Pitavastatin Is a Highly Potent Inhibitor of T-Cell Proliferation.

Repositioning of approved drugs is an alternative time- and cost-saving strategy to classical drug development. Statins are 3-hydroxy-3-methylglutaryl-CoA (HMG CoA) reductase inhibitors that are usually used as cholesterol-lowering medication, and they also exhibit anti-inflammatory effects. In the present study, we observed that the addition of Pitavastatin at nanomolar concentrations inhibits the proliferation of CD3/CD28 antibody-stimulated human T cells of healthy donors in a dose-dependent fashion.

Impact of Different JAK Inhibitors and Methotrexate on Lymphocyte Proliferation and DNA Damage.

Janus kinase inhibitors (JAKis) represent a new strategy in rheumatoid arthritis (RA) therapy. Still, data directly comparing different JAKis are rare. In the present in vitro study, we investigated the immunomodulatory potential of four JAKis (tofacitinib, baricitinib, upadacitinib, and filgotinib) currently approved for RA treatment by the European Medicines Agency.

Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells.

T cell activation mediates immunity to pathogens. On the flipside, T cells are also involved in pathological immune responses during chronic autoimmune diseases. We recently reported that zinc aspartate, a registered drug with high bioavailability, dose-dependently inhibits T cell activation and Th1/Th2/Th17 cytokine production of stimulated human and mouse T cells.

Screening of FDA-Approved Drug Library Identifies Adefovir Dipivoxil as Highly Potent Inhibitor of T Cell Proliferation.

Repositioning of approved drugs for identifying new therapeutic purposes is an alternative, time and cost saving strategy to classical drug development. Here, we screened a library of 786 FDA-approved drugs to find compounds, which can potentially be repurposed for treatment of T cell-mediated autoimmune diseases. Investigating the effect of these diverse substances on mitogen-stimulated proliferation of both, freshly stimulated and pre-activated (48 h) peripheral blood mononuclear cells (PBMCs), we discovered Adefovir Dipivoxil (ADV) as very potent compound, which inhibits T cell proliferation in a nanomolar range.

The potential toxic impact of different gadolinium-based contrast agents combined with 7-T MRI on isolated human lymphocytes.

Background: To investigate a potentially amplifying genotoxic or cytotoxic effect of different gadolinium-based contrast agents (GBCAs) in combination with ultra-high-field 7-T magnetic resonance imaging (MRI) exposure in separated human peripheral blood lymphocytes.

Methods: This in vitro study was approved by the local ethics committee and written informed consent was obtained from all participants. Isolated lymphocytes from twelve healthy donors were incubated with gadobutrol, gadoterate meglumine, gadodiamide, gadopentetate dimeglumine, or gadoxetate either alone or combined with 7-T MRI (1 h).

Impact of in Vivo High-Field-Strength and Ultra-High-Field-Strength MR Imaging on DNA Double-Strand-Break Formation in Human Lymphocytes.

Purpose To determine the impact of different magnetic field strengths (1, 1.5, 3, and 7 T) and the effect of contrast agent on DNA double-strand-break (DSB) formation in patients undergoing magnetic resonance (MR) imaging. Materials and Methods This in vivo study was approved by the local ethics committee, and written informed consent was obtained from each patient.

DNA double-strand breaks and micronuclei in human blood lymphocytes after repeated whole body exposures to 7T Magnetic Resonance Imaging.

Purpose: To examine the extent of genetic damage, assessed from deoxyribonucleic acid (DNA) double-strand breaks (DSBs) and micronuclei (MN) in peripheral blood mononuclear cells obtained from individuals repeatedly exposed to 7T Magnetic Resonance Imaging (MRI).

Materials And Methods: The study protocol was approved by the local ethics committee. Informed consent was obtained from 22 healthy, non-smoking, non-alcoholic male individuals, who had never undergone radio-/chemo-therapy, scintigraphy, and had not undergone X-ray examination one year prior blood withdrawal.

Analysis of DNA Double-Strand Breaks and Cytotoxicity after 7 Tesla Magnetic Resonance Imaging of Isolated Human Lymphocytes.

The global use of magnetic resonance imaging (MRI) is constantly growing and the field strengths increasing. Yet, only little data about harmful biological effects caused by MRI exposure are available and published research analyzing the impact of MRI on DNA integrity reported controversial results. This in vitro study aimed to investigate the genotoxic and cytotoxic potential of 7 T ultra-high-field MRI on isolated human peripheral blood mononuclear cells.

Assessment of modulated cytostatic drug resistance by automated γH2AX analysis.

The efficacy of many chemotherapeutic agents relies on the preferential destruction of rapidly dividing cancer cells by inducing various kinds of DNA damage. The most deleterious type of DNA lesions are DNA double-strand breaks (DSB), which can be detected by immunofluorescence staining of phosphorylated histone protein H2AX (γH2AX). Furthermore, γH2AX has been suggested as clinical pharmacodynamic biomarker in chemotherapeutic cancer treatment.