Biology subjects

Mikhailova, E.

Publications and source records attributed to Mikhailova, E..

4 recordsLinked to original sources

bioRxiv2023

A 3D microtumour system that faithfully represents ovarian cancer minimal residual disease

BackgroundBulk cancer and minimal residual disease (MRD) are characterised by different molecular drivers and therefore necessitate different therapeutic strategies. However, there are currently no 3D models that can faithfully recapitulate MRD ex vivo for therapy development. MethodsA microfluidic technique was implemented to construct 3D microtumours, in which tumour cells, either by themselves or with fibroblasts, were encapsulated in viscous hydrogels. The 3D microtumours were analysed for their response to first-line chemotherapeutics and characterised through RNA-Seq, by comparing them to both 2D cultures and clinical samples. ResultsOur microfluidic platform guarantees the fabrication of 3D microtumours of tailorable size and cell content, which recreate key features of tumours such as hypoxia, characteristic organization of the cytoskeleton and a dose-response to chemotherapeutics close to the physiological range. The 3D microtumours were also used to examine non-genetic heterogeneity in ovarian cancer and could fully reflect the recently described "Oxford Classic" five molecular signatures. The gene expression profile of 3D microtumours following chemotherapy treatment closely resembled that of MRD in ovarian cancer patients, showing the upregulation of genes involved in fatty acid metabolism. We demonstrate that these 3D microtumours are ideal for drug development by showing how they support the identification of a promising inhibitor of fatty acid oxidation, perhexiline, which specifically targets chemotherapy-resistant MRD ovarian cancer cells and not bulk cancer cells. ConclusionWe have obtained the first 3D model of ovarian cancer MRD by using microtumours generated through microfluidics. This system is ideal for high-throughput drug screening and, given its versatility, it can be readily extended to additional types of cancer, as well as accommodate multiple cell types to generate complex tumour microenvironments.

cancer biology↗

bioRxiv2022

Functional Integration of 3D-Printed Cerebral Cortical Tissue into a Brain Lesion

Engineering human tissue with diverse cell types and desired cellular architectures and functions is a considerable challenge. The cerebral cortex, which has a layered cellular architecture composed of layer-specific neurons organised into vertical columns, delivers higher cognition through intricately wired neural circuits. However, current tissue engineering approaches cannot produce such structures. Here, we use a droplet printing technique to fabricate tissues comprising simplified cerebral cortical columns. Human induced pluripotent stem cells (hiPSCs) were differentiated into upper- and deep-layer neural progenitors, which were then printed to form cerebral cortical tissues with a two-layer organization. The tissues showed layer-specific biomarker expression and developed an integrated network of processes. Implantation of the printed cortical tissues into mouse brain explants resulted in substantial implant-host integration across the tissue boundaries as demonstrated by the projection of processes, the migration of neurons and the appearance of correlated Ca2+ signals. The approach we have developed might be used for the evaluation of drugs and nutrients that promote tissue integration. Importantly, our approach might be applied in personalised implantation treatments that restore the cellular structure and function of a damaged brain by using 3D tissues derived from a patients own iPSCs.

bioengineering↗

bioRxiv2018

Facial Emotions Perceptions In Young Female Students With High-Level Anxiety And Subclinical Panic Disorder. ERP And Behavioral Study

ABSRACTThis study investigated facial emotion processing in non-medicated young students (girls) with panic disorder. 13 young girls with panic disorder and 14 matched healthy controls were recruited. Evoked potential (EP) components P100, N150, and P300 in the posterior areas, and N200, P300, and late negativity were evaluated while the participants recognize angry, fearful, happy, and neutral facial stimuli. The girls with panic disorder showed increased levels of situational anxiety compared to healthy controls. EP demonstrated an increased reactivity to facial expression at sensory stage (P100 component), in particular, on angry faces, that indicates a shift automated attention on threat facial stimuli. The increased reactivity was also found in later processing, corresponding to the P300 component, reflecting an enhanced selective attention to socially important events. In subjects with panic disorder, we also found signs of increased activation in the right temporal area in the P300 time window, and the increased late frontal negativity in 350-450 ms time window. It can be assumed, that altered functional state of the prefrontal regions results in reduced top-down modulating effects on the lower limbic and sensory cortex levels.

neuroscience↗

bioRxiv2018

Effects of line orientation in visual evoked potentials. Spatial dynamics, and gender differences of neural oblique effect.

The aim of the study was to investigate neural mechanisms of orientation discrimination in humans by recording the 128-channel event-related potentials (ERPs) of the brain. Stimuli were black-and-white gratings having four orientations: horizontal, vertical, and oblique 45 and 135 deg. from vertical. Thirty-five healthy subjects (16 males, 19 females) participating in the experiments were asked to differentiate the orientations and push the button. The results showed that the orientation processing consists of two main stages. In the occipital, parietal and temporal areas the P100 and N150 components reflecting the early perceptual stage of processing showed amplitudes greater for oblique orientations than for cardinal ones - \"inverse\" oblique effect. Further, in the central-parietal and frontal areas the P300 and N400 components reflecting the later cognitive stage of processing showed the \"classic\" oblique effect with greater amplitudes for cardinal orientations. Females demonstrated lower ERP amplitudes and less pronounced differences between responses elicited by cardinal and oblique orientations. The results suggest that in humans the orientation discrimination occurs in a distributed neural network involving the early sensory as well as higher anterior cortical areas. The classic behavioral oblique effect might be controlled by later processing in the anterior cortical areas. The insufficient neural orientation selectivity observed in females may be considered as the biological basis of their poorer visuospatial abilities.

neuroscience↗