Translational Systems Biology of Inflammation: Potential Applications to Personalized Medicine
Personalized MedicinePublished 1 September 2010Open access
Qi Mi, Nicole Y. K. Li‐Jessen, Cordelia Ziraldo, Ali Ghuma, Maxim Mikheev, Robert H. Squires
Citations64
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
It is suggested that the work aimed at creating a rational, engineering-oriented and evidence-based synthesis of inflammation geared towards rapid clinical application is on the cusp of fulfilling the promise of in silico modeling for personalized medicine for inflammatory disease.
Abstract
A central goal of industrialized nations is to provide personalized, preemptive and predictive medicine, while maintaining healthcare costs at a minimum. To do so, we must confront and gain an understanding of inflammation, a complex, nonlinear process central to many diseases that affect both industrialized and developing nations. Herein, we describe the work aimed at creating a rational, engineering-oriented and evidence-based synthesis of inflammation geared towards rapid clinical application. This comprehensive approach, which we call 'Translational Systems Biology', to date has been utilized for in silico studies of sepsis, trauma/hemorrhage/traumatic brain injury, acute liver failure and wound healing. This framework has now allowed us to suggest how to modulate acute inflammation in a rational and individually optimized fashion using engineering principles applied to a biohybrid device. We suggest that we are on the cusp of fulfilling the promise of in silico modeling for personalized medicine for inflammatory disease.
Keywords
Immunology and MicrobiologyBiochemistry, Genetics and Molecular Biology
NatureOrigin and physiological roles of inflammation
6,385 Citations2008Ruslan Medzhitov
This work has shown that tissue stress or malfunction induces an adaptive response that is intermediate between the basal homeostatic state and a classic inflammatory response, which is referred to here as para-inflammation.
Annals of the New York Academy of SciencesInflamm‐aging: An Evolutionary Perspective on Immunosenescence
5,228 Citations2000Claudio Franceschi, Massimiliano Bonafè +5 more
The beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.
ScienceSystems Biology: A Brief Overview
4,219 Citations2002Hiroaki Kitano
To understand biology at the system level, the authors must examine the structure and dynamics of cellular and organismal function, rather than the characteristics of isolated parts of a cell or organism.
Cellular Physiology and BiochemistryResveratrol Reduces the Proinflammatory Effects and Lipopolysaccharide- Induced Expression of HMGB1 and TLR4 in RAW264.7 Cells
3,255 Citations2014Ying Yang, Shuping Li +10 more
Res can block the inflammatory effects induced by LPS in RAW264.7 cells and may also influence TLR4 expression in the HMGB1-TLR4 signaling pathway.
Journal of Leukocyte BiologyDAMPs, PAMPs and alarmins: all we need to know about danger
2,761 Citations2006Marco E. Bianchi
The term “alarmin” is proposed to categorize such endogenous molecules that signal tissue and cell damage, and can be considered subgroups of a larger set, the damage‐associated molecular patterns (DAMPs).
NaturePoints of control in inflammation
2,655 Citations2002Carl Nathan
The non-inflammatory state does not arise passively from an absence of inflammatory stimuli; rather, maintenance of health requires the positive actions of specific gene products to suppress reactions to potentially inflammatory stimuli that do not warrant a full response.
Proceedings of the National Academy of SciencesEffects of a polymorphism in the human tumor necrosis factor α promoter on transcriptional activation
2,225 Citations1997Anthony G. Wilson, Julian Symons +3 more
It is demonstrated, with reporter genes under the control of the two allelic TNF promoters, that TNF2 is a much stronger transcriptional activator than the common allele (TNF1) in a human B cell line.
Society for Industrial and Applied Mathematics eBooksMathematical Models in Biology
2,012 Citations2005Leah Edelstein‐Keshet
The theory of linear difference equations applied to population growth and the applications of nonlinear difference equations to population biology are explained.
CHEST JournalAnti-Inflammatory Cytokines
1,714 Citations2000Steven M. Opal, Vera A. DePalo
The nature of anti- inflammatory cytokines and soluble cytokine receptors is the focus of this review and the current and future therapeutic uses of these anti-inflammatory cytokines are also reviewed.
ScienceReverse Engineering of Biological Complexity
1,218 Citations2002Marie Csete, John C. Doyle
This review describes insights from engineering theory and practice that can shed some light on biological complexity.
Experimental GerontologyInflammatory mediators in the elderly
918 Citations2004Karen S. Krabbe, M. Hauge +1 more
It is possible that inflammatory mediators constitute a link between life style factors, infections and physiological changes in the process of ageing on the one hand and risk factors for age-associated diseases on the other.
The FASEB JournalCyclooxygenases: new forms, new inhibitors, and lessons from the clinic
624 Citations2004Timothy D. Warner, Jane A. Mitchell
Clinical use of COX‐2‐selective compounds has ignited strong debates regarding potential side effects, most notably those within the cardiovascular system such as myocardial infarctions, strokes, and elevation in blood pressure, and this review will discuss how the latest studies help to understand the roles ofCOX‐1 and COx‐2 and what clinically proven benefits the newer generation of CO X‐2•selective inhibitors offer.
ScienceMechanism-Based Target Identification and Drug Discovery in Cancer Research
610 Citations2000W. Wayt Gibbs
There has been a tremendous increase in the authors' knowledge of the molecular mechanisms and pathophysiology of human cancer, and many of these mechanisms have been exploited as new targets for drug development in the hope that they will have greater antitumor activity with less toxicity to the patient.
Immunological ReviewsHigh‐mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity
596 Citations2007Marco E. Bianchi, Angelo A. Manfredi
High‐mobility group box 1 protein (HMGB1), a nuclear protein that is released passively when necrotic cells lose the integrity of their membranes, acts in an autocrine/paracrine fashion and sustains long‐term repair and defense programs.
Critical CareComplex systems and the technology of variability analysis
437 Citations2004Andrew Seely, Peter T. Macklem
The ubiquitous association between altered variability and illness is highlighted, followed by an analysis of how variability analysis may significantly improve prognostication of severity of illness and guide therapeutic intervention in critically ill patients.
Journal of HepatologyThe importance of immune dysfunction in determining outcome in acute liver failure
364 Citations2008Charalambos G. Antoniades, Philip Berry +2 more
Clinical studies demonstrating the persistence of a compensatory anti-inflammatory response syndrome, leading to functional monocyte deactivation, is a central event in the evolution of systemic immune dysfunction in acute liver failure demonstrate that accurate immune profiling in ALF may permit the development of immunomodulatory strategies in order to improve outcome.
Nature BiotechnologyThe challenges of modeling mammalian biocomplexity
354 Citations2004Jeremy K. Nicholson, Elaine Holmes +2 more
This work has shown that highly complex animals such as humans can be considered 'superorganisms' with an internal ecosystem of diverse symbiotic microbiota and parasites that have interactive metabolic processes that need to be addressed.
Proceedings of the National Academy of SciencesSynaptic pattern formation during cellular recognition
351 Citations2001Shuyan Qi, Jay T. Groves +1 more
The model presented provides a common way of analyzing immunological synapse formation in disparate systems (e.g., T cell/antigen-presenting cell junctions with different MHC-peptides, natural killer cells, etc.).
WIREs Systems Biology and MedicineAgent‐based models in translational systems biology
320 Citations2009Gary An, Qi Mi +2 more
The ability of agent‐based modeling to encompass multiple scales of biological process as well as spatial considerations, coupled with an intuitive modeling paradigm, suggests that this modeling framework is well suited for translational systems biology.
Inflammation & Allergy - Drug TargetsTreatment of Inflammatory Diseases with Mesenchymal Stem Cells
306 Citations2009Robert E. Newman, Dana Yoo +2 more
Human mesenchymal stem cells are rare progenitor cells present in adult bone marrow that have the capacity to differentiate into a variety of tissue types, including bone, cartilage, tendon, fat, and muscle, providing therapeutic potential for treating diseases characterized by the presence of an inflammatory component.
Medical Microbiology and ImmunologyInterleukin-6 and its receptor: from bench to bedside
293 Citations2006Jürgen Scheller, Stefan Rose‐John
Interleukin-6 uses classical signaling via the membrane bound receptor and trans-signaling via the soluble receptor in various physiological and pathophysiological situations and designer cytokines are developed, which can specifically enhance or inhibit IL-6 trans-Signaling.
ScienceGetting Closer to the Whole Picture
269 Citations2007Uwe Sauer, Matthias Heinemann +1 more
A quantitative data set of RNA, proteins, and metabolites provides an unprecedented starting point to understand, at a systems level, the effects of perturbations on a cell.
Journal of Theoretical BiologyA reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammation
259 Citations2006Angela Reynolds, Jonathan E. Rubin +4 more
This work derives a reduced conceptual model for the acute inflammatory response to infection, built up from consideration of direct interactions of fundamental effectors, to explore the importance of dynamic anti-inflammation in promoting resolution of infection and homeostasis.
Current Problems in SurgeryHemorrhagic shock
238 Citations1995Andrew B. Peitzman, Brian G. Harbrecht +4 more
Treatment of hemorrhagicshock includes rapid operative resuscitation to limit activation of the mediator systems and abort the microcirculatory changes that result from hemorrhagic shock.
Proceedings of the National Academy of SciencesApplication of genome-wide expression analysis to human health and disease
235 Citations2005J. Perren Cobb, Michael Mindrinos +15 more
It is demonstrated that the development of a nation-wide program for gene expression analysis with careful attention to analytical details can reduce the variance in the clinical setting to a level where patterns of gene expression are informative among different healthy human subjects, and can be studied with confidence in human disease.
British journal of surgeryExperimental models of Gram-negative sepsis
234 Citations2001Simon Parker, P Watkins
The mortality rate from sepsis has improved little over the past two decades, and one reason for this has been the use of flawed or inappropriate experimental models in preclinical Sepsis studies.
PLoS Computational BiologyTranslational Systems Biology of Inflammation
228 Citations2008Yoram Vodovotz, Marie Csete +3 more
The efforts to use translational systems biology to develop an integrated framework to gain insight into the problem of acute inflammation are described, highlighting the promise of this multidisciplinary field.
Critical Care MedicineIn silico experiments of existing and hypothetical cytokine-directed clinical trials using agent-based modeling*
225 Citations2004Gary An
ABM may provide a synthetic, analytical platform to integrate basic science data on the IIR, thus eventually aiding in formulating and testing future mediator-directed therapies for SIRS/MOF before clinical trials, and it may provide insights into directions of future research.
Current Pharmaceutical DesignThe Epidemiology of Sepsis
217 Citations2008Katherine Hodgin, Marc Moss
Patients who survive their episode of sepsis continue to have increased morbidity and mortality up to five years after their initial illness, although the case fatality rates have diminished over the last two decades.
Nature reviews. ImmunologyMathematical and computational models of immune-receptor signalling
208 Citations2004Byron Goldstein, James R. Faeder +1 more
The application of detailed models to understand signalling through immune receptors that are involved in antigen recognition and offers hope that models might eventually predict the full spectrum of signalling behaviour.
ShockTHE ACUTE INFLAMMATORY RESPONSE IN DIVERSE SHOCK STATES
198 Citations2005Carson C. Chow, Gilles Clermont +10 more
A mathematical model incorporating major elements of the acute inflammatory response in C57Bl/6 mice was developed and found that a single model with different initiators including the autonomic system could describe the response to various insults.
Critical Care MedicineIn silico design of clinical trials: A method coming of age
190 Citations2004Gilles Clermont, John Bartels +4 more
The construction of an in silico clinical trial could provide profound insight into the design of clinical trials of immunomodulatory therapies, ranging from optimal patient selection to individualized dosage and duration of proposed therapeutic interventions.
MedicineComparison of Clinical Manifestations and Outcome of Community-Acquired Bloodstream Infections Among the Oldest Old, Elderly, and Adult Patients
170 Citations2007Chien‐Chang Lee, Shey‐Ying Chen +3 more
ShockEARLY VERSUS LATE ONSET OF MULTIPLE ORGAN FAILURE IS ASSOCIATED WITH DIFFERING PATTERNS OF PLASMA CYTOKINE BIOMARKER EXPRESSION AND OUTCOME AFTER SEVERE TRAUMA
170 Citations2007Bernd Oliver Maier, Rolf Lefering +5 more
It is demonstrated that mortality differs significantly between the development of EMOF and LMOF after traumatic injury and the predictive value of cytokine biomarkers of MOF and lethal outcome and suggested that serum cytokine measurements may be important early biochemical markers for predicting thedevelopment of delayed MOF.
The Journal of ImmunologyInvestigation of Early Events in FcεRI-Mediated Signaling Using a Detailed Mathematical Model
170 Citations2003James R. Faeder, William S. Hlavacek +6 more
The approach was to build a detailed mathematical model of reactions involving Fc epsilon RI, Lyn, Syk, and a bivalent ligand that aggregates Fc(epsilon)RI and applied the model to experiments in which covalently cross-linked IgE dimers stimulate rat basophilic leukemia cells.
Wound Repair and RegenerationAgent‐based model of inflammation and wound healing: insights into diabetic foot ulcer pathology and the role of transforming growth factor‐β1
166 Citations2007Qi Mi, Béatrice Rivière +3 more
An agent‐based model capable of reproducing qualitatively much of the literature data on skin wound healing, including changes in relevant cell populations and their key effector cytokines, is developed and found that these therapies would have similar effects regardless of the initial assumption of the derangement that underlies DFU.
Journal of Theoretical BiologyA reduced mathematical model of the acute inflammatory response II. Capturing scenarios of repeated endotoxin administration
162 Citations2006Judy Day, Jonathan E. Rubin +4 more
The hypothesis that endotoxin tolerance and other related phenomena can be considered as dynamic manifestations of a unified acute inflammatory response, and offer specific predictions related to the dynamics of this response to endotoxin, is supported.
Expert Opinion on Investigational DrugsAnti-inflammatory therapies in sepsis and septic shock
146 Citations2000Bradley D. Freeman, Charles Natanson
Clinical trials in sepsis have focused on inhibiting specific host pro-inflammatory mediators (e.g., TNF, interleukins) and pooling the results of these trials suggest that this approach has a marginal effect, supporting a role for excessive inflammation inSepsis.
ShockAGENT-BASED COMPUTER SIMULATION AND SIRS: BUILDING A BRIDGE BETWEEN BASIC SCIENCE AND CLINICAL TRIALS
136 Citations2001Gary An
An abstracted version of the inflammatory process is constructed using an ABCS that is based at the cellular level and produces non-linear behavior and reproduces the dynamic structure of theinflammatory response.
Mathematical BiosciencesMechanistic simulations of inflammation: Current state and future prospects
136 Citations2008Yoram Vodovotz, Gregory Constantine +4 more
A series of articles in this issue highlights various modeling approaches to inflammation in the larger context of health and disease, from intracellular signaling to whole-animal physiology.
Journal of VoiceVocal Fold Wound Healing: A Review for Clinicians
133 Citations2005Ryan C. Branski, Katherine Verdolini +3 more
The current review seeks to provide a foundation of basic wound healing science and present the most current data regarding the wound healing process in the vocal folds.
Current Opinion in Critical CareMathematical models of the acute inflammatory response
130 Citations2004Yoram Vodovotz, Gilles Clermont +2 more
Theoretical Biology and Medical ModellingIntroduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation
121 Citations2008Gary An
These models represent a qualitative means of integrating basic scientific information on acute inflammation in a multi-scale, modular architecture as a means of conceptual model verification that can potentially be used to concatenate, communicate and advance community-wide knowledge.
ShockPRECLINICAL MODELS OF SHOCK AND SEPSIS: WHAT CAN THEY TELL US?
119 Citations2005John C. Marshall, Edwin A. Deitch +4 more
There is no single ideal model of shock or sepsis, but rather a large number of complementary models that recapitulate some discrete features of the disorders while minimizing others, which means that preclinical studies can shape concepts of disease and can be used to refine decisions regarding optimal patient populations for therapeutic interventional trials.
PLoS ONEA Patient-Specific in silico Model of Inflammation and Healing Tested in Acute Vocal Fold Injury
119 Citations2008Nicole Y. K. Li‐Jessen, Katherine Verdolini +5 more
It is proposed that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains.
PubMedMechanisms for modulating TNF alpha in immune and inflammatory disease.
118 Citations2001John A. Baugh, R. Bucala
The development of the currently available therapeutics and the progressive steps that are being made to improve clinical efficacy of anti-TNF alpha strategies are reviewed.
Current Opinion in Clinical Nutrition & Metabolic CareInflammatory response in the elderly
105 Citations2003Robert F. Grimble
Ageing is associated with increased levels of chronic inflammation, which plays a major role in the decline in immune function and lean body mass, and new evidence suggests that, for the latter nutrient, gene-nutrient interactions occur that alter the effectiveness of dietary therapy.
Current Opinion in Critical CareNonlinear dynamics, complex systems, and the pathobiology of critical illness
104 Citations2004Timothy G. Buchman
Physiologic dynamics in health and in critical illness appear to reflect complex, interconnected systems biology and with knowledge of the structure, therapy could be better focused toward supporting both function and dynamics, offering hope for improved outcomes.
ShockIN SILICO MODELS OF ACUTE INFLAMMATION IN ANIMALS
103 Citations2006Yoram Vodovotz, Carson C. Chow +11 more
A mathematical model is constructed using ordinary differential equations that encompass the dynamics of cells and cytokines of the acute inflammatory response, as well as global tissue dysfunction and may provide insights into the complex dynamics of acute inflammation in a manner that can be tested in vivo using many fewer animals than has been possible previously.
Clinical Orthopaedics and Related ResearchCytokines in Patients with Polytrauma
100 Citations2004William G. DeLong, Christopher T. Born
There is great promise in the study of cytokines through basic science research and clinical trials, and certain cytokine levels, such as the interleukins, can be used in predictive ways to correlate organ failure in multiply injured patients.
PubMedShock: ischemia, reperfusion, and inflammation.
99 Citations1996Kenneth Waxman
Antioxidant therapy has the potential to limit cellular and organ damage from reperfusion and inflammation after shock, and to participate as effectors in the subsequent inflammatory response.
Trends in ImmunologyComplexities of targeting innate immunity to treat infection
98 Citations2007Kelly L. Brown, Céline Cosseau +2 more
Innate immunity is an ancient form of host defence that is activated rapidly to enable, through a multiplicity of effector mechanisms, defence against a broad spectrum of microbial threats, and, as a consequence, the innate immune system has become a major target for the development of therapeutics to control inflammation and immune defences.
Expert Opinion on Biological TherapyAnakinra: an inhibitor of IL-1 for the treatment of rheumatoid arthritis
96 Citations2004Roy Fleischmann, Richard Stern +1 more
Anakinra has been shown to be of benefit in patients with active rheumatoid arthritis, either when given alone or in combination with methotrexate, as assessed by improvement in clinical signs and symptoms, decreased radiographic progression and improvement in patient function, pain and fatigue, although it appears to be effective in fewer patients than anti-TNF agents.
The Journal of Trauma: Injury, Infection, and Critical CareMale Gender is Associated With Excessive IL-6 Expression Following Severe Injury
95 Citations2008Jason L. Sperry, Randall S. Friese +10 more
Persistently elevated IL-6 levels in males are associated with a higher rate of MOF, and further studies are required to elucidate if this early, persistent IL- 6 expression is responsible for the gender-based differential outcomes after injury.
PLoS ONEAgent-Based Modeling of Endotoxin-Induced Acute Inflammatory Response in Human Blood Leukocytes
90 Citations2010Xu Dong, Panagiota T. Foteinou +3 more
InjuryTranslational research: From benchside to bedside
86 Citations2008N. Keramaris, Nikolaos K. Kanakaris +3 more
New academic posts translationally orientated are urgently needed, particularly in the field of trauma medicine, where lack of awareness of this new evolution is evident.
Mathematical BiosciencesModeling endotoxin-induced systemic inflammation using an indirect response approach
86 Citations2008Panagiota T. Foteinou, S E Calvano +2 more
An in silico model that aims at coupling extracellular signals with essential transcriptional responses through a receptor mediated indirect response model is explored and the potential of the model is demonstrated by analyzing scenarios associated with endotoxin tolerance and potentiation effects.
American Journal of Respiratory and Critical Care MedicineGene Silencing in Severe Systemic Inflammation
84 Citations2007Charles E. McCall, Barbara K. Yoza
This critical care perspective appraises reprogramming of gene expression in inflammatory diseases as an emerging concept of clinical importance and discusses in three parts the clinical context and the translational basic science associated with gene silencing during the SIRS continuum of severe systemic inflammation.
ShockANTICYTOKINE THERAPIES FOR ACUTE INFLAMMATION AND THE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME: IL-10 AND ISCHEMIA/REPERFUSION INJURY AS A NEW PARADIGM
80 Citations2000Thomas S. Huber, Gregory C. Gaines +4 more
A Phase I clinical trial examining the role of the anti‐inflammatory cytokine IL‐10 during surgical repair of a thoracoabdominal aortic aneurysm may overcome some of the design limitations of previous anticytokine trials in sepsis, and serve as a paradigm for future anticyTokine therapy trials.
Molecular MedicineIn Silico and In Vivo Approach to Elucidate the Inflammatory Complexity of CD14-deficient Mice
78 Citations2006José M. Prince, Ryan M. Levy +12 more
It is suggested that LPS-CD14 responses do not cause inflammation in surgical trauma/hemorrhagic shock and a novel use of combined in silico and in vivo methods to elucidate the complex inflammatory phenotype of genetically modified animals is demonstrated.
Experimental Biology and MedicinePosttraumatic Inflammation is a Complex Response Based on the Pathological Expression of the Nervous, Immune, and Endocrine Functional Systems
76 Citations2004María‐Angeles Aller, Jaime Árias +4 more
The successive phases that make up both the local and systemic posttraumatic acute inflammatory response could represent the expression of three concatenated pathological or “primitive” functional systems with trophic properties: the nervous, immune, and endocrine ones.
Immunopharmacology and ImmunotoxicologyTranslational Systems Approaches to the Biology of Inflammation and Healing
76 Citations2010Yoram Vodovotz, Gregory Constantine +12 more
An iterative and ongoing program of literature analysis, generation of prospective data, data analysis, and computational modeling in various experimental and clinical inflammatory disease settings has suggested how to modulate acute inflammation in a rational, individually optimized fashion.
Advanced Drug Delivery ReviewsPharmacological approaches for the discovery and development of new anti-inflammatory agents for the treatment of cystic fibrosis
72 Citations2002Michael W. Konstan, Pamela B. Davis
Treating the inflammatory response is important, for the data from the ibuprofen study show that the effects of anti-inflammatory therapy are additive or even synergistic with intensive conventional therapy and alter the rate of decline of pulmonary function, and therefore benefits for survival of patients with CF are to be expected.
Journal of Burn Care & ResearchTranslational Systems Biology: Introduction of an Engineering Approach to the Pathophysiology of the Burn Patient
69 Citations2008Gary An, James R. Faeder +1 more
This study will review the existing applications of TSB in the areas of inflammation and wound healing, relate them to specific areas of interest to the burn community, and present an integrated framework that links TSB with traditional burn research.
PLoS ONEIn Silico Simulation of Corticosteroids Effect on an NFkB- Dependent Physicochemical Model of Systemic Inflammation
65 Citations2009Panagiota T. Foteinou, Steve E. Calvano +2 more
A reversed engineered inflammation model is proposed that seeks to describe how the system responds to a multitude of external signals and lies in qualitative agreement with in vivo human studies exposed both to LPS and corticosteroids under various time intervals thus improving understanding of how interacting modules generate a behavior.
PLoS ONEUsing a Mathematical Model to Analyze the Role of Probiotics and Inflammation in Necrotizing Enterocolitis
65 Citations2010Julia Arciero, G. Bard Ermentrout +3 more
A reduced, experimentally motivated mathematical model is developed that suggests how a certain general set of characteristics of probiotics can lead to beneficial or detrimental outcomes for infants suffering from NEC, depending on the influences of probiotic on defined features of the inflammatory response.
ShockA MATHEMATICAL SIMULATION OF THE INFLAMMATORY RESPONSE TO ANTHRAX INFECTION
58 Citations2007Rukmini Kumar, Carson C. Chow +3 more
It is shown that antibiotics only improve survival if administered early in the course of anthrax infection, and vaccination that leads to the formation of antibodies to protective antigen is anti-inflammatory and beneficial in averting shock and improving survival.
Mathematical BiosciencesA model of TLR4 signaling and tolerance using a qualitative, particle–event-based method: Introduction of spatially configured stochastic reaction chambers (SCSRC)
57 Citations2008Gary An
The spatially configured stochastic reaction chambers (SCSRC), an agent-based modeling framework that incorporates an abstracted molecular 'event' rule system with a spatially explicit representation of the relationship between signaling and synthetic compounds, has promise as a highly modular and flexible modeling method that is suited to the dynamic knowledge representation of intracellular processes.
ShockCOMPLEX SYSTEMS ANALYSIS: A TOOL FOR SHOCK RESEARCH
57 Citations2001Timothy G. Buchman, Perren J. Cobb +2 more
It is proposed that complex systems analysis is an essential tool for shock research and its application to genomic technologies is evaluated and it is suggested that general biological systems failure cannot be interpreted through reliance on reductionist science.
Topics in current geneticsFrom isolation to integration, a systems biology approach for building the Silicon Cell
57 Citations2005Jacky L. Snoep, Hans V. Westerhoff
PLoS ONEAn Adequately Robust Early TNF-α Response Is a Hallmark of Survival Following Trauma/Hemorrhage
54 Citations2009Rajaie Namas, Ali Ghuma +17 more
Contrary to the current dogma, survival in the setting of severe, acute T/HS appears to be associated with an immediate increase in serum TNF-α, which is currently unclear if this response was the cause of this protection, a marker of survival, or both.
Immunological ReviewsMaking sense of inflammation, epigenetics, and memory CD8<sup>+</sup> T‐cell differentiation in the context of infection
53 Citations2006Erika L. Pearce, Hao Shen
Advances in the understanding of T‐cell memory will undoubtedly help design unconventional vaccine strategies for inducing large populations of long‐lived and functional memory CD8+ T cells.
Mathematical BiosciencesA systems-theoretical framework for health and disease: Inflammation and preconditioning from an abstract modeling point of view
50 Citations2008Eberhard O. Voit
A conceptual approach toward formalizing health and disease is proposed and illustrated in the context of inflammation and preconditioning by focusing on simplexes in a high-dimensional biomarker space.
ShockMATHEMATICAL MODELING OF POSTHEMORRHAGE INFLAMMATION IN MICE
49 Citations2009Andrés Torres, Timothy Bentley +8 more
A hardware/software platform is established that allows for highly accurate, reproducible, and mathematically predictable HS in mice to increase the fidelity of the mathematical model and to establish a platform for testing predictions of this model.
Methods in molecular biologySystems Biology and Inflammation
49 Citations2010Yoram Vodovotz, Gary An
This chapter reviews the existing, translational applications of computational simulations and related approaches as applied to inflammation and suggests the concept of translational systems biology, defined as a focused application of computational modeling and engineering principles to pathophysiology primarily in order to revise clinical practice.
Immunologic ResearchDeciphering the Complexity of Acute Inflammation Using Mathematical Models
48 Citations2006Yoram Vodovotz
Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.
Mathematical BiosciencesDetailed qualitative dynamic knowledge representation using a BioNetGen model of TLR-4 signaling and preconditioning
47 Citations2008Gary An, James R. Faeder
The intent of this approach is to demonstrate a method of translating the extensive mechanistic knowledge being generated at the basic science level into an executable framework that allows for both the 'checking' of the dynamic consequences of a mechanistic hypothesis and the creation of an overall model directed at the engineering goal of biomedical research.
The Journal of Trauma: Injury, Infection, and Critical CareMolecular Analysis of Inflammatory Markers in Trauma Patients at Risk of Postinjury Complications
42 Citations2007D. Olga McDaniel, James Hamilton +10 more
A time course study demonstrated a significant difference in cytokines expression profile in septic and aseptic patients before the development of sepsis, suggesting monitoring cytokine expression levels before the disease might predict the outcome of sepsy.
Journal of Critical CareChallenges and rewards on the road to translational systems biology in acute illness: four case reports from interdisciplinary teams
42 Citations2007Gary An, C. Anthony Hunt +3 more
A transdisciplinary approach, which involves team interaction in an iterative fashion to address ambiguity and is supported by educational initiatives, is likely to be necessary for DMM in acute illness.
Mathematical BiosciencesA simple mathematical model of signaling resulting from the binding of lipopolysaccharide with Toll-like receptor 4 demonstrates inherent preconditioning behavior
39 Citations2008Béatrice Rivière, Yekaterina Epshteyn +2 more
Simulations suggest that a simplified model of LPS/TLR4 signaling can account for complex preconditioning phenomena without invoking a specific signaling inhibition mechanism, but rather based on the dynamics of the signaling response itself, as well as the timing and magnitude of the LPS stimuli.
AACN Clinical Issues Advanced Practice in Acute & Critical CareThe Puzzle of Sepsis
35 Citations2004Jane Cunneen, Martina Cartwright
The multimechanistic drotrecogin alfa (activated) has been shown to reduce mortality in the severely septic patient when combined with traditional treatment, and Therapies targeting improved oxygen and blood flow and reduction of apoptosis and free radicals are under investigation.
Annals of Otology Rhinology & LaryngologyBiosimulation of Inflammation and Healing in Surgically Injured Vocal Folds
34 Citations2010Nicole Y. K. Li‐Jessen, Yoram Vodovotz +2 more
A relatively simple ABM such as the one reported in this study can provide new understanding of laryngeal wound healing and generate working hypotheses for further wet-lab studies.
PubMedRole of receptor aggregation in triggering IgE-mediated reactions.
33 Citations1982Anne Kagey‐Sobotka, MacGlashan Dw +1 more
It is shown that for the simple antigens, both the release process and desensitization are a function of the number of cross-links present on the cell surface, and a mathematical model that quantitatively fits the experimental data is generated.
Journal of Pediatric SurgeryMathematical modeling in necrotizing enterocolitis—a new look at an ongoing problem
29 Citations2007Jeffrey S. Upperman, Victoria Camerini +9 more
European Journal of Clinical Microbiology & Infectious DiseasesIncreasing the Efficacy of Anti-Inflammatory Agents Used in the Treatment of Sepsis
27 Citations2003Peter C. Minneci, Katherine J. Deans +2 more
Variation in the risk of death due to sepsis provides a basis for the marked difference in the efficacy of these anti-inflammatory agents in preclinical and clinical trials over the last decade.
Expert Opinion on Investigational DrugsExperimental and emerging therapies for sepsis and septic shock
24 Citations2001Ramon Añel, Anand Kumar
The two novel therapies that have shown clear survival benefit in large, randomised, placebo-controlled, multi-centre trials, low-dose steroids and recombinant activated protein C are included.
The LaryngoscopeTranslational systems biology and voice pathophysiology
23 Citations2009Nicole Y. K. Li‐Jessen, Katherine Verdolini Abbott +4 more
It is suggested that a complementary, systems biology approach using computational modeling may help tackle biological complexity in order to improve ultimate patient care.
Clinics in Geriatric MedicineChronic Inflammation in Older People: Recognition, Consequences, and Potential Intervention
17 Citations1997Stanley P. Ballou, Irving Kushner
Treatment of chronic inflammation in the elderly is often difficult, requiring utmost care and close follow-up by a knowledgeable and dedicated physician, perhaps giving rise to the abnormal acute phase protein levels that are seen with increased frequency with aging.
Baillière s Clinical HaematologyNative cytokine antagonists
16 Citations1992James W. Larrick, Susan C. Wright
This chapter describes antibody inhibition of cytokines, the first example of one endogenous molecule directly blocking the binding of another molecule to its receptor: most forms of regulation occur through independent receptors.
Critical Care MedicineMeningococcal disease as a model to evaluate novel anti-sepsis strategies
9 Citations2000Jonathan Cohen
This work considers the appropriateness of meningococcemia as a clinical entity for the evaluation of anti-endotoxin agents and the extent to which the results can be extrapolated to adult populations with sepsis secondary to nosocomial infection.
Birkhäuser Basel eBooksDrugs in Inflammation
8 Citations1991
The authors present evidence for a key role of IL-1 in cartilage destruction in experimental arthritis and new treatments for Bone and Cartilage Loss in Rheumatoid Arthritis.
Regenerative MedicineInstitutional Profile: Mcgowan Institute for Regenerative Medicine
3 Citations2009Alan J. Russell
The McGowan Institute employs three main pillars of research from which to accelerate research and development in regenerative medicine: tissue engineering and biomaterials, cellular therapy, and medical devices and artificial organs.
…