Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPß- SCD activation in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is associated with mutations in lipopolysaccharide-binding protein ( LBP), but the underlying epigenetic mechanisms remain understudied. Herein, LBP -/- rats with NAFLD were established and used to conduct integrative targeting-active enhancer histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency. Notably, LBP -/- reduced the inflammatory response but markedly aggravated high-fat diet (HFD)-induced NAFLD in rats, with pronounced alterations in the histone acetylome and regulatory transcriptome. In total, 1 128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type (WT) and LBP -/- NAFLD rats. Based on integrative analysis, CCAAT/enhancer-binding protein ß (C/EBPß) was identified as a pivotal transcription factor (TF) and contributor to dysregulated histone acetylome H3K27ac, and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD. This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPß and functional gene SCD as potential regulators and therapeutic targets.

Role of exosomes in metastasis and therapeutic resistance in esophageal cancer.

Esophageal cancer (EC) has a high incidence and mortality rate and is emerging as one of the most common health problems globally. Owing to the lack of sensitive detection methods, uncontrollable rapid metastasis, and pervasive treatment resistance, EC is often diagnosed in advanced stages and is susceptible to local recurrence. Exosomes are important components of intercellular communication and the exosome-mediated crosstalk between the cancer and surrounding cells within the tumor microenvironment plays a crucial role in the metastasis, progression, and therapeutic resistance of EC. Considering the critical role of exosomes in tumor pathogenesis, this review focused on elucidating the impact of exosomes on EC metastasis and therapeutic resistance. Here, we summarized the relevant signaling pathways involved in these processes. In addition, we discussed the potential clinical applications of exosomes for the early diagnosis, prognosis, and treatment of EC.

[Exogenous NO application effectively alleviates the allelochemical stress on cucumber root border cells caused by Eupatorium adenophorum extracts.] / 外源NOç¼“è§£ç´«èŒŽæ³½å °æå–ç‰©å¯¹é»„ç“œæ ¹è¾¹ç¼˜ç»†èƒžçš„åŒ–æ„Ÿèƒè¿«.

Using suspension cultures of cucumber (Cucumis sativus) cultivar Jinyou 35, we investigated the effects of allelochemical stresses induced by Eupatorium adenophorum extracts on root border cells (RBC), and the role of exogenous NO application in alleviation of the damage of root tips exposed to E. adenophorum extracts. The results showed that, 1000 mg·L-1 E. adenophorum extracts had significant damage to the cucumber root tip, resulting in severe tissue damage, exfoliated surface cells and irregular arrangement of inner cells, while those damages could be effectively alleviated by spraying exogenous NO. Compared with the control, E. adenophorum extracts (ZL) markedly reduced RBC numbers and survival rates by 54.5% and 97.2%, respectively, the RBC apoptosis rates were 12.3 times higher, the thicknesses of RBC adhesive layers were increased by 31.4%, and the root cap PME activities were markedly increased. Compared with the ZL treatment, exogenous NO application (ZN) significantly increased RBC numbers and survival rates by 72.4% and 146.0%, respectively, reduced the corresponding RBC apoptosis rates and the thicknesses of RBC adhesive layers by 30.7% and 15.0%, respectively, and inhibited the PME activities by 14.3% upon treatment for 72 hours. Our findings revealed that E. adenophorum extracts showed toxic effects on the cucumber RBC, resulting in cell apoptosis, abolishment of the RBC protection on root tips, and the destruction of root tip structure. Exogenous NO application, to some extent, could prevent the root tip and RBC from cell damage caused by E. adenophorum extracts.

[Effects of exogenous EBR and NO signal on antioxidant system and low response gene expression under cold stress on maize embryo].

In this study, Xianyu 335, a maize hybrid, was used to investigate the effects of 24-Epibrassinolide (EBR, a synthetic BR) on antioxidant capacity and low-temperature response gene expression in maize embryo germination under low temperature (LT) stress. The germination rate of maize seeds under LT stress was not affected by EBR, but the seed activity index and seedling growth were improved. EBR increased the activities of some antioxidative enzymes including SOD, POD, CAT and GR, and the contents of non-enzymatic antioxidants, such as GSH and proline, and induced the accumulation of nitric oxide (NO). NO scavenging c-PTIO and NOS inhibitor L- NAME decreased but NO donor SNP increased the enzyme activities of CAT and POD, and the content of proline, indicating NO mediated the EBR-induced antioxidant capacity. The gene expression pattern analysis showed that the expression of P5CS1, CBF1, CBF3 and COR15a was induced by LT stress, and further increased by EBR treatment in maize embryo, while their expression was suppressed by c-PTIO and L-NAME, and improved by SNP, which implied LT-responsed genes were regulated by NO. These results demonstrated that NO was involved in the EBR-induced LT tolerance in maize embryo by modulating the antioxidative capacity and the expression of LT-responsive genes.