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The Wnt signaling system is a critical pathway that regulates embryonic development and adult homeostasis. Secreted frizzled-related proteins (SFRPs) are extracellular inhibitors of Wnt signaling that act by binding directly to Wnt ligands or Frizzled receptors. SFRPs can act as anti-Wnt agents and suppress cancer growth by blocking the action of Wnt ligands. However, SFRPs are often silenced by promoter methylation in cancer cells, resulting in hyperactivation of the Wnt pathway. Epigenetic modifiers can reverse this silencing and restore SFRPs expression. Despite the potential of SFRPs as a therapeutic target, the effects of SFRPs on tumor development remain unclear. Therefore, a review of the expression of various members of the SFRPs family in different cancers and their potential as therapeutic targets is warranted. This review aims to summarize the current knowledge of SFRPs in cancer, focusing on their expression patterns and their potential as novel therapeutic targets. [Display omitted] ● SFRPs as diagnostic/prognostic biomarkers in cancers. ● SFRPs sensitize cancer cells to chemotherapy and radiotherapy ● SFRPs enhance immune responses and modulate tumor microenvironment. ● Combined SFRPs therapies with chemo/immunotherapy hold cancer therapy potential. ● Epigenetic modifiers restore SFRPs expression, a promising cancer therapy target. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening organ dysfunction with devastating consequences, prominent among which is lung damage. Memantine, an N-methyl- D -aspartic acid receptor (NMDAR) antagonist, is able to alleviate acute lung injury (ALI). Nitric oxide (NO) suppresses NLRP3 inflammasome activation against lipopolysaccharide (LPS)-induced septic shock. MN-08, a novel nitrate derivative of memantine, possesses both the ability to antagonize NMDAR and release NO. In the present study, we aimed to investigate the protective effects of MN-08 against LPS-induced systemic inflammation and septic lung injury in mice, and to explore the underlying mechanisms of MN-08 in LPS-induced mice and THP-1 macrophages. MN-08 significantly increased the survival rate of septic mice, alleviated LPS-induced sepsis in mice via improving systemic inflammatory response syndrome and immune dysfunction, and attenuated pulmonary injury and inflammatory infiltration. More importantly, the therapeutic benefit of MN-08 for sepsis was greater than that of memantine and dexamethasone. Mechanistically, MN-08 exerted anti-inflammatory activity through inhibiting nuclear translocation of NF-κB, activation of the MAPK signaling pathway and the signaling transduction of STAT3/NF-κB. In addition, MN-08 suppressed NLRP3 inflammasome activation. Taken together, our studies demonstrate that MN-08 may be a promising therapeutic agent for sepsis-induced acute lung injury. [Display omitted] • MN-08 significantly increased the survival rate of septic mice. • MN-08 improved SIRS and immune dysfunction. • MN-08 attenuated septic lung injury and inflammatory infiltration. • MN-08 exerts its protection via suppressing NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]