Valeria Rodríguez

Breast cancer is the most prevalent malignancy worldwide. Beyond genetic factors, dietary components like palmitic acid (PA) and sucrose modulate tumor progression and microenvironment dynamics. However, their combined mechanistic impacts on tumor-stroma crosstalk remain undefined. We investigated how dietary PA and sucrose affect breast cancer growth and the tumor microenvironment using a murine model. Mice received Control, high-PA (HPOD), high-sucrose (HCD), or combined (HPCD) diets. We assessed tumor growth, metabolic parameters, membrane fatty acids, histopathology, proliferative indices, and microenvironment markers (CD8, F4/80, α-SMA, HIF-1α, FASN). In vitro assays evaluated PA and fructose effects on LM3 cells and fibroblasts. HCD and HPCD markedly promoted tumor growth versus Control and HPOD. HPOD increased membrane saturated fatty acids, whereas HCD elevated ω-6 PUFAs. Both HCD and HPCD increased macrophage infiltration (F4/80 +), while HPCD specifically activated cancer-associated fibroblasts (α-SMA). HIF-1α protein increased across all experimental diets without mRNA alterations, suggesting post-transcriptional stabilization. FASN protein upregulation occurred in HCD and HPCD, while Fasn mRNA increased specifically in HCD. In vitro, combining PA and fructose enhanced LM3 cell proliferation and viability while reducing apoptosis. Additionally, this co-treatment specifically increased fibroblast viability. Diets rich in PA and sucrose drive breast cancer progression through distinct mechanisms. Carbohydrates transcriptionally activate FASN-mediated lipogenesis, whereas their combination with PA remodels the tumor microenvironment via CAF activation and HIF-1α post-transcriptional stabilization. These findings highlight specific dietary components as critical variables in cancer progression, offering potential implications for nutritional interventions and targeted therapies.

We previously demonstrated that naringin (NAR) protects against liver damage in streptozotocin (STZ)-induced diabetes in rats. The aim of this study was to elucidate whether NAR is also able to protect the functioning, biogenesis and dynamics of the liver mitochondria in diabetic rats (DM). The activities of isocitrate dehydrogenase and malate dehydrogenase from the Krebs cycle, complex I–III from electron chain and adenosine triphosphate synthase were decreased in DM rats, effects that were blocked by NAR. The gene expression of mitofusin-2 and GTPase dynamin-related protein 1, markers of mitochondrial fusion and fission, were decreased in DM rats, which was prevented by NAR. Total glutathione was decreased and protein carbonyl contents as well as the activity of the antioxidant enzymes were increased in DM rats. All these changes were blocked by NAR. In conclusion, NAR protects the liver mitochondria from DM rats avoiding changes in the activity of Krebs cycle, the respiratory chain and the oxidative phosphorylation as well as preventing alterations in the fusion-fission processes. These effects are mediated, at least in part, by decreasing oxidative stress and anomalies in the enzymatic antioxidant system. Further studies are necessary to validate efficacy and safety of NAR for human use.

Introduction/Objective: As in the rest of the world, in Latin America there is a high prevalence of interpersonal violence (IV) in childhood and adolescence, which is associated with psychological consequences in the short, medium and long term. At the international level, progress has been made in the recognition of evidence-based psychotherapies, but the situation in Latin America is unknown. The objective of this systematic literature review is to identify which psychotherapy models or modalities have been shown to be effective in Latin America. Methods: A systematic search of five databases was carried out with search terms relating to psychosocial interventions of people exposed to IV during childhood, based in Latin America. Studies regarding Latino populations based in United States were excluded. Results: 14 papers describing 13 studies and one follow-up were identified. Individual and group interventions (mainly cognitive-behavioural and with psychodynamic influence) were included. Although all showed clinically or statistically significant changes in symptoms of post-traumatic stress, anxiety and depression, most were pilot studies with important methodological limitations and a high risk of bias. Conclusions: It is necessary to develop clinical practice in Latin America with more robust research (i.e., controlled and randomised clinical trials) that produce more reliable evidence regarding the effectiveness of psychosocial interventions for IV involving children and adolescents in the Latin American context.

We analyzed the effect of naringin (NAR), a flavonoid from citric fruits, on bone quality and biomechanical properties, as well as the redox state of bone marrow in rats fed a fructose-rich diet (FRD), an experimental model to mimic human metabolic syndrome. NAR blocked the increase in the number of osteoclasts and adipocytes and the decrease in the number of osteocytes and osteocalcin (+) cells caused by FRD. Trabecular number was significantly higher in the FRD+NAR group. FRD induced a decrease in the femoral trabecular and cortical bone mineral density, which was blocked by NAR. The fracture and ultimate loads were also decreased in the FRD and FRD+NAR groups. NAR increased the number of nodes to terminal trabecula, the number of nodes to node trabecula, the number of nodes, and the number of nodes with 2 terminals and decreased the Dist (mean size of branches) value. FRD decreased bone marrow catalase activity, an effect that was prevented by NAR. In conclusion, FRD has detrimental effects on the long bones, which are associated with oxidative stress in the bone marrow. Most of these changes are prevented by NAR through its antioxidant properties and promotion of bone formation. Novelty: Fructose-rich diets have detrimental effects on long bones, which are associated with oxidative stress in the bone marrow. Most of these changes are prevented by naringin through its antioxidant properties and promotion of bone formation.

Sodium deoxycholate (NaDOC) inhibits the intestinal Ca²⁺ absorption and ursodeoxycholic acid (UDCA) stimulates it. The aim of this study was to determine whether NaDOC and UDCA produce differential effects on the redox state of duodenal mitochondria altering the Krebs cycle and the electron transport chain (ETC) functioning, which could lead to perturbations in the mitochondrial dynamics and biogenesis. Rat intestinal mitochondria were isolated from untreated and treated animals with either NaDOC, UDCA, or both. Krebs cycle enzymes, ETC components, ATP synthase, and mitochondrial dynamics and biogenesis markers were determined. NaDOC decreased isocitrate dehydrogenase (ICDH) and malate dehydrogenase activities affecting the ETC and ATP synthesis. NaDOC also induced oxidative stress and increased the superoxide dismutase activity and impaired the mitochondrial biogenesis and functionality. UDCA increased the activities of ICDH and complex II of ETC. The combination of both bile acids conserved the functional activities of Krebs cycle enzymes, ETC components, oxidative phosphorylation, and mitochondrial biogenesis. In conclusion, the inhibitory effect of NaDOC on intestinal Ca²⁺ absorption is mediated by mitochondrial dysfunction, which is avoided by UDCA. The stimulatory effect of UDCA alone is associated with amelioration of mitochondrial functioning. This knowledge could improve treatment of diseases that affect the intestinal Ca²⁺ absorption.

Background: Naringin (NAR) is a flavonoid enriched in several medicinal plants and fruits. An increasing interest in this molecule has emerged because it has the potential to contribute to alleviating many health problems. Objective:: This review briefly describes the NAR pharmacokinetics and it mainly focuses on the in vitro and in vivo animal studies showing NAR beneficial effects on cardiovascular, metabolic, neurological and pulmonary disorders and cancer. The anabolic effects of NAR on different models of bone and dental diseases are also analyzed. In addition, the evidence of the NAR action on the gastrointestinal tract is reported as well as its influence on the microbiota composition and activity. Finally, current research on NAR formulations and clinical applications are discussed. Methods: The PubMed database was searched until 2019, using the keywords NAR, naringenin, cardiovascular and metabolic disorders, neurological and pulmonary disorders, cancer, bone and dental diseases, gastrointestinal tract, microbiota, NAR formulations, clinical trials. Results: The number of studies related to the bioavailability and pharmacokinetics of NAR is limited. Positive effects of NAR have been reported on cardiovascular diseases, Type 2 Diabetes Mellitus (T2DM), metabolic syndrome, pulmonary disorders, neurodegenerative diseases, cancer, and gastrointestinal pathologies. The current NAR formulations seem to improve its bioavailability, which would allow its clinical applications. Conclusion: NAR is endowed with broad biological effects that could improve human health. Since a scarce number of clinical studies have been performed, the NAR use requires more investigation in order to know better their safety, efficacy, delivery, and bioavailability in humans.