The fundamental novelty in the pathogenesis of renal cell carcinoma (RCC) was discovered as a result of the recent identification of the role of long non-coding RNAs (lncRNAs). Here, we discuss ...several mechanisms for the dysregulation of the expression of protein-coding genes initiated by lncRNAs in the most common and aggressive type of kidney cancer-clear cell RCC (ccRCC). A model of competitive endogenous RNA (ceRNA) is considered, in which lncRNA acts on genes through the lncRNA/miRNA/mRNA axis. For the most studied oncogenic lncRNAs, such as HOTAIR, MALAT1, and TUG1, several regulatory axes were identified in ccRCC, demonstrating a number of sites for various miRNAs. Interestingly, the LINC00973/miR-7109/Siglec-15 axis represents a novel agent that can suppress the immune response in patients with ccRCC, serving as a valuable target in addition to the PD1/PD-L1 pathway. Other mechanisms of action of lncRNAs in ccRCC, involving direct binding with proteins, mRNAs, and genes/DNA, are also considered. Our review briefly highlights methods by which various mechanisms of action of lncRNAs were verified. We pay special attention to protein targets and signaling pathways with which lncRNAs are associated in ccRCC. Thus, these new data on the different mechanisms of lncRNA functioning provide a novel basis for understanding the pathogenesis of ccRCC and the identification of new prognostic markers and targets for therapy.
Our work aimed to differentiate 20 aberrantly methylated miRNA genes that participate at different stages of development and metastasis of ovarian carcinoma (OvCa) using methylation-specific qPCR in ...a representative set of clinical samples: 102 primary tumors without and with metastases (to lymph nodes, peritoneum, or distant organs) and 30 peritoneal macroscopic metastases (PMM). Thirteen miRNA genes (
,
,
,
,
,
,
,
,
,
,
,
, and
) were hypermethylated already at the early stages of OvCa, while hypermethylation of
,
,
, and
was pronounced in metastatic tumors, and
showed high methylation levels specifically in PMM. We confirmed the significant relationship between methylation and expression levels for 11 out of 12 miRNAs analyzed by qRT-PCR. Moreover, expression levels of six miRNAs were significantly decreased in metastatic tumors in comparison with nonmetastatic ones, and downregulation of miR-203a-3p was the most significant. We revealed an inverse relationship between expression levels of miR-203a-3p and those of
and
genes, which are EMT drivers. We also identified three miRNA genes (
,
, and
) that likely regulate EMT-MET reversion in the colonization of PMM. According to the Kaplan-Meier analysis, hypermethylation of several examined miRNA genes was associated with poorer overall survival of OvCa patients, and high methylation levels of
and
were related to the greatest relative risk of death.
The adequacy of a nonlinear equivalent circuit for the electrical admittance of the skin was investigated in relation to the type of decomposition and the number of members in a power series ...approximating the nonlinear conductivity. This work showed that in the case of decompositions of nonlinear components in terms of voltage powers, the response function of the model was adequate for five or more decomposition components, while in the case of decompositions of nonlinear components in terms of test current powers, the response function of the model was inadequate over the whole range of the number of decomposition components studied. These results provide evidence supporting selection of a model for describing the electrical admittance of human skin.
The role of methylation of 9 miRNA genes in the pathogenesis of metastatic clear cell renal cell carcinoma was determined by quantitative methylation-specific PCR (MS-PCR). For 5 genes (
MIR125B-1
,
...MIR137
,
MIR193A
,
MIR34B/C
, and
MIR375
), a significant correlation of high methylation level with late (III-IV) stages, large size (T3+T4) of the tumor, and metastasis to lymph nodes and/or distant organs was revealed. For another group of genes (
MIR125B-1
,
MIR1258
,
MIR193A
,
MIR34B/C
, and
MIR375
), a statistically significant correlation of high methylation level with loss of differentiation in the tumor (G3-G4) was found, and the opposite pattern was found for
MIR203A
. A total of 7 microRNA genes (
MIR125B-1
,
MIR1258
,
MIR137
,
MIR193A
,
MIR203A
,
MIR34B/C
, and
MIR375
) were identified, the methylation of which is associated with the progression of metastatic clear cell renal cell carcinoma. For 6 of them (except
MIR34B/C
) these data were obtained for the first time. Thus, new factors of the development and progression of clear cell renal cell carcinoma were identified as potential biomarkers for the early diagnosis and prognosis of metastatic clear cell renal cell carcinoma.
Neutrons from DD fusion in the interelectrode space of a table‐top, low‐energy, nanosecond vacuum discharge with a deuterium‐loaded Pd anode have been demonstrated earlier. In addition, the principal ...role of a virtual cathode and the corresponding deep potential well formed in the interelectrode space are recognized under detailed particle‐in‐cell simulations of the discharge experimental conditions using a fully electrodynamic code. PIC modelling has allowed the identification of the scheme of small‐scale experiments with a rather old branch of plasma physics as the inertial electrostatic confinement fusion. The goal of this work is to present and discuss in detail the available experimental results on deuteron oscillations followed by pulsating DD neutron yield in this scheme based on nanosecond vacuum discharge. PIC simulations of some experimental regimes of pulsating neutron yield are also shown and discussed, as well as comparisons with an available similar scheme of periodical oscillating plasmas spheres for fusion.
The search for interacting long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs of protein-coding genes through the mechanism of competing endogenous RNAs in tumors of ovarian cancer ...patients was carried out. The levels of expression of 24 lncRNAs, 20 miRNAs, and 28 mRNAs of protein-coding genes involved in oncogenesis were determined by real-time PCR on a set of representative samples. Correlations between lncRNAs/miRNA and miRNA/mRNA levels in ovarian cancer samples were analyzed. We identified 8 pairs of lncRNAs/miRNA and 17 pairs of miRNA/mRNA, the expression levels of which have a negative correlation. Five triplets of potentially interacting lncRNAs/miRNA/mRNA have been identified, among which the most significant triplet is the
OIP5
-
AS1
/
miR-203a-3p
/
ZEB1
. The data obtained determine new epigenetic profiles, as well as new potential biomarkers and targets for targeted therapy of ovarian cancer patients.
The article discusses the results of the experimental research into composition and crystal structures of tungsten and molybdenum nano-oxides. We prove that the starting material of nanostructures is ...amorphous, with particle sizes being less than 1-2 nm. These structures are able to serve as an effective substrate for the analytical method based on the surface enhanced Raman scattering (SERS).
Design features and parameters of a modernized installation of inertial electrostatic confinement based on a low-energy nanosecond vacuum discharge (∼ 1 J) are described when operating in diode ...geometry in the virtual cathode formation mode and the corresponding potential well. The device is used to study the processes of collisional DD synthesis in the interelectrode space, the processes of x-ray generation in complex plasma at various stages of the discharge: from the very initial stage, when the beam of autoelectrons only begins to irradiate the nonideal anode surface, to oscillating plasma configurations in later stages of the discharge. Here, the first steps were done to introduce x-ray spectral diagnostics, as well as to obtain the integral x-ray spectra for visualizations of interelectrode complex plasmas.
The spectra of
3,4
He charged particles produced in stopped pion absorption by nuclei were measured for 17 nuclei in the mass-number range of 6 ≤
A
≤ 209 by means of a semiconductor spectrometer. ...These data were analyzed on the basis of a phenomenological model where the absorption reaction in question is treated as a three-stage process: primary absorption by intranuclear clusters, preequilibrium stage, and evaporation stage. It is shown that a dominant contribution to the production of helium isotopes with energies not less than 20 MeV comes from the preequilibrium stage. The contribution of the knockout and pickup mechanisms to
3,4
He production is estimated.
Earlier, there was demonstrated generation of DD neutrons in an interelectrode medium of a low-energy (∼ 1 J) nanosecond vacuum discharge with a hollow cathode and a deuterium-loaded Pd anode. There ...was revealed essential role of formation of a virtual cathode and a potential well corresponding thereto in the processes of collisional DD synthesis in the interelectrode space. In this work, we have obtained as a result of an experiment and discussed the neutron yield at the very initial stage of the discharge, when the beam of auto-electrons just starts to irradiate the non-ideal surface of the deuterium-loaded Pd anode.
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