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1.
J Drugs Dermatol ; 23(3): 146-151, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38443124

RESUMEN

BACKGROUND: Topical minoxidil (TM) has been a cornerstone in treating various hair loss disorders, while low-dose oral minoxidil (LDOM) is emerging as an effective alternative. Despite their widespread use, there is a notable gap in the literature regarding their use in treating scarring alopecia. OBJECTIVE: This study evaluates the efficacy and safety of TM and LDOM in managing scarring alopecia. METHODS: A systematic literature search identified relevant studies on TM and LDOM use in central centrifugal cicatricial alopecia, frontal fibrosing alopecia, lichen planopilaris, and traction alopecia. Key metrics included disease stabilization, hair thickness improvement, hair regrowth, and side effect profiles. RESULTS: Analysis of the selected studies revealed mixed outcomes. Most participants experienced benefits in terms of disease stabilization and hair regrowth with TM and LDOM. The majority of cases reported good tolerability of the treatment, although some side effects were noted. CONCLUSION: TM and LDOM show promise in scarring alopecia treatment, demonstrating benefits in disease stabilization and hair regrowth. Despite these positive indications, the variability in results and reported side effects underline the need for further research to establish their consistent efficacy and safety profiles in scarring alopecia treatment. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7743.


Asunto(s)
Alopecia , Cicatriz , Minoxidil , Humanos , Alopecia/diagnóstico , Alopecia/tratamiento farmacológico , Cicatriz/tratamiento farmacológico , Cicatriz/etiología , Cabello , Minoxidil/uso terapéutico
2.
J Am Acad Dermatol ; 89(2S): S36-S39, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37591565

RESUMEN

Novel medical and procedural options for androgenetic alopecia have arrived. Low-dose oral minoxidil has made its clinical debut, while data on spironolactone, finasteride, and nutritional supplements have advanced. Minimally invasive technological advancements include photobiomodulation and platelet-rich plasma. Within hair transplantation, follicular unit extraction and robotics are now at the clinicians' fingertips.


Asunto(s)
Alopecia , Finasterida , Humanos , Alopecia/tratamiento farmacológico , Finasterida/uso terapéutico , Terapia Conductista , Minoxidil/uso terapéutico , Suplementos Dietéticos
4.
Biol Cell ; 103(11): 499-517, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21787361

RESUMEN

BACKGROUND INFORMATION: Intestinal absorption of alimentary lipids is a complex process ensured by enterocytes and leading to TRL [TAG (triacylglycerol)-rich lipoprotein] assembly and secretion. The accumulation of circulating intestine-derived TRL is associated with atherosclerosis, stressing the importance of the control of postprandial hypertriglyceridaemia. During the postprandial period, TAGs are also transiently stored as CLDs (cytosolic lipid droplets) in enterocytes. As a first step for determining whether CLDs could play a role in the control of enterocyte TRL secretion, we analysed the protein endowment of CLDs isolated by sucrose-gradient centrifugation from differentiated Caco-2/TC7 enterocytes, the only human model able to secrete TRL in culture and to store transiently TAGs as CLDs when supplied with lipids. Cells were analysed after a 24 h incubation with lipid micelles and thus in a state of CLD-associated TAG mobilization. RESULTS: Among the 105 proteins identified in the CLD fraction by LC-MS/MS (liquid chromatography coupled with tandem MS), 27 were directly involved in lipid metabolism pathways potentially relevant to enterocyte-specific functions. The transient feature of CLDs was consistent with the presence of proteins necessary for fatty acid activation (acyl-CoA synthetases) and for TAG hydrolysis. In differentiated Caco-2/TC7 enterocytes, we identified for the first time LPCAT2 (lysophosphatidylcholine acyltransferase 2), involved in PC (phosphatidylcholine) synthesis, and 3BHS1 (3-ß-hydroxysteroid dehydrogenase 1), involved in steroid metabolism, and confirmed their partial CLD localization by immunofluorescence. In enterocytes, LPCAT2 may provide an economical source of PC, necessary for membrane synthesis and lipoprotein assembly, from the lysoPC present in the intestinal lumen. We also identified proteins involved in lipoprotein metabolism, such as ApoA-IV (apolipoprotein A-IV), which is specifically expressed by enterocytes and has been proposed to play many functions in vivo, including the formation of lipoproteins and the control of their size. The association of ApoA-IV with CLD was confirmed by confocal and immunoelectron microscopy and validated in vivo in the jejunum of mice fed with a high-fat diet. CONCLUSIONS: We report for the first time the protein endowment of Caco-2/TC7 enterocyte CLDs. Our results suggest that their formation and mobilization may participate in the control of enterocyte TRL secretion in a cell-specific manner.


Asunto(s)
Diferenciación Celular , Citosol/metabolismo , Enterocitos/citología , Enterocitos/metabolismo , Lípidos/aislamiento & purificación , Proteoma/metabolismo , Animales , Células CACO-2 , Células Cultivadas , Células HeLa , Humanos , Metabolismo de los Lípidos , Masculino , Ratones , Ratones Endogámicos C57BL , Especificidad de Órganos
5.
Endocr Connect ; 11(12)2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36219843

RESUMEN

Objective: Growth hormone (GH) and insulin-like growth factors (IGFs) are not mandatory for reproductive life, but data suggest their synergistic action with follicle-stimulating hormone throughout ovarian folliculogenesis. We aimed to evaluate the association of IGF-1 level on clinical pregnancy rate after ovarian stimulation, with or without intrauterine insemination, in women with GH deficiency (GHD) treated with GH replacement therapy (GHRT) at conception. Design and methods: Data from 19 women with both GHD and hypogonadotropic hypogonadism referred to our reproductive medicine department were retrospectively collected. IGF-1 levels were assessed in a single laboratory, and values were expressed in s.d. from the mean. Results: Amongst the seven patients receiving GHRT during ovarian stimulation, higher IGF-1 levels were significantly associated with clinical pregnancy (+0.4 s.d. vs-1.6 s.d., P = 0.03). Amongst the 24 pregnancies obtained by the 19 infertile patients, pregnancy loss was less frequent with the addition of GHRT than without (1 miscarriage out of 8 total pregnancies vs 4 miscarriages out of 16 total pregnancies). Conclusions: This is the first study evaluating the association of IGF-1 level on clinical pregnancy rate in GH-treated women at conception. When taking care of female infertility due to hypogonadotropic hypogonadism, practitioners should enquire about the associated GHD and IGF-1 levels. To ensure higher clinical pregnancy chances, practitioners should aim for IGF-1 values at conception, ranging from 0 s.d. to +2 s.d., and, if necessary, could discuss initiation or increase GH treatment. Prospective studies should help strengthen our results.

9.
Nat Commun ; 9(1): 3825, 2018 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-30237420

RESUMEN

It is generally assumed that cells interrogate the mechanical properties of their environment by pushing and pulling on the extracellular matrix (ECM). For instance, acto-myosin-dependent contraction forces exerted at focal adhesions (FAs) allow the cell to actively probe substrate elasticity. Here, we report that a subset of long-lived and flat clathrin-coated structures (CCSs), also termed plaques, are contractility-independent mechanosensitive signaling platforms. We observed that plaques assemble in response to increasing substrate rigidity and that this is independent of FAs, actin and myosin-II activity. We show that plaque assembly depends on αvß5 integrin, and is a consequence of frustrated endocytosis whereby αvß5 tightly engaged with the stiff substrate locally stalls CCS dynamics. We also report that plaques serve as platforms for receptor-dependent signaling and are required for increased Erk activation and cell proliferation on stiff environments. We conclude that CCSs are mechanotransduction structures that sense substrate rigidity independently of cell contractility.


Asunto(s)
Vesículas Cubiertas por Clatrina/metabolismo , Endocitosis , Mecanotransducción Celular , Línea Celular , Proliferación Celular , Vesículas Cubiertas por Clatrina/ultraestructura , Humanos , Sistema de Señalización de MAP Quinasas , Receptores de Vitronectina/metabolismo
11.
Sci Rep ; 6: 35624, 2016 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-27752143

RESUMEN

Acetylation of the lysine 40 of α-tubulin (K40) is a post-translational modification occurring in the lumen of microtubules (MTs) and is controlled by the α-tubulin acetyl-transferase αTAT1. How αTAT1 accesses the lumen and acetylates α-tubulin there has been an open question. Here, we report that acetylation starts at open ends of MTs and progressively spreads longitudinally from there. We observed acetylation marks at the open ends of in vivo MTs re-growing after a Nocodazole block, and acetylated segments growing in length with time. Bias for MTs extremities was even more pronounced when using non-dynamic MTs extracted from HeLa cells. In contrast, K40 acetylation was mostly uniform along the length of MTs reconstituted from purified tubulin in vitro. Quantitative modelling of luminal diffusion of αTAT1 suggested that the uniform acetylation pattern observed in vitro is consistent with defects in the MT lattice providing lateral access to the lumen. Indeed, we observed that in vitro MTs are permeable to macromolecules along their shaft while cellular MTs are not. Our results demonstrate αTAT1 enters the lumen from open extremities and spreads K40 acetylation marks longitudinally along cellular MTs. This mode of tip-directed microtubule acetylation may allow for selective acetylation of subsets of microtubules.


Asunto(s)
Acetiltransferasas/metabolismo , Lisina/metabolismo , Proteínas de Microtúbulos/metabolismo , Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismo , Acetilación , Acetiltransferasas/genética , Adhesión Celular , Células HeLa , Humanos , Proteínas de Microtúbulos/genética , Microtúbulos/patología , Nocodazol/farmacología , Procesamiento Proteico-Postraduccional , ARN Interferente Pequeño/genética , Moduladores de Tubulina/farmacología
12.
Cell Rep ; 8(1): 75-83, 2014 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-24981864

RESUMEN

Transcription is a stochastic process occurring mostly in episodic bursts. Although the local chromatin environment is known to influence the bursting behavior on long timescales, the impact of transcription factors (TFs)--especially in rapidly inducible systems--is largely unknown. Using fluorescence in situ hybridization and computational models, we quantified the transcriptional activity of the proto-oncogene c-Fos with single mRNA accuracy at individual endogenous alleles. We showed that, during MAPK induction, the TF concentration modulates the burst frequency of c-Fos, whereas other bursting parameters remain mostly unchanged. By using synthetic TFs with TALE DNA-binding domains, we systematically altered different aspects of these bursts. Specifically, we linked the polymerase initiation frequency to the strength of the transactivation domain and the burst duration to the TF lifetime on the promoter. Our results show how TFs and promoter binding domains collectively act to regulate different bursting parameters, offering a vast, evolutionarily tunable regulatory range for individual genes.


Asunto(s)
Modelos Genéticos , Proteínas Proto-Oncogénicas c-fos/genética , Factores de Transcripción/metabolismo , Activación Transcripcional , Alelos , Línea Celular Tumoral , Células Cultivadas , ARN Polimerasas Dirigidas por ADN/metabolismo , Humanos , Estructura Terciaria de Proteína , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-fos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Procesos Estocásticos , Factores de Transcripción/química , Factores de Transcripción/genética
14.
PLoS One ; 6(8): e22841, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21857957

RESUMEN

Uncoupling protein 2 is a member of the mitochondrial anion carrier family that is widely expressed in neurons and the immune cells of humans. Deletion of Ucp2 gene in mice pre-activates the immune system leading to higher resistance toward infection and to an increased susceptibility to develop chronic inflammatory diseases as previously exemplified with the Experimental Autoimmune Encephalomyelitis (EAE), a mouse model for multiple sclerosis. Given that oxidative stress is enhanced in Ucp2-/- mice and that nitric oxide (NO) also plays a critical function in redox balance and in chronic inflammation, we generated mice deficient for both Ucp2 and iNos genes and submitted them to EAE. Mice lacking iNos gene exhibited the highest clinical score (3.4+/-0.5 p<0.05). Surprisingly, mice deficient for both genes developed milder disease with reduced immune cell infiltration, cytokines and ROS production as compared to iNos-/- mice.


Asunto(s)
Encefalomielitis Autoinmune Experimental/genética , Canales Iónicos/genética , Proteínas Mitocondriales/genética , Óxido Nítrico Sintasa de Tipo II/genética , Animales , Encéfalo/metabolismo , Encéfalo/patología , Citocinas/genética , Citocinas/metabolismo , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Humanos , Sistema Inmunológico/metabolismo , Sistema Inmunológico/patología , Canales Iónicos/deficiencia , Macrófagos Peritoneales/metabolismo , Macrófagos Peritoneales/patología , Ratones , Ratones Noqueados , Proteínas Mitocondriales/deficiencia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/deficiencia , Oxidación-Reducción , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Índice de Severidad de la Enfermedad , Médula Espinal/metabolismo , Médula Espinal/patología , Proteína Desacopladora 2
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