Biology subjects

Douaki, A.

Publications and source records attributed to Douaki, A..

3 recordsLinked to original sources

bioRxiv2025

ADAMTS3 as a promising novel biomarker for the diagnosis of hepatocellular carcinoma

Early diagnosis of hepatocellular carcinoma (HCC) still represents a significant challenge. The rising of obesity and non-viral liver disease associated HCC further limits the effectiveness of conventional screening approaches such as ultrasonography and alpha-fetoprotein (AFP) testing. In this context, the identification of potential effective biomarkers for rapid and precise diagnosis of HCC still represents an extremely important task. Here, we identify ADAMTS3 as a novel mechanistic serum biomarker for HCC that addresses this shifting etiological landscape. Transcriptome analysis of four independent cohorts-including HCC patients, individuals with obesity-or non-viral liver disease, and healthy controls- reveals four secreted proteins associated with HCC progression. Among them, ADAMTS3 demonstrates strong diagnostic performance by ROC (receiver operating characteristic) and LASSO (least absolute shrinkage and selection operator) analysis. High ADAMTS3 expression correlates with aggressive molecular signature, characterized by enhanced proliferative signaling, suppressed immune effector responses, and a reprogrammed immune microenvironment marked by reduced NK cell infiltration and increased accumulation of immunosuppressive tumor-associated macrophages, driven by extracellular matrix stiffening. Knockdown of ADAMTS3 in cell lines significantly reduced proliferation, and clonogenic potential. Reintroduction of ADAMTS3 partially rescued both phenotypes, further confirming its role in promoting HCC cell growth. Optical tweezer-based measurements further reveal reduced cell stiffness upon ADAMTS3 deficiency, highlighting its role in extracellular matrix (ECM) remodeling. Finally, to provide a simple strategy for HCC diagnosis based on this novel biomarker, we demonstrated a DNA origami-based SERS biosensor capable of detecting ADAMTS3 at 10-11 M. Together, these findings identify ADAMTS3 as a mechanistic biomarker and demonstrate a translational sensing strategy for non-invasive HCC early screening.

cancer biology↗

bioRxiv2023

Theoretical Analysis of Divalent Cation Effects on Aptamer Recognition of Neurotransmitter Targets

Aptamer-based sensing of small molecules such as dopamine and serotonin in the brain, requires characterization of the specific aptamer sequences in solutions mimicking the in vivo environment with physiological ionic concentrations. In particular, divalent cations (Mg2+ and Ca2+) present in brain fluid, have been shown to affect the conformational dynamics of aptamers upon target recognition. Thus, for biosensors that transduce aptamer structure switching as the signal response, it is critical to interrogate the influence of divalent cations on each unique aptamer sequence. Herein, we demonstrate the potential of molecular dynamics (MD) simulations to predict the behaviour of dopamine and serotonin aptamers on sensor surfaces. The simulations enable molecular-level visualization of aptamer conformational changes that, in some cases, are significantly influenced by divalent cations. The correlations of theoretical simulations with experimental findings validate the potential for MD simulations to predict aptamer-specific behaviors on biosensors.

neuroscience↗

bioRxiv2023

Aptamer Conformational Dynamics Modulate Neurotransmitter Sensing in Nanopores

Aptamers that undergo conformational changes upon small-molecule recognition have been shown to gate the ionic flux through nanopores by rearranging charge density within the aptamer-occluded orifice. However, mechanistic insight into such systems where biomolecular interactions are confined in nanoscale spaces, is limited. To understand the fundamental mechanisms that facilitate the detection of small-molecule analytes inside structure-switching aptamer-modified nanopores, we correlated experimental observations to theoretical models. We developed a dopamine aptamer-functionalized nanopore sensor with femtomolar detection limits and compared the sensing behavior with a serotonin sensor fabricated with the same methodology. When sensing these two neurotransmitters with comparable mass and equal charge, the sensors showed an opposite electronic behavior. This distinctive phenomenon was extensively studied using complementary experimental techniques such as quartz crystal microbalance with dissipation monitoring, in combination with theoretical assessment by the finite element method and molecular dynamic simulations. Taken together, our studies demonstrate that the sensing behavior of aptamer-modified nanopores in detecting specific small-molecule analytes correlates to the structure-switching mechanisms of individual aptamers. We believe that such investigations not only improve our understanding of the complex interactions occurring in confined nanoscale environments, but will also drive further innovations in biomimetic nanopore technologies.

neuroscience↗