Anti-HMGB1 monoclonal antibody

Background: Glioblastoma is a grade IV glioma with the highest degree of malignancy and extremely high incidence. Because of the poor therapeutic effect of surgery and radiochemotherapy, glioblastoma has a high recurrence rate and lethality, and is one of the most challenging tumors in the field of oncology. Ethyl pyruvate (EP), a stable lipophilic pyruvic acid derivative, has anti-inflammatory, antioxidant, immunomodulatory and other cellular protective effects. It has been reported that EP has potent anti-tumor effects on many types of tumors, including pancreatic cancer, prostate cancer, liver cancer, gastric cancer. However, whether EP has anti-tumor effect on glioblastoma or not is still unclear. Methods: Glioblastoma U87 and U251 cells were treated with different concentrations of EP for 24 h or 48 h. CCK8 assay and Colony-Formation assay were performed to test the viability and proliferation. Wound-healing assay and Transwell assay were carried out to measure cell invasion and migration. Western blot was not only used to detect the protein expression of epithelial-mesenchymal transition (EMT)-related molecules, but also to detect the expression and activation levels of NF-kappa B (p65) and Extracellular Signal Regulated Kinase (ERK). Results: In glioblastoma U87 and U251 cells treated with EP, the viability, proliferation, migration, invasion abilities were inhibited in a dose-dependent manner. EP inhibited EMT and the activation of NF-kappa B (p65) and ERIC. With NF-kappa B (p65) and ERIC activated, EMT, migration and invasion of U87 and U251 cells were promoted. However the activation of NF-kappa B (p65) and ERIC were decreased, EMT, migration and invasion abilities were inhibited in U87 and U251 cells treated with EP. Conclusion: EP inhibits glioblastoma cells migration and invasion by blocking NF-kappa B and ERIC-mediated EMT.

Aims: Atherosclerosis (AS) is a common cardiovascular disease with complicated pathogenesis. Long non-coding RNAs (lncRNAs) have been reported to be associated with AS progression. We aimed to explore the role and underlying mechanism of HOXA transcript at the distal tip (HOTTIP) in AS. Materials and methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of HOTTIP, miR-490-3p and high mobility group B 1 (HMGB1) in AS patients' sera and oxidized low-density lipoprotein (ox-LDL) induced human aortic vascular smooth muscle cells (HA-VSMCs). Cell Counting Kit-8 (CCK-8) assay and transwell assay were conducted to evaluate the proliferation and migration of HA-VSMCs, respectively. Western blot assay was carried out to determine the levels of proliferating cell nuclear antigen (PCNA), matrix metalloprotein 2 (MMP2), MMP9 and HMGB1. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to verify the targeting association between HOTTIP and miR-4903p, as well as miR-490-3p and HMGB1. Key findings: HOTTIP and HMGB1 were upregulated and miR-490-3p was downregulated in the sera of AS patients and ox-LDL-stimulated HA-VSMCs. HOTTIP knockdown suppressed ox-LDL induced proliferation and migration in HA-VSMCs. MiR-490-3p was identified as a target of HOTTIP and HOTTIP overexpression abolished the inhibition on cell proliferation and migration mediated by miR-490-3p in ox-LDL-induced HA-VSMCs. Moreover, miR-490-3p inhibition promoted cell proliferation and migration by directly targeting HMGB1 in ox-LDL-induced HA-VSMCs. Besides, HOTTIP knockdown repressed the activation of PI3K-AKT signaling pathway. Significance: HOTTIP knockdown suppressed cell proliferation and migration by regulating miR-490-3p/HMGB1 axis and PI3K-AKT pathway in ox-LDL-induced HA-VSMCs.