Oral Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) Spore Powder Ameliorates Murine Colitis by Inhibiting Key Kinases Phosphorylation in MAPK Pathway.

The compound ganoderma lucidum spore powder (GLSP) has emerged as an anti-inflammatory and anti-oxidative regulator. In this study, we explored the roles of GLSP against dextran sulfate sodium (DSS)-induced mouse colitis that can mimic human inflammatory bowel disease (IBD). GLSP was administered by oral gavage at a dosage of 150 mg/kg/day to the acute colitis mice induced by DSS. The DSS-induced mouse weight loss, colonic shortening, diarrhea and bloody stool were observably alleviated after GLSP treatment. The lesion of macroscopic and microscopic signs of the disease was reduced significantly and DSS-induced gut barrier dysfunction was restored via increasing the level of claudin-1, ZO1, Occu, and ZO2 with GLSP. Meanwhile, the levels of IL-6, TNF-α, IL-1ß, and IL-18 in the colon were reduced in the GLSP-treated groups. In addition, phosphorylation of the MAPKs ERK1/2, p38, and AKT was suppressed after GLSP treatment. All these results demonstrated that GLSP owned a protective effect on DSS-induced colitis by inhibition of MAPK pathway, which provides a promising therapeutic approach for the treatment of colitis.

Hollow CeO2 with ROS-Scavenging Activity to Alleviate Colitis in Mice.

INTRODUCTION: Excessive production of reactive oxygen species (ROS) to induce high oxidative stress is one of the main causes of colitis; thus, it has been regarded as a therapeutic target for colitis treatment. And the nanomaterial-based therapeutic strategies are effective against colitis. However, the previous elaborately designed materials exhibit limited application due to the uncertain biocompatibility and complicated manufacturing processes. METHODS: In this study, the highly monodisperse hollow CeO2 nanoparticles (H-CeO2) with uniform morphology were obtained by in situ growing CeO2 on solid silica nanoparticles and subsequently removing the silica core. The H-CeO2 was further modified with PEG, which owned excellent biological stability and biocompatibility. The experimental model of colitis induced by dextran sulfate sodium (DSS) was used to investigate the anti-inflammatory effect of H-CeO2-PEG. RESULTS: The H-CeO2-PEG showed good ROS scavenging efficacy and decreased the levels of proinflammatory cytokines (IL-6, IL-1ß, IL-18, and TNF-α) in DSS-induced colitis mice. Furthermore, H-CeO2-PEG inhibited the activation of the MAPK signalling pathway to alleviate colitis. CONCLUSION: This study reveals the therapeutic effects of CeO2-based nanomedicine toward colitis and elucidates the specific signalling pathway involved, which provides potential alternative therapeutic options for patients with inflammation tissue.

Identification of novel methylated targets in colorectal cancer by microarray analysis and construction of co-expression network.

The present study was conducted to investigate novel methylated targets in colorectal cancer (CRC). The mRNA expression profiles of GSE32323 in 17 cancer and non-cancerous tissues from CRC patients, as well as expression profiles of 5 CRC cell lines prior and subsequent to 5-aza-2'-deoxycytidine (5-aza-dC) treatment, were obtained from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in 5 CRC cell lines prior and subsequent to 5-aza-dC treatment were combined with the CRC-specific gene expression profiling array data. Context likelihood of relatedness algorithm was used to construct the co-expression network of CRC-specific gene expression profile. A sub-network of identified reverse-overlapped DEGs was selected and underwent Kyoto Encyclopedia of Genes and Genomes Pathway Analysis. A total of 6 reverse-overlapped DEGs were identified. This present study verified fibulin 2 (FBLN2) and protein phosphatase 1 regulatory inhibitor subunit 14A (PPP1R14A) to be downregulated in the CRC tissue sample but upregulated in CRC cell lines following 5-aza-dC treatment. The identified reverse-overlapped DEGs were enriched in tumor-associated signaling pathways, including cellular tumor antigen p53, cell cycle and NOD-like receptor (NLR) signaling pathway. A total of 2 silenced genes with abnormal methylation in CRC were identified, including FBLN2 and PPP1R14A. The reverse-overlapped DEGs were enriched in p53, cell cycle and NLR signaling pathways, indicating that reverse-overlapped DEGs, particularly FBLN2 and PPP1R14A, may be important tumor suppressors and that these reverse-overlapped DEGs are inactivated by methylation in CRC.

Identification of biomarkers for the prognosis of pancreatic ductal adenocarcinoma with miRNA microarray data.

BACKGROUND: The aim of this study was to explore the mechanism of chemotherapy resistance and to screen biomarkers of pancreatic ductal adenocarcinoma (PDAC). METHODS: MicroRNA (miRNA) expression profile data for GSE38781 were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs between short-overall survival (OS) and long-OS patients were screened with the limma package in R. The function and protein-protein interaction (PPI) network of the miRNA target genes were further investigated. Finally, multivariate statistical analysis was performed to verify the significant miRNAs obtained in our work. RESULTS: In total, 66 miRNAs were identified to be differentially expressed. Gene ontology (GO) and pathway enrichment analysis showed that 163 miRNA target genes were mainly enriched in heart function, cancer development and angiogenesis. Ten nodes, including TGFBR1, TGFBR2, ACVR1 and SHC1, were found to be hub nodes in the PPI network. Multivariate statistical analysis showed 8 of the most significant miRNAs could completely distinguish the 2 groups of samples. Seven target genes (i.e., RET, ETS1, RHOA, NUMB, TIAM, ITGA5 and YY1) of the 8 significant miRNAs were found to be associated with control of cell fate decisions, T-cell lymphoma invasion and angiogenesis enhancement. CONCLUSIONS: The heart function-related pathway, cell cycle, immune system and angiogenesis may be dysregulated in patients with poorer prognosis. The significant nodes (e.g., TGFBR1, TGFBR2, ACVR1 and SHC1) in the PPI network may be potential biomarkers for predicting outcomes for patients with pancreatic cancer. The significant miRNAs and gene targets may be potential biomarkers or therapeutic targets for PDAC.