Cyclophilin A associates with and regulates the activity of ZAP70 in TCR/CD3-stimulated T cells.

The ZAP70 protein tyrosine kinase (PTK) couples stimulated T cell antigen receptors (TCRs) to their downstream signal transduction pathways and is sine qua non for T cell activation and differentiation. TCR engagement leads to activation-induced post-translational modifications of ZAP70, predominantly by kinases, which modulate its conformation, leading to activation of its catalytic domain. Here, we demonstrate that ZAP70 in TCR/CD3-activated mouse spleen and thymus cells, as well as human Jurkat T cells, is regulated by the peptidyl-prolyl cis-trans isomerase (PPIase), cyclophilin A (CypA) and that this regulation is abrogated by cyclosporin A (CsA), a CypA inhibitor. We found that TCR crosslinking promoted a rapid and transient, Lck-dependent association of CypA with the interdomain B region, at the ZAP70 regulatory domain. CsA inhibited CypA binding to ZAP70 and prevented the colocalization of CypA and ZAP70 at the cell membrane. In addition, imaging analyses of antigen-specific T cells stimulated by MHC-restricted antigen-fed antigen-presenting cells revealed the recruitment of ZAP70-bound CypA to the immunological synapse. Enzymatically active CypA downregulated the catalytic activity of ZAP70 in vitro, an effect that was reversed by CsA in TCR/CD3-activated normal T cells but not in CypA-deficient T cells, and further confirmed in vivo by FRET-based studies. We suggest that CypA plays a role in determining the activity of ZAP70 in TCR-engaged T cells and impact on T cell activation by intervening with the activity of multiple downstream effector molecules.

Augmenting the quality and storage stability of soymilk by incorporation of untreated and ozonated oat 1,4-ß-D-glucan.

The study aimed to improve the quality and storage stability of novel plant-based soymilk with the incorporation of untreated (UtßG) and modified oat derived 1,4-ß-D-glucan (OzßG) at varying concentrations (0, 1, and 2 % labelled as S0, S1 and S2). The treated soymilk was characterized for physical, chemical, nutritional, rheological, particle size, zeta potential, sensory and storage stability characteristics. The results revealed that 1, 4-ß-D-glucan incorporation increased the acidity (0.67 to 0.73 %), viscosity (3.4 to 4.7 Cp) and ash content (0.74 to 0.92 %), however color remains natural. The frequency sweep and shear experiments showed that the 1,4-ß-D-glucan modified the rheological parameters of the soymilk. The sensory analysis (n = 30) indicated that texture, mouthfeel and overall acceptability (8.38). Compared to OzßG-treated soymilk, UtßG soymilk, especially S2, exhibited superior thickening and rheological properties. The storage study indicated minimal phase separation in 1,4-ß-D-glucan-incorporated samples, maintaining stability for 15 days under refrigerated conditions without compromising overall quality. Thus, this study provides valuable insights into the potential application of 1,4-ß-D-glucan for improving the technological quality of soymilk that highlights possible implications for its commercialization potential.

Tryptophol Acetate and Tyrosol Acetate, Small-Molecule Metabolites Identified in a Probiotic Mixture, Inhibit Hyperinflammation.

Probiotic fermented foods are perceived as contributing to human health; however, solid evidence for their presumptive therapeutic systemic benefits is generally lacking. Here we report that tryptophol acetate and tyrosol acetate, small-molecule metabolites secreted by the probiotic milk-fermented yeast Kluyveromyces marxianus, inhibit hyperinflammation (e.g., "cytokine storm"). Comprehensive in vivo and in vitro analyses, employing LPS-induced hyperinflammation models, reveal dramatic effects of the molecules, added in tandem, on mice morbidity, laboratory parameters, and mortality. Specifically, we observed attenuated levels of the proinflammatory cytokines IL-6, IL-1α, IL-1ß, and TNF-α and reduced reactive oxygen species. Importantly, tryptophol acetate and tyrosol acetate did not completely suppress proinflammatory cytokine generation, rather brought their concentrations back to baseline levels, thus maintaining core immune functions, including phagocytosis. The anti-inflammatory effects of tryptophol acetate and tyrosol acetate were mediated through downregulation of TLR4, IL-1R, and TNFR signaling pathways and increased A20 expression, leading to NF-kB inhibition. Overall, this work illuminates phenomenological and molecular details underscoring anti-inflammatory properties of small molecules identified in a probiotic mixture, pointing to potential therapeutic avenues against severe inflammation.

Current trends in the preparation, characterization and applications of oat starch - A review.

Worldwide consumption of oats is gaining popularity due to its composition and multifunctional benefits of individual components. Oat starch being the major component accounts up to 60% of the dry weight of kernel, possess small granule size and high lipid content. Properties of starch substantially affect the quality of the product. Modification and characterization of starch is important for their specific applications that increase the utilization of oat starch. Different modification techniques greatly affect the functional, pasting, gelatinisation, textural, rheological, retrogradation properties and enzymatic digestibility of oat starches in comparison to native starch. Modified oat starch competes against other abundant and inexpensive cereal starches (rice and corn) that are available in modified forms in the market. This review summarises the current knowledge of physicochemical, morphological, pasting, functional, rheological and gelatinization properties, developments in the extraction and modification (physical, chemical and enzymatic) and applications of oat starch. Thus, this review will upgrade the scientific basis on oat starch being a unique source of starch for variety of applications.