71 research outputs found
RNAI-MEDIATED SILENCING OF MATRIX METALLOPROTEINASE 1 IN EPIDERMAL KERATINOCYTES INFLUENCES THE BIOLOGICAL EFFECTS OF INTERLEUKIN 17A
Matrix metalloproteinases (MMPs) are important for the pathogenesis of psoriasis and other autoimmune disorders. In the extracellular matrix, accumulation of proinflammatory cytokines, such as interleukin 17A (IL-17A), leads to induction of several MMPs, including MMP1. MMPs change the composition and other properties of the extracellular matrix. These changes facilitate tissue remodeling and promote the development of psoriatic plaques. The aim of this study was to explore how MMP1 silencing might influence the biological effects of IL-17A on migration and proliferation of human epidermal keratinocytes and the expression of genes involved in their division and differentiation. The experiments were performed with MMP1-deficient and control epidermal keratinocytes, HaCaT-MMP1 and HaCaT-KTR, respectively. Cell proliferation and migration were assessed by comparative analysis of the growth curves and scratch assay, respectively. To quantify cell migration, representative areas of cell cultures were photographed at the indicated time points and compared to each other. Changes in gene expression were analyzed by real-time PCR. The obtained results demonstrated that MMP1 silencing in the cells treated with IL-17A resulted in downregulation of MMP9 and -12, FOSL1, CCNA2, IVL, KRT14 and -17 as well as upregulation of MMP2, CCND1 and LOR. Moreover, MMP1 silencing led to a decrease in cell proliferation and an impairment of cell migration. Thus, MMP1-deficiency in epidermal keratinocytes can be beneficial for psoriasis patients that experience an accumulation of IL-17 in lesional skin. Knocking MMP1 down could influence migration and proliferation of epidermal keratinocytes in vivo, as well as help to control the expression of MMP1, -2, -9 ΠΈ -12, CCNA2, CCND1, KRT14 and -17 that are crucial for the pathogenesis of psoriasis
Protein interference for regulation of gene expression in plants
Transcription factors (TFs) play a central role in the gene regulation associated with a plant's development and its response to the environmental factors. The work of TFs is well regulated at each stage of their activities. TFs usually consist of three protein domains required for DNA binding, dimerization, and transcriptional regulation. Alternative splicing (AS) produces multiple proteins with varying composition of domains. Recent studies have shown that AS of some TF genes form small proteins (small interfering peptide/small interfering protein, siPEP/siPRoT), which lack one or more domains and negatively regulate target TFs by the mechanism of protein interference (peptide interference/protein interference, PEPi/PROTi). The presence of an alternative form for the transcription factor CCA1 of Arabidopsis thaliana, has been shown to be involved in the regulation of the response to cold stress. For the PtFLC protein, one of the isoforms was found, which is formed as a result of alternative splicing and acts as a negative repressor, binding to the full-length TF PtFLC and therefore regulating the development of the Poncirus trifoliata. For A. thaliana, a FLM gene was found forming the FLM-Π± isoform, which acts as a dominant negative regulator and stimulates the development of the flower formation process due to the formation of a heterodimer with SVP TF. Small interfering peptides and proteins can actively participate in the regulation of gene expression, for example, in situations of stress or at different stages of plant development. Moreover, small interfering peptides and proteins can be used as a tool for fundamental research on the function of genes as well as for applied research for permanent or temporary knockout of genes. In this review, we have demonstrated recent studies related to siPEP/siPROT and their involvement in the response to various stresses, as well as possible ways to obtain small proteins
Possible Impurities in Radiopharmaceuticals and Corresponding Test Methods
The main quality attributes of radiopharmaceuticals that ensure their effectiveness and safety and are unique to their specifications are activity, radionuclide identity, radionuclide purity, and radiochemical purity. The aim of this study was to analyse the possibility of formation and methods for determination of various impurities in radiopharmaceuticals based on radionuclides of several groups: technetium-99m and rhenium-188; iodine and fluorine-18 isotopes; and gallium-68 and some other metallic radionuclides used in theranostic schemes combining radionuclide diagnostics and radionuclide therapy. The article analyses the sources for the formation of radionuclide, radiochemical, and chemical impurities; the influence of these impurities on visualisation quality and dosimetric characteristics of radiopharmaceuticals; various approaches to the methods of impurity detection and quantification; compendial requirements to the quality of radiopharmaceuticals; and research results reported in publications. The article demonstrates the need for the development and certification of Russian reference standards for testing quality attributes of radiopharmaceuticals as part of harmonisation of the State Pharmacopoeia of the Russian Federation with the Pharmacopoeia of the Eurasian Economic Union and the European Pharmacopoeia
Spatial and Wavenumber Resolution of Doppler Reflectometry
Doppler reflectometry spatial and wavenumber resolution is analyzed within
the framework of the linear Born approximation in slab plasma model. Explicit
expression for its signal backscattering spectrum is obtained in terms of
wavenumber and frequency spectra of turbulence which is assumed to be radially
statistically inhomogeneous. Scattering efficiency for both back and forward
scattering (in radial direction) is introduced and shown to be inverse
proportional to the square of radial wavenumber of the probing wave at the
fluctuation location thus making the spatial resolution of diagnostics
sensitive to density profile. It is shown that in case of forward scattering
additional localization can be provided by the antenna diagram. It is
demonstrated that in case of backscattering the spatial resolution can be
better if the turbulence spectrum at high radial wavenumbers is suppressed. The
improvement of Doppler reflectometry data localization by probing beam focusing
onto the cut-off is proposed and described. The possibility of Doppler
reflectometry data interpretation based on the obtained expressions is shown.Comment: http://stacks.iop.org/0741-3335/46/114
ΠΡΠΈΡΡΡΡΡΠ²ΠΈΠ΅ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΡΡ ΠΏΡΠΈΠΌΠ΅ΡΠ΅ΠΉ Π² ΡΠ°Π΄ΠΈΠΎΡΠ°ΡΠΌΠ°ΡΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΈΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ
The main quality attributes of radiopharmaceuticals that ensure their effectiveness and safety and are unique to their specifications are activity, radionuclide identity, radionuclide purity, and radiochemical purity. The aim of this study was to analyse the possibility of formation and methods for determination of various impurities in radiopharmaceuticals based on radionuclides of several groups: technetium-99m and rhenium-188; iodine and fluorine-18 isotopes; and gallium-68 and some other metallic radionuclides used in theranostic schemes combining radionuclide diagnostics and radionuclide therapy. The article analyses the sources for the formation of radionuclide, radiochemical, and chemical impurities; the influence of these impurities on visualisation quality and dosimetric characteristics of radiopharmaceuticals; various approaches to the methods of impurity detection and quantification; compendial requirements to the quality of radiopharmaceuticals; and research results reported in publications. The article demonstrates the need for the development and certification of Russian reference standards for testing quality attributes of radiopharmaceuticals as part of harmonisation of the State Pharmacopoeia of the Russian Federation with the Pharmacopoeia of the Eurasian Economic Union and the European Pharmacopoeia.ΠΡΠ½ΠΎΠ²Π½ΡΠΌΠΈ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΡΠΌΠΈ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° Π»ΡΠ±ΠΎΠ³ΠΎ ΡΠ°Π΄ΠΈΠΎΡΠ°ΡΠΌΠ°ΡΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°, ΠΊΠΎΡΠΎΡΡΠ΅ ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°ΡΡ Π΅Π³ΠΎ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΡ, ΠΈ ΠΏΡΠΈ ΡΡΠΎΠΌ ΠΎΡΡΡΡΡΡΠ²ΡΡΡ Π² ΡΠΏΠ΅ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡΡ
Π΄ΡΡΠ³ΠΈΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΡΡΠ΅Π΄ΡΡΠ², ΡΠ²Π»ΡΡΡΡΡ ΠΏΠΎΠ΄Π»ΠΈΠ½Π½ΠΎΡΡΡ ΠΏΠΎ ΡΠ°Π΄ΠΈΠΎΠ½ΡΠΊΠ»ΠΈΠ΄Ρ, Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ, ΡΠ°Π΄ΠΈΠΎΠ½ΡΠΊΠ»ΠΈΠ΄Π½Π°Ρ ΡΠΈΡΡΠΎΡΠ° ΠΈ ΡΠ°Π΄ΠΈΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΠΈΡΡΠΎΡΠ°. Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β Π°Π½Π°Π»ΠΈΠ· Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
Π²ΠΈΠ΄ΠΎΠ² ΠΏΡΠΈΠΌΠ΅ΡΠ΅ΠΉ Π² ΡΠ°Π΄ΠΈΠΎΡΠ°ΡΠΌΠ°ΡΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°Ρ
ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΡΡΠΈΡ
ΠΏΡΠΈΠΌΠ΅ΡΠ΅ΠΉ. Π Π°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΡΠ°Π΄ΠΈΠΎΠ½ΡΠΊΠ»ΠΈΠ΄ΠΎΠ² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
Π³ΡΡΠΏΠΏ: ΡΠ΅Ρ
Π½Π΅ΡΠΈΡ-99ΠΌ ΠΈ ΡΠ΅Π½ΠΈΡ-188; ΠΈΠ·ΠΎΡΠΎΠΏΠΎΠ² ΠΉΠΎΠ΄Π° ΠΈ ΡΡΠΎΡΠ°-18; Π³Π°Π»Π»ΠΈΡ-68 ΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
Π΄ΡΡΠ³ΠΈΡ
ΡΠ°Π΄ΠΈΠΎΠ½ΡΠΊΠ»ΠΈΠ΄ΠΎΠ²-ΠΌΠ΅ΡΠ°Π»Π»ΠΎΠ², ΠΏΡΠΈΠΌΠ΅Π½ΡΠ΅ΠΌΡΡ
Π² ΡΠ΅ΡΠ°Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΡ
Π΅ΠΌΠ°Ρ
Β«ΡΠ°Π΄ΠΈΠΎΠ½ΡΠΊΠ»ΠΈΠ΄Π½Π°Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ°/ΡΠ°Π΄ΠΈΠΎΠ½ΡΠΊΠ»ΠΈΠ΄Π½Π°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡΒ». ΠΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Ρ ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΈ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ ΡΠ°Π΄ΠΈΠΎΠ½ΡΠΊΠ»ΠΈΠ΄Π½ΡΡ
, ΡΠ°Π΄ΠΈΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈ Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΈΠΌΠ΅ΡΠ΅ΠΉ, ΠΈΡ
Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π½Π° ΠΊΠ°ΡΠ΅ΡΡΠ²ΠΎ Π²ΠΈΠ·ΡΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΈ Π΄ΠΎΠ·ΠΈΠΌΠ΅ΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΡΠ°Π΄ΠΈΠΎΡΠ°ΡΠΌΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ², ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Ρ ΠΊ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΈΡ ΠΈ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΠΏΡΠΈΠΌΠ΅ΡΠ΅ΠΉ,Β ΡΠ°ΡΠΌΠ°ΠΊΠΎΠΏΠ΅ΠΉΠ½ΡΠ΅ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡ ΠΊ ΠΊΠ°ΡΠ΅ΡΡΠ²Ρ ΡΠ°Π΄ΠΈΠΎΡΠ°ΡΠΌΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΈ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ, ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Π½ΡΠ΅ Π² Π½Π°ΡΡΠ½ΠΎΠΉ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ΅. ΠΠΎΠΊΠ°Π·Π°Π½Π° Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ ΠΈ Π°ΡΡΠ΅ΡΡΠ°ΡΠΈΠΈ ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΡΡ
ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² Π΄Π»Ρ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° ΡΠ°Π΄ΠΈΠΎΡΠ°ΡΠΌΠ°ΡΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π² ΡΠ°ΠΌΠΊΠ°Ρ
Π³Π°ΡΠΌΠΎΠ½ΠΈΠ·Π°ΡΠΈΠΈ ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠΏΠ΅ΠΈ Ρ Π€Π°ΡΠΌΠ°ΠΊΠΎΠΏΠ΅Π΅ΠΉ ΠΠ²ΡΠ°Π·ΠΈΠΉΡΠΊΠΎΠ³ΠΎ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΎΡΠ·Π° ΠΈ ΠΠ²ΡΠΎΠΏΠ΅ΠΉΡΠΊΠΎΠΉ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠΏΠ΅Π΅ΠΉ
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