Xiuwei Zhu

Publications (4)2.89 Total impact

• Article: Simulation of Arrhythmogenic Effect of Rogue RyRs in Failing Heart by Using a Coupled Model.

  Luyao Lu, Ling Xia, Xiuwei Zhu
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  ABSTRACT: Cardiac cells with heart failure are usually characterized by impairment of Ca(2+) handling with smaller SR Ca(2+) store and high risk of triggered activities. In this study, we developed a coupled model by integrating the spatiotemporal Ca(2+) reaction-diffusion system into the cellular electrophysiological model. With the coupled model, the subcellular Ca(2+) dynamics and global cellular electrophysiology could be simultaneously traced. The proposed coupled model was then applied to study the effects of rogue RyRs on Ca(2+) cycling and membrane potential in failing heart. The simulation results suggested that, in the presence of rogue RyRs, Ca(2+) dynamics is unstable and Ca(2+) waves are prone to be initiated spontaneously. These release events would elevate the membrane potential substantially which might induce delayed afterdepolarizations or triggered action potentials. Moreover, the variation of membrane potential depolarization is indicated to be dependent on the distribution density of rogue RyR channels. This study provides a new possible arrhythmogenic mechanism for heart failure from subcellular to cellular level.
  Computational and Mathematical Methods in Medicine 01/2012; 2012:183978. · 0.68 Impact Factor
• Source

  Available from: cinc.org

  Conference Proceeding: Sarcoplasmic reticulum luminal [Ca2+] regulates the spontaneous Ca2+ release events and consequently arrhythmia

  Luyao Lu, Ling Xia, Xiuwei Zhu
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  ABSTRACT: The role that sarcoplasmic reticulum (SR) luminal Ca²⁺ concentration plays in regulating ryanodine receptors (RyRs) is considered to be very important in process of cardiac excitation-contraction coupling. Here we developed a multi-scale mathematical model by coupling a two-dimensional spatio-temporal Ca²⁺ reaction-diffusion model with an action potential model of the ventricular myocyte. The simulation results showed that 1) the frequency of spontaneous sparks increased when SR Ca²⁺ content was elevated; 2) when SR Ca²⁺ was overloaded, spontaneous Ca²⁺ waves might occur without any external stimulus, and 3) once formed, the propagation of Ca²⁺ waves was accelerated as the SR Ca²⁺ content increased. Moreover, those spontaneously occurred Ca²⁺ release events elevated cytoplasmic [Ca²⁺]i and then activated inward currents which might cause a delayed afterdepolarization (DAD).
  Computing in Cardiology, 2010; 10/2010
• Source

  Available from: Michael Thane Lewis

  Article: Cancer stem cell, niche and EGFR decide tumor development and treatment response: A bio-computational simulation study.

  Xiuwei Zhu, Xiaobo Zhou, Michael T Lewis, Ling Xia, Stephen Wong
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  ABSTRACT: Recent research in cancer biology has suggested the hypothesis that tumors are initiated and driven by a small group of cancer stem cells (CSCs). Furthermore, cancer stem cell niches have been found to be essential in determining fates of CSCs, and several signaling pathways have been proven to play a crucial role in cellular behavior, which could be two important factors in cancer development. To better understand the progression, heterogeneity and treatment response of breast cancer, especially in the context of CSCs, we propose a mathematical model based on the cell compartment method. In this model, three compartments of cellular subpopulations are constructed: CSCs, progenitor cells (PCs), and terminal differentiated cells (TCs). Moreover, (1) the cancer stem cell niche is, considered by modeling its effect on division patterns (symmetric or asymmetric) of CSCs, and (2) the EGFR signaling pathway is integrated by modeling its role in cell proliferation, apoptosis. Our simulation results indicate that (1) a higher probability for symmetric division of CSC may result in a faster expansion of tumor population, and for a larger number of niches, the tumor grows at a slower rate, but the final tumor volume is larger; (2) higher EGFR expression correlates to tumors with larger volumes while a saturation function is observed, and (3) treatments that inhibit tyrosine kinase activity of EGFR may not only repress the tumor volume, but also decrease the CSCs percentages by shifting CSCs from symmetric divisions to asymmetric divisions. These findings suggest that therapies should be designed to effectively control or eliminate the symmetric division of CSCs and to reduce or destroy the CSC niches.
  Journal of Theoretical Biology 10/2010; 269(1):138-49. · 2.21 Impact Factor
• Chapter: A Mathematical Model of Myelodysplastic Syndromes: The Effect of Stem Cell Niches

  Xiuwei Zhu, Ling Xia, Luyao Lu
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  ABSTRACT: While myelodysplastic syndromes (MDS) are commonly observed nowadays, the underlying mechanisms remain unclear, not to mention mathematical models for MDS. In this work, by incorporating the concept of stem cell niches, we proposed a minimal mathematical model that can be used as a platform for studying the formation and treatment of MDS. Our model includes two main compartments: bone marrow and peripheral blood, in both compartment normal and abnormal cells exist. Simulation results show that 1) under normal condition, our model is robust to reproduce the hemopoiesis even with different perturbations; 2) by reducing stem cell niches, formation of MDS can be observed in our model; 3) treatments should be used to improve environment in bone marrow, rather than to kill the abnormal cells only. Keywordsmyelodysplastic syndrome-stem cell niche-bone marrow-peripheral blood
  09/2010: pages 395-403;