Development of multifunctional nanoscale sensors working under physiological conditions enables monitoring of intracellular processes that are important for various biological and medical applications. By attaching paramagnetic gadolinium complexes to nanodiamonds (NDs) with nitrogen-vacancy (NV) centres through surface engineering, we developed a hybrid nanoscale sensor that can be adjusted to directly monitor physiological species through a proposed sensing scheme based on NV spin relaxometry. We adopt a single-step method to measure spin relaxation rates enabling time-dependent measurements on changes in pH or redox potential at a submicrometre-length scale in a microfluidic channel that mimics cellular environments. Our experimental data are reproduced by numerical simulations of the NV spin interaction with gadolinium complexes covering the NDs. Considering the versatile engineering options provided by polymer chemistry, the underlying mechanism can be expanded to detect a variety of physiologically relevant species and variables.

• MeSH
• biosenzitivní techniky metody   MeSH
• časové faktory MeSH
• koncentrace vodíkových iontů MeSH
• konfokální mikroskopie MeSH
• kvantová teorie MeSH
• nanodiamanty chemie   ultrastruktura   MeSH
• nanotechnologie metody   MeSH
• optické zobrazování metody   MeSH
• oxidace-redukce MeSH
• reprodukovatelnost výsledků MeSH
• transmisní elektronová mikroskopie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nanodiamanty MeSH

Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.

• MeSH
• bipolární porucha genetika   MeSH
• celogenomová asociační studie statistika a číselné údaje   MeSH
• genetická predispozice k nemoci genetika   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• modely nemocí na zvířatech MeSH
• potkani Sprague-Dawley MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mikro RNA MeSH

Hyperlipidemia is a well-accepted risk factor in the development of atherosclerosis. MicroRNAs (miRNAs), a novel class of posttranscriptional regulators of gene expression, are involved in a variety of biological and pathological processes, including the regulation of the lipid metabolism and atherosclerosis. As our knowledge of miRNAs expands, a new class of "circulating miRNAs" has recently been described. It includes miRNAs which may be found in various bodily fluids packaged in microvesicles/exosomes, or bound to specific transporting proteins. High-density lipoprotein (HDL) particles have been identified as one such carrier. As this class of miRNAs likely plays a role in intercellular communication, it may also contribute to the atherosclerosis development and progression. This review aims to provide a comprehensive explanation of the roles of distinct miRNAs involved in the regulation of the lipid metabolism. These microRNAs seem to be promising therapeutic agents, as documented in rodents and African green monkeys. The second part of the review focuses on circulating miRNAs and their involvement in the atherosclerosis, especially as their levels have been described as altered in patients with dyslipidemia/hyperlipidemia. Special emphasis is placed on miRNAs transported in a complex with HDL particles and on those which may be considered potential atherosclerosis biomarkers.

• MeSH
• ateroskleróza metabolismus   patofyziologie   MeSH
• biologické markery metabolismus   MeSH
• Cercopithecus aethiops MeSH
• genové regulační sítě * MeSH
• lidé MeSH
• lipoproteiny HDL metabolismus   MeSH
• metabolismus lipidů * MeSH
• mikro RNA metabolismus   MeSH
• myši MeSH
• posttranskripční úpravy RNA MeSH
• progrese nemoci MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• lipoproteiny HDL MeSH
• mikro RNA MeSH

Microribonucleic acids (miRNAs) have been linked with various regulatory functions and disorders, such as cancers and heart diseases. They, therefore, present an important target for detection technologies for future medical diagnostics. We report here a novel method for rapid and sensitive miRNA detection and quantitation using surface plasmon resonance (SPR) sensor technology and a DNA*RNA antibody-based assay. The approach takes advantage of a novel high-performance portable SPR sensor instrument for spectroscopy of surface plasmons based on a special diffraction grating called a surface plasmon coupler and disperser (SPRCD). The surface of the grating is functionalized with thiolated DNA oligonucleotides which specifically capture miRNA from a liquid sample without amplification. Subsequently, an antibody that recognizes DNA*RNA hybrids is introduced to bind to the DNA*RNA complex and enhance sensor response to the captured miRNA. This approach allows detection of miRNA in less than 30 min at concentrations down to 2 pM with an absolute amount at high attomoles. The methodology is evaluated for analysis of miRNA from mouse liver tissues and is found to yield results which agree well with those provided by the quantitative polymerase chain reaction (qPCR).

• MeSH
• biosenzitivní techniky metody   MeSH
• DNA MeSH
• hybridizace nukleových kyselin imunologie   MeSH
• játra chemie   MeSH
• limita detekce MeSH
• metody MeSH
• mikro RNA analýza   MeSH
• myši MeSH
• povrchová plasmonová rezonance metody   MeSH
• protilátky MeSH
• RNA MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• DNA MeSH
• mikro RNA MeSH
• protilátky MeSH
• RNA MeSH

To date, at least 900 different microRNA (miRNA) genes have been discovered in the human genome. These short, single-stranded RNA molecules originate from larger precursor molecules that fold to produce hairpin structures, which are subsequently processed by ribonucleases Drosha/Pasha and Dicer to form mature miRNAs. MiRNAs play role in the posttranscriptional regulation of about one third of human genes, mainly via degradation of target mRNAs. Whereas the target mRNAs are often involved in the regulation of diverse physiological processes ranging from developmental timing to apoptosis, miRNAs have a strong potential to regulate fundamental biological processes also in the lung compartment. However, the knowledge of the role of miRNAs in physiological and pathological conditions in the lung is still limited. This review, therefore, summarizes current knowledge of the mechanism, function of miRNAs and their contribution to lung development and homeostasis. Besides the involvement of miRNAs in pulmonary physiological conditions, there is evidence that abnormal miRNA expression may lead to pathological processes and development of various pulmonary diseases. Next, the review describes current state-of-art on the miRNA expression profiles in smoking-related diseases including lung cancerogenesis, in immune system mediated pulmonary diseases and fibrotic processes in the lung. From the current research it is evident that miRNAs may play role in the posttranscriptional regulation of key genes in human pulmonary diseases. Further studies are, therefore, necessary to explore miRNA expression profiles and their association with target mRNAs in human pulmonary diseases.

• MeSH
• genový targeting * MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• plíce metabolismus   MeSH
• plicní nemoci patofyziologie   MeSH
• regulace genové exprese * MeSH
• zánět patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH

Post-transcriptional control of mRNA by micro-RNAs (miRNAs) represents an important mechanism of gene regulation. miRNAs act by binding to the 3' untranslated region (3'UTR) of an mRNA, affecting the stability and translation of the target mRNA. Here, we present a numerical model of miRNA-mediated mRNA downregulation and its application to analysis of temporal microarray data of HepG2 cells transfected with miRNA-124a. Using the model our analysis revealed a novel mechanism of mRNA accumulation control by miRNA, predicting that specific mRNAs are controlled in a digital, switch-like manner. Specifically, the contribution of miRNAs to mRNA degradation is switched from maximum to zero in a very short period of time. Such behaviour suggests a model of control in which mRNA is at a certain moment protected from binding of miRNA and further accumulates with a basal rate. Genes associated with this process were identified and parameters of the model for all miRNA-124a affected mRNAs were computed.

• MeSH
• buněčné linie MeSH
• down regulace MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• mikro RNA metabolismus   MeSH
• modely genetické * MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stabilita RNA MeSH
• umlčování genů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA MeSH
• mikro RNA MeSH