Luis Alberto Gómez

Non-communicable diseases (NCDs), including type 2 diabetes mellitus (DM), hypertension (HTA), obesity (OB), and cardiovascular disease (CVD), represent a major global health burden and disproportionately affect socially vulnerable populations. Small extracellular vesicles (EVs) are stable carriers of proteins and regulatory RNAs that may reflect endothelial dysfunction and cardiometabolic stress. This study explored plasma-derived EV-associated biomarkers in adults from La Guajira, Colombia, with emphasis on miR-126-3p, miR-21-5p, miR-92a-3p, and SNAIL. Anthropometric, clinical, and biochemical data were obtained from a cross-sectional cohort. Representative plasma samples were selected for EVs isolation by size-exclusion chromatography. Vesicles were characterized by nanoparticle tracking analysis, scanning transmission electron microscopy, protein quantification, Western blotting, and bead-based flow cytometry. Candidate miRNAs were identified by small RNA sequencing and validated by stem-loop RT-qPCR. Bioinformatic enrichment analyses were performed using miRNet 2.0 and KEGG pathway analysis. The epidemiological cohort showed a high cardiometabolic burden, with waist-to-height ratio (WHtR) and triglyceride-glucose (TyG) index emerging as key markers of central adiposity and metabolic dysfunction. Plasma-derived EVs displayed the expected nanoscale morphology and expressed canonical vesicle markers. Protein cargo analyses revealed EMT- and remodeling-associated proteins, including SNAIL and GAL-3. EV-associated miR-126-3p, miR-21-5p, and miR-92a-3p were enriched predominantly in hypertensive and hypertensive-diabetic groups. In an exploratory sub-cohort, CD31-positive EVs showed a trend toward increased expression in individuals with previous myocardial infarction or stroke (p = 0.057). KEGG enrichment analysis linked the identified miRNA signature to pathways involved in endothelial dysfunction, inflammation, vascular remodeling, apoptosis, and extracellular matrix organization. Plasma-derived EVs from individuals with cardiometabolic disorders carry molecular signatures consistent with endothelial stress and vascular remodeling. These findings identify miR-126-3p, miR-21-5p, miR-92a-3p, SNAIL, and CD31-positive EVs as exploratory candidate biomarkers that require validation in larger prospective cohorts.

Doxorubicin (Dox) is not a first-line treatment for melanoma due to limited antitumor efficacy and dose-dependent cardiotoxicity. However, sublethal doses may trigger adaptive cellular responses that influence tumor progression and systemic toxicity. Small extracellular vesicles (EVs) are key mediators of intercellular communication and can carry bioactive molecules that modulate both the tumor microenvironment and distant tissues. This study investigates how sublethal Dox exposure alters EV biogenesis and cargo in A375 melanoma cells and explores the potential implications for cardiovascular function. We treated human A375 melanoma cells with 10 nM dox for 96 h. EVs were isolated using differential ultracentrifugation and size exclusion chromatography. Vesicle characterization included Immunocytochemistry for CD63, CD81, CD9, Rab7 and TSG101, scanning electron microscopy (SEM) Nanoparticle Tracking Analysis (NTA), and Western blotting for CD81 and CytC. We analyzed cytokine content using cytokine membrane arrays. Guinea pig cardiomyocytes were exposed to the isolated vesicles, and mitochondrial activity was evaluated using the MTT assay. Statistical analysis included t-tests, ANOVA, Cohen’s d, and R² and η². Dox exposure significantly increased EV production (13.6-fold; p = 0.000014) and shifted vesicle size distribution. CD81 expression was significantly upregulated (p = 0.0083), and SEM (microscopy) confirmed enhanced vesiculation. EVs from treated cells were enriched in TGF-β (p = 0.0134), VEGF, CXCL1, CXCL12, CCL5, IL-3, IL-4, IL-10, Galectin-3, and KITLG. Cardiomyocytes exposed to these vesicles showed a 2.3-fold reduction in mitochondrial activity (p = 0.0021), an effect absent when vesicles were removed. Bioinformatic analysis linked EV cargo to pathways involved in cardiac hypertrophy, inflammation, and fibrosis. As conclusion, sublethal Doxorubicin reprograms melanoma-derived EVs by enhancing their production and enriching their cargo with profibrotic and immunomodulatory mediators. These vesicles may contribute to tumor progression and cardiovascular physiopathology, suggesting that targeting EVs could improve therapeutic outcomes in cancer and cardiovascular disease.

This document analyzes, from a critical and forward-looking perspective, the main challenges faced by scientific journals in the fields of health and biomedicine in Colombia, as well as strategies for their strengthening. Recognizing that a robust and reliable scientific publication is a cornerstone in the knowledge value chain and the country's development, it outlines a set of coordinated strategies aimed at enhancing scientific and editorial quality, visibility, scientific integrity, and the social impact of national scientific output. Among the key issues addressed is the need to implement rigorous editorial guidelines aligned with international standards to ensure the relevance, methodological soundness, and transparency of manuscripts. The document also highlights recommendations for the use of standardized reporting guidelines that improve the completeness of published information, as well as the promotion of persistent digital identifiers that ensure proper traceability of authorship and scientific content. It proposes moving toward a fairer evaluation of research by incorporating contextualized qualitative and quantitative metrics and outlines concrete actions to improve peer review, diversify editorial boards, foster scientific communities committed to knowledge integrity, and adopt practices aligned with open science. In addition, it emphasizes the potential of artificial intelligence as a complementary tool to modernize editorial processes without compromising ethics or academic quality. This document offers a potential roadmap—based on the experience of the journal *Biomédica*—to transform biomedical publishing in Colombia and serves as an invitation to all actors in the science, technology, and innovation system to engage in the collective construction of a stronger, more inclusive editorial ecosystem that serves public health.

Las Enfermedades Crónicas No Transmisibles (ECNT) representan el 74% de todas las muertes a nivel mundial, siendo las enfermedades cardiovasculares (ECV), el cáncer, las enfermedades respiratorias crónicas y la diabetes las principales causas. En Colombia, estas patologías constituyen el principal factor de carga de enfermedad, generando retos significativos para el sistema de salud, que tradicionalmente ha adoptado modelos convencionales y fragmentados de atención. Antes de presentar la propuesta, es fundamental contextualizar el problema central: las ECNT requieren un cambio de modelo de atención, pasando de enfoques reactivos a estrategias proactivas, integradas y centradas en la persona. Este policy brief propone la Investigación de Acción Participativa (IAP) como una respuesta clave a estos desafíos, destacando su carácter transformador, crítico y educativo, y promoviendo la participación activa de las comunidades en el diseño, ejecución y evaluación de intervenciones en salud. La IAP favorece un abordaje proactivo y planificado, centrado en la persona y su contexto, garantizando una atención de calidad y sostenibilidad en el tiempo.

Cardiovascular diseases and cancer are leading global causes of morbidity and mortality, necessitating advances in diagnosis and treatment. Doxorubicin (Doxo), a potent chemotherapy drug, causes long-term heart damage due to cardiotoxicity. Small extracellular vesicles (sEVs) carry bioactive molecules—such as proteins, lipids, and nucleic acids—that can modulate gene expression and signaling pathways in recipient cells, including cardiomyocytes. Through the delivery of cytokines, microRNAs, and growth factors, sEVs can influence cell survival, which plays a critical role in the development of cardiotoxicity. This study investigates the role of sEVs derived from breast cancer cells treated or not with Doxo and their potential to induce cardiomyocyte damage, thereby contributing to cardiotoxicity. We isolated sEVs from MCF-7 cells treated or not to Doxo using ultracentrifugation and characterized them through Nanoparticle Tracking Analysis (NTA), Scanning Electron Microscopy (SEM), and Western Blotting (WB) for the markers CD63, CD81, and TSG101. We analyzed cytokine profiles using a Multiplex Assay and Cytokine Membrane Array. We exposed Guinea pig cardiomyocytes to different concentrations of sEVs. We assessed their viability (MTT assay), shortening, reactive oxygen species (ROS–DHE dye) production, mitochondrial membrane potential (JC-1 dye), and calcium dynamics (FLUO-4 dye). We performed statistical analyses, including t-tests, ANOVA, Cohen’s d, and η² to validate the robustness of the results. Treatment of MCF-7 cells with 0.01 μM Doxorubicin resulted in increased sEVs production, particularly after 48 h of exposure (~1.79 × 10⁸ ± 2.77 × 10⁷ vs. ~5.1 × 10⁷ ± 1.28 × 10⁷ particles/mL, n = 3, p = 0.0019). These sEVs exhibited protein profiles in the 130–25 kDa range and 93–123 nm sizes. They carried cytokines including TNF-α, IL-1β, IL-4, IFN-γ, and IL-10. Exposure of cardiomyocytes to sEVs (0.025 μg/mL to 2.5 μg/mL) from both Doxo-treated and untreated cells significantly reduced cardiomyocyte viability, shortened cell length by up to 20%, increased ROS production, and disrupted calcium homeostasis and mitochondrial membrane potential, indicating severe cellular stress and cardiotoxicity. These findings suggest that Doxo enhances sEVs production from breast cancer cells, which plays a key role in cardiotoxicity through their cytokine cargo. The study highlights the potential of these sEVs as biomarkers for early cardiotoxicity detection and as therapeutic targets to mitigate cardiovascular risks in chemotherapy patients. Future research should focus on understanding the mechanisms by which Doxorubicin-induced sEVs contribute to cardiotoxicity and exploring their diagnostic and therapeutic potential to improve patient safety and outcomes in cancer therapy.

Doxorubicin (DOX), widely used as a chemotherapeutic agent for various cancers, is limited in its clinical utility by its cardiotoxic effects. Despite its widespread use, the precise mechanisms underlying DOX-induced cardiotoxicity at the cellular and molecular levels remain unclear, hindering the development of preventive and early detection strategies. To characterize the cytotoxic effects of DOX on isolated ventricular cardiomyocytes, focusing on the expression of specific microRNAs (miRNAs) and their molecular targets associated with endogenous cardioprotective mechanisms such as the ATP-sensitive potassium channel (KATP), Sirtuin 1 (SIRT1), FOXO1, and GSK3β. We isolated Guinea pig ventricular cardiomyocytes by retrograde perfusion and enzymatic dissociation. We assessed cell morphology, Reactive Oxygen Species (ROS) levels, intracellular calcium, and mitochondrial membrane potential using light microscopy and specific probes. We determined the miRNA expression profile using small RNAseq and validated it using stem-loop qRT-PCR. We quantified mRNA levels of some predicted and validated molecular targets using qRT-PCR and analyzed protein expression using Western blot. Exposure to 10 µM DOX resulted in cardiomyocyte shortening, increased ROS and intracellular calcium levels, mitochondrial membrane potential depolarization, and changes in specific miRNA expression. Additionally, we observed the differential expression of KATP subunits (ABCC9, KCNJ8, and KCNJ11), FOXO1, SIRT1, and GSK3β molecules associated with endogenous cardioprotective mechanisms. Supported by miRNA gene regulatory networks and functional enrichment analysis, these findings suggest that DOX-induced cardiotoxicity disrupts biological processes associated with cardioprotective mechanisms. Further research must clarify their specific molecular changes in DOX-induced cardiac dysfunction and investigate their diagnostic biomarkers and therapeutic potential.

Antifolates such as methotrexate (MTX) have been largely known as anticancer agents because of their role in blocking nucleic acid synthesis and cell proliferation. Their mechanism of action lies in their ability to inhibit enzymes involved in the folic acid cycle, especially human dihydrofolate reductase (hDHFR). However, most of them have a classical structure that has proven ineffective against melanoma, and, therefore, inhibitors with a non-classical lipophilic structure are increasingly becoming an attractive alternative to circumvent this clinical resistance. In this study, we conducted a protocol combining virtual screening (VS) and cell-based assays to identify new potential non-classical hDHFR inhibitors. Among 173 hit compounds identified (average logP = 3.68; average MW = 378.34 Da), two—herein, called C1 and C2—exhibited activity against melanoma cell lines B16 and A375 by MTT and Trypan-Blue assays. C1 showed cell growth arrest (39% and 56%) and C2 showed potent cytotoxic activity (77% and 51%) in a dose-dependent manner. The effects of C2 on A375 cell viability were greater than MTX (98% vs 60%) at equivalent concentrations and times. Our results indicate that the integrated in silico/in vitro approach provided a benchmark to identify novel promising non-classical DHFR inhibitors showing activity against melanoma cells.