MicroRNAs and JAK/STAT3 signaling: A new promising therapeutic axis in blood cancers.

Blood disorders include a wide spectrum of blood-associated malignancies resulting from inherited or acquired defects. The ineffectiveness of existing therapies against blood disorders arises from different reasons, one of which is drug resistance, so different types of leukemia may show different responses to treatment. Leukemia occurs for a variety of genetic and acquired reasons, leading to uncontrolled proliferation in one or more cell lines. Regarding the genetic defects, oncogene signal transducer and activator of transcription (STAT) family transcription factor, especially STAT3, play an essential role in hematological disorders onset and progress upon mutations, dysfunction, or hyperactivity. Besides, microRNAs, as biological molecules, has been shown to play a dual role in either tumorigenesis and tumor suppression in various cancers. Besides, a strong association between STAT3 and miRNA has been reported. For example, miRNAs can regulate STAT3 via targeting its upstream mediators such as IL6, IL9, and JAKs or directly binding to the STAT3 gene. On the other hand, STAT3 can regulate miRNAs. In this review study, we aimed to determine the role of either microRNAs and STAT3 along with their effect on one another's activity and function in hematological malignancies.

Potential anti-inflammatory effect of anti-HMGB1 in animal models of ICH by downregulating the TLR4 signaling pathway and regulating the inflammatory cytokines along with increasing HO1 and NRF2.

Intracerebral hemorrhage (ICH) is a severe clinical problem without effective treatment; the leading cause is neuroinflammation. High-mobility group box one protein (HMGB1) is an abundant protein in the cell nucleus of most mammalian cells, which exerts its function by binding to chromatin. The present study focused on the therapeutic effect of anti-HMGB1 on ICH via the downregulation of inflammatory pathways. The ICH mice models were created by collagenase IV injection in the striatum of mice. Then, mice were received different medications and divided into three groups: anti-HMGB1, anti-Toll-like receptor 4 (TLR4), and non-treated ICH groups. Cerebrospinal fluid (CSF) was obtained, and ELISA was carried out to determine the levels of inflammatory agents. Microglial cells were isolated from the cerebral hemispheres, and then Real-Time PCR and western blot were performed. The results showed that the anti-inflammatory effects of anti-HMGB1 were tremendous than anti-TLR4. Overall, the results showed that anti-HMGB1 had a more reducer effect on pro-inflammatory cytokines release (****P < 0.0001) and expression (****P < 0.0001) than anti-TLR4 when compared with the control group. It was also determined that anti-HMGB1 increased heme-oxygenase-1 (HO1) and nuclear factor erythroid-derived factor 2-related factor 2 (NRF2) (****P < 0.0001) expression in comparison with the control group while it was not significant for anti-TLR4 (CLI-095). The present study suggested that anti-HMGB1 serves as a potential anti-inflammatory molecule via reducing TLR4-related signaling pathways, pro-inflammatory cytokines production, and increasing the production of the anti-inflammatory cytokine along with heme-oxygenase-1 HO1 and NRF2 increment.