γ-terpinene, α-terpinene, p-cymene, and myrcene are monoterpenes found in many essential oils extracted from a variety of plants and spices. Myrcene also occurs naturally in plants such as hops, cannabis, lemongrass, and verbena and is used as a flavoring agent in food and beverage manufacturing. In this research, the biological efficacy of γ-terpinene, α-terpinene, p-cymene, and myrcene was studied in human cell lines (HeLa, SH-SY5Y, and HDFa). Cytotoxicity, cell proliferation, cell migration, and morphology assays were performed to obtain detailed information on the anticancer properties. Our results show that myrcene has potential biological activity, especially in HeLa cells. In this cell line, it leads to an arrest of proliferation, a decrease in motility and morphological changes with loss of sphericity and thickness, and DNA damage. In addition, the interaction of γ-terpinene, α-terpinene, p-terpinene, and myrcene with calf thymus DNA (ct-DNA) was studied by UV-visible spectrophotometry. DNA binding experiments show that only myrcene can interact with DNA with an apparent dissociation constant (K_d) of 29 × 10⁻⁶ M.

Ferroptosis is a cell death mechanism based on extensive cellular membrane peroxidation, implicated in neurodegenerative and other diseases. The essential oil component γ‐terpinene, a natural monoterpene with a unique highly oxidizable pro‐aromatic 1,4‐cyclohexadiene skeleton, inhibits peroxidation of polyunsaturated lipid in model heterogeneous systems (micelles and liposomes). Upon H‐atom abstraction, an unstable γ‐terpinene‐derived peroxyl radical is formed, that aromatizes to p‐cymene generating HOO⋅ radicals. As HOO⋅ are small and hydrophilic radicals, they quickly diffuse outside the lipid core, blocking the radical chain propagation of polyunsaturated lipids. This unprecedented antioxidant “slingshot” mechanism explains why γ‐terpinene shows a protective activity against ferroptosis, being effective at submicromolar concentrations in human neuroblastoma (SH‐SY5Y) cells.

CDKL5 deficiency disorder (CDD), a developmental encephalopathy caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene, is characterized by a complex and severe clinical picture, including early-onset epilepsy and cognitive, motor, visual, and gastrointestinal disturbances. This disease still lacks a medical treatment to mitigate, or reverse, its course and improve the patient’s quality of life. Although CDD is primarily a genetic brain disorder, some evidence indicates systemic abnormalities, such as the presence of a redox imbalance in the plasma and skin fibroblasts from CDD patients and in the cardiac myocytes of a mouse model of CDD. In order to shed light on the role of oxidative stress in the CDD pathophysiology, in this study, we aimed to investigate the therapeutic potential of Coenzyme Q10 (CoQ10), which is known to be a powerful antioxidant, using in vitro and in vivo models of CDD. We found that CoQ10 supplementation not only reduces levels of reactive oxygen species (ROS) and normalizes glutathione balance but also restores the levels of markers of DNA damage (γ-H2AX) and senescence (lamin B1), restoring cellular proliferation and improving cellular survival in a human neuronal model of CDD. Importantly, oral supplementation with CoQ10 exerts a protective role toward lipid peroxidation and DNA damage in the heart of a murine model of CDD, the Cdkl5 (+/−) female mouse. Our results highlight the therapeutic potential of the antioxidant supplement CoQ10 in counteracting the detrimental oxidative stress induced by CDKL5 deficiency.

Wheat bran forms the outermost part of the kernel, which is typically discarded as a by-product. Depending on the milling process, bran can be separated into four fractions: coarse bran (CB), coarse weatings (CW), fine weatings (FW), and low-grade flour (LGF). This study aimed to analyze the macronutrient and bioactive compound profiles of these four by-products across five cultivars and two wheat mixtures. Dietary fibers, free and bound phenolics, phytic acid, fatty acids, and aleurone layer markers were examined in all samples. The results indicate that insoluble fibers, phenolic compounds, and phytic acid decreased from CB to LGF, whereas soluble fiber content exhibited a greater variability among fractions. In all samples, coarse bran was the richest fraction in the protein 7S globulin. The same fraction from the two commercial mixtures and Manitoba cultivar exhibited significantly higher levels of bound ferulic acid compared to the other cultivars (+34%). Manitoba CB also had the highest oleic acid content (18.04% of total lipid content) among all samples, followed by the Rumeno cultivar (17.75%), which also had the highest linolenic acid content (6.35%). Given their health-promoting and technological potential, these by-products could be selectively used to enrich food products and dietary supplements with functional nutrients.

CDKL5 deficiency disorder (CDD), a developmental encephalopathy caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene, is characterized by a complex and severe clinical picture, including early-onset epilepsy, cognitive, motor, visual, and gastrointestinal disturbances. This disease still lacks a medical treatment to mitigate, or reverse, its course, and improve the patient’s quality of life. Although CDD is primarily a genetic brain disorder, some evidence in-dicates systemic abnormalities, such as the presence of a redox imbalance in plasma and skin fi-broblasts from CDD patients and in cardiac myocytes of a mouse model of CDD. In order to shed light on the role of oxidative stress in the CDD pathophysiology, in this study we aimed to in-vestigate the therapeutic potential of Coenzyme Q10 (CoQ10), which is known to be a powerful antioxidant, using in vitro and in vivo models of CDD. We found that CoQ10 supplementation not only reduces levels of Reactive Oxygen Species (ROS) and normalizes glutathione balance, but also restores the levels of markers of DNA damage (γ-H2AX) and senescence (lamin B1), significantly improving cellular proliferation and survival in a human neuronal model of CDD. Importantly, oral supplementation with CoQ10 exerts a protective role toward lipid peroxidation and DNA damage in the heart of a murine model of CDD, the Cdkl5 (+/−) female mouse. Our results highlight the therapeutic potential of the antioxidant supplement CoQ10 in counteracting the detrimental oxidative stress induced by CDKL5 deficiency.

The approval of immunotherapy has revolutionized the management of hepatocellular carcinoma (HCC) patients. However, sorafenib remains a first-line therapeutic option for advanced patients and, in particular, for patients not eligible for immune checkpoint inhibitors, but its efficacy is limited by the onset of acquired resistance, highlighting the urgent need for predictive biomarkers. This study investigates the role of miR-22 in metabolic reprogramming and its potential as a biomarker in HCC. The analysis of miR-22 expression was performed in HCC patients and preclinical models by qPCR. Functional analyses in HCC cells evaluated GLUT1 as a direct miR-22 target. Cellular and metabolic assays evaluated the miR-22/GLUT1 axis’s role in metabolic changes, tumor aggressiveness, and sorafenib response. Circulating miR-22 was analyzed in sorafenib-treated HCC patients and rats. MiR-22 was downregulated in HCCs and associated with aggressive tumor features. Functionally, miR-22 modulated the HIF1A pathway, enhanced survival in stressful conditions, promoted a glycolytic shift, and enhanced cancer cell plasticity and sorafenib resistance via GLUT1 targeting. In addition, high serum miR-22 levels were associated with sorafenib resistance in HCC patients and rats. GLUT1 inhibition sensitized low miR-22-expressing HCC cells to sorafenib in preclinical models. These findings suggest that circulating miR-22 deserves attention as a predictive biomarker of sorafenib response. GLUT1 inhibition may represent a therapeutic strategy to combine with sorafenib, particularly in patients exhibiting high circulating miR-22 levels.