Contribution of staphylococcal virulence factors in the pathogenesis of thrombosis.

Staphylococci are responsible for many infections in humans, starting with skin and soft tissue infections and finishing with invasive diseases such as endocarditis, sepsis and pneumonia, which lead to high mortality. Patients with sepsis often demonstrate activated clotting pathways, decreased levels of anticoagulants, decreased fibrinolysis, activated endothelial surfaces and activated platelets. This results in disseminated intravascular coagulation and formation of a microthrombus, which can lead to a multiorgan failure. This review describes various staphylococcal virulence factors that contribute to vascular thrombosis, including deep vein thrombosis in infected patients. The article presents mechanisms of action of different factors released by bacteria in various host defense lines, which in turn can lead to formation of blood clots in the vessels.

Evaluation of antioxidant activity of NG-R1 saponin against bacterial cells in induced oxidative stress - a preliminary study.

INTRODUCTION AND OBJECTIVE: Notoginsenoside R1 (NG-R1) is isolated from Panax notoginseng, a medicinal herb well-known for its long use in traditional Chinese medicine. NG-R1 is relatively under-studied in research on bacteria. The aim of the study was to investigate antioxidant properties of NG-R1 saponin of selected bacterial strains of intestinal microbiota that may be involved in the pathogenesis of thromboembolic diseases. Enterococcus faecalis and Escherichia coli were used in the study. MATERIAL AND METHODS: The study determined the concentration of hydroperoxides, the level of lipid peroxidation, as well as carbonyl groups and free thiol groups. The research carried out in this way will allow determination of the influence of the above factors on bacteria living in intestinal microbiota. RESULTS: An evaluation of selected parameters of oxidative stress allowed to check whether the tested compound could reduce the pro-thrombotic activity of bacteria that were stimulated with H2O2. It was found that NG-R1 reduced hydroperoxide levels in both types of bacteria. In turn, lipid peroxidation initiated by H2O2 was suppressed by NG-R1. Hydrogen peroxide led to a strong increase in the level of carbonyl groups in Enterococcus faecalis and, to a lesser extent, in Escherichia coli. The addition of NG-R1 to the medium significantly reduced the level of carbonyls. Additionally, NG-R1 also induced a significant increase in the level of free thiol groups. CONCLUSIONS: Obtained results indicate that NG-R1 may have a protective effect on the intestinal microbiom through mechanisms involving changes in the redox state.

Quenching of Protein Fluorescence by Fullerenol C60(OH)36 Nanoparticles.

The effect of the interaction between fullerenol C60(OH)36 (FUL) and alcohol dehydrogenase (ADH) from Saccharomyces cerevisiae and human serum albumin (HSA) was studied by absorption spectroscopy, fluorescence spectroscopy, and time-resolved fluorescence spectroscopy. As shown in the study, the fluorescence intensities of ADH and HSA at excitation wavelengths λex = 280 nm (Trp, Tyr) and λex = 295 nm (Trp) are decreased with the increase in the FUL concentration. The results of time-resolved measurements indicate that both quenching mechanisms, dynamic and static, are present. The binding constant Kb and the number of binding sites were obtained for HSA and ADH. Thus, the results indicated the formation of FUL complexes and proteins. However, the binding of FUL to HSA is much stronger than that of ADH. The transfer of energy from the protein to FUL was also proved.

Association of Polymorphic Variants in Argonaute Genes with Depression Risk in a Polish Population.

Argonaute (AGO) proteins, through their key role in the regulation of gene expression, participate in many biological processes, including cell differentiation, proliferation, death and DNA repair. Accurate regulation of gene expression appears to be important for the proper development of complex neural circuits. Loss of AGO proteins is known to lead to early embryonic mortality in mice with various malformations, including anomalies of the central nervous system. Single-nucleotide polymorphisms (SNPs) of AGO genes can lead to deregulation of the processes in which AGO proteins are involved. The contribution of different SNPs in depression has been extensively studied. However, there are hardly any studies on the contribution of AGO genes. The aim of our research was to assess the relationship between the occurrence of depression and the presence of SNPs in genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) in a Polish population. One hundred and one subjects in the study group were diagnosed with recurrent depressive disorder by a psychiatrist. The control group comprised 117 healthy subjects. Study participants performed the HDRS (Hamilton Depression Scale) test to confirm or exclude depression and assess severity. The frequency of polymorphic variants of genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) was determined using TaqMan SNP genotyping assays and the TaqMan universal PCR master mix, no AmpErase UNG. The rs4961280/AGO2 polymorphism was associated with a decrease in depression occurrence in the codominant (OR = 0.51, p = 0.034), dominant (OR = 0.49, p = 0.01), and overdominant (OR = 0.58, p = 0.049) models. Based on the obtained results, we found that the studied patients demonstrated a lower risk of depression with the presence of the polymorphic variant of the rs4961280/AGO2 gene-genotype C/A and C/A-A/A.

Factors Affecting the Formation and Treatment of Thrombosis by Natural and Synthetic Compounds.

Venous thromboembolism (VTE) refers to deep vein thrombosis (DVT), whose consequence may be a pulmonary embolism (PE). Thrombosis is associated with significant morbidity and mortality and is the third most common cardiovascular disease after myocardial infarction and stroke. DVT is associated with the formation of a blood clot in a deep vein in the body. Thrombosis promotes slowed blood flow, hypoxia, cell activation, and the associated release of many active substances involved in blood clot formation. All thrombi which adhere to endothelium consist of fibrin, platelets, and trapped red and white blood cells. In this review, we summarise the impact of various factors affecting haemostatic disorders leading to blood clot formation. The paper discusses the causes of thrombosis, the mechanism of blood clot formation, and factors such as hypoxia, the involvement of endothelial cells (ECs), and the activation of platelets and neutrophils along with the effects of bacteria and reactive oxygen species (ROS). Mechanisms related to the action of anticoagulants affecting coagulation factors including antiplatelet drugs have also been discussed. However, many aspects related to the pathogenesis of thrombosis still need to be clarified. A review of the drugs used to treat and prevent thrombosis and natural anticoagulants that occur in the plant world and are traditionally used in Far Eastern medicine has also been carried out.

Microbial Modulation of Coagulation Disorders in Venous Thromboembolism.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third leading cause of cardiovascular death in the world. Important risk factors of thrombosis include bed restraint, surgery, major trauma, long journeys, inflammation, pregnancy, and oral contraceptives, previous venous thromboembolism, cancer, and bacterial infections. Sepsis increases the risk of blood clot formation 2-20 times. In this review, we discussed various mechanisms related to the role of bacteria in venous thrombosis also taking into consideration the role of the human microbiome. Many known bacteria, such as Helicobacter pylori, Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, causing infections may increase the risk of thrombotic complications through platelet activation or may lead to an inflammatory reaction involving the fibrinolytic system. Additionally, the bacteria participate in the production of factors causing or increasing the risk of cardiovascular diseases. An example can be trimethylamine N-oxide (TMAO) but also uremic toxins (indoxyl sulfate), short-chain fatty acids (SCFA) phytoestrogens, and bile acids. Finally, we presented the involvement of many bacteria in the development of venous thromboembolism and other cardiovascular diseases.

A Multiparametric Study of Internalization of Fullerenol C60(OH)36 Nanoparticles into Peripheral Blood Mononuclear Cells: Cytotoxicity in Oxidative Stress Induced by Ionizing Radiation.

The aim of this study was to investigate the uptake and accumulation of fullerenol C60(OH)36 into peripheral blood mononuclear cells (PBMCs). Some additional studies were also performed: measurement of fullerenol nanoparticle size, zeta potential, and the influence of fullerenol on the ionizing radiation-induced damage to PMBCs. Fullerenol C60(OH)36 demonstrated an ability to accumulate in PBMCs. The accumulation of fullerenol in those cells did not have a significant effect on cell survival, nor on the distribution of phosphatidylserine in the plasma membrane. However, fullerenol-induced depolarization of the mitochondrial membrane proportional to the compound level in the medium was observed. Results also indicated that increased fullerenol level in the medium was associated with its enhanced transport into cells, corresponding to its influence on the mitochondrial membrane. The obtained results clearly showed the ability of C60(OH)36 to enter cells and its effect on PBMC mitochondrial membrane potential. However, we did not observe radioprotective properties of fullerenol under the conditions used in our study.

Therapeutic potential of natural compounds in inflammation and chronic venous insufficiency.

The term varicose vein refers to the twisted and swollen vein visible under the skin surface which occurs most commonly in the leg. Epidemiological studies report a varying percentage of incidences from 2 to 56% in men and <1-60% in women. Venous insufficiency is most often caused by the damage to the valves and walls of the veins. The mechanism of varicose vein formation is complex. It is, however, based on hypotensive blood vessels, hypoxia, and other mechanisms associated with inflammation. This work describes mechanisms related to the formation and development of the varicose vein. It discusses risk factors, pathogenesis of chronic venous disease, markers of the epithelial and leukocyte activation, state of hypoxia and inflammation, reactive oxygen species (ROS) generation, and oxidative stress. Additionally, this paper describes substances of plant origin used in the treatment of venous insufficiency. It also considers the structure of the molecules, their properties, and their mechanisms of action, the structure-activity relationship and chemical properties of flavonoids and other substances. The flavonoids include quercetin derivatives, micronized purified flavonoid fraction (Daflon), natural pine bark extract (Pycnogenol), and others such as triterpene saponine, extracts from Ruscus aculeatus and Centella asiatica, Ginkgo biloba extract, coumarin dereivatives that are used in chronic venous insufficiency. Flavonoids are natural substances found in plants, including fruits, vegetables, flowers, and others. They are important to the circulatory system and critical to blood vessels and the blood flow. Additionally, they have antioxidant, antiinflammatory properties.

Anticancer Activity of Natural Compounds from Plant and Marine Environment.

This paper describes the substances of plant and marine origin that have anticancer properties. The chemical structure of the molecules of these substances, their properties, mechanisms of action, their structure⁻activity relationships, along with their anticancer properties and their potential as chemotherapeutic drugs are discussed in this paper. This paper presents natural substances from plants, animals, and their aquatic environments. These substances include the vinca alkaloids, mistletoe plant extracts, podophyllotoxin derivatives, taxanes, camptothecin, combretastatin, and others including geniposide, colchicine, artesunate, homoharringtonine, salvicine, ellipticine, roscovitine, maytanasin, tapsigargin, and bruceantin. Compounds (psammaplin, didemnin, dolastin, ecteinascidin, and halichondrin) isolated from the marine plants and animals such as microalgae, cyanobacteria, heterotrophic bacteria, invertebrates (e.g., sponges, tunicates, and soft corals) as well as certain other substances that have been tested on cells and experimental animals and used in human chemotherapy.

[Fullerenols in therapy and diagnosis of cancer]. / Fulerenole w terapii i diagnostyce chorób nowotworowych.

Malignant tumors are one of the main causes of death in Poland. One of the objectives of contemporary biomedical research is to maximize the effects of therapeutic strategies. The actions undertaken to improve therapeutic agents are aimed at reducing the side effects of cancer treatments. Another direction of investigations is the search for protective substances that reduce the toxicity of the drug to normal cells. Carbon-based nanomaterials (fullerenes and their derivatives, graphene, carbon nanotubes, nanodiamonds) are a broad class of nanoparticles that have potential biomedical applications in both therapy and diagnostics. The aim of this paper is to review biological properties of fullerenols in the context of their use in various strategies of cancer treatments. The authors also discuss the possibility of simultaneous use of nanoparticles in therapy and diagnosis, that is, in theranostics. Current knowledge indicates that fullerenes and their hydrophilic derivatives, especially fullerenols, show low or no toxicity. They may contribute to the inhibition of tumor growth and protection of normal cells through their antioxidant properties, as well as to the regulation of expression of genes involved in apoptosis and angiogenesis, and stimulation of the immune response. Gadoliniumcontaining endohedral fullerenes are less toxic as a contrast agents in magnetic resonance imaging, and they may also inhibit tumor growth, which is a promising result for theranostics. Med Pr 2016;67(6):817-831.