scholarly journals Current model systems for the study of preeclampsia

2018 ◽  
Vol 243 (6) ◽  
pp. 576-585 ◽  
Author(s):  
ML Martinez-Fierro ◽  
GP Hernández-Delgadillo ◽  
V Flores-Morales ◽  
E Cardenas-Vargas ◽  
M Mercado-Reyes ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
In Silico ◽  
Complex Disease ◽  
Model Systems ◽  
Trophoblast Invasion ◽  
Wide Range ◽  
In Silico Models

Preeclampsia (PE) is a pregnancy complex disease, distinguished by high blood pressure and proteinuria, diagnosed after the 20th gestation week. Depending on the values of blood pressure, urine protein concentrations, symptomatology, and onset of disease there is a wide range of phenotypes, from mild forms developing predominantly at the end of pregnancy to severe forms developing in the early stage of pregnancy. In the worst cases severe forms of PE could lead to systemic endothelial dysfunction, eclampsia, and maternal and/or fetal death. Worldwide the fetal morbidity and mortality related to PE is calculated to be around 8% of the total pregnancies. PE still being an enigma regarding its etiology and pathophysiology, in general a deficient trophoblast invasion during placentation at first stage of pregnancy, in combination with maternal conditions are accepted as a cause of endothelial dysfunction, inflammatory alterations and appearance of symptoms. Depending on the PE multifactorial origin, several in vitro, in vivo, and in silico models have been used to evaluate the PE pathophysiology as well as to identify or test biomarkers predicting, diagnosing or prognosing the syndrome. This review focuses on the most common models used for the study of PE, including those related to placental development, abnormal trophoblast invasion, uteroplacental ischemia, angiogenesis, oxygen deregulation, and immune response to maternal–fetal interactions. The advances in mathematical and computational modeling of metabolic network behavior, gene prioritization, the protein–protein interaction network, the genetics of PE, and the PE prediction/classification are discussed. Finally, the potential of these models to enable understanding of PE pathogenesis and to evaluate new preventative and therapeutic approaches in the management of PE are also highlighted. Impact statement This review is important to the field of preeclampsia (PE), because it provides a description of the principal in vitro, in vivo, and in silico models developed for the study of its principal aspects, and to test emerging therapies or biomarkers predicting the syndrome before their evaluation in clinical trials. Despite the current advance, the field still lacking of new methods and original modeling approaches that leads to new knowledge about pathophysiology. The part of in silico models described in this review has not been considered in the previous reports.

In Silico Assessment of ADME Properties: Advances in Caco-2 Cell Monolayer Permeability Modeling

2019 ◽  
Vol 18 (26) ◽  
pp. 2209-2229 ◽  
Author(s):  
Hai Pham-The ◽  
Miguel Á. Cabrera-Pérez ◽  
Nguyen-Hai Nam ◽  
Juan A. Castillo-Garit ◽  
Bakhtiyor Rasulev ◽  
...  
Keyword(s):  
Intestinal Absorption ◽  
In Silico ◽  
Review Paper ◽  
Cell Monolayer ◽  
Cell Permeability ◽  
Drug Substances ◽  
Wide Range ◽  
Modeling Techniques

One of the main goals of in silico Caco-2 cell permeability models is to identify those drug substances with high intestinal absorption in human (HIA). For more than a decade, several in silico Caco-2 models have been made, applying a wide range of modeling techniques; nevertheless, their capacity for intestinal absorption extrapolation is still doubtful. There are three main problems related to the modest capacity of obtained models, including the existence of inter- and/or intra-laboratory variability of recollected data, the influence of the metabolism mechanism, and the inconsistent in vitro-in vivo correlation (IVIVC) of Caco-2 cell permeability. This review paper intends to sum up the recent advances and limitations of current modeling approaches, and revealed some possible solutions to improve the applicability of in silico Caco-2 permeability models for absorption property profiling, taking into account the above-mentioned issues.

scholarly journals Replacement Strategies for Animal Studies in Inhalation Testing

2021 ◽  
Author(s):  
Eleonore Fröhlich
Keyword(s):  
Animal Models ◽  
In Silico ◽  
Particle Deposition ◽  
Drug Testing ◽  
Animal Studies ◽  
Inhalation Exposure ◽  
The Future ◽  
In Silico Models

Testing in animals is mandatory in drug testing and the gold standard for evaluation of toxicity. This situation is expected to change in the future because the 3Rs principle, which stands for replacement, reduction and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animals experiments have increased. The necessity to develop and use of alternatives is influenced by the complexity of the research topic and also by the fact, to which extent the currently used animal models can mimic human physiology and/or exposure. Rodent lung morphology and physiology differs markedly for that of humans and inhalation exposure of the animals are challenging. In vitro and in silico methods can assess important aspects of the in vivo action, namely particle deposition, dissolution, action at and permeation across the respiratory barrier and pharmacokinetics. Out of the numerous homemade in vitro and in silico models some are available commercially or open access. This review discusses limitations of animal models and exposure systems and proposes a panel of in vitro and in silico techniques that, in the future, may replace animal experimentation in inhalation testing.

In-Silico Modeling in Drug Metabolism and Interaction: Current Strategies of Lead Discovery

2019 ◽  
Vol 25 (31) ◽  
pp. 3292-3305 ◽  
Author(s):  
Harekrishna Roy ◽  
Sisir Nandi
Keyword(s):  
Drug Metabolism ◽  
In Silico ◽  
Physiological Status ◽  
Lead Discovery ◽  
Drug Molecules ◽  
Drug Biotransformation ◽  
In Silico Models ◽  
Precise Simulation

Background: Drug metabolism is a complex mechanism of human body systems to detoxify foreign particles, chemicals, and drugs through bio alterations. It involves many biochemical reactions carried out by invivo enzyme systems present in the liver, kidney, intestine, lungs, and plasma. After drug administration, it crosses several biological membranes to reach into the target site for binding and produces the therapeutic response. After that, it may undergo detoxification and excretion to get rid of the biological systems. Most of the drugs and its metabolites are excreted through kidney via urination. Some drugs and their metabolites enter into intestinal mucosa and excrete through feces. Few of the drugs enter into hepatic circulation where they go into the intestinal tract. The drug leaves the liver via the bile duct and is excreted through feces. Therefore, the study of total methodology of drug biotransformation and interactions with various targets is costly. Methods: To minimize time and cost, in-silico algorithms have been utilized for lead-like drug discovery. Insilico modeling is the process where a computer model with a suitable algorithm is developed to perform a controlled experiment. It involves the combination of both in-vivo and in-vitro experimentation with virtual trials, eliminating the non-significant variables from a large number of variable parameters. Whereas, the major challenge for the experimenter is the selection and validation of the preferred model, as well as precise simulation in real physiological status. Results: The present review discussed the application of in-silico models to predict absorption, distribution, metabolism, and excretion (ADME) properties of drug molecules and also access the net rate of metabolism of a compound. Conclusion: : It helps with the identification of enzyme isoforms; which are likely to metabolize a compound, as well as the concentration dependence of metabolism and the identification of expected metabolites. In terms of drug-drug interactions (DDIs), models have been described for the inhibition of metabolism of one compound by another, and for the compound–dependent induction of drug-metabolizing enzymes.

AhR Agonist Activity Confirmation of Polyhalogenated Carbazoles (PHCZs) Using an Integration of in Vitro, in Vivo, and in Silico Models

2019 ◽  
Vol 53 (24) ◽  
pp. 14716-14723 ◽  
Author(s):  
Chenyang Ji ◽  
Chao Shen ◽  
Yixi Zhou ◽  
Kongyang Zhu ◽  
Zhe Sun ◽  
...  
Keyword(s):  
In Silico ◽  
Agonist Activity ◽  
In Silico Models

scholarly journals Organs-on-a-Chip Module: A Review from the Development and Applications Perspective

Micromachines ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 536 ◽  
Author(s):  
Juan Eduardo Sosa-Hernández ◽  
Angel M. Villalba-Rodríguez ◽  
Kenya D. Romero-Castillo ◽  
Mauricio A. Aguilar-Aguila-Isaías ◽  
Isaac E. García-Reyes ◽  
...  
Keyword(s):  
Model Systems ◽  
Proper Function ◽  
Future Research ◽  
High Tech ◽  
In Vivo Models ◽  
Engineering Research ◽  
Microfluidic Technology ◽  
Wide Range

In recent years, ever-increasing scientific knowledge and modern high-tech advancements in micro- and nano-scales fabrication technologies have impacted significantly on various scientific fields. A micro-level approach so-called “microfluidic technology” has rapidly evolved as a powerful tool for numerous applications with special reference to bioengineering and biomedical engineering research. Therefore, a transformative effect has been felt, for instance, in biological sample handling, analyte sensing cell-based assay, tissue engineering, molecular diagnostics, and drug screening, etc. Besides such huge multi-functional potentialities, microfluidic technology also offers the opportunity to mimic different organs to address the complexity of animal-based testing models effectively. The combination of fluid physics along with three-dimensional (3-D) cell compartmentalization has sustained popularity as organ-on-a-chip. In this context, simple humanoid model systems which are important for a wide range of research fields rely on the development of a microfluidic system. The basic idea is to provide an artificial testing subject that resembles the human body in every aspect. For instance, drug testing in the pharma industry is crucial to assure proper function. Development of microfluidic-based technology bridges the gap between in vitro and in vivo models offering new approaches to research in medicine, biology, and pharmacology, among others. This is also because microfluidic-based 3-D niche has enormous potential to accommodate cells/tissues to create a physiologically relevant environment, thus, bridge/fill in the gap between extensively studied animal models and human-based clinical trials. This review highlights principles, fabrication techniques, and recent progress of organs-on-chip research. Herein, we also point out some opportunities for microfluidic technology in the future research which is still infancy to accurately design, address and mimic the in vivo niche.

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