In experiments on Wistar rats, the effect of a new selective JNK inhibitor tryptanthrin oxime (TR-Ox) on parameters of systemic hemodynamics, cardiohemodynamics, and post-infarction fibrosis was studied 4 months after acute myocardial ischemia (1 h) followed by reperfusion. TR-Ox was administered intraperitoneally at a dose of 12 mg/kg 20 min before reperfusion, and then once a day for the next 4 days. Administration of TR-Ox to animals in the acute phase of myocardial infarction contributed to more complete preservation of myocardial viability in the delayed period: a relative increase of muscle elements proportion in the scar, a decrease in the formation of connective tissue areas with complete and >50% replacement of the myocardium, and deceleration of fibrotic scarring in myocardium areas distant from the focus of injury, resulting in improved systolic and diastolic myocardial function.
View Article and Find Full Text PDFThe neuroprotective activity of tryptanthrin and its oxime was compared in male Wistar rats with a model of intraluminal occlusion of the middle cerebral artery. Neurobehavioral tests were performed 4, 24, and 48 h after focal cerebral infarction (FCI) using a modified neurological severity score (mNSS); additionally, the horizontal stability test, the plantar sensitivity test of the fore and hind limbs, holding on the tilted cage top test, and negative geotaxis test were performed. The size of FCI and the severity of brain tissue swelling were examined on day 2 after occlusion.
View Article and Find Full Text PDFBackground: Nanocomposite glycerohydrogels based on biocompatible elementcontaining glycerolates are of practicular interest for biomedical applications.
Objective: Using two biocompatible precursors, silicon and iron glycerolates, a new bioactive nanocomposite silicon‒iron glycerolates hydrogel was obtained by sol-gel method.
Methods: The composition and structural features of the hydrogel were studied using a complex of modern analytical techniques, including TEM, XRD, and AES.
Non-canonical 5'-caps removing RNA hydrolase NudC, along with stress-responsive RNA helicase CsdA, is crucial for 5'-NAD-RNA decapping and bacterial movement.
View Article and Find Full Text PDFThe activation of -Jun N-terminal kinase (JNK) plays an important role in stroke outcomes. Tryptanthrin-6-oxime (TRYP-Ox) is reported to have high affinity for JNK and anti-inflammatory activity and may be of interest as a promising neuroprotective agent. The aim of this study was to investigate the neuroprotective effects of TRYP-Ox in a rat model of transient focal cerebral ischemia (FCI), which involved intraluminal occlusion of the left middle cerebral artery (MCA) for 1 h.
View Article and Find Full Text PDFActivation of c-Jun N-terminal kinases (JNKs) is involved in myocardial injury, left ventricular remodeling (LV), and heart failure (HF) after myocardial infarction (MI). The aim of this research was to evaluate the effects of a selective JNK inhibitor, 11-indeno [1,2-]quinoxalin-11-one oxime (IQ-1), on myocardial injury and acute myocardial ischemia/reperfusion (I/R) in adult male Wistar rats. Intraperitoneal administration of IQ-1 (25 mg/kg daily for 5 days) resulted in a significant decrease in myocardial infarct size on day 5 after MI.
View Article and Find Full Text PDFThe c-Jun -terminal kinases (JNKs) regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival, and cell death. Therefore, JNKs represent attractive targets for therapeutic intervention. In an effort to develop improved JNK inhibitors, we synthesized the lithium salt of 11-indeno[1,2-]quinoxaline-11-one oxime () and evaluated its affinity for JNK and biological activity in vitro and in vivo.
View Article and Find Full Text PDFThe effect of p-tyrosol on the main hemodynamic parameters and contractile function of the heart was studied and a morphometric assessment of left-ventricular remodeling was performed in Wistar rats 2 months after acute 1-h myocardial ischemia followed by reperfusion. p-Tyrosol in a dose of 20 mg/kg was injected intraperitoneally 5 times: 20 min before the start of reperfusion, 4 h after the start of reperfusion, and then once a day over the next 3 days. Administration of p-tyrosol to animals in the acute period of myocardial infarction slowed down the formation of systolic and diastolic myocardial dysfunction, improved the pumping function of the heart, maintained the hemodynamic parameters at a significantly higher level, and reduced left-ventricular remodeling in the late period of myocardial infarction.
View Article and Find Full Text PDFInvestigation of the effect of the polymer synthesis method on physicochemical properties of sorbents is one of the topical problems in the chemistry of macromolecular compounds that has high scientific and practical interest. Determination of the optimal synthesis method will make it possible to create sorbents with physicochemical properties that led to the realization of effective sorption. In this work, we investigated the effect of synthesis methods (Pickering emulsion polymerization and precipitation polymerization in solution) of granular polymers based on 2-hydroxyethyl methacrylate and ethylene glycol dimethacrylate on physicochemical and sorption properties.
View Article and Find Full Text PDFBackground: Targeted installation of designer chemical moieties on biopolymers provides an orthogonal means for their visualisation, manipulation and sequence analysis. Although high-throughput RNA sequencing is a widely used method for transcriptome analysis, certain steps, such as 3' adapter ligation in strand-specific RNA sequencing, remain challenging due to structure- and sequence-related biases introduced by RNA ligases, leading to misrepresentation of particular RNA species. Here, we remedy this limitation by adapting two RNA 2'-O-methyltransferases from the Hen1 family for orthogonal chemo-enzymatic click tethering of a 3' sequencing adapter that supports cDNA production by reverse transcription of the tagged RNA.
View Article and Find Full Text PDFA novel specific inhibitor of c-Jun N-terminal kinase, 11-indeno[1,2-]quinoxalin-11-one oxime sodium salt (IQ-1S), has a high affinity to JNK3 compared to JNK1/JNK2. The aim of this work was to study the mechanisms of neuroprotective activity of IQ-1S in the models of reversible focal cerebral ischemia (FCI) in Wistar rats. The animals were administered with an intraperitoneal injection of IQ-1S (5 and 25 mg/kg) or citicoline (500 mg/kg).
View Article and Find Full Text PDF2,6-Diisobornyl-4-methylphenol (Dibornol, 10 mg/kg intragastrically daily for 5 days after myocardial ischemia/reperfusion) 1.5-fold increased rat survival during the acute post-infarction period in comparison with the control group. In survivors, Dibornol reliably prevented post-ischemic progression of heart failure in the delayed post-infarction period (30 days after ischemia/reperfusion), which was seen from an increase in the left-ventricular developed pressure by 22%, left-ventricular contractility index by 19%, and +dP/dt by 34%.
View Article and Find Full Text PDFTo study clinical and laboratory parameters and morphological characteristics of the endometrium in women with impaired fat metabolism and failed IVF attempts. Clinical examination, laboratory tests, morphological analysis, and immunohistochemistry of the endometrium were conducted in 76 patients with different BMI, followed up with infertility and failed IVF attempts. Patients were divided into four groups by body mass index (BMI): 1 group - 17 women with overweight, BMI = 25.
View Article and Find Full Text PDFc-Jun N-terminal kinase (JNK) is activated by various brain insults and is implicated in neuronal injury triggered by reperfusion-induced oxidative stress. Some JNK inhibitors demonstrated neuroprotective potential in various models, including cerebral ischemia/reperfusion injury. The objective of the present work was to study the neuroprotective activity of a new specific JNK inhibitor, IQ-1S (11-indeno[1,2-]quinoxalin-11-one oxime sodium salt), in the model of global cerebral ischemia (GCI) in rats compared with citicoline (cytidine-5'-diphosphocholine), a drug approved for the treatment of acute ischemic stroke and to search for pleiotropic mechanisms of neuroprotective effects of IQ-1S.
View Article and Find Full Text PDFBackground: The contribution of hypoxic conditions to the chemical composition of membranes is not completely established. Plasmalogens, containing an alkenyl group with aldehydogenic ether linkage, are significant components of membrane lipids and their level can change in oxygen deficiency.
Methods: Analysis of plasmalogens in red blood cells was performed in patients (n = 17) with coronary heart disease, stable angina (functional class II-III) and coronary atherosclerosis.
We developed an improved three-vessel occlusion model of global cerebral ischemia in rats. This method consists in cessation of cerebral blood flow by accessing a. carotis communis sinistra through the ventral surface of the neck as well as tr.
View Article and Find Full Text PDFThe HEN1 RNA 2'-O-methyltransferase plays important roles in the biogenesis of small non-coding RNAs in plants and proved a valuable tool for selective transfer of functional groups from cofactor analogues onto miRNA and siRNA duplexes in vitro. Herein, we demonstrate the versatile HEN1-mediated methylation and alkylation of small RNA strands in heteroduplexes with a range of complementary synthetic DNA oligonucleotides carrying user-defined moieties such as internal or 3'-terminal extensions or chemical reporter groups. The observed DNA-guided covalent functionalization of RNA broadens our understanding of the substrate specificity of HEN1 and paves the way for the development of novel chemo-enzymatic tools with potential applications in miRNomics, synthetic biology, and nanomedicine.
View Article and Find Full Text PDFBackground: Salidroside is a biologically active compound derived from Rhodiola rosea L. Studies showed that salidroside after i.v.
View Article and Find Full Text PDFWe propose a modification to rat model of transient global cerebral ischemia with four-vessel occlusion avoiding pneumothorax and minimizing the consequences of surgery. Survival and neurological deficit in rats in this model was studied over 5 days.
View Article and Find Full Text PDFMicroRNAs regulate gene expression in numerous biological pathways and are typically methylated at their 3'-termini in plants but not in animals. Here we show that the HEN1 RNA 2'-O-methyltransferase from Arabidopsis thaliana catalyzes the transfer of extended propargylic moieties from synthetic AdoMet cofactor analogs to duplex miRNAs or siRNAs. The presented approach permits selective and efficient covalent labeling of small RNA duplexes with a variety of functional or reporter groups for their enrichment and analysis.
View Article and Find Full Text PDFThe HEN1 methyltransferase from Arabidopsis thaliana modifies the 3'-terminal nucleotides of small regulatory RNAs. Although it is one of the best characterized members of the 2'-O-methyltransferase family, many aspects of its interactions with the cofactor and substrate RNA remained unresolved. To better understand the substrate interactions and contributions of individual steps during HEN1 catalysis, we studied the binding and methylation kinetics of the enzyme using a series of unmethylated, hemimethylated and doubly methylated miRNA and siRNA substrates.
View Article and Find Full Text PDFThe article presents the results of analysis of fatty acids and fatty aldehydes of plasma and blood erythrocytes in patients with the syndrome of multiple organ failure. The increase of relative level of mono-unsaturated fatty acids and decrease of poly-saturated fatty acids and saturated stearic acid in blood plasma is demonstrated. The reliable alterations in erythrocytes concerning the content of saturated palmitic and poly-saturated linoleic fatty acids are detected.
View Article and Find Full Text PDFThe authors have ascertained informative laboratory tests for diagnosis of immobilization osteoporosis and prognostic tests of reparative osteogenesis in its presence. A study was conducted in 97 patients (mean age 39.8 +/- 9.
View Article and Find Full Text PDFBiochemistry (Mosc)
September 1998
Activation of highly specific biochemical processes by simple chemical agents is demonstrated for morphogenesis (anlage and development of female gametophyte in cereal) and mitosis (in cell cultures and animal and plant tissues). The effects of these agents are tissue-specific. Structure--activity relationship is analyzed in this group of compounds.
View Article and Find Full Text PDFBiull Eksp Biol Med
September 1995