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1.
Molecules ; 29(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38930831

RESUMO

In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms.


Assuntos
Antineoplásicos , Lactonas , Piperidonas , Sesquiterpenos , Humanos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Lactonas/química , Lactonas/farmacologia , Lactonas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Piperidonas/farmacologia , Piperidonas/química , Glicólise/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Ensaios de Seleção de Medicamentos Antitumorais
2.
Epigenetics Chromatin ; 17(1): 6, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38481282

RESUMO

BACKGROUND: Prostate adenocarcinoma (PRAD) is the second leading cause of cancer-related deaths in men. High variability in DNA methylation and a high rate of large genomic rearrangements are often observed in PRAD. RESULTS: To investigate the reasons for such high variance, we integrated DNA methylation, RNA-seq, and copy number alterations datasets from The Cancer Genome Atlas (TCGA), focusing on PRAD, and employed weighted gene co-expression network analysis (WGCNA). Our results show that only single cluster of co-expressed genes is associated with genomic and epigenomic instability. Within this cluster, TP63 and TRIM29 are key transcription regulators and are downregulated in PRAD. We discovered that TP63 regulates the level of enhancer methylation in prostate basal epithelial cells. TRIM29 forms a complex with TP63 and together regulates the expression of genes specific to the prostate basal epithelium. In addition, TRIM29 binds DNA repair proteins and prevents the formation of the TMPRSS2:ERG gene fusion typically observed in PRAD. CONCLUSION: Our study demonstrates that TRIM29 and TP63 are important regulators in maintaining the identity of the basal epithelium under physiological conditions. Furthermore, we uncover the role of TRIM29 in PRAD development.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/metabolismo , Metilação de DNA , Sequências Reguladoras de Ácido Nucleico , Instabilidade Cromossômica , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética
3.
Artigo em Russo | MEDLINE | ID: mdl-31251858

RESUMO

The craniocerebral injury is a global problem of health care and society. The fatal and incapacitating aftermaths developed because of this type of trauma result in significant social and economic losses. To develop effective measures of decreasing these losses epidemiological studies are needed to be implemented considering gender, age, regional and other characteristics. The purpose of study was to analyze regional and epidemiological characteristics of craniocerebral injury in children population of Russia. The study was based on data of state statistic reports in Russia and in its regions in 2003-2004. During analyzed period, dynamics of children morbidity of craniocerebral injury are characterized by its maximal level reached in 2010 (6.3 per 1,000 of children population) and by its decreasing to initial level (5.4% per 1,000 of children population) in 2014. The two-fold increase of percentage of children of the first year of life in mortality of craniocerebral injury was established against the background of stable decrease of craniocerebral injury mortality among children aged from 0 to 17 years. In 2014, every ninth child who died because of head trauma did not survived age of 1 year. In Russia, decreasing of level of hospitalization of children with craniocerebral injury was established. At that, indices of hospitalized morbidity of children of the first year of life increased up to 30%. The actual statistical reporting in Russian Federation provides no full measure evaluation of true levels of mortality, morbidity and hospitalized morbidity. this condition occurs due to limitations of including additional nosological forms in state statistic reporting and to specificity of main disease codification or leading causes of death. The study established significant regional specificity of craniocerebral injury in children that determines necessity of development effective measures considering established epidemiological characteristics.


Assuntos
Traumatismos Craniocerebrais , Adolescente , Criança , Pré-Escolar , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Craniocerebrais/terapia , Atenção à Saúde , Hospitalização , Humanos , Lactente , Recém-Nascido , Morbidade , Federação Russa/epidemiologia
4.
Data Brief ; 25: 104022, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31223638

RESUMO

Prostate cancer (PCa) is the most frequently diagnosed among men malignant disease that remains poorly characterized at the molecular level. Advanced PCa is not curable, and the current treatment methods can only increase the life expectancy by several months. Identification of the genetic aberrations in tumor cells provides clues to understanding the mechanisms of PCa pathogenesis and the basis for developing new therapeutic approaches. Here we present data on somatic mutations, namely single nucleotide variations (SNVs), small insertions and deletions, detected in prostate tumor tissue obtained from Russian patients with PCa. Moreover, we provide a raw dataset on the whole exome and targeted DNA sequencing of tumor and non-tumor prostate tissue obtained from Russian patients with PCa and benign prostatic hyperplasia (BPH). This data is available at NCBI Sequence Read Archive under Accession No. PRJNA506922.

5.
Biomed Khim ; 65(1): 9-20, 2019 Jan.
Artigo em Russo | MEDLINE | ID: mdl-30816092

RESUMO

Keratoconus is a chronic disorder of the cornea, characterized by its progressive thinning, stretching, and conical protrusion. Diagnostics of subclinical keratoconus, as well as its early stages (forme fruste), is a complex problem. The presence of these forms of keratoconus in a patient is one of the reasons for the development of keratectasia after laser refractive surgery. Currently, the role of genetic factors in keratoconus development has been proven. This indicates the possibility of diagnostics of subclinical and forme fruste keratoconus using genetic markers. Knowledge about the patient's genetic susceptibility to keratoconus would allow correcting the tactics of treatment of refractive anomalies and avoiding serious side effects. The studies of causal mutations indicate the genetic heterogeneity of keratoconus, which complicates the development of a diagnostic panel. Selection of candidate variants from the currently known ones based on clear criteria may be one of the approaches for diagnostic markers search. In this review, we have analyzed articles on keratoconus markers in order to form a list of candidate variants for genotyping in the Russian population. The selection criteria took into account the complexes of symptoms in which a marker was found, populations in which a particular marker was investigated, the presence and results of replication studies. The analysis included markers in VSX1, SOD1, ZEB1, LOX, CAST, DOCK9, TGFBI, HGF, MAP3K19, KCND3, COL4A3, COL4A4, COL5A1, FNDC3B, FOXO1, BANP-ZNF469, MPDZ-NF1B, WNT10A genes. Based on the results of the analysis, the following candidate variants were selected for genotyping in the Russian population of patients with keratoconus: rs1536482 and rs7044529 in the COL5A1 gene, rs5745752 and rs2286194 in the HGF gene, rs4954218 in the MAP3K19 gene, rs4839200 near the KCND3 gene, rs2721051 near the FOXO1 gene, rs1324183 between the MPDZ and the NF1B genes, and rs121908120 in the WNT10A gene.


Assuntos
Proteínas do Olho/genética , Marcadores Genéticos , Ceratocone/diagnóstico , Ceratocone/genética , Colágeno Tipo V/genética , Proteína Forkhead Box O1/genética , Predisposição Genética para Doença , Fator de Crescimento de Hepatócito/genética , Humanos , MAP Quinase Quinase Quinases/genética , Polimorfismo de Nucleotídeo Único , Federação Russa , Canais de Potássio Shal/genética , Proteínas Wnt/genética
6.
Zh Vopr Neirokhir Im N N Burdenko ; 83(6): 111-119, 2019.
Artigo em Russo | MEDLINE | ID: mdl-32031174

RESUMO

Rehabilitation of patients with severe traumatic brain injury (sTBI) is a topical medical and social issue because this pathology is one of the main causes of mortality and disability in the young working age population [1]. The most common sTBI consequences include motor and cognitive impairment as well as depression of consciousness [2, 3]. Despite significant progress in treatment of the consequences of severe traumatic brain injury, there are no treatment and rehabilitation standards for these patients, and the used rehabilitation measures are not always effective. These circumstances substantiate the need for the development of additional methods of neurotherapy. Over the past decade, transcranial electrical and magnetic stimulation (TMS) has been increasingly used as neuromodulatory treatment in clinical practice [4-12]. The accumulated experience has shown that transcranial neurostimulation methods require a more individualized approach in terms of both careful selection of patients and choice of exposure parameters. This review is based on an analysis of the most significant publications and recommendations recognized in the scientific community, as well as on reports of domestic and foreign authors presented at dedicated congresses in comparison with experience of our own research on transcranial stimulation. The paper discusses the main problems of using this method in medical practice of sTMI and their possible solutions.


Assuntos
Lesões Encefálicas Traumáticas , Reabilitação Neurológica , Estimulação Transcraniana por Corrente Contínua , Estimulação Magnética Transcraniana , Algoritmos , Lesões Encefálicas Traumáticas/terapia , Humanos
7.
PLoS One ; 13(11): e0204371, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30388122

RESUMO

Although modern methods of whole genome DNA methylation analysis have a wide range of applications, they are not suitable for clinical diagnostics due to their high cost and complexity and due to the large amount of sample DNA required for the analysis. Therefore, it is crucial to be able to identify a relatively small number of methylation sites that provide high precision and sensitivity for the diagnosis of pathological states. We propose an algorithm for constructing limited subsamples from high-dimensional data to form diagnostic panels. We have developed a tool that utilizes different methods of selection to find an optimal, minimum necessary combination of factors using cross-entropy loss metrics (LogLoss) to identify a subset of methylation sites. We show that the algorithm can work effectively with different genome methylation patterns using ensemble-based machine learning methods. Algorithm efficiency, precision and robustness were evaluated using five genome-wide DNA methylation datasets (totaling 626 samples), and each dataset was classified into tumor and non-tumor samples. The algorithm produced an AUC of 0.97 (95% CI: 0.94-0.99, 9 sites) for prostate adenocarcinoma and an AUC of 1.0 (from 2 to 6 sites) for urothelial bladder carcinoma, two types of kidney carcinoma and colorectal carcinoma. For prostate adenocarcinoma we showed that identified differential variability methylation patterns distinguish cluster of samples with higher recurrence rate (hazard ratio for recurrence = 0.48, 95% CI: 0.05-0.92; log-rank test, p-value < 0.03). We also identified several clusters of correlated interchangeable methylation sites that can be used for the elaboration of biological interpretation of the resulting models and for further selection of the sites most suitable for designing diagnostic panels. LogLoss-BERAF is implemented as a standalone python code and open-source code is freely available from https://github.com/bioinformatics-IBCH/logloss-beraf along with the models described in this article.


Assuntos
Metilação de DNA , Aprendizado de Máquina , Neoplasias da Próstata/genética , Algoritmos , Ilhas de CpG , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Modelos Genéticos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias da Próstata/diagnóstico
8.
Biomed Khim ; 64(6): 517-524, 2018 Nov.
Artigo em Russo | MEDLINE | ID: mdl-30632980

RESUMO

Cancer immunotherapy represents a promising and rapidly developing approach for the treatment of oncological diseases. Among the methods of personalized adjuvant immunotherapy, neoantigenic peptide-based drugs have demonstrated substantial efficiency. These drugs are designed to target mutant proteins arising from somatic alterations in the genome of tumor cells and thus stimulate immune response against tumor tissues. The methods of individual screening for potentially immunogenic mutations are mostly based on next-generation exome sequencing of tumor samples, which is a complex and costly procedure for clinical application. Targeted gene sequencing panels limited to a certain set of genes represent a reasonable alternative to WES. Targeted sequencing is also more efficient when there is a low amount of the sample DNA available. We have estimated the potential efficiency of targeted oncological panels in terms of somatic neoantigen profiling in colorectal cancer (colon and rectal adenocarcinoma). The clinical practice of identification of frequent somatic variants does not provide enough data for designing an efficient personalized drug when applied to low and medium mutated cancers such as colorectal cancer. Our analysis of 11 commercially available panels containing different number of genes has shown that neither the larger size of a panel nor its initial customization for colorectal cancer provides a significantly better estimation of an individual somatic mutation profile. The optimal approach is to use the general-purpose medium-sized cancer panels (2300-11200 amplicons and/or 150-600 genes). These panels allow to detect a sufficient number of immunogenic epitopes (>3) per patient for over 30-50% of patients.


Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Exoma , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação
9.
Data Brief ; 10: 369-372, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28018951

RESUMO

Current prostate cancer (PCa) diagnostic tests suffer from insufficient sensitivity and specificity. Novel biomarkers that can be detected by minimally invasive methods are of a particular value. Here we provide two datasets. The first one is on the whole transcriptome profiling by RNA-seq of urine and plasma obtained from patients with PCa and benign prostatic hyperplasia (BPH). The second one represents targeted sequencing of DNA from urine and plasma of patients with PCa and BPH. Both datasets are available at NCBI Sequence Read Archive under Accession No. SRP093707 and No. SRP093842 respectively.

10.
Urologiia ; (6): 30-33, 2017 Dec.
Artigo em Russo | MEDLINE | ID: mdl-29376591

RESUMO

RELEVANCE: Collagen type I and III have a significant role in the development of pelvic organ prolapse (POP) and urinary incontinence in women. The role of the COL3A1 gene polymorphism remains debatable. Some studies and meta-analyzes have found a direct correlation between genetic defects and POP, while other researchers have not confirmed this association. This study aimed to investigate the association of the 1800255 COL3A1 gene polymorphism with the development of POP and urinary incontinence in women. MATERIALS AND METHODS: The study group comprised 52 patients (mean age 64.4 years) with verified POP and stress urinary incontinence. The control group included 21 patients without pelvic floor dysfunction. Patients were comparable in age and had at least one or more risk factors for developing pelvic floor dysfunction. Exclusion criteria for both groups were Marfan and Ehlers-Danlos syndromes and a history of surgery for POP or incontinence (for the control group). In all women, saliva samples were collected to detect polymorphism at the rs1800255 locus of the COL3A1 gene. Genotyping was conducted by Sanger sequencing. RESULTS: In patients with isolated genital prolapse, homozygous polymorphism (AA) had a low sensitivity (0.06) but an extremely high specificity (0.95). Heterozygote (GA) had the sensitivity of 0.35, the specificity of 0.53, and the AUC of 0.44. For urinary incontinence by homozygote (AA), sensitivity was 0.08, specificity 0.96, and by heterozygote (GA) 0.45 and 0.63, respectively. For the combination of pelvic prolapse and urinary incontinence by homozygote (AA), sensitivity was 0.07, specificity 1.0, and heterozygote (GA) 0.41 and 0.62, respectively. CONCLUSION: Given the high specificity of the polymorphism at the rs1800255 locus of the COL3A1 gene, determined by the Sanger sequencing, it can be concluded that there is an association between this polymorphism and urinary incontinence and POP in women.


Assuntos
Colágeno Tipo III/genética , Prolapso de Órgão Pélvico/genética , Polimorfismo Genético , Incontinência Urinária/genética , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Prolapso de Órgão Pélvico/patologia , Prolapso de Órgão Pélvico/fisiopatologia , Incontinência Urinária/patologia , Incontinência Urinária/fisiopatologia
11.
Biomed Khim ; 62(6): 708-714, 2016 Nov.
Artigo em Russo | MEDLINE | ID: mdl-28026816

RESUMO

There is a clear need in molecular markers for prostate cancer (PC) risk stratification. Alteration of DNA methylation is one of processes that occur during ÐÑ progression. Methylation-sensitive PCR with high resolution melting curve analysis (MS-HRM) can be used for gene methylation analysis in routine laboratory practice. This method requires very small amounts of DNA for analysis. Numerous results have been accumulated on DNA methylation in PC samples analyzed by the Infinium HumanMethylation450 BeadChip (HM450). However, the consistency of MS-HRM results with chip hybridization results has not been examined yet. The aim of this study was to assess the consistency of results of GSTP1, APC and RASSF1 gene methylation analysis in ÐÑ biopsy samples obtained by MS-HRM and chip hybridization. The methylation levels of each gene determined by MS-HRM were statistically different in the group of PC tissue samples and the samples without signs of tumor growth. Chip hybridization data analysis confirmed the results obtained with the MS-HRM. Differences in methylation levels between tumor tissue and histologically intact tissue of each sample determined by MS-HRM and chip hybridization, were consistent with each other. Thus, we showed that the assessment of GSTP1, APC and RASSF1 gene methylation analysis using MS-HRM is suitable for the design of laboratory assays that will differentiate the PC tissue from the tissue without signs of tumor growth.


Assuntos
Proteína da Polipose Adenomatosa do Colo , Metilação de DNA , DNA de Neoplasias , Glutationa S-Transferase pi , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Neoplasias da Próstata , Proteínas Supressoras de Tumor , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Adulto , Idoso , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/instrumentação , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
12.
Artigo em Russo | MEDLINE | ID: mdl-27500871

RESUMO

AIM: To determine the clinical and electrophysiological (EEG) signs of cholinergic deficiency in the process of recovery of consciousness in patients with severe brain injury. MATERIAL AND METHODS: Thirty-seven people (24 men and 13 women, mean age 32±14 years) were studied. A comprehensive study included assessment of neurological status, mental activity, and EEG. RESULTS AND CONCLUSION: A set of neurological symptoms, including reduced muscle tone, autonomic disorders (dry mucous membranes and skin, tachycardia, hypotension, gastrointestinal tract), eye movement disorders, that were,in accordance with the literature, characteristicof the cholinergic deficiency syndrome was found. This syndrome was detected against the background of a comatose state, akinetic mutism and mutism with understanding of speech, disintegration of speech, disorientation and amnestic decline. EEG revealed stable over time (months) characteristic changes: slowing and asymmetric alpha activity, equivalent dipole sources of hippocampal and stem localization, persistent strengthening of intra-hemispheric coherent connections, especially on the left side. The regression of the cholinergic deficiency syndrome was accompanied by an increase of regularity, capacity and frequency of alpha-activity (from 7-8 to 9-10 Hz), prevalence of equivalent dipole sources in the hippocampus with their appearance in the occipital cortex, normalization of connections with right-brain coherence with the preservation of their pathologically high values on the left side.


Assuntos
Acetilcolina/deficiência , Lesões Encefálicas/complicações , Coma/etiologia , Adolescente , Adulto , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/psicologia , Córtex Cerebral/fisiopatologia , Coma/diagnóstico , Coma/fisiopatologia , Coma/psicologia , Confusão/diagnóstico , Confusão/etiologia , Confusão/fisiopatologia , Estado de Consciência , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fala , Síndrome , Adulto Jovem
13.
Fiziol Cheloveka ; 42(5): 23-30, 2016 09.
Artigo em Russo | MEDLINE | ID: mdl-29932546

RESUMO

The study analyzed ERPs in 37 healthy right handed subjects without neurological and psychiatric disorders. Young age group consisted of 18 persons aged 18 to 27; advanced age group included 19 persons aged 32 to 59. ERPs were recorded by 32 scalp electrodes according to 10-20% system. Two toned addball paradigm including standard and target tones was used for ERP-recording. The sound sequence was given to examinees without any preliminary instruction. Complex psychology testing included Stroop color and word test for the attention and interference assessment, and Wisconsin card sorting test. Significantly larger amplitude of N200 was detected in young persons in comparison to ones of advantage age. Wavelet-analysis revealed stronger wavelet-connections in frontal-central area on the time range of P300 in persons of advanced age vs. younger ones. The correlation of data of psychological tests examining executive functions was detected with latency of P300 in young examinees and with amplitude of P300 in advanced age ones. Obtained data suggests that switching from one activity to another is prevalence in young persons and focusing on a current activity in advanced age persons.


Assuntos
Percepção Auditiva , Potenciais Evocados Auditivos , Adolescente , Adulto , Fatores Etários , Atenção , Potenciais Evocados , Função Executiva , Humanos , Pessoa de Meia-Idade , Adulto Jovem
14.
Vopr Onkol ; 62(1): 122-32, 2016.
Artigo em Russo | MEDLINE | ID: mdl-30444590

RESUMO

Using the technology of DNA chips Infinium HumanMethylation 450 BeadChip it was analyzed quantitative DNA methylation status in 12 paired samples of prostate adenocarcinoma, and morphologically altered tissues. Analysis of differentially methylated regions of the genome showed an association with abnormal status for 21610 and 3852 hypomethylated hyper-methylated CpG sites. Dominance in the cancer genome hypermethylated sites and their predominant localization in the regulatory regions of genes indicate their possible role in the implementation of mechanisms of gene suppression in the pathogenesis of prostate cancer (PCa). For 14 genes studied were characterized array maximum values hypermethylation in promoter region (> 50% CpG sites) in combination with a high level of methylation differences between treatment groups (> 40%). Role of hypermethylation in some of them: AOX1, KLF8, ZNF154, TMEM106A in the pathogenesis of prostate cancer has been showed previously. Hypermethylation of genes ACSS3, TAC1, TUBA4B, ZSCAN12 not previously been shown for prostate cancer, but is characterized by the association with other cancers. In turn, the differences in the levels of methylation in genes GPRASP1, NKX2-6, ARX, CYBA, EPSTI1, RHCG been documented as a result of a number of genome-research oncology, but has not been studied in detail. To assess the diagnostic potential of epigenetic markers of prostate cancer there was carried out unbiased selection of individual CpG sites most reliably discriminate against tumor samples from a group of no tumor samples. In selected diagnostic model based on logistic regression included 9 CpG sites. Validation of the model was carried out on an independent dataset of methylation of 40 paired samples from the prostate cancer project Atlas of Cancer Genome (TCGA) analyzed on the same version of the DNA chip. Summarized rates of diagnostic informativeness of a model (specificity 95%, sensitivity of 97%, the area under the curve of the diagnostic test (ROC) - 0,96), obtained after validation, allow us to consider these CpG Sites as potential markers for molecular diagnosis of prostate cancer.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , DNA de Neoplasias/genética , Estudo de Associação Genômica Ampla , Proteínas de Neoplasias/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Neoplasias da Próstata/genética , Adulto , Biomarcadores Tumorais/metabolismo , Ilhas de CpG , DNA de Neoplasias/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/metabolismo
15.
Biomed Khim ; 61(6): 781-4, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26716753

RESUMO

The RNA-seq approach for prostate cancer candidate RNA biomarkers screening in plasma and urine obtained by minimally invasive or noninvasive methods is proved to be feasible. Significant amount of RNA biomarkers associated with prostate cancer according to the literature were found in plasma and urine samples obtained from patients with benign prostatic hyperplasia (BPH). The number of detected markers was shown to vary in accordance with method of library preparation used for transcriptome profiling. The detection of known RNA biomarkers for prostate cancer in urine and plasma samples shows the feasibility of such method for minimally invasive diagnostics. The fact of presence of the same RNA biomarkers in samples from patients with BPH suggests their possible lack of specificity and confirms the need for further research in this area.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Neoplasias da Próstata/sangue , Neoplasias da Próstata/urina , RNA Neoplásico/sangue , RNA Neoplásico/urina , Adulto , Biomarcadores Tumorais/genética , Humanos , Masculino , Neoplasias da Próstata/genética , RNA Neoplásico/genética , Análise de Sequência de RNA
16.
Artigo em Russo | MEDLINE | ID: mdl-26288281

RESUMO

OBJECTIVE: To determine electroencephalographic signs of dopamine deficiency syndrome during the recovery after severe brain injury (SBI). MATERIAL AND METHODS: We studied 35 patients with SBI (23 men and 12 women, mean age 29 ± 13 years). RESULTS AND CONCLUSION: We identified a set of neurological symptoms (increased muscular tone of extrapyramidal type, rest tremor, autonomic disorders, which were most characteristic of the autonomic state, and some forms of mutism associated, according to current conceptions, with the dopaminergic system deficiency syndrome. This clinical picture was accompanied by stable EEG changes: an increase in the severity of beta activity of 13-14 Hz, enhanced in the frontal and anterior temporal areas, synchronized with equivalent dipole source localization in subcortical and frontal/basal areas. Dopamine deficiency regression syndrome was accompanied by an increase in beta EEG activity (from 13 to 16 Hz), but with the persistent abnormal enhancement of coherent hemispheric relations, especially in the occipital-temporal areas.


Assuntos
Ritmo beta , Lesões Encefálicas/complicações , Lesões Encefálicas/fisiopatologia , Dopamina/deficiência , Inconsciência/fisiopatologia , Adolescente , Feminino , Lobo Frontal/fisiopatologia , Humanos , Masculino , Lobo Occipital/fisiopatologia , Síndrome , Lobo Temporal/fisiopatologia , Inconsciência/etiologia , Adulto Jovem
17.
Fiziol Cheloveka ; 41(1): 5-16, 2015.
Artigo em Russo | MEDLINE | ID: mdl-25857172

RESUMO

This paper analyzes the variation of the functional anatomy of the brain in healthy people performing identical activities on the basis of functional magneticresonance imaging (fMRI). According to the authors, this approach allows you to showcase a variety of individual strategies to achieve the same external (behavioral) result intracerebral different means, and to identify the factors that determine this diversity. Investigated hemodynamic (fMRT) brain reactions at activization of attention to opening of eyes, motor (search of the right and left hand fingers) and speech tests (mental transfer of months or days of the week upside-down) at 21 healthy subjects (21-30 years): 14 men, 7 women. Certain variety of fMRT answers is revealed: 3-4 jet types of hemodynamic changes were allocated for test in group, and the percent of supervision of each type fluctuated from 40 to 10%. Shown marked gender differences responses which specificity is determined by the nature of the functional load. In motor and speech tests, performed with his eyes closed, fMRI response in women is characterized by greater specificity and locality than in men. At motor tests fMRT answers of men are accompanied big, than at women, inclusion in reaction of frontal areas of the cortex, providing realization of regulatory functions. When opening of eyes the women's fMRT responses, on the contrary, become more diffusion, and men's--more local.


Assuntos
Movimentos Oculares/fisiologia , Olho , Imageamento por Ressonância Magnética , Caracteres Sexuais , Percepção da Fala/fisiologia , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Masculino
18.
Zh Vopr Neirokhir Im N N Burdenko ; 78(1): 14-25; discussion 25, 2014.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-24761592

RESUMO

The aim of studies of patients in long-term posttraumatic unconscious state (PUS) was to outline prognostically significant EEG-markers of consciousness condition and an assessment of its dynamics orientation. We analysed outcomes of dynamic (from days to 16 years after trauma) EEG studies in 196 patients in TBI-caused PUS and different degrees of mental recovery: from chronic unconscious state up to clear consciousness. These results were compared to clinical protocols and data of MRI. It is revealed that dynamic features of EEC pattern (with the analysis of equivalent dipolar sources of separate components) allow to characterize the severity of patient's current state, to reveal the brain structures with the most expressed dysfunction, to define a zone of local cortical damage, and also the general direction of development of a traumatic illness (as though dynamics of a homeostasis of a brain). Frequency characteristics of EEG power spectrum (average frequency--an effective frequency strip) in a background and at reactions find the greatest predictive importance, especially at their assessment in 2-3 months after a trauma. The background interhemispheric EEG coherence (first of all, frontal) as the integrative characteristic of system brain activity, and its change at reactions to external incentives most reflect degree of consciousness oppression, dynamics and potential of its restoration. It was shown the high informational of the researches EEG changes to indifferent and functionally significant signs for an assessment of CNS functionality, and also of PUS pathogenesis.


Assuntos
Lesões Encefálicas/fisiopatologia , Estado de Consciência , Eletroencefalografia , Inconsciência/fisiopatologia , Adolescente , Adulto , Idoso , Lesões Encefálicas/diagnóstico , Estudos de Casos e Controles , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Criança , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Inconsciência/diagnóstico
19.
Artigo em Russo | MEDLINE | ID: mdl-25710070

RESUMO

Bioelectrical (EEG) and hemodynamic (fMRI) responses of cerebral reactions to active and passive movements by the right hand were analyzed in 17 right-handed healthy persons. Individual and averaged fMRI and EEG data was analyzed. The main cortex fMRI responses (sensorimotor cortex of the contralateral, left hemisphere) were topographically similar during both active and passive movements. This fact allows us to recommend the usage of the passive movement paradigm for the mapping of the motor areas in patients with movement disorders. Including in reactive process of cerebellum and subcortical structures at passive movements was more variability than active ones. FMRI-reactions at passive movements were characterized more individual variability than during active ones at the expense of diversity of cerebellum and subcortical structures answers. The EEG analysis revealed that at both passive and active movements there is a coherence increase in the high-frequency alpha-ban in left central-frontal area of the left, activated hemisphere. The power-frequency changes of the EEG parameters during active and passive movements were primarily shown in a frequency increase and the desynchronization of the beta-band. Consistency with the topography of the fMRI response was not found.


Assuntos
Cérebro/fisiologia , Mãos/fisiologia , Movimento/fisiologia , Córtex Sensório-Motor/fisiologia , Adulto , Mapeamento Encefálico , Cerebelo/fisiologia , Eletroencefalografia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino
20.
Artigo em Russo | MEDLINE | ID: mdl-24450163

RESUMO

Bioelectrical (EEG) and hemodynamic (fMRI-response) cerebral reactions to performance and imaginary motor tasks by right or left hand were analyzed in 15 right-handed healthy persons (21-39 years old). During actual movement the main fMRI-response was registered in the area of central gyrus of the hemisphere contralateral to the working hand. Areas of activation were also revealed in the supplemental motor area and the ipsilateral hemisphere of the cerebellum. EEG data showed coherence increase in high frequency alpha- and beta-bands in the activated hemisphere. In imaginary motor tasks the intensity and topography of fMRI-response became the more variable; response was decreased in the motor area and in cerebellum, they increased in the subcortical structures and in the parietal association zones. EEG changes were very variable in this situation also; it was observe an increase of EEG coherence in the right hemisphere for higher frequency of alpha and beta spectral bands. Changes of power spectrum parameters were similar to performance and imaginary motor tasks. Spectrum power and middle frequency of beta band were increased. Topographically these changes did not correspond to activated hemisphere and it was more in the left hemisphere. These changes were reflected nonspecific component of reaction.


Assuntos
Cerebelo/fisiologia , Eletroencefalografia , Imageamento por Ressonância Magnética , Movimento/fisiologia , Adulto , Feminino , Mãos/fisiologia , Voluntários Saudáveis , Humanos , Masculino
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