Molecularly tailored therapies have opened a new era, chronic myeloid leukemia being the ideal example, in the treatment of cancer. However, available therapeutic options are still unsatisfactory in many types of cancer, and often fail due to the occurrence of resistance mechanisms. With regard to small-molecule compounds targeting the components of the Mitogen-Activated Protein Kinase (MAPK) cascade RAF-MEK1/2-ERK1/2, these drugs may result ineffective as a consequence of the activation of compensatory pro-survival/proliferative signals, including receptor tyrosine kinases, PI3K, as well as other components of the MAPK family such as TPL2/COT. The MAPK ERK5 has been identified as a key signaling molecule in the biology of several types of cancer. In this review, we report pieces of evidence regarding the activation of the MEK5-ERK5 pathway as a resistance mechanism to RAF-MEK1/2-ERK1/2 inhibitors. We also highlight the known and possible mechanisms underlying the cross-talks between the ERK1/2 and the ERK5 pathways, the characterization of which is of great importance to maximize, in the future, the impact of RAF-MEK1/2-ERK1/2 targeting. Finally, we emphasize the need of developing additional therapeutically relevant MEK5-ERK5 inhibitors to be used for combined treatments, thus preventing the onset of resistance to cancer therapies relying on RAF-MEK1/2-ERK1/2 inhibitors.
  Increasing evidence indicates an association between the incidence of Alzheimer's disease (AD) and cancer development. Despite advances being made by comparisons from epidemiological studies, common pathways and molecular mechanisms, little is known about the identities of the circular RNAs (circRNAs) involved in the development and progression of these two pathologies and their possible correlations. The aim of this study was to explore the circRNA relationship between AD and cancer.
 
  In this investigation, circRNAs that were significantly dysregulated in AD or associated with AD diagnosis, clinical dementia severity, and neuropathological severity, were examined in a large panel of 28 cancer types. On the basis of shared abnormal circRNAs in AD and cancers, we constructed a circRNA-micro RNA (miRNA)-messenger RNA (mRNA) network by leveraging experimentally identified miRNA-circRNA and miRNA-mRNA interactions from crosslinking-immunoprecipitation sequencing data.
 
  An inverse correlation of expression pattern was found in acute myeloid leukemia, juvenile myelomonocytic leukemia, renal cell carcinoma, and myelofibrosis. CircRNAs associated with AD diagnosis and clinical severity demonstrated negative correlation in more cancer types. Notably, differentially expressed candidate circRNAs in temporal lobe epilepsy were not associated with any cancers. Gene Ontology and KEGG pathway analysis suggested the circRNA-regulated genes are significantly associated with interleukin-12-mediated signaling and viral response. CircPICALM, circRTN4 and circMAN2A1 are the hub nodes in the circRNA-miRNA-target network.
 
  Our results indicated the relevance of inflammation signaling as a common pathogenesis shared by cancer and AD and provided novel insight for therapeutics targeting circRNAs.
 Our results indicated the relevance of inflammation signaling as a common pathogenesis shared by cancer and AD and provided novel insight for therapeutics targeting circRNAs.In placental mammals, reproductive success, and maternal-fetal health substantially depend on a well-being placenta, the interface between the fetus and the mother.  https://www.selleckchem.com/products/imd-0354.html  Disorders in placental cells are tightly associated with adverse pregnancy outcomes including preeclampsia (PE), fetal growth restriction, etc. MicroRNAs (miRNAs) represent small non-coding RNAs that regulate post-transcriptional gene expression and are integral to a wide range of healthy or diseased cellular proceedings. Numerous miRNAs have been detected in human placenta and increasing evidence is revealing their important roles in regulating placental cell behaviors. Recent studies indicate that placenta-derived miRNAs can be released to the maternal circulation via encapsulating into the exosomes, and they potentially target various maternal cells to provide a hormone-like means of intercellular communication between the mother and the fetus. These placental exosome miRNAs are attracting more and more attention due to their differential expression in pregnant complications, which may provide novel biomarkers for prediction of the diseases. In this review, we briefly summarize the current knowledge and the perspectives of the placenta-derived miRNAs, especially the exosomal transfer of placental miRNAs and their pathophysiological relevance to PE. The possible exosomal-miRNA-targeted strategies for diagnosis, prognosis or therapy of PE are highlighted.The chemokine ligand C-X-C motif chemokine ligand 11 (CXCL11) is involved in the progression of various cancers, but its biological roles in colorectal cancer (CRC) remain confused. Therefore, the prognostic value and underlying mechanism of CXCL11 in CRC were preliminarily evaluated. Three independent datasets were used for mRNA-related analysis one dataset from the Cancer Genome Atlas (TCGA, n = 451) and two single-cell RNA sequencing (scRNA-seq) datasets from Gene Expression Omnibus (GEO) GSE146771 and GSE132465. In addition, a colon adenocarcinoma (COAD) patient cohort (the Yijishan Hospital cohort, YJSHC, n = 108) was utilized for analysis of cell infiltration by immunohistochemistry. We determined the distribution of CXCL11 in tumor tissue across all TCGA cancers and found that CXCL11 expression was significantly upregulated in both COAD and rectal adenocarcinoma (READ). However, the upregulation of CXCL11 mRNA was associated with a better prognosis in COAD, but not in READ. Within the YJSHC, the patients with a high abundance of intratumoral CXCL11+ cells had prolonged survival (p = 0.001). Furthermore, we found that the high CXCL11 expression group had a higher proportion of antitumor immune cells, and a lower proportion of protumor immune cells. Additionally, we discovered the changes of gene expression and enriched immune pathway network mediated by CXCL11. Interestingly, both cytotoxic genes (IFNG, GZMA, GZMB, GZMK, GZMM, and PRF1) and immunosuppressive molecules, including PD-L1, were positively correlated with CXCL11 expression. CXCL11, which promoted antitumor immunity to benefit survival, was identified as an independent prognostic biomarker in patients with COAD.