Iranian Research Organization For Science & Technology

This study investigates the antidiabetic activity, gastrointestinal stability, and permeability of a modified yeast-derived peptide, VLSTSFPPW (VW9), using in vitro gastrointestinal digestion and Caco-2 cell models. LC-MS/MS analysis revealed that VW9 with DPP-IV inhibitory activity, was extensively cleaved during digestion into smaller fragments like PPW, FPPW, FPP, ST, and SFPP. Among these, PPW displayed the highest activity in vitro (IC₅₀: 22.60 ± 0.18 μM) and in situ (IC₅₀: 474 ± 10.2 μM). Kinetic and molecular docking studies indicated that PPW may inhibit the DPP-IV enzyme in a competitive way mainly due to hydrogen-bond interactions between Trp residue at C-terminus of PPW and the active site residues of DPP-IV. PPW could not penetrate epithelial cells, but a modified derivative was found on both apical and basolateral sides without DPP-IV inhibitory activity. These findings highlight the challenges of stability, activity, and permeability of VW9 and its derived peptides for potential therapeutic applications.

Cryopreservation is a key method for conservation of poultry genetic resources but cryopreserved spermatozoa are highly sensitive to oxidative stress and cell damage induced by the freeze-thaw cycle. In this study, the effects of Thymus vulgaris extract addition in the cryopreservation extender on rooster sperm post-thaw quality were evaluated. Semen samples were cryopreserved in the presence of Thymus vulgaris extract at 0, 30, 60, 90, and 120 μg/mL, and post-thaw analysis involved motility, membrane integrity, mitochondrial activity, viability, apoptosis, and oxidative stress markers. The results showed that the 30 μg/mL concentration significantly improved total motility (60.13 ± 0.70 %) and progressive motility (24.76 ± 0.75 %) when compared with the control group (42.78 ± 1.97 % and 18.15 ± 0.71 %, respectively; P < 0.05). Integrity of the plasma membrane (57.23 ± 1.49 %) and mitochondrial function (110.35 ± 3.24 ATP content) were also improved, while apoptotic sperm rates (14.40 ± 1.68 %) and reactive oxygen species levels (2.50 ± 0.06) were significantly lower. In contrast, higher concentrations (90 and 120 μg/mL) exerted a negative effect, leading to compromised motility, elevated apoptosis, and mitochondrial dysfunction. The findings suggest that Thymus vulgaris extract at an optimal concentration improves sperm cryotolerance through the alleviation of oxidative stress and the stabilization of membrane and mitochondrial integrity. The results provide strong evidence for the application of natural antioxidants in avian sperm cryopreservation.

Macrophages are pivotal regulators of immunity, playing dual roles in both propagating and resolving inflammation through their remarkable plasticity. Their ability to polarize into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes makes them attractive targets for treating diseases ranging from cancer to chronic inflammatory disorders. However, precise control over macrophage polarization remains a therapeutic challenge. Recent advances in nanomaterial engineering have unlocked unprecedented opportunities to direct macrophage polarization with high specificity, offering novel strategies for immunomodulation and tissue repair. This review systematically examines the latest breakthroughs in nanomaterial-driven macrophage reprogramming, focusing on how tailored physicochemical properties (e.g., size, surface charge, and composition) of organic, inorganic, and hybrid nanoparticles influence phenotypic outcomes. We highlight key signaling pathways (e.g., NF-κB, STAT, TLR) and biomarkers (e.g., cytokines, metabolic shifts) modulated by nanomaterials, linking these mechanisms to therapeutic applications in cancer immunotherapy, infectious diseases, and regenerative medicine. Furthermore, we discuss emerging trends such as stimuli-responsive nanomaterials and combination therapies that enhance spatiotemporal control over polarization. By bridging gaps between nanotechnology and immunology, this work not only catalogs current achievements but also outlines future directions for precision nanomedicine, advocating for clinically translatable solutions to harness macrophage plasticity for disease therapy.