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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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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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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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Single vs. Dual Agonist Pharmacotherapy for Managing Insufficient Weight Loss and Weight Regain Following Metabolic and Bariatric Surgery: A Comparative Review
(2026)
Reytor González, Claudia
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Martín Campuzano-Donoso
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Gerardo Sarno
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Martha Montalvan
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Raquel Horowitz
Weight management after metabolic and bariatric surgery remains a persistent clinical challenge, particularly when patients experience insufficient weight loss or progressive weight regain following the postoperative nadir. In recent years, pharmacological therapies targeting gut-derived hormones have reshaped the therapeutic approach, offering nonsurgical strategies that directly influence appetite regulation, satiety, and energy balance. Single agonists acting on the glucagon-like peptide one receptor have demonstrated meaningful reductions in body weight among postoperative patients, while dual agonists that target both the glucagon-like peptide one receptor and the glucose-dependent insulinotropic polypeptide receptor have shown even greater weight reduction in early studies, suggesting enhanced therapeutic potential. These benefits, however, must be interpreted within the unique anatomical, nutritional, and behavioral context of individuals who have undergone metabolic and bariatric procedures, as they are inherently at higher risk for micronutrient deficiencies, gastrointestinal intolerance, and maladaptive eating patterns. Successful treatment requires a balanced integration of pharmacotherapy, individualized nutritional guidance, psychological support, and a patient-centered model of long-term care. Although emerging evidence is promising, dedicated clinical trials are still needed to directly compare the efficacy, safety, and sustainability of single versus dual agonist therapies in postoperative populations. Furthermore, culturally sensitive dietary strategies and shared decision-making processes are essential to enhance adherence, optimize long-term outcomes, and ensure equitable access to treatment. Ultimately, these therapies represent a significant advance in addressing postoperative weight challenges, but their full potential will rely on comprehensive, multidisciplinary frameworks that support both biological and behavioral aspects of chronic weight management.
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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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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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