High-throughput genome sequencing and transcriptome analysis have provided researchers with a quantitative basis for detailed modeling of gene expression using a wide variety of mathematical models. Two of the most commonly employed approaches used to model eukaryotic gene regulation are systems of differential equations, which describe time-dependent interactions of gene networks, and thermodynamic equilibrium approaches that can explore DNA-level transcriptional regulation. To combine the strengths of these approaches, we have constructed a new two-layer mathematical model that provides a dynamical description of gene regulatory systems, using detailed DNA-based information, as well as spatial and temporal transcription factor concentration data. We also developed a semi-implicit numerical algorithm for solving the model equations and demonstrate here the efficiency of this algorithm through stability and convergence analyses. To test the model, we used it together with the semi-implicit algorithm to simulate a Drosophila gene regulatory circuit that drives development in the dorsal-ventral axis of the blastoderm-stage embryo, involving three genes. For model validation, we have done both mathematical and statistical comparisons between the experimental data and the model’s simulated data. Where protein and cis-regulatory information is available, our two-layer model provides a method for recapitulating and predicting dynamic aspects of eukaryotic transcriptional systems that will greatly improve our understanding of gene regulation at a global level.
Magnesium (Mg)-based biodegradable materials are promising candidates for the new generation of implantable medical devices, particularly cardiovascular stents and orthopaedic implants. Mg-based cardiovascular stents represent the most innovative stent technology to date. However, these products still do not fully meet clinical requirements with regards to fast degradation rates, late restenosis, and thrombosis. Thus various surface coatings have been introduced to protect Mg-based stents from rapid corrosion and to improve biocompatibility. Similarly, different coatings have been used for orthopaedic implants, e.g., plates and pins for bone fracture fixation or as an interference screw for tendon-bone or ligament-bone insertion, to improve biocompatibility and corrosion resistance. Metal coatings, nanoporous inorganic coatings and permanent polymers have been proved to enhance corrosion resistance; however, inflammation and foreign body reactions have also been reported. By contrast, biodegradable polymers are more biocompatible in general and are favoured over permanent materials. Drugs are also loaded with biodegradable polymers to improve their performance. The key similarities and differences in coatings for Mg-based stents and orthopaedic implants are summarized.
Delayed healing of traumatic wounds often stems from a dysregulated immune response initiated or exacerbated by existing comorbidities, multiple tissue injury or wound contamination. Over decades, approaches towards alleviating wound inflammation have been centered on interventions capable of a collective dampening of various inflammatory factors and/or cells. However, a progressive understanding of immune physiology has rendered deeper knowledge on the dynamic interplay of secreted factors and effector cells following an acute injury. There is a wide body of literature, both in vitro and in vivo, abstracted on the immunomodulatory approaches to control inflammation. Recently, targeted modulation of the immune response via biotechnological approaches and biomaterials has gained attention as a means to restore the pro-healing phenotype and promote tissue regeneration. In order to fully realize the potential of these approaches in traumatic wounds, a critical and nuanced understanding of the relationships between immune dysregulation and healing outcomes is needed. This review provides an insight on paradigm shift towards interventional approaches to control exacerbated immune response following a traumatic injury from an agonistic to a targeted path. We address such a need by (1) providing a targeted discussion of the wound healing processes to assist in the identification of novel therapeutic targets and (2) highlighting emerging technologies and interventions that utilize an immunoengineering-based approach. In addition, we have underscored the importance of immune engineering as an emerging tool to provide precision medicine as an option to modulate acute immune response following a traumatic injury. Finally, an overview is provided on how an intervention can follow through a successful clinical application and regulatory pathway following laboratory and animal model evaluation.
Thermal burn injuries are still a serious public health concern in the United States, due to the initial insult and resulting co-morbidities. Burned patients are increasingly susceptible to colonization by endogenous and exogenous micro-organisms after having lost skin, which acts as the primary protective barrier to environmental contaminants. Furthermore, the onset of additional pathophysiologies, specifically sepsis, becomes more likely in burned patients compared to other injuries. Despite improvements in the early care of burn patients, infections, and sepsis, these pathophysiologies remain major causes of morbidity and mortality and warrant further investigation of potential therapies. Vitamin E may be one such therapy. We aimed to identify publications of studies that evaluated the effectiveness of vitamin E as it pertains to thermal burn injuries, infection, and sepsis. Several investigations ranging from in vitro bench work to clinical studies have examined the impact on, or influence of, vitamin E in vitro, in vivo, and in the clinical setting. To the benefit of subjects it has been shown that enteral or parenteral vitamin E supplementation can prevent, mitigate, and even reverse the effects of thermal burn injuries, infection, and sepsis. Therefore, a large scale prospective observational study to assess the potential benefits of vitamin E supplementation in patients is warranted and could result in clinical care practice paradigm changes.
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