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Selective inhibitors of nuclear export show that CRM1/XPO1 is a target in chronic lymphocytic leukemia KU Leuven
The nuclear export protein XPO1 is overexpressed in cancer, leading to the cytoplasmic mislocalization of multiple tumor suppressor proteins. Existing XPO1-targeting agents lack selectivity and have been associated with significant toxicity. Small molecule selective inhibitors of nuclear export (SINEs) were designed that specifically inhibit XPO1. Genetic experiments and X-ray structures demonstrate that SINE covalently bind to a cysteine ...
Increased frequency of micronuclei in mononucleated lymphocytes and cytome analysis in healthy newborns as an early warning biomarkers of possible future health risks. Vrije Universiteit Brussel
Impact of intrauterine development on health risks during adolescence and adulthood still needs to be investigated. The aim of study was to compare genome damage in newborns and mothers using the cytokinesis blocked micronucleus assay, nuclear division index (NDI), and centromere fluorescence in situ hybridization. The study was performed on 92 mothers and their newborns. Results showed that micronucleus frequency in binuclear T-lymphocytes ...
Changes in immunological profile as a function of urbanization and lifestyle Instituut voor Tropische Geneeskunde
Differences in lifestyle and break with natural environment appear to be associated with changes in the immune system resulting in various adverse health effects. Although genetics can have a major impact on the immune system and disease susceptibility, the contribution of environmental factors is thought to be substantial. Here, we investigated the immunological profile of healthy volunteers living in a rural and an urban area of a ...
Buccal micronucleus cytome assay Vrije Universiteit Brussel
The Buccal Micronucleus Cytome (BMCyt) assay is a minimally invasive method for studying DNA damage, chromosomal instability, cell death and the regenerative potential of human buccal mucosal tissue. This method is increasingly used in molecular epidemiological studies for investigating the impact of nutrition, lifestyle factors, genotoxin exposure and genotype on DNA damage, chromosome malsegregation and cell death. The biomarkers measured in ...
Vitamin D-modulated dendritic cells delay lethal graft-versus-host disease through induction of regulatory T cells KU Leuven
Graft-versus-host disease (GVHD) is the most lethal complication after allogeneic bone marrow transplantation (allo-BMT). Current approaches to prevent GVHD rely on donor lymphocyte/T cell depletion or general immunosuppression, leading to opportunistic infections and cancer relapse. Tolerogenic dendritic cells can induce regulatory T cells (Tregs) with the ability to suppress inflammation and prevent transplant rejection, making them an ...
MALT1 cleaves the E3 ubiquitin ligase HOIL-1 in activated T cells, generating a dominant negative inhibitor of LUBAC-induced NF-U+03BAB signaling Universiteit Gent
Human paracaspase 1 (PCASP1), better known as mucosa associated lymphoid tissue lymphoma translocation 1 (MALT1), plays a key role in immunity and inflammation by regulating gene expression in lymphocytes and other immune cell types. Deregulated MALT1 activity has been implicated in autoimmunity, immunodeficiency and certain types of lymphoma. As a scaffold MALT1 assembles downstream signaling proteins for nuclear factor-B (NF-B) activation, ...
Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients KU Leuven
Transient receptor potential melastatin 3 (TRPM3) cation channels are ubiquitously expressed by multiple cells and have an important regulatory role in calcium-dependent cell signalling to help maintain cellular homeostasis. TRPM3 protein expression has yet to be determined on Natural Killer (NK) cells and B lymphocytes. Multiple single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, ...
Role of the HIV-1 gp120 envelope glycans in the interaction and antiviral activity of carbohydrate-binding agents KU Leuven
Since its identification in the early eighties, HIV became a global health problem of unprecedented dimensions. Although at least 25 anti-HIV-1 compounds against 5 different targets (the virus-encoded reverse transcriptase, protease, envelope gp41 and integrase, and the cellular co-receptor CCR5) are currently available for treatment, toxic side-effects and drug resistance development still compromise a long-term efficient treatment, and viral ...
CXCR4 and CCR5 ligands cooperate in monocyte and lymphocyte migration and in inhibition of dual-tropic (R5/X4) HIV-1 infection KU Leuven
One of the most important functions of chemokines and their receptors is the regulation of directional migration of leukocytes within tissues. In specific tissue compartments, cells are exposed to multiple chemokines presented in complex dimensional and temporal patterns. Therefore, a leukocyte requires the mechanisms to integrate the various directional signals it receives from different chemoattractants. In this study, we report that CCL3, ...