Cancer continues to be a major contributor to global morbidity and mortality, highlighting the need for multitarget therapeutic approaches that can address tumor heterogeneity, therapeutic resistance, and disease recurrence. Curcumin, the primary polyphenol obtained from Curcuma longa, exerts wide-ranging anticancer effects by modulating multiple oncogenic pathways, including NF-κB, STAT3, PI3K/Akt/mTOR, Wnt/β-catenin, MAPK, and Hippo/YAP signaling. However, its movement into clinical use has been constrained by poor aqueous solubility, rapid metabolism, extensive first-pass elimination, and restricted systemic exposure after oral intake. Piperine, an alkaloid extracted from Piper nigrum and Piper longum, has inherent anticancer, anti-inflammatory, and chemosensitizing activities, and it has been extensively studied as a potential enhancer of curcumin pharmacokinetics. Still, the growing body of evidence shows that piperine’s impact on curcumin bioavailability is variable and depends on the formulation, and newer experimental work has raised doubts about the consistency and broad applicability of the pharmacokinetic enhancement described in earlier studies. This review critically integrates current evidence on the therapeutic promise of curcumin–piperine combinations for cancer prevention and treatment, separating experimentally validated results from hypothesized mechanisms. Experimental findings indicate that the combination restrains tumor growth through coordinated regulation of apoptosis, cell-cycle progression, inflammatory signaling, oxidative stress, and cancer stem cell maintenance across multiple malignancies, including colorectal, breast, hepatocellular, lung, glioblastoma, and hematological cancers. Emerging evidence also implies that curcumin and piperine may influence gut microbiota composition, microbial metabolite profiles, intestinal barrier function, and host immune responses, thereby offering an additional—though still developing—mechanistic route through which this combination could affect carcinogenesis and therapeutic responsiveness. Advances in nanotechnology-based delivery systems, such as emulsomes, polymeric nanoparticles, magnetic nanoparticles, and gold nanogels, have substantially improved drug stability, controlled release, intracellular delivery, and antitumor efficacy in preclinical models, providing promising options to mitigate pharmacological limitations. While the available evidence supports the curcumin–piperine combination as a credible multitarget adjunct for cancer prevention and therapy, most data come from in vitro and animal studies, whereas well-designed clinical studies are limited. Future research should emphasize standardized formulations, thorough pharmacokinetic assessment, biomarker-driven clinical trials, careful evaluation of potential drug–drug interactions, and mechanistic studies that clarify host–microbiota–tumor interactions to determine the exact clinical role of curcumin–piperine combinations in precision oncology.
Omega-3 polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), have well-established anti-inflammatory properties and have been increasingly investigated for their potential role in modulating tumor progression. However, the contribution of adipose tissue to these effects remains poorly understood. Here, we investigated whether dietary supplementation with DHA-enriched omega-3 modulates systemic inflammation, adipose tissue phenotype, and adipose tissue–tumor crosstalk, with particular emphasis on the biological activity of brown (BAT) and subcutaneous white adipose tissue (sWAT)-derived secretomes against melanoma cells. Female C57BL/6 mice received DHA-enriched omega-3 supplementation (DHA: EPA ratio 5:1; 1 g/kg body weight/day) for 35 days. Systemic inflammation and cellular redox-associated responses were assessed by serum cytokine profiling and flow cytometric analysis of total peritoneal lavage cells. Adipose tissue depots were evaluated by histological and molecular analyses. Conditioned media (CM) derived from BAT and sWAT of control and supplemented mice were characterized for metabolic and inflammatory mediators and tested for their effects on B16-F10 melanoma cells and NIH/3T3 non-tumoral fibroblasts. DHA-enriched omega-3 supplementation significantly attenuated systemic inflammatory markers and reduced oxidant-sensitive fluorescence in total peritoneal lavage cells without affecting body weight. Supplemented mice exhibited reduced adipose tissue mass, decreased adipocyte size in gonadal white adipose tissue, and lower TGF-β expression in BAT, whereas classical thermogenic and lipolytic markers remained largely unchanged. Adipose tissue–derived CM from supplemented animals displayed depot-specific metabolic and inflammatory changes. Functionally, BAT-derived CM from DHA-enriched omega-3-supplemented mice markedly reduced B16-F10 melanoma cell viability, while preserving NIH/3T3 fibroblast viability. In addition, CM from supplemented animals attenuated melanoma-associated inflammatory signaling, including reduced IL-6 production and normalization of TGF-β levels. These findings demonstrate that DHA-enriched omega-3 supplementation remodels adipose tissue phenotype and secretory function, generating a BAT-derived secretome with selective cytotoxic activity against melanoma cells. Our results identify adipose tissue, particularly BAT, as an active mediator of the systemic and antitumor effects of DHA and highlight adipose tissue–tumor crosstalk as a potential mechanism linking dietary lipids to cancer biology.
Insulin resistance (IR) threatens adolescent health, with delayed intervention increasing adult metabolic disorder risk. Existing diagnostic methods are invasive and complex, limiting large-scale or school-based screening. Here, we developed a non-invasive, scalable IR risk screening and classification model to facilitate early identification/intervention. The study involved adolescents aged 12–20 from the NHANES. Univariate regression and LASSO regression were used to identify independent risk factors. Four ML algorithms determined the optimal model. The calibration chart and DCA are utilized to verify the model. The RCS analysis is carried out for the prediction factors, and the optimal decision threshold is established. A total of 1724 individuals were divided into training set and an internal test set comprising 1206 and 518 individuals. 943 individuals were collected for the historical temporal test set. Among 29 body composition parameters from DXA/BIA, 6 variables were finally selected after LASSO regression. Among the four algorithms, logistic regression (LR) model exhibited superior performance. When compared to the other three models, demonstrating relatively high stability and predictive capability, indicating its optimal status as a forecasting tool for adolescent IR risk. Finally, the integration of the four variables was facilitated by the LR model’s variable importance weight, thereby establishing a prediction nomogram platform for the screening and classification of adolescent IR. A machine learning-based adolescent IR screening and classification model provides optimal threshold for Waist-to-height ratio and trunk fat in adolescents across ages/ genders, facilitating clinical decision-making and early screening, and offering theoretical and technical support for non-invasive metabolic disorder intervention.
Adolescence constitutes a pivotal developmental phase marked by physiological and neurobiological adaptations that may influence oxidative stress responses, especially in the context of rigorous physical exertion. This narrative review critically summarizes current evidence regarding the interactions between aerobic exercise and antioxidant intake/supplementation, including vitamins (C and E), minerals (zinc), endogenous antioxidants like coenzyme Q10 (CoQ10), and polyphenols, to evaluate how these interventions may influence exercise-induced redox adaptations and their potential neurobiological relevance in adolescents. Current evidence suggests a multifaceted and frequently contradictory scenario. Supplementation with vitamins C and E may improve lipid profiles, reduce exercise-induced hemolysis, and elevate specific immune indicators; however, their influence on performance and oxidative stress biomarkers is frequently minimal or context-dependent. CoQ10 exhibits potential protective effects against oxidative stress and exercise-induced muscular damage, with sporadic enhancements in performance, although it does not consistently influence aerobic capacity. Polyphenol-enriched interventions, exemplified by beetroot juice and curcumin, exhibit heterogeneous effects, varying from enhanced exercise capacity and diminished fatigue to possible effects on vascular and redox-sensitive pathways. Evidence supporting direct neurobiological mechanisms, including changes in neuroplasticity- or brain-related pathways, remains limited in adolescent populations and is derived largely from indirect or mechanistic evidence. Collectively, the interplay between antioxidant supplementation and physical exercise in adolescents appears to operate as a double-edged sword, potentially facilitating recovery while simultaneously altering exercise-induced redox adaptations. The available evidence remains limited by methodological heterogeneity, small sample sizes, short intervention durations, and the scarcity of direct adolescent neurobiological outcomes. Further well-controlled studies are required to clarify the context-specific role of antioxidant strategies in adolescent exercise adaptation and brain health. Not applicable.
Diabetes is a growing health concern, and effective glycaemic management is essential to prevent complications. Dietary nitrate- and nitrite-rich foods may influence glycaemic control, but the evidence remains inconsistent. Accordingly, this study systematically synthesised and evaluated the current evidence to determine whether beetroot-derived nitrate and nitrite interventions can improve glycaemic regulation and glucose metabolism. PubMed, Scopus, Web of Science, and Embase were searched from inception to September 2026 using pre-determined keywords to identify RCTs evaluating the chronic effects of dietary inorganic nitrate/nitrite on fasting blood glucose, fasting insulin, HbA1c, and indices of insulin resistance and sensitivity in healthy adults or those with type 2 diabetes. Screening and data extraction were conducted by at least two independent reviewers, and risk of bias was assessed using the RoB2 tool. Out of 5,374 retrieved studies, seven publications (six RCTs) met the eligibility criteria and were included. All used beetroot-based preparations (juice, extract, or powder), with intervention durations ranging from 2 weeks (crossover trials) to 6 months. No consistent or significant improvements in glycaemic indices were observed, suggesting that dietary nitrate/nitrite, particularly from beetroot, is not effective for glycaemic control. Despite observational evidence linking dietary nitrate/nitrite to glucose regulation, RCTs limited to beetroot-derived nitrate/nitrite supplementation has shown no significant effect. Given uncertainties regarding bioavailability and the potential role of other nitrate sources, beetroot-derived nitrate/nitrite interventions cannot currently be recommended specifically for glycaemic control, although nitrate-rich foods remain part of a healthy diet and further research on other sources is warranted.
