Considerable efforts have been made to develop reactive oxygen species (ROS) scavengers for removing high level of ROS. However, most of the reported ROS scavengers are nondegradable and involve harsh reaction conditions as well as utilize various surface ligands. In order to overcome these drawbacks, in the present work, we develop a facile and mild synthesis avenue for preparation of surface-clean hydrogen-doped molybdenum oxide (H0.34MoO3) via simply mixing MoO3 dispersion with aluminum foil under an acidic environment without any surface capping reagents at room temperature. The resulting H0.34MoO3 can act as a broad-spectrum ROS scavenger, including .OH, H2O2, O2−, and 1O2 as well as 2, 2-diphenyl-1-picrylhydrazyl (DPPH). The free radical scavenging activity of H0.34MoO3 achieves as high as 71.6% and 99.1% for .OH and DPPH scavenging, which is comparable and superior to that of ascorbic acid that is a classic free radical scavenger. More significantly, the resulting H0.34MoO3 is degrade, which can be degraded into molybdate ions under a neutral environment (pH 7.4).
Histone deacetylases (HDACs) belong to a group of epigenetic regulatory enzymes that participate in modulating the acetylation level of histone lysine residues as well as non‐histone proteins, and they play a key role in the regulation of gene expression. HDACs are potential anticancer drug targets highly expressed in various kinds of cancer cells. So far, five small molecules targeting HDACs have been approved for the therapy of cancer, and over 20 inhibitors of HDACs are under different phases of clinical trials. Among them, hydroxamate‐based HDAC inhibitors (HDACis) represent a well‐investigated series of chemical entities. The current review covers the recent progress in the discovery process, form SAHA to hydroxamate HDAC inhibitors with branched CAP region and linear linker. At the same time, the pharmacological and structure‐activity relationship (SAR) studies of the specific derivatives from SAHA and the HDACis with branched CAP region and linear linker are also introduced. 相似文献
Euphorbia factor L3, a lathyrane diterpenoid extracted from Euphorbia lathyris, was found to display good anti‐inflammatory activity with very low cytotoxicity. To find more potent anti‐inflammatory drugs, two series of Euphorbia factor L3 derivatives with fatty and aromatic acids were designed and synthesized. Among them, lathyrane derivative 5n exhibited most potent inhibition on LPS‐induced NO production in RAW264.7 cells with no obvious cytotoxicity. To determine the key characteristics of Euphorbia factor L3 derivatives that contribute to anti‐inflammatory activity, we conducted a structure‐activity relationship study of these compounds. 相似文献
Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degradation, in which elevated chondrocyte apoptosis and catabolic activity play an important role. MicroRNA‐155 (miR‐155) has recently been shown to regulate apoptosis and catabolic activity in some pathological circumstances, yet, whether and how miR‐155 is associated with OA pathology remain unexplored. We report here that miR‐155 level is significantly up‐regulated in human OA cartilage biopsies and also in primary chondrocytes stimulated by interleukin‐1β (IL‐1β), a pivotal pro‐catabolic factor promoting cartilage degradation. Moreover, miR‐155 inhibition attenuates and its overexpression promotes IL‐1β‐induced apoptosis and catabolic activity in chondrocytes in vitro. We also demonstrate that the PIK3R1 (p85α regulatory subunit of phosphoinositide 3‐kinase (PI3K)) is a target of miR‐155 in chondrocytes, and more importantly, PIK3R1 restoration abrogates miR‐155 effects on chondrocyte apoptosis and catabolic activity. Mechanistically, PIK3R1 positively regulates the transduction of PI3K/Akt pathway, and a specific Akt inhibitor reverses miR‐155 effects on promoting chondrocyte apoptosis and catabolic activity, phenocopying the results obtained via PIK3R1 knockdown, hence establishing that miR‐155 promotes chondrocyte apoptosis and catabolic activity through targeting PIK3R1‐mediated PI3K/Akt pathway activation. Altogether, our study discovers novel roles and mechanisms of miR‐155 in regulating chondrocyte apoptosis and catabolic activity, providing an implication for therapeutically intervening cartilage degradation and OA progression. 相似文献
Numerous studies have demonstrated that thioredoxin-interacting protein (TXNIP) expression of peripheral blood leucocytes is increased in coronary artery disease (CAD). However, the molecular mechanism of this phenomenon remained unclear. DNA methylation plays important roles in the regulation of gene expression. Therefore, we speculated there might be a close association between the expression of TXNIP and methylation. In this study, we found that compared with controls, DNA methylation at cg19693031 was decreased in CAD, while mRNA expressions of TXNIP and inflammatory factors, NLRP3, IL-1β, IL-18, were increased. Methylation at cg19693031 was negatively associated with TXNIP expression in the cohort, THP-1 and macrophages/foam cells. Furthermore, Transwell assay and co-cultured adhesion assay were performed to investigate functions of TXNIP on the migration of THP-1 or the adhesion of THP-1 on the surface of endothelial cells, respectively. Notably, overexpressed TXNIP promoted the migration and adhesion of THP-1 cells and expressions of NLRP3, IL-18 and IL-1β. Oppositely, knock-down TXNIP inhibited the migration and adhesion of THP-1 and expressions of NLRP3, IL-18. In conclusion, increased TXNIP expression, related to cg19693031 demethylation orientates monocytes towards an inflammatory status through the NLRP3 inflammasome pathway involved in the development of CAD. 相似文献
The case‐control study was designed to investigate the genetic effects of interferon‐gamma (IFN‐γ) rs2069727 and rs1861494 polymorphisms on ankylosing spondylitis (AS) susceptibility in a Chinese Han population. Blood samples were collected from 108 AS patients and 110 healthy controls. IFN‐γ polymorphisms were genotyped by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Hardy‐Weinberg equilibrium (HWE) test was performed in control group. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using chi‐square test to evaluate the association between AS susceptibility and IFN‐γ polymorphisms, and the results were adjusted by logistic regressive analysis. The frequency of rs2069727 CC genotype was much higher in cases than that in controls, suggested its significant association with increased AS risk (adjusted OR = 5.899, 95% CI = 1.563‐22.261; P = .009). In addition, C allele also showed close association with increased risk of AS (adjusted OR = 2.052, 95% CI = 1.286‐1.704, P = 0 .003). While the genotype and allele frequencies of IFN‐γ rs1861494 polymorphism were not significantly different between patients and controls (P > 0.05 for all), IFN‐γ rs2069727 polymorphism is significantly associated with increased AS risk in a Chinese Han Population. 相似文献