RESUMEN
The escalating threat of Cr(VI) pollution to the environment and human health can be effectively controlled through microbial methods, which are promising, safe, and ecofriendly. To enhance Cr(VI) removal efficiency, scholars have been optimizing strains. However, synergies between in-situ soil particles and crucial microorganisms in soil have rarely been investigated. In this study, Cr(VI) was removed by collaborating with in-situ soil particles and key microorganisms in the soil. The results indicated that within 48 hours, the removal rate of Cr(VI) reached over 99% in the soils+microflora system, which was 45% higher than that of the microflora system alone. Factors such as Cr(VI) concentration, soil dosage, pH level, oxygen availability, and electron donors influenced the removal efficiency of Cr(VI) in the soils+microflora system. The cyclic experiments showed that soil particles effectively prevented chromium invasion on microflora, promoting the growth of crucial microorganisms. The addition of microflora can effectively regulate the composition of soil flora and enhance the efficiency of chromium reduction. Moreover, two strains each of Ochrobactrum sp. and Paenarthrobacter sp., exhibiting remarkable tolerance to Cr(VI), were successfully isolated from these soils, significantly enhancing the reduction capacity of the indigenous microflora towards Cr(VI). Additionally, 16S rRNA-PCR sequence analysis revealed that in-situ soil particles not only synergistically collaborated with the resident microflora for efficient removal of Cr(VI), but also facilitated the proliferation of key microbiota such as Ochrobactrum sp. and Paenarthrobacter sp. Remarkably, when exposed to an initial concentration of 50 mg/L Cr(VI), complete removal was achieved by Paenarthrobacter-2 within a time frame as short as 60 hours. This research found four novel highly efficient strains for reducing Cr(VI) and provides an innovative method for the synergistic interaction between indigenous soil microflora and soil particles to remove heavy metal ions from wastewater.
Asunto(s)
Biodegradación Ambiental , Cromo , Microbiología del Suelo , Contaminantes del Suelo , Suelo , Cromo/metabolismo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/análisis , Suelo/química , Ochrobactrum/metabolismo , Oxidación-ReducciónRESUMEN
BACKGROUND: Macrophages at infection sites are considered as the promising therapeutic targets to prevent sepsis development. The Nrf2/Keap1 system acts as a critical modulator of the antibacterial activity of macrophages. Recently, Keap1-Nrf2 protein-protein interaction (PPI) inhibitors have emerged as safer and stronger Nrf2 activators; however, their therapeutic potential in sepsis remains unclear. Herein, we report a unique heptamethine dye, IR-61, as a Keap1-Nrf2 PPI inhibitor that preferentially accumulates in macrophages at infection sites. METHODS: A mouse model of acute lung bacterial infection was used to investigate the biodistribution of IR-61. SPR study and CESTA were used to detect the Keap1 binding behaviour of IR-61 in vitro and in cells. Established models of sepsis in mice were used to determine the therapeutic effect of IR-61. The relationship between Nrf2 levels and sepsis outcomes was preliminarily investigated using monocytes from human patients. FINDINGS: Our data showed that IR-61 preferentially accumulated in macrophages at infection sites, enhanced bacterial clearance, and improved outcomes in mice with sepsis. Mechanistic studies indicated that IR-61 potentiated the antibacterial function of macrophages by activating Nrf2 via direct inhibition of the Keap1-Nrf2 interaction. Moreover, we observed that IR-61 enhanced the phagocytic ability of human macrophages, and the expression levels of Nrf2 in monocytes might be associated with the outcomes of sepsis patients. INTERPRETATIONS: Our study demonstrates that the specific activation of Nrf2 in macrophages at infection sites is valuable for sepsis management. IR-61 may prove to be a Keap1-Nrf2 PPI inhibitor for the precise treatment of sepsis. FUNDING: This work was supported by the National Natural Science Foundation of China (Major program 82192884), the Intramural Research Project (Grants: 2018-JCJQ-ZQ-001 and 20QNPY018), and the Chongqing National Science Foundation (CSTB2022NSCQ-MSX1222).
Asunto(s)
Enfermedades Transmisibles , Sepsis , Humanos , Ratones , Animales , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2/metabolismo , Distribución Tisular , Macrófagos/metabolismo , Sepsis/tratamiento farmacológico , Sepsis/etiología , Sepsis/metabolismo , Unión ProteicaRESUMEN
Pro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs.