Cells is an international, peer-reviewed, open access, journal of cell biology, molecular biology, and biophysics, published semimonthly online by MDPI. http://hdl.handle.net/20.500.12701/1977 2024-05-03T12:21:37Z 2024-05-03T12:21:37Z Spirina, Liudmila V. Yurmazov, Zahar A. Gorbunov, Alexey K. Usynin, Evgeny A. Lushnikova, Nadezhda A. Kovaleva, Irina V. http://hdl.handle.net/20.500.12701/2025 2022-05-12T04:32:50Z 2020-07-13T00:00:00Z

Название: Molecular Protein and Expression Profile in the Primary Tumors of Clear Cell Renal Carcinoma and Metastases Авторы: Spirina, Liudmila V.; Yurmazov, Zahar A.; Gorbunov, Alexey K.; Usynin, Evgeny A.; Lushnikova, Nadezhda A.; Kovaleva, Irina V. Краткий осмотр (реферат): Metastasis involves the spread of cancer cells from the primary tumor to surrounding tissues and distant organs and is the primary cause of cancer morbidity and mortality. The aim of the study was the determination of change in molecular factors expression in primary kidney cancers (ccRCC) and metastatic sites. In total, 62 patients with RCC were enrolled in the study. The mRNA levels of molecular markers were studied by real-time PCR, and the content of the studied parameters was determined by Western blotting and ELISA. The features in the intracellular signal metabolites in the series of normal renal parenchyma, tumor tissue of localized, disseminated kidney cancer and metastatic tissue were studied. A decrease in some indicators in the tissue of the metastatic lesion was noted. Protein products of transcription factors HIF-1, CAIX, PTEN and activated AKT kinase, as well as expression of the VEGFR2 receptor and m-TOR protein kinase were revealed to be reduced in the metastatic sites. In addition, some indicators increased in metastasis: the protein levels of NF-κB p 50, NF-κB p 65, HIF-2, VEGF, VEGFR2, m-TOR and mRNA of HIF-1, CAIX, PTEN and PDK. There were indicators with multidirectional changes. HIF-1, CAIX, PTEN, VEGFR2 and m-TOR mRNA: VEGFR2, m-TOR, HIF-1, CAIX, PTEN and PDK had an opposite change in protein content and mRNA level. PTEN loss resulted in the downstream activation of AKT/mTOR signaling in secondary cancer lesions and determined the overall ccRCC patient’s survival. The AKT/mTOR signaling cascade activation was found in the primary kidney tumors. The PTEN content and mRNA level were correlated with total AKT, GSK-3β, the 70S 6 kinases and AKT expression.

2020-07-13T00:00:00Z Plotnikov, Mark B. Chernysheva, Galina A. Smolyakova, Vera I. Aliev, Oleg I. Trofimova, Eugene S. Sherstoboev, Eugene Y. Osipenko, Anton N. Khlebnikov, Andrei I. Anfinogenova, Yana J. Schepetkin, Igor A. Atochin, Dmitriy N. http://hdl.handle.net/20.500.12701/1996 2022-05-11T04:27:42Z 2020-08-08T00:00:00Z

Название: Neuroprotective Effects of a Novel Inhibitor of c-Jun N-Terminal Kinase in the Rat Model of Transient Focal Cerebral Ischemia Авторы: Plotnikov, Mark B.; Chernysheva, Galina A.; Smolyakova, Vera I.; Aliev, Oleg I.; Trofimova, Eugene S.; Sherstoboev, Eugene Y.; Osipenko, Anton N.; Khlebnikov, Andrei I.; Anfinogenova, Yana J.; Schepetkin, Igor A.; Atochin, Dmitriy N. Краткий осмотр (реферат): A novel specific inhibitor of c-Jun N-terminal kinase, 11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S), has a high affinity to JNK3 compared to JNK1/JNK2. The aim of this work was to study the mechanisms of neuroprotective activity of IQ-1S in the models of reversible focal cerebral ischemia (FCI) in Wistar rats. The animals were administered with an intraperitoneal injection of IQ-1S (5 and 25 mg/kg) or citicoline (500 mg/kg). Administration of IQ-1S exerted a pronounced dose-dependent neuroprotective effect, not inferior to the effects of citicoline. Administration of IQ-1S at doses of 5 and 25 mg/kg reduced the infarct size by 20% and 50%, respectively, 48 h after FCI, whereas administration of citicoline reduced the infarct size by 34%. The administration of IQ-1S was associated with a faster amelioration of neurological status. Control rats showed a 2.0-fold increase in phospho-c-Jun levels in the hippocampus compared to the corresponding values in sham-operated rats 4 h after FCI. Administration of IQ-1S at a dose of 25 mg/kg reduced JNK-dependent phosphorylation of c-Jun by 20%. Our findings suggest that IQ-1S inhibits JNK enzymatic activity in the hippocampus and protects against stroke injury when administered in the therapeutic and prophylactic regimen in the rat model of FCI.

2020-08-08T00:00:00Z Kercheva, Maria Gusakova, Anna M. Ryabova, Tamara R. Suslova, Tatiana E. Kzhyshkowska, Julia Ryabov, Vyacheslav V. http://hdl.handle.net/20.500.12701/1978 2022-04-14T07:12:57Z 2020-09-27T00:00:00Z

Название: Serum Levels of Bone Morphogenetic Proteins 2 and 4 in Patients with Acute Myocardial Infarction Авторы: Kercheva, Maria; Gusakova, Anna M.; Ryabova, Tamara R.; Suslova, Tatiana E.; Kzhyshkowska, Julia; Ryabov, Vyacheslav V. Краткий осмотр (реферат): Background: Bone morphogenetic proteins-2 and -4 (BMPs) have been implicated in left ventricular remodeling (LVR) processes such as an inflammation and fibrogenesis. We hypothesized that this knowledge could be translated into clinics. Methods: We studied the dynamics of serum levels of BMPs, its correlation with markers of LVR and with parameters of echocardiography in patients (n = 31) during the six-month follow-up period after myocardial infarction (MI). Results: Elevated serum levels of BMPs decreased by the six-month follow-up period. BMP-2 decreased from the first day after MI, and BMP-4 decreased from the Day 14. The elevated level of BMP-2 at Day 1 was associated with a lower level of troponin I, reperfusion time and better left ventricular ejection fraction (LV EF) at the six-month follow-up. Elevated serum level of BMP-4 at Day 1 was associated with a lower level of a soluble isoform of suppression of tumorigenicity 2 (sST2), age and reperfusion time. An elevated level of BMP-2 at the six-month follow-up was associated with higher levels of BMP-4, high-sensitivity C-reactive protein (hCRP) and sST2. High serum level of BMP-2 correlated with high levels of hCRP and matrix metalloproteinase (MMP)-9 on Day 7. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day 7. The findings of multivariate analysis support the involvement of BMP-2 in the development of post-infarction LVR. Conclusions: Our research translates experimental data about the BMPs in the development of adverse LVR into the clinic. Elevated serum levels of BMPs decreased by the end of the six-month period after MI. BMP-2 decreased from the first day and BMP-4 decreased from Day 14. BMP-2 and BMP-4 were associated with the development of LVR. Their correlations with markers of inflammation, degradation of the extracellular matrix, hemodynamic stress and markers of myocardial damage further support our hypothesis. Diagnostic and predictive values of these BMPs at the development of post-infarction LVR in vivo should be investigated further.

2020-09-27T00:00:00Z