Synergistic anti-oxidant and anti-inflammatory effects of ceria/resatorvid co-decorated nanoparticles for acute lung injury therapy.

BACKGROUND: Acute lung injury (ALI) is a critical inflammatory response syndrome that rapidly develops into acute respiratory distress syndrome (ARDS). Currently, no effective therapeutic modalities are available for patients with ALI/ARDS. According to recent studies, inhibiting both the release of pro-inflammatory cytokines and the formation of reactive oxygen species (ROS) as early as possible may be a promising therapy for ALI. RESULTS: In this study, a ROS-responsive nano-delivery system based on oxidation-sensitive chitosan (Ox-CS) was fabricated for the simultaneous delivery of Ce NPs and RT. The in vitro experiments have shown that the Ox-CS/Ceria-Resatorvid nanoparticles (Ox-CS/CeRT NPs) were rapidly and efficiently internalised by inflammatory endothelial cells. Biological evaluations validated the significant attenuation of ROS-induced oxidative stress and cell apoptosis by Ox-CS/CeRT NPs, while maintaining mitochondrial function. Additionally, Ox-CS/CeRT NPs effectively inhibited the release of pro-inflammatory factors. After intraperitoneal (i.p.) administration, Ox-CS/CeRT NPs passively targeted the lungs of LPS-induced inflamed mice and released the drug activated by the high ROS levels in inflammatory tissues. Finally, Ox-CS/CeRT NPs significantly alleviated LPS-induced lung injury through inhibiting both oxidative stress and pro-inflammatory cytokine expression. CONCLUSIONS: The created Ox-CS/CeRT NPs could act as a prospective nano-delivery system for a combination of anti-inflammatory and anti-oxidant therapy of ALI.

Corrigendum to "circAR-E2E4-miR-665-STAT3 axis is a potential regulatory network in triple-negative breast cancer" [Heliyon 9(1), January 2023, Article e12654].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e12654.].

Inhibition of SHP2 by the Small Molecule Drug SHP099 Prevents Lipopolysaccharide-Induced Acute Lung Injury in Mice.

Excessive pulmonary inflammation in acute lung injury (ALI) causes high patient mortality. Anti-inflammatory therapy, combined with infection resistance, can help to prevent ALI and save lives. The expression of Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2) was found to be significantly higher in macrophages and lung tissues with ALI, and SHP2-associated MAPK pathways were activated by lipopolysaccharide (LPS). The knockdown of the SHP2 gene suppressed the LPS-induced release of inflammatory factors and the phosphorylation of regulators in the NF-κB pathways in macrophages. Our findings showed crosstalk between the LPS-induced inflammatory pathway and the SHP2-associated MAPK pathways. SHP2 inhibition could be a valuable therapeutic approach for inhibiting excessive inflammation in ALI. We discovered that giving SHP099, a specific allosteric inhibitor of SHP2, to mice with ALI and sepsis relieves ALI and significantly increases animal survival. Our study highlights the important role of SHP2 in ALI development and demonstrates the potential application of SHP099 for treating ALI.

Impact of Guar Gum and Locust Bean Gum Addition on the Pasting, Rheological Properties, and Freeze-Thaw Stability of Rice Starch Gel.

Improving the gel texture and stability of rice starch (RS) by natural hydrocolloids is important for the development of gluten-free starch-based products. In this paper, the effects of guar gum and locust bean gum on the pasting, rheological properties, and freeze−thaw stability of rice starch were investigated by using a rapid visco analyzer, rheometer, and texture analyzer. Both gums can modify the pasting properties, revealed by an increment in the peak, trough, and final viscosities, and prevent the short-term retrogradation tendency of RS. Dynamic viscoelasticity measurements also indicated that the starch−gum system exhibits superior viscoelastic properties compared with starch alone, as revealed by its higher storage modulus (G'). Compared with the control, the hysteresis loop area of the guar gum-containing system and locust bean gum-containing system was reduced by 37.7% and 24.2%, respectively, indicating that the addition of gums could enhance shear resistance and structure recovery properties. The thermodynamic properties indicated that both gums retard short-term retrogradation as well as long-term retrogradation of the RS gels. Interestingly, the textural properties and freeze−thaw stability of the RS gel were significantly improved by the addition of galactomannans (p < 0.05), and guar gum was more effective than locust bean gum, which may be due to the different mannose to galactose ratio. The results provide alternatives for gluten-free recipes with improved texture properties and freeze−thaw stability.

Polysaccharides from Premna microphylla turcz ameliorate inflammation via the enhancement of intestinal resistance in host.

ETHNOPHARMACOLOGICAL RELEVANCE: Premna microphylla turcz is traditionally used as a folk remedy. Its roots, stems and leaves can be invoked as medicines, which have the functions of detoxification, swelling and hemostasis. It belongs to the Premna in the Verbenaceae and is mainly distributed in the mountains of southeastern China. However, there are few reports of in-depth studies on the anti-inflammatory effects of polysaccharide, which was the main component in Premna microphylla turcz. MATERIALS AND METHODS: The flies were fed with standard corn flour-yeast medium to cause inflammation by sodium lauryl sulfate (SDS). The treatment group contained Premna microphylla turcz polysaccharide (pPMTLs) extract. The survival rate was obtained by feeding a vial containing five layers of filter paper, which was infiltrated with the 5% sucrose solution contaminated with SDS or SDS polysaccharide. The microvilli and nucleus of the midgut epithelial cells of different treatments were observed by transmission electron microscope, and the expression of inflammation-related genes was detected by real-time quantitative PCR (qRT-PCR). Finally, 16S rDNA analysis was conducted on the differences in the composition of the intestinal microbes of Drosophila. RESULTS: In the current study, we showed that pPMTLs significantly prolonged the life span of SDS-inflamed flies from 5 days to 6 days. And pPMTLs reduced the rupture of microvilli in the midgut and restored the nuclear structure. In addition, pPMTLs significantly improved expression level of immune-related genes in Inflammation Drosophila especially the defensin (4.32 ± 0.75 vs 9.97 ± 0.52 SDS-polysaccharide group: SDS group, p < 0.001). The analysis of intestinal microbiota showed that pPMTLs decreased the relative abundance of Raoultella while Wolbachia increased (p < 0.05). CONCLUSIONS: Collectively, our results revealed the potential application of pPMTLs in enhancing inflammation defense, which would be enormous significance for the inflammation-related disorders treatment.

[Different virulence Mycobacterium promotes RAW264.7 macrophage autophagy and phosphorylation of mTOR and AKT].

Objective To explore the change of autophagy levels of the macrophages infected by Mycobacterium with different virulence. Methods RAW264.7 cells were infected with Mycobacterium tuberculosis standard strain (H37Rv), Bacille Calmette Guerin (BCG) and Mycobacterium smegmatis (Ms). The cell autophagy was detected by flow cytometry and the colocalization of phagosomes and lysosomes was detected by confocal laser scanning microscopy. Meanwhile, the autophagy-associated protein LC3, mTOR, p-mTOR, AKT and p-AKT were detected by Western blotting. Results At 24 hours after RAW264.7 cells were infected by Mycobacterium with different virulence, flow cytometry showed that the level of autophagy was significantly up-regulated by H37Rv, BCG and Ms infection, and the highest level was in the Ms infection group. The level of LC3-II was significantly up-regulated after H37Rv, BCG and Ms infection, and the tendency was consistent with the result of flow cytometry. The colocalization rates of phagosomes and lysosomes after H37Rv, BCG and Ms infection were (11.33±0.88)%, (18.33±0.88)% and (48.67±0.66)%. The expression of mTOR and AKT had no significant changes after H37Rv, BCG and Ms infection, but the phosphorylation level significantly increased, which meant that PI3K-AKT-mTOR was activated. Conclusion Mycobacterium infection can induce the autophagy in macrophages and promote the phosphorylation of mTOR and AKT.