Category Archives: Uncategorized
Ca(2+)-dependent mechanisms of mitochondria-targeted calix[4]arene C-772 effect on uterine smooth muscle contractile activity
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1Department of Muscle Biochemistry, Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
2Department of Molecular Biotechnology and Bioinformatics, Educational Scientific Institute
of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
3Department of Chemistry of Macrocyclic Compounds, Institute of Organic Chemistry,
National Academy of Sciences of Ukraine, Kyiv;
*e-mail: danylovychanna@ukr.net
Received: 06 April 2026; Revised: 06 May 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026
Background. Identification of non-toxic exogenous compounds capable of selective influencing intracellular Ca2+-dependent processes and smooth muscle contractility remains an important task of molecular biotechnology. Calix[4]arenes are considered promising modulators of cellular functions, and calix[4]arene C-772 is suggested to selective effect mitochondrial Ca2+ handling. Objective. The aim of this study was to evaluate the effect of calix[4]arene C-772 on Ca2+ transport in mitochondria of uterine smooth muscle, nitric oxide production in myocytes, and the contractile activity of myometrial strips. Methods. Non-pregnant Wistar rats were used in experiments, confocal microscopy, spectrofluorimetry, flow cytometry, and mechanokinetic analysis were applied. Results. Mitochondrial localization of calix[4]arenes in myocytes was confirmed by colocalization of the сalix[4]arene–FITC conjugate C-1308 with Mitotracker Orange CM-H2TMRos. Calix[4]arene C-772 (10 μM) interacted with cardiolipin in mitochondrial membranes, inhibited nitric oxide synthesis, reduced Ca2+ accumulation in isolated mitochondria and increased the amplitude of rat myometrial smooth muscle spontaneous contractions. Mechanokinetic analysis demonstrated increased force, velocity, and impulse parameters of contraction–relaxation cycles. Conclusions. These findings indicate that calix[4]arene C-772 at micromolar concentrations can serve as an effective modulator of mitochondrial functional activity and uterine smooth muscle contractility.
Leukocyte telomere length and clinical characteristics in patients with type 2 diabetes mellitus with and without chronic kidney disease
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1SI “D.F. Chebotarev Institute of Gerontology, National Academy
of Medical Sciences of Ukraine”, Kyiv;
2SI “Center for Cardiology and Cardiac Surgery of the Ministry
f Health of Ukraine”, Kyiv;
3P.L. Shupyk National University of Health Care of Ukraine, Kyiv;
*e-mail: yaninarebr@gmail.com
Received: 05 January 2026; Revised: 19 March 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026
Background. Telomeric mechanisms are considered important contributors to chronic kidney disease progression in patients with type 2 diabetes mellitus, although data on telomere length in diabetic kidney disease remain limited. Objective. To evaluate the relationship between telomere length and clinical characteristics in patients with type 2 diabetes mellitus with and without chronic kidney disease. Methods. The study included 100 patients with T2DM, divided into two groups: 50 with and 50 without CKD. Routine clinical and biochemical blood tests were performed for all subjects. Leukocyte telomere length was assessed by quantitative real-time polymerase chain reaction following the method described by Cawthon. Results. T2DM patients with CKD were significantly older, had a longer duration of diabetes, exhibited significantly lower estimated glomerular filtration rate (eGFR), higher urine albumin-to-creatinine ratio and frequency of cardiovascular complications compared with non-CKD patients. No significant correlations were found between telomere length and age, eGFR, albuminuria, or cardiovascular desease in either group. In patients with type 2 diabetes mellitus chronic kidney disease was associated with higher frequency of pathologically short telomeres (20.8%) versus non-CKD patients (2.1%), suggesting accelerated cellular aging in CKD independent of chronological age. Conclusions. Shortened telomeres in patients with type 2 diabetes mellitus and chronic kidney disease may reflect accelerated cellular aging and could serve as an additional marker for biological risk stratification beyond traditional renal indicators.
Keywords: telomeres, type 2 diabetes mellitus, chronic kidney disease, cellular aging.
Association of estrogen and progesterone receptor status and metabolic hormones with tumor progression in endometrial cancer
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1Middle Technical University, Community Health Technologies Department, Iraq;
2Department of Anesthesia Techniques, College of Health
and Medical Technologies, University of Mashreq, Baghdad, Iraq;
3Department of Pharmacy, Medical Technical Institute of Kirkuk,
Northern Technical University, Community Health Technologies Department, Iraq;
4Department of Medical Laboratory Techniques, Mazaya University College,
Main Laboratory Unit, Thi-Qar Health Directorate, Al Habbobi Teaching Hospital, Thi-Qar, Iraq;
*e-mail: saif.hasan@uom.edu.iq
Received: 27 February 2026; Revised: 27 April 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026
Background. It is recognized that endometrial physiology and carcinogenesis depend on the balance of estrogen and progesterone. Eхpression status of estrogen (ER) and progesterone (PR) receptors has been utilized clinically as a prognostic predictor of endometrial cancer (EC). Nevertheless there is growing evidence that insulin resistance and changes in adipokine secretory system are also important risk factor of EC. Objective. To investigate the association between tumor estrogen and progesterone receptors expression combined with metabolic hormone serum levels and tumor progression in patients with endometrial cancer. Methods. The study included 100 patients with endometrial cancer patients and 50 age-matched healthy controls. Serum estradiol, progesterone, insulin, leptin and adiponectin were analyzed with a chemiluminescent immunoassay. Tumor tissue samples were stained using monoclonal antibodies against ER and PR with a standard streptavidin-biotin method. Nuclear staining ≥10% was considered positive. Results. It was shown that the majority of the tumors were ER-positive (68%) and PR-positive (54%) while 27% were double-negative. Serum estradiol, leptin, and insulin levels were significantly higher in advanced-stage patients, while progesterone and adiponectin levels were significantly lower compared to early-stage patients. Correlation and regression results showed that the independent variables that predicted tumor progression were ER and PR negativity, high estradiol, high leptin, and low adiponectin. Conclusions. The loss of ER/PR expression and a metabolic hormonal imbalance – characterized by elevated levels of estradiol and leptin and reduced levels of adiponectin – are closely associated with the progression of endometrial cancer. These changes may contribute to proliferative signaling pathways and inflammatory processes, leading to increased tumor aggressiveness and disease progression.
Curcumin boosts doxorubicin cytotoxicity in breast cancer cells
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1Department of Molecular Immunology, Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
2Department of Technologies of Medical Diagnostics and Treatment,
ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Ukraine;
3Department of General and Soil Microbiology, D.K. Zabolontny Institute of Microbiology
and Virology, National Academy of Sciences of Ukraine, Kyiv;
4Department of Microbiology and Immunology,
ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Ukraine
*e-mail: andriisiromolot@knu.ua
Received: 04 February 2026; Revised: 13 April 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026
Background. Breast cancer remains the leading cause of cancer mortality in women due to the resistance to chemotherapy and severe side effects of doxorubicin (Doxo). One of the approaches to overcome this problem is to search for phytocompounds that can enhance the efficacy of chemotherapy and prevent the development of side effects. Objective. This work aimed to investigate in vitro whether the polyphenol curcumin (Cur) from turmeric (Curcuma longa) in combination with the commercial drug Doxo-HCl can enhance the cytotoxic effect of Doxo on breast cancer cell lines MDA-MB-231 and MCF-7 and to exhibit chemoprotective activity against normal HEK-293 cells. Methods. Cell viability was assessed with MTT assay, apoptosis induction by flow cytometry with Annexin V–eGFP and PI, reactive oxygen species (ROS) generation by the DCFH-DA probe. The combination index (CI) calculation method and CompuSyn, Biosoft software were used to determine the synergism or antagonism of the components. Results. The study revealed dose-dependent cytotoxicity, increased ROS formation, and increased morphological aberrations in cells when using the combination of Cur with Doxo-HCl compared to Doxo-HCl. Cur acted as a chemosensitizer, which synergistically enhanced the antitumor activity of Doxo-HCl while simultaneously reducing its cytotoxic effects in normal cells by reducing ROS production. Conclusions. The use of Cur in combination with Doxo-HCl will likely reduce the effective therapeutic dose of Doxo and increase the effectiveness of breast cancer chemotherapy.
Association of BNP gene SNP rs198389 with NT-proBNP levels in hypothyroid patients prior to treatment
Ishtar Medical Technical Institute, Iraq;
e-mail: alaas3223@gmail.com
Received: 22 March 2026; Revised: 21 April 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026
Background. Cardiovascular system is particularly responsive to fluctuations in thyroid hormone levels and hypothyroid patients are at an increased risk of worse cardiovascular outcomes. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a recognised biomarker for heart failure. Several studies indicate that thyroid disorders may influence blood NT-proBNP level, nevertheless, a consensus has not been established. Objective. To investigate the impact of the single nucleotide polymorphism rs198389 in NT-proBNP gene on the NT-proBNP serum level in patients with untreated primary hypothyroidism. Methods. The study included 100 newly diagnosed hypothyroid patients and 100 healthy controls, with NT-proBNP level measured with enzyme-linked fluorescent assay and genetic analysis conducted via PCR. Results. Our findings indicated significantly elevated NT-proBNP level across all genotypes (CC, CT, TT) in hypothyroid patients compared to controls. This elevation correlated strongly with thyroid-stimulating hormone level. Conclusions. The study demonstrated that NT-proBNP can discriminate between hypothyroid patients and healthy controls, but further studies are needed to establish its role in cardiovascular risk prediction.
Serum apelin and corin as biochemical markers of polycystic ovary syndrome
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1Al-Turath University, College of Pharmacy, Baghdad, Iraq;
2Department of Biotechnology, College of Science,
University of Baghdad, Baghdad, Iraq;
3Department of Clinical Laboratory Sciences, College of Pharmacy,
Al-Nahrain University, Baghdad, Iraq;
4Department of Chemistry and Biochemistry, College of Medicine,
Al-Nahrain University, Baghdad, Iraq
*e-mail: Nesreen.ahmed@nahrainuniv.edu.iq
Received: 13 January 2026; Revised: 05 March 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026
Background. Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease with reproductive dysfunction, intricate hormonal imbalance, elevated risk of cardiovascular disease and obesity in women of reproductive age. Apelin, an adipokine, and corin, a serine protease which activates natriuretic peptide as a cardiovascular regulator, could be involved in the connection between reproductive endocrine imbalance and cardiometabolic regulation in this condition. Objective. To determine apelin and corin levels in the blood of women with PCOS and to evaluate whether they can be useful biochemical predictors for characterizing the disease and stratifying risks. Methods. The case-control study was conducted on 60 women, comprising 30 patients with PCOS and 30 healthy age- and demographically-matched controls. The levels of serum apelin and corin were evaluated with ELISA, that of hormones, 25-hydroxyvitamin D and B12 were analyzed with the help of a Finecare analyser. Results. Much higher apelin and corin levels, increased luteinizing hormone (LH) level and LH/follicle-stimulating hormone ratio, and lower 25-hydroxyvitamin D level in the serum of PCOS patients compared to healthy group were detected. Conclusions. The analysis of ROC curves showed significantly positive relationship between hormonal disturbance and the levels of circulating apelin and corin, indicating their higher PCOS diagnostic accuracy compared to the traditional hormonal markers.
Antioxidant balance and dihydrogen sulfide content in the salivary glands of rats under conditions of immobilization stress and SO(2) donor administration
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1Department of Bioorganic and Biological Chemistry,
Poltava State Medical University, Poltava, Ukraine;
2Faculty of Dentistry, Poltava State Medical University, Poltava, Ukraine;
3Medical Faculty No 1, Poltava State Medical University, Poltava, Ukraine;
*e-mail: a.mykytenko@pdmu.edu.ua
Received: 15 April 2026; Revised: 14 May 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026
Background. Sulfur dioxide (SO2) is proposed as a novel gasotransmitter that is endogenously formed depending on the activity of aspartate aminotransferase, glutathione synthetase, and dihydrogen sulfide content. SO2 and its donors can potentially have a corrective effect in reducing oxidative stress-induced injuries under conditions of adaptation syndrome. Salivary glands are highly sensitive to stressors, but SO2 role in these organs under stress and general adaptation syndrome is largely unknown. Objective. The aim of our study was to determine the effect of the inorganic SO2 donor on the prooxidant-antioxidant balance and dihydrogen sulfide content in the salivary glands of rats under conditions of immobilization stress. Methods. Experiments were performed on 24 white male Wistar rats divided into groups: intact; injected intraperitoneally with SO2 donor Na2SO3/NaHSO3 (0.54 mmol/kg/0.18 mmol/kg) daily; immobilized on their backs for 1 h daily; injected intraperitoneally with Na2SO3/NaHSO3 daily 30 min before immobilization. Animals were withdrawn from the experiment on the 5th day, salivary glands were removed, homogenised, the supernatant was used for biochemical studies. Results. It was shown that the introduction of SO2 donor against the background of the general adaptation syndrome modeling led to a decrease in the blood plasma content of corticosterone, mitigation of lipid peroxidation and oxidative damage of proteins, cystathionine β-synthase and cystathionine γ-lyase activation and dihydrogen sulfide content restoration in the salivary glands. Conclusions. It was concluded that correction of stress-induced changes in the salivary glands of rats with sulfur dioxide led to the prevention of the development of oxidative stress and the restoration of dihydrogen sulfide production from cystathionine β-synthase and cystathionine γ-lyase and an increase in the activity of aspartate aminotransferase.
Adipocyte-derived mesenchymal stem cells injection attenuates neuronal apoptosis and enhances cognitive recovery after moderate traumatic brain injury in rats
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1Neurosurgery Division, Department of Surgery, Faculty of Medicine
Universitas Udayana, Denpasar, Bali, Indonesia;
2Department of Microbiology, Faculty of Medicine Universitas Udayana,
Denpasar, Bali, Indonesia;
3Department of Neurosurgery, Airlangga University Teaching Hospital,
Surabaya, East Java, Indonesia;
4Neurosurgical Residency Program, Faculty of Medicine
Universitas Udayana, Denpasar, Bali, Indonesia;
*e-mail: febby_pratama@unud.ac.id
Received: 25 January 2026; Revised: 30 March 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026
Background. Traumatic brain injury (TBI) remains one of the leading causes of long-term disability worldwide. The secondary brain injury phase, which develops hours to days after primary trauma, is a critical therapeutic window for therapeutic interventions, however, no available therapy has been proven effective. Objective. To estimate the effect of adipose-derived mesenchymal stem cells (AD-MSCs) therapy on neuronal apoptosis, brain-derived neurotrophic factor (BDNF) level, and cognitive function in a rat model of moderate TBI. Methods. AD-MSCs from rat adipose tissue were isolated and analyzed using standardized techniques. Adult male Wistar rats were anesthetized, a left-sided craniectomy was performed and a moderate traumatic brain injury was induced by releasing a metal cylinder through a guiding tube. Following the impact, the incision was closed using absorbable sutures. At 24 hours following TBI, eight microinjections each consisting of 2·105 AD-MSCs in 5 µl PBS were administered in the pericontusional cortex. Control animals received equivalent volumes of sterile saline. Animals were euthanized on 7th or 14th day and the brain was collected for analysis. At the time point prior to euthanasia, rats underwent cognitive testing. Apoptotic index was evaluated by TUNEL assay, BDNF level by ELISA, cognitive performance by Barnes maze test. Results. Macroscopic brain examination revealed enhanced cortical regeneration and vascularization in AD-MSCs treated rats compared with controls. The apoptotic index was significantly lower in the AD-MSCs group on both 7th and 14th days. Cognitive performance improved markedly in the AD-MSCs group, with shorter escape times in the Barnes maze on both 7th and 14th days. In contrast, BDNF levels did not differ between groups at either time point. Conclusion. These findings demonstrate both neuroprotective and neuroregenerative effects of AD-MSCs and highlight its administration as a promising therapeutic strategy for mitigating secondary brain injury after TBI.
Nitric oxide system parameters in the basal magnocellular nucleus of the rat brain following intracerebroventricular administration of colchicine
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1Department of Pathological Physiology with the Course of Normal Physiology,
Zaporizhzhia State Medical and Pharmaceutical University, Zaporizhzhia, Ukraine;
2Department of Physical, Colloid and Analytical Chemistry,
Zaporizhzhia State Medical and Pharmaceutical University, Zaporizhzhia, Ukraine;
*e-mail: danukalo.m.v@zsmu.edu.ua
Received: 25 February 2026; Revised: 18 May 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026
Background. The basal magnocellular nucleus (BMN) is a brain structure that provides cholinergic innervation of the neocortex. Disruption of BMN functional activity is observed in many neurodegenerative diseases. One of the key regulatory systems of neuronal activity in the brain is the nitric oxide (NO) system, however, the interactions among NO system components during neurodestruction have not yet been fully elucidated. Objective. The aim of the study was to determine L-arginine, nitrites, nitrotyrosine levels, iNOS, and nNOS expression in the rat BMN in a model of colchicine-induced neurodestruction. Methods. The study involved 30 male Wistar rats divided into three groups: intact, sham-operated with intracerebroventricular (ICV) administration of 3 μl of NaCl, and colchicine group with ICV injection of colchicine (15 μg/3 μl NaCl). ICV injections were carried out using a digital stereotaxic apparatus. Two weeks after colchicine administration, the animals developed cognitive deficits evidenced by behavioral testing. Following euthanasia, the brain tissue was rapidly removed for further processing. iNOS and nNOS expression was assessed via immunofluorescence microscopy, nitric oxide metabolites were measured using the Griess method, L-arginine concentration via HPLC-MS, and nitrotyrosine level via ELISA. Results. Intracerebroventricular administration of colchicine was followed by a decrease in L-arginine level accompanied by a significant increase in NO metabolites and nitrotyrosine levels in the BMN of rats. Immunofluorescent analysis revealed increased density of iNOS-positive and a progressive reduction of nNOS-positive cells in the BMN cell population of colchicine-injected rats. Correlation analysis confirmed that NO-system imbalance plays a significant role in neurodestruction. Conclusions. Colchicine-induced neurodestruction in the rat BMN is associated with imbalance of the nitric oxide system characterized by decreased L-arginine levels, increased NO metabolites and nitrotyrosine content, elevated iNOS expression, and reduced nNOS-positive cell density. These alterations may contribute to neurodegenerative processes in the BMN.