“The acute effect of budesonide/formoterol in COPD : a multi-slice computed tomography and lung function study”. De Backer LA, Vos W, de Backer J, Van Holsbeke C, Vinchurkar S, de Backer W, European Respiratory Journal 40, 298 (2012). http://doi.org/10.1183/09031936.00072511
Abstract: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of chronic obstructive pulmonary disease (COPD) does not always match with other clinical disease descriptors such as exacerbation frequency and quality of life, indicating that forced expiratory volume in 1 s (FEV1) is not a perfect descriptor of the disease. The aim of this study was to find out whether changes in airway geometry after inhalation of the most commonly used inhalation therapy in severe COPD can more adequately be described with an image-based approach than with spirometry. 10 COPD GOLD stage III patients were assessed in a double-blind crossover study. Airway volumes were analysed using segmentation of multi-slice computed tomography (MSCT) images; airway resistance was determined using computational fluid dynamics (CFD). Distal airway volume significantly increased (p=0.011) in patients 4 h after receiving a budesonide/formoterol combination from 9.6+/-4.67 cm(3) to 10.14+/-4.81 cm(3). Also CFD-determined airway resistance significantly decreased (p=0.047) from 0.051+/-0.021 kPa.s.L-1 to 0.043+/- 0.019 kPa.s.L-1. None of the lung function parameters showed a significant change. Only functional residual capacity (FRC) showed a trend to decline (p=0.056). Only the image-based parameters were able to predict the visit at which the combination product was administered. This study showed that imaging is a sensitive, complementary tool to describe changes in airway structure.
Keywords: A1 Journal article; Biophysics and Biomedical Physics; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 10.569
Times cited: 37
DOI: 10.1183/09031936.00072511
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“Detailed nitrogen and phosphorus flow analysis, nutrient use efficiency and circularity in the agri-food system of a livestock-intensive region”. Vingerhoets R, Spiller M, De Backer J, Adriaens A, Vlaeminck SE, Meers E, Journal of cleaner production 410, 137278 (2023). http://doi.org/10.1016/J.JCLEPRO.2023.137278
Abstract: The agri-food value chain is a major cause of nitrogen (N) and phosphorus (P) emissions and associated environmental and health impacts. The EU's farm-to-fork strategy (F2F) demands an agri-food value chain approach to reduce nutrient emissions by 50% and fertilizer use by 20%. Substance flow analysis (SFA) is a method that can be applied to study complex systems such as the agri-food chain. A review of 60 SFA studies shows that they often lack detail by not sufficiently distinguishing between nodes, products and types of emissions. The present study aims to assess the added value of detail in SFAs and to illustrate that valuable indicators can be derived from detailed assessments. This aim will be attained by presenting a highly-detailed SFA for the livestock-intensive region of Flanders, Belgium. The SFA distinguishes 40 nodes and 1827 flows that are classified into eight different categories (e.g. by-products, point source emissions) following life cycle methods. Eight novel indicators were calculated, including indicators that assess the N and P recovery potential. Flanders has a low overall nutrient use efficiency (11% N, 18% P). About 55% of the N and 56% of the P embedded in recoverable streams are reused providing 35% and 37% of the total N and P input. Optimized nutrient recycling could replace 45% of N and 48% of P of the external nutrient input, exceeding the target set by the F2F strategy. Detailed accounting for N and P flows and nodes leads to the identification of more recoverable streams and larger N and P flows. More detailed flow accounting is a prerequisite for the quantification of technological intervention options. Future research should focus on including concentration and quality as a parameter in SFAs.
Keywords: A1 Journal article; Engineering sciences. Technology; Sustainable Energy, Air and Water Technology (DuEL)
Impact Factor: 11.1
DOI: 10.1016/J.JCLEPRO.2023.137278
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“Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response”. De Backer J, Lin A, Berghe WV, Bogaerts A, Hoogewijs D, Redox Biology 55, 102399 (2022). http://doi.org/10.1016/j.redox.2022.102399
Abstract: Melanoma arises from pigment-producing cells called melanocytes located in the basal layers of the epidermis of the skin. Cytoglobin (CYGB) is a ubiquitously expressed hexacoordinated globin that is highly enriched in melanocytes and frequently downregulated during melanomagenesis. Previously, we showed that non-thermal plasma (NTP)-produced reactive oxygen and nitrogen species (RONS) lead to the formation of an intra molecular disulfide bridge that would allow CYGB to function as a redox-sensitive protein. Here, we investigate the cytotoxic effect of indirect NTP treatment in two melanoma cell lines with divergent endogenous CYGB expression levels, and we explore the role of CYGB in determining treatment outcome. Our findings are consistent with previous studies supporting that NTP cytotoxicity is mediated through the production of RONS and leads to apoptotic cell death in melanoma cells. Furthermore, we show that NTP-treated solutions elicit an antioxidant response through the activation of nuclear factor erythroid 2–related factor 2 (NRF2). The knock down and overexpression of CYGB respectively sensitizes and protects melanoma cells from RONS-induced apoptotic cell death. The presence of CYGB enhances heme-oxygenase 1 (HO-1) and NRF2 protein expression levels, whereas the absence impairs their expression. Moreover, analysis of the CYGB-dependent transcriptome demonstrates the tumor suppressor long non-coding RNA maternally expressed 3 (MEG3) as a hitherto unde scribed link between CYGB and NRF2. Thus, the presence of CYGB, at least in melanoma cells, seems to play a central role in determining the therapeutic outcome of RONS-inducing anticancer therapies, like NTP-treated solutions, possessing both tumor-suppressive and oncogenic features. Hence, CYGB expression could be of in terest either as a biomarker or as a candidate for future targeted therapies in melanoma.
Keywords: A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Proteinscience, proteomics and epigenetic signaling (PPES)
Impact Factor: 11.4
DOI: 10.1016/j.redox.2022.102399
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Verhulst SL, de Backer J, Van Gaal L, de Backer W, Desager K (2008) Adenotonsillectomy as first-line treatment for sleep-disordered breathing in obese children. New York, 1399
Keywords: L1 Letter to the editor; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 13.204
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“Acquired non-thermal plasma resistance mediates a shift towards aerobic glycolysis and ferroptotic cell death in melanoma”. Lin A, Sahun M, Biscop E, Verswyvel H, De Waele J, De Backer J, Theys C, Cuypers B, Laukens K, Berghe WV, Smits E, Bogaerts A, Drug resistance updates 67, 100914 (2023). http://doi.org/10.1016/j.drup.2022.100914
Abstract: To gain insights into the underlying mechanisms of NTP therapy sensitivity and resistance, using the firstever
NTP-resistant cell line derived from sensitive melanoma cells (A375).
Methods: Melanoma cells were exposed to NTP and re-cultured for 12 consecutive weeks before evaluation
against the parental control cells. Whole transcriptome sequencing analysis was performed to identify differentially
expressed genes and enriched molecular pathways. Glucose uptake, extracellular lactate, media acidification,
and mitochondrial respiration was analyzed to determine metabolic changes. Cell death inhibitors were
used to assess the NTP-induced cell death mechanisms, and apoptosis and ferroptosis was further validated via
Annexin V, Caspase 3/7, and lipid peroxidation analysis.
Results: Cells continuously exposed to NTP became 10 times more resistant to NTP compared to the parental cell
line of the same passage, based on their half-maximal inhibitory concentration (IC50). Sequencing and metabolic
analysis indicated that NTP-resistant cells had a preference towards aerobic glycolysis, while cell death analysis
revealed that NTP-resistant cells exhibited less apoptosis but were more vulnerable to lipid peroxidation and
ferroptosis.
Conclusions: A preference towards aerobic glycolysis and ferroptotic cell death are key physiological changes in
NTP-resistance cells, which opens new avenues for further, in-depth research into other cancer types.
Keywords: A1 Journal article; Pharmacology. Therapy; ADReM Data Lab (ADReM); Center for Oncological Research (CORE); Proteinscience, proteomics and epigenetic signaling (PPES); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Impact Factor: 24.3
DOI: 10.1016/j.drup.2022.100914
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