Jing Zhao

(1) Background: The mitochondrial permeability transition pore (mPTP) contributes to mitochondrial dysfunction under pathological conditions. Cyclophilin D (CypD), a key regulator of sustained mPTP opening, represents an important molecular target. However, systematic strategies for selecting an appropriate CypD crystal structure for virtual screening and efficiently identifying CypD-binding natural polyphenols remain limited. (2) Methods: Six CypD crystal structures were evaluated by receiver operating characteristic analysis using reported CypD inhibitors and approximately 4000 decoys. The optimal receptor structure was subsequently used to screen 484 dietary polyphenols by molecular docking. Selected top-ranked candidates were further characterized by ¹⁵N–¹H HSQC NMR titration and surface plasmon resonance (SPR). (3) Results: PDB 6R8L exhibited the best virtual-screening performance, particularly in early enrichment. Several polyphenol glucuronides ranked among the top candidates. NMR analysis showed that apigenin 7-glucuronide and luteolin 7-glucuronide induced pronounced chemical shift perturbations at CypD residues F60, M61, I117, and W121, with F60, M61, and W121 located within or near the docking-predicted S1 binding region. SPR independently confirmed direct binding, yielding K_D values of 66 μM and 84 μM for apigenin 7-glucuronide and luteolin 7-glucuronide, respectively. (4) Conclusions: Integrating systematic receptor evaluation, molecular docking, and complementary NMR and SPR characterization provides a practical workflow for identifying and characterizing natural CypD-binding compounds. Apigenin 7-glucuronide and luteolin 7-glucuronide were identified as micromolar CypD-binding candidates, highlighting polyphenol glucuronides as a chemical class warranting further investigation in CypD ligand discovery.

Sarcopenia is a degenerative condition that imposes a substantial global public health burden, yet safe and effective interventions remain limited. Nutritional support is regarded as an important strategy to mitigate age-related muscle loss and improve physical function in older adults. Due to time and cost constraints, dexamethasone (DEX)-treated models are often used as an alternative to age-related sarcopenia models. This study investigated the effects of pumpkin seed protein peptides (PSPP) and vitamin D on DEX-treated mice. In vitro, PSPP attenuated senescence-associated phenotypes, reduced cellular injury, and partially alleviated DEX-treated myofibrillar atrophy, as evidenced by decreased Atrogin-1 and MuRF1 expression and increased MyoD expression. In vivo, PSPP and vitamin D, particularly in combination, ameliorated DEX-treated declines in muscle mass, grip strength, and endurance. Histological analyses further demonstrated improvements in myofibrillar architecture and muscle fiber cross-sectional area. In addition, each intervention was associated with increased ATP content, elevated interleukin-10 and insulin-like growth factor-1 levels, and reduced tumor necrosis factor-α and malondialdehyde levels. Collectively, these findings suggest that PSPP, either alone or combined with vitamin D, may alleviate DEX-treated sarcopenia, potentially through the modulation of mitochondrial homeostasis, attenuation of oxidative stress and inflammatory responses, and promotion of myogenic regeneration.

BACKGROUND: Construction of meat analogs based on pea protein isolate (PPI) alone by high moisture extrusion (HME) is diffocult as a result of the lack of anisotropic structures. In the present study, 0%–15% of whey protein (WP) was introduced to PPI to make hybrid blends, which were used to construct HME extrudates.RESULTS: WP enhanced the hardness, adhesive, cohesiveness and gumminess of the extrudates and facilitated the formation of a distinct anisotropic structure of PPI. The fibrous degrees of the extrudates containing 10% and 15% WP were around 1.50. The addition of WP, which has more ‐SH groups, increased the disulfide bonds and hydrogen bonding in the extrudates, leading to a denser cross‐linked structure. Particle size distribution and Fourier transform infrared analysis showed that WP induced more compact structured aggregates and more β‐sheet structures in the extrudates. Furthermore, the higher hydration capacity of WP may also help form a dilute melt and generate a more pronounced plug flow, assisting the formation of fiber structures of PPI.CONCLUSION: The present study demonstrates that WP is a potential modifier, which could be used to improve the structure of PPI‐based meat analogs. © 2024 Society of Chemical Industry.

The effects of courgette polysaccharides (CP) and coumalic acid (COA) on gelatinization, rheology, thermodynamics, microstructure, freeze–thaw stability, and in vitro digestibility of potato starch (PS) were studied. The synergistic effect of CP and COA on PS was further analyzed. The results showed that peak viscosity (PV) decreased from 6649.00 to 3462.50 mPa s and 3825.00 mPa s, respectively, after CP and COA were added. Under the combined effect of the two, it will be as low as 3225.50 mPa s. Besides, trough viscosity (TV), breakdown viscosity (BV), and final viscosity (FV) had the same trend. The presence of CP and COA can significantly delay the short‐term retrogradation of PS, especially in the case of high dose of CP and low dose of COA. Rheological tests showed that all sample gels belonged to the weak gel system (tan δ < 1) and pseudoplastic fluids. Meanwhile, the results of thermodynamic, Fourier transform infrared, and Raman spectroscopy exhibited that the presence of CP and COA significantly retarded the retrogradation of PS, especially at higher levels. In addition, the presence of CP and COA significantly reduced the formation of PS gel structures, especially when acting together. Furthermore, CP and COA reduced the content of rapidly digestible starch in PS and increased the content of resistant starch. Differently, CP can increase the slowly digestible starch content, whereas COA did the opposite. In the ternary composite system, CP and COA will also interact and restrict each other. Hence, the characteristics of PS can be better improved by adjusting the ratio of CP and COA. Meanwhile, the results of the study can provide potential possibilities for the application of CP and COA in food and improve the quality of PS‐related products.