Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity.

The MTS cell viability test was used to screen a mini library of natural and synthetic 1,4-naphthoquinone derivatives (1,4-NQs) from marine sources. This screening identified two highly effective compounds, and , which showed potential in protecting Neuro-2a neuroblastoma cells from the toxic effects of rotenone in an in vitro model of neurotoxicity. The selected 1,4-NQs demonstrated the capability to reduce oxidative stress by decreasing the levels of reactive oxygen species (ROS) and nitric oxide (NO) in Neuro-2a neuroblastoma cells and RAW 264.

Estimation of Renal Clearance in Hypertensive Rats According to fMRI Data.

Renal clearance in Wistar rats with multifactorial cardiovasorenal model of arterial hypertension was assessed by fMRI using (EPI_Diffusion_map) protocol after injection of extracellular contrast agent gadolinium Gd-DTPA. Linear regression analysis was used to assess local concentrations of the contrast agent in the abdominal aorta, kidney compartments, pelvis, and bladder areas. Detection of marker clearance in order to verify the glomerular filtration rate was performed by the RPP (Rutland-Patlak plot) method.

Holothurian triterpene glycoside cucumarioside A-2 induces macrophages activation and polarization in cancer immunotherapy.

Background: Despite intensive developments of adoptive T cell and NK cell therapies, the efficacy against solid tumors remains elusive. Our study demonstrates that macrophage-based cell therapy could be a potent therapeutic option against solid tumors.

Methods: To this end, we determine the effect of a natural triterpene glycoside, cucumarioside A-2 (CA-2), on the polarization of mouse macrophages into the M1 phenotype, and explore the antitumor activity of the polarized macrophage.

Tetracyclic 1,4-Naphthoquinone Thioglucoside Conjugate U-556 Blocks the Purinergic P2X7 Receptor in Macrophages and Exhibits Anti-Inflammatory Activity In Vivo.

P2X7 receptors (P2X7Rs) are ligand-gated ion channels that play a significant role in inflammation and are considered a potential therapeutic target for some inflammatory diseases. We have previously shown that a number of synthetic 1,4-naphthoquinones are capable of blocking P2X7Rs in neuronal and macrophage cells. In the present investigation, we have demonstrated the ability of the tetracyclic quinone-thioglucoside conjugate , derived from 1,4-naphthoquinone thioglucoside, to inhibit ATP-induced Ca influx and YO-PRO-1 dye uptake, which indicates blocking P2X7R in RAW 264.

Structural and Functional Changes of the Thoracic Aorta in Experimental Arterial Hypertension.

The functional characteristics of the thoracic aorta in Wistar rat with experimental arterial hypertension were studied using MRI. The intravital images of the aorta were obtained using a synchronizer of cardiac and respiratory cycles. The pulse-gradient Turbo-spin-echo sequence and the BODY CARDIAC movie 10 mode were used.

Magnetic Resonance Imaging of Rat Brain in Assessment of the Neuroprotective Properties of Histochrome in Experimental Arterial Hypertension.

The neuroprotective effects of the course therapy with Histochrome in Wistar rats with modeled arterial hypertension were studied by using magnetic resonance imaging (MRI) in diffusion-weighted mode. The behavioral status of the animals was assessed using the open-field test. MRI analysis revealed more pronounced increase in the signaling characteristics of the brain tissue in hypertensive rats in comparison with the control (intact) animals.

Photophysics, photochemistry and bioimaging application of 8-azapurine derivatives.

New 2-aryl-1,2,3-triazolopyrimidines were designed, synthesized, and characterized. Their optical properties were thoroughly studied in the solid phase, in solution and in a biological environment. Density Functional Theory (DFT) based calculations were performed, including the molecular geometry optimization for both the ground state and the first singlet excited state, the prediction of the UV-Vis absorption and fluorescence spectra, the determination of the molecular electrostatic properties and the solvent effect on the optical properties.

Estimation of the Morphofunctional Status of the Brain in Hypertensive Wistar Rats Using Diffusion-Weighted MRI.

Morphofunctional changes of the brain tissues of Wistar rats were studied based on the development of a multifactor cardiovasorenal model of arterial hypertension using MRI. An increase of the signal on the diffusion brain maps was recorded in 3 months, which indicated fluid accumulation in the intra- and extracellular space of the brain tissue. The data characterize the development of the pathogenetic mechanism of the hypervolemic variant of experimental arterial hypertension.

Magnetic Resonance Imaging in Assessment of Cardiac Remodeling in Rats with Experimental Arterial Hypertension.

Magnetic resonance imaging was employed to examine the morphofunctional status of myocardium in Wistar rats with multifactor cardiovasorenal model of arterial hypertension. In 3 months after the onset of experiment, the rats demonstrated a pronounced hypertrophy in left ventricular myocardium mostly due to thickening of the posterior and lateral walls against the background of relatively stable thickness of ventricular septum. The left ventricular endsystolic volume markedly increased in parallel with moderate increase of the end-diastolic volume.

Low-dose action of tryptanthrin and its derivatives against developing embryos of the sea urchin Strongylocentrotus intermedius.

Nine tryptanthrin derivatives, including tryptanthrin itself, were synthesized using different methods, including oxidation of the corresponding isatins to obtain 1-4, the reaction of tryptanthrin 1 with hydrazine and its derivatives to obtain 5-7, and aldol condensation of 1 with acetone and methylethylketone to obtain 8 and 9. The action of 1-9 in doses corresponding to the IC against developing embryos of the sea urchin Strongylocentrotus intermedius and in the sperm test allowed us to estimate to potency of all the compounds and to determine which were cytotoxic. In addition, these studies showed that compounds 3, 4, 8, and 9 had a stimulatory effect at lower doses.

Assessment of Nephroprotective Potential of Histochrome during Induced Arterial Hypertension.

Magnetic resonance tomography was employed to verify endothelial dysfunction of renal arteries in Wistar and OXYS rats under conditions of induced arterial hypertension. Angiography revealed changes in the size and form of renal arteries of hypertensive animals. In hypertensive rats, histochrome exerted a benevolent therapeutic effect in renal arteries: it decreased BP, diminished thrombus formation in fi ne capillaries and arterioles, demonstrated the anticoagulant properties, partially improved endothelial dysfunction of small renal arteries, and up-regulated the glomerular filtration.

Vasomotor activity of the aorta during chronic smoking modeling.

We studied vasomotor responses of aortic endothelium in a rat model of chronic smoking. It was found that long-term exposure to tobacco smoke (inhalation) impaired vasomotor function of the aortic endothelium leading to insufficient vasodilator activity and enhanced vasoconstriction. After the cessation of inhalations, vasomotor disturbances were not only preserved, but also exacerbated because of increased pathological endothelium-independent vasoconstriction.

Evaluation of effects of histochrome and mexidol on structural and functional characteristics of the brain in senescence-accelerated OXYS rats by magnetic resonance imaging.

The effects of histochrome and mexidol on the morphology and function of the brain and behavior were studied in senescence-accelerated OXYS and Wistar rats. MRI showed that signs of neurodegenerative changes were present in OXYS rats at the age of 3 months and were pronounced at the age of 12 months. Histochrome (1 mg/kg, 5 days) more effectively than mexidol (4 mg/kg, 7 days) reduced anxiety and increased exploratory activity of 1-year-old OXYS rats.

Highly hydroxylated steroids of the starfish Archaster typicus from the Vietnamese waters.

Five new steroidal compounds, including an unusual glucoside, along with several known steroids were isolated from the starfish Archaster typicus collected in shallow waters of Quang Ninh province (Vietnam). Three new compounds are 27-nor-cholestane derivatives and the other two are 24,26-dihydroxycholestane derivatives. A biogenesis pathway for the unusual side chain of 27-nor-cholestane derivatives is proposed.

Antitumor activity of the immunomodulatory lead Cumaside.

A new immunomodulatory lead Cumaside that is a complex of monosulfated triterpene glycosides from the sea cucumber Cucumaria japonica and cholesterol possesses significantly less cytotoxic activity against sea urchin embryos and Ehrlich carcinoma cells than the corresponding glycosides. Nevertheless Cumaside has an antitumor activity against different forms of experimental mouse Ehrlich carcinoma in vivo both independently and in combination with cytostatics. The highest effect occurs at a treatment once a day for 7 days before the tumor inoculation followed by Cumaside treatment once a day for 7 days.

[Pathophysiological mechanisms of hemorrhagic stroke and the ways of differential therapy].

The changes developing in the perifocal area of hematoma and perspectives of antioxidant and chelate therapy were studied on the model of experimental hemorrhagic stroke and in clinical conditions. Microcirculatory, ischemic and inflammation disturbances with a certain time sequence were found in the perifocal areas. These changes, along with hypostasis and oxidative stress, form the pathobiochemical cascade of changes in hemorrhagic stroke and are potential therapeutic targets.

Endothelial dysfunction of cerebral and major arteries during chronic obstructive disease.

Vasomotor activity of the major and cerebral arteries was studied in mice with chronic obstructive pulmonary disease. Regional differences were revealed in the endothelium-dependent response of arteries. The development of chronic obstructive pulmonary disease was associated with a paradoxical response of the dilatational component of vasoregulation against the background of increased constrictive influences of the vascular endothelium in the major and cerebral vessels.

Immunomodulatory properties of frondoside A, a major triterpene glycoside from the North Atlantic commercially harvested sea cucumber Cucumaria frondosa.

Frondoside A, a major triterpene glycoside from North Atlantic commercially harvested sea cucumber Cucumaria frondosa, possesses strong immunomodulatory properties in subtoxic doses. Frondoside A stimulates lysosomal activity of mouse macrophages in vivo at a maximal effective stimulatory dose of 0.2 microg per mouse and is maintained over 10 days.

[Characteristics of a vasomotor endothelial function of the major and cerebral arteries in bronchial asthma].

We investigated endothelium dependent and independent activity of major and cerebral arteries in mice with experimental bronchial asthma. Regional features of endothelium dependent reactions of arteries were established. It was found that the carotid artery has greater vasomotor activity than the medial cerebral artery.

[Interrelation of vasomotor effects in the endothelium of the cerebral and main arteries in obstructive pulmonary diseases].

We have investigated vasomotor activity of the trunk and cerebral arteries in mice with obstructive pulmonary diseases. It was established, that endothelial dysfunction depends on the form of pulmonary disease and has regional vascular features. It was determined, that the maximal disturbances are shown in mice with chronic obstructive pulmonary disease.

Anticancer activity of 3-demethylubiquinone Q2. In vivo experiments and probable mechanism of action.

Background: 3-Demethylubiquinone Q2 (3DMUbQ2), isolated from the ascidian Aplidium glabrum and later synthesized, is known as a natural product inhibiting EGF-induced malignant JB6 P+ Cl 41 cell transformation. However, its in vivo anticancer properties and probable mechanism of this action have not been studied.

Materials And Methods: Preventive and curable effects of3DMUbQ2 on mice with inoculated Ehrlich carcinoma tumors were examined by magnetic resonance tomography.

Magnetic resonance imaging of mouse Ehrlich carcinoma growth inhibition by thiacarpine, an analogue of cytotoxic marine alkaloid polycarpine.

The anticancer effect of thiacarpine, a synthetic analogue of the known cytotoxic alkaloid polycarpine isolated from the Pacific ascidian Polycarpa aurata, was investigated in vivo in experiments using mouse solid Ehrlich carcinoma tumor as the target. A high-resolution magnetic resonance imaging (MRI) technique using a MR tomograph "PharmaScan" US70/16 (Bruker, Ettlingen, Germany) was used for visualization and quantification of tumor size. Fluorescence microscopy and image analysis were applied to determine Ehrlich carcinoma cell chromatin condensing (apoptosis) and necrosis in Ehrlich carcinoma cells at the action of thiacarpine in in vitro experiments.

Steroidal triglycosides, kurilensosides A, B, and C, and other polar steroids from the Far Eastern starfish Hippasteria kurilensis.

Three novel steroidal triglycosides, designated as kurilensosides A, B, and C (1- 3), were isolated along with a new steroidal diglycoside, kurilensoside D (4), and two new (6, 7) and one known (5) polyhydroxysteroid from the alcoholic extract of the Far Eastern starfish Hippasteria kurilensis. Compounds 1-3 are the first triglycosides containing two carbohydrate chains found from starfish. The structures of 1-7 were elucidated by spectroscopic methods (mainly 2D NMR) and chemical derivatization.

Peculiarities of vasomotor reaction of cerebral vessels in arterial hypertension.

We studied vasomotor activity of rat cerebral vessels. Peculiarities of endothelium-dependent reactions of cerebral arteries in induced arterial hypertension were revealed. Quantitative and qualitative relationships between the parameters of the vasomotor apparatus of cerebral arteries and parameters of circulatory homeostasis were determined.

Effect of histochrome on brain vessels and research and exploratory activity of senescence-accelerated OXYS rats.

Changes in the diameter of brain vessels and intensity of collateral blood flow typical of chronic ischemia were detected by magnetic resonance imaging in senescence-accelerated OXYS rats demonstrating reduced (compared to Wistar rats) research and exploratory activity. Histochrome (antioxidant drug) produced positive effects on cerebral vessels in OXYS rats by stimulating collateral blood flow and acting as a vasodilator agent. Analysis of correlations showed that these effects of histochrome were closely related to its capacity to activate research and exploratory activity and reduce anxiety of OXYS rats in the open field test.