A5044558046- S100 Proteins and Annexins
- Osteoarthritis Treatment and Mechanisms
- Inflammatory mediators and NSAID effects
- Immune Response and Inflammation
- Aquaculture Nutrition and Growth
- Thyroid Disorders and Treatments
- Physiological and biochemical adaptations
- Stress Responses and Cortisol
- Bone Tissue Engineering Materials
- Rheumatoid Arthritis Research and Therapies
- Dental Implant Techniques and Outcomes
- Mesenchymal stem cell research
- Pharmacological Effects of Natural Compounds
- Glycosylation and Glycoproteins Research
- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Antimicrobial Peptides and Activities
- Bone health and treatments
- Neuropeptides and Animal Physiology
- Monoclonal and Polyclonal Antibodies Research
- Periodontal Regeneration and Treatments
- Protease and Inhibitor Mechanisms
- Inflammasome and immune disorders
- Cutaneous Melanoma Detection and Management
- Signaling Pathways in Disease
Radboud University Nijmegen
2011-2021
Radboud University Medical Center
2013-2021
University Medical Center
2016-2021
Leptin is a key factor in the regulation of food intake and an important pathophysiology obesity. However, more than decade after discovery leptin mouse, information regarding any nonmammalian species still scant. We report identification duplicate genes common carp (Cyprinus carpio). The unique gene structure, conservation both cysteines that form leptin's single disulfide bridge, stable clustering phylogenetic analyses substantiate unambiguous orthology mammalian leptins, despite low amino...
Simlukafusp alfa (FAP-IL2v, RO6874281/RG7461) is an immunocytokine comprising antibody against fibroblast activation protein α (FAP) and IL-2 variant with a retained affinity for IL-2Rβγ > Rβγ abolished binding to Rα. Here, we investigated the immunostimulatory properties of FAP-IL2v its combination programmed cell death 1 (PD-1) checkpoint inhibition, CD40 agonism, T bispecific antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. The were in vitro compared FAP-IL2wt. Tumor...
Alarmins S100A8/A9 regulate pathology in experimental osteoarthritis (OA). Paquinimod is an immunomodulatory compound preventing S100A9 binding to TLR-4. We investigated the effect of paquinimod on OA and human synovium. Two mouse models differing level synovial activation were treated prophylactic with paquinimod. Synovial thickening, osteophyte size cartilage damage measured histologically, using arbitrary score, adapted Pritzker OARSI score or imaging software, respectively. Human synovia...
Cortisol release from fish head kidney during the acute phase of stress response is controlled by adrenocorticotropic hormone (ACTH) pituitary pars distalis (PD). Alpha-melanocyte-stimulating (α-MSH) and β-endorphin, intermedia (PI), have been implicated in cortisol chronic phase. The present study addresses regulation ACTH α-MSH common carp ( Cyprinus carpio) includes characterization their receptors, namely, melanocortin-2 melanocortin-5 receptors (MC2R MC5R). We could not demonstrate...
The effect of experimental hyperthyroidism, realized by T(4) injection, on central mediators the hypothalamo-pituitary-interrenal axis (HPI-axis) in common carp (Cyprinus carpio L.) was studied. Our results show that hyperthyroidism evokes a marked 3.2-fold reduction basal plasma cortisol levels. Corticotropin-releasing hormone-binding protein (CRH-BP) mRNA levels hypothalamus, measured real-time quantitative PCR, were significantly elevated 40%, but CRH, urotensin-I, prepro-TRH, prohormone...
Monocytes are dominant cells present within the inflamed synovium during osteoarthritis (OA). In mice, two functionally distinct monocyte subsets described: pro-inflammatory Ly6Chigh and patrolling Ly6Clow monocytes. Alarmins S100A8/A9 locally released by inflammatory OA for prolonged periods may be proteins involved in stimulating recruitment of monocytes from circulation to joint. Our objective was investigate role mobilization monocytic populations joint collagenase-induced (CiOA). S100A8...
SUMMARY In teleosts, the thyroid gland is mostly found in subpharyngeal region. However, several species follicles are in, for example,heart, head kidney and kidney. Such heterotopic active,and considered to work concert with thyroid. Mozambique tilapia (Oreochromis mossambicus) activity is,indeed, restricted region; common carp (Cyprinus carpio) functional endocrine associated renal tissues. The of comprise only 10% total tissue, these neither accumulate iodide nor synthesize or secrete...
Craniomaxillofacial bone defects represent a clinical challenge in the fields of maxillofacial surgery and (implant) dentistry. Regeneration these requires application graft materials that facilitate new formation safe, reliable, predictive manner. In addition to autologous graft, several types (synthetic) substitute have become clinically available, still major efforts are focused on improving such by optimizing their properties. Given regulatory necessity evaluate performance for...
Recruitment of leukocytes from the blood to sites inflammation poses a promising target for new diagnostic and therapeutic approaches.We aimed develop novel method non-invasively analyze molecular mechanisms leukocyte migration in pre-clinical models vivo.Methods: We used ER-HoxB8 system transiently immortalize murine myeloid precursors wildtype CD18-as well as MRP14-deficient mice.A VLA4α-/-cell line was generated by CRISPR/Cas9-mediated gene editing.We analyzed knockout vivo optical...
Seronegative joint diseases are characterized by a lack of well-defined biomarkers since autoantibodies not elevated. Calprotectin (S100A8/A9) is damage-associated molecular pattern (DAMP) which released activated phagocytes, and high levels found in seronegative arthritides. In this study, we investigated the biomarker potential systemic local these S100 proteins to assess inflammation destruction an experimental model for arthritis. Serum S100A8/A9 various cytokines were monitored during...
In teleostean fishes the hypothalamic–pituitary–thyroid axis (HPT axis) and hypothalamic–pituitary–interrenal (HPI regulate release of thyroid hormones (THs) cortisol respectively. Since many actions both are involved in regulation metabolic processes, communication between signal pathways can be anticipated. this study, we describe central peripheral sites for direct interaction mediators neuroendocrine axes common carp ( Cyprinus carpio ). Despite suggestions literature that CRH is...
Background: Injection of adipose-derived mesenchymal stromal cells (ASCs) into murine knee joints after induction inflammatory collagenase-induced osteoarthritis (CiOA) reduces development joint pathology. This protection is only achieved when ASCs are applied in early CiOA, which characterized by synovitis and high S100A8/A9 IL-1β levels, suggesting that inflammation a prerequisite for the protective effect ASCs. Our objective was to gain more insight interplay between ASC-mediated...
Abstract Background Synovitis-associated pain is mediated by inflammatory factors that may include S100A8/9, which able to stimulate nociceptive neurons via Toll-like receptor 4. In this study, we investigated the role of S100A9 in response during acute synovitis. Methods Acute synovitis was induced streptococcal cell wall (SCW) injection knee joint C57Bl/6 (WT) and −/− mice. The expression S100A8/A9 determined serum synovium ELISA immunohistochemistry. Inflammation 99m Tc accumulation,...
Testosterone and alendronate have been identified as two bone healing compounds which, when combined, synergistically stimulate regeneration. This study describes the development of a novel ultrasonic spray coating for sustained release ancillary amounts testosterone encapsulated in PLGA 5004A carrier. Due to low used, sensitive vitro assays were developed determine release. The technology was optimized titanium screws pericardial collagen membranes, with aim improve osseo-integration...
Inhibition of the V600E mutated BRAF kinase gene (BRAF(V600E) ) is an important and effective approach to treating melanomas. A new specific small molecule inhibitor BRAF(V600E) , PLX3603, showed potent melanoma growth-inhibiting characteristics in preclinical studies currently under clinical investigation. In this study we investigated feasibility (18) F-FDG F-FLT-PET monitor early effects mice with xenografts. SCID/beige subcutaneous (s.c.) A375 xenografts, expressing received twice daily...
The purpose of the present in vivo study was to evaluate whether pericard collagen membranes coated with ancillary amounts testosterone and alendronate a poly-lactic glycolic acid (PLGA) carrier as compared uncoated will improve early bone regeneration.In each 16 minipigs, four standardized mandibular intraosseous defects were made bilaterally. filled Bio-Oss® granules covered non-coated or membrane. Membranes spray-coated 4 layers PLGA containing resulting 20, 50 125 μg/cm2 20 µg/cm2 (F20,...
Abstract IL-2 therapy can lead to durable responses in cancer patients, but is associated with significant toxicity. None of the described IL-2-based immunocytokines has progressed beyond Phase II trials due various constraints their design: 1) pM affinity for IL-2Rαβγ on immune cells and pulmonary vascular endothelium compromising tumor targeting fusion two wildtype moieties antibody, together FcγR binding same cells; 2) Rapid systemic clearance short half-life high binding; 3) Preferential...
A bstract : We have investigated the effect of adaptation to low salinity water on thyroid status euryhaline teleost, Sparus auratus . show that, following adaptation, plasma T 4 concentration increases and branchial deiodination activities , 3 rT decrease. Moreover, hepatic enzyme that are putatively involved in hormone metabolism respond differentially conditions. Our results indicate involvement hormones osmoregulation. gills appear well equipped play an important role modulation titers.
Abstract Background Excessive osteoclast activity, which is strongly stimulated by pro-inflammatory mediators, results in bone and cartilage degeneration as central features of many arthritides. Levels the alarmin S100A8/A9 interleukin (IL)-1β are both increased arthritis patients correlate with disease activity progression tissue erosion. We previously presented a good biomarker for joint inflammation pathology under circumstances high IL-1 signaling mice that lack gene encoding receptor...
Abstract Introduction: IL-2 therapy can lead to durable responses in a modest proportion of cancer patients, but the treatment is associated with significant toxicity. Over last decades, various IL-2-based immunocytokines have been generated by fusing tumor-targeting antibodies. However, none these molecules progressed beyond Phase II trials and they are hampered liabilities: 1) High functional affinity (low pM) for IL-2Rabg on immune cells pulmonary vascular endothelium (Krieg et al., PNAS,...