Salicylic acid (SA) is a hormone that modulates plant defenses by inducing changes in gene expression. The mechanisms that control SA accumulation are essential for understanding the defensive process. TGA transcription factors from clade II in Arabidopsis, which include the proteins TGA2, TGA5, and TGA6, are known to be key positive mediators for the transcription of genes such as PR-1 that are induced by SA application. However, unexpectedly, stress conditions that induce SA accumulation, such as infection with the avirulent pathogen P. syringae DC3000/AvrRPM1 and UV-C irradiation, result in enhanced PR-1 induction in plants lacking the clade II TGAs (tga256 plants). Increased PR-1 induction was accompanied by enhanced isochorismate synthase-dependent SA production as well as the upregulation of several genes involved in the hormone’s accumulation. In response to avirulent P. syringae, PR-1 was previously shown to be controlled by both SA-dependent and -independent pathways. Therefore, the enhanced induction of PR-1 (and other defense genes) and accumulation of SA in the tga256 mutant plants is consistent with the clade II TGA factors providing negative feedback regulation of the SA-dependent and/or -independent pathways. Together, our results indicate that the TGA transcription factors from clade II negatively control SA accumulation under stress conditions that induce the hormone production. Our study describes a mechanism involving old actors playing new roles in regulating SA homeostasis under stress.

The origin of life possibly required processes in confined systems that facilitated simple chemical reactions and other more complex reactions impossible to achieve under the condition of infinite dilution. In this context, the self-assembly of micelles or vesicles derived from prebiotic amphiphilic molecules is a cornerstone in the chemical evolution pathway. A prime example of these building blocks is decanoic acid, a short-chain fatty acid capable of self-assembling under ambient conditions. This study explored a simplified system made of decanoic acids under temperatures ranging from 0 °C to 110 °C to replicate prebiotic conditions. The study revealed the first point of aggregation of decanoic acid into vesicles and examined the insertion of a prebiotic-like peptide in a primitive bilayer. The information gathered from this research provides critical insights into molecule interactions with primitive membranes, allowing us to understand the first nanometric compartments needed to trigger further reactions that were essential for the origin of life.

Oxidative stress on the mitochondria in a human cell is attributed to several life-risking conditions, and as such, the importance of molecular structures packed with antioxidant properties and structural characteristics to enter the cell to help prevent such stress has been substantially relevant in recent years. In this study, we investigated the antioxidant properties of triphenylphosphonium (TPP)-conjugated phenolic acids encapsulated in β-cyclodextrin (β-CD). We synthesized TPP conjugates of caffeic, coumaric, and cinnamic acids and formed inclusion complexes with β-CD. Our results showed successful encapsulation of TPP conjugates in β-CD with high efficiency. The TPP conjugates maintained antioxidant activity, with slight reductions observed in β-CD complexes. Furthermore, cell viability studies showed low cytotoxicity of the dds. Computational analyses revealed that TPP conjugation preserved the chemical reactivity of the phenolic acids. Molecular dynamics simulations demonstrated stable inclusion complexes with β-CD and the free energy calculations indicated that TPP conjugation significantly enhanced the ability of caffeic acid to translocate across mitochondrial membranes. These results highlight the potential of TPP-conjugated phenolic acids encapsulated in β-CD as effective antioxidants with improved mitochondrial targeting capabilities.

Poly(amidoamine) (PAMAM) dendrimers are widely recognized as versatile nanocarriers due to their tunable architecture and ability to associate with bioactive molecules. In this study, generation 3 PAMAM dendrimers functionalized with triphenylphosphonium (TPP) were employed to investigate the association of structurally related phenolic compounds—caffeic acid, p-coumaric acid, and cinnamic acid—through either covalent conjugation or non-covalent encapsulation. Physicochemical characterization by NMR, dynamic light scattering, and zeta potential measurements revealed the formation of supramolecular aggregates rather than isolated dendrimer units, with hydrodynamic diameters ranging from 127 to 260 nm and positive surface charge across all formulations. Encapsulation efficiencies determined by HPLC reached 93.8% for caffeic acid, 78.9% for p-coumaric acid, and 71% for cinnamic acid, indicating differential association behavior. Molecular dynamics simulations over 1 μs supported these findings, showing stronger and more stable interactions for polar antioxidants, particularly caffeic acid, driven by hydrogen bonding and electrostatic interactions, while cinnamic acid displayed preferential binding in more hydrophobic dendrimer regions. Radical scavenging assays (DPPH• and ABTS•+) demonstrated that all formulations retained antioxidant capacity, although dendrimer association modulated scavenging kinetics. In cellular assays under oxidative stress, free caffeic acid exhibited the strongest immediate reduction of intracellular reactive oxygen species, whereas dendrimer-associated systems showed reduced but significant activity, consistent with decreased solvent accessibility and slower release predicted by simulations. Overall, these results highlight a trade-off between molecular retention and immediate biological efficacy, demonstrating that the mode of association governs antioxidant accessibility and performance. This combined experimental and computational approach provides a mechanistic framework for the rational design of dendrimer-based delivery systems aimed at balancing stability and functional activity.