Processes2015, 3(1), 50-70; doi:10.3390/pr3010050 - published 14 January 2015 Show/Hide Abstract
Abstract: Interleukin-6 (IL-6) is a systemic inflammatory mediator that triggers the human body’s acute phase response to trauma or inflammation. Although mathematical models for IL-6 signaling pathways have previously been developed, reactions that describe the expression of acute phase proteins were not included. To address this deficiency, a recent model of IL-6 signaling was extended to predict the dynamics of acute phase protein expression in IL-6-stimulated HepG2 cells (a human hepatoma cell line). This included reactions that describe the regulation of haptoglobin, fibrinogen, and albumin secretion by nuclear transcription factors STAT3 dimer and C/EBPβ. This new extended model was validated against two different sets of experimental data. Using the validated model, a sensitivity analysis was performed to identify seven potential drug targets to regulate the secretion of haptoglobin, fibrinogen, and albumin. The drug-target binding kinetics for these seven targets was then integrated with the IL-6 kinetic model to rank them based upon the influence of their pairing with drugs on acute phase protein dynamics. It was found that gp80, JAK, and gp130 were the three most promising drug targets and that it was possible to reduce the therapeutic dosage by combining drugs aimed at the top three targets in a cocktail. These findings suggest hypotheses for further experimental investigation.
Processes2015, 3(1), 46-49; doi:10.3390/pr3010046 - published 12 January 2015 Show/Hide Abstract
Abstract: Tissue engineering and, more broadly, regenerative medicine is moving into a phase where we are seeing potential therapies moving ‘slowly but surely’ from the laboratory into the clinic, i.e.,from research to the clinic and into manufacturing. The numbers of cells required for cell therapy protocols can vary from tens of millions, to billions , and it is widely considered that such cell numbers can be produced in bioreactor systems. Thus, the bioreactor is becoming a key tool for culturing clinical numbers of human cells and the regenerative medicine industry will become increasingly reliant on such systems at the centre of cell therapy production and tissue engineering.[...]
Processes2015, 3(1), 25-45; doi:10.3390/pr3010025 - published 8 January 2015 Show/Hide Abstract
Abstract: This paper gives an analysis of the efficacy of PFC strategies. PFC is widely used in industry for simple loops with constraint handling, as it is very simple and cheap to implement. However, the algorithm has had very little exposure in the mainstream literature. This paper gives some insight into when a PFC approach is expected to be successful and, conversely, when one should deploy with caution.
Processes2015, 3(1), 19-22; doi:10.3390/pr3010019 - published 26 December 2014 Show/Hide Abstract
Abstract: Reaction-oriented research in flow chemistry and microreactor has been extensively focused upon in special journal issues and books. On a process level, this resembled the “drop-in” (retrofit) concept with the microreactor replacing a conventional (batch) reactor. Meanwhile, with the introduction of the mobile, compact, modular container technology, the focus is more on the process side, including also providing an end-to-end vision of intensified process design. Exactly this is the focus of the current special issue “Design and Engineering of Microreactor and Smart-Scaled Flow Processes” of the journal “Processes”. This special issue comprises three review papers, five research articles and two communications. [...]
Processes2015, 3(1), 1-18; doi:10.3390/pr3010001 - published 26 December 2014 Show/Hide Abstract
Abstract: Inflammation is a beneficial mechanism that is usually triggered by injury or infection and is designed to return the body to homeostasis. However, uncontrolled or sustained inflammation can be deleterious and has been shown to be involved in the etiology of several diseases, including inflammatory bowel disorder and asthma. Therefore, effective anti-inflammatory signaling is important in the maintenance of homeostasis in the body. However, the inter-play between pro- and anti-inflammatory signaling is not fully understood. In the present study, we develop a mathematical model to describe integrated pro- and anti-inflammatory signaling in macrophages. The model incorporates the feedback effects of de novo synthesized pro-inflammatory (tumor necrosis factor α; TNF-α) and anti-inflammatory (interleukin-10; IL-10) cytokines on the activation of the transcription factor nuclear factor κB (NF-κB) under continuous lipopolysaccharide (LPS) stimulation (mimicking bacterial infection). In the model, IL-10 upregulates its own production (positive feedback) and also downregulates TNF-α production through NF-κB (negative feedback). In addition, TNF-α upregulates its own production through NF-κB (positive feedback). Eight model parameters are selected for estimation involving sensitivity analysis and clustering techniques. We validate the mathematical model predictions by measuring phosphorylated NF-κB, de novo synthesized TNF-α and IL-10 in RAW 264.7 macrophages exposed to LPS. This integrated model represents a first step towards modeling the interaction between pro- and anti-inflammatory signaling.