Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis.

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function.

Assessing Transcriptomic Responses to Oxidative Stress: Contrasting Wild-Type Arabidopsis Seedlings with dss1(I) and dss1(V) Gene Knockout Mutants.

Oxidative stress represents a critical facet of the array of abiotic stresses affecting crop growth and yield. In this paper, we investigated the potential differences in the functions of two highly homologous Arabidopsis DSS1 proteins in terms of maintaining genome integrity and response to oxidative stress. In the context of homologous recombination (HR), it was shown that overexpressing AtDSS1(I) using a functional complementation test increases the resistance of the Δdss1 mutant of Ustilago maydis to genotoxic agents. This indicates its conserved role in DNA repair via HR. To investigate the global transcriptome changes occurring in dss1 plant mutant lines, gene expression analysis was conducted using Illumina RNA sequencing technology. Individual RNA libraries were constructed from three total RNA samples isolated from dss1(I), dss1(V), and wild-type (WT) plants under hydrogen peroxide-induced stress. RNA-Seq data analysis and real-time PCR identification revealed major changes in gene expression between mutant lines and WT, while the dss1(I) and dss1(V) mutant lines exhibited analogous transcription profiles. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed significantly enriched metabolic pathways. Notably, genes associated with HR were upregulated in dss1 mutants compared to the WT. Otherwise, genes of the metabolic pathway responsible for the synthesis of secondary metabolites were downregulated in both dss1 mutant lines. These findings highlight the importance of understanding the molecular mechanisms of plant responses to oxidative stress.

Physicochemical properties and stability of oil-in-water emulsions stabilized by soy protein isolate and xanthan gum.

The aim of this work was to determine rheological and disperse characteristics and stability of oil-in-water emulsions stabilized by soy protein isolate (SPI) and xanthan gum (XG), as natural components. The effects of their combination on emulsion stabilization have not been investigated yet. The existence of interactions between the two macromolecules were indicated by the influence of XG on SPI surface hydrophobicity and surface tension values. Increase in SPI concentration from 1 to 3 % shift of distribution curves towards smaller particle size, while the opposite effects of further increase of SPI was obtained. The emulsions stabilized by SPI showed shear-thinning flow behavior, which changed to thixotropic at 5 % of SPI concentration. The presence of XG in emulsions at low concentrations did not affect the size distribution of the droplets, while at 0.1 % of XG Sauter mean diameter value raised and distribution curves were shifted towards a higher particle size. The presence of XG at higher concentration resulted in thixotropic flow behavior of emulsions. Also, increase in XG concentration led to the increase in consistency index and extent of non-Newtonian behavior of emulsions and enhanced the influence of the elastic modulus and creaming stability of the systems.

Characterization of Oil-in-Water Emulsions Prepared with Triblock Copolymer Poloxamer 407 and Low-Molecular-Mass Surfactant Mixtures as Carriers of Grape Pomace Waste Polyphenols.

BACKGROUND: Natural antioxidants, such as grape pomace polyphenols, can be extracted by a surfactant-based green technology and incorporated into various emulsions. Therefore, this work aimed to investigate the physical stability and rheological characteristics of oil-in-water emulsions stabilized with poloxamer 407 (P407) and its mixtures with the low-molecular-mass surfactants Brij S20 (BS20) and Tween 60 (T60). Also, the influence of polyphenolic grape pomace extracts on the physical stability and rheological characteristics of the emulsions was examined. METHODS: Grape pomace polyphenols were extracted by aqueous solutions of P407 and BS20/P407 and T60/P407 mixtures. Two different types of oil-in-water emulsions were examined: emulsions prepared with pure surfactants and emulsions prepared with surfactant-based polyphenol extracts of grape pomace. Both types contained 20% sunflower oil. Characterization of the emulsions comprised droplet size evaluation, rheology characteristics and creaming stability. RESULTS: All the emulsions showed shear-thinning flow, while the rheological characteristics and creaming instability depended on the proportion of P407 in the emulsifier mixtures. Incorporation of grape pomace extracts had no effect on the investigated properties of the emulsions. CONCLUSION: The presence of extracted polyphenols in emulsifier mixtures had no significant effects on the emulsions' physico-chemical characteristics and stability. Therefore, the investigated emulsions can be considered suitable carriers for polyphenol-rich extracts.

Search for new biologically active compounds: in vitro studies of antitumor and antimicrobial activity of dirhodium(II,II) paddlewheel complexes.

Four neutral Rh1-Rh4 complexes of the general formula [Rh2(CH3COO)4L2], where L is an N-alkylimidazole ligand, were synthesized and characterized using various spectroscopic techniques, and in the case of Rh4 the crystal structure was confirmed. Investigation of the interactions of these complexes with HSA by fluorescence spectroscopy revealed that the binding constants Kb are moderately strong (∼104 M-1), and site-marker competition experiments showed that the complexes bind to Heme site III (subdomain IB). Competitive binding studies for CT DNA using EB and HOE showed that the complexes bind to the minor groove, which was also confirmed by viscosity experiments. Molecular docking confirmed the experimental data for HSA and CT DNA. Antimicrobial tests showed that the Rh2-Rh4 complexes exerted a strong inhibitory effect on G+ bacteria B. cereus and G- bacteria V. parahaemolyticus as well as on the yeast C. tropicalis, which showed a higher sensitivity compared to fluconazole. The cytotoxic activity of Rh1-Rh4 complexes tested on three cancer cell lines (HeLa, HCT116 and MDA-MB-231) and on healthy MRC-5 cells showed that all investigated complexes elicited more efficient cytotoxicity on all tested tumor cells than on control cells. Investigation of the mechanism of action revealed that the Rh1-Rh4 complexes inhibit cell proliferation via different mechanisms of action, namely apoptosis (increase in expression of the pro-apoptotic Bax protein and caspase-3 protein in HeLa and HCT116 cells; changes in mitochondrial potential and mitochondrial damage; release of cytochrome c from the mitochondria; cell cycle arrest in G2/M phase in both HeLa and HCT116 cells together with a decrease in the expression of cyclin A and cyclin B) and autophagy (reduction in the expression of the protein p62 in HeLa and HCT116 cells).