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Mol Biol (Mosk) ; 55(4): 598-605, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34432777


Recently, a wealth of data have been accumulating on the role of long non-coding RNAs (lncRNAs) in the fine-tuning of mRNA expression. Four new lncRNAs, namely, TMEM92-AS1, FAM222A-AS, TXLNB, and lnc-CCL28, were identified as differentially expressed in ovarian tumors using deep machine learning. The levels of lnc-CCL28 transcripts in both tumors and normal tissue samples were sufficient for further analysis by RT-PCR. In addition, the promising ovarian cancer biomarkers, lncRNAs LINC00152, NEAT 1 and SNHG17 were added to RT-PCR analysis. For the first time, an increase in the level of lnc-CCL28 and SNHG 17 lncRNAs was found in ovarian tumors, and the overexpression of LINC00152 and NEAT1 was confirmed. It seems that lnc-CCL28 is involved in carcinogenesis and, in particular, in ovarian cancer progression. Overexpression of LINC00152 and lnc-CCL28 was significantly associated with the later stages and metastasis.

Neoplasias Ovarianas , RNA Longo não Codificante , Carcinogênese/genética , Feminino , Humanos , Neoplasias Ovarianas/genética , RNA Longo não Codificante/genética
Bull Exp Biol Med ; 167(4): 546-555, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31502132


In in vitro experiments on cultures of human multipotent stem cells from the human bonearrow and dental pulp, we studied direct reprogramming towards neuro-glial lineage cells using a cocktail of small molecules. Reprogramming by the previously published protocol (with a cocktail containing ß-mercaptoethanol, LIF, VPA, CHIR99021, and RepSox) and by the optimized protocol (VPA, RG108, А83-01, dorsomorphin, thiazovivin, CHIR99021, forskolin, and Isx9) allows obtaining cells with immunophenotypic and genetic signs of neural stem cells. However, neither the former, nor the optimized protocols allowed preparing neural progenitors capable of adequate terminal differentiation from both bone marrow-derived mesenchymal stem cells and nestin-positive neural crest-derived mesenchymal stem cells. Real-time PCR demonstrated the expression of some neurogenesis markers, but neural stem cell-specific expression pattern was not observed. The findings lead us to a conclusion that reprogramming with small molecules without additional factors modifying gene expression does not allow reproducible production of human neural stem cell-like progenitors that can be used as the source of neural tissue for the regenerative therapy.

Células-Tronco Neurais/citologia , Diferenciação Celular/efeitos dos fármacos , Reprogramação Celular/efeitos dos fármacos , Humanos , Mercaptoetanol/farmacologia , Células-Tronco Mesenquimais , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Pirazóis/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real
Osteoporos Int ; 29(1): 211-221, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28980049


Hypercortisolism in humans suppresses osteoblastogenesis and osteoblast function through the upregulation of Wnt-signaling antagonists (sclerostin, Dkk1) and changes in microRNAs levels (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) which are associated with mesenchymal stem-cell commitment to adipocytes or cartilage cells over the osteoblasts. INTRODUCTION: The purpose of this study was to evaluate the responses of bone to chronic glucocorticoid (GC) excess by measuring the levels of selected mRNA and microRNA (miR) in bone samples of patients with Cushing's disease (CD). METHODS: Bone samples were obtained during transsphenoidal adenomectomy from the sphenoid bone (sella turcica) from 16 patients with clinically and biochemically evident CD and 10 patients with clinically non-functioning pituitary adenomas (NFPA) matched by sex, age, and body mass index. Quantitative polymerase chain reactions (qPCR) were used to examine the expression of genes (mRNA and miRs) known to be involved in bone remodeling regulation based on studies in animals and cell culture. RESULTS: Hypercortisolism was associated with the downregulation of genes involved in osteoblast function and maturation (ACP5, ALPL, BGLAP, COL1A1, COL1A2, BMP2, RUNX2, TWIST1). An excess of GC caused increased expression of Wnt-signaling antagonists (Dkk1, SOST) and changes in the levels of miRs that are known to suppress osteoblastogenesis (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) p < 0.05, q < 0.1. Interestingly, compensatory mechanisms were found in long-term hypercortisolism: upregulation of Wnt10b, LRP5, and LRP6; downregulation of SFRP4; changes in miRs involved in osteoblastogenesis (miR-210-5p, miR-135a-5p, miR-211, miR-23a-3p, miR-204-5p); and downregulation of genes associated with osteoclastogenesis. None of these changes prevented the suppression of bone formation. CONCLUSIONS: An excess of endogenous GC in humans suppresses bone formation through the upregulation of Wnt-signaling antagonists and dysregulation of miRs involved in mesenchymal stem-cell commitment. Both Wnt-signaling antagonists and miRs seem to be promising targets for further research in therapeutic intervention in glucocorticoid-induced osteoporosis.

Remodelação Óssea/genética , Regulação da Expressão Gênica/fisiologia , Hipersecreção Hipofisária de ACTH/genética , Osso Esfenoide/metabolismo , Adulto , Densidade Óssea/genética , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Diferenciação Celular/genética , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Osteoblastos/patologia , Osteoclastos/fisiologia , Osteoporose/etiologia , Osteoporose/genética , Osteoporose/patologia , Osteoporose/fisiopatologia , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/metabolismo , Hipersecreção Hipofisária de ACTH/patologia , RNA Mensageiro/genética , Osso Esfenoide/patologia , Via de Sinalização Wnt/genética , Via de Sinalização Wnt/fisiologia
Biomed Khim ; 62(6): 638-644, 2016 Nov.
Artigo em Russo | MEDLINE | ID: mdl-28026806


The presence of activating mutations in the EGFR gene influences cell proliferation, angiogenesis, and increases metastatic ability; it has a significant impact on the choice of medical therapy of non-small cell lung cancer (NSCLC). The use of targeted therapy with tyrosine kinase inhibitors requires performance of appropriate genetic tests. The aim of this study was to design a real-time PCR-based diagnostic kit for fast and cheap of EGFR mutations testing in paraffin blocks and plasma, and kit validation using samples from patients with NSCLC, and also comparative estimation of diagnostic features of real-time PCR with wild type blocking and digital PCR for mutation testing in blood plasma. The study included 156 patients with various types of adenocarcinoma differentiation. It was designed a simple and efficient real-time PCR-based method of detecting L858R activating mutation and del19 deletion in the EGFR gene for DNA isolated from paraffin blocks. Kit for EGFR mutations was validated using 411 samples of paraffin blocks. The proposed system showed high efficiency for DNA testing from paraffin blocks: a concordance with results of testing with therascreen® EGFR RGQ PCR Kit ("Qiagen", Germany) was 100%. It has been shown the possibility of using this test system for the detection of mutations in plasma.

Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Proteínas de Neoplasias , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Análise Mutacional de DNA , Receptores ErbB/sangue , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Masculino , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética