Inflammation is implicated in various diseases, such as inflammatory bowel disease and cancer. Ascochlorin (ASC) and its derivatives have been shown to modulate inflammatory responses in many previous studies. Trichostatin A solubility dmso However, the effects of 4-O-methylascochlorin (MAC), one of the ASC derivatives, on inflammatory responses have yet to be reported. In addition, the consequences of chemical modification of ASC on protein signaling and immunity have yet to be fully understood. The fourth carbon in MAC is methylated, which may result in modulation of immune response differently compared with ASC. Hence, we have investigated the role of MAC in inflammatory response induced by lipopolysaccharide in murine macrophage cells. Here, we found that MAC treatment decreased the inflammatory response by murine macrophages. When murine macrophages were treated with MAC, the transcription and translation of various pro-inflammatory indicators such as iNOS and COX-2 decreased. In addition, the ELISA results showed that the expression of TNF-α, IL-6, and IL-1β, which are pro-inflammatory cytokines, was successfully decreased by MAC. Such effects of MAC appear to be mediated via downregulation of MAPK signaling and the transactivational activity of NF-κB. Lipopolysaccharide upregulates MAPK protein phosphorylation and NF-κB translocation, which in turn enhances the transactivation of genes related to NF-κB. Such results of lipopolysaccharide were attenuated by MAC. Collectively, our results indicate that MAC alleviated the inflammatory responses induced by lipopolysaccharide in murine macrophages successfully by modulating MAPK signaling pathway and NF-κB-related genes. This study shows that MAC, similar to other ASC derivatives, can potentially be used therapeutically to reduce the harmful damage induced by prolonged inflammation. In addition, the structural differences between ASC and its derivatives as well as their effect on intracellular signaling will also be discussed.Inflammation plays an important role in the pathogenesis of cerebral ischemia. Syringin (SYR) is an active substance isolated from Acanthopanax senticosus plants, and possesses anti-inflammatory and neuroprotective properties. However, its effects on cerebral ischemic injury, as well as the underlying molecular events, are still unclear. The purpose of this study was to investigate the effect of SYR in a rat model of cerebral ischemia and address the related molecular mechanism. A middle cerebral artery occlusion/reperfusion model (MCAO) was used to simulate ischemic injury. SYR treatment clearly reduced the infarct volume, decreased cerebral water content, improved the neurological score, and attenuated neuronal death. Moreover, SYR decreased the expression of NF-κB, IL-1β, IL-6, TNF-α, and MPO, promoted FOXO3a phosphorylation and cytoplasmic retention, and inhibited the nuclear translocation of NF-κB. FOXO3a knockdown by RNA interference significantly prevented SYR-induced inhibition of NF-κB-mediated inflammation. Confocal microscopy revealed that SYR reduced NF-κB translocation to the nucleus, and FOXO3a silencing reversed this effect. Finally, immunofluorescence and CO-IP experiments showed that SYR promoted the interaction between FOXO3a and NF-κB. In conclusion, SYR exerted a protective effect against brain I/R injury by reducing the inflammation accompanying cerebral ischemia. This effect was mediated by the FOXO3a /NF-κB pathway.

Immune system instability and poor prognosis are the two major clinical performance of hepatocellular carcinoma (HCC). Abnormal expression of MiR-424-5p has been reported to accelerate the progression of liver cancer, but it mediated immune cell infiltration imbalance is still unknown. We aim to mine the immune-related genes (IRGs) targeted by miR-424-5p and construct a multi-gene signature to improve the prognostic prediction of HCC.

The HCC-related data of the cancer genome atlas (TCGA) database and the GSE14520 dataset of the gene expression omnibus (GEO) database were downloaded as the discovery dataset and the validation dataset, respectively. Weighted gene co-expression network analysis (WGCNA), the deconvolution algorithm of CIBERSORT and LASSO algorithm participated in the identification of IRGs and the development of prognostic signature and nomogram.

Our study found that the abundance of macrophages M0, M1 and M2 are all drastically changed during the cancerous process. A total of 920 macrophae novel macrophages-related 4-gene signature is expected to become a potential prognostic marker in liver cancer.

Carbonic anhydrase-IX (CA-IX) is markedly overexpressed in many types of solid tumors promoting tumorigenicity and tumor growth. We synthesized novel

Ga-labeled imidazothiadiazole sulfonamide (IS) derivatives ([

Ga]Ga-DO3A-IS1 and [

Ga]Ga-DO2A-IS2), and evaluated their utility as positron emission tomography (PET) probes targeting CA-IX.

[

Ga]Ga-DO3A-IS1 and [

Ga]Ga-DO2A-IS2 were synthesized from corresponding precursors by ligand substitution reaction in acetate buffer. Cell binding assays were performed using HT-29 cells, which highly express CA-IX, and MDA-MB-231 cells, which show lower-level expression of CA-IX, and a biodistribution assay with model mice bearing the HT-29 or MDA-MB-231 tumor was performed. [

Ga]Ga-DO3A-IS1 was further evaluated by PET/CT.

To evaluate their fundamental properties, [

Ga]Ga-DO3A-IS1 and [

Ga]Ga-DO2A-IS2 were synthesized by conjugation with

Ga, which has a much longer decay half-life and can be utilized more easily than

Ga. [

Ga]Ga-DO3A-IS1 and [

Ga]Ga-DO2A-IS2 were prepared from corresponding precursors with preferable yield and purity. [

Ga]Ga-DO3A-IS1 and [

Ga]Ga-DO2A-IS2 showed significantly greater binding to HT-29 cells than MDA-MB-231 cells in vitro and the binding of [

Ga]Ga-DO2A-IS2 to HT-29 cells was much greater than that of [

Ga]Ga-DO3A-IS1, suggesting multivalent interactions. [

Ga]Ga-DO3A-IS1 and [

Ga]Ga-DO2A-IS2 showed significant selectivity for the HT-29 tumor in vivo, while tumor uptake of [

Ga]Ga-DO3A-IS1 was greater than that of [

Ga]Ga-DO2A-IS2. PET/CT of [

Ga]Ga-DO3A-IS1 showed selectivity for the HT-29 tumor, although [

Ga]Ga-DO3A-IS1 could not be used to visualize the HT-29 tumor clearly because of its strong background signals.

These results indicate that

Ga-labeled IS derivatives may be useful

Ga-PET probes targeting CA-IX with further structural modifications.

These results indicate that 68Ga-labeled IS derivatives may be useful 68Ga-PET probes targeting CA-IX with further structural modifications.