Abstract:
:Today, in silico studies and trial simulations already complement experimental approaches in pharmaceutical R&D and have become indispensable tools for decision making and communication with regulatory agencies. While biology is multiscale by nature, project work, and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. We present a modeling and simulation software platform consisting of PK-Sim(®) and MoBi(®) capable of building and simulating models that integrate across biological scales. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization. Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression. In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials. The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drug-drug, or drug-metabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach.
journal_name
Front Physioljournal_title
Frontiers in physiologyauthors
Eissing T,Kuepfer L,Becker C,Block M,Coboeken K,Gaub T,Goerlitz L,Jaeger J,Loosen R,Ludewig B,Meyer M,Niederalt C,Sevestre M,Siegmund HU,Solodenko J,Thelen K,Telle U,Weiss W,Wendl T,Willmann S,Lippert Jdoi
10.3389/fphys.2011.00004subject
Has Abstractpub_date
2011-02-24 00:00:00pages
4issn
1664-042Xjournal_volume
2pub_type
杂志文章abstract::Background: Dental aberrations have been mentioned in relation to non-surgical hypoparathyroidism (Ns-HypoPT) and pseudohypoparathyroidism (PHP). However, a systematic review of dental characteristics have not been performed. The present systematic review describes the dental findings in patients with Ns-HypoPT and PH...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00701
更新日期:2018-06-19 00:00:00
abstract::This study was designed to investigate the effects of a newly synthesized carboxymethyl-glucan (CM-G) on blood pressure (BP), baroreflex sensitivity (BRS) and sympathetic vascular modulation in renovascular hypertensive rats. Male Wistar rats were divided into four groups: Sham (n = 10); 2K1C (subjected to renal arter...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00607
更新日期:2018-05-23 00:00:00
abstract::Glucose metabolism is a biologically important metabolic process. Glycogen synthase kinase (GSK-3) is a key enzyme located in the middle of the sugar metabolism pathway that can regulate the energy metabolism process in the body through insulin signaling. This paper mainly explores the regulatory effect of glycogen sy...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.518876
更新日期:2020-11-25 00:00:00
abstract::The vascular myogenic response is characterized by arterial constriction in response to an increase in intraluminal pressure and dilatation to a decrease in pressure. This mechanism is important for the regulation of blood flow, capillary pressure, and arterial pressure. The identity of the mechanosensory mechanism(s)...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2010.00165
更新日期:2010-12-29 00:00:00
abstract::Genome-wide association studies and physiological investigations have linked alterations in acid-base transporters to hypertension. Accordingly, Na(+)-coupled HCO(-) 3-transporters, Na(+)/H(+)-exchangers, and anion-exchangers have emerged as putative mechanistic components in blood pressure disturbances. Even though h...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2013.00388
更新日期:2013-12-24 00:00:00
abstract::To fully unravel the ixodid ticks' role as vectors of viral pathogens, their susceptibility to new control measures, and their ability to develop acaricide resistance, acclimatization of ticks under laboratory conditions is greatly needed. However, the unique and complicated feeding behavior of these ticks compared to...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2018.01728
更新日期:2018-12-04 00:00:00
abstract::Trace conditioning is a form of associative learning that can be induced by presenting a conditioned stimulus (CS) and an unconditioned stimulus (US) following each other, but separated by a temporal gap. This gap distinguishes trace conditioning from classical delay conditioning, where the CS and US overlap. To bridg...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2013.00067
更新日期:2013-08-23 00:00:00
abstract::Transport processes between aquaculture facilities activate the stress response in fish. To deal with these situations, the hypothalamic-pituitary-interrenal (HPI) axis releases cortisol, leading to an increase in circulating energy resources to restore homeostasis. However, if the allostatic load generated exceeds fi...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00612
更新日期:2019-05-31 00:00:00
abstract::Although motor output of the postural function clearly influences postural performance in young and older subjects, no relationship has been formally established between them. However, the relationship between lower-extremity muscle strength/power and postural performance is often pointed out, especially in older subj...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2017.00585
更新日期:2017-08-15 00:00:00
abstract::Background: High altitude (HA) exposure can lead to changes in resting heart rate variability (HRV), which may be linked to acute mountain sickness (AMS) development. Compared with traditional HRV measures, non-linear HRV appears to offer incremental and prognostic data, yet its utility and relationship to AMS have be...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00390
更新日期:2018-04-16 00:00:00
abstract::Myokines are peptides known to modulate brain neuroplasticity, adipocyte metabolism, bone mineralization, endothelium repair and cell growth arrest in colon and breast cancer, among other processes. Repeated skeletal muscle contraction induces the production and secretion of myokines, which have a wide range of functi...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2019.01463
更新日期:2019-11-28 00:00:00
abstract::Many studies have investigated the physiological response to microgravity in both astronauts and animals. However, while space agencies have sought to deploy more women on their missions; animal models rarely include females studies or comparisons between males and females. Therefore, we exposed adult female rats to 2...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00302
更新日期:2020-04-03 00:00:00
abstract::Mild normobaric hypoxia (NH) and modest exercise have multiple beneficial effects on health, but the changes in physiological function induced by NH and/or exercise remain unclear. The purpose of this investigation was to examine the specific effects of NH and/or exercise on cardiac function and myocardial structure a...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.01610
更新日期:2020-01-21 00:00:00
abstract::Objective: Unexpectedly wide distribution (<10 to >90%) of hemoglobin oxygen saturation (sO2) within red cell concentrates (RCCs) has recently been observed. Causes of such variability are not yet completely explained whereas the roles of oxygen and oxidative lesions during the storage of RCCs are known. The objective...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.616457
更新日期:2020-12-23 00:00:00
abstract::Human physiological signals are inherently rhythmic and have a hallmark feature in that even distant intrasignal measurements are related to each other. This relationship is termed long-range correlation and has been recognized as an indicator of the optimal state of the observed physiological systems, among which the...
journal_title:Frontiers in physiology
pub_type:
doi:10.3389/fphys.2020.00562
更新日期:2020-06-23 00:00:00
abstract::Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. Moderate HB can induce acute neurological disorders while severe HB has been linked to a higher incidence of apneas of prematurity. The present study aimed to test the hypothesis that even moderate HB disrupts cardiorespiratory control in preterm lambs. Two gr...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00437
更新日期:2016-09-30 00:00:00
abstract::Congenital haemolytic anaemias are inherited disorders caused by red blood cell membrane and cytoskeletal protein defects, deviant hemoglobin synthesis and metabolic enzyme deficiencies. In many cases, although the causing mutation might be known, the pathophysiology and the connection between the particular mutation ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00386
更新日期:2019-04-16 00:00:00
abstract::Biological aging is an inevitable part of life that has intrigued individuals for millennia. The progressive decline in biological systems impacts cardiac function and increases vulnerability to stress contributing to morbidity and mortality in aged individuals. Yet, our understanding of the molecular, biochemical and...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00048
更新日期:2020-02-07 00:00:00
abstract::To understand dynamic changes in polyamines (PAs) forms and components of polyamine metabolism in zoysiagrass (Zoysia japonica Steud.) response to salt stress with exogenous spermidine (Spd) application, two Chinese zoysia cultivars, z081 and z057, were exposed to sodium chloride stress for 2, 4, 6, and 8 days. The z0...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00208
更新日期:2017-04-06 00:00:00
abstract::Surface electromyography (sEMG) is a popular research tool in sport and rehabilitation sciences. Common study designs include the comparison of sEMG amplitudes collected from different muscles as participants perform various exercises and techniques under different loads. Based on such comparisons, researchers attempt...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2017.00985
更新日期:2018-01-04 00:00:00
abstract::To date, there has been no study on the long-term effects of resistance exercise on sarcopenia and obesity indices for people with sarcopenia. The present study thus aimed to determine the effect of 18 months of periodized, high-velocity/intensity/effort progressive resistance training (HIT-RT) on body composition and...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.01014
更新日期:2020-08-27 00:00:00
abstract::Microbiopsies of human skeletal muscle are increasingly adopted by physiologists for a variety of experimental assays given the reduced invasiveness of this procedure compared to the classic Bergstrom percutaneous biopsy technique. However, a recent report demonstrated lower mitochondrial respiration in saponin-permea...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2015.00360
更新日期:2015-12-18 00:00:00
abstract::The fluid transport and mixing induced by beating cilia, present in the bronchial airways, are studied using a coupled lattice Boltzmann-Immersed Boundary solver. This solver allows the simulation of both single and multi-component fluid flows around moving solid boundaries. The cilia are modeled by a set of Lagrangia...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00161
更新日期:2018-03-06 00:00:00
abstract::γ-Aminobutyric Acid (GABA) and its receptors, GABAA,B,C, are expressed in several locations along the gastrointestinal tract. Nevertheless, a role for GABA in enteric synaptic transmission remains elusive. In this study, we characterized the expression and function of GABA in the myenteric plexus of the mouse ileum. A...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00097
更新日期:2018-02-13 00:00:00
abstract::The aim of this study was to investigate the effects of two consecutive Crossfit® training sessions (24 h apart) designed to enhance work-capacity that involved both cardiovascular and muscular exercises on cytokines, muscle power, blood lactate and glucose. Nine male members of the CrossFit® community (age 26.7 ± 6.6...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00260
更新日期:2016-06-28 00:00:00
abstract::Mitochondria are the major source of superoxide radicals and superoxide overproduction contributes to cardiovascular diseases and metabolic disorders. Endothelial dysfunction and diminished nitric oxide levels are early steps in the development of these pathological conditions. It is known that physiological productio...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00907
更新日期:2017-11-07 00:00:00
abstract::Tumor necrosis factor (TNF)-α, a major part in inflammatory, infectious and tumor processes, and is pivotal at the early stages of gastric cancer. Relationship between its risk and TNF-α rs361525 polymorphism has been demonstrated, but remains conflicting and controversial. Therefore, a meta-analysis was conducted to ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00469
更新日期:2018-05-15 00:00:00
abstract:Introduction:MTHFR methylation status is associated with microvascular complications in diabetes, but the factors influencing this profile remain unknown. Objective:The aim of this study was to evaluate the influence of physical activity level and nutritional status on the methylation profile of the MTHFR gene in pati...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.618672
更新日期:2021-01-12 00:00:00
abstract::Adaptation of arm reaching in a novel force field involves co-contraction of upper limb muscles, but it is not known how the co-ordination of multiple muscle activation is orchestrated. We have used intermuscular coherence (IMC) to test whether a coherent intermuscular coupling between muscle pairs is responsible for ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00668
更新日期:2017-01-09 00:00:00
abstract::Signaling pathways of red blood cells' (RBCs) micromechanics regulation, which are responsible for maintaining microcirculation, constitute an important property of RBC physiology. Selective control over these processes may serve as an indispensable tool for correction of hemorheological disorders, which accompany a n...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00923
更新日期:2019-08-14 00:00:00