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The Gerty Cori phenomenon: the first woman Nobel laureate in Physiology and Medicine
V. M. Danilova, M. V. Grigorieva, S. V. Komisarenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kiyv;
e-mail: valdan@biochem.kiev.ua
Received: 08 June 2024; Revised: 08 July 2024;
Accepted: 25 July 2024; Available on-line: 04 September 2024
Gerty Cori was the first woman awarded the Nobel Prize in Physiology or Medicine, the first woman the Nobel Prize laureate in the United States, and the third woman the Nobel Prize laureate worldwide following Marie Curie-Skłodowska and her daughter, Irene Joliot-Curie. Despite a challenging and lengthy path to recognition, Gerty Cori’s exceptional qualities and strong character led to her success. In 1947, she was awarded the Nobel Prize in Physiology or Medicine jointly with her husband and lifelong research partner Carl Cori “for their discovery of the course of the catalytic conversion of glycogen”. The Nobel Committee recognized this discovery as one of the most outstanding achievements in biochemistry.
NET-inducing diamond nanoparticles with adsorbed hydrophobic SARS-CoV-2 antigens serving as vaccine candidate
G. Bila, V. Vovk, V. Utka, R. Grytsko, A. Havrylyuk, V. Chopyak, R. Bilyy*
Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
*e-mail: r.bilyy@gmail.com
Received: 14 April 2024; Revised: 17 May 2024;
Accepted: 25 July 2024; Available on-line: 04 September 2024
This study addresses the current need for vaccine adjuvants able to induce an immune response to novel or mutated pathogens. It exploits the ability of nanodiamonds (ND) to induce the formation of neutrophil extracellular traps (NETs) triggering inflammation, accompanied by immune response to co-injected antigens. Hydrophobic nanodiamonds 10 nm in diameter were covered with 194 a.a. sequence of the receptor-binding domain of Spike protein of SARS-CoV-2 via passive adsorption. It was shown that antigen-covered ND induce activation of human neutrophils and stimulate NETs formation and ROS production. When used for immunization antigen-covered ND induced long-lasting immune response in mice with prevailing IgG1 among antibody subclasses. The injected nanoparticles were sequestered by NETs and safely covered with connective tissues when examined 1 year after injection.
Thiacalix[4]arene chalcone amides effect on myometrium contraction
O. V. Tsymbalyuk1*, S. G. Shlykov2, L. G. Babich2, О. Yu. Chunikhin2,
R. V. Rodik3, S. G. Vyshnevskyi3, O. A. Yesypenko3, S. O. Kosterin2
1Educational and Scientific Institute of High Technologies,
Taras Shevchenko National University of Kyiv, Ukraine;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
3Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: otsymbal@knu.ua
Received: 26 April 2024; Revised: 26 June 2024;
Accepted: 25 July 2024; Available on-line: 04 September 2024
Calixarenes are macrocyclic compounds, the biochemical effects of which are actively studied. In this study we synthesized thiacalix[4]arene chalcone amides С-1191 and С-1192, which have a sulfur atom in their structure and different spatial arrangement of chalcone amide groups, and studied their effect on myometrium functioning. Experiments were conducted with the use of rat uterine smooth muscles preparations, isolated myometrial mitochondria and permeabilized myometrial cells. The relative value of mitochondria membrane potential (Δψ) was assayed with a voltage-sensitive fluorescent probe TMRM. The spontaneous contractive activity was studied by tenzometric method followed by mechanokinetic analysis. It was shown that C-1191 and C-1192 induced mitochondria hyperpolarization and increased the basal tension of myometrium smooth muscle preparation. Thiacalix[4]arene С-1191 did not change the uterine cycle, but increased the force, velocity and impulse parameters of muscle contractive activity. On the contrary, С-1192 modified the uterine cycle considerably, increased the total efficiency of the myometrium spontaneous contractive activity and decreased the force, time and impulse parameters. It is concluded that changes in the mechanokinetic parameters of myometrial contractile activity induced by С-1191 and С-1192 are determined by the functional activity of mitochondria.
MiR-378a-3p and miR-181b-5p as nonalcoholic steatohepatitis non-invasive diagnostic biomarkers and their correlations with liver fibrosis
T. I. Ahmed1, E. Mamdouh2, N. R. Ismael2, O. O. Abdelaleem3*,
N. F. Hemeda4, M. A. Hegazy5, R. A. Ali1
1Departments of Internal Medicine, Faculty of Medicine, Fayoum University, Fayoum, Egypt;
2Departments of Zoology, Faculty of Science, Fayoum University, Fayoum, Egypt;
3Departments of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Fayoum, Egypt;
4Department of Genetics, Faculty of Agriculture, Fayoum University, Fayoum, Egypt;
5Departments of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
*e-mail: dr.omayma@yahoo.com
Received: 24 March 2024; Revised: 09 May 2024;
Accepted: 25 July 2024; Available on-line: 04 September 2024
Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases that is diagnosed by biopsy and, therefore, requires the development of non-invasive tests for diagnosis. Serum levels of microRNAs were shown to correlate with the severity of various liver diseases, but the role of miR-378a and miR-181b-5p in NASH remains unclear. The current study aims to assess the serum expression level of miR-378a-3p and miR-181b-5p in patients with NASH and to find out the correlation of these indices with liver fibrosis. The case-control research was carried out on 60 patients with confirmed NASH relative to 50 healthy subjects. Extraction and reverse transcription of micro RNAs was performed using miRCURY LNA RT Kit (Qiagen, Maryland, USA) Detection of miR-378a-3p and miR-181b-5p was done using qPCR. It was shown that serum expression level of miR-378a-3p in NASH patients was downregulated with a median range fold change 0.29, while that of miR-181b-5p was upregulated with a median range fold change 13.08. The ROC curve was constructed to discriminate the NASH group from the healthy group. The optimal cut-off value of miR-378a-3p was ≤0.031 with a sensitivity of 65%, the optimal cut-off value of miR-181b-5p was ≥ 0.063 with a sensitivity of 93.3%. Statistically significant positive correlation between miR-181b-5p level and fibroscan data was demonstrated. The present study showed that serum miR-378a-3p and miR-181b-5p could be used as biomarkers of NASH.
High level of RNA HAS2-AS1 in the buffy coat of a patient blood sample is a more informative prognostic marker of COVID-19 clinical course compared to the level of hyaluronic acid in plasma
E. Dubrovskyi*, T. Drevytska, V. Dosenko, D. Stroy
Department of General and Molecular Pathophysiology,
Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: udjin1785@gmail.com
Received: 21 March 2024; Revised: 13 May 2024;
Accepted: 25 July 2024; Available on-line: 04 September 2024
Numerous studies have confirmed the association of COVID-19 clinical course with the blood levels of hyaluronic acid and long non-coding RNA HAS2-AS1 as a positive regulator of hyaluronan synthase. We aimed to estimate both the level of hyaluronic acid in plasma and the level of RNA HAS2-AS1 in leukocytes (buffy coat) from the same blood sample at the time of patient admission to the hospital and to analyze the specificity of these indicators as biomarkers of COVID-19 severity. The study involved 78 patients with confirmed COVID-19 who underwent treatment between 2020 and 2021 at the Kyiv City Clinical Hospital N 4. The patients were divided into three groups based on the severity of the disease and classified as mild (n = 12), moderate (n = 36), and severe (n = 30). The level of hyaluronic acid in plasma was determined using the Hyaluronic Acid ELISA kit “Abcam” (USA). The buffy coat was isolated by centrifugation of the blood stabilized with EDTA-K and further aspiration of the leukocyte “cloud”. The expression level of HAS2-AS1 in buffy coat leukocytes was estimated using reverse transcription and real-time PCR. According to the obtained data, the level of hyaluronic acid in the plasma of patients with moderate and severe illness was 1.5 and 2.2 times higher compared to the mild illness group, respectively. Meanwhile, the level of RNA HAS2-AS1 in blood lymphocytes (buffy coat) of patient with moderate and severe illness was increased by 7.7 and 22.6 times compared to patients with mild illness. The results of our study demonstrate that, unlike the level of hyaluronic acid in plasma, the level of HAS2-AS1 in a buffy coat is a more reliable prognostic criterion for severe COVID-19 and allows distinguishing patients with varying clinical severity during hospitalization.
Spexin level in growth hormone deficiency Iraqi children
L. A. Ghannawi*, K. Gharab, M. A. Hadi,
O. Y. Shakir, A. M. Rahmah
National Diabetes Center, Mustansiriyah University, Baghdad, Iraq;
*e-mail: lujainghannawi@uomustansiriyah.edu.iq
Received: 03 May 2024; Revised: 27 May 2024;
Accepted: 25 July 2024; Available on-line: 04 September 2024
Spexin (SPX) is a newly discovered brain adipokine implicated in various homeostatic functions including metabolism, energy balance, endocrine processes and growth hormone (GH) production in particular. At the same time, the growth-promoting effects of GH are influenced by Insulin-like growth factor-1 (IGF‑1) and vitamin D3. The aim of this study was to investigate the possible involvement of SPX in growth hormone deficiency (GHD) in children. The research involved 90 children (40 with growth hormone deficiency and 50 healthy controls aged 5-14). Serum levels of GH, IGF and vitamin D3 were tested using a chemiluminescent immunoassay, that of SPX – by Elabscience ELISA Kit. The results revealed that children with GHD had significantly higher SPX levels compared to the control group. No significant difference in IGF-1 and vitamin D3 levels between patients and control groups was observed. In the GHD group, we found a significant negative correlation between SPX and GH levels; at the same time, there was no correlation between SPX and D3 levels. These findings suggest that the changes in SPX levels may contribute to growth hormone deficiency.
The level of inflammatory markers in patients with myocardial infarction after percutaneous coronary intervention
Hadeel S. Abd-Alwahab1, Bayadir Abdul Hussein Mahmeed1,
Nesreen Ahmed Nasser1, Osama A. Mohsein2,3*
1College of Medicine, Al-Nahrain University, Baghdad, Iraq;
2Main Laboratory Unit, Al Habbobi Teaching Hospital,
Thi-Qar Health Directorate, Thi-Qar, Iraq;
3Department of Medical Laboratory Techniques,
Mazaya University College, Thi-Qar, Iraq;
*e-mail: osamaakram889@gmail.com
Received: 04 April 2024; Revised: 20 June 2024;
Accepted: 25 July 2024; Available on-line: 04 September 2024
Cardiovascular diseases are among the most widespread diseases in the world that affect all ages and sometimes can lead to death. Atherosclerosis, coronary syndrome and myocardial infarction are usually associated with artery occlusion and require percutaneous coronary intervention (PCI) as a non-surgical procedure to restore blood flow to the heart. Inflammatory biomarkers, especially interleukins and cardiac biomarkers, have an important role in diagnosing the state of patients with heart damage. The goal of the study was to estimate the serum levels of interleukins and cardiac biomarkers after PCI to reduce the risk of acute coronary syndrome. The study included 100 persons between the ages of 40 and 69 diagnosed with acute coronary syndrome who had successful PCI and a control group consisting of 50 healthy participants of the same age. The levels of interleukins, сreatine kinase MB and myoglobin were measured using an enzyme-linked immunosorbent assay. Troponin and D-dimer levels were measured using immunoassay. It was found that patients before PCI had significantly higher levels of IL-1β, IL-6, IL-8, cardiac troponin I, D-dimer, creatine kinase-MB and myoglobin compared to the control group. One day after PCI, the levels of IL -6, IL-8, cardiac troponin I and D-dimer remained elevated. One week after PCI, the levels of IL-1β, IL-6, IL-8, CK-MB and myoglobin did not show significant differences compared to the control group, while the levels of cardiac troponin I and D-dimer remained higher. Results obtained indicate that in patients after PCI, the levels of interleukins decreased, indicating the reduction of inflammatory processes, but cardiac damage persists to a certain degree, even a week after PCI.
Sex differences in respiration and redox homeostasis of heart mitochondria in rats on high-fructose diet
O. Ivanova1, N. Gorbenko1, O. Borikov2, T. Kiprych1, K. Taran1
1SI “V. Danilevsky Institute for Endocrine Pathology Problems
of the NAMS of Ukraine”, Kharkiv, Ukraine;
2V. N. Karazin Kharkiv National University, Kharkiv, Ukraine;
*e-mail: ivolga3006@ukr.net
Received: 05 April 2024; Revised: 27 May 2024;
Accepted: 25 July 2024; Available on-line: 04 September 2024
Sex hormones play a leading role in the sexual dimorphism of mitochondrial dysfunction and oxidative stress that are associated with Metabolic Syndrome (MetS) and considered as possible causes of cardiovascular disease. The aim of the work was to determine mitochondrial respiration and redox homeostasis in the heart mitochondria of high-fructose diet-fed (НFD) rats depending on sex. MetS was induced in Wistar rats by 8 weeks intake of fructose (200 g/l) with drinking water. The experiment was performed on 30 rats divided into five groups: control males, control females, HFD-fed males, HFD- fed females with intact ovaries, ovariectomized HFD-fed females. Heart mitochondria were isolated and indicators of redox homeostasis as well as mitochondrial oxygen consumption rate were determined. Heart mitochondria of intact female rats were characterized by a lower intensity of lipid peroxidation, a higher activity of antioxidant defense system and state 3 respiration in comparison with control males. HFD was shown to induce more expressed oxidative stress due to significant inhibition of enzymatic and non-enzymatic components of antioxidant defese and more pronounced dysregulation of mitochondrial respiration in the heart mitochondria of ovariectomized females as compared to males. This data may partially explain the greater cardiovascular risk in women with low estrogen sufficiency and justify the necessity of new sex-specific prevention and treatment of cardiovascular risk approaches.
Effect of long-term ethanol consumption and a high-fat diet on mitochondrial respiration in rat pancreatic acinar cells and hepatocytes
O. O. Bilonoha*, H. M. Mazur, B. O. Manko,
O. R. Kulachkovsky, V. V. Manko
Ivan Franko National University of Lviv, Lviv, Ukraine;
*e-mail: olha.bilonoha@lnu.edu.ua
Received: 26 March 2024; Revised: 09 May 2024;
Accepted: 25 July 2024; Available on-line: 04 September b2024
Chronic alcohol consumption may cause pancreatitis and alcohol-related liver diseases. Both adaptation and damage of liver mitochondria in animals on chronic ethanol and high-fat diets were demonstrated. It is currently not clear if ethanol or its metabolites such as fatty acid ethyl esters can cause mitochondrial damage to the pancreas. The present study aimed to evaluate the effect of chronic ethanol administration in combination with a high-fat diet on mitochondrial respiration in both pancreatic acinar cells and hepatocytes of rats. Wistar male rats on a high-fat diet (35% calories) were administered ethanol (6 g/kg body weight) by oral gavage for 14 days. Pancreatic acini cells and hepatocytes were isolated with collagenase digestion. The respiration of isolated cells was studied with a Clark electrode. Ethanol administration to rats kept on a high-fat diet was followed by a rapid loss of animal weight during the first 5 days of the experiment and diminished secretory response of pancreatic acini to acetylcholine, however, no changes in acinar cells ultrastructure, basal, oligomycin-insensitive or FCCP-uncoupled respiration were found. Meanwhile ethanol caused a significant (~40%) increase in basal and maximal FCCP-uncoupled respiration rate of isolated hepatocytes. In conclusion, chronic ethanol administration to rats on a high-fat diet does not cause mitochondrial damage in the pancreas, while mitochondria of the liver adapt to ethanol by increasing respiration rate.