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Biomechanical investigation on the influence of the regional material degeneration of an intervertebral disc in a lower lumbar spinal unit: A finite element study

Masni-Azian, Tanaka M

Comput Biol Med, 2018 07 01;98:26-38.
PMID: 29758454 DOI: 10.1016/j.compbiomed.2018.05.010

Intervertebral disc degeneration involves changes in its material properties that affect the mechanical functions of the spinal system. However, the alteration of the biomechanics of a spinal segment through specific material degradation in a specific region is poorly understood. In this study, the influence of the constitutive material degeneration of disc tissues on the mechanics of a lower lumbar spinal unit was examined using a three-dimensional nonlinear finite element model of the L4-L5 functional spinal unit. Different grades of disc degeneration were simulated by introducing a degeneration factor to the corresponding material properties to represent fibrous nucleus, increased fibre and ground substance laxity, increased fibre stiffness and total annular fracture along posterior and posterolateral regions. The model was loaded with an axial compression of 500 N and pure moments of up to 10 Nm to simulate extension, flexion, lateral bending and axial rotation. To validate the model, the spinal motion and intradiscal pressure of healthy and degenerated discs with existing in vitro data were compared. The disc with a fibrous nucleus and the presence of intradiscal pressure increase the spinal instability during flexion and axial rotation, and the absence of intradiscal pressure increases the spinal instability in all directions. Bulging displacement and shear strains in the disc with total fracture and ground substance laxity are high in all of the loading cases. Our study could provide useful information to enhance our understanding of the influence of each constitutive component of the intervertebral disc on the mechanics of the spinal segment.

Matched MeSH terms: Models, Biological
Finite element analysis of the wrist in stroke patients: the effects of hand grip

Ramlee MH, Beng GK, Bajuri N, Abdul Kadir MR

Med Biol Eng Comput, 2018 Jul;56(7):1161-1171.
PMID: 29209961 DOI: 10.1007/s11517-017-1762-3

The provision of the most suitable rehabilitation treatment for stroke patient remains an ongoing challenge for clinicians. Fully understanding the pathomechanics of the upper limb will allow doctors to assist patients with physiotherapy treatment that will aid in full arm recovery. A biomechanical study was therefore conducted using the finite element (FE) method. A three-dimensional (3D) model of the human wrist was reconstructed using computed tomography (CT)-scanned images. A stroke model was constructed based on pathological problems, i.e. bone density reductions, cartilage wane, and spasticity. The cartilages were reconstructed as per the articulation shapes in the joint, while the ligaments were modelled using linear links. The hand grip condition was mimicked, and the resulting biomechanical characteristics of the stroke and healthy models were compared. Due to the lower thickness of the cartilages, the stroke model reported a higher contact pressure (305 MPa), specifically at the MC1-trapezium. Contrarily, a healthy model reported a contact pressure of 228 MPa. In the context of wrist extension and displacement, the stroke model (0.68° and 5.54 mm, respectively) reported a lower magnitude than the healthy model (0.98° and 9.43 mm, respectively), which agrees with previously reported works. It was therefore concluded that clinicians should take extra care in rehabilitation treatment of wrist movement in order to prevent the occurrence of other complications. Graphical abstract ᅟ.

Matched MeSH terms: Models, Biological
Fulltext Cell entry of a host-targeting protein of oomycetes requires gp96

Trusch F, Loebach L, Wawra S, Durward E, Wuensch A, Iberahim NA, et al.

Nat Commun, 2018 06 14;9(1):2347.
PMID: 29904064 DOI: 10.1038/s41467-018-04796-3

The animal-pathogenic oomycete Saprolegnia parasitica causes serious losses in aquaculture by infecting and killing freshwater fish. Like plant-pathogenic oomycetes, S. parasitica employs similar infection structures and secretes effector proteins that translocate into host cells to manipulate the host. Here, we show that the host-targeting protein SpHtp3 enters fish cells in a pathogen-independent manner. This uptake process is guided by a gp96-like receptor and can be inhibited by supramolecular tweezers. The C-terminus of SpHtp3 (containing the amino acid sequence YKARK), and not the N-terminal RxLR motif, is responsible for the uptake into host cells. Following translocation, SpHtp3 is released from vesicles into the cytoplasm by another host-targeting protein where it degrades nucleic acids. The effector translocation mechanism described here, is potentially also relevant for other pathogen-host interactions as gp96 is found in both animals and plants.

Matched MeSH terms: Models, Biological
Fulltext The Protective Effects of a Synthetic Geranyl Acetophenone in a Cellular Model of TNF-α-Induced Pulmonary Epithelial Barrier Dysfunction

Sim TY, Harith HH, Tham CL, Md Hashim NF, Shaari K, Sulaiman MR, et al.

Molecules, 2018 Jun 05;23(6).
PMID: 29874809 DOI: 10.3390/molecules23061355

Alveolar epithelial barrier dysfunction contributes to lung edema and can lead to acute lung injury (ALI). The features include increased epithelial permeability, upregulation of inflammatory mediators and downregulation of junctional complex molecules; these changes are often induced by inflammation. tHGA is an acetophenone analogue with therapeutic potential in asthma. Its therapeutic potential in ALI is presently unknown. Herein, the effects of tHGA on epithelial barrier dysfunction were determined in TNF-α-induced human alveolar epithelial cells. The anti-inflammatory properties of tHGA were assessed by monocyte adhesion assay and analysis of MCP-1 and ICAM-1 expression. The epithelial barrier function was assessed by paracellular permeability and transepithelial electrical resistance (TEER) assays, and analysis of junctional complex molecules expression. To elucidate the mechanism of action, the effects of tHGA on the NF-κB and MAPK pathways were determined. Gene and protein expression were analyzed by RT-PCR and Western blotting or ELISA, respectively. tHGA suppressed leukocyte adhesion to TNF-α-induced epithelium and reduced MCP-1 and ICAM-1 gene expression and secretion. tHGA also increased TEER readings, reduced epithelial permeability and enhanced expression of junctional complex molecules (zona occludens-1, occludin and E-cadherin) in TNF-α-induced cells. Correspondingly, the NF-κB, ERK and p38 MAPK pathways were also inhibited by tHGA. These findings suggest that tHGA is able to preserve alveolar epithelial barrier function in response to acute inflammation, via its anti-inflammatory activity and stabilization of epithelial barrier integrity, mediated by NF-κB, ERK and p38 MAPK signaling.

Matched MeSH terms: Models, Biological*
The role of bevacizumab on tumour angiogenesis and in the management of gynaecological cancers: A review

Chellappan DK, Leng KH, Jia LJ, Aziz NABA, Hoong WC, Qian YC, et al.

Biomed Pharmacother, 2018 Jun;102:1127-1144.
PMID: 29710531 DOI: 10.1016/j.biopha.2018.03.061

OBJECTIVE: The study aims to analyze the effectiveness of bevacizumab in addressing the complications associated with gynecological cancers and evaluates effective treatments for various gynecological cancers.
METHODS: The study follows a systematic review approach that has been implemented to analyze the qualitative published data from previous studies. Studies related with the trials of angiogenesis and bevacizumab were selected in the review.
RESULTS: In general, the management of gynecological cancers include chemotherapy, surgery and radiation therapy. Results suggest bevacizumab as an effective treatment modality for cervical and several other cancers. Overall, bevacizumab showed promising results in improving the overall survival rate of gynecological cancer patients through the combination of bevacizumab with other chemotherapeutic agents.
CONCLUSION: Bevacizumab possess less documented adverse effects when compared to other chemotherapeutic agents. The manifestation and severity of adverse effects reported varied according to the chemotherapeutic agent(s) that were used with bevacizumab in combination therapy. Overall, bevacizumab effectively improved the survival rate in patients with several gynaecological cancers.

Matched MeSH terms: Models, Biological
Developmental Approach for Behavior Learning Using Primitive Motion Skills

Dawood F, Loo CK

Int J Neural Syst, 2018 May;28(4):1750038.
PMID: 29022403 DOI: 10.1142/S0129065717500381

Imitation learning through self-exploration is essential in developing sensorimotor skills. Most developmental theories emphasize that social interactions, especially understanding of observed actions, could be first achieved through imitation, yet the discussion on the origin of primitive imitative abilities is often neglected, referring instead to the possibility of its innateness. This paper presents a developmental model of imitation learning based on the hypothesis that humanoid robot acquires imitative abilities as induced by sensorimotor associative learning through self-exploration. In designing such learning system, several key issues will be addressed: automatic segmentation of the observed actions into motion primitives using raw images acquired from the camera without requiring any kinematic model; incremental learning of spatio-temporal motion sequences to dynamically generates a topological structure in a self-stabilizing manner; organization of the learned data for easy and efficient retrieval using a dynamic associative memory; and utilizing segmented motion primitives to generate complex behavior by the combining these motion primitives. In our experiment, the self-posture is acquired through observing the image of its own body posture while performing the action in front of a mirror through body babbling. The complete architecture was evaluated by simulation and real robot experiments performed on DARwIn-OP humanoid robot.

Matched MeSH terms: Models, Biological
Fate, uptake, and distribution of nanoencapsulated pesticides in soil-earthworm systems and implications for environmental risk assessment

Mohd Firdaus MA, Agatz A, Hodson ME, Al-Khazrajy OSA, Boxall ABA

Environ Toxicol Chem, 2018 05;37(5):1420-1429.
PMID: 29341233 DOI: 10.1002/etc.4094

Nanopesticides are novel plant protection products offering numerous benefits. Because nanoparticles behave differently from dissolved chemicals, the environmental risks of these materials could differ from conventional pesticides. We used soil-earthworm systems to compare the fate and uptake of analytical-grade bifenthrin to that of bifenthrin in traditional and nanoencapsulated formulations. Apparent sorption coefficients for bifenthrin were up to 3.8 times lower in the nano treatments than in the non-nano treatments, whereas dissipation half-lives of the nano treatments were up to 2 times longer. Earthworms in the nano treatments accumulated approximately 50% more bifenthrin than those in the non-nano treatments. In the non-nano treatments, most of the accumulated material was found in the earthworm tissue, whereas in the nano treatments, the majority resided in the gut. Evaluation of toxicokinetic modeling approaches showed that models incorporating the release rate of bifenthrin from the nanocapsule and distribution within the earthworm provided the best estimations of uptake from the nano-formulations. Overall, our findings indicate that the risks of nanopesticides may be different from those of conventional formulations. The modeling presented provides a starting point for assessing risks of these materials but needs to be further developed to better consider the behavior of the nanoencapsulated pesticide within the gut system. Environ Toxicol Chem 2018;37:1420-1429. © 2018 SETAC.

Matched MeSH terms: Models, Biological
Optimal approach for complete liver tumor ablation using radiofrequency ablation: a simulation study

Givehchi S, Wong YH, Yeong CH, Abdullah BJJ

Minim Invasive Ther Allied Technol, 2018 Apr;27(2):81-89.
PMID: 28612670 DOI: 10.1080/13645706.2017.1330757

PURPOSE: To investigate the effect of radiofrequency ablation (RFA) electrode trajectory on complete tumor ablation using computational simulation.
MATERIAL AND METHODS: The RFA of a spherical tumor of 2.0 cm diameter along with 0.5 cm clinical safety margin was simulated using Finite Element Analysis software. A total of 86 points inside one-eighth of the tumor volume along the axial, sagittal and coronal planes were selected as the target sites for electrode-tip placement. The angle of the electrode insertion in both craniocaudal and orbital planes ranged from -90° to +90° with 30° increment. The RFA electrode was simulated to pass through the target site at different angles in combination of both craniocaudal and orbital planes before being advanced to the edge of the tumor.
RESULTS: Complete tumor ablation was observed whenever the electrode-tip penetrated through the epicenter of the tumor regardless of the angles of electrode insertion in both craniocaudal and orbital planes. Complete tumor ablation can also be achieved by placing the electrode-tip at several optimal sites and angles.
CONCLUSIONS: Identification of the tumor epicenter on the central slice of the axial images is essential to enhance the success rate of complete tumor ablation during RFA procedures.

Matched MeSH terms: Models, Biological
Fulltext Assessing mechanical ventilation asynchrony through iterative airway pressure reconstruction

Chiew YS, Tan CP, Chase JG, Chiew YW, Desaive T, Ralib AM, et al.

Comput Methods Programs Biomed, 2018 Apr;157:217-224.
PMID: 29477430 DOI: 10.1016/j.cmpb.2018.02.007

BACKGROUND AND OBJECTIVE: Respiratory mechanics estimation can be used to guide mechanical ventilation (MV) but is severely compromised when asynchronous breathing occurs. In addition, asynchrony during MV is often not monitored and little is known about the impact or magnitude of asynchronous breathing towards recovery. Thus, it is important to monitor and quantify asynchronous breathing over every breath in an automated fashion, enabling the ability to overcome the limitations of model-based respiratory mechanics estimation during asynchronous breathing ventilation.
METHODS: An iterative airway pressure reconstruction (IPR) method is used to reconstruct asynchronous airway pressure waveforms to better match passive breathing airway waveforms using a single compartment model. The reconstructed pressure enables estimation of respiratory mechanics of airway pressure waveform essentially free from asynchrony. Reconstruction enables real-time breath-to-breath monitoring and quantification of the magnitude of the asynchrony (MAsyn).
RESULTS AND DISCUSSION: Over 100,000 breathing cycles from MV patients with known asynchronous breathing were analyzed. The IPR was able to reconstruct different types of asynchronous breathing. The resulting respiratory mechanics estimated using pressure reconstruction were more consistent with smaller interquartile range (IQR) compared to respiratory mechanics estimated using asynchronous pressure. Comparing reconstructed pressure with asynchronous pressure waveforms quantifies the magnitude of asynchronous breathing, which has a median value MAsyn for the entire dataset of 3.8%.
CONCLUSION: The iterative pressure reconstruction method is capable of identifying asynchronous breaths and improving respiratory mechanics estimation consistency compared to conventional model-based methods. It provides an opportunity to automate real-time quantification of asynchronous breathing frequency and magnitude that was previously limited to invasively method only.

Matched MeSH terms: Models, Biological*
Modelling the Impact of Different Tuberculosis Control Interventions on the Prevalence of Tuberculosis in an Overcrowded Prison

Naning H, Al-Darraji HAA, McDonald S, Ismail NA, Kamarulzaman A

Asia Pac J Public Health, 2018 04;30(3):235-243.
PMID: 29502429 DOI: 10.1177/1010539518757229

The aim of this study was to simulate the effects of tuberculosis (TB) treatment strategies interventions in an overcrowded and poorly ventilated prison with both high (5 months) and low (3 years) turnover of inmates against improved environmental conditions. We used a deterministic transmission model to simulate the effects of treatment of latent TB infection and active TB, or the combination of both treatment strategies. Without any intervention, the TB prevalence is estimated to increase to 8.8% for a prison with low turnover of inmates but modestly stabilize at 5.8% for high-turnover prisons in a 10-year period. Reducing overcrowding from 6 to 4 inmates per housing cell and increasing the ventilation rate from 2 to 12 air changes per hour combined with any treatment strategy would further reduce the TB prevalence to as low as 0.98% for a prison with low inmate turnover.

Matched MeSH terms: Models, Biological
Modeling of passengers' safety perception for buses on mountainous roads

Khoo HL, Ahmed M

Accid Anal Prev, 2018 Apr;113:106-116.
PMID: 29407657 DOI: 10.1016/j.aap.2018.01.025

This study had developed a passenger safety perception model specifically for buses taking into consideration the various factors, namely driver characteristics, environmental conditions, and bus characteristics using Bayesian Network. The behaviour of bus driver is observed through the bus motion profile, measured in longitudinal, lateral, and vertical accelerations. The road geometry is recorded using GPS and is computed with the aid of the Google map while the perceived bus safety is rated by the passengers in the bus in real time. A total of 13 variables were derived and used in the model development. The developed Bayesian Network model shows that the type of bus and the experience of the driver on the investigated route could have an influence on passenger's perception of their safety on buses. Road geometry is an indirect influencing factor through the driver's behavior. The findings of this model are useful for the authorities to structure an effective strategy to improve the level of perceived bus safety. A high level of bus safety will definitely boost passenger usage confidence which will subsequently increase ridership.

Matched MeSH terms: Models, Biological
Fulltext Effect of tropical forest disturbance on the competitive interactions within a diverse ant community

Gray REJ, Ewers RM, Boyle MJW, Chung AYC, Gill RJ

Sci Rep, 2018 03 23;8(1):5131.
PMID: 29572517 DOI: 10.1038/s41598-018-23272-y

Understanding how anthropogenic disturbance influences patterns of community composition and the reinforcing interactive processes that structure communities is important to mitigate threats to biodiversity. Competition is considered a primary reinforcing process, yet little is known concerning disturbance effects on competitive interaction networks. We examined how differences in ant community composition between undisturbed and disturbed Bornean rainforest, is potentially reflected by changes in competitive interactions over a food resource. Comparing 10 primary forest sites to 10 in selectively-logged forest, we found higher genus richness and diversity in the primary forest, with 18.5% and 13.0% of genera endemic to primary and logged respectively. From 180 hours of filming bait cards, we assessed ant-ant interactions, finding that despite considered aggression over food sources, the majority of ant interactions were neutral. Proportion of competitive interactions at bait cards did not differ between forest type, however, the rate and per capita number of competitive interactions was significantly lower in logged forest. Furthermore, the majority of genera showed large changes in aggression-score with often inverse relationships to their occupancy rank. This provides evidence of a shuffled competitive network, and these unexpected changes in aggressive relationships could be considered a type of competitive network re-wiring after disturbance.

Matched MeSH terms: Models, Biological*
Genome-scale metabolic models as platforms for identification of novel genes as antimicrobial drug targets

Mienda BS, Salihu R, Adamu A, Idris S

Future Microbiol, 2018 03;13:455-467.
PMID: 29469596 DOI: 10.2217/fmb-2017-0195

The growing number of multidrug-resistant pathogenic bacteria is becoming a world leading challenge for the scientific community and for public health. However, advances in high-throughput technologies and whole-genome sequencing of bacterial pathogens make the construction of bacterial genome-scale metabolic models (GEMs) increasingly realistic. The use of GEMs as an alternative platforms will expedite identification of novel unconditionally essential genes and enzymes of target organisms with existing and forthcoming GEMs. This approach will follow the existing protocol for construction of high-quality GEMs, which could ultimately reduce the time, cost and labor-intensive processes involved in identification of novel antimicrobial drug targets in drug discovery pipelines. We discuss the current impact of existing GEMs of selected multidrug-resistant pathogenic bacteria for identification of novel antimicrobial drug targets and the challenges of closing the gap between genome-scale metabolic modeling and conventional experimental trial-and-error approaches in drug discovery pipelines.

Matched MeSH terms: Models, Biological*
Fulltext Next-generation, personalised, model-based critical care medicine: a state-of-the art review of in silico virtual patient models, methods, and cohorts, and how to validation them

Chase JG, Preiser JC, Dickson JL, Pironet A, Chiew YS, Pretty CG, et al.

Biomed Eng Online, 2018 Feb 20;17(1):24.
PMID: 29463246 DOI: 10.1186/s12938-018-0455-y

Critical care, like many healthcare areas, is under a dual assault from significantly increasing demographic and economic pressures. Intensive care unit (ICU) patients are highly variable in response to treatment, and increasingly aging populations mean ICUs are under increasing demand and their cohorts are increasingly ill. Equally, patient expectations are growing, while the economic ability to deliver care to all is declining. Better, more productive care is thus the big challenge. One means to that end is personalised care designed to manage the significant inter- and intra-patient variability that makes the ICU patient difficult. Thus, moving from current "one size fits all" protocolised care to adaptive, model-based "one method fits all" personalised care could deliver the required step change in the quality, and simultaneously the productivity and cost, of care. Computer models of human physiology are a unique tool to personalise care, as they can couple clinical data with mathematical methods to create subject-specific models and virtual patients to design new, personalised and more optimal protocols, as well as to guide care in real-time. They rely on identifying time varying patient-specific parameters in the model that capture inter- and intra-patient variability, the difference between patients and the evolution of patient condition. Properly validated, virtual patients represent the real patients, and can be used in silico to test different protocols or interventions, or in real-time to guide care. Hence, the underlying models and methods create the foundation for next generation care, as well as a tool for safely and rapidly developing personalised treatment protocols over large virtual cohorts using virtual trials. This review examines the models and methods used to create virtual patients. Specifically, it presents the models types and structures used and the data required. It then covers how to validate the resulting virtual patients and trials, and how these virtual trials can help design and optimise clinical trial. Links between these models and higher order, more complex physiome models are also discussed. In each section, it explores the progress reported up to date, especially on core ICU therapies in glycemic, circulatory and mechanical ventilation management, where high cost and frequency of occurrence provide a significant opportunity for model-based methods to have measurable clinical and economic impact. The outcomes are readily generalised to other areas of medical care.

Matched MeSH terms: Models, Biological*
Fulltext Thymic involution and rising disease incidence with age

Palmer S, Albergante L, Blackburn CC, Newman TJ

Proc Natl Acad Sci U S A, 2018 02 20;115(8):1883-1888.
PMID: 29432166 DOI: 10.1073/pnas.1714478115

For many cancer types, incidence rises rapidly with age as an apparent power law, supporting the idea that cancer is caused by a gradual accumulation of genetic mutations. Similarly, the incidence of many infectious diseases strongly increases with age. Here, combining data from immunology and epidemiology, we show that many of these dramatic age-related increases in incidence can be modeled based on immune system decline, rather than mutation accumulation. In humans, the thymus atrophies from infancy, resulting in an exponential decline in T cell production with a half-life of ∼16 years, which we use as the basis for a minimal mathematical model of disease incidence. Our model outperforms the power law model with the same number of fitting parameters in describing cancer incidence data across a wide spectrum of different cancers, and provides excellent fits to infectious disease data. This framework provides mechanistic insight into cancer emergence, suggesting that age-related decline in T cell output is a major risk factor.

Matched MeSH terms: Models, Biological
Fulltext Nitrogen dynamics in flooded soil systems: an overview on concepts and performance of models

Nurulhuda K, Gaydon DS, Jing Q, Zakaria MP, Struik PC, Keesman KJ

J Sci Food Agric, 2018 Feb;98(3):865-871.
PMID: 28940491 DOI: 10.1002/jsfa.8683

Extensive modelling studies on nitrogen (N) dynamics in flooded soil systems have been published. Consequently, many N dynamics models are available for users to select from. With the current research trend, inclined towards multidisciplinary research, and with substantial progress in understanding of N dynamics in flooded soil systems, the objective of this paper is to provide an overview of the modelling concepts and performance of 14 models developed to simulate N dynamics in flooded soil systems. This overview provides breadth of knowledge on the models, and, therefore, is valuable as a first step in the selection of an appropriate model for a specific application. © 2017 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Matched MeSH terms: Models, Biological
Fulltext Suboptimal Acclimation of Photosynthesis to Light in Wheat Canopies

Townsend AJ, Retkute R, Chinnathambi K, Randall JWP, Foulkes J, Carmo-Silva E, et al.

Plant Physiol, 2018 Feb;176(2):1233-1246.
PMID: 29217593 DOI: 10.1104/pp.17.01213

Photosynthetic acclimation (photoacclimation) is the process whereby leaves alter their morphology and/or biochemistry to optimize photosynthetic efficiency and productivity according to long-term changes in the light environment. The three-dimensional architecture of plant canopies imposes complex light dynamics, but the drivers for photoacclimation in such fluctuating environments are poorly understood. A technique for high-resolution three-dimensional reconstruction was combined with ray tracing to simulate a daily time course of radiation profiles for architecturally contrasting field-grown wheat (Triticum aestivum) canopies. An empirical model of photoacclimation was adapted to predict the optimal distribution of photosynthesis according to the fluctuating light patterns throughout the canopies. While the photoacclimation model output showed good correlation with field-measured gas-exchange data at the top of the canopy, it predicted a lower optimal light-saturated rate of photosynthesis at the base. Leaf Rubisco and protein contents were consistent with the measured optimal light-saturated rate of photosynthesis. We conclude that, although the photosynthetic capacity of leaves is high enough to exploit brief periods of high light within the canopy (particularly toward the base), the frequency and duration of such sunflecks are too small to make acclimation a viable strategy in terms of carbon gain. This suboptimal acclimation renders a large portion of residual photosynthetic capacity unused and reduces photosynthetic nitrogen use efficiency at the canopy level, with further implications for photosynthetic productivity. It is argued that (1) this represents an untapped source of photosynthetic potential and (2) canopy nitrogen could be lowered with no detriment to carbon gain or grain protein content.

Matched MeSH terms: Models, Biological*
Fulltext Pulsatile stretch as a novel modulator of amyloid precursor protein processing and associated inflammatory markers in human cerebral endothelial cells

Gangoda SVS, Avadhanam B, Jufri NF, Sohn EH, Butlin M, Gupta V, et al.

Sci Rep, 2018 01 26;8(1):1689.
PMID: 29374229 DOI: 10.1038/s41598-018-20117-6

Amyloid β (Aβ) deposition is a hallmark of Alzheimer's disease (AD). Vascular modifications, including altered brain endothelial cell function and structural viability of the blood-brain barrier due to vascular pulsatility, are implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature are often not considered in in vitro models of the blood-brain barrier. We demonstrate, for the first time, that pulsatile stretch of brain vascular endothelial cells modulates amyloid precursor protein (APP) expression and the APP processing enzyme, β-secretase 1, eventuating increased-Aβ generation and secretion. Concurrent modulation of intercellular adhesion molecule 1 and endothelial nitric oxide synthase (eNOS) signaling (expression and phosphorylation of eNOS) in response to pulsatile stretch indicates parallel activation of endothelial inflammatory pathways. These findings mechanistically support vascular pulsatility contributing towards cerebral Aβ levels.

Matched MeSH terms: Models, Biological
Modeling and development of screen-printed impedance biosensor for cytotoxicity studies of lung carcinoma cells

Mansor AFM, Ibrahim I, Zainuddin AA, Voiculescu I, Nordin AN

Med Biol Eng Comput, 2018 Jan;56(1):173-181.
PMID: 29247387 DOI: 10.1007/s11517-017-1756-1

Electrical cell-substrate impedance sensing (ECIS) is a powerful technique to monitor real-time cell behavior. In this study, an ECIS biosensor formed using two interdigitated electrode structures (IDEs) was used to monitor cell behavior and its response to toxicants. Three different sensors with varied electrode spacing were first modeled using COMSOL Multiphysics and then fabricated and tested. The silver/silver chloride IDEs were fabricated using a screen-printing technique and incorporated with polydimethylsiloxane (PDMS) cell culture wells. To study the effectiveness of the biosensor, A549 lung carcinoma cells were seeded in the culture wells together with collagen as an extracellular matrix (ECM) to promote cell attachment on electrodes. A549 cells were cultured in the chambers and impedance measurements were taken at 12-h intervals for 120 h. Cell index (CI) for both designs were calculated from the impedance measurement and plotted in comparison with the growth profile of the cells in T-flasks. To verify that the ECIS biosensor can also be used to study cell response to toxicants, the A549 cells were also treated with anti-cancer drug, paclitaxel, and its responses were monitored over 5 days. Both simulation and experimental results show better sensitivity for smaller spacing between electrodes. Graphical abstract The fabricated impedance biosensor used screen-printed silver/silver chloride IDEs. Simulation and experimental results show better sensitivity for smaller between electrodes.

Matched MeSH terms: Models, Biological*
Fulltext Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity

Maherally Z, Fillmore HL, Tan SL, Tan SF, Jassam SA, Quack FI, et al.

FASEB J, 2018 01;32(1):168-182.
PMID: 28883042 DOI: 10.1096/fj.201700162R

The blood-brain barrier (BBB) consists of endothelial cells, astrocytes, and pericytes embedded in basal lamina (BL). Most in vitro models use nonhuman, monolayer cultures for therapeutic-delivery studies, relying on transendothelial electrical resistance (TEER) measurements without other tight-junction (TJ) formation parameters. We aimed to develop reliable, reproducible, in vitro 3-dimensional (3D) models incorporating relevant human, in vivo cell types and BL proteins. The 3D BBB models were constructed with human brain endothelial cells, human astrocytes, and human brain pericytes in mono-, co-, and tricultures. TEER was measured in 3D models using a volt/ohmmeter and cellZscope. Influence of BL proteins-laminin, fibronectin, collagen type IV, agrin, and perlecan-on adhesion and TEER was assessed using an electric cell-substrate impedance-sensing system. TJ protein expression was assessed by Western blotting (WB) and immunocytochemistry (ICC). Perlecan (10 µg/ml) evoked unreportedly high, in vitro TEER values (1200 Ω) and the strongest adhesion. Coculturing endothelial cells with astrocytes yielded the greatest resistance over time. ICC and WB results correlated with resistance levels, with evidence of prominent occludin expression in cocultures. BL proteins exerted differential effects on TEER, whereas astrocytes in contact yielded higher TEER values and TJ expression.-Maherally, Z., Fillmore, H. L., Tan, S. L., Tan, S. F., Jassam, S. A., Quack, F. I., Hatherell, K. E., Pilkington, G. J. Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity.

Matched MeSH terms: Models, Biological

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