Tim K. Tso

Orally administered mycelial culture of Phellinus linteus exhibits antitumor effects in hepatoma cell-bearing mice

AIM OF THE STUDY The aim of this study was to evaluate the anticancer effect of a mycelial culture from Phellinus linteus PL-7 (MCPL-7) and to elucidate its potential mechanism in vivo. MATERIALS AND METHODS SCID CB-17 mice received a transplant of Hep3B cells followed by daily MCPL-7 administrations for 8 weeks. Following tumor implantation, groups C-E were subcutaneously administered 50 mg/kg, 100 mg/kg, or 250 mg/kg MCPL-7 powder per day, respectively, for 8 weeks. Groups A and B received saline solution subcutaneously for 8 weeks. RESULTS MCPL-7 administration induced a significant reduction in tumor size and was associated with a significant increase in T cell numbers; IL-12, IFN-γ and TNF-α secretion; NK cell activity; and phagocytic ability. Therefore, increased numbers of CD4(+) cells could have been caused by greater numbers of dendritic cells and macrophages in the spleen. Furthermore, the activation of dendritic cells and macrophages resulted in increased IL-12 secretion, which could upregulate NK cell activation. The increased secretion of IL-12, IFN-γ, and TNF-α enhanced the activity and phagocytic ability of NK cells. Thus, MCPL-7 may provide a potential therapeutic approach for both immunomodulatory and antitumor effects.

Elevation of fasting insulin and its association with cardiovascular disease risk in women with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis. We previously showed that SLE patients have a higher risk of insulin resistance (IR) and abnormal insulin secretion. The present study was to further investigate the relationship between fasting insulin levels and both classic and novel cardiovascular risk factors in patients with SLE. Body mass index (BMI), fasting glucose and insulin, lipid profile, oxidation markers, fibrinolytic factors, vascular function factors, and disease-specific variables were determined in a total of 87 female SLE patients. The homeostasis model assessment (HOMA) was used to evaluate the IR and secretion. SLE patients had significantly higher fasting insulin, HOMA IR, HOMA β-cell, titers of autoantibodies against oxidized low density lipoprotein, systolic blood pressure, homocysteine, and brachial-ankle pulse wave velocity (baPWV) than age-matched healthy controls. There were no statistical differences in disease duration, anti-dsDNA, C3, C4, disease activity, and medication dosage between SLE patients stratified by fasting insulin levels. However, mean values for BMI, insulin, HOMA IR, HOMA β-cell, triglyceride (TG), homocysteine, and baPWV were significantly higher in the SLE patients with hyperinsulinemia when compared with those SLE controls. In addition, fasting insulin levels were positively correlated with TG, homocysteine, blood pressure, plasminogen activator inhibitor 1, and baPWV in SLE patients. The elevation of fasting insulin levels in SLE patients is not only associated with IR, but is related to classic and novel cardiovascular risk factors. This study concludes that there is an insulin-related cardiovascular disease risk in SLE.

Enhanced oxidative status but not corresponding elevated antioxidative status by anticardiolipin antibody and disease activity in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis, and an increased susceptibility of plasma lipids and lipoproteins to oxidation could at least in part promote atherogenesis. The objective of this study was to identify the effects of anticardiolipin antibody (aCL) and disease activity on oxidative and antioxidative status in patients with SLE. In this study, patients in SLE/aCL+ group and in SLE disease activity index >3 group had significantly higher thiobarbituric acid reactive substance (TBARS) levels, titers of autoantibodies against oxidized low-density lipoprotein (ox-LDL), and glutathione peroxidase activity than that of healthy controls. However, only TBARS and titers of autoantibodies against ox-LDL but not antioxidant enzyme activities were significantly different between SLE subgroups. Thus, enhanced oxidative status but not corresponding elevated antioxidative status by the presence of aCL and active disease activity make potent antioxidant therapy valuable for these SLE patients in preventing oxidative damage.

Distinct impacts of syndesmophyte formation on male and female patients with ankylosing spondylitis

Aim:  Ankylosing spondylitis (AS), a chronic inflammatory autoimmune disease, mainly affects the axial skeleton, leading to sacroiliitis and rigidity of the spine. Both spinal rigidity and syndesmophyte development can affect bone formation and resorption. In addition, inflammatory cytokines and cell adhesion molecules are correlated with bone metabolism. The aim of this study was to investigate the effects of gender difference and syndesmophyte formation on cytokines, adhesion molecules and bone metabolism markers in AS patients.

An Exploratory Study of Factors Influencing Audience's Attitudes Toward Imported Television Programs in Taiwan

The diffusion of international television programs has been an important area of international communication research. In this article, we use theoretical constructs from country-of-origin and cultural proximity literatures and develop a model to explain audiences attitudes toward and willingness to watch imported television programs from China. Our study used a questionnaire survey method to collect data from 553 respondents in Taiwan. We examined television programs imported from China, a country that has tried to invade Taiwan to destroy its democracy in the past decades. Regression analyses found that, whereas cultural proximity was an important predictor, animosity turned out to be a more powerful predictor of Taiwanese audiences attitudes toward television programs from China. The results also demonstrated that if the Taiwanese audience perceived China as holding less animosity and more cultural proximity, they had more positive attitudes and were more willing to watch television programs imported from China.

Canna indica L. attenuates high-glucose- and lipopolysaccharide-induced inflammatory mediators in monocyte/macrophage

ETHNOPHARMACOLOGICAL RELEVANCE Canna indica L. (CI) has been widely used as a folklore medicine in tropical and subtropical areas with beneficial effects in numerous diseases, including infection, rheumatism, hepatitis, and it has also been identified as an antioxidant. MATERIALS AND METHODS The present study aimed to investigate the effect of Canna indica CI ethanolic extract (CIE) on productions of nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-1β (IL-1β) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. In addition, the effects of CIE in high glucose (HG)-induced U937 monocytes on mRNA expressions of IL-8 and monocyte chemoattractant protein-1 (MCP-1), and regulation of mitogen-activated protein kinase (MAPK) pathways were also identified. RESULTS CIE was found to inhibit the production of inflammatory mediators including NO, IL-1β, and PGE2 from LPS-induced RAW 264.7 macrophages. The increases in HG-induced mRNA expressions of IL-8 and MCP-1 were also significantly inhibited by CIE. Stimulation of HG in U937 monocytes resulted in activation of p38 MAPK, ERK1/2, and JNK. However, CIE treatment significantly decreased phosphorylation of p38 MAPK, ERK1/2, and JNK. CONCLUSION The present study demonstrated that CIE suppressed the LPS-induced inflammatory mediator production and also inhibited HG-induced inflammatory mediator expression by the regulation of MAPK pathway.

Impaired phagocytosis of apoptotic cell material in serologically active clinically quiescent patients with systemic lupus erythematosis

Serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE) account for 8–12% of all patients with SLE, but there is disagreement about whether such patients are indeed clinically stable. Patients with clinically active SLE have decreased macrophage function, although the status of SACQ patients with SLE is unclear.

Etoricoxib improves osteoarthritis pain relief, joint function, and quality of life in the extreme elderly

Etoricoxib is a selective cyclooxygenase-2 inhibitor, with a lower risk of gastrointestinal toxicity compared to traditional nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the effectiveness and tolerability of etoricoxib in extremely elderly patients with chronic pain due to osteoarthritis (OA). A prospective, single-center, single-arm study was conducted, enrolling 19 extremely elderly men with OA (mean age 85.9, range 79-96 years), who responded inadequately to NSAIDs or other analgesics. Patients were switched to etoricoxib, 60 mg once daily for 4 weeks, without prior medication washout. Data were recorded before and after etoricoxib treatment. The primary endpoint was improvement in pain, assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) after the 4-week treatment. Other endpoints included the Brief Pain Inventory Short Form (BPI-SF), Treatment Satisfaction Questionnaire for Medication (TSQM), Short Form 36 (SF36), and European Quality of Life-5 Dimensions (EQ-5D). Safety and tolerability were assessed by collecting adverse events data. Pain and disability scores measured by WOMAC index were lower after treatment (pain, p ≤ 0.001; disability, p = 0.020). BPI-SF showed a significant improvement in joint function when walking and performing normal work (walking, p = 0.021; normal work, p = 0.030). SF36 scores improved for 7 out of 11 items after etoricoxib treatment (#1, p = 0.032; #4, p = 0.026; #5, p = 0.017; #6, p = 0.008; #7, p = 0.009; #8, p = 0.013; and #10, p = 0.038). EQ-5D showed a significant improvement in visual analogue scale scores (p = 0.036). TSQM results demonstrated a higher patient perception of overall satisfaction. No adverse events were reported. Pain relief, joint function, quality of life, and treatment satisfaction improved significantly in elderly patients with OA after etoricoxib administration.

Impaired transglutaminase 2 expression in patients with systemic lupus erythematosus

第二型轉麩胺酶是一種多功能蛋白，會造成蛋白的聚合或多胺類的嵌入的酵素，它們的交互作用已經被證實與細胞外鈣引入（Ca2+-influx）的分子機制有關。先前的研究也證實第二型轉麩胺酶是參與細胞凋亡及凋亡小體形成的潛在因子。這個研究的目的是要檢驗全身性紅斑性狼瘡患者，周邊血液單核球第二型轉麩胺酶表現量及與臨床表現關聯性。38位台中榮民總醫院過敏免疫風濕科門診病患及32位健康對照組參與此研究。取得受試者的血液樣本並分離出周邊血液單核球後，利用Trizol試劑來抽取細胞RNA，之後藉由反轉錄聚合酶反應將RNA轉錄為cDNA，將cDNA編碼至第二型轉麩胺酶和GAPDH特異性引子，再反轉錄聚合酶反應後用洋菜膠電泳呈現。研究結果顯示，全身性紅斑性狼瘡患者平均年紀為42.66±12.84歲，SLEDAI平均為2.63±2.42，全身性紅斑性狼瘡患者周邊血液單核球第二型轉麩胺酶表現量有顯著高於健康對照組。但是，其他的臨床因子，包括年紀、疾病活動度、病期及血清數據皆無統計學顯著相關。先前的研究顯示，周邊血液單核球第二型轉麩胺酶過度表現會強化細胞凋亡的速度。目前的研究結果尚且無法證實巨噬細胞吞噬能力低落的關連性，推測可能因此造成分化成巨噬細胞吞噬功能低落，更強化先前研究推論內在因素（intrinsic factor）影響的可能性，未來可能需要更多的研究分析證實其相關性。

AB0560 Expression of Regulatory Factors Related to Reverse Cholesterol Transport in Patients with Systemic Lupus Erythematosus

Background Systemic lupus erythematosus (SLE) is the autoimmune disease that patients with chronic inflammatory phenomena can induce early atherosclerosis, thereby increasing the risk of cardiovascular disease. Objectives The aim of this study was to investigate the peroxisome proliferator-activated receptor γ (PPAR γ)- liver X receptors α (LXRα)-ATP binding cassette transporter-A1 (ABCA1) pathway in reverse cholesterol transport and its association with cholesterol removal factors including lecithin cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and ABCA1. Methods A total of 68 subjects including thirty-eight SLE patients and thirty healthy subjects participated in this study. PPARα, PPARγ, LXRα and ABCA1 mRNA levels in peripheral blood mononuclear cells were analyzed by RT-PCR analysis and plasma levels of LCAT, CETP and ABCA1 were determined by enzyme-linked immunosorbent assay. Results PPARα, PPARγ, LXRα, and ABCA1 mRNA levels of SLE patients were significantly lower than those in healthy controls. With respect to insulin resistance, patients with HOMA IR>2 had higher levels of glucose, insulin, and triglyceride (TG) than patients with HOMA IR<2. However, HOMA-IR values were not related to factors involved in cholesterol efflux in this study. In addition, total cholesterol (TC) levels were significantly correlated to CETP and LCAT. Plasma TG levels were significantly correlated to CETP, and high-density lipoprotein cholesterol (HDL-C) levels were significantly correlated to PPARα, CETP, and LCAT in patients with SLE. The PPARγ mRNA expression was much more associated with HDL-C than TC and TG. The plasma levels of lipids in SLE seemed to be more associated with PPARα, PPARγ, LXRα and ABCA1 mRNA expressions than plasma level of ABCA1. Conclusions PPARα, PPARγ, LXRα and ABCA1 mRNA expressions were significantly decreased in SLE patients, suggesting the reduction of the reverse cholesterol transport in terms of PPARγ-LXRα-ABCA1 pathway may at least in part play an important role in the risk of atherosclerosis in SLE. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4141