Anti-inflammatory sesquiterpenoids from Ligularia fischeriTurcz.

Ligularia fischeriTurcz. is a medicinal plant for the treatment of inflammation in China and Korea. Its chemical components in anti-sepsis activity and the related molecular mechanisms remain unknown yet. In this study, two undescribed eremophilane sesquiterpenoids fischerins A (1) and B (2), together with 8 known sesquiterpenoid derivatives (3-10), were isolated from the whole plant of L. fischeri. Their structures were identified by detailed spectroscopic and ECD analyses. 3-Oxo-8-hydroxyeremophila-1,7(11)-dien-12,8-olide (6) showed the most inhibitory effect on NO production in LPS-stimulated RAW 264.7 cells with the IC50 value of 6.528 µM. Meanwhile, compound 6 also decreased the mRNA expression of pro-inflammatory factors IFN-γ, IL-1ß, IL-6 and TNF-α via downregulating NF-κB signaling pathway in vitro. Furthermore, compound 6 reduced the mortality, murine sepsis score, the serum TNF-α level and organic damage in a mouse model of sepsis. These findings indicated that compound 6 possessed the potent anti-inflammatory activity and had the potential as a promising drug candidate for sepsis therapy.

Anti-inflammatory polyoxygenated cyclohexene derivatives from Uvaria macclurei.

Two undescribed polyoxygenated seco-cyclohexene derivatives named macclureins A and B, and three undescribed polyoxygenated cyclohexene derivatives macclureins C-E, together with 15 known analogues were isolated from the twigs and leaves of Uvaria macclurei. Their structures were established by extensive spectroscopic and circular dichroism analyses. Macclurein C is a chlorinated polyoxygenated cyclohexene. All isolates were evaluated for their anti-inflammatory activities on NO generation in the LPS-stimulated RAW 264.7 cells. (-)-Zeylenone showed the most potent effect against NO production with the IC50 value of 20.18 µM. Meanwhile, (-)-zeylenone also decreased the mRNA expression of pro-inflammatory factors IFN-γ, iNOS, IL-6 and TNF-α via downregulating NF-κB signaling pathway. Further in vivo experiments using a mouse model of sepsis showed that (-)-zeylenone significantly alleviated sepsis severity by measuring weight, murine sepsis score, survival rate and the serum levels of pro-inflammatory factors TNF-α and IL-6.

Axitinib attenuates the progression of liver fibrosis by restoring mitochondrial function.

Liver fibrosis can progress to cirrhosis and hepatocellular carcinoma, which may eventually lead to liver failure and even death. No direct anti-fibrosis drugs are available at present. Axitinib is a new generation of potent multitarget tyrosine kinase receptor inhibitors, but its role in liver fibrosis remains unclear. In this study, a CCl4-induced hepatic fibrosis mouse model and a TGF-ß1-induced hepatic stellate cell model were used to explore the effect and mechanism of axitinib on hepatic fibrosis. Results confirmed that axitinib could alleviate the pathological damage of liver tissue induced by CCl4 and inhibit the production of glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. It also inhibited collagen and hydroxyproline deposition and the protein expression of Col-1 and α-SMA in CCl4-induced liver fibrosis. In addition, axitinib inhibited the expression of CTGF and α-SMA in TGF-ß1-induced hepatic stellate cells. Further studies showed that axitinib inhibited mitochondrial damage and reduced oxidative stress and NLRP3 maturation. The use of rotenone and antimycin A confirmed that axitinib could restore the activity of mitochondrial complexes I and III, thereby inhibiting the maturation of NLRP3. In summary, axitinib inhibits the activation of HSCs by enhancing the activity of mitochondrial complexes I and III, thereby alleviating the progression of liver fibrosis. This study reveals the strong potential of axitinib in the treatment of liver fibrosis.

FOXO3 regulates Smad3 and Smad7 through SPON1 circular RNA to inhibit idiopathic pulmonary fibrosis.

Forkhead box protein O3 (FOXO3) has good inhibition ability toward fibroblast activation and extracellular matrix, especially for the treatment of idiopathic pulmonary fibrosis. How FOXO3 regulates pulmonary fibrosis remains unclear. In this study, we reported that FOXO3 had binding sequences with F-spondin 1 (SPON1) promoter, which can activate its transcription and selectively promote the expression of SPON1 circRNA (circSPON1) but not mRNA expression. We further demonstrated that circSPON1 was involved in the extracellular matrix deposition of HFL1. In the cytoplasm, circSPON1 directly interacted with TGF-ß1-induced Smad3 and inhibited the activation of fibroblasts by inhibiting nuclear translocation. Moreover, circSPON1 bound to miR-942-5p and miR-520f-3p that interfered with Smad7 mRNA and promoted Smad7 expression. This study revealed the mechanism of FOXO3-regulated circSPON1 in the development of pulmonary fibrosis. Potential therapeutic targets and new insights into the diagnosis and treatment of idiopathic pulmonary fibrosis based on circRNA were also provided.

Preparation of Polytetrafluoroethylene Superhydrophobic Materials by Femtosecond Laser Processing Technology.

In recent years, superhydrophobic surfaces have attracted significant attention due to their promising applications, especially in ice prevention, reduction in air resistance, and self-cleaning. This study utilizes femtosecond laser processing technology to prepare different surface microstructures on polytetrafluoroethylene (PTFE) surfaces. Through experiments, it investigates the relationship between the solid-liquid contact ratio and surface hydrophobicity. The shape of water droplets on different microstructure surfaces is simulated using ANSYS, and the relationship between surface microstructures and hydrophobicity is explored in the theoretical model. A superhydrophobic surface with a contact angle of up to 166° was obtained by machining grooves with different spacings in polytetrafluoroethylene sheets with femtosecond laser technology. Due to the micro- and nanostructures on the surface, the oleophobicity of the processed oleophilic PTFE surface is enhanced.

Nintedanib Alleviates Experimental Colitis by Inhibiting CEBPB/PCK1 and CEBPB/EFNA1 Pathways.

The super-enhancer, a cluster of enhancers with strong transcriptional activity, has become one of the most interesting topics in recent years. This study aimed to investigate pathogenic super-enhancer-driven genes in IBD and screen therapeutic drugs based on the results. In this study, through the analysis of differentially expressed genes in colitis patients from the GEO database and the analysis of the super-enhancer-associated database, we found that the super-enhancer pathogenic genes PCK1 and EFNA1 were simultaneously regulated by transcription factor CEBPB through two super-enhancers (sc-CHR20-57528535 and sc-CHR1-155093980). Silencing CEBPB could significantly inhibit the expression of PCK1 and EFNA1 and enhance the expression of epithelial barrier proteins claudin-1, occludin, and ZO-1. In LPS-induced Caco-2 cells, drugs commonly used in clinical colitis including tofacitinib, oxalazine, mesalazine, and sulfasalazine inhibited mRNA levels of CEBPB, PCK1, and EFNA1. In the drug screening, we found that nintedanib significantly inhibited the mRNA and protein levels of CEBPB, PCK1, and EFNA1. In vivo experiments, nintedanib significantly alleviated DSS-induced colitis in mice by inhibiting CEBPB/PCK1 and CEBPB/EFNA1 signaling pathways. At the genus level, nintedanib improved the composition of the gut microbiota in mice with DSS-induced experimental colitis. In conclusion, we found that PCK1 and EFNA1 are highly expressed in colitis and they are regulated by CEBPB through two super-enhancers, and we further demonstrate their role in vivo and in vitro. Nintedanib may be a potential treatment for IBD. Super-enhancers may be a new way to explore the pathogenesis of colitis.