Biology subjects

Hosseini, S. A.

Publications and source records attributed to Hosseini, S. A..

4 recordsLinked to original sources

bioRxiv2026

HIPPOCAMPAL TAU RELATED SIGNAL INDEXES HYPEREXCITABILITY AND NREM SLEEP MEMORY DYSFUNCTION IN TEMPORAL LOBE EPILEPSY

Background Sleep and memory disturbances are common in temporal lobe epilepsy (TLE), yet their relationship with tau-targeted neuroimaging measures remains unclear. We investigated whether in-vivo temporal 18F-MK6240 tracer retention relates to seizure burden, non-rapid eye movement (NREM) sleep microstructure, and memory performance in TLE. Methods This cross-sectional study was conducted from 2019 to 2024 at the Montreal Neurological Institute-Hospital. Eligible patients had unilateral TLE diagnosed according to International League Against Epilepsy criteria and underwent overnight electroencephalography (EEG) recordings, research-protocol 3T magnetic resonance imaging, and 18F-MK6240 positron emission tomography. Regional 18F-MK6240 standardized uptake value ratios (SUVRs), using the cerebellum as the reference region, were quantified in the ipsilateral hippocampus (defined a priori as the primary region of interest), as well as in peri-hippocampal and lateral temporal regions. Electroclinical and neuropsychological measures, including seizure burden (high vs low), N2 interictal epileptiform discharge frequency (frequent vs non-frequent), and memory performance (impaired vs intact), were classified according to predefined clinical criteria. N2 spindle rate and N3 slow-wave rate were quantified from overnight EEG recordings. Findings Of 70 eligible patients, 25 were included (eight [32%] females; mean age 35.2 years [SD 12.1]). Higher ipsilateral hippocampal 18F-MK6240 uptake was observed in participants with greater focal seizure burden (median [IQR] 0.70 [0.67-0.78] vs 0.64 [0.58-0.65], rank-biserial correlation=-0.58, 95% CI -0.82 to -0.19; p=0.02), was associated with lower N2 spindle rate (r=-0.42, 95% CI -0.70 to -0.03; p=0.04) and higher N3 slow-wave rate (r=0.47; 95% CI 0.09 to 0.73; p=0.02), and was also higher in participants with impaired than intact memory performance (n=21; mean [SD] 0.80 [0.12] vs 0.68 [0.10], Cohen's d=1.15, 95% CI 0.07 to 2.21; p=0.04). Associations outside the hippocampus were generally less consistent and less precise, with the largest non-hippocampal estimate observed in peri-hippocampal regions. Interpretation Higher hippocampal 18F-MK6240 uptake was associated with greater focal seizure burden, altered NREM sleep microstructure, and impaired memory performance in TLE. These findings suggest that hippocampal 18F-MK6240 uptake may represent a candidate marker of circuit vulnerability associated with NREM sleep-memory dysfunction in TLE, warranting validation in larger longitudinal studies.

neuroscience↗

bioRxiv2025

Altered Dynamic Functional Connectivity of the Frontoparietal Network in Major Depressive Disorder: Evidence for Hypoconnectivity and Reduced State Transitions

Major depressive disorder (MDD) is a prevalent psychiatric condition characterized by affective disturbances and cognitive deficits. Among these, cognitive inflexibility and executive dysfunction are particularly prominent, yet the temporal dynamics of the frontoparietal control network (FPN), a core substrate of cognitive control, remain poorly understood. Using harmonized resting-state fMRI data from the REST-meta-MDD consortium (n = 887; 442 MDD, 445 healthy controls), we investigated dynamic functional connectivity (dFC) within the FPN. Time-varying correlations among 21 FPN nodes were estimated using a sliding-window approach and clustered via k-means to identify recurring connectivity states. Temporal metrics included fractional occupancy, mean dwell time, and transition counts. Three unique FPN states were recognized. In comparison to healthy individuals, those with Major Depressive Disorder (MDD) exhibited prolonged durations in a hypoconnected state, extended dwell times in this configuration, and fewer total transitions, indicating diminished neural flexibility. Direct transitions between low-connectivity (hypoconnected) and high-connectivity (hyperconnected) states were selectively diminished, indicating a disruption in the direct transition between two functionally distinct states of the FPN. Overall, these findings reveal a fundamental disruption in the temporal organization of frontoparietal connectivity in MDD, marked by predominant hypoconnectivity, reduced flexibility, and constrained state transitions. By delineating the dynamic properties of network function, this study advances a mechanistic framework for interpreting prior inconsistencies in static connectivity research and underscores the necessity of time-resolved approaches in characterizing large-scale network dysfunction in psychiatric disorders.

neuroscience↗

bioRxiv2024

A hybrid bioprinting-electrospinning platform integrating nanofibers and mesenchymal cell spheroids for customizable wound healing dressings

We introduce a platform for the fabrication of customizable wound healing dressing. The platform integrates electrospun nanofibers, bioprinted hydrogels, and cellular spheroids into hierarchical, fiber-reinforced hybrid constructs. The construct leverages the mechanical strength of polycaprolactone (PCL) nanofibers and the ECM-like properties of GelMA/PEGDA hydrogel. These materials support the incorporation of bone marrow-derived mesenchymal stem cell (BM-hMSC) spheroids, which act as a supportive "cell niche," enhancing the viability of the hMSC during and after bioprinting, and facilitating their spreading across the construct during the maturation phase. The characterization of the hybrid constructs demonstrated strong structural integrity and enhanced mechanical properties, making them well-suited for clinical wound dressing applications. In vitro assays, including live/dead staining, MTT assays, and scratch assays, revealed increased cell attachment, proliferation, and migration. The spheroids maintained their viability over extended periods, significantly contributing to wound closure in the scratch assay. This innovative approach, which combines electrospinning and light-based bioprinting, offers a promising strategy for the development of customizable wound dressings that closely adapt to the complex architecture of human skin. The bioprinting approach allows for the creation of tailored geometries for specific clinical requirements. Future research will focus on optimizing scaffold design and conducting long-term in vivo studies to validate the platforms clinical potential.

cell biology↗

bioRxiv2023

Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model

BackgroundCancer treatment resistance is a consequence of cell diversity and tumor heterogeneity. Tumor cell-cell and cell-microenvironment interactions significantly influence tumor progression and invasion, which have important implications for diagnosis, therapeutic treatment and chemoresistance. MethodIn this study, we develop 3D bioprinted in vitro models of the breast cancer tumor microenvironment (TME) made of co-cultured cells distributed in a hydrogel matrix with controlled architecture to model tumor heterogeneity. We hypothesize that the tumor could be represented by a cancer cell-laden co-culture hydrogel construct, whereas its microenvironment can be modeled in a microfluidic chip capable of producing a chemical gradient. Breast cancer cells (MCF7 and MDA-MB-231) and non-tumorigenic mammary epithelial cells (MCF10) were embedded in the alginate-gelatine hydrogels and printed using a multi-cartridge extrusion bioprinter. ResultsOur method gives special control on the cell positions in the co-culture system, whereas different tumor architectures can be designed. Cellularly heterogeneous samples comprised of two different cancer cells with controlled density are developed in specific initial locations, i.e. two cell types randomly mixed or positioned in sequential layers. A migration-inducing chemical microenvironment was created in a chamber with a gradual chemical gradient to study the cell migration in the complex tumor construct toward the chemoattractant. As a proof of concept, the different migration pattern of MC7 cells toward the epithelial growth factor gradient was studied with presence of MCF10 in different ratio in this device. ConclusionCombining 3D bioprinting with microfluidic device in our method provides a great tool to create different tumor architectures as can be seen in different patients, and study cancer cells behaviour with accurate special and temporal resolution.

bioengineering↗