Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research.

Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices.

Development of Antiatherosclerotic Drugs on the basis of Natural Products Using Cell Model Approach.

Atherosclerosis including its subclinical form is one of the key medical and social problems. At present, there is no therapy available for widespread use against subclinical atherosclerosis. The use of synthetic drugs for the prevention of arteriosclerosis in its early stages is not sufficient because of the limited indications for severe side effects and high cost of treatment.

Specific Lipoprotein(a) apheresis attenuates progression of carotid intima-media thickness in coronary heart disease patients with high lipoprotein(a) levels.

Background: To date, there have been no studies evaluating the effect of isolated lipoprotein(a) (Lp(a)) lowering therapy on carotid atherosclerosis progression.

Methods: We enrolled 30 patients who had coronary heart disease (CHD) verified by angiography, Lp(a) level ≥50 mg/dL, and low density lipoprotein cholesterol (LDL-C) level ≤2.6 mmol/L (100 mg/dL) on chronic statin therapy.

Lowering of lipoprotein(a) level under niacin treatment is dependent on apolipoprotein(a) phenotype.

Background: Lipoprotein(a) [Lp(a)] is a cardiovascular risk factor; in addition to being a low-density lipoprotein (LDL)-like particle, it contains highly heterogeneous apolipoprotein(a) [apo(a)]. No prior studies have evaluated extended-release (ER) niacin effect on Lp(a) level depending on apo(a) phenotype.

Methods: For this 24-week, prospective, open-label clinical trial we recruited 30 men (mean age 46.

[Transcatheter Treatment of Degenerative Critical Aortic Valve Stenosis in a Patient With Severe Heart Failure and Chronic Lymphocytic Leukemia].

Surgical aortic valve replacement is the standard therapy for severe aortic valve stenosis, however one third of patients are rejected because of high surgical risk. Under medical treatment alone these patients have a very poor prognosis with a high mortality rate. We present a case of 70-year-old male patient with degenerative symptomatic critical aortic stenosis and chronic lymphocytic leukemia.

Dramatic fate of a young coronary heart disease patient rescued with specific lipoprotein(a) apheresis.

Lipoprotein(a) [Lp(a)] is acknowledged to be an independent atherothrombotic risk factor. Although genetic studies have highlighted the causal relationship between coronary disease and Lp(a), it is uncertain which strategies maximize the therapeutic benefit of patients with high Lp(a) levels. We report the challenging case of a young coronary heart disease (CHD) patient who underwent 10 percutaneous coronary interventions due to repeated acute coronary syndromes (2006-2009) despite an optimally controlled, traditional risk-factor profile.

Approach to reduction of blood atherogenicity.

We have earlier found that blood sera of patients with coronary heart disease (CHD) increase lipid levels in cells cultured from subendothelial intima of human aorta. We have also revealed that the ability of blood sera to raise intracellular cholesterol; that is, their atherogenicity is caused by at least modified low density lipoprotein (LDL) circulating in the blood of patients and autoantibodies to modified LDL. In the present work we have demonstrated significant impact of nonlipid factor(s) to blood atherogenicity.

Efficacy of a new class III drug niferidil in cardioversion of persistent atrial fibrillation and flutter.

Aims: To study the efficacy and safety of the new class III antiarrhythmic agent niferidil for pharmacological cardioversion in patients with persistent atrial fibrillation (AF) and atrial flutter (AFl).

Methods And Results: One hundred thirty-four adults (aged 57.8 ± 11 years, 90 males) were included with median AF duration of 3 (1.

Alpha-fetoprotein contributes to THP-1 cell invasion and chemotaxis via protein kinase and Gi-protein-dependent pathways.

Alpha-fetoprotein (AFP) for long was known as immunomodulator and tumor marker having multifaceted actions on the activity of normal and transformed cells. In present study, we have investigated the involvement of AFP in regulation of THP-1 cell line invasion and underlying mechanisms. Treatment with human recombinant AFP causes up-regulation of MMP9 expression, chemotaxis and calcium mobilization, and increases invasion through Matrigel, with no significant impact on THP-1 cell growth or viability.

Halogenated phospholipids regulate secretory phospholipase A2 group IIA activity.

Secretory phospholipase A2 group IIA (sPLA2-IIA) is an active participant of inflammation. The enzyme destroys bacterial cell wall and induces production of biologically active lipid mediators. It is involved in various pathological processes and high serum content and activity of sPLA2-IIA are associated with adverse cardiovascular events.

Insulin resistance and adipogenesis: role of transcription and secreted factors.

Insulin stimulates carbohydrate uptake by cells and induces their conversion into lipids as a more efficient form of energy storage. Insulin resistance is associated with a decrease in glucose uptake by muscle and adipose cells and also with a decrease in glycogen synthesis on retention of glucose synthesis by liver cells. Disorders in the insulin signaling cascade on development of insulin resistance can be caused by both changes in functioning of transcriptional factors and in the secretion profile of hormone-like substances.

Myosin-activating protein kinases are possible regulators of nonmuscle myosin in developing human heart.

We studied the localization of myosin-activating protein kinases in cardiomyocytes obtained from fetal human heart at 8-9 weeks gestation. It was found that at this developmental stage, smooth muscle/nonmuscle myosin light chain kinase (MLCK, 108 kDa) and its high-molecular weight isoform (MLCK, 210 kDa), skeletal MLCK and death-associated protein kinase (DAPK) are co-localized with nonmuscle myosin IIB in the premyofibrils. The data obtained suggest that cardiac nonmuscle myosin at 8-9 weeks gestation may serve as the substrate of the studied myosin-activating protein kinases that are likely to cooperatively regulate the formation of myofibrils.

RNase footprinting demonstrates antigenomic hepatitis delta virus ribozyme structural rearrangement as a result of self-cleavage reaction.

Background: Hepatitis delta virus (HDV) is a satellite virus of hepatitis B. During viral replication the 1700-nucleotide-long genomic RNA and its complement, the antigenomic RNA, undergo self-cleavage catalyzed by internal ribozyme motifs that are essential for propagation of the virus in vivo. These self-cleavage activities are provided by 85-nucleotide-long sequence elements, the genomic and antigenomic forms of HDV ribozyme.

Oxidative stress in patients with chronic heart failure and type 2 diabetes mellitus.

Parameters of oxidative stress were studied in patients with chronic heart failure and/or type 2 diabetes mellitus. Chronic heart failure was accompanied by severe oxidative stress, while in patients with type 2 diabetes mellitus the signs of oxidative stress were less pronounced. The intensity of free radical oxidation in patients with chronic heart failure and type 2 diabetes mellitus was not higher compared to patients with chronic heart failure.

Atrial appendage transcriptional profile in patients with atrial fibrillation with structural heart diseases.

During the last few years DNA microarray studies of gene expression changes in human atrial tissues from patients with and without atrial fibrillation (AF) have been performed. For this purpose, tissue samples are usually collected from AF patients undergoing open heart surgery. These investigations have limitations associated with the unavoidable heterogeneity of compared groups which is due to the presence of various structural changes accompanying different sets of underlying heart diseases in both groups.

Metabolic correction reduces the area of acute ischemic myocardial infarction in rats.

The possibility of decreasing the degree of irreversible alterations in cardiomyocytes with original saline reperfusion solution enriched with L-aspartic acid, D-glucose, and Dmannitol was studied on experimental rats with regional ischemia and reperfusion. Infusion of the test solution into the left ventricle during the early reperfusion stage significantly reduced the area of myocardial infraction. This effect was accompanied by improvement of energy metabolism and decrease in damage to cell membranes in the risk zone.

Low daily dose of antioxidant probucol decreases incidence and severity of restenosis after transluminal coronary balloon angioplasty.

Antioxidant probucol in both high (1000 mg) and low (250 mg) daily doses effectively reduced manifestations of oxidative stress in patients with atherosclerosis (assessed by in vivo accumulation of lipoperoxides in atherogenic LDL). When probucol was administered in a dose of 250 mg/day for 7-10 days before transluminal balloon coronary angioplasty and then for 6 months after surgery, the incidence of restenosis decreased to 25% compared to 45% in the control (without probucol therapy). In the group of operated patients receiving probucol (250 mg/day for 6 months) the minimal artery lumen was significantly higher, and the degree of artery occlusion significantly lower than in the control group not treated with probucol.

Heart resistance to oxidative stress in rats of different genetic strains.

In August rats reperfusion after regional myocardial ischemia in situ or intracoronary administration of hydrogen peroxide less significantly suppressed contractile activity of the heart compared to Wistar rats. Activities of catalase and superoxide dismutase in the myocardium during reperfusion remained unchanged in August rats. In Wistar rats a profound inhibition of cardiac function was accompanied by a decrease in enzyme activity.

A complex of antioxidant vitamins effectively inhibits free-radical oxidation of LDL phospholipids in blood plasma and membrane structures of the liver and myocardium.

Antioxidant effect of a complex preparation including antioxidant vitamins C, E, provitamin A and selenium was studied on the model of Cu(2+)-initiated free-radical oxidation of LDL isolated from human blood plasma. The antioxidant effect of combined administration of alpha-tocopherol+ascorbic acid and alpha-tocopherol+beta-carotene is far more pronounced that the antioxidant effect of individual components of these cocktails. Moreover, in the model system the combined action of all antioxidant components completely inhibited free-radical oxidation of LDL.

Oxidative stress in patients with primary pulmonary hypertension.

We studied the role of oxidative stress in the pathogenesis of primary pulmonary hypertension. In patients with primary pulmonary hypertension the content of malonic dialdehyde in the plasma was higher than in healthy volunteers (5.18 0.

Antioxidant activity of parapharmaceutics containing natural inhibitors of free radical processes.

The duration of lag phase of ascorbate-dependent free radical oxidation of endogenous polyenic lipids in rat liver and myocardium considerably increased after oral administration of lacrinat containing licorice Glycyrrhiza glabra root powder for 1 month. Lacrinat markedly decreased the content of lipid peroxides in rat liver. Ex vivo antioxidant effects of lacrinat in rat liver were comparable with those of beta-carotene-containing preparations carinat and carinat CD.