RESUMEN
Copper nanoparticles (CuNPs) have attracted great interest in various biomedical research fields due to their superior optical and plasmonic properties. In the present study, we synthesized bovine serum albumin (BSA)-coated CuNPs (BSA-CuNPs) by adopting the aqueous reduction method in 2-step procedures. The prepared BSA-CuNPs were characterized in vitro for their physical characteristics and photothermal activity. The successful synthesis of BSA-CuNPs was verified through transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and ultraviolet-visible (UV-VIS) light spectroscopy. The prepared BSA-CuNPs revealed a great light-to-heat conversion capacity and good photothermal stability. Notably, accompanied by laser irradiation, the BSA-CuNPs elicited significantly higher cytotoxicity on tumor cells than the control group. Preliminary animal studies to determine the biosafety and pharmacokinetics (PK) profiles exhibited that the BSA-CuNPs have a maximum tolerable dose (MTD) of 16 mgCu/kg and a relatively long plasma half-life of 1.98 h. Overall, our findings demonstrated that BSA-CuNPs might be a potential photothermal therapeutic agent for cancer treatment.
RESUMEN
The tomato (Solanum lycopersicum) is widely consumed globally and renowned for its health benefits, including the reduction of cardiovascular disease and prostate cancer risk. However, tomato production faces significant challenges, particularly due to various biotic stresses such as fungi, bacteria, and viruses. To address this challenges, we employed the CRISPR/Cas9 system to modify the tomato NUCLEOREDOXIN (SlNRX) genes (SlNRX1 and SlNRX2) belonging to the nucleocytoplasmic THIOREDOXIN subfamily. CRISPR/Cas9-mediated mutations in SlNRX1 (slnrx1) plants exhibited resistance against bacterial leaf pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326, as well as the fungal pathogen Alternaria brassicicola. However, the slnrx2 plants did not display resistance. Notably, the slnrx1 demonstrated elevated levels of endogenous salicylic acid (SA) and reduced levels of jasmonic acid after Psm infection, in comparison to both wild-type (WT) and slnrx2 plants. Furthermore, transcriptional analysis revealed that genes involved in SA biosynthesis, such as ISOCHORISMATE SYNTHASE 1 (SlICS1) and ENHANCED DISEASE SUSCEPTIBILITY 5 (SlEDS5), were upregulated in slnrx1 compared to WT plants. In addition, a key regulator of systemic acquired resistance, PATHOGENESIS-RELATED 1 (PR1), exhibited increased expression in slnrx1 compared to WT. These findings suggest that SlNRX1 acts as a negative regulator of plant immunity, facilitating infection by the Psm pathogen through interference with the phytohormone SA signaling pathway. Thus, targeted mutagenesis of SlNRX1 is a promising genetic means to enhance biotic stress resistance in crop breeding.
Asunto(s)
Ácido Salicílico , Solanum lycopersicum , Ácido Salicílico/metabolismo , Solanum lycopersicum/genética , Fitomejoramiento , Pseudomonas syringae/fisiología , Transducción de Señal/genética , Ciclopentanos/metabolismo , Enfermedades de las Plantas/microbiología , Regulación de la Expresión Génica de las PlantasRESUMEN
Traditional vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors can manage angiogenesis; however, severe toxicity and resistance limit their long-term applications in clinical therapy. Shikonin (SHK) and its derivatives could be promising to inhibit the VEGFR-2 mediated angiogenesis, as they are reported to bind in the catalytic kinase domain with low affinity. However, the detailed molecular insights and binding dynamics of these natural inhibitors are unknown, which is crucial for potential SHK based lead design. Therefore, the present study employed molecular modeling and simulations techniques to get insight into the binding behaviors of SHK and its two derivates, ß-hydroxyisovalerylshikonin (ß-HIVS) and acetylshikonin (ACS). Here the intermolecular interactions between protein and ligands were studied by induced fit docking approach, which were further evaluated by treating QM/MM (quantum mechanics/molecular mechanics) and molecular dynamics (MD) simulation. The result showed that the naphthazarin ring of the SHK derivates is vital for strong binding to the catalytic domain; however, the binding stability can be modulated by the side chain modification. Because of having electrostatic potential, this ring makes essential interactions with the DFG (Asp1046 and Phe1047) motif and also allows interacting with the allosteric binding site. Taken together, the studies will advance our knowledge and scope for the development of new selective VEGFR-2 inhibitors based on SHK and its analogs.