International Journal of Molecular Sciences

Common wheat breeding programs prioritize the development of high grain protein content (GPC) varieties, as GPC influences milling efficiency and end-use quality. However, the molecular basis of protein and gluten accumulation in wheat grains remains insufficiently understood, particularly regarding genetic differences between spring and winter types. We analyzed 170 winter wheat varieties from diverse domestic and international breeding programs cultivated in the European part of Russia over two growing seasons. Genome-wide association study identified 26 markers linked to GPC and 23 to gluten content (p < 0.001), with the strongest associations on chromosomes 4A and 2D. Variation in NAM-A1 also significantly affected GPC: varieties with the NAM-A1d allele showed lower protein content than NAM-A1a/c carriers (p < 0.01). We combined associations identified here with our previous GWAS results for GPC in spring wheat and further compared them with 17 additional studies including both spring and winter varieties. This analysis highlighted loci on chromosomes 3DL, 5AL, and 6AS (confirmed in at least two previous studies) for marker-assisted selection to improve grain quality. The distribution of loci showed no clear distinction between spring and winter wheat, suggesting that, despite environmental and developmental differences, the genetic basis of protein accumulation is largely shared.

The active efflux of drugs by adenosine triphosphate (ATP)-binding cassette (ABC) trans-porters, such as multidrug resistance protein 1 (MDR1/ABCB1), multidrug resistance-associated protein 1 and 2 (MRP1/ABCC1; MRP2/ABCC2), and breast cancer resistance protein (BCRP/ABCG2), is a well-established mechanism contributing to multidrug resistance (MDR). Interestingly, various vitamin A-based molecules have been found to influence the expression or function of these transporters. This work investigated the current evidence on the effects of retinoids, rexinoids, and carotenoids on ABC transporters and their potential to reverse MDR. Several studies indicated that these compounds could inhibit ABC transporter activity at non-toxic concentrations, either by downregulating gene/protein expression or by directly blocking efflux function. These effects were often associated with increased chemosensitivity to several conventional anticancer agents. Overall, the degree of inhibition varied depending on several factors, including compound type and their chemical modification, dose, incubation time, treatment timing, the type of target cells, method of transporter overexpression, and coadministration with other compounds. Although particular attention was paid to elucidating the underlying mechanisms, current knowledge in this area remains limited. Moreover, extensive in vivo and clinical studies validating these findings are still lacking, emphasizing the need for further research to evaluate their translational potential.

Reactive oxygen species (ROS), inevitable by-products of aerobic metabolism, act both as regulators of signaling pathways and as mediators of oxidative stress and aging-related damage. Protein oxidative post-translational modifications (Ox-PTMs) are recognized hallmarks of aging and metabolic decline, yet the persistence of protein oxidation under different physiological conditions, such as age and diet, remains unclear. Here, we applied proteomics to mitochondrial and membrane-enriched fractions of male Fischer 344 rat cerebrum and heart, comparing Ox-PTMs across young and aged animals subjected to ad libitum nutrition (AL) or calorie restriction (CR). We identified 139 mitochondrial and membrane-associated proteins consistently exhibiting high levels of oxidation, including tricarboxylic acid (TCA) cycle enzymes, respiratory chain subunits, ATP synthase components, cytoskeletal proteins, and synaptic vesicle regulators. Functional enrichment and network analyses revealed that oxidized proteins clustered in modules related to mitochondrial energy metabolism, membrane transport, and excitation–contraction coupling. Notably, many proteins remained persistently oxidized, predominantly as mono-oxidation, without significant changes during aging or CR. Moreover, the enzymatic activity of mitochondrial complexes was not only preserved but significantly enhanced in specific contexts, and the structural integrity of the respiratory chain was maintained. These findings indicate a dual strategy for coping with oxidative stress: CR reduces ROS production to limit oxidative burden, while protein and network robustness enable functional adaptation to persistent oxidation, collectively shaping mitochondrial function and cellular homeostasis under differing physiological conditions.