Biology subjects

Victorio, C. B. L.

Publications and source records attributed to Victorio, C. B. L..

3 recordsLinked to original sources

bioRxiv2026

Lung FDG-PET is an early pharmacodynamic biomarker of antiviral efficacy in preclinical influenza

Background. Influenza remains a major cause of global morbidity and mortality. Pharmacodynamic biomarkers that quantify treatment response within the lung could accelerate influenza therapeutic development. We evaluated [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG-PET) as a non-invasive biomarker of antiviral efficacy. Methods. Serial [18F]-FDG-PET was evaluated in two murine H1N1 influenza models using mouse-adapted PR8 strain and CA-09 clinical isolate following treatment with favipiravir, baloxavir marboxil, or ribavirin. PET measures were compared with pulmonary viral burden, inflammatory cytokine expression, computed tomography (CT) imaging, and respiratory function measured by whole-body plethysmography (WBP). Results. Antiviral treatment in PR8 infection model reduced lung [18F]-FDG uptake by 27-49% and metabolic lung volume (MLV) by 40.5-74.6% (both p < 0.001). Antiviral response was detectable as early as 3 days post-infection, when uptake decreased by 28.7-53.2% and MLV by 33.8-75.0%. Lung uptake also strongly correlated with MLV (r = 0.93, p < 0.001) and with pulmonary viral burden and inflammatory mediators. These findings were reproduced in a model of pandemic H1N1/CA-09, where baloxavir reduced uptake by 37.4% (p = 0.02) and MLV by 67.5% (p < 0.001) at day 3. In both models, changes in [18F]-FDG-PET parameters preceded improvements in lung CT and respiratory function. Conclusions. Lung [18F]-FDG-PET provides an early, quantitative measure of antiviral response in experimental influenza, supporting its further evaluation as a translational pharmacodynamic endpoint.

microbiology↗

bioRxiv2026

Myeloperoxidase (MPO) exacerbates dengue-associated liver injury and contributes to disease pathogenesis in mouse models

Severe dengue can damage the liver through unestablished mechanisms. We investigated the role of myeloperoxidase (MPO), a neutrophil enzyme, in dengue through patients, fatal liver samples, and mouse infection models. Observations from two independent clinical cohorts revealed elevated plasma MPO levels in dengue and, in one cohort, MPO was further linked to liver injury markers during the critical phase of disease, whereas livers from dengue fatal cases revealed MPO build-up in the vicinity of CD177+ activated neutrophils. In mice, dengue led to MPO overexpression, oxidative damage, and broad activation of innate and systemic inflammatory pathways in livers. Blocking MPO activity alleviated these and improved survival in one model and delayed disease progression without preventing death in another. These findings establish MPO as a functional mediator of severe dengue-associated liver injury and inflammation, which warrants further preclinical investigation into its hepatic pathogenic mechanism and its validity as target for therapeutic intervention.

pathology↗

bioRxiv2026

Nanoluciferase reporter preserves immunocompetent glioma model fidelity while facilitating longitudinal molecular imaging

Glioblastoma studies employ syngeneic orthotopic models to preserve tumor-immune interactions, but intracranial tumor burden is challenging to monitor longitudinally. Bioluminescence imaging enables non-invasive assessment, although reporter immunogenicity may compromise model fidelity. We engineered murine GL261 glioma cells to stably express nanoluciferase (NLuc) and compared them with parental GL261 (WT) and GL261 cells expressing red-shifted firefly luciferase (Red-FLuc). In vitro, GL261-NLuc retained growth kinetics and morphology comparable to GL261-WT and produced >100-fold stronger bioluminescence than GL261-Red-FLuc. In immunocompetent mice, GL261-NLuc formed lethal brain tumors with survival and tumor histopathology, immune profile, and response patterns to experimental oncolytic virus therapy broadly resembling GL261-WT. In contrast, GL261-Red-FLuc tumors regressed and exhibited heightened inflammation and increased infiltration of activated CD8+ T-cells. Longitudinal imaging of GL261-NLuc tumors detected treatment-associated changes in growth kinetics not captured by survival alone. These establish GL261-NLuc as a practical reporter for longitudinal immunocompetent glioblastoma studies amenable to immunotherapy evaluations.

molecular biology↗