DFIFA. Artículos del Departamento de Fisiología y Farmacología

Targeting a Glioblastoma Cancer Stem-Cell Population Defined by EGF Receptor Variant III

Sat, 15 Feb 2014 00:00:00 GMT

[EN]The relationship between mutated proteins and the cancer stem-cell population is unclear. Glioblastoma tumors frequently express EGFRvIII, an EGF receptor (EGFR) variant that arises via gene rearrangement and amplification. However, expression of EGFRvIII is restricted despite the prevalence of the alteration. Here, we show that EGFRvIII is highly coexpressed with CD133 and that EGFRvIII+/CD133+ defines the population of cancer stem cells (CSC) with the highest degree of self-renewal and tumor-initiating ability. EGFRvIII+ cells are associated with other stem/progenitor markers, whereas markers of differentiation are found in EGFRvIII− cells. EGFRvIII expression is lost in standard cell culture, but its expression is maintained in tumor sphere culture, and cultured cells also retain the EGFRvIII+/CD133+ coexpression, self-renewal, and tumor initiating abilities. Elimination of the EGFRvIII+/CD133+ population using a bispecific antibody reduced tumorigenicity of implanted tumor cells better than any reagent directed against a single epitope. This work demonstrates that a mutated oncogene can have CSC-specific expression and be used to specifically target this population.

Evolutionary Origins of Metabolic Reprogramming in Cancer

Tue, 11 Oct 2022 00:00:00 GMT

[EN]Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. These changes are not specific to tumors but also take place during the physiological growth of tissues. Indeed, the cellular and tissue mechanisms present in the tumor have their physiological counterpart in the repair of tissue lesions and wound healing. These molecular mechanisms have been acquired during metazoan evolution, first to eliminate the infection of the tissue injury, then to enter an effective regenerative phase. Cancer itself could be considered a phenomenon of antagonistic pleiotropy of the genes involved in effective tissue repair. Cancer and tissue repair are complex traits that share many intermediate phenotypes at the molecular, cellular, and tissue levels, and all of these are integrated within a Systems Biology structure. Complex traits are influenced by a multitude of common genes, each with a weak effect. This polygenic component of complex traits is mainly unknown and so makes up part of the missing heritability. Here, we try to integrate these different perspectives from the point of view of the metabolic changes observed in cancer.

Intermediate molecular phenotypes to identify genetic markers of anthracycline-induced cardiotoxicity risk

Thu, 27 Jul 2023 00:00:00 GMT

[EN]Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

The role of GAB1 in cancer

Sun, 20 Aug 2023 00:00:00 GMT

[EN]GRB2-associated binder 1 (GAB1) is the inaugural member of the GAB/DOS family of pleckstrin homology (PH) domain-containing proteins. Upon receiving various stimuli, GAB1 transitions from the cytoplasm to the membrane where it is phosphorylated by a range of kinases. This event recruits SH2 domain-containing proteins like SHP2, PI3K's p85 subunit, CRK, and others, thereby activating distinct signaling pathways, including MAPK, PI3K/AKT, and JNK. GAB1-deficient embryos succumb in utero, presenting with developmental abnormalities in the heart, placenta, liver, skin, limb, and diaphragm myocytes. Oncogenic mutations have been identified in the context of cancer. GAB1 expression levels are disrupted in various tumors, and elevated levels in patients often portend a worse prognosis in multiple cancer types. This review focuses on GAB1's influence on cellular transformation particularly in proliferation, evasion of apoptosis, metastasis, and angiogenesis-each of these processes being a cancer hallmark. GAB1 also modulates the resistance/sensitivity to antitumor therapies, making it a promising target for future anticancer strategies.

The use of Pharmacology-Focused journal clubs in health sciences education: a descriptive study

Tue, 18 Feb 2025 00:00:00 GMT

[EN]Introduction: Physicians and nurses have a responsibility to provide evidence-based care to patients, which requires continuing education. The journal club model is an educational and collaborative tool widely used in healthcare for this purpose. However, further studies investigating the effectiveness and perception of participants are needed. The aim of this study is to explore the experience of medical and nursing students with the journal club approach applied to the subject of pharmacology. Methods: Journal club sessions were developed within the pharmacology class of the medical and nursing degrees during the academic year 2023-2024. A total of 208 students participated in the study. 90 students (43.3%) were enrolled in the nursing degree course, while 118 (56.7%) were enrolled in the medical degree course. Students' perceptions were assessed through a qualitative questionnaire of 30 questions with 3 options. Results: This study validated that this format is effective as a learning model, enhancing educational competences and non-educational competences required in health professionals. Our results showed the good acceptance of this format. Conclusion: It is concluded that the journal club strategy enhances the educational and non-educational skills necessary for doctors and nurses to develop the competencies required in today's world.

Nursing-led strategy to combat antimicrobial resistance: multi-method design

Thu, 25 Sep 2025 00:00:00 GMT

[EN]Background: Antimicrobial resistance is currently a global health threat. Numerous efforts have been made to prevent or mitigate this phenomenon, but all have been insufficient. Although numerous studies have postulated nursing as a potential mediator to address this problem, no research has been conducted to put it into practice. This study aims to contextualize the problem of inappropriate antibiotic use and antimicrobial resistance, as well as to develop and implement a nurse-led educational intervention aimed at mitigating it, emphasizing the role of nurses in health education. Methods: Two different groups of participants were recruited using convenience sampling. Nurses administered a survey to 782 citizens in a population from Spain to assess their knowledge of the correct use of antibiotics and antimicrobial resistance. After completing the survey, nurses explained to the participants how to use antibiotics correctly and the problem of antimicrobial resistance. Furthermore, an educational intervention led by nurses was carried out with 104 adolescents, consisting of an oral presentation to raise awareness about the issue. The effectiveness of this intervention was evaluated through a comparative analysis before and after the activity (pre-test and post-test). Results: Our results indicated that the level of knowledge about the correct use of antibiotics and antimicrobial resistance is not statistically significant related to sex in the general population (p > 0.05). However, it is statistically significant related to age (p < 0.05), educational level (p < 0.0001) and study area (p < 0.0001). In addition, the nurse-led educational intervention increased significantly the level of knowledge on the topic among adolescents (p < 0.0001). Conclusions: These findings highlight the low level of knowledge in the population about the correct use of antibiotics and antimicrobial resistance. It also demonstrates how nurses, through their role in health education, can actively contribute to addressing the issue, providing a rationale for the inclusion of nursing in the design and implementation of strategies to prevent or mitigate antimicrobial resistance.

Development of an EGFRvIII specific recombinant antibody

Thu, 07 Oct 2010 00:00:00 GMT

[EN]Background: EGF receptor variant III (EGFRvIII) is the most common variant of the EGF receptor observed in human tumors. It results from the in frame deletion of exons 2-7 and the generation of a novel glycine residue at the junction of exons 1 and 8. This novel juxtaposition of amino acids within the extra-cellular domain of the EGF receptor creates a tumor specific and immunogenic epitope. EGFRvIII expression has been seen in many tumor types including glioblastoma multiforme (GBM), breast adenocarcinoma, non-small cell lung carcinoma, ovarian adenocarcinoma and prostate cancer, but has been rarely observed in normal tissue. Because this variant is tumor specific and highly immunogenic, it can be used for both a diagnostic marker as well as a target for immunotherapy. Unfortunately many of the monoclonal and polyclonal antibodies directed against EGFRvIII have cross reactivity to wild type EGFR or other non-specific proteins. Furthermore, a monoclonal antibody to EGFRvIII is not readily available to the scientific community. Results: In this study, we have developed a recombinant antibody that is specific for EGFRvIII, has little cross reactivity for the wild type receptor, and which can be easily produced. We initially designed a recombinant antibody with two anti-EGFRvIII single chain Fv’s linked together and a human IgG1 Fc component. To enhance the specificity of this antibody for EGFRvIII, we mutated tyrosine H59 of the CDRH2 domain and tyrosine H105 of the CDRH3 domain to phenylalanine for both the anti-EGFRvIII sequence inserts. This mutated recombinant antibody, called RAbDMvIII, specifically detects EGFRvIII expression in EGFRvIII expressing cell lines as well as in EGFRvIII expressing GBM primary tissue by western blot, immunohistochemistry (IHC) and immunofluorescence (IF) and FACS analysis. It does not recognize wild type EGFR in any of these assays. The affinity of this antibody for EGFRvIII peptide is 1.7 × 107 M-1 as determined by enzyme-linked immunosorbent assay (ELISA). Conclusion: This recombinant antibody thus holds great potential to be used as a research reagent and diagnostic tool in research laboratories and clinics because of its high quality, easy viability and unique versatility. This antibody is also a strong candidate to be investigated for further in vivo therapeutic studies.

Pathophysiological Integration of Metabolic Reprogramming in Breast Cancer

Mon, 10 Jan 2022 00:00:00 GMT

[EN]Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. The triggers of these metabolic changes are located in the tumor parenchymal cells, where oncogenic mutations induce an imperative need to proliferate and cause tumor initiation and progression. Cancer cells undergo significant metabolic reorganization during disease progression that is tailored to their energy demands and fluctuating environmental conditions. Oxidative stress plays an essential role as a trigger under such conditions. These metabolic changes are the consequence of the interaction between tumor cells and stromal myofibroblasts. The metabolic changes in tumor cells include protein anabolism and the synthesis of cell membranes and nucleic acids, which all facilitate cell proliferation. They are linked to catabolism and autophagy in stromal myofibroblasts, causing the release of nutrients for the cells of the tumor parenchyma. Metabolic changes lead to an interstitium deficient in nutrients, such as glucose and amino acids, and acidification by lactic acid. Together with hypoxia, they produce functional changes in other cells of the tumor stroma, such as many immune subpopulations and endothelial cells, which lead to tumor growth. Thus, immune cells favor tissue growth through changes in immunosuppression. This review considers some of the metabolic changes described in breast cancer.

Optimizing Opioid Use in Pain Management: A Comprehensive Review of Clinical Benefits, Risks, and Dependence

Thu, 01 Jan 2026 00:00:00 GMT

[EN]Highlights: What are the main findings? Opioids are essential for managing severe acute and cancer-related pain; however, their role in chronic non-cancer pain remains controversial. Concerns regarding dependence, tolerance, and misuse have intensified during the opioid crisis. This narrative review synthesizes recent evidence on opioid pharmacology, clinical applications, dependence risk factors, and the influence of genetic, psychological, and social determinants of opioid use. It highlights emerging safer therapies, opioid rotation, and multimodal strategies that combine pharmacological and nonpharmacological approaches. Health policies should promote equitable access to essential opioids while minimizing their misuse through individualized prescribing, regular patient monitoring, and the integration of non-pharmacological interventions. Reducing prescription bias and addressing disparities are critical for improving global pain care. What are the implications of the main findings? Clinicians should prioritize a patient-centered, multimodal approach to pain management, reserving opioids for clearly indicated situations and combining them with non-pharmacological therapies to reduce long-term risks and improve functional outcomes. Health systems and policymakers should implement prescribing strategies that balance access and safety, including risk stratification, regular reassessment, and efforts to reduce social and racial disparities in opioid availability and pain treatment efficacy. Effective pain management is central to anesthesia, critical care, and perioperative medicine, and opioids remain essential agents for moderate-to-severe pain despite ongoing concerns regarding their safety and misuse. This narrative review synthesizes the current knowledge on opioid mechanisms, clinical indications, safety considerations, and evolving strategies aimed at optimizing their use. Opioids exert their analgesic effects primarily through μ-, δ-, and κ-opioid receptors, which modulate central and peripheral nociceptive pathways. They maintain a well-established role in acute postoperative and cancer-related pain, whereas their use in chronic non-cancer pain remains controversial. Contemporary evidence suggests that physiological dependence and addiction are less frequent in appropriately selected and monitored patients, although the risk increases in the presence of psychological comorbidity, prior substance use, or adverse social determinants of health. Unequal access, prescribing variability, and persistent disparities further complicate global opioid management strategies. Recent advances, including partial agonists such as buprenorphine, dual-mechanism agents such as tapentadol, individualized titration, opioid rotation, and the integration of multimodal analgesia, support safer and more tailored prescribing. Non-pharmacological interventions, including behavioral and physical therapies, increasingly complement pharmacological strategies to minimize opioid exposure and improve functional outcomes. Clinicians must balance analgesic efficacy with adverse effects, such as tolerance, opioid-induced hyperalgesia, sedation, and respiratory depression, particularly in perioperative and critically ill populations. Opioids remain indispensable for selected indications but should be incorporated into a comprehensive, patient-centered, multimodal analgesic approach that prioritizes safety, ongoing reassessment, and individualized risk mitigation.

New platinum derivatives selectively cause double-strand DNA breaks and death in naïve and cisplatin-resistant cholangiocarcinomas

Sat, 01 Nov 2025 00:00:00 GMT

[EN]Patients with cholangiocarcinoma (CCA) have poor prognosis. Current cisplatin-based first-line chemotherapy offers limited survival benefit. Cisplatin induces single-strand DNA breaks, activating DNA repair mechanisms that diminish its effectiveness. Here, we present the design, chemical synthesis, and therapeutic evaluation of a new generation of chemotherapeutic agents (Aurkines) with unique polyelectrophilic properties. These agents cause a high frequency of double-strand DNA breaks, bypassing DNA repair, and promoting cancer cell death. Two novel compounds, Aurkine 16 and Aurkine 18, were designed and evaluated for their antitumor effects in both naïve and cisplatin-resistant CCA cells, cancer-associated fibroblasts, healthy cholangiocytes, and in vivo models. Aurkines effectively induced double-strand DNA breaks, leading to increased DNA damage and elevated levels of reactive oxygen species, resulting in greater cytotoxicity than cisplatin in CCA cells. Phosphoproteomic and molecular analysis revealed that cisplatin activates DNA repair pathways, while Aurkines primarily induce apoptosis. Importantly, Aurkines also triggered apoptosis in cisplatin-resistant CCA cells and cancer-associated fibroblasts without harming healthy cholangiocytes. Additionally, Aurkines demonstrated cytotoxicity in other cisplatin-resistant cancers, such as breast and ovarian cancer. This tumor selectivity results from reduced uptake, increased efflux, and compact chromatin structure in normal cells, limiting Aurkine-DNA interactions. In vivo, Aurkines inhibited the growth of subcutaneous naïve and cisplatin-resistant CCA tumors, as well as orthotopic tumors in immunocompetent mice, promoting antitumor immune cell recruitment without any adverse events. Transport studies revealed that Aurkines were selectively taken up by OCT1, OCT3, CTR1, and OATP1A2, whereas only CTR1 transported cisplatin. Aurkines represent promising therapeutic drugs for both naïve and cisplatin-resistant cancers due to their unique polyelectrophilic properties and selective targeting of malignant cells. This study introduces a novel therapeutic strategy designed to induce frequent double-strand DNA breaks selectively in both naïve and cisplatin-resistant cancer cells, without evident toxic side effects at therapeutic doses. This approach may form the basis for new strategies to overcome the critical challenge of drug resistance in cancer treatment and has the potential to be a breakthrough not only for the treatment of biliary tumors but also for other cancers.

NEDD8-specific protease 1 deficiency as a novel driver of hepatoblastoma development through dysregulation of the CAND1-NEDD8 pathway

Fri, 14 Nov 2025 00:00:00 GMT

[EN]Hepatoblastoma (HB) is the most common malignant liver tumor in children. Despite advances in multimodal treatment, chemoresistance and relapses remain major clinical challenges. NEDDylation, a post-translational modification involving the ubiquitin-like molecule NEDD8, has been implicated in cancer, but its role in HB remains poorly understood. This study investigates the functional relevance of the deNEDDylase NEDP1 and its downstream target CAND1 in HB progression and therapy response. Transcriptomic and proteomic analyses of HB patient samples, cell lines, patient-derived xenograft (PDX) cells, and transgenic mouse models revealed a significant reduction in NEDP1 expression and activity, accompanied by global hyper-NEDDylation. Functional studies demonstrated that NEDP1 overexpression restored deNEDDylation, induced apoptosis, impaired tumor cell proliferation and metabolism, and significantly restrained tumor growth and metastasis in both in vivo mouse models and in the chorioallantoic membrane (CAM) assay. Proteomic profiling identified CAND1 as a key NEDDylated substrate regulated by NEDP1. High CAND1 expression was associated with aggressive molecular HB subtypes (C2-pure, Epi-CB) and poor clinical outcomes, including reduced overall survival. Rescue experiments confirmed that CAND1 overexpression counteracted the antitumor effects of NEDP1. NEDP1 acts as a tumor suppressor in HB by modulating the NEDDylation status of key regulatory proteins, particularly CAND1. Restoration of NEDP1 activity suppresses tumorigenesis and metastasis, underscoring the NEDDylation pathway as a promising therapeutic target. CAND1 is proposed as a potential prognostic biomarker and actionable oncogenic driver in HB.

Isopetasin and S-isopetasin as novel P-glycoprotein inhibitors against multidrug-resistant cancer cells

Tue, 01 Jun 2021 00:00:00 GMT

[EN]A major problem of cancer treatment is the development of multidrug resistance (MDR) to chemotherapy. MDR is caused by different mechanisms such as the expression of the ABC-transporters P-glycoprotein (P-gp, MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). These transporters efflux xenobiotic toxins, including chemotherapeutics, and they were found to be overexpressed in different cancer types. Identification of novel molecules that overcome MDR by targeting ABC-transporters. Resazurin reduction assay was used for cytotoxicity test. AutoDock 4.2. was used for molecular docking. The function of P-gp and BCRP was tested using a doxorubicin uptake assay and an ATPase assay. ROS generation was detected using flow cytometry for the measurement of H2DCFH-DA fluorescence. Annexin/PI staining was applied for the detection of apoptosis. Bioinformatic analyses were performed using LigandScout 3.12. software and DataWarrior software. In our search for new molecules that selectively act against resistant phenotypes, we identified isopetasin and S-isopetasin, which are bioactive natural products from Petasites formosanus. They exerted collateral sensitivity towards leukemia cells with high P-gp expression in CEM/ADR5000 cells, compared to sensitive wild-type CCRF-CEM leukemia cells. Also, they revealed considerable activity towards breast cancer cells overexpressing breast cancer resistance protein, MDA-MB-231-BCRP clone 23. This motivated us to investigate whether the function of P-gp was inhibited. In-silico results showed the compounds bound with high affinity and interacted with key amino acid residues in P-gp . Then, we found that the two compounds increased doxorubicin accumulation in P-gp overexpressing CEM/ADR5000 by three-fold compared to cells without inhibitor. P-gp-mediated drug efflux was ATP-dependent. Isopetasin and S-isopetasin increased the ATPase activity of human P-gp in a comparable fashion as verapamil used as control P-gp inhibitor. As isopetasin and S-isopetasin exerted dual roles, first as cytotoxic compounds and then as P-gp inhibitors, we suggested that their P-gp inhibition is part of a larger complex of mechanisms to induce cell death in cancer patients. P-gp dysfunction induces mitochondrial stress to generate ATP. Upon continuing stress by P-gp inhibition, the mitochondria generate reactive oxygen species (ROS). Initially established for verapamil, this theory was validated in the present study for isopetasin and S-isopetasin, as treatment with the two candidates increased ROS levels in CEM/ADR5000 cells followed by apoptosis. Our study highlights the importance of isopetasin and S-isopetasin as novel ROS-generating and apoptosis-inducing P-gp inhibitors.

Relevance of transportome among the mechanisms of chemoresistance in hepatoblastoma

Tue, 01 Jul 2025 00:00:00 GMT

[EN]Approximately 20 % of hepatoblastomas (HBs) exhibit a poor response to conventional chemotherapy due to mechanisms of chemoresistance (MOCs), such as reduced intracellular drug accumulation. This study evaluated the role of transportome in the multidrug resistance (MDR) of HB. Paired HB and adjacent liver tissue samples (n = 19) and HB-derived cell lines (HepG2, HuH6) were analyzed for their resistome characterization at mRNA (RT-qPCR, Taqman Low-Density Array, sequencing) and protein (western blot, immunohistochemistry, immunofluorescence) levels. Cell viability (MTT test) proliferation and migration (holographic microscopy) were determined. The impact of short-term (72 h) and long-term (>10 months) exposure of HB cells to cisplatin or doxorubicin on the transportome was investigated. Solute carrier (SLC) family of transporters showed minor relevance in HB MDR, while drug export pumps, particularly MRP2, were associated with poor response to chemotherapy. Exposure of HB cells to doxorubicin or cisplatin up-regulated MDR1, MRP1 and MRP2. In cells with induced persistent chemoresistance, the expression of genes involved in other MOCs, and epigenetic machinery was altered. Chemoresistant cells showed cross-resistance to several anticancer drugs but maintained sensitivity to cabozantinib. In conclusion, drug export pumps, but not SLC uptake transporters, are key contributors to HB chemoresistance. Cabozantinib emerges as a potential therapeutic option for HBs resistant to conventional chemotherapy.

Overexpression of the short endoglin isoform reduces renal fibrosis and inflammation after unilateral ureteral obstruction

Thu, 01 Sep 2016 00:00:00 GMT

[EN]Transforming growth factor beta 1 (TGF-β1) is one of the most studied cytokines involved in renal tubulo-interstitial fibrosis, which is characterized by myofibroblast abundance and proliferation, and high buildup of extracellular matrix in the tubular interstitium leading to organ failure. Endoglin (Eng) is a 180-kDa homodimeric transmembrane protein that regulates a great number of TGF-β1 actions in different biological processes, including ECM synthesis. High levels of Eng have been observed in experimental models of renal fibrosis or in biopsies from patients with chronic kidney disease. In humans and mice, two Eng isoforms are generated by alternative splicing, L-Eng and S-Eng that differ in the length and composition of their cytoplasmic domains. We have previously described that L-Eng overexpression promotes renal fibrosis after unilateral ureteral obstruction (UUO). However, the role of S-Eng in renal fibrosis is unknown and its study would let us analyze the possible function of the cytoplasmic domain of Eng in this process. For this purpose, we have generated a mice strain that overexpresses S-Eng (S-ENG+) and we have performed an UUO in S-ENG+ and their wild type (WT) control mice. Our results indicate that obstructed kidney of S-ENG+ mice shows lower levels of tubulo-interstitial fibrosis, less inflammation and less interstitial cell proliferation than WT littermates. Moreover, S-ENG+ mice show less activation of Smad1 and Smad2/3 pathways. Thus, S-Eng overexpression reduces UUO-induced renal fibrosis and some associated mechanisms. As L-Eng overexpression provokes renal fibrosis we conclude that Eng-mediated induction of renal fibrosis in this model is dependent on its cytoplasmic domain.

Implementing the service-learning methodology in nursing education: A case study

Wed, 01 Jan 2025 00:00:00 GMT

[EN]Nurses play a crucial role in global health promotion, and innovative teaching strategies are vital to addressing modern educational challenges. Service-learning, a credit-based approach, integrates community service with academic learning, enhancing students' understanding of course content while fostering civic values. Although established in the United States of America and growing in Europe, most studies on service-learning focus on student learning outcomes, often overlooking its impact on the communities served. Aims: The purpose of this study is to test whether the service-learning practice of nursing students teaching a pharmacology curriculum topic to school children promotes knowledge of the topic in both the nursing students and the school children. Design: This research involves two pretest-posttest quantitative analyses and two satisfaction surveys. Participants: Seventy-six nursing students participated during the 2022–2023 academic year, and 69 primary school pupils received the service-learning intervention. Results: Post-test scores of nursing students were significantly higher than pre-test scores (p = 0.0009). The percentage of correct answers post-intervention was significantly higher than pre-intervention (p < 0.0001). Additionally, 98.7 % of nursing students found the service-learning experience beneficial for learning, and 94.7 % reported increased social awareness. For the school children, the percentage of correct responses after the service-learning experience was statistically significantly higher than before the activity (p < 0.0001). The percentage of correct answers from pupils in each primary grade (fourth, fifth, and sixth) was statistically significantly higher after the application of the learning experience compared to before (p < 0.0001, p < 0.0001, and p < 0.001, respectively). The satisfaction survey indicated high acceptance of the methodology among both nursing students and school pupils. Conclusions: Service-learning enhances knowledge of the pharmacology topic in both nursing students and school children.

Dietary weight loss intervention improves subclinical atherosclerosis and oxidative stress markers in leukocytes of obese humans

Tue, 01 Jan 2019 00:00:00 GMT

[EN]The relationship between caloric restriction-mediated weight loss and the generation of ROS and its effects on atherosclerotic markers in obesity is not fully understood. Therefore, we set out to investigate whether dietary weight loss intervention improves markers of oxidative stress in leukocytes and subclinical parameters of atherosclerosis. This was an interventional study of 59 obese subjects (BMI > 35 kg/m2) who underwent 6 months of dietary therapy, including a 6-week very-low-calorie diet (VLCD) followed by an 18-week low-calorie diet (LCD). We determined clinical parameters, inflammatory markers-hsCRP, TNFα and NFκB -, oxidative stress parameters-total superoxide, glutathione, catalase activity and protein carbonyl groups-, soluble cellular adhesion molecules-sICAM, sP-selectin, sPSGL-1 -, myeloperoxidase (MPO), leukocyte-endothelium cell interactions-rolling flux, velocity and adhesion-and LDL subfractions, before and after the dietary intervention. After losing weight, an improvement was observed in the patients' anthropometric, blood pressure and metabolic parameters, and was associated with reduced inflammatory response (hsCRP, TNFα and NFκB). Oxidative stress parameters improved, since superoxide production and protein carbonyl content were reduced and antioxidant systems were enhanced. In addition, a significant reduction of subclinical markers of atherosclerosis-small and dense LDL particles, MPO, sP-selectin and leukocyte adhesion-and an increase in soluble PSGL-1 were reported. Our findings reveal that the improvement of subclinical atherosclerotic markers after dietary weight loss intervention is associated with a reduction of oxidative stress in leukocytes and inflammatory pathways, suggesting that these are the underlying mechanisms responsible for the reduced risk of cardiovascular disease in obese subjects after losing weight.