Biology subjects

Luz, I.

Publications and source records attributed to Luz, I..

3 recordsLinked to original sources

bioRxiv2026

Neuroblastoma-derived Extracellular Vesicles Disrupt the Integrity of Central Nervous System Barriers via Tight Junction Modulation

Neuroblastoma (NB) is a pediatric malignancy that predominantly affects young children and can be associated with neurological complications even in the absence of direct central nervous system (CNS) invasion. The CNS is protected by specialized endothelial barriers whose integrity depends on tightly regulated intercellular junctions and extracellular matrix homeostasis. Here, we investigated whether extracellular vesicles (EVs) released by NB cells contribute to CNS endothelial barrier dysfunction and examined the underlying molecular mechanisms.

cancer biology↗

bioRxiv2026

β-endorphin primes NK cells and NK-derived Extracellular Vesicle to enhance anti-tumor cytotoxicity

Psychoneuroimmunology suggests that positive physiological states, including laughter, could affect anti-tumor immunity, but the underlying mechanisms remain unclear. Here, we investigated whether {beta}-endorphin (BE), an endogenous opioid peptide associated with positive physiological stimuli, modulates Natural Killer (NK) cell cytotoxicity and the anti-tumor activity of NK-derived extracellular vesicles (EVs). Using NK-92 cells, we assessed cytotoxicity against JIMT1 breast cancer cells, CD107a mobilization, cytotoxic activity of conditioned medium (CM), and EV yield, cargo, and function. BE enhanced NK-92-mediated killing of JIMT1 cells without increasing CD107a mobilization, suggesting that improved cytotoxicity was not driven by classical degranulation. Consistently, CM from BE-treated NK cells retained contact-independent cytotoxicity. NK-EVs were enriched in granzyme B and perforin following BE treatment exhibiting enhanced cytotoxicity against JIMT1 and BW tumor cells. BE also increased the cytotoxic activity of primary human NK cells, and BE-conditioned NK-EVs primed naive NK-92 cells for enhanced tumor killing. These findings indicate that BE enhances NK anti-tumor immunity by remodeling the cytotoxic secretome and generating EVs that act as both direct cytotoxic effectors and mediators of NK cell priming. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=119 HEIGHT=200 SRC="FIGDIR/small/741417v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1c1dfc5org.highwire.dtl.DTLVardef@14a190eorg.highwire.dtl.DTLVardef@1b32665org.highwire.dtl.DTLVardef@9db6e3_HPS_FORMAT_FIGEXP M_FIG C_FIG Proposed neuroendocrine-immune model linking positive physiological stimuli, NK cell-derived extracellular vesicles (EVs), and anti-tumor activity. Laughter is depicted as a conceptual upstream trigger of hypothalamic-pituitary signaling leading to {beta}-endorphin (BE) release. BE conditioning enhanced NK-92 cytotoxicity and the anti-tumor activity of NK-derived EVs, consistent with granzyme B and perforin enrichment and supporting EV-mediated contact-independent cancer cell killing.

cancer biology↗

bioRxiv2025

Rapid CE-MS with Real-Time Eco-AI Resolves Proteomic Heterogeneity Among Single Human Neutrophils

Single-cell proteomics by mass spectrometry is advancing rapidly, yet throughput and sensitivity remain limiting--particularly for small, protein-poor cell types such as neutrophils. As the most abundant circulating leukocytes in humans, neutrophils are central to immune defense and inflammation, but their proteomes comprehensive single-cell level characterization has only concurrently been reported1 and remains limited. Here, we introduce a rapid capillary electrophoresis-mass spectrometry (CE-MS) platform, which integrates electrophoresis-correlative real-time data acquisition with sub-7-minute separations and artificial intelligence (AI)-based data processing software to achieve deep, high-throughput profiling. Using single-cell-equivalent HeLa digests, the Rapid Eco-AI platform identified [~]1,350 proteins from 300 pg and [~]835 proteins from 75 pg of input-- approaching the complexity of a mammalian cell proteome. Applied to freshly isolated human neutrophils, the workflow identified 151 proteins from [~]2 pg of material, [~]3% of the total cell proteome. Analysis of 13 individual cells revealed marked functional heterogeneity across pathways of degranulation, neutrophil extracellular trap (NET) formation, chemotaxis, and innate immunity, with hierarchical clustering resolving at least four distinct proteomic subtypes. These results establish Rapid Eco-AI as a sensitive, scalable, and broadly applicable CE-MS approach for immune-cell phenotyping at single-cell and subcellular resolution, facilitating new research opportunities in systems immunology and clinical proteomics.

developmental biology↗