Usefulness of High Mobility Group Box 1 Protein as a Plasma Biomarker in Patient with Peripheral Artery Disease

Atherosclerosis is often associated with chronic vascular inflammation. High-mobility group box 1 protein (HMGB1) plays various roles, not only as a transcriptional regulatory factor in the nucleus, but also as an inflammatory mediator. A previous study suggested that fibrinogen is an important factor associated with atherosclerosis progression. The present study was performed to examine the levels of plasma HMGB1 protein in atherosclerosis patients. We studied 24 patients with peripheral artery disease (PAD) with atherosclerosis, and 10 healthy controls. We found that the concentrations of HMGB1 were increased in the plasma of the patients with atherosclerosis, and there were significant correlations between the plasma HMGB1 and fibrinogen levels. Plasma HMGB1 may play a key role in the pathogenesis of clinical and experimental atherosclerosis

Adrenocorticotropic hormone at pathophysiological concentration modulates the proliferation and differentiation of bone cells

SummaryBackground/purposeAdrenocorticotropic hormone (ACTH) plays a vital role in maintaining the function of the hypothalamic–pituitary–adrenal axis. Recent studies have demonstrated that ACTH directly affects the proliferation and differentiation of bone cells. However, the ACTH concentrations used in these studies appear to be markedly higher than the physiological concentrations. Here, we investigated whether ACTH at pathophysiological concentration affects the proliferation and differentiation of osteoblasts and osteoclasts.Materials and methodsWe evaluated the effect of ACTH at pathophysiological concentration on osteoclasts using tartrate-resistant acid phosphatase staining and on osteoblasts using alkaline phosphatase activity assay. Additionally, we conducted reverse transcriptase-polymerase chain reaction analysis.ResultsWe found that at pathophysiological concentration, ACTH does not affect osteoblast proliferation and inhibits osteoblast differentiation. Moreover, we showed that at pathophysiological concentration, ACTH does not affect the proliferation of bone marrow macrophages, but promotes differentiation of osteoclasts and induces expression of genes involved in bone resorption.ConclusionTaken together, our findings suggest that ACTH modulates the proliferation and differentiation of bone cells in vitro at pathophysiological concentration

Hepatocyte growth factor prevents lupus nephritis in a murine lupus model of chronic graft-versus-host disease

Chronic graft-versus-host disease (GVHD) induced in (C57BL/6 × DBA/2) F1 (BDF1) mice by the injection of DBA/2 mouse spleen cells represents histopathological changes associated with systemic lupus erythematosus (SLE), primary biliary cirrhosis (PBC) and Sjogren's syndrome (SS), as indicated by glomerulonephritis, lymphocyte infiltration into the periportal area of the liver and salivary glands. We determined the therapeutic effect of hepatocyte growth factor (HGF) gene transfection on lupus using this chronic GVHD model. Chronic GVHD mice were injected in the gluteal muscle with either HVJ liposomes containing 8 μg of the human HGF expression vector (HGF-HVJ liposomes) or mock vector (untreated control). Gene transfer was repeated at 2-week intervals during 12 weeks. HGF gene transfection effectively prevented the proteinuria and histopathological changes associated with glomerulonephritis. While liver and salivary gland sections from untreated GVHD mice showed prominent PBC- and SS-like changes, HGF gene transfection reduced these histopathological changes. HGF gene transfection greatly reduced the number of splenic B cells, host B cell major histocompatibility complex class II expression, and serum levels of IgG and anti-DNA antibodies. IL-4 mRNA expression in the spleen, liver, and kidneys was significantly decreased by HGF gene transfection. CD28 expression on DBA/2 CD4+ T cells was decreased by the addition of recombinant HGF in vitro. Furthermore, IL-4 production by DBA/2 CD4+ T cells stimulated by irradiated BDF1 dendritic cells was significantly inhibited by the addition of recombinant HGF in vitro. These results suggest that HGF gene transfection inhibited T helper 2 immune responses and reduced lupus nephritis, autoimmune sialoadenitis, and cholangitis in chronic GVHD mice. HGF may represent a novel strategy for the treatment of SLE, SS and PBC

For Vol.68, No.3 pp157-162 Usefulness of High Mobility Group Box 1 Protein as a Plasma Biomarker in Patient with Peripheral Artery Disease

Atherosclerosis is often associated with chronic vascular inflammation. High-mobility group box 1 protein (HMGB1) plays various roles, not only as a transcriptional regulatory factor in the nucleus, but also as an inflammatory mediator. A previous study suggested that fibrinogen is an important factor associated with atherosclerosis progression. The present study was performed to examine the levels of plasma HMGB1 protein in atherosclerosis patients. We studied 24 patients with peripheral artery disease (PAD) with atherosclerosis, and 10 healthy controls. We found that the concentrations of HMGB1 were increased in the plasma of the patients with atherosclerosis, and there were significant correlations between the plasma HMGB1 and fibrinogen levels. Plasma HMGB1 may play a key role in the pathogenesis of clinical and experimental atherosclerosis

Optimization of Ladle Tilting Speed for Preventing Temperature Drops in the Die Casting Process

In die casting, molten metal poured into a shot sleeve is pressed into a mold by a plunger at high speed. The temperature of the metal drops significantly while it is being poured from the ladle to the shot sleeve, resulting in casting defects such as misrun flow lines. Although it is important to control the temperature at all stages of the process, a method for minimizing temperature loss has not yet been clarified to date. In this study, the cause of the temperature drop in the shot sleeve was clarified, and a method of optimizing the ladle tilting speed was proposed to prevent temperature drop. First, experiments were conducted to measure the decrease in metal temperature in the sleeve during pouring. These experiments revealed that the metal cools significantly from the moment it touches the shot sleeve. Therefore, the time from the first contact between the shot sleeve and the metal to the start of pouring was set as the objective function. A genetic algorithm was then used to derive the optimal ladle tilting speed pattern to suppress the temperature drop. This analysis confirmed that the metal was poured without flowing out or running ahead and that the immediate liquid level vibration after pouring was suppressed, thus ensuring stable pouring

Conversion of ethanol to propylene over HZSM-5(Ga) co-modified with lanthanum and phosphorous

Conversion of ethanol to propylene was carried out over HZSM-5(Ga) co-modified with lanthanum and phosphorous (La/P/HZSM-5(Ga)). The propylene yield was strongly dependent on both the La/Ga and P/Ga ratios, and the highest value of ca.29 C-% was obtained at a P/Ga ratio of 1 and a La/Ga ratio of 0.4. FT-IR, P-31 MAS NMR, and Ga-71 MAS NMR measurements demonstrate that the introduced lanthanum reacts with the pre-introduced phosphorous to regenerate some of Bronsted acid sites (Si(OH)Ga), and accordingly, the Bronsted acid sites are homogeneously distributed within the zeolite framework. In addition, the catalytic stability as well as the catalytic activity of HZSM-5(Ga) was effectively enhanced by co-modification with lanthanum and phosphorous because of the suppression of carbonaceous deposition and elimination of gallium from the zeolite framework

Novel antimyeloma therapeutic option with inhibition of the HDAC1-IRF4 axis and PIM kinase

Multiple myeloma (MM) preferentially expands and acquires drug resistance in the bone marrow (BM). We herein examined the role of histone deacetylase 1 (HDAC1) in the constitutive activation of the master transcription factor IRF4 and the prosurvival mediator PIM2 kinase in MM cells. The knockdown or inhibition of HDAC1 by the class I HDAC inhibitor MS-275 reduced the basal expression of IRF4 and PIM2 in MM cells. Mechanistically, the inhibition of HDAC1 decreased IRF4 transcription through histone hyperacetylation and inhibiting the recruitment of RNA polymerase II at the IRF4 locus, thereby reducing IRF4-targeting genes, including PIM2. In addition to the transcriptional regulation of PIM2 by the HDAC1-IRF4 axis, PIM2 was markedly upregulated by external stimuli from BM stromal cells and interleukin-6 (IL-6). Upregulated PIM2 contributed to the attenuation of the cytotoxic effects of MS-275. Class I HDAC and PIM kinase inhibitors cooperatively suppressed MM cell growth in the presence of IL-6 and in vivo. Therefore, the present results demonstrate the potential of the simultaneous targeting of the intrinsic HDAC1-IRF4 axis plus externally activated PIM2 as an efficient therapeutic option for MM fostered in the BM