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Obesity rates among children are growing rapidly worldwide, placing massive pressure on healthcare systems. Untargeted metabolomics can expand our understanding of the pathogenesis of obesity and elucidate mechanisms related to its symptoms. However, the metabolic signatures of obesity in children have not been thoroughly investigated. Herein, we explored metabolites associated with obesity development in childhood. Untargeted metabolomic profiling was performed on fasting serum samples from 27 obese Caucasian children and adolescents and 15 sex- and age-matched normal-weight children. Three metabolomic assays were combined and yielded 726 unique identified metabolites: gas chromatography-mass spectrometry (GC-MS), hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LC-MS/MS), and lipidomics. Univariate and multivariate analyses showed clear discrimination between the untargeted metabolomes of obese and normal-weight children, with 162 significantly differentially expressed metabolites between groups. Children with obesity had higher concentrations of branch-chained amino acids and various lipid metabolites, including phosphatidylcholines, cholesteryl esters, triglycerides. Thus, an early manifestation of obesity pathogenesis and its metabolic consequences in the serum metabolome are correlated with altered lipid metabolism. Obesity metabolite patterns in the adult population were very similar to the metabolic signature of childhood obesity. Identified metabolites could be potential biomarkers and used to study obesity pathomechanisms.

A complex of the natural flavonoid kaempferol with zinc (Kam-Zn) was synthesized, and its physicochemical properties were investigated using spectroscopic methods such as Fourier transform infrared spectroscopy (FT-IR), ultraviolet–visible (UV-Vis) spectroscopy and theoretical chemistry. Biological studies were conducted to evaluate the cytotoxic and antiproliferative effects of these complexes on MCF-7 breast cancer cells. Treatment with Kam 100 µM (84.86 ± 7.79%; 64.37 ± 8.24%) and Kam-Zn 100 µM (91.87 ± 3.80%; 87.04 ± 13.0%) showed no significant difference in proliferation between 16 h and 32 h, with the gap width remaining stable. Both Kam-Zn 100 μM and 200 μM demonstrated effective antiproliferative and cytotoxic activity, significantly decreasing cell viability and causing cell death and morphology changes. Antioxidant assays revealed that Kam (IC50 = 5.63 ± 0.06) exhibited higher antioxidant potential compared to Kam-Zn (IC50 = 6.80 ± 0.075), suggesting that zinc coordination impacts the flavonoid's radical scavenging activity by the coordination of metal ion to hydroxyl groups. Computational studies revealed significant modifications in the electronic structure and properties of Kam upon forming 1:1 complexes with Zn2+ ions. Spectroscopy analyses confirmed structural changes, highlighting shifts in absorption peaks and alterations in functional group vibrations indicative of metal–ligand interactions. FT-IR and UV-Vis spectra analysis suggested that Zn coordinates with the 3-OH and 4C=O groups of ligand. These findings suggest that the Kam-Zn complex exhibits interesting antiproliferative, cytotoxic and modified antioxidant effects on MCF-7 cells, providing valuable insights into their structural and anticancer properties. [ABSTRACT FROM AUTHOR]

Apigenin, a naturally derived flavonoid, is increasingly being acknowledged for its potential therapeutic applications, especially in oncology. This research explores apigenin's capacity to modulate cancer cell viability, emphasizing its roles beyond its minimal antioxidant activity attributed to its basic molecular structure devoid of hydroxyl groups. We investigated apigenin's effects on two breast cancer cell lines, estrogen-dependent MCF-7 and non-estrogen-dependent MDA-MB-231 cells. Our findings reveal that apigenin exerts a dose-dependent cytotoxic and anti-migratory impact on these cells. Interestingly, both apigenin and doxorubicin—a standard chemotherapeutic agent—induced lipid droplet accumulation in a dose-dependent manner in MDA-MB-231 cells. This phenomenon was absent in MCF-7 cells and not evident when doxorubicin and apigenin were used concurrently, suggesting distinct cellular responses to these treatments that imply that their synergistic effects might be mediated through mechanisms unrelated to lipid metabolism. A further chemoinformatics analysis indicated that apigenin and doxorubicin might interact primarily at the level of ATP-binding cassette (ABC) transporter proteins, with potential indirect influences from the AKT and MYC signaling pathways. These results highlight the importance of understanding the nuanced interactions between apigenin and conventional chemotherapeutic drugs, as they could lead to more effective strategies for cancer treatment. This study underscores apigenin's potential as a modulator of cancer cell dynamics through mechanisms independent of its direct antioxidant effects, thereby contributing to the development of flavonoid-based adjunct therapies in cancer management. [ABSTRACT FROM AUTHOR]