Category Archives: Uncategorized

The level of sex and fertility hormones in the serum of male patients recovered from COVID-19

M. K. Albayaty1*, M. S. Ali2, A. Y. AL-Tarboolee1, R. H. Yousif3

1Department of Molecular and Medical Biotechnology,
College of Biotechnology, Al-Nahrain University, Jadriya, Baghdad, Iraq;
2University of Technology-Iraq, Applied Sciences Department,
Branch of Chemistry, Baghdad, Iraq;
3Department of Forensic Evidence Sciences, College of Medical Technology,
Al-Farahidi University, Baghdad, Iraq;

Received: 20 March 2024; Revised: 30 April 2024
Accepted: 31 May 2024; Available on-line: 17 June 2024

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that generated the COVID­-19 pandemic is a broad-spectrum infection that besides the respiratory tract, can attack multiple organs, including­ the digestive, circulatory, and urinary systems. However, the negative consequences of SARS-CoV-2 on the male reproductive system have been largely ignored. The aim of this research was to see how SARS-CoV-2 affects the production of hormones, which are the markers of male reproductive function and fertility. The 350 Iraqi male participants were classified into two groups consisting of 150 COVID-19 recovered patients with a mean age of (32 ± 7.9) years and COVID-19 diagnosis confirmed by RT-PCR, and 200 apparently healthy male volunteers of similar age. The patients’ group was further divided into three groups depending on the recovery period of 3, 5 and 7 months. Serum levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin were measured using the Mindray CL-1000i automated chemiluminescence analyzer provided with matching kits. When comparing the indices of COVID-19 recovered participants to the control group, the results revealed a decrease in testosterone level that was positively associated with the recovery period and an increase in the LH, FSH and prolactin levels that were negatively associated with the recovery period. It is supposed that infection with SARS-CoV-2 may be followed by a temporary condition of testicular failure.

Phenformin attenuates the oxidative-nitrosative stress in the liver of rats under long-term ethanol administration

A. Mykytenko1*, O. Akimov2, G. Yeroshenko3, K. Neporada1

1Department of Bioorganic and Biological Chemistry,
Poltava State Medical University, Poltava, Ukraine;
2Department of Pathophysiology, Poltava State Medical University, Poltava, Ukraine;
3Department of Medical Biology, Poltava State Medical University, Poltava, Ukraine;

Received: 09 March 2024; Revised: 29 April 2024;
Accepted: 31 May 2024; Available on-line: 17 June 2024

Modulation of the AMP-activated protein kinase (AMPK) pathway activity is considered to be a promi­sing option in the development of approaches to chronic alcoholic hepatitis treatment. Phenformin, which is a biguanide, has been reported to increase AMPK activity. The aim of this work was to estimate the effect of phenformin as AMPK activator on the development of oxidative-nitrosative stress in the liver of rats under conditions of long-term ethanol administration. The experiments were performed on 24 male Wistar rats, divided into 4 groups: control; animals, which received phenformin hydrochloride orally at a dose of 10 mg/kg daily for 63 days; animals with a forced intermittent alcoholization for 5 days by intraperitoneal administration of 16.5% ethanol solution in 5% glucose at the rate of 4 ml/kg b.w. and subsequent transfer to 10% ethanol as the only source of drinking; animals with chronic alcohol hepatitis simulation and phenformin administration. Superoxide dismutase, catalase, NO synthase isoforms activity, superoxide anion radical production, concentration of malonic dialdehyde, peroxynitrite, nitrites, nitrosothiols concentration and oxidative modification of proteins (OMP) were estimated in liver homogenates. The increased production of oxygen and nitrogen active forms and OMP intensification in the liver of rats under long-term administration of ethanol was detected. Phenformin introduction under long-term ethanol administration was shown to limit the excess peroxynitrite formation and to prevent oxidative damage to rat liver proteins.

Plasminogen influence on the PAI-1 release by human platelets

O. I. Yusova*, T. V. Grinenko, T. F. Drobot’ko, A. O. Tykhomyrov

Department of Enzyme Chemistry and Biochemistry, Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;

Received: 06 February 2024; Revised: 27 March 2024;
Accepted: 31 May 2024; Available on-line: 17 June 2024

РАІ-1 (plasminogen activator inhibitor type 1), as a major physiological inhibitor of tissue plasminogen activator and urokinase, plays a key role in the regulation of fibrinolysis in vivo. Besides, PAI-1 suppresses plasmin formation and affects cell migration through interaction with vitronectin. РАІ-1 is secreted from α-granules of platelets upon stimulation of cells by agonists. The aim of our study was to explore the effects of Glu- and Lys-forms of plasminogen on PAI-1 secretion by platelets and to evaluate the possible role of plasminogen in modulation of agonist-induced PAI-1 release. The secretion of PAI-1 by platelets was investigated by the Western blot analysis. It has been established that depending on the agonist, PAI-1 can be released from platelets in a free form, in a complex with a tissue plasminogen activator, as well as in the form of high-molecular complexes that contain a tissue activator and vitronectin molecules. The revealed induction of PAI-1 secretion under the action of Gly- and Lys-forms of plasminogen indicates their ability to activate intracellular signaling pathways that regulate the release of platelet α-granules. Our findings may be of importance for elucidating the pathogenetic mechanisms of many diseases associated with abnormally enhanced platelet function and PAI-1-related disorders.

ATP as a signaling molecule

L. G. Babich*, S. G. Shlykov, S. O. Kosterin

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;

Received: 22 January 2024; Revised: 13 February 2024;
Accepted: 31 May 2024; Available on-line: 17 June 2024

The review considers the effects of extracellular ATP mediated by plasma membrane purinoreceptors in the cells of different tissues, in particular, myometrium. Recently published results suggest that cytosolic ATP may also play a role of signaling molecule, as indicated by the detection of the ATP receptor not only in the plasma membrane, but also in mitochondria. The authors have shown that ionized Ca2+ concentration in the rat myometrium mitochondria matrix is regulated by ATP at the absence of exogenous Ca2+. ATP concentration-dependent increase of [Ca2+]m was not affected in the presence of the mitochondrial Ca2+-uniporter blocker ruthenium red, the mitochondrial pore blocker cyclosporine A, or ATP synthase inhibitor oligomycin. It is assumed that cytosolic ATP could be a signaling molecule that regulates at least the Ca2+ ions exchange in mitochondria.

Contents UBJ, 2024, Volume 96, Issue 2

Research capacity building, networks, define research strategy, and funding opportunities in RECOOP HST Association

Sandor G. Vari

Director, International Research, and Innovation in Medicine Program
Cedars – Sinai Medical Center, Los Angeles, CA, USA;

I built research capacity and networks for the first ten years in the RECOOP Research Consortium from 2002 to 2012. The RECOOP HST Consortium, with the financial support of Cedars–Sinai Medical Center­ (CSMC), applied for the International Visegrad Fund (IVF) grants. We applied for 20 Standard Grants and won 14 Standard Grants to support forming and managing research networks and multinational–multidisciplinary research projects. The IVF grants won by CSMC – RECOOP helped move toward the 21st Century and broaden the scope of activities in RECOOP. Also, the IVF grants helped to build support networks for biosafety and biosecurity, animal use in research, clinical research management, and research and Innovation management training. RECOOP HST Association implemented the Common Mechanism of Diseases (CMD) research program for innovative life science research in member countries. The objectives were to increase the number of young scientists participating in creative research. Knowledge sharing is the most essential element of collaborative research. Within the context of RECOOP, my final endeavor will focus on investigating the diagnosis and management of Post-Traumatic Stress Disorder (PTSD) in Ukraine. As of January 2024, an estimated 6.3 million people have been forced to flee Ukraine, with 94 percent of them hosted in European countries, representing 5.9 million refugees. In Ukraine, an estimated 7.8 million people need health assistance, and 11.5 million need protection assistance and services. Studies of PTSD report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. We, as researchers, must continually share our research findings and diligently replicate established methods and protocols. These tasks can often feel akin to the labor of Sisyphus. Moreover, within the scientific community, integrity is paramount; dishonesty is swiftly met with consequences akin to the justice administered by Zeus. Therefore, we researchers must roll a boulder up a hill again and again, and after we have proved that the published scientific work is sound, the “boulder” and the scientist will stay on top of the hill.

Inhibitory action of methylene bisphosphonic acid on metabolic activity and viability of J774A.1 cells

D. O. Labudzynskyi*, E. P. Pasichna, O. I. Krynina, М. M. Veliky

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;

Received: 01 February 2024; Revised: 22 March 2024;
Accepted: 24 March 2024; Available on-line: 30 April 2024

Bisphosphonates (BPs) are primary agents in the current pharmacological arsenal against osteoclast-related bone loss due to osteoporosis, Paget’s disease and bone tumors. Due to the lack of complete understanding of the molecular mechanism of their action in bone tissue and the overlap of key properties between BPs of different generations, integral studies of BPs inhibitory and antiresorptive properties are relevant today. The present work was carried out to establish a comprehensive study of the inhibitory effects of methylene bisphosphonic acid (MBPA) on the mevalonate pathway, metabolic activity and cell death in vitro compared to zoledronic acid (Zol). Farnesyl pyrophosphate synthase activity of MBPA-treated J774A.1 cells was inhibited by 80%, compared with a 79% reduction in Zol-treated samples. The ability of MBPA to decrease the percentage of viable cells in culture is slightly lower compared with Zol. After 24 h of incubation with lowest concentration, the percentage of inhibition of metabolic activity was 10.6 and 25%, respectively. After 48 h, these values were 34.8 and 55.6%, respectively. The inhibitory effects of MBPA and Zol on the intensity of incorporation of radioactively labeled precursor [14C]-acetate to the cholesterol fraction were 76.2 and 59.1%, respectively. In the case of isoprenoid fraction, the inhibitory effects were 40.9% and 51.2%, respectively. MBPA and Zol differently induced apoptosis in the J774A.1 cells culture, increased count of apoptotic cells in 2.4 and 6.3 times, and also increased the number of propidium iodide-positive cells in 7.4 and 19 times, respectively. MBPA and Zol also increased the number of TUNEL-positive cells in macrophage culture in 2.6 and 5 times, respectively. Zoledronate significantly reduced carbonic anhydrase 2 and nuclear factor of activated T-cells 1 gene expression levels compared to the MBPA action. Thus, the use of MBPA in future research and therapy of both cancer and osteoporosis looks promising due to lower cytotoxicity, high efficiency of mevalonate pathway inhibition and the possibility of dosage variation.

ECG patterns in post-COVID-19 patients

M. V. Hrebenyk1, S. M. Maslii1, O. O. Shevchuk1*,
M. M. Korda1, S. G. Vari2

1Ivan Horbachevsky Ternopil National Medical University
of the Ministry of Health of Ukraine, Ternopil, Ukraine;
2International Research and Innovation in Medicine Program,
Cedars–Sinai Medical Center, Los Angeles, CA, USA;

Received: 06 January 2024; Revised: 17 March 2024;
Accepted: 17 March 2024; Available on-line: 30 April 2024

COVID-19 has been associated with a wide range of cardiac sequelae after the acute phase. The goal of the study is to evaluate the spectrum of arrhythmias in the aspects of age, comorbidity and survival rate using ECG patterns in patients after COVID-19 during 2 months of recovery. ECG data of 758 patients were examined and analyzed, including 256 (33.6%) males and 503 (66.4%) females aged 15 to 90 (52.99 ± 11.68) years. A total of 848 ECGs were performed in acute period and recovery. ECG changes were classified according to the Minnesota code (MC) classes. It was found that age, sex, severity of COVID-19, presence of concomitant hypertension and diabetes mellitus have a significant impact on ECG changes. Age correlated with the severity of COVID-19 (r = 0.485, P < 0.001), concomitant hypertension (r = 0.471, P < 0.001), diabetes (r = 0.346, P < 0.001) and obesity (r = 0.179, P < 0.001). Correlations were established between age and the presence of baseline previous pathological ECGs (r = 0.290, P < 0.0001). We established that heart rhythm disorders related to the severity of the COVID course are significantly influenced by oxygen saturation (r = -0.211, P < 0.001) and, to a lesser extent, the percentage of lung damage according to CT data (r = 0.127, P = 0.060). The results of the arrhythmias screening in patients with COVID-19 demonstrate the association mainly with the severity of the disease, and comorbidity, especially diabetes mellitus. So, we may consider arrhythmogenesis in COVID-19 through the prism of inflammation, intoxication, hypoxia, metabolic disorders, and drug effects.

Diet-induced and age-related changes in rats: the impact of N-stearoylethanolamine intake on plasma lipoproteins, adiponectin, and adipocyte cholesterol-phospholipid composition

O. S. Tkachenko*, H. V. Kosiakova

Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv, Ukraine;

Received: 26 January 2024; Revised: 19 March 2024;
Accepted: 19 March 2024; Available on-line: 30 April 2024

Adiponectin is secreted by adipose tissue, associated with lipoprotein (LP) metabolism, down-regulated­ in insulin resistance states, and reduced in individuals suffering from obesity and cardiovascular diseases. Phospholipids and cholesterol are the main components of cell membranes and play a critical role in storage and secretory adipocyte functions. N-stearoylethanolamine (NSE) is a minor lipid affecting cell membrane lipids’ composition. Our study aimed to investigate plasma levels of adiponectin and cholesterol of low- and high-density LP (LDL and HDL) and adipocyte cholesterol-phospholipid (Chol-PL) composition of different age rats with high-fat diet (HFD)-induced obesity and insulin resistance and their changes under NSE administration. Our study demonstrated that chronic dietary fat overloading leads to obesity accompanied by impairment of glucose tolerance, a manifestation of dyslipidemia, and changes in plasma adiponectin levels in rats from two age groups (10-month-old and and 24-month-old). Prolonged HFD led to a reduction in plasma adiponectin levels and the growth of adipocyte cholesterol content in rats of different ages. A significant increase in plasma LDL-Chol level and main adipocyte PLs (phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and lysophosphatidylcholine) was observed in younger rats, whereas not detected in elder animals after dietary fats overloading. The decrease in the content of anionic phospholipids (phosphatidylinositol + phosphatidylserine) was also detected in 10-month-old HFD rats compared to the control animals. NSE administration positively affected the normalization of adiponectin levels in both age HFD groups. It significantly impacted the reduction of LDL-Chol levels and the growth of HDL-Chol concentration in the blood plasma of 10-month-old rats as well as PL-composition of young HFD rats and anionic PL restoring in 24-month-old rats. The positive effect on investigated parameters makes NSE a prospective agent for treating diet-induced and age-related metabolic disorders threatening cardiovascular diseases.

Effect of metal nanoparticles usage on oxidative stress indicators and endotoxemia parameters under DMH-induced carcinogenesis

S. B. Kramar1*, I. Ya. Andriichuk2, N. V. Ohinska1, Yu. V. Soroka3,
Z. M. Nebesna1, S. M. Dybkova4, L. S. Rieznichenko4, N. Ye. Lisnychuk2

1Department of Histology and Embryology,
I. Horbachevsky Ternopil National Medical University, Ukraine;
2Central Research Laboratory, I. Horbachevsky Ternopil National Medical University, Ukraine;
3Department of Anaestesiology and Intensive Care,
I. Horbachevsky Ternopil National Medical University, Ukraine;
4F.D. Ovcharenko Institute of Biocolloidal Chemistry,
National Academy of Sciences of Ukraine, Kyiv;

Received: 10 February 2024; Revised: 19 March 2024;
Accepted: 19 March 2024; Available on-line: 30 April 2024

One of the properties of nanoparticles is their ability to correct manifestations of oxidative stress and endotoxemia, which are critical factors in cancer development. Therefore, the work aimed to investigate the effect of the usage of Au/Ag/Fe nanoparticles on oxidative stress indicators and endotoxemia parameters in experimental colon carcinogenesis. The study was performed on 90 white male rats kept in standard vivarium conditions. The division into groups: I – intact animals; II – intact animals with 21 days NPs administration; III – animals injected with N,N-dimethylhydrazine dihydrochloride for 30 weeks; ІV – animals to which Au/Ag/Fe nanoparticles were intragastrically administered daily for 21 days after induced adenocarcinoma. According­ to our results, the concentration of oxidative stress indicators significantly increases under DMH-induced carcinogenesis conditions. It was established that the 21-day intragastric administration of NP Au/Ag/Fe composition caused a significant (P < 0.001) decrease in the concentration of TBARS in the blood serum by 1.33 times, in the content of diene and triene conjugates by 1.63 and 1.98 times, respectively compared to the third experimental group. The introduction of NPs in the fourth experimental group reduces the concentration of the Schiff bases by 1.34 times (P < 0.001), decreases the content of POMP370 and POMP430 by 1.25 (P < 0.001) and 1.37 times (P < 0.001), respectively, compared to the third experimental group. We also observed the reduction of endotoxemia levels in a fourth experimental animal group based on a significant decrease in MMM indexis and EII percentage.