Articulos Científicos Anat. Emb.

Anti-Inflammatory Effects of the Algal Diterpenoid Ruguloptone A by Modulation of M2 Response in Early Diabetic Retinopathy

2026-11-04T05:05:01Z

Anti-Inflammatory Effects of the Algal Diterpenoid Ruguloptone A by Modulation of M2 Response in Early Diabetic Retinopathy Cuevas, Belén; Zubía Mendoza, Eva; Martín Loro, Francisco; Arroba Espinosa, Ana Isabel Background/Objectives: Inflammation is a critical contributor to the development of diabetic retinopathy (DR). In the early stages of DR, the compromised permeability of the blood–retina barrier facilitates the infiltration of macrophages and the activation of microglia. These specific retinal immune cells can adopt morphologies M1 or M2, linked to pro- or anti-inflammatory responses, respectively. This dual response represents a new therapeutic target against DR progression. This study aimed to investigate the modulation of the response M1/M2 and the molecular mechanism of two algal diterpenoids, rugukadiol A (RK) and ruguloptone A (RL), in the early inflammatory events associated with DR. Methods: LPS-stimulated microglial (Bv.2) and macrophage (RAW264.7) cells and an ex vivo physiological model of DR were used to analyze the effects of RK and RL on M1 and M2 inflammatory markers. Results: Compounds RK and RL, besides decreasing the expression of the M1 pro-inflammatory factors iNOS, Il6 mRNA, and NLRP3 in LPS-stimulated Bv.2 cells, caused enhancements in Arg-1 mRNA and Il10 mRNA expression consistent with the induction of an M2 anti-inflammatory response. RK promoted p38α-MAPK phosphorylation, suggesting a non-classical activation of p38α related to the induction of anti-inflammatory responses. Consistently, treatment of retinal explants of BB rats in the early stages of DR with RL decreased M1 pro-inflammatory mediators and induced M2 anti-inflammatory markers, with a reduction in gliosis and a phenotype switch from activated to resting microglia. Conclusions: This study provides the first evidence of algal diterpenoids attenuating pro-inflammatory mediators and promoting the resolution of inflammation in a diabetic retinopathy context, thus opening the way to further explore this class of marine natural products and analogs for early DR management.

Dynamic cytokine profiles across the progression of Type 1 diabetes mellitus are associated with diabetic retinopathy development

2026-07-30T04:01:10Z

Dynamic cytokine profiles across the progression of Type 1 diabetes mellitus are associated with diabetic retinopathy development Martín Loro, Francisco; Cano Cano, Fátima; Lara Barea, Almudena; Gómez Jaramillo, María Laura; González Montelongo, María del Carmen; Roca Rodríguez, María del Mar; López Tinoco, Cristina; Álvarez Ramos, Pablo; Jiménez-Gómez, Gema; Campos Caro, Antonio; Aguilar Diosdado, Manuel; Arroba Espinosa, Ana Isabel El estudio analizó 48 citocinas circulantes y alteraciones retinianas mediante OCT y OCTA en 74 pacientes con DM1 de distinta duración y 23 controles sanos. En las fases iniciales de la DM1 se observaron niveles elevados de citocinas proinflamatorias, especialmente IL-1β, TNF-α, IL-2Rα e IL-8. Algunas de estas alteraciones persistieron en fases posteriores y se asociaron con adelgazamiento retiniano, aumento de la zona avascular foveal y neovascularización. Los resultados sugieren que determinados perfiles de citocinas podrían actuar como biomarcadores precoces de retinopatía diabética y contribuir a su prevención y seguimiento.; Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by chronic inflammation that contributes to diabetic complications such as diabetic retinopathy (DR). This cross-sectional observational study aimed to characterize circulating cytokine profiles across different stages of T1DM and assess their association with early retinal alterations. 74 individuals with T1DM were categorized according to disease duration: <3 months (A), ≥ 3 months to ≤ 1 year (B), ≥ 1 to < 5 years (C) ≥ 5 years (D). 23 subjects were included as healthy controls (H). 48 serum cytokines were quantified using a standardized human cytokine assay. Retinal morphology and vascular parameters were assessed through OCT and OCTA images. Early-staged patients (A) showed elevated concentrations of IL-1β, TNF-α, IL2-Ra and IL-8, compared to controls (H). IL-8 remained increased in group C, alongside with higher Eotaxin, IL-12(p70) and IL-17 and anti-inflammatory cytokines IL-4 and LIF. Retinal thinning and enlarged foveal avascular and neovascularization areas correlated with these cytokine patterns. Distinct inflammatory cytokine profiles characterize T1DM progression and correlate with early events-associated to DR indicators, supporting their potential as immunological biomarkers and aiding in the prevention and management of T1DM and its specific complications such as DR.

Interference of Type 2 Diabetes Mellitus in the Early Diagnosis of Sepsis: Clinical Challenges and Biomarkers

2026-07-29T04:08:06Z

Interference of Type 2 Diabetes Mellitus in the Early Diagnosis of Sepsis: Clinical Challenges and Biomarkers Contreras-Virues, Mario Raul; Vera Jiménez, José Carlos; Brea-Salvago, Juan Francisco; Moreno Corbacho, Ignacio; García Ortiz, José Carlos; Díaz Gómez, Alfredo Luis; Ribelles García, Antonio; Pérez Arana, Gonzalo Martín Background/Objectives: Type 2 diabetes mellitus (T2DM) substantially increases the risk of infection and sepsis while modifying host immune responses, clinical presenta-tion, and biomarker performance. This review summarizes the pathophysiological mechanisms by which T2DM interferes with the early recognition of sepsis and criti-cally evaluates the performance of conventional and emerging biomarkers in this spe-cific population. Methods: A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science. Original studies, systematic reviews, me-ta-analyses, international guidelines, and landmark publications addressing the inter-action between T2DM, sepsis, immune dysfunction, and sepsis biomarkers were criti-cally analyzed. Results: Chronic hyperglycemia induces immune dysregulation, endo-thelial dysfunction, and persistent low-grade inflammation, resulting in atypical infec-tion presentations and reduced sensitivity of conventional clinical assessment tools. Baseline elevations and altered kinetics of C-reactive protein, procalcitonin, interleu-kin-6, and other inflammatory biomarkers may reduce their diagnostic specificity. Lactate retains prognostic value but should be interpreted cautiously in patients with diabetic ketoacidosis or other metabolic disturbances. Emerging biomarkers, including presepsin, pro-adrenomedullin, soluble urokinase plasminogen activator receptor, cell-free DNA, and 16S rRNA, show promising diagnostic potential, although evidence in diabetic populations remains limited. Conclusions: T2DM represents a distinct clin-ical phenotype in sepsis that requires individualized interpretation of biomarkers. Multimarker strategies integrating clinical, metabolic, and laboratory data may im-prove early sepsis recognition, but prospective validation studies in diabetic popula-tions are still needed.

Human upper limbs and low‑cost phantom models for ultrasound‑guided learning of peripheral vascular access

2026-05-28T04:02:35Z

Human upper limbs and low‑cost phantom models for ultrasound‑guided learning of peripheral vascular access García Ortiz, José Carlos; Gracia Romero, Manuel Ángel; Díaz Gómez, Alfredo Luis; Marchante Casas, Guillermo Joaquín; Ribelles García, Antonio; Pérez Arana, Gonzalo Martín; Visiedo García, Francisco Manuel; Guerrero Ramírez, Soledad; Prada Oliveira, José Arturo Background: Clinical ultrasound has become a core competency for 21st-century physicians, offering real-time diagnostic support. Its integration into early undergraduate medical curricula is progressively increasing. This study presents a strategy developed by our teaching group and evaluates its satisfaction and feasibility in an early clinical ultrasound training intervention Methods: To assess the educational impact of ultrasound training and needle aspiration, we developed several self-designed models. A group of second-year medical students participated in an ultrasound assisted practical lesson using these models. We prepared specialised practical lessons focused on ultrasound-guided vessels puncture using low-cost ballistic gel models. Additionally, dissected human upper limbs were used to cannulated brachial arteries and guide vascular puncture skills. A questionnaire measuring student satisfaction, perceived utility, and timing of the training was designed to quantify its significance. Results: Students highly appreciated the early approach to ultrasonography learning and demonstrate significant anatomical knowledge acquisition. The ballistic gel models surpassed commercial simulators in usability and image quality and were rated as more comfortable for learning. Nevertheless, the human model received the highest student scores. Conclusions: We present several models to increase ultrasound skills in medical students. These models were experienced as a useful and realistic practice compared to commercial alternatives. Their ease of creation and anatomical fidelity combined with low-cost make them valuable tools. Furthermore, the designed human upper limb model proved improving students´satisfaction and the ultrasound-guided vascular approach