Advanced Glycation End-Products in Blood Serum-Novel Ischemic Stroke Risk Factors? Implication for Diabetic Patients.

New predictors of ischemic incidents are constantly sought since they raise the awareness of patients and their doctors of stroke occurrence. The goal was to verify whether Advanced Glycation End Products (AGEs), in particular AGE10, could be one of them. The AGE10 measurement was conducted using a non-commercial ELISA assay in the blood serum of neurological patients without cerebrovascular event (n = 24), those with transient brain attack (TIA) (n = 17), and severe ischemic stroke (n = 35).

Heterogeneity of Extracellular Vesicles and Particles: Molecular Voxels in the Blood Borne "Hologram" of Organ Function, Disfunction and Cancer.

Extracellular vesicles (EVs) and particles (EPs) serve as unique carriers of complex molecular information with increasingly recognized roles in health and disease. Individual EVs/EPs collectively contribute to the molecular fingerprint of their producing cell, reflecting its identity, state, function and phenotype. This property is of particular interest in cancer where enormous heterogeneity of cancer cells is compounded by the presence of altered stromal, vascular and immune cell populations, which is further complicated by systemic responses elicited by the disease in individual patients.

The Contrasting Delayed Effects of Transient Exposure of Colorectal Cancer Cells to Decitabine or Azacitidine.

(1) Background: Decitabine and azacitidine are cytosine analogues representing the class of drugs interfering with DNA methylation. Due to their molecular homology and similar clinical application, both drugs are often regarded as interchangeable. Despite their unique mechanism of action the studies designed for observation and comparison of the prolonged activity of these drugs are rare.

A newly established canine NK-type cell line and its cytotoxic properties.

We established a canine natural killer (NK)-type cell line called CNK-89 derived from a dog with NK cell neoplasia. Immunophenotyping analysis showed positive staining for CD5, CD8, CD45, CD56, CD79a and NKp46, while negative for CD3, CD4, CD14, CD20, CD21, CD34, Thy1, IgG, IgM and MHCII. Polymerase chain reaction analysis revealed the presence of CD56, NKG2D, NKp30, NKp44, NKp46 and perforin, but the absence of CD16, Ly49 and granzyme B mRNA.

Gallato Zirconium (IV) Phtalocyanine Complex Conjugated with SiO2 Nanocarrier as a Photoactive Drug for Photodynamic Therapy of Atheromatic Plaque.

A new conjugate of gallato zirconium (IV) phthalocyanine complexes (PcZrGallate) has been obtained from alkilamino-modified SiO nanocarriers (SiO-(CH)-NHNPs), which may potentially be used in photodynamic therapy of atherosclerosis. Its structure and morphology have been investigated. The photochemical properties of the composite material has been characterized.

Hypoxia increases the apoptotic response to betulinic acid and betulin in human non-small cell lung cancer cells.

Betulinic acid and betulin show promising activity against cancers cells, but the mechanism of their action is still unclear. In this study, non-small cell lung cancer (NSCLC) cell lines: A549, H358 and NCI-H1703 were treated with betulinic acid and betulin under normoxic and hypoxic conditions as hypoxia is critically involved in the response of solid tumors to chemotherapy. The treatment inhibits viability and proliferation of NSCLC cells.

Anti-Inflammatory Activity of a Cyclic Tetrapeptide in Mouse and Human Experimental Models.

A cyclic tetrapeptide Pro-Pro-Pheβho-Phe (4B8M) was tested for immunosuppressive activity and potential therapeutic utility in several in vitro and in vivo mouse and human models. The tetrapeptide was less toxic for mouse splenocytes in comparison to cyclosporine A (CsA) and a parent cyclolinopeptide (CLA). The tetrapeptide demonstrated potent anti-inflammatory properties in antigen-specific skin inflammatory reactions to oxazolone and toluene diisocyanate as well to nonspecific irritants such as salicylic acid.

Therapeutic effects of an azaphenothiazine derivative in mouse experimental colitis.

Phenothiazines represent a class of compounds of potential therapeutic utility. In this report we evaluated therapeutic value of an azaphenothiazine derivative, 6-acetylaminobutyl-9-chloroquino[3,2-b]benzo[1,4]thiazine (QBT), given intragastrically, in the model of dextran sodium sulfate-induced colitis in C57BL/6 mice using 5-aminosalicylic acid (5-ASA) as a reference drug. Colitis symptoms such as body weight loss, diarrhea and hematochezia (blood in stool) were observed and registered and disease activity index (DAI) was calculated.

Ceramides and sphingosine-1-phosphate as potential markers in diagnosis of ischaemic stroke.

Background: Brain imaging in stroke diagnostics is a powerful tool, but one that can fail in more challenging cases, and one that is not particularly useful in identifying transient ischaemic attacks (TIAs). Thus, new reliable blood biomarkers of cerebral ischaemia are constantly sought.

Objective: We studied the potential usefulness of sphingolipids (SFs) as biomarkers of acute ischaemic stroke and TIA.

Prolongation of skin graft survival in mice by an azaphenothiazine derivative.

Azaphenothiazines are predominantly immunosuppressive compounds. We evaluated the efficacy of an azaphenothiazine derivative, 6-chloroethylureidoethyldiquino[3,2-b;2',3'-e][1,4]thiazine (DQT) in prolongation of survival of skin allografts between BALB/c and C57Bl/6 mice. The mice were treated intraperitoneally (i.

Toxicity Mechanism of Low Doses of NaGdF₄:Yb,Er Upconverting Nanoparticles in Activated Macrophage Cell Lines.

Gadolinium-doped nanoparticles (NPs) are regarded as promising luminescent probes. In this report, we studied details of toxicity mechanism of low doses of NaGdF₄-based fluorescent nanoparticles in activated RAW264.7, J774A.

Functionalized CD133 antibody coated stent surface simultaneously promotes EPCs adhesion and inhibits smooth muscle cell proliferation-A novel approach to prevent in-stent restenosis.

We report a multistep strategy of biochemical surface modifications that resulted in the synthesis of new, effective and biocompatible intravascular implants coating with immobilized anti-CD133 antibodies, that proved to be the most effective in endothelial progenitor cells capture and reduced smooth muscle cells growth. Biomolecules were immobilized on differently functionalized surfaces. The distribution, nanostructural characteristics and intramolecular interactions of anti-CD133 molecules as well as their ability to bind EPCs was evaluated.

Sorafenib in Combination with Betulinic Acid Synergistically Induces Cell Cycle Arrest and Inhibits Clonogenic Activity in Pancreatic Ductal Adenocarcinoma Cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers in the world due to late diagnosis and poor response to available treatments. It is important to identify treatment strategies that will increase the efficacy and reduce the toxicity of the currently used therapeutics. In this study, the PDAC cell lines AsPC-1, BxPC-3, and Capan-1 were treated with sorafenib and betulinic acid alone and in combination.

An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells.

An azaphenothiazine derivative, 6-chloroethylureidoethyldiquino[3,2-b;2',3'-e][1,4]thiazine (DQT), has recently been shown to exhibit immunosuppressive activities in mouse models. It also inhibited the expression of CXCL10 at the protein level, at non-toxic concentrations, in the culture of KERTr cells treated with double-stranded RNA, poly(I:C). In this report, we demonstrated that DQT inhibits the transcription of the CXCL10 gene.

Topically applied azaphenothiazines inhibit experimental psoriasis in mice.

The therapeutic efficacy of topically applied azaphenothiazine derivatives: 9-chloro-6-acetylaminobutylquinobenzo[3,2-b][1,4]thiazine (compound 4) and 6-chloroethylureidoethyldiquino[3,2-b;2';3'-e][1,4]thiazine (compound 5) in the amelioration of inflammatory symptoms of imiquimod-induced psoriasis in mice was investigated. Clobederm®, containing clobetasol propioniate, served as a reference drug. The application of the compounds led to thinning of the epidermis and reduction of the cell layers.

Synergistic activity of sorafenib and betulinic acid against clonogenic activity of non-small cell lung cancer cells.

The highly selective multi-targeted agent sorafenib is an inhibitor of a number of intracellular signaling kinases with anti-proliferative, anti-angiogenic and pro-apoptotic effects in various types of tumors, including human non-small cell lung cancer (NSCLC). Betulin displays a broad spectrum of biological and pharmacological properties, including anticancer and chemopreventive activity. Combination of drugs with different targets is a logical approach to overcome multilevel cross-stimulation among key signaling pathways in NSCLC progression.

Opioid Receptors in Psoriatic Skin: Relationship with Itch.

Psoriasis is an inflammatory immunogenetic skin disease, often accompanied by itch. Opioid receptors are known regulators of itch sensation in the central nervous system. In the brain, μ-opioid receptors may potentiate itch, while activation of κ-opioid receptors may reduce or even alleviate itch; however, the role of opioid receptors in itch perception in the skin is poorly understood.

Long-lasting reduction in clonogenic potential of colorectal cancer cells by sequential treatments with 5-azanucleosides and topoisomerase inhibitors.

Background: The currently approved therapies fail in a substantial number of colorectal cancer (CRC) patients due to the molecular heterogeneity of CRC, hence new efficient drug combinations are urgently needed. Emerging data indicate that 5-azanucleosides are able to sensitize cancer cells to the standard chemotherapeutic agents and contribute to overcoming intrinsic or acquired chemoresistance.

Methods: CRC cells with different genetic backgrounds (HCT116, DLD-1, HT-29) were sequentially treated with 5-azanucleosides and topoisomerase inhibitors.

A novel canine B-cell leukaemia cell line. Establishment, characterisation and sensitivity to chemotherapeutics.

We established a new B-cell leukaemia cell line CLB70 from a dog with chronic lymphocytic leukaemia. This cell line is positive for CD20, CD45, CD79a, MHC class II, IgG, IgM; weakly positive for CD21; and negative for CD3, CD4, CD5, CD8, CD14, CD34, CD117. PCR for antigen receptor gene rearrangement (PARR) analysis revealed a biclonal immunoglobulin heavy chain (IgH) gene rearrangement and negative result for TCRγ.

Cytotoxic interactions of bare and coated NaGdF4:Yb(3+):Er(3+) nanoparticles with macrophage and fibroblast cells.

The lanthanide nano-compounds are well suited to serve as fluorescent and magnetic contrast agents and luminescent labels. Although they are considered as promising materials for bio-imaging and bio-sensors in vivo or in vitro, the amount of data is still insufficient for deep understanding the toxicity of these nanomaterials. This knowledge is of great importance in the light of growing use of the biofunctionalized nanoparticles, which raises some questions about safety of these materials.

Non-genomic effects of the NR4A1/Nur77/TR3/NGFIB orphan nuclear receptor.

The orphan nuclear receptor NR4A1/Nur77/TR3/NGFIB acts primarily as a transcription factor to regulate the expression of multiple genes. However, increasing research attention has recently been given to non-genomic activities of NR4A1. The first description of a non-genomic action of NR4A1 referred to the conversion of anti-apoptotic Bcl-2 into a pro-apoptotic protein by direct interaction with NR4A1.

The interplay between epigenetic silencing, oncogenic KRas and HIF-1 regulatory pathways in control of BNIP3 expression in human colorectal cancer cells.

Bcl-2/adenovirus E1B-19kDa-interacting protein 3 (BNIP3) is an important mediator of cell survival and a member of the Bcl-2 family of proteins that regulate programmed cell death and autophagy. We have previously established a link between the expression of oncogenic HRas and up-regulation of BNIP3 and the control of autophagy in cancer cells. However, in view of varied expression of BNIP3 in different tumor types and emerging uncertainties as to the role of epigenetic silencing, oncogenic regulation and the role of BNIP3 in cancer are still poorly understood.

Novel genistein derivatives induce cell death and cell cycle arrest through different mechanisms.

Genistein is a natural compound belonging to isoflavone family of secondary plant metabolites, characterized by pleiotropic biological activity. Here we present the results of a study on new analogs and polysaccharide complexes of genistein as potent antiproliferative and cell death-inducing agents. Most potent were 2 analogs (i.

[Autophagy and BNIP3 protein in tumorogenesis].

Autophagy is a process necessary for maintaining cell homeostasis in physiological conditions, as well as during certain stresses like nutrients or oxygen deprivation. Autophagy also plays an essential role in tumorigenesis. It prevents cell transformation, but on the other hand, autophagy enables existing cancer cells to adapt to harmful conditions and increased glucose demand, supports maintaining of cellular metabolism and accelerates tumor growth.