Tonicity-responsive enhancer-binding protein promotes hepatocellular carcinogenesis, recurrence and metastasis

Objectives: Hepatocellular carcinoma (HCC) is a common cancer with high rate of recurrence and mortality. Diverse aetiological agents and wide heterogeneity in individual tumours impede effective and personalised treatment. Tonicity-responsive enhancer-binding protein (TonEBP) is a transcriptional cofactor for the expression of proinflammatory genes. Although inflammation is intimately associated with the pathogenesis of HCC, the role of TonEBP is unknown. We aimed to identify function of TonEBP in HCC. Design: Tumours with surrounding hepatic tissues were obtained from 296 patients with HCC who received completion resection. TonEBP expression was analysed by quantitative reverse transcription-quantitative real-time PCR (RT-PCR) and immunohfistochemical analyses of tissue microarrays. Mice with TonEBP haplodeficiency, and hepatocyte-specific and myeloid-specific TonEBP deletion were used along with HCC and hepatocyte cell lines. Results: TonEBP expression is higher in tumours than in adjacent non-tumour tissues in 92.6% of patients with HCC regardless of aetiology associated. The TonEBP expression in tumours and adjacent non-tumour tissues predicts recurrence, metastasis and death in multivariate analyses. TonEBP drives the expression of cyclo-oxygenase-2 (COX-2) by stimulating the promoter. In mouse models of HCC, three common sites of TonEBP action in response to diverse aetiological agents leading to tumourigenesis and tumour growth were found: cell injury and inflammation, induction by oxidative stress and stimulation of the COX-2 promoter. Conclusions: TonEBP is a key component of the common pathway in tumourigenesis and tumour progression of HCC in response to diverse aetiological insults. TonEBP is involved in multiple steps along the pathway, rendering it an attractive therapeutic target as well as a prognostic biomarker

Causes and Treatment Outcomes of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in 82 Adult Patients

original article korean j intern med 2012;27:203-21

The presence of high level soluble herpes virus entry mediator in sera of gastric cancer patients

The development of gastric cancer (GC) is closely related to chronic inflammation caused by Helicobacter pylori infection, and herpes virus entry mediator (HVEM) is a receptor expressed on the surface of leukocytes that mediates potent inflammatory responses in animal models. However, the role of HVEM in human GC has not been studied. Previously, we showed that the interaction of HVEM on human leukocytes with its ligand LIGHT induces intracellular calcium mobilization, which results in inflammatory responses including induction of proinflammatory cytokine production and anti-bacterial activities. In this study, we report that leukocytes from GC patients express lower levels of membrane HVEM (mHVEM) and have lower LIGHT-induced bactericidal activities than those from healthy controls (HC). In contrast, levels of soluble HVEM (sHVEM) in the sera of GC patients were significantly higher than in those of HC. We found that monocyte membrane-bound HVEM is released into the medium when cells are activated by proinflammatory cytokines such as TNF-α and IL-8, which are elevated in the sera of GC patients. mHVEM level dropped in parallel with the release of sHVEM, and release was completely blocked by the metalloprotease inhibitor, GM6001. We also found that the low level of mHVEM on GC patient leukocytes was correlated with low LIGHT-induced bactericidal activities against H. pylori and S. aureus and production of reactive oxygen species. Our results indicate that mHVEM on leukocytes and sHVEM in sera may contribute to the development and/or progression of GC

Addition of Na3PO4 for Enhanced Positive Electrode Performance in All-Solid-State Sodium Batteries

All-solid-state sodium secondary batteries have attracted attention as next-generation batteries owing to their balanced performances in terms of energy density, battery life, abundant availability of sodium resources, and resulting cost reduction. For the positive electrode materials, NaFe0.5Mn0.5O2 is promising because it consists of abundant elements. However, its application in all-solid-state batteries with sulfide solid electrolytes are hindered by side reactions with the solid electrolytes, which lower the operating voltage. In this study, the electrode performances of all-solid-state sodium batteries were enhanced by mixing Na3PO4 with NaFe0.5Mn0.5O2 particles. Subsequent heat treatment further improved the electrode performance, resulting in an increased discharge voltage and a reversible capacity of 140 mAh g−1

The ClpP Protease of Streptococcus pneumoniae Modulates Virulence Gene Expression and Protects against Fatal Pneumococcal Challenge

Streptococcus pneumoniae usually colonizes the nasopharynx of humans asymptomatically but occasionally translocates from this niche to the lungs, the brain, and the blood, causing potentially fatal infections. Spread to other host tissues requires a significant morphological change and the expression of virulence factors, such as capsular polysaccharide, and virulence proteins, such as pneumolysin (Ply), PspA, and CbpA. Modulation of the expression of pneumococcal virulence genes by heat shock and by heat shock proteins ClpL and ClpP, as well as the attenuation of virulence of a clpP mutant in a murine intraperitoneal infection model, was demonstrated previously. In this study, we further investigated the underlying mechanism of virulence attenuation by the clpP mutation. The half-lives of the mRNAs of ply and of the first gene of the serotype 2 capsule synthesis locus [cps(2)A] in the clpP mutant were more than twofold longer than those of the parent after heat shock, suggesting that the mRNA species were regulated posttranscriptionally by ClpP. In addition, the clpP mutant was defective in colonization of the nasopharynx and survival in the lungs of mice after intranasal challenge. The mutant was also killed faster than the parent in the murine macrophage RAW264.7 cell line, indicating that ClpP is required for colonization and intracellular survival in the host. Furthermore, fractionation studies demonstrated that ClpP was translocated into the cell wall after heat shock, and immunization of mice with ClpP elicited a protective immune response against fatal systemic challenge with S. pneumoniae D39, making ClpP a potential vaccine candidate for pneumococcal disease

Modulation of Adherence, Invasion, and Tumor Necrosis Factor Alpha Secretion during the Early Stages of Infection by Streptococcus pneumoniae ClpL▿

Heat shock proteins (HSPs) play a pivotal role as chaperones in the folding of native and denatured proteins and can help pathogens penetrate host defenses. However, the underlying mechanism(s) of modulation of virulence by HSPs has not been fully determined. In this study, the role of the chaperone ClpL in the pathogenicity of Streptococcus pneumoniae was assessed. A clpL mutant adhered to and invaded nasopharyngeal or lung cells much more efficiently than the wild type adhered to and invaded these cells in vitro, as well as in vivo, although it produced the same amount of capsular polysaccharide. However, the level of secretion of tumor necrosis factor alpha (TNF-α) from macrophages infected with the clpL mutant was significantly lower than the level of secretion elicited by the wild type during the early stages of infection. Interestingly, treatment of the human lung epithelial carcinoma A549 and murine macrophage RAW 264.7 cell lines with cytochalasin D, an inhibitor of actin polymerization, increased adherence of the mutant to the host cells. In contrast, cytochalasin D treatment of RAW 264.7 cells decreased TNF-α secretion after infection with either the wild type or the mutant. However, pretreatment of cell lines with the actin polymerization activator jasplakinolide reversed these phenotypes. These findings indicate, for the first time, that the ClpL chaperone represses adherence of S. pneumoniae to host cells and induces secretion of TNF-α via a mechanism dependent upon actin polymerization during the initial infection stage

Lossless Decompression Accelerator for Embedded Processor with GUI

The development of the mobile industry brings about the demand for high-performance embedded systems in order to meet the requirement of user-centered application. Because of the limitation of memory resource, employing compressed data is efficient for an embedded system. However, the workload for data decompression causes an extreme bottleneck to the embedded processor. One of the ways to alleviate the bottleneck is to integrate a hardware accelerator along with the processor, constructing a system-on-chip (SoC) for the embedded system. In this paper, we propose a lossless decompression accelerator for an embedded processor, which supports LZ77 decompression and static Huffman decoding for an inflate algorithm. The accelerator is implemented on a field programmable gate array (FPGA) to verify the functional suitability and fabricated in a Samsung 65 nm complementary metal oxide semiconductor (CMOS) process. The performance of the accelerator is evaluated by the Canterbury corpus benchmark and achieved throughput up to 20.7 MB/s at 50 MHz system clock frequency

Lossless Decompression Accelerator for Embedded Processor with GUI

The development of the mobile industry brings about the demand for high-performance embedded systems in order to meet the requirement of user-centered application. Because of the limitation of memory resource, employing compressed data is efficient for an embedded system. However, the workload for data decompression causes an extreme bottleneck to the embedded processor. One of the ways to alleviate the bottleneck is to integrate a hardware accelerator along with the processor, constructing a system-on-chip (SoC) for the embedded system. In this paper, we propose a lossless decompression accelerator for an embedded processor, which supports LZ77 decompression and static Huffman decoding for an inflate algorithm. The accelerator is implemented on a field programmable gate array (FPGA) to verify the functional suitability and fabricated in a Samsung 65 nm complementary metal oxide semiconductor (CMOS) process. The performance of the accelerator is evaluated by the Canterbury corpus benchmark and achieved throughput up to 20.7 MB/s at 50 MHz system clock frequency