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1.
Artigo em Inglês | MEDLINE | ID: mdl-38536434

RESUMO

Targeting lung cancer stem cells (LC-SCs) for metastasis may be an effective strategy against lung cancer. This study is the first on epithelial-mesenchymal transition (EMT) properties of boric acid (BA) in LC-SCs. LC-SCs were isolated using the magnetic cell sorting (MACS) method. Tumor-sphere formation and flow cytometry confirmed CSC phenotype. The cytotoxic effect of BA was measured by MTT analysis, and the effect of BA on EMT was examined by migration analysis. The expression levels of ZEB1, SNAIL1, ITGA5, CDH1, ITGB1, VIM, COL1A1, and LAMA5 genes were analyzed by RT-qPCR. E-cadherin, Collagen-1, MMP-3, and Vimentin expressions were analyzed immunohistochemically. Boric acid slightly reduced the migration of cancer cells. Increased expression of transcription factor SNAIL (p < 0.001), but not ZEB1, was observed in LC-SCs. mRNA expression levels of ITGB1 (p < 0.01), ITGA5 (p < 0.001), COL1A1 (p < 0.001), and LAMA5 (p < 0.001) increased; CDH1 and VIM decreased in LC-SCs. Moreover, while E-cadherin (p < 0.001) and Collagen-1 (p < 0.01) immunoreactivities significantly increased, MMP-3 (p < 0.001) and Vimentin (p < 0.01) immunoreactivities decreased in BA-treated LC-SCs. To conclude, the current study provided insights into the efficacy and effects of BA against LC-SCs regarding proliferation, EMT, and cell death for future studies.

2.
Gene ; 865: 147337, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-36878417

RESUMO

This study aimed to investigate the differences between the exosomal microRNA-127-5p expression profiles of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and human synovial fluid-derived mesenchymal stem cells (hSF-MSCs) during chondrogenesis in terms of regenerative treatment of cartilage. Synovial fluid-derived mesenchymal stem cells, adipose tissue-derived mesenchymal stem cells, and human fetal chondroblast cells (hfCCs) were directed to chondrogenic differentiation. Alcian Blue and Safranin O stainings were performed to detect chondrogenic differentiation histochemically. Exosomes derived from chondrogenic differentiated cells and their exosomes were isolated and characterized. microRNA-127-5p expressions were measured by Quantitative reverse transcription PCR (qRT-PCR). Significantly higher levels of microRNA-127-5p expression in differentiated hAT-MSCs exosomes, similar to human fetal chondroblast cells, which are the control group in the chondrogenic differentiation process, were observed. hAT-MSCs are better sources of microRNA-127-5p than hSF-MSCs for stimulating chondrogenesis or in the regenerative therapy of cartilage-related pathologies. hAT-MSCs exosomes are rich sources of microRNA-127-5p and can be an essential candidate for cartilage regeneration treatments.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Líquido Sinovial/metabolismo , Exossomos/genética , Exossomos/metabolismo , Condrogênese/genética , Diferenciação Celular , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células Cultivadas
3.
Neurobiol Aging ; 106: 332.e1-332.e11, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34162492

RESUMO

Just as its clinical heterogeneity, genetic basis of Frontotemporal dementia (FTD) is also diverse and multiple molecular pathways are thought to be involved in disease pathogenesis. In the present study, FTD- related genes were evaluated in a Turkish cohort of 175 index FTD patients with a gene panel including GRN, MAPT, TARDBP, FUS, CHMP2B and VCP genes. Potential genetic associations were prospected in 16 patients (9.1%); five variants (p.(Gly35Glufs) and p.(Cys253Ter) in GRN; p.(Arg95Cys) in VCP; p.(Met405Val) in TARDBP and p.(Pro636Leu) in MAPT) were classified as pathogenic (P) or likely pathogenic (LP), in four familial and one sporadic patients. Three novel variants in MAPT, CHMP2B and FUS were also identified in familial cases. The most common pathogenic variants were observed in the GRN gene with a frequency of 1.14% (2/175) and this rate was 4.57% (8/175), including variants of uncertain significance (VUS). In this study with the largest cohort of Turkish FTD patients, GRN and MAPT variants were identified as the most common genetic associations; and rare causes like VCP, TARDBP, CHMP2B and FUS variants are recommended to be considered in patients with compatible clinical findings.


Assuntos
Demência Frontotemporal/epidemiologia , Demência Frontotemporal/genética , Frequência do Gene/genética , Estudos de Associação Genética/métodos , Variação Genética/genética , Progranulinas/genética , Proteínas tau/genética , Idoso , Estudos de Coortes , Proteínas de Ligação a DNA/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Proteína FUS de Ligação a RNA/genética , Turquia/epidemiologia , Proteína com Valosina/genética
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