Search results for "INHIBITOR"

Parvovirus B19V Nonstructural Protein NS1 Induces Double-Stranded Deoxyribonucleic Acid Autoantibodies and End-Organ Damage in Nonautoimmune Mice

2018

Abstract Background Viral infection is implicated in development of autoimmunity. Parvovirus B19 (B19V) nonstructural protein, NS1, a helicase, covalently modifies self double-stranded deoxyribonucleic acid (dsDNA) and induces apoptosis. This study tested whether resulting apoptotic bodies (ApoBods) containing virally modified dsDNA could induce autoimmunity in an animal model. Methods BALB/c mice were inoculated with (1) pristane-induced, (2) B19V NS1-induced, or (3) staurosporine-induced ApoBods. Serum was tested for dsDNA autoantibodies by Crithidia luciliae staining and enzyme-linked immunosorbent assay. Brain, heart, liver, and kidney pathology was examined. Deposition of self-antigens…

Nutritional Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflammation via Activation of Myeloid Cells.

2016

Background & Aims Wheat amylase-trypsin inhibitors (ATIs) are nutritional activators of innate immunity, via activation of the toll-like receptor 4 (TLR4) on myeloid cells. We aimed to characterize the biologic activity of ATIs in various foods and their effect on intestinal inflammation. Methods We selected 38 different gluten-containing and gluten-free products, either unprocessed (such as wheat, rye, barley, quinoa, amaranth, soya, lentils, and rice) or processed (such as pizza, pasta, bread, and biscuits). ATIs were extracted and their biological activities determined in TLR4-responsive mouse and human cell lines. Effects of oral ATIs on intestinal inflammation were determined in health…

The β3 -adrenoceptor agonist mirabegron increases human atrial force through β1 -adrenoceptors: an indirect mechanism?

2017

Background and Purpose Mirabegron has been classified as a β3-adrenoceptor agonist approved for overactive bladder syndrome. We investigated possible cardiac effects of mirabegron in the absence or presence of β-adrenoceptor subtype antagonists. In view of its phenylethanolamine structure, we investigated whether mirabegron has indirect sympathomimetic activity by using neuronal uptake blockers. Experimental Approach Right atrial trabeculae, from non-failing hearts, were paced and contractile force measured at 37°C. Single concentrations of mirabegron were added in the absence or presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), β3 (L-748,337), β1 (CGP 20712A),…

In vitro study of antimicrobial activity on Klebsiella Pneumoniae biofilms in endotracheal tubes

2019

Effective treatment approaches for biofilms in endotracheal tubes (ETTs) are lacking. In this study, we evaluated the in vitro effects of five antimicrobials against biofilms formed by Klebsiella pneumoniae in ETTs. K. pneumoniae was added to minimal mucin medium prior to inoculation in microtiter plates containing ETT fragments. Biofilm susceptibility was assessed by crystal violet staining. At 24 h, the antimicrobials significantly reduced biofilm formation. At 48 h, all of the antimicrobial agents exhibited significant reductions in biofilm formation, even at concentrations above the minimum inhibitory concentration (MIC). Tigecycline and fosfomycin showed the greatest inhibition capacit…

Curcumin at Low Doses Potentiates and at High Doses Inhibits ABT-737-Induced Platelet Apoptosis

2021

Curcumin is a natural bioactive component derived from the turmeric plant Curcuma longa, which exhibits a range of beneficial activities on human cells. Previously, an inhibitory effect of curcumin on platelets was demonstrated. However, it is unknown whether this inhibitory effect is due to platelet apoptosis or procoagulant platelet formation. In this study, curcumin did not activate caspase 3-dependent apoptosis of human platelets, but rather induced the formation of procoagulant platelets. Interestingly, curcumin at low concentration (5 µM) potentiated, and at high concentration (50 µM) inhibited ABT-737-induced platelet apoptosis, which was accompanied by inhibition of ABT-737-mediated…

Chemoresistance and chemosensitization in cholangiocarcinoma

2017

One of the main difficulties in the management of patients with advanced cholangiocarcinoma (CCA) is their poor response to available chemotherapy. This is the result of powerful mechanisms of chemoresistance (MOC) of quite diverse nature that usually act synergistically. The problem is often worsened by altered MOC gene expression in response to pharmacological treatment. Since CCA includes a heterogeneous group of cancers their genetic signature coding for MOC genes is also diverse; however, several shared traits have been defined. Some of these characteristics are shared with other types of liver cancer, namely hepatocellular carcinoma and hepatoblastoma. An important goal in modern onco…

2018

Haplotypes of the Gabra2 gene encoding the α2-subunit of the GABAA receptor (GABAAR) are associated with drug abuse, suggesting that α2-GABAARs may play an important role in the circuitry underlying drug misuse. The genetic association of Gabra2 haplotypes with cocaine addiction appears to be evident primarily in individuals who had experienced childhood trauma. Given this association of childhood trauma, cocaine abuse and the Gabra2 haplotypes, we have explored in a mouse model of early life adversity (ELA) whether such events influence the behavioral effects of cocaine and if, as suggested by the human studies, α2-GABAARs in the nucleus accumbens (NAc) are involved in these perturbed beha…

High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice

2015

BACKGROUND AND PURPOSE The link between type 2 diabetes mellitus (T2DM) and depression is bidirectional. However, the possibility that metabolic disorders may elicit anxiogenic-like/depressive-like symptoms or alter the efficacy of antidepressant drugs remains poorly documented. This study explored the influence of T2DM on emotionality and proposed a therapeutic strategy that might be used in depressed diabetic patients. EXPERIMENTAL APPROACH Mice were fed a high-fat diet (HFD) and subjected to a full comprehensive metabolic and behavioural analysis to establish correlations between metabolic and psychiatric disorders. In vivo intra-hippocampal microdialysis was also applied to propose a me…

Cytotoxic activity of medicinal plants of the Kakamega County (Kenya) against drug-sensitive and multidrug-resistant cancer cells

2018

Abstract Ethnopharmacological relevance The geographical location of Kakamega County proximal to the Kakamega Rain Forest in Kenya and its rich flora represents an interesting resource of traditional medicinal plants. The medicinal plants in the present study are traditionally used to treat cancer in Kakamega County as recorded in published literature. Aim of the study Due to multidrug resistance (MDR) and severe side effects of currently used drugs in clinical oncology, new candidate compounds are urgently required to improve treatment outcome. The present study explored the in vitro cytotoxic potential of 34 organic and 19 aqueous extracts of Kakamega medicinal plants towards sensitive an…

Bistacrine derivatives as new potent antimalarials

2016

Linking two tacrine molecules results in a tremendous increase of activity against Plasmodia in comparison to the monomer. This finding prompted the synthesis of a library of monomeric and dimeric tacrine derivatives in order to derive structure-activity relationships. The most active compounds towards chloroquine sensitive Plasmodium strain 3D7 and chloroquine resistant strain Dd2 show IC50 values in the nanomolar range of concentration, low cytotoxicity and target the cysteine protease falcipain-2, which is essential for parasite growth.