No abstract

SummaryAplastic anaemia (AA) is thought to be an autoimmune-mediated disease with active destruction of haematopoietic cells through a T helper type 1 (Th1) cell response. Interleukin (IL)-17 is a potent proinflammatory cytokine produced by activated memory T cells. Recent studies indicate that IL-17 might be an essential effector cytokine in the T-cell mediated autoimmune process. It can drive the production of tumour necrosis factor-a (TNF-a), IL-1 b, IL-6 and IL-8 by a variety of cells. The present study investigated the genetic and protein expression of IL-17 in patients with AA. The effect of IL-17 on IL-6 and IL-8 production by macrophages was also studied. AA patients showed an elevated expression of IL17A mRNA in bone marrow mononuclear cells and peripheral blood mononuclear cells. Higher IL-17 in bone marrow and peripheral blood plasma was also observed in AA patients compared with normal controls. IL-17 induced the production of IL-6 and IL-8 by macrophages both from patients with AA and normal controls. IL-17 stimulation also resulted in the production of TNF-a. These results suggested that elevated expression of IL-17 and IL-17-induced IL-6, IL-8 and TNF-a may be involved in the mechanisms of AA.

Abstract-In this paper, the multiagent coordination problem is studied. This problem is addressed for a class of robots for which control Lyapunov functions can be found. The main result is a suite of theorems about formation maintenance, task completion time, and formation velocity. It is also shown how to moderate the requirement that, for each individual robot, there exists a control Lyapunov function. An example is provided that illustrates the soundness of the method.

Abstract. Berberine (BBR) is a botanical alkaloid that has been reported to have effects in cardiovascular diseases; however, the mechanisms involved are not yet fully understood. In the present study, the protective effects of BBR were evaluated, and the underlying molecular mechanisms were investigated. The effects of a combination of atorvastatin and BBR on foam cell formation were also investigated. THP-1-derived macrophages were pre-treated with BBR (5, 10 and 20 mg/l) for 2 h prior to the addition of oxidized low density lipoprotein (ox-LDL; 50 mg/l). Small interfering RNA (siRNA) targeting sirtuin 1 (SIRT1) and the adenosine 5'-monophosphate-activated protein kinase (AMPK) inhibitor, compound C, were used to investigate the mechanisms through which BBR exerts its effects. To determine the effect of a combination of atorvastatin and BBR, the macrophages were treated with atorvastatin and BBR separately or jointly for 2 h, and then treated with ox-LDL (50 mg/l) or lipopolysaccharide (LPS; 10 µM) for 12 h. Oil Red O staining was used to detect foam cell formation. Lipid amounts were assessed by high-performance liquid chromatography (HPLC). Gene and protein expression was evaluated by RT-qPCR, western blot analysis and enzyme-linked immunosorbent assay (ELISA) carried out separately or jointly. The results from Oil Red O staining and HPLC revealed that BBR effectively suppressed foam cell formation and lipid and cholesterol accumulation. Furthermore, BBR upregulated the expression of SIRT1 and AMPK and downregulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ). Pre-treatment of the cells with SIRT1-siRNA or compound C attenuated the anti-atherosclerotic effects of BBR. The results obtained in the present study demonstrate that the combination of atorvastatin and BBR is more effective in inhibiting foam cell formation than using atorvastatin alone. These data suggest that BBR suppresses foam cell formation by activating the AMPK-SIRT1-PPAR-γ pathway and diminishing the uptake of ox-LDL. Combination therapy with BBR and atorvastatin was more effective in preventing atherosclerotic processes than atorvastatin alone.

Elevated expression of survivin is observed in a number of cancer types, including human osteosarcoma. Few studies have demonstrated that survivin expression levels can be considered an independent predictor of survival for human osteosarcoma patients. However, the underlying molecular mechanisms of survivin in the process of human osteosarcoma carcinogenesis remain unclear. In the current study, we evaluated the biological effects of survivin knockdown on osteosarcoma cell proliferation, colony formation rate, and sensitivity to the chemotherapeutic agent cisplatin. We found that two different osteosarcoma cell lines, U2OS and Saos-2, have relatively higher expression levels of survivin, and specific knockdown of survivin resulted in a number of effects, such as inhibition of cell proliferation, decreased colony formation rate, cell cycle arrest at G2/M phase, induction of apoptosis, and increased sensitivity to cisplatin. In addition, we identified two microRNAs, miR-34a and miR-203, that are aberrantly expressed in human osteosarcoma cells and specifically target survivin by inhibiting its expression, therefore repressing osteosarcoma cell maintenance and proliferation.

Abstract. Studies have shown that the oxidative modification of low-density lipoprotein (oxLDL) plays a major role in atherogenesis. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediated the transport of oxLDL into macrophages, which promoted foam cell formation. Targeting LOX-1 may therefore be a promising approach to inhibit atherosclerosis. In the present study, we aimed to investigate the effect of berberine combined with atorvastatin on LOX-1 and explore the underlying molecular mechanism involved. Expression of LOX-1 in monocyte-derived macrophages (MDMs) exposed to berberine (0, 0.1, 1, 10 and 100 nM) and atorvastatin (100 nM) were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis. Results showed that the expression of LOX-1 was decreased in a dose-dependent manner. Additionally, knockdown of the endothelin-1 (ET-1) receptor significantly blocked the inhibitory effect of berberine on LOX-1 expression. Body weight (BW), liver weight (LW) and kidney weight (KW) in the model rats were markedly increased at concentrations of berberine ≥1 µmol/kg, while heart weight (HW) and spleen weight (SW) remained constant among all groups. Berberine combined with atorvastatin also decreased serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C) levels in the rat model as well as inflammation and oxidative stress. Furthermore, plasma ET-1 levels and LOX-1 expression were decreased by berberine combined with atorvastatin treatment, and the inhibitory effect on LOX-1 was impeded by an ET-1 receptor antagonist. The results demonstrated that berberine combined with atorvastatin downregulates LOX-1 expression through ET-1 receptors in monocyte/macrophages in vitro and in vivo.

No abstract

The anti-multiple myeloma (MM) potential of natural killer (NK) cells has been of rising interest in recent years. However, the molecular mechanism of NK cell cytotoxicity to myeloma cells remains unclear. In the present study, we investigated the expressions of human leukocyte antigen (HLA) class I and HLA-G in patient myeloma cells, and determined their relevance in patient tumor-cell susceptibility to NK cell cytotoxicity. Our results showed that patient myeloma cells (n 5 12) were relatively resistant to NK-92 cell lysis, compared with myeloma cell lines (n 5 7, P < 0.01). Gene expression profiling and flow cytometry analysis showed that both mRNA and protein of HLA class I were highly expressed in 12 patient myeloma cells. Interestingly, no or low HLA-G surface expression was detected, although multiple HLA-G transcripts were detected in these myeloma cells. NK cell function assay showed that down-regulating HLA class I expression on patient cells by acid treatment significantly increased the susceptibility of MM cells to NK-mediated lysis. Furthermore, we found that the blocking of membrane-bound HLA class I rather than HLA-G using antibodies on myeloma samples markedly increased their susceptibility to NK-mediated killing. These results demonstrated that the resistance of patient MM cells to NK lysis mainly involves an HLA class Idependent mechanism, suggesting that HLA class I may be involved in protecting MM cells from NK-mediated attack and contribute to their immune escape in vivo.