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ObjectiveThe aim of this study was to investigate the role of CD109 in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and to evaluate its potential as a therapeutic target.MethodsCD109 expression was examined in synovial tissues and FLSs from RA patients and collagen-induced arthritis (CIA) model mice. CD109-deficient mice were developed to evaluate the severity of CIA. Small interfering RNAs and a neutralising antibody against CD109 (anti-CD109) were designed for functional or treatment studies in RA FLSs and CIA.ResultsCD109 was found to be abundantly expressed in the synovial tissues from RA patients and CIA mice. CD109 expression in RA FLSs was upregulated by inflammatory stimuli, such as interleukin-1β and tumour necrosis factor-α. Silencing of CD109 or anti-CD109 treatment reduced proinflammatory factor production, cell migration, invasion, chemoattractive potential and osteoclast differentiation, thereby reducing the deleterious inflammatory response of RA FLSs in vitro. Mice lacking CD109 were protected against arthritis in the CIA model. Anti-CD109 treatment prevented the onset and ameliorated the severity of CIA lesions.ConclusionOur study uncovers an antiarthritic role for CD109 and suggests that CD109 inhibition might serve as a promising novel therapeutic strategy for RA.

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Although the Epstein-Barr virus (EBV) infection is usually asymptomatic, a primary encounter with the virus can cause mononucleosis. EBV infection is also strongly associated with lymphoma and epithelial cancers. The structure and infection mechanism of EBV have been well studied, but the EBV-encoded G protein-coupled receptor, BILF1, is not fully understood. Here, it was found that the EBV BILF1 was expressed early in the viral lytic cycle and its ectopic expression strikingly upregulated the ICAM-1 expression in Raji cells. The positive effect of BILF1 on the ICAM-1 promoter was observed and the BILF1 deficiency attenuated ICAM-1 promoter activity. Moreover, NF-κB binding sites were important for the regulation of ICAM-1 promoter by BILF1. Furthermore, BILF1 reduced the constitutive level of the IқB-a protein and increased the amount of nuclear NF-қB in Raji cells. In conclusion, this study determined that BILF1 upregulated ICAM-1 in a mechanism involving NF-қB.

Objective: To analyze the efficacy and safety of decitabine combined with CAG ((cytarabine + aclacinomycin + granulocyte colony stimulating factor)) regimen and CAG regimen alone in the treatment of elderly acute myeloid leukemia. Methods: 96 elderly patients with acute myeloid leukemia who were admitted to our hospital from July 2015 to July 2017 were randomly divided into an observation group and a control group, 48 cases in each group. The patients in the control group were treated with CAG regimen, while the patients in the observation group were treated with decitabine on the basis of the control group. The clinical curative effect, changes of immune indicators, occurrence of adverse reactions and survival rate at different time after treatment were compared between the two groups. Results: The total effective rate of the observation group was significantly higher than that of the control group (P<0.05). After treatment, the indicators of cellular immunity in the two groups were significantly lower than those before treatment, and the indicators of cellular immunity in the observation group were significantly lower than those in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). The 9-month survival rate and 1-year survival rate in the observation group were significantly higher than those in the control group (P<0.05). Conclusion: The combination of decitabine and CAG regimen is effective in the treatment of elderly patients with acute myeloid leukemia. The therapy can fully inhibit cellular immune function and improve long-term survival rate, and its safety has a small difference with that of CAG regimen alone. It is worth clinical promotion. doi: https://doi.org/10.12669/pjms.36.2.850 How to cite this:Zhao H, Wang C, Yu F, Guo Q. Decitabine combined with CAG regimen in the treatment of elderly patients with acute myeloid leukemia. Pak J Med Sci. 2020;36(2):---------. doi: https://doi.org/10.12669/pjms.36.2.850 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Background: CircLARP4 is reported to act as a tumor suppressor in some cancers. However, the detailed roles and molecular basis of circLARP4 in non-small cell lung cancer (NSCLC) tumorigenesis are still unclear. The aim of the study is to explore the potential roles and molecular basis of circLARP4 in NSCLC tumorigenesis. Materials and Methods: qRT-PCR was taken to detect circLARP4 and miR-135b expressions. MTT assay, transwell invasion assay and flow cytometry analysis were applied to evaluate cell proliferation, invasion and apoptosis, respectively. Glycolysis was assessed by measuring hexokinase2 (HK2) expression, glucose consumption and lactate production. Association between circLARP4 and miR-135a was examined by luciferase reporter and RIP assays. The changes of the phosphatase and tension homolog (PTEN)/protein kinase B (AKT)/hypoxia-inducible factor-1α (HIF-1α) pathway were evaluated by Western blot. The nude mouse xenograft models were applied to verify the regulation of circLARP4 in vivo. Results: CircLARP4 was decreased in NSCLC tissues and cells. CircLARP4 overexpression blocked cell proliferation and invasion, and facilitated apoptosis in NSCLC cells. Meanwhile, circLARP4 overexpression suppressed glycolysis in NSCLC cells, as evidenced by the reduced HK2, glucose consumption and lactate production levels. Further analyses proved a downregulation of miR-135b by circLARP4 in a ceRNA-dependent manner in NSCLC cells. CircLARP4-mediated tumor suppression on NSCLC progression was partially overturned by overexpressing miR-135b. Moreover, we confirmed that circLARP4 had antitumor effect on xenograft tumors and downregulated miR-135b. Furthermore, circLARP4 overexpression inhibited the PTEN/AKT/HIF-1α pathway in NSCLC cells and xenograft tumors by downregulating miR-135b. Conclusion: Our findings suggested that circLARP4 suppressed NSCLC progression by sponging miR-135b through inactivation of the PTEN/AKT/HIF-1α pathway, which broadens our understanding concerning the roles of circLARP4 in NSCLC tumorigenesis.

Summary. -Epstein-Barr virus (EBV) replication and transcription activator (Rta) is an immediate-early transcription factor that mediates the switch from latent to lytic infection. DNA viruses often modulate the function of critical cell cycle proteins to maximize the efficiency of virus replication. Here we have examined the effect of Rta on cell cycle progression. Cell cycle analysis revealed that Rta induced HeLa cells in G0/G1-phase to reenter the S-phase. Analysis of the expression pattern of a key set of cell cycle regulators revealed that expression of Rta inhibited the expression of Rb and p53 and induced the expression of E 2 F 1 . These findings suggest that Rta plays an active role in redirecting HeLa cell physiology through an Rta-mediated cell cycle transformation.