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Instability and invariant measure in the mathematical model for oxidative phosphorylation and ATP synthesis in the cell
V. I. Grytsay
Bogolyubov Institute for Theoretical Physics, National Academy of Sciences of Ukraine, Kyiv;
e-mail: vigrytsay@gmail.com
Received: 13 October 2023; Revised: 28 November 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023
The aim of this work was to analyze the process of oxidative phosphorylation and ATP synthesis in a cell using a mathematical model. The scenario of occurrence of the autoperiodic and chaotic modes depending on the ATP dissipation values was determined. The invariant measure of the strange attractor was calculated, and histograms of its projections on the phase plane were plotted. Some recommendations were made on how to eliminate biochemically the chaotic mode and restore the stability of the self-organization of the cell biosystem.
Response of the antioxidant system of wheat seedlings with different genotypes to exogenous prooxidants: the relationship with resistance to abiotic stressors
T. O. Yastreb1,2, A. I. Kokorev2, B. E. Makaova3, N. I. Ryabchun2,
T. V. Sakhno3, A. P. Dmitriev4, Yu. E. Kolupaev2,3*
1Crop Research Institute, Prague, Czech Republic;
2Yuriev Plant Production Institute, National Academy
of Agrarian Sciences of Ukraine, Kharkiv;
3Poltava State Agrarian University, Poltava, Ukraine;
4Institute of Cell Biology and Genetic Engineering, National Academy
of Sciences of Ukraine, Kyiv, Ukraine;
*e-mail: plant_biology@ukr.net
Received: 08 September 2023; Revised: 03 November 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023
Oxidative stress is an important component of heat- and drought-induced damage in plants. However, information on the relationship between the resistance of cultivated plants with different genotypes to environmental factors and their ability to maintain a pro-/antioxidant balance remains contradictory. This study aimed to compare the growth responses and adaptation ability of the antioxidant system in different wheat cultivars to oxidative stress agents hydrogen peroxide and iron(II) sulfate. Etiolated seedlings of common winter wheat (Triticum aestivum L.) Antonivka and Tobak (heat- and drought-tolerant), and Avgustina and Doskonala (not resistant to heat and drought) were used for the study. Three-day-old etiolated seedlings were exposed to 50 mM H2O2 or 5 mM FeSO4 for one day. It was found that seedlings of Antonivka and Tobak cultivars treated with H2O2 or FeSO4 were able to maintain relatively intensive growth, accumulated significantly lower amounts of endogenous hydrogen peroxide and lipid peroxidation products, significantly increased anthocyanin content and had a higher activity of SOD and catalase as compared with non-resistant cultivars. The non-tolerant cultivars’ response to stress agents was only to increase proline content with a simultaneous decrease in SOD activity and anthocyanins content. The identified varietal markers of the antioxidant system adaptive strategy can be used to develop new approaches for screening wheat cultivars with cross-resistance to major abiotic stressors.
Cytotoxicity of dextran-graft-polyacrylamide/zinc oxide nanoparticles against doxorubicin-resistant breast cancer cells
P. A. Virych1, V. A. Chumachenko2, P. A. Virych2,
V. O. Pavlenko2, N. V. Kutsevol2
1Laboratory of Mechanisms of Drug Resistance, R.E. Kavetsky Institute for Experimental Pathology,
Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv;
2Chemistry Department, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine;
*e-mail: anabenasp@gmail.com
Received: 24 August 2023; Revised: 08 October 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023
The toxicity of drugs for chemotherapy and cell resistance to their action are the main obstacles in anticancer therapy. Advances in nanotechnology may offer an alternative to traditional methods of anticancer therapy and overcoming drug resistance. The study was carried out on doxorubicin-resistant MCF-7/Dox breast cancer cells and BALB/3T3 clone A31 as a model of normal fibroblasts with the use of Dextran-graft-polyacrylamide/zinc oxide (D-PAA/ZnO) nanoparticles. Cytomorphological analysis was carried out after cells staining with acridine orange. Immunocytochemical study of Ki-67, p53, Bcl-2, Bax, E-cadherin, N-cadherin, СD44 expression was done. Cytotoxicity of D-PAA/ZnO nanoparticles (EC50 = 2.2 mM) against MCF-7/Dox cancer cells but not against normal fibroblasts was demonstrated. The increased expression of proapoptotic proteins, E-cadherin, CD44 and decreased expression of proliferation-associated marker Ki-67 in cancer cells treated with D-PAA/ZnO was revealed. Cytotoxicity of D-PAA/ZnO NPs against MCF-7/Dox cancer cells can be potentially used for elaboration of new approaches to cancer treatment.
AUT-M enterosorbent stabilizes glutathione system in vincristine-treated rats with dimethylhydrazine-induced colon cancer
O. I. Kachur*, L. S. Fira, P. H. Lykhatskyі,
I. R. Bekus, M. V. Kyryliv
I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine;
*e-mail: oksana.kachur2012@gmail.com
Received: 15 August 2023; Revised: 17 October 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023
Colorectal cancer is one of the leading causes of mortality in the world. The search for new methods of therapy for this disease that could correct the state of oxidative stress during the development of neoplasms is up to date. The aim of this work was to study the level of reduced glutathione and the activity of glutathione-dependent enzymes in the development of 1,2 dimethylhydrazine-induced colon cancer in rats while treated with vincristine and the use of enterosorbent. To induce carcinogenesis, dimethylhydrazine was administered to male rats subcutaneously for 30 weeks at a dose of 7.2 mg/kg of body weight. The rats with induced colon cancer received entorosorbent per os at a dose of 0.2 g per 100 g of body weight daily for 21 days. After detoxification therapy, the rats were administered cytostatic vincristine daily at a dose of 0.23 mg/kg for 14 days. A decrease in the content of reduced glutathione, the activity of glutathione reductase and glutathione peroxidase in the blood and liver tissue of rats with colorectal cancer was established. The use of enterosorbent AUT-M was shown to be effective in stabilizing the indicators of the glutathione system in rats with induced colon cancer. Cytostatic vincristine did not significantly affect the change of the studied indicators, confirming the effectiveness of previous sorption measures.
Cytotoxic effect of Ziziphus Spina-Christi extract alone and in combination with doxorubicin on breast cancer cells
E. S. El-Shafey, E. S. Elsherbiny*
Biochemistry Department, Faculty of Science, Damietta University, Damietta, Egypt;
*e-mail: eslamsamy1@yahoo.com
Received: 17 July 2023; Revised: 23 October 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023
Ziziphus Spina-Christi (L.) (ZSC) is a traditional Arabian medicinal plant used to treat inflammatory symptoms, swellings and pain since long. Triple negative breast cancer (TNBC) is a form of cancer with a poor prognosis owing to the paucity of therapy alternatives. Two of the most critical pathways of TNBC development are Wnt/β-catenin signaling and autophagy. In the present study, we intended to identify the possible mechanisms of the cytotoxic effects mediated by ZSC extract on MDA-MB-231 breast cancer cells and to improve the efficacy of DOX in combination with ZSC. The MTT test was used to estimate cell viability and IC50 values. Apoptosis was detected using AnnexinV-FITC detection kit. ELISA was used to measure caspase-3 levels. Cell cycle and the level of autophagosome marker LC3-II were analysed using flow cytometry. Acidic vesicular organelle (AVOs) formation was observed by fluorescence microscopy. Real-time PCR was used to monitor changes in gene expression of β-catenin and autophagic adapter NBR1. It was shown that ZSC treatment dose-dependently inhibited MDA-MB-231 cell viability and induced apoptosis with accompanying elevation of caspase-3 level. Besides ZSC caused a significant elevation in LC3II level and downregulation of NBR1 gene expression with subsequent downregulation of β-catenin gene expression, indicating the inhibition of the oncogenic Wnt pathway. ZSC and DOX combination had synergistic cytotoxic effect by more effective suppression of Wnt pathway and induction of apoptosis and autosis.
Phenobarbital ameliorates hyperglycemia-induced angiogenesis in diabetic nephropathy-possible intervention at the HIF-1α/VEGF axis
M. M. Mohammed1*, S. R. A. Rehim1, A. M. M. Okasha1, H. El-Mezayen2,
D. G. A. N. Mohammed2, W. Gomaa3, F. Mourad4, E. G. Ayad2
1Department of Biochemistry, Faculty of Medicine, Minia University, El-Minia, Egypt;
2Department of Chemistry, Faculty of Science, Helwan University, Helwan, Egypt;
3Department of Pathology, Faculty of Medicine, Minia University, El-Minia, Egypt;
4MSP, Faculty of Pharmacy, Deraya University, El-Minia, Egypt;
*e-mail: mostafa.mohamed@mu.edu.eg
Received: 17 September 2023; Revised: 17 November 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023
Hyperglycemia contributes to a cascade of inflammatory responses in kidneys that result in the development of renal hypoxia and angiogenesis with subsequent chronic renal failure. As the hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) axis is a key pathway for neovascularization, the inhibition of this axis is a target for renal angiogenesis therapy. We speculate that Phenobarbital (PB) which has a potential to reduce vascularization in clinical settings might have an influence on the development of angiogenesis in diabetic kidney. The aim of the study was to explore the effects of PB on the HIF-1α and VEGF expression and angiogenesis in renal tissue of rats with hyperglycemia and diabetic nephropathy. Sixty-four male Wistar rats were devided into 4 groups: control group received a single intraperitoneal saline injection; PB group received 0.05% PB orally in drinking water; diabetic group received a single intra-peritoneal STZ (65 mg/kg) injection; PB-STZ group received 0.05% PB orally two weeks before STZ administration. At the end of the experiment period (8 weeks), the kidneys were removed and used for biochemical analyses. Serum glucose, urea and creatinine levels, IL-6 levels in kidney homogenate and changes in HIF-1α and VEGF gene expression were estimated. Hematoxylin-eosin staining was performed for histopathological examination. The results obtained showed that both HIF-1α and VEGF gene expression and IL6 level in diabetic rat group were significantly elevated compared to that in control group, whereas in PB and PB-STZ groups, these indices were significantly down-regulated compared to the diabetic group. Abundant glomerular congestion and mesangial proliferation were detected in diabetic rat renal tissues. However, in PB-treated diabetic group, newly formed vessels were significantly decreased. These findings confirmed that phenobarbital, affecting the HIF-1α/VEGF signaling pathway, ameliorates angiogenesis after hyperglycemic kidney injury.
Benzodiazepine receptor agonist carbacetam modulates the level of vascular endothelial growth factor in the retina of rats with streptozotocin-induced diabetes
S. V. Ziablitsev1*, D. B. Zhupan1, A. O. Tykhomyrov2, O. O. Dyadyk3
1Bogomolets National Medical University, Kyiv, Ukraine;
2Palladin Institute of Biochemistry, National Academy
of Sciences of Ukraine, Kyiv, Ukraine;
3Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine;
*e-mail: zsv1965@gmail.com
Received: 07 September 2023; Revised: 19 October 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023
One of the primary mechanisms of retinal neurodegeneration in diabetes mellitus is gamma-aminobutyric acid (GABA) deficiency that makes the use of GABA-benzodiazepine receptor modulators a promising option for the correction of this diabetic complication. The aim of this study was to determine the effect of the benzodiazepine receptor agonist carbacetam on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in retina of rats with hyperglycemia. Experimental diabetes was modeled by a single administration of streptozotocin (50 mg/kg) to three-month-old male Wistar rats. Immunoblotting and immunohistochemical studies were performed using monoclonal antibodies against VEGF and HIF-1α. It was shown that the development of diabetic retinopathy (DR) at the early stages was accompanied by a progressive multifold increase in the retina content of VEGF on 7-28 days and HIF-1α on 28th day. Insulin and insulin+carbacetam treatment significantly alleviated diabetes-induced overexpression of both HIF-1α and VEGF. Carbacetam was shown to block the diabetogenic increase in VEGF content in retina. The introduction of insulin with carbacetam significantly reduced the expression of VEGF and the development of specific morphological manifestations of DR. Thus, restoration of GABA-ergic signaling can be used as a promising therapeutic option for the correction of DR disorders.
Thiacalix[4]arene С-1087 is the selective inhibitor of the calcium pump of smooth muscle cells plasma membrane
Т. О. Veklich1*, R. V. Rodik2, О. V. Tsymbalyuk3,
О. V. Shkrabak1, O. V. Maliuk1, S. O. Karakhim1,
S. H. Vyshnevskyi3, V. І. Kalchenko3, S. O. Kosterin1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: veklich@biochem.kiev.ua;
2Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
3Educational and Scientific Institute of High Technologies,
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine;
Received: 01 September 2023; Revised: 23 October 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023
The enzymatic and kinetic analyses were used to demonstrate that 5,11,17,23-tetra(trifluoro)methyl(phenylsulfonylimino)methylamino-25,27-dihexyloxy-26,28-dihydroxythiacalix[4]arene С-1087 effectively inhibited the Са2+,Mg2+-АТРase activity of the rat myometrium cells plasma membrane (І0.5 = 9.4 ± 0.6 µM) with no effect on the relative activity of other membrane ATPases. With the use of confocal microscopy and Ca2+-sensitive fluorescent probe fluo-4, it was shown that the application of thiacalix[4]arene С-1087 to the immobilized uterus myocytes increased the cytosolic concentration of Ca2+. Tenzometric studies of rat uterus smooth muscles with the subsequent mechanokinetic analysis revealed that thiacalix[4]arene С-1087 considerably decreased the maximal velocity of the relaxation of both spontaneous contractile response and contraction induced by hyperpotassium solution.