University of Puerto Rico at Ponce

Carbon dots (C-Dots) have attracted significant interest due to their strong photoluminescence, aqueous stability, and tunable surface chemistry; however, their environmental safety remains incompletely understood. In this work, C-Dots were synthesized via a rapid microwave-assisted method using two different carbon precursors, D-glucose and ascorbic acid, with ethylenediamine as a passivating agent. The resulting nanoparticles exhibited predominantly amorphous structures with sizes below 10 nm, characteristic absorption bands at ~280–330 nm, and blue photoluminescence centered at ~450 nm. Acute toxicity was evaluated using Brine shrimp at concentrations ranging from 10 to 2000 ppm after 24 and 48 h of exposure. C-Dots synthesized from ascorbic acid showed significant toxicity at 2000 ppm, inducing higher mortality rates after 24 h, whereas D-glucose-derived C-Dots exhibited minimal toxic effects under the same conditions. These findings demonstrate that carbon precursor selection plays a critical role in determining the environmental toxicity of C-Dots and highlight the importance of precursor-dependent design strategies to minimize potential ecological risks associated with carbon-based nanomaterials.

Abstract Ovarian cancer (OC) is the fifth leading cause of cancer-related deaths among women in the U.S. Studies show that cancer patients have elevated stress hormones due to various stressors, which can disrupt cancer progression and immune response in the tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSCs) are immature, immunosuppressive cells that play a key role in the TME and are linked to poor prognoses in cancer patients by disrupting several pathways, including the Notch signaling pathway (NSP). In various cancers, NSP dysregulation contributes to cancer progression. Increasing evidence suggests that chronic stress enhances MDSC infiltration, promoting immunosuppression in the TME. However, the role of the NSP in stress-mediated MDSC infiltration and OC progression remains poorly understood. This study explores how chronic stress influences NSP and MDSC biology in the OC TME and its role in disease progression. We hypothesize that chronic stress increases MDSC infiltration in the OC TME, enhancing NSP activity in OC cells. To test this, we inoculated female C57BL/6 mice with ID8Luc or IG10Luc OC cells and subjected them to daily restraint stress. Mice were sacrificed weekly for tumor and bone marrow collection, followed by immunofluorescence and flow cytometry analyses to characterize MDSCs and immune cells based on surface markers. We also isolated bone marrow from naïve C57BL/6 mice to differentiate myeloid cell precursors into MDSCs. These cells were then exposed to stress hormones (norepinephrine (NE), epinephrine (EPI), and corticosterone (CC)) for 72 hours to analyze MDSC populations. Our results showed that chronic restraint stress increased MDSC infiltration and enriched polymorphonuclear-MDSCs (PMN-MDSCs) in the TME and bone marrow of both OC mouse models. Also, results showed that chronic restraint stress decreased the CD8+ and CD4+ T cells in the TME of both OC mouse models. Ex vivo experiments indicated increased PMN-MDSC enrichment alongside a depletion of monocytic-MDSCs in groups treated with stress hormones. To further examine how stress hormones impact NSP dysregulation, we treated OC cells (ID8 and IG10) in vitro with NE, EPI, or CC. Our findings revealed elevated levels of Notch1, Jagged2, and Hes1 mRNA and protein in the stress hormone groups mediated by GSK-3β phosphorylation. Additionally, we analyzed NSP member expression in tumors from the in vivo experiments. The results indicated higher levels of Notch1, Jagged2, NICD, and HES1 in tumors from mice subjected to restraint stress. In addition, Milliplex analysis of cytocytokine/chemokine profiles from ID8Luc or IG10Luc OC-bearing mice serum samples subjected to chronic restraint stress showed higher levels of IL-1β, IL-6, GM-CSF, G-CSF, MCP-1, RANTES, TNF-α, and low levels of IFN-γ associated with MDSC biology and function. These data suggest that chronic stress may induce MDSC infiltration and activity, possibly mediated by NSP activation, thereby contributing to an immunosuppressive TME and OC progression. Citation Format: Yadiel A. Rivera-Lopez, Luinet L. Meléndez-Rodríguez, Alanis P. Torres-Rosado, Jaydiel A. Casiano-Martínez, Melanie Ortiz-León, Luis M. Rivera-Pérez, Orlando I. Torres-Rodríguez, Sofia M. Hernández-Carrasquillo, Raian Imad-Hamad, Zuliann S. Galarza-Ruiz, Paulo C. Rodríguez, Guillermo N. Armaiz-Pena. Chronic stress impairs anti-tumor immunity in ovarian cancer via MDSCs and notch pathway activation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr A014.

Although levodopa remains the gold standard treatment for Parkinson's disease (PD), its chronic use is associated with levodopa-induced dyskinesia (LID), a motor complication that impacts prognosis, quality of life, and treatment costs. Most known LID-associated factors have been identified in European-descendant populations. To describe the epidemiology of LID in Latin American and Caribbean (LATAM) countries and assess the relevance of known and novel LID-associated factors in this population. We conducted a cross-sectional study using data from the Latin American Research consortium on the Genetics of Parkinson's Disease (LARGE-PD). We included PD patients with information on LID status and levodopa use from eight LATAM countries. LID prevalence was calculated overall and by country. Countries were compared on demographic and clinical variables. Logistic regression was used to identify associations with LID. A total of 3,695 PD patients (58.8% male) were included. Overall LID prevalence was 25.4% [95% CI: 24.06-26.87], ranging from 9.3% in Colombia to 45.1% in Puerto Rico. Prevalence increased progressively with longer disease duration. Country comparisons showed that not all known LID-associated factors explained prevalence differences. In logistic regression, fast disease progression was significantly associated with LID (OR: 1.55, 95%CI: 1.16-2.07), while sex was not (OR: 1.02, 95%CI: 0.87-1.18). This is the largest study on LID epidemiology in LATAM. While some known risk factors remain relevant, others, like sex, do not, underscoring the need for population-specific studies. Future work should integrate environmental, clinical, and genetic data to better understand LID mechanisms.

Carbon dots (C-Dots) have garnered significant attention in various fields, including biomedical applications, photocatalysis, sensing, and optoelectronics, due to their high luminescence, biocompatibility, and ease of functionalization. However, concerns regarding their potential toxicity persist. Conventional synthesis methods for C-Dots often require long reaction times, high pressures, expensive equipment, extreme temperatures, and toxic reagents. In contrast, microwave irradiation provides a rapid, cost-effective, and scalable alternative for the synthesis of high-quality C-Dots. In this study, we report the single-step, 3-min synthesis of water-stable carbon dots at 100 °C, 120 °C, and 140 °C using microwave irradiation. Particle stability was achieved through polyethyleneimine (PEI) functionalization. The toxicity of the synthesized carbon dots was evaluated in marine crustaceans, revealing that C-Dots with an estimated size below 10 nm did not exhibit toxicity after 24 and 48 h of exposure. These findings demonstrate the potential of microwave-synthesized carbon dots as non-toxic, water-stable nanomaterials for environmental and biomedical applications.

e13098 Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen, progesterone, or human epidermal growth factor 2 (HER2) receptor expression. TNBC has poor prognosis due to its high metastatic potential and limited treatment options. Shugoshin-1 (Sgo1), a centromeric protein that maintains stability in chromatids during mitosis, has been thought to play an important role in the progression of TNBC. Previous publications from our group have shown that the transient downregulation of Sgo1 in TNBC cells decrease the epithelial-to-mesenchymal transition (EMT), which is a precursor of metastasis. Our purpose with this study is to evaluate the role of long-term effects of Sgo1 downregulation in cell invasion, cell migration, tumor growth, and metastasis. Methods: To achieve our goal, MDA-MB-231 cells were stably transfected with a lentivirus containing a shRNA Sgo1 sequence or a scramble shRNA control. Cell invasion and migration were evaluated by Boyden chamber assays. Meanwhile, tumor growth and metastasis were evaluated using an immunocompromised orthotopic mice model. Female NOD-SCID Gamma (NSG) mice were injected either with 2.5 X 106 shRNA Control (n= 10) or shRNA Sgo1 (n= 10) MDA-MB-231 cells. Tumor growth was measured for eight weeks using a vernier caliper. Afterwards, primary, and metastatic tumors as well as primary organs were harvested. Lung and liver samples were embedded in paraffin and stained with hematoxylin and eosin. A Student t test was used to evaluate the differences between groups. A p-value < 0.05 was considered significant. Results: Our results show a significant reduction in cell invasion and migration in MDA-MB-231 cells treated with shRNA Sgo1. Moreover, we observed a significant reduction in tumor growth and metastasis to lymph nodes, liver, and lungs in the mice treated with shRNA Sgo1 when compared to shRNA Control group. Conclusions: These results suggest that Sgo1 is an important regulator in TNBC tumor growth and metastasis through the modulation of EMT genes. Thus, targeting Sgo1 early in the course of TNBC can be a potential therapeutic treatment of TNBC.

Increased long-chain C20:0 ceramides have been found in the serum of patients with depression. Moreover, ceramides are linked with increased microglia reactivity and inflammatory cytokine production, which are associated with depression. Since ceramides can readily cross the blood brain barrier, peripheral C20:0 ceramides could enter the brain, activate microglia, and induce depressive-like behavior. In this study, we determined whether localized infusion of C20:0 ceramides into the ventral hippocampus (VH) of rats is sufficient to activate microglia and induce depressive-like behaviors. Adult male and female rats received infusions of C20:0 ceramides or vehicle solution every other day for 2 weeks. After the third infusion, C20:0-infused animals showed reduced sucrose preference suggesting anhedonia-like behavior. In contrast, infusions of C20:0 ceramides did not affect immobility in the forced swim test or sucrose grooming suggesting that the behavioral effects of ceramides are task dependent. Furthermore, C20:0-infusions did not increase Iba-1 + microglia or inflammatory markers in the VH suggesting that localized increases in C20:0 ceramides in the VH are sufficient to induce anhedonia-like behavior without microglia activation.