Search

Graphical abstract Abstract Magnesium Isoglycyrrhizinate (MgIG), a novel molecular compound extracted from licorice root, has exhibited greater anti-inflammatory activity and hepatic protection than glycyrrhizin and β-glycyrrhizic acid. In this study, we investigated the anti-inflammatory effect and the potential mechanism of MgIG on Lipopolysaccharide (LPS)-treated RAW264.7 cells. MgIG down-regulated LPS-induced pro-inflammatory mediators and enzymes in LPS-treated RAW264.7 cells, including TNF-α, IL-6, IL-1β, IL-8, NO and iNOS. The generation of reactive oxygen species (ROS) in LPS-treated RAW264.7 cells was also reduced. MgIG attenuated NF-κB translocation by inhibiting IKK phosphorylation and IκB-α degradation. Simultaneously, MgIG also inhibited LPS-induced activation of MAPKs, including p38, JNK and ERK1/2. Taken together, these results suggest that MgIG suppresses inflammation by blocking NF-κB and MAPK signaling pathways, and down-regulates ROS generation and inflammatory mediators. [ABSTRACT FROM AUTHOR]

Inflammation and host stromal activation contribute significantly to ovarian cancer (OC) initiation and malignant progression. However, the complex reciprocal interactions between them are largely unknown. Here, we discovered that the tumor suppressor gene Dicer was paradoxically overexpressed in ovarian tumor stroma, and induced fibroblast activation and stromal inflammation. Dicer transformed normal fibroblasts to a carcinoma-associated fibroblast (CAF)-like state, which was morphologically spread out and functionally activated to fuel tumor invasion and metastasis. Attenuation of Dicer hampered CAF characteristics, diminished stromal inflammation and the role of fibroblasts in supporting tumor growth. Moreover, Dicer drove the expression of an “inflammatory signature” in fibroblasts that could be used to discriminate normal and cancerous stroma and predict the survival of patients with OC. Finally, the nuclear factor κ B (NFκB) signaling was demonstrated to be responsible for Dicer effect on fibroblast activation and stromal inflammation, through microRNA (miR)-6780b. Our study represents the first report that characterizes Dicer expression and function in the tumor stroma, and highlights its pro-metastatic role in this context. Additionally, we suggest that the Dicer-miR6780b-NFκB cascade is an attractive target of choice in stroma-oriented OC therapy. [ABSTRACT FROM AUTHOR]

Objective To examine whether curcumin has protective effect on insulin resistance induced by bisphenol A (BPA) in LO2 cells and whether this effect was mediated by inhibiting the inflammatory mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways. Methods LO2 cells were stimulated with BPA in the presence or absence of curcumin for 5 days. Glucose consumption, activation of insulin signaling, MAPKs and NF-κB pathways, levels of inflammatory cytokines and MDA production were analyzed. Results Curcumin prevented BPA-induced reduction of glucose consumption and suppression of insulin signaling pathway, indicating curcumin alleviated BPA-triggered insulin resistance in LO2 cells. mRNA and proteins levels of TNF-α and IL-6, as well as MDA level in LO2 cells treated with BPA were decreased by curcumin. Furthermore, curcumin downregulated the activation of p38, JNK, and NF-κB pathways upon stimulation with BPA. Inhibition of JNK pathway, but not p38 nor NF-κB pathway, improved glucose consumption and insulin signaling in BPA-treated LO2 cells. Conclusion Curcumin inhibits BPA-induced insulin resistance by suppressing JNK pathway. [ABSTRACT FROM AUTHOR]

• BPS induced oxidative stress at human serum relevant concentration in macrophages. • BPS triggered inflammatory response in macrophages. • BPS activated the NLRP3 inflammasome, TLR4, Nrf2 and MAPK pathways. • NAC pretreatment diminished these effects triggered by BPS exposure. Bisphenol S is considered as a safer alternative to bisphenol A. In the present study, we used murine macrophages to investigate the effects of BPS exposure on oxidative stress and inflammatory response as well as the underlying mechanism. Cells were exposed to BPS at various concentrations for short period of times. Results showed that 10−8 M BPS triggered oxidative stress by increasing ROS/RNS production, increased the levels of oxidant enzyme NOX1/2, and decreased the levels of antioxidant enzymes SOD1/2, CAT and GSH-Px. 10−8 M BPS exposure significantly induced the production of proinflammatory mediators. Activation of the NLRP3 inflammasome, TLR4, and MAPK pathways was involved in this process. Furthermore, we illustrated that NAC pretreatment diminished these effects triggered by BPS exposure. Collectively, our data suggested that BPS at a dose relevant to human serum concentration induced oxidative stress and inflammatory response in macrophages. These novel findings shed light on the concerns regarding the potential adverse effects of BPS exposure that requires further careful attention. [ABSTRACT FROM AUTHOR]