RESUMO
5-Fluorouracil (5-FU) is an antineoplastic agent known for its low bioavailability and limited cellular penetration, often resulting in adverse effects on healthy cells. Thus, finding vehicles that enhance bioavailability, enable controlled release, and mitigate adverse effects is crucial. The study focuses on encapsulating 5-FU within soy lecithin vesicles (SLVs) and assessing its impact on the carrier's properties and functionality. Results show that incorporating 5-FU does not affect SLVs' size or polydispersity, even postlyophilization. Liberation of 5-FU from SLVs requires system disruption rather than spontaneous release, with an encapsulation efficiency of approximately 43% determined using Square Wave Voltammetry. Cytotoxicity assays on colorectal cancer cells reveal SLV-based delivery's significant efficacy, surpassing free drug solution effects with 45% cell viability after 72 h vs 73% viability. The research addresses 5-FU's limited bioavailability by creating a biocompatible nanocarrier for efficient drug delivery, highlighting SLVs as promising for targeted cancer therapy due to sustained antiproliferative effects and improved cellular uptake. The study underscores the importance of tailored drug delivery systems in enhancing therapeutic outcomes and suggests SLV/5-FU formulations as a potential advancement in cancer treatment strategies.
Assuntos
Sobrevivência Celular , Portadores de Fármacos , Fluoruracila , Glycine max , Lecitinas , Fluoruracila/química , Fluoruracila/farmacologia , Lecitinas/química , Humanos , Portadores de Fármacos/química , Sobrevivência Celular/efeitos dos fármacos , Glycine max/química , Liberação Controlada de Fármacos , Técnicas Eletroquímicas , Nanopartículas/químicaRESUMO
Goats have played a key role as source of nourishment for humans in their expansion all over the world in long land and sea trips. This has guaranteed a place for this species in the important and rapid episode of livestock expansion triggered by Columbus' arrival in the Americas in the late 1400s. The aims of this study are to provide a comprehensive perspective on genetic diversity in American goat populations and to assess their origins and evolutionary trajectories. This was achieved by combining data from autosomal neutral genetic markers obtained in more than two thousand samples that encompass a wide range of Iberian, African and Creole goat breeds. In general, even though Creole populations differ clearly from each other, they lack a strong geographical pattern of differentiation, such that populations of different admixed ancestry share relatively close locations throughout the large geographical range included in this study. Important Iberian signatures were detected in most Creole populations studied, and many of them, particularly the Cuban Creole, also revealed an important contribution of African breeds. On the other hand, the Brazilian breeds showed a particular genetic structure and were clearly separated from the other Creole populations, with some influence from Cape Verde goats. These results provide a comprehensive characterisation of the present structure of goat genetic diversity, and a dissection of the Iberian and African influences that gave origin to different Creole caprine breeds, disentangling an important part of their evolutionary history. Creole breeds constitute an important reservoir of genetic diversity that justifies the development of appropriate management systems aimed at improving performance without loss of genomic diversity.
Assuntos
Cruzamento , Variação Genética , Cabras , Animais , Brasil , Marcadores Genéticos , Cabras/genética , FilogeniaRESUMO
The Lidia bovine breed is distinguished for its low genetic exchangeability given its selection on aggressive behavior, its management uniqueness and its subdivided structure. In this study, we present a comprehensive genome-wide analysis of genetic diversity, population structure and admixture of 468 animals from Mexican and Spanish Lidia breed populations and 64 samples belonging to 10 Spanish native and American-creole breeds using 37 148 single nucleotide polymorphisms. We found similar average inbreeding values in the Lidia breed, with different distributions within groups; variability of inbreeding values among Spanish lineages was significant and no differences were found among the Mexican sub-populations. Together, the high FIS of the lineages and the behavior of the runs of homozygosity are consequences of the lineage's small effective population sizes, contributing to their inbreeding increase. Population admixture analysis discarded any influence on the genetic structure of the Lidia populations from the Spanish native and American-creole breeds. In addition, both Lidia populations depicted different genetic origins, with the exception of some Mexican individuals whose origins traced back to recent Spanish importations.
Assuntos
Cruzamento , Bovinos/genética , Genética Populacional , Animais , Homozigoto , Endogamia , México , Polimorfismo de Nucleotídeo Único , Densidade Demográfica , EspanhaRESUMO
Lidia bovine breed exists since the XIV century in the Iberian Peninsula. These animals were initially produced for meat but some, showing an aggressive behaviour which difficulted their management, were used to participate in popular traditional and social events. A specialization of the breed giving rise to the original Lidia population is documented in Spain since mid-XVIII century. Following the same tradition than in the Spanish population, Mexico used aggressive animals at the beginning of the XX century until two families of breeders started importing Lidia breed bovines from Spain with the aim of specializing their production. Each family (Llaguno and González) followed different breeding managements, and currently, most of the Lidia Mexican population derives from the Llaguno line. Although genetic structure and diversity of the Spanish population have been studied (using autosomal microsatellite markers, Y chromosome DNA markers and mitochondrial DNA sequences), the Mexican population is not analysed. The aim of the study was to assess both the genetic structure and diversity of the Mexican Lidia breed and its relationship with the original Spanish population using the same molecular tools. A total of 306 animals belonging to 20 breeders issued from both existing Mexican families were genotyped, and the genetic information was compared to the previously existing Spanish information. Slightly higher levels of genetic diversity in Mexican population were found when comparing to the Spanish population, and the variability among populations accounted for differences within them showing mean values of 0.18 and 0.12, respectively. Animals from the Mexican breeders, belonging to each of the two families, clustered together, and there was little evidence of admixture with the Spanish population. The analysis of Y chromosome diversity showed a high frequency of the H6 haplotype in the Mexican population, whereas this haplotype is rare in the Spanish, which is only found in the Miura (100%) and Casta Navarra (38%) lineages. Mitochondrial DNA revealed similar haplotypic pattern in both Spanish and Mexican populations, which is in accordance with most of the Mediterranean bovine breeds. In conclusion, as the Mexican Lidia population had initially a small number of founders and its current population has been reared isolated from their Spanish ancestors since a long time, these bottleneck effects and a combination of mixed cattle origin are the factors that might erase any trace of the Spanish origin of this population.
Assuntos
Cruzamento , Bovinos/genética , DNA Mitocondrial/genética , Variação Genética , Genética Populacional , Repetições de Microssatélites , Cromossomo Y , Animais , Bovinos/classificação , Genótipo , Masculino , México , Espanha , Especificidade da EspécieRESUMO
Although in the cow the genetic resistance to brucellosis has been previously attributed to the Slc11A1 gene encoding Nramp1 protein, none of the mutations described to date seems to be the cause. To be able to associate another polymorphism of the gene to brucellosis resistance, we characterized the gene and identified in different breeds of Bos taurus and Bos indicus, six new variants among a total of 11 single nucleotide mutations, of which five occurred in the coding sequence (three are missense mutations), one in the promoter region and five in introns. The allelic and genotypic frequencies calculated revealed differences (p < 0.05) among the breeds studied.
Assuntos
Proteínas de Transporte de Cátions/genética , Bovinos/genética , Variação Genética , Alelos , Sequência de Aminoácidos , Animais , Cruzamento , Bovinos/classificação , Frequência do Gene , Íntrons , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Homologia de Sequência de Aminoácidos , Especificidade da EspécieRESUMO
The genetic structure of 4 Colombian Creole cattle breeds, namely, Costeño con Cuernos, Blanco Orejinegro (BON), Romosinuano (ROMO), and Sanmartinero (SM), was studied with an analysis of the available pedigree data. The comparison between the effective number of founders (f(e)) and the effective number of ancestors (f(a)) revealed a decrease in the genetic variation that was rather important for the ROMO and San Martinero breeds, which had the lowest f(a)/f(e) ratios (0.34 and 0.53, respectively). All breeds showed similar values for the number of equivalent generations traced, ranging from 3.1 in BON to 4.8 in ROMO. These 2 populations also had the lowest and the highest population sizes, respectively. The lowest average inbreeding coefficient considering the whole pedigree was obtained by BON (0.18%), whereas the highest was attained by ROMO (1.22%). Finally, the percentage of individuals with an inbreeding level greater than 6.25% in the reference population was high, indicating that the existing conservation management strategies could be improved to successfully maintain the genetic variability of these populations.