A lesson for cancer research : placental microarray gene analysis in preeclampsia

Tumor progression and pregnancy share many common features, such as immune tolerance and invasion. The invasion of trophoblasts in the placenta into the uterine wall is essential for fetal development, and is thus precisely regulated. Its deregulation has been implicated in preeclampsia, a leading cause for maternal and perinatal mortality and morbidity. Pathogenesis of preeclampsia remains to be defined. Microarray-based gene profiling has been widely used for identifying genes responsible for preeclampsia. In this review, we have summarized the recent data from the microarray studies with preeclamptic placentas. Despite the complex of gene signatures, suggestive of the heterogeneity of preeclampsia, these studies identified a number of differentially expressed genes associated with preeclampsia. Interestingly, most of them have been reported to be tightly involved in tumor progression. We have discussed these interesting genes and analyzed their potential molecular functions in preeclampsia, compared with their roles in malignancy development. Further investigations are warranted to explore the involvement in molecular network of each identified gene, which may provide not only novel strategies for prevention and therapy for preeclampsia but also a better understanding of cancer cells. The trophoblastic cells, with their capacity for proliferation and differentiation, apoptosis and survival, migration, angiogenesis and immune modulation by exploiting similar molecular pathways, make them a compelling model for cancer research

Modeling Cerebral Blood Flow Dependence on Carbon Dioxide and Mean Arterial Blood Pressure in the Immature Brain With Accounting for the Germinal Matrix

Intraventricular hemorrhage (IVH) is one of the most critical complications in the development of preterm infants. The likelihood of IVH is strongly associated with disturbances in cerebral blood flow (CBF) and with microvascular fragility in the germinal matrix (GM). The CBF value and its reactivity to changes in arterial carbon dioxide pressure (pCO2) and mean arterial blood pressure (MABP) are relevant indicators in the clinical assessment of preterm infants. The objective of the present study is mathematical modeling of the influence of pCO2 and MABP on CBF in immature brain, based on clinical data collected from 265 preterm infants with 23–30 gestational weeks. The model was adapted to the peculiarities of immature brain by taking into account the morphological characteristics of the GM capillary network and vascular reactivity, according to gestational and postnatal age. An analysis of model based values of CBF and its reactivity to changes in MABP and pCO2 was performed separately for each gestational week and for the first two days of life both for preterm infants with and without IVH. The developed model for the estimation of CBF was validated against equivalent experimental measurements taken from the literature. A good agreement between the estimated values of CBF, as well as its reaction on changes in MABP and pCO2 and the equivalent values obtained in experimental studies was shown

Germinal Matrix-Intraventricular Hemorrhage of the Preterm Newborn and Preclinical Models: Inflammatory Considerations

The germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most important complications of the preterm newborn. Since these children are born at a critical time in brain development, they can develop short and long term neurological, sensory, cognitive and motor disabilities depending on the severity of the GM-IVH. In addition, hemorrhage triggers a microglia-mediated inflammatory response that damages the tissue adjacent to the injury. Nevertheless, a neuroprotective and neuroreparative role of the microglia has also been described, suggesting that neonatal microglia may have unique functions. While the implication of the inflammatory process in GM-IVH is well established, the difficulty to access a very delicate population has lead to the development of animal models that resemble the pathological features of GM-IVH. Genetically modified models and lesions induced by local administration of glycerol, collagenase or blood have been used to study associated inflammatory mechanisms as well as therapeutic targets. In the present study we review the GM-IVH complications, with special interest in inflammatory response and the role of microglia, both in patients and animal models, and we analyze specific proteins and cytokines that are currently under study as feasible predictors of GM-IVH evolution and prognosis

Cell-Oriented Modeling of Angiogenesis

Due to its significant involvement in various physiological and pathological conditions, angiogenesis (the development of new blood vessels from an existing vasculature) represents an important area of the actual biological research and a field in which mathematical modeling proved particularly useful in supporting the experimental work. In this paper, we focus on a specific modeling strategy, known as “cell-centered” approach. This type of mathematical models work at a “mesoscopic scale,” assuming the cell as the natural level of abstraction for computational modeling of development. They treat cells phenomenologically, considering their essential behaviors to study how tissue structure and organization emerge from the collective dynamics of multiple cells. The main contributions of the cell-oriented approach to the study of the angiogenic process will be described. From one side, they have generated “basic science understanding” about the process of capillary assembly during development, growth, and pathology. On the other side, models were also developed supporting “applied biomedical research” for the purpose of identifying new therapeutic targets and clinically relevant approaches for either inhibiting or stimulating angiogenesis

Data-driven modelling of the FRC network for studying the fluid flow in the conduit system

The human immune system is characterized by enormous cellular and anatomical complexity. Lymph nodes are key centers of immune reactivity, organized into distinct structural and functional modules including the T-cell zone, fibroblastic reticular cell (FRC) network and the conduit system. A thorough understanding of the modular organization is a prerequisite for lymphoid organ tissue-engineering. Due to the biological complexity of lymphoid organs, the development of mathematical models capable of elaborating the lymph node architecture and functional organization, has remained a major challenge in computational biology. Here, we present a computational method to model the geometry of the FRC network and fluid flow in the conduit system. It differs from the blood vascular network image-based reconstruction approaches as it develops the parameterized geometric model using the real statistics of the node degree and the edge length distributions. The FRC network model is then used to analyze the fluid flow through the underlying conduit system. A first observation is that the pressure gradient is approximately linear, which suggests homogeneity of the network. Furthermore, calculated permeability values View the MathML source show the generated network is isotropic, while investigating random variations of pipe radii (with a given mean and standard deviation) shows a significant effect on the permeability. This framework can now be further explored to systematically correlate fundamental characteristics of the FRC conduit system to more global material properties such as permeability