Simancas Racines, Daniel

Preferred name

Main Affiliation

Facultad de Ciencias de la Salud y Bienestar Humano

Ambato

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Natural Products Targeting Key Molecular Hallmarks in Gastric Cancer: Focus on Apoptosis, Inflammation, and Chemoresistance
(2026)
Simancas Racines, Daniel
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Cagua Ordoñez, Jaen
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Angamarca Iguago, Jaime
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Parise Vasco, Juan Marcos
;
Reytor González, Claudia
Natural products have emerged as promising multi-target agents for addressing the complex biology of gastric cancer, a malignancy characterized by marked molecular heterogeneity, late clinical presentation, and frequent resistance to systemic therapies. This narrative synthesis integrates primarily preclinical evidence, with emerging clinical data, on how naturally derived compounds modulate three central molecular processes that drive gastric tumor progression and therapeutic failure: evasion of programmed cell death, persistent tumor-promoting inflammation, and chemoresistance. Compounds such as curcumin, resveratrol, berberine, ginsenosides, quercetin, and epigallocatechin gallate restore apoptotic competence by shifting the balance between pro-survival and pro-death proteins, destabilizing mitochondrial membranes, promoting cytochrome c release, and activating caspase-dependent pathways. These agents also exert potent anti-inflammatory effects by inhibiting nuclear factor kappa B and signal transducer and activator of transcription signaling, suppressing pro-inflammatory cytokine production, reducing cyclooxygenase activity, and modulating the tumor microenvironment through changes in immune cell behavior. In parallel, multiple natural compounds function as chemo-sensitizers by inhibiting drug efflux transporters, reversing epithelial–mesenchymal transition, attenuating cancer stem cell-associated traits, and suppressing pro-survival signaling pathways that sustain resistance. Collectively, these mechanistic actions highlight the capacity of natural products to simultaneously target interconnected hallmarks of gastric cancer biology. Ongoing advances in formulation strategies may help overcome pharmacokinetic limitations; however, rigorous biomarker-guided studies and well-designed clinical trials remain essential to define the translational relevance of these compounds.
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Interpreting Resting Energy Expenditure in Critically Ill Patients with Obesity: Clinical Impact of Weight Adjustment
(2026)
Sebastián Chapela
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Cagua Ordoñez, Jaen
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Parise Vasco, Juan Marcos
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Daniel Tettamanti Miranda
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Claudia Kecskes
Accurately estimating resting energy expenditure (REE) in critically ill obese patients remains a significant clinical challenge, as predictive equations are consistently inadequate. Metabolic heterogeneity across obesity classes and the role of substrate utilization are insufficiently characterized. Objective: To evaluate the impact of different weight-normalization methods on the interpretation of REE and to identify independent metabolic determinants of weight-adjusted energy expenditure in critically ill patients with obesity. Methods: Bicentric cross-sectional study of 148 critically ill adults with obesity undergoing indirect calorimetry. REE normalized by actual body weight (REE/kg), ideal body weight (REE/IBW), and adjusted body weight (REE/AdjBW) was calculated. Multivariable models with robust standard errors (HC3), stratified analyses by obesity class (I–III) with a Chow test, and internal validation were performed using 10-fold cross-validation and bootstrap resampling (1000 iterations). Results: Absolute REE did not differ significantly between BMI categories (p = 0.679), while REE/kg progressively decreased from normal weight (27.8 kcal/kg/day) to class III obesity (16.9 kcal/kg/day; p < 0.001). The respiratory quotient (RQ) emerged as the most robust independent correlate of adjusted REE (β = −13 to −15 kcal·kg−1·day−1; p < 0.001), whereas clinical severity scores (SOFA, APACHE II) and comorbidity (Charlson) did not show significant associations. Stratified analyses revealed significant structural heterogeneity between obesity classes (F = 4.545, p = 0.0001), with no significant predictors identified in class III obesity, likely reflecting limited statistical power in this subgroup. Conclusions: Normalizing REE using different weight indices fundamentally alters its metabolic interpretation. RQ surpasses traditional clinical scores as a correlate of adjusted REE, consistent with a phenotype of metabolic inflexibility. The heterogeneity between obesity classes underscores the need for individualized indirect calorimetry rather than reliance on predictive equations.
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Alcohol and Substance Use After Bariatric Surgery: Nutritional Risks and Clinical Implications in Long-Term Postoperative Care
(2026)
Martín Campuzano-Donoso
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Reytor González, Claudia
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Gerardo Sarno
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Martha Montalvan
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Luigi Barrea
Metabolic and bariatric surgery (MBS) has evolved into a highly effective neurohormonal intervention for severe obesity; however, it introduces unique long-term vulnerabilities, particularly regarding alcohol (AUD) and substance use disorders (SUD). This review synthesizes the epidemiological, pharmacokinetic, and neurobiological drivers of postoperative substance misuse. Procedures like Roux-en-Y gastric bypass (RYGB) radically alter ethanol metabolism, eliminating first-pass metabolism and accelerating gastric emptying, while simultaneously recalibrating reward pathways, creating a “reward gap” that facilitates addiction transfer. These physiological shifts exacerbate critical micronutrient deficiencies (thiamine, B12, iron), increase the risk of post-bariatric hypoglycemia, and correlate with higher rates of liver cirrhosis and suicide. Furthermore, substance use is a primary driver of suboptimal weight loss trajectories and weight regain. Mitigation requires a lifelong, multidisciplinary framework involving preoperative risk stratification, validated screening (e.g., AUDIT-C), and targeted nutritional supplementation to safeguard the long-term metabolic and psychological benefits of MBS.
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Endometriosis as a Systemic and Complex Disease: Toward Phenotype-Based Classification and Personalized Therapy
(2026)
Simancas Racines, Daniel
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Emilia Jiménez-Flores
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Martha Montalvan
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Raquel Horowitz
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Valeria Araujo
Endometriosis is traditionally conceptualized as a pelvic lesion–centered disease; however, mounting evidence indicates it is a chronic, systemic, and multifactorial inflammatory disorder. This review examines the molecular dialog between ectopic endometrial tissue, the immune system, and peripheral organs, highlighting mechanisms that underlie disease chronicity, symptom variability, and therapeutic resistance. Ectopic endometrium exhibits distinct transcriptomic and epigenetic signatures, disrupted hormonal signaling, and a pro-inflammatory microenvironment characterized by inflammatory mediators, prostaglandins, and matrix metalloproteinases. Immune-endometrial crosstalk fosters immune evasion through altered cytokine profiles, extracellular vesicles, immune checkpoint molecules, and immunomodulatory microRNAs, enabling lesion persistence. Beyond the pelvis, systemic low-grade inflammation, circulating cytokines, and microRNAs reflect a molecular spillover that contributes to chronic pain, fatigue, hypothalamic–pituitary–adrenal axis dysregulation, and emerging gut–endometrium interactions. Furthermore, circulating biomarkers—including microRNAs, lncRNAs, extracellular vesicles, and proteomic signatures—offer potential for early diagnosis, patient stratification, and monitoring of therapeutic responses. Conventional hormonal therapies demonstrate limited efficacy, whereas novel molecular targets and delivery systems, including angiogenesis inhibitors, immune modulators, epigenetic regulators, and nanotherapeutics, show promise for precision intervention. A systems medicine framework, integrating multi-omics analyses and network-based approaches, supports reconceptualizing endometriosis as a systemic inflammatory condition with gynecologic manifestations. This perspective emphasizes the need for interdisciplinary collaboration to advance diagnostics, therapeutics, and individualized patient care, ultimately moving beyond a lesion-centered paradigm toward a molecularly informed, holistic understanding of endometriosis.
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The Oral–Gut–Immune–Nutrition Axis in Rheumatoid Arthritis: Molecular Mechanisms and Therapeutic Implications
(2026)
Reytor González, Claudia
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Náthaly Mercedes Román-Galeano
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Lenin Saul Aules-Curicama
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Camila Doménica Cevallos-Villacis
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Erik González
Rheumatoid arthritis is a chronic systemic autoimmune disease that arises from complex interactions among genetic susceptibility, environmental factors, and immune dysregulation. Growing evidence indicates that microorganisms residing in the oral cavity and gastrointestinal tract, together with dietary factors, play a central role in shaping inflammatory and autoimmune responses in rheumatoid arthritis, forming an interconnected microbiome–immune–nutrition axis. Alterations in the composition and function of oral and intestinal microbial communities are associated with disruption of mucosal barrier integrity, activation of innate and adaptive immune pathways, increased differentiation of proinflammatory T lymphocyte subsets, and loss of immune tolerance that promotes autoantibody production. In addition, microbially derived metabolites, particularly short-chain fatty acids, provide a mechanistic link between microbial ecology, immune regulation, and bone metabolism. Diet represents a key upstream modulator of this axis. Dietary patterns rich in anti-inflammatory nutrients support microbial diversity and immunoregulatory metabolite production, whereas diets high in processed foods and saturated fats favor proinflammatory microbial profiles. Accumulating clinical evidence suggests that nutritional strategies and microbiome-targeted dietary interventions may reduce systemic inflammation and disease-related comorbidities when used alongside standard pharmacological treatments. Taken together, the microbiome–immune–nutrition axis represents a modifiable and clinically meaningful target in rheumatoid arthritis, emphasizing the need for interdisciplinary research and well-designed clinical trials to translate these insights into personalized approaches for disease management. The aim of this review is to integrate current mechanistic and clinical evidence on the interactions between the microbiome, immune system, and nutrition in rheumatoid arthritis, with a focus on their pathogenic relevance, therapeutic potential, and implications for personalized, diet-based interventions.
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Nutrition and longevity – diet in centenarians
(2026)
Evelyn Frias-Toral
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Reytor González, Claudia
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Giuseppe Annunziata
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Ludovica Verde
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Emilia Jimenez-Flores
Background: Nutrition plays a central role in the biological mechanisms that shape aging, health span, and longevity. Micronutrients—including vitamins, trace elements, and polyphenols—support genomic stability, mitochondrial integrity, and antioxidant defense, while dietary patterns rich in plant-based foods modulate inflammation, metabolic regulation, and epigenetic processes. Centenarian populations consuming Mediterranean, Okinawan, Nordic, and Nicoyan diets offer a natural model for understanding how nutrient-rich, minimally processed foods, moderate caloric intake, and balanced lifestyles interact with molecular pathways to extend functional life. Main Body: This review synthesizes current evidence on how micronutrients influence DNA repair, oxidative stress reduction, and mitochondrial protection, particularly through the actions of vitamins C and E, niacin-dependent PARP activity, folate-mediated methylation, and metal cofactors involved in antioxidant enzymes. Plant-based diets rich in fiber and polyphenols enhance microbial diversity and promote beneficial taxa such as Akkermansia and Bifidobacterium, supporting gut barrier integrity and immune balance. Caloric restriction and intermittent fasting activate nutrient-sensing pathways, including AMPK and sirtuins, reduce mTOR activity, and stimulate autophagy, collectively improving cellular resilience. Findings from centenarian regions highlight the convergence of lifestyle, nutrition, and cultural practices that reduce systemic inflammation, maintain metabolic flexibility, and support healthy aging trajectories. Conclusions: Diet emerges as a decisive modifiable determinant of lifespan and health span. The convergence of molecular nutrition, microbiome composition, and traditional dietary habits underlies the exceptional longevity observed in centenarian populations. Future research should integrate nutrigenomics, metabolomics, and microbiome profiling to clarify causal mechanisms and guide precision nutrition strategies for aging societies. © The Author(s) 2026.
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The Role of Gut Microbiota in Postmenopausal Women: Implications for Lipid Metabolism and Targeted Nutritional Interventions
(2026)
Reytor González, Claudia
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Ludovica Verde
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Giuseppe Annunziata
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Náthaly Mercedes Román-Galeano
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Raquel Horowitz
Purpose of Review: This review explores the complex interplay between menopause, estrogen decline, lipid metabolism, and gut microbiota alterations. It highlights the physiological and metabolic changes that predispose postmenopausal women to dyslipidemia and increased cardiovascular disease risk, with particular emphasis on the emerging role of the gut microbiota in modulating lipid homeostasis and inflammatory pathways. In addition, it examines the therapeutic potential of microbiota-targeted nutritional strategies to restore metabolic balance and improve cardiometabolic outcomes in postmenopausal women. Recent Findings: Recent clinical and experimental evidence indicates that menopause-related hormonal changes and aging are associated with gut microbiota dysbiosis, which may contribute to adverse lipid profiles through mechanisms involving bile acid metabolism, short-chain fatty acid production, and low-grade systemic inflammation. Associations between specific microbial taxa and lipid metabolic patterns have been reported; however, findings remain heterogeneous and causal relationships are difficult to establish due to confounding factors such as diet, lifestyle, and medication use. Nutritional interventions aimed at modulating the gut microbiota—including Mediterranean, plant-based, and DASH dietary patterns, increased dietary fiber intake, and supplementation with prebiotics, probiotics, polyphenols, phytoestrogens, and omega-3 fatty acids—have shown potential to improve lipid profiles and cardiometabolic risk markers. Summary: The gut microbiota emerges as a relevant contributor to menopause-associated dyslipidemia and cardiovascular risk. While microbiota-targeted nutritional strategies are promising, further longitudinal and interventional studies are needed to clarify causal pathways and identify clinically actionable microbial signatures. Integrating microbiome-informed nutritional approaches into clinical practice may represent a future strategy to improve cardiometabolic health in postmenopausal women. © The Author(s) 2026.
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Traditional Foods, Oral Microbiome, and Systemic Health: Molecular Pathways Linking Nutrition and Oral Disease Prevention
(2026)
Parise Vasco, Juan Marcos
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Angamarca Iguago, Jaime
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Cagua Ordoñez, Jaen
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Beatriz Cabrera
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Dolores Jima Gavilanes
Periodontal disease affects 10–50% of the global population and is associated with various systemic conditions, including diabetes, cardiovascular disease and adverse pregnancy outcomes. Emerging evidence highlights diet as a critical, modifiable factor that influences the composition of the oral microbiome and periodontal health. This narrative review explores the molecular mechanisms through which traditional foods modulate the oral microbiome and contribute to oral and systemic health. A comprehensive literature search was conducted in PubMed/MEDLINE, the Cochrane Library, LILACS and Epistemonikos, prioritizing systematic reviews, meta-analyses and randomized controlled trials. The oral microbiome harbors over 700 bacterial species, and dysbiosis, characterized by pathogen enrichment, drives periodontal inflammation. Anti-inflammatory dietary patterns, including the Mediterranean diet, demonstrate protective effects. Omega-3 fatty acids, vitamins C and D, polyphenols and dietary fiber support periodontal health, whereas refined carbohydrates, saturated fats and pro-inflammatory nutrients can exacerbate disease. Probiotics show promise as an adjunctive therapy. However, the translation to clinical guidelines is impeded by methodological challenges, including the limited number of randomized controlled trials with oral endpoints, confounding by hygiene practices, and the lack of standardized multi-omics approaches. Nutritional counselling should be integrated into periodontal care as a modifiable risk factor. Future research priorities include precision nutrition approaches, the validation of salivary biomarkers, and interprofessional collaboration between dental and nutrition professionals. © 2026 by the authors.
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Bioactive Natural Compounds in Triple-Negative Breast Cancer: Molecular Targets and Therapeutic Perspectives
(2026)
Emilia Jiménez-Flores
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Reytor González, Claudia
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Dolores Jima Gavilanes
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Cesar Carrillo
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Raquel Horowitz
Triple-negative breast cancer represents one of the most aggressive and therapeutically challenging subtypes of breast malignancies, characterized by marked biological heterogeneity, rapid progression, and limited targeted treatment options. Conventional therapies are frequently constrained by drug resistance, systemic toxicity, and high rates of recurrence. In this context, natural products have gained increasing attention as multifunctional agents capable of modulating several hallmarks of triple-negative breast cancer. Bioactive compounds, including polyphenols, terpenoids, alkaloids, and marine-derived molecules, exhibit pleiotropic antitumor effects by interfering with key oncogenic pathways. Importantly, these compounds have demonstrated the ability to counteract major mechanisms of therapeutic resistance, modulate the tumor immune microenvironment, and enhance the efficacy of standard chemotherapy and immunotherapy. Advances in drug delivery strategies, such as nanoparticle-based systems and tumor-targeted formulations, together with patient-specific molecular profiling, further expand the potential of these agents within personalized treatment approaches. This narrative review critically examines the role of natural compounds in targeting the hallmarks of triple-negative breast cancer and their potential synergistic use to improve therapeutic efficacy while reducing treatment-related toxicity. Overall, the integration of natural product-based strategies into precision oncology frameworks may offer more effective, less toxic, and individualized therapeutic options for this aggressive breast cancer subtype.
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Molecular Bases of Myopathies and Their Impact on Clinical Practice: Advances and Future Perspectives
(2026)
Martín Campuzano-Donoso
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Reytor González, Claudia
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Melannie Toral-Noristz
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Yamilia González
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Simancas Racines, Daniel
Myopathies represent a highly heterogeneous group of primary muscle disorders, traditionally classified based on clinical presentation and histopathological findings. Recent breakthroughs in molecular genetics, immunology, and pathophysiology have revolutionized the understanding, diagnosis, and management of these conditions. Both inherited and acquired forms of myopathy, including structural, metabolic, inflammatory, endocrine, and mitochondrial subtypes, are now recognized to arise from diverse pathogenic mechanisms such as impaired calcium handling, mitochondrial dysfunction, chronic inflammation, altered metabolism, and defective muscle regeneration. The advent of next-generation sequencing technologies has enabled more precise diagnosis of genetic forms, while the discovery of novel molecular biomarkers and immunological signatures offers promising avenues for disease monitoring and stratification across the broader spectrum. Importantly, molecular and mechanistic insights have redefined clinical classifications, allowing for better prognostic predictions and patient-tailored therapeutic approaches. Innovative treatments, including gene therapy, antisense oligonucleotide therapies, immune-modulating agents, metabolic support strategies, and targeted pharmacological interventions, are progressively translating molecular knowledge into clinical applications. However, technical limitations, biological variability, and ethical considerations continue to pose significant challenges to the implementation of precision medicine in myopathies. In this narrative review, we comprehensively discuss the latest molecular findings, their integration into clinical practice, and the emerging therapeutic strategies based on these discoveries. We also highlight current limitations and propose future research directions aimed at bridging the gap between molecular insights and effective, equitable patient care.
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Simancas Racines, Daniel

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