Browsing by Author "Dosenko, Viktor"

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A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures.
(Diagnostics (Basel), 2023-05-25) Dosenko, Viktor; Dons’koi, Boris; Baksheev, Serhiy
Aim: NKp46 is an NK cell receptor uniquely expressed by NK cells and a small subset of innate lymphoid cells. In our previous studies, we suggested a tight connection between the activity of NK cells and the expression of NKp46 and supported the clinical significance of NKp46 expression in NK cells in women with reproductive failures. In this study, we investigated the expression of NKp46 in NK cells in the peripheral blood of women in early pregnancy and analyzed its association with pregnancy loss. Methods: In a blinded study, we examined blood samples and analyzed the subsequent pregnancy outcomes from 98 early pregnant women (5th-7th week of gestation-w.g.) and 66 women in the 11th-13th week of pregnancy who served as controls. We studied the expression of NKp46 and the levels of anti-cardiolipin antibodies (aCL). The results of aCL were shared with the clinic, while the expression of NKp46 was blinded and not analyzed until the end of the study. Results: A misbalance in the NKp46+NK cells subpopulations was associated with an unfavorable ongoing pregnancy. A decreased level of NKp46high cells (<14%) was strongly associated with miscarriage. A decreased level of the double-bright subpopulation (NKp46hightCD56++) also was a negative prognostic factor for the pregnancy course, but its increased level (>4%) was strongly associated with a successful pregnancy course. Conclusions: Our results showed that accentuated levels of NKp46+NK cells lead to a negative prognosis for early pregnancy courses in women.
Quercetin is a potential therapy for post-infarction NETosis formation.
(Naunyn-Schmiedeberg's Archives of Pharmacology, 2024-11-28) Goshovska, Yulia; Dosenko, Viktor; Pashevin, Denys
The surgical intervention during myocardial infarction (MI) is associated with the risk of reperfusion injury, infiltration of tissues with polymorphonuclear neutrophils, and neutrophil extracellular trap (NET) formation. We hypothesized that inhibition of NETs with the use of quercetin might be a promising cardioprotective strategy. Wistar rats underwent LAD occlusion (MI) for 40 min followed by 90 min of reperfusion. The MI + Q group received a water-soluble form of quercetin (50 mg/kg, "Corvitin," BCPP, Ukraine) into the tail vein 10 min before reperfusion. The post-MI administration of quercetin significantly alleviated cardiac dysfunction. End-systolic pressure, stroke volume, cardiac output, and stroke work were significantly improved in the MI + Q vs. MI group. NET formation (examined by fluorescence microscopy and Hoechst staining) as well as free DNA in blood plasma was reduced in the MI + Q group that might be one of the mechanisms of the cardioprotective effect of quercetin. Postconditioning with quercetin might be used as a therapeutic tool for the alleviation of reperfusion injury and NETosis inhibition in vivo.
Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment.
(Life (Basel), 2022-03-16) Pashevin, Denys; Dosenko, Viktor; Serebrovska, Zoya; Xi, Lei
Intermittent hypoxia-hyperoxia training (IHHT) is a non-pharmacological therapeutic modality for management of some chronic- and age-related pathologies, such as Alzheimer’s disease (AD). Our previous studies demonstrated significant improvement of cognitive function after IHHT in the patients with mild cognitive impairment (MCI). The present study further investigated the effects of IHHT on pro-inflammatory factors in healthy elderly individuals and patients with early signs of AD. Twenty-nine subjects (13 healthy subjects without signs of cognitive impairment syndrome and 16 patients diagnosed with MCI; age 52 to 76 years) were divided into four groups: Healthy+Sham (n = 7), Healthy+IHHT (n = 6), MCI+Sham (n = 6), and MCI+IHHT (n = 10). IHHT was carried out 5 days per week for 3 weeks (total 15 sessions), and each daily session included 4 cycles of 5-min hypoxia (12% FIO2) and 3-min hyperoxia (33% FIO2). Decline in cognitive function indices was observed initially in both MCI+Sham and MCI+IHHT groups. The sham training did not alter any of the parameters, whereas IHHT resulted in improvement in latency of cognitive evoked potentials, along with elevation in APP110, GDF15 expression, and MMP9 activity in both healthy subjects and those with MCI. Increased MMP2 activity, HMGB1, and P-selectin expression and decreased NETs formation and Aβ expression were also observed in the MCI+IHHT group. There was a negative correlation between MoCA score and the plasma GDF15 expression (R = −0.5799, p < 0.05) before the initiation of IHHT. The enhanced expression of GDF15 was also associated with longer latency of the event-related potentials P330 and N200 (R = 0.6263, p < 0.05 and R = 0.5715, p < 0.05, respectively). In conclusion, IHHT upregulated circulating levels of some inflammatory markers, which may represent potential triggers for cellular adaptive reprogramming, leading to therapeutic effects against cognitive dysfunction and neuropathological changes during progression of AD. Further investigation is needed to clarify if there is a causative relationship between the improved cognitive function and the elevated inflammatory markers following IHHT.
The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine.
(Heliyon, 2022-10-31) Dosenko, Viktor; Kosiakova, Halyna; Berdyshev, Andrey
Background: N-stearoylethanolamine (NSE) is a bioactive lipid amine with a wide range of biological activities. Anti-inflammatory properties of NSE were previously confirmed on multiple animal models. However, the molecular mechanisms of anti-inflammatory action of NSE remain unclear. In the current study, we examined the involvement of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in the NF-kB -dependent pathway of anti-inflammatory action of NSE using different methodological approaches. Methods: Molecular modeling calculated the possibility of NSE binding PPAR. Ex vivo experiment, using selective agonist of PPARα/γ - LY-171883 and antagonist of PPARγ - GW9662, examined the role of PPARα/γ in the NSE's effect on nuclear NF-kB translocation in LPS-activated rat peritoneal macrophages. Finally, the NSE's action on mRNA level of PPARγ-dependent genes was studied in the liver of insulin-resistant rats. Results: The results of molecular docking showed that NSE could bind to PPARγ and compete for the binding site with antagonist GW9662 and agonist LY-171883. These data was supported by in vitro study where pre-treatment with NSE prevented further LPS-induced NF-kB translocation into the nuclei of rat peritoneal macrophages. NSE treatment before GW9662 and LPS addition normalized the level of NF-kB translocation and IL-1β content. This finding confirmed a competitive binding of NSE with GW9662 for the ligand-binding domain of PPARγ. Additional in vivo study showed that NSE administration changed the mRNA expression of several PPARγ target genes, including SLC27A1 encoding fatty acid transport protein-1 and IL1RN - interleukin-1 receptor antagonist in insulin resistant rats. Conclusion: NSE suppressed nuclear translocation of NF-κB in LPS-stimulated peritoneal macrophages via PPARγ and changed hepatic mRNA expression of PPARγ target genes (SLC27A1, IL1RN) in insulin resistant rats.