFDPC proliferation by activating the Wnt/ß-catenin signaling pathway. Additionally, JPAE increased the expression of Wnt targets, such as cyclin D1 and VEGF, by promoting the translocation of ß-catenin to the nucleus. Administration of JPAE reduced hair loss, increased hair thickness, and enhanced hair shine in an AGA mouse model. Furthermore, it increased the expression of p-GSK-3ß and ß-catenin in the dorsal skin of the mice. These findings imply that JPAE promotes the proliferation of HFDPC and prevents hair loss in an AGA mouse model. JPAE can therefore be used as a functional food and natural treatment option for AGA to prevent hair loss.


Asunto(s)
Género Justicia , beta Catenina , Humanos , Ratones , Animales , beta Catenina/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Alopecia/inducido químicamente , Alopecia/prevención & control , Alopecia/metabolismo , Cabello/metabolismo , Vía de Señalización Wnt
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...