Category Archives: Uncategorized
Bacteriophage–derived double-stranded RNA (larifan) exerts variable effects on human blood monocytes depending on age and sex of donors
R. Dovhyi1*, M. Rudyk1, T. Serhiichuk1, Yu. Yumyna1,
A. Dvukhriadkina1, K. Ostrovska1, D. Pjanova2, L. Skivka1
1ESC “Institute of Biology and Medicine”,
Taras Shevchenko National University of Kyiv, Ukraine;
2Latvian Biomedical Research and Study Centre, Riga, Latvia;
*e-mail: roman_dovhyi@knu.ua
Received: 26 July 2024; Revised: 17 September 2024;
Accepted: 07 October 2024; Available on-line: 28 October 2024
To date, great attention is paid to sex and age differences in the therapeutic effectiveness of drugs, including those that impact the immune system. Bacteriophage-derived dsRNA is the main component of the medicinal product Larifan, which exhibits interferonogenic activity. This study aimed to estimate the effect of Larifan on the activation status of human peripheral blood monocytes collected from donors of different ages and sex. Blood samples were obtained from the healthy volunteers, divided into 4 groups: young men and young women aged from 20 to 39 years, aged men and aged women from 54 to 69 years old. EDTA-anticoagulated blood samples were exposed to 200 μg/ml Larifan for 30 min, cells were washed and treated to study phagocytic index, ROS generation and expression of phenotypic markers. Only live monocytes selected by flow cytometry were included in the analysis. It was shown that monocytes from young as well as from aged females turned out to be quite inert to the treatment with Larifan. Monocytes from young males after the treatment demonstrated a minor decrease in phagocytic activity and significant down-regulation of ROS generation. Monocytes from aged adults showed clear sex-based differences in the basal cell phenotype. Thus, compared to monocytes from women, the monocytes from men over 50 after the treatment with Larifan showed decreased phagocytic activity and CD86 expression along with increased CD206 expression. Taken together, these results indicate the need for further studies of Larifan focused on developing personalized treatment depending on the age and sex of an individual.
Protein expression of estrogen, progesterone, and human epidermal growth factor receptors in young Iraqi women with breast cancer
K. A. Al-Hilali1*, R. Q. Aljawher2, S. A. Faris3
1Directorate of Education in Thi-Qar, Thi-Qar, Iraq;
2College of Medicine University of Thi-Qar, Thi-Qar, Iraq;
3College of Education for Pure Since- University of Thi-Qar, Thi-Qar, Iraq;
*e-mail: khadijaaziz711@gmail.com
Received: 13 April 2024; Revised: 24 June 2024;
Accepted: 07 October 2024; Available on-line: 28 October 2024
Breast cancer is currently evaluated by the presence of hormonal receptors in the tumor tissue, which are among the most important prognostic and predictive markers used at present. The current study was conducted in Thi-Qar Governorate (Iraq) on women aged 20-40 years who have breast cancer (BC), highlighting the spread of this disease among young groups. The expression of estrogen (ER), progesterone (PR), and human epidermal growth factor (Her2/neu) receptors in breast tissues using immunohistochemical analysis was estimated. Breast tissue samples were collected from patients undergoing breast surgery and biopsy. Formalin-fixed paraffin-embedded samples were divided into BC (80), and control (20) groups. The study found that protein expression of both ER and PR was positive in 87.5% and negative in 12.5%, Her2/neu positive in 60% and negative in 40% of BC samples. The subtypes identified were luminal A (58.75%), luminal B (31.25%), HER2-positive (6.25%), and triple-negative (3.75%) BC. The high percentage of luminal A molecular subtype of BC is considered a good prognosis and treatable by anti-hormonal therapy.
Osteopontin as a biomarker for diagnosing the severity of osteoarthritis
M. A. Taha, Z. M. A. A. Hamodat*
Department of Chemistry, College of Science, University of Mosul, Iraq;
*e-mail: zahraahamodat@uomosul.edu.iq
Received: 25 April 2024; Revised: 30 August 2024;
Accepted: 07 October 2024; Available on-line: 28 October 2024
Osteoarthritis (OA) is the most common type of arthritis. It is characterized by the loss of cartilage and pain ultimately leading to difficulty in movement. Glycoprotein osteopontin (OPN) is an essential regulator that plays a critical role in developing osteoarthritis. The study aims to determine the level of OPN in the serum of patients with OA and its correlation with the content of calcium (Ca), phosphorus (P), and magnesium (Mg). The study was conducted on 92 male and female patients aged between 30 and 65, categorized into mild, moderate, and severe groups through clinical examination and X-rays. The control group consist of 58 healthy males and females 30-65-year old. OPN was measured using the ELISA technique, and minerals were estimated using spectrophotometry. It was shown that in OA patients, OPN level increased highly significant when compared with the control group (10.7 ± 3.4 ng/ml) and depended on OA severity. In patients with severe OA, it was higher (47.5 ± 8.1 ng/ml) than in groups with moderate (14.8 ± 4.5 ng/ml) and mild (12.1 ± 3.1 ng/ml) extent of the disease. We showed a significant positive relationship between OPN and phosphorus levels and a negative significant correlation between OPN and calcium, calcium/phosphorus ratio, and magnesium. These findings underscore the potential of OPN as a valuable biomarker for diagnosing the severity of osteoarthritis and monitoring the effectiveness of treatment.
L-arginine, aminoguanidine and mesenchymal stem cells reduce the level of endoplasmic reticulum stress markers and D-dimer in the lungs of mice with antiphospholipid syndrome
N. Ya. Mekhno*, A. I. Dovgalyuk, O. S. Tokarskyy,
M. M. Korda, O. Z. Yaremchuk*
I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine;
*e-mail: mekhno_nyar@tdmu.edu.ua; yaremchuk@tdmu.edu.ua
Received: 22 May 2024; Revised: 20 July 2024;
Accepted: 07 October 2024; Available on-line: 28 October 2024
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by damage to the intima of the microcirculatory blood vessels as a result of the formation of autoimmune antibodies to phospholipids of cell membranes. Recent data indicate a possible link between the occurrence of autoimmune diseases and endoplasmic reticulum stress, impaired nitric oxide availability, high plasma D-dimer level. The aim of the study was to estimate the effect of nitric oxide synthesis modulators L-arginine and aminoguanidine, and mesenchymal stem cells on the level of inositol-requiring enzyme-1a (IRE-1a), glucose-regulated protein 78 (GRP-78) as ER stress markers, and the level of D-dimer in the lung tissue of female BALB/c line mice with experimental APS induced with cardiolipin administration. 30 experimental animals were divided into five groups: 1 – control animals; 2 – mice with APS; 3 – mice with APS, injected intraperitoneally with L-arginine hydrochloride (25 mg/kg) and aminoguanidine (10 mg/kg); 4 – mice with APS, injected intraperitoneally with stem cells (5×106/kg); 5 – mice with APS, injected with L-arginine hydrochloride, aminoguanidine and stem cells in combination. After 10 days post APS formation animals were removed from the experiment, proteins were extracted from the lung tissue and their level was determined with Western blotting. It was established that in group with APS the levels of IRE-1, GRP-78 and D-dimer were substantially increased as compared to the control group. After separate administration of both arginine with aminoguanidine and MSC, as well as with their combined use, the level of IRE-1, GRP-78 and D-dimer decreased compared to the indices in animals with induced APS. The obtained data indicated that this effect is probably due to the reduction of ER stress through iNOS inhibition and the anti-inflammatory action of MSCs.
Heparin-binding EGF-like growth factor: mechanisms of biological activity and potential therapeutic applications
L. M. Dronko1, T. M. Lutsenko1*, N. V. Korotkevych2,
I. O. Vovk2, D. A. Zhukova2, S. I. Romaniuk2,
A. A. Siromolot2, A. J. Labyntsev2, D. V. Kolybo2
1National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute”, Kyiv;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: lutsenko.tetiana@lll.kpi.ua
Received: 06 August 2024; Revised: 18 September 2024;
Accepted: 07 October 2024; Available on-line: 28 October 2024
The diphtheria toxin receptor on sensitive mammalian cells is known as the membrane anchored precursor of heparin-binding EGF-like growth factor (HB-EGF). When the precursor is cleaved by metalloproteinases, a soluble form (sHB-EGF) is formed that can bind to the EGF receptors, resulting in activation of signaling pathways that regulate cell proliferation, differentiation, migration, and inhibition of apoptosis. The ability of HB-EGF to cause both positive and negative consequences for organism underscores the complexity of its biological functions and the need for a nuanced understanding of its role in health and disease. In this review the data on the HB-EGF structure, biological activity, involvement in the mechanism of diphtheria toxin action, wound healing, tumor progression as well as the methods of HB-EGF delivery are summarized.
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.