Publicaties

In mechanically ventilated preterm infants, the combination of immaturity, volutrauma, oxidative stress, and inflammatory processes can lead to chronic lung injury. Mitochondrial DNA (mtDNA) is more susceptible to oxidative damage than nuclear DNA. We aimed to investigate the level of mtDNA damage (deletions, mutations and changes in copy number) in bronchoalveolar lavage (BAL) cells from 10 preterm infants (27-30 weeks). A first BAL (BAL1) was ...

Newborns have to cope with hypoxia during delivery and a sudden increase in oxygen at birth. Oxygen will partly be released as reactive oxygen species having the potential to cause damage to DNA and proteins. In utero, increase of most (non)-enzymatic antioxidants occurs during last weeks of gestation, making preterm neonates probably more sensitive to oxidative stress. Moreover, it has been hypothesized that oxidative stress might be the common ...

Genetic information is constantly being attacked by intrinsic and extrinsic damaging agents, such as reactive oxygen species, atmospheric radiation, environmental chemicals, and chemotherapeutics. If DNA modifications persist, they can adversely affect the polymerization of DNA or RNA, leading to replication fork collapse or transcription arrest, or can serve as mutagenic templates during nucleic acid synthesis reactions. To combat the ...

Spinal cord injury is a devastating condition that affects about 21 million people worldwide, leading to severe disabilities. These injuries impact motor functions, sensory perception, autonomic processes, psychological well-being, and social interactions, significantly burdening patients, their families, and healthcare systems. Unfortunately, despite extensive research, there is no cure for spinal cord injury yet. This PhD Thesis focuses on how ...

Multiple myeloma (MM) is still an incurable plasma cell malignancy, thus highlighting the need for alternative treatment options. Currently, strategies for therapy are being developed targeting epigenetic modification using epigenetic modulating agents like histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi). 5-aza-2'-deoxycitidine or decitabine (DAC) is a DNMTi and is FDA approved for treatment of myelodysplastic ...

Oxidative stress occurs at various phases of spinal cord injury (SCI), promoting detrimental processes such as free radical injury of proteins, nucleic acids, lipids, cytoskeleton, and organelles. Oxidative DNA damage is likely a major contributor to the pathogenesis of SCI, as a damaged genome cannot be simply turned over to avert detrimental molecular and cellular outcomes, most notably cell death. Surprisingly, the evidence to support this ...

BACKGROUND: A considerable part of the worldwide production of surgical instruments takes place in Sialkot, Pakistan. Many children work in hazardous conditions in this industry. OBJECTIVE: We investigated exposure to metals and possible health effects among children working in surgical instruments manufacturing units compared with schoolchildren from the same city. METHODS: In a cross-sectional study we studied a convenience sample of 104 male ...

Cockayne syndrome (CS) is an autosomal recessive genetic disorder characterized by photosensitivity, developmental defects, neurological abnormalities, and premature aging. Mutations in CSA (ERCC8), CSB (ERCC6), XPB, XPD, XPG, XPF (ERCC4) and ERCC1 can give rise to clinical phenotypes resembling classic CS. Using a yeast two-hybrid (Y2H) screening approach, we identified LEO1 (Phe381Ser568 region) as an interacting protein partner of full-length ...

DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) are under investigation for the treatment of cancer, including the plasma cell malignancy multiple myeloma (MM). Evidence exists that DNA damage and repair contribute to the cytotoxicity mediated by the DNMTi decitabine. Here, we investigated the DNA damage response (DDR) induced by decitabine in MM using 4 human MM cell lines and the murine 5T33MM model. In ...