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1.
Nano Lett ; 24(20): 6174-6182, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38739468

RESUMEN

Accumulated reactive oxygen species (ROS) and their resultant vascular dysfunction in androgenic alopecia (AGA) hinder hair follicle survival and cause permanent hair loss. However, safe and effective strategies to rescue hair follicle viability to enhance AGA therapeutic efficiency remain challenging. Herein, we fabricated a quercetin-encapsulated (Que) and polydopamine-integrated (PDA@QLipo) nanosystem that can reshape the perifollicular microenvironment to initial hair follicle regeneration for AGA treatment. Both the ROS scavenging and angiogenesis promotion abilities of PDA@QLipo were demonstrated. In vivo assays revealed that PDA@QLipo administrated with roller-microneedles successfully rejuvenated the "poor" perifollicular microenvironment, thereby promoting cell proliferation, accelerating hair follicle renewal, and facilitating hair follicle recovery. Moreover, PDA@QLipo achieved a higher hair regeneration coverage of 92.5% in the AGA mouse model than minoxidil (87.8%), even when dosed less frequently. The nanosystem creates a regenerative microenvironment by scavenging ROS and augmenting neovascularity for hair regrowth, presenting a promising approach for AGA clinical treatment.


Asunto(s)
Alopecia , Folículo Piloso , Indoles , Polímeros , Quercetina , Especies Reactivas de Oxígeno , Alopecia/tratamiento farmacológico , Alopecia/patología , Quercetina/farmacología , Quercetina/administración & dosificación , Quercetina/química , Animales , Indoles/química , Indoles/farmacología , Folículo Piloso/efectos de los fármacos , Folículo Piloso/crecimiento & desarrollo , Polímeros/química , Ratones , Especies Reactivas de Oxígeno/metabolismo , Regeneración/efectos de los fármacos , Humanos , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Proliferación Celular/efectos de los fármacos , Microambiente Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino
2.
Int J Biol Macromol ; 242(Pt 3): 124907, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37230451

RESUMEN

Reptiles can evolve adaptive colors in different environments, but relatively little is known about the genetic mechanisms. Here, we identified the MC1R gene and its association with intraspecific color variation in the lizard Phrynocephalus erythrurus. Analysis of the MC1R sequence in 143 individuals from dark South Qiangtang Plateau (SQP) and light North Qiangtang plateau (NQP) populations, revealed two amino acid sites that showed significant differences in frequency between two areas. One SNP, corresponding to Glu183Lys residue, was found to be a highly significant outlier and differentially fixed for SQP and NQP populations. This residue is located in an extracellular area in the second small extracellular loop within the secondary structure of MC1R, which represents an "attachment pocket" part of the 3D structure. Cytological expression of MC1R alleles with the Glu183Lys replacement showed a 39 % increase in intracellular agonist-induced cyclic AMP levels and a 23.18 % greater cell surface expression of MC1R protein in the SQP relative to the NQP allele. Further in silico 3D modeling and in vitro binding experiments indicated a higher MC1R-α-MSH binding for the SQP allele, and elevated melanin synthesis. We provide an overview of how a single amino acid replacement leads to fundamental changes in MC1R function, and hence shapes variation in dorsal pigmentation in lizards from different environments.


Asunto(s)
Lagartos , Animales , Humanos , Lagartos/genética , Aminoácidos/metabolismo , Tibet , Pigmentación/genética , Alelos
3.
Mitochondrial DNA B Resour ; 7(7): 1406-1407, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35923642

RESUMEN

Nymphoides peltata is an aquatic floating weed widely distributed in the northern hemisphere of Eurasia. To better determine its phylogenetic relationships with other Nymphoides species and other aquatic plant species, the chloroplast genome of N. peltata was sequenced. The chloroplast genome size is 152,198 bp, consisting of a large single-copy region (84,223 bp) and a small single-copy region (17,817 bp) separated by a pair of inverted repeats with a length of 25,079 bp. The chloroplast genome contains 127 genes, including 85 protein-coding genes, 34 tRNA genes, and eight rRNAs. The maximum-likelihood phylogenetic tree showed that N. peltata is more closely related to other Nymphoides species, providing new insight into the evolution and genetic diversity of aquatic weeds.

4.
Genome Biol Evol ; 12(12): 2303-2313, 2020 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-33095228

RESUMEN

Identification of the role of the MC1R gene has provided major insights into variation in skin pigmentation in several organisms, including humans, but the evolutionary genetics of this variation is less well established. Variation in this gene and its relationship with degree of melanism was analyzed in one of the world's highest-elevation lizards, Phrynocephalus theobaldi from the Qinghai-Tibetan Plateau. Individuals from the low-elevation group were shown to have darker dorsal pigmentation than individuals from a high-elevation group. The existence of climatic variation across these elevations was quantified, with lower elevations exhibiting higher air pressure, temperatures, and humidity, but less wind and insolation. Analysis of the MC1R gene in 214 individuals revealed amino acid differences at five sites between intraspecific sister lineages from different elevations, with two sites showing distinct fixed residues at low elevations. Three of the four single-nucleotide polymorphisms that underpinned these amino acid differences were highly significant outliers, relative to the generalized MC1R population structuring, suggestive of selection. Transfection of cells with an MC1R allele from a lighter high-elevation population caused a 43% reduction in agonist-induced cyclic AMP accumulation, and hence lowered melanin synthesis, relative to transfection with an allele from a darker low-elevation population. The high-elevation allele led to less efficient integration of the MC1R protein into melanocyte membranes. Our study identifies variation in the degree of melanism that can be explained by four or fewer MC1R substitutions. We establish a functional link between these substitutions and melanin synthesis and demonstrate elevation-associated shifts in their frequencies.


Asunto(s)
Altitud , Lagartos/genética , Pigmentación/genética , Receptor de Melanocortina Tipo 1/genética , Animales , Femenino , Lagartos/metabolismo , Masculino , Polimorfismo de Nucleótido Simple , Transducción de Señal , Tibet
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