https://hdl.handle.net/10481/31054 Sat, 11 Apr 2026 07:42:48 GMT 2026-04-11T07:42:48Z https://hdl.handle.net/10481/112388 Pain Outcome Determines the Sensitivity to Peripheral Opioid Antagonism of Morphine, Ibuprofen, and Their Combination in Laparotomized Mice Hasoun, Makeya A; Santos-Caballero, Miriam; Huerta, Miguel Á; Robles-Funes, María; Puerto Moya, Amada; Ruiz-Cantero, M Carmen; Cobos, Enrique J; González Cano, Rafael Background/Objectives: Postoperative pain pharmacology is complex. We investigated the sensitivity of analgesic-like effects induced by morphine, ibuprofen, and their combination to peripheral opioid antagonism in a mouse laparotomy model. Methods: Mechanical hypersensitivity was assessed using von Frey filaments, and ongoing pain (abdominal licking and facial expressions) was evaluated using artificial intelligence algorithms. We tested the sensitivity of the analgesic treatments to the opioid antagonist naloxone or its peripherally restricted analog, naloxone methiodide. We also tested the effects of neutrophil depletion using an anti-Ly6G antibody. Gastrointestinal transit and pupillary diameter were measured to assess non-analgesic opioid effects. Results: Morphine reversed all pain-related behaviors; its effect on mechanical hypersensitivity was reversed by peripheral opioid antagonism, whereas its effects on ongoing pain were not. Ibuprofen reduced mechanical hypersensitivity and facial expressions but failed to alter licking. Interestingly, the ibuprofen effect on mechanical hypersensitivity depended on peripheral opioid receptors and neutrophils at the injury site. The morphine–ibuprofen combination produced synergistic analgesia across all endpoints without enhancing opioid-induced gastrointestinal inhibition or mydriasis. Peripheral opioid antagonism reversed the effect of the combination on mechanical hypersensitivity and facial expressions but not on licking. Conclusions: Our results replicate the key clinical phenomena relevant to the postoperative pain context, including the potentiation of morphine analgesia by ibuprofen without the exacerbation of adverse effects. Our results suggest that drug effects on different postoperative pain measures rely on distinct neurobiological mechanisms and are not interchangeable. Therefore, the use of a battery of complementary pain endpoints in preclinical pharmacology studies is advisable. https://hdl.handle.net/10481/112388 https://hdl.handle.net/10481/111889 Silk Fibroin Sheets Improve the Strength of Colon Anastomoses in Wistar Rats Mohamed Chairi, Mohamed Hassin; Huertas Peña, Francisco José; García García, Jorge; López Escánez, Laura; Aznar Cervantes, Salvador D.; Becerra Massare, Patricia; Gálvez Peralta, Julio Juan; Anderson, Per Olof; Molina Tijeras, José Alberto; Rodríguez Cabezas, María Elena Colorectal resection and subsequent anastomosis are the standard curative procedures for a variety of colorectal pathologies. However, anastomotic leakage (AL) is an early and frequent complication that can have life-threatening outcomes. The study aimed to evaluate the effect of silkworm fibroin sheets on colon anastomotic strength and wound healing early after intervention in Wistar rats. Male Wistar rats were randomized into two groups, control (N = 11) and fibroin (N = 11), and subjected to end-to-end colo-colic anastomosis. In the fibroin group, a single layer of fibroin membrane was applied externally around the anastomosis. The animals were sacrificed three days after the operation (POD3) and intestinal adhesions, anastomotic bursting pressure and histological parameters based on the eosin, hematoxylin, and Masson’s trichrome stains were compared between the groups. Fibroin-treated rats showed a significant increase in anastomotic bursting pressure com pared to control animals (69 (18) vs. 41 (28) mmHg), whereas no differences in the intestinal adhesion scores were detected. No significant differences in the numbers of granulocytes, monocytes/macrophages and fibroblasts, nor the amount of collagen fibers, as measured by Masson’s trichrome stain, were found between the groups. These results indicate that fibroin sheets could represent a simple and promising tool to provide mechanical support and improve colonic anastomotic strength early after intervention. https://hdl.handle.net/10481/111889 https://hdl.handle.net/10481/111495 The Early Safety Signal of Sacituzumab Govitecan-Related Toxicity and the UGT1A1*28 Genotype in Metastatic Breast Cancer: A Real-World Preliminary Report Martínez Pérez, María; Nieto-Sánchez, María Teresa; Díaz Villamarín, Xando; Torres García, Alicia; Fernández Varón, Emilio; Prados-Carmona, Alvaro; Legerén, Marta; Cabeza-Barrera, José; Blancas López-Barajas, María Isabel; Morón Romero, María Rocío Background/Objectives: Sacituzumab govitecan (SG) releases SN-38, the same active me tabolite as irinotecan, thereby sharing key metabolic pathways and toxicity mechanisms. The clearance of SN-38 is strongly influenced by UGT1A1 polymorphisms, particularly the UGT1A1*28 allele. While UGT1A1*28 genotyping routinely guides irinotecan dosing, no such recommendations exist for SG. This study describes the relationship between UGT1A1*28 and severe SG-related toxicity in real-world practice, identifying early safety signals and exploring the clinical and economic impact. Methods: This retrospective ob servational study (2021–2025) included patients with metastatic breast cancer treated with SG and patients with advanced gastrointestinal malignancies treated with irinotecan at a tertiary hospital. In the SG cohort, genotyping followed grade ≥3 toxicity; in the irinotecan cohort, it was performed prospectively. Toxicity (Common Terminology Criteria for Ad verse Events version 5.0) and healthcare costs related to hospitalizations were estimated using official institutional tariffs. Results: All nine SG patients with severe toxicity (100%) carried the UGT1A1*28 allele. In the irinotecan cohort (n = 74), which was managed with genotype-guided dosing, severe toxicity and hospitalization were less frequent. SG was associated with higher mean costs per treated patient (€2817.01 vs. €1233.63), driven by toxicity-related admissions (33.3% vs. 10.8%). Genotyping costs (€10.51) were negligible compared to daily hospitalization expenses (up to €1984.90). Conclusions: Severe SG-re lated toxicity reveals a consistent UGT1A1*28-associated vulnerability. Given the drug’s recent approval in Spain, these data represent an urgent real-world safety signal. The marked disparity between low genotyping costs and high hospitalization expenses sup ports implementing preventive UGT1A1 testing to optimize the safety and sustainability of sacituzumab govitecan therapy. https://hdl.handle.net/10481/111495 https://hdl.handle.net/10481/111474 Extracellular Vesicles and Endocrine Disruption: How Environmental Pollutants Modulate the Loading and Release of Extracellular Vesicles for Cancer Promotion and Progression Buján, Sol; Esquivel-Ruiz, Sergio; Olivas Martínez, Alicia; Miret, Noelia V.; Fernández Cabrera, Mariana Fátima; Randi, Andrea Intercellular communication is mediated by extracellular vesicles (EVs), particles released by all cell types that transfer bioactive cargo (proteins, lipids, nucleic acids) to recipient cells, influencing their function. Furthermore, the human population is simultaneously exposed to mixtures of endocrine-disrupting chemicals (EDCs), capable of altering hormonal homeostasis. Epidemiological and experimental evidence, in animal and cellular models, show that EDCs can contribute to the initiation, development, and progression of carcinogenesis. This review analyzes the EDC–EV–Cancer axis, connecting the biology of EVs to environmental toxicology and the processes that lead to tumor development. It has been examined how specific pollutants—arsenic, polyhalogenated aromatic hydrocarbons, bisphenol A, phthalates, particulate matter 2.5, and cigarette smoke—modify the secretion and content of EVs. These altered EVs may subsequently trigger critical oncogenic mechanisms in recipient cells, including proliferation, angiogenesis, migration, immunosuppression, and metastasis. Specific mechanisms, pathways, miRNAs, and proteins have been identified, following exposure to various EDCs that are capable of modulating cells and the tumor microenvironment to induce carcinogenesis and tumor progression. Therefore, EVs represent a promising platform for investigating the role of exposome in tumor development, serving as a real-time monitoring system that would allow tracking of combined and dynamic human environmental exposure and help in cancer prevention. https://hdl.handle.net/10481/111474 https://hdl.handle.net/10481/110839 Deleterious effect of human umbilical cord blood mononuclear cell transplantation on thioacetamide-induced chronic liver damage in rats Álvarez Mercado, Ana Isabel; García-Mediavilla, María V; Sánchez-Campos, Sonia; Abadía Molina, Francisco; Sáez Lara, María José; Cabello Donayre, María; Gil Hernández, Ángel; González Gallego, Javier; Fontana Gallego, Luis https://hdl.handle.net/10481/110839