Background: M2000 is a newly designed and safe Non-Steroidal Anti-Inflammatory Drug (NSAID). The aim of this study was to assess the effects of M2000 on expression levels of Suppressor of Cytokine Signaling-1 (SOCS-1) and Src Homology-2 domaincontaining inositol-5’-phosphatase 1 (SHIP1) proteinsvia Toll-Like Receptor (TLR) 2/microRNA-155 pathway.Methods: HEK293 TLR2 cell line and Peripheral Blood Mononuclear Cells (PBMCs) were treated by different concentrations of M2000 in MTT assay. RNA was extracted by miRNeasy Mini kit. Then, cDNA was synthesized and the expression levels of SOCS1, SHIP1 and miRNA155 were evaluated by Quantitative Real time PCR.Results: Our results showed that M2000 significantly increased the expression levels of SOCS1 and SHIP-1 in Lipopolysachride (LPS) -treated and non-treated cells. Moreover, M2000 decreased expression level of miR-155 in LPS treated PBMCs.Conclusion: M2000 can be used as NSAID in LPS induced inflammation and decrease inflammatory cytokines production by targeting SOCS1, SHIP1 and miR-155 in autoimmune and inflammatory diseases.

Background: The available evidence has increasingly demonstrated that a combination of genetic and epigenetic factors, such as DNA methylation, could be considered as causing leukemia. Epigenetic changes and methylation of the suppressor of the cytokine signaling 1 promoter (SOCS1) CpG region silence SOCS1 expression in cancer. In the current study, we evaluated the impact of epigallocatechin gallate (EGCG) and RG108 on SOCS1 promoter methylation and expression in U937 cells. Methods: In the current study, U937 leukemic cells were treated with EGCG and RG108 for 12, 24, 48, and 72 h and SOCS1 promoter methylation and its expression were measured by methylationspecific PCR (MSP) and quantitative real-time PCR, respectively. Results: The outcomes indicated that the SOCS1 promoter is methylated in U937 cells, and treatment of these cells with either EGCG or RG108 reduced its methylation. Moreover, we observed that SOCS1 expression was significantly upregulated in a time-dependent manner by both EGCG and RG108 in U937 cells compared with control cells. In the RG108-treated group at 12, 24, 48, and 72 h, SOCS1 expression was upregulated by 1, 4. 2, 16. 6, and 32. 6-fold respectively, and in the EGCG-treated group, by 0. 5, 3. 2, 10. 8, and 22. 3-fold, respectively. Conclusions: Treatment with either EGCG or RG108 reduced SOCS1 promoter methylation and increased SOCS1 expression in U937 cells in a time-dependent manner, which may play a role in leukemia therapy.

Background & Objective:  Acute myeloid leukemia (AML) is a diverse blood cancer that predominantly affects adults. In addition to genetic mutations, epigenetic processes, including DNA methylation and histone modifications are key factors in leukemogenesis. This study investigated the relationship between the Suppressor of Cytokine Signaling 1 (SOCS1) gene methylation and the Enhancer of Zeste Homolog 2 (EZH2) gene expression in patients with AML.  Materials & Methods:  This cross-sectional study included 85 AML patients admitted to Ghaem Hospital (Mashhad, Iran) between April 2017 and March 2023. Patients were diagnosed based on the World Health Organization (WHO) guidelines and the French-American-British (FAB) classification. The EZH2 expression level and SOCS1 methylation patterns were analyzed. The associations between these epigenetic alterations, demographic characteristics, and clinical outcomes were assessed. Results:  Our findings indicated a significant inverse relationship between EZH2 expression and SOCS1 gene methylation. Furthermore, EZH2 overexpression and SOCS1 hypomethylation were associated with reduced overall survival. Conclusion:  This study suggests that EZH2 and SOCS1 may jointly influence AML progression and patient outcomes through epigenetic changes—their prognostic relevance and therapeutic potential merit further research in larger studies.

Background: Silibinin (silibinin A) is the most active silymarin component, which acts both as a hepatoprotective [1] and an antiviral agent. The present study investigated the silibinin effect on IFN-related innate immune genes in PBMCs from HCV-infected patients. Method: 22 chronic HCV patients, including 10 IFN responders and 12 non-responders, were included. Their isolated PBMCs were treated for 6 hours in the presence of silibinin, IFN-α , or their combination. The transcription level of TLR7, ISG15, and SOCS1 genes was compared using real-time PCR. Result: Our result showed that IFN-α induced a significant up-regulation of TLR7 and ISG15 in PBMCs of both responder and non-responder groups. Nevertheless, the SOCS1 gene was not significantly changed in the non-responder group (P=0. 32). The combination of IFNα-and silibinin showed a similar pattern to IFN-α alone. By itself, silibinin did not leave a significant change on the expression level of the studied genes. Conclusion: The results indicated that silibinin did not enhance or suppress the expression level of TLR7, ISG15, and SOCS1 genes. Therefore, it has been suggested that its anti-inflammatory role might be devoid of IFN pathways.