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During cardiac surgery, as well as on-pump CABG, it is crucial to monitor arterial blood parameters in order to assess the condition of patients and risks that might occur in the operating room. In some cases, the cardiac activity of patients undergoing on-pump CABG cannot be self-restored and resuscitation measures are required. Thus, the aim of the study was to analyze the differences between the two groups of patients (self-restoration of cardiac activity vs additional resuscitation measures were required) and identify arterial blood parameters potentially indicating that the patient is at risk. The data of 21 patients were analyzed with Python packages. Statistically significant differences were found between the control group (self-restoration of cardiac activity) and the test group (additional resuscitation measures were required) in the following arterial blood parameters: the levels of sodium, chloride, glucose and blood osmolality. We believe that hyponatremia and blood hypoosmolality might be a reason for cell edema which creates a greater load on the heart and leads to inability of self-restoration of cardiac activity.

The effect of molecular hydrogen (H₂) on the functional state of spermatozoa through signaling pathways was studied. In the work, drugs that affect elements of intracellular signaling cascades were used to study the mechanisms of action of H₂. We used the adenylatecyclase stimulator – forskolin, the Ca²⁺-channel blocker – verapamil, and the proteinkinase C inhibitor – staurosporine. We studied concentrations of MDA, ATP, the percentage of total motility and the average speed of spermatozoa under the action of H₂ against the background of the action of drugs and without the action of drugs. It was shown that the concentration of MDA in all series did not change. Forskolin causes an increase in sperm motility and velocity. The use of H₂ increased the effects stimulated by forskolin: sperm motility and average velocity increased. The concentration of ATP, the percentage of motility and the velocity of sperm decreased under the action of staurosporine and verapamil. The combined action of H₂ and verapamil as well as the combined action of H₂ and staurosporine determined an increase in sperm motility and velocity. Thus, H₂ had a modulating effect through signaling pathways and caused an increase in the functional indices of sperm.

This study investigates the effects of omaveloxolone, a Keap1 inhibitor, on mitochondrial network (MN) dynamics and cell survival under oxidative stress in control fibroblasts and fibroblasts from a Parkinson's disease patient with a PINK1 mutation. The PINK1-mutant fibroblasts showed increased sensitivity to hydrogen peroxide-induced stress. Omaveloxolone pre-treatment improved cell viability under stress conditions in both cell types. Under normal conditions, PINK1-mutant fibroblasts exhibited lower MN connectivity compared to control cells. Oxidative stress reduced MN density in both cell types, while omaveloxolone treatment normalized MN connectivity in PINK1-mutant cells and maintained higher MN connectivity under stress. Similar effects were observed for mitochondrial branch length. Omaveloxolone (50 nM) also increased mitophagy in both cell types under normal conditions. Our findings demonstrate that omaveloxolone exerts protective effects by maintaining mitochondrial dynamics and activating mitophagy. It enhances mitophagy under normal conditions and supports MN structure under oxidative stress, improving cell viability in both control and PINK1-mutant fibroblasts. These results highlight omaveloxolone's potential as a therapeutic agent for protecting cells in diseases associated with impaired mitochondrial dynamics, particularly Parkinson's disease linked to PINK1 mutations.

The transition of the ion channel between the open and closed states is traditionally considered random. Current experimental data indicated the presence of oscillatory modes of regulation of open/closed states, and possible connections between these modes. The canonical methods Fourier or wavelet transforms, fractal analysis and mathematical modelling can evaluate open/closed states oscillatory modes, but cannot describe their relationship to each other. We first applied the method of bispectral analysis to solve this problem. The well-described potassium channels potential-dependent Kv, calcium-dependent KCa and the modelled potassium channel KcsA were studied. The relationship between fluctuations open/closed lifetimes at frequencies ~0.1, ~1 and ~10 Hz was shown. These frequencies correspond to rhythmic processes in cardiovascular and nervous systems functioning, including those regulated by potassium channels. The normalised integrated bispectrum index was chosen to quantitatively evaluate the interrelation of ion channel opening/closing states. The normalised bispectrum index notable increased upon alteration of the membrane potential from 0 to 20 mV. The obtained data expand our understanding of ion channel functioning principles and can be used in the search for new approaches to the pathological states (channelopathies) therapy.

This work is devoted to the study of mRNA expression patterns and the relative content of selenoproteins in mice with TAA-induced liver fibrosis and TAA-induced HCC. The main objective of this study is to evaluate the activation or suppression of selenoprotein synthesis during HCC progression and directly in the tumor in one TAA-treated mouse model, which is a pilot study and allows us to closely approximate the situation observed during HCC progression in vivo. It was found that as HCC progresses, there is an increase in the mRNA expression of thioredoxin reductases TXNRD1 and TXNRD2, deiodinase DIO3, glutathione peroxidases GPX1, GPX2, GPX4, and an inverse correlation in the expression of mRNA was characteristic of GPX3. In addition, the mRNA expression of endoplasmic reticulum resident selenoproteins: SELENOM, SELENON, SELENOT and SELENOS changed significantly. Also, in tumor liver samples and directly in the tumor itself, an increase in the expression of the selenoprotein SELENOP was recorded. The information obtained from the results of this work will significantly complement the existing data on the role of mammalian selenoproteins in various liver pathologies and in oncogenesis in general.

The aim: determination of correlation dependence of adaptogenic defense reactions in rats in the acute phase of pain stress on laser-puncture exposure to low-intensity IR radiation. Material and methods. Four groups of rats were used in the work: "experimental", which received after the injury a 10-day course of PPBM, and three comparison groups ("intact", "no exposure" and "placebo"). The intensity of lipid peroxidation, specific activity of antioxidant enzymes, protein concentration, malonic dialdehyde content in blood plasma and erythrocytes were determined by spectrophotometric method. Microcirculation indices were evaluated according to the previous series of our studies. Emotional and behavioral reactions were studied in the "open field" test. Results. Normalization of metabolic, microcirculatory and behavioral indices was registered in the experimental group. The correlation coefficients between the microcirculation index and the data of behavioral activity under pain stress were significantly less than the correlation coefficients between oxidative stress and cognitive functions, which confirms the determining role of oxidative metabolism disturbance in the formation of cognitive disorders. Conclusion: the registered adaptation and stress-limiting effect of PPBM in conditions of experimental pain stress allows us to recommend the technology of laser acupuncture for use in complex rehabilitation of patients with pain syndrome.

The paper presents an analysis of literature data on the characteristics of microbiocenoses across a wide range of infectious and somatic pathologies, as well as the results of our research on changes in the composition of the gastrointestinal tract microbiota in patients with various diseases. It is demonstrated that the microbiota responds consistently to any pathological changes occurring in the host organism, primarily manifested as a disruption in the balance between anaerobic (bifidobacteria, lactobacilli, bacteroids, clostridia, etc.) and aerobic components of the microbiocenosis. The predominance or suppression of specific types of microorganisms is primarily influenced by the composition of the individual's indigenous microbiota, rather than the specific pathology associated with dysbiosis.

In the present study, we investigated the effect of α1-adrenergic receptor stimulation on the electrical activity of the right atrium cardiomyocytes with imposed rhythm in rats of different ages using methoxamine and methoxamine against the background of selective blockade of phospholipase C inhibitor (U-73122). Methoxamine increased the duration of the repolarization phase of the action potential. However, there were no changes in the other electrophysiological parameters studied. U-73122 markedly blocked all effects of α1-adrenoreceptor stimulation on the parameters of the electrical activity of working cardiomyocytes in 7-, 21-, and 100-day-old rats.

Mycobacterium tuberculosis, a species of pathogenic bacteria in the Mycobacteriaceae family, is the infectious agent that causes tuberculosis (TB), one of the most progressive bacterial pathogens in human history. The pathogen is the first cause of mortality linked to a single pathogen worldwide, especially in poor and developing countries. There are two clinical manifestations of disease caused by this bacterium: pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB). A single nucleotide polymorphism (SNP) in the human caspase recruitment domain-containing protein 8 (CARD8) gene of TB infection plays a critical role in the disease progression. Combining this SNP with the CARD8 polymorphism increased the effect, indicating a new link between the CARD8 gene and TB infection. The present study was conducted to determine the association between the polymorphism of the CARD8 gene and EPTB infection in humans. The study included patients (males and females) infected with PTB (n = 50), and EPTB (n = 50), as well as 50 healthy individuals as a control group. Blood samples were collected from all the participants and used to isolate DNA. Using a self-designed nested tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR) assay, the genotypes in CARD8 A/T SNPs were identified. The results showed that there were no significant differences between the types of patients themselves and no significant differences between patients and healthy individuals in the results of ARMS-PCR. The findings of the present study revealed a correlation between patients with EPTB and polymorphisms in CARD8 (rs2043211).

Background: the nucleus pulposus NP pulls on the ruptured annulus fibrosus AF, bulging the intervertebral disc IVD and releasing chemicals that may irritate nerves and cause inflammation and pain. This produces histological changes to the IVD, including less gelatinous NP, cracks and fissures, decreased matrix water content, and proteoglycan composition changes. Aim of study: this study aims to investigate the histopathological changes in the Herniated Disc HD tissue, as well as cartilage histopathology grade and stage assessment. Materials and methods: fourty tissue samples of lumbar HD obtained after the operations were kept in 10% formalin. Then all HD sections were processed, and embedded, after that, 5 μm thick glass mounted sections were stained with Hematoxylin and Eosin and Alcian blue (pH 0.02) and examined microscopically for histopathological changes and grading scoring was also conducted based on cell density, structural alterations of collagen fibers, and proteoglycan degeneration. Results: hemorrhage with fibrin deposition, mucous degeneration around chondrocyte clones and degeneration, increased chondrocyte density, expanded lacunae with degenerated chondrocytes, fiber disorientation, cleft formation, mucoid matrix changes, and inflammatory cell infiltration with fibrocyte prefiltration were the most histopathological changes in HD samples. Along with necrotic chondrocyte increase and tissue fiber alterations. Histological cell density grade indicated different-sized clones. All HD tissues revealed collagen fiber structural alterations, with gradients (52.5%) being most common. All HD samples showed mucous (proteoglycans) degradation, especially in gradients abundantly present and intermediate between 1 and 3 (45% and 42.5%). Conclusions: histopathological changes in intervertebral disc associated with HD infection.

Haemophilus influenzae is one of the most common causative agents of community-acquired pneumonia (CAP). Gene recombinations and high polymorphism make it difficult to diagnose the pathogen even by methods of molecular genetics. The development of DNA microarrays for H. influenzae detection in clinical samples of patients with CAP is promising. The aim of this work was to evaluate the possibility of detection of H. influenzae in clinical samples of patients with CAP using DNA microarray. Oligonucleotide probes were selected using disprose program and sequences from NCBI Nucleotide. Probes capable of cross-linking with H. haemolyticus and H. parainfluenzae DNA were removed in order to exclude nonspecific interaction. Probes were tested as part of DNA microarray design using samples of nucleic acid from tracheal aspirates of children with CAP. H. influenzae detection frequency in clinical samples was determined using sputum samples, tracheal aspirates and pharyngeal swabs of children and adults with CAP. The prevalence of the hybridization signal of the specific probes over 3 standard deviations of the hybridization signal of the negative control probes was interpreted as positive. The results were validated by PCR. 22 probes for H. influenzae detection with DNA microarray were selected. The hybridization signal of probes exceeded the threshold while testing samples containing H. influenzae DNA and did not exceed the threshold value while testing negative samples. H. influenzae detection frequency among patients with CAP was assessed. The results can be used for development of diagnostic tools for establishing the etiological factor of CAP.

The aim was to study macrolide resistance of erm B -positive H.pylori in patients with newly diagnosed and recurrent helicobacteriosis in Nizhny Novgorod. Materials and methods: PCR detection of H.pylori DNA in gastric juice and biotopes of the mucous membrane of the gastric antrum was performed in 3450 patients with gastroenterological diseases. To identify the ermB gene associated with macrolide resistance, domestic commercial PCR test systems were used. Results: from 2005 to 2023 there was a progressive reduction in visits for gastric and duodenal ulcers. The dynamics of primary and secondary genetic H.pylori macrolide resistance increased continuously from 2011 to 2014 and stabilized thereafter. From 2014 to 2023, the proportion of patients with ermB gene positive H.pylori infection increased approximately 2-fold (to 17.0% in 2018). In patients with a history of eradication therapy, the minimum detection rate of the ermB gene was established in 2011. Since 2012, there has been an increasing detection rate of secondary H.pylori macrolide resistance to 35.4% in 2022. Conclusions: during the observation period, a progressive reduction in the proportion of patients with gastric and duodenal ulcers among patients with gastroenterological diseases was revealed. The study of primary and secondary H.pylori macrolide resistance showed an increase in the detection rate of resistant isolates in Nizhny Novgorod. The study of genetic H.pylori macrolide resistance is necessary when re-identifying in patients with a history of eradication therapy and in patients who took clarithromycin for other reasons for the optimal selection of drugs included in the re-treatment regimen of infection.

Epigenetic regulation of spatiotemporal gene expression in ontogenesis is determined by programmed species-specific activations of retroelements in successive cell divisions. Evolutionary selection of this genome control mechanism is aimed at achieving a mature state, after which unprogrammed activation of retroelements occurs, which expression products stimulate interferon response, aseptic inflammation and aging-associated diseases development, such as atherosclerosis. Interferon in atherosclerosis stimulates pro-inflammatory macrophage phenotype, which contributes to pathological immune response, foam cell formation and atherosclerosis progression. Activation of retroelements occurs under the influence of viral infections, which role in atherosclerosis development has been proven, which confirms my hypothesis. Dysfunctional foam macrophages produce HERV-K102, which stimulates innate immunity, HERV-K HML2 expression correlates with macrophage immune activation and interferon response. Data were obtained on association with atherosclerosis of microRNAs derived from retroelements, which are involved in the disease pathogenesis due to their influence on cholesterol metabolism (miR-498, -520d), immune processes (miR-1257, -28, -2909), activation of DNMT1 (miR-1264) and EZH2 (miR-630), gene expression in endothelial cells (10 specific miRNAs), vascular smooth muscle cells (14 specific miRNAs) and macrophages (miR-320b, -326, -378, -384), contributing to pathological phenotype of these cells. In atherosclerosis microRNAs derived from retroelements interact with circular RNAs (miR-495, -576, -579, -630, -633, -637, -942) and long non-coding RNAs (miR-326, -4731, -495, - 616, -641, -664a) the key sources of which are retroelements. Role of ANRIL, NEAT1, PAPIA, MAARS, VINAS, H19, AK136714, MIAT, and interaction of Alu elements with ANRIL and NEAT1, identified in atherosclerosis development. The data obtained can become the basis for targeted effect on retroelements activation in atherosclerosis using microRNAs.

Injury to the proximal part of the equine suspensory ligament (SL), called proximal suspensory desmitis (PSD), commonly causes lameness in horses. PSD is extremely difficult to manage and treat, with present methods often unable to achieve full recovery, especially in chronic cases. The present study was the first to use gene therapy to restore moderate and severe injuries of the proximal suspensory ligament in horses. Plasmid DNA encoding species specific bone morphogenetic protein 2 (bmp2) and vascular endothelial growth factor (vegf164) was injected into the site of proximal suspensory ligament injury, followed by box rest and a controlled exercise program. Clinical observations and ultrasound imaging were used to evaluate effectiveness over a period of 12 months. No negative side effects were observed. Clinical improvements were observed, especially in the forelimb affected horses, by day 30. In horses with chronic hindlimb PSD, few clinical improvements were reported. Echogenicity and the fiber alignment scoring improved but no concomitant changes to cross section area, dorsopalmar thickness or lateromedial width of the proximal suspensory ligament were observed. The transfer of bmp2 and vegf164 genes into the equine PSL exhibited beneficial effects in horses with acute or subacute forms of lesions, primarily in the forelimb.

Obesity is recognized as a multifactorial health condition characterized by excess body fat accumulation. Orlistat is a well-known effective anti-obesity therapeutic drug, however, like many other medications on the market, it has certain unpleasant side effects. Medical herbs have recently acquired popularity in the treatment of obesity. The current project's intention was to evaluate the effect of treatment with Artemisia annua extract (AAE) to ameliorate hepato-renal dysfunction in obese rats. 40 male Sprague Dawley (SD) rats were divided into 4 groups (n = 10). The 1^st group (Gp1) served as a negative control, and Gp2 was used as a positive control and given a high-fat diet (HFD) for a period of 12 weeks. For a period of 8 weeks, Gp3 and Gp4 received HFD and daily treatments of orlistat (30 mg/kg) or AAE (150 mg/kg), respectively. Hematological, biochemical, and histopathological parameters were determined. The results demonstrated that obese rats, Gp2, had hepato-renal impairment. Moreover, hepato-renal dysfunctions were exacerbated when orlistat was administered to obese rats of Gp3. In contrast, AAE-treated obese rats, Gp4, have shown alleviated hematological changes and resulted in considerable improvements in hepato-renal function. Taken together, AAE administration demonstrated potential ameliorative effects against hepato-renal dysfunctions in obese rats when compared to treatment with orlistat.

Breast cancer (BC) is one of the most common causes of death among women in the world. This study investigated the role of global DNA methylation (5mC) and hypoxia-inducible factor 1 alpha (HIF-1α) levels in BC disease progression. Blood samples were collected from 40 patients with benign breast tumors, 40 patients with malignant breast tumors, and 40 healthy subjects. Patients with malignant breast tumors were divided into two groups: women in stage II (low-level), and patients in stages III and IV (high-level). Genomic DNA was isolated from whole blood samples from the subjects and used for global DNA methylation. Furthermore, the levels of HIF-1α expression were measured. The results showed that the levels of 5mC in patients with BC and benign breast tumors were considerably lower (0.538 ± 0.03 and 0.432 ± 0.04%, respectively), compared to the control (0.619 ± 0.05%). Furthermore, there was a significant (p ≤ 0.05) decrease in levels of 5mC in BC patients at stages III and IV compared to control. However, there were no significant differences between low-level and high-level stages. The HIF-1α levels of patients in both the benign breast tumors and BC were insignificant (923.35 ± 72.42 and 1386.03 ± 102.01pg/ml, respectively), compared to the control (825.5 ± 62.36 pg/ml). Although, BC patients at low levels showed no significant difference in HIF-1α levels compared with patients at high levels. The findings indicated that variations in 5mC levels across different stages and types of breast tumors may serve as a prognostic indicator for the development of BC and also implicated HIF-1α in the development of BC.

The effect of gas-discharge plasma radiation on the biochemical parameters of blood and urine of intact animals and animals with acute alcohol intoxication was investigated. Measurements of the content of medium-mass molecules (MMM), creatinine, urea, glucose, lactate and hemoglobin in the blood and 14 physicochemical indicators of the urine test were carried out. Acute alcohol intoxication (AAI) was simulated by intraperitoneal injection of 33% ethanol at a dose of LD50. The treatment was carried out by an experimental pulsed (10 Hz) device generating radiation of spark discharge plasma. It was revealed that exposure to plasma radiation does not lead to changes in the biochemical parameters of blood and urine of intact animals. In the model of AAI, the development of protein-creatininia, urobilinogenuria, and an increase in the specific gravity of rat’s urine was observed. The total level of MMM and hemoglobin in the blood increased, lactic acidosis developed. After exposure to plasma radiation in animals with AAI, blood and urine parameters normalized, which is probably associated with the activation of the organism's adaptive and antioxidant reserves. Thus, the positive effect of spark discharge plasma radiation on the organism during acute ethanol intoxication has been shown.

Currently, data are accumulating on the antioxidant properties of bilirubin and its protective role in various diseases. This review considers the dose-dependent effect of bilirubin on its cytoprotective and antioxidant properties, the relationship between the level of bilirubin and the pathophysiological manifestations of bronchial asthma, in the pathogenesis of which chronic inflammation induced by oxidative stress plays a significant role. The article also focuses on the potential therapeutic use of bilirubin in the treatment of bronchial asthma.

Ophthalmic diseases are common problems in dogs of various breeds and ages.  In recent years, ophthalmologists have been paying more attention to stem cell (SC) therapies, since the renewal and regeneration of any tissue in the adult body depends on somatic SC, and eye tissues are no exception. The aim of the present work was to determine the influence of allogenic mesenchymal stem cells (MSC) in healing ulcerative keratitis of dogs. Our research showed that subconjunctival injections of allogeneic MSCs from adipose tissue was clinically safe for use in dogs during the follow-up period. These injections contributed to the decrease of the clinical manifestations of ulcerative keratitis in dogs, as evidenced by a decrease the intensity and area of the affected areas of the cornea compared to classic therapy. 

Breast cancer (BC) is the predominant type of cancer among the female population in Iraq, and one of the most common causes of death among females. Through the period from 2018 until 2020, A total of eighty- two Formalin Fixed-Paraffin embedded FFPE tissue blocks were collected from the archive of Histopathology Department in Teaching Laboratories of Medical City, Teaching Hospital of Al-Yarmouk, and a privately-owned laboratory in Baghdad, Iraq. The clinical information regarding age, gender, tumor size, tumor stage and grade, lymph nodes metastasis, in addition to the findings of estrogen receptor (ER), progesterone receptor (PR) and receptor of human epidermal growth factor (HER)-2 were acquired from carefully reviewing patients' medical records and pathology reports. Results showed that a high incidence of BC in patients at sixth and decades of age, most of tumors′ specimens were within group size of (2-5 cm) in both malignant and benign groups, comprising 57.14% and 80% respectively, the most prevalent histologic type was invasive ductal carcinoma (IDC) encompassing 73.8%. About 59.52% of cases had positive lymph node tumor metastasis, the majority of cases were in grade II 64%. Stage III of the disease had highest rate, most of the cases were ER positive (66%), PR positive (57%) and for the HER most of the cases were HER negative.

The study was carried out in Anbar from September to December 2022 with the aim of identifying genetic variations in the IL-37 subunit gene among persons with chronic hepatitis. We investigated the correlation between the impact of IL-37 gene single nucleotide polymorphisms (SNPs) and hepatitis B and C virus infections. The four-arm primer approach was employed to identify single nucleotide polymorphisms (SNPs) in a cohort consisting of 90 patients and 100 healthy controls from the Iraqi population. Four single nucleotide polymorphisms (SNPs) of the IL-37 gene were determined through genotyping. Patients exhibited significantly higher frequencies of the rs2708967 G allele and GG genotype in comparison to controls. On the other hand, the rates of the A allele and AA genotype were comparatively lower, while the frequencies of the AG genotype were same. The patients demonstrated markedly elevated frequencies of the T allele and TT genotype compared to the controls. In addition, they exhibited markedly reduced frequencies of the C allele and CC genotype compared to the control group. The frequencies of CT genotypes, allele A, and AG and AA frequencies for the rs3811047 SNP did not show any significant differences in patients compared to controls. Our work indicates that mutations in the IL-37 gene are responsible for the genetic risk factors that contribute to the high occurrence of HBV and HCV infections in the Iraqi population.

The safety of titanium dioxide nano-particles (TiO2NPs) is currently being questioned. TiO2NPs have multiple uses in disinfectants, plastics, cosmetics, and food coloring. Our goal was to determine if administering Baicalin (50 mg/kg body weight) could help lessen the harmful effects caused by TiO2NPs (100 mg/kg body weight) in rats. By reducing kidney damage from TiO2NPs, treatment with Bai led to lower levels of creatinine (Cr), urea (Ur), and uric acid (UA). The harmful effects of TiO2NPs can be counteracted by Baicalin, which has demonstrated its ability to protect the kidneys. Additionally, it can restore balance between oxidation and antioxidants by increasing CAT, SOD, GSH, and reducing malondialdehyde levels. Not only does it exhibit anti-inflammatory effects by downregulating IL-6 and TNF- and increasing IL-10, but it also contributes to maintaining equilibrium in the body.