686 research outputs found
Food and Food Groups in Inflammatory Bowel Disease (IBD):The Design of the Groningen Anti-Inflammatory Diet (GrAID)
Diet plays a pivotal role in the onset and course of inflammatory bowel disease (IBD). Patients are keen to know what to eat to reduce symptoms and flares, but dietary guidelines are lacking. To advice patients, an overview of the current evidence on food (group) level is needed. This narrative review studies the effects of food (groups) on the onset and course of IBD and if not available the effects in healthy subjects or animal and in vitro IBD models. Based on this evidence the Groningen anti-inflammatory diet (GrAID) was designed and compared on food (group) level to other existing IBD diets. Although on several foods conflicting results were found, this review provides patients a good overview. Based on this evidence, the GrAID consists of lean meat, eggs, fish, plain dairy (such as milk, yoghurt, kefir and hard cheeses), fruit, vegetables, legumes, wheat, coffee, tea and honey. Red meat, other dairy products and sugar should be limited. Canned and processed foods, alcohol and sweetened beverages should be avoided. This comprehensive review focuses on anti-inflammatory properties of foods providing IBD patients with the best evidence on which foods they should eat or avoid to reduce flares. This was used to design the GrAID
Structural basis of the chiral selectivity of Pseudomonas cepacia lipase
To investigate the enantioselectivity of Pseudomonas cepacia lipase, inhibition studies were performed with SC- and RC-(RP,SP)-1,2-dialkylcarbamoylglycero-3-O-p-nitrophenyl alkylphosphonates of different alkyl chain lengths. P. cepacia lipase was most rapidly inactivated by RC-(RP,SP)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl octylphosphonate (RC-trioctyl) with an inactivation half-time of 75 min, while that for the SC-(RP,SP)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl octyl-phosphonate (SC-trioctyl) compound was 530 min. X-ray structures were obtained of P. cepacia lipase after reaction with RC-trioctyl to 0.29-nm resolution at pH 4 and covalently modified with RC-(RP,SP)-1,2-dibutylcarbamoylglycero-3-O-p-nitrophenyl butyl-phosphonate (RC-tributyl) to 0.175-nm resolution at pH 8.5. The three-dimensional structures reveal that both triacylglycerol analogues had reacted with the active-site Ser87, forming a covalent complex. The bound phosphorus atom shows the same chirality (SP) in both complexes despite the use of a racemic (RP,SP) mixture at the phosphorus atom of the triacylglycerol analogues. In the structure of RC-tributyl-complexed P. cepacia lipase, the diacylglycerol moiety has been lost due to an aging reaction, and only the butyl phosphonate remains visible in the electron density. In the RC-trioctyl complex the complete inhibitor is clearly defined; it adopts a bent tuning fork conformation. Unambiguously, four binding pockets for the triacylglycerol could be detected: an oxyanion hole and three pockets which accommodate the sn-1, sn-2, and sn-3 fatty acid chains. Van der Waals’ interactions are the main forces that keep the radyl groups of the triacylglycerol analogue in position and, in addition, a hydrogen bond to the carbonyl oxygen of the sn-2 chain contributes to fixing the position of the inhibitor.
Clinical Value of Multiomics-Based Biomarker Signatures in Inflammatory Bowel Diseases:Challenges and Opportunities
Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are complex and heterogeneous diseases characterized by a multifactorial etiology, therefore demanding a multimodal approach to disentangle the main pathophysiological components driving disease onset and progression. Adoption of a systems biology approach is increasingly advocated with the advent of multi-omics profiling technologies, aiming to improve disease classification, to identify disease biomarkers and to accelerate drug discovery for patients with IBD. However, clinical translation of multi-omics-derived biomarker signatures is lagging behind, since there are several obstacles that need to be addressed in order to realize clinically useful signatures. Multi-omics integration and IBD-specific identification of molecular networks, standardization and clearly defined outcomes, strategies to tackle cohort heterogeneity, and external validation of multi-omics-based signatures are critical aspects. While striving for personalized medicine in IBD, careful consideration of these aspects is however needed to adequately match biomarker targets (e.g. the gut microbiome, immunity or oxidative stress) with their corresponding utilities (e.g. early disease detection, endoscopic and clinical outcome). Theory-driven disease classifications and predictions are still governing clinical practice, while this could be improved by adopting an unbiased, data-driven approach relying on molecular data structures integrated with patient and disease characteristics. In the foreseeable future, the main challenge will lie in the complexity and impracticality of implementing multi-omics-based signatures into clinical practice. Still, this could be achieved by developing easy-to-use, robust and cost-effective tools incorporating omics-derived predictive signatures and through the design and execution of prospective, longitudinal, biomarker-stratified clinical trials
Letter: disentangling the role of redox-active compounds in the development of inflammatory bowel diseases – moving towards causal associations
Women trafficking networks:Structure and stages of women trafficking in five Dutch small-scale networks
In this study, we investigated the relation between the different stages of women trafficking (i.e. recruitment, entrance, accommodation, labor, and finance) and the structure of five criminal networks involved in women trafficking in the Netherlands (Ns ranging from 6 to 15). On the one hand, it could be argued that for efficiency and avoidance of being detected by law enforcement agencies, the network structure might align with the different stages, resulting in a cell-structured network with collaboration between actors within rather than across stages. On the other hand, criminal actors might prefer to collaborate and rely on a few others, whom they trust in order to circumvent the lack of formal opportunities to enforce collaboration and agreements, resulting in a core-periphery network with actors also collaborating across stages. Results indicate that three of the five networks were characterized by a core-periphery structure, whereas the two other networks exhibit a mixture of both a cell-structured and core-periphery network. Furthermore, using an Exponential Random Graph Model (ERGM), we found that actors were likely to form ties with each other in the stages of recruitment, accommodation, and exploitation, but not in the stages of transport and finance.</p
Review:Local Tumor Necrosis Factor-alpha Inhibition in Inflammatory Bowel Disease
Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) are associated with disease activity and severity. Anti- TNF-α therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-α inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-α inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-α therapy was achieved with antibodies, antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative review summarizes and discusses these approaches in view of the clinical relevance of local TNF-α inhibition in IBD
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